Biology subjects

Rizvi, A. H.

Publications and source records attributed to Rizvi, A. H..

4 recordsLinked to original sources

bioRxiv2026

Opposing Experiences Shape Parvalbumin Interneuron Plasticity through Distinct Molecular Programs

Life experiences profoundly influence brain function, yet how opposing experiences are encoded remains unclear. Here, we show that opposing experiences, chronic stress (CS) and voluntary running (VR), induce largely distinct molecular programs rather than a simple bidirectional modulation of a shared molecular program in parvalbumin interneurons (PVIs). PVI-specific translational profiling across frontal cortex and dorsal and ventral hippocampus reveals that experience-dependent gene expression is organized into brain region-specific architectures, which are further structured into distinct co-expression modules. We uncovered CS-induced upregulation of histone acetyltransferase KAT6A and H3K23 acetylation specifically in PVIs of the frontal cortex accompanied by altered genome-wide redistribution of acetylated H3K23, including genes implicated in neuropsychiatric disorders. Targeted elevation of KAT6A in PVIs recapitulates CS-induced morphological and behavioral alterations. Together, our findings reveal that opposing experiences engage distinct and region-specific molecular programs in PVIs and identify a stress-responsive epigenetic pathway underlying inhibitory circuit plasticity.

neuroscience↗

bioRxiv2025

Enhancer Dynamics and Spatial Organization Drive Anatomically Restricted Cellular States in the Human Spinal Cord

Here, we report the spatial organization of RNA transcription and associated enhancer dynamics in the human spinal cord at single-cell and single-molecule resolution. We expand traditional multiomic measurements to reveal epigenetically poised and bivalent active transcriptional enhancer states that define cell type specification. Simultaneous detection of chromatin accessibility and histone modifications in spinal cord nuclei reveals previously unobserved cell-type specific cryptic enhancer activity, in which transcriptional activation is uncoupled from chromatin accessibility. Such cryptic enhancers define both stable cell type identity and transitions between cells undergoing differentiation. We also define glial cell gene regulatory networks that reorganize along the rostrocaudal axis, revealing anatomical differences in gene regulation. Finally, we identify the spatial organization of cells into distinct cellular organizations and address the functional significance of this observation in the context of paracrine signaling. We conclude that cellular diversity is best captured through the lens of enhancer state and intercellular interactions that drive transitions in cellular state. This study provides fundamental insights into the cellular organization of the healthy human spinal cord.

neuroscience↗

bioRxiv2019

Acquisition of cross-resistance to bedaquiline and clofazimine following treatment for tuberculosis in Pakistan

We report on the first six cases of acquired resistance to bedaquiline in Pakistan. Seventy sequential culture isolates from 30 drug-resistant tuberculosis patients on bedaquiline-containing regimen were tested for minimum inhibitory concentration (MIC) and whole genome sequencing. An increase in MICs associated with cross-resistance to clofazimine and appearance of specific mutations was documented in six cases. The study underlines that appropriate monitoring is mandatory for the introduction of new drugs.

microbiology↗

bioRxiv2018

CALCIUM-INDUCED DIFFERENTIATION IN NORMAL HUMAN COLONOID CULTURES: Cell-cell / cell-matrix adhesion, barrier formation and tissue integrity

Colonoid cultures were established from histologically-normal human colon tissue and maintained in a low-calcium (0.25 mM) medium or in medium supplemented with an amount of calcium (1.5 - 3.0 mM) that was shown in a previous study to induce differentiation in colonoids derived from large adenomas. Calcium alone was compared to Aquamin, a multi-mineral natural product that contains magnesium and detectable levels of 72 additional trace elements in addition to calcium. Unlike the previously-studied tumor-derived colonoids (which remained un-differentiated in the absence of calcium-supplementation), normal tissue colonoids underwent differentiation as indicated by gross and microscopic appearance, a low proliferative index and high-level expression of cytokeratin 20 (CK20) in the absence of intervention. Only modest additional changes were seen in these parameters with either calcium alone or Aquamin (providing up to 3.0 mM calcium). In spite of this, proteomic analysis and immunohistochemistry revealed that both interventions induced strong up-regulation of proteins that promote cell-cell and cell-matrix adhesive functions, barrier formation and tissue integrity. Transmission electron microscopy revealed an increase in desmosomes in response to intervention. These findings demonstrate that histologically normal human colonoids can undergo differentiation in the presence of a low ambient calcium concentration. However, higher calcium levels can induce elaboration of proteins that promote cell-cell and cell-matrix adhesion. These changes could lead to improved barrier function and improved colon tissue health.

molecular biology↗