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Rahim, F.

Publications and source records attributed to Rahim, F..

3 recordsLinked to original sources

Molecular signature of neutrophils in antiphospholipid syndrome based on epigenomic and transcriptome analysis

BackgroundAntiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and pregnancy loss. Recent studies indicate that neutrophils, particularly neutrophil extracellular traps (NETs), contribute to the development and progression of APS. However, the precise underlying mechanisms remain unclear. MethodsTo address this, we analyzed epigenome and transcriptome data to identify key differentially expressed genes (DEGs) of neutrophils in APS using weighted gene co-expression network analysis (WGCNA). Two datasets (GSE102215 and GSE124565) were obtained from the GEO database. The Limma R package was used to identify DEGs, while ChAMP R was applied to analyze differentially methylated genes (DMGs) between APS patients and healthy controls. Enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed using ClusterProfiler, and TISIDB was used to examine associations with immunomodulators, chemokines, and receptors. GeneCards and Connectivity Map databases were further used for disease-related gene analysis and drug prediction. ResultsGO enrichment analysis revealed that DEGs were primarily enriched in leukocyte cell-cell adhesion, regulation of leukocyte cell-cell adhesion, and cytokine-mediated signaling pathways. Correspondingly, KEGG enrichment analysis demonstrated that DEGs were mainly enriched in the ribosome, NF-kB signaling pathway, NOD-like receptor signaling pathway, and other related pathways. Through WGCNA analysis, we identified two key intersection genes, CCL5 and ITK, which were positively correlated with CD8+ T cells and eosinophils, while being negatively correlated with neutrophils and follicular helper T cells. Gene set enrichment analysis (GSEA) indicated that CCL5 was enriched in hematopoietic cell lineage, ribosome, and ribosome biogenesis in eukaryotes, and ITK was enriched in ribosome, ribosome biogenesis in eukaryotes, and T-cell receptor signaling. Similarly, gene set variation analysis (GSVA) showed that CCL5 and ITK were associated with IL-2-STAT5 signaling and the P53 pathway as well as MTORC1 signaling. Furthermore, gene regulatory network analysis suggested that CCL5 and ITK are modulated by common mechanisms involving multiple transcription factors. By examining APS-related genes in the GeneCards database, we observed a significant negative correlation between CCL5 and phosphatase and tensin homolog (PTEN) (R = -0.624), and a strong positive correlation between ITK and CD40LG (R = 0.933). Finally, drug perturbation expression profiles revealed that RS-56812, acebutolol, emetine, and proscillaridin exhibited the most significant negative correlation with disease-associated expression profiles. ConclusionThese data nominate CCL5 and ITK as APS-associated genes in neutrophils and indicate associations with multiple signaling pathways. Moreover, drugs targeting these genes may represent potential therapeutic strategies for APS.

immunology↗

Beyond winglets: evolution of flight-related morphology in stick insects (Phasmatodea)

The first winged insects evolved from a wingless ancestor, but details of the transition to a fully-winged morphology remain unclear. Studying extant pterygotes with partial wings, such as the stick insects (Order Phasmatodea), may help us to understand such a transition. Here, we address how a series of flight-related morphological parameters may correlate with flight evolution by studying different phasmids representing a volancy continuum ranging from miniaturized to full-sized wings. Variation in phasmid wing shape, venation, wing mass and the mass of flight muscle can be described by specific scaling laws referenced to wing length and wing loading. Also, the mass distribution of the body-leg system is conserved in spite of a wide range of variation in body shape. With reduced wing size and increased wing loading, the longitudinal position of the wing-bearing thoracic segments is shifted closer to the insects center of body mass. These results demonstrate complex reconfiguration of the flight system during wing morphological transitions in phasmids, with various anatomical features potentially correlated with reduced flight performance attained with partial wings. Although these data represent phasmid-specific features of the flight apparatus and body plan, the associated scaling relationships can provide insight into functionality of intermediate conditions between wingless and fully-winged insects more generally.

evolutionary biology↗

A tale of winglets: evolution of flight morphology in stick insects

The evolutionary transition between winglessness and a full-winged morphology requires selective advantage for intermediate forms. Conversely, repeated secondary wing reductions among the pterygotes indicates relaxation of such selection. However, evolutionary trajectories of such transitions are not well characterized. The stick insects (Phasmatodea) exhibit diverse wing sizes at both interspecific and intersexual levels, and thus provide a system for examining how selection on flight capability, along with other selective forces, drives the evolution of flight-related morphology. Here, we examine variation in relevant morphology for stick insects using data from 1100+ individuals representing 765 species. Although wing size varies along a continuous spectrum, taxa with either long or miniaturized wings are the most common, whereas those with intermediate-sized wings are relatively rare. In a morphological space defined by wing and body size, the aerodynamically relevant parameter termed wing loading (the average pressure exerted on the air by the wings) varies according to sex-specific scaling laws; volant but also flightless forms are the most common outcomes in both sexes. Using phylogenetically-informed analyses, we show that relative wing size and body size are inversely correlated in long-winged insects regardless of sexual differences in morphology and ecology. These results demonstrate the diversity of flight-related morphology in stick insects, and also provide a general framework for addressing evolutionary coupling between wing and body dimensions. We also find indirect evidence for a fitness valley associated with intermediate-sized wings, suggesting relatively rapid evolutionary transitions between wingless and volant forms.

evolutionary biology↗