Biology subjects

Gupta, B.

Publications and source records attributed to Gupta, B..

At least 19 recordsLinked to original sources

bioRxiv2026

Tools for genetic mapping and gene identification in Caenorhabditis briggsae

The nematode Caenorhabditis briggsae serves as an important companion species for Caenorhabditis elegans for comparative studies. Because C. briggsae exhibits androdioecious reproduction and ease of laboratory culture similar to C. elegans, it has long been used for genetic studies in cross-species comparisons of mutant phenotypes to uncover the evolution of gene function. Here, we provide an updated toolkit for C. briggsae genetic experiments, leveraging the resource of recently improved C. briggsae genome sequence assemblies with variant mapping tools and gene identification methods. We identify and validate a set of indel variants between CGC2 (AF16) and two divergent strains, HK104 and VX34. We then use these variants to genetically map 10 previously isolated mutations and identify the impacted genes using high-throughput sequencing. We combine these new genes with others curated from the literature into an updated map with 73 genes, providing an enriched resource for C. briggsae genetic studies.

genetics↗

bioRxiv2026

Characterization of artificial riboswitches for Coxsackievirus B3 detection using machine learning

With the increase of recycled water to offset water demand, the potential possibility to spread contagious RNA viruses, such as Coxsackievirus B3, increases. However, detection of viral particles remains challenging because of low viral concentrations in wastewater and high mutation rates of the RNA virus. Robust monitoring is needed with low cost and low infrastructure technologies to increase accessibility of monitoring technologies worldwide. Novel viral detection methods have been developed, based on synthetic riboswitches that bind to the target virus and trigger a reporter gene, thus amplifying the detection signals. Such monitoring technologies can leverage machine learning to optimize the candidate nucleic acid sequences used for detection. To support the design of effective riboswitches, we present a machine learning model for classifying riboswitch performance, integrating RNA sequence data with secondary structural features based on free energy calculations and parameters that represent single strandedness. This model uses a sparsely gated Mixture of Experts (MoE) architecture to route sequence and thermodynamic features to specialized experts, achieving strong generalization performance across cross-validation and held-out testing. When evaluated against baseline Decision Tree, Random Forest, Gaussian Naive Bayes, and Dense Neural Network classifiers, the MoE model demonstrated near-zero classification errors. Furthermore, post-hoc feature importance and k-mer analyzes reveal that near-perfect predictive performance in silico is strongly driven by sequence constructs in addition to generalizable folding mechanics. An ablation study of numerical feature and sequence inputs showed that while the Dense Neural Network also achieved high accuracy across all ablation conditions, the MoE architecture was retained as the primary model because its specialized subnetworks do not require all model parameters to be activated offering a potential computational advantage.

bioinformatics↗

bioRxiv2026

Targeted depletion of CD38+ autoreactive T cells prevents type 1 diabetes

Type 1 diabetes (T1D) is caused by T cell-mediated autoimmune destruction of insulin-producing islet {beta}-cells. Treatment with T-cell depleting therapies delays the progression of stage 2 and 3 T1D, but these agents exert broad immunosuppressive effects on T cell populations, including T regulatory cells (Tregs), which are key in promoting immune tolerance. We evaluated non-obese diabetic (NOD) mice and recently diagnosed T1D patients and identified CD38 as a marker for pathogenic T cell populations. Using adoptive T-cell transfer in Recombination Activating Gene 1 knockout NOD mice and in a humanized mouse model of autoimmune diabetes, we demonstrated that CD38-expressing autoreactive T cells drive diabetes pathogenesis. Furthermore, we found that selective depletion of CD38+ cells, using an anti-CD38 monoclonal antibody (mAb), prevents insulitis and diabetes onset without depleting CD4+CD25+ Tregs. Administration of anti-CD38 mAb did not adversely affect islet function and may selectively eliminate immunogenic senescent islet {beta}-cells. These results support the strategy of selectively depleting diabetogenic T cells using an anti-CD38 mAb to treat T1D and restore immune tolerance. Therefore, transient depletion of autoreactive T cells using anti-CD38 mAb may provide a novel strategy to prevent or abrogate {beta}-cell autoimmunity in T1D. One sentence summaryPathogenic autoreactive are characterized by CD38 overexpression, and their selective depletion with anti-CD38 monoclonal antibody prevents autoimmune diabetes.

immunology↗

bioRxiv2026

Enhanced production of nitrogenase components in Nicotiana benthamiana through co-expression with Bacterioferritin A

O_LIEngineering nitrogen fixing crops requires not only transferring the nitrogenase structural genes, but also the accessory genes to synthesize its iron-sulphur cofactors. Scaffold protein NifU is a critical element in this system as the starting point of nitrogenase cofactor assembly. NifU has been successfully produced in plants, however, its optimal production required high levels of iron in the medium. This is likely due to a faulty connection with the endogenous iron trafficking network C_LIO_LITo identify specific elements targeting iron to NifU, pull-down assays were performed to identify showing bacterioferritin A (BfrA) as a likely candidate. Co-immunopurification, mutant characterization, iron transfer assays, and co-expression in Nicotiana benthamiana assays were carried out. C_LIO_LIBfrA transfers iron to NifU through protein-protein interactions. When these two proteins were co-expressed in N. benthamiana leaves, there was an increase in NifU production. In turn, it led to doubling NifH synthesis, a nitrogenase structural protein that is also required for the synthesis of the more complex nitrogenase cofactors. C_LIO_LIOur results provide a new element towards engineering nitrogen-fixing crops. They also underscore the importance of transferring the metal delivery systems when expressing metalloproteins in heterologous systems. C_LI

Plant Biology↗

bioRxiv2026

Astrocyte immunosuppressive activity in glioblastoma depends on ZEB1 and is counteracted by CXCL14

Glioblastomas are incurable and lethal brain cancers. Immunotherapies offer new and promising treatment options for glioblastoma patients, but the highly immunosuppressive nature of these cancers presents a challenging clinical obstacle. Glioblastoma immune evasion is driven by cell-cell interactions in the tumor microenvironment and recent studies have identified astrocytes as important contributors to immune silencing [1, 2]. Cell plasticity is a key feature of reactive astrocytes that drives heterogeneous, pro- or anti-inflammatory states [3], but the molecular regulators of astrocyte-immune interactions remain incompletely understood. Here, we investigate whether cell plasticity of glioblastoma-associated astrocytes promotes or opposes tumor progression and show that loss of astrocyte plasticity results in T-cell recruitment and immune activation. We evaluate how astrocytic cell plasticity contributes to immune functions in the glioblastoma microenvironment using single cell sequencing from preclinical models, in vivo genetic perturbations and in vitro mouse and human experimental systems. We show that astrocytes surrounding glioblastoma express the stem cell-associated transcription factor, ZEB1, and that conditional-inducible astrocytic deletion of Zeb1 remarkably reduces glioblastoma growth and extends survival. Increased recruitment and activation of T cells in astrocytic Zeb1-deficient mouse models is linked to increased expression of the immunoattractant cytokine CXCL14, and viral delivery of CXCL14 in experimental glioblastoma models increases survival. Our data support that CXCL14 is a candidate therapeutic target for reprogramming the tumor microenvironment that can restrict and reduce glioblastoma growth and progression.

cancer biology↗

bioRxiv2026

Donor-derived CD8+CD122+ Tregs generated in mixed donor chimeric NOD mice delete autoreactive T cells

The establishment of mixed hematopoietic chimerism is a promising way to induce immune tolerance for islet replacement therapy and to treat the underlying autoimmunity in type 1 diabetes (T1D). Mixed chimerism not only promotes effective thymic negative selection of autoreactive cells but also restores regulatory T cell (Treg) function and peripheral tolerance. In the current study, we determined that a novel class of donor-derived CD8+CD44+CD122+ Tregs (d-CD8+CD122+ Tregs) plays a crucial role in controlling autoimmunity in non-obese diabetic (NOD) mice with induced mixed chimerism. Using adoptive T cell transfer experiments, we showed that d-CD8+CD122+ Tregs abrogate autoimmunity by selectively depleting the exogenously injected diabetogenic T cells in Recombination-Activating Gene deficient NOD mice. These d-CD8+CD122+ Tregs from NOD chimeras show upregulation of Helios, Programmed cell death protein 1, perforin, granzyme-B, CD39, Folate receptor 4, and downregulation of proinflammatory markers like Scart1 and Scart2. Using in vitro assays, we show that d-CD8+CD122+ Tregs respond specifically to a Complementarity-Determining Region-3 peptide sequence derived from T cell receptors of islet antigen-specific autoreactive T cells. Similarly, we found that individuals with T1D have a deficiency in CD8+CD122+ Tregs, suggesting a potential loss of regulatory function accompanies disease onset. Revitalizing CD8+CD122+ Tregs may offer a new therapeutic strategy of restoring immune tolerance in autoimmune diabetes.

immunology↗

bioRxiv2025

Genetic differentiation in Anopheles stephensi from India and Ethiopia: insights from mitochondrial genome analysis

Anopheles stephensi is a primary malaria vector, particularly in urban areas of South Asia and the Middle East. Its recent spread into Africa has raised significant interest in understanding its genetic structure and evolutionary history. This study presents a comprehensive analysis of 98 mitochondrial genomes of An. stephensi from India, Pakistan, and Ethiopia, providing critical insights into the species genetic diversity patterns. High genetic diversity was observed among Indian samples, with two distinct genetic ancestries identified. While one ancestry was more prevalent in specific geographical regions, both lineages were found across all study sites, suggesting the co-existence of multiple lineages within these areas. Further analysis revealed significant genetic differentiation between Indian and Ethiopian populations, with limited overlap in shared mutations. Although some Ethiopian samples showed genetic relatedness to the SDA500 strain from Pakistan (used in genome sequencing by the Broad Institute), the majority of Ethiopian samples showed distinct genetic ancestry. The distinctiveness of Ethiopian populations, compared to other countries outside of Africa, was also reflected in the COI datasets analyzed in this study. However, further expanding the mitogenome dataset to include additional wild samples from regions such as Pakistan, Iran, Saudi Arabia, Sri Lanka and other African countries will provide a more comprehensive understanding of An. stephensis invasion history. Overall, the findings of this study highlight the significant genetic differentiation between Ethiopian and Indian An. stephensi populations, and existence of multiple lineages in Ethiopia indicating multiple independent introductions from different countries.

zoology↗

bioRxiv2025

Reinforced CRISPR interference enables reliable multiplex gene repression in phylogenetically distant bacteria

Genetic screens are essential for uncovering novel molecular mechanisms and identifying the functions of hypothetical proteins. CRISPR interference (CRISPRi) is a powerful, programmable, and sequence-specific gene repression technology that can be used for high-throughput screening and targeted gene repression. Despite its ease of use, the initial development of CRISPRi systems is labor-intensive in many non-model organisms. Our goal is to simplify this by establishing a host-agnostic CRISPRi platform that utilizes the serine recombinase-assisted genome engineering (SAGE) system. This system integrates CRISPRi machinery directly into the bacterial chromosome, overcoming the limitations of plasmid-based systems and enabling wide sharing across diverse bacteria. We demonstrate the design and optimization of multiplexed CRISPRi to repress multiple genes simultaneously in phylogenetically distant bacteria. We use a Francisella novicida-derived Cas12a system that processes multiple distinct CRISPR RNAs, each targeting a unique gene sequence, from a single transcript. This allows easy multi-gene repression. By reinforcing gene repression with multiple guides targeting a single gene, we achieve robust genetic perturbations without the need to pre-screen the efficacy of guide RNAs. Using this toolkit, we perturb multiple combinations of growth and visual phenotypes in Pseudomonas fluorescens and demonstrate simultaneous repression of multiple fluorescent proteins to near background levels in bacteria from various other genera. While the tools are directly portable to all SAGE-compatible microbes, we illustrate the utility of SAGE by optimizing CRISPRi performance in Rhodococcus jostii through a combinatorial screen of Cas protein and CRISPR array expression variants. The efficient integration of CRISPRi machinery via the SAGE system paves the way for versatile genetic screening, enabling profound insights into gene functions both in laboratory conditions and relevant naturalistic scenarios.

microbiology↗

bioRxiv2024

Whole mitochondrial genome analysis of Aedes aegypti reveal association with Wolbachia infection

The mitochondrial genomes (mitogenomes) of nine Aedes aegypti samples from India were analysed along with 34 mitogenomes from global samples retrieved from GenBank. The mitogenome size of Indian samples ranged from 15,730 bp to 16,374 bp. A total of 199 genetic variants were identified among Indian samples, with the majority (90%) occurring in protein-coding genes, followed by rRNA and tRNA genes. Phylogenetic analysis of the 43 genomes revealed two major clades. The similar clustering pattern was observed in the traditional mitochondrial markers for which extensive global data is available, indicating that individual mitochondrial markers of Ae. aegypti share the common genealogy as reflected by the complete mitogenome. In addition to exploring genetic diversity, we investigated the relationship of these two mitochondrial clades with Wolbachia infection. Our analysis revealed that Wolbachia-infected samples were predominantly located within one of the mitochondrial clades, suggesting a potential association between specific mitochondrial lineage and Wolbachia infection. This analysis demonstrates the extent of genetic diversity in Ae. aegypti mitogenome and highlights how this diversity is associated with Wolbachia infection, a maternally inherited endosymbiont. These findings have implications for the effectiveness of Wolbachia-based mosquito control strategies.

genomics↗

bioRxiv2024

Genetic diversity in the IIS6 domain of Voltage Gated Sodium Channel (VGSC) gene among Aedes aegypti populations from different geographical regions in India

This study provides critical insights into the genetic diversity of the IIS6 domain of the VGSC gene in Aedes aegypti populations across various regions in India, focusing on two mutations: S989P and V1016G. Samples were collected from seven different cities across the country, including Dibrugarh, Kolkata, Berhampur, Bhopal, Bengaluru, Ghaziabad, and Aurangabad. The IIS6 domain was amplified and sequenced, revealing that the V1016G mutation was found at a higher frequency compared to the S989P mutation. The S989P mutation was most prevalent in Berhampur, followed by Bengaluru, while V1016G mutation showed high frequencies in Dibrugarh, followed by Berhampur. Additionally, the study identified intron polymorphisms within the VGSC gene, with the type A intron being relatively rare. However, the type A intron was observed in samples harbouring both mutant and wild alleles for both mutations. The regional variation in the frequencies of these mutations indicates complex evolutionary dynamics potentially influenced by local environmental factors and insecticide application practices. Interestingly, the high frequency of these alleles also correlated with the genetic structure of the mosquito populations, suggesting that gene flow might be playing a role in spreading these mutations. Regular monitoring of these mutations could serve as important indicators in assessing the status of resistance to pyrethroids and guide nationwide mosquito control efforts. This research underscores the necessity for localized vector control strategies and continuous genetic surveillance to manage insecticide resistance effectively.

genetics↗

bioRxiv2024

Genome-wide variant analysis reveals divergent genetic signatures in Aedes aegypti and its morphological variant Aedes aegypti var. luciensis

In this study, we analysed the genetic diversity between the two morphotypes of Aedes aegypti by identifying and characterizing genomic variants from low-coverage resequencing data. Four samples from each morphotype were sequenced, and high-quality variants were identified. Variants from the four samples of each morphotype were combined, considering only those present in all samples (missing variants were excluded). This resulted in 7,181 variants in the normal type and 4,513 in the variant type, with only 1,180 shared variants identified between the two morphotypes. Most variants in both types were found in non-coding regions. Chromosomal distribution showed comparable variant frequencies between morphotypes, with similar transition/transversion ratios. The neighbor-joining tree indicated distinct genetic clusters for each morphotype, likely driven by different demographic histories. We have not obtained much data on variations in the coding regions, probably due to low sequencing coverage. However, the significant genetic differentiation between the two morphotypes indicates important evolutionary processes at play. Understanding these variations is crucial from an epidemiological perspective, as they may lead to differences in vector competence for pathogens, potentially affecting transmission dynamics and disease risk.

genomics↗

bioRxiv2024

All-Diamond Boron-Doped Microelectrodes for Neurochemical Sensing with Fast-Scan Cyclic Voltammetry

Neurochemical sensing with implantable devices has gained remarkable attention over the last few decades. A promising area of this research is the progress of novel electrodes as electrochemical tools for neurotransmitter detection in the brain. The boron-doped diamond (BDD) electrode is one such candidate that previously has been reported for its excellent electrochemical properties, including a wide working potential, superior chemical inertness and mechanical stability, good biocompatibility and resistance to fouling. Meanwhile, limited research has been conducted on the BDD as a microelectrode for neurochemical detection. Our team has developed a freestanding, all diamond microelectrode consisting of a boron-doped polycrystalline diamond core, encapsulated in an insulating polycrystalline diamond shell, with a cleaved planar tip for electrochemical sensing. This all-diamond electrode is advantageous due to its - (1) batch fabrication using wafer technology that eliminates traditional hand fabrication errors and inconsistencies, (2) absence of metal-based wires, or foundations, to improve biocompatibility and flexibility, and (3) sp3 carbon surface with resistance to biofouling, i.e. adsorption of proteins or unwanted molecules at the electrode surface in a biological environment that impedes overall electrode performance. Here, we provide findings on further in vitro testing and development of the freestanding boron-doped diamond microelectrode (BDDME) for neurotransmitter detection using fast scan cyclic voltammetry (FSCV). In this report, we elaborate on - 1) an updated fabrication scheme and work flow to generate all diamond BDDMEs, 2) slow scan cyclic voltammetry measurements of reference and target analytes to understand basic electrochemical behavior of the electrode, and 3) FSCV characterization of common neurotransmitters, and overall favorability of serotonin (5-HT) detection. The BDDME showed a 2-fold increased FSCV response for 5-HT in comparison to dopamine (DA), with a limit of detection of 0.16 {micro}M for 5-HT and 0.26 {micro}M for DA. These results are intended to expand on the development of the next generation BDDME and guide future in vivo experiments, adding to the growing body of literature on implantable devices for neurochemical sensing.

neuroscience↗

bioRxiv2024

Single cell resolution analysis of multi-tissue derived human iNKT cells reveals novel transcriptional paradigms

Invariant natural killer T (iNKT) cells are evolutionarily conserved innate lymphocytes important for host defense against pathogens. Further, they are increasingly recognized to play a role in tumor immune surveillance and in protection against graft versus host disease, and they are of particular importance as a universal donor for cellular therapies. Therefore, a thorough understanding of the biology of iNKT cells is critical. Murine studies have revealed the existence of transcriptionally and functionally distinct subsets, similar to T helper cell subsets. However, a comprehensive study of human iNKT cell heterogeneity is lacking. Herein, we define the transcriptomic heterogeneity of human iNKT cells derived from multiple immunologically relevant tissues, including peripheral blood, cord blood, bone marrow, and thymus, using single cell RNA-sequencing. We describe human iNKT cells with a naive/precursor transcriptional pattern, a Th2-like signature, and Th1/17/NK-like gene expression. This combined Th1/17 pattern of gene expression differs from previously described murine iNKT subsets in which Th1- and Th17- like iNKT cells are distinct populations. We also describe transcription factors regulating human iNKT cells with distinct gene expression patterns not previously described in mice. Further, we demonstrate a novel T effector memory RA+ (TEMRA)-like pattern of expression in some human iNKT cells. Additionally, we provide an in-depth transcriptional analysis of human CD8+ iNKT cells, revealing cells with two distinct expression patterns--one consistent with naive/precursor cells and one consistent with Th1/17/NK-like cells. Collectively, our data provide critical insights into the transcriptional heterogeneity of human iNKT cells, providing a platform to facilitate future functional studies and to inform the development of iNKT-based cellular therapies.

immunology↗

bioRxiv2023

In-silico identification, characterization, and expression analysis of RNA recognition motif (RRM) containing RNA binding proteins in Aedes aegypti

BackgroundRNA binding proteins (RBPs) are the proteins that bind RNAs and regulate their functioning. RBPs in mosquitoes are gaining attention due to their ability to bind flaviviruses and regulate their replication and transmission. Despite their relevance, RBPs in mosquitoes have not been explored much. In this study, we screened the whole genome of Aedes aegypti, the primary vector of several pathogenic viruses, and identified the proteins containing RNA recognition motif (RRM), the most abundant protein domain in eukaryotes. ResultsUsing several in-silico strategies, a total of 135 RRM containing RBPs were identified in Ae. aegypti. The proteins were characterized based on their available annotations and the sequence similarity with the Drosophila melanogaster. Ae. aegypti RRM containing RBPs included serine/arginine-rich (SR) proteins, polyadenylate binding proteins (PABP), heteronuclear ribonucleoproteins (hnRNP), small nuclear ribonucleoproteins (snRNP), splicing factors, eukaryotic initiation factors, transformers, nucleolysins, etc. Phylogenetic analysis revealed that the proteins and the domain organisation is conserved among Ae. aegypti, Bombyx mori and Drosophila melanogaster. However, the gene length and the intron-exon organisation varied across the insect species. Expression analysis of the genes encoding RBPs using publicly available RNA sequencing data for different developmental time points of the mosquito life cycle starting from the ovary and eggs up to the adults revealed stage-specific expression with several genes preferentially expressed in early embryonic stages and blood-fed female ovary. ConclusionsThis is the first database for the Ae. aegypti RBPs that can serve as the reference base for future investigations. The stage-specific genes can be further explored to determine their role in mosquito growth and development with a focus to develop novel mosquito control strategies.

bioinformatics↗

bioRxiv2023

Identification of Therapeutic Leads from Ficus hispida Fruit Phytochemicals against Prostate Cancer Using Pharmacoinformatic and Molecular Dynamics Simulation Approach

Prostate cancer is one of the leading causes of death and the most common cancer type in men. In this study, potential leads from the phytochemicals of Ficus hispida fruit were screened using in silico tools against androgen receptor (AR), a known target for prostate cancer. PASS online and ADMET tools were used to screen specific phytochemicals that are relevant to prostate cancer treatment and have drug-like properties. Of 13, a total of 10 phytochemicals passed PASS online and ADMET screening. Next, a total of three phytochemicals, including nodakenetin (CID: 26305), isowigtheone hydrate (CID: 66728267), and 7-hydroxycoumarin (CID: 5281426) were selected based on their docking scores (-9.946 to -7.653 kcal/mol) and relevance to selective bioactivity. The MD simulation further confirmed the binding stability of these three phytochemicals with their target AR protein and determined that the main amino acid residues mainly responsible for this stability including RMSD, RMSF, and post simulation binding free energies. These findings suggest that these three phytochemicals of Ficus hispida fruit can further be developed as prospective therapeutics against prostate cancer.

bioinformatics↗

bioRxiv2023

PITAR, a DNA damage-inducible Cancer/Testis long noncoding RNA, inactivates p53 by binding and stabilizing TRIM28 mRNA

In tumors with WT p53, alternate mechanisms of p53 inactivation are reported. Here, we have identified a long noncoding RNA, PITAR (p53 Inactivating TRIM28 associated RNA), as an inhibitor of p53. PITAR is an oncogenic Cancer/testis lncRNA and is highly expressed in glioblastoma (GBM) and glioma stem-like cells (GSC). We establish that TRIM28 mRNA, which encodes a p53-specific E3 ubiquitin ligase, is a direct target of PITAR. PITAR interaction with TRIM28 RNA stabilized TRIM28 mRNA, which resulted in increased TRIM28 protein levels and reduced p53 steady-state levels due to enhanced p53 ubiquitination. DNA damage activated PITAR, in addition to p53, in a p53-independent manner, thus creating an incoherent feedforward loop to inhibit the DNA damage response by p53. While PITAR silencing inhibited the growth of WT p53 containing GSCs in vitro and reduced glioma tumor growth in vivo, its overexpression enhanced the tumor growth in a TRIM28-dependent manner and promoted resistance to Temozolomide. Thus, we establish an alternate way of p53 inactivation by PITAR, which maintains low p53 levels in normal cells and attenuates the DNA damage response by p53. Finally, we propose PITAR as a potential GBM therapeutic target.

cancer biology↗

bioRxiv2023

Selective targeting of α4β7/MAdCAM-1 axis suppresses fibrosis progression in chronic liver disease

Integrin 4{beta}7+ T cells perpetuate tissue injury in chronic inflammatory diseases, yet their role in hepatic fibrosis progression remains poorly understood. Here we report increased accumulation of 4{beta}7+ T cells in the liver of people with cirrhosis relative to disease controls. Similarly, hepatic fibrosis in the established mouse model of CCl4-induced liver fibrosis was associated with enrichment of intrahepatic 4{beta}7+ CD4 and CD8 T cells. Monoclonal antibody (mAb)-mediated blockade of 4{beta}7 or its ligand mucosal addressin cell adhesion molecule (MAdCAM)-1 attenuated hepatic inflammation and prevented fibrosis progression in CCl4 treated mice. Improvement in liver fibrosis was associated with a significant decrease in the infiltration of 4{beta}7+ CD4 and CD8 T cells suggesting that 4{beta}7/MAdCAM-1 axis regulates both CD4 and CD8 T cell recruitment to the fibrotic liver, and 4{beta}7+ T cells promote hepatic fibrosis progression. Analysis of hepatic 4{beta}7+ and 4{beta}7-CD4 T cells revealed that 4{beta}7+ CD4 T cells enriched for markers of activation and proliferation demonstrating an effector phenotype. Notably, blockade of 4{beta}7 or MAdCAM-1 did not affect the recruitment of Foxp3+ regulatory T cells, demonstrating the specificity of 4{beta}7/MAdCAM-1 axis in regulating effector T cell recruitment to the liver. The findings suggest that 4{beta}7+ T cells play a critical role in promoting hepatic fibrosis progression, and mAb-mediated blockade of 4{beta}7 or MAdCAM-1 represents a promising therapeutic strategy for slowing hepatic fibrosis progression in chronic liver diseases.

immunology↗

bioRxiv2022

A natural language fMRI dataset for voxelwise encoding models

Speech comprehension is a complex process that draws on humans abilities to extract lexical information, parse syntax, and form semantic understanding. These sub-processes have traditionally been studied using separate neuroimaging experiments that attempt to isolate specific effects of interest. More recently it has become possible to study all stages of language comprehension in a single neuroimaging experiment using narrative natural language stimuli. The resulting data are richly varied at every level, enabling analyses that can probe everything from spectral representations to high-level representations of semantic meaning. We provide a dataset containing BOLD fMRI responses recorded while 8 subjects each listened to 27 complete, natural, narrative stories (~6 hours). This dataset includes pre-processed and raw MRIs, as well as hand-constructed 3D cortical surfaces for each participant. To address the challenges of analyzing naturalistic data, this dataset is accompanied by a python library containing basic code for creating voxelwise encoding models. Altogether, this dataset provides a large and novel resource for understanding speech and language processing in the human brain.

neuroscience↗