Biology subjects

Shi, Y.

Publications and source records attributed to Shi, Y..

At least 397 records · Page 22Linked to original sources

bioRxiv2020

Honeybee gut microbiota modulates host behaviors and neurological processes

Honeybee is a highly social insect with a reach behavioral repertoire and is a versatile model for neurobiological research. The honeybee gut microbiota is composed of a limited number of bacterial phylotypes that play an important role in host health. However, it remains unclear whether the microbiota can shape brain profiles and behaviors. Here, we revealed that the gut microbiota is requisite for the olfactory learning and memory ability of honeybees and alters the level of neurotransmitters in the brain. Transcriptomic and proteomic analysis showed distinctive gene expression and protein signatures for gnotobiotic bees associated with different gut bacteria. Specifically, genes related to olfactory functions and labor division are most upregulated. Moreover, differentially spliced genes in the brains of colonized bees largely overlapped with the datasets for human autism. The circulating metabolome profiles identified that different gut species regulated specific module of metabolites in the host hemolymph. Most altered metabolites are involved in the amino acid and glycerophospholipid metabolism pathways for the production of neuroactive compounds. Finally, antibiotic treatment disturbed the gut community and the nursing behavior of worker bees under field conditions. The brain transcripts and gut metabolism was also greatly interfered in treated bees. Collectively, we demonstrate that the gut microbiota regulates honeybee behaviors, brain gene transcription, and the circulating metabolism. Our findings highlight the contributions of honeybee gut microbes in the neurological processes with striking parallels to those found in other animals, thus providing a promising model to understand the host-microbe interactions via the gut-brain axis.

microbiology↗

bioRxiv2020

Scalable Analysis of Multi-Modal Biomedical Data

Targeted diagnosis and treatment options are dependent on insights drawn from multi-modal analysis of large-scale biomedical datasets. Advances in genomics sequencing, image processing, and medical data management have supported data collection and management within medical institutions. These efforts have produced large-scale datasets and have enabled integrative analyses that provide a more thorough look of the impact of a disease on the underlying system. The integration of large-scale biomedical data commonly involves several complex data transformation steps, such as combining datasets to build feature vectors for learning analysis. Thus, scalable data integration solutions play a key role in the future of targeted medicine. Though large-scale data processing frameworks have shown promising performance for many domains, they fail to support scalable processing of complex datatypes. To address these issues and achieve scalable processing of multi-modal biomedical data, we present TraNCE, a framework that automates the difficulties of designing distributed analyses with complex biomedical data types. We outline research and clinical applications for the platform, including data integration support for building feature sets for classification. We show that the system is capable of outperforming the common alternative, based on "flattening" complex data structures, and runs efficiently when alternative approaches are unable to perform at all. Key PointsO_LIModern biomedical analyses are integrated pipelines of data access mechanisms and analysis components that operate on and produce datasets in a variety of complex, domain specific formats. C_LIO_LIScalable data integration and aggregation solutions that support joint inference on such large-scale datasets play a key role advancing biomedical analysis. C_LIO_LIQuery compilation techniques that optimize nested data processing are essential for scaling multi-modal, biomedical analysis. C_LI

bioinformatics↗

bioRxiv2020

The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. In consequence, PLANE promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor patient outcomes. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.

cancer biology↗

bioRxiv2020

Deletion of PI3-Kinase Promotes Myelodysplasia Through Dysregulation of Autophagy in Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) maintain the blood system through a delicate equilibrium between self-renewal and differentiation. Most hematopoietic growth factors and cytokines signal through phosphoinositide 3-kinase (PI3K) via three Class IA catalytic PI3K isoforms (P110, {beta}, and {delta}), encoded by Pik3ca, Pik3cb, and Pik3cd, respectively. The PI3K/AKT pathway is commonly activated in acute myeloid leukemia (AML), and PI3K is a common therapeutic target in cancer. However, it is not known whether PI3K is required for HSC differentiation or self-renewal. We previously demonstrated that individual PI3K isoforms are dispensable in HSCs1,2. To determine the redundant roles of PI3K isoforms in HSCs, we generated a triple knockout (TKO) mouse model with deletion of all three Class IA PI3K isoforms in the hematopoietic system. Surprisingly, we observed significant expansion of TKO HSCs after transplantation, with decreased differentiation capacity and impaired multilineage repopulation. Additionally, the bone marrow of TKO mice exhibited myelodysplastic features with chromosomal abnormalities. Interestingly, we found that macroautophagy (thereafter autophagy) is impaired in TKO HSCs, and that pharmacologic induction of autophagy improves their differentiation. Therefore, we have uncovered important roles for PI3K in autophagy regulation in HSCs to maintain the balance between self-renewal and differentiation.

cancer biology↗

bioRxiv2020

3D Genome Contributes to Protein-Protein Interactome

Numerous computational methods have been proposed to predict protein-protein interactions, none of which however, considers the original DNA loci of the interacting proteins in the perspective of 3D genome. Here we retrospect the DNA origins of the interacting proteins in the context of 3D genome and discovered that 1) if a gene pair is more proximate in 3D genome, their corresponding proteins are more likely to interact. 2) signal peptide involvement of PPI affects the corresponding gene-gene proximity in 3D genome space. 3) by incorporating 3D genome information, existing PPI prediction methods can be further improved in terms of accuracy. Combining our previous discoveries, we conjecture the existence of 3D genome driven cellular compartmentalization, meaning the co-localization of DNA elements lead to increased probability of the co-localization of RNA elements and protein elements.

bioinformatics↗

bioRxiv2020

Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation

Eukaryotic gene expression is extensively regulated by cellular stress and pathogen infections. We have previously shown that herpes simplex virus 1 (HSV-1) and several cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes and that the viral immediate early factor ICP27 plays an important role in HSV-1-induced DoTT. Here, we show that HSV-1 infection also leads to widespread changes in alternative polyadenylation (APA) of host mRNAs. In the majority of cases, polyadenylation shifts to upstream poly(A) sites (PAS), including many intronic PAS. Mechanistically, ICP27 contributes to HSV-1-mediated APA regulation. HSV-1- and ICP27-induced activation of intronic PAS is sequence-dependent and does not involve general inhibition of U1 snRNP. HSV1-induced intronic polyadenylation is accompanied by early termination of RNAPII. Finally, HSV-1-induced mRNAs polyadenylated at intronic PAS are exported into the cytoplasm while APA isoforms with extended 3 UTRs are sequestered in the nuclei, both preventing the expression of the full-length gene products. Together with other recent studies, our results suggest that viral infection and cellular stresses induce a multi-faceted host shutoff response that includes DoTT and changes in APA profiles.

molecular biology↗

bioRxiv2020

Basal Neural Stem Cells in the Subventricular Zone Drive Postnatal Neurogenesis with Apical Stem Cells Acting as Proliferation Gatekeepers

According to the current consensus, neural stem cells (NSCs) apically contacting the lateral ventricle generate differentiated progenitors by rare asymmetric divisions or by relocating to the basal side of the ventricular-subventricular zone V-SVZ. Both processes will then ultimately lead to the generation of adult-born olfactory bulb (OB) interneurons. In contrast to this view, we here found that adult-born OB interneurons largely derive from an additional NSC type resident in the basal V-SVZ. Despite being both capable of self-renewal and long-term quiescence, apical and basal NSCs differ in Nestin expression, primary cilia extension and frequency of cell division. The expression of Notch-related genes also differed between the two NSC groups and Notch-activation was greatest in apical NSCs. Apical downregulation of Notch-effector Hes1 decreased Notch activation while increasing proliferation across the niche and neurogenesis from apical NSCs. Underscoring their different roles in neurogenesis, lactation-dependent increase in neurogenesis was paralleled by extra activation of basal but not apical NSCs. Thus, basal NSCs support OB neurogenesis whereas apical NSCs impart Notch-mediated lateral inhibition across the V-SVZ.

cell biology↗

bioRxiv2020

Insulin Resistance Mediates Crosstalk between Skeletal Muscle and the Heart to Prevent Cardiac Dysfunction

Obesity and type 2 diabetes milieus (T2DM) are the leading causes of cardiovascular morbidity and mortality. Although insulin resistance is believed to underlie these disorders, a paradox exists that obese patients with cardiovascular diseases have better prognoses relative to leaner patients with the same diagnoses, whereas improvement of insulin sensitivity by thiazolidines significantly increases the risk of heart failure in T2DM patients. Using mice with skeletal muscle-specific deletion of the insulin receptor gene (MIRKO), we resolved this dilemma by demonstrating that insulin resistance in the skeletal muscle prevents myocardial hypertrophy and dysfunction in response to diet-induced obesity. In spite of aggregating obesity, insulin resistance selectively protected the heart, but not other metabolic tissues, from mitochondrial dysfunction and insulin resistance in MIRKO mice, leading to significant attenuation of inflammation and apoptosis of cardiomyocytes. Together, our findings revealed an unexpected role of insulin resistance as a double edge sword, calling for reevaluation of ongoing efforts for targeting insulin resistance for the treatment of metabolic diseases. Significance statementInsulin resistance is commonly recognized as one of the major causes of T2DM and other aging-related chronic diseases. However, cumulative efforts in targeting insulin resistance for the treatment of T2DM and other metabolic disorders have not met with great success due to unwanted side effects on heart failure. Here we report that insulin resistance in skeletal muscle is a double edge sword. On one hand, insulin resistance in skeletal muscle aggregates obesity and its related metabolic syndromes, and on the other it protects the heart from the development of myocardial hypertrophy, dysfunction, and apoptosis in response to DIO. Our findings call for reevaluation of the ongoing strategies in targeting insulin resistance as a novel treatment for T2DM and other metabolic diseases.

cell biology↗

bioRxiv2020

The Preclinical Inhibitor GS441524 in Combination with GC376 Efficaciously Inhibited the Proliferation of SARS-CoV-2 in the Mouse Respiratory Tract

The unprecedented coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious threat to global public health. Development of effective therapies against SARS-CoV-2 is urgently needed. Here, we evaluated the antiviral activity of a remdesivir parent nucleotide analog, GS441524, which targets the coronavirus RNA-dependent RNA polymerase enzyme, and a feline coronavirus prodrug, GC376, which targets its main protease, using a mouse-adapted SARS-CoV-2 infected mouse model. Our results showed that GS441524 effectively blocked the proliferation of SARS-CoV-2 in the mouse upper and lower respiratory tracts via combined intranasal (i.n.) and intramuscular (i.m.) treatment. However, the ability of high-dose GC376 (i.m. or i.n. and i.m.) was weaker than GS441524. Notably, low-dose combined application of GS441524 with GC376 could effectively protect mice against SARS-CoV-2 infection via i.n. or i.n. and i.m. treatment. Moreover, we found that the pharmacokinetic properties of GS441524 is better than GC376, and combined application of GC376 and GS441524 had a synergistic effect. Our findings support the further evaluation of the combined application of GC376 and GS441524 in future clinical studies. ImportanceSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has seriously threatened global public health and economic development. Currently, effective therapies to treat COVID-19 are urgently needed. In this study, we assessed the efficacy of the preclinical inhibitors GC376 and GS441524 using a mouse-adapted SARS-CoV-2 infected mouse model for the first time. Our results showed that low-dose combined application of GC376 and GS441524 could effectively protect mice from HRB26M infection in the upper and lower respiratory tracts. Hence, the combined application should be developed and considered for future clinic practice.

microbiology↗

bioRxiv2020

NyuWa Genome Resource: Deep Whole Genome Sequencing Based Chinese Population Variation Profile and Reference Panel

The lack of Chinese population specific haplotype reference panel and whole genome sequencing resources has greatly hindered the genetics studies in the worlds largest population. Here we presented the NyuWa genome resource based on deep (26.2X) sequencing of 2,999 Chinese individuals, and constructed NyuWa reference panel of 5,804 haplotypes and 19.3M variants, which is the first publicly available Chinese population specific reference panel with thousands of samples. Compared with other panels, NyuWa reference panel reduces the Han Chinese imputation error rate by the range of 30% to 51%. Population structure and imputation simulation tests supported the applicability of one integrated reference panel for both northern and southern Chinese. In addition, a total of 22,504 loss-of-function variants in coding and noncoding genes were identified, including 11,493 novel variants. These results highlight the value of NyuWa genome resource to facilitate genetics research in Chinese and Asian populations.

genomics↗

bioRxiv2020

A Mycobacterium tuberculosis effector protein attacks host innate immunity by acting as an unusual ubiquitinating enzyme

Protein kinase G (PknG), a eukaryotic type serine-threonine protein kinase (STPK) in Mycobacterium tuberculosis (Mtb), is secreted into the cytosol of infected macrophages to promote intracellular survival of mycobacteria and has been considered as a promising therapeutic target for tuberculosis (TB) treatment. However, the molecular details of Mtb PknG-host intracellular interactions remain obscure. Here, we demonstrate that PknG serves as both the ubiquitin-activating enzyme (E1) and the ubiquitin ligase (E3) to promote ubiquitination and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TGF-{beta}-activated kinase 1 (TAK1), and thus inhibits the NF-{kappa}B-mediated host innate immune responses. Surprisingly, PknG promotes the attachment of ubiquitin (Ub) to ubiquitin-conjugating enzyme (E2) UbcH7 via an isopeptide bond (UbcH7 K82-Ub), instead of a usual C86-Ub thiol-ester bond, and then promotes the discharge of Ub from UbcH7 by acting as an isopeptidase before attaching Ub to its substrates TRAF2 and TAK1. These results demonstrate that Mtb PknG promotes ubiquitination of the key components of the host innate immunity by acting as an unusual ubiquitinating enzyme to suppress innate immunity. Our findings provide a potential TB treatment via targeting unconventional ubiquitinating activities of PknG. SignificanceMycobacterium tuberculosis (Mtb) protein kinase G (PknG), which is critical for Mtb intracellular survival, is a promising target for tuberculosis (TB) treatment. However, the molecular mechanisms underlying PknG-host interactions remain largely unclear. Here we demonstrate that PknG serves as both the ubiquitin-activating enzyme and the ubiquitin ligase to promote the ubiquitination and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TGF-{beta}-activated kinase 1 (TAK1), thus inhibiting NF-{kappa}B signaling activation. PknG promotes the attachment of ubiquitin to ubiquitin-conjugating enzyme UbcH7 via an isopeptide bond, instead of a usual thiol-ester bond, and releases the ubiquitin from UbcH7 by acting as an isopeptidase. These findings provide important information for rational development of TB treatment via targeting unconventional ubiquitinating activity of PknG.

microbiology↗

bioRxiv2020

Brunner syndrome associated MAOA dysfunction in human dopaminergic neurons results in NMDAR hyperfunction and increased network activity.

BackgroundMonoamine neurotransmitter abundance affects motor control, emotion, and cognitive function and is regulated by monoamine oxidases. Amongst these, monoamine oxidase A (MAOA) catalyzes the degradation of dopamine, norepinephrine, and serotonin into their inactive metabolites. Loss-of-function mutations in the X-linked MAOA gene cause Brunner syndrome, which is characterized by various forms of impulsivity, maladaptive externalizing behavior, and mild intellectual disability. Impaired MAOA activity in individuals with Brunner syndrome results in bioamine aberration, but it is currently unknown how this affects neuronal function. MethodsWe generated human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons from three individuals with Brunner syndrome carrying different mutations, and used CRISPR/Cas9 mediated homologous recombination to rescue MAOA function. We used these lines to characterize morphological and functional properties of DA neuronal cultures at the single cell and neuronal network level in vitro. ResultsBrunner syndrome DA neurons showed reduced synaptic density but hyperactive network activity. Intrinsic functional properties and -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission were not affected by MAOA dysfunction. Instead, we show that the neuronal network hyperactivity is mediated by upregulation of the GRIN2A and GRIN2B subunits of the N-methyl-D-aspartate receptor (NMDAR), and rescue of MAOA results in normalization of NMDAR function as well as restoration of network activity. ConclusionsOur data suggest that MAOA dysfunction in Brunner syndrome increases activity of dopaminergic neurons through upregulation of NMDAR function, which may contribute to Brunner syndrome associated phenotypes.

neuroscience↗

bioRxiv2020

eDNA metabarcoding outperforms traditional fisheries sampling and reveals fine-scale heterogeneity in a temperate freshwater lake

Understanding biodiversity in aquatic systems is critical to ecological research and conservation efforts, but accurately measuring species richness using traditional methods can be challenging. Environmental DNA (eDNA) metabarcoding, which uses high-throughput sequencing and universal primers to amplify DNA from multiple species present in an environmental sample, has shown great promise for augmenting results from traditional sampling to characterize fish communities in aquatic systems. Few studies, however, have compared exhaustive traditional sampling with eDNA metabarcoding of corresponding water samples at a small spatial scale. We intensively sampled Boardman Lake (137 ha) in Michigan, USA from May to June in 2019 using gill and fyke nets and paired each net set with lake water samples collected in triplicate. We analyzed water samples using eDNA metabarcoding with 12S and 16S fish-specific primers and compared estimates of fish diversity among methods. In total, we set 60 nets and analyzed 180 1 L lake water samples. We captured a total of 12 fish species in our traditional gear and detected 40 taxa in the eDNA water samples, which included all the species observed in nets. The 12S and 16S assays detected a comparable number of taxa, but taxonomic resolution varied between the two genes. In our traditional gear, there was a clear difference in the species selectivity between the two net types, and there were several species commonly detected in the eDNA samples that were not captured in nets. Finally, we detected spatial heterogeneity in fish community composition across relatively small scales in Boardman Lake with eDNA metabarcoding, but not with traditional sampling. Our results demonstrated that eDNA metabarcoding was substantially more efficient than traditional gear for estimating community composition, highlighting the utility of eDNA metabarcoding for assessing species diversity and informing management and conservation.

genomics↗

bioRxiv2020

Structural basis of SARS-CoV-2 polymerase inhibition by Favipiravir

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into an unprecedented global pandemic. Nucleoside analogues, such as Remdesivir and Favipiravir, can serve as the first-line broad-spectrum antiviral drugs against the newly emerging viral diseases. Recent clinical trials of these two drugs for SARS-CoV-2 treatment revealed antiviral efficacies as well as side effects with different extents1-4. As a pyrazine derivative, Favipiravir could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides, which may further lead to mutations in progeny RNA copies due to the non-conserved base-pairing capacity5. Here, we determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARS-CoV-2 in the pre-catalytic state. This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues which may explain its capacity for mimicking both adenine and guanine nucleotides. These findings shed lights on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.

microbiology↗

bioRxiv2020

De Novo Lipid Labeling for Comprehensive Analysis of Subcellular Distribution and Trafficking in Live Cells

Lipids exert dynamic biological functions which are determined both by their fatty acyl compositions and precise spatiotemporal distributions inside the cell. There are more than 1000 lipid species in a typical mammalian cell. However, it remains a daunting task to investigate any of these features in live cells for each of the more than 1000 lipid species. Here we resolved this issue by developing a de novo lipid labeling method for major lipid species, including glycerolipids, glycerophospholipids, and cholesterol esters by using a single fluorescent probe. The method not only allowed us to probe the precise subcellular distribution and trafficking of individual lipid species in live cells, but also uncovered some unexpected biological functions of previously reported lipid metabolic enzymes that were not possible by conventional biochemical methods. We envision that this method will become an indispensable tool for the functional analysis of individual lipid species and numerous lipid metabolic enzymes and transporters in live cells.

cell biology↗

bioRxiv2020

Si-C: method to infer biologically valid super-resolution intact genome structure from single-cell Hi-C data

There is a strong demand for the methods that can efficiently reconstruct biologically valid super-resolution intact genome 3D structures from sparse and noise single-cell Hi-C data. Here, we developed Single-Cell Chromosome Conformation Calculator (Si-C) within the Bayesian theory framework and applied this approach to reconstruct intact genome 3D structures from the single-cell Hi-C data of eight G1-phase haploid mouse ES cells. The inferred 100-kb and 10-kb structures consistently reproduce the known conserved features of chromatin organization revealed by independent imaging experiments. The analysis of the 10-kb resolution 3D structures revealed cell-to-cell varying domain structures in individual cells and hyperfine structures in domains, such as loops. An average of 0.2 contact reads per divided bin is sufficient for Si-C to obtain reliable structures. The valid super-resolution structures constructed by Si-C demonstrates the potential for visualizing and investigating interactions between all chromatin loci at genome scale in individual cells.

bioinformatics↗

bioRxiv2020

Reduction of neuronal activity mediated by blood-vessel regression in the brain

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we reported that a substantial proportion of blood vessels in the adult brain sporadically occluded and regressed. Their regression proceeded through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels were found to be widespread in mouse, monkey and human brains. Both brief occlusions of the middle cerebral artery and lipopolysaccharide-mediated inflammation induced an increase of vessel regression. Blockage of leukocyte adhesion to endothelial cells alleviated LPS-induced vessel regression. We further revealed that blood vessel regression caused a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and glutamate production. Our results elucidate the mechanism of vessel regression and its role in neuronal function in the adult brain.

neuroscience↗

bioRxiv2020

Sensory feedback-dependent coding of arm position in local field potentials of the posterior parietal cortex

Although multisensory integration is crucial for sensorimotor function, it is still unclear how sensory cues provided by the visual and proprioceptive systems are combined in the brain during motor behaviors. Here we characterized the effects of multisensory interactions on local field potential (LFP) activity obtained from the superior parietal lobule (SPL) as non-human primates performed an arm position maintenance task with either unimodal (proprioceptive) or bimodal (visual-proprioceptive) sensory feedback. Based on previous analyses of spiking activity, and observations that LFP and spikes are highly correlated in some cortical areas, we hypothesized that evoked LFP responses would be tuned to arm location but would be suppressed on bimodal trials, relative to unimodal trials. We also expected to see a substantial number of recording sites with enhanced beta band spectral power for only one set of feedback conditions, as was previously observed for spiking activity. We found that evoked activity and beta band power were tuned to arm location at many individual sites, though this tuning often differed between unimodal and bimodal trials. At the population level, both evoked and beta band activity were consistent with feedback-dependent tuning to arm location, while beta band activity also showed evidence of suppression on bimodal trials. The results suggest that multisensory interactions can alter the tuning and gain of arm position-related LFP activity in the SPL and that this activity can be used to decode the arms location under varying sensory conditions.

neuroscience↗