bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 evolution in animals suggests mechanisms for rapid variant selection
Authors: Bashor Laura , Gagne Roderick B. , Bosco-Lauth Angela , Bowen Richard , Stenglein Mark , VandeWoude Sue 
Published: March 2021

AbstractSARS-CoV-2 spillback from humans into domestic and wild animals has been well-documented. We compared variants of cell culture-expanded SARS-CoV-2 inoculum and virus recovered from four species following experimental exposure. Five nonsynonymous changes in nsp12, S, N and M genes were near fixation in the inoculum, but reverted to wild-type sequences in RNA recovered from dogs, cats and hamsters within 1-3 days post-exposure. Fourteen emergent variants were detected in viruses recovered from animals, including substitutions at spike positions H69, N501, and D614, which also vary in human lineages of concern. The rapidity of in vitro and in vivo SARS-CoV-2 selection reveals residues with functional significance during host-switching, illustrating the potential for spillback reservoir hosts to accelerate evolution, and demonstrating plasticity of viral adaptation in animal models.One-Sentence SummarySARS-CoV-2 variants rapidly arise in non-human hosts, revealing viral evolution and potential risk for human reinfection.
Optimal Time Lags from Causal Prediction Model Help Stratify and Forecast Nervous System Pathology
Authors: Bermperidis Theodoros , Rai Richa , Ryu Jihye , Zanotto Damiano , Agrawal Sunil K , Lalwani Anil K. , Torres Elizabeth B 
Published: March 2021

AbstractTraditional clinical approaches diagnose disorders of the nervous system using standardized observational criteria. Although aiming for homogeneity of symptoms, this method often results in highly heterogeneous disorders. A standing question thus is how to automatically stratify a given random cohort of the population, such that treatment can be better tailored to each cluster’s symptoms, and severity of any given group forecasted to provide neuroprotective therapies. In this work we introduce new methods to automatically stratify a random cohort of the population composed of healthy controls of different ages and patients with different disorders of the nervous systems. Using a simple walking task and measuring micro-fluctuations in their biorhythmic motions, we combine non-linear causal network connectivity analyses in the temporal and frequency domains with stochastic mapping. The methods define a new type of internal motor timings. These are amenable to create personalized clinical interventions tailored to self-emerging clusters signaling fundamentally different types of gait pathologies. We frame our results using the principle of reafference and operationalize them using causal prediction, thus renovating the theory of internal models for the study of neuromotor control.
Trp53ablation fails to prevent microcephaly in mouse pallium with impaired minor intron splicing
Authors: White Alisa K. , Baumgartner Marybeth , Lee Madisen F. , Drake Kyle D. , Aquino Gabriela S. , Kanadia Rahul N. 
Published: March 2021

AbstractMutations in minor spliceosome component RNU4ATAC, a small nuclear RNA (snRNA), are linked to primary microcephaly. We have reported that in the conditional knockout (cKO) mice forRnu11, another minor spliceosome snRNA, minor intron splicing defect in minor intron-containing genes (MIGs) regulating cell cycle resulted in cell cycle defects, with a concomitant increase in γH2aX+ cells and p53-mediated apoptosis.Trp53ablation in theRnu11cKO mice did not prevent microcephaly. However, RNAseq analysis of the double knockout (dKO) pallium reflected transcriptomic shift towards the control from the Rnu11 cKO. We found elevated minor intron retention and alternative splicing across minor introns in the dKO. Disruption of these MIGs resulted in cell cycle defects that were more severe and detected earlier in the dKO, but with delayed detection of γH2aX+ DNA damage. Thus, p53 might also play a role in causing DNA damage in the developing pallium. In all, our findings further refine our understanding of the role of the minor spliceosome in cortical development and identify MIGs underpinning microcephaly in minor spliceosome-related diseases.
Dynamic Training of a Novelty Classifier Algorithm for Real-Time Early Seizure Onset Detection
Authors: Ehrens Daniel , Cervenka Mackenzie C. , Bergey Gregory K. , Jouny Christophe C. 
Published: March 2021

AbstractThe objective of this study was to develop an adaptive framework for seizure detection in real-time that is practical to use in the Epilepsy Monitoring Unit (EMU) as a warning signal, and whose output helps characterize epileptiform activity. Our framework uses a one-class Support Vector Machine (SVM) that is being trained dynamically according to past activity in all available channels. This is done to evaluate the novelty of the current instance according to previous activity. Our algorithm was tested on intracranial EEG from human epilepsy patients that are admitted to the EMU for presurgical evaluation. In this study, we compared multiple configurations for using a one-class SVM to assess if there is significance over specific neural features or electrode locations. Our results show our algorithm is capable of running in real-time and achieving a high performance for early seizure-onset detection with a low false-positive rate and robustness to different types of seizure-onset patterns as well as to the number of channels used. This algorithm offers a solution to warning systems in the EMU as well as a tool for seizure characterization during post-hoc analysis of intracranial EEG data for surgical resection of the epileptogenic network.HighlightsThis study proposes a dynamic training algorithm that efficiently detects sudden novel changes in intracranial electroencephalographic activity, creating a reliable seizure onset detection algorithm that does not need prior training.The algorithm described has the capability to be implemented in real-time, independently of the number of channels that are being analyzed.The presented detector shows high performance and reliability to be easily implemented in the Epilepsy Monitoring Unit to quickly alert clinical staff of seizure events.
A novel Rab11-Rab3a cascade required for lysosome exocytosis
Authors: Escrevente Cristina , Bento-Lopes Liliana , Ramalho José S , Barral Duarte C 
Published: March 2021

AbstractLysosomes are dynamic organelles, capable of undergoing exocytosis. This process is crucial for several cellular functions, namely plasma membrane repair. Nevertheless, the molecular machinery involved in this process is poorly understood.Here, we identify Rab11a and Rab11b as regulators of calcium-induced lysosome exocytosis. Interestingly, Rab11-positive vesicles transiently interact with lysosomes at the cell periphery, indicating that this interaction is required for the last steps of lysosome exocytosis. Additionally, we found that the silencing of the exocyst subunit Sec15, a Rab11 effector, impairs lysosome exocytosis independently of the exocyst complex, suggesting that Sec15 acts together with Rab11 in the regulation of lysosome exocytosis. Furthermore, we show that Rab11 binds the guanine nucleotide exchange factor for Rab3a (GRAB) and also Rab3a, which we described previously as a regulator of the positioning and exocytosis of lysosomes.Thus, our studies suggest that Rab11-positive vesicles transport GRAB to activate Rab3a on lysosomes, establishing a Rab11-Rab3 cascade that is essential for lysosome exocytosis.
SAMGEP: A Novel Method for Prediction of Phenotype Event Times Using the Electronic Health Record
Authors: Ahuja Yuri , Hong Chuan , Xia Zongqi , Cai Tianxi 
Published: March 2021

ABSTRACTObjectiveWhile there exist numerous methods to predict binary phenotypes using electronic health record (EHR) data, few exist for prediction of phenotype event times, or equivalently phenotype state progression. Estimating such quantities could enable more powerful use of EHR data for temporal analyses such as survival and disease progression. We propose Semi-supervised Adaptive Markov Gaussian Embedding Process (SAMGEP), a semi-supervised machine learning algorithm to predict phenotype event times using EHR data.MethodsSAMGEP broadly consists of four steps: (i) assemble time-evolving EHR features predictive of the target phenotype event, (ii) optimize weights for combining raw features and feature embeddings into dense patient-timepoint embeddings, (iii) fit supervised and semi-supervised Markov Gaussian Process models to this embedding progression to predict marginal phenotype probabilities at each timepoint, and (iv) take a weighted average of these supervised and semi-supervised predictions. SAMGEP models latent phenotype states as a binary Markov process, conditional on which patient-timepoint embeddings are assumed to follow a Gaussian Process.ResultsSAMGEP achieves significantly improved AUCs and F1 scores relative to common machine learning approaches in both simulations and a real-world task using EHR data to predict multiple sclerosis relapse. It is particularly adept at predicting a patient’s longitudinal phenotype course, which can be used to estimate population-level cumulative probability and count process estimators. Reassuringly, it is robust to a variety of generative model parameters.DiscussionSAMGEP’s event time predictions can be used to estimate accurate phenotype progression curves for use in downstream temporal analyses, such as a survival study for comparative effectiveness research.
Motor neuron boutons remodel through membrane blebbing
Authors: Fernandes Andreia R. , Mendes César S. , Gomes Edgar R. , Teodoro Rita O. 
Published: March 2021

AbstractWired neurons form new presynaptic boutons in response to increased synaptic activity, but the mechanism by which this occurs remains uncertain. The neuromuscular junction (NMJ) is a synapse formed between motor neurons (MNs) and skeletal muscle fibers and is critical for control of muscle contraction. BecauseDrosophilaMNs have clearly discernible boutons that display robust structural plasticity, it is the ideal system in which to study bouton genesis. Here we show usingex-vivoand by live imaging that in response to depolarization, MNs form new boutons by membrane blebbing, a pressure-driven mechanism used in 3-D migration, but never described as a neuronal remodeling strategy. In accordance, F-actin is decreased during bouton growth (a hallmark of blebs) and we show that non-muscle myosin-II (a master regulator of blebbing) is recruited to newly formed boutons. Furthermore, we discovered that muscle contraction plays a mechanical role in activity-dependent plasticity, promoting bouton addition by increasing MNs confinement. Overall, we provide a novel mechanism by which established circuits create new boutons allowing their structural expansion and plasticity, using trans-synaptic physical forces as the main driving force. Understanding MN-muscle interplay during activity-dependent plasticity can help clarify the mechanisms leading to MN degeneracy observed in neuromuscular diseases.
A Fundamental Distinction in Early Neural Processing of Implicit Social Interpretation in Schizophrenia and Bipolar Disorder
Authors: Madeira Nuno Gonçalo Gomes Fernandes , Martins Ricardo Filipe Alves , Duarte João Valente , Costa Gabriel Nascimento Ferreira , Santos António João Ferreira Macedo , Castelo-Branco Miguel Sá Sousa 
Published: March 2021

ABSTRACTBackgroundSocial cognition impairment is a key phenomenon in serious mental disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). Although genetic and neurobiological studies have suggested common neural correlates, here we hypothesized that a fundamental dissociation of social processing occurs at an early level in these conditions.MethodsBased on the hypothesis that key structures in the social brain, namely the temporoparietal junction, should present distinctive features in SCZ and BPD during low-level social judgment, we conducted a case-control study in SCZ (n=20) and BPD (n=20) patients and controls (n=20), using task-based fMRI during a Theory-of-Mind (ToM) visual paradigm leading to interpretation of social meaning based on simple geometric figures.ResultsWe found opposite neural responses in two core ToM regions : SCZ patients showed social content-related deactivation (relative to controls and BPD) of the right supramarginal gyrus, a region which activity is required to overcome egocentric “overmentalizing”, while the opposite pattern was found in BPD; reverse patterns, relative to controls and SCZ, were found in the left posterior superior temporal gyrus, a region involved in inferring other’s intentions. Receiver-operating-characteristic curve analysis showed 88% accuracy in discriminating the two clinical groups based on these neural responses.ConclusionsThese contrasting activation patterns of the temporoparietal junction in SCZ and BPD represent mechanistic differences of social cognitive dysfunction that may be explored as biomarkers or therapeutic targets.
A general computational framework for COVID-19 modelling with applications to testing varied interventions in education environments
Authors: Moore Joshua W. , Lau Zechariah , Kaouri Katerina , Dale Trevor C. , Woolley Thomas E. 
Published: March 2021

AbstractWe construct a spatially-compartmental individual-based model of the spread of Covid-19 in indoor spaces. The model can be used to predict the infection rates in a variety of locations when various non-pharmaceutical interventions (NPIs) are introduced. Tasked by the Welsh Government, we apply the model to secondary schools and Further and Higher Education environments. Specifically, we consider student populations mixing in a classroom and in halls of residence. We focus on assessing the potential efficacy of Lateral Flow Devices (LFDs) when used in broad-based screens for asymptomatic infection or in ‘test-to-release’ scenarios in which individuals who have been exposed to infection are released from isolation given a negative result. LFDs are also compared to other NPIs; we find that, although LFD testing can be used to mitigate the spread of Covid-19, it is more effective to invest in personal protective equipment, e.g. masks, and in increasing ventilation quality. In addition, we provide an open-access and user-friendly online applet that simulates the individual-based model, complete with user tutorials to encourage the use of the model to aid educational policy decisions as input infection data evolves (https://bit.ly/CV19_INTER_IBM).
Underwater photo-identification of marine megafauna: an identity card catalogue of sperm whales (Physeter macrocephalus) off Mauritius Island
Authors: Véronique Sarano , François Sarano , Justine Girardet , Axel Preud’homme , Hugues Vitry , René Heuzey , Marion Sarano , Fabienne Delfour , Hervé Glotin , Olivier Adam , Bénédicte Madon , Jean-Luc Jung 
Published: March 2021

ABSTRACTThe long-term monitoring of long-lived animal populations often requires individual identification. For cetacean populations, this identification is mostly based on morphological characters observable from a boat such as shape, spots and cuts of the back, caudal and dorsal fins. This is well suited for species easily displaying their caudal fins, such as the humpback whalesMegaptera novaeangliae, or those whose skin pigmentation patterns enable individual identification.However, for elusive or shier species such as the sperm whalesPhyseter macrocephalus, this approach may be more challenging as individuals display a rather uniform skin pigmentation. They also do not show very often their caudal fin that must be photographed perpendicularly to the water surface, vertically and fully emerged, uneasing the individual identification from a boat. Immature sperm whales that usually have a caudal fin without any distinctive marks may sometimes be excluded from photo-identification catalogues.Within the framework of the Maubydick project, focusing on the long-term monitoring of sperm whales in Mauritius, passive underwater observation and video recording were used to identify long-lasting body markers (e.g., sex, ventral white markings, cut outs of fins) to improve individual identification. A catalogue of individual identity cards was developed and 38 individuals were recorded (six adult males, 18 adult females and 14 immatures). This catalogue was used in the field and enabled observers to record some nearly-daily and yearly recaptures. Advantages and disadvantages of this method are presented here.Such catalogues represent a robust baseline for conducting behavioural, genetic and acoustic studies in marine megafauna social species. Benefits of such newly acquired knowledge are of first importance to implement relevant conservation plans in the marine realm.
Allicin From Garlic Disrupts the Cytoskeleton in Plants
Authors: Noll Ulrike , Schreiber Miriam , Hermanns Monika , Mertes Christopher A. , Slusarenko Alan J. , Gruhlke Martin C.H. 
Published: March 2021

AbstractAllicin is a defence substance produced by garlic cells upon injury. It is a thiosulfinate showing redox-activity and a broad range of antimicrobial and biocidal activity. It is known that allicin efficiently oxidizes thiol-groups and it has been described as a redox toxin. In order to learn more about the effect of allicin on plants we used pure synthetized allicin, and investigated cytoplasmic streaming in sterile filaments ofTradescantia fluminensis, organelle movement using transgenicArabidopsiswith organelle-specifics GFP-tags, and effects on actin and tubulin in the cytoskeleton using GFP-tagged lines. Auxin distribution in roots was investigated using PIN1:GFP, PIN3:GFP, DR5:GFP and DII-VENUS Arabidopsis reporter lines.Allicin inhibited cytoplasmic streaming inT. fluminensisand organelle movement of peroxisomes and the Golgi apparatus in a concentration-dependent manner, inhibited root growth and destroyed the correct root tip distribution of auxin.We speculate that the cytoskeleton can be a primary “receptor” for allicin’s oxidizing properties and as a consequence cytoskeleton-dependent cellular processes are disrupted.
Allopregnanolone mediates affective switching through modulation of oscillatory states in the basolateral amygdala
Authors: Antonoudiou Pantelis , Colmers Phillip LW , Walton Najah L , Weiss Grant L , Smith Anne C , Nguyen David P , Lewis Mike , Quirk Michael C , Melon Laverne C , Maguire Jamie L 
Published: March 2021

AbstractBrexanolone (allopregnanolone), was recently approved by the FDA for the treatment of post-partum depression, demonstrating long-lasting antidepressant effects. Despite our understanding of the mechanism of action of neurosteroids as positive allosteric modulators (PAMs) of GABAareceptors, we still do not fully understand how allopregnanolone exerts these persistent antidepressant effects. Here, we demonstrate that allopregnanolone and similar synthetic neuroactive steroid analogs, SGE-516 (tool-compound) and zuranolone (SAGE-217, investigational-compound), are capable of modulating oscillatory states across species, which we propose may contribute to long-lasting changes in behavioral states. We identified a critical role for interneurons in generating oscillations in the basolateral amygdala (BLA) and a role for delta-containing GABAaRs in mediating the ability of neurosteroids to modulate network and behavioral states. Actions of allopregnanolone in the BLA is sufficient to alter behavioral states and enhance BLA high-theta oscillations (6-12Hz) through delta-containing GABAareceptors, a mechanism distinct from other GABAaPAMs, such as benzodiazepines. Moreover, treatment with the allopregnanolone analog SGE-516 induces long-lasting protection from chronic stress-induced disruption of network states, which correlates with improved behavioral outcomes. Our findings demonstrate a novel molecular and cellular mechanism mediating the well-established anxiolytic and antidepressant effects of neuroactive steroids.
Characterizing neural phase-space trajectories via Principal Louvain Clustering
Authors: Dekker Mark M. , França Arthur S. C. , Panja Debabrata , Cohen Michael X 
Published: March 2021

AbstractBackgroundWith the growing size and richness of neuroscience datasets in terms of dimension, volume, and resolution, identifying spatiotemporal patterns in those datasets is increasingly important. Multivariate dimension-reduction methods are particularly adept at addressing these challenges.New MethodIn this paper, we propose a novel method, which we refer to as Principal Louvain Clustering (PLC), to identify clusters in a low-dimensional data subspace, based on time-varying trajectories of spectral dynamics across multisite local field potential (LFP) recordings in awake behaving mice. Data were recorded from prefrontal cortex, hippocampus, and parietal cortex in eleven mice while they explored novel and familiar environments.ResultsPLC-identified subspaces and clusters showed high consistency across animals, and were modulated by the animals’ ongoing behavior.ConclusionsPLC adds to an important growing literature on methods for characterizing dynamics in high-dimensional datasets, using a smaller number of parameters. The method is also applicable to other kinds of datasets, such as EEG or MEG.
Synergism between potassium and nitrate enhances the alleviation of ammonium toxicity in rice seedling root
Authors: Fang Gen , Yang Jing , Sun Tong , Wang Xiaoxin , Li Yangsheng 
Published: March 2021

AbstractAmmonium toxicity in plants is considered a global phenomenon, but the primary mechanisms remain poorly characterized. Here, we showed that although the addition of potassium (K+) or nitrate (NO3−) partially alleviated the inhibition of rice root growth caused by ammonium toxicity, the coexistence of K+and NO3−clearly improved the alleviation via a synergistic mechanism. The synergism led to significantly improved alleviation effects on root biomass, length, surface area, number and meristem cell number. The aberrant auxin distribution in root tips, rhizosphere acidification level and abnormal cell morphology in the root cap and elongation zone caused by ammonium toxicity could be recovered by this synergism. RNA sequencing and the weighted gene correlation network analysis (WGCNA) revealed that the mechanism of this synergism involves cellulose synthesis, auxin and gibberellin metabolism regulation at the transcription level.
ANCHOR, a technical approach to monitor single-copy locus localizationin planta
Authors: Meschichi Anis , Ingouff Mathieu , Picart Claire , Mirouze Marie , Desset Sophie , Gallardo Franck , Bystricky Kerstin , Picault Nathalie , Rosa Stefanie , Pontvianne Frédéric 
Published: March 2021

RESUMEGene expression is governed by several layers of regulation which in addition to genome organization, local chromatin structure, gene accessibility and the presence of transcription factors also includes gene positioning. Although basic mechanisms are expected to be conserved in Eukaryotes, surprisingly little information on the role of gene positioning is available in plant cells, mainly due to the lack of a highly resolutive approach. In this manuscript, we adapted the use of the ANCHOR system to perform real-time single-locus detectionin planta.ANCHOR is a DNA-labelling tool derived from the partitioning system. We demonstrate its suitability to monitor a single-locusin plantaand used this approach to track chromatin mobility during cell differentiation in Arabidopsis root epidermal cells. Finally, we discuss the potential of this approach to investigate the role of gene positioning during transcription and DNA repair in plants.