Journals

Scars typically evolve through a series of successive stages with characteristic tissue morphologies. These panels show second harmonic generation images of, from left to right, normal skin tissue, hypertrophic scar and mature scar that are precisely diagnosed by a computer. Autofluorescence is shown green. Image height: 1.5 mm. (Picture: T. Kelf et al., pp 159–167 in this issue)

http://dx.doi.org/10.1002%2Fjbio.201290000

http://dx.doi.org/10.1002%2Fjbio.201290001

http://dx.doi.org/10.1002%2Fjbio.201200501

http://dx.doi.org/10.1002%2Fjbio.201200501

http://dx.doi.org/10.1002%2Fjbio.201290001

Scars typically evolve through a series of successive stages with characteristic tissue morphologies. These panels show second harmonic generation images of, from left to right, normal skin tissue, hypertrophic scar and mature scar that are precisely diagnosed by a computer. Autofluorescence is shown green. Image height: 1.5 mm. (Picture: T. Kelf et al., pp 159–167 in this issue)

http://dx.doi.org/10.1002%2Fjbio.201290000

Although it is increasingly recognized that the tumor biology is influenced by the tumor stroma, prognostic gene signatures are usually derived from tissue consisting of tumor cells and surrounding stroma. This study presents a compartment‐specific transcriptome analysis of lung squamous cell carcinoma (SCC) samples microdissected into tumor parenchyma and stroma fractions. Typical tumor and stroma genes were identified based on the expression ratios between the two compartments. Our results indicate that in SCC many markers related to longer survival are predominantly expressed in the stroma, particularly genes of the MHC‐II complex. Stromal upregulation of MHC‐II genes seems crucial for a clinically relevant antitumor immune response in SCC. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

http://dx.doi.org/10.1002%2Fjbio.201100115

Applying intravital fluorescence microscopy, we assessed sinusoidal delivery and biliary clearance of two different polymethine dyes. DY635, a benzopyrylium‐based hemocyanine dye with shorter excitation wavelength than indocyanine green (ICG), was validated for assessment of hepatic excretory function. Decrease of DY635 and ICG reflecting transcellular transport was 83 ± 4% (DY635) and 14 ± 2% (ICG; p < 0.05) over 35 minutes, respectively. In cholestasis, hepatobiliary excretion of DY635 was markedly impaired (control 3176 ± 148 pmol vs. cholestatic 1929 ± 179 pmol; p < 0.05). DY635 even enabled an analysis at high resolution suggesting 1.) hepatocyte uncoupling and 2.) failure of primarily the canalicular pole, allowing in vivo insights into molecular mechanisms of this critical facet of hepatobiliary function. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

http://dx.doi.org/10.1002%2Fjbio.201100118

The authors describe the interaction of biological nanostructures formed by β2‐microglobulin amyloid fibrils with three‐dimensional silicon microstructures consisting in periodic arrays of vertical silicon walls (≈3 μm‐thick) separated by 50 μm‐deep air gaps (≈5 μm‐wide). These structures are of great interest from a biological point of view since they well mimic the interstitial environment typical of amyloid deposition in vivo. Moreover, they behave as hybrid photonic crystals, potentially applicable as optical transducers for label‐free detection of the kinetics of amyloid fibrils formation. Fluorescence and atomic force microscopy (AFM) show that a uniform distribution of amyloid fibrils is achieved when fibrillogenesis occurs directly on silicon. The high resolution AFM images also demonstrate that amyloid fibrils grown on silicon are characterized by the same fine structure typically ensured by fibrillogenesis in solution. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

http://dx.doi.org/10.1002%2Fjbio.201100132

Amyloid fibrils are known to be responsible for diseases such as Alzheimer's disease. A detailed insight into the structure of amyloid fibrils is fundamental since it is not yet understood what triggers the misfolding of proteins to the fiber like structures. The molecular structure of fibril surfaces on a single amino acid level has not been revealed so far but would present a valuable contribution to this question. Here we demonstrate the direct molecular distinction of selected amino acids on insulin fibril surfaces with a lateral resolution better than 2 nm by applying tip‐enhanced Raman spectroscopy (TERS). This approach provides simultaneously a way to directly reveal conformational changes in the secondary structure, namely α‐helix, β‐sheet, on the fibril surface with nanometer resolution. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

http://dx.doi.org/10.1002%2Fjbio.201100142

Christian G. Parigger, Alexander Woods, James O. HornkohlWe present analysis of superposition spectra following laser-induced breakdown (LIB) of methane. Both hydrogen-beta and hydrogen-gamma lines contain discernible contributions from diatomic carbon emissions for time delays of 1 to 2 μs from pulsed, 8 ns, infrared Nd:YAG laser radiation LIB. ... [Appl. Opt. 51, B1-B6 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ao-51-7-B1

Jennifer L. GottfriedThe feasibility of exploiting plasma chemistry to study the chemical reactions between metallic nanoparticles and molecular explosives such as cyclotrimethylenetrinitramine (RDX) has been demonstrated. This method, based on laser-induced breakdown spectroscopy, involves the production of ... [Appl. Opt. 51, B13-B21 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ao-51-7-B13

Daniel Gagnon, Simon Lessard, Marc Verhaegen, Patrick Mutchmore, Paul Bouchard, François R. Doucet, Mohamad SabsabiDetection of sulfur by optical emission spectroscopy generally presents some difficulties because the strongest lines are in the vacuum UV below 185 nm and therefore are readily absorbed by oxygen molecules in air. A novel concept for a low-cost and efficient system to detect sulfur using near-IR ... [Appl. Opt. 51, B7-B12 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ao-51-7-B7

Tingbi Yuan, Zhe Wang, Lizhi Li, Zongyu Hou, Zheng Li, Weidou NiQuantitative carbon measurement in anthracites remains difficult with laser-induced breakdown spectroscopy (LIBS) due to its relatively high measurement uncertainty. To improve the measurement repeatability, binders to bind the anthracite powder together were utilized for LIBS measurement. Results ... [Appl. Opt. 51, B22-B29 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ao-51-7-B22

Tingbi Yuan, Zhe Wang, Lizhi Li, Zongyu Hou, Zheng Li, Weidou NiQuantitative carbon measurement in anthracites remains difficult with laser-induced breakdown spectroscopy (LIBS) due to its relatively high measurement uncertainty. To improve the measurement repeatability, binders to bind the anthracite powder together were utilized for LIBS measurement. Results ... [Appl. Opt. 51, B22-B29 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ao-51-7-B22

Daniel Gagnon, Simon Lessard, Marc Verhaegen, Patrick Mutchmore, Paul Bouchard, François R. Doucet, Mohamad SabsabiDetection of sulfur by optical emission spectroscopy generally presents some difficulties because the strongest lines are in the vacuum UV below 185 nm and therefore are readily absorbed by oxygen molecules in air. A novel concept for a low-cost and efficient system to detect sulfur using near-IR ... [Appl. Opt. 51, B7-B12 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ao-51-7-B7

Jennifer L. GottfriedThe feasibility of exploiting plasma chemistry to study the chemical reactions between metallic nanoparticles and molecular explosives such as cyclotrimethylenetrinitramine (RDX) has been demonstrated. This method, based on laser-induced breakdown spectroscopy, involves the production of ... [Appl. Opt. 51, B13-B21 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ao-51-7-B13

Christian G. Parigger, Alexander Woods, James O. HornkohlWe present analysis of superposition spectra following laser-induced breakdown (LIB) of methane. Both hydrogen-beta and hydrogen-gamma lines contain discernible contributions from diatomic carbon emissions for time delays of 1 to 2 μs from pulsed, 8 ns, infrared Nd:YAG laser radiation LIB. ... [Appl. Opt. 51, B1-B6 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ao-51-7-B1

Rikard Heimsten, Douglas G. MacMynowski, Torben Andersen, Mette Owner-PetersenWhile it is attractive to integrate a deformable mirror (DM) for adaptive optics (AO) into the telescope itself rather than using relay optics within an instrument, the resulting large DM can be expensive, particularly for extremely large telescopes. A low-cost approach for building a large DM is ... [Appl. Opt. 51, 515-524 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ao-51-5-515

Wen Xiong, C. S. Cai, Xuan KongScour is one of the main causes of bridge failures. In order to measure and monitor scour depth variations including deposition (refilling) process, three designs for a scour monitoring system using fiber Bragg grating (FBG) sensors are discussed in the present study. By a comparative study, one of ... [Appl. Opt. 51, 547-557 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ao-51-5-547

Edward Judokusumo, Erdem Tabdanov, Sudha Kumari, Michael L. Dustin, Lance C. Kam. Mechanical forces play an increasingly recognized role in modulating cell function. This report demonstrates mechanosensing by T cells, using polyacrylamide gels presenting ligands to CD3 and CD28....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05408-7

Sunilkumar Puthenpurackal Narayanan, Akihiro Maeno, Hiroshi Matsuo, Masayuki Oda, Hisayuki Morii, Kazuyuki Akasaka. We studied conformational fluctuations of the transcription factor c-Myb R2 subdomain (52 residues with three Trp) at high pressure and low temperature (5°C) using two different spectroscopic meth....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05416-6

Huan Lei, George Em Karniadakis. Sickle erythrocytes exhibit abnormal morphology and membrane mechanics under deoxygenated conditions due to the polymerization of hemoglobin S. We employed dissipative particle dynamics to extend ....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05403-8

Pawel Gniewek, Andrzej Kolinski. We designed a simple coarse-grained model of the glycocalyx layer, or adhesive mucus layer (AML), covered by mucus gel (luminal mucus layer) using a polymer lattice model and stochastic sampling (....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05361-6

Richard J. Powers, Sitikantha Roy, Erdinc Atilgan, William E. Brownell, Sean X. Sun, Peter G. Gillespie, Alexander A. Spector. In hair cells, although mechanotransduction channels have been localized to tips of shorter stereocilia of the mechanically sensitive hair bundle, little is known about how force is transmitted to....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05424-5

Adam Kapela, Jaimit Parikh, Nikolaos M. Tsoukias. The intercellular synchronization of spontaneous calcium (Ca2+) oscillations in individual smooth muscle cells is a prerequisite for vasomotion. A detailed mathematical model of Ca....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05461-0

Satoru Akama, Masayuki Yamamura, Takanori Kigawa. Multiphysics modeling, which integrates the models studied in different disciplines so far, is an indispensable approach toward a comprehensive understanding of biological systems composed of dive....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05415-4

Aslak Tveito, Glenn Terje Lines, Mary M. Maleckar. Reduced conduction velocity (CV) in the myocardium is well known to increase the probability of arrhythmia and can be caused by structural changes, reduced excitability of individual myocytes, or ....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05367-7

Tianzhi Luo, Krithika Mohan, Vasudha Srivastava, Yixin Ren, Pablo A. Iglesias, Douglas N. Robinson. Myosin II is a central mechanoenzyme in a wide range of cellular morphogenic processes. Its cellular localization is dependent not only on signal transduction pathways, but also on mechanical stre....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05422-1

Philippe Robert, Milos Aleksic, Omer Dushek, Vincenzo Cerundolo, Pierre Bongrand, P. Anton van der Merwe. Adaptive immune responses are driven by interactions between T cell antigen receptors (TCRs) and complexes of peptide antigens (p) bound to Major Histocompatibility Complex proteins (MHC) on the s....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05402-6

Fatemeh Khalili-Araghi, Emad Tajkhorshid, Benoît Roux, Klaus Schulten. Voltage sensor domains (VSD) are transmembrane proteins that respond to changes in membrane voltage and modulate the activity of ion channels, enzymes, or in the case of proton channels allow perm....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05349-5

Maria Musgaard, Lea Thøgersen, Birgit Schiøtt, Emad Tajkhorshid. Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) transports two Ca2+ ions across the membrane of the sarco(endo)plasmic reticulum against the concentration gradient, harvesti....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05406-3

Adela Rendón, David Gil Carton, Jesús Sot, Marcos García-Pacios, Ruth Montes, Mikel Valle, José-Luis R. Arrondo, Felix M. Goñi, Kepa Ruiz-Mirazo. Oleic acid vesicles have been used as model systems to study the properties of membranes that could be the evolutionary precursors of more complex, stable, and impermeable phospholipid biomembrane....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05455-5

Juliane Zimmermann, Claudia Brunner, Mihaela Enculescu, Michael Goegler, Allen Ehrlicher, Josef Käs, Martin Falcke. Cells migrate through a crowded environment during processes such as metastasis or wound healing, and must generate and withstand substantial forces. The cellular motility responses to environment....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05425-7

Naoko Tokuda, Tomoki P. Terada, Masaki Sasai. Eukaryotic genome is organized in a set of chromosomes each of which consists of a chain of DNA and associated proteins. Processes involving DNA such as transcription, duplication, and repair, the....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05401-4

Michael Bieri, Jesse I. Mobbs, Ann Koay, Gavin Louey, Yee-Foong Mok, Danny M. Hatters, Jong-Tae Park, Kwan-Hwa Park, Dietbert Neumann, David Stapleton, Paul R. Gooley. AMP-activated protein kinase interacts with oligosaccharides and glycogen through the carbohydrate-binding module (CBM) containing the β-subunit, for which there are two isoforms (β<....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05413-0

Yu-Shan Lin, Gregory R. Bowman, Kyle A. Beauchamp, Vijay S. Pande. The aggregation of amyloid beta (Aβ) peptides plays an important role in the development of Alzheimer's disease. Despite extensive effort, it has been difficult to characterize the secondar....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05365-3

Shailesh Tripathi, Vukica Šrajer, Namrta Purwar, Robert Henning, Marius Schmidt. Visualizing the three-dimensional structures of a protein during its biological activity is key to understanding its mechanism. In general, protein structure and function are pH-dependent. Changin....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05411-7

Nuria Plattner, Markus Meuwly. Myoglobin (Mb) is a model system for ligand binding and migration. The energy barriers (ΔG) for ligand migration in Mb have been studied in the past by experiment and theory and significant....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05351-3

Daniel Aioanei, Marco Brucale, Isabella Tessari, Luigi Bubacco, Bruno Samorì. We show via single-molecule mechanical unfolding experiments that the osmolyte glycerol stabilizes the native state of the human cardiac I27 titin module against unfolding without shifting its unf....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05404-X

Andreas Maximilian Stadler, Eric Pellegrini, Mark Johnson, Jörg Fitter, Giuseppe Zaccai. The removal of the heme group from myoglobin (Mb) results in a destabilization of the protein structure. The dynamic basis of the destabilization was followed by comparative measurements on holo- ....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05460-9

Katharina Klein, Alexander M. Gigler, Thomas Aschenbrenner, Roberto Monetti, Wolfram Bunk, Ferdinand Jamitzky, Gregor Morfill, Robert W. Stark, Jürgen Schlegel. Confocal Raman spectroscopy is a noninvasive alternative to established cell imaging methods because it does not require chemical fixation, the use of fluorescent markers, or genetic engineering. ....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05456-7

Danielle L. Leiske, Christopher I. Leiske, Daniel R. Leiske, Michael F. Toney, Michelle Senchyna, Howard A. Ketelson, David L. Meadows, Gerald G. Fuller. Meibomian lipids are the primary component of the lipid layer of the tear film. Composed primarily of a mixture of lipids, meibum exhibits a range of melt temperatures. Compositional changes that ....

http://www.cell.com/biophysj/abstract/S0006-3495(11)05419-1

Sam Walcott, Dong-Hwee Kim, Denis Wirtz, Sean X. Sun.

http://www.cell.com/biophysj/fulltext/S0006-3495(11)05463-4

Bhaskar Banerjee, Timothy Renkoski, Logan R. Graves et al. Detection of flat neoplasia is a major challenge in colorectal cancer screening, as missed lesions can lead to the development of an unexpected `incident' cancer prior to the subsequent endoscopy. The use of a tryptophan-related autofluorescence has been reported to be increased in murine intestinal ... [J. Biomed. Opt. 17, 016003 (2012)] published Wed Feb 1, 2012.

http://link.aip.org/link/?JBO/17/016003/1&agg=rss

Caigang Zhu and Quan Liu We present a hybrid method that combines a multilayered scaling method and a perturbation method to speed up the Monte Carlo simulation of diffuse reflectance from a multilayered tissue model with finite-size tumor-like heterogeneities. The proposed method consists of two steps. In the first step, a ... [J. Biomed. Opt. 17, 010501 (2012)] published Wed Feb 1, 2012.

http://link.aip.org/link/?JBO/17/010501/1&agg=rss

Yeongri Jung, Guangying Guan, Chen-wei Wei et al. Several imaging modalities such as optical coherence tomography, photothermal, photoacoustic and magnetic resonance imaging, are sensitive to different physical properties (i.e. scattering, absorption and magnetic) that can provide contrast within biological tissues. Usually exogenous agents are des ... [J. Biomed. Opt. 17, 016015 (2012)] published Wed Feb 1, 2012.

http://link.aip.org/link/?JBO/17/016015/1&agg=rss

Tomasz Buchwald, Krzysztof Niciejewski, Marek Kozielski et al. Raman microspectroscopy was used to examine the biochemical composition and molecular structure of extracellular matrix in spongy and subchondral bone collected from patients with clinical and radiological evidence of idiopathic osteoarthritis of the hip and from patients who underwent a femoral nec ... [J. Biomed. Opt. 17, 017007 (2012)] published Wed Feb 1, 2012.

http://link.aip.org/link/?JBO/17/017007/1&agg=rss

Tomasz Buchwald, Krzysztof Niciejewski, Marek Kozielski et al. Raman microspectroscopy was used to examine the biochemical composition and molecular structure of extracellular matrix in spongy and subchondral bone collected from patients with clinical and radiological evidence of idiopathic osteoarthritis of the hip and from patients who underwent a femoral nec ... [J. Biomed. Opt. 17, 017007 (2012)] published Wed Feb 1, 2012.

http://link.aip.org/link/?JBO/17/017007/1&agg=rss

Yeongri Jung, Guangying Guan, Chen-wei Wei et al. Several imaging modalities such as optical coherence tomography, photothermal, photoacoustic and magnetic resonance imaging, are sensitive to different physical properties (i.e. scattering, absorption and magnetic) that can provide contrast within biological tissues. Usually exogenous agents are des ... [J. Biomed. Opt. 17, 016015 (2012)] published Wed Feb 1, 2012.

http://link.aip.org/link/?JBO/17/016015/1&agg=rss

Caigang Zhu and Quan Liu We present a hybrid method that combines a multilayered scaling method and a perturbation method to speed up the Monte Carlo simulation of diffuse reflectance from a multilayered tissue model with finite-size tumor-like heterogeneities. The proposed method consists of two steps. In the first step, a ... [J. Biomed. Opt. 17, 010501 (2012)] published Wed Feb 1, 2012.

http://link.aip.org/link/?JBO/17/010501/1&agg=rss

Bhaskar Banerjee, Timothy Renkoski, Logan R. Graves et al. Detection of flat neoplasia is a major challenge in colorectal cancer screening, as missed lesions can lead to the development of an unexpected `incident' cancer prior to the subsequent endoscopy. The use of a tryptophan-related autofluorescence has been reported to be increased in murine intestinal ... [J. Biomed. Opt. 17, 016003 (2012)] published Wed Feb 1, 2012.

http://link.aip.org/link/?JBO/17/016003/1&agg=rss

Susanne Lange-Asschenfeldt, Jasmin Babilli, Marc Beyer et al. Reflectance confocal microscopy (RCM) represents a noninvasive imaging technique that has previously been used for characterization of mycosis fungoides (MF) in a pilot study. We aimed to test the applicability of RCM for diagnosis and differential diagnosis of MF in a clinical study. A total of 39 ... [J. Biomed. Opt. 17, 016001 (2012)] published Tue Jan 31, 2012.

http://link.aip.org/link/?JBO/17/016001/1&agg=rss

Julien Mandon, Marieann Hogman, Peter J. F. M. Merkus et al. Fractional exhaled nitric oxide (FNO) is considered an indicator in the diagnostics and management of asthma. In this study we present a laser-based sensor for measuring FNO. It consists of a quantum cascade laser (QCL) combined with a multi-pass cell and wavelength modulation spectroscopy for the d ... [J. Biomed. Opt. 17, 017003 (2012)] published Tue Jan 31, 2012.

http://link.aip.org/link/?JBO/17/017003/1&agg=rss

Nature Photonics celebrated its fifth birthday in January this year. Now is a good time to recap what we have done in the past, the current state of play and what we look forward to in the future.

http://feeds.nature.com/~r/nphoton/rss/current/~3/i7-fO4iKLKI/nphoton.2012.10

http://feeds.nature.com/~r/nphoton/rss/current/~3/avhvWLJEXfY/nphoton.2012.12

http://feeds.nature.com/~r/nphoton/rss/current/~3/7JJgUapbd0M/nphoton.2012.13

http://feeds.nature.com/~r/nphoton/rss/current/~3/FpQxqMdIt4k/nphoton.2012.14

http://feeds.nature.com/~r/nphoton/rss/current/~3/lQ74yVgXrXk/nphoton.2012.15

http://feeds.nature.com/~r/nphoton/rss/current/~3/gkMpYJ-hG2U/nphoton.2012.16

http://feeds.nature.com/~r/nphoton/rss/current/~3/ZEiCbSMJuRI/nphoton.2012.17

http://feeds.nature.com/~r/nphoton/rss/current/~3/jXDZFbdt_TE/nphoton.2012.18

http://feeds.nature.com/~r/nphoton/rss/current/~3/45luUPQFEX0/nphoton.2012.19

http://feeds.nature.com/~r/nphoton/rss/current/~3/5JzjgI17k9A/nphoton.2012.20

Researchers have shown that organic light-emitting diodes with transparent graphene electrodes are more flexible and exhibit higher efficiencies than those whose electrodes are made from rigid indium tin oxide.

http://feeds.nature.com/~r/nphoton/rss/current/~3/MDsWopCCgOc/nphoton.2011.349

By using a one-dimensional optical lattice to control and confine the location of cold 87Rb atoms, researchers have created a distributed Bragg reflector that enables optical parametric oscillation solely from atoms.

http://feeds.nature.com/~r/nphoton/rss/current/~3/qmgmf_MSrnk/nphoton.2012.9

http://feeds.nature.com/~r/nphoton/rss/current/~3/BDGLWHAM9Nw/nphoton.2011.351

Researchers have developed a semiconductor structure capable of supporting quantum correlations between photons and strong single-photon nonlinearities, thus paving the way for the development of chip-based devices for quantum secure communications and quantum information processing.

http://feeds.nature.com/~r/nphoton/rss/current/~3/ZxDsW-Ni7Xc/nphoton.2012.6

Photonic manipulation of the spatial distribution of charge in relativistic electron bunches provides a promising way to generate intense coherent terahertz radiation.

http://feeds.nature.com/~r/nphoton/rss/current/~3/TvaNPEAuMN8/nphoton.2011.348

http://feeds.nature.com/~r/nphoton/rss/current/~3/a9TEZIXoce4/nphoton.2012.5

Using extremely broadband ultrafast near-infrared pulses, scientists have demonstrated simultaneous second-harmonic-generation, third-harmonic-generation and four-wave-mixing microscopy, enabling a range of different structures and functional groups in a biological sample to be imaged at once.

http://feeds.nature.com/~r/nphoton/rss/current/~3/5oMM_tZRh-Q/nphoton.2011.347

http://feeds.nature.com/~r/nphoton/rss/current/~3/fgwUeqwfZ5A/nphoton.2012.3

An efficient continuous-wave source of terahertz radiation that combines the outputs from two near-infrared semiconductor lasers in a novel photomixer looks set to benefit applications in spectroscopy and imaging.

http://feeds.nature.com/~r/nphoton/rss/current/~3/MZNs1IiBh78/nphoton.2012.8

Amalgamating the interdisciplinary domains of nanotechnology and terahertz technology, particularly the field of terahertz science in nanomaterials and nanodevices, seems to be where the terahertz research community is now heading.

http://feeds.nature.com/~r/nphoton/rss/current/~3/BRxUJxLs0e4/nphoton.2012.4

http://feeds.nature.com/~r/nphoton/rss/current/~3/HHcuhuE3tO8/nphoton.2011.346

http://feeds.nature.com/~r/nphoton/rss/current/~3/o_RHvnXf0F4/nphoton.2012.21

http://feeds.nature.com/~r/nphoton/rss/current/~3/twhT_jmIy5k/nphoton.2011.345

A semiconductor is usually opaque to any light whose photon energy is larger than the semiconductor bandgap. Nature Photonics spoke to Stephen Durbin about how to render GaAs semiconductor crystals transparent using intense X-ray pulses.

http://feeds.nature.com/~r/nphoton/rss/current/~3/9hLEpZVIGr0/nphoton.2012.7

An expansion of Porphyromonadaceae in the gut is linked to the pathogenesis and progression of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in the mouse.

http://feeds.nature.com/~r/nature/rss/aop/~3/5LwF3Damo28/nature10809

Quantum computers could be used to solve certain problems exponentially faster than classical computers, but are challenging to build because of their increased susceptibility to errors. However, it is possible to detect and correct errors without destroying coherence, by using quantum error correcting codes. The simplest of these are three-quantum-bit (three-qubit) codes, which map a one-qubit state to an entangled three-qubit state; they can correct any single phase-flip or bit-flip error on one of the three qubits, depending on the code used. Here we demonstrate such phase- and bit-flip error correcting codes in a superconducting circuit. We encode a quantum state, induce errors on the qubits and decode the error syndrome—a quantum state indicating which error has occurred—by reversing the encoding process. This syndrome is then used as the input to a three-qubit gate that corrects the primary qubit if it was flipped. As the code can recover from a single error on any qubit, the fidelity of this process should decrease only quadratically with error probability. We implement the correcting three-qubit gate (known as a conditional-conditional NOT, or Toffoli, gate) in 63 nanoseconds, using an interaction with the third excited state of a single qubit. We find 85 ± 1 per cent fidelity to the expected classical action of this gate, and 78 ± 1 per cent fidelity to the ideal quantum process matrix. Using this gate, we perform a single pass of both quantum bit- and phase-flip error correction and demonstrate the predicted first-order insensitivity to errors. Concatenation of these two codes in a nine-qubit device would correct arbitrary single-qubit errors. In combination with recent advances in superconducting qubit coherence times, this could lead to scalable quantum technology.

http://feeds.nature.com/~r/nature/rss/aop/~3/bzkJHTpVyyE/nature10786

Transcription factors and chromatin modifiers are important in the programming and reprogramming of cellular states during development. Transcription factors bind to enhancer elements and recruit coactivators and chromatin-modifying enzymes to facilitate transcription initiation. During differentiation a subset of these enhancers must be silenced, but the mechanisms underlying enhancer silencing are poorly understood. Here we show that the histone demethylase lysine-specific demethylase 1 (LSD1; ref. 5), which demethylates histone H3 on Lys 4 or Lys 9 (H3K4/K9), is essential in decommissioning enhancers during the differentiation of mouse embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes that are critical for control of the state of ESCs. However, LSD1 is not essential for the maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to differentiate fully, and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At active enhancers, LSD1 is a component of the NuRD (nucleosome remodelling and histone deacetylase) complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1–NuRD complex decommissions enhancers of the pluripotency program during differentiation, which is essential for the complete shutdown of the ESC gene expression program and the transition to new cell states.

http://feeds.nature.com/~r/nature/rss/aop/~3/fZkcfPVzUbo/nature10805

http://feeds.nature.com/~r/nature/rss/aop/~3/HlrA2aOop0w/nature10156

http://feeds.nature.com/~r/nature/rss/aop/~3/EuBdwt8GMxk/nature10133

http://feeds.nature.com/~r/nature/rss/aop/~3/TxrdFuAGaoc/nature10186

Transcription factors and chromatin modifiers are important in the programming and reprogramming of cellular states during development. Transcription factors bind to enhancer elements and recruit coactivators and chromatin-modifying enzymes to facilitate transcription initiation. During differentiation a subset of these enhancers must be silenced, but the mechanisms underlying enhancer silencing are poorly understood. Here we show that the histone demethylase lysine-specific demethylase 1 (LSD1; ref. 5), which demethylates histone H3 on Lys 4 or Lys 9 (H3K4/K9), is essential in decommissioning enhancers during the differentiation of mouse embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes that are critical for control of the state of ESCs. However, LSD1 is not essential for the maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to differentiate fully, and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At active enhancers, LSD1 is a component of the NuRD (nucleosome remodelling and histone deacetylase) complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1–NuRD complex decommissions enhancers of the pluripotency program during differentiation, which is essential for the complete shutdown of the ESC gene expression program and the transition to new cell states.

http://feeds.nature.com/~r/nature/rss/aop/~3/fZkcfPVzUbo/nature10805

Quantum computers could be used to solve certain problems exponentially faster than classical computers, but are challenging to build because of their increased susceptibility to errors. However, it is possible to detect and correct errors without destroying coherence, by using quantum error correcting codes. The simplest of these are three-quantum-bit (three-qubit) codes, which map a one-qubit state to an entangled three-qubit state; they can correct any single phase-flip or bit-flip error on one of the three qubits, depending on the code used. Here we demonstrate such phase- and bit-flip error correcting codes in a superconducting circuit. We encode a quantum state, induce errors on the qubits and decode the error syndrome—a quantum state indicating which error has occurred—by reversing the encoding process. This syndrome is then used as the input to a three-qubit gate that corrects the primary qubit if it was flipped. As the code can recover from a single error on any qubit, the fidelity of this process should decrease only quadratically with error probability. We implement the correcting three-qubit gate (known as a conditional-conditional NOT, or Toffoli, gate) in 63 nanoseconds, using an interaction with the third excited state of a single qubit. We find 85 ± 1 per cent fidelity to the expected classical action of this gate, and 78 ± 1 per cent fidelity to the ideal quantum process matrix. Using this gate, we perform a single pass of both quantum bit- and phase-flip error correction and demonstrate the predicted first-order insensitivity to errors. Concatenation of these two codes in a nine-qubit device would correct arbitrary single-qubit errors. In combination with recent advances in superconducting qubit coherence times, this could lead to scalable quantum technology.

http://feeds.nature.com/~r/nature/rss/aop/~3/bzkJHTpVyyE/nature10786

An expansion of Porphyromonadaceae in the gut is linked to the pathogenesis and progression of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in the mouse.

http://feeds.nature.com/~r/nature/rss/aop/~3/5LwF3Damo28/nature10809

US National Science Advisory Board for Biosecurity explains recommendation to publish H5N1 work in a form that withholds essential data.

http://feeds.nature.com/~r/nature/rss/aop/~3/Ka4q8IF25kI/482156a

Jellyfish will bloom as ocean health declines, warn biologists. Are they already taking over?

http://feeds.nature.com/~r/nature/rss/current/~3/AqAlBr4ZXQY/482020a

For decades, Robert Daum has studied the havoc wreaked by methicillin-resistant Staphylococcus aureus. Now he thinks he can stop it for good.

http://feeds.nature.com/~r/nature/rss/current/~3/LkMdxnGrKVM/482023a

Yusuke Nakamura blames government inertia for his move to the United States.

http://feeds.nature.com/~r/nature/rss/current/~3/teSrKnxX71I/482018a

The week in science: sequencing stock rebounds after takeover bid for Illumina; drug companies and nations team up against neglected diseases; and turmoil at the Global Fund.

http://feeds.nature.com/~r/nature/rss/current/~3/C1yc51ZYaMs/482010a

Lab-management software and electronic notebooks are here — and this time, it's more than just talk.

http://feeds.nature.com/~r/nature/rss/current/~3/lojhcC4W-C0/481430a

Armed with high-tech methods, researchers are scouring the Aegean Sea for the world's oldest shipwrecks.

http://feeds.nature.com/~r/nature/rss/current/~3/Of2vWaxxCpA/481426a

Public-health benefits of controversial research questioned.

http://feeds.nature.com/~r/nature/rss/current/~3/IXV1TLNbizM/481417a

Adaptive optics put the observatory at the cutting edge.

http://feeds.nature.com/~r/nature/rss/current/~3/NViVZvHQhB0/481251a

Legislation to increase availability of new medicines has delayed approvals.

http://feeds.nature.com/~r/nature/rss/current/~3/uq__3m_lKdc/481250a

Scientists wanting to implement change must collaborate between disciplines. An ambitious Amazon study shows them how, says Paulo Artaxo.

http://feeds.nature.com/~r/nature/rss/current/~3/LjkpzOA-k3A/481239a

Shiyun Lin, Kenneth B. CrozierWe demonstrate an integrated microparticle passive sorting system based on the near-field optical forces exerted by a 3-dB optical splitter that consists of a slot waveguide and a conventional channel waveguide. We show that 320 nm and 2 µm polystyrene particles brought into the splitter are ... [Opt. Express 20, 3367-3374 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3367

Shiro Ikeda, Hidetoshi KonoIn this paper, we propose the SPR (sparse phase retrieval) method, which is a new phase retrieval method for coherent x-ray diffraction imaging (CXDI). Conventional phase retrieval methods effectively solve the problem for high signal-to-noise ratio measurements, but would not be sufficient for ... [Opt. Express 20, 3375-3387 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3375

John Fredy Barrera, Myrian Tebaldi, Carlos Ríos, Edgar Rueda, Néstor Bolognini, Roberto TorrobaWe present the first experimental technique to encrypt a movie under a joint transform correlator architecture. We also extend the method to multiplex several movies in a single package. We use a Mach-Zehnder interferometer to encrypt experimentally each movie. One arm of the interferometer is the ... [Opt. Express 20, 3388-3393 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3388

Martha Segura, Martin Kadankov, Xavier Mateos, Maria Cinta Pujol, Joan Josep Carvajal, Magdalena Aguiló, Francesc Díaz, Uwe Griebner, Valentin PetrovSingle pulse energies as high as 145 µJ were generated with a passively Q-switched diode-pumped Tm:KLu(WO_4)_2 laser using poly-crystalline Cr^2+:ZnS as a saturable absorber. The maximum average power reached 0.39 W at a pulse repetition rate of 2.7 kHz with pulse durations in the 25 – ... [Opt. Express 20, 3394-3400 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3394

Vincenzo Spagnolo, Lei Dong, Anatoliy A. Kosterev, Frank K. TittelThe application of an innovative spectroscopic balancing technique to measure the isotope ^18O/^16O ratio in water vapor is reported. Quartz enhanced photoacoustic spectroscopy has been employed as the absorption sensing technique. Two isotope absorption lines with the same quantum numbers, with ... [Opt. Express 20, 3401-3407 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3401

P. Neutens, L. Lagae, G. Borghs, P. Van DorpeWe present the numerical and experimental demonstration of plasmonic Bragg filters and resonators inside metal-insulator-metal (MIM) waveguides. The presented filters and resonators are fabricated using standard top down lithography methods. The optical bandgap of the integrated Bragg filters is ... [Opt. Express 20, 3408-3423 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3408

Tatiana Pikuz, Anatoly Faenov, Yuji Fukuda, Masaki Kando, Paul Bolton, Alexander Mitrofanov, Alexander Vinogradov, Mitsuru Nagasono, Haruhiko Ohashi, Makina Yabashi, Kensuke Tono, Yashinori Senba, Tadashi Togashi, Tetsuya IshikawaOptical features of point defects photoluminescence in LiF crystals, irradiated by soft X-ray pulses of the Free Electron Laser with wavelengths of 17.2 – 61.5 nm, were measured. We found that peak of photoluminescence spectra lies near of 530 nm and are associated with emission of F_3 ^+ ... [Opt. Express 20, 3424-3433 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3424

G. H. Kim, J. Yang, S. A. Chizhov, E. G. Sall, A. V. Kulik, V. E. Yashin, D. S. Lee, U. KangA diode-pumped, ultrafast Yb:KYW laser system utilizing chirped-pulse amplification in a dual-slab regenerative amplifier with spectral shaping of seeding pulse from a master oscillator has been developed. A train of compressed pulses with pulse length of 181 fs, repetition rate up to 200 kHz, and ... [Opt. Express 20, 3434-3442 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3434

Sandro Klingebiel, Izhar Ahmad, Christoph Wandt, Christoph Skrobol, Sergei A. Trushin, Zsuzsanna Major, Ferenc Krausz, Stefan KarschIn an optically synchronized short-pulse optical-parametric chirped-pulse amplification (OPCPA) system, we observe a few-100 fs-scale timing jitter. With an active timing stabilization system slow fluctuations are removed and the timing jitter can be reduced to 100 fs standard deviation (Std). As ... [Opt. Express 20, 3443-3455 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3443

Shellee D. Dyer, Michael G. Tanner, Burm Baek, Robert H. Hadfield, Sae Woo NamWe demonstrate a high-accuracy distributed fiber-optic temperature sensor using superconducting nanowire single-photon detectors and single-photon counting techniques. Our demonstration uses inexpensive single-mode fiber at standard telecommunications wavelengths as the sensing fiber, which enables ... [Opt. Express 20, 3456-3466 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3456

Felipe Beltrán-Mejía, Cristiano M. B. Cordeiro, Pedro Andrés, Enrique SilvestreA photonic crystal fiber is optimized for chromatic dispersion compensation by using inner cladding modes. To this end, a photonic-oriented version of the downhill-simplex algorithm is employed. The numerical results show a dispersion profile that accurately compensates the targeted dispersion ... [Opt. Express 20, 3467-3472 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3467

Chul Han KimThe maximum reach in a WDM-PON using a broadband light source (BLS) seeded optical source has been experimentally evaluated by taking into account both effects of dispersion-induced pulse broadening and excess intensity noise (EIN) increase. In order to investigate the impact of BLS seed source ... [Opt. Express 20, 3473-3478 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3473

Yung-Chi Yao, Meng-Tsan Tsai, Hsu-Cheng Hsu, Li-Wei She, Chun-Mao Cheng, Yi-Ching Chen, Chien-Jang Wu, Ya-Ju LeeTwo-dimensional (2D) Si-nanorod arrays offer a promising architecture that has been widely recognized as attractive devices for photovoltaic applications. To further reduce the Fresnel reflection that occurs at the interface between the air and the 2D Si-nanorod array because of the large ... [Opt. Express 20, 3479-3489 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3479

Jin Wen, Hongjun Liu, Nan Huang, Qibing Sun, Wei ZhaoA femtosecond optical parametric oscillator (OPO) based on silicon-on-insulator (SOI) waveguide is proposed and analyzed numerically. By utilizing split-step Fourier method (SSFM), it is demonstrated that ultra-wide tunable wavelength femtosecond pulse can be realized under the phase matching ... [Opt. Express 20, 3490-3498 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3490

Igor Gvozdovskyy, Oleg Yaroshchuk, Marina Serbina, Rumiko YamaguchiStructural changes caused by the optically induced helical inversion in the cholesteric liquid crystal cells with homeotropic anchoring are studied. In a one-step exposure, a sequence of structural transformations “lying left-handed helix – unwound homeotropic state – lying ... [Opt. Express 20, 3499-3508 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3499

Chun Liang Wang, Zhi Hui Kang, Si Cong Tian, Jin Hui WuWe demonstrate coherent control of spontaneous emission from an indirectly coupled transition in a microwave driven four-level atomic system. The transition of concern is not directly coupled by any laser fields, while the ground state is coupled to another ground state by a microwave field. We ... [Opt. Express 20, 3509-3518 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3509

Nadav Gutman, W. Hugo Dupree, Yue Sun, Andrey A. Sukhorukov, C. Martijn de SterkeWe develop novel designs enabling slow-light propagation with vanishing group-velocity dispersion (“frozen light”) and slow-light with large delay-bandwidth product, in periodic nanowires. Our design is based on symmetry-breaking of periodic nanowire waveguides and we demonstrate its ... [Opt. Express 20, 3519-3528 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3519

Takayuki Kurihara, Yasuhiro TakakiWe propose a hologram calculation technique that enables reconstructing a shaded three-dimensional (3D) image. The amplitude distributions of zone plates, which generate the object points that constitute a 3D object, were two-dimensionally modulated. Two-dimensional (2D) amplitude modulation was ... [Opt. Express 20, 3529-3540 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3529

Ki Ho Han, Wang Joo LeeWe propose and demonstrate a novel first-order polarization mode dispersion (PMD) compensator separating principal-states-of-polarization (PSP) control from differential-group-delay (DGD) control by using two independent feedback monitoring signals. To verify the proposed operating principle, we ... [Opt. Express 20, 3541-3549 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3541

Kevin Schires, Rihab Al Seyab, Antonio Hurtado, Ville-Markus Korpijärvi, Mircea Guina, Ian D. Henning, Michael J. AdamsWe report the first room temperature optical spin-injection of a dilute nitride 1300 nm vertical-cavity surface-emitting laser (VCSEL) under continuous-wave optical pumping. We also present a novel experimental protocol for the investigation of optical spin-injection with a fiber setup. The ... [Opt. Express 20, 3550-3555 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3550

Jin Tae Kim, Choon-Gi ChoiPlanar-lightwave-circuit (PLC)-type graphene polarizers are fabricated by using a low loss optical polymer waveguide. The optical characteristics are investigated at a wavelength of 1.31 µm. By interface engineering with a UV-curable perfluorinated acrylate polymer resin, the ... [Opt. Express 20, 3556-3562 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3556

O. V. Angelsky, A. Ya. Bekshaev, P. P. Maksimyak, A. P. Maksimyak, S. G. Hanson, C. Yu. ZenkovaThe internal energy flow in a light beam can be divided into the “orbital” and “spin” parts, associated with the spatial and polarization degrees of freedom of light. In contrast to the orbital one, experimental observation of the spin flow seems problematic because it ... [Opt. Express 20, 3563-3571 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3563

Kuo-Wei Lai, Yi-Shan Lee, Ying-Jhe Fu, Sheng-Di LinWe propose and demonstrate a novel device structure of resonant cavity-enhanced photodetector (RCE-PD). The new RCE-PD structure consists of a bottom distributed Bragg reflector (DBR), a cavity with InGaAs multiple quantum wells (MQWs) for light absorption and a top mirror of sub-wavelength ... [Opt. Express 20, 3572-3579 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3572

Ke Chen, Wenfang Wang, Jianming Chen, Jinhui Wen, Tianshu LaiA transmission-grating-modulated time-resolved pump-probe absorption spectroscopy is developed and formularized. The spectroscopy combines normal time-resolved pump-probe absorption spectroscopy with a binary transmission grating, is sensitive to the spatiotemporal evolution of photoinjected ... [Opt. Express 20, 3580-3585 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3580

Yi Zhao, Dalziel J. Wilson, K.-K. Ni, H. J. KimbleExtraneous thermal motion can limit displacement sensitivity and radiation pressure effects, such as optical cooling, in a cavity-optomechanical system. Here we present an active noise suppression scheme and its experimental implementation. The main challenge is to selectively sense and suppress ... [Opt. Express 20, 3586-3612 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3586

Gil Porat, Yaron Silberberg, Ady Arie, Haim SuchowskiWe study the case of two simultaneous three-wave-mixing processes, where one frequency is converted to another through an intermediate frequency. The common assumption is that these processes can occur only when the material is transparent at all participating frequencies. Here we show ... [Opt. Express 20, 3613-3619 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3613

S. Herath, N. P. Puente, E. I. Chaikina, A. YamilovWe develop and experimentally verify a theory of evolution of polarization in artificially-disordered multi-mode optical fibers. Starting with a microscopic model of photo-induced index change, we obtain the first and second order statistics of the dielectric tensor in a Ge-doped fiber, where a ... [Opt. Express 20, 3620-3632 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3620

Kazuhisa Onda, Fumihito AraiA multi-beam bilateral teleoperation system of holographic optical tweezers accelerated by a graphics processing unit is proposed and evaluated. This double-arm teleoperation system is composed of two haptic devices and two laser-trapped micro-beads. Each micro-bead is trapped and moved following ... [Opt. Express 20, 3633-3641 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3633

S. Zwick, R. Feßler, J. Jegorov, G. NotniPicture-generating freeform surfaces are able to generate a picture in a defined plane by incoherent beam shaping comparable to illumination purposes. No classical imaging is performed. Therefore the classical Rayleigh criterion of the diffraction limit cannot be applied. In this paper, we ... [Opt. Express 20, 3642-3653 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3642

Uwe Petzold, Andreas Büchel, Thomas HalfmannWe present systematic experimental investigations on the effects of laser polarization and interface orientation in second and third harmonic generation microscopy. We find that the laser polarization has no measurable effect on signal strength and resolution in third harmonic microscopy, while the ... [Opt. Express 20, 3654-3662 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3654

Jesper Jung, Thomas G. PedersenThe polarizability of a nanostructure is an important parameter that determines the optical properties. An exact semi-analytical solution of the electrostatic polarizability of a general geometry consisting of two segments forming a cylinder that can be arbitrarily buried in a substrate is derived ... [Opt. Express 20, 3663-3674 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3663

Yuqing Jiao, Bauke W. Tilma, Junji Kotani, Richard Nötzel, Meint K. Smit, Sailing He, Erwin A. J. M. BenteIn this paper a study of waveguide photodetectors based on InAs/InP(100) quantum dot (QD) active material are presented for the first time. These detectors are fabricated using the layer stack of semiconductor optical amplifiers (SOAs) and are compatible with the active-passive integration ... [Opt. Express 20, 3675-3692 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3675

Avner Yanai, Meir Orenstein, Uriel LevyWe study the interaction of an incident plane wave with a metamaterial periodic structure consisting of alternating layers of positive and negative refractive index with average zero refractive index. We show that the existence of very narrow resonance peaks for which giant absorption - 50% at ... [Opt. Express 20, 3693-3702 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3693

Gene OlczakThe dispersed fringe sensor (DFS) has been demonstrated as an effective means of measuring mirror segment piston error for telescopes with primary mirror apertures below 10 meters. With larger proposed telescopes such as The Thirty Meter Telescope (TMT) and The European Large Telescope (ELT) ... [Opt. Express 20, 3703-3710 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3703

Xiaodong He, Shi Yu, Peng Xu, Jin Wang, Mingsheng ZhanWe propose and demonstrate a scheme for strong radial confinement of a single ^87Rb atom by a bichromatic far-off resonance optical dipole trap (BFORT). The BFORT is composed of a blue-detuned Laguerre-Gaussian LG01 beam and a red-detuned Gaussian beam. The atomic oscillation frequency ... [Opt. Express 20, 3711-3724 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3711

Hironori Igarashi, Ayumu Makida, Motohiko Ito, Taro SekikawaSingle 32.6 eV high harmonic pulses from a time-delay compensated monochromator were compressed down to 11 ± 3 fs by completely compensating for the pulse-front tilt. The photon flux was intensified up to 5.7×10^9 photons/s on target by implementing high harmonic generation under a ... [Opt. Express 20, 3725-3732 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3725

Wei Wang, Shaomin Wu, Randy. J. Knize, Kitt Reinhardt, Yalin Lu, Shaochen ChenOverall performance of a thin film solar cell is determined by the efficiency of converting photons to electrons through light absorption, carrier generation, and carrier collection. Recently, photon management has emerged as a powerful tool to further boost this conversion efficiency. Here we ... [Opt. Express 20, 3733-3743 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3733

Giulia Ghielmetti, Christof M. AegerterRecently, we have proposed a method to image fluorescent structures behind turbid layers at diffraction limited resolution using wave-front shaping and the memory effect. However, this was limited to a raster scanning of the wave-front shaped focus to a two dimensional plane. In applications, it ... [Opt. Express 20, 3744-3752 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3744

E. S. Gómez, W. A. T. Nogueira, C. H. Monken, G. LimaThe state of spatially correlated down-converted photons is usually treated as a two-mode Gaussian entangled state. While intuitively this seems to be reasonable, it is known that new structures in the spatial distributions of these photons can be observed when the phase-matching conditions are ... [Opt. Express 20, 3753-3772 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3753

Shinji Matsuo, Koji Takeda, Tomonari Sato, Masaya Notomi, Akihiko Shinya, Kengo Nozaki, Hideaki Taniyama, Koichi Hasebe, Takaaki KakitsukaWe have developed a wavelength-scale embedded active-region photonic-crystal laser using lateral p-i-n structure. Zn diffusion and Si ion implantation are used for p- and n-type doping. Room-temperature continuous-wave lasing behavior is clearly observed from the injection current dependence of the ... [Opt. Express 20, 3773-3780 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3773

L. Marazzi, P. Parolari, R. Brenot, G. de Valicourt, M. MartinelliA network-embedded self-tuning cavity is proved in wavelength division multiplexed passive optical network transmission over 32 channels. The external source-less topology takes advantage of a reflective element at the remote node and a reflective semiconductor optical amplifier at the optical ... [Opt. Express 20, 3781-3786 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3781

Francesco Pedaci, Zhuangxiong Huang, Maarten van Oene, Nynke H. DekkerThe optical torque wrench is a laser trapping technique that expands the capability of standard optical tweezers to torque manipulation and measurement, using the laser linear polarization to orient tailored microscopic birefringent particles. The ability to measure torque of the order of kBT ... [Opt. Express 20, 3787-3802 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3787

Bo Zhou, Lili Tao, Yuen H. Tsang, Wei Jin, Edwin Yue-Bun PunPraseodymium(Pr^3+)-doped fluorotellurite glasses were synthesized and broadband photoluminescence (PL) covering a wavelength range from 1.30 to 1.67 μm was observed under both 488 and 590 nm wavelength excitations. The broadband PL emission is mainly due to the radiative transition from the ... [Opt. Express 20, 3803-3813 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3803

Richard Soref, Joshua Hendrickson, Justin W. ClearyHeavily doped n-type Ge and GeSn are investigated as plasmonic conductors for integration with undoped dielectrics of Si, SiGe, Ge, and GeSn in order to create a foundry-based group IV plasmonics technology. N-type Ge_1-xSnx with compositions of 0 ≤ x ≤ 0.115 are investigated ... [Opt. Express 20, 3814-3824 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3814

C. Stamatiadis, L. Stampoulidis, D. Kalavrouziotis, I. Lazarou, K. Vyrsokinos, L. Zimmermann, K. Voigt, G. B. Preve, L. Moerl, J. Kreissl, H. AvramopoulosWe present a hybrid integrated photonic circuit on a silicon-on-insulator substrate that performs ultra high-speed all-optical wavelength conversion. The chip incorporates a 1.25 mm non-linear SOA mounted on the SOI board using gold-tin bumps as small as 14 μm. Τhe device performs chirp ... [Opt. Express 20, 3825-3831 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3825

Andrey Okhrimchuk, Vladimir Mezentsev, Alexander Shestakov, Ian BennionA depressed cladding waveguide with record low loss of 0.12 dB/cm is inscribed in YAG:Nd(0.3at.%) crystal by femtosecond laser pulses with an elliptical beam waist. The waveguide is formed by a set of parallel tracks which constitute the depressed cladding. It is a key element for compact and ... [Opt. Express 20, 3832-3843 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3832

Nikolai B. Chichkov, Christian Hapke, Jörg Neumann, Dietmar Kracht, Dieter Wandt, Uwe MorgnerWe investigate the scaling properties of mode-locked all-normal dispersion fiber oscillators in terms of output pulse energy and compressed pulse duration. Experimental results are achieved by stepwise variation of the resonator dispersion, total fiber length, and the spectral filter bandwidth. ... [Opt. Express 20, 3844-3852 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3844

Wen Chen, Xudong Chen, Colin J. R. SheppardWe propose a new method using coherent diffractive imaging for optical color-image encryption and synthesis in the Fresnel domain. An optical multiple-random-phase-mask encryption system is applied, and a strategy based on lateral translations of a phase-only mask is employed during image ... [Opt. Express 20, 3853-3865 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3853

S. Fathololoumi, E. Dupont, C.W.I. Chan, Z.R. Wasilewski, S.R. Laframboise, D. Ban, A. Mátyás, C. Jirauschek, Q. Hu, H. C. LiuA new temperature performance record of 199.5 K for terahertz quantum cascade lasers is achieved by optimizing the lasing transition oscillator strength of the resonant phonon based three-well design. The optimum oscillator strength of 0.58 was found to be larger than that of the previous record ... [Opt. Express 20, 3866-3876 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3866

A. Hachmeister, M. Nölle, L. Molle, R. Freund, M. RohdeWe performed long-haul WDM transmission experiments to compare 10 Gbit/s MSK and QPSK modulation with a channel grid of 12.5 GHz. A standard link setup with inline dispersion compensation was applied in combination with coherent detection and following offline signal processing. Both modulation ... [Opt. Express 20, 3877-3882 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3877

Kai Wu, Cheng-Chung Lee, Tzu-Ling NiA monitoring technique using the equivalent optical admittance loci of thin films to control the deposition is presented. Real-time broadband spectrum measurements are employed to extract the real-time thin film refraction index and thickness, and the corresponding equivalent optical admittance is ... [Opt. Express 20, 3883-3889 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3883

Peter Fuchs, Jochen Friedl, Sven Höfling, Johannes Koeth, Alfred Forchel, Lukas Worschech, Martin KampWe report the fabrication of single mode quantum cascade lasers using a shallow-etched distributed Bragg reflector as frequency selective element. Quasi-continuous single mode tuning over 15 cm^−1 at room temperature and 25 cm^−1 via temperature tuning at Peltier temperatures is ... [Opt. Express 20, 3890-3897 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3890

Kazuaki SakodaIt is shown by analytical calculation based on the tight-binding approximation that the isotropic Dirac cone in the Brillouin zone center can be created in two- and three-dimensional periodic metamaterials by accidental degeneracy of two modes. In the case of two dimensions, the combination of a ... [Opt. Express 20, 3898-3917 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3898

Yasuhiro Takaki, Masahito YokouchiEye accommodation is considered to function properly for three-dimensional (3D) images generated by holography. We developed a horizontally scanning holographic display technique that enlarges both the screen size and viewing zone angle. A 3D image generated by this technique can be easily seen by ... [Opt. Express 20, 3918-3931 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3918

Huining Wang, Ziwu Ji, Shuang Qu, Gang Wang, Yongzhi Jiang, Baoli Liu, Xiangang Xu, Hirofumi MinoExcitation power and temperature dependences of the photoluminescence (PL) spectra are studied in InGaN/GaN multiple quantum wells (MQWs). The excitation power dependences of the PL peak energy and linewidth indicate that the emission process of the MQWs is dominated first by the Coulomb screening ... [Opt. Express 20, 3932-3940 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3932

Gray Lin, Pei-Yin Su, Hsu-Chieh ChengLow threshold and widely tunable InAs/GaAs quantum-dot lasers are implemented with grating-coupled external-cavity arrangement. Throughout the tuning range of 130 nm, from 1160 to 1290 nm, the threshold current density is not more than 0.9 kA/cm^2 and no noticeable threshold jump is observed. For a ... [Opt. Express 20, 3941-3947 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3941

Yan Sheng, Vito Roppo, Mingliang Ren, Ksawery Kalinowski, Crina Cojocaru, Jose Trull, Zhiyuan Li, Kaloian Koynov, Wieslaw KrolikowskiWe study Čerenkov-type second-harmonic generation in a two-dimensional quasi-periodically poled LiNbO_3 crystal. We employ a new geometry of interaction to observe simultaneous emission of multi-directional nonlinear Čerenkov radiation with comparable intensities. This opens a way to ... [Opt. Express 20, 3948-3953 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3948

Tetsuya Hoshino, Toyohiko Yatagai, Masahide ItohWe found that the distances between isolated scatterers with similar columnar shapes could be measured by taking a single Fourier transform of their diffraction intensity. If the scatterers have different shapes, the distances between similar shapes can be selected from the distances between all ... [Opt. Express 20, 3954-3966 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3954

Sebastian D. Saliba, Corey T. Putkunz, David V. Sheludko, Andrew J. McCulloch, Keith A. Nugent, Robert E. ScholtenWe describe the spatial coherence properties of a cold atom electron source in the framework of a quasihomogeneous wavefield. The model is used as the basis for direct measurements of the transverse spatial coherence length of electron bunches extracted from a cold atom electron source. The ... [Opt. Express 20, 3967-3974 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3967

Adam M. Zysk, Robert W. Schoonover, Qiaofeng Xu, Mark A. AnastasioDespite the extensive use of polycapillary x-ray optics for focusing and collimating applications, there remains a significant need for characterization of the coherence properties of the output wavefield. In this work, we present the first quantitative computational method for calculation of the ... [Opt. Express 20, 3975-3982 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3975

Mizuki Shirao, Takashi Sato, Noriaki Sato, Nobuhiko Nishiyama, Shigehisa AraiRoom-temperature pulsed operation of a 1.3-µm wavelength transistor laser (TL), consisting of a buried heterostructure (BH) with an npn configuration and an AlGaInAs/InP multiple-quantum-well (MQW) active region, was successfully attained. A threshold base current of 18 mA (threshold emitter ... [Opt. Express 20, 3983-3989 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3983

Alexandros Selimis, George J. Tserevelakis, Sotiria Kogou, Paraskevi Pouli, George Filippidis, Natalia Sapogova, Nikita Bityurin, Costas FotakisA new diagnostic approach for assessing the in-depth laser induced modifications upon ultraviolet polymer irradiation is presented. The methodology relies on the observation of morphological alterations in the bulk material (Paraloid B72) by using third harmonic generation. This non destructive ... [Opt. Express 20, 3990-3996 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3990

Florian Jansen, Fabian Stutzki, Hans-Jürgen Otto, Tino Eidam, Andreas Liem, Cesar Jauregui, Jens Limpert, Andreas TünnermannThermally induced waveguide changes become significant for very large mode area fibers. This results in a reduction of the mode-field diameter, but simultaneously in an improvement of the beam quality. In this work the first systematic experimental characterization of the reduction of the ... [Opt. Express 20, 3997-4008 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-3997

Xiangkai Zeng, Lai Wei, Yingjun Pan, Shengping Liu, Xiaohui ShiIn this paper the analytic models (AMs) of the spectral responses of fiber-grating-based interferometers are derived from the Fourier mode coupling (FMC) theory proposed recently. The interferometers include Fabry-Perot cavity, Mach-Zehnder and Michelson interferometers, which are constructed by ... [Opt. Express 20, 4009-4017 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4009

Jiantong Weng, Tomoyoshi Shimobaba, Naohisa Okada, Hirotaka Nakayama, Minoru Oikawa, Nobuyuki Masuda, Tomoyoshi ItoWe report the generation of a real-time large computer generated hologram (CGH) using the wavefront recording plane (WRP) method with the aid of a graphics processing unit (GPU). The WRP method consists of two steps: the first step calculates a complex amplitude on a WRP that is placed between a 3D ... [Opt. Express 20, 4018-4023 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4018

Moritz M. Vogel, Martin Rumpel, Birgit Weichelt, Andreas Voss, Matthias Haefner, Christof Pruss, Wolfgang Osten, Marwan Abdou Ahmed, Thomas GrafA single-layer resonant-waveguide grating consisting of a sub-wavelength grating coupler etched into a waveguide is proposed in order to achieve high polarization and high spectral selectivity inside an Yb:YAG thin-disk laser resonator. The designed structure was fabricated with the help of a ... [Opt. Express 20, 4024-4031 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4024

Li Chen, Ronald M. ReanoAn electric field sensor based on the indirect bonding of submicrometer thin films of lithium niobate to silicon microring resonators is presented using benzocyclobutene as an intermediate bonding layer. The hybrid material system combines the electro-optic functionality of lithium niobate with the ... [Opt. Express 20, 4032-4038 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4032

J. Gulden, O. M. Yefanov, A. P. Mancuso, R. Dronyak, A. Singer, V. Bernátová, A. Burkhardt, O. Polozhentsev, A. Soldatov, M. Sprung, I. A. VartanyantsA coherent x-ray diffraction experiment was performed on an isolated colloidal crystal grain at the coherence beamline P10 at PETRA III. Using azimuthal rotation scans the three-dimensional (3D) scattered intensity from the sample in the far-field was measured. It includes several Bragg peaks as ... [Opt. Express 20, 4039-4049 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4039

Cristina Canavesi, William J. Cassarly, Jannick P. RollandWe implemented the linear programming approach proposed by Oliker and by Wang to solve the single reflector problem for a point source and a far-field target. The algorithm was shown to produce solutions that aim the input rays at the intersections between neighboring reflectors. This feature makes ... [Opt. Express 20, 4050-4055 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4050

Jung Woo Leem, Yunhae Yeh, Jae Su YuWe fabricated surface nanostructures with different pillar and cone shapes on glass substrates using thermally dewetted gold (Au) nanoparticles as etch masks by dry etching. Their optical total transmittance characteristics, together with theoretical predictions using rigorous coupled-wave analysis ... [Opt. Express 20, 4056-4066 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4056

Gopakumar Ramakrishnan, Nishant Kumar, Paul C. M. Planken, Daisuke Tanaka, Kotaro KajikawaEmission of terahertz radiation is observed when surface plasmons are excited on a thin film of gold, in the Kretschmann geometry. When a hemicyanine-terminated alkanethiol self-assembled monolayer of thickness 1.2 nm is deposited on the gold film, stronger terahertz emission is observed. Our ... [Opt. Express 20, 4067-4073 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4067

Mathieu Paurisse, Louis Lévèque, Marc Hanna, Frédéric Druon, Patrick GeorgesWe propose and demonstrate the use of a wavefront analyzer based on lateral shearing interferometry to characterize the modal content of multimode fibers. This wavefront measurement technique is applied to large mode area fibers, and allows us to recover both the intensity and relative phase of ... [Opt. Express 20, 4074-4084 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4074

Ali R. Motamedi, Amir H. Nejadmalayeri, Anatol Khilo, Franz X. Kärtner, Erich P. IppenResults of a self-consistent ultrafast study of nonlinear optical properties of silicon nanowaveguides using heterodyne pump-probe technique are reported. The two-photon absorption coefficient and free-carrier absorption effective cross-section were determined to be 0.68cm/GW, and 1.9x10^−17 ... [Opt. Express 20, 4085-4101 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4085

Michelle Y. Sander, Sergey Frolov, Joseph Shmulovich, Erich P. Ippen, Franz X. KärtnerCoherent pulse interleaving implemented in planar waveguide technology is presented as a compact and robust solution to generate high repetition rate frequency combs. We demonstrate a 10 GHz pulse train from an Er-doped femtosecond fiber laser that is coupled into waveguide interleavers and ... [Opt. Express 20, 4102-4113 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4102

Leandro Matiolli Machado, Ricardo Elgul Samad, Wagner de Rossi, Nilson Dias Vieira JuniorWe report the validation of the Diagonal Scan (D-Scan) technique to determine the incubation parameter for ultrashort laser pulses ablation. A theory to calculate the laser pulses superposition and a procedure for quantifying incubation effects are described, and the results obtained for BK7 ... [Opt. Express 20, 4114-4123 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4114

T-P. Vo, M. Mivelle, S. Callard, A. Rahmani, F. Baida, D. Charraut, A. Belarouci, D. Nedeljkovic, C. Seassal, G.W. Burr, T. GrosjeanWe study the near-field probing of the slow Bloch laser mode of a photonic crystal by a bowtie nano-aperture (BNA) positioned at the end of a metal-coated fiber probe. We show that the BNA acts as a polarizing nanoprobe allowing us to extract information about the polarization of the near-field of ... [Opt. Express 20, 4124-4135 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4124

Mario Mangold, Valentin J. Wittwer, Oliver D. Sieber, Martin Hoffmann, Igor L. Krestnikov, Daniil A. Livshits, Matthias Golling, Thomas Südmeyer, Ursula KellerWe present the first full gain characterization of two vertical external cavity surface emitting laser (VECSEL) gain chips with similar designs operating in the 960-nm wavelength regime. We optically pump the structures with continuous-wave (cw) 808-nm radiation and measure the nonlinear ... [Opt. Express 20, 4136-4148 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4136

Stephan Kassemeyer, Jan Steinbrener, Lukas Lomb, Elisabeth Hartmann, Andrew Aquila, Anton Barty, Andrew V. Martin, Christina Y. Hampton, Saša Bajt, Miriam Barthelmess, Thomas R.M. Barends, Christoph Bostedt, Mario Bott, John D. Bozek, Nicola Coppola, Max Cryle, Daniel P. DePonte, R. Bruce Doak, Sascha W. Epp, Benjamin Erk, Holger Fleckenstein, Lutz Foucar, Heinz Graafsma, Lars Gumprecht, Andreas Hartmann, Robert Hartmann, Günter Hauser, Helmut Hirsemann, André Hömke, Peter Holl, Olof Jönsson, Nils Kimmel, Faton Krasniqi, Mengning Liang, Filipe R.N.C. Maia, Stefano Marchesini, Karol Nass, Christian Reich, Daniel Rolles, Benedikt Rudek, Artem Rudenko, Carlo Schmidt, Joachim Schulz, Robert L. Shoeman, Raymond G. Sierra, Heike Soltau, John C. H. Spence, Dmitri Starodub, Francesco Stellato, Stephan Stern, Gunter Stier, Martin Svenda, Georg Weidenspointner, Uwe Weierstall, Thomas A. White, Cornelia Wunderer, Matthias Frank, Henry N. Chapman, Joachim Ullrich, Lothar Strüder, Michael J. Bogan, Ilme SchlichtingWe describe femtosecond X-ray diffraction data sets of viruses and nanoparticles collected at the Linac Coherent Light Source. The data establish the first large benchmark data sets for coherent diffraction methods freely available to the public, to bolster the development of algorithms that are ... [Opt. Express 20, 4149-4158 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4149

I. Y. Petrov, Y. Petrov, D. S. Prough, I. Cicenaite, D. J. Deyo, R. O. EsenalievMonitoring (currently invasive) of cerebral venous blood oxygenation is a key to avoiding hypoxia-induced brain injury resulting in death or severe disability. Noninvasive, optoacoustic monitoring of cerebral venous blood oxygenation can potentially replace existing invasive methods. To the best of ... [Opt. Express 20, 4159-4167 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4159

M. Krishnamurthi, J. R. Sparks, R. He, I. A. Temnykh, N. F. Baril, Z. Liu, P. J. A. Sazio, J. V. Badding, V. GopalanThe proof-of-concept of an infrared imaging tip by an array of infrared waveguides tapered as small as 2 μm is demonstrated. The fabrication is based on a high-pressure chemical fluid deposition technique to deposit precisely defined periodic arrays of Ge and Si waveguides within a ... [Opt. Express 20, 4168-4175 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4168

Giuseppe Toscano, Søren Raza, Antti-Pekka Jauho, N. Asger Mortensen, Martijn WubsWe study the effect of nonlocal optical response on the optical properties of metallic nanowires, by numerically implementing the hydrodynamical Drude model for arbitrary nanowire geometries. We first demonstrate the accuracy of our frequency-domain finite-element implementation by benchmarking it ... [Opt. Express 20, 4176-4188 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=oe-20-4-4176

Alexander S. Solntsev, Andrey A. SukhorukovWe suggest an application of pump-degenerate four-wave mixing process in tapered waveguides for generation of ultrashort pulses with central frequency tunable over the material transparency range. Our method can produce strongly compressed frequency-converted pulses in presence of group-velocity ... [Opt. Lett. 37, 446-448 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-446

R. Miloua, Z. Kebbab, F. Chiker, K. Sahraoui, M. Khadraoui, N. BenramdaneWe propose the use of a pattern search optimization technique in combination with a seed preprocessing procedure to determine the optical constants and thickness of thin films using only the transmittance spectra. The approach is quite flexible, straightforward to implement, and efficient in ... [Opt. Lett. 37, 449-451 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-449

D. Noordegraaf, P. M. W. Skovgaard, R. H. Sandberg, M. D. Maack, J. Bland-Hawthorn, J. S. Lawrence, J. LægsgaardWe demonstrate efficient multimode (MM) to single-mode (SM) conversion in a 19-port photonic lantern with a 50 μm core MM delivery fiber. The photonic lantern can be used within the field of astrophotonics for coupling MM starlight to an ensemble of SM fibers in order to perform ... [Opt. Lett. 37, 452-454 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-452

S. Benjamin Weiss, Mark E. Weber, Gregory D. GoodnoWe demonstrate a method for single-detector coherent sensing and automated coalignment of group delays in a coherently combined laser array, enabling robust coherent combining of broadband sources despite initial path mismatches exceeding the laser coherence length. The method is based on ... [Opt. Lett. 37, 455-457 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-455

Avner Safrani, Ibrahim AbdulhalimWe developed an ultrahigh-resolution full-field optical coherence tomography (FF-OCT) microscope that is based on the spatial, rather than the temporal, coherence gating. The microscope is capable of observing three-dimensional microbiological structures as small as ... [Opt. Lett. 37, 458-460 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-458

Y. F. Chen, H. C. Liang, J. C. Tung, K. W. Su, Y. Y. Zhang, H. J. Zhang, H. H. Yu, J. Y. WangWe explore the operation of spontaneous mode locking in a diode-pumped Nd:SrGdGa_3O_7 disordered crystal laser. The first- and second-order autocorrelations are simultaneously performed to evaluate the temporal characteristics. An 80 GHz pulse train with a pulse duration as short as 616 fs is ... [Opt. Lett. 37, 461-463 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-461

Biao Sun, Anting Wang, Lixin Xu, Chun Gu, Zhongxi Lin, Hai Ming, Qiwen ZhanWe propose and demonstrate a low-threshold single-wavelength all-fiber laser generating cylindrical vector beams using a few-mode fiber Bragg grating. Both radially and azimuthally polarized beams have been generated with very good modal symmetry and polarization purity higher than 94%. The ... [Opt. Lett. 37, 464-466 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-464

Shyh-Tsong Lin, Liang-Chia Chen, Sheng-Lih Yeh, Hu’ng-Xuân Trinh, Hung-Pin ChenThis Letter introduces a polarization phase-shifting Newton interferometer that can be utilized for plane optical surface measurements, a setup constructed to realize the interferometer, and the experimental results from the use of the setup. The results confirm not only the validity but also the ... [Opt. Lett. 37, 467-469 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-467

P. S. Salter, A. Jesacher, J. B. Spring, B. J. Metcalf, N. Thomas-Peter, R. D. Simmonds, N. K. Langford, I. A. Walmsley, M. J. BoothWe demonstrate an improved method for fabricating optical waveguides in bulk materials by means of femtosecond laser writing. We use an LC spatial light modulator (SLM) to shape the beam focus by generating adaptive slit illumination in the pupil of the objective lens. A diffraction grating is ... [Opt. Lett. 37, 470-472 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-470

K. I. Popov, A. F. Pegoraro, A. Stolow, L. RamunnoWe investigate the role of a spatially inhomogenous nonresonant background medium on several Raman-based imaging modalities. In particular, we consider a small resonant bead submerged in a spatially heterogeneous nonresonant χ^(3) background. Using detailed 3D electrodynamic simulations, we ... [Opt. Lett. 37, 473-475 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-473

J. S. Pelc, Q. Zhang, C. R. Phillips, L. Yu, Y. Yamamoto, M. M. FejerWe present a device for two-stage frequency upconversion of single-photon-level signals in the 1.55 μm telecom band to the green spectral region with low excess noise, suitable for detection by low-timing-jitter silicon single-photon avalanche photodiodes (APDs). We achieve a net conversion ... [Opt. Lett. 37, 476-478 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-476

Wouter J. Westerveld, Jose Pozo, Peter J. Harmsma, Ruud Schmits, Erik Tabak, Teun C. van den Dool, Suzanne M. Leinders, Koen W.A. van Dongen, H. Paul Urbach, Mirvais YousefiRecently there has been growing interest in sensing by means of optical microring resonators in photonic integrated circuits that are fabricated in silicon-on-insulator (SOI) technology. Taillaert et al. [Proc. SPIE6619, 661914 (2007)PSISDG0277-786X10.1117/12.738412] proposed the use of a ... [Opt. Lett. 37, 479-481 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-479

Sören Richter, Fei Jia, Matthias Heinrich, Sven Döring, Ulf Peschel, Andreas Tünnermann, Stefan NolteWe investigate the role of self-trapped excitons (STEs) and defects in the formation of femtosecond laser pulse induced nanogratings (NGs) in fused silica. Our experiments reveal strongly enhanced NG formation for pulse separations up to the STE lifetime. In addition, the absorption spectra show ... [Opt. Lett. 37, 482-484 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-482

U. Naether, J. M. Meyer, S. Stützer, A. Tünnermann, S. Nolte, M. I. Molina, A. SzameitWe investigate experimentally the light evolution inside a two-dimensional finite periodic array of weakly coupled optical waveguides with a disordered boundary. For a completely localized initial condition away from the surface, we find that the disordered boundary induces an asymptotic ... [Opt. Lett. 37, 485-487 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-485

Se-Heon Kim, Jingqing Huang, Axel SchererA photonic crystal (PhC) nanocavity formed in an optically very thick slab can support reasonably high-Q modes for lasing. Experimentally, we demonstrate room-temperature pulsed lasing operation from the PhC dipole mode emitting at 1324 nm, which is fabricated in an InGaAsP slab with thickness (T) ... [Opt. Lett. 37, 488-490 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-488

Graeme Brown, Robert R. Thomson, Ajoy K. Kar, Nicholas D. Psaila, Henry T. BookeyWe report the fabrication of high-strength (>30??dB) first order Bragg-grating waveguides in borosilicate glass substrates using ultrafast laser inscription. The cross section of each waveguide was controlled using the well known multiscan fabrication technique, where the desired waveguide cross ... [Opt. Lett. 37, 491-493 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-491

Jie Huang, Xinwei Lan, Tao Wei, Qun Han, Zhan Gao, Zhi Zhou, Hai XiaoThis paper proposes an actively mode-locked fiber ring laser for sensing applications. Mode-locking of the laser is achieved by driving an electro-optic amplitude modulator at an RF corresponding to the fundamental beat frequency between the longitudinal modes. The change of the cavity length ... [Opt. Lett. 37, 494-496 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-494

Rongtao Su, Pu Zhou, Xiaolin Wang, Yanxing Ma, Xiaojun XuWe report on active coherent beam combining of two single-frequency nanosecond fiber amplifiers by using stochastic parallel gradient descent algorithm. Each fiber amplifier produces an average power of more than 100?W by using three-stage cascaded amplification. The two laser beams are actively ... [Opt. Lett. 37, 497-499 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-497

Stéphane Randoux, Pierre SuretWe present an experiment in which the intracavity broadened spectrum of a Raman fiber laser is sliced by using a narrow-bandwidth optical filter. High-contrast fast fluctuations of the Stokes power are observed at the output of the optical filter. The statistics of the power fluctuations strongly ... [Opt. Lett. 37, 500-502 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-500

Birgitta Bernhardt, Akira Ozawa, Andreas Vernaleken, Ioachim Pupeza, Jan Kaster, Yohei Kobayashi, Ronald Holzwarth, Ernst Fill, Ferenc Krausz, Theodor W. Hänsch, Thomas UdemWe present the first (to our best knowledge) femtosecond enhancement cavity in the visible wavelength range for ultraviolet frequency comb generation. The cavity is seeded at 518 nm by a frequency-doubled Yb fiber laser and operates at a peak intensity of 1.2×10^13??W/cm^2. High harmonics of ... [Opt. Lett. 37, 503-505 (2012)]

http://www.opticsinfobase.org/abstract.cfm?URI=ol-37-4-503

Author(s): S. Veran-Tissoires, M. Marcoux, and M. PratEfflorescence refers to crystallized salt structures that form at the surface of a porous medium. The challenge is to understand why these structures do not form everywhere at the surface of the porous medium but at some specific locations and why there exists an exclusion distance around an efflore... [Phys. Rev. Lett. 108, 054502] Published Fri Feb 03, 2012

http://link.aps.org/doi/10.1103/PhysRevLett.108.054502

Author(s): S. Veran-Tissoires, M. Marcoux, and M. PratEfflorescence refers to crystallized salt structures that form at the surface of a porous medium. The challenge is to understand why these structures do not form everywhere at the surface of the porous medium but at some specific locations and why there exists an exclusion distance around an efflore... [Phys. Rev. Lett. 108, 054502] Published Fri Feb 03, 2012

http://link.aps.org/doi/10.1103/PhysRevLett.108.054502

Author(s): Tsutomu Momoi, Philippe Sindzingre, and Kenn KuboWe figure out that the ground state of a multiple-spin exchange model applicable to thin films of solid 3He possesses an octahedral spin nematic order. In the presence of a magnetic field, it is deformed into an antiferroquadrupolar order in the perpendicular spin plane, in which lattice Z3 rotation...[Phys. Rev. Lett. 108, 057206] Published Thu Feb 02, 2012

http://link.aps.org/doi/10.1103/PhysRevLett.108.057206

Author(s): A. Dewes, F. R. Ong, V. Schmitt, R. Lauro, N. Boulant, P. Bertet, D. Vion, and D. EsteveWe report the characterization of a two-qubit processor implemented with two capacitively coupled tunable superconducting qubits of the transmon type, each qubit having its own nondestructive single-shot readout. The fixed capacitive coupling yields the √iSWAP two-qubit gate for a suitable interacti...[Phys. Rev. Lett. 108, 057002] Published Thu Feb 02, 2012

http://link.aps.org/doi/10.1103/PhysRevLett.108.057002

Author(s): J. L. Cohn, B. D. White, C. A. M. dos Santos, and J. J. NeumeierThe Nernst coefficient for the quasi-one-dimensional metal, Li0.9Mo6O17, is found to be among the largest known for metals (ν≃500  μV/KT at T∼20  K), and is enhanced in a broad range of temperature by orders of magnitude over the value expected from Boltzmann theory for carrier diffusion. A comparat... [Phys. Rev. Lett. 108, 056604] Published Thu Feb 02, 2012

http://link.aps.org/doi/10.1103/PhysRevLett.108.056604

Author(s): G. Bellini et al. (Borexino Collaboration)We observed, for the first time, solar neutrinos in the 1.0–1.5 MeV energy range. We determined the rate of pep solar neutrino interactions in Borexino to be 3.1±0.6stat±0.3syst  counts/(day·100  ton). Assuming the pep neutrino flux predicted by the standard solar model, we obtained a constraint on ... [Phys. Rev. Lett. 108, 051302] Published Thu Feb 02, 2012

http://link.aps.org/doi/10.1103/PhysRevLett.108.051302

Author(s): Hongbin Zhang, Cesar Lazo, Stefan Blügel, Stefan Heinze, and Yuriy MokrousovBased on first-principles calculations, we predict that 5d transition metals on graphene present a unique class of hybrid systems exhibiting topological transport effects that can be manipulated effectively by external electric fields. The origin of this phenomenon lies in the exceptional magnetic p...[Phys. Rev. Lett. 108, 056802] Published Wed Feb 01, 2012

http://link.aps.org/doi/10.1103/PhysRevLett.108.056802

Author(s): Lars StixrudeFirst-principles calculations show that compression-induced electronic transitions produce a rich phase diagram featuring reentrant stability of the fcc phase with an extremum on the fcc to hcp boundary at 23 Mbar and 19 000 K, conditions similar to those expected at the center of super-Earth exopla...[Phys. Rev. Lett. 108, 055505] Published Wed Feb 01, 2012

http://link.aps.org/doi/10.1103/PhysRevLett.108.055505

Author(s): Johannes Bosbach, Stephan Weiss, and Guenter AhlersUsing compressed gases with Prandtl numbers near 0.7, we obtained flow visualizations of turbulent Rayleigh-Bénard convection in a cylindrical sample with an aspect ratio Γ≡D/L≅10 (D is the diameter and L the height) by the shadowgraph method. Focusing on the plumes under the top plate, we found tha...[Phys. Rev. Lett. 108, 054501] Published Wed Feb 01, 2012

http://link.aps.org/doi/10.1103/PhysRevLett.108.054501

Author(s): Artur M. Ankowski, Omar Benhar, Takaaki Mori, Ryuta Yamaguchi, and Makoto SakudaIt has long been recognized that the observation of γ rays originating from nuclear deexcitation can be exploited to identify neutral-current neutrino-nucleus interactions in water-Cherenkov detectors. We report the results of a calculation of the neutrino- and antineutrino-induced γ-ray production ...[Phys. Rev. Lett. 108, 052505] Published Wed Feb 01, 2012

http://link.aps.org/doi/10.1103/PhysRevLett.108.052505

Extraterrestrial quasicrystalpnas;109/5/1355/UNFIG01F1unfig01Rock sample from the mineral collection of the Museo di Storia Naturale in Florence, previously unearthed in the Koryak Mountains in Russia.Unlike crystalline solids, quasicrystals contain a near-periodic arrangement of atoms and symmetries not normally found in crystals. Luca Bindi et al. (pp. 1396–1401) performed mass spectrometry and oxygen isotope analysis on quasicrystalline grains of iron, aluminum, and copper arranged in a pattern with icosahedral symmetry—six separate axes of five-fold symmetry—and embedded in a fragment of rock previously unearthed in the Koryak Mountains in Russia. The quasicrystals, the authors report, were intermeshed with silicates and crystalline metals. In addition,...

http://www.pnas.org/content/109/5/1355.short?rss=1

Electrospray ionization (ESI) made the transfer of nonvolatile molecules, such as proteins, from solution into the gas phase without covalent bond dissociation possible, revolutionizing MS for biological applications. However, whether the gaseous ions from ESI can preserve their biologically active native structure for characterization by MS is still controversial. The method described in ref. 1 claimed this preservation using femtosecond laser pulses to vaporize native proteins from solution into the electrospray plume used for conventional ESI/MS; the low net charge value measured for the resulting molecular ions was used as preservation evidence. Instead, however, charge value data has only been...

http://www.pnas.org/content/109/5/E206.short?rss=1

An important goal for the field of mass spectrometry is the development of methods capable of measuring biomolecular structure in the condensed phase. Recently, we reported a femtosecond laser vaporization method for transferring protein from the condensed phase into the gas phase intact, with electrospray postionization evidence that the folded conformation was preserved on vaporization, even at an incident laser intensity of 1013 W cm−2 (1). In PNAS, the letter by Breuker et al. (2) suggests that we claimed a method capable of transferring protein from the condensed phase into a vacuum while maintaining the native structure. We made no...

http://www.pnas.org/content/109/5/E207.short?rss=1

We agree with Halfwerk et al. (1) on the importance of including the receivers when studying the impact of anthropogenic noise. However, we find the conclusion that the use of low-frequency song is sexually selected in great tits and that noisy conditions affect male–female communication premature for several reasons.First, the evidence that low-frequency songs are more potent than high-frequency songs is not convincing in great tits or in other songbirds. The only evidence in great tits came from the observation that noncuckolded males sing lower-frequency songs than cuckolded males (1). However, this comparison is based on a very small sample...

http://www.pnas.org/content/109/5/E208.short?rss=1

Eens et al.(1) question (i) whether our data are sufficient to state that low-frequency songs are sexually selected and (ii) whether anthropogenic noise really affects male–female communication, as males may just get closer to make their songs more audible.In reply to the first criticism, we do not see any reason in their arguments that would raise doubts about whether our statistical reality is reflecting a biological reality. We performed an adequate test on 22 male great tits and found cuckolded males to sing higher-frequency songs compared with noncuckolded males(2). Furthermore, although we could not assign the genetic fathers for all...

http://www.pnas.org/content/109/5/E209.short?rss=1

The death of Anthony E. (Tony) Siegman on October 7, 2011, was a profound shock to the worldwide optical science and laser community. An esteemed scientist and educator, Tony was also a kind and gentle man.Tony was born November 23, 1931, and raised in rural Michigan. As an early National Merit Scholar, he attended Harvard University and received an AB degree summa cum laude in 3 years. After 2 years on a cooperative plan with the University of California, Los Angeles, and Hughes Research Laboratories, he obtained an MS degree in Applied Physics in 1954. He went north to Stanford...

http://www.pnas.org/content/109/5/1379.short?rss=1

The scientific literature is replete with studies of the influence of weak magnetic fields on biological systems. Often motivated by alleged health hazards of the stray electromagnetic fields that accompany the distribution and use of electrical power, the majority of these articles report definite effects. However, in the relatively few cases in which independent replication has been attempted, the original results have usually proved irreproducible (1, 2). The situation is not helped by the scarcity of (bio)physical mechanisms by which weak magnetic fields might interact with biology. With no hypothetical mechanism to guide experimental design, the majority of these investigations...

http://www.pnas.org/content/109/5/1357.short?rss=1

When the host encounters a pathogen, the ensuing immune response involves a complex set of cellular responses distributed across many different types of cells. In T and B lymphocytes of the adaptive immune system, these responses include irreversible differentiation events that generate functionally specialized subpopulations of cells (1). Understanding how pathogens and vaccines influence the number, type, and efficacy of specific differentiation states in the T-cell compartment is a major goal in immunology. The study by Han et al. in PNAS (2) interrogates the functional response of individual T cells over time using a nanofluidic platform. Their experiments reveal that...

http://www.pnas.org/content/109/5/1359.short?rss=1

Secondary active transporters use electrochemical gradients provided by primary ion pumps to translocate metabolites or drugs “uphill” across membranes. Here we report the ion-coupling mechanism of cystinosin, an unusual eukaryotic, proton-driven transporter distantly related to the proton pump bacteriorhodopsin. In humans, cystinosin exports the proteolysis-derived dimeric amino acid cystine from lysosomes and is impaired in cystinosis. Using voltage-dependence analysis of steady-state and transient currents elicited by cystine and neutralization-scanning mutagenesis of conserved protonatable residues, we show that cystine binding is coupled to protonation of a clinically relevant aspartate buried in the membrane. Deuterium isotope substitution experiments are consistent with an access of this aspartate from the lysosomal lumen through a deep proton channel. This aspartate lies in one of the two PQ-loop motifs shared by cystinosin with a set of eukaryotic membrane proteins of unknown function and is conserved in about half of them, thus suggesting that other PQ-loop proteins may translocate protons.

http://www.pnas.org/content/109/5/E210.short?rss=1

Myosin Va (myoV) is a processive molecular motor that transports intracellular cargo along actin tracks with each head taking multiple 72-nm hand-over-hand steps. This stepping behavior was observed with a constitutively active, truncated myoV, in which the autoinhibitory interactions between the globular tail and motor domains (i.e., heads) that regulate the full-length molecule no longer exist. Without cargo at near physiologic ionic strength (100 mM KCl), full-length myoV adopts a folded (approximately 15 S), enzymatically-inhibited state that unfolds to an extended (approximately 11 S), active conformation at higher salt (250 mM). Under conditions favoring the folded, inhibited state, we show that Quantum-dot-labeled myoV exhibits two types of interaction with actin in the presence of MgATP. Most motors bind to actin and remain stationary, but surprisingly, approximately 20% are processive. The moving motors transition between a strictly gated and hand-over-hand stepping pattern typical of a constitutively active motor, and a new mode with a highly variable stepping pattern suggestive of altered gating. Each head of this partially inhibited motor takes longer-lived, short forward (35 nm) and backward (28 nm) steps, presumably due to globular tail-head interactions that modify the gating of the individual heads. This unique mechanical state may be an intermediate in the pathway between the inhibited and active states of the motor.

http://www.pnas.org/content/109/5/E218.short?rss=1

Global disruption of transient receptor potential-melastatin-like 7 (Trpm7) in mice results in embryonic lethality before embryonic day 7. Using tamoxifen-inducible disruption of Trpm7 and multiple Cre recombinase lines, we show that Trpm7 deletion before and during organogenesis results in severe tissue-specific developmental defects. We find that Trpm7 is essential for kidney development from metanephric mesenchyme but not ureteric bud. Disruption of neural crest Trpm7 at early stages results in loss of pigment cells and dorsal root ganglion neurons. In contrast, late disruption of brain-specific Trpm7 after embryonic day 10.5 does not alter normal brain development. We developed induced pluripotent stem cells and neural stem (NS) cells in which Trpm7 disruption could be induced. Trpm7−/− NS cells retained the capacities of self-renewal and differentiation into neurons and astrocytes. During in vitro differentiation of induced pluripotent stem cells to NS cells, Trpm7 disruption prevents the formation of the NS cell monolayer. The in vivo and in vitro results demonstrate a temporal requirement for the Trpm7 channel kinase during embryogenesis.

http://www.pnas.org/content/109/5/E225.short?rss=1

The pigmentation patterns of shells in the genus Conus can be generated by a neural-network model of the mantle. We fit model parameters to the shell pigmentation patterns of 19 living Conus species for which a well resolved phylogeny is available. We infer the evolutionary history of these parameters and use these results to infer the pigmentation patterns of ancestral species. The methods we use allow us to characterize the evolutionary history of a neural network, an organ that cannot be preserved in the fossil record. These results are also notable because the inferred patterns of ancestral species sometimes lie outside the range of patterns of their living descendants, and illustrate how development imposes constraints on the evolution of complex phenotypes.

http://www.pnas.org/content/109/5/E234.short?rss=1

Despite compelling evidence supporting key roles for glycogen synthase kinase 3β (GSK3β), mitochondrial adenosine triphosphate-sensitive K+ (mitoKATP) channels, and mitochondrial connexin 43 (Cx43) in cytoprotection, it is not clear how these signaling modules are linked mechanistically. By patch-clamping the inner membrane of murine cardiac mitochondria, we found that inhibition of GSK3β activated mitoKATP. PKC activation and protein phosphatase 2a inhibition increased the open probability of mitoKATP channels through GSK3β, and this GSK3β signal was mediated via mitochondrial Cx43. Moreover, (i) PKC-induced phosphorylation of mitochondrial Cx43 was reduced in GSK3β-S9A mice; (ii) Cx43 and GSK3β proteins associated in mitochondria; and (iii) SB216763-mediated reduction of infarct size was abolished in Cx43 KO mice in vivo, consistent with the notion that GSK3β inhibition results in mitoKATP opening via mitochondrial Cx43. We therefore directly targeted mitochondrial Cx43 by the Cx43 C-terminal binding peptide RRNYRRNY for cardioprotection, circumventing further upstream pathways. RRNYRRNY activated mitoKATP channels via Cx43. We directly recorded mitochondrial Cx43 channels that were activated by RRNYRRNY and blocked by the Cx43 mimetic peptide 43GAP27. RRNYRRNY rendered isolated cardiomyocytes in vitro and the heart in vivo resistant to ischemia/reperfusion injury, indicating that mitochondrial Cx43- and/or mitoKATP-mediated reduction of infarct size was not undermined by RRNYRRNY-related opening of sarcolemmal Cx43 channels. Our results demonstrate that GSK3β transfers cytoprotective signaling through mitochondrial Cx43 onto mitoKATP channels and that Cx43 functions as a channel in mitochondria, being an attractive target for drug treatment against cardiomyocyte injury.

http://www.pnas.org/content/109/5/E242.short?rss=1

Defining the molecular genetic alterations underlying pancreatic cancer may provide unique therapeutic insight for this deadly disease. Toward this goal, we report here an integrative DNA microarray and sequencing-based analysis of pancreatic cancer genomes. Notable among the alterations newly identified, genomic deletions, mutations, and rearrangements recurrently targeted genes encoding components of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex, including all three putative DNA binding subunits (ARID1A, ARID1B, and PBRM1) and both enzymatic subunits (SMARCA2 and SMARCA4). Whereas alterations of each individual SWI/SNF subunit occurred at modest-frequency, as mutational “hills” in the genomic landscape, together they affected at least one-third of all pancreatic cancers, defining SWI/SNF as a major mutational “mountain.” Consistent with a tumor-suppressive role, re-expression of SMARCA4 in SMARCA4-deficient pancreatic cancer cell lines reduced cell growth and promoted senescence, whereas its overexpression in a SWI/SNF-intact line had no such effect. In addition, expression profiling analyses revealed that SWI/SNF likely antagonizes Polycomb repressive complex 2, implicating this as one possible mechanism of tumor suppression. Our findings reveal SWI/SNF to be a central tumor suppressive complex in pancreatic cancer.

http://www.pnas.org/content/109/5/E252.short?rss=1

More than 120 human papillomaviruses (HPVs) have now been identified and have been associated with a variety of clinical lesions. To understand the molecular differences among these viruses that result in lesions with distinct pathologies, we have begun a MS-based proteomic analysis of HPV–host cellular protein interactions and have created the plasmid and cell line libraries required for these studies. To validate our system, we have characterized the host cellular proteins that bind to the E7 proteins expressed from 17 different HPV types. These studies reveal a number of interactions, some of which are conserved across HPV types and others that are unique to a single HPV species or HPV genus. Binding of E7 to UBR4/p600 is conserved across all virus types, whereas the cellular protein ENC1 binds specifically to the E7s from HPV18 and HPV45, both members of genus alpha, species 7. We identify a specific interaction of HPV16 E7 with ZER1, a substrate specificity factor for a cullin 2 (CUL2)-RING ubiquitin ligase, and show that ZER1 is required for the binding of HPV16 E7 to CUL2. We further show that ZER1 is required for the destabilization of the retinoblastoma tumor suppressor RB1 in HPV16 E7-expressing cells and propose that a CUL2–ZER1 complex functions to target RB1 for degradation in HPV16 E7-expressing cells. These studies refine the current understanding of HPV E7 functions and establish a platform for the rapid identification of virus–host interactions.

http://www.pnas.org/content/109/5/E260.short?rss=1

Measuring the abundance of many proteins over a broad dynamic range requires accurate quantitation. We show empirically that, in MS experiments, relative quantitation using summed dissociation-product ion-current intensities is accurate, albeit variable from protein to protein, and outperforms spectral counting. By applying intensities to quantify proteins in two complex but related tissues, chick auditory and vestibular sensory epithelia, we find that glycolytic enzymes are enriched threefold in auditory epithelia, whereas enzymes responsible for oxidative phosphorylation are increased at least fourfold in vestibular epithelia. This striking difference in relative use of the two ATP-production pathways likely reflects the isolation of the auditory epithelium from its blood supply, necessary to prevent heartbeat-induced mechanical disruptions. The global view of protein expression afforded by label-free quantitation with a wide dynamic range reveals molecular specialization at a tissue or cellular level.

http://www.pnas.org/content/109/5/E268.short?rss=1

The bed nucleus of the stria terminalis (BNST) is a critical region for alcohol/drug-induced negative affect and stress-induced reinstatement. NMDA receptor (NMDAR)-dependent plasticity, such as long-term potentiation (LTP), has been postulated to play key roles in alcohol and drug addiction; yet, to date, little is understood regarding the mechanisms underlying LTP of the BNST, or its regulation by ethanol. Acute and chronic exposure to ethanol modulates glutamate transmission via actions on NMDARs. Despite intense investigation, tests of subunit specificity of ethanol actions on NMDARs using pharmacological approaches have produced mixed results. Thus, we use a conditional GluN2B KO mouse line to assess both basal and ethanol-dependent function of this subunit at glutamate synapses in the BNST. Deletion of GluN2B eliminated LTP, as well as actions of ethanol on NMDAR function. Further, we show that chronic ethanol exposure enhances LTP formation in the BNST. Using KO-validated pharmacological approaches with Ro25-6981 and memantine, we provide evidence suggesting that chronic ethanol exposure enhances LTP in the BNST via paradoxical extrasynaptic NMDAR involvement. These findings demonstrate that GluN2B is a key point of regulation for ethanol's actions and suggest a unique role of extrasynaptic GluN2B-containing receptors in facilitating LTP.

http://www.pnas.org/content/109/5/E278.short?rss=1

The first carcinogenic virus was discovered in chickens in 1911. More than 70 years later, Harald zur Hausen demonstrated that human papillomavirus (HPV) can cause cervical cancer, for which he garnered the 2008 Nobel Prize in Medicine or Physiology. A professor emeritus at the German Cancer Research Center and recently elected member of the National Academy of Sciences, zur Hausen’s contributions to the field of virology have reshaped our understanding of the connections between infectious and chronic diseases. PNAS recently spoke with the Nobel laureate about HPV, undercooked beef, and scientific “dogma.”pnas;109/5/1378/UNFIG01F1unfig01Harald zur Hausen.PNAS:In general, how do viruses cause cancer?zur...

http://www.pnas.org/content/109/5/1378.short?rss=1

Maize (Zea mays ssp. mays) is among the world's most important and ancient domesticated crops. Although the chronology of its domestication and initial dispersals out of Mexico into Central and South America has become more clear due to molecular and multiproxy archaeobotanical research, important problems remain. Among them is the paucity of information on maize's early morphological evolution and racial diversification brought about in part by the poor preservation of macrofossils dating to the pre-5000 calibrated years before the present period from obligate dispersal routes located in the tropical forest. We report newly discovered macrobotanical and microbotanical remains of maize that shed significant light on the chronology, land race evolution, and cultural contexts associated with the crop's early movements into South America and adaptation to new environments. The evidence comes from the coastal Peruvian sites of Paredones and Huaca Prieta, Peru; dates from the middle and late preceramic and early ceramic periods (between ca. 6700 and 3000 calibrated years before the present); and constitutes some of the earliest known cobs, husks, stalks, and tassels. The macrobotanical record indicates that a diversity of racial complexes characteristic of the Andean region emerged during the preceramic era. In addition, accelerator mass spectrometry radiocarbon determinations carried out directly on different structures of preserved maize plants strongly suggest that assays on burned cobs are more reliable than those on unburned cobs. Our findings contribute to knowledge of the early diffusion of maize and agriculture and have broader implications for understanding the development of early preindustrial human societies.

http://www.pnas.org/content/109/5/1755.short?rss=1

We present evidence that a rock sample found in the Koryak Mountains in Russia and containing icosahedrite, an icosahedral quasicrystalline phase with composition Al63Cu24Fe13, is part of a meteorite, likely formed in the early solar system about 4.5 Gya. The quasicrystal grains are intergrown with diopside, forsterite, stishovite, and additional metallic phases [khatyrkite (CuAl2), cupalite (CuAl), and β-phase (AlCuFe)]. This assemblage, in turn, is enclosed in a white rind consisting of diopside, hedenbergite, spinel (MgAl2O4), nepheline, and forsterite. Particularly notable is a grain of stishovite (from the interior), a tetragonal polymorph of silica that only occurs at ultrahigh pressures (≥10 Gpa), that contains an inclusion of quasicrystal. An extraterrestrial origin is inferred from secondary ion mass spectrometry 18O/16O and 17O/16O measurements of the pyroxene and olivine intergrown with the metal that show them to have isotopic compositions unlike any terrestrial minerals and instead overlap those of anhydrous phases in carbonaceous chondrite meteorites. The spinel from the white rind has an isotopic composition suggesting that it was part of a calcium-aluminum-rich inclusion similar to those found in CV3 chondrites. The mechanism that produced this exotic assemblage is not yet understood. The assemblage (metallic copper-aluminum alloy) is extremely reduced, and the close association of aluminum (high temperature refractory lithophile) with copper (low temperature chalcophile) is unexpected. Nevertheless, our evidence indicates that quasicrystals can form naturally under astrophysical conditions and remain stable over cosmic timescales, giving unique insights on their existence in nature and stability.

http://www.pnas.org/content/109/5/1396.short?rss=1

A simple, versatile approach to the directed self-assembly of block copolymers into a macroscopic array of unidirectionally aligned cylindrical microdomains on reconstructed faceted single crystal surfaces or on flexible, inexpensive polymeric replicas was discovered. High fidelity transfer of the line pattern generated from the microdomains to a master mold is also shown. A single-grained line patterns over arbitrarily large surface areas without the use of top-down techniques is demonstrated, which has an order parameter typically in excess of 0.97 and a slope error of 1.1 deg. This degree of perfection, produced in a short time period, has yet to be achieved by any other methods. The exceptional alignment arises from entropic penalties of chain packing in the facets coupled with the bending modulus of the cylindrical microdomains. This is shown, theoretically, to be the lowest energy state. The atomic crystalline ordering of the substrate is transferred, over multiple length scales, to the block copolymer microdomains, opening avenues to large-scale roll-to-roll type and nanoimprint processing of perfectly patterned surfaces and as templates and scaffolds for magnetic storage media, polarizing devices, and nanowire arrays.

http://www.pnas.org/content/109/5/1402.short?rss=1

The organization of cells into epithelium depends on cell interaction with both the extracellular matrix (ECM) and adjacent cells. The role of cell–cell adhesion in the regulation of epithelial topology is well-described. ECM is better known to promote cell migration and provide a structural scaffold for cell anchoring, but its contribution to multicellular morphogenesis is less well-understood. We developed a minimal model system to investigate how ECM affects the spatial organization of intercellular junctions. Fibronectin micropatterns were used to constrain the location of cell–ECM adhesion. We found that ECM affects the degree of stability of intercellular junction positioning and the magnitude of intra- and intercellular forces. Intercellular junctions were permanently displaced, and experienced large perpendicular tensional forces as long as they were positioned close to ECM. They remained stable solely in regions deprived of ECM, where they were submitted to lower tensional forces. The heterogeneity of the spatial organization of ECM induced anisotropic distribution of mechanical constraints in cells, which seemed to adapt their position to minimize both intra- and intercellular forces. These results uncover a morphogenetic role for ECM in the mechanical regulation of cells and intercellular junction positioning.

http://www.pnas.org/content/109/5/1506.short?rss=1

Helicases are ubiquitous enzymes that unwind double-stranded DNA (dsDNA) to reveal single-stranded DNA (ssDNA) during essential processes such as replication, transcription, or repair. The Escherichia coli RecQ protein is a 3′ to 5′ helicase, which functions in the processes of homologous recombination and replication fork restart. Here, we analyzed the relationship between ATP hydrolysis by RecQ and its translocation on ssDNA. We monitored a single round of RecQ translocation on ssDNA by measuring the rates of inorganic phosphate release during translocation, and the dissociation of RecQ from ssDNA. We find that RecQ translocates with a rate of 16( ± 4) nucleotides/s and moves on average only 36( ± 2) nucleotides before dissociating. Fitting to an n-step kinetic model suggests that the helicase displays a nonuniform translocation mechanism in which it moves approximately five nucleotides rapidly before undergoing a rate-limiting kinetic slow step. Unexpectedly, RecQ requires a length of 34( ± 3) nucleotides to bind and translocate on ssDNA. This large site size suggests that several monomers are required to bind DNA prior to translocation. Energetically, the RecQ helicase couples the hydrolysis of one ATP molecule to the translocation of more than one nucleotide (1.6 ± 0.3). Thus, our data show that RecQ translocates on ssDNA by efficiently coupling the hydrolysis of one ATP molecule into structural alterations that result in movement of approximately two nucleotides, presumably by an inchworm mechanism. These attributes are consistent with the function of RecQ in recombination and replication.

http://www.pnas.org/content/109/5/1443.short?rss=1

ATP8A2 is a P4-ATPase (“flippase”) located in membranes of retinal photoreceptors, brain cells, and testis, where it mediates transport of aminophospholipids toward the cytoplasmic leaflet. It has long been an enigma whether the mechanism of P4-ATPases resembles that of the well-characterized cation-transporting P-type ATPases, and it is unknown whether the flippases interact directly with the lipid and with counterions. Our results demonstrate that ATP8A2 forms a phosphoenzyme intermediate at the conserved aspartate (Asp416) in the P-type ATPase signature sequence and exists in E1P and E2P forms similar to the archetypical P-type ATPases. Using the properties of the phosphoenzyme, the partial reaction steps of the transport cycle were examined, and the roles of conserved residues Asp196, Glu198, Lys873, and Asn874 in the transport mechanism were elucidated. The former two residues in the A-domain T/D-G-E-S/T motif are involved in catalysis of E2P dephosphorylation, the glutamate being essential. Transported aminophospholipids activate the dephosphorylation similar to K+ activation of dephosphorylation in Na+,K+-ATPase. Lys873 mutants (particularly K873A and K873E) display a markedly reduced sensitivity to aminophospholipids. Hence, Lys873, located in transmembrane segment M5 at a “hot spot” for cation binding in Ca2+-ATPase and Na+,K+-ATPase, appears to participate directly in aminophospholipid binding or to mediate a crucial interaction within the ATP8A2-CDC50 complex. By contrast, Lys865 is unimportant for aminophospholipid sensitivity. Binding of Na+, H+, K+, Cl-, or Ca2+ to the E1 form as a counterion is not required for activation of phosphorylation from ATP. Therefore, phospholipids could be the only substrate transported by ATP8A2.

http://www.pnas.org/content/109/5/1449.short?rss=1

The epithelial growth factor receptor plays an important role in cell migration and cancer metastasis, but the underlying molecular mechanism is not fully understood. We show here that differential regulation of the rhodopsin-GTPase-activating (Rho-GAP) activity of deleted in liver cancer 1 (DLC1) by tensin3 and COOH-terminal tensin-like protein (cten) controls EGF-driven cell migration and transformation. Tensin3 binds DLC1 through its actin-binding domain, a region that is missing in cten, and thereby releases an autoinhibitory interaction between the sterile alpha motif and Rho-GAP domains of DLC1. Consequently, tensin3, but not cten, promotes the activation of DLC1, which, in turn, leads to inactivation of RhoA and decreased cell migration. Depletion of endogenous tensin3, but not cten, augmented the formation of actin stress fibers and focal adhesions and enhanced cell motility. These effects were, however, ablated by an inhibitor of the Rho-associated protein kinase. Importantly, activation of DLC1 by tensin3 or its actin-binding domain drastically reduced the anchorage-independent growth of transformed cells. Our study therefore links dynamic regulation of tensin family members by EGF to Rho-GAP through DLC1 and suggests that the tensin-DLC1-RhoA signaling axis plays an important role in tumorigenesis and cancer metastasis, and may be explored for cancer intervention.

http://www.pnas.org/content/109/5/1455.short?rss=1

Historically, rate constants were determined in vitro and it was unknown whether they were valid for in vivo biological processes. Here, we bridge this gap by measuring binding dynamics between a pair of proteins in living HeLa cells. Binding of a β-lactamase to its protein inhibitor was initiated by microinjection and monitored by Förster resonance energy transfer. Association rate constants for the wild-type and an electrostatically optimized mutant were only 25% and 50% lower than in vitro values, whereas no change in the rate constant was observed for a slower binding mutant. These changes are much smaller than might be anticipated considering the high macromolecular crowding within the cell. Single-cell analyses of association rate constants and fluorescence recovery after photobleaching reveals a naturally occurring variation in cell density, which is translated to an up to a twofold effect on binding rate constants. The data show that for this model protein interaction the intracellular environment had only a small effect on the association kinetics, justifying the extrapolation of in vitro data to processes in the cell.

http://www.pnas.org/content/109/5/1461.short?rss=1

The 26S proteasome is at the executive end of the ubiquitin-proteasome pathway for the controlled degradation of intracellular proteins. While the structure of its 20S core particle (CP) has been determined by X-ray crystallography, the structure of the 19S regulatory particle (RP), which recruits substrates, unfolds them, and translocates them to the CP for degradation, has remained elusive. Here, we describe the molecular architecture of the 26S holocomplex determined by an integrative approach based on data from cryoelectron microscopy, X-ray crystallography, residue-specific chemical cross-linking, and several proteomics techniques. The “lid” of the RP (consisting of Rpn3/5/6/7/8/9/11/12) is organized in a modular fashion. Rpn3/5/6/7/9/12 form a horseshoe-shaped heterohexamer, which connects to the CP and roofs the AAA-ATPase module, positioning the Rpn8/Rpn11 heterodimer close to its mouth. Rpn2 is rigid, supporting the lid, while Rpn1 is conformationally variable, positioned at the periphery of the ATPase ring. The ubiquitin receptors Rpn10 and Rpn13 are located in the distal part of the RP, indicating that they were recruited to the complex late in its evolution. The modular structure of the 26S proteasome provides insights into the sequence of events prior to the degradation of ubiquitylated substrates.

http://www.pnas.org/content/109/5/1380.short?rss=1

Two canonical subunits of the 26S proteasome, Rpn10 and Rpn13, function as ubiquitin (Ub) receptors. The mutual arrangement of these subunits—and all other non-ATPase subunits—in the regulatory particle is unknown. Using electron cryomicroscopy, we calculated difference maps between wild-type 26S proteasome from Saccharomyces cerevisiae and deletion mutants (rpn10Δ, rpn13Δ, and rpn10Δrpn13Δ). These maps allowed us to localize the two Ub receptors unambiguously. Rpn10 and Rpn13 mapped to the apical part of the 26S proteasome, above the N-terminal coiled coils of the AAA-ATPase heterodimers Rpt4/Rpt5 and Rpt1/Rpt2, respectively. On the basis of the mutual positions of Rpn10 and Rpn13, we propose a model for polyubiquitin binding to the 26S proteasome.

http://www.pnas.org/content/109/5/1479.short?rss=1

Riboswitches are motifs in the untranslated regions (UTRs) of RNA transcripts that sense metabolite levels and modulate the expression of the corresponding genes for metabolite import, export, synthesis, or degradation. All riboswitches contain an aptamer: an RNA structure that, upon binding ligand, folds to expose or sequester regulatory elements in the adjacent sequence through alternative nucleotide pairing. The coupling between ligand binding and aptamer folding is central to the regulatory mechanisms of thiamine pyrophosphate (TPP) riboswitches and has not been fully characterized. Here, we show that TPP aptamer folding can be decomposed into ligand-independent and -dependent steps that correspond to the formation of secondary and tertiary structures, respectively. We reconstructed the full energy landscape for folding of the wild-type (WT) aptamer and measured perturbations of this landscape arising from mutations or ligand binding. We show that TPP binding proceeds in two steps, from a weakly to a strongly bound state. Our data imply a hierarchical folding sequence, and provide a framework for understanding molecular mechanism throughout the TPP riboswitch family.

http://www.pnas.org/content/109/5/1485.short?rss=1

Proteins fold into three-dimensional structures in a funneled energy landscape. This landscape is also used for functional activity. Frustration in this landscape can arise from the competing evolutionary pressures of biological function and reliable folding. Thus, the ensemble of partially folded states can populate multiple routes on this journey to the native state. Although protein folding kinetics experiments have shown the presence of such routes for several proteins, there has been sparse information about the structural diversity of these routes. In addition, why a given protein populates a particular route more often than another protein of similar structure and sequence is not clear. Whereas multiple routes are observed in theoretical studies on the folding of interleukin-1β (IL-1β), experimental results indicate one dominant route where the central portion of the protein folds first, and is then followed by closure of the barrel in this β-trefoil fold. Here we show, using a combination of computation and experiment, that the presence of functionally important regions like the β-bulge in the signaling protein IL-1β strongly influences the choice of folding routes. By deleting the β-bulge, we directly observe the presence of route-switching. This route-switching provides a direct link between route selection and the folding and functional landscapes of a protein.

http://www.pnas.org/content/109/5/1490.short?rss=1

The ability to engineer novel protein folds, conformations, and enzymatic activities offers enormous potential for the development of new protein therapeutics and biocatalysts. However, many de novo and redesigned proteins exhibit poor hydrophobic packing in their predicted structures, leading to instability or insolubility. The general utility of rational, structure-based design would greatly benefit from an improved ability to generate well-packed conformations. Here we present an automated protocol within the RosettaDesign framework that can identify and improve poorly packed protein cores by selecting a series of stabilizing point mutations. We apply our method to previously characterized designed proteins that exhibited a decrease in stability after a full computational redesign. We further demonstrate the ability of our method to improve the thermostability of a well-behaved native protein. In each instance, biophysical characterization reveals that we were able to stabilize the original proteins against chemical and thermal denaturation. We believe our method will be a valuable tool for both improving upon designed proteins and conferring increased stability upon native proteins.

http://www.pnas.org/content/109/5/1494.short?rss=1

Axin is a tumor suppressor and a key negative regulator of the Wnt/β-catenin signaling pathway. Axin turnover is controlled by its poly-ADP-ribosylation catalyzed by tankyrase (TNKS), which requires the direct interaction of Axin with TNKS. This interaction is thus an attractive drug target for treating cancers, brain injuries, and other diseases where β-catenin is involved. Here we report the crystal structure of a mouse TNKS1 fragment containing ankyrin-repeat clusters 2 and 3 (ARC2-3) in a complex with the TNKS-binding domain of mouse Axin1. Surprisingly, we found that Axin contains two discrete TNKS-binding segments, both of which bind simultaneously to the two ARC2 domains in the ARC2-3 homodimer. Our crystal structure shows that in each TNKS-binding segment of Axin there is a conserved glycine residue that lies in the bottom of a narrow “gate” formed by two parallel tyrosine side chains on the TNKS surface. This glycine-selection gate is crucial for TNKS-Axin interactions, as mutation of the TNKS gate-forming residues, or mutation of either glycine residue in the two Axin segments, completely abolishes the binding of the corresponding Axin segment to TNKS. The bivalent binding of Axin to TNKS is required for Axin turnover, since mutations in either gate-binding glycine residue in Axin lead to Axin stabilization in the cell. In addition, our analyses also reveal the structural basis for TNKS substrate recruitment, and shed light on the overall structure of TNKS that should help in developing specific inhibitors of Wnt/β-catenin signaling.

http://www.pnas.org/content/109/5/1500.short?rss=1

Following infection with Epstein–Barr virus (EBV), the virus is carried for life in the memory B-cell compartment in a silent state (latency I/0). These cells do not resemble the proliferating lymphoblastoid cells (LCLs) (latency III) that are generated after infection. It is of fundamental significance to identify how the different EBV expression patterns are established in the latently infected cell. In view of the prompt activatability of CD4+ T cells in primary EBV infection, and their role in B-cell differentiation, we studied the involvement of CD4+ T cells in the regulation of EBV latency. Lymphoblastoid cell lines (LCLs) were cocultured with autologous or allogeneic CD4+ T cells. Activated T cells influenced the expression of two key viral proteins that determine the fate of the infected B cell. EBNA2 was down-regulated, whereas LMP1 was unregulated and the cells proliferated less. This was paralleled by the down-regulation of the latency III promoter (Cp). Experiments performed in the transwell system showed that this change does not require cell contact, but it is mediated by soluble factors. Neutralizing experiments proved that the up-regulation of LMP1 is, to some extent, mediated by IL21, but this cytokine was not responsible for EBNA2 down-regulation. This effect was partly mediated by soluble CD40L. We detected similar regulatory functions of T cells in in vitro-infected lymphocyte populations. In conclusion, our results revealed an additional mechanism by which CD4+ T cells can control the EBV-induced B-cell proliferation.

http://www.pnas.org/content/109/5/1512.short?rss=1

The metabolic state of a cell is a key determinant in the decision to live and proliferate or to die. Consequently, balanced energy metabolism and the regulation of apoptosis are critical for the development and maintenance of differentiated organisms. Hypoxia occurs physiologically during development or exercise and pathologically in vascular disease, tumorigenesis, and inflammation, interfering with homeostatic metabolism. Here, we show that the hypoxia-inducible factor (HIF)-1–regulated glycolytic enzyme hexokinase II (HKII) acts as a molecular switch that determines cellular fate by regulating both cytoprotection and induction of apoptosis based on the metabolic state. We provide evidence for a direct molecular interactor of HKII and show that, together with phosphoprotein enriched in astrocytes (PEA15), HKII inhibits apoptosis after hypoxia. In contrast, HKII accelerates apoptosis in the absence of PEA15 and under glucose deprivation. HKII both protects cells from death during hypoxia and functions as a sensor of glucose availability during normoxia, inducing apoptosis in response to glucose depletion. Thus, HKII-mediated apoptosis may represent an evolutionarily conserved altruistic mechanism to eliminate cells during metabolic stress to the advantage of a multicellular organism.

http://www.pnas.org/content/109/5/1518.short?rss=1

Filamin A (FLNA) is an actin-binding protein with a well-established role in the cytoskeleton, where it determines cell shape and locomotion by cross-linking actin filaments. Mutations in FLNA are associated with a wide range of genetic disorders. Here we demonstrate a unique role for FLNA as a nucleolar protein that associates with the RNA polymerase I (Pol I) transcription machinery to suppress rRNA gene transcription. We show that depletion of FLNA by siRNAs increased rRNA expression, rDNA promoter activity and cell proliferation. Immunodepletion of FLNA from nuclear extracts resulted in a decrease in rDNA promoter-driven transcription in vitro. FLNA coimmunoprecipitated with the Pol I components actin, TIF-IA, and RPA40, and their occupancy of the rDNA promoter was increased in the absence of FLNA in vivo. The FLNA actin-binding domain is essential for the suppression of rRNA expression and for inhibiting recruitment of the Pol I machinery to the rDNA promoter. These findings reveal an additional role for FLNA as a regulator of rRNA gene expression and have important implications for our understanding of the role of FLNA in human disease.

http://www.pnas.org/content/109/5/1524.short?rss=1

The loss of the epithelial architecture and cell polarity/differentiation is known to be important during the tumorigenic process. Here we demonstrate that the brush border protein Myosin Ia (MYO1A) is important for polarization and differentiation of colon cancer cells and is frequently inactivated in colorectal tumors by genetic and epigenetic mechanisms. MYO1A frame-shift mutations were observed in 32% (37 of 116) of the colorectal tumors with microsatellite instability analyzed, and evidence of promoter methylation was observed in a significant proportion of colon cancer cell lines and primary colorectal tumors. The loss of polarization/differentiation resulting from MYO1A inactivation is associated with higher tumor growth in soft agar and in a xenograft model. In addition, the progression of genetically and carcinogen-initiated intestinal tumors was significantly accelerated in Myo1a knockout mice compared with Myo1a wild-type animals. Moreover, MYO1A tumor expression was found to be an independent prognostic factor for colorectal cancer patients. Patients with low MYO1A tumor protein levels had significantly shorter disease-free and overall survival compared with patients with high tumoral MYO1A (logrank test P = 0.004 and P = 0.009, respectively). The median time-to-disease recurrence in patients with low MYO1A was 1 y, compared with >9 y in the group of patients with high MYO1A. These results identify MYO1A as a unique tumor-suppressor gene in colorectal cancer and demonstrate that the loss of structural brush border proteins involved in cell polarity are important for tumor development.

http://www.pnas.org/content/109/5/1530.short?rss=1

The yeast AGC kinase orthologs Ypk1 and Ypk2 control several important cellular processes, including actin polarization, endocytosis, and sphingolipid metabolism. Activation of Ypk1/2 requires phosphorylation by kinases localized at the plasma membrane (PM), including the 3-phosphoinositide-dependent kinase 1 orthologs Pkh1/Pkh2 and the target of rapamycin complex 2 (TORC2). Unlike their mammalian counterparts SGK and Akt, Ypk1 and Ypk2 lack an identifiable lipid-targeting motif; therefore, how these proteins are recruited to the PM has remained elusive. To explore Ypk1/2 function, we constructed ATP analog-sensitive alleles of both kinases and monitored global changes in gene expression following their inhibition, where we observed increased expression of stress-responsive target genes controlled by Ca2+-dependent phosphatase calcineurin. TORC2 has been shown previously to negatively regulate calcineurin in part by phosphorylating two related proteins, Slm1 and Slm2, which associate with the PM via plextrin homology domains. We therefore investigated the relationship between Slm1 and Ypk1 and discovered that these proteins interact physically and that Slm1 recruits Ypk1 to the PM for phosphorylation by TORC2. We observed further that these steps facilitate subsequent phosphorylation of Ypk1 by Pkh1/2. Remarkably, a requirement for Slm1, can be bypassed by fusing the plextrin homology domain of Slm1 alone onto Ypk1, demonstrating that the essential function of Slm1 is largely attributable to its role in Ypk1 activation. These findings both extend the scope of cellular processes regulated by Ypk1/2 to include negative regulation of calcineurin and broaden the repertoire of mechanisms for membrane recruitment and activation of a protein kinase.

http://www.pnas.org/content/109/5/1536.short?rss=1

Spermiogenesis is a series of poorly understood morphological, physiological and biochemical processes that occur during the transition of immotile spermatids into motile, fertilization-competent spermatozoa. Here, we identified a Serpin (serine protease inhibitor) family protein (As_SRP-1) that is secreted from spermatids during nematode Ascaris suum spermiogenesis (also called sperm activation) and we showed that As_SRP-1 has two major functions. First, As_SRP-1 functions in cis to support major sperm protein (MSP)-based cytoskeletal assembly in the spermatid that releases it, thereby facilitating sperm motility acquisition. Second, As_SRP-1 released from an activated sperm inhibits, in trans, the activation of surrounding spermatids by inhibiting vas deferens-derived As_TRY-5, a trypsin-like serine protease necessary for sperm activation. Because vesicular exocytosis is necessary to create fertilization-competent sperm in many animal species, components released during this process might be more important modulators of the physiology and behavior of surrounding sperm than was previously appreciated.

http://www.pnas.org/content/109/5/1542.short?rss=1

Silicon nanowires (NWs) could enable low-cost and efficient photovoltaics, though their performance has been limited by nonideal electrical characteristics and an inability to tune absorption properties. We overcome these limitations through controlled synthesis of a series of polymorphic core/multishell NWs with highly crystalline, hexagonally-faceted shells, and well-defined coaxial (p/n) and p/intrinsic/n (p/i/n) diode junctions. Designed 200–300 nm diameter p/i/n NW diodes exhibit ultralow leakage currents of approximately 1 fA, and open-circuit voltages and fill-factors up to 0.5 V and 73%, respectively, under one-sun illumination. Single-NW wavelength-dependent photocurrent measurements reveal size-tunable optical resonances, external quantum efficiencies greater than unity, and current densities double those for silicon films of comparable thickness. In addition, finite-difference-time-domain simulations for the measured NW structures agree quantitatively with the photocurrent measurements, and demonstrate that the optical resonances are due to Fabry-Perot and whispering-gallery cavity modes supported in the high-quality faceted nanostructures. Synthetically optimized NW devices achieve current densities of 17 mA/cm2 and power-conversion efficiencies of 6%. Horizontal integration of multiple NWs demonstrates linear scaling of the absolute photocurrent with number of NWs, as well as retention of the high open-circuit voltages and short-circuit current densities measured for single NW devices. Notably, assembly of 2 NW elements into vertical stacks yields short-circuit current densities of 25 mA/cm2 with a backside reflector, and simulations further show that such stacking represents an attractive approach for further enhancing performance with projected efficiencies of > 15% for 1.2 μm thick 5 NW stacks.

http://www.pnas.org/content/109/5/1407.short?rss=1

A series of azido-PEG-succinimide ester oligomers with a number of repeating PEG units of 0, 4, 8, and 12 (azPEG0, 4, 8, and 12) was investigated using a relaxation-assisted two-dimensional infrared (RA 2DIR) spectroscopy method. The RA 2DIR method relies on the energy transport in molecules and is capable of correlating the frequencies of vibrational modes separated by large through-bond distances. Excitation of the azido group in the compounds at ca. 2,100 cm-1 generates an excess energy which propagates in the molecule as well as dissipates into the solvent. We discovered that a part of the excess energy propagates ballistically via the covalent backbone of the molecules with a constant speed of ca. 550 m/s. The transport is described as a propagation of a vibrational wavepacket having a mean-free-path length of 10–15 Å. The discovery has the potential for developing new efficient signal transduction strategies for molecular electronics and biochemistry. It also permits extending the distances accessible in RA 2DIR structural measurements up to ca. 60 Å.

http://www.pnas.org/content/109/5/1413.short?rss=1

An exhaustive description of the molecular recognition mechanism between a ligand and its biological target is of great value because it provides the opportunity for an exogenous control of the related process. Very often this aim can be pursued using high resolution structures of the complex in combination with inexpensive computational protocols such as docking algorithms. Unfortunately, in many other cases a number of factors, like protein flexibility or solvent effects, increase the degree of complexity of ligand/protein interaction and these standard techniques are no longer sufficient to describe the binding event. We have experienced and tested these limits in the present study in which we have developed and revealed the mechanism of binding of a new series of potent inhibitors of Adenosine Deaminase. We have first performed a large number of docking calculations, which unfortunately failed to yield reliable results due to the dynamical character of the enzyme and the complex role of the solvent. Thus, we have stepped up the computational strategy using a protocol based on metadynamics. Our approach has allowed dealing with protein motion and solvation during ligand binding and finally identifying the lowest energy binding modes of the most potent compound of the series, 4-decyl-pyrazolo[1,5-a]pyrimidin-7-one.

http://www.pnas.org/content/109/5/1467.short?rss=1

Embryonic development is controlled by networks of interacting regulatory genes. The individual linkages of gene regulatory networks (GRNs) are customarily validated by functional cis-regulatory analysis, but an additional approach to validation is to rewire GRN circuitry to test experimentally predictions derived from network structure. Here we use this synthetic method to challenge specific predictions of the sea urchin embryo endomesoderm GRN. Expression vectors generated by in vitro recombination of exogenous sequences into BACs were used to cause elements of a nonskeletogenic mesoderm GRN to be deployed in skeletogenic cells and to detect their effects. The result of reengineering the regulatory circuitry in this way was to divert the developmental program of these cells from skeletogenesis to pigment cell formation, confirming a direct prediction of the GRN. In addition, the experiment revealed previously undetected cryptic repression functions.

http://www.pnas.org/content/109/5/1548.short?rss=1

Gradients of the plant hormone auxin, which depend on its active intercellular transport, are crucial for the maintenance of root meristematic activity. This directional transport is largely orchestrated by a complex interaction of specific influx and efflux carriers that mediate the auxin flow into and out of cells, respectively. Besides these transport proteins, plant-specific polyphenolic compounds known as flavonols have been shown to act as endogenous regulators of auxin transport. However, only limited information is available on how flavonol synthesis is developmentally regulated. Using reduction-of-function and overexpression approaches in parallel, we demonstrate that the WRKY23 transcription factor is needed for proper root growth and development by stimulating the local biosynthesis of flavonols. The expression of WRKY23 itself is controlled by auxin through the AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 transcriptional response pathway. Our results suggest a model in which WRKY23 is part of a transcriptional feedback loop of auxin on its own transport through local regulation of flavonol biosynthesis.

http://www.pnas.org/content/109/5/1554.short?rss=1

Floral organs are specified by the combinatorial action of MADS-domain transcription factors, yet the mechanisms by which MADS-domain proteins activate or repress the expression of their target genes and the nature of their cofactors are still largely unknown. Here, we show using affinity purification and mass spectrometry that five major floral homeotic MADS-domain proteins (AP1, AP3, PI, AG, and SEP3) interact in floral tissues as proposed in the “floral quartet” model. In vitro studies confirmed a flexible composition of MADS-domain protein complexes depending on relative protein concentrations and DNA sequence. In situ bimolecular fluorescent complementation assays demonstrate that MADS-domain proteins interact during meristematic stages of flower development. By applying a targeted proteomics approach we were able to establish a MADS-domain protein interactome that strongly supports a mechanistic link between MADS-domain proteins and chromatin remodeling factors. Furthermore, members of other transcription factor families were identified as interaction partners of floral MADS-domain proteins suggesting various specific combinatorial modes of action.

http://www.pnas.org/content/109/5/1560.short?rss=1

In the dorsal spinal cord, distinct interneuron classes relay specific somatosensory information, such as touch, heat, and pain, from the periphery to higher brain centers via ipsilateral and contralateral axonal pathways. The transcriptional mechanisms by which dorsal interneurons choose between ipsilateral and contralateral projection fates are unknown. Here, we show that a single transcription factor (TF), BARHL2, regulates this choice in proprioceptive dI1 interneurons by selectively suppressing cardinal dI1contra features in dI1ipsi neurons, despite expression by both subtypes. Strikingly, dI1ipsi neurons in Barhl2-null mice exhibit a dI1contra cell settling pattern in the medial deep dorsal horn, and, most importantly, they project axons contralaterally. These aberrations are preceded by ectopic dI1ipsi expression of the defining dI1contra TF, LHX2, and down-regulation of the dI1ipsi-enriched TF, BARHL1. Taken together, these results elucidate BARHL2 as a critical postmitotic regulator of dI1 subtype diversification, as well as its intermediate position in the dI1 genetic hierarchy.

http://www.pnas.org/content/109/5/1566.short?rss=1

Epidermal growth factor receptor (EGFR) controls a wide range of developmental events, from body axes specification in insects to cardiac development in humans. During Drosophila oogenesis, a gradient of EGFR activation patterns the follicular epithelium. Multiple transcriptional targets of EGFR in this tissue have been identified, but their regulatory elements are essentially unknown. We report the regulatory elements of broad (br) and pipe (pip), two important targets of EGFR signaling in Drosophila oogenesis. br is expressed in a complex pattern that prefigures the formation of respiratory eggshell appendages. We found that this pattern is generated by dynamic activities of two regulatory elements, which display different responses to Pointed, Capicua, and Mirror, transcription factors involved in the EGFR-mediated gene expression. One of these elements is active in a pattern similar to pip, a gene repressed by EGFR and essential for establishing the dorsoventral polarity of the embryo. We demonstrate that this similarity of expression depends on a common sequence motif that binds Mirror in vitro and is essential for transcriptional repression in vivo.

http://www.pnas.org/content/109/5/1572.short?rss=1

Vertebrate Dlx genes have been implicated in the differentiation of multiple neuronal subtypes, including cortical GABAergic interneurons, and mutations in Dlx genes have been linked to clinical conditions such as epilepsy and autism. Here we show that the single Drosophila Dlx homolog, distal-less, is required both to specify chemosensory neurons and to regulate the morphologies of their axons and dendrites. We establish that distal-less is necessary for development of the mushroom body, a brain region that processes olfactory information. These are important examples of distal-less function in an invertebrate nervous system and demonstrate that the Drosophila larval olfactory system is a powerful model in which to understand distal-less functions during neurogenesis.

http://www.pnas.org/content/109/5/1578.short?rss=1

The medial Permian (∼270–260 Ma: Guadalupian) was a time of important tetrapod faunal changes, in particular reflecting a turnover from pelycosaurian- to therapsid-grade synapsids. Until now, most knowledge on tetrapod distribution during the medial Permian has come from fossils found in the South African Karoo and the Russian Platform, whereas other areas of Pangaea are still poorly known. We present evidence for the presence of a terrestrial carnivorous vertebrate from the Middle Permian of South America based on a complete skull. Pampaphoneus biccai gen. et sp. nov. was a dinocephalian “mammal-like reptile” member of the Anteosauridae, an early therapsid predator clade known only from the Middle Permian of Russia, Kazakhstan, China, and South Africa. The genus is characterized, among other features, by postorbital bosses, short, bulbous postcanines, and strongly recurved canines. Phylogenetic analysis indicates that the Brazilian dinocephalian occupies a middle position within the Anteosauridae, reinforcing the model of a global distribution for therapsids as early as the Guadalupian. The close phylogenetic relationship of the Brazilian species to dinocephalians from South Africa and the Russian Platform suggests a closer faunistic relationship between South America and eastern Europe than previously thought, lending support to a Pangaea B-type continental reconstruction.

http://www.pnas.org/content/109/5/1584.short?rss=1

The early history of crustaceans is obscured by strong biases in fossil preservation, but a previously overlooked taphonomic mode yields important complementary insights. Here we describe diverse crustacean appendages of Middle and Late Cambrian age from shallow-marine mudstones of the Deadwood Formation in western Canada. The fossils occur as flattened and fragmentary carbonaceous cuticles but provide a suite of phylogenetic and ecological data by virtue of their detailed preservation. In addition to an unprecedented range of complex, largely articulated filtering limbs, we identify at least four distinct types of mandible. Together, these fossils provide the earliest evidence for crown-group branchiopods and total-group copepods and ostracods, extending the respective ranges of these clades back from the Devonian, Pennsylvanian, and Ordovician. Detailed similarities with living forms demonstrate the early origins and subsequent conservation of various complex food-handling adaptations, including a directional mandibular asymmetry that has persisted through half a billion years of evolution. At the same time, the Deadwood fossils indicate profound secular changes in crustacean ecology in terms of body size and environmental distribution. The earliest radiation of crustaceans is largely cryptic in the fossil record, but “small carbonaceous fossils” reveal organisms of surprisingly modern aspect operating in an unfamiliar biosphere.

http://www.pnas.org/content/109/5/1589.short?rss=1

The original double auction studies of supply and demand markets established their strong efficiency and equilibrium convergence behavior using economically unsophisticated and untrained subjects. The results were unexpected because all individual costs and values were private and dependent entirely on the market trading process to aggregate the dispersed information into socially desirable outcomes. The exchange environment, however, corresponded to that of perishable, and not re-traded goods in which participants were specialized as buyers or sellers. We report experiments in repeated single-period markets where tradability, and buyer-seller role specialization, is varied by imposing or relaxing a restriction on re-trade within each period. In re-trade markets scope is given to speculative motives unavailable where goods perish on purchase. We observe greatly increased trade volume and decreased efficiency but subject experience increases efficiency. Observed speculation slows convergence by impeding the process whereby individuals learn from the market whether their private circumstances lead them to specialize as buyers or sellers.

http://www.pnas.org/content/109/5/1425.short?rss=1

The release of cytokines by T cells defines a significant part of their functional activity in vivo, and their ability to produce multiple cytokines has been associated with beneficial immune responses. To date, time-integrated end-point measurements have obscured whether these polyfunctional states arise from the simultaneous or successive release of cytokines. Here, we used serial, time-dependent, single-cell analysis of primary human T cells to resolve the temporal dynamics of cytokine secretion from individual cells after activation ex vivo. We show that multifunctional, Th1-skewed cytokine responses (IFN-γ, IL-2, TNFα) are initiated asynchronously, but the ensuing dynamic trajectories of these responses evolve programmatically in a sequential manner. That is, cells predominantly release one of these cytokines at a time rather than maintain active secretion of multiple cytokines simultaneously. Furthermore, these dynamic trajectories are strongly associated with the various states of cell differentiation suggesting that transient programmatic activities of many individual T cells contribute to sustained, population-level responses. The trajectories of responses by single cells may also provide unique, time-dependent signatures for immune monitoring that are less compromised by the timing and duration of integrated measures.

http://www.pnas.org/content/109/5/1607.short?rss=1

Multicellularity was one of the most significant innovations in the history of life, but its initial evolution remains poorly understood. Using experimental evolution, we show that key steps in this transition could have occurred quickly. We subjected the unicellular yeast Saccharomyces cerevisiae to an environment in which we expected multicellularity to be adaptive. We observed the rapid evolution of clustering genotypes that display a novel multicellular life history characterized by reproduction via multicellular propagules, a juvenile phase, and determinate growth. The multicellular clusters are uniclonal, minimizing within-cluster genetic conflicts of interest. Simple among-cell division of labor rapidly evolved. Early multicellular strains were composed of physiologically similar cells, but these subsequently evolved higher rates of programmed cell death (apoptosis), an adaptation that increases propagule production. These results show that key aspects of multicellular complexity, a subject of central importance to biology, can readily evolve from unicellular eukaryotes.

http://www.pnas.org/content/109/5/1595.short?rss=1

Scaling of cardiac electrophysiology with body mass requires large changes in the ventricular action potential duration and heart rate in mammals. These changes in cellular electrophysiological function are produced by systematic and coordinated changes in the expression of multiple ion channel and transporter genes. Expression of one important potassium current, the transient outward current (Ito), changes significantly during mammalian evolution. Changes in Ito expression are determined, in part, by variation in the expression of an obligatory auxiliary subunit encoded by the KChIP2 gene. The KChIP2 gene is expressed in both cardiac myocytes and neurons and transcription in both cell types is initiated from the same CpG island promoter. Species-dependent variation of KChIP2 expression in heart is mediated by the evolution of the cis-regulatory function of this gene. Surprisingly, the major locus of evolutionary change for KChIP2 gene expression in heart lies within the CpG island core promoter. The results demonstrate that CpG island promoters are not simply permissive for gene expression but can also contribute to tissue-selective expression and, as such, can function as an important locus for the evolution of cis-regulatory function. More generally, evolution of the cis-regulatory function of voltage-gated ion channel genes appears to be an effective and efficient way to modify channel expression levels to optimize electrophysiological function.

http://www.pnas.org/content/109/5/1601.short?rss=1

Cluster of differentiation 81 (CD81) is a widely expressed tetraspanin molecule that physically associates with CD4 and CD8 on the surface of human T cells. Coengagement of CD81 and CD3 results in the activation and proliferation of T cells. CD81 also costimulated mouse T cells that lack CD28, suggesting either a redundant or a different mechanism of action. Here we show that CD81 and CD28 have a preference for different subsets of T cells: Primary human naïve T cells are better costimulated by CD81, whereas the memory T-cell subsets and Tregs are better costimulated by CD28. The more efficient activation of naïve T cells by CD81 was due to prolonged signal transduction compared with that by CD28. We found that IL-6 played a role in the activation of the naïve T-cell subset by CD81. Combined costimulation through both CD28 and CD81 resulted in an additive effect on T-cell activation. Thus, these two costimulatory molecules complement each other both in the strength of signal transduction and in T-cell subset inclusions. Costimulation via CD81 might be useful for expansion of T cells for adoptive immunotherapy to allow the inclusion of naïve T cells with their broad repertoire.

http://www.pnas.org/content/109/5/1613.short?rss=1

A deficit in early clearance of Pseudomonas aeruginosa (P. aeruginosa) is crucial in nosocomial pneumonia and in chronic lung infections. Few studies have addressed the role of Toll-like receptors (TLRs), which are early pathogen associated molecular pattern receptors, in pathogen uptake and clearance by alveolar macrophages (AMs). Here, we report that TLR5 engagement is crucial for bacterial clearance by AMs in vitro and in vivo because unflagellated P. aeruginosa or different mutants defective in TLR5 activation were resistant to AM phagocytosis and killing. In addition, the clearance of PAK (a wild-type P. aeruginosa strain) by primary AMs was causally associated with increased IL-1β release, which was dramatically reduced with PAK mutants or in WT PAK-infected primary TLR5−/− AMs, demonstrating the dependence of IL-1β production on TLR5. We showed that this IL-1β production was important in endosomal pH acidification and in inducing the killing of bacteria by AMs through asparagine endopeptidase (AEP), a key endosomal cysteine protease. In agreement, AMs from IL-1R1−/− and AEP−/− mice were unable to kill P. aeruginosa. Altogether, these findings demonstrate that TLR5 engagement plays a major role in P. aeruginosa internalization and in triggering IL-1β formation.

http://www.pnas.org/content/109/5/1619.short?rss=1

Foxp3+CD4+CD25high regulatory T cell (Treg) suppression of inflammation depends on T-cell receptor-mediated Nuclear Factor of Activated T cells c1 (NFATc1) activation with reduced Akt activity. We investigated the role of the scaffold protein Disc large homolog 1 (Dlgh1) in linking the T-cell receptor to this unique signaling outcome. The Treg immunological synapse (IS) recruited fourfold more Dlgh1 than conventional CD4+ T-cell IS. Tregs isolated from patients with active rheumatoid arthritis, or treated with tumor necrosis factor-α, displayed reduced function and diminished Dlgh1 recruitment to the IS. Furthermore, Dlgh1 silencing abrogated Treg function, impaired NFATc1 activation, reduced phosphatase and tensin homolog levels, and increased Akt activation. Dlgh1 operates independently of the negative feedback pathway mediated by the related adapter protein Carma1 and thus presents an array of unique targets to selectively manipulate Treg function.

http://www.pnas.org/content/109/5/1625.short?rss=1

In healthy individuals, T cells react against incoming pathogens, but remain tolerant to self-antigens, thereby preventing autoimmune reactions. CD4 regulatory T cells are major contributors in induction and maintenance of peripheral tolerance, but a regulatory role has been also reported for several subsets of CD8 T cells. To determine the molecular basis of peripheral CD8 T-cell tolerance, we exploited a double transgenic mouse model in which CD8 T cells are neonatally tolerized following interaction with a parenchymal self-antigen. These tolerant CD8 T cells have regulatory capacity and can suppress T cells in an antigen-specific manner during adulthood. Dickkopf-3 (DKK3) was found to be expressed in the tolerant CD8 T cells and to be essential for the observed CD8 T-cell tolerance. In vitro, genetic deletion of DKK3 or blocking with antibodies restored CD8 T-cell proliferation and IL-2 production in response to the tolerizing self-antigen. Moreover, exogenous DKK3 reduced CD8 T-cell reactivity. In vivo, abrogation of DKK3 function reversed tolerance, leading to eradication of tumors expressing the target antigen and to rejection of autologous skin grafts. Thus, our findings define DKK3 as a immune modulator with a crucial role for CD8 T-cell tolerance.

http://www.pnas.org/content/109/5/1631.short?rss=1

Processes that promote cancer progression such as angiogenesis require a functional interplay between malignant and nonmalignant cells in the tumor microenvironment. The metalloprotease aminopeptidase N (APN; CD13) is often overexpressed in tumor cells and has been implicated in angiogenesis and cancer progression. Our previous studies of APN-null mice revealed impaired neoangiogenesis in model systems without cancer cells and suggested the hypothesis that APN expressed by nonmalignant cells might promote tumor growth. We tested this hypothesis by comparing the effects of APN deficiency in allografted malignant (tumor) and nonmalignant (host) cells on tumor growth and metastasis in APN-null mice. In two independent tumor graft models, APN activity in both the tumors and the host cells cooperate to promote tumor vascularization and growth. Loss of APN expression by the host and/or the malignant cells also impaired lung metastasis in experimental mouse models. Thus, cooperation in APN expression by both cancer cells and nonmalignant stromal cells within the tumor microenvironment promotes angiogenesis, tumor growth, and metastasis.

http://www.pnas.org/content/109/5/1637.short?rss=1

Dominant mutations or DNA amplification of tyrosine kinases are rare among the oncogenic alterations implicated in prostate cancer. We demonstrate that castration-resistant prostate cancer (CRPC) in men exhibits increased tyrosine phosphorylation, raising the question of whether enhanced tyrosine kinase activity is observed in prostate cancer in the absence of specific tyrosine kinase mutation or DNA amplification. We generated a mouse model of prostate cancer progression using commonly perturbed non-tyrosine kinase oncogenes and pathways and detected a significant up-regulation of tyrosine phosphorylation at the carcinoma stage. Phosphotyrosine peptide enrichment and quantitative mass spectrometry identified oncogene-specific tyrosine kinase signatures, including activation of EGFR, ephrin type-A receptor 2 (EPHA2), and JAK2. Kinase:substrate relationship analysis of the phosphopeptides also revealed ABL1 and SRC tyrosine kinase activation. The observation of elevated tyrosine kinase signaling in advanced prostate cancer and identification of specific tyrosine kinase pathways from genetically defined tumor models point to unique therapeutic approaches using tyrosine kinase inhibitors for advanced prostate cancer.

http://www.pnas.org/content/109/5/1643.short?rss=1

Maintenance of skeletal muscle structure and function requires efficient and precise metabolic control. Autophagy plays a key role in metabolic homeostasis of diverse tissues by recycling cellular constituents, particularly under conditions of caloric restriction, thereby normalizing cellular metabolism. Here we show that histone deacetylases (HDACs) 1 and 2 control skeletal muscle homeostasis and autophagy flux in mice. Skeletal muscle-specific deletion of both HDAC1 and HDAC2 results in perinatal lethality of a subset of mice, accompanied by mitochondrial abnormalities and sarcomere degeneration. Mutant mice that survive the first day of life develop a progressive myopathy characterized by muscle degeneration and regeneration, and abnormal metabolism resulting from a blockade to autophagy. HDAC1 and HDAC2 regulate skeletal muscle autophagy by mediating the induction of autophagic gene expression and the formation of autophagosomes, such that myofibers of mice lacking these HDACs accumulate toxic autophagic intermediates. Strikingly, feeding HDAC1/2 mutant mice a high-fat diet from the weaning age releases the block in autophagy and prevents myopathy in adult mice. These findings reveal an unprecedented and essential role for HDAC1 and HDAC2 in maintenance of skeletal muscle structure and function and show that, at least in some pathological conditions, myopathy may be mitigated by dietary modifications.

http://www.pnas.org/content/109/5/1649.short?rss=1

The management of castration-resistant prostate cancer (CRPC) presents a clinical challenge because of limitations in efficacy of current therapies. Novel therapeutic strategies for the treatment of CRPC are needed. Antagonists of hypothalamic growth hormone-releasing hormone (GHRH) inhibit growth of various malignancies, including androgen-dependent and independent prostate cancer, by suppressing diverse tumoral growth factors, especially GHRH itself, which acts as a potent autocrine/paracrine growth factor in many tumors. We evaluated the effects of the GHRH antagonist, JMR-132, on PC-3 human androgen-independent prostate cancer cells in vitro and in vivo. JMR-132 suppressed the proliferation of PC-3 cells in vitro in a dose-dependent manner and significantly inhibited growth of PC-3 tumors by 61% (P < 0.05). The expression of GHRH, GHRH receptors, and their main splice variant, SV1, in PC-3 cells and tumor xenografts was demonstrated by RT-PCR and Western blot. The content of GHRH protein in PC-3 xenografts was lowered markedly, by 66.3% (P < 0.01), after treatment with JMR-132. GHRH induced a significant increase in levels of ERK, but JMR-132 abolished this outcome. Our findings indicate that inhibition of PC-3 prostate cancer by JMR-132 involves inactivation of Akt and ERK. The inhibitory effect produced by GHRH antagonist can result in part from inactivation of the PI3K/Akt/mammalian target of rapamycin and Raf/MEK/ERK pathways and from the reduction in GHRH produced by cancer cells. Our findings support the role of GHRH as an autocrine growth factor in prostate cancer and suggest that antagonists of GHRH should be considered for further development as therapy for CRPC.

http://www.pnas.org/content/109/5/1655.short?rss=1

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset neurological disease resulting from mutations in the SACS gene encoding sacsin, a 4,579-aa protein of unknown function. Originally identified as a founder disease in Québec, ARSACS is now recognized worldwide. Prominent features include pyramidal spasticity and cerebellar ataxia, but the underlying pathology and pathophysiological mechanisms are unknown. We have generated an animal model for ARSACS, sacsin knockout mice, that display age-dependent neurodegeneration of cerebellar Purkinje cells. To explore the pathophysiological basis for this observation, we examined the cell biological properties of sacsin. We show that sacsin localizes to mitochondria in non-neuronal cells and primary neurons and that it interacts with dynamin-related protein 1, which participates in mitochondrial fission. Fibroblasts from ARSACS patients show a hyperfused mitochondrial network, consistent with defects in mitochondrial fission. Sacsin knockdown leads to an overly interconnected and functionally impaired mitochondrial network, and mitochondria accumulate in the soma and proximal dendrites of sacsin knockdown neurons. Disruption of mitochondrial transport into dendrites has been shown to lead to abnormal dendritic morphology, and we observe striking alterations in the organization of dendritic fields in the cerebellum of knockout mice that precedes Purkinje cell death. Our data identifies mitochondrial dysfunction/mislocalization as the likely cellular basis for ARSACS and indicates a role for sacsin in regulation of mitochondrial dynamics.

http://www.pnas.org/content/109/5/1661.short?rss=1

Increased flux through the glycerolipid synthesis pathway impairs the ability of insulin to inhibit hepatic gluconeogenesis, but the exact mechanism remains unknown. To determine the mechanism by which glycerolipids impair insulin signaling, we overexpressed glycerol-3-phosphate acyltransferase-1 (GPAT1) in primary mouse hepatocytes. GPAT1 overexpression impaired insulin-stimulated phosphorylation of Akt-S473 and -T308, diminished insulin-suppression of glucose production, significantly inhibited mTOR complex 2 (mTORC2) activity and decreased the association of mTOR and rictor. Conversely, in hepatocytes from Gpat1−/− mice, mTOR-rictor association and mTORC2 activity were enhanced. However, this increase in mTORC2 activity in Gpat1−/− hepatocytes was ablated when rictor was knocked down. To determine which lipid intermediate was responsible for inactivating mTORC2, we overexpressed GPAT1, AGPAT, or lipin to increase the cellular content of lysophosphatidic acid (LPA), phosphatidic acid (PA), or diacylglycerol (DAG), respectively. The inhibition of mTOR/rictor binding and mTORC2 activity coincided with the levels of PA and DAG species that contained 16:0, the preferred substrate of GPAT1. Furthermore, di-16:0-PA strongly inhibited mTORC2 activity and disassociated mTOR/rictor in vitro. Taken together, these data reveal a signaling pathway by which phosphatidic acid synthesized via the glycerol-3-phosphate pathway inhibits mTORC2 activity by decreasing the association of rictor and mTOR, thereby down-regulating insulin action. These data demonstrate a critical link between nutrient excess, TAG synthesis, and hepatic insulin resistance.

http://www.pnas.org/content/109/5/1667.short?rss=1

Interleukin-33 (IL-33) (NF-HEV) is a chromatin-associated nuclear cytokine from the IL-1 family, which has been linked to important diseases, including asthma, rheumatoid arthritis, ulcerative colitis, and cardiovascular diseases. IL-33 signals through the ST2 receptor and drives cytokine production in type 2 innate lymphoid cells (ILCs) (natural helper cells, nuocytes), T-helper (Th)2 lymphocytes, mast cells, basophils, eosinophils, invariant natural killer T (iNKT), and natural killer (NK) cells. We and others recently reported that, unlike IL-1β and IL-18, full-length IL-33 is biologically active independently of caspase-1 cleavage and that processing by caspases results in IL-33 inactivation. We suggested that IL-33, which is released upon cellular damage, may function as an endogenous danger signal or alarmin, similar to IL-1α or high-mobility group box 1 protein (HMGB1). Here, we investigated the possibility that IL-33 activity may be regulated by proteases released during inflammation. Using a combination of in vitro and in vivo approaches, we demonstrate that neutrophil serine proteases cathepsin G and elastase can cleave full-length human IL-331–270 and generate mature forms IL-3395–270, IL-3399–270, and IL-33109–270. These forms are produced by activated human neutrophils ex vivo, are biologically active in vivo, and have a ∼10-fold higher activity than full-length IL-33 in cellular assays. Murine IL-33 is also cleaved by neutrophil cathepsin G and elastase, and both full-length and cleaved endogenous IL-33 could be detected in the bronchoalveolar lavage fluid in an in vivo model of acute lung injury associated with neutrophil infiltration. We propose that the inflammatory microenvironment may exacerbate disease-associated functions of IL-33 through the generation of highly active mature forms.

http://www.pnas.org/content/109/5/1673.short?rss=1

Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment modalities cannot be performed or are ineffective. In the past, the stimulation of blood vessel growth was pursued using direct delivery of growth factors, angiogenic gene therapy, or cellular therapy. Although therapeutic angiogenesis holds great promise for treating patients with ischemia, current methods have not found success in clinical trials. Fibroblast growth factor-2 (FGF-2) was one of the first growth factors to be tested for use in therapeutic angiogenesis. Here, we present a method for improving the biological activity of FGF-2 by codelivering the growth factor with a liposomally embedded coreceptor, syndecan-4. This technique was shown to increase FGF-2 cellular signaling, uptake, and nuclear localization in comparison with FGF-2 alone. Delivery of syndecan-4 proteoliposomes also increased endothelial proliferation, migration, and angiogenic tube formation in response to FGF-2. Using an animal model of limb ischemia, syndecan-4 proteoliposomes markedly improved the neovascularization following femoral artery ligation and recovery of perfusion of the ischemic limb. Taken together, these results support liposomal delivery of syndecan-4 as an effective means to improving the potential of using growth factors to achieve therapeutic neovascularization of ischemic tissue.

http://www.pnas.org/content/109/5/1679.short?rss=1

The p53 transcription factor modulates gene expression programs that induce cell cycle arrest, senescence, or apoptosis, thereby preventing tumorigenesis. However, the mechanisms by which these fates are selected are unclear. Our objective is to understand p53 target gene selection and, thus, enable its optimal manipulation for cancer therapy. We have generated targeted transgenic reporter mice in which EGFP expression is driven by p53 transcriptional activity at a response element from either the p21 or Puma promoter, which induces cell cycle arrest/senescence and apoptosis, respectively. We demonstrate that we could monitor p53 activity in vitro and in vivo and detect variations in p53 activity depending on the response element, tissue type, and stimulus, thereby validating our reporter system and illustrating its utility for preclinical drug studies. Our results also show that the sequence of the p53 response element itself is sufficient to strongly influence p53 target gene selection. Finally, we use our reporter system to provide evidence for p53 transcriptional activity during early embryogenesis, showing that p53 is active as early as embryonic day 3.5 and that p53 activity becomes restricted to embryonic tissue by embryonic day 6.5. The data from this study demonstrate that these reporter mice could serve as powerful tools to answer questions related to basic biology of the p53 pathway, as well as cancer therapy and drug discovery.

http://www.pnas.org/content/109/5/1685.short?rss=1

Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1–11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses.

http://www.pnas.org/content/109/5/1691.short?rss=1

Elongation of many rod-shaped bacteria occurs by peptidoglycan synthesis at discrete foci along the sidewall of the cells. However, within the Rhizobiales, there are many budding bacteria, in which new cell growth is constrained to a specific region. The phylogeny of the Rhizobiales indicates that this mode of zonal growth may be ancestral. We demonstrate that the rod-shaped bacterium Agrobacterium tumefaciens grows unidirectionally from the new pole generated after cell division and has an atypical peptidoglycan composition. Polar growth occurs under all conditions tested, including when cells are attached to a plant root and under conditions that induce virulence. Finally, we show that polar growth also occurs in the closely related bacteria Sinorhizobium meliloti, Brucella abortus, and Ochrobactrum anthropi. We find that unipolar growth is an ancestral and conserved trait among the Rhizobiales, which includes important mutualists and pathogens of plants and animals.

http://www.pnas.org/content/109/5/1697.short?rss=1

Almost nothing is known about the mechanisms of dissimilatory metal reduction by Gram-positive bacteria, although they may be the dominant species in some environments. Thermincola potens strain JR was isolated from the anode of a microbial fuel cell inoculated with anaerobic digester sludge and operated at 55 °C. Preliminary characterization revealed that T. potens coupled acetate oxidation to the reduction of hydrous ferric oxides (HFO) or anthraquinone-2,6-disulfonate (AQDS), an analog of the redox active components of humic substances. The genome of T. potens was recently sequenced, and the abundance of multiheme c-type cytochromes (MHCs) is unusual for a Gram-positive bacterium. We present evidence from trypsin-shaving LC-MS/MS experiments and surface-enhanced Raman spectroscopy (SERS) that indicates the expression of a number of MHCs during T. potens growth on either HFO or AQDS, and that several MHCs are localized to the cell wall or cell surface. Furthermore, one of the MHCs can be extracted from cells with low pH or denaturants, suggesting a loose association with the cell wall or cell surface. Electron microscopy does not reveal an S-layer, and the precipitation of silver metal on the cell surface is inhibited by cyanide, supporting the involvement of surface-localized redox-active heme proteins in dissimilatory metal reduction. These results provide unique direct evidence for cell wall-associated cytochromes and support MHC involvement in conducting electrons across the cell envelope of a Gram-positive bacterium.

http://www.pnas.org/content/109/5/1702.short?rss=1

We describe a functional profiling strategy to identify and characterize subtypes of neurons present in a peripheral ganglion, which should be extendable to neurons in the CNS. In this study, dissociated dorsal-root ganglion neurons from mice were exposed to various pharmacological agents (challenge compounds), while at the same time the individual responses of >100 neurons were simultaneously monitored by calcium imaging. Each challenge compound elicited responses in only a subset of dorsal-root ganglion neurons. Two general types of challenge compounds were used: agonists of receptors (ionotropic and metabotropic) that alter cytoplasmic calcium concentration (receptor–agonist challenges) and compounds that affect voltage-gated ion channels (membrane–potential challenges). Notably, among the latter are K-channel antagonists, which elicited unexpectedly diverse types of calcium responses in different cells (i.e., phenotypes). We used various challenge compounds to identify several putative neuronal subtypes on the basis of their shared and/or divergent functional, phenotypic profiles. Our results indicate that multiple receptor–agonist and membrane–potential challenges may be applied to a neuronal population to identify, characterize, and discriminate among neuronal subtypes. This experimental approach can uncover constellations of plasma membrane macromolecules that are functionally coupled to confer a specific phenotypic profile on each neuronal subtype. This experimental platform has the potential to bridge a gap between systems and molecular neuroscience with a cellular-focused neuropharmacology, ultimately leading to the identification and functional characterization of all neuronal subtypes at a given locus in the nervous system.

http://www.pnas.org/content/109/5/1388.short?rss=1

Decision-making in the presence of other competitive intelligent agents is fundamental for social and economic behavior. Such decisions require agents to behave strategically, where in addition to learning about the rewards and punishments available in the environment, they also need to anticipate and respond to actions of others competing for the same rewards. However, whereas we know much about strategic learning at both theoretical and behavioral levels, we know relatively little about the underlying neural mechanisms. Here, we show using a multi-strategy competitive learning paradigm that strategic choices can be characterized by extending the reinforcement learning (RL) framework to incorporate agents’ beliefs about the actions of their opponents. Furthermore, using this characterization to generate putative internal values, we used model-based functional magnetic resonance imaging to investigate neural computations underlying strategic learning. We found that the distinct notions of prediction errors derived from our computational model are processed in a partially overlapping but distinct set of brain regions. Specifically, we found that the RL prediction error was correlated with activity in the ventral striatum. In contrast, activity in the ventral striatum, as well as the rostral anterior cingulate (rACC), was correlated with a previously uncharacterized belief-based prediction error. Furthermore, activity in rACC reflected individual differences in degree of engagement in belief learning. These results suggest a model of strategic behavior where learning arises from interaction of dissociable reinforcement and belief-based inputs.

http://www.pnas.org/content/109/5/1419.short?rss=1

An estrogen receptor (ER) β ligand (LY3201) with a preference for ERβ over ERα was administered in s.c. pellets releasing 0.04 mg/d. The brains of these mice were examined 3 d after treatment had begun. Although estradiol-17β is known to increase spine density and glutaminergic signaling, as measured by Golgi staining, a clear reduction in spines was evident on the dendritic branches in LY3201-treated mice but no morphological alteration and no difference in the number of dendritic spines on dendritic stems were observed. In the LY3201-treatment group, there was higher expression of glutamic acid decarboxylase (GAD) in layer V of cortex and in the CA1 of hippocampus, more GAD+ terminals surrounding the pyramidal neurons and less glutamate receptor (NMDAR) on the neurons in layer V. There were no alterations in expression of Iba1 or in Olig2 or CNPase. However, GFAP+ astrocytes were increased in the LY3201-treatment group. There were also more projections characteristic of activated astrocytes and increased expression of glutamine synthetase (GS). No expression of ERβ was detectable in the nuclei of astrocytes. Clearly, LY3201 caused a shift in the balance between excitatory and inhibitory neurotransmission in favor of inhibition. This shift was due in part to increased synthesis of GABA and increased removal of glutamate from the synaptic cleft by astrocytes. The data reveal that treatment with a selective ERβ agonist results in changes opposite to those reported in estradiol-17β–treated mice and suggests that ERα and ERβ play opposing roles in the brain.

http://www.pnas.org/content/109/5/1708.short?rss=1

Emerging evidence suggests that the pathogenesis of depressive disorders (DDs) is associated with neuronal abnormalities in brain microtubule function, including changes in α-tubulin isoforms. Currently available antidepressant drugs may act by rescuing these alterations, but only after long-term treatment explaining their delayed therapeutic efficacy. The microtubule associated protein type-2 (MAP-2) modulates neuronal microtubule dynamics. Our hypothesis is that MAP-2 represents an innovative target for the treatment of DDs. The synthetic pregnenolone-derivative MAP4343 (3β-methoxy-pregnenolone) binds MAP-2 in vitro and increases its ability to stimulate tubulin assembly. Here, we show that MAP4343 has antidepressant efficacy in rats and advantages compared with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. A single injection of MAP4343 changes the expression of α-tubulin isoforms indicative of increased microtubule dynamics in the hippocampus of naïve Sprague–Dawley rats, whereas fluoxetine had no effects. MAP4343 has positive efficacy in the rat forced swimming test (FST), the most used assay to screen potential antidepressant drugs by decreasing immobility behavior. In the rat isolation-rearing model of depression, administration of MAP4343 showed more rapid and more persistent efficacy compared with fluoxetine in recovering “depressive-like” behaviors. These effects were accompanied by modifications of α-tubulin isoforms in the hippocampus, amygdala, and prefrontal cortex. Our findings suggest the potential therapeutic use of MAP4343 for the treatment of DDs, based on a unique mechanism of action.

http://www.pnas.org/content/109/5/1713.short?rss=1

Adolescents often respond differently than adults to the same salient motivating contexts, such as peer interactions and pleasurable stimuli. Delineating the neural processing differences of adolescents is critical to understanding this phenomenon, as well as the bases of serious behavioral and psychiatric vulnerabilities, such as drug abuse, mood disorders, and schizophrenia. We believe that age-related changes in the ways salient stimuli are processed in key brain regions could underlie the unique predilections and vulnerabilities of adolescence. Because motivated behavior is the central issue, it is critical that age-related comparisons of brain activity be undertaken during motivational contexts. We compared single-unit activity and local field potentials in the nucleus accumbens (NAc) and dorsal striatum (DS) of adolescent and adult rats during a reward-motivated instrumental task. These regions are involved in motivated learning, reward processing, and action selection. We report adolescent neural processing differences in the DS, a region generally associated more with learning than reward processing in adults. Specifically, adolescents, but not adults, had a large proportion of neurons in the DS that activated in anticipation of reward. More similar response patterns were observed in NAc of the two age groups. DS single-unit activity differences were found despite similar local field potential oscillations. This study demonstrates that in adolescents, a region critically involved in learning and habit formation is highly responsive to reward. It thus suggests a mechanism for how rewards might shape adolescent behavior differently, and for their increased vulnerabilities to affective disorders.

http://www.pnas.org/content/109/5/1719.short?rss=1

Neuronal morphology is regulated by cytoskeletons. Kinesin superfamily protein 2A (KIF2A) depolymerizes microtubules (MTs) at growth cones and regulates axon pathfinding. The factors controlling KIF2A in neurite development remain totally elusive. Here, using immunoprecipitation with an antibody specific to KIF2A, we identified phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKα) as a candidate membrane protein that regulates the activity of KIF2A. Yeast two-hybrid and biochemical assays demonstrated direct binding between KIF2A and PIPKα. Partial colocalization of the clusters of punctate signals for these two molecules was detected by confocal microscopy and photoactivated localization microscopy. Additionally, the MT-depolymerizing activity of KIF2A was enhanced in the presence of PIPKα in vitro and in vivo. PIPKα suppressed the elongation of axon branches in a KIF2A-dependent manner, suggesting a unique PIPK-mediated mechanism controlling MT dynamics in neuronal development.

http://www.pnas.org/content/109/5/1725.short?rss=1

Intracranial recording is an important diagnostic method routinely used in a number of neurological monitoring scenarios. In recent years, advancements in such recordings have been extended to include unit activity of an ensemble of neurons. However, a detailed functional characterization of excitatory and inhibitory cells has not been attempted in human neocortex, particularly during the sleep state. Here, we report that such feature discrimination is possible from high-density recordings in the neocortex by using 2D multielectrode arrays. Successful separation of regular-spiking neurons (or bursting cells) from fast-spiking cells resulted in well-defined clusters that each showed unique intrinsic firing properties. The high density of the array, which allowed recording from a large number of cells (up to 90), helped us to identify apparent monosynaptic connections, confirming the excitatory and inhibitory nature of regular-spiking and fast-spiking cells, thus categorized as putative pyramidal cells and interneurons, respectively. Finally, we investigated the dynamics of correlations within each class. A marked exponential decay with distance was observed in the case of excitatory but not for inhibitory cells. Although the amplitude of that decline depended on the timescale at which the correlations were computed, the spatial constant did not. Furthermore, this spatial constant is compatible with the typical size of human columnar organization. These findings provide a detailed characterization of neuronal activity, functional connectivity at the microcircuit level, and the interplay of excitation and inhibition in the human neocortex.

http://www.pnas.org/content/109/5/1731.short?rss=1

N-methyl-d-aspartate receptors (NMDARs) mediate critical CNS functions, whereas excessive activity contributes to neuronal damage. At physiological glycine concentrations, NMDAR currents recorded from cultured rodent hippocampal neurons exhibited strong desensitization in the continued presence of NMDA, thus protecting neurons from calcium overload. Reducing copper availability by specific chelators (bathocuproine disulfonate, cuprizone) induced nondesensitizing NMDAR currents even at physiologically low glycine concentrations. This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrPC), a key copper-binding protein in the CNS. Acute ablation of PrPC by enzymatically cleaving its cell-surface GPI anchor yielded similar effects. Biochemical studies and electrophysiological measurements revealed that PrPC interacts with the NMDAR complex in a copper-dependent manner to allosterically reduce glycine affinity for the receptor. Synthetic human Aβ1–42 (10 nM–5 μM) produced an identical effect that could be mitigated by addition of excess copper ions or NMDAR blockers. Taken together, Aβ1–42, copper chelators, or PrPC inactivation all enhance the activity of glycine at the NMDAR, giving rise to pathologically large nondesensitizing steady-state NMDAR currents and neurotoxicity. We propose a physiological role for PrPC, one that limits excessive NMDAR activity that might otherwise promote neuronal damage. In addition, we provide a unifying molecular mechanism whereby toxic species of Aβ1–42 might mediate neuronal and synaptic injury, at least in part, by disrupting the normal copper-mediated, PrPC-dependent inhibition of excessive activity of this highly calcium-permeable glutamate receptor.

http://www.pnas.org/content/109/5/1737.short?rss=1

The influence of isotopically enriched magnesium on the creatine kinase catalyzed phosphorylation of adenosine diphosphate is examined in two independent series of experiments where adenosine triphosphate (ATP) concentrations were determined by a luciferase-linked luminescence end-point assay or a real-time spectrophotometric assay. No increase was observed between the rates of ATP production with natural Mg, 24Mg, and 25Mg, nor was any significant magnetic field effect observed in magnetic fields from 3 to 1,000 mT. Our results are in conflict with those reported by Buchachenko et al. [J Am Chem Soc 130:12868–12869 (2008)], and they challenge these authors’ general claims that a large (two- to threefold) magnetic isotope effect is “universally observable” for ATP-producing enzymes [Her Russ Acad Sci 80:22–28 (2010)] and that “enzymatic phosphorylation is an ion-radical, electron-spin-selective process” [Proc Natl Acad Sci USA 101:10793–10796 (2005)].

http://www.pnas.org/content/109/5/1437.short?rss=1

Energy transfer (ET) between B850 and B875 molecules in light harvesting complexes LH2 and LH1/RC (reaction center) complexes has been investigated in membranes of Rhodopseudomonas palustris grown under high- and low-light conditions. In these bacteria, illumination intensity during growth strongly affects the type of LH2 complexes synthesized, their optical spectra, and their amount of energetic disorder. We used a specially built femtosecond spectrometer, combining tunable narrowband pump with broadband white-light probe pulses, together with an analytical method based on derivative spectroscopy for disentangling the congested transient absorption spectra of LH1 and LH2 complexes. This procedure allows real-time tracking of the forward (LH2 → LH1) and backward (LH2←LH1) ET processes and unambiguous determination of the corresponding rate constants. In low-light grown samples, we measured lower ET rates in both directions with respect to high-light ones, which is explained by reduced spectral overlap between B850 and B875 due to partial redistribution of oscillator strength into a higher energetic exciton transition. We find that the low-light adaptation in R. palustris leads to a reduced elementary backward ET rate, in accordance with the low probability of two simultaneous excitations reaching the same LH1/RC complex under weak illumination. Our study suggests that backward ET is not just an inevitable consequence of vectorial ET with small energetic offsets, but is in fact actively managed by photosynthetic bacteria.

http://www.pnas.org/content/109/5/1473.short?rss=1

The attrition of telomeres, the ends of eukaryote chromosomes, is thought to play an important role in cell deterioration with advancing age. The observed variation in telomere length among individuals of the same age is therefore thought to be related to variation in potential longevity. Studies of this relationship are hampered by the time scale over which individuals need to be followed, particularly in long-lived species where lifespan variation is greatest. So far, data are based either on simple comparisons of telomere length among different age classes or on individuals whose telomere length is measured at most twice and whose subsequent survival is monitored for only a short proportion of the typical lifespan. Both approaches are subject to bias. Key studies, in which telomere length is tracked from early in life, and actual lifespan recorded, have been lacking. We measured telomere length in zebra finches (n = 99) from the nestling stage and at various points thereafter, and recorded their natural lifespan (which varied from less than 1 to almost 9 y). We found telomere length at 25 d to be a very strong predictor of realized lifespan (P < 0.001); those individuals living longest had relatively long telomeres at all points at which they were measured. Reproduction increased adult telomere loss, but this effect appeared transient and did not influence survival. Our results provide the strongest evidence available of the relationship between telomere length and lifespan and emphasize the importance of understanding factors that determine early life telomere length.

http://www.pnas.org/content/109/5/1743.short?rss=1

Ca2+ influx via L-type Cav1.2 channels is essential for multiple physiological processes, including gene expression, excitability, and contraction. Amplification of the Ca2+ signals produced by the opening of these channels is a hallmark of many intracellular signaling cascades, including excitation-contraction coupling in heart. Using optogenetic approaches, we discovered that Cav1.2 channels form clusters of varied sizes in ventricular myocytes. Physical interaction between these channels via their C-tails renders them capable of coordinating their gating, thereby amplifying Ca2+ influx and excitation-contraction coupling. Light-induced fusion of WT Cav1.2 channels with Cav1.2 channels carrying a gain-of-function mutation that causes arrhythmias and autism in humans with Timothy syndrome (Cav1.2-TS) increased Ca2+ currents, diastolic and systolic Ca2+ levels, contractility and the frequency of arrhythmogenic Ca2+ fluctuations in ventricular myocytes. Our data indicate that these changes in Ca2+ signaling resulted from Cav1.2-TS increasing the activity of adjoining WT Cav1.2 channels. Collectively, these data support the concept that oligomerization of Cav1.2 channels via their C termini can result in the amplification of Ca2+ influx into excitable cells.

http://www.pnas.org/content/109/5/1749.short?rss=1

CLE peptides, named for the CLV3/ESR-related peptide family, participate in intercellular-signaling pathways. Here we investigated members of the CLE-like (CLEL) gene family that encode peptide precursors recently designated as root growth factors [Matsuzaki Y et al. (2010) Science 329:1065–1067]. CLEL precursors share a similar domain structure with CLE precursors (i.e., they contain a putative N-terminal signal peptide and a C-terminal conserved 13-amino-acid CLEL motif with a variable middle portion). Our evidence shows that, unlike root growth factor, CLEL peptides are (i) unmodified and (ii) function in the regulation of the direction of root growth and lateral root development. Overexpression of several CLEL genes in Arabidopsis resulted in either long roots or long and wavy roots that also showed altered lateral root patterning. Exogenous application of unmodified synthetic 13-amino-acid peptides derived from two CLEL motifs resulted in similar phenotypic changes in roots of wild-type plants. In CLEL peptide-induced long roots, the root apical meristem (RAM) was enlarged and consisted of an increased number of cells, compared with wild-type root apical meristems. The wavy-root phenotype appeared to be independent of other responses of the roots to the environment (e.g., gravitropism, phototropism, and thigmotropism). Results also showed that the inhibition of lateral initiation by CLEL overexpression was not overcome by the application of auxin. These findings establish CLEL as a peptide family with previously unrecognized regulatory functions controlling the pattern of root growth and lateral root development in plants.

http://www.pnas.org/content/109/5/1760.short?rss=1

MtPAR (Medicago truncatula proanthocyanidin regulator) is an MYB family transcription factor that functions as a key regulator of proanthocyanidin (PA) biosynthesis in the model legume Medicago truncatula. MtPAR expression is confined to the seed coat, the site of PA accumulation. Loss-of-function par mutants contained substantially less PA in the seed coat than the wild type, whereas levels of anthocyanin and other specialized metabolites were normal in the mutants. In contrast, massive accumulation of PAs occurred when MtPAR was expressed ectopically in transformed hairy roots of Medicago. Transcriptome analysis of par mutants and MtPAR-expressing hairy roots, coupled with yeast one-hybrid analysis, revealed that MtPAR positively regulates genes encoding enzymes of the flavonoid–PA pathway via a probable activation of WD40-1. Expression of MtPAR in the forage legume alfalfa (Medicago sativa) resulted in detectable levels of PA in shoots, highlighting the potential of this gene for biotechnological strategies to increase PAs in forage legumes for reduction of pasture bloat in ruminant animals.

http://www.pnas.org/content/109/5/1766.short?rss=1

Lignins are complex phenylpropanoid polymers mostly associated with plant secondary cell walls. Lignins arise primarily via oxidative polymerization of the three monolignols, p-coumaryl, coniferyl, and sinapyl alcohols. Of the two hydroxycinnamyl alcohols that represent incompletely methylated biosynthetic products (and are not usually considered to be monolignols), 5-hydroxyconiferyl alcohol is now well established as incorporating into angiosperm lignins, but incorporation of caffeyl alcohol has not been shown. We report here the presence of a homopolymer of caffeyl alcohol in the seed coats of both monocot and dicot plants. This polymer (C-lignin) is deposited to high concentrations in the seed coat during the early stages of seed development in the vanilla orchid (Vanilla planifolia), and in several members of the Cactaceae. The lignin in other parts of the Vanilla plant is conventionally biosynthesized from coniferyl and sinapyl alcohols. Some species of cacti contain only C-lignin in their seeds, whereas others contain only classical guaiacyl/syringyl lignin (derived from coniferyl and sinapyl alcohols). NMR spectroscopic analysis revealed that the Vanilla seed-coat polymer was massively comprised of benzodioxane units and was structurally similar to the polymer synthesized in vitro by peroxidase-catalyzed polymerization of caffeyl alcohol. CD spectroscopy did not detect any optical activity in the seed polymer. These data support the contention that the C-lignin polymer is produced in vivo via combinatorial oxidative radical coupling that is under simple chemical control, a mechanism analogous to that theorized for classical lignin biosynthesis.

http://www.pnas.org/content/109/5/1772.short?rss=1

Plant and metazoan microRNAs (miRNAs) guide ARGONAUTE (AGO) protein complexes to regulate expression of complementary RNAs via base pairing. In the plant Arabidopsis thaliana, the main miRNA effector is AGO1, but few other factors required for miRNA activity are known. Here, we isolate the genes defined by the previously described miRNA action deficient (mad) mutants, mad3 and mad4. Both genes encode enzymes involved in isoprenoid biosynthesis. MAD3 encodes 3-hydroxy-3-methylglutaryl CoA reductase (HMG1), which functions in the initial C5 building block biogenesis that precedes isoprenoid metabolism. HMG1 is a key regulatory enzyme that controls the amounts of isoprenoid end products. MAD4 encodes sterol C-8 isomerase (HYDRA1) that acts downstream in dedicated sterol biosynthesis. Using yeast complementation assays and in planta application of lovastatin, a competitive inhibitor of HMG1, we show that defects in HMG1 catalytic activity are sufficient to inhibit miRNA activity. Many isoprenoid derivatives are indispensable structural and signaling components, and especially sterols are essential membrane constituents. Accordingly, we provide evidence that AGO1 is a peripheral membrane protein. Moreover, specific hypomorphic mutant alleles of AGO1 display compromised membrane association and AGO1-membrane interaction is reduced upon knockdown of HMG1/MAD3. These results suggest a possible basis for the requirement of isoprenoid biosynthesis for the activity of plant miRNAs, and unravel mechanistic features shared with their metazoan counterparts.

http://www.pnas.org/content/109/5/1778.short?rss=1

In all eukaryotic cells, a membrane-trafficking system connects the post-Golgi organelles, such as the trans-Golgi network (TGN), endosomes, vacuoles, and the plasma membrane. This complex network plays critical roles in several higher-order functions in multicellular organisms. The TGN, one of the important organelles for protein transport in the post-Golgi network, functions as a sorting station, where cargo proteins are directed to the appropriate post-Golgi compartments. Unlike its roles in animal and yeast cells, the TGN has also been reported to function like early endosomal compartments in plant cells. However, the physiological roles of the TGN functions in plants are not understood. Here, we report a study of the SYP4 group (SYP41, SYP42, and SYP43), which represents the plant orthologs of the Tlg2/syntaxin16 Qa-SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) that localizes on the TGN in yeast and animal cells. The SYP4 group regulates the secretory and vacuolar transport pathways in the post-Golgi network and maintains the morphology of the Golgi apparatus and TGN. Consistent with a secretory role, SYP4 proteins are required for extracellular resistance responses to a fungal pathogen. We also reveal a plant cell-specific higher-order role of the SYP4 group in the protection of chloroplasts from salicylic acid-dependent biotic stress.

http://www.pnas.org/content/109/5/1784.short?rss=1

Plant genomes contain large numbers of cell surface leucine-rich repeat (LRR) and intracellular nucleotide binding (NB)-LRR immune receptors encoded by resistance (R) genes that recognize specific pathogen effectors and trigger resistance responses. The unregulated expression of NB-LRR genes can trigger autoimmunity in the absence of pathogen infection and inhibit plant growth. Despite the potential serious consequence on agricultural production, the mechanisms regulating R-gene expression are not well understood. We identified microRNA (miRNA) progenitor genes precursor transcripts, and two miRNAs [nta-miR6019 (22-nt) and nta-miR6020 (21-nt)] that guide cleavage of transcripts of the Toll and Interleukin-1 receptor-NB-LRR immune receptor N from tobacco that confers resistance to tobacco mosaic virus (TMV). We further showed that cleavage by nta-miR6019 triggers RNA-dependent RNA polymerase 6- and ribonuclease Dicer-like 4-dependent biogenesis of 21-nt secondary siRNAs “in phase” with the 22-nt miR6019 cleavage site. Furthermore, we found that processing of the 22-nt nta-miR6019 depended on an asymmetric bulge caused by mismatch in the nta-miR6019 precursor. Interestingly, coexpression of N with nta-miR6019 and nta-miR6020 resulted in attenuation of N-mediated resistance to TMV, indicating that these miRNAs have functional roles in NB-LRR regulation. Using a bioinformatics approach, we identified six additional 22-nt miRNA and two 21-nt miRNA families from three Solanaceae species—tobacco, tomato, and potato. We show that members of these miRNA families cleave transcripts of predicted functional R genes and trigger production of phased secondary 21-nt siRNAs. Our results demonstrate a conserved role for miRNAs and secondary siRNAs in NB-LRR/LRR immune receptor gene regulation and pathogen resistance in Solanaceae.

http://www.pnas.org/content/109/5/1790.short?rss=1

Successful visually guided behavior requires information about spatiotopic (i.e., world-centered) locations, but how accurately is this information actually derived from initial retinotopic (i.e., eye-centered) visual input? We conducted a spatial working memory task in which subjects remembered a cued location in spatiotopic or retinotopic coordinates while making guided eye movements during the memory delay. Surprisingly, after a saccade, subjects were significantly more accurate and precise at reporting retinotopic locations than spatiotopic locations. This difference grew with each eye movement, such that spatiotopic memory continued to deteriorate, whereas retinotopic memory did not accumulate error. The loss in spatiotopic fidelity is therefore not a generic consequence of eye movements, but a direct result of converting visual information from native retinotopic coordinates. Thus, despite our conscious experience of an effortlessly stable spatiotopic world and our lifetime of practice with spatiotopic tasks, memory is actually more reliable in raw retinotopic coordinates than in ecologically relevant spatiotopic coordinates.

http://www.pnas.org/content/109/5/1796.short?rss=1

The mechanisms underlying the acquisition of speech-production ability in human infancy are not well understood. We tracked 4–12-mo-old English-learning infants’ and adults’ eye gaze while they watched and listened to a female reciting a monologue either in their native (English) or nonnative (Spanish) language. We found that infants shifted their attention from the eyes to the mouth between 4 and 8 mo of age regardless of language and then began a shift back to the eyes at 12 mo in response to native but not nonnative speech. We posit that the first shift enables infants to gain access to redundant audiovisual speech cues that enable them to learn their native speech forms and that the second shift reflects growing native-language expertise that frees them to shift attention to the eyes to gain access to social cues. On this account, 12-mo-old infants do not shift attention to the eyes when exposed to nonnative speech because increasing native-language expertise and perceptual narrowing make it more difficult to process nonnative speech and require them to continue to access redundant audiovisual cues. Overall, the current findings demonstrate that the development of speech production capacity relies on changes in selective audiovisual attention and that this depends critically on early experience.

http://www.pnas.org/content/109/5/1431.short?rss=1

The quality of sensing and response to external stimuli constitutes a basic element in the selective performance of living organisms. Here we consider the response of Escherichia coli to chemical stimuli. For moderate amplitudes, the bacterial response to generic profiles of sensed chemicals is reconstructed from its response function to an impulse, which then controls the efficiency of bacterial motility. We introduce a method for measuring the impulse response function based on coupling microfluidic experiments and inference methods: The response function is inferred using Bayesian methods from the observed trajectories of bacteria swimming in microfluidically controlled chemical fields. The notable advantages are that the method is based on the bacterial swimming response, it is noninvasive, without any genetic and/or mechanical preparation, and assays the behavior of the whole flagella bundle. We exploit the inference method to measure responses to aspartate and α-methylaspartate—measured previously by other methods—as well as glucose, leucine, and serine. The response to the attractant glucose is shown to be biphasic and perfectly adapted, as for aspartate. The response to the attractant serine is shown to be biphasic yet imperfectly adapted, that is, the response function has a nonzero (positive) integral. The adaptation of the response to the repellent leucine is also imperfect, with the sign of the two phases inverted with respect to serine. The diversity in the bacterial population of the response function and its dependency upon the background concentration are quantified.

http://www.pnas.org/content/109/5/1802.short?rss=1

PSYCHOLOGICAL AND COGNITIVE SCIENCES, GENETICS Correction for “Thin-slicing study of the oxytocin receptor (OXTR) gene and the evaluation and expression of the prosocial disposition,” by Aleksandr Kogan, Laura R. Saslow, Emily A. Impett, Christopher Oveis, Dacher Keltner, and Sarina Rodrigues Saturn, which appeared in issue 48, November 29, 2011, of Proc Natl Acad Sci USA (108:19189–19192; first published November 14, 2011; 10.1073/pnas.1112658108).The authors note that Fig. 1 appeared incorrectly. The corrected figure and its legend appear below. This error does not affect the conclusions of the article.pnas;109/5/1808/FIG01F1fig01Fig. 1.Differences in prosociality ratings of targets by genotype. Targets homozygous for the G...

http://www.pnas.org/content/109/5/1808.1.short?rss=1

PHARMACOLOGY Retraction for “Structural basis for nucleotide exchange on Gαi subunits and receptor coupling specificity,” by Christopher A. Johnston and David P. Siderovski, which appeared in issue 6, February 6, 2007, of Proc Natl Acad Sci USA (104:2001–2006; first published January 30, 2007; 10.1073/pnas.0608599104).The authors wish to note the following: “In our paper, a co-crystal structure at 2.2 Å resolution was described of the heterotrimeric G-protein alpha subunit Gαi1 bound to two peptides: one from an artificial sequence that promotes nucleotide exchange (KB-752) and a second peptide (D2N) from the third intracellular loop of the D2 dopamine receptor (PDB ID...

http://www.pnas.org/content/109/5/1808.2.short?rss=1

The projected start of the ITER fusion reactor in France looks set to slip by another 10 months. The new completion date is now November 2019.Author: Daniel Clery

http://www.sciencemag.org/cgi/content/full/327/5972/1434?rss=1

The show includes how corals respond to climate change, inherited factors for drug addiction, 2011 Visualization Challenge winners, and more.

http://www.sciencemag.org/content/335/6068/605.2.full?rss=1

A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.

http://www.sciencemag.org/content/335/6068/605.1.full?rss=1

Reconstruction of whole genomes from a complex microbial community has revealed an evolutionary surprise.Authors: Vaughn Iverson, Robert M. Morris, Christian D. Frazar, Chris T. Berthiaume, Rhonda L. Morales, E. Virginia Armbrust

http://www.sciencemag.org/content/335/6068/587.full?rss=1

The effects of female leaders on girls occur via policy changes in the short run and parental aspirations in the longer run.Authors: Lori Beaman, Esther Duflo, Rohini Pande, Petia Topalova

http://www.sciencemag.org/content/335/6068/582.full?rss=1

Increasing the representation of competition-averse individuals does not alter overall output.Authors: Loukas Balafoutas, Matthias Sutter

http://www.sciencemag.org/content/335/6068/579.full?rss=1

Resistance to avermectin, an anti-nematode drug, is conferred by a deletion in a glutamate-gated chloride channel.Authors: Rajarshi Ghosh, Erik C. Andersen, Joshua A. Shapiro, Justin P. Gerke, Leonid Kruglyak

http://www.sciencemag.org/content/335/6068/574.full?rss=1

Iron catalysts offer a potentially cheaper route than platinum for certain commercially useful carbon-silicon compounds.Authors: Aaron M. Tondreau, Crisita Carmen Hojilla Atienza, Keith J. Weller, Susan A. Nye, Kenrick M. Lewis, Johannes G. P. Delis, Paul J. Chirik

http://www.sciencemag.org/content/335/6068/567.full?rss=1

Radiocarbon measurements of deep-sea corals reveal the presence of old, carbon-rich water in the Southern Ocean.Authors: Andrea Burke, Laura F. Robinson

http://www.sciencemag.org/content/335/6068/557.full?rss=1

Super high-resolution microscopy resolves neuron dynamics in the cerebral cortex of a living mouse.Authors: Sebastian Berning, Katrin I. Willig, Heinz Steffens, Payam Dibaj, Stefan W. Hell

http://www.sciencemag.org/content/335/6068/551.full?rss=1

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http://wsjournals.wspc.com.sg/jiohs/05/0501/S1793545812500034.html

http://www.photonik.de/index.php?id=5&artid=4227&tp=na

http://www.photonik.de/index.php?id=5&artid=4227&tp=na

http://www.photonik.de/index.php?id=5&artid=4226&tp=na

Ab Sommer 2012 starten zwanzig Airbus A320 mit dem norwegischen Frühwarnsystem AVOID. Es soll die Sicherheit beim Überfliegen aktiver Vulkangebiete erhöhen.

http://www.photonik.de/index.php?id=5&artid=4225&tp=na

http://www.photonik.de/index.php?id=5&artid=4224&tp=na

http://www.photonik.de/index.php?id=5&artid=4223&tp=na

Mit dem Öffnen der Tore begann am 24. Januar (Dienstag) der Ansturm auf die Aussteller der Photonics West 2012. Wenn das Jahr so verläuft, wie es auf dieser Messe begonnen hat, dann sollten die Umsätze neue Rekordhöhen erreichen.

http://www.photonik.de/index.php?id=5&artid=4222&tp=na

Jenoptik beruft einen neuen Geschäftsführer für den Bereich Laseranlagen und für die Automatisierungstechnik.

http://www.photonik.de/index.php?id=5&artid=4221&tp=na

http://www.photonik.de/index.php?id=5&artid=4220&tp=na

http://www.photonik.de/index.php?id=5&artid=4219&tp=na