Biology subjects

Mohsin, A.

Publications and source records attributed to Mohsin, A..

9 recordsLinked to original sources

bioRxiv2026

Pleiotropic antimalarial activities and immunomodulation exhibited by Himalayan Buransh (Rhododendron arboreum) in human and rodent malaria models

Emerging drug resistance against the malaria parasite is worrisome and necessitates the development of novel antimalarials. Himalayan Buransh (Rhododendron arboreum) is a well-known medicinal plant found in the northern states of India. In this study, we observed the pleiotropic antimalarial activities and immunomodulation exhibited by the aqueous extract of Buransh flower (AEBF). AEBF demonstrated significant IC50 values (16-29 {micro}g/ml) against the asexual stages of various P. falciparum strains (3D7, Dd2-chloroquine-resistant and C580Y-artemisinin resistant). The oral administration of AEBF (200 mg/kg) in mice, suppressed [~]80% P. berghei parasitemia, improved mean survival time (MST-23.5 days) and prevented splenomegaly. Notably, the combination of AEBF and artesunate not only cleared primary infection, but also conferred sustained immunity. This immunomodulatory effect, driven by protective IFN-{gamma} resulted in reduced parasitemia during a homologous challenge without the need for further treatment. It is important to highlight the malaria transmission blocking activity of AEBF, resulting in reduced sexual stage male gametocyte exflagellation. Furthermore, the virtual drug screening of selected bioactive constituents from Buransh flower demonstrated potent binding against multiple P. falciparum proteins, suggested a pleiotropic mode of action. Altogether, our results corroborated the first ever evidence of the multistage antimalarial potential of Buransh flower, supported by in vitro cell studies, in vivo rodent malaria model and in silico docking analyses. Based on our studys findings and the traditional use of Buransh juice as a medicinal beverage in Uttarakhand, India, we propose exploring it as an adjunct therapy for drug-resistant malaria, subject to further clinical validation.

pathology↗

bioRxiv2026

Aging restricts maturation of CXCL13+ T follicular helper cells in human immunity

A decline in specific antibody responses is a hallmark of human aging, yet the differential contributions of B and T lymphocytes and their interactions remain unclear. CXCL13 is a critical chemokine that shapes germinal center organization, but the regulation of human-specific CXCL13+ Tfh cells during aging is not known. Using human tonsil organoids, single-cell RNA sequencing, and CRISPR perturbations, we mapped age-associated changes in T follicular helper (Tfh) cells, the cell type that provides T cell "help" to B cells in germinal centers (GCs). Tonsil organoids from older donors generated weaker influenza-specific antibody responses, which we traced to Tfh cell defects rather than B cells. Single-cell profiling revealed a selective loss of mature CXCL13 GC-Tfh cells accompanied by accumulation of Tfh precursor states. Trajectory analysis showed that aging arrests Tfh cell maturation at the early activated precursor transition, and CRISPR perturbations identified BACH2 and SOX4 as transcriptional regulators of differentiation reduced with age. These findings reveal a human-specific mechanism of immune aging with implications for strategies to restore humoral immunity.

immunology↗

bioRxiv2026

Inter-individual variation of cellular and gene-expression properties of the human striatum

The human brain varies from person to person in ways that shape behaviors and vulnerabilities, yet the cellular and molecular bases for inter-individual variation are largely unknown. Here we describe an analysis of cellular and gene-expression variation in four key structures of the striatum complex - the caudate, putamen, nucleus accumbens, and internal capsule - as well as the prefrontal cortex, from single-nucleus RNA-seq analysis of 3.9 million nuclei from 178 adult brain donors. We found that people with more astrocytes in any one brain region tended to have this property in all brain regions sampled; the same was true of striatal interneurons, microglia, and oligodendrocyte precursor cells (OPCs). OPCs showed attrition with age, declining in numbers by approximately 40% between age 30 and age 80 in both gray matter and white matter regions. We identified thousands of age-associated (but few sex-associated) variations in gene expression; the vast majority of these effects of age were cell-type-specific. Aging most strongly affected gene expression in projection neurons - especially striatal medium spiny neurons (MSNs/SPNs) - and had a much smaller effect on gene expression in interneurons. Individuals ages could be predicted to within about five years based on RNA-expression patterns from any of the striatal cell types. Common genetic variants detectably affected the expression levels of some ten thousand genes; the great majority of these effects were cell-type-specific. These data will provide a foundation for exploring natural inter-individual variation, aging, and tissue-based studies of human brain vulnerabilities.

neuroscience↗

bioRxiv2026

Mesoscale molecular architecture of the human striatum across cell types and lifespan

The human striatum is a central hub for a diverse array of motor, cognitive, and affective behaviors, yet it lacks obvious cytoarchitectural boundaries that define functional territories. Here, we uncover a robust and molecularly defined mesoscale architecture in the human striatum. Using Slide-tags, a scalable single-nucleus spatial transcriptomics technology, we profiled 1.1 million cells across the full span of the anterior striatum of 19 postmortem donors, spatially mapping all striatal populations. Our data uncover a natural subdivision of the striatum into six zones, each defined by molecularly distinct populations of medium spiny neurons, and featuring spatially coordinated neuron-astrocyte signaling. Relative to MSNs in ventral zones, MSNs in dorsal zones exhibit higher expression of genes for synaptic remodeling and plasticity via ephrin and TGF-beta, while the ventral zone is defined by greater expression of semaphorin, protein chaperone, and hedgehog signaling pathways. By imputing zonal identities onto a larger single-nucleus RNA-seq cohort of 131 donors, we find that the dorsal zones exhibit greater age-related transcriptional changes, and that overall, the gene-expression differences that define spatial zonation patterns are attenuated with advancing age. This atlas provides a mesoscale molecular definition of human striatal anatomy, linking cell type identity to functional specialization and aging susceptibility.

neuroscience↗

bioRxiv2025

Cytokine Regulation of Human Antibody Responses to Influenza Vaccines

Studies show that human vaccine responses widely vary. Here, we analyzed data measuring 66 cytokines from 4 different inactivated influenza vaccine (IIV) cohorts over 5 seasons (N=581) and identified a significant correlation between baseline/day 0 serum IL-18 and IFN-{beta} concentrations and the vaccine-specific antibody response on day 28, suggesting these factors may have an adjuvant-like effect. To investigate this further, we tested the impact of 19 cytokines on the development of anti-influenza antibody response when administered together with the IIV vaccine in human tonsil and spleen organoids. We found that Type I IFNs (IFN-{beta} and others), IL-21, IL-12, IL-10, but not IL-18 or IFN-{gamma}, enhanced the antibody response. The live attenuated influenza vaccine (LAIV) induced a stronger antibody response than the inactivated one in organoids. Adding a single cytokine, IFN-{beta}, to IIV stimulation recapitulated most of the live vaccine-specific cytokine activation program. It increased the antibody response of the inactivated vaccine to that of the LAIV. Two other antibody-boosting cytokines, IL-12 and IL-21, were induced by LAIV but not by Type I IFNs, indicating different cytokines can affect different pathways leading to a robust antibody response. We then generated cytokine mRNA lipid nanoparticles (LNPs) to test the effect of cytokines on IIV response in a mouse model of immunization. We found that IL-21-LNPs augmented the quantity and breadth of the antibody responses, while IFN-{beta} LNPs enhanced durability. These findings identified parallel cytokine pathways regulating human vaccine responses and provide a rationale for using cytokines as adjuvants to mimic the effectiveness of live-attenuated vaccines without the risk of viral replication.

immunology↗

bioRxiv2025

A water-based platform test of paired or group social dominance and neural activity in male and female mice

Social hierarchy is an evolutionarily-conserved phenomenon determined by social dominance behavior that has profound influence on health and relevance in neuropsychiatric disorders. Despite this, the neural mechanisms underlying social dominance remain unclear and current behavioral tests are limited. Here, we describe a novel platform test of social dominance where mice compete for space on a small, elevated platform surrounded by cold water and rank is calculated by total time spent on platform. To validate this assay, we conducted tube test followed by platform test in cages of male and female mice. We observed stable rank in both sexes using the platform test and saw notable differences in overall cage hierarchy between tube and platform. Motivated behavior as measured by attempts to get on the platform was reduced over time. Cooperative behavior as measured by shared time on platform was observed across all ranks but predominantly demonstrated by subordinate mice. Corticosterone levels were significantly higher in females but showed no rank-specific differences. Neuronal activity in the prefrontal cortex was not rank-dependent, however activity in the habenula scaled with rank in both sexes and was significantly correlated with dominance in males. We also investigated group social dynamics using the platform test and identified stable hierarchies with more exaggerated dominance compared to paired platform testing. These results introduce the platform test as a novel method for assessing social dominance behavior in male and female mice, which can be used to further our understanding of the neurobiology underlying social hierarchy.

neuroscience↗

bioRxiv2023

BRWD1 orchestrates chromatin topology by converting static to dynamic cohesin complexes

Lymphocyte development consists of sequential and mutually exclusive cell states of proliferative selection and antigen receptor gene recombination1. Transitions between each state require large, coordinated changes in epigenetic landscapes and transcriptional programs2,3. How this occurs remains unclear. Herein, we demonstrate that in small pre-B cells, the lineage and stagespecific epigenetic reader Bromodomain and WD Repeating Containing Protein 1 (BRWD1)2,4 reorders three-dimensional chromatin topology to affect transition between proliferative and gene recombination molecular programs. BRWD1 regulated the switch between poised and active enhancers interacting with promoters and coordinated this with Igk locus contraction. BRWD1 did so by converting chromatin-bound static cohesin to dynamic complexes competent to mediate long-range looping. Remarkably, ATP depletion recapitulated cohesin distributions observed in Brwd1-/- cells. Therefore, in small pre-B cells, cohesin conversion is the main energetic mechanism dictating where dynamic looping occurs in the genome. Our findings provide a new mechanism of cohesin regulation and reveal how cohesin function can be dictated by lineage contextual mechanisms to facilitate specific cell fate transitions.

immunology↗

bioRxiv2020

FiberAI: A Deep Learning model for automated analysis of nascent DNA Fibers

All life forms undergo cell division and are dependent on faithful DNA replication to maintain the stability of their genomes. Both intrinsic and extrinsic factors can stress the replication process and multiple checkpoint mechanisms have evolved to ensure genome stability. Understanding these molecular mechanisms is crucial for preventing and treating genomic instability associated diseases including cancer. DNA replicating fiber fluorography is a powerful technique that directly visualizes the replication process and a cells response to replication stress. Analysis of DNA-fiber microscopy images provides quantitative information about replication fitness. However, a bottleneck for high throughput DNA-fiber studies is that quantitative measurements are laborious when performed manually. Here we introduce FiberAI, which uses state-of-the art deep learning frameworks to detect and quantify DNA-fibers in high throughput microscopy images. FiberAI efficiently detects DNA fibers, achieving a bounding box average precision score of 0.91 and a segmentation average precision score of 0.90. We then use FiberAI to measure the integrity of replication checkpoints. FiberAI is publicly available and allows users to view model predicted selections, add their own manual selections, and easily analyze multiple image sets. Thus, FiberAI can help elucidate DNA replication processes by streamlining DNA-fiber analyses.

bioinformatics↗

bioRxiv2020

In situ humoral selection in human lupus tubulointerstitial inflammation

ABSTRACTIn human lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ expansion of B cells expressing anti-vimentin antibodies (AVAs). The mechanism by which AVAs are selected is unclear. Herein, we demonstrate that AVA somatic hypermutation and selection increase affinity for vimentin. However, enzyme-linked immunosorbent assays (ELISAs) suggested that affinity maturation might be a non-specific consequence of increasing polyreactivity. Subsequent multi-color confocal microscopy studies indicated that while TII AVAs often appeared polyreactive by ELISA, they bound selectively to vimentin fibrils in whole cells or inflamed renal tissue. Using a novel machine learning pipeline (CytoSkaler) to quantify the cellular distribution of antibody staining, we demonstrated that TII AVAs were selected for both enhanced binding and specificity in situ. These data suggest a new approach to assess and define antibody polyreactivity based on quantifying the distribution of binding to native and contextually relevant antigens.Competing Interest StatementThe authors have declared no competing interest.View Full Text

immunology↗