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   ISSN (Print) 1544-9173 - ISSN (Online) 1545-7885
   Published by PLoS Homepage  [13 journals]
  • Tongue-driven sonar beam steering by a lingual-echolocating fruit bat

    • Authors: Wu-Jung Lee Benjamin Falk Chen Chiu Anand Krishnan Jessica H. Arbour Cynthia F. Moss
      Abstract: by Wu-Jung Lee, Benjamin Falk, Chen Chiu, Anand Krishnan, Jessica H. Arbour, Cynthia F. MossAnimals enhance sensory acquisition from a specific direction by movements of head, ears or eyes. As active sensing animals, echolocating bats also aim their directional sonar beam to selectively “illuminate” a confined volume of space, facilitating efficient information processing by reducing echo interference and clutter. Such sonar beam control is generally achieved by head movements or shape changes of the sound-emitting mouth or nose. However, lingual-echolocating Egyptian fruit bats, Rousettus aegyptiacus, which produce sound by clicking their tongue, can dramatically change beam direction at very short temporal intervals without visible morphological changes. The mechanism supporting this capability has remained a mystery. Here we measured signals from free-flying Egyptian fruit bats and discovered a systematic angular sweep of beam focus across increasing frequency. This unusual signal structure has not been observed in other animals, and cannot be explained by the conventional and widely used “piston model” that describes the emission pattern of other bat species. Through modeling we show that the observed beam features can be captured by an array of tongue-driven sound sources located along the side of the mouth, and that the sonar beam direction can be steered parsimoniously by inducing changes to the pattern of phase differences through moving tongue location. The effects are broadly similar to those found in a phased array–an engineering design widely found in human-made sonar systems that enables beam direction changes without changes in the physical transducer assembly. Our study reveals an intriguing parallel between biology and human engineering in solving problems in fundamentally similar ways.
      PubDate: 2017-12-15T22:00:00Z
      DOI: 10.1371/journal.pbio.2003148
  • Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory
           heterogeneity in yeast responding to stress

    • Authors: Audrey P. Gasch Feiqiao Brian Yu James Hose Leah E. Escalante Mike Place Rhonda Bacher Jad Kanbar Doina Ciobanu Laura Sandor Igor V. Grigoriev Christina Kendziorski Stephen R. Quake Megan N. McClean
      Abstract: by Audrey P. Gasch, Feiqiao Brian Yu, James Hose, Leah E. Escalante, Mike Place, Rhonda Bacher, Jad Kanbar, Doina Ciobanu, Laura Sandor, Igor V. Grigoriev, Christina Kendziorski, Stephen R. Quake, Megan N. McCleanFrom bacteria to humans, individual cells within isogenic populations can show significant variation in stress tolerance, but the nature of this heterogeneity is not clear. To investigate this, we used single-cell RNA sequencing to quantify transcript heterogeneity in single Saccharomyces cerevisiae cells treated with and without salt stress to explore population variation and identify cellular covariates that influence the stress-responsive transcriptome. Leveraging the extensive knowledge of yeast transcriptional regulation, we uncovered significant regulatory variation in individual yeast cells, both before and after stress. We also discovered that a subset of cells appears to decouple expression of ribosomal protein genes from the environmental stress response in a manner partly correlated with the cell cycle but unrelated to the yeast ultradian metabolic cycle. Live-cell imaging of cells expressing pairs of fluorescent regulators, including the transcription factor Msn2 with Dot6, Sfp1, or MAP kinase Hog1, revealed both coordinated and decoupled nucleocytoplasmic shuttling. Together with transcriptomic analysis, our results suggest that cells maintain a cellular filter against decoupled bursts of transcription factor activation but mount a stress response upon coordinated regulation, even in a subset of unstressed cells.
      PubDate: 2017-12-14T22:00:00Z
      DOI: 10.1371/journal.pbio.2004050
  • Rethinking 3R strategies: Digging deeper into AnimalTestInfo promotes
           transparency in in vivo biomedical research

    • Authors: Bettina Bert Antje Dörendahl Nora Leich Julia Vietze Matthias Steinfath Justyna Chmielewska Andreas Hensel Barbara Grune Gilbert Schönfelder
      Abstract: by Bettina Bert, Antje Dörendahl, Nora Leich, Julia Vietze, Matthias Steinfath, Justyna Chmielewska, Andreas Hensel, Barbara Grune, Gilbert SchönfelderIn the European Union (EU), animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS) of each authorised research project involving animals is published by the respective Member State. However, the NTSs remain sleeping beauties if their contents are not easily and systematically accessible. The German web-based NTS database AnimalTestInfo is a unique channel for scientists to communicate their work, and provides the opportunity for large-scale analyses of planned animal studies to inform researchers and the public. For an in-depth meta-analysis, we classified the duly completed NTSs submitted to AnimalTestInfo in 2014 and 2015 according to the International Classification of Diseases and Related Health Problems (ICD) system. Indexing the NTSs with ICD codes provided a fine-grained overview of the prospective uses of experimental animals. Using this approach, transparency, especially for highly controversial animal research involving, for example, nonhuman primates, is fostered, as it enables pinpointing the envisaged beneficiary down to the level of the addressed disease. Moreover, research areas with many planned projects involving animals can be specified in detail. The development of 3R (replacement, reduction, and refinement) measures in these research areas may be most efficient, as a large number of experimental animals would benefit from it. Indexing NTSs with ICD codes can support governments and funding agencies in advancing target-oriented funding of 3R research. Data drawn from NTSs can provide a basis for the development, validation, and implementation of directed 3R strategies as well as guidance for rethinking the role of animal research models.
      PubDate: 2017-12-14T22:00:00Z
      DOI: 10.1371/journal.pbio.2003217
  • Dual role of starvation signaling in promoting growth and recovery

    • Authors: Yonat Gurvich Dena Leshkowitz Naama Barkai
      Abstract: by Yonat Gurvich, Dena Leshkowitz, Naama BarkaiGrowing cells are subject to cycles of nutrient depletion and repletion. A shortage of nutrients activates a starvation program that promotes growth in limiting conditions. To examine whether nutrient-deprived cells prepare also for their subsequent recovery, we followed the transcription program activated in budding yeast transferred to low-phosphate media and defined its contribution to cell growth during phosphate limitation and upon recovery. An initial transcription wave was induced by moderate phosphate depletion that did not affect cell growth. A second transcription wave followed when phosphate became growth limiting. The starvation program contributed to growth only in the second, growth-limiting phase. Notably, the early response, activated at moderate depletion, promoted recovery from starvation by increasing phosphate influx upon transfer to rich medium. Our results suggest that cells subject to nutrient depletion prepare not only for growth in the limiting conditions but also for their predicted recovery once nutrients are replenished.
      PubDate: 2017-12-13T22:00:00Z
      DOI: 10.1371/journal.pbio.2002039
  • Disentangling metabolic functions of bacteria in the honey bee gut

    • Authors: Lucie Kešnerová Ruben A. T. Mars Kirsten M. Ellegaard Michaël Troilo Uwe Sauer Philipp Engel
      Abstract: by Lucie Kešnerová, Ruben A. T. Mars, Kirsten M. Ellegaard, Michaël Troilo, Uwe Sauer, Philipp EngelIt is presently unclear how much individual community members contribute to the overall metabolic output of a gut microbiota. To address this question, we used the honey bee, which harbors a relatively simple and remarkably conserved gut microbiota with striking parallels to the mammalian system and importance for bee health. Using untargeted metabolomics, we profiled metabolic changes in gnotobiotic bees that were colonized with the complete microbiota reconstituted from cultured strains. We then determined the contribution of individual community members in mono-colonized bees and recapitulated our findings using in vitro cultures. Our results show that the honey bee gut microbiota utilizes a wide range of pollen-derived substrates, including flavonoids and outer pollen wall components, suggesting a key role for degradation of recalcitrant secondary plant metabolites and pollen digestion. In turn, multiple species were responsible for the accumulation of organic acids and aromatic compound degradation intermediates. Moreover, a specific gut symbiont, Bifidobacterium asteroides, stimulated the production of host hormones known to impact bee development. While we found evidence for cross-feeding interactions, approximately 80% of the identified metabolic changes were also observed in mono-colonized bees, with Lactobacilli being responsible for the largest share of the metabolic output. These results show that, despite prolonged evolutionary associations, honey bee gut bacteria can independently establish and metabolize a wide range of compounds in the gut. Our study reveals diverse bacterial functions that are likely to contribute to bee health and provide fundamental insights into how metabolic activities are partitioned within gut communities.
      PubDate: 2017-12-12T22:00:00Z
      DOI: 10.1371/journal.pbio.2003467
  • A persistent lack of international representation on editorial boards in
           environmental biology

    • Authors: Johanna Espin Sebastian Palmas Farah Carrasco-Rueda Kristina Riemer Pablo E. Allen Nathan Berkebile Kirsten A. Hecht Kay Kastner-Wilcox Mauricio M. Núñez-Regueiro Candice Prince Constanza Rios Erica Ross Bhagatveer Sangha Tia Tyler Judit Ungvari-Martin Mariana Villegas Tara T. Cataldo Emilio M. Bruna
      Abstract: by Johanna Espin, Sebastian Palmas, Farah Carrasco-Rueda, Kristina Riemer, Pablo E. Allen, Nathan Berkebile, Kirsten A. Hecht, Kay Kastner-Wilcox, Mauricio M. Núñez-Regueiro, Candice Prince, Constanza Rios, Erica Ross, Bhagatveer Sangha, Tia Tyler, Judit Ungvari-Martin, Mariana Villegas, Tara T. Cataldo, Emilio M. BrunaThe scholars comprising journal editorial boards play a critical role in defining the trajectory of knowledge in their field. Nevertheless, studies of editorial board composition remain rare, especially those focusing on journals publishing research in the increasingly globalized fields of science, technology, engineering, and math (STEM). Using metrics for quantifying the diversity of ecological communities, we quantified international representation on the 1985–2014 editorial boards of 24 environmental biology journals. Over the course of 3 decades, there were 3,827 unique scientists based in 70 countries who served as editors. The size of the editorial community increased over time—the number of editors serving in 2014 was 4-fold greater than in 1985—as did the number of countries in which editors were based. Nevertheless, editors based outside the “Global North” (the group of economically developed countries with high per capita gross domestic product [GDP] that collectively concentrate most global wealth) were extremely rare. Furthermore, 67.18% of all editors were based in either the United States or the United Kingdom. Consequently, geographic diversity—already low in 1985—remained unchanged through 2014. We argue that this limited geographic diversity can detrimentally affect the creativity of scholarship published in journals, the progress and direction of research, the composition of the STEM workforce, and the development of science in Latin America, Africa, the Middle East, and much of Asia (i.e., the “Global South”).
      PubDate: 2017-12-12T22:00:00Z
      DOI: 10.1371/journal.pbio.2002760
  • Correction: Novel Role of NOX in Supporting Aerobic Glycolysis in Cancer
           Cells with Mitochondrial Dysfunction and as a Potential Target for Cancer

    • Authors: Weiqin Lu Yumin Hu Gang Chen Zhao Chen Hui Zhang Feng Wang Li Feng Helene Pelicano Hua Wang Michael J. Keating Jinsong Liu Wallace McKeehan Huamin Wang Yongde Luo Peng Huang
      Abstract: by Weiqin Lu, Yumin Hu, Gang Chen, Zhao Chen, Hui Zhang, Feng Wang, Li Feng, Helene Pelicano, Hua Wang, Michael J. Keating, Jinsong Liu, Wallace McKeehan, Huamin Wang, Yongde Luo, Peng Huang
      PubDate: 2017-12-11T22:00:00Z
      DOI: 10.1371/journal.pbio.1002616
  • The Ink4a/Arf locus operates as a regulator of the circadian clock
           modulating RAS activity

    • Authors: Rukeia El-Athman Nikolai N. Genov Jeannine Mazuch Kaiyang Zhang Yong Yu Luise Fuhr Mónica Abreu Yin Li Thomas Wallach Achim Kramer Clemens A. Schmitt Angela Relógio
      Abstract: by Rukeia El-Athman, Nikolai N. Genov, Jeannine Mazuch, Kaiyang Zhang, Yong Yu, Luise Fuhr, Mónica Abreu, Yin Li, Thomas Wallach, Achim Kramer, Clemens A. Schmitt, Angela RelógioThe mammalian circadian clock and the cell cycle are two major biological oscillators whose coupling influences cell fate decisions. In the present study, we use a model-driven experimental approach to investigate the interplay between clock and cell cycle components and the dysregulatory effects of RAS on this coupled system. In particular, we focus on the Ink4a/Arf locus as one of the bridging clock-cell cycle elements. Upon perturbations by the rat sarcoma viral oncogene (RAS), differential effects on the circadian phenotype were observed in wild-type and Ink4a/Arf knock-out mouse embryonic fibroblasts (MEFs), which could be reproduced by our modelling simulations and correlated with opposing cell cycle fate decisions. Interestingly, the observed changes can be attributed to in silico phase shifts in the expression of core-clock elements. A genome-wide analysis revealed a set of differentially expressed genes that form an intricate network with the circadian system with enriched pathways involved in opposing cell cycle phenotypes. In addition, a machine learning approach complemented by cell cycle analysis classified the observed cell cycle fate decisions as dependent on Ink4a/Arf and the oncogene RAS and highlighted a putative fine-tuning role of Bmal1 as an elicitor of such processes, ultimately resulting in increased cell proliferation in the Ink4a/Arf knock-out scenario. This indicates that the dysregulation of the core-clock might work as an enhancer of RAS-mediated regulation of the cell cycle. Our combined in silico and in vitro approach highlights the important role of the circadian clock as an Ink4a/Arf-dependent modulator of oncogene-induced cell fate decisions, reinforcing its function as a tumour-suppressor and the close interplay between the clock and the cell cycle network.
      PubDate: 2017-12-07T22:00:00Z
      DOI: 10.1371/journal.pbio.2002940
  • Slam protein dictates subcellular localization and translation of its own

    • Authors: Shuling Yan Sreemukta Acharya Stephanie Gröning Jörg Großhans
      Abstract: by Shuling Yan, Sreemukta Acharya, Stephanie Gröning, Jörg GroßhansMany mRNAs specifically localize within the cytoplasm and are present in RNA-protein complexes. It is generally assumed that localization and complex formation of these RNAs are controlled by trans-acting proteins encoded by genes different than the RNAs themselves. Here, we analyze slow as molasses (slam) mRNA that prominently colocalizes with its encoded protein at the basal cortical compartment during cellularization. The functional implications of this striking colocalization have been unknown. Here, we show that slam mRNA translation is spatiotemporally controlled. We found that translation was largely restricted to the onset of cellularization when Slam protein levels at the basal domain sharply increase. Slam mRNA was translated locally, at least partially, as not yet translated mRNA transiently accumulated at the basal region. Slam RNA accumulated at the basal domain only if Slam protein was present. Furthermore, a slam RNA with impaired localization but full coding capacity was only weakly translated. We detected a biochemical interaction of slam mRNA and protein as demonstrated by specific co-immunoprecipitation from embryonic lysate. The intimate relationship of slam mRNA and protein may constitute a positive feedback loop that facilitates and controls timely and rapid accumulation of Slam protein at the prospective basal region.
      PubDate: 2017-12-04T22:00:00Z
      DOI: 10.1371/journal.pbio.2003315
  • Task relevance modulates the behavioural and neural effects of sensory

    • Authors: Ryszard Auksztulewicz Karl J. Friston Anna C. Nobre
      Abstract: by Ryszard Auksztulewicz, Karl J. Friston, Anna C. NobreThe brain is thought to generate internal predictions to optimize behaviour. However, it is unclear whether predictions signalling is an automatic brain function or depends on task demands. Here, we manipulated the spatial/temporal predictability of visual targets, and the relevance of spatial/temporal information provided by auditory cues. We used magnetoencephalography (MEG) to measure participants’ brain activity during task performance. Task relevance modulated the influence of predictions on behaviour: spatial/temporal predictability improved spatial/temporal discrimination accuracy, but not vice versa. To explain these effects, we used behavioural responses to estimate subjective predictions under an ideal-observer model. Model-based time-series of predictions and prediction errors (PEs) were associated with dissociable neural responses: predictions correlated with cue-induced beta-band activity in auditory regions and alpha-band activity in visual regions, while stimulus-bound PEs correlated with gamma-band activity in posterior regions. Crucially, task relevance modulated these spectral correlates, suggesting that current goals influence PE and prediction signalling.
      PubDate: 2017-12-04T22:00:00Z
      DOI: 10.1371/journal.pbio.2003143
  • Sonic Kayaks: Environmental monitoring and experimental music by citizens

    • Authors: Amber G. F. Griffiths Kirsty M. Kemp Kaffe Matthews Joanne K. Garrett David J. Griffiths
      Abstract: by Amber G. F. Griffiths, Kirsty M. Kemp, Kaffe Matthews, Joanne K. Garrett, David J. GriffithsThe Sonic Kayak is a musical instrument used to investigate nature and developed during open hacklab events. The kayaks are rigged with underwater environmental sensors, which allow paddlers to hear real-time water temperature sonifications and underwater sounds, generating live music from the marine world. Sensor data is also logged every second with location, time and date, which allows for fine-scale mapping of water temperatures and underwater noise that was previously unattainable using standard research equipment. The system can be used as a citizen science data collection device, research equipment for professional scientists, or a sound art installation in its own right.
      PubDate: 2017-11-30T22:00:00Z
      DOI: 10.1371/journal.pbio.2004044
  • Perceptual integration rapidly activates dorsal visual pathway to guide
           local processing in early visual areas

    • Authors: Ling Liu Fan Wang Ke Zhou Nai Ding Huan Luo
      Abstract: by Ling Liu, Fan Wang, Ke Zhou, Nai Ding, Huan LuoRapidly grouping local elements into an organized object (i.e., perceptual integration) is a fundamental yet challenging task, especially in noisy contexts. Previous studies demonstrate that ventral visual pathway, which is widely known to mediate object recognition, engages in the process by conveying object-level information processed in high-level areas to modulate low-level sensory areas. Meanwhile, recent evidence suggests that the dorsal visual pathway, which is not typically attributable to object recognition, is also involved in the process. However, the underlying whole-brain fine spatiotemporal neuronal dynamics remains unknown. Here we used magnetoencephalography (MEG) recordings in combination with a temporal response function (TRF) approach to dissociate the time-resolved neuronal response that specifically tracks the perceptual grouping course. We demonstrate that perceptual integration initiates robust and rapid responses along the dorsal visual pathway in a reversed hierarchical manner, faster than the ventral pathway. Specifically, the anterior intraparietal sulcus (IPS) responds first (i.e., within 100 ms), followed by activities backpropagating along the dorsal pathway to early visual areas (EVAs). The IPS activity causally modulates the EVA response, even when the global form information is task-irrelevant. The IPS-to-EVA response profile fails to appear when the global form could not be perceived. Our results support the crucial function of the dorsal visual pathway in perceptual integration, by quickly extracting a coarse global template (i.e., an initial object representation) within first 100 ms to guide subsequent local sensory processing so that the ambiguities in the visual inputs can be efficiently resolved.
      PubDate: 2017-11-30T22:00:00Z
      DOI: 10.1371/journal.pbio.2003646
  • Evaluation of RNAi and CRISPR technologies by large-scale gene expression
           profiling in the Connectivity Map

    • Authors: Ian Smith Peyton G. Greenside Ted Natoli David L. Lahr David Wadden Itay Tirosh Rajiv Narayan David E. Root Todd R. Golub Aravind Subramanian John G. Doench
      Abstract: by Ian Smith, Peyton G. Greenside, Ted Natoli, David L. Lahr, David Wadden, Itay Tirosh, Rajiv Narayan, David E. Root, Todd R. Golub, Aravind Subramanian, John G. DoenchThe application of RNA interference (RNAi) to mammalian cells has provided the means to perform phenotypic screens to determine the functions of genes. Although RNAi has revolutionized loss-of-function genetic experiments, it has been difficult to systematically assess the prevalence and consequences of off-target effects. The Connectivity Map (CMAP) represents an unprecedented resource to study the gene expression consequences of expressing short hairpin RNAs (shRNAs). Analysis of signatures for over 13,000 shRNAs applied in 9 cell lines revealed that microRNA (miRNA)-like off-target effects of RNAi are far stronger and more pervasive than generally appreciated. We show that mitigating off-target effects is feasible in these datasets via computational methodologies to produce a consensus gene signature (CGS). In addition, we compared RNAi technology to clustered regularly interspaced short palindromic repeat (CRISPR)-based knockout by analysis of 373 single guide RNAs (sgRNAs) in 6 cells lines and show that the on-target efficacies are comparable, but CRISPR technology is far less susceptible to systematic off-target effects. These results will help guide the proper use and analysis of loss-of-function reagents for the determination of gene function.
      PubDate: 2017-11-30T22:00:00Z
      DOI: 10.1371/journal.pbio.2003213
  • Correction: Approach-Induced Biases in Human Information Sampling

    • Authors: Laurence T. Hunt Robb B. Rutledge W. M. Nishantha Malalasekera Steven W. Kennerley Raymond J. Dolan
      Abstract: by Laurence T. Hunt, Robb B. Rutledge, W. M. Nishantha Malalasekera, Steven W. Kennerley, Raymond J. Dolan
      PubDate: 2017-11-30T22:00:00Z
      DOI: 10.1371/journal.pbio.1002618
  • Regulation of actions and habits by ventral hippocampal trkB and
           adolescent corticosteroid exposure

    • Authors: Elizabeth T. Barfield Kyle J. Gerber Kelsey S. Zimmermann Kerry J. Ressler Ryan G. Parsons Shannon L. Gourley
      Abstract: by Elizabeth T. Barfield, Kyle J. Gerber, Kelsey S. Zimmermann, Kerry J. Ressler, Ryan G. Parsons, Shannon L. GourleyIn humans and rodents, stress promotes habit-based behaviors that can interfere with action—outcome decision-making. Further, developmental stressor exposure confers long-term habit biases across rodent—primate species. Despite these homologies, mechanisms remain unclear. We first report that exposure to the primary glucocorticoid corticosterone (CORT) in adolescent mice recapitulates multiple neurobehavioral consequences of stressor exposure, including long-lasting biases towards habit-based responding in a food-reinforced operant conditioning task. In both adolescents and adults, CORT also caused a shift in the balance between full-length tyrosine kinase receptor B (trkB) and a truncated form of this neurotrophin receptor, favoring the inactive form throughout multiple corticolimbic brain regions. In adolescents, phosphorylation of the trkB substrate extracellular signal-regulated kinase 42/44 (ERK42/44) in the ventral hippocampus was also diminished, a long-term effect that persisted for at least 12 wk. Administration of the trkB agonist 7,8-dihydroxyflavone (7,8-DHF) during adolescence at doses that stimulated ERK42/44 corrected long-lasting corticosterone-induced behavioral abnormalities. Meanwhile, viral-mediated overexpression of truncated trkB in the ventral hippocampus reduced local ERK42/44 phosphorylation and was sufficient to induce habit-based and depression-like behaviors. Together, our findings indicate that ventral hippocampal trkB is essential to goal-directed action selection, countering habit-based behavior otherwise facilitated by developmental stress hormone exposure. They also reveal an early-life sensitive period during which trkB—ERK42/44 tone determines long-term behavioral outcomes.
      PubDate: 2017-11-29T22:00:00Z
      DOI: 10.1371/journal.pbio.2003000
  • Connectivity and systemic resilience of the Great Barrier Reef

    • Authors: Karlo Hock Nicholas H. Wolff Juan C. Ortiz Scott A. Condie Kenneth R. N. Anthony Paul G. Blackwell Peter J. Mumby
      Abstract: by Karlo Hock, Nicholas H. Wolff, Juan C. Ortiz, Scott A. Condie, Kenneth R. N. Anthony, Paul G. Blackwell, Peter J. MumbyAustralia’s iconic Great Barrier Reef (GBR) continues to suffer from repeated impacts of cyclones, coral bleaching, and outbreaks of the coral-eating crown-of-thorns starfish (COTS), losing much of its coral cover in the process. This raises the question of the ecosystem’s systemic resilience and its ability to rebound after large-scale population loss. Here, we reveal that around 100 reefs of the GBR, or around 3%, have the ideal properties to facilitate recovery of disturbed areas, thereby imparting a level of systemic resilience and aiding its continued recovery. These reefs (1) are highly connected by ocean currents to the wider reef network, (2) have a relatively low risk of exposure to disturbances so that they are likely to provide replenishment when other reefs are depleted, and (3) have an ability to promote recovery of desirable species but are unlikely to either experience or spread COTS outbreaks. The great replenishment potential of these ‘robust source reefs’, which may supply 47% of the ecosystem in a single dispersal event, emerges from the interaction between oceanographic conditions and geographic location, a process that is likely to be repeated in other reef systems. Such natural resilience of reef systems will become increasingly important as the frequency of disturbances accelerates under climate change.
      PubDate: 2017-11-28T22:00:00Z
      DOI: 10.1371/journal.pbio.2003355
  • Pseudomonas aeruginosa exoproducts determine antibiotic efficacy against
           Staphylococcus aureus

    • Authors: Lauren Radlinski Sarah E. Rowe Laurel B. Kartchner Robert Maile Bruce A. Cairns Nicholas P. Vitko Cindy J. Gode Anne M. Lachiewicz Matthew C. Wolfgang Brian P. Conlon
      Abstract: by Lauren Radlinski, Sarah E. Rowe, Laurel B. Kartchner, Robert Maile, Bruce A. Cairns, Nicholas P. Vitko, Cindy J. Gode, Anne M. Lachiewicz, Matthew C. Wolfgang, Brian P. ConlonChronic coinfections of Staphylococcus aureus and Pseudomonas aeruginosa frequently fail to respond to antibiotic treatment, leading to significant patient morbidity and mortality. Currently, the impact of interspecies interaction on S. aureus antibiotic susceptibility remains poorly understood. In this study, we utilize a panel of P. aeruginosa burn wound and cystic fibrosis (CF) lung isolates to demonstrate that P. aeruginosa alters S. aureus susceptibility to bactericidal antibiotics in a variable, strain-dependent manner and further identify 3 independent interactions responsible for antagonizing or potentiating antibiotic activity against S. aureus. We find that P. aeruginosa LasA endopeptidase potentiates lysis of S. aureus by vancomycin, rhamnolipids facilitate proton-motive force-independent tobramycin uptake, and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) induces multidrug tolerance in S. aureus through respiratory inhibition and reduction of cellular ATP. We find that the production of each of these factors varies between clinical isolates and corresponds to the capacity of each isolate to alter S. aureus antibiotic susceptibility. Furthermore, we demonstrate that vancomycin treatment of a S. aureus mouse burn infection is potentiated by the presence of a LasA-producing P. aeruginosa population. These findings demonstrate that antibiotic susceptibility is complex and dependent not only upon the genotype of the pathogen being targeted, but also on interactions with other microorganisms in the infection environment. Consideration of these interactions will improve the treatment of polymicrobial infections.
      PubDate: 2017-11-27T22:00:00Z
      DOI: 10.1371/journal.pbio.2003981
  • Correction: Perceived Effort for Motor Control and Decision-Making

    • Authors: Ignasi Cos
      Abstract: by Ignasi Cos
      PubDate: 2017-11-22T22:00:00Z
      DOI: 10.1371/journal.pbio.1002617
  • Nucleic acid purification from plants, animals and microbes in under 30

    • Authors: Yiping Zou Michael Glenn Mason Yuling Wang Eugene Wee Conny Turni Patrick J. Blackall Matt Trau Jose Ramon Botella
      Abstract: by Yiping Zou, Michael Glenn Mason, Yuling Wang, Eugene Wee, Conny Turni, Patrick J. Blackall, Matt Trau, Jose Ramon BotellaNucleic acid amplification is a powerful molecular biology tool, although its use outside the modern laboratory environment is limited due to the relatively cumbersome methods required to extract nucleic acids from biological samples. To address this issue, we investigated a variety of materials for their suitability for nucleic acid capture and purification. We report here that untreated cellulose-based paper can rapidly capture nucleic acids within seconds and retain them during a single washing step, while contaminants present in complex biological samples are quickly removed. Building on this knowledge, we have successfully created an equipment-free nucleic acid extraction dipstick methodology that can obtain amplification-ready DNA and RNA from plants, animals, and microbes from difficult biological samples such as blood and leaves from adult trees in less than 30 seconds. The simplicity and speed of this method as well as the low cost and availability of suitable materials (e.g., common paper towelling), means that nucleic acid extraction is now more accessible and affordable for researchers and the broader community. Furthermore, when combined with recent advancements in isothermal amplification and naked eye DNA visualization techniques, the dipstick extraction technology makes performing molecular diagnostic assays achievable in limited resource settings including university and high school classrooms, field-based environments, and developing countries.
      PubDate: 2017-11-21T22:00:00Z
      DOI: 10.1371/journal.pbio.2003916
  • Sugar industry sponsorship of germ-free rodent studies linking sucrose to
           hyperlipidemia and cancer: An historical analysis of internal documents

    • Authors: Cristin E. Kearns Dorie Apollonio Stanton A. Glantz
      Abstract: by Cristin E. Kearns, Dorie Apollonio, Stanton A. GlantzIn 1965, the Sugar Research Foundation (SRF) secretly funded a review in the New England Journal of Medicine that discounted evidence linking sucrose consumption to blood lipid levels and hence coronary heart disease (CHD). SRF subsequently funded animal research to evaluate sucrose’s CHD risks. The objective of this study was to examine the planning, funding, and internal evaluation of an SRF-funded research project titled “Project 259: Dietary Carbohydrate and Blood Lipids in Germ-Free Rats,” led by Dr. W.F.R. Pover at the University of Birmingham, Birmingham, United Kingdom, between 1967 and 1971. A narrative case study method was used to assess SRF Project 259 from 1967 to 1971 based on sugar industry internal documents. Project 259 found a statistically significant decrease in serum triglycerides in germ-free rats fed a high sugar diet compared to conventional rats fed a basic PRM diet (a pelleted diet containing cereal meals, soybean meals, whitefish meal, and dried yeast, fortified with a balanced vitamin supplement and trace element mixture). The results suggested to SRF that gut microbiota have a causal role in carbohydrate-induced hypertriglyceridemia. A study comparing conventional rats fed a high-sugar diet to those fed a high-starch diet suggested that sucrose consumption might be associated with elevated levels of beta-glucuronidase, an enzyme previously associated with bladder cancer in humans. SRF terminated Project 259 without publishing the results. The sugar industry did not disclose evidence of harm from animal studies that would have (1) strengthened the case that the CHD risk of sucrose is greater than starch and (2) caused sucrose to be scrutinized as a potential carcinogen. The influence of the gut microbiota in the differential effects of sucrose and starch on blood lipids, as well as the influence of carbohydrate quality on beta-glucuronidase and cancer activity, deserve further scrutiny.
      PubDate: 2017-11-21T22:00:00Z
      DOI: 10.1371/journal.pbio.2003460
  • Mutualism in museums: A model for engaging undergraduates in biodiversity

    • Authors: Anna E. Hiller Carla Cicero Monica J. Albe Theresa L. W. Barclay Carol L. Spencer Michelle S. Koo Rauri C. K. Bowie Eileen A. Lacey
      Abstract: by Anna E. Hiller, Carla Cicero, Monica J. Albe, Theresa L. W. Barclay, Carol L. Spencer, Michelle S. Koo, Rauri C. K. Bowie, Eileen A. LaceyMuseums have an untapped potential to engage students in hands-on learning. Here, we describe the development of a tiered museum-based program at the University of California, Berkeley as a model for engaging undergraduates in biodiversity science. This decade-long effort to increase student participation in collections demonstrates the mutual benefits of undergraduate involvement. Museums benefit from critical help in collections care and an increased intellectual vitality, while students simultaneously gain essential research skills and an unparalleled exposure to biodiversity. Five first steps to creating a program are: dedicate a coordinator, offer credit, diversify participation, create a tiered structure, and build community.
      PubDate: 2017-11-21T22:00:00Z
      DOI: 10.1371/journal.pbio.2003318
  • Drivers of genetic diversity in secondary metabolic gene clusters within a
           fungal species

    • Authors: Abigail L. Lind Jennifer H. Wisecaver Catarina Lameiras Philipp Wiemann Jonathan M. Palmer Nancy P. Keller Fernando Rodrigues Gustavo H. Goldman Antonis Rokas
      Abstract: by Abigail L. Lind, Jennifer H. Wisecaver, Catarina Lameiras, Philipp Wiemann, Jonathan M. Palmer, Nancy P. Keller, Fernando Rodrigues, Gustavo H. Goldman, Antonis RokasFilamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here, we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide within-species variation revealed 5 general types of variation in SM gene clusters: nonfunctional gene polymorphisms; gene gain and loss polymorphisms; whole cluster gain and loss polymorphisms; allelic polymorphisms, in which different alleles corresponded to distinct, nonhomologous clusters; and location polymorphisms, in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms, the detection of which requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and nonhomologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, and genomic deletion and insertion events as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within A. fumigatus have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns.
      PubDate: 2017-11-17T22:00:00Z
      DOI: 10.1371/journal.pbio.2003583
  • The prehistory of biology preprints: A forgotten experiment from the

    • Authors: Matthew Cobb
      Abstract: by Matthew CobbIn 1961, the National Institutes of Health (NIH) began to circulate biological preprints in a forgotten experiment called the Information Exchange Groups (IEGs). This system eventually attracted over 3,600 participants and saw the production of over 2,500 different documents, but by 1967, it was effectively shut down following the refusal of journals to accept articles that had been circulated as preprints. This article charts the rise and fall of the IEGs and explores the parallels with the 1990s and the biomedical preprint movement of today.
      PubDate: 2017-11-16T22:00:00Z
      DOI: 10.1371/journal.pbio.2003995
  • Conservation demands safe gene drive

    • Authors: Kevin M. Esvelt Neil J. Gemmell
      Abstract: by Kevin M. Esvelt, Neil J. GemmellInterest in developing gene drive systems to control invasive species is growing, with New Zealand reportedly considering the nascent technology as a way to locally eliminate the mammalian pests that threaten its unique flora and fauna. If gene drives successfully eradicated these invasive populations, many would rejoice, but what are the possible consequences' Here, we explore the risk of accidental spread posed by self-propagating gene drive technologies, highlight new gene drive designs that might achieve better outcomes, and explain why we need open and international discussions concerning a technology that could have global ramifications.
      PubDate: 2017-11-16T22:00:00Z
      DOI: 10.1371/journal.pbio.2003850
  • Correlates of decisional dynamics in the dorsal anterior cingulate cortex

    • Authors: Habiba Azab Benjamin Y. Hayden
      Abstract: by Habiba Azab, Benjamin Y. HaydenWe hypothesized that during binary economic choice, decision makers use the first option they attend as a default to which they compare the second. To test this idea, we recorded activity of neurons in the dorsal anterior cingulate cortex (dACC) of macaques choosing between gambles presented asynchronously. We find that ensemble encoding of the value of the first offer includes both choice-dependent and choice-independent aspects, as if reflecting a partial decision. That is, its responses are neither entirely pre- nor post-decisional. In contrast, coding of the value of the second offer is entirely decision dependent (i.e., post-decisional). This result holds even when offer-value encodings are compared within the same time period. Additionally, we see no evidence for 2 pools of neurons linked to the 2 offers; instead, all comparison appears to occur within a single functionally homogenous pool of task-selective neurons. These observations suggest that economic choices reflect a context-dependent evaluation of attended options. Moreover, they raise the possibility that value representations reflect, to some extent, a tentative commitment to a choice.
      PubDate: 2017-11-15T22:00:00Z
      DOI: 10.1371/journal.pbio.2003091
  • Pioneer cells established by the [SWI+] prion can promote dispersal and
           out-crossing in yeast

    • Authors: Gregory A. Newby Susan Lindquist
      Abstract: by Gregory A. Newby, Susan LindquistTo thrive in an ever-changing environment, microbes must widely distribute their progeny to colonize new territory. Simultaneously, they must evolve and adapt to the stresses of unpredictable surroundings. In both of these regards, diversity is key—if an entire population moved together or responded to the environment in the same way, it could easily go extinct. Here, we show that the epigenetic prion switch [SWI+] establishes a specialized subpopulation with a “pioneer” phenotypic program in Saccharomyces cerevisiae. Cells in the pioneer state readily disperse in water, enabling them to migrate and colonize new territory. Pioneers are also more likely to find and mate with genetically diverse partners, as inhibited mating-type switching causes mother cells to shun their own daughters. In the nonprion [swi−] state, cells instead have a “settler” phenotype, forming protective flocs and tending to remain in their current position. Settler cells are better able to withstand harsh conditions like drought and alkaline pH. We propose that these laboratory observations reveal a strategy employed in the wild to rapidly diversify and grant distinct, useful roles to cellular subpopulations that benefit the population as a whole.
      PubDate: 2017-11-14T22:00:00Z
      DOI: 10.1371/journal.pbio.2003476
  • The poverty-related neglected diseases: Why basic research matters

    • Authors: Peter J. Hotez
      Abstract: by Peter J. HotezTogether, malaria and the neglected tropical diseases (NTDs) kill more than 800,000 people annually, while creating long-term disability in millions more. International support for mass drug administration, bed nets, and other preventive measures has resulted in huge public health gains, while support for translational research is leading to the development of some new neglected disease drugs, diagnostics, and vaccines. However, funding for basic science research has not kept up, such that we are missing opportunities to create a more innovative pipeline of control tools for parasitic and related diseases. There is an urgent need to expand basic science approaches for neglected diseases, especially in the areas of systems biology and immunology; ecology, evolution, and mathematical biology; functional and comparative OMICs; gene editing; expanded use of model organisms; and a new single-cell combinatorial indexing RNA sequencing approach. The world’s poor deserve access to innovation for neglected diseases. It should be considered a fundamental human right.
      PubDate: 2017-11-09T22:00:00Z
      DOI: 10.1371/journal.pbio.2004186
  • Capacity of tTreg generation is not impaired in the atrophied thymus

    • Authors: Jiyoung Oh Weikan Wang Rachel Thomas Dong-Ming Su
      Abstract: by Jiyoung Oh, Weikan Wang, Rachel Thomas, Dong-Ming SuPostnatal thymic epithelial cell (TEC) homeostatic defect- or natural aging-induced thymic atrophy results in a decline in central T-cell tolerance establishment, which is constituted by thymocyte negative selection and cluster of differentiation (CD) 4+ thymic regulatory T (tTreg) cell generation. Emerging evidence shows this decline mainly results from defects in negative selection, but there is insufficient evidence regarding whether tTreg cell generation is also impaired. We mechanistically studied tTreg cell generation in the atrophied thymus by utilizing both postnatal TEC-defective (resulting from FoxN1-floxed conditional knockout [cKO]) and naturally aged mouse models. We found that the capacity of tTreg cell generation was not impaired compared to CD4+ thymic conventional T cells, suggesting thymic atrophy positively influences tTreg cell generation. This is potentially attributed to decreased T cell receptor (TCR) signaling strength due to inefficiency in promiscuous expression of self-antigens or presenting a neo-self-antigen by medullary TECs, displaying decreased negative selection-related marker genes (Nur77 and CD5high) in CD4 single positive (SP) thymocytes. Our results provide evidence that the atrophied thymus attempts to balance the defective negative selection by enhancing tTreg cell generation to maintain central T-cell tolerance in the elderly. Once the balance is broken, age-related diseases could take place.
      PubDate: 2017-11-08T22:00:00Z
      DOI: 10.1371/journal.pbio.2003352
  • Glutamine deficiency induces DNA alkylation damage and sensitizes cancer
           cells to alkylating agents through inhibition of ALKBH enzymes

    • Authors: Thai Q. Tran Mari B. Ishak Gabra Xazmin H. Lowman Ying Yang Michael A. Reid Min Pan Timothy R. O’Connor Mei Kong
      Abstract: by Thai Q. Tran, Mari B. Ishak Gabra, Xazmin H. Lowman, Ying Yang, Michael A. Reid, Min Pan, Timothy R. O’Connor, Mei KongDriven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON) or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.
      PubDate: 2017-11-06T22:00:00Z
      DOI: 10.1371/journal.pbio.2002810
  • Stochastic loss and gain of symmetric divisions in the C. elegans
           epidermis perturbs robustness of stem cell number

    • Authors: Dimitris Katsanos Sneha L. Koneru Lamia Mestek Boukhibar Nicola Gritti Ritobrata Ghose Peter J. Appleford Maria Doitsidou Alison Woollard Jeroen S. van Zon Richard J. Poole Michalis Barkoulas
      Abstract: by Dimitris Katsanos, Sneha L. Koneru, Lamia Mestek Boukhibar, Nicola Gritti, Ritobrata Ghose, Peter J. Appleford, Maria Doitsidou, Alison Woollard, Jeroen S. van Zon, Richard J. Poole, Michalis BarkoulasBiological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens.
      PubDate: 2017-11-06T22:00:00Z
      DOI: 10.1371/journal.pbio.2002429
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