bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of auditory responses by visual inputs in the mouse auditory cortex
Authors: Sharma Sudha , Srivastava Hemant Kumar , Bandyopadhyay Sharba 
Published: January 2021

AbstractSo far, our understanding on the role of the auditory cortex (ACX) in processing visual information has been limited to infragranular layers of the ACX, which have been shown to respond to visual stimulation. Here, we investigate the neurons in supragranular layers of the mouse ACX using 2-photon calcium imaging. Contrary to previous reports, here we show that more than 20% of responding neurons in layer2/3 of the ACX respond to full-field visual stimulation. These responses occur by both excitation and hyperpolarization. The primary ACX (A1) has a greater proportion of visual responses by hyperpolarization compared to excitation likely driven by inhibitory neurons of the infragranular layers of the ACX rather than local layer 2/3 inhibitory neurons. Further, we found that more than 60% of neurons in the layer 2/3 of A1 are multisensory in nature. We also show the presence of multisensory neurons in close proximity to exclusive auditory neurons and that there is a reduction in the noise correlations of the recorded neurons during multisensory presentation. This is evidence in favour of deep and intricate visual influence over auditory processing. The results have strong implications for decoding visual influences over the early auditory cortical regions.Significance statementTo understand, what features of our visual world are processed in the auditory cortex (ACX), understanding response properties of auditory cortical neurons to visual stimuli is important. Here, we show the presence of visual and multisensory responses in the supragranular layers of the ACX. Hyperpolarization to visual stimulation is more commonly observed in the primary ACX. Multisensory stimulation results in suppression of responses compared to unisensory stimulation and an overall decrease in noise correlation in the primary ACX. The close-knit architecture of these neurons with auditory specific neurons suggests the influence of non-auditory stimuli on the auditory processing.
Antidiabetic action of Mcy protein through the regulation of number and affinity of insulin receptors
Authors: Marella Saritha , Kotha Peddanna , Nabi S. Abdul , Girish B.P. , Badri Kameswara Rao , Chippada Apparao 
Published: January 2021

AbstractEvidence based immunological cross-reactivity studies and anti-diabetic investigations have suggested the presence of insulin-like peptides in plants. Mcy protein, isolated from the fruits ofMomordicacymbalaria, was shown to have antihyperglycemic, antihyperlipidemic activities along with renal as well as hepatoprotective activities in Streptozotocin induced diabetic rats.Mcy protein was shown to have insulin like and/or insulin secretagoguestructure and/or functions. Hence, the present study was conducted to elucidate molecular mechanism wherebyMcy protein elicits its therapeutic role and also to know whether the Mcyprotein has any structural and functional similarity with insulin. Results of our experiments revealed that the Mcyprotein is insulin like protein. Further, we assessed the effect of treatment of Mcy protein on the levels of glucose transport (glucose transporter (GLUT-2) and on the levels of key regulators of glucose and lipid metabolisms like hepatic glucokinase (GK) and sterol regulated element binding protein-1c (SREBP-1c). Our findings demonstrated that Mcy protein decreased the elevated expressions of GK, SREBP-1c and GLUT-2 that were observed in diabetic animals. Insulin-receptor binding studies using rat erythrocytes demonstrated that mean specific binding of insulin with insulin receptors was significantly increased in Mcy treated diabetic rats when compared to diabetic control rats. Scatchard analyses of insulin-binding studies yielded curvilinear plots, and the number of receptor sites per cell was found to be 180±21.1 in Mcy treated diabetic animals calculated to be significantly superior to that of diabetic control animals. Kinetic analyses also revealed an increase in the average receptor affinity of erythrocytes from Mcy treated rats compared to diabetic control rats suggesting acute alteration in the number and affinity of insulin receptors on the membranes of erythrocytes.
SARS-CoV-2 seroprevalence among healthcare workers in general hospitals and clinics in Japan
Authors: Yoshihara Tatsuya , Ito Kazuya , Zaitsu Masayoshi , Chung Eunhee , Aoyagi Izumi , Kaji Yoshikazu , Tsuru Tomomi , Yonemura Takuma , Yamaguchi Koji , Nakayama Shinichi , Tanaka Yosuke , Yurino Nobuo , Koyanagi Hideki , Matsuki Shunji , Urae Ryuji , Irie Shin 
Published: January 2021

SummaryCoronavirus disease 2019 (COVID-19) has become a serious public health problem worldwide. However, little is known about the prevalence of COVID-19 among healthcare workers in Japan. We aimed to examine the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies among 2,160 healthcare workers in general hospitals and clinics in Japan. The prevalence of SARS-CoV-2 immunoglobulin G was 1.2% in August and October 2020, which is relatively higher than that in the general population in Japan. Because of the higher risk of COVID-19 infection, healthcare workers should be the top priority for further social support and vaccination against SARS-CoV-2.
ENOX2 NADH Oxidase: A BCR-ABL1-dependent cell surface and secreted redox protein in chronic myeloid leukemia (CML)
Authors: Baykal-Köse Seda , Voldoire Maud , Desterke Christophe , Sorel Nathalie , Cayssials Emilie , Johnson-Ansah Hyacinthe , Guerci-Bresler Agnes , Bennaceur-Griscelli Annelise , Chomel Jean-Claude , Turhan Ali G 
Published: January 2021

AbstractChronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the acquisition ofBCR-ABL1fusion in a hematopoietic stem cell. We identified theENOX2gene as up-regulated inBCR-ABL1-expressing UT-7 cell lines through a transcriptome assay. The oncofoetal ENOX2 protein (Ecto-Nicotinamide Adenine Dinucleotide Oxidase Disulfide Thiol Exchanger 2) is expressed on the external plasma membrane surface of cancer cells and can be released in cancer patients’ serum. Considering these data, we studied ENOX2 expression in CML cell lines and patients using quantitative RT-PCR, western-blots, the ELISA method, and transcriptomic dataset reanalysis. We confirmed increasedENOX2mRNA expression in theBCR-ABL1-expressing UT-7 cell line. Comparable results were obtained in CML patients at diagnosis. Western-blot analyses on UT-7 and TET-inducible Ba/F3 cell lines established the up-regulation of ENOX2 protein. BCR-ABL1 has been found to induce ENOX2 overexpression in a kinase-dependent manner. In a series of 41 patients with CML, ELISA assays showed a highly significant increase of ENOX2 protein levels in the plasma of patients with CML (p < 0.0001) as compared to controls (n=28). Transcriptomic dataset (GSE4170) reanalyzes have shown specificENOX2mRNA overexpression in the chronic phase of the disease. Bioinformatic analyses identified several genes whose mRNA expression was positively correlated toENOX2. Some of them encode proteins involved in cellular functions compatible with the growth deregulation observed in CML. All in all, our results demonstrate for the first time the upregulation of a secreted Redox protein in a BCR-ABL1-dependent manner in CML. Our data suggest that ENOX2 (through its transcriptional program) plays a significant role in the BCR-ABL1 leukemogenesis. Further studies are required to clarify the relationship between BCR-ABL1 and ENOX2.
Computational reconstruction of clonal hierarchies from bulk sequencing data of acute myeloid leukemia samples
Authors: Stiehl Thomas , Marciniak-Czochra Anna 
Published: January 2021

AbstractAcute myeloid leukemia is an aggressive cancer of the blood forming system. The malignant cell population is composed of multiple clones that evolve over time. Clonal data reflect the mechanisms governing treatment response and relapse. Single cell sequencing provides most direct insights into the clonal composition of the leukemic cells, however it is still not routinely available in clinical practice. In this work we develop a computational algorithm that allows identifying all clonal hierarchies that are compatible with bulk variant allele frequencies measured in a patient sample. The clonal hierarchies represent descendance relations between the different clones and reveal the order in which mutations have been acquired. The proposed computational approach is tested using single cell sequencing data that allow comparing the outcome of the algorithm with the true structure of the clonal hierarchy. We investigate which problems occur during reconstruction of clonal hierarchies from bulk sequencing data. Our results suggest that in many cases only a small number of possible hierarchies fits the bulk data. This implies that bulk sequencing data can be used to obtain insights in clonal evolution.
An Efficient Algorithm for Estimating Population History from Genetic Data
Authors: Rogers Alan R. 
Published: January 2021

AbstractThe Legofit statistical package uses genetic data to estimate parameters describing population history. Previous versions used computer simulations to estimate probabilities, an approach that limited both speed and accuracy. This article describes a new deterministic algorithm, which makes Legofit faster and more accurate. The speed of this algorithm declines as model complexity increases. With very complex models, the deterministic algorithm is slower than the stochastic one. In an application to simulated data sets, the estimates produced by the deterministic and stochastic algorithms were essentially identical. Reanalysis of a human data set replicated the findings of a previous study and provided increased support for the hypotheses that (a) early modern humans contributed genes to Neanderthals, and (b) a “superarchaic” population (which separated from all other humans early in the Pleistocene) was either large or deeply subdivided.
Disaggregating proportional multistate lifetables by population heterogeneity to estimate intervention impacts on inequalities
Authors: Andersen Patrick , Mizdrak Anja , Wilson Nick , Davies Anna , Bablani Laxman , Blakely Tony 
Published: January 2021

AbstractBackgroundSimulation models can be used to quantify the projected health impact of interventions. Quantifying heterogeneity in these impacts, for example by socioeconomic status, is important to understand impacts on health inequalities.We aim to disaggregate one type of Markov macro-simulation model, the proportional multistate lifetable, ensuring that under business-as-usual (BAU) the sum of deaths across disaggregated strata in each time step returns the same as the initial non-disaggregated model. We then demonstrate the application by deprivation quintiles for New Zealand (NZ), for: hypothetical interventions (50% lower all-cause mortality, 50% lower coronary heart disease mortality) and a dietary intervention to substitute 59% of sodium with potassium chloride in the food supply.MethodsWe developed a disaggregation algorithm that iteratively rescales mortality, incidence and case fatality rates by time-step of the model to ensure correct total population counts were retained at each step.To demonstrate the algorithm on deprivation quintiles in NZ, we used the following inputs: overall (non-disaggregated) all-cause mortality &morbidity rates, coronary heart disease incidence &case fatality rates; stroke incidence &case fatality rates. We also obtained rate ratios by deprivation for these same measures. Given all-cause and cause-specific mortality rates by deprivation quintile, we derived values for the incidence, case fatality and mortality rates for each quintile, ensuring rate ratios across quintiles and the total population mortality and morbidity rates were returned when averaged across groups.The three interventions were then run on top of these scaled BAU scenarios.ResultsThe algorithm exactly disaggregated populations by strata in BAU. The intervention scenario life years and health adjusted life years (HALYs) gained differed slightly when summed over the deprivation quintile compared to the aggregated model, due to the stratified model (appropriately) allowing for differential background mortality rates by strata. Modest differences in health gains (health adjusted life years) resulted from rescaling of sub-population mortality and incidence rates to ensure consistency with the aggregate population.ConclusionPolicy makers ideally need to know the effect of population interventions estimated both overall, and by socioeconomic and other strata. We demonstrate a method and provide code to do this routinely within proportional multistate lifetable simulation models and similar Markov models.
Social, economic, and environmental factors influencing the basic reproduction number of COVID-19 across countries
Authors: Kong Jude D. , Tekwa Edward W. , Gignoux-Wolfsohn Sarah A. 
Published: January 2021

AbstractObjectiveTo assess whether the basic reproduction number (R0) of COVID-19 is different across countries and what national-level demographic, social, and environmental factors characterize initial vulnerability to the virus.MethodsWe fit logistic growth curves to reported daily case numbers, up to the first epidemic peak. This fitting estimates R0. We then use a generalized additive model to discern the effects, and include 5 random effect covariates to account for potential differences in testing and reporting that can bias the estimated R0.FindingsWe found that the mean R0 is 1.70 (S.D. 0.57), with a range between 1.10 (Ghana) and 3.52 (South Korea). We identified four factors-population between 20-34 years old (youth), population residing in urban agglomerates over 1 million (city), social media use to organize offline action (social media), and GINI income inequality-as having strong relationships with R0. An intermediate level of youth and GINI inequality are associated with high R0, while high city population and high social media use are associated with high R0. Environmental and climate factors were not found to have strong relationships with R0.ConclusionStudies that aim to measure the effectiveness of interventions should account for the intrinsic differences between populations.
Meta-analysis reveals consistent immune response patterns in COVID-19 infected patients at single-cell resolution
Authors: Garg Manik , Li Xu , Moreno Pablo , Papatheodorou Irene , Shu Yuelong , Brazma Alvis , Miao Zhichao 
Published: January 2021

AbstractA number of single-cell RNA studies looking at the human immune response to the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recently published. However, the number of samples used in each individual study typically is small, moreover the technologies and protocols used in different studies vary, thus somewhat restricting the range of conclusions that can be made with high confidence. To better capture the cellular gene expression changes upon SARS-CoV-2 infection at different levels and stages of disease severity and to minimise the effect of technical artefacts, we performed meta-analysis of data from 9 previously published studies, together comprising 143 human samples, and a set of 16 healthy control samples (10X). In particular, we used generally accepted immune cell markers to discern specific cell subtypes and to look at the changes of the cell proportion over different disease stages and their consistency across the studies. While half of the observations reported in the individual studies can be confirmed across multiple studies, half of the results seem to be less conclusive. In particular, we show that the differentially expressed genes consistently point to upregulation of type I Interferon signal pathway and downregulation of the mitochondrial genes, alongside several other reproducibly consistent changes. We also confirm the presence of expanded B-cell clones in COVID-19 patients, however, no consistent trend in T-cell clonal expansion was observed.
Homozygosity at its Limit: Inbreeding Depression in WildArabidopsis arenosaPopulations
Authors: Barragan A. Cristina , Collenberg Maximilian , Schwab Rebecca , Kerstens Merijn , Bezrukov Ilja , Bemm Felix , Požárová Doubravka , Kolář Filip , Weigel Detlef 
Published: January 2021

AbstractNew combinations of genetic material brought together through hybridization can lead to unfit offspring as a result of outbreeding or inbreeding depression. In selfing plants such asArabidopsis thaliana, outbreeding depression is typically the result of pairwise deleterious epistatic interactions between two alleles that can geographically co-occur. What remains elusive is how often alleles resulting in genetic incompatibilities co-occur in natural populations of outcrossing plant species. To address this question, we screened over two thousand five hundred wildArabidopsis arenosahybrid plants in search for potential genetic mismatches. We show that although abnormal deleterious phenotypes are common, the transcriptional profiles of these abnormalA. arenosaplants differ substantially from those seen in incompatibleA. thalianahybrids. The abnormal hybrid phenotypes inA. arenosahad different underlying genetic architectures, yet a repeated theme was increased homozygosity, indicating that inbreeding rather than outbreeding depression gives rise to some of the deleterious phenotypes segregating in wildA. arenosapopulations.
The structural basis of odorant recognition in insect olfactory receptors
Authors: del Mármol Josefina , Yedlin Mackenzie , Ruta Vanessa 
Published: January 2021

AbstractOlfactory systems must detect and discriminate an enormous diversity of chemicals in the environment. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors (ORs), thus allowing a finite number of receptors to detect an almost infinite chemical world. Although most individual ORs are sensitive to a variety of odorants, the structural basis for such flexible chemical recognition remains unknown. Here, we combine cryo-electron microscopy with functional studies of receptor tuning to gain insight into the structural and mechanistic basis of promiscuous odorant recognition. We show that OR5 from the jumping bristletail,Machilis hrabei, assembles as a homo-tetrameric odorant-gated ion channel with broad chemical tuning. We elucidated the structure of OR5 in multiple gating states, alone and in complex with two of its agonists—the odorant eugenol and the insect repellent DEET. Both ligands bind to a common binding site located in the transmembrane region of each subunit, composed of a simple geometric arrangement of aromatic and hydrophobic residues. We reveal that binding is mediated by hydrophobic, non-directional interactions with residues distributed throughout the binding pocket, enabling the flexible recognition of structurally distinct odorants. Mutation of individual residues lining the binding pocket predictably altered OR5’s sensitivity to eugenol and DEET and broadly reconfigured the receptor’s tuning, supporting a model in which diverse odorants share the same structural determinants for binding. Together, these studies provide structural insight into odorant detection, shedding light onto the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity.
An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19
Authors: Wang Julia Y. , Zhang Wei , Roehrl Michael W. , Roehrl Victor B. , Roehrl Michael H. 
Published: January 2021

AbstractCOVID-19 is accompanied by a myriad of both transient and long-lasting autoimmune responses. Dermatan sulfate (DS), a glycosaminoglycan crucial for wound healing, has unique affinity for autoantigens (autoAgs) from apoptotic cells. DS-autoAg complexes are capable of stimulating autoreactive B cells and autoantibody production. Using DS affinity, we identified an autoantigenome of 408 proteins from human fetal lung fibroblast HFL11 cells, at least 231 of which are known autoAgs. Comparing with available COVID data, 352 proteins of the autoantigenome have thus far been found to be altered at protein or RNA levels in SARS-Cov-2 infection, 210 of which are known autoAgs. The COVID-altered proteins are significantly associated with RNA metabolism, translation, vesicles and vesicle transport, cell death, supramolecular fibrils, cytoskeleton, extracellular matrix, and interleukin signaling. They offer clues to neurological problems, fibrosis, smooth muscle dysfunction, and thrombosis. In particular, 150 altered proteins are related to the nervous system, including axon, myelin sheath, neuron projection, neuronal cell body, and olfactory bulb. An association with the melanosome is also identified. The findings from our study illustrate a strong connection between viral infection and autoimmunity. The vast number of COVID-altered proteins with propensity to become autoAgs offers an explanation for the diverse autoimmune complications in COVID patients. The variety of autoAgs related to mRNA metabolism, translation, and vesicles raises concerns about potential adverse effects of mRNA vaccines. The COVID autoantigen atlas we are establishing provides a detailed molecular map for further investigation of autoimmune sequelae of the pandemic.Summary sentenceAn autoantigenome by dermatan sulfate affinity from human lung HFL1 cells may explain neurological and autoimmune manifestations of COVID-19