Biology subjects

Tahir, A.

Publications and source records attributed to Tahir, A..

5 recordsLinked to original sources

bioRxiv2026

Potassium-Selective Nanoelectrode Arrays for Single-Cell Profiling of human iPSC-Derived Cardiomyocytes

Potassium ion (K) dynamics are central to cardiac electrophysiology, with early disruptions in K flux often preceding arrhythmia and contractile dysfunction. However, current sensing technologies, such as patch-clamp, Microelectrode arrays (MEAs), and fluorescent indicators, either lack chemical specificity for K or are unsuitable for long-term, single-cell analysis. Conventional ion-selective electrodes (ISEs), while more selective, are limited by bulk-phase design and poor spatial resolution. To address these limitations, we present KINESIS (K-Ion Nano-Electrode Selective Interface System), a nanofabricated, cell-compliant platform that enables direct, label-free potentiometric measurement of K gradients with subcellular precision. KINESIS features high-aspect-ratio nanopillars coated with a valinomycin-based K recognition membrane, forming a stable, non-invasive interface with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This architecture allows localized, Nernstian sensing of K efflux or depletion without disrupting cell membranes. Pharmacological validation shows distinct potential shifts in response to caffeine and ouabain. KINESIS thus offers a highly selective, spatially resolved approach for studying K handling in cardiotoxicity screening and patient-specific disease modeling.

pharmacology and toxicology↗

bioRxiv2025

LipidQMap - An Open-Source Tool for Quantitative Mass Spectrometry Imaging of Lipids

Mass spectrometry imaging (MSI) is a powerful tool in both basic and clinical research, enabling spatial visualization of biomolecules and drugs in tissue sections. However, factors influencing mass spectrometric response during imaging are increasingly recognized for their impact on apparent molecular distribution. Quantitative mass spectrometry imaging (qMSI) addresses this variability by incorporating analytical standards that undergo the same processes as analytes. While qMSI sample preparation protocols for omics-scale quantitative lipidomics are actively evolving, software solutions for downstream data processing remain scarce. Here, we introduce LipidQMap, the first open-source platform for processing omics-scale qMSI lipidomics data. LipidQMap applies one-point calibration, normalizing annotated lipid signals against class-specific standards on a pixel-by-pixel basis, and generates concentration heat maps in pmol/mm2. The software supports centroided data import, recalibration, and lipid identification using a built-in, user-modifiable lipid database. LipidQMap resolves Na/H adduct isobaric overlaps by leveraging sodiated-to-protonated adduct ratios of standards, validated across several MSI platforms using mouse brain sections. Type II isobaric overlaps are corrected using predicted isotopic patterns. Extensive validation demonstrates that LipidQMap is robust across MSI platforms and harmonizes qMSI data, enabling more accurate and reproducible spatial lipid quantification.

bioinformatics↗

bioRxiv2025

Aging of the blood-brain barrier: Metabolic signatures of mouse brain endothelial cell senescence

The blood-brain barrier (BBB) declines with age, with endothelial senescence implicated as a contributor, yet its metabolic features remain incompletely defined. We induced senescence in mouse brain endothelial cells (BECs) using the chemotherapeutic doxorubicin and the oxidative stress mediator hydrogen peroxide and performed untargeted mass spectrometry of cell lysates and supernatants. Senescence was confirmed by increased senescence-associated {beta}-galactosidase activity and elevated cyclin-dependent kinase inhibitors p16 and p21, along with increased Il-6 mRNA as senescence-associated secretory phenotype marker. At the BBB structural level, occludin was consistently reduced, ZO-1 decreased with H2O2 (with a similar trend under doxorubicin), and claudin-5 showed a variable, non-significant reduction, indicating target- and inducer-specific junctional remodeling. Pathway mapping highlighted prominent remodeling of lipid metabolism (including glycerophospholipids, sphingolipids, acylcarnitines) and amino-acid pathways, with both shared and inducer-specific shifts. These discovery-stage in vitro results recapitulate several metabolites previously associated with senescence across tissues and nominate additional candidates for hypothesis testing. To increase mechanistic and translational relevance, we outline a staged roadmap: validation in advanced multicellular and flow-based BBB models followed by in vivo studies, with attention to route-specific BBB readouts. Overall, this work provides a curated snapshot of metabolic remodeling in brain endothelial senescence that co-occurs with selective tight-junction alterations relevant to BBB aging. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/670255v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1644442org.highwire.dtl.DTLVardef@1bd5821org.highwire.dtl.DTLVardef@1e4efd5org.highwire.dtl.DTLVardef@13d942d_HPS_FORMAT_FIGEXP M_FIG C_FIG Mouse brain endothelial cells exposed to doxorubicin (Dox) or hydrogen peroxide (H2O2) underwent senescence ({uparrow}SA-{beta}-gal activity, p16/p21 expression), accompanied by selective reductions in tight-junction proteins. Untargeted mass spectrometry profiled metabolites in cell lysates and supernatants. Lipids, followed by amino acid metabolites, comprised the largest share of alterations, highlighting these pathways as major components of metabolic reprogramming associated in endothelial senescence.

neuroscience↗

bioRxiv2024

Causality Mapping Using Resting-state fMRI Reveals Hyperactivity and Hypoconnectivity in Schizophrenia Patients

Schizophrenia (SZ) is a debilitating disorder in which patients exhibit psychotic behavior due to aberrant connectivity between different regions of the brain. Advances in neuroimaging have now enabled the diagnosis and analysis of SZ in order to elucidate the whole brain functional connectivity networks. In the present study, we have used resting-state functional magnetic resonance imaging (rs-fMRI) to elucidate the causal relationships amongst the differentially activated brain regions between SZ patients (n=10) and healthy controls (n=10). Vector auto-regression (VAR) model and Granger causality (GC) were then applied to construct a functional connectivity network and analyze the causal effects in SZ patients. Our results revealed that the average voxel activation in the frontal lobe (FL), basal ganglia (BG), and ventricular system (VS) was significantly higher in patients indicating hyper-activity as compared to controls. Conversely, cerebellum white matter (CBWM) showed higher activation in the controls as compared to patients. A higher Pearson correlation was observed between the controls as compared to patients while VAR and GC showed higher functional connectivity among all the regions of interest (ROIs) along with more causal relations in the controls. Finally, mediation analysis showed that right middle superior frontal gyrus acts as a strong partial mediator between left accumbens area and left middle superior frontal gyrus. Taken together, this study decodes the dysregulated brain activity in schizophrenia showing hyperactivation in patients when compared with the healthy controls which leads to alterations in neural connections resulting in hypoconnectivity.

neuroscience↗

bioRxiv2020

Extreme acid resistance of human cheek epithelial cells.

Human cheek epithelial cells, despite residing in an almost neutral environment of the mouth, are exposed to many acidic stimuli, so these cells may possess acid resistance. Our researchs objective is to find out if isolated human cheek epithelial cells can survive in highly acidic conditions, and whether there is any difference in acid resistance between cheek epithelial cells of males and females; and to establish a protocol. We collected 3 buccal swab samples from each male or female participant and gave following 3 different treatments to their samples: (i) Milli-Q water (ii) HCl with pH of -0.48 (iii) HCl with pH of - 0.48 and, then, rehydration with Milli-Q water. Staining and microscopic analysis showed that cheek epithelial cells did not burst after acid treatment. However, they slightly shrunk in size and were stained substantially darker. Moreover, cells that were rehydrated after acid treatment, provided further evidence of their survival because these cells, as a result of rehydration, had substantially regained bigger size as well as lighter staining. Furthermore, at pH of -0.48, no difference was observed in acid resistance of the cells from the two genders. Results of this study, which is the only one to incubate cheek epithelial cells at pH < 2.0, manifest that the human cheek epithelial cells, isolated from any of the two genders, are extremely acid-resistant and do not burst in highly acidic conditions. Besides, these cells may also be useful as model cells for the study of acid-resistant pathogens and acid-resistant cancer cells.

cell biology↗