Biology subjects

Bilal, M.

Publications and source records attributed to Bilal, M..

6 recordsLinked to original sources

bioRxiv2026

Integrated transcriptomics and proteomics define the TRP channel hierarchy in mouse cortex

Transient receptor potential (TRP) channels are evolutionarily conserved polymodal cation channels that mediate diverse sensory functions across the animal kingdom. Although TRP channels play key roles in peripheral sensation, their expression and functional relevance in the cerebral cortex remain poorly defined. Here, we integrate long- and short-read transcriptomics, targeted qPCR and membrane-aware proteomics to quantify TRP family members in adult mouse cortex. Across transcriptomic platforms, cortical TRP expression is dominated by TRPML, TRPC, and TRPM subfamilies, with lower representation of TRPP/TRPV, whereas Trpa1 and Trpv1 lie near empirical detection thresholds. Our proteomic workflow yields reproducible protein-level evidence for a subset of cortical TRPs, including TRPV2, TRPC4, TRPM3, TRPM7 and TRPP2, consistent with transcript rank order, while TRPA1/TRPV1 do not meet replicate-level protein-group detection criteria under 1% FDR control. Together, these multi-platform measurements establish a quantitative reference for cortical TRP biology and a framework for profiling low-abundance ion channels in complex brain tissue.

molecular biology↗

bioRxiv2026

Elevating Neuronal CYLD Causes Frontotemporal Dementia (FTD)-Relevant Behavioral and Physiological Deficits

Frontotemporal dementia (FTD), a leading form of presenile dementia disrupting behavior, language and/or movement, is linked to mutations of a number of genes, including CYLD that encodes a Lys63 (K63) deubiquitinating enzyme. Among several CYLD variants found in FTD patients, a gain-of-function missense mutant, M719V, has been proposed to be pathogenic, but its pathogenicity in vivo and the underlying mechanism remain unknown. Here, we have developed transgenic mice that express either wildtype (WT) or M719V-CYLD in neurons throughout the mouse brain using adeno-associated virus (AAV) mediated somatic brain transgenesis. We show that somatic M719V-CYLD transgenic mice display profound FTD-associated behavioral impairments, including risk-taking, reduced social interaction, and loss of empathy that emerge from early stages and worsen with aging. Furthermore, M719V-CYLD mice also show significant early neurophysiological impairments in the prefrontal cortex (PFC), including depolarized resting membrane potential, decreased synaptic transmission, and reduced neuronal excitability. Surprisingly, however, M719V-CYLD mouse brain exhibits elevated autophagy activity and decreased Akt-mTOR signaling without overt neuronal cell loss or microgliosis even at 12 months of age. Most M719V-CYLD-associated cellular and behavioral phenotypes are also recapitulated but to a lesser extent in WT-CYLD mice, suggesting CYLD activation is responsible for the observed neural circuit deficits and the M719V mutation is gain-of-function in nature. Our results uncover important roles of neuronal CYLD in PFC function and social behaviors and establish a unique animal model to investigate pathogenic mechanisms of FTD, in particular its social behavioral deficits, at molecular, cellular, synaptic and circuit levels.

neuroscience↗

bioRxiv2025

Single-molecule multimodal timing of in vivo mRNA synthesis

mRNA synthesis requires extensive pre-mRNA maturation, the organisation of which remains unclear. Here, we directly sequence pre-mRNA without metabolic labelling or amplification to resolve transcription and multimodal pre-mRNA processing at single-molecule resolution. Using poly(A) tail measurement, we distinguish transcriptionally engaged pre-mRNA from polyadenylated transcripts, revealing that splicing is substantially delayed compared to previous estimates. Splicing is rare for at least 10 kb behind elongating RNA polymerase II such that thousands of genes remain largely unspliced during transcription, revising the notion that splicing is predominantly co-transcriptional. Progressive splicing becomes apparent only on polyadenylated transcripts, suggesting that splicing is commonly activated after 3' end formation. Unexpectedly, we find abundant m6A on unspliced pre-mRNA, indicating that a substantial portion of RNA methylation precedes splicing. This m6A methylation is suppressed around exon boundaries, indicating that m6A topology is established prior to exon junction complex deposition. Finally, we demonstrate that 3' end cleavage occurs multiple kilobases behind transcription in coordination with efficient transcription termination, and further highlight recursive 3' end formation across hundreds of genes. Conserved from human cells to mouse tissues, we illustrate a revised timeline for mRNA synthesis wherein cleavage, termination, and m6A deposition occur earlier than, or at least partially decoupled from, the bulk of splicing, reframing the sequence of early mammalian gene expression.

genomics↗

bioRxiv2023

Different Diets Modulate the Gut Microbiome Compositions and Promote the Health of Apis mellifera.

Honey bee (Apis mellifera) health is crucial for honey bee products, and effective pollination and is closely associated with gut bacteria. Various factors such as reduced habitat, temperature, disease, and diet affect the health of honey bees, by disturbing the homeostasis of the gut microbiota. In this study, high-throughput 16S rRNA gene sequencing was used to analyze the gut microbiota of Apis mellifera subjected to seven different diets. The identified microbiota in the Apis mellifera gut from all the diets consisted of Lactobacillus (62%), followed by Rhizobiaceae (21%), Snodgrassella (4%), and Erwiniaceae (4%) among other 33 genera. Based on diet types, Lactobacillus a lactic acid bacteria (LAB), dominates the microbiota with the highest relative abundance in AIGT+SAC (91%), AIGT+Soytide (88%), and AIGT+Apple juice (69%) diet groups. Bifidobacterium and Commensalibacter appeared as the second most abundant genera in AIGT+SAC and AIGT+Soytide diet groups, respectively. These bacteria are important markers for honey bee health. Considering the importance of these diets in shaping their host microbiome into a healthy status. Individual honey bee health (IHH) was observed to validate the quality and correlation between the microbiota and honey bee health. The results were consistent, indicating that Apis mellifera fed on AIGT+Soytide and AIGT+SAC diet showed the highest health expression level of vitellogenin. The group with 60%Syrup possessing Rhizobiaceae as the dominant taxa showed poor health status. This finding paved the way for establishing a link between gut microbiota and IHH under different diets.

genomics↗

bioRxiv2023

Isoxanthohumol improves obesity and glucose metabolism via inhibiting intestinal lipid absorption with a bloom of Akkermansia muciniphila in mice

AimsDysbiosis is an important factor that leads to metabolic disorders by disrupting energy balance and insulin sensitivity. A decrease in Akkermansia muciniphila is a phenotype of obesity-induced dysbiosis. Although interventions to increase A. muciniphila are expected to improve glucose metabolism, the underlying mechanism has not been fully understood. MethodsIsoxanthohumol (IX), a prenylated flavonoid found in beer hops was administered to high fat diet-fed mice. We analyzed glucose metabolism, gene expression profiles and histology of liver, epididymal adipose tissue and colon. Lipase activity, fecal lipid profiles and plasma metabolomic analysis were assessed. Fecal 16s rRNA sequencing was obtained and selected bacterial species were used for in vitro studies. Fecal microbiota transplantation and monocolonization were conducted to antibiotic-treated or germ-free (GF) mice. ResultsThe administration of IX lowered weight gain, decreased steatohepatitis and improved glucose metabolism. Mechanistically, IX inhibited pancreatic lipase activity and lipid absorption by decreasing the expression of the fatty acid transporter CD36 in the small intestine, which was confirmed by increased lipid excretion in feces. IX administration improved the gut barrier function and reduced metabolic endotoxemia. In contrast, the effects of IX were nullified by antibiotics. As revealed using 16S rRNA sequencing, the microbial community structure changed with a significant increase in the abundance of A. muciniphila in the IX-treated group. An anaerobic chamber study showed that IX selectively promoted the growth of A. muciniphila while exhibiting antimicrobial activity against some Bacteroides and Clostridium species. To further explore the direct effect of A. muciniphila on lipid and glucose metabolism, we monocolonized either A. muciniphila or Bacteroides thetaiotaomicron to GF mice. A. muciniphila monocolonization decreased CD36 expression in the jejunum and improved glucose metabolism, with decreased levels of multiple classes of fatty acids determined using plasma metabolomic analysis. ConclusionOur study confirmed a direct role of A. muciniphila in energy metabolism, which was induced by microbial actions of IX. These highlight new treatment strategies for preventing metabolic syndrome by boosting the gut microbiota with food components.

microbiology↗

bioRxiv2021

TIAToolbox: An End-to-End Toolbox for Advanced Tissue Image Analytics

Computational Pathology (CPath) has seen rapid growth in recent years, driven by advanced deep learning (DL) algorithms. These algorithms typically share the same sequence of steps. However, due to the sheer size and complexity of handling large multi-gigapixel whole-slide images, there is no open-source software library that provides a generic end-to-end API for pathology image analysis using best practices for CPath. Most researchers have designed custom pipelines from the bottom-up, restricting the development of advanced CPath algorithms to specialist users. To help overcome this bottleneck, we present TIAToolbox, a Python toolbox designed to make CPath more accessible to new and advanced CPath scientists and pathologists alike. We provide a usable and adaptable library with efficient, cutting-edge and unit-tested tools for data loading, pre-processing, model inference, post-processing and visualization. This enables all kinds of users to easily build upon recent DL developments in the CPath literature. TIAToolbox provides a user-friendly modular API to enable seamless integration of advanced DL algorithms. We show with the help of examples how state-of-the-art DL algorithms can be streamlined using TIAToolbox.

bioengineering↗