Biology subjects

Ibrahim, R.

Publications and source records attributed to Ibrahim, R..

7 recordsLinked to original sources

bioRxiv2026

Barcoding biology: Chemotype predicts variation in genotype, physiology, and stress response

Predicting biological responses to perturbations such as stress, nutrition, or pharmaceuticals could transform healthcare and biosciences. The task is challenging because complex interactions among many factors interactively drive biological variation, and thereby alter responses. However, metabolism integrates these drivers of variation, suggesting that emergent biological states may be reflected in aggregate chemical states. We define such states as chemotypes and test their predictive utility. Using Fourier-transform infrared (FTIR) spectroscopy coupled with machine learning in Drosophila melanogaster, we show that chemotypes serve as proxies for biological variation driven by sex, genotype, nutrition and age, and - critically - predict among-population variation in stress response. These findings indicate that chemotypes provide a computable and integrative representation of organismal biology, predicting genotype, phenotype, and response to perturbation.

systems biology↗

bioRxiv2025

Lifespan and fecundity impacts of reduced insulin signalling can be directed by mito-nuclear epistasis in Drosophila

The changing demography of human populations has motivated a search for interventions that promote healthy ageing, and especially for evolutionarily-conserved mechanisms that can be studied in lab systems to generate hypotheses about function in humans. Reduced Insulin/IGF signalling (IIS) is leading example, which can extend healthy lifespan in a range of animals; but whether benefits and costs of reduced IIS vary genetically within species is under-studied. This information is critical for any putative translation. Here, in Drosophila, we test for genetic variation in lifespan response to a dominant-negative form of the insulin receptor, along with a metric of fecundity to evaluate corollary fitness costs/benefits. We also partition genetic variation between DNA variants in the nucleus (nDNA) and mitochondrial DNA (mtDNA), in a fully-factorial design that allows us to assess "mito-nuclear" epistasis. We show that reduced IIS can have either beneficial or detrimental effects on lifespan, depending on the combination of mtDNA and nDNA. This suggests that, while insulin signalling has a conserved effect on ageing among species, intraspecific effects can vary genetically, and the combination of mtDNA and nDNA can act as gatekeeper.

genetics↗

bioRxiv2025

Microbiota/gut/neuron axis promotes Drosophila ageing via Acetobacter, Tachykinin, and TkR99D

Gut microbiota exert an evolutionarily conserved influence on ageing, from invertebrates to humans. How do microbes that are physically confined to the gut lumen affect the systemic physiological process of ageing? In female Drosophila, we show that microbiota increase expression of the peptide hormone Tachykinin (Tk), which corresponds to reduced lifespan. Tk is required for microbiota to shorten lifespan, with knockdown rendering flies constitutively long-lived even in the presence of an intact microbiota. This lifespan extension does not come with canonical costs to fecundity or feeding, but impacts on triacylglyceride (TAG) storage suggest adaptive functions in metabolic homeostasis. In flies with defined (gnotobiotic) microbiotas, we show that we can model Tk-dependent effects of microbiota on lifespan and TAG by monoassociation with Acetobacter pomorum. These effects require Tk in the midgut, and the cognate TK receptor TkR99D in neurons, implicating a microbiota-gut-neuron relay. This relay also appears to compromise gut barrier function in aged flies, indicating roles in healthspan as well as lifespan. However, the effect of TkR99D is independent of its reported role in insulin signalling and adipokinetic hormone signalling which, respectively, are canonical regulators of lifespan and TAG metabolism, suggesting a non-canonical role for TkR99D elsewhere in the nervous system. Altogether our results implicate a microbiota-gut-neuron axis in ageing, via a specific bacterium modulating activity of a specific and evolutionarily-conserved hormone.

genetics↗

bioRxiv2023

Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2

Long COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple "omics" assays (CyTOF, RNAseq/scRNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of individuals with clear LC and non-LC clinical trajectories, 8 months following infection and prior to receipt of any SARS-CoV-2 vaccine. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis. Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses. RNAseq/scRNAseq and Olink analyses similarly revealed immune dysregulatory mechanisms, along with non-immune associated perturbations, in individuals with LC. Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of persistent virus, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition.

immunology↗

bioRxiv2020

TIRAP drives myelosuppression through an Ifnγ-Hmgb1 axis that disrupts the marrow microenvironment

Activation of inflammatory pathways is associated with bone marrow failure syndromes, but how specific molecules impact on the marrow microenvironment is not well elucidated. We report a novel role for the miR-145 target, Toll/Interleukin-1 receptor domain containing adaptor protein (TIRAP), in driving bone marrow failure. We show that TIRAP is overexpressed in various types of myelodysplastic syndromes (MDS), and suppresses all three major hematopoietic lineages.. Constitutive expression of TIRAP in hematopoietic stem/progenitor cells (HSPC) promotes upregulation of Ifn{gamma}, leading to bone marrow failure. Myelopoiesis is suppressed through Ifn{gamma}-Ifn{gamma}r-mediated release of the alarmin, Hmgb1, which disrupts the marrow endothelial niche. Deletion of Ifn{gamma} or Ifn{gamma}r blocks Hmgb1 release and is sufficient to reverse the endothelial defect and prevent myelosuppression. In contrast, megakaryocyte and erythroid production is repressed independently of the Ifn{gamma} receptor. Contrary to current dogma, TIRAP-activated Ifn{gamma}-driven marrow suppression is independent of T cell function or pyroptosis. In the absence of Ifn{gamma}, TIRAP drives myeloproliferation, implicating Ifn{gamma} in suppressing the transformation of bone marrow failure syndromes to myeloid malignancy. These findings reveal novel, non-canonical roles of TIRAP, Hmgb1 and Ifn{gamma} function in the marrow microenvironment,and provide insight into the pathophysiology of preleukemic syndromes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/967018v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@d033fborg.highwire.dtl.DTLVardef@104bab9org.highwire.dtl.DTLVardef@17ed484org.highwire.dtl.DTLVardef@1b228ed_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract: Model of proposed mechanism of TIRAP-induced BMFConstitutive TIRAP expression in marrow cells releases Ifn{gamma}, which directly impacts on megakaryocyte and erythroid production, but indirectly suppresses myelopoiesis through the release of the alarmin, Hmgb1, which disrupts the marrow endothelial compartment. C_FIG

cancer biology↗

bioRxiv2019

Harnessing Digital Health to Objectively Assess Cognitive Impairment in People undergoing Hemodialysis Process: The Impact of Cognitive Impairment on Mobility Performance Measured by Wearables

BackgroundCognitive impairment is prevalent but still poorly diagnosed in hemodialysis adults, mainly because of the impracticality of current tools. This study examined whether remotely monitoring mobility performance can help identifying digital measures of cognitive impairment in hemodialysis patients.\n\nMethodsSixty-nine hemodialysis patients (age=64.1{+/-}8.1years, body mass index=31.7{+/-}7.6kg/m2) were recruited. According to the Mini-Mental State Exam, 44 (64%) were determined as cognitive-intact, and 25 (36%) as cognitive-impaired. Mobility performance, including cumulated posture duration (sitting, lying, standing, and walking), daily walking performance (step and unbroken walking bout), as well as postural-transition (daily number and average duration), were measured using a validated pendant-sensor for a continuous period of 24-hour during a non-dialysis day. Motor capacity was quantified by assessing standing balance and gait performance under single-task and dual-task conditions.\n\nResultsNo between-group difference was observed for the motor capacity. However, the mobility performance was different between groups. The cognitive-impaired group spent significantly higher percentage of time in sitting and lying (Cohens effect size d=0.78, p=0.005) but took significantly less daily steps (d=0.69, p=0.015) than the cognitive-intact group. The largest effect of reduction in number of postural-transition was observed in walk-to-sit transition (d=0.65, p=0.020). Regression models based on demographics, addition of daily walking performance, and addition of other mobility performance metrics, led to area-under-curves of 0.76, 0.78, and 0.93, respectively, for discriminating cognitive-impaired cases.\n\nConclusionsThis study suggests that mobility performance metrics could be served as potential digital biomarkers of cognitive impairment among HD patients. It also highlights the additional value of measuring cumulated posture duration and postural-transition to improve the detection of cognitive impairment. Future studies need to examine potential benefits of mobility performance metrics for early diagnosis of cognitive impairment/dementia and timely intervention.

neuroscience↗

bioRxiv2019

Health workers’ perspectives on the outcomes, enablers, and barriers to the implementation of HIV “Treat All” guidelines in Abuja Nigeria

IntroductionTo improve access to lifesaving treatment for all people living with HIV (PLHIV), Nigeria implemented the Treat All guidelines in 2016. However, health workers perspectives on the implementation of the guidelines have not been evaluated.\n\nMethodsWe conducted in-depth interviews to explore health workers perspectives on the Treat All guidelines. Using purposive sampling, 20 health workers providing HIV patient care were recruited from six primary health care hospitals in Abuja to participate in semi-structured interviews. Data exploration was conducted using thematic content analysis.\n\nResultsThe five main themes that emerged were (1) the perceived benefits of guidelines use, (2) the perceived disadvantages of using the guidelines, (3) reported patients response to guideline change, (4) perceived barriers/enablers to guideline use and (5) health workers recommendations for improvement. Health workers perceived that the implementation of the Treat All guidelines has considerably improved patient care, particularly in increasing access to skilled health care, reducing stress on patients, and increasing hope for a better health outcome among patients. Other perceived benefits were reduced mortality, reduced pre-treatment attrition, reduction in delays between case detection and initiation on treatment. Perceived major disadvantages were increased workload and overcrowded clinics. Health workers reported that most patients were willing to start treatment early. Perceived key factors enabling guidelines use were health workers interest, patient benefits, training and availability of tools for implementation of guidelines, government supervisory visits and hospital management support. Perceived key barriers were poverty, inadequate human resources, lack of familiarity with guidelines, and lack of consistent supply of HIV test kits at some sites.\n\nConclusionsImplementation of the Treat All guidelines led to perceived improvement in patient care. Further improvements could be achieved by implementing an efficient supply chain system for HIV rapid test kits, and through guidelines distribution and training. Additionally, implementing differentiated approaches that decongest clinics, and programs that economically empower patients could improve access to treatment.

epidemiology↗