The haemodynamics of the human placenta in utero
by Neele S. Dellschaft, George Hutchinson, Simon Shah, Nia W. Jones, Chris Bradley, Lopa Leach, Craig Platt, Richard Bowtell, Penny A. Gowland We have used magnetic resonance imaging (MRI) to provide important new insights into the function of the human placenta in utero. We have measured slow net flow and high net oxygenation in the placenta in vivo, which are consistent with efficient delivery of oxygen from mother to fetus. Our experi mental evidence substantiates previous hypotheses on the effects of spiral artery remodelling in utero and also indicates rapid venous drainage from the placenta, which is important becau...
Source: PLoS Biology: Archived Table of Contents - May 28, 2020 Category: Biology Authors: Neele S. Dellschaft Source Type: research

Dilp-2 –mediated PI3-kinase activation coordinates reactivation of quiescent neuroblasts with growth of their glial stem cell niche
by Xin Yuan, Conor W. Sipe, Miyuki Suzawa, Michelle L. Bland, Sarah E. Siegrist Dietary nutrients provide macromolecules necessary for organism growth and development. In response to animal feeding, evolutionarily conserved growth signaling pathways are activated, leading to increased rates of cell proliferation and tissue growth. It remains unclear how different cell types w ithin developing tissues coordinate growth in response to dietary nutrients and whether coordinated growth of different cell types is necessary for proper tissue function. Here, we report thatDrosophila neural stem cells, known as neuroblasts, reacti...
Source: PLoS Biology: Archived Table of Contents - May 28, 2020 Category: Biology Authors: Xin Yuan Source Type: research

Predictive whisker kinematics reveal context-dependent sensorimotor strategies
by Avner Wallach, David Deutsch, Tess Baker Oram, Ehud Ahissar Animals actively move their sensory organs in order to acquire sensory information. Some rodents, such as mice and rats, employ cyclic scanning motions of their facial whiskers to explore their proximal surrounding, a behavior known as whisking. Here, we investigated the contingency of whisking ki nematics on the animal’s behavioral context that arises from both internal processes (attention and expectations) and external constraints (available sensory and motor degrees of freedom). We recorded rat whisking at high temporal resolution in 2 experimental c...
Source: PLoS Biology: Archived Table of Contents - May 26, 2020 Category: Biology Authors: Avner Wallach Source Type: research

Behavioral flexibility is associated with changes in structure and function distributed across a frontal cortical network in macaques
by J érôme Sallet, MaryAnn P. Noonan, Adam Thomas, Jill X. O’Reilly, Jesper Anderson, Georgios K. Papageorgiou, Franz X. Neubert, Bashir Ahmed, Jackson Smith, Andrew H. Bell, Mark J. Buckley, Léa Roumazeilles, Steven Cuell, Mark E. Walton, Kristine Krug, Rogier B. Mars, Matthew F. S. Rushworth One of the most influential accounts of central orbitofrontal cortex—that it mediates behavioral flexibility—has been challenged by the finding that discrimination reversal in macaques, the classic test of behavioral flexibility, is unaffected when lesions are made by excitotoxin injection rat h...
Source: PLoS Biology: Archived Table of Contents - May 26, 2020 Category: Biology Authors: J érôme Sallet Source Type: research

HIV-1 Tat-mediated astrocytic amyloidosis  involves the HIF-1α/lncRNA BACE1-AS axis
We report here, in simian immunodeficiency virus (SIV)+ rhesus macaques and patients diagnosed with HIV, brain region–specific up-regulation of amyloid precursor protein (APP) and Aβ (40 and 42) in astrocytes. In addition, we find increased expression of β-site cleaving enzyme (BACE1), APP, and Aβ in human primary astrocytes (HPAs) exposed to Tat. Mechanisms involved up-regulation of hypoxia- inducible factor (HIF-1α), its translocation and binding to the long noncoding RNA (lncRNA) BACE1‐antisense transcript (BACE1-AS), resulting, in turn, in the formation of the BACE1-AS/BACE1 RNA complex, su...
Source: PLoS Biology: Archived Table of Contents - May 26, 2020 Category: Biology Authors: Susmita Sil Source Type: research

The evolution of the type VI secretion system as a disintegration weapon
by William P. J. Smith, Andrea Vettiger, Julius Winter, Till Ryser, Laurie E. Comstock, Marek Basler, Kevin R. Foster The type VI secretion system (T6SS) is a nanomachine used by many bacteria to drive a toxin-laden needle into other bacterial cells. Although the potential to influence bacterial competition is clear, the fitness impacts of wielding a T6SS are not well understood. Here we present a new agent-based model that enables detailed study of the evolutionary costs and benefits of T6SS weaponry during competition with other bacteria. Our model identifies a key problem with the T6SS. Because of its short range, T6SS...
Source: PLoS Biology: Archived Table of Contents - May 26, 2020 Category: Biology Authors: William P. J. Smith Source Type: research

Anticipation-induced delta phase reset improves human olfactory perception
In this study, we used human intracranial electroencephalography (iEEG) to show that anticipation resets the phase of delta oscillations in piriform corte x prior to odor arrival. Anticipatory phase reset correlates with ensuing odor-evoked theta power and improvements in perceptual accuracy. These effects were consistently present in each individual subject and were not driven by potential confounds of pre-inhale motor preparation or power changes. T ogether, these findings suggest that states of anticipation enhance olfactory perception through phase resetting of delta oscillations in piriform cortex. (Source: PLoS Biolo...
Source: PLoS Biology: Archived Table of Contents - May 26, 2020 Category: Biology Authors: Ghazaleh Arabkheradmand Source Type: research

Structure of TBC1D23 N-terminus reveals a novel role for rhodanese domain
by Dingdong Liu, Fan Yang, Zhe Liu, Jinrui Wang, Wenjie Huang, Wentong Meng, Daniel D. Billadeau, Qingxiang Sun, Xianming Mo, Da Jia Members of the Tre2-Bub2-Cdc16 (TBC) family often function to regulate membrane trafficking and to control signaling transductions pathways. As a member of the TBC family, TBC1D23 is critical for endosome-to-Golgi cargo trafficking by serving as a bridge between Golgi-bound golgin-97/245 and the W ASH/FAM21 complex on endosomal vesicles. However, the exact mechanisms by which TBC1D23 regulates cargo transport are poorly understood. Here, we present the crystal structure of the N-terminus of ...
Source: PLoS Biology: Archived Table of Contents - May 26, 2020 Category: Biology Authors: Dingdong Liu Source Type: research

Dynamical footprints enable detection of disease emergence
by Tobias S. Brett, Pejman Rohani Developing methods for anticipating the emergence or reemergence of infectious diseases is both important and timely; however, traditional model-based approaches are stymied by uncertainty surrounding the underlying drivers. Here, we demonstrate an operational, mechanism-agnostic detection algorit hm for disease (re-)emergence based on early warning signals (EWSs) derived from the theory of critical slowing down. Specifically, we used computer simulations to train a supervised learning algorithm to detect the dynamical footprints of (re-)emergence present in epidemiological data. Our algo...
Source: PLoS Biology: Archived Table of Contents - May 20, 2020 Category: Biology Authors: Tobias S. Brett Source Type: research

NASA ’s first ground-based Galactic Cosmic Ray Simulator: Enabling a new era in space radiobiology research
by Lisa C. Simonsen, Tony C. Slaba, Peter Guida, Adam Rusek With exciting new NASA plans for a sustainable return to the moon, astronauts will once again leave Earth’s protective magnetosphere only to endure higher levels of radiation from galactic cosmic radiation (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, a nd surface habitats will be designed to protect crew against SPEs with vehicle optimization, storm shelter concepts, and/or active dosimetry; however, the ever penetrating GCR will continue to pose the most significant health risks especially as lunar missions incre...
Source: PLoS Biology: Archived Table of Contents - May 19, 2020 Category: Biology Authors: Lisa C. Simonsen Source Type: research

Correction: Representation of abstract semantic knowledge in populations of human single neurons in the medial temporal lobe
by Thomas P. Reber, Marcel Bausch, Sina Mackay, Jan Bostr öm, Christian E. Elger, Florian Mormann (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - May 19, 2020 Category: Biology Authors: Thomas P. Reber Source Type: research

Humanization of yeast genes with multiple human orthologs reveals functional divergence between paralogs
by Jon M. Laurent, Riddhiman K. Garge, Ashley I. Teufel, Claus O. Wilke, Aashiq H. Kachroo, Edward M. Marcotte Despite over a billion years of evolutionary divergence, several thousand human genes possess clearly identifiable orthologs in yeast, and many have undergone lineage-specific duplications in one or both lineages. These duplicated genes may have been free to diverge in function since their expansi on, and it is unclear how or at what rate ancestral functions are retained or partitioned among co-orthologs between species and within gene families. Thus, in order to investigate how ancestral functions are retained o...
Source: PLoS Biology: Archived Table of Contents - May 18, 2020 Category: Biology Authors: Jon M. Laurent Source Type: research

Discovery of genes required for body axis and limb formation by global identification of retinoic acid –regulated epigenetic marks
by Marie Berenguer, Karolin F. Meyer, Jun Yin, Gregg Duester Identification of target genes that mediate required functions downstream of transcription factors is hampered by the large number of genes whose expression changes when the factor is removed from a specific tissue and the numerous binding sites for the factor in the genome. Retinoic acid (RA) reg ulates transcription via RA receptors bound to RA response elements (RAREs) of which there are thousands in vertebrate genomes. Here, we combined chromatin immunoprecipitation sequencing (ChIP-seq) for epigenetic marks and RNA-seq on trunk tissue from wild-type andAldh...
Source: PLoS Biology: Archived Table of Contents - May 18, 2020 Category: Biology Authors: Marie Berenguer Source Type: research

Correction: Publication reform to safeguard wildlife from researcher harm
by Kate A. Field, Paul C. Paquet, Kyle Artelle, Gilbert Proulx, Ryan K. Brook, Chris T. Darimont (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - May 18, 2020 Category: Biology Authors: Kate A. Field Source Type: research

Antibiotics can be used to contain drug-resistant bacteria by maintaining sufficiently large sensitive populations
by Elsa Hansen, Jason Karslake, Robert J. Woods, Andrew F. Read, Kevin B. Wood Standard infectious disease practice calls for aggressive drug treatment that rapidly eliminates the pathogen population before resistance can emerge. When resistance is absent, this elimination strategy can lead to complete cure. However, when resistance is already present, removing drug-sensitiv e cells as quickly as possible removes competitive barriers that may slow the growth of resistant cells. In contrast to the elimination strategy, a containment strategy aims to maintain the maximum tolerable number of pathogens, exploiting competitive...
Source: PLoS Biology: Archived Table of Contents - May 15, 2020 Category: Biology Authors: Elsa Hansen Source Type: research

Vascularized human cortical organoids (vOrganoids) model cortical development in vivo
by Yingchao Shi, Le Sun, Mengdi Wang, Jianwei Liu, Suijuan Zhong, Rui Li, Peng Li, Lijie Guo, Ai Fang, Ruiguo Chen, Woo-Ping Ge, Qian Wu, Xiaoqun Wang Modeling the processes of neuronal progenitor proliferation and differentiation to produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. We demonstrated a novel paradigm for the generation of vascularized organoid s (vOrganoids) consisting of typical human cortical cell types and a vascular structure for over 200 days as a vascularized and functional brain organoid model. The observation of...
Source: PLoS Biology: Archived Table of Contents - May 13, 2020 Category: Biology Authors: Yingchao Shi Source Type: research

Thalamic, cortical, and amygdala involvement in the processing of a natural sound cue of danger
This study suggests a role for the auditory offset pathway in processing a natural sound cue of threat. (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - May 12, 2020 Category: Biology Authors: Ana G. Pereira Source Type: research

Genuine cross-frequency coupling networks in human resting-state electrophysiological recordings
In conclusion, these results provide evidence for interareal CFS and PAC being 2 distinct mechan isms for coupling oscillations across frequencies in large-scale brain networks. (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - May 6, 2020 Category: Biology Authors: Felix Siebenh ühner Source Type: research

Haplotype of the astrocytic water channel AQP4 is associated with slow wave energy regulation in human NREM sleep
by Sara Marie Ulv Larsen, Hans-Peter Landolt, Wolfgang Berger, Maiken Nedergaard, Gitte Moos Knudsen, Sebastian Camillo Holst Cerebrospinal fluid (CSF) flow through the brain parenchyma is facilitated by the astrocytic water channel aquaporin 4 (AQP4). Homeostatically regulated electroencephalographic (EEG) slow waves are a hallmark of deep non–rapid eye movement (NREM) sleep and have been implicated in the regulation of parenchymal CSF flow and brain clearance. The humanAQP4 gene harbors several single nucleotide polymorphisms (SNPs) associated with AQP4 expression, brain-water homeostasis, and neurodegenerative di...
Source: PLoS Biology: Archived Table of Contents - May 5, 2020 Category: Biology Authors: Sara Marie Ulv Larsen Source Type: research

Single-cell transcription analysis of < i > Plasmodium vivax < /i > blood-stage parasites identifies stage- and species-specific profiles of expression
by Juliana M. Sa, Matthew V. Cannon, Ramoncito L. Caleon, Thomas E. Wellems, David SerrePlasmodium vivax andP.falciparum, the parasites responsible for most human malaria worldwide, exhibit striking biological differences, which have important clinical consequences. Unfortunately,P.vivax, unlikeP.falciparum, cannot be cultivated continuously in vitro, which limits our understanding of its biology and, consequently, our ability to effectively control vivax malaria. Here, we describe single-cell gene expression profiles of 9,215P.vivax parasites from bloodstream infections ofAotus andSaimiri monkeys. Our results show that tr...
Source: PLoS Biology: Archived Table of Contents - May 4, 2020 Category: Biology Authors: Juliana M. Sa Source Type: research

Early correction of synaptic long-term depression improves abnormal anxiety-like behavior in adult GluN2B-C456Y-mutant mice
by Wangyong Shin, Kyungdeok Kim, Benjamin Serraz, Yi Sul Cho, Doyoun Kim, Muwon Kang, Eun-Jae Lee, Hyejin Lee, Yong Chul Bae, Pierre Paoletti, Eunjoon Kim Extensive evidence linksGlutamate receptor,ionotropic,NMDA2B (GRIN2B), encoding the GluN2B/NR2B subunit of N-methyl-D-aspartate receptors (NMDARs), with various neurodevelopmental disorders, including autism spectrum disorders (ASDs), but the underlying mechanisms remain unclear. In addition, it remains unknown whether mutations in GluN2B, which starts to be expressed early in development, induces early pathophysiology that can be corrected by early treatments for long-...
Source: PLoS Biology: Archived Table of Contents - April 30, 2020 Category: Biology Authors: Wangyong Shin Source Type: research

“Frozen evolution” of an RNA virus suggests accidental release as a potential cause of arbovirus re-emergence
by David J. Pascall, Kyriaki Nomikou, Emmanuel Br éard, Stephan Zientara, Ana da Silva Filipe, Bernd Hoffmann, Maude Jacquot, Joshua B. Singer, Kris De Clercq, Anette Bøtner, Corinne Sailleau, Cyril Viarouge, Carrie Batten, Giantonella Puggioni, Ciriaco Ligios, Giovanni Savini, Piet A. van Rijn, Peter P. C. Mertens, Roman Biek, Massimo Palmarini The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an arthropod-borne virus of ruminants, emerged in livestock in northern Europe in 2006, spreading to m...
Source: PLoS Biology: Archived Table of Contents - April 28, 2020 Category: Biology Authors: David J. Pascall Source Type: research

A single-cell atlas of adult < i > Drosophila < /i > ovary identifies transcriptional programs and somatic cell lineage regulating oogenesis
by Allison Jevitt, Deeptiman Chatterjee, Gengqiang Xie, Xian-Feng Wang, Taylor Otwell, Yi-Chun Huang, Wu-Min Deng Oogenesis is a complex developmental process that involves spatiotemporally regulated coordination between the germline and supporting, somatic cell populations. This process has been modeled extensively using theDrosophila ovary. Although different ovarian cell types have been identified through traditional means, the large-scale expression profiles underlying each cell type remain unknown. Using single-cell RNA sequencing technology, we have built a transcriptomic data set for the adultDrosophila ovary and c...
Source: PLoS Biology: Archived Table of Contents - April 27, 2020 Category: Biology Authors: Allison Jevitt Source Type: research

TRIC-A shapes oscillatory Ca < sup > 2+ < /sup > signals by interaction with STIM1/Orai1 complexes
by Niroj Shrestha, Bernadett Bacsa, Hwei Ling Ong, Susanne Scheruebel, Helmut Bischof, Roland Malli, Indu Suresh Ambudkar, Klaus Groschner Trimeric intracellular cation (TRIC) channels have been proposed to modulate Ca2+ release from the endoplasmic reticulum (ER) and determine oscillatory Ca2+ signals. Here, we report that TRIC-A –mediated amplitude and frequency modulation of ryanodine receptor 2 (RyR2)-mediated Ca2+ oscillations and inositol 1,4,5-triphosphate receptor (IP3R)-induced cytosolic signals is based on attenuating store-operated Ca2+ entry (SOCE). Further, TRIC-A –dependent delay in ER Ca2+ store...
Source: PLoS Biology: Archived Table of Contents - April 24, 2020 Category: Biology Authors: Niroj Shrestha Source Type: research

Leveraging open hardware to alleviate the burden of COVID-19 on global health systems
by Andre Maia Chagas, Jennifer C. Molloy, Lucia L. Prieto-Godino, Tom Baden With the current rapid spread of COVID-19, global health systems are increasingly overburdened by the sheer number of people that need diagnosis, isolation and treatment. Shortcomings are evident across the board, from staffing, facilities for rapid and reliable testing to availability of hospital beds and key medical-grade equipment. The scale and breadth of the problem calls for an equally substantive response not only from frontline workers such as medical staff and scientists, but from skilled members of the public who have the time, facilitie...
Source: PLoS Biology: Archived Table of Contents - April 24, 2020 Category: Biology Authors: Andre Maia Chagas Source Type: research

A salt-induced kinase is required for the metabolic regulation of sleep
by Jeremy J. Grubbs, Lindsey E. Lopes, Alexander M. van der Linden, David M. Raizen Many lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unknown. DuringCaenorhabditis elegans sleep, energetic stores are allocated to nonneural tasks with a resultant drop in the overall fat stores and energy charge. Mutants lacking KIN-29, theC.elegans homolog of a mammalian Salt-Inducible Kinase (SIK) that signals sleep pressure, have low ATP levels despite high-fat stores, indicating a defective response to cellular energy deficits. Liberating energy stores ...
Source: PLoS Biology: Archived Table of Contents - April 21, 2020 Category: Biology Authors: Jeremy J. Grubbs Source Type: research

Resident microbial communities inhibit growth and antibiotic-resistance evolution of < i > Escherichia coli < /i > in human gut microbiome samples
by Michael Baumgartner, Florian Bayer, Katia R. Pfrunder-Cardozo, Angus Buckling, Alex R. Hall Countering the rise of antibiotic-resistant pathogens requires improved understanding of how resistance emerges and spreads in individual species, which are often embedded in complex microbial communities such as the human gut microbiome. Interactions with other microorganisms in such communities might suppress growth and resistance evolution of individual species (e.g., via resource competition) but could also potentially accelerate resistance evolution via horizontal transfer of resistance genes. It remains unclear how these d...
Source: PLoS Biology: Archived Table of Contents - April 20, 2020 Category: Biology Authors: Michael Baumgartner Source Type: research

Interhemispheric connections between olfactory bulbs improve odor detection
by Florence Kermen, Pradeep Lal, Nicholas G. Faturos, Emre Yaksi Interhemispheric connections enable interaction and integration of sensory information in bilaterian nervous systems and are thought to optimize sensory computations. However, the cellular and spatial organization of interhemispheric networks and the computational properties they mediate in verteb rates are still poorly understood. Thus, it remains unclear to what extent the connectivity between left and right brain hemispheres participates in sensory processing. Here, we show that the zebrafish olfactory bulbs (OBs) receive direct interhemispheric projectio...
Source: PLoS Biology: Archived Table of Contents - April 20, 2020 Category: Biology Authors: Florence Kermen Source Type: research

Visualization of two architectures in class-II CAP-dependent transcription activation
by Wei Shi, Yanan Jiang, Yibin Deng, Zigang Dong, Bin Liu Transcription activation by cyclic AMP (cAMP) receptor protein (CAP) is the classic paradigm of transcription regulation in bacteria. CAP was suggested to activate transcription on class-II promoters via a recruitment and isomerization mechanism. However, whether and how it modifies RNA polymerase (RNAP) to initiate transcription remains unclear. Here, we report cryo–electron microscopy (cryo-EM) structures of an intactEscherichia coli class-II CAP-dependent transcription activation complex (CAP-TAC) with and without de novo RNA transcript. The structures rev...
Source: PLoS Biology: Archived Table of Contents - April 20, 2020 Category: Biology Authors: Wei Shi Source Type: research

A pedagogical approach to science outreach
by Marni B. McClure, Kacey C. Hall, Erin F. Brooks, Catherine T. Allen, Kenneth S. Lyle Encouragement of students across all communities through scientific outreach programs is critical to engaging the next generation, exciting young minds to pursue careers in science and medicine. Herein, we present a uniquely structured and widely influential science outreach program. Founded in 20 05, the Duke Chemistry Outreach (DCO) employs a pedagogical approach to outreach that aims to teach its audience a new scientific concept, while instilling a pure enjoyment of science. DCO has performed 583 events reaching over 70,000 partici...
Source: PLoS Biology: Archived Table of Contents - April 16, 2020 Category: Biology Authors: Marni B. McClure Source Type: research

Portable sequencing as a teaching tool in conservation and biodiversity research
by Mrinalini Watsa, Gideon Andrew Erkenswick, Aaron Pomerantz, Stefan Prost As biodiversity loss continues to accelerate, there is a critical need for education and biomonitoring across the globe. Portable technologies allow for in situ molecular biodiversity monitoring that has been historically out of reach for many researchers in habitat nations. In the realm of educat ion, portable tools such as DNA sequencers facilitate in situ hands-on training in real-time sequencing and interpretation techniques. Here, we provide step-by-step protocols as a blueprint for a terrestrial conservation genetics field training program t...
Source: PLoS Biology: Archived Table of Contents - April 16, 2020 Category: Biology Authors: Mrinalini Watsa Source Type: research

Ultralow-frequency neural entrainment to pain
by Yifei Guo, Rory John Bufacchi, Giacomo Novembre, Marina Kilintari, Massieh Moayedi, Li Hu, Gian Domenico Iannetti Nervous systems exploit regularities in the sensory environment to predict sensory input, adjust behavior, and thereby maximize fitness. Entrainment of neural oscillations allows retaining temporal regularities of sensory information, a prerequisite for prediction. Entrainment has been extensively described at the frequencies of periodic inputs most commonly present in visual and auditory landscapes (e.g.,>0.5 Hz). An open question is whether neural entrainment also occurs for regularities at much longer...
Source: PLoS Biology: Archived Table of Contents - April 13, 2020 Category: Biology Authors: Yifei Guo Source Type: research

ORANGE: A CRISPR/Cas9-based genome editing toolbox for epitope tagging of endogenous proteins in neurons
by Jelmer Willems, Arthur P. H. de Jong, Nicky Scheefhals, Eline Mertens, Lisa A. E. Catsburg, Rogier B. Poorthuis, Fred de Winter, Joost Verhaagen, Frank J. Meye, Harold D. MacGillavry The correct subcellular distribution of proteins establishes the complex morphology and function of neurons. Fluorescence microscopy techniques are invaluable to investigate subcellular protein distribution, but they suffer from the limited ability to efficiently and reliably label endogenous prot eins with fluorescent probes. We developed ORANGE: Open Resource for the Application of Neuronal Genome Editing, which mediates targeted genomic...
Source: PLoS Biology: Archived Table of Contents - April 10, 2020 Category: Biology Authors: Jelmer Willems Source Type: research

Precise genomic mapping of 5-hydroxymethylcytosine via covalent tether-directed sequencing
by Povilas Gibas, Milda Narmont ė, Zdislav Staševskij, Juozas Gordevičius, Saulius Klimašauskas, Edita Kriukienė 5-hydroxymethylcytosine (5hmC) is the most prevalent intermediate on the oxidative DNA demethylation pathway and is implicated in regulation of embryogenesis, neurological processes, and cancerogenesis. Profiling of this relatively scarce genomic modification in clinical samples requires cost-effe ctive high-resolution techniques that avoid harsh chemical treatment. Here, we present a bisulfite-free approach for 5hmC profiling at single-nucleotide resolution, named hmTOP-seq (5hmC-specific teth...
Source: PLoS Biology: Archived Table of Contents - April 10, 2020 Category: Biology Authors: Povilas Gibas Source Type: research

Rab5c-mediated endocytic trafficking regulates hematopoietic stem and progenitor cell development via Notch and AKT signaling
by Jian Heng, Peng Lv, Yifan Zhang, Xinjie Cheng, Lu Wang, Dongyuan Ma, Feng Liu It is well known that various developmental signals play diverse roles in hematopoietic stem and progenitor cell (HSPC) production; however, how these signaling pathways are orchestrated remains incompletely understood. Here, we report that Rab5c is essential for HSPC specification by endocytic tr afficking of Notch and AKT signaling in zebrafish embryos. Rab5c deficiency leads to defects in HSPC production. Mechanistically, Rab5c regulates hemogenic endothelium (HE) specification by endocytic trafficking of Notch ligands and receptor. We fur...
Source: PLoS Biology: Archived Table of Contents - April 10, 2020 Category: Biology Authors: Jian Heng Source Type: research

Crosslinking-guided geometry of a complete CXC receptor-chemokine complex and the basis of chemokine subfamily selectivity
by Tony Ngo, Bryan S. Stephens, Martin Gustavsson, Lauren G. Holden, Ruben Abagyan, Tracy M. Handel, Irina Kufareva Chemokines and their receptors are orchestrators of cell migration in humans. Because dysregulation of the receptor-chemokine system leads to inflammation and cancer, both chemokines and receptors are highly sought therapeutic targets. Yet one of the barriers for their therapeutic targeting is the limited understanding of the structural principles behind receptor-chemokine recognition and selectivity. The existing structures do not include CXC subfamily complexes and lack information about the receptor dista...
Source: PLoS Biology: Archived Table of Contents - April 9, 2020 Category: Biology Authors: Tony Ngo Source Type: research

YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators
by Qili Fei, Zhongyu Zou, Ian A. Roundtree, Hui-Lung Sun, Chuan He TheN6-methyladenosine (m6A) modification regulates mRNA stability and translation. Here, we show that transcriptomic m6A modification can be dynamic and the m6A reader protein YTHN6-methyladenosine RNA binding protein 2 (YTHDF2) promotes mRNA decay during cell cycle. Depletion of YTHDF2 in HeLa cells leads to the delay of mitotic entry due to overaccumulation of negative regulators of cell cycle such as Wee1-like protein kinase (WEE1). We demonstrate that WEE1 transcripts contain m6A modification, which promotes their decay through YTHDF2. Moreover, we fou...
Source: PLoS Biology: Archived Table of Contents - April 8, 2020 Category: Biology Authors: Qili Fei Source Type: research

Single-cell mapping reveals new markers and functions of lymphatic endothelial cells in lymph nodes
by Noriki Fujimoto, Yuliang He, Marco D ’Addio, Carlotta Tacconi, Michael Detmar, Lothar C. Dieterich Lymph nodes (LNs) are highly organized secondary lymphoid organs that mediate adaptive immune responses to antigens delivered via afferent lymphatic vessels. Lymphatic endothelial cells (LECs) line intranodal lymphatic sinuses and organize lymph and antigen distribution. LECs also directly regulat e T cells, mediating peripheral tolerance to self-antigens, and play a major role in many diseases, including cancer metastasis. However, little is known about the phenotypic and functional heterogeneity of LN LECs. Using ...
Source: PLoS Biology: Archived Table of Contents - April 6, 2020 Category: Biology Authors: Noriki Fujimoto Source Type: research

Neurophysiological evidence for crossmodal (face-name) person-identity representation in the human left ventral temporal cortex
by Ang élique Volfart, Jacques Jonas, Louis Maillard, Sophie Colnat-Coulbois, Bruno Rossion Putting a name to a face is a highly common activity in our daily life that greatly enriches social interactions. Although this specific person–identity association becomes automatic with learning, it remains difficult and can easily be disrupted in normal circumstances or neurological condition s. To shed light on the neural basis of this important and yet poorly understood association between different input modalities in the human brain, we designed a crossmodal frequency-tagging paradigm coupled to brain activity r...
Source: PLoS Biology: Archived Table of Contents - April 3, 2020 Category: Biology Authors: Ang élique Volfart Source Type: research

BigBrain 3D atlas of cortical layers: Cortical and laminar thickness gradients diverge in sensory and motor cortices
We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. It was derived from a 3D histological atlas of the human brain at 20-micrometer isotropic resolution (BigBrain), us ing a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D, and the resultant laminar atlas provides an unprecedented level of precision and detail. W e utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in s...
Source: PLoS Biology: Archived Table of Contents - April 3, 2020 Category: Biology Authors: Konrad Wagstyl Source Type: research

Every fifth published metagenome is not available to science
by Ester M. Eckert, Andrea Di Cesare, Diego Fontaneto, Thomas U. Berendonk, Helmut B ürgmann, Eddie Cytryn, Despo Fatta-Kassinos, Andrea Franzetti, D. G. Joakim Larsson, Célia M. Manaia, Amy Pruden, Andrew C. Singer, Nikolina Udikovic-Kolic, Gianluca Corno Have you ever sought to use metagenomic DNA sequences reported in scientific publications? Were you successful? Here, we reveal that metagenomes from no fewer than 20% of the papers found in our literature search, published between 2016 and 2019, were not deposited in a repository or were simply i naccessible. The proportion of inaccessible data within the l...
Source: PLoS Biology: Archived Table of Contents - April 3, 2020 Category: Biology Authors: Ester M. Eckert Source Type: research

Thinking small: Next-generation sensor networks close the size gap in vertebrate biologging
by Simon P. Ripperger, Gerald G. Carter, Rachel A. Page, Niklas Duda, Alexander Koelpin, Robert Weigel, Markus Hartmann, Thorsten Nowak, J örn Thielecke, Michael Schadhauser, Jörg Robert, Sebastian Herbst, Klaus Meyer-Wegener, Peter Wägemann, Wolfgang Schröder-Preikschat, Björn Cassens, Rüdiger Kapitza, Falko Dressler, Frieder Mayer Recent advances in animal tracking technology have ushered in a new era in biologging. However, the considerable size of many sophisticated biologging devices restricts their application to larger animals, whereas older techniques often still represent the state-o...
Source: PLoS Biology: Archived Table of Contents - April 2, 2020 Category: Biology Authors: Simon P. Ripperger Source Type: research

Over a century of cancer research: Inconvenient truths and promising leads
by Carlos Sonnenschein, Ana M. Soto Despite over a century of intensive efforts, the great gains promised by the War on Cancer nearly 50 years ago have not materialized. Since 1999, we have analyzed the lack of progress in explaining and “curing” cancer by examining the merits of the premises that determine how cancer is underst ood and treated. Our ongoing critical analyses have aimed at clarifying the sources of misunderstandings at the root of the cancer puzzle while providing a plausible and comprehensive biomedical perspective as well as a new theory of carcinogenesis that is compatible with evolutionary ...
Source: PLoS Biology: Archived Table of Contents - April 1, 2020 Category: Biology Authors: Carlos Sonnenschein Source Type: research

Dynamics in the murine norovirus capsid revealed by high-resolution cryo-EM
by Joseph S. Snowden, Daniel L. Hurdiss, Oluwapelumi O. Adeyemi, Neil A. Ranson, Morgan R. Herod, Nicola J. Stonehouse Icosahedral viral capsids must undergo conformational rearrangements to coordinate essential processes during the viral life cycle. Capturing such conformational flexibility has been technically challenging yet could be key for developing rational therapeutic agents to combat infections. Norovirus es are nonenveloped, icosahedral viruses of global importance to human health. They are a common cause of acute gastroenteritis, yet no vaccines or specific antiviral agents are available. Here, we use genetics ...
Source: PLoS Biology: Archived Table of Contents - March 31, 2020 Category: Biology Authors: Joseph S. Snowden Source Type: research

The future of < i > PLOS Biology < /i >
by Nonia Pariente, on behalf of the PLOS Biology Staff Editors (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - March 31, 2020 Category: Biology Authors: Nonia Pariente Source Type: research

Interactive youth science workshops benefit student participants and graduate student mentors
by Pallavi Kompella, Brant Gracia, Lucy LeBlanc, Shelly Engelman, Chinmayee Kulkarni, Niral Desai, Viviana June, Stephen March, Sarah Pattengale, Gabriel Rodriguez-Rivera, Seung Woo Ryu, Isabel Strohkendl, Pooja Mandke, Greg Clark Science communication and outreach are essential for training the next generation of scientists and raising public awareness for science. Providing effective science, technology, engineering, and mathematics (STEM) educational outreach to students in classrooms is challenging because of the need t o form partnerships with teachers, the time commitment required for the presenting scientist, and t...
Source: PLoS Biology: Archived Table of Contents - March 30, 2020 Category: Biology Authors: Pallavi Kompella Source Type: research

Vocal learning: Beyond the continuum
by Pedro Tiago Martins, Cedric Boeckx Vocal learning is the ability to modify vocal output on the basis of experience. Traditionally, species have been classified as either displaying or lacking this ability. A recent proposal, the vocal learning continuum, recognizes the need to have a more nuanced view of this phenotype and abandon the yes–no dichotomy. However, it also limits vocal learning to production of novel calls through imitation, moreover subserved by a forebrain-to-phonatory-muscles circuit. We discuss its limitations regarding the characterization of vocal learning across species and argue for a more pe...
Source: PLoS Biology: Archived Table of Contents - March 30, 2020 Category: Biology Authors: Pedro Tiago Martins Source Type: research

A compact Cas9 ortholog from < i > Staphylococcus Auricularis < /i > (SauriCas9) expands the DNA targeting scope
by Ziying Hu, Shuai Wang, Chengdong Zhang, Ning Gao, Miaomiao Li, Deqian Wang, Daqi Wang, Dong Liu, Huihui Liu, Sang-Ging Ong, Hongyan Wang, Yongming Wang Compact CRISPR/Cas9 systems that can be packaged into an adeno-associated virus (AAV) hold great promise for gene therapy. Unfortunately, currently available small Cas9 nucleases either display low activity or require a long protospacer adjacent motif (PAM) sequence, limiting their extensive appli cations. Here, we screened a panel of Cas9 nucleases and identified a small Cas9 ortholog fromStaphylococcus auricularis (SauriCas9), which recognizes a simple NNGG PAM, displ...
Source: PLoS Biology: Archived Table of Contents - March 30, 2020 Category: Biology Authors: Ziying Hu Source Type: research

Combating antiscience:  Are we preparing for the 2020s?
by Peter J. Hotez In the last half of the 2010s, we saw an upswing in antiscience movements and unprecedented attacks on scientists in the United States and elsewhere. All indications suggest that this trend will not slow or reverse anytime soon, and it is now increasingly apparent that it will fall to the scientis ts themselves to respond, engage a skeptical public, and lead the defense of science. Accordingly, we must recognize opportunities to both reorganize science doctoral and postdoctoral training and incentivize senior scientists as a means to establish a new ecosystem for science public engagement. Su ch activiti...
Source: PLoS Biology: Archived Table of Contents - March 27, 2020 Category: Biology Authors: Peter J. Hotez Source Type: research

Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice
by Bo Xia, Xiao Chen Shi, Bao Cai Xie, Meng Qing Zhu, Yan Chen, Xin Yi Chu, Guo He Cai, Min Liu, Shi Zhen Yang, Grant A. Mitchell, Wei Jun Pang, Jiang Wei Wu Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora–derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse eff ects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mecha...
Source: PLoS Biology: Archived Table of Contents - March 27, 2020 Category: Biology Authors: Bo Xia Source Type: research