Biology subjects

Fatima, K.

Publications and source records attributed to Fatima, K..

4 recordsLinked to original sources

bioRxiv2026

Extracellular Vesicles Mediate Activation and Trafficking of Splenic Immune Cells to the Heart Post-Myocardial Infarction

BackgroundMyocardial infarction (MI) triggers splenic immune cell trafficking to the heart. Vehicles that carry these signals and mediate this crosstalk are unknown. HypothesisWe hypothesize that extracellular vesicles (EVs) released post-MI mediate splenic immune trafficking to the heart. MethodsMice were treated daily with an EV biogenesis inhibitor (GW4869) or vehicle. Splenic/cardiac immune cells were assessed at 3d while survival, cardiac function, hypertrophy, and fibrosis were evaluated at 8w post-MI. Plasma EVs from 1d MI mice or from the hearts that underwent MI/sham in a Langendorff system induced splenic immune trafficking to the heart within 3d and systolic dysfunction at 8w in naive mice. ResultsGW4869 i) inhibited splenic regression, ii) increased splenic retention of neutrophils, monocytes, dendritic cells (DCs), and CD4 T-cells, iii) decreased cardiac gene expression of pro-inflammatory cytokines/chemokines, and iv) decreased trafficking of immune cells to the hearts at 3d post-MI, and iii) improved systolic function and attenuated hypertrophy at 8w post-MI. MI EVs accumulated in the spleen and promoted egress of matured splenic immune cells upon administration to naive mice. Cardiac pro-inflammatory cytokines/chemokines expression and CCR2+MHC-IIhi infiltrating macrophages, CD11c+ DCs, and CD4+ and CD4+TNF+ T-cell levels were also increased in naive mice at 3d post-injection. Importantly, transfer of MI EVs for 2 days induced systolic dysfunction, cellular hypertrophy, and fibrosis in naive mice at 8 w post-injection. DCs process MI EVs for T-cells activation. ConclusionsEVs mobilize splenic immune cells to the heart post-MI and their inhibition can subdue inflammatory tissue-damage to promote healing post-MI.

immunology↗

bioRxiv2024

Ribosome-binding protein 1, RRBP1, maintains peroxisomal biogenesis

Peroxisomes are single membrane-bound organelles essential for human health, yet the mechanisms of peroxisome biogenesis are not fully understood. Here using a systematic double screening approach, we identified ribosome-binding protein 1, RRBP1, as a novel peroxisome biogenesis factor in human cells. Deletion of RRBP1 in HEK293T cells led to a reduction in both peroxisome number and peroxisomal protein levels as well as in defects in processing of peroxisomal matrix proteins, such as ACOX1 and thiolase. However, cell proliferation and protein translation were not altered in cells lacking RRBP1. RRBP1 depletion did not affect peroxisome-ER contact sites, and pexophagy did not contribute to the reduction of peroxisomes in RRBP1 KO cells. Instead, in the absence of RRBP1, peroxisomal proteins were processed by proteasomal degradation, suggesting that RRBP1 plays a role in the insertion of these proteins into ER membranes and their stabilization. Altogether our results showed that RRBP1 promotes peroxisome biogenesis in human cells highlighting the power of systematic approaches in discovering novel factors of organellar biogenesis.

cell biology↗

bioRxiv2023

Peroxisomal tail-anchored proteins do not reach peroxisomes via ER, instead mitochondria can be involved.

Peroxisomes are membrane-enclosed organelles with important roles in fatty acid breakdown, glycolysis, and biosynthesis of sterols and ether lipids. Defects in peroxisome biogenesis result in severe neurological diseases, such as Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, and myelopathies. However, many aspects of peroxisomal biogenesis are not well understood. Here we investigated delivery of tail-anchored (TA) proteins to peroxisomes in mammalian cells. Using glycosylation assays we showed that peroxisomal TA proteins do not enter ER in both WT and peroxisome-lacking cells. We observed that in cells lacking the essential peroxisome biogenesis factor, PEX19, peroxisomal TA proteins localize mainly to mitochondria. However, in PEX3 KO cells, which lack peroxisomes as well, the endogenous TA protein, ACBD5, does not target mitochondria, suggesting that PEX3 plays an important role in targeting of peroxisomal TA proteins to mitochondria. Finally, to investigate peroxisomal TA protein targeting in cells with fully functional peroxisomes we used a proximity biotinylation approach. We showed that while ER-targeted TA construct was exclusively inserted into the endoplasmic reticulum (ER), peroxisome-targeted TA construct was inserted to both peroxisomes and mitochondria. Thus, in contrast to previous studies, our data suggest that peroxisomal TA proteins do not insert to the ER prior to their delivery to peroxisomes. Instead, mitochondria can play a role in the targeting of TA proteins to peroxisomes.

cell biology↗

bioRxiv2021

Assessment and Comparative Study of Biofilm Formation with frequency of Multi Drug Resistance in strains of Staphylococcus aureus

BackgroundThe study was conducted to identify the role of biofilms in the antibiotic susceptibility in the strains of Staphylococcus aureus. A total of 19 non repeated pus/wound swab samples from different anatomic locations and 17 samples that were previously identified as S. aureus and preserved in the labs were included in the study. The Staphylococcus aureus was identified on the basis of colony morphology, Grams stain, biochemical tests (catalase and coagulase tests) and molecular identification through PCR amplification. MethodologyA total of 26 samples were recovered out of the 31 samples. Kirby-Bauer disk diffusion susceptibility test was used to determine the sensitivity or resistance of S. aureus to methicillin. Out of the 26 strains, 4 were highly resistant, 10 were moderately resistant and 12 strains were sensitive. Three different protocols (Tube Method, Congo Red Agar Method and Tissue Culture plate method) were used for the detection of biofilm formation for both resistant and sensitive strains. ResultComparative analysis of the antibiotic susceptibility and biofilm formation by different protocols showed that 70% strains that are resistant to antibiotic methicillin produced moderate-strong biofilms. 50% have produced the moderate-strong biofilms in all 3 protocols. In case of sensitive, 50% strains had produced none-weak biofilms in all 3 protocols. DecisionsThe strains that had zone of inhibition of close to resistance produced weak-strong biofilms but they all produced weak biofilms in CRA method. It can be concluded that the strains of S. aureus that have the ability to produce biofilms become methicillin resistant.

microbiology↗