Biology subjects

Suleiman, M.

Publications and source records attributed to Suleiman, M..

14 recordsLinked to original sources

bioRxiv2026

Spatial and functional mapping of the human pancreas reveals endocrine and exocrine cell states in health and metabolic disease

The human pancreas contains diverse endocrine and exocrine cell populations whose spatial organization is essential for tissue physiology. While single-cell and spatial transcriptomics revealed molecular heterogeneity across pancreatic cell types, linking these states to physiological activity in situ has remained challenging. Here, we combined single-nucleus RNA sequencing, spatial transcriptomics, and functional calcium imaging across pancreatic samples in health and metabolic disease. We identified heterogeneous endocrine and exocrine cell states associated with obesity and diabetes, including inflammatory remodeling of acinar and ductal populations. To directly couple tissue physiology with molecular state, we developed Slice-seq, which integrates calcium imaging with spatial transcriptomics in acute pancreatic slices. Slice-seq linked local endocrine composition and transcriptional programs with {beta} cell activity and identified extra-islet {beta} cells with reduced glucose responsiveness and mitochondrial oxidative metabolism. Together, our study provides a framework for linking pancreatic cell states to tissue organization and physiological activity in health and disease.

genomics↗

bioRxiv2026

Expansion microscopy reveals insulin granule clustering in human β-cells in type 2 diabetes

Aims/hypothesisQuantitative nanoscale analysis of insulin secretory granules (ISGs) in human pancreatic tissue has been limited by the lack of imaging methods that combine high resolution with large-scale sampling. We aimed to establish expansion microscopy (ExM) as a platform for in situ, quantitative analysis of ISG organisation in human {beta}-cells and to assess whether type 2 diabetes (T2D) is associated with alterations in granule size, abundance or spatial organisation. MethodsWe applied Magnify ExM to PFA-fixed, paraffin-embedded pancreatic tissue sections from 6 human donors, 3 non-diabetic (ND) and 3 T2D, enabling super-resolution optical imaging of insulin-labelled granules. Insulin-positive structures were segmented and analysed using a morphometric pipeline to quantitatively assess size, shape and spatial features. Granule clustering was quantified based on combined area and roundness criteria. ResultsThe diameter distribution of highly circular granules was similar between ND and T2D samples and estimates of granule number per cell indicated only a modest reduction in T2D ([~]25%). In contrast, mapping insulin-positive structures in a roundness-area space revealed a marked enrichment of large, irregular objects consistent with granule clustering in T2D. The fraction of clustered granules was significantly increased in T2D and strongly inversely correlated with insulin stimulation index (r = -0.85). Conclusions/interpretationThese results establish expansion microscopy as a powerful platform for quantitative nanoscale analysis of human pancreatic tissue and identify altered spatial organisation of insulin granules, rather than marked granule depletion, as a prominent feature associated with {beta}-cell dysfunction in T2D. Research in contextO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LI{beta}-cell dysfunction in type 2 diabetes is often attributed to reduced insulin content or {beta}-cell loss. C_LIO_LIInsulin secretory granules (ISGs) have been characterised ultrastructurally, but quantitative analysis in human tissue remains limited. C_LIO_LISuper-resolution approaches, including expansion microscopy, are emerging tools for nanoscale imaging in biological tissues. C_LI What is the key question?O_LIIs {beta}-cell dysfunction in type 2 diabetes associated with depletion of insulin granules or with altered spatial organisation? C_LI What are the new findings?O_LIInsulin granule size distribution is largely preserved in type 2 diabetes, with only a modest reduction in granule number per cell. C_LIO_LIA significant increase in insulin granule clustering is observed in diabetic {beta}-cells. C_LIO_LIGranule clustering is strongly inversely correlated with insulin secretion in the same donor tissues. C_LI How might this impact on clinical practice in the foreseeable future?O_LIIdentifying altered granule organisation as a feature of {beta}-cell dysfunction may help refine the understanding of disease mechanisms and guide future strategies targeting {beta}-cell function. C_LI

biophysics↗

bioRxiv2026

Micropollutant-driven bacterial adaptation enables resilient pharmaceuticals biodegradation at trace concentrations in biologically treated wastewater.

Pharmaceutical residues are persistent contaminants that resist conventional wastewater treatment and can disrupt ecosystems; however, microorganisms provide a promising biobased solution to transform or mineralize these complex xenobiotics. Whether pollutant-adapted communities maintain their degradative capacity under realistic environmental conditions remains a long-standing debate in environmental biotechnology. Here, microbial consortia enriched in six membrane bioreactors under high pharmaceutical concentration (100 mg/L) retained full biodegradation capacity across a 5000-fold concentration range. After prolonged exposure to six model compounds (atenolol, caffeine, diclofenac, enalapril, ibuprofen, and paracetamol) complete removal occurred for all except diclofenac. Degradation remained efficient even at lower and environmentally relevant concentrations (1 mg/L-20 {micro}g/L) and recovered rapidly upon re-exposure to higher loads (100 mg/L). Metagenomic profiling revealed enrichment of oxygenase-mediated catabolic pathways supporting this resilience. When transferred to a 7 liters bioreactor treating real wastewater, the adapted community removed targeted and untargeted pharmaceuticals, demonstrating robustness, scalability, and strong potential for sustainable micropollutant remediation. Environmental ImplicationPharmaceuticals and their metabolites are environmentally hazardous because these bioactive micropollutants are persistent and continuously discharged via wastewater, thereby endangering both ecosystem and human health. This study shows that pollutant-adapted microbial consortia can address this challenge, retaining strong degradative function across large concentration fluctuations, including environmentally relevant levels. It also demonstrates scalability: the adapted community can be transferred to real-wastewater operation to remove both targeted and additional pharmaceuticals, supporting a bio-based "polishing" step for wastewater treatment plants. Overall, these findings support more sustainable biological mitigation strategies to reduce micropollutant loads.

microbiology↗

bioRxiv2025

Pharmaceuticals residues lead to enrichment of Human, Animal, and Plant Pathogens in Wastewater

Wastewater forms a reservoir for diverse microbial pathogens, posing significant risks to public health and aquatic ecosystems. They further contain several pharmaceutical residues that can induce profound shifts in the wastewater microbiome. In this study, we assessed whether common non-antimicrobial pharmaceuticals such as pain killers and blood pressure regulators impact wastewater pathogen profiles. We spiked wastewater with caffeine (stimulant), atenolol (beta-blocker), paracetamol (analgesic), ibuprofen (anti-inflammatory) and enalapril (ACE-inhibitor), and monitored microbiome 16S rRNA gene profiles. We then matched species composition to a comprehensive database of human, animal, and plant pathogens. All pharmaceuticals significatively increased abundance and biodiversity for zoonotic, plant, and animal pathogens. These findings highlight that pharmaceutical contamination poses a biohazard risk by fostering pathogen growth. We call for a paired, continuous monitoring of chemical and biological pollutants and a more stringent removal of pharmaceutical residues from wastewater.

microbiology↗

bioRxiv2025

Compost bacteria as a promising new solution for degradation of diclofenac and related pharmaceuticals for water treatment processes

Diclofenac, a widely used pharmaceutical, poses a significant environmental problem due to its persistence in aquatic systems and resistance to conventional degradation processes. Mesophilic microorganisms, commonly employed in wastewater treatment, often struggle to break down diclofenac, necessitating alternative approaches for its removal. In this study, we investigated thermophilic compost microorganisms and their ability to degrade diclofenac. Compost communities were cultivated for 20 weeks at 50{degrees}C in a membrane bioreactor, with a continuous supply of 2 mg/L diclofenac as the sole carbon source. After two weeks, the microbial community steadily enhanced its ability to remove diclofenac, achieving removal rates up to 60%. The consortium demonstrated flexibility in the degradation of further pollutants, namely sulfamethoxazole, paracetamol, and ciprofloxacin, with changes in their community structure depending on the substrates. In addition, thermophilic isolates Chelatococcus sp. strain D3 and Mycobacterium sp. strain D1 were characterized and demonstrated variation in the first reaction of transforming diclofenac, which is the crucial step in mineralization of this pollutant, resulting in either 4-hydroxy-diclofenac or diclofenac-lactam, respectively. Furthermore, Chelotococcus sp. strain D3 demonstrated the capability to catalyze the biotransformation of diclofenac into 4-hydroxydiclofenac in treated wastewater. Notably, this transformation was effectively carried out even at lower temperatures (25 {degrees}C and 37{degrees}C). These results show that the use of thermophilic consortia can be applied for efficient bioremediation in wastewater treatment plants, specifically for compounds that mesophilic organisms degrade poorly.

microbiology↗

bioRxiv2023

Pollutome complexity determines the removal of recalcitrant pharmaceuticals

Organic pollutants are an increasing threat for wildlife and humans. Managing their removal is however complicated by the difficulties in predicting degradation rates. In this work we demonstrate that the complexity of the pollutome, the set of co-existing contaminants, is a major driver of biodegradation. We built representative assemblages out of one to five common pharmaceuticals (caffeine, atenolol, paracetamol, ibuprofen, and enalapril) selected along a gradient of biodegradability. We followed their individual removal by wastewater microbial communities. The presence of multichemical background pollution was essential for the removal of recalcitrant molecules such as ibuprofen. Crucially, high order interactions between pollutants were a determinant, with the addition of new molecules particularly impacting assemblages of multiple compounds. We explain these interactions by shifts in the microbiome, with degradable molecules such as paracetamol enriching species and pathways involved in the removal of several organic molecules. We conclude that pollutants should be treated as part of a complex system, with emerging pollutants potentially showing cascading effects and offering leverage to promote bioremediation.

microbiology↗

bioRxiv2023

Identification of microbial communities and their removal efficiency of multiple pharmaceutical micropollutants combined in Membrane-Bioreactors

Pharmaceuticals are of concern to our planet and health as they can accumulate in the environment. The impact of these biologically active compounds on ecosystems is hard to predict and information on their biodegradation is necessary to establish sound risk assessment. Microbial communities are promising candidates for the biodegradation of pharmaceuticals such as ibuprofen, but little is known yet about their degradation-capacity of multiple micropollutants at higher concentrations (100 mg/L). In this work, microbial communities were cultivated in lab-scale Membrane Bioreactors (MBRs) exposed to increasing concentrations of a mixture of six micropollutants (ibuprofen, diclofenac, enalapril, caffeine, atenolol, paracetamol). Key players of biodegradation were identified using a combinatorial approach of 16S rRNA sequencing and analytics. Microbial community structure changed with increasing pharmaceutical intake (from 1 mg/L to 100 mg/L) and reached a steady-state during incubation for 7 weeks on 100 mg/L. HPLC analysis revealed a fluctuating but significant degradation (30-100%) of five pollutants (caffeine, paracetamol, ibuprofen, atenolol, enalapril) by an established and stable microbial community mainly composed of Achromobacter, Cupriavidus, Pseudomonas and Leucobacter. By using the microbial community from MBR1 as inoculum for further batch culture experiments on single micropollutants (400 mg/L substrate, respectively), different active microbial consortia were obtained for each single micropollutant. Microbial genera potentially responsible for degradation of the respective micropollutant were identified, i.e. Pseudomonas sp. and Sphingobacterium sp. for ibuprofen, caffeine and paracetamol, Sphingomonas sp. for atenolol, and Klebsiella sp. for enalapril. Our study demonstrates the feasibility of cultivating stable microbial communities capable of degrading simultaneously a mixture of highly concentrated pharmaceuticals in lab-scale MBRs and the identification of microbial genera potentially responsible for the degradation of specific pollutants. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/536351v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@14ff045org.highwire.dtl.DTLVardef@12747d0org.highwire.dtl.DTLVardef@1dbbfd8org.highwire.dtl.DTLVardef@103640_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Establishment of beta cell heterogeneity via differential CpG methylation at Nnat

Aims/hypothesisBeta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly-connected hub cells, important for the propagation of intercellular Ca2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood. Changes at the level of the epigenome provide one such possibility which we explore here by focussing on the imprinted gene neuronatin (Nnat), which is required for normal insulin synthesis and secretion. MethodsSingle cell RNA-seq datasets were examined using Seurat 4.0 and ClusterProfiler running under R. Transgenic mice expressing eGFP under the control of the Nnat enhancer/promoter regions were generated for fluorescence-activated cell (FAC) sorting of beta cells and downstream analysis of CpG methylation by bisulphite and RNA sequencing, respectively. Animals deleted for the de novo methyltransferase, DNMT3A from the pancreatic progenitor stage were used to explore control of promoter methylation. Proteomics was performed using affinity purification mass spectrometry and Ca2+ dynamics explored by rapid confocal imaging of Cal-520 and Cal-590. Insulin secretion was measured using Homogeneous Time Resolved Fluorescence Imaging. ResultsNnat mRNA was differentially expressed in a discrete beta cell population in a developmental stage- and DNA methylation (DNMT3A)-dependent manner. Thus, pseudo-time analysis of embryonic data sets demonstrated the early establishment of Nnat-positive and negative subpopulations during embryogenesis. NNAT expression is also restricted to a subset of beta cells across the human islet that is maintained throughout adult life. NNAT+ beta cells also displayed a discrete transcriptome at adult stages, representing a sub-population specialised for insulin production, reminiscent of recently-described "{beta}HI" cells and were diminished in db/db mice. Hub cells were less abundant in the NNAT+ population, consistent with epigenetic control of this functional specialization. Conclusions/interpretationThese findings demonstrate that differential DNA methylation at Nnat represents a novel means through which beta cell heterogeneity is established during development. We therefore hypothesise that changes in methylation at this locus may thus contribute to a loss of beta cell hierarchy and connectivity, potentially contributing to defective insulin secretion in some forms of diabetes. Research in contextWhat is already known about this subject? - Neuronatin (Nnat/NNAT) is an imprinted gene in humans and mice and is required for glucose-stimulated insulin secretion in vivo - Pancreatic beta cells are functionally heterogeneous with specific highly-connected subpopulations known to coordinate islet wide Ca2+ dynamics - Functional subpopulations have been described in human beta cells and their distribution is altered in type 2 diabetes What is the key question? - Does NNAT mark a discrete subpopulation of functional beta cells and which epigenetic pathways coordinate its formation and maintenance? What are the new findings? - A subpopulation of NNAT+ beta cells is established prior to the first week of postnatal life in mice via de novo DNA methylation at the Nnat promoter - NNAT+ beta cells are transcriptionally highly differentiated and appear to be functionally specialised for insulin production, possibly corresponding to recently-described "{beta}HI" and "CD63hi" beta cells. NNAT is expressed in a subset of beta cells across the human islet, and its deficiency in human beta cells diminishes glucose-stimulated insulin secretion - NNAT+ cells are likelier to belong to the population of follower, rather than hub cells, consistent with a role in insulin production rather than glucose detection How might this impact on clinical practice in the foreseeable future? - Epigenome-modifying compounds may provide a way of enhancing beta cell function and the ensemble behaviour of the islet to stimulate insulin secretion

cell biology↗

bioRxiv2022

piRNA-like small RNAs target transposable elements in a Clade IV parasitic nematode

The small RNA (sRNA) pathways identified in the model organism Caenorhabditis elegans are not widely conserved across nematodes. For example, the PIWI pathway and PIWI-interacting RNAs (piRNAs) are involved in regulating and silencing transposable elements (TE) in most animals but have been lost in nematodes outside of the Caenorhabditis elegans group (Clade V), and little is known about how nematodes regulate TEs in the absence of the PIWI pathway. Here, we investigated the role of sRNAs in the Clade IV parasitic nematode Strongyloides ratti by comparing two genetically identical adult stages (the parasitic female and free-living female). We identified putative small-interfering RNAs, microRNAs and tRNA-derived sRNA fragments that are differentially expressed between the two adult stages. Two classes of sRNAs were predicted to regulate TE activity including (i) a parasite-associated class of 21-22 nt long sRNAs with a 5 uracil (21-22Us) and monophosphate modification, and (ii) 27 nt long sRNAs with a 5 guanine/adenine (27GAs) and polyphosphate modification. The 21-22Us show striking resemblance to the 21U PIWI-interacting RNAs found in C. elegans, including an AT rich upstream sequence, overlapping loci and physical clustering in the genome.

genomics↗

bioRxiv2021

Stratified microbial communities are highly sensitive towards multiple combined global change factors, revealing antagonistic and synergistic effects

Microbial communities in many ecosystems are facing a broad range of global change drivers, such as nutrient enrichment, chemical pollution, and temperature change. These drivers can cause changes in the abundance of taxa, the composition of communities, and the properties of ecosystems. While the influence of single drivers is already described in numerous studies, the effect and predictability of multiple drivers changing simultaneously is still poorly understood. In this study, we used 240 highly replicable oxic/anoxic aquatic lab microcosms and four drivers (fertilizer, glyphosate, metal pollution, antibiotics) in all possible combinations at three different temperatures (20 {degrees}C, 24 {degrees}C, and 28 {degrees}C) to shed light into consequences of multiple drivers on different levels of organization, ranging from species abundance to community and ecosystem parameters. We found (i) that at all levels of ecological organisation, combinations of drivers can change the biological consequence and direction of effect compared to single drivers (ii), that effects of combinations are further modified by temperature, (iii) that a larger number of drivers occurring simultaneously is often quite closely related to their effect size, and (iv) that there is little evidence that any of these effects are associated with the level of ecological organisation of the state variable. These findings suggest that, at least in this experimental ecosystem approximating a stratified aquatic ecosystem, there may be relatively little scope for predicting the effects of combinations of drivers from the effects of individual drivers, or by accounting for the level of ecological organisation in question, though there may be some scope for prediction based on the number of drivers that are occurring simultaneous. A priority, though also a considerable challenge, is to extend such research to consider continuous variation in the magnitude of multiple drivers acting together.

microbiology↗

bioRxiv2021

Genetic regulation of RNA splicing in human pancreatic islets

Genetic variants that influence transcriptional regulation in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D). For many susceptibility loci, however, the mechanisms are unknown. We examined splicing QTLs (sQTLs) in islets from 399 donors and observed that genetic variation has a widespread influence on splicing of genes with important functions in islet biology. In parallel, we profiled expression QTLs, and used transcriptome-wide association and co-localization studies to assign islet sQTLs or eQTLs to T2D susceptibility signals that lacked candidate effector genes. We found novel T2D associations, including an sQTL that creates a nonsense isoform in ERO1B, a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effectors revealed overrepresented pathways, including regulators of G-protein-mediated cAMP production. This data exposes an underappreciated layer of genetic regulation in pancreatic islets, and nominates molecular mediators of T2D susceptibility.

genetics↗

bioRxiv2021

Contrasting resistance and resilience of the coupled oxic and anoxic componentsof an experimental microbial ecosystem

Understanding how microbial communities of aquatic ecosystems respond to environmental change remains a critical challenge in microbial ecology. In this study, we used phototrophic oxic-anoxic micro-ecosystems to understand how the functioning and diversity of aerobic and anaerobic lake analog communities is affected by light deprivation. Continuous measurements were performed to describe oxygen dynamics (mean/min/max/amplitude) and time-series of full-length 16S rRNA sequencing were used to quantify changes in alpha- and beta-diversity. In the top oxic layer, oxygen concentration decreased significantly under light deprivation, but showed resilience in mean, minimum and maximum after light conditions were restored. Only the amplitude of diurnal fluctuations in oxygen concentrations did not recover fully, and instead tended to remain lower in treated ecosystems. Alpha-diversity of the top oxic layer communities showed a delayed increase after light conditions were restored, and was not resilient. In contrast, alpha-diversity of the anoxic bottom layer communities increased due to the stressor, but was resilient. Community composition changed significantly during light deprivation, showed resilience in the oxic layer and lack of resilience in the anoxic layer. Alpha-diversity and the amplitude of oxygen within and among treatments were strongly correlated, suggesting that higher diversity could lead to less variable oxygen concentrations, or vice versa. Our experiment showed that light deprivation induces multifaceted responses of community function and structure, hence focusing on a single stability component could potentially be misleading.

microbiology↗

bioRxiv2021

TIGER: The gene expression regulatory variation landscape of human pancreatic islets

GWAS have identified more than 700 genetic signals associated with type 2 diabetes (T2D). To gain insight into the underlying molecular mechanisms, we created the Translational human pancreatic Islet Genotype tissue-Expression Resource (TIGER), aggregating >500 human islet RNA-seq and genotyping datasets. We imputed genotypes using 4 reference panels and meta-analyzed cohorts to improve coverage of expression quantitative trait loci (eQTL) and developed a method to combine allele-specific expression across samples (cASE). We identified >1 million islet eQTLs (56% novel), of which 53 colocalize with T2D signals (60% novel). Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identified 8 novel cASE colocalizations, among which an SLC30A8 T2D associated variant. We make all the data available through the open-access TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translate this into therapeutic insight and precision medicine for T2D.

bioinformatics↗

bioRxiv2020

Large and interacting effects of temperature and nutrient addition on stratified aquatic ecosystems-results from a model micro-ecosystem

Aquatic ecosystems are often stratified, with cyanobacteria in oxic layers and phototrophic sulfur bacteria in anoxic ones. Changes in stratification caused by global environmental change are an ongoing concern. Increasing understanding how such aerobic and anaerobic microbial communities, and associated abiotic conditions, respond to multifarious environmental changes is an important endeavor in microbial ecology. Insights can come from observational and experimental studies of naturally occurring stratified aquatic ecosystems, from theoretical models of ecological processes, and from experimental studies of replicated microbial communities in the laboratory. Here we demonstrate a laboratory-based approach with small, replicated, and liquid dominated Winogradsky columns, with distinct oxic/anoxic strata in a highly replicable manner. Our objective is to apply simultaneous global change scenarios (temperature, nutrient addition) on this micro-ecosystem to report how the microbial communities (full-length 16SrRNA-seq.) and the abiotic conditions (O2, H2S, TOC) of the oxic/anoxic layer responded to these environmental changes. Composition of the strongly stratified microbial communities was greatly affected by temperature and by the interaction of temperature and nutrient addition, demonstrating the need of investigating global change treatments simultaneously. Especially phototrophic sulfur bacteria dominated the water column at higher temperatures, and may indicate the presence of alternative stable states. We show that the establishment of such a micro-ecosystem has potential to test global change scenarios in stratified eutrophic limnic systems.

microbiology↗