Biology subjects

Qayyum, S.

Publications and source records attributed to Qayyum, S..

5 recordsLinked to original sources

bioRxiv2026

Molecular control of replication licensing speed by c-MYC

A critical prerequisite for DNA replication is genome-wide origin licensing, a process tightly restricted to the G1 cell cycle phase. This restriction means that short G1 cells must license quickly or risk incomplete replication and genome instability, but mechanisms to increase licensing speed are largely unknown. Using quantitative single cell approaches, we identify here a non-canonical role for c-MYC as a potent origin licensing accelerator. Importantly, a point mutation separates c-MYC-induced rapid licensing from the well-known c-MYC gene expression function. c-MYC accelerates licensing through the TRRAP lysine acetyltransferase adapter and GCN5 acetyltransferase. In addition c-MYC has the unexpected ability to induce widespread linker histone H1 eviction. Moreover, directly reducing chromatin-bound histone H1 is sufficient to accelerate licensing. In addition, c-MYC stimulates licensing in heterochromatin, a typically slow-licensing genome compartment. We suggest that global chromatin opening promotes rapid licensing when G1 phase is short such as during early development, rapid progenitor cell proliferation, and adaptation to oncogene activation.

molecular biology↗

bioRxiv2026

Ether glycerophospholipid control of peroxisome degradation confers protection from ischemia

Ether glycerophospholipids (ether lipids) are a subclass of glycerophospholipids that are synthesized at the peroxisome and constitute nearly 20% of the total phospholipid content in metazoans. Biochemically, ether lipids have an alkyl chain attached by an ether bond at the sn-1 position of the glycerol backbone (alkyl-ether) primarily containing choline or ethanolamine head groups. Some ether lipids contain a cis bond adjacent to the ether linkage (alkenyl-ether) and are commonly referred to as plasmalogens. While the importance of ether lipids in humans is clear, highlighted by the severity of inherited peroxisomal disorders caused by ether lipid deficiency, the molecular roles of these lipids remain poorly understood. Here, we identify a link between ether lipid metabolism, peroxisome degradation, and oxygen availability. We find Fatty acyl-CoA-reductase 1 (FAR1), the rate-limiting enzyme in peroxisomal ether lipid metabolism, acts as a peroxisome receptor necessary for peroxisome degradation when oxygen is limiting. Hypoxia increases choline ether lipid abundance, promotes autophagy activation, and peroxisome degradation. Mechanistically, FAR1 binds ATG8-family protein LC3B and is necessary and sufficient to control peroxisome degradation under hypoxia. FAR1s enzymatic function as well as its capacity to bind LC3B is necessary to degrade peroxisomes under hypoxia. Similarly, loss of multiple components of peroxisomal ether lipid metabolism blocks peroxisome degradation under hypoxia in cells and in vivo. In mouse models of chronic HIF activation, Far1 is a direct HIF target gene and is necessary for peroxisome degradation in this setting. Increasing ether lipids using ether lipid precursors activates autophagy and promotes autophagy-dependent cardioprotection against ischemic injury. This work reveals FAR1 as a critical regulator of peroxisome homeostasis in the setting of oxygen limitation.

cell biology↗

bioRxiv2026

DEPP1 connects nutrient and oxygen availability to maintenance of muscle mass

Nutrients and oxygen are sensed within the muscle to control growth and disruption of either signal is sufficient to lead to muscle atrophy. While nutrient limitation is sensed via a conserved transcriptional atrophy program (commonly referred to as atrogenes) dictated via the Forkhead box O (FoxO) transcription factors, how low oxygen promotes muscle loss remains unknown. Accordingly, the downstream mechanisms that initiate muscle loss when oxygen and nutrients are limiting are only partly understood. Here, we find Hypoxia Inducible Factor (HIF), the master regulator of our adaptation to low oxygen, is necessary and sufficient to mediate muscle loss under hypoxia in mice. RNA sequencing in skeletal muscle isolated from starved or hypoxic mice identifies Decidual Protein Induced by Progesterone 1 (Depp1), which is induced in skeletal muscle when nutrients or oxygen is limiting via FoxO1 and HIF activation, respectively. Whole body Depp1 loss in mice reduces muscle loss under fasting and hypoxia and skeletal muscle Depp1 overexpression is sufficient to mediate muscle atrophy. Mechanistically, Depp1 localizes to the mitochondria and is necessary to control autophagy activation and mitochondrial degradation in skeletal muscle. Taken together, our studies nominate Depp1 as a new atrogene necessary for muscle loss under multiple atrophy scenarios involving FoxO and HIF.

physiology↗

bioRxiv2022

Open-source versatile 3D-print animal conditioning platform design for in-vivo preclinical brain imaging in awake mice and anesthetized mice and rats

Proper animal conditioning is a key factor in the quality and success of preclinical neuroimaging applications. We introduce an open-source easy-to-modify multi-modal 3D printable design for rodent conditioning for magnetic resonance imaging (MRI) or other imaging modalities. Our design can be used for brain imaging in anesthetized or awake mice and anesthetized rats. We show ease-of-use and reproducibility of subject conditioning with anatomical T2-weighted imaging for both mice and rats. We also demonstrate application of our design for awake fMRI in mice using both visual evoked potential and olfactory stimulation paradigms. In addition, we demonstrate that our proposed cradle design can be extended to multiple imaging modalities combining MRI, Positron emission tomography and X-ray computed tomography.

neuroscience↗

bioRxiv2021

ASSOCIATION STUDY OF SIX CANDIDATE GENES WITH MAJOR DEPRESSIVE DISORDER IN THE NORTH-WESTERN POPULATION OF PAKISTAN

People around the world are currently affected by Major Depressive Disorder (MDD). Despite its many aspects, symptoms, manifestations and impacts, efforts have been made to identify the root causes of the disorder. In particular, genetic studies have concentrated on identifying candidate genes for MDD and exploring associations between these genes and some specific group of individuals. The aim of this research was to find out the association between single nucleotide polymorphisms in 6 candidate genes linked to the neurobiology of major depressive disorder in the North-Western population of Pakistan. We performed a case-control analysis, with 400 MDD and 232 controls. A trained psychiatrist or clinical psychologists evaluated the patients. Six polymorphisms were genotyped and tested for allele and genotype association with MDD. There were no statistical variations between MDD patients and healthy controls for genotypic and allelic distribution of all the polymorphisms observed. Thus, our analysis does not support the major role of these polymorphisms in contributing to MDD susceptibility, although it does not preclude minor impact. The statistically significant correlation between six polymorphisms and major depressive disorder in the studied population was not observed. There are inconsistencies in investigations around the world. Future research, including GWAS and association analysis on larger scale should be addressed for further validation and replication of the present findings.

genetics↗