Biology subjects

Jalali, S.

Publications and source records attributed to Jalali, S..

6 recordsLinked to original sources

bioRxiv2026

Dynamic remodeling of chromatin during human mucosal-associated invariant T cell development

T cell development in the thymus is a tightly regulated process where epigenetic modifications, such as histone 3 lysine 27 acetylation (H3K27ac), play a crucial role in controlling the activation of genes. The epigenetic regulation of human mucosal-associated invariant T (MAIT) cell development is unknown; we mapped the regulatory chromatin landscape in the three developmental stages of thymic MAIT cells to identify the regulatory elements and enhancer activity involved in thymic maturation and analysed whether these chromatin dynamics are associated with the acquisition of effector programs in developing MAIT cells. Utilising cleavage under target and tagmentation (CUT&Tag), genome-wide H3K27ac profiles were generated and combined with transcriptome data from thymic MAIT cells, which revealed how developmental shifts in enhancer activity correspond to changes in gene expression. In total, 41,958 genomic regions with H3K27ac signal were identified in MAIT cells across the three development stages, of which 1,200 regions showed acetylation changes during differentiation from stage 1 to stage 3. At dynamic regions, the greatest differences were observed between stage 1 and stage 3, highlighting a progressive gain or loss of H3K27ac during MAIT cell development. Overall, MAIT cell maturation was associated with the gradual accumulation of H3K27ac at promoters and enhancers, which closely correlated with gene expression changes during development. Stage-specific enrichment of H3K27ac was observed at key transcription factor gene loci involved in MAIT cell development, including ZBTB16 (PLZF), EOMES, RUNX3, NFATC2, FOXO1, TGIF1, IRF1, and MAF genes. Epigenetic remodelling was also observed at cytokine and cytokine receptors (IL7R, IL18R1, IL23R, IFNG), chemokines and chemokine receptors (CCL4, CCL5, CCR5, CCR9, CXCR4, CXCR6), as well as several surface molecules with known immunological function. Our work reveals a previously uncharacterised epigenetic profile of human MAIT cells that regulates and inuences their development.

immunology↗

bioRxiv2025

Discovering new amyloid-like peptides using all-atom simulations and artificial intelligence.

Establishing the fundamental relationships between peptide sequences and fibril formation is critical both for understanding protein misfolding processes and for guiding biomaterial design. Here, we combine all-atom molecular dynamics (MD) simulations with artificial intelligence (AI) to investigate how subtle variations in the arrangement of a short peptide sequence affect its propensity to form fibrils. Our results show that small shifts in the distribution of hydrophobic residues and charge clusters can significantly influence both the nucleation rate and the stability of cross-{beta} structures. To rapidly extend this analysis over a wide sequence space, we developed an active learning-enhanced framework--Machine Learning for Molecular Dynamics (ML4MD)--that iteratively refines its predictions based on MD-derived aggregation data. ML4MD efficiently screens numerous peptide permutations and guides the discovery of previously unrecognized fibril-prone sequences, achieving an area under the receiver operating characteristic (ROC) curve (AUC) of 0.939. Overall, ML4MD streamlines the rational design of amyloid-like peptides by integrating detailed atomistic simulations with rapid and high-accuracy ML predictions.

biophysics↗

bioRxiv2024

The Changing Immune Landscape of Innate-like T Cells and Innate Cells Throughout Life

Spectral flow cytometry is an advanced immunological tool that enables comprehensive analysis of the immune system by simultaneously comparing innate and adaptive immune cells. Here, using a 40-colour antibody panel we advance our knowledge of innate and innate-like T cells by investigating chemokine receptors, activation and maturation markers not usually assessed on these populations and examine age-related effects to these immune cell subsets. We characterised phenotypic changes of peripheral blood mononuclear cells (PBMC) in three age groups: newborn (cord blood), adults aged 20-30 years, and adults aged 70-80 years, focusing on innate-like T cells and innate cells, including MAIT cells, NKT cells, {gamma}{delta} T cells, ILCs, and Natural Killer (NK) cells. We identify subsets of double-negative (DN) T cells (CD4- CD8-) and CD161+ T cells that increase in an age-related manner and exhibit a phenotype similar to innate-like T cells, MAIT cells and {gamma}{delta} T cells. Innate-like T cell subsets express similar patterns of the chemokine receptors and maturation markers CCR4, CCR6, CD27, CD38, CD57 and CD45RA, and resemble memory subsets of conventional CD4+ T cells and CD8+ T cells. We could detect ILCs in all age ranges, although the frequency of ILC1, ILC2, and ILC3 subsets decreased with age. Notably, we identify the NK maturation marker, CD57, as a universal marker that defines ageing populations of innate and adaptive immune cells. This study enhances our understanding of the ontogeny of human immune cells, highlighting significant age-related changes in the frequency and phenotype of immune cells.

immunology↗

bioRxiv2023

Role of maternal, fetal and placental histopathology factors in the pathogenesis of retinopathy of prematurity.

PurposeTo investigate if maternal, fetal and placental vascular and/or molecular changes predict the risk for retinopathy of prematurity in preterm infants. MethodologyThe postnatal and antenatal data and placental histopathological changes; H&E staining of placental sections and molecular findings; gene expression analysis by qRT-PCR and protein expression by IHC at the maternal-fetal interface were collected from 20 placental samples and categorized into 3 groups: full-term (n=10), preterm without ROP (n=7) and preterm with ROP (n=6). ResultsThe correlation analysis indicated significant association of increased monocytes (p=0.042), fetal growth retardation (p=0.000), apnoeic spell (p=0.033), ventilation (p=0.009), length in hospital stay (p=0.001) and decreased RBC (p=0.02), Hb (p=0.048), PCV (p=0.010), gestational age (p=0.003), birth weight (p=0.000) with increased risk of ROP. Along with these factors, placental weight(p=0.001), diameter (p=0.019), Tenny-Parker changes (p=0.025), alternating area of small and short hyper mature villi (p=0.033) are also found to be significant determinants of the disease. Gene expression analysis revealed significant increase in hypoxia (HIF-1 gene expression; p=0.007) and non-significant increase in the pro-inflammatory marker IL-6. The protein expression also showed the significantly increased activation of complement pathway (CFH) and NF- KB at maternal-fetal interface. ConclusionsOur preliminary results support the changes in the maternal-fetal factors, placental histopathology and molecular alterations related to hypoxia, inflammation and complement activation at maternal-fetal interface in preterm with ROP placentas. These changes have the potential to predict the risk of the disease but the results are required to be further validated in larger cohort.

pathology↗

bioRxiv2022

Detailed investigation on the role of lipid metabolizing enzymes in the pathogenesis of retinopathy of prematurity among preterm infants.

PurposeExtremely preterm infants are at risk of developing retinopathy of prematurity (ROP), characterized by an initial insufficient vascular network development in the retina (due to hyperoxia) that progress to neovascularization and neuroinflammation (hypoxic phase) ultimately leading to partial or total vision loss. Lipid metabolism has been shown to be a significant pathway that is involved in the regulation of angiogenesis, inflammation, and apoptosis in oxygen induced retinopathy mouse model, however, it is not explored in human ROP patients. The present study aimed to explore the association of lipid metabolizing, angiogenic and apoptotic genes with altered lipid metabolites in the ROP patients with different severity. MethodsThe blood, vitreous humor (VH), and fibrovascular membrane (FVM) samples were collected from premature infants diagnosed with ROP and controls. Gene expression of lipid metabolizing enzymes, angiogenesis, and apoptotic genes were performed using semi-quantitative PCR in blood. Lipid metabolites were identified and quantified by LC-MS in VH and were correlated with gene expression. The expression of key lipid metabolizing enzymes in severe stages of ROP was assessed by measuring their expression in FVM by immunohistochemistry. ResultsGenes coding for the lipid metabolizing enzymes such as CYP1B1, CYP2C8, COX2, and ALOX15 were upregulated while EPHX2 responsible for the conversion of epoxide fatty acids into diol fatty acids was significantly downregulated in ROP cases. The increase in the metabolic intermediates generated from the lipid metabolism pathway further confirmed the role of these enzymes in ROP. except for EPHX2 which did not show any change in its activity. The glial cells in the FVM of ROP infants too showed a lack of EPHX2 expression. A significantly higher expression of genes involved in angiogenesis (VEGF165/189, NOTCH1, and APH1B) and apoptosis (CASP3/8) correlated with altered activity of lipid metabolizing enzymes (based on metabolites levels) among ROP cases. ConclusionsLipid metabolism may play a significant role in ROP development and progression. EPHX2 activity is a key step in the metabolic pathway of arachidonic acid that mediates and regulates inflammation and vascular pathology in preterm infants.

genomics↗

bioRxiv2021

Age-related decline in function of ON and OFF visual pathways

PurposeSimple psychophysical paradigm is available as a digital application in iOS devices such as iPad to measure the function of ON and OFF visual pathways. However, an age-matched normative database is not readily available. The purpose of the study is to evaluate the response of ON and OFF visual pathways as a function of age. Methods158 normal healthy adults (84 males and 74 females) whose age ranged 18-80 years participated in the study. None of them had any ocular disease (except cataract of grade II or less) and visual acuity of [≤] 20/25. Monocular testing (only one eye) was performed on the EyeSpeed application on an iPad at 40cm distance. The targets ranged between 1 to 3 light or dark squares presented randomly in a noise background and participants responded by indicating the number of squares by touching the screen as fast as possible. The main outcome variables are reaction time, accuracy and performance index (1 / speed * accuracy). ResultsThe median reaction time was shorter (Median (IQR): 1.53s (0.49) [dark] Vs 1.76s (0.58) [light], p < 0.001) and accuracy was higher (97.21% (3.30) [dark] Vs 95.15% (5.10) [light], p < 0.001) for dark targets than the light targets. Performance index and reaction time for both target types significantly correlated with age ({rho} = -0.41 to -0.43; p < 0.001). ConclusionsThis normative database will be useful to quantify disease-specific defects. More importantly, the ON pathway function can potentially serve as a surrogate for rod photoreceptor function.

neuroscience↗