bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental genomics points to non-diazotrophicTrichodesmiumspecies abundant and widespread in the open ocean
Authors: Delmont Tom O. 
Published: March 2021

AbstractFilamentous and colony-forming cells within the cyanobacterial genusTrichodesmiummight account for nearly half of nitrogen fixation in the sunlit ocean, a critical mechanism that sustains plankton’s primary productivity at large-scale. Here, we report the genome-resolved metagenomic characterization of two newly identified marine species we tentatively named ‘Ca.Trichodesmium miru’ and ‘Ca.Trichodesmium nobis’. Near-complete environmental genomes for those closely related candidate species revealed unexpected functional features including a lack of the entire nitrogen fixation gene apparatus and hydrogen recycling genes concomitant with the enrichment of nitrogen assimilation genes and apparent acquisition of thenirbgene from a non-cyanobacterial lineage. These comparative genomic insights were cross-validated by complementary metagenomic investigations. Our results contrast with the current paradigm thatTrichodesmiumspecies are necessarily capable of nitrogen fixation. The black queen hypothesis could explain gene loss linked to nitrogen fixation amongTrichodesmiumspecies, possibly triggered by gene acquisitions from the colony epibionts. Critically, the candidate species are not only widespread in the 3-2000 μm planktonic size fraction of the surface of the oceans and seas, but might also substantially expand the ecological niche ofTrichodesmium, stressing the need to disconnect taxonomic signal for this genus from a microbial community’s ability to fix nitrogen. Especially, differentiating diazotrophic from non-diazotrophic populations when countingTrichodesmiumfilaments and colonies might help refine our understanding of the marine nitrogen balance. While culture representatives are needed to move beyond metagenomic insights, we are reminded that established links between taxonomic lineages and functional traits might not always hold true.
Individual Variability in the Innate Functional Organization of the Human Brain
Authors: Molloy M. Fiona , Saygin Zeynep M. 
Published: March 2021

AbstractThe adult brain is organized into distinct functional networks, forming the basis of information processing and determining individual differences in behavior. Is this network organization genetically determined and present at birth? And what is the individual variability in this organization in neonates? Here, we use unsupervised learning to uncover intrinsic functional brain organization using resting-state connectivity from a large cohort of neonates (Developing Human Connectome Project). We identified a set of symmetric, hierarchical, and replicable networks: sensorimotor, visual, default mode, ventral attention, and high-level vision. We quantified individual variability across neonates, and found the most individual variability in the ventral attention networks. Crucially, the variability of these networks were not driven by SNR differences or differences from adult networks (Yeo et al., 2011). Finally, differential gene expression provided a potential explanation for the emergence of these distinct networks and identified potential genes of interest for future developmental and individual variability research. Overall, we found neonatal connectomes (even at the voxel-level) can reveal broad individual- specific information processing units. The presence of individual differences in neonates and the framework for personalized parcellations demonstrated here has the potential to improve prediction of behavior and future outcomes from neonatal and infant brain data.
The use of non-functional clonotypes as a natural calibrator for quantitative bias correction in adaptive immune receptor repertoire profiling
Authors: Smirnova Anastasia , Miroshnichenkova Anna , Olshanskaya Yulia , Maschan Michael , Lebedev Yuri , Chudakov Dmitriy , Mamedov Ilgar , Komkov Alexander 
Published: March 2021

AbstractHigh-throughput sequencing of adaptive immune receptor repertoires is a valuable tool for receiving insights in adaptive immunity studies. Several powerful TCR/BCR repertoire reconstruction and analysis methods have been developed in the past decade. However, detecting and correcting the discrepancy between real and experimentally observed lymphocyte clone frequencies is still challenging. Here we discovered a hallmark anomaly in the ratio between read count and clone count-based frequencies of non-functional clonotypes in multiplex PCR-based immune repertoires. Calculating this anomaly, we formulated a quantitative measure of V- and J-genes frequency bias driven by multiplex PCR during library preparation called Over Amplification Rate (OAR). Based on the OAR concept, we developed an original software for multiplex PCR-specific bias evaluation and correction named iROAR: Immune Repertoire Over Amplification Removal (https://github.com/smiranast/iROAR). The iROAR algorithm was successfully tested on previously published TCR repertoires obtained using both 5’ RACE (Rapid Amplification of cDNA Ends)-based and multiplex PCR-based approaches and compared with a biological spike-in-based method for PCR bias evaluation. The developed approach can increase the accuracy and consistency of repertoires reconstructed by different methods making them more applicable for comparative analysis.
Extremely Fast pRF Mapping for Real-Time Applications
Authors: Bhat Salil , Lührs Michael , Goebel Rainer , Senden Mario 
Published: March 2021

AbstractPopulation receptive field (pRF) mapping is a popular tool in computational neuroimaging that allows for the investigation of receptive field properties, their topography and interrelations in health and disease. Furthermore, the possibility to invert population receptive fields provides a decoding model for constructing stimuli from observed cortical activation patterns. This has been suggested to pave the road towards pRF-based brain-computer interface (BCI) communication systems, which would be able to directly decode internally visualized letters from topographically organized brain activity. A major stumbling block for such an application is, however, that the pRF mapping procedure is computationally heavy and time consuming. To address this, we propose a novel and fast pRF mapping procedure that is suitable for real-time applications. The method is build upon hashed-Gaussian encoding of the stimulus, which significantly reduces computational resources. After the stimulus is encoded, mapping can be performed using either ridge regression for fast offline analyses or gradient descent for real-time applications. We validate our model-agnostic approachin silico, as well as on empirical fMRI data obtained from 3T and 7T MRI scanners. Our approach is capable of estimating receptive fields and their parameters for millions of voxels in mere seconds. This method thus facilitates real-time applications of population receptive field mapping.
Independent Markov Decomposition: Towards modeling kinetics of biomolecular complexes
Authors: Hempel Tim , del Razo Mauricio J. , Lee Christopher T. , Taylor Bryn C. , Amaro Rommie E. , Noé Frank 
Published: March 2021

In order to advance the mission ofin silicocell biology, modeling the interactions of large and complex biological systems becomes increasingly relevant. The combination of molecular dynamics (MD) and Markov state models (MSMs) have enabled the construction of simplified models of molecular kinetics on long timescales. Despite its success, this approach is inherently limited by the size of the molecular system. With increasing size of macromolecular complexes, the number of independent or weakly coupled subsystems increases, and the number of global system states increase exponentially, making the sampling of all distinct global states unfeasible. In this work, we present a technique called Independent Markov Decomposition (IMD) that leverages weak coupling between subsystems in order to compute a global kinetic model without requiring to sample all combinatorial states of subsystems. We give a theoretical basis for IMD and propose an approach for finding and validating such a decomposition. Using empirical few-state MSMs of ion channel models that are well established in electrophysiology, we demonstrate that IMD can reproduce experimental conductance measurements with a major reduction in sampling compared with a standard MSM approach. We further show how to find the optimal partition of all-atom protein simulations into weakly coupled subunits.Significance StatementMolecular simulations of proteins are often interpreted using Markov state models (MSMs), in which each protein configuration is assigned to a global state. As we explore larger and more complex biological systems, the size of this global state space will face a combinatorial explosion, rendering it impossible to gather sufficient sampling data. In this work, we introduce an approach to decompose a system of interest into separable subsystems. We show that MSMs built for each subsystem can be later coupled to reproduce the behaviors of the global system. To aid in the choice of decomposition we also describe a score to quantify its goodness. This decomposition strategy has the promise to enable robust modeling of complex biomolecular systems.
New detection of SARS-CoV-2 in two cats height months after COVID-19 outbreak appearance in France
Authors: Fritz Matthieu , Nesi Nicolas , Denolly Solène , Boson Bertrand , Legros Vincent , Rosolen Serge G. , Briend-Marchal Alexandra , Gouilh Meriadeg Ar , Leroy Eric M. 
Published: March 2021

AbstractAlthough there are several reports in the literature of SARS-CoV-2 infection in cats, few SARS-CoV-2 sequences from infected cats have been published. In this report, SARS-CoV-2 infection was evaluated in two cats by clinical observation, molecular biology (qPCR and NGS), and serology (Microsphere immunoassay and seroneutralization). Following the observation of symptomatic SARS-CoV-2-infection in two cats, infection status was confirmed by RT-qPCR and, in one cat, serological analysis for antibodies against N-protein and S-protein, as well as neutralizing antibodies. Comparative analysis of five SARS-CoV-2 sequence-fragments obtained from one of the cats showed that this infection was not with one of the three recently emerged variants of SARS-CoV-2. This study provides additional information on the clinical, molecular, and serological aspects of SARS-CoV-2 infection in cats.
Interchangeability of Periplasmic Adaptor Proteins AcrA and AcrE in forming functional efflux pumps with AcrD inSalmonellaTyphimurium
Authors: Alav Ilyas , Bavro Vassiliy N. , Blair Jessica M. A. 
Published: March 2021

AbstractBackgroundRND efflux pumps are important mediators of antibiotic resistance. RND pumps including the principal multidrug-efflux pump AcrAB-TolC inSalmonella, are tripartite systems, with an inner membrane RND-transporter, a periplasmic adaptor protein (PAP) and an outer membrane factor (OMF). We previously identified the residues required for binding between the PAP AcrA and the RND-transporter AcrB and have demonstrated that PAPs can function with non-cognate transporters. AcrE and AcrD/AcrF are homologues of AcrA and AcrB, respectively. Here, we show that AcrE can interact with AcrD, which does not possess its own PAP, and establish that the residues previously identified in AcrB-binding are also involved in AcrD-binding.MethodsTheacrDandacrEgenes were expressed into a strain lackingacrABDEF(Δ3RND). PAP residues involved in promiscuous interactions were predicted based on previously defined PAP-RND interactions and corresponding mutations generated inacrAandacrE. Antimicrobial susceptibility of the mutant strains was determined.ResultsCo-expression ofacrDandacrEsignificantly decreased susceptibility of the Δ3RND strain to AcrD substrates showing that AcrE can form a functional complex with AcrD. The substrate profile ofSalmonellaAcrD differed from that ofE. coliAcrD. Mutations targeting the previously defined PAP-RND interaction sites in AcrA/AcrE impaired efflux of AcrD-dependent substrates.ConclusionsThese data indicate that AcrE forms an efflux-competent pump with AcrD and thus presents an alternative PAP for this pump. Mutagenesis of the conserved RND-binding sites validates the interchangeability of AcrA and AcrE, highlighting them as potential drug targets for efflux inhibition.
A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants
Authors: Schmitz Aaron J. , Turner Jackson S. , Liu Zhuoming , Aziati Ishmael D. , Chen Rita E. , Joshi Astha , Bricker Traci L. , Darling Tamarand L. , Adelsberg Daniel C. , Alsoussi Wafaa B. , Case James Brett , Lei Tingting , Thapa Mahima , Amanat Fatima , O’Halloran Jane A. , Shi Pei-Yong , Presti Rachel M. , Krammer Florian , Bajic Goran , Whelan Sean P.J. , Diamond Michael S. , Boon Adrianus C. M. , Ellebedy Ali H. 
Published: March 2021

AbstractThe emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.One Sentence SummaryProtection against SARS-CoV-2 variants by a potently neutralizing vaccine-induced human monoclonal antibody.
The role of the Andean uplift as an asymmetrical barrier to gene flow in the Neotropical leaf-cutting antAtta cephalotes
Authors: Muñoz-Valencia Vanessa , Vélez-Matínez Glever Alexander , Montoya-Lerma James , Díaz Fernando 
Published: March 2021

ABSTRACTNeotropical diversification by the Andean uplift is typically addressed on a large evolutionary scale (e.g. speciation), even though many species are still distributed in both sides of the mountains. The three parallel mountain ranges in the northern Andes (Colombia) impose a major geographical barrier to species’ migration from South to Central America. How important these barriers are for conspecific diversification of cross-Andean species such as the leaf-cutting ants remains largely unknown. To answer this question, we studied themtCOIgene ofAtta cephalotes, the most widely distributed leaf-cutting ant species. Our hierarchical analyzes evidenced substantial genetic structure among regions and populations, suggesting a more complex biogeographical history of Andean populations than previously thought. These mountains seem to isolate Central American and Western Colombian populations from the rest ofA. cephalotesin South America. Population and migration modelling are consistent with the origin of this species in South America and a major role of the Eastern cordillera as a geographical barrier to historical gene flow, restricting dispersion from north to south. These findings provide insights into the role of the Andean uplift as barrier to gene flow and, eventually, implications for monitoring and designing management strategies for leaf-cutting ants.
Loss of STAT5 in adipocytes increases subcutaneous fat mass via sex-dependent and depot-specific pathways
Authors: Richard Allison J. , Hang Hardy , Allerton Timothy D. , Zhao Peng , Ghosh Sujoy , Elks Carrie M. , Stephens Jacqueline M. 
Published: March 2021

SUMMARYThe STAT (Signal Transducers and Activators of Transcription) family of transcription factors contributes to adipocyte development and function. STAT5A and STAT5B are induced during adipocyte differentiation and are primarily activated by growth hormone (GH). Studies in mice lacking adipocyte GH receptor or STAT5 support their roles in lipolysis-mediated reduction of adipose tissue mass. We have generated a mouse model lacking both STAT5 genes specifically in adipocytes (STAT5AKO). Notably, both sexes of STAT5AKOmice have increased inguinal adipose tissue without any changes in gonadal fat mass. However, both depots exhibit substantial differences in fat cell size. Study of STAT5AKOmice also have revealed that GH’s ability to induce insulin resistance is dependent upon STAT5 in adipocytes, but its ability to reduce adipose tissue mass is STAT5 independent. Additional observations, which were not predicted, indicate that the causes and regulation of increased fat mass in STAT5AKOmice are sex- and depot-dependent.
C9ORF72dipeptide repeat proteins disrupt formation of GEM bodies and induce aberrant accumulation of survival of motor neuron protein
Authors: Kato Yuma , Yokogawa Minnie , Nakagawa Ikuma , Onodera Kazunari , Okano Hideyuki , Inoue Haruhisa , Hattori Mitsuharu , Okada Yohei , Tsuiji Hitomi 
Published: March 2021

AbstractA GGGGCC repeat expansion in theC9ORF72gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease. In the neurons of ALS patients, dipeptide repeat proteins (DPRs) are produced from repeat-containing RNAs by an unconventional form of translation, and some of these proteins, especially those containing poly(glycine-arginine) and poly(proline-arginine), are toxic to neurons. Gemini of coiled bodies (GEMs) are nuclear structures that harbor survival of motor neuron (SMN) protein, and SMN is essential for the assembly of U-rich small nuclear ribonucleoproteins (snRNPs) that are central for splicing. We previously reported that GEMs are lost and that snRNP biogenesis is misregulated in the motor neurons of ALS patients. Here we show that DPRs interfere with GEM formation and proper SMN localization in HeLa cells and iPSC-derived motor neurons from an ALS patient with theC9ORF72mutation. The accumulation of poly(glycine-arginine) markedly reduced the number of GEMs and caused the formation of aberrant cytoplasmic RNA granules that sequestered SMN. These findings indicate the functional impairment of SMN in motor neurons expressing DPRs and may provide a mechanism to explain the vulnerability of motor neurons of C9ORF72-ALS patients.
Inhibition of microbial deconjugation of micellar bile acids protects against intestinal permeability and liver injury
Authors: Li Darrick K. , Chaudhari Snehal N. , Sojoodi Mozhdeh , Lee Yoojin , Adhikari Arijit A. , Zukerberg Lawrence , Shroff Stuti , Barrett Stephen Cole , Tanabe Kenneth , Chung Raymond T. , Devlin A. Sloan 
Published: March 2021

AbstractAltered host-microbe interactions and increased intestinal permeability have been implicated in the pathogenesis of a range of diseases. However, the mechanisms by which gut microbes affect epithelial barrier integrity remain unclear. Few host-produced metabolites that protect against epithelial damage have been identified, and whether microbial metabolism of host factors alters intestinal barrier function is unknown. Here, we investigate the effects of bacterial metabolism of host-produced bile acid (BA) metabolites on epithelial barrier integrity. We observe that rats fed a choline-deficient, high-fat diet (CDAHFD) exhibit reduced abundance of host-produced conjugated BAs in the intestine at early timepoints coinciding with increased permeability. We show that in vitro, conjugated BAs protect gut epithelial monolayers from damage caused by bacterially produced unconjugated BAs through micelle formation. We then demonstrate that inhibition of BA deconjugation using a small molecule inhibitor of gut bacterial bile salt hydrolase (BSH) enzymes prevents development of pathologic intestinal permeability and hepatic inflammation in CDAHFD-fed rats. Finally, we show that the predominant conjugated BAs in humans protect against epithelial barrier disruption in vitro. Our study identifies a protective role for conjugated BAs in intestinal epithelial barrier function and suggests that rational manipulation of microbial BA metabolism could be leveraged to regulate gut barrier integrity.
The N400 ERP component reflects a learning signal during language comprehension
Authors: Hodapp Alice , Rabovsky Milena 
Published: March 2021

AbstractThe functional significance of the N400 ERP component is still actively debated. Based on neural network modeling it was recently proposed that the N400 component can be interpreted as the change in a probabilistic representation corresponding to an internal temporal-difference prediction error at the level of meaning that drives adaptation in language processing. These computational modeling results imply that increased N400 amplitudes should correspond to greater adaptation. To investigate this model derived hypothesis, the current study manipulated expectancy in a sentence reading task, which influenced N400 amplitudes, and critically also later implicit memory for the manipulated word: reaction times in a perceptual identification task were significantly faster for previously unexpected words. Additionally, it could be demonstrated that this adaptation seems to specifically depend on the process underlying N400 amplitudes, as participants with larger N400 differences also exhibited a larger implicit memory benefit. These findings support the interpretation of the N400 as an implicit learning signal in language processing.
Autophagy promotes photomorphogenesis during seedling development in Arabidopsis in carbon limiting conditions
Authors: Wijerathna-Yapa Akila , Signorelli Santiago , Fenske Ricarda , Ganguly Diep R. , Stroeher Elke , Li Lei , Pogson Barry J. , Duncan Owen , Millar A. Harvey 
Published: March 2021

AbstractAutophagy is a conserved catabolic process that plays an essential role under nutrient starvation condition and influences different developmental processes. We observed that seedlings of autophagy mutants (atg2,atg5,atg7,andatg9) germinated in the dark showed delayed chloroplast development following illumination. The delayed chloroplast development was characterized by a decrease in photosynthetic and chlorophyll biosynthetic proteins, lower chlorophyll content, reduced chloroplast size, and increased levels of proteins involved in lipid biosynthesis. Confirming the biological impact of these differences, photosynthetic performance was impaired in autophagy mutants 12h post illumination. We investigated if the delayed chloroplast development could be explained by lower lipid import to the chloroplast or lower triglyceride (TAG) turnover. We observed that the limitations in the chloroplast lipid import imposed bytrigalactosyldiacylglycerol1are unlikely to explain the delay in photomorphogenesis. However, we found that lower TAG mobility in the triacylglycerol lipase mutantsugardependent1significantly affected photomorphogenesis. Moreover, we showed that lower levels of carbon resources exacerbated the delay in photomorphogenesis whereas higher levels of carbon resources had an opposite effect. This work provides evidence that autophagic process operate during de-etiolation in a manner that contributes to photomorphogenesis through increasing lipid turnover to physically or energetically sustain photomorphogenesis.