Attenuation of chronic antiviral T-cell responses through constitutive COX2-dependent prostanoid synthesis by lymph node fibroblasts
by Karin Schaeuble, H élène Cannelle, Stéphanie Favre, Hsin-Ying Huang, Susanne G. Oberle, Daniel E. Speiser, Dietmar Zehn, Sanjiv A. Luther Lymphoid T-zone fibroblastic reticular cells (FRCs) actively promote T-cell trafficking, homeostasis, and expansion but can also attenuate excessive T-cell responses via inducible nitric oxide (NO) and constitutive prostanoid release. It remains unclear how these FRC-derived mediators dampen T-cel l responses and whether this occurs in vivo. Here, we confirm that murine lymph node (LN) FRCs produce prostaglandin E2 (PGE2) in a cyclooxygenase-2 (COX2)-dependent an...
Source: PLoS Biology: Archived Table of Contents - July 15, 2019 Category: Biology Authors: Karin Schaeuble Source Type: research

Activity patterns in mammals: Circadian dominance challenged
by David G. Hazlerigg, Nicholas J. C. Tyler The evidence that diel patterns of physiology and behaviour in mammals are governed by circadian ‘clocks’ is based almost entirely on studies of nocturnal rodents. The emergent circadian paradigm, however, neglects the roles of energy metabolism and alimentary function (feeding and digestion) as determinants of activity pattern. The temporal control of activity varies widely across taxa, and ungulates, microtine rodents, and insectivores provide examples in which circadian timekeeping is vestigial. The nocturnal rodent/human paradigm of circadian organisation is unhe...
Source: PLoS Biology: Archived Table of Contents - July 15, 2019 Category: Biology Authors: David G. Hazlerigg Source Type: research

Spectrin-based membrane skeleton supports ciliogenesis
by Ru Jia, Dongdong Li, Ming Li, Yongping Chai, Yufan Liu, Zhongyun Xie, Wenxin Shao, Chao Xie, Liuju Li, Xiaoshuai Huang, Liangyi Chen, Wei Li, Guangshuo Ou Cilia are remarkable cellular devices that power cell motility and transduce extracellular signals. To assemble a cilium, a cylindrical array of 9 doublet microtubules push out an extension of the plasma membrane. Membrane tension regulates cilium formation; however, molecular pathways that link m echanical stimuli to ciliogenesis are unclear. Using genome editing, we introduced hereditary elliptocytosis (HE)- and spinocerebellar ataxia (SCA)-associated mutations int...
Source: PLoS Biology: Archived Table of Contents - July 12, 2019 Category: Biology Authors: Ru Jia Source Type: research

Successful validation of a larval dispersal model using genetic parentage data
by Michael Bode, Jeffrey M. Leis, Luciano B. Mason, David H. Williamson, Hugo B. Harrison, Severine Choukroun, Geoffrey P. Jones Larval dispersal is a critically important yet enigmatic process in marine ecology, evolution, and conservation. Determining the distance and direction that tiny larvae travel in the open ocean continues to be a challenge. Our current understanding of larval dispersal patterns at management-releva nt scales is principally and separately informed by genetic parentage data and biological-oceanographic (biophysical) models. Parentage datasets provide clear evidence of individual larval dispersal ev...
Source: PLoS Biology: Archived Table of Contents - July 12, 2019 Category: Biology Authors: Michael Bode Source Type: research

Macaque anterior cingulate cortex deactivation impairs performance and alters lateral prefrontal oscillatory activities in a rule-switching task
by Liya Ma, Jason L. Chan, Kevin Johnston, Stephen G. Lomber, Stefan Everling In primates, both the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (dlPFC) are key regions of the frontoparietal cognitive control network. To study the role of the dACC and its communication with the dlPFC in cognitive control, we recorded local field potentials (LFPs) from the dlPFC before and during the reversible deactivation of the dACC, in macaque monkeys engaging in uncued switches between 2 stimulus-response rules, namely prosaccade and antisaccade. Cryogenic dACC deactivation impaired response accuracy ...
Source: PLoS Biology: Archived Table of Contents - July 11, 2019 Category: Biology Authors: Liya Ma Source Type: research

A novel Ca2+-binding protein that can rapidly transduce auxin responses during root growth
by Ora Hazak, Elad Mamon, Meirav Lavy, Hasana Sternberg, Smrutisanjita Behera, Ina Schmitz-Thom, Daria Bloch, Olga Dementiev, Itay Gutman, Tomer Danziger, Netanel Schwarz, Anas Abuzeineh, Keithanne Mockaitis, Mark Estelle, Joel A. Hirsch, J örg Kudla, Shaul Yalovsky Signaling cross talks between auxin, a regulator of plant development, and Ca2+, a universal second messenger, have been proposed to modulate developmental plasticity in plants. However, the underlying molecular mechanisms are largely unknown. Here, we report that inArabidopsis roots, auxin elicits specific Ca2+ signaling patterns that spatially coincide ...
Source: PLoS Biology: Archived Table of Contents - July 11, 2019 Category: Biology Authors: Ora Hazak Source Type: research

Correction: Attention promotes the neural encoding of prediction errors
by Cooper A. Smout, Matthew F. Tang, Marta I. Garrido, Jason B. Mattingley (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - July 10, 2019 Category: Biology Authors: Cooper A. Smout Source Type: research

Spermine in semen of male sea lamprey acts as a sex pheromone
by Anne M. Scott, Zhe Zhang, Liang Jia, Ke Li, Qinghua Zhang, Thomas Dexheimer, Edmund Ellsworth, Jianfeng Ren, Yu-Wen Chung-Davidson, Yao Zu, Richard R. Neubig, Weiming Li Semen is fundamental for sexual reproduction. The non-sperm part of ejaculated semen, or seminal plasma, facilitates the delivery of sperm to the eggs. The seminal plasma of some species with internal fertilization contains anti-aphrodisiac molecules that deter promiscuity in post-copulatory femal es, conferring fitness benefits to the ejaculating male. By contrast, in some taxa with external fertilization such as fish, exposure to semen promotes spawn...
Source: PLoS Biology: Archived Table of Contents - July 9, 2019 Category: Biology Authors: Anne M. Scott Source Type: research

Novel antibiotics effective against gram-positive and -negative multi-resistant bacteria with limited resistance
by Ir ène Nicolas, Valérie Bordeau, Arnaud Bondon, Michèle Baudy-Floc’h, Brice Felden Antibiotics are a medical wonder, but an increasing frequency of resistance among most human pathogens is rendering them ineffective. If this trend continues, the consequences for public health and for the general community could be catastrophic. The current clinical pipeline, however, is very lim ited and is dominated by derivatives of established classes, the “me too” compounds. Here, we have exploited our recent identification of a bacterial toxin to transform it into antibiotics active on multid...
Source: PLoS Biology: Archived Table of Contents - July 9, 2019 Category: Biology Authors: Ir ène Nicolas Source Type: research

Global proteomic analyses define an environmentally contingent Hsp90 interactome and reveal chaperone-dependent regulation of stress granule proteins and the R2TP complex in a fungal pathogen
This study provides a global view of the Hsp90 interactome in a fungal pathogen, demonstrates the dynamic role of Hsp90 in response to environmental perturbations, and highlights a novel connection between Hsp90 and the regulation of mRNA-associated protein granules. (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - July 8, 2019 Category: Biology Authors: Teresa R. O ’Meara Source Type: research

Human visual cortex is organized along two genetically opposed hierarchical gradients with unique developmental and evolutionary origins
by Jesse Gomez, Zonglei Zhen, Kevin S. Weiner Human visual cortex is organized with striking consistency across individuals. While recent findings demonstrate an unexpected coupling between functional and cytoarchitectonic regions relative to the folding of human visual cortex, a unifying principle linking these anatomical and functional feat ures of the cortex remains elusive. To fill this gap in knowledge, we combined independent and ground truth measurements of cytoarchitectonic regions and genetic tissue characterization within human occipitotemporal cortex. Using a data-driven approach, we examined whether differenti...
Source: PLoS Biology: Archived Table of Contents - July 3, 2019 Category: Biology Authors: Jesse Gomez Source Type: research

Dissecting the transcriptome landscape of the human fetal neural retina and retinal pigment epithelium by single-cell RNA-seq analysis
by Yuqiong Hu, Xiaoye Wang, Boqiang Hu, Yunuo Mao, Yidong Chen, Liying Yan, Jun Yong, Ji Dong, Yuan Wei, Wei Wang, Lu Wen, Jie Qiao, Fuchou Tang The developmental pathway of the neural retina (NR) and retinal pigment epithelium (RPE) has been revealed by extensive research in mice. However, the molecular mechanisms underlying the development of the human NR and RPE, as well as the interactions between these two tissues, have not been well defined. Here, we analyzed 2,421 individual cells from human fetal NR and RPE using single-cell RNA sequencing (RNA-seq) technique and revealed the tightly regulated spatiotemporal gene ...
Source: PLoS Biology: Archived Table of Contents - July 3, 2019 Category: Biology Authors: Yuqiong Hu Source Type: research

Social intolerance is a consequence, not a cause, of dispersal in spiders
by Violette Chiara, Felipe Ramon Portugal, Raphael Jeanson From invertebrates to vertebrates, a wealth of species display transient sociality during their life cycle. Investigating the causes of dispersal in temporary associations is important to better understand population dynamics. It is also essential to identify possible mechanisms involved in the ev olutionary transition from transient to stable sociality, which has been documented repeatedly across taxa and typically requires the suppression of dispersal. In many animals, the onset of dispersal during ontogeny coincides with a sharp decline in social tolerance, but...
Source: PLoS Biology: Archived Table of Contents - July 2, 2019 Category: Biology Authors: Violette Chiara Source Type: research

Targeted genetic screening in mice through haploid embryonic stem cells identifies critical genes in bone development
by Meizhu Bai, Yujiao Han, Yuxuan Wu, Jiaoyang Liao, Lin Li, Lijun Wang, Qing Li, Wenhui Xing, Luonan Chen, Weiguo Zou, Jinsong Li Mutagenic screening is powerful for identifying key genes involved in developmental processes. However, such screens are successful only in lower organisms. Here, we develop a targeted genetic screening approach in mice through combining androgenetic haploid embryonic stem cells (AG-haESCs) and cl ustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 (CRISPR-Cas9) technology. We produced a mutant semi-cloned (SC) mice pool by oocyte injection of AG-haESCs carrying const...
Source: PLoS Biology: Archived Table of Contents - July 2, 2019 Category: Biology Authors: Meizhu Bai Source Type: research

Uncoordinated maturation of developing and regenerating postnatal mammalian vestibular hair cells
by Tian Wang, Mamiko Niwa, Zahra N. Sayyid, Davood K. Hosseini, Nicole Pham, Sherri M. Jones, Anthony J. Ricci, Alan G. Cheng Sensory hair cells are mechanoreceptors required for hearing and balance functions. From embryonic development, hair cells acquire apical stereociliary bundles for mechanosensation, basolateral ion channels that shape receptor potential, and synaptic contacts for conveying information centrally. T hese key maturation steps are sequential and presumed coupled; however, whether hair cells emerging postnatally mature similarly is unknown. Here, we show that in vivo postnatally generated and regenerate...
Source: PLoS Biology: Archived Table of Contents - July 1, 2019 Category: Biology Authors: Tian Wang Source Type: research

The Human Brain Project —Synergy between neuroscience, computing, informatics, and brain-inspired technologies
by Katrin Amunts, Alois C. Knoll, Thomas Lippert, Cyriel M. A. Pennartz, Philippe Ryvlin, Alain Destexhe, Viktor K. Jirsa, Egidio D ’Angelo, Jan G. Bjaalie The Human Brain Project (HBP) is a European flagship project with a 10-year horizon aiming to understand the human brain and to translate neuroscience knowledge into medicine and technology. To achieve such aims, the HBP explores the multilevel complexity of the brain in space and time; transfers the acquired knowledge to brain-derived applications in health, computing, and technology; and provides shared and open computing tools and data through the HBP European...
Source: PLoS Biology: Archived Table of Contents - July 1, 2019 Category: Biology Authors: Katrin Amunts Source Type: research

A polymorphic helix of a Salmonella needle protein relays signals defining distinct steps in type III secretion
by Emily Z. Guo, Daniel C. Desrosiers, Jan Zalesak, James Tolchard, M élanie Berbon, Birgit Habenstein, Thomas Marlovits, Antoine Loquet, Jorge E. Galán Type III protein-secretion machines are essential for the interactions of many pathogenic or symbiotic bacterial species with their respective eukaryotic hosts. The core component of these machines is the injectisome, a multiprotein complex that mediates the selection of substrates, their passage through the bacterial envelope, and ultimately their delivery into eukaryotic target cells. The injectisome is composed of a large cytoplasmic complex or sorting pl...
Source: PLoS Biology: Archived Table of Contents - July 1, 2019 Category: Biology Authors: Emily Z. Guo Source Type: research

Mouse HSA < sup > + < /sup > immature cardiomyocytes persist in the adult heart and expand after ischemic injury
by Mariana Valente, Tatiana Pinho Resende, Diana Santos Nascimento, Odile Burlen-Defranoux, Francisca Soares-da-Silva, Benoit Dupont, Ana Cumano, Perp étua Pinto-do-Ó The assessment of the regenerative capacity of the heart has been compromised by the lack of surface signatures to characterize cardiomyocytes (CMs). Here, combined multiparametric surface marker analysis with single-cell transcriptional profiling and in vivo transplantation identify the main mous e fetal cardiac populations and their progenitors (PRGs). We found that CMs at different stages of differentiation coexist during development. We ide...
Source: PLoS Biology: Archived Table of Contents - June 27, 2019 Category: Biology Authors: Mariana Valente Source Type: research

Fully automated leg tracking of < i > Drosophila < /i > neurodegeneration models reveals distinct conserved movement signatures
by Shuang Wu, Kah Junn Tan, Lakshmi Narasimhan Govindarajan, James Charles Stewart, Lin Gu, Joses Wei Hao Ho, Malvika Katarya, Boon Hui Wong, Eng-King Tan, Daiqin Li, Adam Claridge-Chang, Camilo Libedinsky, Li Cheng, Sherry Shiying Aw Some neurodegenerative diseases, like Parkinsons Disease (PD) and Spinocerebellar ataxia 3 (SCA3), are associated with distinct, altered gait and tremor movements that are reflective of the underlying disease etiology.Drosophila melanogaster models of neurodegeneration have illuminated our understanding of the molecular mechanisms of disease. However, it is unknown whether specific gait and ...
Source: PLoS Biology: Archived Table of Contents - June 27, 2019 Category: Biology Authors: Shuang Wu Source Type: research

Improving big citizen science data: Moving beyond haphazard sampling
by Corey T. Callaghan, Jodi J. L. Rowley, William K. Cornwell, Alistair G. B. Poore, Richard E. Major Citizen science is mainstream: millions of people contribute data to a growing array of citizen science projects annually, forming massive datasets that will drive research for years to come. Many citizen science projects implement a “leaderboard” framework, ranking the contributions based on number of records or species, encouraging further participation. But is every data point equally “valuable?” Citizen scientists collect data with distinct spatial and temporal biases, leading to unfortunate ga...
Source: PLoS Biology: Archived Table of Contents - June 27, 2019 Category: Biology Authors: Corey T. Callaghan Source Type: research

Inferring the distribution of fitness effects of spontaneous mutations in < i > Chlamydomonas reinhardtii < /i >
by Katharina B. B öndel, Susanne A. Kraemer, Toby Samuels, Deirdre McClean, Josianne Lachapelle, Rob W. Ness, Nick Colegrave, Peter D. Keightley Spontaneous mutations are the source of new genetic variation and are thus central to the evolutionary process. In molecular evolution and quantitative genetics, the nature of genetic variation depends critically on the distribution of effects of mutations on fitness and other quantitative traits. Spontaneous mutation accumulation (MA) experiments have been the principal approach for investigating the overall rate of occurrence and cumulative effect of mutations but have not...
Source: PLoS Biology: Archived Table of Contents - June 26, 2019 Category: Biology Authors: Katharina B. B öndel Source Type: research

Harnessing robotic automation and web-based technologies to modernize scientific outreach
by Orna Dahan, Bat-Shahar Dorfman, Serkan Sayin, Brittany Rosener, Tiffany Hua, Anat Yarden, Amir Mitchell Technological breakthroughs in the past two decades have ushered in a new era of biomedical research, turning it into an information-rich and technology-driven science. This scientific revolution, though evident to the research community, remains opaque to nonacademic audiences. Such knowledge gap s are likely to persist without revised strategies for science education and public outreach. To address this challenge, we developed a unique outreach program to actively engage over 100 high-school students in the investi...
Source: PLoS Biology: Archived Table of Contents - June 26, 2019 Category: Biology Authors: Orna Dahan Source Type: research

Simulations reveal challenges to artificial community selection and possible strategies for success
by Li Xie, Alex E. Yuan, Wenying Shou Multispecies microbial communities often display “community functions” arising from interactions of member species. Interactions are often difficult to decipher, making it challenging to design communities with desired functions. Alternatively, similar to artificial selection for individuals i n agriculture and industry, one could repeatedly choose communities with the highest community functions to reproduce by randomly partitioning each into multiple “Newborn” communities for the next cycle. However, previous efforts in selecting complex communities have gene...
Source: PLoS Biology: Archived Table of Contents - June 25, 2019 Category: Biology Authors: Li Xie Source Type: research

A temporal integration mechanism enhances frequency selectivity of broadband inputs to inferior colliculus
by Chen Chen, Heather L. Read, Monty A. Escab í Accurately resolving frequency components in sounds is essential for sound recognition, yet there is little direct evidence for how frequency selectivity is preserved or newly created across auditory structures. We demonstrate that prepotentials (PPs) with physiological properties resembling presy naptic potentials from broadly tuned brainstem inputs can be recorded concurrently with postsynaptic action potentials in inferior colliculus (IC). These putative brainstem inputs (PBIs) are broadly tuned and exhibit delayed and spectrally interleaved excitation and inhibiti...
Source: PLoS Biology: Archived Table of Contents - June 24, 2019 Category: Biology Authors: Chen Chen Source Type: research

An endocytic-secretory cycle participates in < i > Toxoplasma gondii < /i > in motility
by Simon Gras, Elena Jimenez-Ruiz, Christen M. Klinger, Katja Schneider, Andreas Klingl, Leandro Lemgruber, Markus Meissner Apicomplexan parasites invade host cells in an active process involving their ability to move by gliding motility. While the acto-myosin system of the parasite plays a crucial role in the formation and release of attachment sites during this process, there are still open questions regarding the in volvement of other mechanisms in parasite motility. In many eukaryotes, a secretory-endocytic cycle leads to the recycling of receptors (integrins), necessary to form attachment sites, regulation of surface...
Source: PLoS Biology: Archived Table of Contents - June 24, 2019 Category: Biology Authors: Simon Gras Source Type: research

Selection and characterization of ultrahigh potency designed ankyrin repeat protein inhibitors of < i > C < /i > . < i > difficile < /i > toxin B
by Rudo Simeon, Mengqiu Jiang, Ana M. Chamoun-Emanuelli, Hua Yu, Yongrong Zhang, Ran Meng, Zeyu Peng, Joanita Jakana, Junjie Zhang, Hanping Feng, Zhilei ChenClostridium difficile infection (CDI) is a major nosocomial disease associated with significant morbidity and mortality. The pathology of CDI stems primarily from the 2C.difficile–secreted exotoxins—toxin A (TcdA) and toxin B (TcdB)—that disrupt the tight junctions between epithelial cells leading to the loss of colonic epithelial barrier function. Here, we report the engineering of a series of monomeric and dimeric designed ankyrin repeat proteins (D...
Source: PLoS Biology: Archived Table of Contents - June 24, 2019 Category: Biology Authors: Rudo Simeon Source Type: research

Competition for hosts modulates vast antigenic diversity to generate persistent strain structure in < i > Plasmodium falciparum < /i >
by Shai Pilosof, Qixin He, Kathryn E. Tiedje, Shazia Ruybal-Pes ántez, Karen P. Day, Mercedes Pascual In their competition for hosts, parasites with antigens that are novel to the host immune system will be at a competitive advantage. The resulting frequency-dependent selection can structure parasite populations into strains of limited genetic overlap. For the causative agent of malaria,Plasmodium falciparum, the high recombination rates and associated vast diversity of its highly antigenic and multicopyvar genes preclude such clear clustering in endemic regions. This undermines the definition of strains as specifi...
Source: PLoS Biology: Archived Table of Contents - June 24, 2019 Category: Biology Authors: Shai Pilosof Source Type: research

Evolution of protein kinase substrate recognition at the active site
by David Bradley, Pedro Beltrao Protein kinases catalyse the phosphorylation of target proteins, controlling most cellular processes. The specificity of serine/threonine kinases is partly determined by interactions with a few residues near the phospho-acceptor residue, forming the so-called kinase-substrate motif. Kinases have b een extensively duplicated throughout evolution, but little is known about when in time new target motifs have arisen. Here, we show that sequence variation occurring early in the evolution of kinases is dominated by changes in specificity-determining residues. We then analysed kinase specificity ...
Source: PLoS Biology: Archived Table of Contents - June 24, 2019 Category: Biology Authors: David Bradley Source Type: research

Pleiotropy and synergistic cooperation
by David C. Queller Some forms of stable cooperation can evolve though pleiotropy with a beneficial private trait. This Formal Comment addresses a recent challenge to this idea, arguing that for synergistic, frequency-dependent cooperation, pleiotropy can raise the frequency up to a point where cooperation is favoure d on its own. (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - June 21, 2019 Category: Biology Authors: David C. Queller Source Type: research

DPPA2/4 and SUMO E3 ligase PIAS4 opposingly regulate zygotic transcriptional program
by Yao-Long Yan, Chao Zhang, Jing Hao, Xue-Lian Wang, Jia Ming, Li Mi, Jie Na, Xinli Hu, Yangming Wang The molecular mechanism controlling the zygotic genome activation (ZGA) in mammals remains poorly understood. The 2-cell (2C)-like cells spontaneously emerging from cultures of mouse embryonic stem cells (ESCs) share some key transcriptional and epigenetic programs with 2C-stage embryos. By studyi ng the transition of ESCs into 2C-like cells, we identified developmental pluripotency associated 2 and 4 (Dppa2/4) as important regulators controlling zygotic transcriptional program through directly up-regulating the expressi...
Source: PLoS Biology: Archived Table of Contents - June 21, 2019 Category: Biology Authors: Yao-Long Yan Source Type: research

The interleukin-4/PPAR γ signaling axis promotes oligodendrocyte differentiation and remyelination after brain injury
by Qingxiu Zhang, Wen Zhu, Fei Xu, Xuejiao Dai, Ligen Shi, Wei Cai, Hongfeng Mu, T. Kevin Hitchens, Lesley M. Foley, Xiangrong Liu, Fang Yu, Jie Chen, Yejie Shi, Rehana K. Leak, Yanqin Gao, Jun Chen, Xiaoming Hu The repair of white matter damage is of paramount importance for functional recovery after brain injuries. Here, we report that interleukin-4 (IL-4) promotes oligodendrocyte regeneration and remyelination. IL-4 receptor expression was detected in a variety of glial cells after ischemic brain injur y, including oligodendrocyte lineage cells. IL-4 deficiency in knockout mice resulted in greater deterioration of whit...
Source: PLoS Biology: Archived Table of Contents - June 21, 2019 Category: Biology Authors: Qingxiu Zhang Source Type: research

A natural histone H2A variant lacking the Bub1 phosphorylation site and regulated depletion of centromeric histone CENP-A foster evolvability in < i > Candida albicans < /i >
by Cedric A. Brimacombe, Jordan E. Burke, Jahan-Yar Parsa, Sandra Catania, Teresa R. O ’Meara, Jessica N. Witchley, Laura S. Burrack, Hiten D. Madhani, Suzanne M. Noble Eukaryotes have evolved elaborate mechanisms to ensure that chromosomes segregate with high fidelity during mitosis and meiosis, and yet specific aneuploidies can be adaptive during environmental stress. Here, we identify a chromatin-based system required for inducible aneuploidy in a human pathog en.Candida albicans utilizes chromosome missegregation to acquire tolerance to antifungal drugs and for nonmeiotic ploidy reduction after mating. We discov...
Source: PLoS Biology: Archived Table of Contents - June 21, 2019 Category: Biology Authors: Cedric A. Brimacombe Source Type: research

Challenges and recommendations to improve the installability and archival stability of omics computational tools
by Serghei Mangul, Thiago Mosqueiro, Richard J. Abdill, Dat Duong, Keith Mitchell, Varuni Sarwal, Brian Hill, Jaqueline Brito, Russell Jared Littman, Benjamin Statz, Angela Ka-Mei Lam, Gargi Dayama, Laura Grieneisen, Lana S. Martin, Jonathan Flint, Eleazar Eskin, Ran Blekhman Developing new software tools for analysis of large-scale biological data is a key component of advancing modern biomedical research. Scientific reproduction of published findings requires running computational tools on data generated by such studies, yet little attention is presently allocated to the installability and archival stability of computat...
Source: PLoS Biology: Archived Table of Contents - June 20, 2019 Category: Biology Authors: Serghei Mangul Source Type: research

Applying the science of measurement to biology: Why bother?
by Carmen H. Coxon, Colin Longstaff, Chris Burns Both basic and translational research are continuously evolving, but the principles that underpin research integrity remain constant. These include rational, hypothesis-driven, and adequately planned and controlled science, which is carried out openly, honestly, and ethically. An important compone nt of this should be minimising experimental irreproducibility. Biological systems, in particular, are inherently variable due to the nature of cells and tissues, as well as the complex molecules within them. As a result, it is important to understand and identify sources of varia...
Source: PLoS Biology: Archived Table of Contents - June 20, 2019 Category: Biology Authors: Carmen H. Coxon Source Type: research

FishNET: An automated relational database for zebrafish colony management
by Abiud Cantu Gutierrez, Manuel Cantu Gutierrez, Alexander M. Rhyner, Oscar E. Ruiz, George T. Eisenhoffer, Joshua D. Wythe The zebrafishDanio rerio is a powerful model system to study the genetics of development and disease. However, maintenance of zebrafish husbandry records is both time intensive and laborious, and a standardized way to manage and track the large amount of unique lines in a given laboratory or centralized facility has not been embraced by the field. Here, we present FishNET, an intuitive, open-source, relational database for managing data and information related to zebrafish husbandry and maintenance....
Source: PLoS Biology: Archived Table of Contents - June 20, 2019 Category: Biology Authors: Abiud Cantu Gutierrez Source Type: research

Neutrality in the Metaorganism
by Michael Sieber, Luc ía Pita, Nancy Weiland-Bräuer, Philipp Dirksen, Jun Wang, Benedikt Mortzfeld, Sören Franzenburg, Ruth A. Schmitz, John F. Baines, Sebastian Fraune, Ute Hentschel, Hinrich Schulenburg, Thomas C. G. Bosch, Arne Traulsen Almost all animals and plants are inhabited by diverse communities of microorganisms, the microbiota, thereby forming an integrated entity, the metaorganism. Natural selection should favor hosts that shape the community composition of these microbes to promote a beneficial host-microbe symbiosis. Indeed, animal hosts often pose selective environments, which only a subs...
Source: PLoS Biology: Archived Table of Contents - June 19, 2019 Category: Biology Authors: Michael Sieber Source Type: research

Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody
by Sunita Gulati, Frank J. Beurskens, Bart-Jan de Kreuk, Marcel Roza, Bo Zheng, Rosane B. DeOliveira, Jutamas Shaughnessy, Nancy A. Nowak, Ronald P. Taylor, Marina Botto, Xianbao He, Robin R. Ingalls, Trent M. Woodruff, Wen-Chao Song, Janine Schuurman, Peter A. Rice, Sanjay Ram Multidrug-resistantNeisseria gonorrhoeae is a global health problem. Monoclonal antibody (mAb) 2C7 recognizes a gonococcal lipooligosaccharide epitope that is expressed by>95% of clinical isolates and hastens gonococcal vaginal clearance in mice. Chimeric mAb 2C7 (human immunoglobulin G1 [IgG1]) with an E430G Fc modification that enhances Fc:Fc ...
Source: PLoS Biology: Archived Table of Contents - June 19, 2019 Category: Biology Authors: Sunita Gulati Source Type: research

Scientific Community Image Forum: A discussion forum for scientific image software
by Curtis T. Rueden, Jeanelle Ackerman, Ellen T. Arena, Jan Eglinger, Beth A. Cimini, Allen Goodman, Anne E. Carpenter, Kevin W. Eliceiri Forums and email lists play a major role in assisting scientists in using software. Previously, each open-source bioimaging software package had its own distinct forum or email list. Although each provided access to experts from various software teams, this fragmentation resulted in many scientist s not knowing where to begin with their projects. Thus, the scientific imaging community lacked a central platform where solutions could be discussed in an open, software-independent manner. I...
Source: PLoS Biology: Archived Table of Contents - June 19, 2019 Category: Biology Authors: Curtis T. Rueden Source Type: research

Birds invest wingbeats to keep a steady head and reap the ultimate benefits of flying together
by Lucy A. Taylor, Graham K. Taylor, Ben Lambert, James A. Walker, Dora Biro, Steven J. Portugal Flapping flight is the most energetically demanding form of sustained forwards locomotion that vertebrates perform. Flock dynamics therefore have significant implications for energy expenditure. Despite this, no studies have quantified the biomechanical consequences of flying in a cluster flock or pair relative to flying solo. Here, we compared the flight characteristics of homing pigeons (Columba livia) flying solo and in pairs released from a site 7 km from home, using high-precision 5 Hz global positioning system (GPS) and ...
Source: PLoS Biology: Archived Table of Contents - June 18, 2019 Category: Biology Authors: Lucy A. Taylor Source Type: research

Individual metabolomic signatures of circadian misalignment during simulated night shifts in humans
by Laura Kervezee, Nicolas Cermakian, Diane B. Boivin Misalignment of the daily sleep-wake and fasting-feeding cycles with the endogenous circadian timing system is an inevitable consequence of night shift work and is associated with adverse metabolic health effects. However, a detailed characterisation of the effects of night shifts on 24-h rhythms in the metabolome is missing. We performed targeted metabolomic profiling on plasma samples collected every 2 h from healthy human subjects during two 24-h measurement periods at baseline and on the fourth day of a simulated night shift protocol, in which the habitual sleep-wa...
Source: PLoS Biology: Archived Table of Contents - June 18, 2019 Category: Biology Authors: Laura Kervezee Source Type: research

Shining new light on mammalian diving physiology using wearable near-infrared spectroscopy
by J. Chris McKnight, Kimberley A. Bennett, Mathijs Bronkhorst, Debbie J. F. Russell, Steve Balfour, Ryan Milne, Matt Bivins, Simon E. W. Moss, Willy Colier, Ailsa J. Hall, Dave Thompson Investigation of marine mammal dive-by-dive blood distribution and oxygenation has been limited by a lack of noninvasive technology for use in freely diving animals. Here, we developed a noninvasive near-infrared spectroscopy (NIRS) device to measure relative changes in blood volume and haemoglobi n oxygenation continuously in the blubber and brain of voluntarily diving harbour seals. Our results show that seals routinely exhibit preparat...
Source: PLoS Biology: Archived Table of Contents - June 18, 2019 Category: Biology Authors: J. Chris McKnight Source Type: research

Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models
We examined neuroinflammation in the auditory cortex following noise-induced hearing loss (NIHL) and its role in tinnitus in rodent models. Our results indicate that NIHL is associated with elevated expression of proinflammatory cytokines and microglial activation—two defining features of neuroinfla mmatory responses—in the primary auditory cortex (AI). Genetic knockout of tumor necrosis factor alpha (TNF-α) or pharmacologically blocking TNF-α expression prevented neuroinflammation and ameliorated the behavioral phenotype associated with tinnitus in mice with NIHL. Conversely, infusion of T NF-&alph...
Source: PLoS Biology: Archived Table of Contents - June 18, 2019 Category: Biology Authors: Weihua Wang Source Type: research

Identification of N-linked glycans as specific mediators of neuronal uptake of acetylated α-Synuclein
by Melissa Birol, Slawomir P. Wojcik, Andrew D. Miranker, Elizabeth Rhoades Cell-to-cell transmission of toxic forms of α-Synuclein (αS) is thought to underlie disease progression in Parkinson disease. αS in humans is constitutively N-terminally acetylated (αSacetyl), although the impact of this modification is relatively unexplored. Here, we report that αSacetyl is more effective at inducing intracellular aggregation in primary neurons than unmodified αS (αSun). We identify complex N-linked glycans as binding partners for αSacetyl and demonstrate that cellular internalizati...
Source: PLoS Biology: Archived Table of Contents - June 18, 2019 Category: Biology Authors: Melissa Birol Source Type: research

The object space task shows cumulative memory expression in both mice and rats
by Lisa Genzel, Evelien Schut, Tim Schr öder, Ronny Eichler, Mehdi Khamassi, Angela Gomez, Irene Navarro Lobato, Francesco Battaglia Declarative memory encompasses representations of specific events as well as knowledge extracted by accumulation over multiple episodes. To investigate how these different sorts of memories are created, we developed a new behavioral task in rodents. The task consists of 3 distinct conditions (stab le, overlapping, and random). Rodents are exposed to multiple sample trials, in which they explore objects in specific spatial arrangements, with object identity changing from trial to trial. ...
Source: PLoS Biology: Archived Table of Contents - June 17, 2019 Category: Biology Authors: Lisa Genzel Source Type: research

Star nanoparticles delivering HIV-1 peptide minimal immunogens elicit near-native envelope antibody responses in nonhuman primates
by Joseph R. Francica, Richard Laga, Geoffrey M. Lynn, Gabriela Mu žíková, Ladislav Androvič, Baptiste Aussedat, William E. Walkowicz, Kartika Padhan, Ramiro Andrei Ramirez-Valdez, Robert Parks, Stephen D. Schmidt, Barbara J. Flynn, Yaroslav Tsybovsky, Guillaume B. E. Stewart-Jones, Kevin O. Saunders, Faezzah Baharom, Constantinos Petrovas, Barton F. Haynes, Ro bert A. Seder Peptide immunogens provide an approach to focus antibody responses to specific neutralizing sites on the HIV envelope protein (Env) trimer or on other pathogens. However, the physical characteristics of peptide immunogens can limit the...
Source: PLoS Biology: Archived Table of Contents - June 17, 2019 Category: Biology Authors: Joseph R. Francica Source Type: research

Flagellin hypervariable region determines symbiotic properties of commensal < i > Escherichia coli < /i > strains
This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of differentE.coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensalE.coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22 –mediated protection of mice against DSS-induced colitis. F...
Source: PLoS Biology: Archived Table of Contents - June 17, 2019 Category: Biology Authors: Alex Steimle Source Type: research

Cytosine-5 RNA methylation links protein synthesis to cell metabolism
by Nikoletta A. Gkatza, Cecilia Castro, Robert F. Harvey, Matthias Hei ß, Martyna C. Popis, Sandra Blanco, Susanne Bornelöv, Abdulrahim A. Sajini, Joseph G. Gleeson, Julian L. Griffin, James A. West, Stefanie Kellner, Anne E. Willis, Sabine Dietmann, Michaela Frye Posttranscriptional modifications in transfer RNA (tRNA) are often critical for normal development because they adapt protein synthesis rates to a dynamically changing microenvironment. However, the precise cellular mechanisms linking the extrinsic stimulus to the intrinsic RNA modification pathwa ys remain largely unclear. Here, we identified the cyt...
Source: PLoS Biology: Archived Table of Contents - June 14, 2019 Category: Biology Authors: Nikoletta A. Gkatza Source Type: research

Atomic view into < i > Plasmodium < /i > actin polymerization, ATP hydrolysis, and fragmentation
by Esa-Pekka Kumpula, Andrea J. Lopez, Leila Tajedin, Huijong Han, Inari KursulaPlasmodium actins form very short filaments and have a noncanonical link between ATP hydrolysis and polymerization. Long filaments are detrimental to the parasites, but the structural factors constrainingPlasmodium microfilament lengths have remained unknown. Using high-resolution crystallography, we show that magnesium binding causes a slight flattening of thePlasmodium actin I monomer, and subsequent phosphate release results in a more twisted conformation. Thus, the Mg-bound monomer is closer in conformation to filamentous (F) actin than the...
Source: PLoS Biology: Archived Table of Contents - June 14, 2019 Category: Biology Authors: Esa-Pekka Kumpula Source Type: research

Protein interactions and consensus clustering analysis uncover insights into herpesvirus virion structure and function relationships
This study presents our efforts to unravel the complexity of the inter actome of herpes simplex virus type 1 (HSV1), the prototypical herpesvirus species. Inspired by our previous work, we present an improved and more integrative computational pipeline for the protein–protein interaction (PPI) network reconstruction in HSV1, together with a newly developed consensus clustering framework, which allowed us to extend the analysis beyond binary physical interactions and revealed a system-level layout of higher-order functional associations in the virion proteome. Additionally, the analysis provided new functional annotat...
Source: PLoS Biology: Archived Table of Contents - June 14, 2019 Category: Biology Authors: Anna Hern ández Durán Source Type: research

Specific activation of pro-Infliximab enhances selectivity and safety of rheumatoid arthritis therapy
by Yun-Chi Lu, Chih-Hung Chuang, Kuo-Hsiang Chuang, I-Ju Chen, Bo-Cheng Huang, Wen-Han Lee, Hsin-Ell Wang, Jia-Je Li, Yi-An Cheng, Kai-Wen Cheng, Jaw-Yuan Wang, Yuan-Chin Hsieh, Wen-Wei Lin, Tian-Lu Cheng During rheumatoid arthritis (RA) treatment, long-term injection of antitumor necrosis factor α antibodies (anti-TNFα Abs) may induce on-target toxicities, including severe infections (tuberculosis [TB] or septic arthritis) and malignancy. Here, we used an immunoglobulin G1 (IgG1) hinge as an Ab lock to cover the TNFα-binding site of Infliximab by linking it with matrix metalloproteinase (MMP) -2/9 subst...
Source: PLoS Biology: Archived Table of Contents - June 13, 2019 Category: Biology Authors: Yun-Chi Lu Source Type: research