Biology subjects

Rahman, F.

Publications and source records attributed to Rahman, F..

10 recordsLinked to original sources

bioRxiv2026

Multiphoton tomographic fluorescence lifetime imaging microscopy -TomoFLIM

Fluorescence lifetime imaging microscopy provides quantitative, concentration-independent contrast for probing molecular interactions, biochemical environments and cellular physiology. However, the requirement to acquire sufficient time-resolved photon statistics makes FLIM inherently slow, limiting its application to dynamic biological processes. In live-cell applications, including calcium signalling and vesicular trafficking, acquisition times can exceed the timescale of the underlying biology, causing temporal averaging, motion artefacts and loss of transient information. Methods that increase FLIM acquisition speed while preserving quantitative lifetime accuracy are therefore required. We report on a high-speed, compressive, multiphoton fluorescence lifetime imaging technique (TomoFLIM). Two-photon fluorescence is excited using a line focus projected tomographically across the sample, while time-tagged fluorescence is acquired using time-correlated single-photon counting. Time-resolved fluorescence data are reconstructed using Lucy-Richardson deconvolution followed by a computationally efficient centre-of-mass method lifetime estimator. In addition, TomoFLIM Net, a physics-informed neural-network, directly reconstructs fluorescence intensity and lifetime from compressed time-resolved tomographic data. TomoFLIM was benchmarked against raster-scanned fluorescence lifetime measurements using calibrated fluorescence lifetime beads and biological specimens. We demonstrate imaging at compression ratios exceeding 90%, with Pearson correlation coefficients above 80% relative to reference images. A raster-scanned FLIM dataset acquired in 60 s was reproduced using TomoFLIM in 3.75 s, representing a 16-fold increase in frame rate and equivalent reduction in accumulated dark counts. TomoFLIM Net recovered distinct experimental bead lifetime populations, demonstrating a direct route from compressed measurements to quantitative lifetime maps. TomoFLIM therefore offers significant potential for rapid live-cell imaging of dynamic biological processes, including deep within turbid biological specimens.

biophysics↗

bioRxiv2026

Identifying Convergent Therapeutic Targets and Pathways for Post-Traumatic Stress Disorder, Schizophrenia And Bipolar Disorder via In Silico Approaches

ObjectiveThe objective of this study is to provide a concise overview of the various molecular problems and possible treatment targets that have been linked and associated with the onset of certain psychiatric diseases. MethodsObtaining the data from NCBI, we applied GREIN to analyze our datasets. The protein-protein interaction, gene regulatory network, protein-drug-chemical, gene ontology, and pathway network were constructed using STRING, Funrich and DAVID libraries. In order to display our suggested network, we utilized Cytoscape and R studio, verifying our hub gene using roc analysis. ResultsWe discovered a number of strong candidate hub proteins in significant pathways, namely out of 32 (HLA-DRA, HLA-A, HLA-B, HLA-DOB and BRD2) common genes. We also identified a number of TFs (FOXC1, NFYA, RELA, GATA2, FOXL1, SRF and NFIC); miRNA (hsa-mir-129-2-3p, hsa-mir-148b-3p, hsa-mir-196a-5p, hsa-mir-26a-5p, hsa-mir-27a-3p, hsa-mir-23b-3p, hsa-mir-500a-3p, hsa-mir-423-5p, hsa-miR-142-5p, and hsa-miR-671-5p) and chemicals (Estradiol, Antirheumatic Agents, Valproic Acid, Selenium, Vitamin E, ICG 001, Ifosfamide, Tetrachlorodibenzodioxin, arsenic trioxide, entinostat, sodium arsenite and Hydralazine) may control DEGs in transcription as well as post-transcriptional expression levels. ConclusionIn summary, our computational methods have identified distinct potential biomarkers that demonstrate the impact of PTSD, Schizophrenia, and BD on autoimmune inflammation and infectious diseases. Additionally, we have identified pathways and gene regulators through which these psychiatric disorders may affect biological processes. Graphical AbstractThe graphical abstract demonstrates the thorough strategy of combining systems biology and computational technologies to identify significant markers and pathways in blood tissues impacted by post-traumatic stress disorder, Schizophrenia, and Bipolar disorder. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/708243v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1cd13bforg.highwire.dtl.DTLVardef@cb6392org.highwire.dtl.DTLVardef@f634cforg.highwire.dtl.DTLVardef@532bd_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Mapping the nuclear landscape with multiplexed super-resolution fluorescence microscopy

The nucleus coordinates many different processes. Visualizing how these are spatially organized requires imaging protein complexes, epigenetic marks, and DNA across scales from single molecules to the whole nucleus. To accomplish this, we developed a multiplexed imaging protocol to localize 13 different nuclear targets with nanometer precision in single cells. We show that nuclear specification into active and repressive states exists along a spectrum of length scales, emerging below one micron and becoming strengthened at the nanoscale with unique organizational principles in both heterochromatin and euchromatin. HP1- was positively correlated with DNA at the microscale but uncorrelated at the nanoscale. RNA Polymerase II, p300, and CDK9 were positively correlated at the microscale but became partitioned below 300 nm. Perturbing histone acetylation or transcription disrupted nanoscale organization but had less effect at the microscale. We envision that our imaging and analysis pipeline will be useful to reveal the organizational principles not only of the cell nucleus but also other cellular compartments.

cell biology↗

bioRxiv2024

A series of spontaneously blinking dyes for super-resolution microscopy

Spontaneously blinking fluorophores permit the detection and localization of individual molecules without reducing buffers or caging groups, thus simplifying single-molecule localization microscopy (SMLM). The intrinsic blinking properties of such dyes are dictated by molecular structure and modulated by environment, which can limit utility. We report a series of tuned spontaneously blinking dyes with duty cycles that span two orders of magnitude, allowing facile SMLM in cells and dense biomolecular structures.

cell biology↗

bioRxiv2023

Determinants of cerebral blood flow and arterial transit time in healthy older adults

Cerebral blood flow (CBF) and arterial transit time (ATT), markers of brain vascular health, worsen with age. The primary aim of this cross-sectional study was to identify modifiable determinants of CBF and ATT in healthy older adults (n=78, aged 60-81 yrs). Associations between cardiorespiratory fitness and CBF or ATT were of particular interest as the impact of cardiorespiratory fitness is not clear in existing literature. Secondly, this study assessed whether CBF or ATT relate to cognitive function in older adults. Results from multiple linear regressions found higher BMI was associated with lower global CBF ({beta}=-0.35, P=0.008) and a longer global ATT ({beta}=0.30, P=0.017), global ATT lengthened with increasing age ({beta}=0.43, P=0.004), and higher cardiorespiratory fitness was associated with longer ATT in parietal ({beta}=0.44, P=0.004) and occipital ({beta}=0.45, P=0.003) regions. Global or regional CBF or ATT were not associated with processing speed, working memory, or attention. In conclusion, preventing excessive weight gain may help attenuate age-related declines in brain vascular health. ATT may be more sensitive to age-related decline than CBF, and therefore useful for early detection and management of cerebrovascular impairment. Finally, cardiorespiratory fitness appears to have little effect on CBF but may induce longer ATT in specific regions.

physiology↗

bioRxiv2023

Lifestyle and brain health determinants of word-finding failures in healthy ageing

Cognitive decline associated with healthy ageing is multifactorial: brain-based and lifestyle factors uniquely and jointly contribute to distinct neurocognitive trajectories of ageing. To evaluate existing models of neurocognitive ageing such as compensation, maintenance, or reserve, we explore how various known brain-based and cardiorespiratory fitness factors intersect to better understand cognitive decline. In a pre-registered study (https://osf.io/6fqg7), we tested 73 healthy older adults aged 60--81 (M = 65.51, SD = 4.94) and collected neuroimaging (functional, structural, and perfusion MRI), cardiorespiratory fitness, and cognitive data to investigate a prominent challenge for older adults: word-finding failures. fMRI signal was recorded while participants responded to a definition-based tip-of-the-tongue task, T1-weighted imaging estimated grey matter volume, and cerebral blood flow was indexed using multi-delay pseudo-continuous arterial spin labelling. Commonality analyses were used to analyse these multi-domain data (neuroimaging, cardiorespiratory fitness, language skills, demographic characteristics) and uncover associations between predictors in explaining age-related tip-of-the-tongue rates. Commonality analyses revealed that functional activation of language networks associated with tip-of-the-tongue states is in part linked with age and, interestingly, cardiorespiratory fitness: the combination of higher cardiorespiratory fitness and functional recruitment in some older adults offsets part of the age-related variance in tip-of-the-tongues. Moreover, age-associated atrophy and perfusion in regions other than those showing functional differences accounted for variance in tip-of-the-tongues. Our findings can be interpreted in the context of the classic models of neurocognitive ageing, suggesting compensation. Brain health indices in concordance with cardiorespiratory fitness can provide a more holistic explanation of individual differences in age-related cognitive decline. HighlightsO_LIWord-finding problems are linked to brain health and cardiorespiratory fitness (CRF) C_LIO_LIBrain activity linked to word-finding failures is modulated by CRF and age C_LIO_LIDistinct contribution of structure and perfusion also associated with word-finding C_LIO_LILinking brain and CRF factors provides better account of age-related cognitive decline C_LI

neuroscience↗

bioRxiv2023

MetaLLM: Residue-wise Metal ion Prediction UsingDeep Transformer Model

Proteins bind to metals such as copper, zinc, magnesium, etc., serving various purposes such as importing, exporting, or transporting metal in other parts of the cell as ligands and maintaining stable protein structure to function properly. A metal binding site indicates the single amino acid position where a protein binds a metal ion. Manually identifying metal binding sites is expensive, laborious, and time-consuming. A tiny fraction of the millions of proteins in UniProtKB - the most comprehensive protein database - are annotated with metal binding sites, leaving many millions of proteins waiting for metal binding site annotation. Developing a computational pipeline is thus essential to keep pace with the growing number of proteins. A significant shortcoming of the existing computational methods is the consideration of the long-term dependency of the residues. Other weaknesses include low accuracy, absence of positional information, hand-engineered features, and a pre-determined set of residues and metal ions. In this paper, we propose MetaLLM, a metal binding site prediction technique, by leveraging the recent progress in self-supervised attention-based (e.g. Transformer) large language models (LLMs) and a considerable amount of protein sequences publicly available. LLMs are capable of modelling long residual dependency in a sequence. The proposed MetaLLM uses a transformer pre-trained on an extensive database of protein sequences and later fine-tuned on metal-binding proteins for multi-label metal ions prediction. A 10-fold cross-validation shows more than 90% precision for the most prevalent metal ions.

bioinformatics↗

bioRxiv2022

Green synthesis of ZnO nanoparticles using Cocos nucifera leaf extract: Characterization, antimicrobial, antioxidant, and photocatalytic activity

Zinc oxide nanoparticles (ZnO NPs) have been successfully prepared using Cocos nucifera leaf extract and investigated with their antimicrobial, antioxidant, and photocatalytic activity. The structural, compositional, and morphological properties of the NPs were recorded and studied systematically to confirm the synthesis. The aqueous suspension of NPs showed a UV-Vis. absorption maxima of 370 nm indicating primarily its formation. The XRD analysis identified the NPs with hexagonal wurtzite structure with an average particle size of 16.6 nm. The FTIR analysis identified some biomolecules and functional groups in the leaf extract as responsible for the encapsulation and stabilization of ZnO NPs. The EDX analysis showed the desired elemental compositions in the material. A flower-shaped morphology of ZnO NPs was observed by SEM with a grain size of around 15 nm. The optical properties of the NPs were studied by UV-Vis spectroscopy and the band gap was calculated as 3.37 eV. The prepared ZnO NPs have demonstrated antimicrobial activity against T. harzianum and S. aureus with a ZOI (zone of inhibition) of 14 and 10 mm, respectively. The photocatalytic behavior of ZnO NPs showed absorbance degradation at around 640 nm and discolored methylene blue dye after one hour with a degradation maximum of 84.29 %. Thus, the prepared ZnO NPs could be used potentially in antibiotic development, pharmaceutical industries, and as photocatalysts.

biochemistry↗

bioRxiv2020

DYNC1LI2 regulates localization of the chaperone-mediated autophagy-receptor LAMP2A and improves cellular homeostasis in cystinosis

The dynein motor protein complex is required for retrograde transport but the functions of the intermediate-light chains that form the cargo-binding complex are not elucidated and the importance of individual subunits in the maintenance of cellular homeostasis is unknown. Here, using mRNA arrays and protein analysis, we show that the dynein subunit, intermediate chain 2 (DYNC1LI2) is downregulated in cystinosis, a lysosomal storage disorder caused by genetic defects in the lysosomal cystine transporter, cystinosin. Reconstitution of the expression of DYNC1LI2 in Ctns-/- cells re-established endolysosomal dynamics. Defective vesicular trafficking in cystinotic cells was rescued by DYNC1LI2 expression which correlated with decreased endoplasmic reticulum stress manifested as decreased expression levels of the chaperone Grp78. Mitochondrial fragmentation in cystinotic fibroblasts was also rescued by DYNC1LI2. Survival of cystinotic cells to oxidative stress insult was increased by DYNC1LI2 reconstitution but not by its paralog DYNC1LI1, which also failed to decrease ER stress levels and mitochondrial fragmentation. Restoring DYNC1LI2 expression rescued the localization of the chaperone-mediated autophagy receptor, LAMP2A, and restored cellular homeostasis of cystinotic proximal tubule cells, the primary cell type affected in cystinosis. DYNC1LI2 failed to rescue phenotypes in cystinotic cells when LAMP2A was downregulated or when co-expressed with dominant negative (DN) RAB7 or DN-RAB11, which impair LAMP2A trafficking. DYNC1LI2 emerges as a new target to repair underlying trafficking and CMA defects in cystinosis, a mechanism that is not restored by currently used lysosomal depletion therapies.

cell biology↗

bioRxiv2020

In Silico Investigations on Curcuminoids from Curcuma longa as Positive Regulators of Wnt/β-catenin Signaling Pathway in Wound Healing

Curcuma longa (Turmeric) is a traditionally used herb in wound healing. The efficacy of fresh Turmeric paste to heal wound has already been investigated in multiple ethnobotanical studies. Wnt/{beta}-catenin signaling pathway plays a significant role in wound healing and injury repair processes which has been evident in different in vitro studies. This study aims to analyze the potentiality of Curcuminoids (Curcumin I, Curcumin II and Curcumin III) from Curcuma longa to bind and enhance the activity of two intracellular signaling proteins-Casein Kinase-1 (CK1) and Glycogen Synthase Kinase-3{beta} (GSK3B) involved in Wnt/{beta}-catenin signaling pathway. Present study is largely based on computer-based molecular docking program which mimics the in vivo condition and works on specific algorithm to interpret the binding affinity and poses of a ligand molecule to a receptor. Curcumin I showed better affinity of binding with CK1 (-10.31 Kcal/mol binding energy) and Curcumin II showed better binding affinity (-7.55 Kcal/mol binding energy) for GSK3B. Subsequently, Drug likeness property, ADME/Toxicity profile, Pharmacological activity and Site of metabolism of the Curcuminoids were also analyzed. All of the ligand molecules showed quite similar pharmacological properties.

bioinformatics↗