Biology subjects

Rahim, M.

Publications and source records attributed to Rahim, M..

6 recordsLinked to original sources

bioRxiv2026

Cardiac Myosin Activation Enhances Contractility While Preserving Myocardial Energetics Compared With β-Adrenergic Stimulation

Impaired contractility and reduced myocardial energetic reserve underlie heart failure with reduced ejection fraction. Catecholaminergic inotropes such as dobutamine are used to augment cardiac output. However, dobutamine increases Ca{superscript 2} cycling, raising ATP demand and worsening energetic stress. The myotrope CK-138 increases contractility by directly activating myosin, sparing the added energetic cost of Ca{superscript 2} handling. This study compares CK-138 and dobutamine with respect to the relationship between contractile performance and myocardial energetic state, including high-energy phosphate balance, energetic efficiency, and substrate-specific metabolic fluxes. Isolated rat hearts were perfused with escalating concentrations of CK-138 or dobutamine. Contractility was assessed by measuring left ventricular pressure and rate-pressure product. Myocardial energetics were analyzed using 31P-NMR, and metabolic fluxes by 13C NMR and mass spectrometry. Unlike dobutamine, CK-138 increased LV contractility without increasing heart rate or LV end-diastolic pressure. CK-138 preserved ATP and phosphocreatine levels, maintaining a stable phosphocreatine-to-ATP ratio and free energy of ATP hydrolysis, whereas dobutamine progressively depleted both. At comparable workload, dobutamine exhibited higher glycolytic flux and lactate production, indicating greater reliance on glycolysis relative to mitochondrial oxidative metabolism, whereas CK-138 exhibited a 13% higher rate of ATP synthesis and [~]50% lower anaplerotic flux, consistent with preserved mitochondrial efficiency. In conclusion, CK-138 enhances cardiac contractility while preserving myocardial energetic state and substrate utilization. Unlike dobutamine, which depletes ATP reserves and shifts metabolism toward glycolysis, CK-138 maintains ATP homeostasis and supports oxidative metabolism. These findings support cardiac myosin activators, including CK-138 and omecamtiv mecarbil, as a mechanistically distinct class of energy-efficient inotropes.

physiology↗

bioRxiv2025

Modeling patient tissues at molecular resolution with Eva

Tissue structure is essential to function and homeostasis in all organs, and disruptions to structure usually indicate disease. Modeling relationships between structural, molecular, and clinical aspects of tissues could advance new diagnostics and treatment strategies. Although profiling techniques like spatial proteomics can capture these relationships, the data remain challenging to extract insight from. Here, we present Eva, a foundation model for tissue imaging data that learns multi-scale spatial representations of tissues at the molecular, cellular, and sample level. Eva uses a novel vision transformer architecture and is pre-trained on masked reconstruction of over 40 million matched spatial proteomics and histopathology images. We show that Eva excels at a variety of tasks, including cross-modal inference from H&E to proteomics stains, quality control, data annotation, zero-shot retrieval, survival modeling, and patient stratification. Extensive evaluations on held-out validation data demonstrate the versatility and generalizability of the learned embeddings. We anticipate that Eva will accelerate translational science by bridging basic research and clinical practice.

bioinformatics↗

bioRxiv2024

Coordinated variation in the immune systems and microbiomes of healthy humans is linked to tonic interferon states

Human immune systems are highly variable, with most variation attributable to non-genetic sources. The gut microbiome crucially shapes the immune system; however, its relationship with the baseline immune states of healthy humans remains incompletely understood. Therefore, we performed multi-omic profiling of 110 healthy participants through the ImmunoMicrobiome study. A factor-based integrative approach identified coordinated variation, revealing that the tonic interferon response was amongst the most variable immune features in healthy participants. Microbiome composition, pathways, and stool metabolites varied concomitantly with interferon response pathways. Distinct transcriptional programs involving inflammation and TGF-{beta} in SIGLEC-1high monocytes and CD69high activated MAIT and NK cells were representative of these programs. Our study provides extensive data to examine the relationship between the immune states and microbiomes of healthy individuals at steady state, which paves the way for delineating inter-individual differences relevant for disease susceptibility and responses to therapy.

immunology↗

bioRxiv2021

Unbuttoning the impact of N501Y mutant RBD on viral entry mechanism: A computational insight

The ongoing coronavirus disease 2019 (COVID-19) pandemic has become a serious global threat. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for this pandemic has imposed a severe burden on the medical settings. The spike (S) protein of SARS-CoV-2 is an important structural protein playing a key role in the viral entry. This protein is responsible for the receptor recognition and cell membrane fusion process. The recent reports of the appearance and spread of new SARS-CoV-2 strain has raised alarms. It was reported that this new variant containing the prominent active site mutation in the RBD (N501Y) was rapidly spreading within the population. The reported N501Y mutation within the spikes essential part, known as the receptor-binding domain has raised several questions. Here in this study we have tried to explore the effect of N501Y mutation within the spike protein using several in silico approaches

bioinformatics↗

bioRxiv2020

CRISPR-mediated isogenic cell-SELEX approach for generating highly specific aptamers against native membrane proteins

IntroductionThe generation of affinity reagents that bind native membrane proteins with high specificity remains challenging. Most in vitro selection paradigms utilize different cell types for positive and negative rounds of selection (where the positive selection is against a cell that expresses the desired membrane protein and the negative selection is against a cell that lacks the protein). However, this strategy can yield affinity reagents that bind unintended membrane proteins on the target cells. To address this issue, we developed a systematic evolution of ligands by exponential enrichment (SELEX) scheme that utilizes isogenic pairs of cells generated via CRISPR techniques. MethodsUsing a Caco-2 epithelial cell line with constitutive Cas9 expression, we knocked out the SLC2A1 gene (encoding the GLUT1 glucose transporter) via lipofection with synthetic gRNAs. Cell-SELEX rounds were carried out against wild-type and GLUT1-null cells using a single-strand DNA (ssDNA) library. Next-generation sequencing (NGS) was used to quantify enrichment of prospective binders to the wild-type cells. Results10 rounds of cell-SELEX were conducted via simultaneous exposure of ssDNA pools to wild-type and GLUT1-null Caco-2 cells under continuous perfusion. The top binders identified from NGS were validated by flow cytometry and immunostaining for their specificity to the GLUT1 receptor. ConclusionsOur data indicate that highly specific aptamers can be isolated with a SELEX strategy that utilizes isogenic cell lines. This approach should be broadly useful for generating affinity reagents that selectively bind to membrane proteins in their native conformations on the cell surface.

bioengineering↗

bioRxiv2016

Predicting brain-age from multimodal imaging data captures cognitive impairment

The disparity between the chronological age of an individual and their brain-age measured based on biological information has the potential to offer clinically-relevant biomarkers of neurological syndromes that emerge late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional brain data, here we investigate how multimodal brainimaging data improves age prediction. Using cortical anatomy and whole-brain functional connectivity on a large adult lifespan sample (N = 2354, age 19-82), we found that multimodal data improves brain-based age prediction, resulting in a mean absolute prediction error of 4.29 years. Furthermore, we found that the discrepancy between predicted age and chronological age captures cognitive impairment. Importantly, the brain-age measure was robust to confounding effects: head motion did not drive brain-based age prediction and our models generalized reasonably to an independent dataset acquired at a different site (N = 475). Generalization performance was increased by training models on a larger and more heterogeneous dataset. The robustness of multimodal brain-age prediction to confounds, generalizability across sites, and sensitivity to clinically-relevant impairments, suggests promising future application to the early prediction of neurocognitive disorders.\n\nHighlightsO_LIBrain-based age prediction is improved with multimodal neuroimaging data.\nC_LIO_LIParticipants with cognitive impairment show increased brain aging.\nC_LIO_LIAge prediction models are robust to motion and generalize to independent datasets from other sites.\nC_LI

neuroscience↗