Biology subjects

Ahmed, K. M.

Publications and source records attributed to Ahmed, K. M..

3 recordsLinked to original sources

bioRxiv2025

NOTCH1 Acts as a Tumor Suppressor That Induces Early Differentiation in Head and Neck Cancer

We identified frequent inactivating notch1 mutations in HNSCC over a decade ago, indicating its role as a tumor suppressor--unlike its oncogenic function in leukemias and salivary gland tumors. However, there has been much debate in the literature regarding a possible oncogenic role in HNSCC as well, based on reports that notch1 signaling drives tumor growth and a cancer stem cell phenotype in some HNSCC tumor lines and patient samples. Clarifying whether NOTCH1 occasionally functions as an oncogenic driver in HNSCC is crucial to the prognosis and personalized therapy of patients with either wild-type or mutated NOTCH1. Here we present a systematic and comprehensive investigation unequivocally demonstrating that notch1 signaling functions as a tumor suppressor in HNSCC regardless of mutation or activation status and leads to reduction in frequency of cancer stem cells. We develop a robust gene expression signature of notch1 activation based on experimental data that when applied to patient samples shows notch1 signaling is associated with very early differentiation, an altered tumor microenvironment, and better prognosis-- consistent with a tumor suppressive role. Our work unifies the field by reconciling conflicting data and providing critical insights into the biological and clinical significance of the NOTCH1 pathway in HNSCC.

cancer biology↗

bioRxiv2021

Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2

The mTOR pathway is an essential regulator of cell growth and metabolism. Midbrain dopamine neurons are particularly sensitive to mTOR signaling status as activation or inhibition of mTOR alters their morphology and physiology. mTOR exists in two distinct multiprotein complexes termed mTORC1 and mTORC2. How each of these complexes affect dopamine neuron properties and whether they act together or independently is unknown. Here we investigated this in mice with dopamine neuron-specific deletion of Rptor or Rictor, which encode obligatory components of mTORC1 or mTORC2, respectively. We find that inhibition of mTORC1 strongly and broadly impacts dopamine neuron structure and function causing somatodendritic and axonal hypotrophy, increased intrinsic excitability, decreased dopamine production, and impaired dopamine release. In contrast, inhibition of mTORC2 has more subtle effects, with selective alterations to the output of ventral tegmental area dopamine neurons. As mTOR is involved in several brain disorders caused by dopaminergic dysregulation including Parkinsons disease and addiction, our results have implications for understanding the pathophysiology and potential therapeutic strategies for these diseases.

neuroscience↗

bioRxiv2020

Microbiological water quality of Managed Aquifer Recharge systems in the salinity-prone southwest coastal Bangladesh

Managed aquifer recharge (MAR), a hydro-geological intervention designed to dilute groundwater salinity, pumps pond water treated through a slow sand filter into the underground aquifers. We evaluated the microbiological safety of the resulting MAR water at sites from three districts in southwest coastal Bangladesh. We collected monthly paired pond-MAR water samples from July 2016-June 2017 and enumerated fecal coliforms and E. coli using the IDEXX quanti-tray technique, by the most probable number (MPN) method. We used WHO risk categories for microbiological quality; no risk (<1 MPN), low risk (1-10 MPN) and moderate to high risk (>10 MPN per 100 mL water). We estimated the difference in mean log10 MPN in pond and MAR water using linear mixed effect models with random intercepts and cluster adjusted robust standard error. Almost all pond water samples (292/299, 98%) had moderate- to high-risk level (>10 MPN) fecal coliforms and E. coli (283/299, 95%). In contrast, 81% (242/300) of MAR water samples had no or low risk level fecal coliforms (0-10 MPN), of which 60% (179/300) had no fecal coliforms. We detected no or low risk level E. coli in 94% (283/300) of MAR water samples of these 80% (240/300) had no E. coli. MAR samples had lower mean log10 MPN fecal coliforms (-2.37; 95% CI: -2.56, -2.19) and E. coli (-2.26; 95% CI: - 2.43, -2.09) than pond water; microbial reductions remained consistent during the wet (May-October) and dry seasons. MAR-systems provided water with reduced fecal indicator bacteria compared to infiltered pond water.

microbiology↗