bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular structure image classification with small targeted training samples
Authors: Wang Dali , Lu Zheng , Xu Yichi , Wang Zi , Li Chengcheng , Santella Anthony , Bao Zhirong 
Published: February 2019

AbstractMotivationCell shapes provide crucial biology information on complex tissues. Different cell types often have distinct cell shapes, and collective shape changes usually indicate morphogenetic events and mechanisms. The identification and detection of collective cell shape changes in an extensive collection of 3D time-lapse images of complex tissues is an important step in assaying such mechanisms but is a tedious and time-consuming task. Machine learning provides new opportunities to automatically detect cell shape changes. However, it is challenging to generate sufficient training samples for pattern identification through deep learning because of a limited amount of images and annotations.ResultWe present a deep learning approach with minimal well-annotated training samples and apply it to identify multicellular rosettes from 3D live images of the Caenorhabditis elegans embryo with fluorescently labelled cell membranes. Our strategy is to combine two approaches, namely, feature transfer and generative adversarial networks (GANs), to boost image classification with small training samples. Specifically, we use a GAN framework and conduct an unsupervised training to capture the general characteristics of cell membrane images with 11,250 unlabelled images. We then transfer the structure of the GAN discriminator into a new Alex-style neural network for further learning with several dozen labelled samples. Our experiments showed that with 10-15 well-labelled rosette images and 30-40 randomly selected non-rosette images our approach can identify rosettes with over 80% accuracy and capture over 90% of the model accuracy achieved with a training dataset that is five times larger. We also established a public benchmark dataset for rosette detection. This GAN-based transfer approach can be applied to study other cellular structures with minimal training samples.Contactdwang7@utk.edu, baoz@mskcc.org
scGEApp: a Matlab app for feature selection on single-cell RNA sequencing data
Authors: Cai James J. 
Published: February 2019

AbstractMotivationThe recent development of single-cell technologies, especially single-cell RNA sequencing (scRNA-seq), provides an unprecedented level of resolution to the cell type heterogeneity. It also enables the study of gene expression variability across individual cells within a homogenous cell population. Feature selection algorithms have been used to select biologically meaningful genes while controlling for sampling noise. An easy-to-use application for feature selection on scRNA-seq data requires integration of functions for data filtering, normalization, visualization, and enrichment analyses. Graphic user interfaces (GUIs) are desired for such an application.ResultsWe used native Matlab and App Designer to develop scGEApp for feature selection on singlecell gene expression data. We specifically designed a new feature selection algorithm based on the 3D spline fitting of expression mean (μ), coefficient of variance (CV), and dropout rate (rdrop), making scGEApp a unique tool for feature selection on scRNA-seq data. Our method can be applied to single-sample or two-sample scRNA-seq data, identify feature genes, e.g., those with unexpectedly high CV for given μ and rdrop of those genes, or genes with the most feature changes. Users can operate scGEApp through GUIs to use the full spectrum of functions including normalization, batch effect correction, imputation, visualization, feature selection, and downstream analyses with GSEA and GOrilla.Availabilityhttps://github.com/jamesjcai/scGEAppContact:jcai@tamu.eduSupplementary informationSupplementary data are available at Bioinformatics online.
Increase in weighting of vision vs. proprioception associated with force field adaptation
Authors: Sexton Brandon M. , Liu Yang , Block Hannah J. 
Published: February 2019

AbstractHand position can be encoded by vision, via an image on the retina, and proprioception (position sense), via sensors in the joints and muscles. The brain is thought to weight and combine available sensory estimates to form an integrated multisensory estimate of hand position with which to guide movement. Force field adaptation, a form of cerebellum-dependent motor learning in which reaches are systematically adjusted to compensate for a somatosensory perturbation, is associated with both motor and proprioceptive changes. The cerebellum has connections with parietal regions thought to be involved in multisensory integration; however, it is unknown if force adaptation is associated with changes in multisensory perception. One possibility is that force adaptation affects all relevant sensory modalities similarly, such that the brain’s weighting of vision vs. proprioception is maintained. Alternatively, the somatosensory perturbation might be interpreted as proprioceptive unreliability, resulting in vision being up-weighted relative to proprioception. We assessed visuo-proprioceptive weighting with a perceptual estimation task before and after subjects performed straight-ahead reaches grasping a robotic manipulandum. Each subject performed one session with a clockwise or counter-clockwise velocity-dependent force field, and one session in a null field to control for perceptual changes not specific to force adaptation. Subjects increased their weight of vision vs. proprioception in the force field session relative to the null field session, regardless of force field direction, in the straight-ahead dimension (F1,44 = 5.13, p = 0.029). This suggests that force field adaptation is associated with an increase in the brain’s weighting of vision vs. proprioception.
Horizontal transfer of prokaryotic cytolethal distending toxin B genes to eukaryotes
Authors: Verster Kirsten I. , Wisecaver Jennifer H. , Duncan Rebecca P. , Karageorgi Marianthi , Gloss Andrew D. , Armstrong Ellie , Price Donald K. , Menon Aruna R. , Ali Zainab M. , Whiteman Noah K. 
Published: February 2019

AbstractCytolethal distending toxins (CDTs) are tripartite eukaryotic genotoxins encoded in diverse bacterial and phage genomes. The cdtB subunit is a DNAse that causes eukaryotic cell cycle arrest and apoptosis, and in one context, is associated with resistance against parasitoid wasp infections. Here we report the discovery of functional cdtB copies in the nuclear genomes of insect species from two distantly related insect orders, including fruit flies (Diptera: Drosophilidae) and aphids (Hemiptera: Aphididae). Insect cdtB copies are most closely related to bacteriophage copies, were horizontally transferred to insect genomes > 40 million years ago and encode a protein that retains ancestral DNase activity. This phage-derived toxin has been domesticated by diverse insects and we hypothesize that it is used as a defensive weapon against parasitoid wasps.One Sentence SummaryWe report horizontal transfer of the gene cytolethal distending toxin B, which encodes a DNase, into eukaryotic genomes from bacteriophage.SignificanceCytolethal distending toxins (CDTs) are secreted by diverse pathogenic bacterial species to kill animal cells. The cdtB subunit enters cell nuclei, damaging the DNA and leading to mitotic arrest and apoptosis. In the pea aphid, a bacterial endosymbiont provides protection against wasp attack, possibly via cdtB. We discovered that this same endosymbiont-encoded lineage of cdtB was transferred to the genomes of Diptera and Hemiptera species and retains ancestral DNase activity. This is the first report of cdtB outside of bacteria or phages. A toxin that first evolved to kill eukaryotic cells has been co-opted by insects, potentially to their benefit.
Insular Cortex Projections to Nucleus Accumbens Core Mediate Social Approach to Stressed Juvenile Rats
Authors: Rogers-Carter Morgan M. , Djerdjaj Anthony , Gribbons Katherine B. , Varela Juan A. , Christianson John P. 
Published: February 2019

Social interactions are shaped by features of the interactants including age, emotion, sex and familiarity. Age-specific responses to social affect are evident when an adult male rat is presented with a pair of unfamiliar male conspecifics, one of which is stressed via 2 footshocks and the other naïve to treatment. Adult test rats prefer to interact with stressed juvenile (PN30) conspecifics, but avoid stressed adult (PN50) conspecifics. This pattern depends upon the insular cortex (IC) which is anatomically connected to the nucleus accumbens core (NAc). The goal of this work was to test the necessity of IC projections to NAc during social affective behavior. Here, bilateral pharmacological inhibition of the NAc with tetrodotoxin (1µM; 0.5ul/side) abolished the preference for stressed PN30, but did not alter interactions with PN50 conspecifics. Using a combination of retrograding tracing and c-Fos immunohistochemistry, we report that social interactions with stressed PN30 conspecifics elicit greater Fos immunoreactivity in IC → NAc neurons than interactions with naïve PN30 conspecifics. Chemogenetic stimulation of IC terminals in the NAc increased social exploration with juvenile, but not adult, conspecifics, while chemogenetic inhibition of this tract blocked the preference to investigate stressed PN30 conspecifics, which expands upon our previous finding that optogenetic inhibition of IC projection neurons mediated approach and avoidance. These new findings suggest that outputs of IC to the NAc modulate social approach, which provides new insight to the neural circuitry underlying social decision-making.Significance StatementSocial decision-making underlies an animal’s behavioral response to others in a range of social contexts. Previous findings indicate the insular cortex (IC) and the nucleus accumbens (NAc) play important roles in a range of social behaviors, and human neuroimaging implicates both IC and NAc in autism and other psychiatric disorders characterized by aberrant social cognition. To test whether IC projections to the NAc are involved in social decision making, circuit-specific chemogenetic manipulations demonstrated that the IC → NAc pathway mediates social approach toward distressed juvenile, but not adult, conspecifics. This finding is the first to implicate this circuit in rodent socioemotional behaviors and may be a neuroanatomical substrate for integration of emotion with social reward.
Helicobacter pylori Senses Bleach as a Chemoattractant Using a Cytosolic Chemoreceptor
Authors: Perkins Arden , Tudorica Dan A. , Amieva Manuel R. , Remington S. James , Guillemin Karen 
Published: February 2019

SUMMARYThe gastric pathogenHelicobacter pylorirequires a non-canonical cytosolic chemoreceptor transducer-like protein D (TlpD) for efficient colonization of the mammalian stomach. Here we reconstituted a complete chemotransduction signaling complexin vitrowith TlpD and the chemotaxis proteins CheW and CheA, enabling quantitative assays for potential chemotaxis ligands. We found that TlpD is selectively sensitive at micromolar concentrations to bleach (hypochlorous acid, HOCl), a potent antimicrobial produced by neutrophil myeloperoxidase during inflammation. Counterintuitively, HOCl acts as a chemoattractant by reversibly oxidizing a conserved cysteine within a 3His/1Cys Zn-binding motif in TlpD that inactivates the chemotransduction signaling complex. We found thatH. pyloriis resistant to killing by millimolar concentrations of HOCl and responds to bleach in the micromolar range by increasing its smooth swimming behavior, leading to chemoattraction to HOCl sources. We found that related protein domains fromSalmonella entericaandEscherichia colishowed a similar reactivity toward bleach. We propose that this family of proteins enables host-associated bacteria to sense sites of tissue inflammation, a strategy thatH. pyloriuses to aid in colonizing and persisting in inflamed gastric tissue.
Age and sex-dependent patterns of gut microbial diversity in human adults
Authors: de la Cuesta-Zuluaga Jacobo , Kelley Scott T. , Chen Yingfeng , Escobar Juan S. , Mueller Noel T. , Ley Ruth E. , McDonald Daniel , Huang Shi , Swafford Austin D. , Knight Rob , Thackray Varykina G. 
Published: February 2019

AbstractGut microbial diversity changes throughout the human lifespan and is known to be affected by host sex. We investigated the association of age, sex and gut bacterial alpha diversity in three large cohorts of adults from four geographical regions: US and UK cohorts in the American Gut Project, and two independent cohorts of Colombians and Chinese. In three of the four cohorts, we observed a strong positive association between age and alpha diversity in young adults that plateaued after age 40. We also found pronounced sex-dependent differences in younger but not middle-aged adults, and women had higher alpha diversity than men. In contrast, no association of alpha diversity with age or sex was observed in the Chinese cohort. These associations were maintained after adjusting for cardiometabolic parameters in the Colombian cohort and antibiotic usage in the AGP cohort, suggesting that these factors do not affect the association of alpha diversity with age and sex. We also used a machine learning approach to predict individual age based on the gut microbiome. Consistent with our alpha diversity-based findings, women had significantly higher predicted age than men in the US and UK cohort, with a reduced difference above age 40. This was not observed in the Colombian cohort and only in the group of middle-age adults in the Chinese cohort. Together, our results provide new insights into the influence of age and sex on biodiversity of the human gut microbiota during adulthood while highlighting similarities and differences across diverse cohorts.
Physiological and Evolutionary Implications of Tetrameric Photosystem I in Cyanobacteria
Authors: Li Meng , Calteau Alexandra , Semchonok Dmitry A. , Witt Thomas A. , Nguyen Jonathan T. , Sassoon Nathalie , Boekema Egbert J. , Whitelegge Julian , Gugger Muriel , Bruce Barry D. 
Published: February 2019

AbstractPhotosystem I (PSI) were reported as trimeric complexes in most characterized cyanobacteria, yet monomers in plants and algae PSI. Recent reports on tetrameric PSI raised questions regarding its structural basis, physiological role, phylogenetic distribution and evolutionary significance. In this study, by examining PSI in 61 cyanobacteria, we show that tetrameric PSI, correlating with a uniquepsaLgene and genomic structure, is widespread in the heterocyst-forming cyanobacteria and their close relatives. Physiological studies on these cyanobacteria revealed that tetrameric PSI is favored under high light, with an increased content of novel PSI-bound carotenoids (myxoxanthophyll, canthaxanthan and echinenone). Together this work suggests that tetrameric PSI is an adaptation to high light, along with results showing that change in PsaL leads to trimeric PSI monomerization, supporting the hypothesis of tetrameric PSI being the evolutionary intermediate in the transition from cyanobacterial trimeric PSI to monomeric PSI in plants and algae.
Cold-induced switch in direction of chloroplast relocation occurs independently of changes in endogenous phototropin expression
Authors: Fujii Yuta , Ogasawara Yuka , Takahashi Yamato , Sakata Momoko , Tamura Saori , Kodama Yutaka 
Published: February 2019

AbstractWhen exposed to fluctuating light intensity, chloroplasts move towards weak light (accumulation response), and away from strong light (avoidance response). In addition, cold treatment (5°C) induces the avoidance response even under weak light conditions (cold-avoidance response). These three responses are mediated by the phototropin (phot), which is a blue-light photoreceptor and has also been found to act as a thermosensory protein that perceives temperature variation. Our previous report indicated that cold-induced changes in phot biochemical activity initiate the cold-avoidance response. In this study, we further explored the induction mechanism of the cold-avoidance response in the liverwort Marchantia polymorpha and examined the relationship between changes in the amount of phot and the induction of the cold-avoidance response. The switch between the accumulation and avoidance responses occurs at a so-called ‘transitional’ light intensity. Our physiological experiments revealed that a cold-mediated decrease in the transitional light intensity leads to the induction of the cold-avoidance response. While artificial overexpression of phot decreased the transitional light intensity as much as cold treatment did, the amount of endogenous phot remained unchanged by cold treatment in wild-type M. polymorpha. Taken together, these findings show that the cold-avoidance response is initiated by a cold-mediated reduction of the transitional light intensity, independent of the amount of endogenous phot. This study provides a clue to understand the mechanism underlying the switch in direction of chloroplast relocation in response to light and temperature.
Homotypic and heterotypic trans-assembly of human Rab-family small GTPases in reconstituted membrane tethering
Authors: Segawa Kazuya , Tamura Naoki , Mima Joji 
Published: February 2019

AbstractMembrane tethering is a highly regulated event that occurs during the initial physical contact between membrane-bounded transport carriers and their target subcellular membrane compartments, thereby ensuring the spatiotemporal specificity of intracellular membrane trafficking. Although Rab-family small GTPases and specific Rab-interacting effectors, such as coiled-coil tethering proteins and multisubunit tethering complexes, are known to be involved in membrane tethering, how these protein components directly act upon the tethering event remains enigmatic. Here, we investigated the molecular basis of membrane tethering by comprehensively and quantitatively evaluating the intrinsic capacities of 10 representative human Rab-family proteins (Rab1a, 3a, 4a, 5a, 6a, 7a, 9a, 11a, 27a, and 33b) to physically tether two distinct membranes via homotypic and heterotypic Rab-Rab assembly in a chemically defined reconstitution system. All of the Rabs tested, except Rab27a, specifically caused homotypic membrane tethering at physiologically relevant Rab densities on membrane surfaces (e.g., Rab-to-lipid molar ratios of 1:100-1:3,000). Notably, endosomal Rab5a retained its intrinsic potency to drive efficient homotypic tethering even at concentrations below the Rab-to-lipid ratio of 1:3,000. Comprehensive reconstitution studies further uncovered that heterotypic combinations of human Rab-family isoforms, including Rab1a/6a, Rab1a/9a, and Rab1a/33b, can directly and selectively mediate membrane tethering. Rab1a and Rab9a, in particular, synergistically triggered very rapid and efficient membrane tethering reactions through their heterotypic trans-assembly on two opposing membranes. Thus, our findings establish that, in the physiological context, homotypic and heterotypic trans-assembly of Rab-family small GTPases can provide the essential molecular machinery necessary to drive membrane tethering in eukaryotic endomembrane systems.
Comparative genome analysis of 12 Shigella sonnei strains: virulence, resistance, and their interactions
Authors: Zhu Zuobin , Wang Liang , Gu Feng , Li Ying , Zhang Heng , Chen Ying , Shi Jiajia , Ma Ping , Gu Bing 
Published: February 2019

AbstractShigellosis is a highly infectious disease that are mainly transmitted via faecal-oral contact of the bacteria Shigella. Four species have been identified in Shigella genus, among which S. flexneri is used to be the most prevalent species globally and commonly isolated from developing countries. However, it is being replaced by S. sonnei that is currently the main causative agent for dysentery pandemic in many emerging industrialized countries such as Asia and the Middle East with unclear reasons. For a better understanding of S. sonnei virulence and antibiotic resistance, we sequenced 12 clinical S. sonnei strains with varied antibiotic-resistance profiles collected from four cities in Jiangsu Province, China. Phylogenomic analysis clustered antibiotic sensitive and resistant S. sonnei into two distinct groups while pangenome analysis reveals the presence and absence of featured genes in each group. Screening of 31 classes of virulence factors found out that type 2 secretion system is doubled in resistant strains. Further principle component analysis based on the interactions between virulence and resistance indicated that abundant virulence factors are associated with higher resistant phenotypes. The result present here is based on statistical analysis of a small sample size and serves basically as a guidance for further experimental and theoretical studies.
Rhodopsin-based voltage imaging tools for use in excitable cells of Caenorhabditis elegans
Authors: Hashemi Negin Azimi , Bergs Amelie C. F. , Scheiwe Rebecca , Costa Wagner Steuer , Liewald Jana F. , Gottschalk Alexander 
Published: February 2019

AbstractGenetically encoded voltage indicators (GEVIs) based on microbial rhodopsins utilize the voltage-sensitive fluorescence of the all-trans retinal (ATR) cofactor, while in electrochromic (eFRET) sensors, donor fluorescence drops when the rhodopsin acts as depolarization-sensitive acceptor. We systematically assessed Arch(D95N), Archon, and QuasAr, as well as the eFRET sensors MacQ-mCitrine and QuasAr-mOrange, in C. elegans. ATR-bearing rhodopsins reported on voltage changes in body wall muscles (BWMs) and the pharynx, the feeding organ, where Arch(D95N) showed ca. 125 % ΔF/F increase per 100 mV. The ATR fluorescence is very dim, however, using the retinal analog dimethylaminoretinal (DMAR), it was boosted 250-fold. eFRET sensors provided sensitivities of 45 % to 78 % ΔF/F per 100 mV, induced by BWM action potentials (APs). All sensors reported differences in muscle depolarization induced by a voltage-gated Ca2+-channel mutant. Optogenetically evoked de-or hyperpolarization of motor neurons increased or eliminated AP activity and caused a rise or drop in BWM sensor fluorescence. Last, we could analyze voltage dynamics across the entire pharynx, showing uniform depolarization but compartmentalized repolarization of anterior and posterior parts. Our work establishes all-optical, non-invasive electrophysiology in intact C. elegans.