Biology subjects

Abdallah, S.

Publications and source records attributed to Abdallah, S..

5 recordsLinked to original sources

bioRxiv2026

Brain-resident myeloid cells promote rapid leukocyte adhesion in leptomeningeal vessels after anti-Aβ immunotherapy

Anti-amyloid {beta} (A{beta}) immunotherapy improves cognitive outcomes in Alzheimer's disease (AD) but is associated with amyloid-related imaging abnormalities (ARIA), through poorly understood mechanisms. To define how anti-A{beta} antibodies acutely engage brain immune and vascular compartments, we developed a longitudinal in vivo two-photon imaging platform to track microglial dynamics, peripheral immune cell recruitment, and vascular responses in APP/PS1 mice. Anti-A{beta} antibodies, including aducanumab and lecanemab, rapidly initiated microglial activation and spatial reorganization within 24 hours of dosing, with recruitment to plaque-associated regions, stabilizing plaque growth. Aducanumab and lecanemab also triggered a rapid and transient cerebrovascular immune response characterized by rolling and adhesion of peripheral immune cells along leptomeningeal vessels, accompanied by endothelial activation. Immune cell characterization revealed recruitment of innate immune cells (Iba1Ki67 monocytes and Ly6G neutrophils) and proliferative CD3 T cells into the vascular compartment following treatment. Prophylactic treatment with high-dose dexamethasone reduced the number of adherent cells without affecting microglial activation. Depletion of brain-resident immune cells similarly reduced peripheral immune cell recruitment, supporting their contribution to leukocyte recruitment. Postmortem brain tissue from an AD patient treated with lecanemab showed higher proliferation-associated monocyte signature scores, suggesting translational relevance to the proliferative myeloid response observed in our mouse models. These findings demonstrate that anti-A{beta} immunotherapy rapidly initiates a coordinated central and peripheral immune response at the leptomeningeal interface. These early immune-vascular interactions represent a plausible initiating mechanism for ARIA and provide a mechanistic framework to guide strategies for mitigating ARIA risk

neuroscience↗

bioRxiv2025

HaploCharmer: a Snakemake workflow for read-scale haplotype calling adapted to polyploids

The advent of next-generation sequencing (NGS) has revolutionized the study of single nucleotide polymorphisms (SNPs), making it increasingly cost-effective. Haplotypes, which combine alleles from adjacent variants, offer several advantages over bi-allelic SNPs, including enhanced information content, reduced dimensionality, and improved statistical power in genomic studies. These benefits are particularly significant for polyploid species, where distinguishing all homologous copies using SNP markers alone can be challenging. This article introduces HaploCharmer, a flexible workflow designed for read-scale haplotype calling from NGS data. HaploCharmer identifies haplotypes within preconfigured genomic regions smaller than a sequencing read, ensuring direct comparability across individuals. It integrates a series of processing steps including mapping, haplotype identification, filtration, and reporting of haplotype sequences, as presence-absence, in the panel of accessions analyzed. The performance of HaploCharmer was validated by building a genetic map using whole-genome sequencing data from a highly polyploid sugarcane cultivar (R570) and its self-progeny, and performing a diversity analysis in the polyploid Saccharum genus using targeted sequencing data. The workflow successfully identified a large number of high-quality haplotypes, with less than 1% of false positives. The dense genetic map obtained using single-dose haplotypes accurately depicted the known genome architecture of the R570 cultivar, including large chromosome rearrangements. The diversity analysis accurately reflected the known genetic structure within this genus. It also allowed inferring ancestral origins to mapped haplotypes and the corresponding chromosome segments in the R570 genetic map. HaploCharmer provides a robust method for diversity, genetic mapping, and quantitative genetics studies in both diploid and polyploid species.

bioinformatics↗

bioRxiv2024

Genomic Analysis of Salmonella enterica from cattle, beef and humans in the Greater Tamale Metropolis of Ghana

Salmonella enterica is a bacterial foodborne pathogen notorious for infecting humans and animals. Proper control of Salmonella requires routine surveillance and interventions across the food-production chain. However, due to limited resources the dynamics and transmission of non-typhoidal Salmonella serotypes remain poorly understood in several African settings, including within Ghana. Here, we employed bacterial culture and whole genome sequencing (WGS) to investigate the prevalence, virulence and antimicrobial resistance determinants of Salmonella enterica isolates from beef, cattle blood and human patient stool in Greater Tamale Metropolis, Ghana. Enrichment and culture of the specimens yielded 62 isolates in total from beef (31), bovine blood (28) and human diarrhoeal specimens (3). We identified at least 15 STs and 18 different Salmonella serovars. The most common serovars detected were Poona (n=13), Montevideo (n=10) and Poano (n=7) with S. Montevideo being the most common from cattle blood. Thirty-two isolates belonged to novel sequence types (STs), with ST2609 (n=9) being most common. Four raw beef isolates harboured at least one gene conferring resistance to beta-lactam (blaTEM-1), chloramphenicol (catA), fosfomycin (fosA7), quinolone (qnrD1) or tetracycline (tet(A)). Eight isolates carried at an IncF, IncI and/orCol3M plasmid replicon. This study recovered Salmonella, often belonging to previously undocumented STs, at high frequencies from cattle and beef and demonstrated that isolates from human diarrhoeal patients are closely related to bovine isolates. The data highlight the need for broader and sustained surveillance and the urgent need for food safety interventions in Ghana.

microbiology↗

bioRxiv2023

Evidence of the ability of endocrine disrupting compounds to induce testicular germ cell cancer in humans.

Testicular cancer is an increasing burden in modern societies and the most common malignancy among young adult males. Environment contaminants, especially endocrine disrupting compounds (EDC), may play a significant role in the development of these cancers through epigenetic alterations occurring during fetal and neonatal development. As long-term studies in humans and suitable experimental models with the potential to develop testicular cancer are lacking, no causal link can be established between endocrine disruptor exposure and testicular cancer incidence. Therefore, we developed an experimental model that recapitulates the differentiation of germ cells from primordial germ cells (pluripotency) into spermatocytes (meiosis) by using xenografted human fetal testis combined with germ cell transplantation into adult testis compartments. Using this model, we demonstrate that long-term fetal exposure (until 12 weeks) to a mixture of Di-2-ethylhexylphthalate (DEHP) and Bisphenol A (BPA), two most prevalent plasticizers, could interfere with fetal germ cell differentiation, leading to carcinogenesis and seminomas. Transcriptome, methylome, and histological analyses reveal that BPA/DEHP exposure induced some significant hallmarks of germ cell tumors to occur: persistent pluripotent and proliferative germ cells, global hypomethylation of CpGs in germ cells, abnormal expression of meiotic markers and fibrotic signatures in fetal testis. Additionally, we found that EDC-exposed fetal germ cells were more likely to develop seminoma in a context that allows spermatogenesis to begin. This study proposes the first experimental evidence that EDC exposure can cause long-term, irreversible lesions in fetal germ cells, which then lead to testicular tumorigenesis in adults.

cancer biology↗

bioRxiv2020

DNA oxidation induced by fetal exposure to BPA agonists impairs female meiosis

Many endocrine disruptors have been proven to impair the meiotic process that is mandatory to produce healthy gametes. Bisphenol A is emblematic as it impairs meiotic prophase I and causes oocyte aneuploidy following in utero exposure. However, the mechanisms underlying these deleterious effects remain poorly understood. Furthermore, the increasing uses of BPA analogs raise concerns for public health. Here, we investigated the effect on oogenesis in mouse of fetal exposure to two BPA analogs, Bisphenol A Diglycidyl Ether (BADGE) or Bisphenol AF (BPAF). These analogs delay meiosis initiation, increase MLH1 foci per cell and induce oocyte aneuploidy. We further demonstrate that these defects are accompanied by a deregulation of gene expression and aberrant mRNA splicing in fetal premeiotic germ cells. Interestingly, we observed an increase in DNA oxidation after exposure to BPA analogs. Specific induction of oxidative DNA damages during fetal germ cell differentiation causes similar defects during oogenesis, as observed in 8-Oxoguanine DNA Glycosylase (OGG1) deficient mice or after in utero exposure to potassium bromate (KBrO3), an inducer of oxidative DNA damages. Moreover, the supplementation of N-acetylcysteine (NAC) with BPA analogs counteracts the bisphenol-induced meiotic effect. Together our results position oxidative stress as a central event that negatively impacts the female meiosis with major consequences on oocyte quality. This could be a common mechanism of action for so called endocrine disruptors pollutants and it could lead to novel strategies for reprotoxic compounds.

molecular biology↗