Biology subjects

Rizwan, M.

Publications and source records attributed to Rizwan, M..

5 recordsLinked to original sources

bioRxiv2026

Cornealia: automated collective order analysis reveals density-dependent reorganization of donor corneal endothelium

The corneal endothelium is a non-regenerative monolayer whose health determines transplant success, yet donor tissue is assessed only by single-cell metrics that ignore how the monolayer is organized collectively. A physics-based spring constant K, derived from the radial distribution function of cell positions, captures this collective order but has remained limited to semi-manual studies without physical interpretation. Here we present Cornealia, an automated pipeline for collective-order and intercellular-force analysis. In cultured endothelial cells, collective order declines with passaging and is higher under growth-factor conditions that preserve N-cadherin junctions, differences invisible to cell density and hexagonality. Across 2,177 donor cornea images from two cohorts, collective order, distinct from classical metrics, responds most to mechanical perturbation: corneas with endothelial cell density above 2,400 cells/mm^2 mostly gain order, whereas less dense ones lose it, on one curve shared by both cohorts. Reconstructed intercellular forces track these changes. This switch lies within the minimum donor densities used by eye banks, suggesting a mechanical basis for these clinical thresholds and establishing collective order as an automatable measure of endothelial quality.

bioinformatics↗

bioRxiv2025

The SMARCA5-DMRT1 Pioneer Complex Establishes Epigenetic Priming to Direct Male Germline Development

The establishment of cell type-specific chromatin landscapes is essential for cellular identity, but how these landscapes are generated remains poorly understood. Here, we demonstrate that the chromatin remodeler SMARCA5 establishes epigenetic priming that is required for retinoic acid (RA)-induced differentiation in the male germline. Germ cell-specific deletion of Smarca5 results in a complete loss of differentiating spermatogonia, phenocopying vitamin A-deficient mice that lack RA signaling. During the perinatal transition from prospermatogonia to undifferentiated spermatogonia, SMARCA5 is recruited to binding sites of the pioneer transcription factor DMRT1, which are located at distal putative enhancers and promoters of germline genes. The SMARCA5-DMRT1 pioneer complex establishes chromatin accessibility at these loci, generating poised enhancers and promoters that serve as RA receptor (RAR)-binding sites. Thus, SMARCA5 licenses transcriptional responses to RA that enable spermatogenic differentiation. Our findings uncover a mechanism linking pioneer factor activity to external signal responsiveness. HighlightsSMARCA5 is required for spermatogonial differentiation The SMARCA5-DMRT1 pioneer complex establishes epigenetic priming for differentiation SMARCA5 remodels inaccessible DMRT1-binding sites to an accessible state SMARCA5 shapes chromatin states that enable retinoic acid responsiveness

developmental biology↗

bioRxiv2024

Genomic characterization of plasmids harboring blaNDM-1,-5,-7 carbapenemase alleles in clinical Klebsiella pneumoniae in Pakistan

Klebsiella pneumoniae is notorious for causing healthcare-associated infections, which become more complicated by the acquisition of blaNDM genes via mobile genetic elements. Although Pakistan is a well-established hot spot of blaNDM-positive K. pneumoniae, detailed molecular descriptions of blaNDM-carrying plasmids are scarce. Seven K. pneumoniae isolates harboring blaNDM were recovered from clinical sample sources during a six-month period and tested for antimicrobial susceptibility. A long-read approach was used for whole genome sequencing to obtain circularized plasmids and chromosomes for typing, annotation, and comparative analysis. The isolates were susceptible to colistin and tigecycline only among the tested antibiotics. We identified five STs: ST11, ST16, ST716, ST464, and ST2856. Notably, three strains possessed the hypervirulent capsule KL2, while five were classified as O locus type O2a. Evidence of genetic diversity was further highlighted by the presence of four IncC plasmids harboring blaNDM-1, two IncX3 plasmids harboring blaNDM-5, and a single hybrid IncFIB/IncHI1B plasmid harboring blaNDM-7. These plasmids also carried additional ARGs conferring resistance to aminoglycosides, cephalosporins, and fluoroquinolones. We identified the plasmidome of the K. pneumoniae isolates and characterized the NDM-carrying plasmids. Genetic analysis confirmed the presence of blaNDM-1 and blaNDM-5 on broad host range plasmids and blaNDM-7 in a previously unreported hybrid plasmid backbone. We emphasized the critical role of plasmids in spreading blaNDM in the clinical setting in Pakistan. Hence, we stressed the urgent need for enhanced surveillance, not least in LMICs, infection control measures, and adherence to the AWaRe guidelines in antibiotics use.

microbiology↗

bioRxiv2022

Viscoelastic Notch Signaling Hydrogel Induces Liver Bile Duct Organoid Growth and Morphogenesis

Cholangiocyte organoids can be used to model liver biliary disease; however, both a defined matrix in which to emulate cholangiocyte self-assembly and the mechano-transduction pathways involved therein remain elusive. We designed a series of defined viscoelastic hyaluronan hydrogels in which to culture primary cholangiocytes and found that by mimicking the stress relaxation rate of liver tissue, we could induce cholangiocyte organoid growth and significantly increase expression of Yes-associated protein (YAP) target genes. Strikingly, inhibition of matrix metalloproteinases (MMPs) did not significantly affect organoid growth in 3D culture, suggesting that mechanical remodeling of the viscoelastic microenvironment - and not MMP-mediated degradation - is key to cholangiocyte organoid growth. By immobilizing jagged1 to the hyaluronan, stress relaxing hydrogel, self-assembled bile duct structures formed in organoid culture, indicating the synergistic effects of Notch signaling and viscoelasticity. By uncovering critical roles of hydrogel viscoelasticity, YAP signaling and Notch activation, we controlled cholangiocyte organogenesis, thereby paving the way for their use in disease modeling and/or transplantation.

bioengineering↗

bioRxiv2021

Leptin regulates glucose homeostasis via the canonical WNT pathway.

Leptin is a body weight regulatory hormone, but it is arguably even more potent at regulating blood glucose levels. To further our understanding of the molecular mechanisms by which leptin controls glucose homeostasis, we have used transgenic zebrafish models and conditional deletion of beta catenin in the mediobasal hypothalamus of adult mice to show that Wnt signalling in the brain mediates glucoregulatory effects of leptin. In zebrafish, under normal feeding conditions, leptin regulates glucose homeostasis but not adipostasis. In times of nutrient excess, we found that leptin also regulates body weight and size in this species. Using a Wnt signalling reporter fish, we show that leptin directly activates the canonical Wnt pathway in vivo. Pharmacological inhibition of this pathway prevented the leptin-induced improvement in glucose tolerance. In adult mice, conditional deletion of the key Wnt effector molecule, {beta}-catenin, in the mediobasal hypothalamus of male mice confirmed the essential role of the Wnt pathway in mediating leptin action and the neuroendocrine regulation of glucose homeostasis. Adult-onset {beta}-catenin deletion in the mediobasal hypothalamus led to glucose intolerance, exacerbation of caloric intake and body weight gain under high fat diet, as well as resistance to exogenous leptin.

physiology↗