Biology subjects

Ismail, M.

Publications and source records attributed to Ismail, M..

11 recordsLinked to original sources

bioRxiv2025

Alpha rhythm subharmonics underlie responsiveness to theta burst stimulation via calcium metaplasticity

AO_SCPLOWBSTRACTC_SCPLOWRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique to modulate brain activity, often used in treating Major Depressive Disorder (MDD) by targeting fronto-limbic circuitry. Despite its clinical utility, optimizing rTMS protocols remains challenging due to the complex and variable effects of stimulation parameter changes on synaptic plasticity. Oscillatory brain activity, measurable via Electroencephalography (EEG), serves as a biomarker for functional circuits and treatment response. To better understand the impact of rTMS on brain oscillations and connectivity, we used computational modeling of corticothalamic circuits to explore the mechanisms of stimulus-induced plasticity. We integrated calcium-dependent plasticity (CaDP) with Bienenstock-Cooper-Munro (BCM) metaplasticity formulations in a neural population model of resting-state EEG. By varying protocol parameters, we simulated iTBS effects on spectral power, synaptic efficacy, and calcium concentrations. Our findings highlight a resonance between theta stimulation and individual resting-state alpha rhythms, enhancing incoming excitatory long-term depression (LTD) and inhibitory long-term potentiation (LTP), leading to corticothalamic feed-forward inhibition (FFI). Induced effects were encapsulated by a weakening of corticothalamic loops and enhancement of intrathalamic loops. This work offers a novel paradigm for individualizing iTBS treatments, provides insights into the neurophysiological basis of clinical responsiveness, and offers a framework with which to derive tailored protocols.

neuroscience↗

bioRxiv2024

Covalent inhibitors of the RAS binding domain of PI3Ka impair tumor growth driven by RAS and HER2

Genetic disruption of the RAS binding domain (RBD) of PI 3-kinase (PI3K) prevents the growth of mutant RAS driven tumors in mice and does not impact PI3Ks role in insulin mediated control of glucose homeostasis. Selectively blocking the RAS-PI3K interaction may represent an attractive strategy for treating RAS-dependent cancers as it would avoid the toxicity associated with inhibitors of PI3K lipid kinase activity such as alpelisib. Here we report compounds that bind covalently to cysteine 242 in the RBD of PI3K p110 and block the ability of RAS to activate PI3K activity. These inhibitors have a profound impact on the growth of RAS mutant and also HER2 over-expressing tumors, particularly when combined with other inhibitors of the RAS/MAPK pathway, without causing hyperglycemia.

cancer biology↗

bioRxiv2024

Optimization of citric acid production from sugarcane molasses using Aspergillus niger by submerged Fermentation

The potentiality of citric acid on economy is high because of its multi-purpose uses, particularly in the food and pharmaceutical industries. Bangladesh spent more than million US dollars to import citric acid mostly from India and China. Its consumption is increasing 3.5-4%, annually, indicating the need for better manufacturing alternatives. Globally, citric acid is primarily produced through microbial fermentation with Aspergillus niger. To support the massive scale of production of citrate, the manufacturing process must be eco-friendly which should be inexpensive and available raw materials for maintaining high yielding in a cost-effective manner. In Bangladesh prospective, the current study has undertaken to optimize citric acid production using one of the most abundant raw materials sugarcane molasses. Moreover, the aim of this study was to determine the optimum conditions to produce citric acid from sugarcane molasses using Aspergillus niger (F-81) by submerged fermentation. The amount of citric acid production was determined by Marier-Boulet colorimetric method. The optimization data suggested that 10% substrate (from processed cane molasses), 4% inoculum size of A. niger, and initial pH 6.0 allowed to produce around 25.8 g/L citric acid. Further study is warranted to assess the feasibility of citrate production in an industrial level as well as improvement of microbial strains is needed to further enhance citric acid production.

microbiology↗

bioRxiv2024

Investigating the Triple Code Model in Numerical Cognition Using Stereotactic Electroencephalography

The ability to conceptualize numerical quantities is an essential human trait. According to the "Triple Code Model" (TCM) in numerical cognition, distinct neural substrates encode the processing of visual, auditory, and nonsymbolic numerical representations. While our contemporary understanding of human number cognition has benefited greatly from advances in clinical imaging, limited studies have investigated the intracranial electrophysiological correlates of number processing. In this study, 13 subjects undergoing stereotactic electroencephalography for epilepsy participated in a number recognition task. Drawing upon postulates of the TCM, we presented subjects with numerical stimuli varying in representation type (symbolic vs. non-symbolic) and mode of stimuli delivery (visual vs. auditory). Time-frequency spectrograms were dimensionally reduced with principal component analysis and passed into a linear support vector machine classification algorithm to identify regions associated with number perception compared to inter-trial periods. Across representation formats, the highest classification accuracy was observed in the bilateral parietal lobes. Auditory (spoken and beeps) and visual (Arabic) number formats preferentially engaged the superior temporal cortices and the frontoparietal regions, respectively. The left parietal cortex was found to have the highest classification for number dots. Notably, the putamen exhibited robust classification accuracies in response to numerical stimuli. Analyses of spectral feature maps revealed that non-gamma frequency below 30 Hz held greater than chance classification value and could be potentially used to characterize format specific number representations. Taken together, our findings obtained from intracranial recordings provide further support and expand on the TCM model for numerical cognition.

neuroscience↗

bioRxiv2024

Androgen deprivation therapy-resistant club cells are linked to myeloid cell-driven immunosuppression in the prostate tumor microenvironment

Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated the mechanisms through which cancer cells escape treatment, but their relation toward the tumor microenvironment (TME) remains elusive. Here we present a comprehensive transcriptomic landscape of the prostate TME at multiple points in the standard treatment timeline employing single-cell RNA-sequencing and spatial transcriptomics data from 110 patients. We identify club-like cells as a key epithelial cell subtype that acts as an interface between the prostate and the immune system. Tissue areas enriched with club-like cells have depleted androgen signaling and upregulated expression of luminal progenitor cell markers. Club-like cells display a senescence-associated secretory phenotype and their presence is linked to increased polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) activity. Our results indicate that club-like cells partake in inducing myeloid inflammation previously associated with androgen deprivation therapy resistance, providing a rationale for their therapeutic targeting.

cancer biology↗

bioRxiv2024

Community assesses differential cell communication using large multi-sample case-control scRNAseq datasets.

Cell-cell communication is essential for physiological tissue function. In disease, this communication often gets disbalances by changes in the tissue cell type composition, fraction of cell engaged in communication and the rising or dropping expression levels of ligands, receptors and adhesion molecules. The changes in all these components of communication can be studied using single cell RNA-sequencing (scRNAseq) methods. With dropping sequencing costs, it is now possible to perform scRNAseq studies in larger cohorts of case and control samples to better address the heterogeneity of diseases. Here we present community, an R-based tool that is designed to perform differential communication analysis using scRNAseq between large cohorts of cases and controls. Community is able to reconstruct communication between different cell types both in the case and the control cohort of a dataset, and subsequently analyze which communication channels are affected in disease. Community is the first tool that integrates cell type abundance into the calculation of an interaction strength. Community is also able to disentangle the mechanisms underlying these changes, as well as detect interactions that are kept compensated by a sender or a receiver despite the disbalanced signaling from the counterpart. We tested community on two disease entities, ulcerative colitis and acute myeloid leukemia, using published scRNAseq datasets. We compared the performance of our tool to other differential communication pipelines, which community outperformed in speed and robustness. Overall, community is a fast, well-scalable, user-friendly R tool to assess differential cell-cell communication using large case-control scRNAseq datasets disentangling the driving mechanisms of communication shifts in disease.

bioinformatics↗

bioRxiv2022

Treatment-mediated selection of lethal prostate cancer clones defined by copy number architectures

Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient relationships of metastases that evade treatment, we performed genomewide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 142 metastatic regions from 10 organs harvested post-mortem from nine men who died from prostate cancer. We identified diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number change, we confirmed a common clone of origin across metastases and diagnostic biopsies; and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. Autosome-defined clusters were characterized by cluster-specific AR gene architectures that in two index cases were topologically more congruent than by chance (p-values 0.03, 3.07x10-8). Integration with anatomical site suggested patterns of spread and points of genomic divergence. Copy number boundaries identified treatment-selected clones with putatively distinct lethal trajectories. Statement of significanceLethal prostate cancer evolves from a single clone of origin and upon a treatment-mediated selection, progresses to lethal disease via a limited number of related clones harboring patient-unique androgen receptor gene architectures.

cancer biology↗

bioRxiv2022

Pattern Of Some Inflammatory Mediators Among Adult Patients With Bronchial Asthma On Corticosteroids Attending Aminu Kano Teaching Hospital, Kano, Nigeria

BackgroundBronchial asthma in adults is typified by lingering allergic inflammation associated with elevation in the levels of certain acute phase reactants and indicators of mast cell activation. This study investigated the effect of corticosteroid treatment on the levels of C reactive protein (CRP), serum baseline tryptase (sBT), erythrocyte sedimentation rate (ESR) and granulocyte monocyte colony stimulating factor (GM-CSF) among asthmatics. MethodForty five adult patients with bronchial asthma on treatment with inhaled corticosteroids were enrolled. Forty five blood donors were used as control. Serum levels of CRP, sBT, ESR and GM-CSF were measured using sandwich ELISA. ResultThe GM-CSF, CRP, ESR and sBT were significantly elevated among asthmatics on treatment compared to normal healthy control. Significant difference in the level of GM-CSF, ESR and CRP was observed between asthmatics with mild and moderate disease severity. ConclusionTreatment with inhaled corticosteroids doesnt restore the levels of GM-CSF, CRP, sBT and ESR to normalcy among asthmatics.

immunology↗

bioRxiv2021

Crystal Structures of Ferritin Grown by the Microbatch Method in the Presence of Agarose and Electric Field Shows Enhanced Metal Binding

Ferritin is an ubiquitous iron storage protein found in all kingdoms of life. Ferritin is essential for iron homeostasis and is involved in a wide range of physiological and pathological processes. Several structures of ferritin in complex with small molecules and metal ions have been reported. Here we report the crystal structures of Horse Spleen Ferritin, in which the crystals were grown by employing a novel approach adopting the microbatch experiments performed in the presence and absence of electric field using a 2% agarose pellet of CdSO4. We observed that 1) these structures contain increased number of Cd ions as compared to the crystallization of same protein by others using different methods. 2) The externally applied electric field reduced the number of nucleation and with fewer nucleation the size of the crystals increased. 3) There is no significant conformational change observed among these structures. 4) Irrespective of the externally applied electric field, this agarose microbatch crystallization method facilitates the retaining of increased number of bound metal ions with ferritin to mimic the possible in vivo environment.

biochemistry↗

bioRxiv2019

The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes

The human naive T-cell receptor (TCR) repertoire is extremely diverse and accurately estimating its distribution is challenging. We address this challenge by combining a quantitative sequencing protocol of TCRA and TCRB sequences with computational modelling. We observed the vast majority of TCR chains only once in our samples, confirming the enormous diversity of the naive repertoire. However, a substantial number of sequences were observed multiple times within samples, and we demonstrated that this is due to expression by many cells in the naive pool. We reason that and {beta} chains are frequently observed due to a combination of selective processes and summation over multiple clones expressing these chains. We test the contribution of both mechanisms by predicting samples from phenomenological and mechanistically modelled repertoire distributions. By comparing these with sequencing data, we show that frequently observed chains are likely to be derived from multiple clones. Still, a neutral model of T-cell homeostasis cannot account for the observed distributions. We conclude that the data are only compatible with distributions of many small clones in combination with a sufficient number of very large naive T-cell clones, the latter most likely as a result of peripheral selection.

immunology↗

bioRxiv2019

Prevalence and Risk Factors for Child Labour and Violence against Child issues in Egypt using Bayesian Geospatial Modelling with Multiple Imputation

BackgroundThe incidence of child labour, especially across the developing nations is of global concern. The use of children in employment in developing economies constitutes a major threat to the societies, and concerted efforts are made by the relevant stakeholders towards addressing some of the factors/issues responsible for the menace. Significant risk factors include socio-demographic and economic factors, including poverty, neglect, lack of adequate care, and exposure of children to various grades of violence, parental education status, gender, place of residence, household size, residences type or size, wealth index, parental survivorship and household size. ObjectivesThis study, therefore, focuses on identifying socio-demographic/economic and geospatial factors associated with child labour participation. MethodsWe utilised 2014 Demographic and Health Survey (EDHS) from the Ministry health and Population in Egypt, with the record of 20, 560 never married children aged 5-17years engaging in economic activities, in and out of their home. The data focused on demographic and socio-economic characteristics of household members. Multivariate Bayesian geo-additive models were employed to examine the demographical and socio-economic factors for children working less than 16hrs; between 16 and 45hrs and above 45hrours weekly. ResultsThe results showed that at least 31.6% of the children in the age group from 5-10 were working, 68.5% of children aged 11-17 years engaging in child labour (wage), while 44.7 of the children in the age group from 5-10 were engaged in hazard work. From the multivariate Bayesian geo-additive models, the female children (with male children as reference category) working at least 16hrs (OR: 1.3; with 95% CI: 1.2-1.5) are more likely to be engaged in child labour than those working 16 to 45hours (OR: 1; 95% CI: 0.3-1.5). Children born to women without formal education, under non-hazardous jobs, irrespective of the hours spent at work, were mostly exposed to child labour with following percentages: 52.9%, 56.8%, 62.4%, compared to children of mothers with some levels of education. Finally, children that have experienced psychological aggression and physical punishment are mostly exposed to child labour than those without such experience across the job types and hours spent. ConclusionThis study revealed a significant influence of socio-demographic and economic factors on the children labour and violence against children in Egypt. Poverty neglects, lack of adequate care and exposures of children to various grades of violence are major drivers of child labour across the country. North-eastern region of Egypt has a higher likelihood of child labour than most other regions, while children who live in Delta are more engaged in hazard work.

epidemiology↗