Biology subjects

Saleh, N.

Publications and source records attributed to Saleh, N..

4 recordsLinked to original sources

bioRxiv2023

Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors

Colorectal cancer exhibits dynamic cellular and genetic heterogeneity during progression from precursor lesions toward malignancy. Leveraging spatial molecular information to construct a phylogeographic map of tumor evolution can reveal individualized growth trajectories with diagnostic and therapeutic potential. Integrative analysis of spatial multi-omic data from 31 colorectal specimens revealed simultaneous microenvironmental and clonal alterations as a function of progression. Copy number variation served to re-stratify microsatellite stable and unstable tumors into chromosomally unstable (CIN+) and hypermutated (HM) classes. Phylogeographical maps classified tumors by their evolutionary dynamics, and clonal regions were placed along a global pseudotemporal progression trajectory. Cell-state discovery from a single-cell cohort revealed recurring epithelial gene signatures and infiltrating immune states in spatial transcriptomics. Charting these states along progression pseudotime, we observed a transition to immune exclusion in CIN+ tumors as characterized by a novel gene expression signature comprised of DDR1, TGFBI, PAK4, and DPEP1. We demonstrated how these genes and their protein products are key regulators of extracellular matrix components, are associated with lower cytotoxic immune infiltration, and show prognostic value in external cohorts. Through high-dimensional data integration, this atlas provides insights into co-evolution of tumors and their microenvironments, serving as a resource for stratification and targeted treatment of CRC.

systems biology↗

bioRxiv2022

A Non-invasive, Biomarker Assay for Detecting Chronic Wasting Disease Pathology in White-tailed Deer

We describe a blood test that exploits differences in the abundance of diagnostic miRNA biomarkers associated with prion infections in cervids. Using sera from 93 pen-raised white-tailed deer euthanized after unintentional exposure to Chronic Wasting Disease (CWD), quantification of candidate reference and diagnostic miRNAs revealed sensitivity of the q-RT-PCR method to interference from sample degradation, requiring exclusion of 60 specimens that exhibited excessive hemolysis or yielded poor amplification of reference or diagnostic miRNAs. Subsequent quantification of three potentially diagnostic and two control miRNAs in the 33 remaining, minimally degraded sera established diagnostic criteria congruent (100% sensitivity, 92.3% specificity, 93.9% accuracy) with results from standard CWD diagnosis by microscopic detection of immunoreactivity in obex and/or medial retropharyngeal lymph nodes (conducted by the National Veterinary Services Laboratory, NVSL, Ames, IA). Overall, the miRNA assay proved to be at least as accurate and sensitive as other CWD testing alternatives to immunohistochemical diagnosis, albeit supported by data from relatively few animals owing to the challenge of acquiring usable specimens from animals euthanized in a mass depopulation. Nevertheless, for sera acquired antemortem, this biomarker-based test may represent a useful new resource for managing spread of CWD that offers the advantages of being rapid, sensitive, non-invasive, and amenable to high throughput scaling.

molecular biology↗

bioRxiv2020

Suspended multiwalled, acid-functionalized carbon nanotubes promote aggregation of the opportunistic pathogen Pseudomonas aeruginosa

The increasing prevalence of carbon nanotubes (CNTs) as components of new functional materials has the unintended consequence of causing increases in CNT concentrations in aqueous environments. Aqueous systems are reservoirs for bacteria, including human and animal pathogens, that can form biofilms. At high concentrations, CNTs have been shown to display biocidal effects; however, at low concentrations, the interaction between CNTs and bacteria is more complicated, and antimicrobial action is highly dependent upon the properties of the CNTs in suspension. Here, impact of low concentrations of multiwalled CNTs (MWCNTs) on the biofilm-forming opportunistic human pathogen Pseudomonas aeruginosa is studied. Using phase contrast and confocal microscopy, flow cytometry, and antibiotic tolerance assays, it is found that sub-lethal concentrations (2 mg/L) of MWCNTs promote aggregation of P. aeruginosa into multicellular clusters. However, the antibiotic tolerance of these "young" bacterial-CNT aggregates is similar to that of CNT-free cultures. Overall, our results indicate that the co-occurrence of MWCNTs and P. aeruginosa in aqueous systems, which promotes the increased number and size of bacterial aggregates, could increase the dose to which humans or animals are exposed.

microbiology↗

bioRxiv2017

The Nuclear And Mitochondrial Genomes Of The Facultatively Eusocial Orchid Bee Euglossa dilemma

Bees provide indispensable pollination services to both agricultural crops and wild plant populations, and several species of bees have become important models for the study of learning and memory, plant-insect interactions and social behavior. Orchid bees (Apidae: Euglossini) are especially important to the fields of pollination ecology, evolution, and species conservation. Here we report the nuclear and mitochondrial genome sequences of the orchid bee Euglossa dilemma Bembe & Eltz. Euglossa dilemma was selected because it is widely distributed, highly abundant, and it was recently naturalized in the southeastern United States. We provide a high-quality assembly of the 3.3 giga-base genome, and an official gene set of 15,904 gene annotations. We find high conservation of gene synteny with the honey bee throughout 80 million years of divergence time. This genomic resource represents the first draft genome of the orchid bee genus Euglossa, and the first draft orchid bee mitochondrial genome, thus representing a valuable resource to the research community.

genomics↗