Biology subjects

Shehreen, S.

Publications and source records attributed to Shehreen, S..

4 recordsLinked to original sources

bioRxiv2026

Cognitive engagement induces area-specific fingerprints of dopamine, acetylcholine, serotonin, glutamate and GABA in prefrontal cortex and striatum

Cholinergic, dopaminergic and serotonergic neuromodulation has pervasive effects on circuit functions in prefrontal cortex (PFC) and striatum and interact with glutamatergic and GABAergic transmission. But how these neurochemicals interact during cognitive engagement is largely unknown and inferred from studying few neuromodulators at a time. Here, we sampled the extracellular availabilities of five neurochemicals in the PFC and striatum of nonhuman primates and tested how they changed when subjects switched from rest to engage in a cognitive set shifting task using miniaturized probes for diffusion-based solid-phase microextraction. Cognitive engagement was best predicted by GABAergic and cholinergic changes in the PFC, and dopaminergic and cholinergic changes in the striatum. Glutamate co-modulated with acetylcholine across states in both the PFC and striatum, while serotonin changes in PFC and striatum correlated consistent with common external modulation. These findings document an area-specific multi-neuromodulatory fingerprint of an adaptive cognitive state in the fronto-striatal network of the nonhuman primate brain. TeaserEngaging in a cognitive task reshapes neurochemical profiles across the fronto-striatal network of the primate brain

neuroscience↗

bioRxiv2025

Adaptive trade-offs between niche-driven defence system selection and horizontal gene transfer suggests clinical success in Acinetobacter spp.

2.IntroductionBacteria face relentless selective pressure from both antibiotics and bacteriophages, driving the evolution of diverse defence systems and shaping horizontal gene transfer (HGT) dynamics. Gap StatementThe relationship between bacterial defence system repertoires and horizontal gene transfer in clinically relevant Acinetobacter species remains poorly understood, limiting our ability to predict resistance evolution and design targeted phage therapies. AimTo characterize defence arsenal across Acinetobacter species and investigate their associations with different HGT markers MethodologyWe performed a comparative genomic analysis of 132 genomes from 18 Acinetobacter species, focusing on the interplay between defence architectures and HGT markers. ResultsOur result reveals pronounced differences in defence system repertoires between lineages: while most Acinetobacter spp. harbour a multilayered arsenal, the clinically dominant A. baumannii international clone 2 (IC2) exhibits a depleted but specialised defence landscape, notably enriched in the phosphorothioation-based SspBCDE system and nearly devoid of restriction-modification systems. Strikingly, many defence systems display mutual exclusivity, and defence system is tightly linked to the presence of mobile elements, antibiotics, and heavy metal resistance. Plasmid-borne defence systems, especially BREX, are prevalent, highlighting the role of mobile elements in distributing both immunity and resistance traits. These patterns suggest that successful clinical lineages finely balance immune defences and genetic plasticity, facilitating rapid adaptation under antimicrobial selection and phage threats. ConclusionThese findings provide insights into evolutionary trade-offs underpinning multidrug resistance and have implications for designing targeted phage therapies against recalcitrant Acinetobacter infections. 3. Data summaryAll bioinformatics analysis workflows, custom scripts, and R code are publicly available at https://github.com/vikos77/Acinetobacter-defence-systems. The repository includes bash scripts for genome downloading and tool execution (scripts 1-10), R scripts for statistical analysis and visualization (scripts 1-9), and conda environment files for reproducible software installation. Complete analysis protocols are documented in the repository README and individual script headers. All software versions and parameters are specified in the code documentation. 4. Impact StatementThis study reveals how defence system composition in Acinetobacter species is shaped by ecological niche and linked to horizontal gene transfer, antibiotic resistance, and mobile genetic elements. Notably, the clinically dominant A. baumannii IC2 lineage exhibits a streamlined defence repertoire favouring genetic plasticity, facilitating rapid adaptation under antibiotic and phage pressure. These findings enhance our understanding of resistance evolution and support the rational design of phage-based therapies targeting multidrug-resistant pathogens.

bioinformatics↗

bioRxiv2020

Discovery of multiple anti-CRISPRs uncovers anti-defense gene clustering in mobile genetic elements

Many prokaryotes employ CRISPR-Cas systems to combat invading mobile genetic elements (MGEs). In response, some MGEs have evolved Anti-CRISPR (Acr) proteins to bypass this immunity, yet the diversity, distribution and spectrum of activity of this immune evasion strategy remain largely unknown. Here, we uncover 11 new type I anti-CRISPR genes encoded on numerous chromosomal and extrachromosomal mobile genetic elements within Enterobacteriaceae and Pseudomonas. Candidate genes were identified adjacent to anti-CRISPR associated gene 5 (aca5) and assayed against a panel of six type I systems: I-F (Pseudomonas, Pectobacterium, and Serratia), I-E (Pseudomonas and Serratia), and I-C (Pseudomonas), revealing the type I-F and/or I-E acr genes and a new aca (aca9). We find that acr genes not only associate with other acr genes, but also with inhibitors of distinct bacterial defense systems. These genomic regions appear to be "anti-defense islands", reminiscent of the clustered arrangement of "defense islands" in prokaryotic genomes. Our findings expand on the diversity of CRISPR-Cas inhibitors and reveal the potential exploitation of acr loci neighborhoods for identifying new anti-defense systems.

microbiology↗

bioRxiv2019

SVCurator: A Crowdsourcing app to visualize evidence of structural variants for the human genome

A high quality benchmark for small variants encompassing 88 to 90% of the reference genome has been developed for seven Genome in a Bottle (GIAB) reference samples. However a reliable benchmark for large indels and structural variants (SVs) is yet to be defined. In this study, we manually curated 1235 SVs which can ultimately be used to evaluate SV callers or train machine learning models. We developed a crowdsourcing app - SVCurator - to help curators manually review large indels and SVs within the human genome, and report their genotype and size accuracy.\n\nSVCurator is a Python Flask-based web platform that displays images from short, long, and linked read sequencing data from the GIAB Ashkenazi Jewish Trio son [NIST RM 8391/HG002], We asked curators to assign labels describing SV type (deletion or insertion), size accuracy, and genotype for 1235 putative insertions and deletions sampled from different size bins between 20 and 892,149 bp. The crowdsourced results were highly concordant with 37 out of the 61 curators having at least 78% concordance with a set of expert curators, where there was 93% concordance amongst expert curators. This produced high confidence labels for 935 events. When compared to the heuristic-based draft benchmark SV callset from GIAB, the SVCurator crowdsourced labels were 94.5% concordant with the benchmark set. We found that curators can successfully evaluate putative SVs when given evidence from multiple sequencing technologies.

genomics↗