PLOS Biology: New Articles PLOS Publishing science info:doi/10.1371/feed.pbio This work is licensed under a Creative Commons Attribution-Share Alike 3.0 License${webserver-url}images/favicon.ico${webserver-url}images/favicon.ico 2015-10-05T23:32:45Z Subscribe with My Yahoo!Subscribe with NewsGatorSubscribe with My AOLSubscribe with BloglinesSubscribe with NetvibesSubscribe with GoogleSubscribe with Pageflakes Synaptotagmin-1 and -7 Are Redundantly Essential for Maintaining the Capacity of the Readily-Releasable Pool of Synaptic Vesicles Taulant Bacaj et al. info:doi/10.1371/journal.pbio.1002267 2015-10-05T21:00:00Z 2015-10-05T21:00:00Z <p>by Taulant Bacaj, Dick Wu, Jacqueline Burré, Robert C. Malenka, Xinran Liu, Thomas C. Südhof</p> In forebrain neurons, Ca<sup>2+</sup> triggers exocytosis of readily releasable vesicles by binding to synaptotagmin-1 and -7, thereby inducing fast and slow vesicle exocytosis, respectively. Loss-of-function of synaptotagmin-1 or -7 selectively impairs the fast and slow phase of release, respectively, but does not change the size of the readily-releasable pool (RRP) of vesicles as measured by stimulation of release with hypertonic sucrose, or alter the rate of vesicle priming into the RRP. Here we show, however, that simultaneous loss-of-function of both synaptotagmin-1 and -7 dramatically decreased the capacity of the RRP, again without altering the rate of vesicle priming into the RRP. Either synaptotagmin-1 or -7 was sufficient to rescue the RRP size in neurons lacking both synaptotagmin-1 and -7. Although maintenance of RRP size was Ca<sup>2+</sup>-independent, mutations in Ca<sup>2+</sup>-binding sequences of synaptotagmin-1 or synaptotagmin-7—which are contained in flexible top-loop sequences of their C2 domains—blocked the ability of these synaptotagmins to maintain the RRP size. Both synaptotagmins bound to SNARE complexes; SNARE complex binding was reduced by the top-loop mutations that impaired RRP maintenance. Thus, synaptotagmin-1 and -7 perform redundant functions in maintaining the capacity of the RRP in addition to nonredundant functions in the Ca<sup>2+</sup> triggering of different phases of release.<img src="" height="1" width="1" alt=""/> Dual-Function Exocytosis Regulator Has Yet Another Job Richard Robinson info:doi/10.1371/journal.pbio.1002268 2015-10-05T21:00:00Z 2015-10-05T21:00:00Z <p>by Richard Robinson</p><img src="" height="1" width="1" alt=""/> Meta-research: Evaluation and Improvement of Research Methods and Practices John P. A. Ioannidis et al. info:doi/10.1371/journal.pbio.1002264 2015-10-02T21:00:00Z 2015-10-02T21:00:00Z <p>by John P. A. Ioannidis, Daniele Fanelli, Debbie Drake Dunne, Steven N. Goodman</p> As the scientific enterprise has grown in size and diversity, we need empirical evidence on the research process to test and apply interventions that make it more efficient and its results more reliable. Meta-research is an evolving scientific discipline that aims to evaluate and improve research practices. It includes thematic areas of methods, reporting, reproducibility, evaluation, and incentives (how to do, report, verify, correct, and reward science). Much work is already done in this growing field, but efforts to-date are fragmented. We provide a map of ongoing efforts and discuss plans for connecting the multiple meta-research efforts across science worldwide.<img src="" height="1" width="1" alt=""/> Map of Visual Activity in the Infant Brain Sheds Light on Neural Development Janelle Weaver info:doi/10.1371/journal.pbio.1002261 2015-09-29T21:00:00Z 2015-09-29T21:00:00Z <p>by Janelle Weaver</p><img src="" height="1" width="1" alt=""/> BOLD Response Selective to Flow-Motion in Very Young Infants Laura Biagi et al. info:doi/10.1371/journal.pbio.1002260 2015-09-29T21:00:00Z 2015-09-29T21:00:00Z <p>by Laura Biagi, Sofia Allegra Crespi, Michela Tosetti, Maria Concetta Morrone</p> In adults, motion perception is mediated by an extensive network of occipital, parietal, temporal, and insular cortical areas. Little is known about the neural substrate of visual motion in infants, although behavioural studies suggest that motion perception is rudimentary at birth and matures steadily over the first few years. Here, by measuring Blood Oxygenated Level Dependent (BOLD) responses to flow versus random-motion stimuli, we demonstrate that the major cortical areas serving motion processing in adults are operative by 7 wk of age. Resting-state correlations demonstrate adult-like functional connectivity between the motion-selective associative areas, but not between primary cortex and temporo-occipital and posterior-insular cortices. Taken together, the results suggest that the development of motion perception may be limited by slow maturation of the subcortical input and of the cortico-cortical connections. In addition they support the existence of independent input to primary (V1) and temporo-occipital (V5/MT+) cortices very early in life.<img src="" height="1" width="1" alt=""/> Neuromodulation to the Rescue: Compensation of Temperature-Induced Breakdown of Rhythmic Motor Patterns via Extrinsic Neuromodulatory Input Carola Städele et al. info:doi/10.1371/journal.pbio.1002265 2015-09-29T21:00:00Z 2015-09-29T21:00:00Z <p>by Carola Städele, Stefanie Heigele, Wolfgang Stein</p> Stable rhythmic neural activity depends on the well-coordinated interplay of synaptic and cell-intrinsic conductances. Since all biophysical processes are temperature dependent, this interplay is challenged during temperature fluctuations. How the nervous system remains functional during temperature perturbations remains mostly unknown. We present a hitherto unknown mechanism of how temperature-induced changes in neural networks are compensated by changing their neuromodulatory state: activation of neuromodulatory pathways establishes a dynamic coregulation of synaptic and intrinsic conductances with opposing effects on neuronal activity when temperature changes, hence rescuing neuronal activity. Using the well-studied gastric mill pattern generator of the crab, we show that modest temperature increase can abolish rhythmic activity in isolated neural circuits due to increased leak currents in rhythm-generating neurons. Dynamic clamp-mediated addition of leak currents was sufficient to stop neuronal oscillations at low temperatures, and subtraction of additional leak currents at elevated temperatures was sufficient to rescue the rhythm. Despite the apparent sensitivity of the isolated nervous system to temperature fluctuations, the rhythm could be stabilized by activating extrinsic neuromodulatory inputs from descending projection neurons, a strategy that we indeed found to be implemented in intact animals. In the isolated nervous system, temperature compensation was achieved by stronger extrinsic neuromodulatory input from projection neurons or by augmenting projection neuron influence via bath application of the peptide cotransmitter <i>Cancer borealis</i> tachykinin-related peptide Ia (CabTRP Ia). CabTRP Ia activates the modulator-induced current I<sub>MI</sub> (a nonlinear voltage-gated inward current) that effectively acted as a negative leak current and counterbalanced the temperature-induced leak to rescue neuronal oscillations. Computational modelling revealed the ability of I<sub>MI</sub> to reduce detrimental leak-current influences on neuronal networks over a broad conductance range and indicated that leak and I<sub>MI</sub> are closely coregulated in the biological system to enable stable motor patterns. In conclusion, these results show that temperature compensation does not need to be implemented within the network itself but can be conditionally provided by extrinsic neuromodulatory input that counterbalances temperature-induced modifications of circuit-intrinsic properties.<img src="" height="1" width="1" alt=""/> Seeing and Feeling Motion: Canonical Computations in Vision and Touch Christopher C. Pack et al. info:doi/10.1371/journal.pbio.1002271 2015-09-29T21:00:00Z 2015-09-29T21:00:00Z <p>by Christopher C. Pack, Sliman J. Bensmaia</p> While the different sensory modalities are sensitive to different stimulus energies, they are often charged with extracting analogous information about the environment. Neural systems may thus have evolved to implement similar algorithms across modalities to extract behaviorally relevant stimulus information, leading to the notion of a canonical computation. In both vision and touch, information about motion is extracted from a spatiotemporal pattern of activation across a sensory sheet (in the retina and in the skin, respectively), a process that has been extensively studied in both modalities. In this essay, we examine the processing of motion information as it ascends the primate visual and somatosensory neuraxes and conclude that similar computations are implemented in the two sensory systems.<img src="" height="1" width="1" alt=""/> Insulator Protein Helps Organize the Gaps in the Axon's Insulation Richard Robinson info:doi/10.1371/journal.pbio.1002259 2015-09-25T21:00:00Z 2015-09-25T21:00:00Z <p>by Richard Robinson</p><img src="" height="1" width="1" alt=""/> HDAC1/2-Dependent P0 Expression Maintains Paranodal and Nodal Integrity Independently of Myelin Stability through Interactions with Neurofascins Valérie Brügger et al. info:doi/10.1371/journal.pbio.1002258 2015-09-25T21:00:00Z 2015-09-25T21:00:00Z <p>by Valérie Brügger, Stefanie Engler, Jorge A. Pereira, Sophie Ruff, Michael Horn, Hans Welzl, Emmanuelle Münger, Adrien Vaquié, Páris N. M. Sidiropoulos, Boris Egger, Peter Yotovski, Luis Filgueira, Christian Somandin, Tessa C. Lühmann, Maurizio D’Antonio, Teppei Yamaguchi, Patrick Matthias, Ueli Suter, Claire Jacob</p> The pathogenesis of peripheral neuropathies in adults is linked to maintenance mechanisms that are not well understood. Here, we elucidate a novel critical maintenance mechanism for Schwann cell (SC)–axon interaction. Using mouse genetics, ablation of the transcriptional regulators histone deacetylases 1 and 2 (HDAC1/2) in adult SCs severely affected paranodal and nodal integrity and led to demyelination/remyelination. Expression levels of the HDAC1/2 target gene myelin protein zero (P0) were reduced by half, accompanied by altered localization and stability of neurofascin (NFasc)155, NFasc186, and loss of Caspr and septate-like junctions. We identify P0 as a novel binding partner of NFasc155 and NFasc186, both in vivo and by in vitro adhesion assay. Furthermore, we demonstrate that HDAC1/2-dependent P0 expression is crucial for the maintenance of paranodal/nodal integrity and axonal function through interaction of P0 with neurofascins. In addition, we show that the latter mechanism is impaired by some P0 mutations that lead to late onset Charcot-Marie-Tooth disease.<img src="" height="1" width="1" alt=""/> A New Role of the Mosquito Complement-like Cascade in Male Fertility in Anopheles gambiae Julien Pompon et al. info:doi/10.1371/journal.pbio.1002255 2015-09-22T21:00:00Z 2015-09-22T21:00:00Z <p>by Julien Pompon, Elena A. Levashina</p> Thioester-containing protein 1 (TEP1) is a key immune factor that determines mosquito resistance to a wide range of pathogens, including malaria parasites. Here we report a new allele-specific function of TEP1 in male fertility. We demonstrate that during spermatogenesis TEP1 binds to and removes damaged cells through the same complement-like cascade that kills malaria parasites in the mosquito midgut. Further, higher fertility rates are mediated by an allele that renders the mosquito susceptible to <i>Plasmodium</i>. By elucidating the molecular and genetic mechanisms underlying TEP1 function in spermatogenesis, our study suggests that pleiotropic antagonism between reproduction and immunity may shape resistance of mosquito populations to malaria parasites.<img src="" height="1" width="1" alt=""/> Vibrissa Self-Motion and Touch Are Reliably Encoded along the Same Somatosensory Pathway from Brainstem through Thalamus Jeffrey D. Moore et al. info:doi/10.1371/journal.pbio.1002253 2015-09-22T21:00:00Z 2015-09-22T21:00:00Z <p>by Jeffrey D. Moore, Nicole Mercer Lindsay, Martin Deschênes, David Kleinfeld</p> Active sensing involves the fusion of internally generated motor events with external sensation. For rodents, active somatosensation includes scanning the immediate environment with the mystacial vibrissae. In doing so, the vibrissae may touch an object at any angle in the whisk cycle. The representation of touch and vibrissa self-motion may in principle be encoded along separate pathways, or share a single pathway, from the periphery to cortex. Past studies established that the spike rates in neurons along the lemniscal pathway from receptors to cortex, which includes the principal trigeminal and ventral-posterior-medial thalamic nuclei, are substantially modulated by touch. In contrast, spike rates along the paralemniscal pathway, which includes the rostral spinal trigeminal interpolaris, posteromedial thalamic, and ventral zona incerta nuclei, are only weakly modulated by touch. Here we find that neurons along the lemniscal pathway robustly encode rhythmic whisking on a cycle-by-cycle basis, while encoding along the paralemniscal pathway is relatively poor. Thus, the representations of both touch and self-motion share one pathway. In fact, some individual neurons carry both signals, so that upstream neurons with a supralinear gain function could, in principle, demodulate these signals to recover the known decoding of touch as a function of vibrissa position in the whisk cycle.<img src="" height="1" width="1" alt=""/> Shifts of Gamma Phase across Primary Visual Cortical Sites Reflect Dynamic Stimulus-Modulated Information Transfer Michel Besserve et al. info:doi/10.1371/journal.pbio.1002257 2015-09-22T21:00:00Z 2015-09-22T21:00:00Z <p>by Michel Besserve, Scott C. Lowe, Nikos K. Logothetis, Bernhard Schölkopf, Stefano Panzeri</p> Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50–80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections.<img src="" height="1" width="1" alt=""/> Mosquitoes Trade Fertility for Immune Defense against Malaria Caitlin Sedwick info:doi/10.1371/journal.pbio.1002256 2015-09-22T21:00:00Z 2015-09-22T21:00:00Z <p>by Caitlin Sedwick</p><img src="" height="1" width="1" alt=""/> Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation Dhakshin S. Ramanathan et al. info:doi/10.1371/journal.pbio.1002263 2015-09-18T21:00:00Z 2015-09-18T21:00:00Z <p>by Dhakshin S. Ramanathan, Tanuj Gulati, Karunesh Ganguly</p> Despite many prior studies demonstrating offline behavioral gains in motor skills after sleep, the underlying neural mechanisms remain poorly understood. To investigate the neurophysiological basis for offline gains, we performed single-unit recordings in motor cortex as rats learned a skilled upper-limb task. We found that sleep improved movement speed with preservation of accuracy. These offline improvements were linked to both replay of task-related ensembles during non-rapid eye movement (NREM) sleep and temporal shifts that more tightly bound motor cortical ensembles to movements; such offline gains and temporal shifts were not evident with sleep restriction. Interestingly, replay was linked to the coincidence of slow-wave events and bursts of spindle activity. Neurons that experienced the most consistent replay also underwent the most significant temporal shift and binding to the motor task. Significantly, replay and the associated performance gains after sleep only occurred when animals first learned the skill; continued practice during later stages of learning (i.e., after motor kinematics had stabilized) did not show evidence of replay. Our results highlight how replay of synchronous neural activity during sleep mediates large-scale neural plasticity and stabilizes kinematics during early motor learning.<img src="" height="1" width="1" alt=""/> Time Adaptation Shows Duration Selectivity in the Human Parietal Cortex Masamichi J. Hayashi et al. info:doi/10.1371/journal.pbio.1002262 2015-09-17T21:00:00Z 2015-09-17T21:00:00Z <p>by Masamichi J. Hayashi, Thomas Ditye, Tokiko Harada, Maho Hashiguchi, Norihiro Sadato, Synnöve Carlson, Vincent Walsh, Ryota Kanai</p> Although psychological and computational models of time estimation have postulated the existence of neural representations tuned for specific durations, empirical evidence of this notion has been lacking. Here, using a functional magnetic resonance imaging (fMRI) adaptation paradigm, we show that the inferior parietal lobule (IPL) (corresponding to the supramarginal gyrus) exhibited reduction in neural activity due to adaptation when a visual stimulus of the same duration was repeatedly presented. Adaptation was strongest when stimuli of identical durations were repeated, and it gradually decreased as the difference between the reference and test durations increased. This tuning property generalized across a broad range of durations, indicating the presence of general time-representation mechanisms in the IPL. Furthermore, adaptation was observed irrespective of the subject’s attention to time. Repetition of a nontemporal aspect of the stimulus (i.e., shape) did not produce neural adaptation in the IPL. These results provide neural evidence for duration-tuned representations in the human brain.<img src="" height="1" width="1" alt=""/> Extremely High Mutation Rate of HIV-1 In Vivo José M. Cuevas et al. info:doi/10.1371/journal.pbio.1002251 2015-09-16T21:00:00Z 2015-09-16T21:00:00Z <p>by José M. Cuevas, Ron Geller, Raquel Garijo, José López-Aldeguer, Rafael Sanjuán</p> Rates of spontaneous mutation critically determine the genetic diversity and evolution of RNA viruses. Although these rates have been characterized in vitro and in cell culture models, they have seldom been determined in vivo for human viruses. Here, we use the intrapatient frequency of premature stop codons to quantify the HIV-1 genome-wide rate of spontaneous mutation in DNA sequences from peripheral blood mononuclear cells. This reveals an extremely high mutation rate of (4.1 ± 1.7) × 10<sup>−3</sup> per base per cell, the highest reported for any biological entity. Sequencing of plasma-derived sequences yielded a mutation frequency 44 times lower, indicating that a large fraction of viral genomes are lethally mutated and fail to reach plasma. We show that the HIV-1 reverse transcriptase contributes only 2% of mutations, whereas 98% result from editing by host cytidine deaminases of the A3 family. Hypermutated viral sequences are less abundant in patients showing rapid disease progression compared to normal progressors, highlighting the antiviral role of A3 proteins. However, the amount of A3-mediated editing varies broadly, and we find that low-edited sequences are more abundant among rapid progressors, suggesting that suboptimal A3 activity might enhance HIV-1 genetic diversity and pathogenesis.<img src="" height="1" width="1" alt=""/> Cellular Defense Enzyme Drives Exceptionally High Rate of Mutation in HIV Richard Robinson info:doi/10.1371/journal.pbio.1002252 2015-09-16T21:00:00Z 2015-09-16T21:00:00Z <p>by Richard Robinson</p><img src="" height="1" width="1" alt=""/> The Fitness Effects of Love Roland G. Roberts info:doi/10.1371/journal.pbio.1002249 2015-09-14T21:00:00Z 2015-09-14T21:00:00Z <p>by Roland G. Roberts</p><img src="" height="1" width="1" alt=""/> Fitness Benefits of Mate Choice for Compatibility in a Socially Monogamous Species Malika Ihle et al. info:doi/10.1371/journal.pbio.1002248 2015-09-14T21:00:00Z 2015-09-14T21:00:00Z <p>by Malika Ihle, Bart Kempenaers, Wolfgang Forstmeier</p> Research on mate choice has primarily focused on preferences for quality indicators, assuming that all individuals show consensus about who is the most attractive. However, in some species, mating preferences seem largely individual-specific, suggesting that they might target genetic or behavioral compatibility. Few studies have quantified the fitness consequences of allowing versus preventing such idiosyncratic mate choice. Here, we report on an experiment that controls for variation in overall partner quality and show that zebra finch (<i>Taeniopygia guttata</i>) pairs that resulted from free mate choice achieved a 37% higher reproductive success than pairs that were forced to mate. Cross-fostering of freshly laid eggs showed that embryo mortality (before hatching) primarily depended on the identity of the genetic parents, whereas offspring mortality during the rearing period depended on foster-parent identity. Therefore, preventing mate choice should lead to an increase in embryo mortality if mate choice targets genetic compatibility (for embryo viability), and to an increase in offspring mortality if mate choice targets behavioral compatibility (for better rearing). We found that pairs from both treatments showed equal rates of embryo mortality, but chosen pairs were better at raising offspring. These results thus support the behavioral, but not the genetic, compatibility hypothesis. Further exploratory analyses reveal several differences in behavior and fitness components between “free-choice” and “forced” pairs.<img src="" height="1" width="1" alt=""/> How to Turn On an Ancient Metabolic Enzyme? Add Insulin and Deacetylate Richard Robinson info:doi/10.1371/journal.pbio.1002244 2015-09-10T21:00:00Z 2015-09-10T21:00:00Z <p>by Richard Robinson</p><img src="" height="1" width="1" alt=""/> Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation of PGK1 Shiwen Wang et al. info:doi/10.1371/journal.pbio.1002243 2015-09-10T21:00:00Z 2015-09-10T21:00:00Z <p>by Shiwen Wang, Bowen Jiang, Tengfei Zhang, Lixia Liu, Yi Wang, Yiping Wang, Xiufei Chen, Huaipeng Lin, Lisha Zhou, Yukun Xia, Leilei Chen, Chen Yang, Yue Xiong, Dan Ye, Kun-Liang Guan</p> Phosphoglycerate kinase 1 (PGK1) catalyzes the reversible transfer of a phosphoryl group from 1, 3-bisphosphoglycerate (1, 3-BPG) to ADP, producing 3-phosphoglycerate (3-PG) and ATP. PGK1 plays a key role in coordinating glycolytic energy production with one-carbon metabolism, serine biosynthesis, and cellular redox regulation. Here, we report that PGK1 is acetylated at lysine 220 (K220), which inhibits PGK1 activity by disrupting the binding with its substrate, ADP. We have identified KAT9 and HDAC3 as the potential acetyltransferase and deacetylase, respectively, for PGK1. Insulin promotes K220 deacetylation to stimulate PGK1 activity. We show that the PI3K/AKT/mTOR pathway regulates HDAC3 S424 phosphorylation, which promotes HDAC3-PGK1 interaction and PGK1 K220 deacetylation. Our study uncovers a previously unknown mechanism for the insulin and mTOR pathway in regulation of glycolytic ATP production and cellular redox potential via HDAC3-mediated PGK1 deacetylation.<img src="" height="1" width="1" alt=""/> The Maternal Maverick/GDF15-like TGF-β Ligand Panda Directs Dorsal-Ventral Axis Formation by Restricting Nodal Expression in the Sea Urchin Embryo Emmanuel Haillot et al. info:doi/10.1371/journal.pbio.1002247 2015-09-09T21:00:00Z 2015-09-09T21:00:00Z <p>by Emmanuel Haillot, Maria Dolores Molina, François Lapraz, Thierry Lepage</p> Specification of the dorsal-ventral axis in the highly regulative sea urchin embryo critically relies on the zygotic expression of <i>nodal</i>, but whether maternal factors provide the initial spatial cue to orient this axis is not known. Although redox gradients have been proposed to entrain the dorsal-ventral axis by acting upstream of <i>nodal</i>, manipulating the activity of redox gradients only has modest consequences, suggesting that other factors are responsible for orienting <i>nodal</i> expression and defining the dorsal-ventral axis. Here we uncover the function of Panda, a maternally provided transforming growth factor beta (TGF-β) ligand that requires the activin receptor-like kinases (Alk) Alk3/6 and Alk1/2 receptors to break the radial symmetry of the embryo and orient the dorsal-ventral axis by restricting <i>nodal</i> expression. We found that the double inhibition of the bone morphogenetic protein (BMP) type I receptors Alk3/6 and Alk1/2 causes a phenotype dramatically more severe than the BMP2/4 loss-of-function phenotype, leading to extreme ventralization of the embryo through massive ectopic expression of <i>nodal</i>, suggesting that an unidentified signal acting through BMP type I receptors cooperates with BMP2/4 to restrict <i>nodal</i> expression. We identified this ligand as the product of maternal Panda mRNA. Double inactivation of <i>panda</i> and <i>bmp2/4</i> led to extreme ventralization, mimicking the phenotype caused by inactivation of the two BMP receptors. Inhibition of maternal <i>panda</i> mRNA translation disrupted the early spatial restriction of <i>nodal</i>, leading to persistent massive ectopic expression of <i>nodal</i> on the dorsal side despite the presence of Lefty. Phylogenetic analysis indicates that Panda is not a prototypical BMP ligand but a member of a subfamily of TGF-β distantly related to Inhibins, Lefty, and TGF-β that includes Maverick from <i>Drosophila</i> and GDF15 from vertebrates. Indeed, overexpression of Panda does not appear to directly or strongly activate phosphoSmad1/5/8 signaling, suggesting that although this TGF-β may require Alk1/2 and/or Alk3/6 to antagonize <i>nodal</i> expression, it may do so by sequestering a factor essential for Nodal signaling, by activating a non-Smad pathway downstream of the type I receptors, or by activating extremely low levels of pSmad1/5/8. We provide evidence that, although <i>panda</i> mRNA is broadly distributed in the early embryo, local expression of <i>panda</i> mRNA efficiently orients the dorsal-ventral axis and that Panda activity is required locally in the early embryo to specify this axis. Taken together, these findings demonstrate that maternal <i>panda</i> mRNA is both necessary and sufficient to orient the dorsal-ventral axis. These results therefore provide evidence that in the highly regulative sea urchin embryo, the activity of spatially restricted maternal factors regulates patterning along the dorsal-ventral axis.<img src="" height="1" width="1" alt=""/> Resolving Conflicts between Agriculture and the Natural Environment Andrew J. Tanentzap et al. info:doi/10.1371/journal.pbio.1002242 2015-09-09T21:00:00Z 2015-09-09T21:00:00Z <p>by Andrew J. Tanentzap, Anthony Lamb, Susan Walker, Andrew Farmer</p> Agriculture dominates the planet. Yet it has many environmental costs that are unsustainable, especially as global food demand rises. Here, we evaluate ways in which different parts of the world are succeeding in their attempts to resolve conflict between agriculture and wild nature. We envision that coordinated global action in conserving land most sensitive to agricultural activities and policies that internalise the environmental costs of agriculture are needed to deliver a more sustainable future.<img src="" height="1" width="1" alt=""/> Face Patch Resting State Networks Link Face Processing to Social Cognition Caspar M. Schwiedrzik et al. info:doi/10.1371/journal.pbio.1002245 2015-09-08T21:00:00Z 2015-09-08T21:00:00Z <p>by Caspar M. Schwiedrzik, Wilbert Zarco, Stefan Everling, Winrich A. Freiwald</p> Faces transmit a wealth of social information. How this information is exchanged between face-processing centers and brain areas supporting social cognition remains largely unclear. Here we identify these routes using resting state functional magnetic resonance imaging in macaque monkeys. We find that face areas functionally connect to specific regions within frontal, temporal, and parietal cortices, as well as subcortical structures supporting emotive, mnemonic, and cognitive functions. This establishes the existence of an extended face-recognition system in the macaque. Furthermore, the face patch resting state networks and the default mode network in monkeys show a pattern of overlap akin to that between the social brain and the default mode network in humans: this overlap specifically includes the posterior superior temporal sulcus, medial parietal, and dorsomedial prefrontal cortex, areas supporting high-level social cognition in humans. Together, these results reveal the embedding of face areas into larger brain networks and suggest that the resting state networks of the face patch system offer a new, easily accessible venue into the functional organization of the social brain and into the evolution of possibly uniquely human social skills.<img src="" height="1" width="1" alt=""/> A Change in the Ion Selectivity of Ligand-Gated Ion Channels Provides a Mechanism to Switch Behavior Jennifer K. Pirri et al. info:doi/10.1371/journal.pbio.1002238 2015-09-08T21:00:00Z 2015-09-08T21:00:00Z <p>by Jennifer K. Pirri, Diego Rayes, Mark J. Alkema</p> Behavioral output of neural networks depends on a delicate balance between excitatory and inhibitory synaptic connections. However, it is not known whether network formation and stability is constrained by the sign of synaptic connections between neurons within the network. Here we show that switching the sign of a synapse within a neural circuit can reverse the behavioral output. The inhibitory tyramine-gated chloride channel, LGC-55, induces head relaxation and inhibits forward locomotion during the <i>Caenorhabditis elegans</i> escape response. We switched the ion selectivity of an inhibitory LGC-55 anion channel to an excitatory LGC-55 cation channel. The engineered cation channel is properly trafficked in the native neural circuit and results in behavioral responses that are opposite to those produced by activation of the LGC-55 anion channel. Our findings indicate that switches in ion selectivity of ligand-gated ion channels (LGICs) do not affect network connectivity or stability and may provide an evolutionary and a synthetic mechanism to change behavior.<img src="" height="1" width="1" alt=""/> Centre of the Cell: Science Comes to Life Frances Balkwill et al. info:doi/10.1371/journal.pbio.1002240 2015-09-04T21:00:00Z 2015-09-04T21:00:00Z <p>by Frances Balkwill, Katie Chambers</p> Centre of the Cell is a unique biomedical science education centre, a widening participation and outreach project in London’s East End. This article describes Centre of the Cell’s first five years of operation, the evolution of the project in response to audience demand, and the impact of siting a major public engagement project within a research laboratory.<img src="" height="1" width="1" alt=""/> Correction: Diffusion Magnetic Resonance Imaging: What Water Tells Us about Biological Tissues Denis Le Bihan et al. info:doi/10.1371/journal.pbio.1002246 2015-09-03T21:00:00Z 2015-09-03T21:00:00Z <p>by Denis Le Bihan, Mami Iima</p><img src="" height="1" width="1" alt=""/> The Actin Nucleator Cobl Is Controlled by Calcium and Calmodulin Wenya Hou et al. info:doi/10.1371/journal.pbio.1002233 2015-09-03T21:00:00Z 2015-09-03T21:00:00Z <p>by Wenya Hou, Maryam Izadi, Sabine Nemitz, Natja Haag, Michael M. Kessels, Britta Qualmann</p> Actin nucleation triggers the formation of new actin filaments and has the power to shape cells but requires tight control in order to bring about proper morphologies. The regulation of the members of the novel class of WASP Homology 2 (WH2) domain-based actin nucleators, however, thus far has largely remained elusive. Our study reveals signal cascades and mechanisms regulating Cordon-Bleu (Cobl). Cobl plays some, albeit not fully understood, role in early arborization of neurons and nucleates actin by a mechanism that requires a combination of all three of its actin monomer–binding WH2 domains. Our experiments reveal that Cobl is regulated by Ca<sup>2+</sup> and multiple, direct associations of the Ca<sup>2+</sup> sensor Calmodulin (CaM). Overexpression analyses and rescue experiments of Cobl loss-of-function phenotypes with Cobl mutants in primary neurons and in tissue slices demonstrated the importance of CaM binding for Cobl’s functions. Cobl-induced dendritic branch initiation was preceded by Ca<sup>2+</sup> signals and coincided with local F-actin and CaM accumulations. CaM inhibitor studies showed that Cobl-mediated branching is strictly dependent on CaM activity. Mechanistic studies revealed that Ca<sup>2+</sup>/CaM modulates Cobl’s actin binding properties and furthermore promotes Cobl’s previously identified interactions with the membrane-shaping F-BAR protein syndapin I, which accumulated with Cobl at nascent dendritic protrusion sites. The findings of our study demonstrate a direct regulation of an actin nucleator by Ca<sup>2+</sup>/CaM and reveal that the Ca<sup>2+</sup>/CaM-controlled molecular mechanisms we discovered are crucial for Cobl’s cellular functions. By unveiling the means of Cobl regulation and the mechanisms, by which Ca<sup>2+</sup>/CaM signals directly converge on a cellular effector promoting actin filament formation, our work furthermore sheds light on how local Ca<sup>2+</sup> signals steer and power branch initiation during early arborization of nerve cells—a key process in neuronal network formation.<img src="" height="1" width="1" alt=""/> Short Lives with Long-Lasting Effects: Filopodia Protrusions in Neuronal Branching Morphogenesis George Leondaritis et al. info:doi/10.1371/journal.pbio.1002241 2015-09-03T21:00:00Z 2015-09-03T21:00:00Z <p>by George Leondaritis, Britta Johanna Eickholt</p> The branching behaviors of both dendrites and axons are part of a neuronal maturation process initiated by the generation of small and transient membrane protrusions. These are highly dynamic, actin-enriched structures, collectively called filopodia, which can mature in neurons to form stable branches. Consequently, the generation of filopodia protrusions is crucial during the formation of neuronal circuits and involves the precise control of an interplay between the plasma membrane and actin dynamics. In this issue of <i>PLOS Biology</i>, Hou and colleagues identify a Ca<sup>2+</sup>/CaM-dependent molecular machinery in dendrites that ensures proper targeting of branch formation by activation of the actin nucleator Cobl.<img src="" height="1" width="1" alt=""/> From Friend to Foe: Toxicity Trade-Offs Govern Staphylococcus aureus Infection Severity Lauren A. Richardson info:doi/10.1371/journal.pbio.1002230 2015-09-02T21:00:00Z 2015-09-02T21:00:00Z <p>by Lauren A. Richardson</p><img src="" height="1" width="1" alt=""/>