bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated strain separation in low-complexity metagenomes using long reads
Authors: Vicedomini R. , Quince C. , Darling A. E. , Chikhi R. 
Published: February 2021

AbstractHigh-throughput short-read metagenomics has enabled large-scale species-level analysis and functional characterization of microbial communities. Microbiomes often contain multiple strains of the same species, and different strains have been shown to have important differences in their functional roles. Despite this, strain-level resolution from metagenomic sequencing remains challenging. Recent advances on long-read based methods enabled accurate assembly of bacterial genomes from complex microbiomes and an as-yet-unrealized opportunity to resolve strains. Here we present Strainberry, a metagenome assembly method that performs strain separation in single-sample low-complexity metagenomes and that relies uniquely on long-read data. We benchmarked Strainberry on mock communities and showed it consistently produces strain-resolved assemblies with near-complete reference coverage and 99.9% base accuracy. We also applied Strainberry on real datasets for which it improved assemblies generating 20-118% additional genomic material than conventional metagenome assemblies on individual strain genomes. Our results hence demonstrate that strain separation is possible in low-complexity microbiomes using a single regular long read dataset. We show that Strainberry is also able to refine microbial diversity in a complex microbiome, with complete separation of strain genomes. We anticipate this work to be a starting point for further methodological improvements aiming to provide better strain-resolved metagenome assemblies in environments of higher complexities.
Power spectra reveal distinct BOLD resting‐state time courses in white matter
Authors: Li Muwei , Gao Yurui , Ding Zhaohua , Gore John C. 
Published: February 2021

AbstractAccurate characterization of the time courses of BOLD signal changes is crucial for the analysis and interpretation of functional MRI data. While several studies have shown that white matter (WM) exhibits distinct BOLD responses evoked by tasks, there have been no comprehensive investigations into the time courses of spontaneous signal fluctuations in WM. We measured the power spectra of the resting‐state time courses in a set of regions within WM identified as showing synchronous signals using independent components analysis. In each component, a clear separation between voxels into two categories was evident, based on their power spectra: one group exhibited a single peak, the other had an additional peak at a higher frequency. Their groupings are location‐specific, and their distributions reflect unique neurovascular and anatomical configurations. Importantly, the two categories of voxels differed in their engagement in functional integration, revealed by differences in the number of inter‐ regional connections based on the two categories separately. Moreover, the power spectral measurements in voxels with two peaks in specific components predict specific human behaviors. Taken together, these findings suggest WM signals are heterogeneous in nature and depend on local structural‐vascular‐functional associations.
Human blood lipoprotein predictions from1H NMR spectra: protocol, model performances and cage of covariance
Authors: Khakimov Bekzod , Hoefsloot Huub C.J. , Mobaraki Nabiollah , Aru Violetta , Kristensen Mette , Lind Mads V. , Holm Lars , Castro-Mejía Josué L , Nielsen Dennis S , Jacobs Doris M. , Smilde Age K. , Engelsen Søren Balling 
Published: February 2021

AbstractLipoprotein subfractions are biomarkers for early diagnosis of cardiovascular diseases. The reference method, ultracentrifugation, for measuring lipoproteins is time consuming and there is a need to develop a rapid method for cohort screenings. Here we present partial least squares regression models developed using1H-NMR spectra and concentrations of lipoproteins as measured by ultracentrifugation on 316 healthy Danes. Different regions of the1H-NMR spectra representing signals of the lipoproteins and different lipid species were investigated to develop parsimonious, reliable and best performing prediction models. 65 LP main and subfractions were predictable with an accuracy Q2of > 0.6 on test set samples. The models were tested on an independent cohort of 290 healthy Swedes with predicted and reference values matching by up to 85-95%. The software was developed to predict lipoproteins in human blood using1H-NMR spectra and made freely available to be applied for future cohort screenings.
Perception of biological motion in point-light displays by jumping spiders
Authors: De Agrò Massimo , Rößler Daniela C. , Kim Kris , Shamble Paul S. 
Published: February 2021

AbstractOver the last 50 years, point-light displays have been successfully used to explore how animals respond to dynamic visual stimuli—specifically, differentiation of the biological from the non-biological. These stimuli are designed to preserve movement patterns while minimizing static detail, with single dots representing each of the main joints of a moving animal. Imposed by their internal skeleton, vertebrate movements follow a specific semi-rigid dynamic pattern, termed “biological-motion”, which can be used to distinguish animate from inanimate objects. Although biological motion detection has not been studied in invertebrates, rigid exoskeletons force many species to also follow semi-rigid movement principles. Due to their highly developed visual system and complex visual behaviors, we investigated the capability of jumping spiders to discriminate biological from non-biological motion using point-light display stimuli. By constraining spiders so that they could rotate but not move directionally, we simultaneously presented two point-light display stimuli with specific dynamic traits and registered their preference by observing which pattern they turned towards. Jumping spiders clearly demonstrated the ability to discriminate between stimuli. However, spiders showed no preference when both stimuli presented patterns with semi-rigid movements, results that are directly comparable to responses in vertebrate systems. This represents the first demonstration of biological motion recognition in an invertebrate, posing crucial questions about the evolutionary history of this ability and complex visual processing in non-vertebrate systems.
Cryo-EM study on the homo-oligomeric ring formation of yeast TRiC/CCT subunits reveals TRiC ring assembly mechanism
Authors: Liu Caixuan , Wang Huping , Jin Mingliang , Han Wenyu , Wang Shutian , Wang Yanxing , Wang Fangfang , Su Chun , Hong Xiaoyu , Zhao Qiaoyu , Cong Yao 
Published: February 2021

AbstractThe complex eukaryotic chaperonin TRiC/CCT helps maintain cellular protein homeostasis, however, its assembly mechanism remains largely unknown. To address the subunit specificity in TRiC assembly, we express each of the individual yeast TRiC subunit inE. coli. Our cryo-EM structural study and biochemical analyses demonstrate that CCT1/2/6 can form TRiC-like homo-oligomeric double ring (HR) complex, however ATP-hydrolysis cannot trigger their ring closure; after deletion of the long N-terminal extension, CCT5 can form the closed double-ring structure; while CCT3/4/7/8 cannot form the HRs. It appears that CCT1 forms a HR in a unique spiral configuration, and ATP-hydrolysis can drive it to re-assemble with an inserted extra subunit-pair. Our data suggest that CCT5 could be the leading subunit in ATP-hydrolysis-driven TRiC ring closure. Moreover, we demonstrate that ADP is sufficient to trigger the assembly of the HRs and TRiC from the assembly intermediate micro-complex form. Our study reveals that through evolution, the more ancestral subunits may have evolved to take more responsibilities in TRiC ring assembly, and we propose a possible assembly mechanism of TRiC involving subunit-pair insertion. Collectively, our study gives hints on the structural basis of subunit specificity in TRiC assembly and cooperativity, beneficial for future TRiC-related therapeutic strategy development.
REMY: A platform for the rapid interrogation of epigenome modifications on yeast
Authors: Waldman Alison C. , Rao Balaji M. , Keung Albert J. 
Published: February 2021

AbstractHistone proteins are decorated with a combinatorially and numerically diverse set of biochemical modifications. Here we describe a versatile and scalable platform termedRapid interrogation ofEpigenomeModifications usingYeast surface display (REMY), which enables efficient characterization of histone modifications without the need for recombinant protein production. As proof-of-concept, we first used REMY to rapidly profile the histone H3 and H4 residue writing specificities of the human histone acetyltransferase, p300. Subsequently, we used REMY to screen a large panel of commercially available anti-acetylation antibodies for their specificities, identifying many suitable and unsuitable reagents. Further, use of REMY enabled efficient mapping of the large binary crosstalk space between acetylated residues on histones H3 and H4, and uncovered previously unreported residue interdependencies affecting p300 activity. Our results show that REMY is a useful tool that can advance our understanding of chromatin biology by enabling efficient interrogation of the complexity of epigenome modifications.
The mitochondrial pyruvate carrier (MPC) complex is one of three pyruvate-supplying pathways that sustain Arabidopsis respiratory metabolism
Authors: Le Xuyen H. , Lee Chun-Pong , Millar A. Harvey 
Published: February 2021

AbstractMalate oxidation by plant mitochondria enables the generation of both oxaloacetate (OAA) and pyruvate for tricarboxylic acid (TCA) cycle function, potentially eliminating the need for pyruvate transport into mitochondria in plants. Here we show that the absence of the mitochondrial pyruvate carrier 1 (MPC1) causes the co-commitment loss of its orthologs, MPC3/MPC4, and eliminates pyruvate transport into Arabidopsis mitochondria, proving it is essential for MPC complex function. While the loss of either MPC or mitochondrial pyruvate-generating NAD-malic enzyme (NAD-ME) did not cause vegetative phenotypes, the lack of both reduced plant growth and caused an increase in cellular pyruvate levels, indicating a block in respiratory metabolism, and elevated the levels of branched-chain amino acids at night, a sign of alterative substrate provision for respiration.13C-pyruvate feeding of leaves lacking MPC showed metabolic homeostasis were largely maintained except for alanine and glutamate, indicating that transamination contributes to restoration of the metabolic network to an operating equilibrium by delivering pyruvate independently of MPC into the matrix. Inhibition of alanine aminotransferases (AlaAT) when MPC1 is absent resulted in extremely retarded phenotypes in Arabidopsis, suggesting all pyruvate-supplying enzymes work synergistically to support the TCA cycle for sustained plant growth.
Urea nitrogen recycling via gut symbionts increases in hibernators over the winter fast
Authors: Regan Matthew D. , Chiang Edna , Liu Yunxi , Tonelli Marco , Verdoorn Kristen M. , Gugel Sadie R. , Suen Garret , Carey Hannah V. , Assadi-Porter Fariba M. 
Published: February 2021

AbstractHibernation is a mammalian strategy that uses metabolic plasticity to reduce energy demands and enable long-term fasting. Fasting mitigates winter food scarcity but eliminates dietary nitrogen, jeopardizing body protein balance. Here, we reveal gut microbiome-mediated urea nitrogen recycling in hibernating 13-lined ground squirrels (TLGS). Ureolytic gut microbes incorporate urea nitrogen into organic compounds that are absorbed by the host, with the nitrogen reincorporated into the TLGS protein pool. Urea nitrogen recycling is greatest after prolonged fasting in late winter, when urea transporter abundance in gut tissue and urease gene abundance in the microbiome are highest. These results reveal a functional role for the gut microbiome in hibernation and suggest mechanisms by which urea nitrogen recycling contributes to protein balance in other monogastric animals, including humans.One Sentence SummaryGround squirrels and their gut symbionts benefit from urea nitrogen recycling throughout hibernation.
Condensation of theDrosophilaNerve Cord is Oscillatory and depends on Coordinated Mechanical Interactions
Authors: Karkali Katerina , Tiwari Prabhat , Singh Anand , Tlili Sham , Jorba Ignasi , Navajas Daniel , Muñoz José J. , Saunders Timothy E. , Martin-Blanco Enrique 
Published: February 2021

AbstractDuring development, organs must form with precise shapes and sizes. Organ morphology is not always obtained through growth; a classic counterexample is condensation of the nervous system duringDrosophilaembryogenesis. The mechanics underlying such condensation remain poorly understood. Here, we combinein totolive-imaging, biophysical and genetic perturbations, and atomic force microscopy to characterize the condensation of theDrosophilaventral nerve cord (VNC) during embryonic development at both subcellular and tissue scales. This analysis reveals that condensation is not a unidirectional continuous process, but instead occurs through oscillatory contractions alternating from anterior and posterior ends. The VNC mechanical properties spatially and temporally vary during its condensation, and forces along its longitudinal axis are spatially heterogeneous, with larger ones exerted between neuromeres. We demonstrate that the process of VNC condensation is dependent on the coordinated mechanical activities of neurons and glia. Finally, we show that these outcomes are consistent with a viscoelastic model of condensation, which incorporates time delays due to the different time scales on which the mechanical processes act, and effective frictional interactions. In summary, we have defined the complex and progressive mechanics driving VNC condensation, providing insights into how a highly viscous tissue can autonomously change shape and size.
Biased removal and loading of centromeric histone H3 during reproduction underlies uniparental genome elimination
Authors: Marimuthu Mohan P.A. , Maruthachalam Ravi , Bondada Ramesh , Kuppu Sundaram , Tan Ek-Han , Britt Anne , Chan Simon S.W. , Comai Luca 
Published: February 2021

AbstractUniparental genome elimination is a dramatic case of centromeric failure, resulting in the postzygotic loss of a parental chromosome set. Genome partitioning during cell division relies on centromere attachment to spindle fibers through kinetochores. Centromeres are epigenetically specified by CENP-A (CENH3), a conserved centromeric specific histone H3 variant. In Arabidopsis, CENH3 modification results in haploid inducers, whose genome is eliminated frequently when crossed to the wild type. To investigate the underlying mechanism, we dissected the timing and molecular features of genome elimination. In zygotes and early embryos from genome elimination crosses, CENH3 occupied only the centromeres contributed by the wild-type parent. Haploid inducer chromosomes had defective kinetochores and missegregated, often forming micronuclei. This uniparental loss of centromere identity is initiated by the removal of altered CENH3 at fertilization, while wild-type CENH3 persists and maintains strong centromeric identity. Weak centromeres were capable of rebuilding functional kinetochores, but often failed when in competition with normal ones. We induced a similar weak state by mitotic dilution of wild-type CENH3. Furthermore, weakness was suppressed by crosses of haploid inducers to other variants of haploid inducers, and enhanced by mutations inVIM1, a ubiquitin ligase known to modify CENH3 and centromeric DNA methylation.. The differential stability of altered CENH3 during reproduction has important genetic and evolutionary implications.
NADPH Oxidase 2 Derived Reactive Oxygen Species Promote CD8+T cell Effector Function
Authors: Chen Jing , Liu Chao , Chernatynskaya Anna V. , Newby Brittney , Brusko Todd M. , Xu Yuan , Morgan Nadine , Santarlas Christopher P. , Reeves Westley H. , Tse Hubert M. , Leiding Jennifer W. , Mathews Clayton E. 
Published: February 2021

ABSTRACTOxidants participate in lymphocyte activation and function. We previously demonstrated that eliminating the activity of NADPH oxidase 2 (NOX2) significantly impaired the effectiveness of autoreactive CD8+cytotoxic T lymphocytes (CTL). However, the molecular mechanisms impacting CTL function remain unknown. Here, we studied the role of NOX2 in both non-obese diabetic (NOD) mouse and human CTL function. Genetic ablation or chemical inhibition of NOX2 in CTL significantly suppressed activation-induced expression of the transcription factor T-bet, the master transcription factor of the Tc1 cell lineage, and T-bet target effectors genes such as IFNγ and granzyme B. Inhibition of NOX2 in both human and mouse CTL prevented target cell lysis. We identified that superoxide generated by NOX2 must be converted into hydrogen peroxide to transduce the redox signal in CTL. Further, we show that NOX2-generated oxidants deactivate the Tumor Suppressor Complex leading to mTOR complex 1 activation and CTL effector function. These results indicate that NOX2 plays a non-redundant role in T cell receptor-mediated CTL effector function.
Dynamics of anteroposterior axis establishment in a mammalian embryo-like system
Authors: Anlaş Kerim , Gritti Nicola , Oriola David , Arató Krisztina , Nakaki Fumio , Lim Jia Le , Sharpe James , Trivedi Vikas 
Published: February 2021

1.AbstractIn the mammalian embryo, specification of the anteroposterior (AP) axis demarcates one of the first steps of body plan formation. While this process requires interactions with extra-embryonic tissues in the native embryo, minimalin vitrosystems from embryonic stem cells (ESCs) undergo initial AP polarization in the absence of any localized, external cues. This self-organizing potential of stem cells remains not well understood. Here, we study such an initial symmetry breaking event in gastruloids, an establishedin vitromodel for mammalian body plan formation, using the mesodermal marker gene Brachyury or T (Bra/T) to denote the onset of AP axis specification and concomitant germ layer formation. Through aggregate fusion experiments and manipulation of initial culture conditions as well as key developmental signalling pathways, we probe the dynamics of Bra/T polarization. We further conduct single-cell (sc) RNA sequencing of gastruloids at early stages to identify incipient molecular signatures of germ layer commitment and differences between Bra/T+and Bra/T−populations during as well as after symmetry breaking. Moreover, we transcriptionally compare early development of gastruloids to the mouse embryo and conclude that gastruloids reproducibly undergo AP axis and germ layer specification in a parallel, but distinct manner: While their primed pluripotent cell populations adopt a more mesenchymal state in lieu of an epithelial epiblast-like transcriptome, the emerging mesendodermal lineagesin vitroare nevertheless similar to their in vivo equivalents. Altogether, this study provides a comprehensive analysis of self-organized body plan establishment in a minimalin vitrosystem of early mammalian patterning and highlights the regulative capacity of mESCs, thereby shedding light on underlying principles of axial polarity formation.
Decoding the brain state-dependent relationship between pupil dynamics and resting state fMRI signal fluctuation
Authors: Sobczak Filip , Pais-Roldán Patricia , Takahashi Kengo , Yu Xin 
Published: February 2021

AbstractPupil dynamics serve as a physiological indicator of cognitive processes and arousal states of the brain across a diverse range of behavioral experiments. Pupil diameter changes reflect brain state fluctuations driven by neuromodulatory systems. Resting state fMRI (rs-fMRI) has been used to identify global patterns of neuronal correlation with pupil diameter changes, however, the linkage between distinct brain state-dependent activation patterns of neuromodulatory nuclei with pupil dynamics remains to be explored. Here, we identified four clusters of trials with unique activity patterns related to pupil diameter changes in anesthetized rat brains. Going beyond the typical rs-fMRI correlation analysis with pupil dynamics, we decomposed spatiotemporal patterns of rs-fMRI with principal components analysis (PCA) and characterized the cluster-specific pupil-fMRI relationships by optimizing the PCA component weighting via decoding methods. This work shows that pupil dynamics are tightly coupled with different neuromodulatory centers in different trials, presenting a novel PCA-based decoding method to study the brain state-dependent pupil-fMRI relationship.
Domestication effects on aggressiveness: Comparison of biting motivation and bite force between wild and domesticated finches
Authors: Suzuki Kenta , Okanoya Kazuo 
Published: February 2021

ABSTRACTDomesticated animals evolve unique traits, known as domestication phenotypes or the domestication syndrome, due to their adaptation to a captive environment and changes in selection pressures. After being tamed, the Bengalese finch (Lonchura striatavar.domestica) has undergone behavioural and physiological trait changes that differ from those of its wild ancestor, the white-rumped munia (Lonchura striata). The Bengalese finch has complex songs, lower fear response, and lower corticosterone levels than those in the white-rumped munia. We hypothesized that domesticated finches increase the effort to reproduce in lieu of maintaining fitness for survival as needed in the wild. Aggressiveness and bite performance affect survival rates and reproductive success, and are good indicators of adaptability in the natural environment. Therefore, we compared the aggressiveness and biting force of white-rumped munias with those of Bengalese finches to explore the evolutionary mechanisms of behavioural changes due to domestication. We found that the Bengalese finch had decreased aggressiveness (incidence of aggressive biting birds and the number of bite responses) and bite force than those in the white-rumped munia due to domestication. Therefore, we believe they could allocate more resources for breeding that would otherwise be needed for coping with predators through aggression.