Biology subjects

Ali, U.

Publications and source records attributed to Ali, U..

5 recordsLinked to original sources

bioRxiv2026

Differential Nucleotide Inhibition Profile of Mouse and Human UCP1 Expressed in Liver Mitochondria Is Associated with an F88S Mutation

Uncoupling protein 1 (UCP1) mediates thermogenesis in brown adipose tissue. Whether human-UCP1 shares the bioenergetic properties established for rodent UCP1 (innate uncoupling, GDP sensitivity, fatty acid (re)activation) is not known. Therefore, we expressed human and mouse UCP1 in mouse liver, using adeno-associated viral vectors, and characterized their properties in isolated liver mitochondria. Both UCP1s induced marked innate uncoupling, characterized by increased substrate-supported respiration and decreased membrane potential, in the absence of exogenous fatty acids. Mouse-UCP1 in liver retained the classical regulatory properties of native brown-fat UCP1, including potent inhibition by GDP and reactivation by oleate. In contrast, human-UCP1 was only weakly inhibited by GDP but was strongly responsive to fatty acids. However, ATP potently inhibited human-UCP1, with an apparent IC of {approx}0.4 mM compared with {approx}1.4 mM for GDP, and ATP markedly decreased the sensitivity of human-UCP1 to oleate (re)activation. Despite substantial UCP1-mediated uncoupling, oxidative phosphorylation capacity and mitochondrial OXPHOS protein levels were preserved. Molecular dynamics simulations suggested a structural basis for the species difference. GDP formed persistent interactions with F88 in mouse-UCP1, an interaction absent at the corresponding S88 residue in human-UCP1. In-silico substitution of F88 by serine reduced GDP interaction at this site. Thus, human and mouse UCP1 share innate thermogenic activity but differ fundamentally in nucleotide regulation. The F88/S88 difference may contribute to the preferential GDP sensitivity of mouse-UCP1, whereas ATP provides effective nucleotide control of human-UCP1.

biochemistry↗

bioRxiv2025

Lipolytic and Anti-Adipogenic Effect of Capsaicin, Camphor, and Caffeic acid on Human SGBS Adipocytes

Excess fat accumulation contributes to metabolic disorders such as insulin resistance, type 2 diabetes, cardiovascular disease and increases risk of dementia. Promoting lipolysis and inhibiting adipogenesis through natural compounds offers a promising therapeutic approach to obesity. This study investigates the lipolytic and anti-adipogenic effects of capsaicin, camphor, and caffeic acid in human Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte model. First, we determined appropriate treatment concentrations using MTT assays, which demonstrated a dose dependent reduction in cell viability for all three compounds. Selected doses were applied to differentiating SGBS cells until day 14. Lipid droplet accumulation and free fatty acid release were assessed using Oil Red O (ORO) staining and a lipolysis assay kit, respectively. Gene expression of adipogenic and lipolytic markers was analysed by RT-PCR and TRPV1 receptor involvement was examined by immunofluorescence. A network pharmacology approach incorporating GeneCards, STITCH, and other databases revealed downregulation of PPARG, CEBPA, and FABP4, and upregulation of HSL, ATGL, and PLIN1. TRPV1 activation was prominent in capsaicin treated cells. Network analysis identified shared regulatory hubs such as PPARG, STAT3, and MTOR. All treatments significantly reduced lipid accumulation and increased lipolysis, with capsaicin showing the strongest effects. Combination treatments, especially capsaicin with caffeic acid, exhibited synergistic effects. While the previous studies showed interference of these compounds in the molecular pathways involved in fat cell metabolism, our work establishes for the first time potential thermogenic capacity of camphor individually and of combinatory effects of three compounds to inhibit adipogenesis and promote lipolysis in human adipocytes, potentially through TRPV1 signalling and modulation of metabolic gene networks. These findings highlight their therapeutic potential for metabolic disorders.

cell biology↗

bioRxiv2023

Widespread readthrough events in plants reveal unprecedented plasticity of stop codons

Stop codon readthrough (SCR), the decoding of a stop codon as a sense codon by the ribosome, has important biological implications but remains largely uncharacterized in plants. Here, we identified 1,009 SCR events in two monocots (maize, rice) and two dicots (soybean, Arabidopsis) using a proteogenomic strategy with 80 customized databases. SCR transcripts were mostly significantly shorter and had fewer components than non-SCR transcripts in two monocot plants, although these differences were not as significant in the dicots. Mass spectrometry evidence revealed that all three stop codons involved in SCR events could be recoded as 20 standard amino acids, some of which were also supported by suppressor transfer RNA analysis. In addition, we observed multiple functional signals in the C-terminal extensions of 34 maize SCR proteins, and characterized the structural and subcellular localization changes in the extended protein of BASIC TRANSCRIPTION FACTOR 3. Overall, our study not only demonstrates that SCR events are widespread in plants but also reveals the unprecedented recoding plasticity of stop codons, which provides important new insights into the flexibility of genetic decoding.

plant biology↗

bioRxiv2022

Treatment of prostate cancer with CD46 targeted 225Ac alpha particle radioimmunotherapy

Radiopharmaceutical therapy is changing the standard of care in prostate cancer (PCa) and other malignancies. We previously reported high CD46 expression in PCa and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody. Our radiolabeled antibody retains binding efficacy and shows a high tumor to background ratio in PCa xenografts. Furthermore, we show that radiolabeled antibody was able to suppress the growth of cell-derived and patient-derived xenografts, including PSMA-positive and deficient models. Nephrotoxicity, not seen at low radioactive doses, is evident at higher radioactivity dose levels, likely due to redistribution of daughter isotope 213Bi. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46 targeted radioligand therapy in PCa.

cancer biology↗

bioRxiv2021

LNCRNA expression landscape and specificity between brain regions

Long noncoding RNAs (lncRNAs) are transcribed into low potential protein coding RNA molecules, which account for over 70% of mammalian transcriptional products. The role of lncRNAs and their expression is still largely unknown, and the subject of recent investigations. Here, we used bulk RNA sequencing data from the Genotype-Tissue Expression (GTEx) project to reveal the occurrence and identify the specificity of lncRNAs in 13 brain regions (1000 samples). We observed that these highly specific lncRNA were co-expressed with previously known mRNA markers for the 13 study regions of the brain. Further investigation revealed that splicing could influence the divergent biogenesis and enrichment of specific lncRNA alleles in different brain regions. Overall, we demonstrate the use of lncRNA as an independent tool for deconvolving brain regions and further highlights its use for cell-type identification from bulk transcriptome data.

bioinformatics↗