Biology subjects

Pan, J.

Publications and source records attributed to Pan, J..

At least 91 records · Page 5Linked to original sources

bioRxiv2023

The prospect of universal coronavirus immunity: a characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses

T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19). Therefore, T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of "common cold". In turn, SARS-CoV2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV2 spike, nucleocapsid and membrane proteins and corresponding antigens from - and {beta}-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV2 spike-specific T cells reliably recognized most SARS-CoV2 variants, however cross-reactivity against the omicron variant was reduced by approximately 50%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between - and {beta}-hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV2 antigens, whereas a distinct anti-SARS-CoV2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.

immunology↗

bioRxiv2022

FCGRT, a cancer-derived immunoglobulin G binding protein, mediates the malignant phenotype of glioma

CIgG has received increasing attention, and was first discovered by our group to indicate poor prognosis in glioma. Furthermore, by protein mass spectrometry, we found that FCGRT can combine with CIgG. However, the study of FCGRT in glioma has not been reported. We used the CGGA325, TCGA dataset and immunohistochemistry to verify the importance of FCGRT on the prognosis of glioma patients. Single cell sequencing data analysis evaluated that the role of FCGRT in the microenvironment of glioma. Estimate, ssGSEA, EPIC and xCell were used for immune infiltration analysis. FCGRT was knocked down in U251 cells to detect the effect of FCGRT on the malignant development of glioma. These results showed that patients with higher FCGRT expression had a shorter overall survival. FCGRT was closely related to the tumor microenvironment, especially to macrophages in the tumor microenvironment (r=0.743, p<0.001). Interestingly we also found that FCGRT was positively correlated with IGHG1. Finally, we found that knock-down of FCGRT resulted in a decrease in proliferation, migration and invasion of U251 cells. Taken together, we believe that FCGRT is an independent prognostic factor for glioma patients, and its possible mechanism is to promote proliferation and invasion of tumor cells by interacting with CIgG.

bioinformatics↗

bioRxiv2022

Japanese Encephalitis Virus NS1 Protein regulates the expression and distribution of TIM-1 to promote viral infection

Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus, which may cause severe encephalitis in humans, horses, and other animals. TIM-1 has been identified to be a receptor that promotes various viruses to enter into target cells in recent years. In the present study, we found that TIM-1 protein was significantly increased in A549 cells at the late stage of JEV infection, while the transcription levels of TIM-1 remained unaltered. Interestingly, we found that NS1 protein plays a key role in increasing the expression of TIM-1 in cells infected with JEV. Further, we found that the NS1 protein also efficiently regulates TIM-1 protein to distribute in the cytoplasm in JEV-infected cells, and the amount of TIM-1 protein located on the cell membrane was reduced instead. As a consequence, NS1 protein antagonize TIM-1 mediated viral restriction for further viral infection and propagation in the late stage of infection. In molecular mechanism, the molecular weight of TIM-1 increased a bit in the present of NS1. Expression of NEU1 down-regulated TIM-1 expression and oseltamivir treatment increased the expression of TIM-1. Therefore, our data indicated that JEV NS1 protein facilitated the sialylation modification of TIM-1 to up-regulate the level of TIM-1 expression and regulate its distribution. Collectively, our study revealed that JEV NS1 protein regulates the expression and distribution of TIM-1 by facilitating its sialylation to antagonize TIM-1-mediated JEV restriction for further infection. Understanding the functional interplays between TIM-1 and NS1 proteins will offer new insights into virushost interaction. IMPORTANCET-cell immunoglobulin and mucin domain protein 1 (TIM-1) is known to promote cellular entry of various enveloped viruses. We discovered a novel phenomenon of dynamic expression and functional regulation of TIM-1 during JEV infection. Firstly, TIM-1 protein increased in the cytoplasm at the late stage of JEV infection. Furthermore, JEV NS1 protein up-regulated the intracellular expression of TIM-1 and antagonize TIM-1-mediated viral restriction for further viral infection. In molecular mechanism, JEV NS1 protein facilitated the sialylation of TIM-1 to increase the level of TIM-1 expression and cytoplasm distribution. Taken together, at the late stage of infection, JEV employs a strategy in which NS1 promotes JEV release by promoting the sialylation of TIM-1, causing it to be primarily localized in the cytoplasm. Therefore, we discovered new functions of TIM-1 and JEV NS1 during the process of JEV infection, and provide a new insight into the interactions between JEV and cell hosts.

microbiology↗

bioRxiv2022

Immunogenic fusion proteins induce neutralizing SARS-CoV-2 antibodies in the serum and milk of sheep

Antigen-specific polyclonal immunoglobulins derived from the serum, colostrum, or milk of immunized ruminant animals have potential as scalable therapeutics for the control of viral diseases such as COVID-19. Enhancing the efficacy of vaccine antigens to induce robust and specific antibody responses remains central to developing highly effective formulations. The direct fusion of immunoglobulin (IgG) Fc domains or other immune-stimulating proteins to antigens has shown promise in several mammalian species but has not yet been tested and optimized in commercially-relevant ruminant species. Here we show that the immunization of sheep with fusions of the receptor binding domain (RBD) of SARS-CoV-2 to ovine IgG2a Fc domains promotes significantly higher levels of antigen-specific antibodies compared to native RBD or full-length spike antigens. This antibody population was shown to contain elevated levels of neutralizing antibodies that suppress binding between the RBD and soluble hACE2 receptors in vitro. The parallel evaluation of a second immune-stimulating fusion candidate, Granulocyte-macrophage colony-stimulating factor (GM-CSF), induced high neutralizing responses in select animals but narrowly missed achieving significance at the group level. Furthermore, we demonstrate that the antibodies induced by these fusion antigens are transferred from maternal serum into colostrum/milk. These antibodies also demonstrate cross-neutralizing activity against diverse SARS-CoV-2 variants including delta and omicron. Our findings highlight a new pathway for recombinant antigen design in ruminant animals with applications in immune milk production and animal health.

bioengineering↗

bioRxiv2022

One-Step PCR Amplicon Library Construction (OSPALC, version 1)

High-throughput sequencing of amplicons has been widely used to precisely and efficiently identify species compositions and analyze community structures, greatly promoting biological studies involving large amounts of complex samples, especially those involving environmental and pathogen-monitoring ones. However, commercial library preparation kits for amplicon sequencing, which generally require multiple steps, including adapter ligation and indexing, are expensive and time-consuming, especially for applications at a large scale. Here, to overcome this technical hurdle, we present a one-step PCR amplicon library construction (OSPALC) protocol for amplicon library preparations in the lab along with a QIIME2-based amplicon analysis pipeline. High-quality reads have been generated by this approach to reliably identify species compositions of mock bacterial communities and environmental samples. With this protocol, the amplicon library construction is completed through one regular PCR with long primers, and the total cost per DNA/cDNA sample decreases to just 1/15 of the typical cost via service providers. Empirically tested primers to construct OSPALC libraries for 16S rDNA V4 regions are demonstrated as a case study. Criteria to design primers targeting at any regions of prokaryotic and eukaryotic genomes are also suggested. In principle, OSPALC can be conveniently used in amplicon library constructions of any target gene of both prokaryotes and eukaryotes at the DNA or RNA levels, and will facilitate research in numerous fields.

genomics↗

bioRxiv2022

Identifying Patients with Cognitive Motor Dissociation Using Resting-state Temporal Stability

BackgroundUsing task-dependent neuroimaging techniques, recent studies discovered a fraction of patients with disorders of consciousness (DOC) who had no command-following behaviors but showed a clear sign of awareness, which was defined as cognitive motor dissociation (CMD). Although many efforts were made to identify the CMD, existing task-dependent approaches might fail when patients had multiple cognitive function (e.g., attention, memory) impairments, and thus lead to false-negative findings. However, recent advances in resting-state fMRI (rs-fMRI) analysis allow investigation of the dynamic change of spontaneous brain activity, which might be a powerful tool to test the patients cognitive functions, while its capacity in identifying CMD was unclear. MethodsThe rs-fMRI study included 119 participants from three independent research sites. A sliding-window approach was used to investigate the dynamic functional connectivity of the brain in two aspects: the global and regional temporal stability, which measures how stable the brain functional architecture is across time. The temporal stability was compared in the first dataset (36/16 DOC/controls), and then a Support Vector Machine (SVM) classifier was built to discriminate DOC patients from controls. Furthermore, the generalizability of the SVM classifier was tested in the second independent dataset (35/21 DOC/controls). Finally, the SVM classifier was applied to the third independent dataset where patients underwent an rs-fMRI and brain-computer interface assessment (4/7 CMD/potential non-CMD), to test its performance in identifying CMD. ResultsOur results showed that the global and regional temporal stability were impaired in DOC patients, especially in regions from the cingulo-opercular task control, default mode, fronto-parietal task control, and salience network. Using the temporal stability as features, the SVM model not only showed a good performance in the first dataset (accuracy = 90 %), but a good generalizability in the second dataset (accuracy = 82 %). Most importantly, the SVM model generalized well in identifying CMD in the third dataset (accuracy = 91 %). ConclusionThe current findings suggested that rs-fMRI could be a potential tool to assist in diagnosing CMD. Furthermore, the temporal stability investigated in this study also contributed to a deeper understanding of the neural mechanism of the consciousness.

neuroscience↗

bioRxiv2022

TMEM100, a Lung-Specific Endothelium Gene

The heterogeneity of endothelium across different organs was recently explored using single-cell RNA-sequencing analysis. Compared to other organs, the lung exhibits a distinct structure composed of a thin layer of capillary for efficient gas exchange. In this study, we demonstrate that Tmem100 is a lung-specific endothelium gene.

physiology↗

bioRxiv2022

Causal contributions to sensory-based decision-making by cell-type specific circuits in the tail striatum

The striatum comprises distinct types of neurons giving rise to the direct and indirect basal ganglia pathways and local circuits. A large amount of work has been focusing on cell-type specific striatal circuits in the context of movement control, proposing several models on their functional roles. But it remains to be elucidated how the cell-type specific striatal circuits contribute to decision-making behavior and whether the existing models apply. Here, we investigate the causal roles of the cell-type specific circuits in the posterior tail of the dorsal striatum (TS) of mice in an auditory-guided decision-making behavior. Transient unilateral activation of the direct- or indirect-pathway striatal spiny projection neurons (dSPNs or iSPNs) both biased decisions in opposite directions. These effects, however, were not due to a direct influence on movement, but was specific to the decision period preceding action execution. Optogenetic inactivation of dSPNs and iSPNs revealed their opposing causal contributions to decisions. At the local circuit level, simutaneous optical recording and manipulation of dSPNs and iSPNs revealed their antagnizing interactions. Inactivation of PV interneurons, a common inhibitory input to both dSPNs and iSPNs, facilitated contraversive choices, supporting a causal contribution of coordinated striatal circuits. Using a neural circuit model, we further demonstrated the computational implemenation of the causal circuit mechanism. Our results indicate that while the causal roles of the cell-type specific striatal circuits in decision-making largely agree with classic models in movement control, they show decision task-related specificity involving local circuit coordination.

neuroscience↗

bioRxiv2022

Environmental Stability of Enveloped Viruses is Impacted by the Initial Volume and Evaporation Kinetics of Droplets

Efficient spread of respiratory viruses requires the virus to maintain infectivity in the environment. Environmental stability of viruses can be influenced by many factors, including temperature and humidity. Our study measured the impact of initial droplet volume (50, 5, and 1 {micro}L) and relative humidity (RH: 40%, 65%, and 85%) on the stability of influenza A virus, bacteriophage, Phi6, a common surrogate for enveloped viruses, and SARS-CoV-2 under a limited set of conditions. Our data suggest that the drying time required for the droplets to reach quasi-equilibrium (i.e. a plateau in mass) varied with RH and initial droplet volume. The macroscale physical characteristics of the droplets at quasi-equilibrium varied with RH but not with initial droplet volume. We observed more rapid virus decay when the droplets were still wet and undergoing evaporation, and slower decay after the droplets had dried. Initial droplet volume had a major effect on virus viability over the first few hours; whereby the decay rate of influenza virus was faster in smaller droplets. In general, influenza virus and SARS-CoV-2 decayed similarly. Overall, this study suggests that virus decay in media is closely correlated with the extent of droplet evaporation, which is controlled by RH. Taken together, these data suggest that decay of different viruses is more similar at higher RH and in smaller droplets and is distinct at lower RH and in larger droplets. Importantly, accurate assessment of transmission risk requires use of physiologically relevant droplet volumes and careful consideration of the use of surrogates. FundingNational Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institutes of Health; Department of Health and Human Services; Flu Lab. ImportanceDuring the COVID-19 pandemic, policy decisions were being driven by virus stability experiments involving SARS-CoV-2 applied to surfaces in large droplets at various humidity conditions. The results of our study indicate that determination of half-lives for emerging pathogens in large droplets likely over-estimates transmission risk for contaminated surfaces, as occurred during the COVID-19 pandemic. Our study implicates the need for the use of physiologically relevant droplet sizes with use of relevant surrogates in addition to what is already known about the importance of physiologically relevant media for risk assessment of future emerging pathogens.

microbiology↗

bioRxiv2022

Multi-Domain Characterization and Rapid Detection Technology for Cocaine and Methamphetamine Acute Abuse based on EEG

Multi-domain characterization and a new fast detection method for acute illegal psychostimulants abuse detection based on waking-state EEG of mice is proposed in this paper. To get corftical electroencephalogram (EEG), three groups of mice were injected with cocaine (Coca), methamphetamine (Meth), and saline (Sali) respectively following the experimental paradigm of drug abuse. The EEG features were extracted out by multi-domain views, including time, frequency, complexity, dynamics, and independent domains to obtain acute drug abuse effects on the brain. New strategy combing time domain with frequency domain is developed as multi-domain input and by means of dimension transformation approach preserving temporal information, the performance of drug abuse detection is greatly improved with deep learning models of ResNet50. Results show that comparing to support vector machine (SVM), k nearest neighbor (kNN), random forest (RF), and long short-term memory fully convolutional networks (LSTM-FCN), ResNet50 based on our proposed multi-domain features has best F1-score of 95.10%. This promising method provides a low-cost, fast, and widely assisted technology for psychostimulants abuse identification.

bioinformatics↗

bioRxiv2022

The immunogenomic landscape of cattle

Here, we report the de novo assembly of a cattle genome using ultra-long-read nanopore sequencing in conjunction with other advanced technologies. The assembled genome contains only 145 contigs (N50 [~] 74.0 Mb). Compare to the current reference cattle genome ARS-UCD1.2, 154 gaps are closed, and 467 scaffolds are further placed in our assembly. Importantly, except two remained gaps in the T-cell receptor /{delta} (TRA/TRD) region, the gene loci of other TRs and immunoglobulins (IGs) are seamlessly assembled and exquisitely annotated. With the characterization of 258 IG genes and 626 TR genes that distributed in seven genomic loci, we illustrate the highest immune gene diversity in mammals to our knowledge. Moreover, the gene structures of major histocompatibility complex (MHC) are integrally depicted with properly phased haplotypes. Thus, our work not only reports a cattle genome with the most continuity and completeness, but also provide a comprehensive view of the complex immune- genome.

genomics↗

bioRxiv2022

Notch signaling in tumor vasculature programs cancer-associated fibroblasts to suppress anti-tumor immunity

Scarcity of tumor-infiltrating T cells poses significant challenges to cancer treatment, but mechanisms that regulate T cell recruitment into the tumor microenvironment are unclear. Here we ask if the endothelial lining of tumor vasculature suppresses T cell infiltration. Using mouse pancreatic ductal adenocarcinoma models, we found that Notch signaling in endothelial cells (ECs) inhibits the pro-inflammatory functions of cancer-associated fibroblasts (CAFs) and prevents CAFs from secreting CXCL10, a chemokine that recruits anti-tumor T cells via its receptor CXCR3. Abrogation of canonical Notch signaling in ECs reprogrammed the phenotype of CAFs from myofibroblasts into pro-inflammatory fibroblasts, unleashed interferon gamma (IFN{gamma}) responses in the tumor, and stimulated CXCL10/CXCR3-mediated recruitment of T cells to inhibit tumor growth. Collectively, these data uncover an important role of endothelial Notch signaling in shaping the tumor immune microenvironment, and suggest the potential of targeting EC-CAF crosstalk as an approach to enhance anti-tumor immunity in immunologically cold tumors. In briefHow blood vasculature shapes the tumor immune microenvironment is poorly defined. This study demonstrates that tumor endothelial cells reprogram cancer-associated fibroblasts to limit anti-tumor T cell recruitment, and suggests the potential of targeting endothelium-fibroblast crosstalk to overcome T cell scarcity in "cold" tumors and enhance anti-tumor immunity.

cancer biology↗

bioRxiv2022

An NKX-COUP-TFII genomic code for mucosal vascular addressins and organ morphogenesis

Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules, providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3+ capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define a genomic address code for targeted expression of mucosal vascular addressins and implicate NCCE in fundamental processes in cell specification and development.

immunology↗

bioRxiv2022

Germline-soma Supply Mitochondria for mtDNA Inheritance in Mouse Oogenesis

Maternal transmission paradigm of mtDNA remains controversial in mammalian oogenesis. Germline-soma-to-oocyte communication by numerous transzonal nanotubes (TZTs) reminds whether intercellular mitochondrial transfer is associated with maternal inheritance. Here, we found that mouse oocytes egocentrically receive mitochondria via TZTs, which projected from germline-soma, to achieve 105 copies, instead of de novo synthesis of mtDNA subpopulation in growing oocytes. De novo assembled TZTs amongst germline-soma and oocytes accumulated mtDNA amounts of the oocytes in vitro. However, mitochondrial supplement from germline-soma gradually diminished along with oocyte growth and was terminated by meiosis resumption, in line with a decrease in the proportion of germline-soma with thriving mtDNA replication and FSH capture capability. Thus, germline-soma-to-oocyte mitochondrial transfer is responsible for mammalian mtDNA inheritance as well as oogenesis and aging. One-sentence summariesThe maternal mtDNA transmission accompanied by oogenesis is inseparable from germline-soma mitochondrial transport.

developmental biology↗

bioRxiv2021

Activation of retinoic acid receptor reduces metastatic prostate cancer bone lesions through blocking endothelial-to-osteoblast transition

Metastatic prostate cancer (PCa) in bone induces bone-forming lesions that contribute to progression and therapy resistance. Currently strategies targeting PCa-induced bone formation are lacking. We previously showed that PCa-induced bone originates from endothelial cells (EC) that have undergone endothelial-to-osteoblast (EC-to-OSB) transition in response to tumor-secreted BMP4. Here, we show that activation of retinoic acid receptor (RAR) inhibits EC-to-OSB transition and reduces PCa-induced bone formation. We found that palovarotene, a RAR{gamma} agonist being tested for heterotopic ossification in fibrodysplasia ossificans progressiva, inhibited EC-to-OSB transition and osteoblast mineralization in vitro, and decreased tumor-induced bone formation and tumor growth in several osteogenic PCa models. RAR/{beta}/{gamma} isoform knockdown in 2H11 ECs blocked EC-to-OSB transition and osteoblast mineralization. Pan-RAR agonist ATRA inhibited MycCaP-BMP4-induced bone formation and tumor growth under castration. Furthermore, palovarotene or ATRA reduced plasma Tenascin C, a factor secreted by EC-OSB cells, which may be used to monitor treatment response. Mechanistically, BMP4-activated pSmad1 forms a complex with RAR in the nucleus of 2H11 cells. RAR activation by palovarotene or ATRA causes pSmad1 degradation by recruiting E3-ubiquitin ligase Smurf1 into the nuclear pSmad1/RAR{gamma} complex. Our findings suggest that palovarotene can be repurposed to target PCa-induced bone formation to improve clinical outcomes for bone metastasis.

cancer biology↗

bioRxiv2021

Non-rapid eye movement sleep and wake neurophysiology in schizophrenia

Motivated by the potential of objective neurophysiological markers to index thalamocortical function in patients with severe psychiatric illnesses, we comprehensively characterized key NREM sleep parameters across multiple domains, their interdependencies, and their relationship to waking event-related potentials and symptom severity. In 130 schizophrenia (SCZ) patients and controls, we confirmed a marked reduction in sleep spindle density in SCZ and extended these findings to show that only slow spindles predicted symptom severity, and that fast and slow spindle properties were largely uncorrelated. We also describe a novel measure of slow oscillation and spindle interaction that was attenuated in SCZ. The main sleep findings were replicated in a demographically distinct sample, and a joint model, based on multiple NREM components, predicted disease status in the replication cohort. Although also altered in patients, auditory event-related potentials elicited during wake were unrelated to NREM metrics. Consistent with a growing literature implicating thalamocortical dysfunction in SCZ, our characterization identifies independent NREM and wake EEG biomarkers that may index distinct aspects of SCZ pathophysiology and point to multiple neural mechanisms underlying disease heterogeneity. This study lays the groundwork for evaluating these neurophysiological markers, individually or in combination, to guide efforts at treatment and prevention as well as identifying individuals most likely to benefit from specific interventions.

neuroscience↗

bioRxiv2021

A multi-class gene classifier for SARS-CoV-2 variants based on convolutional neural network

Surveillance of circulating variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great importance in controlling the coronavirus disease 2019 (COVID-19) pandemic. We propose an alignment-free in silico approach for classifying SARS-CoV-2 variants based on their genomic sequences. A deep learning model was constructed utilizing a stacked 1-D convolutional neural network and multilayer perceptron (MLP). The pre-processed genomic sequencing data of the four SARS-CoV-2 variants were first fed to three stacked convolution-pooling nets to extract local linkage patterns in the sequences. Then a 2-layer MLP was used to compute the correlations between the input and output. Finally, a logistic regression model transformed the output and returned the probability values. Learning curves and stratified 10-fold cross-validation showed that the proposed classifier enables robust variant classification. External validation of the classifier showed an accuracy of 0.9962, precision of 0.9963, recall of 0.9963 and F1 score of 0.9962, outperforming other machine learning methods, including logistic regression, K-nearest neighbor, support vector machine, and random forest. By comparing our model with an MLP model without the convolution-pooling network, we demonstrate the essential role of convolution in extracting viral variant features. Thus, our results indicate that the proposed convolution-based multi-class gene classifier is efficient for the variant classification of SARS-CoV-2.

bioinformatics↗

bioRxiv2021

Asymmetrical choice-related ensemble activity in direct and indirect-pathway striatal neurons drives perceptual decisions

Sensory-guided decision-making is a vital brain function critically depending on the striatum, a key brain structure transforming sensorimotor information into actions. However, how the two opposing striatal pathways work in concert to select actions during decision-making remains controversial. Here, using cell-type specific two-photon imaging and optogenetic perturbations from the posterior dorsal striatum during decision-making behavior in mice, we uncover the population coding and causal mechanisms of the direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs) in decision-related action selection. Unexpected from prevailing models, we found that both dSPNs and iSPNs contain divergent subpopulations representing competing choices, and exhibit ensemble-level asymmetry: stronger contralateral dominance in dSPNs than in iSPNs. Such multi-ensemble competition/cooperation causally contributes to decision-related action selection, as supported by systematic optogenetic manipulations and verified by computational modeling. Our results unravel a multi-ensemble coordination mechanism in the striatum for action selection during decision-making.

neuroscience↗