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Suleiman, M.

Publications and source records attributed to Suleiman, M..

6 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗