Search bioRxiv⌕ Search

Biology subjects

Ali, S. S.

Publications and source records attributed to Ali, S. S..

7 recordsLinked to original sources

Identification of an Endothelial Senotype Predicted by Ion Channel Expression in Aged Murine Perigonadal Adipose Tissue

Adipose tissue plays a key role in metabolic health, contributing to systemic dysfunction upon obesity or aging. A major driving factor of adipose-driven dysfunction is the accumulation of senescent cells (SnCs), but identification and characterization of specific SnCs is limited. To identify age-dependent SnCs, we performed snRNA-Seq on young and old adipose using two independent analytical strategies. The first, a SenMayo-based approach and the second, dependent on SEAC guidelines and Pearson correlation identified senescent nuclei in endothelial clusters. Subsequent subclustering and cell-to-cell communication analyses identified endothelial capillary nuclei that overexpress macrophage migration inhibitory factor (Mif), which exemplifies the specific characteristics and microenvironment of SnCs. Finally, rank analysis identified ion channel transport genes as the most predictive of the SnCs. Overall, these results highlight new defining features of senescence in endothelial adipose tissue and provide novel age-dependent biomarkers.

cell biology↗

Intraspecies sequence-graph analysis of the Phytophthora theobromicola genome reveals a dynamic structure and variable effector repertoires

Phytophthora theobromicola is an emerging cacao pathogen recently identified in Brazil as an aggressive agent of black pod rot. We generated genome assemblies for two P. theobromicola isolates using long-read sequencing and five additional isolates using short reads. Comparative analysis revealed a genome size and predicted gene content comparable to P. citrophthora, a closely related species with a broad host range that includes both citrus and cacao. An intraspecies sequence-graph analysis revealed a highly dynamic genome structure with high proportion of variable effectors. Syntenic orthology analysis across 13 Phytophthora species identified orthologous gene groups conserved only in cacao pathogens and others specific to P. theobromicola. RxLR effectors and CAZymes were particularly enriched among lineage-specific syntenic groups, with RxLRs preferentially located near transposable elements and within gene-sparse, repeat-rich regions. Transcriptome analysis of infected cacao tissues showed that 88% of predicted effectors were expressed, with pods exhibiting the highest number of upregulated genes. Notably, several RxLRs classified as P. theobromicola-specific syntenic orthologs were highly expressed in infected tissues, suggesting that these lineage-specific effectors may play key roles in host-pathogen interactions unique to cacao. Together, our findings highlight the dynamic architecture and functional plasticity of the P. theobromicola genome, providing foundational insights into its virulence strategies and supporting future studies on host adaptation and effector evolution in emerging cacao pathogens.

genomics↗

Evidence associating neutrophilia, lung damage, hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality in critically ill COVID-19 patients

BackgroundCOVID-19 severity and high in-hospital mortality are often associated with severe hypoxemia, hyperlactatemia, and acidosis. Since neutrophil numbers in severe COVID-19 can exceed 80% of the total circulating leukocytes and that they are massively recruited to infected lungs, we investigated whether metabolic acidosis mediated by the glycolytic neutrophils is associated with lung damage and impaired oxygen delivery in critically ill patients. MethodsBased on prospective mortality outcome, 102 critically ill-hospitalized COVID-19 patients were divided into two groups: ICU-Survivors (ICU-S, n=36) and ICU-Non-survivors (ICU-NS, n=66). Blood samples were collected from patients and control subjects to explore correlations between neutrophil counts, lung damage, glycolysis, blood lactate, blood pH, hemoglobin oxygen saturation, and mortality outcome. We also interrogated isolated neutrophils for glycolytic activities and for apoptosis using high-throughput fluorescence imaging complemented with transcriptomic analyses. Stratified survival analyses were conducted to estimate mortality risk associated with higher lactate among predefined subgroups. ResultsNeutrophil counts were consistently higher in critically ill patients while exhibiting remarkably lower apoptosis. Transcriptomic analysis revealed miRNAs associated with downregulation of genes involved in neutrophils apoptosis. Both CT lung damage scores and neutrophil counts predicted mortality. Severinghaus fitting of hemoglobin oxygen saturation curve revealed a right-shift indicating lower oxygen capacity in non-survivors, which is consistent with lower blood-pH observed in the same group. Levels of blood lactate were increased in patients but significantly more in the ICU-NS relative to the control group. ROC analysis followed by Kaplan-Meyer survival analysis stratified to the obtained cut-off values showed that CT damage scores, neutrophil counts, and lactate levels are predictors of mortality within 15 days following blood collection. ConclusionThe current results implicate neutrophilia as a potential player in metabolic acidosis and deranged oxygen delivery associating SARS-CoV-2 infection thus contributing to mortality outcome.

immunology↗

A generic sequential stimulation adapter for reducing muscle fatigue during functional electrical stimulation

BackgroundClinical applications of conventional functional electrical stimulation (FES) administered via a single electrode is limited by rapid onset neuromuscular fatigue. "Sequential" (SEQ) stimulation, involving rotation of pulses between multiple active electrodes, has been shown to reduce fatigue compared to conventional FES. However, there has been limited adoption of SEQ in research and clinical settings. MethodsThe SEQ adapter is a small, battery-powered device that transforms the output of any commercially available electrical stimulator into SEQ stimulation. We examined the output of the adaptor across a range of clinically relevant stimulation pulse parameters to verify the signal integrity preservation ability of the SEQ adapter. Pulse frequency, amplitude, and duration were varied across discrete states between 4-200 Hz, 10-100 mA, and 50-2000 s, respectively. ResultsA total of 420 trials were conducted, with 80 stimulation pulses per trial. The SEQ adapter demonstrated excellent preservation of signal integrity, matching the pulse characteristics of the originating stimulator within 1% error. The SEQ adapter operates as expected at pulse frequencies up to 160 Hz, with a noted failure mode at 200 Hz. ConclusionThe SEQ adapter represents an effective and low-cost solution to increase the utilization of SEQ in existing rehabilitation paradigms.

bioengineering↗

Grain Fe and Zn Contents Linked SSR Markers Based Genetic Diversity Reveal Perspective for Marker Assisted Biofortification Breeding in Rice

Rice is critical for sustainable food and nutritional security; however, nominal micronutrient quantities in grains aggravate malnutrition in rice-eating poor populations. Here, we assessed genetic diversity in grain iron (Fe) and zinc (Zn) contents using trait-linked simple sequence repeat (SSR) markers in 56 fine and coarse grain rice accessions of different geographical origin. Aromatic fine gain accessions contained relatively higher Fe and Zn contents in brown rice (BR) than coarse grain accessions. Genotyping with 24 SSR markers identified 21 polymorphic markers, among which seventeen demonstrated higher gene diversity and polymorphism information content (PIC) values, strongly indicating that markers used in current research were moderate to highly informative for evaluating genetic diversity. Population structure, principal coordinate and phylogenetic analyses classified studied rice accessions into two fine grain specific and one fine and coarse grain admixture subpopulations. Single marker analysis recognized four ZnBR and single FeBR significant marker-trait associations (MTAs), contributing 15.41-39.72% in total observed phenotypic variance. Furthermore, high grain Fe and Zn contents linked marker alleles from significant MTAs were also identified. Collectively, these results indicate availability of wide genetic diversity in rice germplasm and perspective for marker-assisted biofortification breeding.

genetics↗

Computational vaccinology based development of multi-epitope subunit vaccine for protection against the Norovirus infections

Human Norovirus belong to family Calciviridae, it was identified in the outbreak of gastroenteritis in Norwalk, due to its seasonal prevalence known as "winter vomiting disease". Treatment of Norovirus infection is still mysterious because there is no effective antiviral drugs or vaccine developed to protect against the infection, to eradicate the infection an effective vaccine should be developed. In this study capsid protein (A7YK10), small protein (A7YK11) and polyprotein (A7YK09) were utilized. These proteins were subjected to B and T cell epitopes prediction by using reliable immunoinformatics tools. The antigenic and non-allergenic epitopes were selected for subunit vaccine, which can activate cellular and humoral immune responses. Linkers joined these epitopes together. The vaccine structure was modelled and validated by using Errat, ProSA and rampage servers. The modelled vaccine was docked with TLR-7. Stability of the docked complex was evaluated by MD simulation. In order to apply the concept in a wet lab, the reverse translated vaccine sequence was cloned in pET28a (+). The vaccine developed in this study requires experimental validation to ensure its effectiveness against the disease.

immunology↗

The unique genome architecture of the devastating West African cacao black pod pathogen Phytophthora megakarya

Phytophthora megakarya (Pmeg) and P. palmivora (Ppal) are oomycete pathogens that cause black pod rot of cacao (Theobroma cacao), the most economically important disease on cacao globally. While Ppal is a cosmopolitan pathogen, Pmeg, which is more aggressive on cacao than Ppal, has been reported only in West and Central Africa where it has been spreading and devastating cacao farms since the 1950s. In this study, we reconstructed the complete diploid genomes of multiple isolates of both species using single-molecule sequencing. Thirty-one additional genotypes were sequenced to analyze inter- and intra-species genomic diversity. These resources make it possible to better understand the molecular basis of virulence differences in closely related and consequential pathogens and study their evolutionary history. The Pmeg genome is exceptionally large (222 Mbp) and nearly twice the size Ppal (135 Mbp) and most known Phytophthora species ([~]100 Mbp on average). We show that the genomes of both species recently expanded by independent whole-genome duplications (WGD). WGD and the dramatic transposable element associated expansion of a few gene families led to the exceptionally large genome and transcriptome of Pmeg and the diversification of virulence-related genes including secreted RxLR effectors. Finally, this study provides evidence of adaptive evolution among well-known effectors and discusses the implications of effector expansion and diversification.

genomics↗