bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronavirus Disease (COVID-19) Global Prediction Using Hybrid Artificial Intelligence Method of ANN Trained with Grey Wolf Optimizer
Authors: Ardabili Sina , Mosavi Amir , Band Shahab S. , Varkonyi-Koczy Annamaria R. 
Published: October 2020

AbstractAn accurate outbreak prediction of COVID-19 can successfully help to get insight into the spread and consequences of infectious diseases. Recently, machine learning (ML) based prediction models have been successfully employed for the prediction of the disease outbreak. The present study aimed to engage an artificial neural network-integrated by grey wolf optimizer for COVID-19 outbreak predictions by employing the Global dataset. Training and testing processes have been performed by time-series data related to January 22 to September 15, 2020 and validation has been performed by time-series data related to September 16 to October 15, 2020. Results have been evaluated by employing mean absolute percentage error (MAPE) and correlation coefficient (r) values. ANN-GWO provided a MAPE of 6.23, 13.15 and 11.4% for training, testing and validating phases, respectively. According to the results, the developed model could successfully cope with the prediction task.
Is increased mortality by multiple exposures to COVID-19 an overseen factor when aiming for herd immunity?
Authors: Helle Kristina B. , Sadiku Arlinda , Zelleke Girma M. , Bouba Aliou , Ibrahim Toheeb B. , Obama H. Christian Tsoungui , Appiah Vincent , Ngwa Gideon A. , Teboh-Ewungkem Miranda I. , Schneider Kristan A. 
Published: October 2020

AbstractBackgroundGovernments across the globe responded with different strategies to the COVID-19 pandemic. While some countries adapted draconic measures, which have been perceived controversial others pursued a strategy aiming for herd immunity. The latter is even more controversial and has been called unethical by the WHO Director-General. Inevitably, without proper control measure, viral diversity increases and multiple infectious exposures become common, when the pandemic reaches its maximum. This harbors not only a potential threat overseen by simplified theoretical arguments in support of herd immunity, but also deserves attention when assessing response measures to increasing numbers of infection.Methods and findingsWe extend the simulation model underlying the pandemic preparedness web interface CovidSim 1.1 (http://covidsim.eu/) to study the hypothetical effect of increased morbidity and mortality due to ‘multi infections’, either acquired at by successive infective contacts during the course of one infection or by a single infective contact with a multi-infected individual.The simulations are adjusted to reflect roughly the situation in the East Coast of the USA. We assume a phase of general contact reduction (‘lockdown’) at the beginning of the epidemic and additional case-isolation measures. We study the hypothetical effects of varying enhancements in morbidity and mortality, different likelihoods of multi-infected individuals to spread multi infections and different susceptibility to multi infectious in different disease phases. It is demonstrated that multi infections lead to a slight reduction in the number of infections, as these are more likely to get isolated due to their higher morbidity. However, the latter substantially increases the number of deaths. Furthermore, simulations indicate that a potential second lockdown can substantially decrease the epidemic peak, the number of multi-infections and deaths.ConclusionsEnhanced morbidity and mortality due to multiple disease exposure is a potential threat in the COVID-19 pandemic that deserves more attention. Particularly it underlines another facet questioning disease management strategies aiming for herd immunity.
Dysregulation of Pulmonary Responses in Severe COVID-19
Authors: Wu Dandan , Yang Xuexian O. 
Published: October 2020

AbstractPatients with coronavirus disease 2019 (COVID-19) predominantly have a respiratory tract infection with various symptoms and high mortality is associated with respiratory failure second to severe disease. The risk factors leading to severe disease remain unclear. Here, we reanalyzed a published single-cell RNA-Seq (scRNA-Seq) dataset and found that bronchoalveolar lavage fluid (BALF) of patients with severe disease compared to those with mild disease contained decreased TH17 type cells, decreased IFNA1 expressing cells with lower expression of toll-like receptor 7 (TLR7) and TLR8, increased IgA expressing B cells, and increased hyperactive epithelial cells (and/or macrophages) expressing matrix metalloproteinases (MMPs), Hyaluronan synthase 2 (HAS2), and Plasminogen activator inhibitor-1 (PAI-1), which may together contribute to the pulmonary pathology in severe COVID-19. We propose IFN-I (and TLR7/TLR8) and PAI-1 as potential biomarkers to predict the susceptibility to severe COVID19.
Statistical learning occurs during practice while high-order rule learning during rest period
Authors: Quentin Romain , Fanuel Lison , Kiss Mariann , Vernet Marine , Vékony Teodóra , Janacsek Karolina , Cohen Leonardo , Nemeth Dezso 
Published: October 2020

AbstractKnowing when the brain learns is crucial for both the comprehension of memory formation and consolidation, and for developing new training and neurorehabilitation strategies in healthy and patient populations. Recently, a rapid form of offline learning developing during short rest periods has been shown to account for most of procedural learning, leading to the hypothesis that the brain mainly learns during rest between practice periods. Nonetheless, procedural learning has several subcomponents not disentangled in previous studies investigating learning dynamics, such as acquiring the statistical regularities of the task, or else the high-order rules that regulate its organization. Here, we analyzed 506 behavioral sessions of implicit visuomotor deterministic and probabilistic sequence learning tasks, allowing the distinction between general skill learning, statistical learning and high-order rule learning. Our results show that the temporal dynamics of apparently simultaneous learning processes differ. While general skill and high-order rule learning are acquired offline, statistical learning is evidenced online. These findings open new avenues on the short-scale temporal dynamics of learning and memory consolidation and reveal a fundamental distinction between statistical and high-order rule learning, the former benefiting from online evidence accumulation and the latter requiring short rest periods for rapid consolidation.
TCR affinity controls the dynamics but not the functional specification of the Th1 response to mycobacteria
Authors: Bhattacharyya Nayan D , Counoupas Claudio , Daniel Lina , Zhang Guoliang , Cook Stuart J , Cootes Taylor A , Stifter Sebastian A , Bowen David G , Triccas James A , Bertolino Patrick , Britton Warwick J , Feng Carl G 
Published: October 2020

AbstractThe quality of T cell responses depends on the lymphocytes’ ability to undergo clonal expansion, acquire effector functions and traffic to the site of infection. Although TCR signal strength is thought to dominantly shape the T cell response, by using TCR transgenic CD4+T cells with different pMHC binding affinity, we reveal that TCR affinity does not control Th1 effector function acquisition nor the functional output of individual effectors following mycobacterial infection. Rather, TCR affinity calibrates the rate of cell division to synchronize the distinct processes of T cell proliferation, differentiation and trafficking. By timing cell division-dependent IL-12R expression, TCR affinity controls when T cells become receptive to Th1-imprinting IL-12 signals, determining the emergence and magnitude of the Th1 effector pool. These findings reveal a distinct yet cooperative role for IL-12 and TCR signalling in Th1 differentiation and suggests that the temporal activation of clones with different TCR affinity is a major strategy to coordinate immune surveillance against persistent pathogens.
Pallidal deep brain stimulation alters cortico-striatal synaptic communication in dystonic hamsters
Authors: Heerdegen Marco , Zwar Monique , Franz Denise , Neubert Valentin , Plocksties Franz , Niemann Christoph , Timmermann Dirk , Bahls Christian , van Rienen Ursula , Paap Maria , Perl Stefanie , Lüttig Annika , Richter Angelika , Köhling Rüdiger 
Published: October 2020

AbstractBackgroundDeep brain stimulation (DBS) of the globus pallidus internus (GPi) is considered to be the most relevant therapeutic option for patients with severe dystonias, which are thought to arise from a disturbance in striatal control of the GPi, possibly resulting in thalamic disinhibition. The mechanisms of GPi-DBS are far from understood. Hypotheses range from an overall silencing of target nuclei (due to e.g. depolarisation block), via differential alterations in thalamic firing, to disruption of oscillatory activity in the β-range. Although a disturbance of striatal function is thought to play a key role in dystonia, the effects of DBS on cortico-striatal function are unknown.ObjectiveWe hypothesised that DBS, via axonal backfiring, or indirectly via thalamic and cortical coupling, alters striatal network function. We aimed to test this hypothesis in thedtsz-hamster, an animal model of inherited generalised, paroxysmal dystonia.MethodsHamsters (dtsz-dystonic and non-dystonic controls) were bilaterally implanted with stimulation electrodes targeting the entopeduncular nucleus (EPN, equivalent of human GPi). DBS (130 Hz), and sham DBS, were performed in unanaesthetised animals for 3 hours. Synaptic cortico-striatal field potential responses, as well as miniature excitatory postsynaptic currents (mEPSC) and firing properties of medium spiny striatal neurons were subsequently recorded in brain slice preparations obtained from these animals immediately after EPN-DBS, to gauge synaptic responsiveness of cortico-striatal projections, their inhibitory control, and striatal neuronal excitability.ResultsDBS increased cortico-striatal responses in slices from control, but not dystonic animals. Inhibitory control of these responses, in turn, was differentially affected: DBS increased inhibitory control in dystonic, and decreased it in healthy tissue. A modulation of presynaptic mechanisms is likely involved, as mEPSC frequency was reduced strongly in dystonic, and less prominently in healthy tissues, while cellular properties of medium-spiny neurons remained unchanged.ConclusionDBS leads to dampening of cortico-striatal communication with restored inhibitory tone.
Diurnal changes in perineuronal nets and parvalbumin neurons in the rat medial prefrontal cortex
Authors: Harkness John H. , Gonzalez Angela E. , Bushana Priyanka N. , Jorgensen Emily T. , Hegarty Deborah M. , Di Nardo Ariel A. , Prochiantz Alain , Wisor Jonathan P. , Aicher Sue A. , Brown Travis E. , Sorg Barbara A. 
Published: October 2020

ABSTRACTPerineuronal nets (PNNs) surrounding fast-spiking, parvalbumin (PV) inhibitory interneurons are vital for providing excitatory:inhibitory balance within cortical circuits, and this balance is impaired in disorders such as schizophrenia, autism spectrum disorder, and substance use disorders. These disorders are also associated with altered diurnal rhythms, yet few studies have examined the diurnal rhythms of PNNs or PV cells. We measured the intensity and number of PV cells and PNNs labeled withWisteria floribundaagglutinin (WFA) in the rat prelimbic medial prefrontal cortex (mPFC) at Zeitgeber times (ZT) ZT0, 6, 12, and 18. We also measured the oxidative stress marker 8-oxo-deoxyguanosine (8-oxo-dG). Relative to ZT0, the intensities of PNN and PV staining were increased in the dark (active) phase compared with the light (inactive) phase. The intensity of 8-oxo-dG was decreased from ZT0 at all time points (ZT6,12,18), in both PV cells and non-PV cells. To examine corresponding changes in inhibitory and excitatory inputs, we measured GAD 65/67 and vGlut1 puncta apposed to PV cells with and without PNNs. Relative to ZT6, there were more excitatory puncta on PV cells surrounded by PNNs at ZT18, but no changes in PV cells devoid of PNNs. No changes in inhibitory puncta were observed. Whole-cell slice recordings in fast-spiking (PV) cells with PNNs showed an increased ratio of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor:N-methyl-D-aspartate receptor (AMPA:NMDA) at ZT18vs. ZT6. The number of PV cells and co-labeled PV/PNN cells containing the transcription factor orthodenticle homeobox 2 (OTX2), which maintains PNNs, showed a strong trend toward an increase from ZT6 to ZT18. These diurnal fluctuations in PNNs and PV cells are expected to alter cortical excitatory:inhibitory balance and provide new insights into treatment approaches for diseases impacted by imbalances in sleep and circadian rhythms.
Nascent RNA sequencing identifies a widespread sigma70-dependent pausing regulated by Gre factors in bacteria
Authors: Sun Zhe , Yakhnin Alexander , FitzGerald Peter C. , Mclntosh Carl E. , Kashlev Mikhail 
Published: October 2020

ABSTRACTPromoter-proximal pausing regulates expression of many eukaryotic genes and serves as checkpoints for assembly of elongation/splicing machinery. Little is known how broadly the pausing is employed in transcriptional regulation in bacteria. We applied NET-seq combined with RNase I footprinting for genome-wide analysis of σ70-dependent transcription pauses inEscherichia coli. ManyE. coligenes appear to contain clusters of strong backtracked pauses at 10-20-bp distance from the transcription start site caused by retention of σ70subunit in RNA polymerase. The pauses in 10-15-bp register of the promoter are dictated by binding of σ70to canonical −10 element, 6-7 nt spacer and “YR+1Y” motif centered at transcription start site all characteristic for strongE. colipromoters. The promoters for the pauses in 16-20-bp register contain an additional −10-like sequence positioned on the same face of the DNA duplex as the original −10 element suggesting that σ70hopping was responsible for these pauses. Ourin vitroanalysis reveals that RNA polymerase backtracking and DNA scrunching are involved in these pauses that are relieved by Gre transcript cleavage factors. The genes coding for transcription factors are enriched in these pauses suggesting that σ70and Gre proteins regulate transcription in response to changing environmental cues.
Acoustic stimulation increases implicit adaptation in sensorimotor adaptation
Authors: Leow Li-Ann , Tresilian James R. , Uchida Aya , Koester Dirk , Spingler Tamara , Riek Stephan , Marinovic Welber 
Published: October 2020

AbstractSensorimotor adaptation is an important part of our ability to perform novel motor tasks (i.e., learning of motor skills). Efforts to improve adaptation in healthy and clinical patients using non-invasive brain stimulation methods have been hindered by interindividual and intra-individual variability in brain susceptibility to stimulation. Here, we explore unpredictable loud acoustic stimulation as an alternative method of modulating brain excitability to improve sensorimotor adaptation. In two experiments, participants moved a cursor towards targets, and adapted to a 30° rotation of cursor feedback, either with or without unpredictable acoustic stimulation. Acoustic stimulation improved initial adaptation to sensory prediction errors in Study 1, and improved overnight retention of adaptation in Study 2. Unpredictable loud acoustic stimulation might thus be a potent method of modulating sensorimotor adaptation in healthy adults.
Distinct autoinhibitory mechanisms regulate vinculin binding by αT-catenin and αE-catenin
Authors: Heier Jonathon A. , Pokutta Sabine , Dale Ian W. , Kim Sun Kyung , Hinck Andrew P. , Weis William I. , Kwiatkowski Adam V. 
Published: October 2020

ABSTRACTα-catenin binds directly to β-catenin and connects the cadherin-catenin complex to the actin cytoskeleton. Tension regulates α-catenin conformation: actomyosin-generated force stretches the middle(M)-region to relieve autoinhibition and reveal a binding site for the actin-binding protein vinculin. Here we describe the biochemical properties of αT(testes)-catenin, an α-catenin isoform critical for cardiac function, and how intramolecular interactions regulate vinculin binding autoinhibition. Isothermal titration calorimetry (ITC) showed that αT-catenin binds the β-catenin/N-cadherin complex with a similar low nanomolar affinity to that of αE-catenin. Limited proteolysis revealed that the αT-catenin M-region adopts a more open conformation than αE-catenin. The αT-catenin M-region binds the vinculin N-terminus with low nanomolar affinity, indicating that the isolated αT-catenin M-region is not autoinhibited and thereby distinct from αE-catenin. However, the αT-catenin head (N- and M-regions) binds vinculin 1000-fold more weakly (low micromolar affinity), indicating that the N-terminus regulates M-region binding to vinculin. In cells, αT-catenin recruitment of vinculin to cell-cell contacts requires the actin-binding domain and actomyosin-generated tension, indicating that force regulates vinculin binding. Together, our results indicate that the αT-catenin N-terminus is required to maintain M-region autoinhibition and modulate vinculin binding. We postulate that the unique molecular properties of αT-catenin allow it to function as a scaffold for building specific adhesion complexes.
Non-apoptotic enteroblast-specific role of the initiator caspase Dronc for development and homeostasis of theDrosophilaintestine
Authors: Lindblad Jillian L. , Tare Meghana , Amcheslavsky Alla , Shields Alicia , Bergmann Andreas 
Published: October 2020

SummaryThe initiator caspase Dronc is the only CARD-domain containing caspase inDrosophilaand is essential for apoptosis. Here, we report that homozygousdroncmutant adult animals are short-lived due to the presence of a poorly developed, defective and leaky intestine. Interestingly, this mutant phenotype can be significantly rescued by enteroblast-specific expression ofdronc+indroncmutant animals, suggesting that proper Drone function specifically in enteroblasts, one of four cell types in the intestine, is critical for normal development of the intestine. Furthermore, enteroblast-specific knockdown ofdroncin adult intestines triggers hyperplasia and differentiation defects. These enteroblast-specific functions of Drone do not require the apoptotic pathway and thus occur in a non-apoptotic manner. In summary, we demonstrate that an apoptotic initiator caspase has a very critical non-apoptotic function for normal development and for the control of the cell lineage in the adult midgut and therefore for proper physiology and homeostasis.Highlightsdroncmutants die from a fragile and leaky intestinedronchas a critical function in enteroblasts of the intestinedronccontrols proliferation and differentiation in the intestinedroncperforms these functions in an apoptosis-independent (non-apoptotic) manner
Biological insights from the whole genome analysis of human embryonic stem cells
Authors: Merkle Florian T. , Ghosh Sulagna , Genovese Giulio , Handsaker Robert E. , Kashin Seva , Karczewski Konrad , O’Dushlaine Colm , Pato Carlos , Pato Michele , MacArthur Daniel G. , McCarroll Steven A. , Eggan Kevin 
Published: October 2020

ABSTRACTThere has not yet been a systematic analysis of hESC whole genomes at a single nucleotide resolution. We therefore performed whole genome sequencing (WGS) of 143 hESC lines and annotated their single nucleotide and structural genetic variants. We found that while a substantial fraction of hESC lines contained large deleterious structural variants, finer scale structural and single nucleotide variants (SNVs) that are ascertainable only through WGS analyses were present in hESCs genomes and human blood-derived genomes at similar frequencies. However, WGS did identify SNVs associated with cancer or other diseases that will likely alter cellular phenotypes and may compromise the safety of hESC-derived cellular products transplanted into humans. As a resource to enable reproducible hESC research and safer translation, we provide a user-friendly WGS data portal and a data-driven scheme for cell line maintenance and selection.GRAPHICAL ABSTRACTIN BRIEFMerkle and Ghosh et al. describe insights from the whole genome sequences of commonly used human embryonic stem cell (hESC) lines. Analyses of these sequences show that while hESC genomes had more large structural variants than humans do from genetic inheritance, hESCs did not have an observable excess of finer-scale variants. However, many hESC lines contained rare loss-of-function variants and combinations of common variants that may profoundly shape their biological phenotypes. Thus, genome sequencing data can be valuable to those selecting cell lines for a given biological or clinical application, and the sequences and analysis reported here should facilitate such choices.HIGHLIGHTSOne third of hESCs we analysed are siblings, and almost all are of European ancestryLarge structural variants are common in hESCs, but finer-scale variation is similar to that human populationsMany strong-effect loss-of-function mutations and cancer-associated mutations are present in specific hESC linesWe provide user-friendly resources for rational hESC line selection based on genome sequence
Countermeasures to Japan's declining birthrate: history, current situation and problems
Authors: Nishimura Takahiro 
Published: October 2020

PurposeSince 1974, Japan's total fertility rate has been constantly below replacement level. The purpose of this paper is to focus on Japan's low fertility issue and countermeasures that were adopted, in order to explore the reasons why the countermeasures were unable to solve the problem?Design/methodology/approachThe paper analyzes both the historical changes and the current situation of Japan's countermeasures. It also focuses on how in Japan marriage behavior and couples' fertility behavior changed during the implementation of the countermeasures from both objective and subjective perspectives. Based on results of the analysis, the paper explores the inherent problems regarding the countermeasures.FindingsThe paper shows that there is no sign that Japan's low fertility could be overcome, and puts forward three problems regarding the countermeasures. The paper suggests paying greater attention to the contradictions in the current policies and to go beyond the field of family policy and population policy to consider the following questions from a more macro perspective: (1) how to make fertility more desirable and meaningful and (2) how to encourage the related social systems to promote people's spontaneity both in marriage and childbearing.Originality/valueThe paper uses the latest data and focuses on analyzing the countermeasures from a more macro perspective rather than discussing specific problems of the countermeasures. Based on both objective data and subjective views and, given the characteristics of Japanese society, the paper explores in depth the problems regarding the countermeasures. By improving empirical knowledge, the paper seeks to contribute more generally to low fertility countries' “fertility revival”.