Biology subjects

Islam, S. S.

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

8 recordsLinked to original sources

bioRxiv2026

Gene transcriptional profiling to assess Chinook salmon osmoregulatory resilience to salinity challenges

Given unprecedented environmental change, Pacific salmonids are becoming increasingly threatened; however, genomic technologies provide an opportunity to assess Pacific salmonid resilience to on-going environmental change. Also, given increasing conservation and animal welfare concerns, non-lethal tissue sampling is emerging for assessing the physiological status of wild species. Relatively few studies, however, have compared the transcriptomic response of fish sampled non-lethally versus lethally for fish health and stress quantification. Here, we conducted a comparative gene transcriptional profiling study using 28 qPCR assays on the OpenArray platform as an osmoregulatory stress transcriptional profiling chip. We sampled both non-lethal (gill biopsies, skin swabs, and water [eRNA]) and lethal (whole gill and liver) tissue samples from Chinook salmon (Oncorhynchus tshawytscha) smolts exposed for 0 h, 24 h, and 72 h to freshwater (0 PSU), brackish water (15 PSU) or seawater (30 PSU). We observed that most assays showed higher qPCR amplification success in both non-lethal gill biopsies and lethal gill tissues, compared to other tissues. We found more significant differences in transcript abundance in traditional lethal tissues compared to non-lethal tissues. With increasing duration of salinity exposure, gene transcript levels were typically upregulated in seawater samples compared to freshwater samples for both non-lethal and lethal tissues. The targeted genes for both non-lethal and lethal tissues were significantly and positively correlated across time points. Our findings support the use of non-lethal tissue sampling to improve Chinook salmon hatchery rearing, inform hatchery release timing, and facilitate future field application for the conservation of wild stocks.

genomics↗

bioRxiv2026

Genetically engineered rapamycin responsive K2P channels

Establishment of electrical potentials across biological membranes is a universal feature of all cells. Tandem pore domain (K2P) potassium ion channels play pivotal roles in maintaining cellular membrane potentials, shaping physiological responses across a diverse range of cell types. With only a limited repertoire of high-aAinity and subtype-selective K2P modulators available for experimental or therapeutic use, we devised a strategy to genetically engineer K2P channels that are potently activated by rapamycin or non-immunomodulatory rapamycin analogs. Insertion of the FRB domain of mTOR into a short flexible cytoplasmic loop between the second and third transmembrane (TM) domains of the TREK1 K2P channel yielded fusion channels that are activated by nanomolar concentrations of rapamycin. Rapamycin-induced potentiation requires recruitment of an FKBP binding partner, from either the endogenous pool of FKBP within the cell or through fusion of FKBP to the C-terminus of TREK1. Formation of an FRB/rapamycin/FKBP ternary complex within the core of the TREK1 channel leads to an increase in TREK1 single-channel open probability and unitary current, mimicking positive modulatory eAects of conventional TREK1 activating cues. Cryo-EM structures demonstrate that rapamycin-induced ternary complex formation rigidifies the position of the FRB and stabilizes the TM2/TM3 loop in an active channel conformation. We demonstrate that FRB fusion can be employed to successfully activate several K2P channel isoforms, providing chemogenetically targetable tools for direct manipulation of cellular membrane potential.

bioengineering↗

bioRxiv2025

Investigating the prognostic value of KCNN4 gene expression in human pancreatic adenocarcinoma by bioinformatic analysis

Finding accurate biomarkers for early detection and prognosis is critical because pancreatic adenocarcinoma (PAAD) is a deadly cancer with a poor prognosis. Though its function in PAAD is still unknown, the gene KCNN4, which codes for a calcium-activated potassium channel, has been linked to a number of malignancies. In this work, the cancer studies of the CPTAC, TCGA, and GTEx projects were targeted using a thorough database mining technique. Several analytical methods were used to examine full-scale molecular, expression, and prognostic profiles of the KCNN4 gene in pancreatic adenocarcinoma tissues. It was discovered that the majority of the cancerous tissue had different levels of mRNA and protein expression for this gene. The results of comparative immunohistochemistry also revealed that normal pancreatic tissues had reduced expression of the KCNN4 protein. An analysis overview of copy-number alterations and KCNN4 mutations in PAAD samples was also conducted. Furthermore, there was a correlation found between the expression of KCNN4 and both overall and disease-free survival in pancreatic adenocarcinoma. In pancreatic adenocarcinoma tissue, co-expressed genes of KCNN4 were found to be involved in cell maintenance-related functions, according to gene coexpression, additional ontology, and pathway analysis. When it comes to cancer diagnosis and treatment, the experimental findings of this study should aid in integrating KCNN4 into clinical applications.

bioinformatics↗

bioRxiv2024

Transcriptional profiling provides insights on sublethal thermal stress thresholds in juvenile bull trout

Bull trout (Salvelinus confluentus) inhabit mainly cold-water streams in their Western North American range. Multiple anthropogenic stressors, including climate change, have caused population declines and range reduction, leading to classification of bull trout as threatened. Characterizing how fish respond to increasing temperature can identify key thresholds beyond which fish health is impacted, which is useful for developing species recovery strategies. Juvenile bull trout were acclimated to a range of relevant temperatures (6-21 {degrees}C), after which mRNA transcripts involved in responding to thermal stress were measured using high- throughput qPCR, and their upper thermal tolerance (critical thermal maximum, CTmax) was determined. Beyond 18 {degrees}C appears to be a critical sublethal threshold for bull trout: capacity to increase CTmax through acclimation was lost, growth and survival decreased, and transcriptional data suggest widespread activation of cellular stress and growth suppression. Below 18 {degrees}C, transcriptional data suggest subtler metabolic adjustments in response to acclimation temperature, preceding changes in whole-animal performance. Altogether, these data provide insight into thermal responses in bull trout, and their capacity to cope with climate-change related warming.

physiology↗

bioRxiv2024

Development of multi-species qPCR assays for a stress transcriptional profiling (STP) Chip to assess the resilience of salmonids to changing environments

Ecologically and socio-economically important salmonid fishes in Canada are threatened by diverse environmental stressors. However, predicting species responses to environmental change requires understanding the underlying molecular mechanisms governing environmental stress tolerance. Developing advanced molecular genetic tools will provide opportunities to predict how salmonid fishes will respond to environmental stressors and assess their adaptive potential and vulnerability into the future. Here, we developed a panel of Taqman quantitative PCR (qPCR) assays designed to measure mRNA transcript abundance at selected candidate loci for use across salmonids. We designed and applied those assays for use in a high-throughput nanofluidic OpenArray Stress Transcriptional Profiling Chip (STP-Chip) capable of 2688 simultaneous qPCR at multiple gene loci (112 targets for 12 samples in duplicate). Using the nanofluidic STP-Chip, we tested these 112 multi-species qPCR assays using gill, liver and muscle tissue from eight species of salmonids across four genera. Of the selected 112 assays, 69 assays showed amplification in gill, 64 in liver, and 67 in muscle across all eight salmonid species. The percentage of assays that showed amplification across three tissues varied between genera: In general, Salmo, Oncorhynchus, and Salvelinus species showed a higher success rate than Coregonus species. Stress, circadian rhythm, apoptosis, growth-metabolism, and detoxification-relevant assays showed high success rates for amplification across all salmonid species for all three tissues. In contrast, neural plasticity, appetite regulation, osmoregulation, immune function, endocrine disruption, and hypoxia-relevant assays showed low success. Not surprisingly, we observed tissue-specific variation among qPCR amplification patterns. There were significant differences in mRNA transcript abundance among species across the four genera, but we did not see variation between species from the same genus. These qPCR assays can be used to design custom STP-Chips that can be used for quantifying stress in salmonid fish, improving health through more accurate diagnostic tests for disease, and monitoring adaptation to accelerated climate change regionally and globally.

genomics↗

bioRxiv2023

Neurovascular Mechanisms of Cognitive Aging: Arteriosclerosis Precipitates Demyelination and Cognitive Decline

Arterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimers disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to ones biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data (N = 203, age range = 18-87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity. By applying a novel piecewise regression approach to our cross-sectional sample to support Granger-like causality inferences, we show that, on average, a precipitous decline in cerebral arterial elasticity (measured with diffuse optical imaging of the cerebral arterial pulse; pulse-DOT) temporally precedes an acceleration in the development of white matter lesions by nearly a decade, with women protected from these deleterious effects until approximately age 50, the average onset of menopause. By employing multiple-mediator path analyses while controlling for sex, we show that age may impair cognition via the sequential indirect effects of arteriosclerosis and white matter atrophy on fluid, but not crystallized, abilities. Importantly, we replicate these results using pulse pressure, an independent index of arterial health, thereby providing converging evidence for the central role of arteriosclerosis as an accelerating factor in normal and pathological aging and identifying robust sex-related differences in the progression of cerebral arteriosclerosis and white matter degradation.

neuroscience↗

bioRxiv2020

Single generation exposure to a captive diet: a primer for domestication selection in a salmonid fish?

Millions of wild animals in captivity are reared on diets that differ in their uptake and composition from natural conditions. Few studies have investigated whether such novel diets elicit unintentional domestication selection in captive rearing and supplementation programs. In highly fecund salmonid fishes, natural and captive mortality is highest in the first few months of exogenous feeding. This high early mortality might be a potent driver of unintentional selection because wild fish normally forage on live prey whereas they are fed almost exclusively pellet feed in captivity: fish that do not adapt pellet feed well under captive conditions experience reduced growth and/or die. We tested this hypothesis by generating a large number of families from F1 captive and wild fish originating from the same three populations and then rearing them each on pellet and natural, live, drifting feed for three months at the beginning of exogenous feeding. We found that captive fish of every population grew faster than wild fish in all diet treatments. Populations exhibited an idiosyncratic response to diet treatment, with two populations exhibiting faster growth on a pellet diet versus the natural diet but another population exhibiting similar growth in both diet treatments. Fish exposed to a natural diet also exhibited higher survival relative to those given a pellet diet. Captive and wild fish did not differ in survival, regardless of population of origin. Overall, we found evidence that rapid domestication selection associated with a single generation exposure to a novel captive diet generates genetically-based changes to individual fitness (e.g., growth and survival) in a wild fish.

evolutionary biology↗

bioRxiv2020

In Silico Analysis of Some Phytochemicals as Potential Anti-cancer Agents Targeting Cyclin Dependent Kinase-2, Human Topoisomerase IIa and Vascular Endothelial Growth Factor Receptor-2

Cancer is caused by a variety of pathways, involving numerous types of enzymes, among them three enzymes: Cyclin dependent kinase-2 (CDK-2), Human topoisomerase II and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) are three most common enzymes that are involved in the cancer development. Although many chemical drugs are available in the market, plant sources are known to contain a wide variety of agents that are known to possess anticancer activity. In this experiment, total thirty compounds were analysed against the mentioned enzymes using different tools of bioinformatics and in silico biology like molecular docking study, druglikeness property experiment, ADME/T test, PASS prediction and P450 site of metabolism prediction as well as DFT calculations to determine three best ligands that have the capability to inhibit the mentioned enzymes. Form the experiment, Epigallocatechin gallate was found to be the best ligand to inhibit CDK-2, Daidzein showed best inhibitory activities towards Human topoisomerase II and Quercetin was predicted to be the best agent against VEGFR-2. They were also predicted to be quite safe and effective agents to treat cancer. However, more in vivo and in vitro analysis are required to confirm their safety and efficacy in this regard.

bioinformatics↗