bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA break formation induces Scc2/cohesin-dependent recruitment of condensin to meiotic chromosomes
Authors: Markowitz Tovah E. , Heldrich Jonna , Hochwagen Andreas 
Published: July 2020

AbstractMeiotic chromosome pairing, recombination, and fertility depends on the conserved loop-axis architecture of meiotic chromosomes. This architecture is modulated by condensin, a structural maintenance of chromosome (SMC) complex that catalyzes chromatin loop formation. Here, we investigated how condensin is recruited to meiotic chromosomes inSaccharomyces cerevisiae. We show that double-strand-break (DSB) formation, the initiating event of meiotic recombination, causes condensin redistribution from the nucleolus to DSB hotspots, pericentromeric regions, and axis attachment sites. Hotspot association of condensin correlates weakly with break probability but does not depend on local DSB formation, whereas association with axis sites and pericentromeric regions depends on the Scc2-associated pool of cohesin, another SMC complex. Intriguingly, Scc2 distribution also changes in response to DSB formation. As condensin and Scc2-cohesin both catalyze chromatin loop extrusion, their redistribution upon DSB formation implies a profound change in chromatin loop dynamics that may help promote proper chromosome pairing and DNA repair.
Hierarchical motor adaptations negotiate failures during force field learning
Authors: Ikegami Tsuyoshi , Ganesh Gowrishankar , Gibo Tricia L. , Yoshioka Toshinori , Osu Rieko , Kawato Mitsuo 
Published: July 2020

AbstractHumans have the amazing ability to learn the dynamics of the body and environment to develop motor skills. Traditional motor studies using arm reaching paradigms have viewed this ability as the process of ‘internal model adaptation’. However, the behaviors have not been fully explored in the case when reaches fail to attain the intended target. Here we examined human reaching under two force fields types; one that induces failures (i.e., target errors), and the other that does not. Our results show the presence of a distinct failure-driven adaptation process that enables quick task success after failures, and before completion of internal model adaptation, but that can result in persistent changes to the undisturbed trajectory. These behaviors can be explained by considering a hierarchical interaction between internal model adaptation and the failure-driven adaptation of reach direction. Our findings suggest that movement failure is negotiated using hierarchical motor adaptations by humans.
Upper body and ankle strategies compensate for reduced lateral stability at very slow walking speeds
Authors: Best Aaron N. , Wu Amy R. 
Published: July 2020

AbstractAt the typical walking speeds of healthy humans, step placement seems to be the primary strategy to maintain gait stability, with ankle torques and upper body momentum providing additional compensation. The average walking speeds of populations with an increased risk of falling, however, are much slower and may require differing control strategies. The purpose of this study was to analyze mediolateral gait stability and the contributions of the different control strategies at very slow walking speeds. We analyzed an open dataset including kinematics and kinetics from eight healthy subjects walking at speeds from 0.1 to 0.6 m/s as well as a self-selected speed. As gait speed slowed, we found that the margin of stability decreased linearly. Increased lateral excursions of the extrapolated centre of mass, caused by increased lateral excursions of the trunk, were not compensated for by an equivalent increase in the lateral centre of pressure, leading to decreased margin of stability. Additionally, both the ankle eversion torque and hip abduction torque at the minimum margin of stability event increased at the same rate as gait speed slowed. These results suggest that the contributions of both the ankle and the upper body to stability are more crucial than stepping at slow speeds, which have important implications for populations with slow gait and limited motor function.
Structures of an intact yeast V-ATPase alone and in complex with bacterial effector VopQ
Authors: Peng Wei , Fernandez Jessie , Casey Amanda K. , Kinch Lisa N. , Tomchick Diana R. , Orth Kim 
Published: July 2020

AbstractVacuolar-type ATPase (V-ATPase) is a rotary protein pump involved in proton translocation across various cellular membranes using the energy of ATP hydrolysis. Despite previous studies on bacterial and eukaryotic V-ATPases, information on the intact structure of a eukaryotic V-ATPase is missing. Here we report cryo-EM structures of the intact yeast V-ATPase and this complex bound to a bacterial effector. We reveal the interaction of the elusive regulatory subunit H with its neighboring subunits. Insight for the catalysis mechanism is gained by determining conformations of the catalytic subunits either empty or bound with nucleotides.
Dopamine axons to dorsal striatum encode contralateral stimuli and actions
Authors: Moss Morgane M , Zatka-Haas Peter , Harris Kenneth D , Carandini Matteo , Lak Armin 
Published: July 2020

AbstractMidbrain dopamine neurons play key roles in decision-making by regulating reward valuation and actions. These roles are thought to depend on dopamine neurons innervating striatum. In addition to actions and rewards, however, efficient decisions often involve consideration of uncertain sensory signals. The functions of striatal dopamine during sensory decisions remains unknown. We trained mice in a task that probed decisions based on sensory evidence and reward value, and recorded the activity of striatal dopamine axons. Dopamine axons in ventral striatum (VS) responded to bilateral stimuli and trial outcomes, encoding prediction errors that scaled with decision confidence and reward value. By contrast, dopamine axons in dorsal striatum (DS) responded to contralateral stimuli and contralateral actions. Thus, during sensory decisions, striatal dopamine signals are anatomically organized. VS dopamine resembles prediction errors suitable for reward maximization under sensory uncertainty whereas DS dopamine encodes specific combinations of stimuli and actions in a lateralized fashion.
Perceptual responses to microstimulation frequency are spatially organized in human somatosensory cortex
Authors: Hughes Christopher L. , Flesher Sharlene N. , Weiss Jeffrey M. , Boninger Michael , Collinger Jennifer L. , Gaunt Robert 
Published: July 2020

SummaryMicrostimulation in the somatosensory cortex can evoke artificial tactile percepts and can be incorporated into bidirectional brain-computer interfaces (BCIs) to restore function after injury or disease. However, little is known about how stimulation parameters themselves affect perception. Here, we stimulated through microelectrode arrays implanted in the somatosensory cortex of a human participant with a cervical spinal cord injury and varied the stimulus amplitude, duration, and frequency. Increasing the amplitude and duration increased the perceived intensity on all tested electrodes. Surprisingly, we found that increasing the frequency evoked more intense percepts on some electrodes but evoked less intense percepts on most electrodes. Electrodes divided into three groups which evoked distinct perceptual qualities that depended on the stimulus frequency and were spatially organized in cortex. These results contribute to our growing understanding of the structure and function of the somatosensory cortex and will facilitate principled development of stimulation strategies for bidirectional BCIs.
Microscopic Chromosomal Structural and Dynamical Origin of Cell Differentiation and Reprogramming
Authors: Chu Xiakun , Wang Jin 
Published: July 2020

AbstractAs an essential and fundamental process of life, cell development involves large-scale reorganization of the three-dimensional genome architecture, which forms the basis of gene regulation. Here, we develop a landscape-switching model to explore the microscopic chromosomal structural origin of the embryonic stem cell (ESC) differentiation and the somatic cell reprogramming. We show that chromosome structure exhibits significant compartment-switching in the unit of topologically associating domain. We find that the chromosome during differentiation undergoes monotonic compaction with spatial re-positioning of active and inactive chromosomal loci towards the chromosome surface and interior, respectively. In contrast, an over-expanded chromosome, which exhibits universal localization of loci at the chromosomal surface with erasing the structural characteristics formed in the somatic cells, is observed during reprogramming. We suggest an early distinct differentiation pathway from the ESC to the terminally differentiated cell, giving rise to early bifurcation on the Waddington landscape for the ESC differentiation. Our theoretical model including the non-equilibrium effects, draws a picture of the highly irreversible cell differentiation and reprogramming processes, in line with the experiments. The predictions from our model provide a physical understanding of cell differentiation and reprogramming from the chromosomal structural and dynamical perspective and can be tested by future experiments.
TMEM180 contributes to colorectal cancer proliferation through intracellular metabolic pathways
Authors: Anzai Takahiro , Saijou Shinji , Ohnuki Yoshitsugu , Kurosawa Hiroshi , Yasunaga Masahiro , Matsumura Yasuhiro 
Published: July 2020

AbstractTMEM180, a novel colon cancer–specific membrane protein with a 12-transmembrane topology, is upregulated at low oxygen. Previously, we established a humanized monoclonal antibody against TMEM180 aimed at clinical trials. Prior to such trials, it is necessary to clarify the function of this molecule in cancer. To compare SW480 human colon cancer cells and their TMEM180-knockdown derivatives, we analyzed proliferation and oxygen consumption, and also performed phosphorylation proteomics, metabolomics, and next-generation sequencing. The results revealed that TMEM180 promoted the growth of colon cancer but had almost no effect on oxygen consumption or expression of phosphorylated proteins. By contrast, glycolysis differed dramatically between SW480 and TMEM180-knockdown cells. TMEM180 promotes nitric oxide synthesis, suggesting that it promotes glucose metabolism and glutamine metabolism, thereby contributing to cancer growth. Overall, the results of this study support the clinical development of an anti-TMEM180 antibody.
Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA
Authors: Park Mi Seul , Sim GeunYoung , Kehling Audrey C. , Nakanishi Kotaro 
Published: July 2020

AbstractRNA interfering is a eukaryote-specific gene silencing by 20∼23 nucleotide (nt) microRNAs and small interfering RNAs that recruit Argonaute proteins to complementary RNAs for degradation. In humans, Argonaute2 (AGO2) has been known as the only slicer while Argonaute3 (AGO3) barely cleaves RNAs. Therefore, the intrinsic slicing activity of AGO3 remains controversial and a long-standing question. Here, we report 14-nt 3′ end-shortened variants of let-7a, miR-27a, and specific miR-17-92 families that make AGO3 an extremely competent slicer by an ∼ 82-fold increase in target cleavage. These RNAs, named cleavage-inducing tiny guide RNAs (cityRNAs), conversely lower the activity of AGO2, demonstrating that AGO2 and AGO3 have different optimum guide lengths for target cleavage. Our study sheds light on the role of tiny guide RNAs.
Organoid-derived adult human colonic epithelium responds to co-culture with a probiotic strain ofBifidobacterium longum
Authors: Lauder Emma , Kim Kwi , Schmidt Thomas Mitchell , Golob Jonathan Louis 
Published: July 2020

AbstractIn germ-free animals the lack of microbes within the gut results in a propensity to mucosal inflammation among other immune deficits. This suggests microbes are essential for the healthy function of the human gut, but we have lacked a reproducible mechanistic model of interactions between human colonic epithelium and the anaerobic microbes within the gut. To establish the physiological effect of a common anaerobe in the human gut, we co-cultured a probiotic strain ofBifidobacterium longum(35624) with organoid-derived adult human colonic epithelium in asymmetric gas conditions (anoxic apically, 5% oxygen basolaterally) and compared to axenic (‘germ-free’) epithelium. Bacteria proliferated and retained their normal cellular morphology in the presence of the human colonic epithelium. The human colonic mucosa retained trans-epithelial electrical resistance (TEER) consistent with an intact epithelium but lower than in axenic conditions. Changes in TEER corresponded to changes in Claudin-family gene expression. Inflammation was repressed in co-culture as compared to axenic, with reduced expression of executor and pyroptosis caspases; reduced expression of activators and increased expression of inhibitors ofNFKB; reduced expression of toll-like-receptors (TLRs) and increased expression ofTOLLIP(a negative regulator of TLRs). Consistent with the presence of actively fermenting bacteria that produce lactate and acetate but do not produce butyrate,PPARAexpression was increased whilePPARGexpression was reduced. As in germ-free animal experiments, axenic human colonic mucosa is poised for inflammation. Co-culture withBifidobacterium longumresolved the pro-inflammatory state while modulating barrier function (via Claudin genes) and cellular energetics (viaPPARAandPPARGgenes).ImportanceExperiments in animals demonstrate the importance of microbes with the gut for the health of the gut. Many of the microbes within the healthy gut are strictly anaerobic and cannot grow in the presence of oxygen; human tissues require some oxygen to live. Here we observe the effect of growing an anaerobic bacterium -Bifidobacterium longum- typically found in the human gut with human colonic tissue. We observed that the human tissue responded favorably to being cultivated with the microbe as compared to being alone. This experiment confirms human colonic tissues reduce their inflammation in the presence of a bacteria typically found in the gut.
Taxonomic classification of strain PO100/5 shows a broader geographic distribution and genetic markers of the recently describedCorynebacterium silvaticum
Authors: Canário Viana Marcus Vinicius , Profeta Rodrigo , da Silva Alessandra Lima , Hurtado Raquel , Cerqueira Janaína Canário , Sampaio Ribeiro Bruna Ferreira , Almeida Marcelle Oliveira , Morais-Rodrigues Francielly , Oliveira Manuela , Tavares Luís , Figueiredo Henrique , Wattam Alice Rebecca , Barh Debmalya , Ghosh Preetam , Silva Artur , Azevedo Vasco 
Published: July 2020

AbstractThe bacterial strain PO100/5 was isolated from a skin abscess of a pig (Sus scrofa domesticus) in the Alentejo region of southern Portugal. It was identified asCorynebacterium pseudotuberculosisusing biochemical tests, multiplex PCR and Pulsed Field Gel Electrophoresis. After genome sequencing andrpoBphylogeny, the strain was classified asC. ulcerans. To better understand the taxonomy of this strain and improve identification methods, we compared strain PO100/5 to other publicly available genomes from theC. diphtheriaegroup. Taxonomic analysis reclassified it and three others strains as belonging to the recently describedC. silvaticum, which have been isolated from wild boar and roe deer in Germany and Austria. The results showed that PO100/5 is the first sequenced genome of aC. silvaticumstrain from a domestic animal and a different geographical region, is a putative producer of thediphtheriaetoxin, and has a unique sequence type. Genomic analysis of PO100/5 showed four prophages and eight conserved genomic islands when compared toC. ulcerans. Pangenome analysis of 38C. silvaticumand 76C. ulceranssamples suggest thatC. silvaticumis a clonal species, with 73.6% of conserved genes and a pangenome near to being closed (α > 0.952). 172 conserved genes are unique toC. silvaticumwhen compared toC. ulcerans, with most related to nutrient uptake and metabolism, prophages or immune evasion. These unique genes could be used as genetic markers for species identification. This information can be useful for identification and surveillance of this pathogen, especially in regard to the possibility of zoonotic transmission.
VAE-SNE: a deep generative model for simultaneous dimensionality reduction and clustering
Authors: Graving Jacob M. , Couzin Iain D. 
Published: July 2020

AbstractScientific datasets are growing rapidly in scale and complexity. Consequently, the task of understanding these data to answer scientific questions increasingly requires the use of compression algorithms that reduce dimensionality by combining correlated features and cluster similar observations to summarize large datasets. Here we introduce a method for both dimension reduction and clustering called VAE-SNE (variational autoencoder stochastic neighbor embedding). Our model combines elements from deep learning, probabilistic inference, and manifold learning to produce interpretable compressed representations while also readily scaling to tens-of-millions of observations. Unlike existing methods, VAE-SNE simultaneously compresses high-dimensional data and automatically learns a distribution of clusters within the data — without the need to manually select the number of clusters. This naturally creates a multi-scale representation, which makes it straightforward to generate coarse-grained descriptions for large subsets of related observations and select specific regions of interest for further analysis. VAE-SNE can also quickly and easily embed new samples, detect outliers, and can be optimized with small batches of data, which makes it possible to compress datasets that are otherwise too large to fit into memory. We evaluate VAE-SNE as a general purpose method for dimensionality reduction by applying it to multiple real-world datasets and by comparing its performance with existing methods for dimensionality reduction. We find that VAE-SNE produces high-quality compressed representations with results that are on par with existing nonlinear dimensionality reduction algorithms. As a practical example, we demonstrate how the cluster distribution learned by VAE-SNE can be used for unsupervised action recognition to detect and classify repeated motifs of stereotyped behavior in high-dimensional timeseries data. Finally, we also introduce variants of VAE-SNE for embedding data in polar (spherical) coordinates and for embedding image data from raw pixels. VAE-SNE is a robust, feature-rich, and scalable method with broad applicability to a range of datasets in the life sciences and beyond.
Increased alcohol self-administration following exposure to the predator odor TMT in high stress-reactive female rats
Authors: Ornelas Laura C. , Tyler Ryan E. , Irukulapati Preethi , Paladugu Sudheesha , Besheer Joyce 
Published: July 2020

AbstractPost-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid. Additionally, individual differences in response to stress suggest resilient and susceptible populations. The current study exposed male and female Long Evans rats to the synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to examine individual differences in stress-reactive behaviors (digging and immobility) and whether these differences could predict lasting consequences of TMT and increases in alcohol drinking. Male and female Long Evans rats were trained on operant alcohol self-administration. After 9 sessions, rats underwent exposure to TMT or water (Control) in a distinct context. 6 days after TMT exposure, rats underwent re-exposure to the TMT-paired context (without TMT), and a series of behavioral assessments (acoustic startle, zero maze, light/dark box), after which rats resumed alcohol self-administration. Rats were divided into two TMT-subgroups using a ratio of digging and immobility behavior during TMT exposure: TMT-subgroup 1 (low digging/immobility ratio) and TMT-subgroup 2 (high digging/immobility ratio). Digging/immobility ratio scores predicted elevated corticosterone levels during TMT exposure and reactivity during context re-exposure in males and females (TMT-subgroup 2), as well as elevated corticosterone levels after context re-exposure and hyperarousal behavior in females (TMT-subgroup 1). Furthermore, TMT stress reactivity predicted increases in alcohol self-administration, specifically in females. These data show that stress-reactivity can predict lasting behavioral changes which may lead to a better understanding of increases in alcohol drinking following stress in females and that individual differences in stress-reactive behaviors using TMT may be helpful to understand resilience/susceptibility to the lasting consequences of stress.HighlightsExposure to the predator odor TMT produces distinct behavioral phenotypes in male and female ratsMale and female high stress reactive rats show enhanced reactivity to the TMT-paired contextStress-reactivity during TMT predicts increases in alcohol self-administration, in femalesStress-reactivity may help to understand resilience/susceptibility and impact on alcohol drinking
Optimisation of archival processes involving digitisation of typewritten documents
Authors: Stančić Hrvoje , Trbušić Željko 
Published: July 2020

PurposeThe authors investigate optical character recognition (OCR) technology and discuss its implementation in the context of digitisation of archival materials.Design/methodology/approachThe typewritten transcripts of the Croatian Writers' Society from the mid-60s of the 20th century are used as the test data. The optimal digitisation setup is investigated in order to obtain the best OCR results. This was done by using the sample of 123 pages digitised at different resolution settings and binarisation levels.FindingsA series of tests showed that different settings produce significantly different results. The best OCR accuracy achieved at the test sample of the typewritten documents was 95.02%. The results show that the resolution is significantly more important than binarisation pre-processing procedure for achieving better OCR results.Originality/valueBased on the research results, the authors give recommendations for achieving optimal digitisation process setup with the aim of increasing the quality of OCR results. Finally, the authors put the research results in the context of digitisation of cultural heritage in general and discuss further investigation possibilities.
Do analysts’ recommendations reflect co-opted boards?
Authors: Papangkorn Suwongrat , Chatjuthamard Pattanaporn , Jiraporn Pornsit , Phiromswad Piyachart 
Published: July 2020

Purpose
This study aims to examine whether co-opted directors influence analysts’ recommendations. As information intermediaries, financial analysts should incorporate the quality of corporate governance into their valuation because well-governed firms are associated with lower agency costs and better performance. Co-opted directors are those appointed after the incumbent chief executive officer assumes office. The authors investigate whether board co-option has an effect on analyst recommendations.

Design/methodology/approach
The present study uses univariate analysis, multi-variate regression analysis and conduct a natural experiment using the Sarbanes-Oxley as an exogenous shock.

Findings
The results show that firms with fewer co-opted directors tend to receive more favorable recommendations, suggesting that analysts favor firms with strong corporate governance. The results hold even after controlling for various firm characteristics, including the traditional measures of board quality, i.e. board size and independent directors.

Originality/value
The paper is the first of its kind and offers evidence on the effect of co-opted directors on analyst recommendations. The results contribute to the literature both in corporate governance and in financial intermediaries, where analysts play a crucial role in providing information to the various participants in financial markets.