bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term patterns of an interconnected core marine microbiota
Authors: Krabberød Anders K. , Deutschmann Ina M. , Bjorbækmo Marit F. M. , Balagué Vanessa , Giner Caterina R. , Ferrera Isabel , Garcés Esther , Massana Ramon , Gasol Josep M. , Logares Ramiro 
Published: March 2021

ABSTRACTBackgroundOcean microbes constitute ∼70% of the marine biomass, are responsible for ∼50% of the Earth’s primary production, and are crucial for global biogeochemical cycles. Marine microbiotas include core taxa that are usually key for ecosystem function. Despite their importance, core marine microbes are relatively unknown, which reflects the lack of consensus on how to identify them. So far, most core microbiotas have been defined based on species occurrence and abundance. Yet, species interactions are also important to identify core microbes, as communities include interacting species. Here, we investigate interconnected bacteria and small protists of the core pelagic microbiota populating a long-term marine-coastal observatory in the Mediterranean Sea over a decade.ResultsCore microbes were defined as those present in >30% of the monthly samples over 10 years, with the strongest associations. The core microbiota included 259 Operational Taxonomic Units (OTUs) including 182 bacteria, 77 protists, and 1,411 strong and mostly positive (∼95%) associations. Core bacteria tended to be associated with other bacteria, while core protists tended to be associated with bacteria. The richness and abundance of core OTUs varied annually, decreasing in stratified warmers waters and increasing in colder mixed waters. Most core OTUs had a preference for one season, mostly winter, which featured subnetworks with the highest connectivity. Groups of highly associated taxa tended to include protists and bacteria with predominance in the same season, particularly winter. A group of 13 highly-connected hub-OTUs, with potentially important ecological roles dominated in winter and spring. Similarly, 18 connector OTUs with a low degree but high centrality were mostly associated with summer or autumn and may represent transitions between seasonal communities.ConclusionsWe found a relatively small and dynamic interconnected core microbiota in a model temperate marine-coastal site, with potential interactions being more deterministic in winter than in other seasons. These core microbes would be essential for the functioning of this ecosystem over the year. Other non-core taxa may also carry out important functions but would be redundant and non-essential. Our work contributes to the understanding of the dynamics and potential interactions of core microbes possibly sustaining ocean ecosystem function.
On the genetic architecture of rapidly adapting and convergent life history traits in guppies
Authors: Whiting James R , Paris Josephine R , Parsons Paul J , Matthews Sophie , Reynoso Yuridia , Hughes Kimberly A. , Reznick David , Fraser Bonnie A 
Published: March 2021

ABSTRACTThe genetic basis of traits can shape and constrain how adaptation proceeds in nature; rapid adaptation can be facilitated by polygenic traits, whereas polygenic traits may restrict re-use of the same genes in adaptation (genetic convergence). The rapidly evolving life histories of guppies in response to predation risk provide an opportunity to test this proposition. Guppies adapted to high- (HP) and low-predation (LP) environments in northern Trinidad evolve rapidly and convergently among natural populations. This system has been studied extensively at the phenotypic level, but little is known about the underlying genetic architecture. Here, we use an F2 QTL design to examine the genetic basis of seven (five female, two male) guppy life history phenotypes. We use RAD-sequencing data (16,539 SNPs) from 370 male and 267 female F2 individuals. We perform linkage mapping, estimates of genome-wide and per-chromosome heritability (multi-locus associations), and QTL mapping (single-locus associations). Our results are consistent with architectures of many-loci of small effect for male age and size at maturity and female interbrood period. Male trait associations are clustered on specific chromosomes, but female interbrood period exhibits a weak genome-wide signal suggesting a potentially highly polygenic component. Offspring weight and female size at maturity are also associated with a single significant QTL each. These results suggest rapid phenotypic evolution of guppies may be facilitated by polygenic trait architectures, but these may restrict gene-reuse across populations, in agreement with an absence of strong signatures of genetic convergence from recent population genomic analyses of wild HP-LP guppies.
Discovery of a Novel Non-Narcotic Analgesic Derived from the CL-20 Explosive: Synthesis, Pharmacology and Target Identification of Thio-wurtzine, a Potent Inhibitor of the Opioid Receptors and the Voltage-Dependent Calcium Channels
Authors: Aguero Stephanie , Megy Simon , Fournier Mailys , Kulagina Daria A. , Sysolyatin Sergey V. , Kalashnikov Alexander I. , Krylova Svetlana G. , Vorozhtsov Alexander B. , Zhdanov Vadim V. , Terreux Raphael 
Published: March 2021

ABSTRACTThe number of candidate molecules for new non-narcotic analgesics is extremely limited. Here we report the identification of thiowurtzine, a new potent analgesic molecule with promising application in chronic pain treatment. We describe the chemical synthesis of this unique compound derived from the hexaazaisowurtzitane (CL-20) explosive molecule. Then we use animal experiments to assess its analgesic activityin vivoupon chemical, thermal and mechanical exposures, compared to the effect of several reference drugs. Finally, we investigate the potential receptors of thiowurtzine in order to better understand its complex mechanism of action. We use docking, molecular modeling and molecular dynamics simulations to identify and characterize the potential targets of the drug and confirm the results of the animal experiments. Our findings finally indicate that thiowurtzine may have a complex mechanism of action, by targeting the mu, kappa, delta and ORL1 opioid receptors, and the voltage-gated calcium channels as well.
The archaeal triphosphate tunnel metalloenzymeSaTTM defines structural determinants for the diverse activities in the CYTH protein family
Authors: Vogt Marian S. , Nguepbeu Roi R. Ngouoko , Mohr Michael K. F. , Albers Sonja-Verena , Essen Lars-Oliver , Banerjee Ankan 
Published: March 2021

AbstractCYTH is a large protein superfamily that is conserved in all three domains of life with its unique triphosphate tunnel metalloenzyme (TTM) fold. Besides phosphatase functions, e.g. as RNA triphosphatase, inorganic polyphosphatase or thiamine triphosphatase, some CYTH orthologs cyclize nucleotide triphosphates to 3’,5’-cyclic nucleotides. So far, archaeal CYTH proteins are annotated as adenylyl cyclases although experimental evidence is lacking. To address this gap, we characterized a CYTH ortholog,SaTTM, from the crenarchaeoteSulfolobus acidocaldarius. Our initialin silicostudies suggested a close relationship between archaeal CYTH enzymes and class IV adenylyl cyclases compared to the other CYTH-subclasses, but biochemical data showed no cyclic nucleotide production. Instead, our structural and functional analyses show a classical TTM behavior. The Ca2+-inhibited Michaelis complex indicates a two-metal ion reaction mechanism analogous to other TTMs. Different co-crystal structures ofSaTTM further reveal conformational dynamics inSaTTM, let us to assume feedback inhibition in TTMs due to tunnel closure in the product state. Combining our structural insights with sequence-similarity network basedin silicoanalysis, we further set out a firm molecular basis for distinguishing CYTH orthologs with phosphatase activities from class IV adenylyl cyclases.Major highlights-CyaB-like class IV adenylyl cyclase homologs in archaea are triphosphatases.-The co-crystal structure ofSaTTM in sulfate and triphosphate bound state revealed conformational transition of the TTM tunnel during catalysis.-Atomic insights into TTM inhibition by calcium and pyrophosphate.-In silicoand structure-function analysis revealed the molecular determinant for functional diversification among CYTH proteins.
Transcriptional condensates formed by phase-separated ALOG family proteins control shoot meristem maturation for flowering
Authors: Huang Xiaozhen , Xiao Nan , Xie Yue , Tang Lingli , Zhang Yueqin , Yu Yuan , Xu Cao 
Published: March 2021

AbstractPlants have evolved remarkable diversity in inflorescence architecture. At the center of this diversity lies a meristem maturation program featured by transition of stem cell populations from a vegetative state into a reproductive growth, determining when, where, and how many flowers are produced on inflorescences. Here we identified a new meristem maturation regulatorTMF FAMILY MEMBER3(TFAM3) that encodes an ALOG family transcription factor. Loss ofTFAM3results in early flowering and simplified inflorescences with fewer flowers. Genetic analysis by creating high-order mutants ofTFAM3with three key regulators of tomato shoot meristem maturation,TERMINATING FLOWER(TMF),TMF FAMILY MEMBER1(TFAM1) andTMF FAMILY MEMBER2(TFAM2), suggested that they synergistically control flowering transition and inflorescence architecture. The four paralogous ALOG proteins share the prion-like properties and undergo liquid-liquid phase separationin vitro. Strikingly, TMF can recognize cognate TFAM proteins and selectively recruit them into phase separated condensates. Supporting this, they interact with themselves and each other to form biomolecular condensates in the nucleus. Their interaction induces formation of transcriptional condensates that directly repress expression of floral identity geneANANTHA. Our study revealed a selective-recruitment phase separation mechanism for transcriptional condensation by which plants achieve optimal coordination of functional overlapped paralogs within a protein family to enable precise control of shoot meristem maturation for flowering and production of compound inflorescences.
Variants with the N501Y mutation extend SARS-CoV-2 host range to mice, with contact transmission
Authors: Montagutelli Xavier , Prot Matthieu , Levillayer Laurine , Salazar Eduard Baquero , Jouvion Grégory , Conquet Laurine , Beretta Maxime , Donati Flora , Albert Mélanie , Gambaro Fabiana , Behillil Sylvie , Enouf Vincent , Rousset Dominique , Mouquet Hugo , Jaubert Jean , Rey Felix , van der Werf Sylvie , Simon-Loriere Etienne 
Published: March 2021

SummaryReceptor recognition is a major determinant of viral host range, infectivity and pathogenesis. Emergences have been associated with serendipitous events of adaptation upon encounters with novel hosts, and the high mutation rate of RNA viruses may explain their frequent host shifts. SARS-CoV-2 extensive circulation in humans results in the emergence of variants, including variants of concern (VOCs) with diverse mutations notably in the spike, and increased transmissibility or immune escape. Here we show that, unlike the initial and Delta variants, the three VOCs bearing the N501Y mutation can infect common laboratory mice. Contact transmission occurred from infected to naive mice through two passages. This host range expansion likely results from an increased binding of the spike to the mouse ACE2. Together with the observed contact transmission, it raises the possibility of wild rodent secondary reservoirs enabling the emergence of new variants.
The N-terminal domain of RfaH plays an active role in protein fold-switching
Authors: Galaz-Davison Pablo , Román Ernesto A. , Ramírez-Sarmiento César A. 
Published: March 2021

AbstractThe bacterial elongation factor RfaH promotes the expression of virulence factors by specifically binding to RNA polymerases (RNAP) stalled at a DNA signal known asops. This behavior is unlike that of its paralog NusG, the major representative of the protein family to which RfaH belongs. Both proteins have an N-terminal domain (NTD) bearing an RNAP binding site, yet NusG C-terminal domain (CTD) is folded as a β-barrel while RfaH CTD is forming an α-hairpin blocking such site. Upon recognition of theopsexposed by RNAP, RfaH is activated via interdomain dissociation and complete CTD structural rearrangement into a β-barrel structurally identical to NusG CTD.Although RfaH transformation has been extensively characterized computationally, most studies employ tertiary biases towards each native state, hampering the analysis of sequence-encoded interactions on fold-switching. Here, we used Associative Water-mediated Structure and Energy Model (AWSEM) molecular dynamics to characterize the transformation of RfaH, spotlighting the sequence-dependent effects of NTD on CTD fold stabilization. Umbrella sampling simulations guided by native contacts recapitulate the thermodynamic equilibrium experimentally observed for RfaH and its isolated CTD. Temperature refolding simulations of full-length RfaH show a high success towards α-folded CTD, whereas the NTD interferes with βCTD folding, becoming trapped in a β-barrel intermediate. Meanwhile, NusG CTD refolding is unaffected by the presence of RfaH NTD, showing that these NTD-CTD interactions are encoded in RfaH sequence. Altogether, these results suggest that the NTD of RfaH favors the α-folded RfaH by specifically orienting the αCTD upon interdomain binding and also by favoring β-barrel rupture into an intermediate from which fold-switching proceeds.
Critical behaviour of the stochastic Wilson-Cowan model
Authors: de Candia Antonio , Sarracino Alessandro , Apicella Ilenia , de Arcangelis Lucilla 
Published: March 2021

AbstractSpontaneous brain activity is characterized by bursts and avalanche-like dynamics, with scale-free features typical of critical behaviour. The stochastic version of the celebrated Wilson-Cowan model has been widely studied as a system of spiking neurons reproducing non-trivial features of the neural activity, from avalanche dynamics to oscillatory behaviours. However, to what extent such phenomena are related to the presence of a genuine critical point remains elusive. Here we address this central issue, providing analytical results in the linear approximation and extensive numerical analysis. In particular, we present results supporting the existence of a bona fide critical point, where a second-order-like phase transition occurs, characterized by scale-free avalanche dynamics, scaling with the system size and a diverging relaxation time-scale. Moreover, our study shows that the observed critical behaviour falls within the universality class of the mean-field branching process, where the exponents of the avalanche size and duration distributions are, respectively, −3/2 and −2. We also provide an accurate analysis of the system behaviour as a function of the total number of neurons, focusing on the time correlation functions of the firing rate in a wide range of the parameter space.Author summaryNetworks of spiking neurons are introduced to describe some features of the brain activity, which are characterized by burst events (avalanches) with power-law distributions of size and duration. The observation of this kind of noisy behaviour in a wide variety of real systems led to the hypothesis that neuronal networks work in the proximity of a critical point. This hypothesis is at the core of an intense debate. At variance with previous claims, here we show that a stochastic version of the Wilson-Cowan model presents a phenomenology in agreement with the existence of a bona fide critical point for a particular choice of the relative synaptic weight between excitatory and inhibitory neurons. The system behaviour at this point shows all features typical of criticality, such as diverging timescales, scaling with the system size and scale-free distributions of avalanche sizes and durations, with exponents corresponding to the mean-field branching process. Our analysis unveils the critical nature of the observed behaviours.
Brain Water as a Function of Age and Weight in Normal Rats
Authors: Gottschalk Allan , Scafidi Susanna , Toung Thomas J. K. 
Published: March 2021

AbstractRats are frequently used to study water content of normal and injured brain, as well as changes in response to various osmotherapeutic regimens. Magnetic resonance imaging in humans has shown that brain water content declines with age as a result of progressive myelination. The purpose of this study was to quantify changes in brain water content during rat development and aging. Brain water content was measured by standard techniques in 129 normal male Sprague-Dawley rats that ranged in age (weight) from 13 to 149 days (18 to 759 g). Overall, the results demonstrated a decrease from 85.59% to 76.56% water content with increasing age (weight). Nonlinear allometric functions relating brain water to age and weight were determined. These findings provide age-related context for prior rat studies of brain water, emphasize the importance of using similarly aged controls in studies of brain water, and indicate that age-related changes in brain water content are not specific to humans.
Large-scale computational discovery and analysis of virus-derived microbial nanocompartments
Authors: Andreas Michael P. , Giessen Tobias W. 
Published: March 2021

AbstractProtein compartments represent an important strategy for subcellular spatial control and compartmentalization. Encapsulins are a class of microbial protein compartments defined by the viral HK97-fold of their capsid protein, self-assembly into icosahedral shells, and dedicated cargo loading mechanism for sequestering specific enzymes. Encapsulins are often misannotated and traditional sequence-based searches yield many false positive hits in the form of phage capsids. This has hampered progress in understanding the distribution and functional diversity of encapsulins. Here, we develop an integrated search strategy to carry out a large-scale computational analysis of prokaryotic genomes with the goal of discovering an exhaustive and curated set of all HK97-fold encapsulin-like systems. We report the discovery and analysis of over 6,000 encapsulin-like systems in 31 bacterial and 4 archaeal phyla, including two novel encapsulin families as well as many new operon types that fall within the two already known families. We formulate hypotheses about the biological functions and biomedical relevance of newly identified operons which range from natural product biosynthesis and stress resistance to carbon metabolism and anaerobic hydrogen production. We conduct an evolutionary analysis of encapsulins and related HK97-type virus families and show that they share a common ancestor. We conclude that encapsulins likely evolved from HK97-type bacteriophages. Our study sheds new light on the evolutionary interplay of viruses and cellular organisms, the recruitment of protein folds for novel functions, and the functional diversity of microbial protein organelles.
EMBED: Essential Microbiome Dynamics, a dimensionality reduction approach for longitudinal microbiome studies
Authors: Shahin Mayar , Ji Brian , Dixit Purushottam D. 
Published: March 2021

AbstractDimensionality reduction can offer unique insights into high dimensional microbiome dynamics by leveraging collective abundance fluctuations of multiple bacteria driven by similar ecological perturbations. However, methods providing lower-dimensional representations of microbiome dynamics both at the community and individual taxa level are not currently available. To that end, we present EMBED:EssentialMicroBiomE Dynamics, a probabilistic non-linear tensor factorization approach. Similar to normal mode analysis in structural biophysics, EMBED infers ecological normal modes (ECNs), which represent the unique orthogonal modes capturing the collective behavior of microbial communities. A very small number of ECNs can accurately approximate microbiome dynamics across multiple data sets. Inferred ECNs reflect specific ecological behaviors, providing natural templates along which the dynamics of individual bacteria may be partitioned. Moreover, the multi-subject treatment in EMBED systematically identifies subject-specific and universal abundance dynamics that are not detected by traditional approaches. Collectively, these results highlight the utility of EMBED as a versatile dimensionality reduction tool for studies of microbiome dynamics.
Angiotensin II disrupts the cytoskeletal architecture of human urine-derived podocytes and results in activation of the renin-angiotensin system
Authors: Erichsen Lars , Bohndorf Martina , Rahman Md. Shaifur , Wruck Wasco , Adjaye James 
Published: March 2021

AbstractHigh blood pressure is one of the major public health problems which causes severe disorders in several tissues including the human kidney. One of the most important signaling pathways associated with the regulation of blood pressure is the renin-angiotensin system (RAS), with its main mediator angiotensin II (ANGII). Elevated levels of circulating and intracellular ANGII and aldosterone lead to pro-fibrotic, -inflammatory and -hypertrophic milieu that causes remodelling and dysfunction in cardiovascular and renal tissues. Furthermore, ANGII has been recognized as major risk factor for the induction of apoptosis in podocytes, ultimately leading to chronic kidney disease (CDK).In the past, disease modeling of kidney-associated malignancies was extremely difficult, as the derivation of kidney originated cells is very challenging. Here we describe a differentiation protocol for reproducible differentiation of SIX2-positive urine derived renal progenitor cells (UdRPCs) into mature podocytes bearing typical foot processes. The UdRPCs-derived podocytes show the ability to execute Albumin endocytosis and the activation of the renin-angiotensin system by being responsive to ANGII stimulation. Our data reveals the ANGII dependent downregulation ofNPHS1andSYNPO, resulting in the disruption of the complex podocyte cytoskeletal architecture, as shown by immunofluorescence-based detection of α–ACTININ. In the present manuscript we confirm and propose UdRPCs as a unique cell type useful for studying nephrogenesis and associated diseases. Furthermore, the responsiveness of UdRPCs-derived podocytes to ANGII implies potential applications in nephrotoxicity studies and drug screening.
Structural intermediates observed only in intactEscherichia coliindicate a mechanism for TonB-dependent transport
Authors: Nilaweera Thushani D. , Nyenhuis David A. , Cafiso David S. 
Published: March 2021

AbstractOuter membrane TonB-dependent transporters facilitate the uptake of trace nutrients and carbohydrates in Gram negative bacteria and are essential for pathogenic bacteria and the health of the microbiome. Despite this, their mechanism of transport is still unknown. Here, pulse EPR measurements were made in intact cells on the Escherichia coli vitamin B12transporter, BtuB. Substrate binding was found to alter the C-terminal region of the core and shift an extracellular substrate binding loop 2 nm towards the periplasm; moreover, this structural transition is regulated by an ionic lock that is broken upon binding of the inner membrane protein TonB. Significantly, this structural transition is not observed when BtuB is reconstituted into phospholipid bilayers. These measurements suggest an alternative to existing models of transport, where TonB binding alone is sufficient to produce allosteric rearrangements in the transporter. They also demonstrate the importance of studying outer membrane proteins in their native environment.