Project description:This model was reconstructed from single-nucleus RNA-seq (snRNA-seq) data of human postmortem brain and curated using published metabolomics data from human iPSC-derived neurons and cerebrospinal fluid (CSF), together with gene expression data from the Human Protein Atlas. It more accurately simulates human neuronal metabolic flux in neurodegenerative conditions such as Alzheimer's disease (AD).
Project description:Ulcerative colitis is a chronic inflammatory disorder for which a definitive cure is still missing. This is characterized by an overwhelming inflammatory milieu in the colonic tract where a composite set of immune and non-immune cells orchestrate its pathogenesis. Over the last years, a growing body of evidence has been pinpointing gut virome dysbiosis as underlying its progression. Nonetheless, its role during the early phases of chronic inflammation is far from being fully defined. Here we show the gut virome-associated Hepatitis B virus protein X, most likely acquired after an event of zoonotic spillover, to be associated with the early stages of ulcerative colitis and to induce colonic inflammation in mice. It acts as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering mucosal immunity at the level of both innate and adaptive immunity. This study paves the way to the comprehension of the aetiopathogenesis of intestinal inflammation and encourages further investigations of the virome as a trigger also in other scenarios. Moreover, it provides a brand-new standpoint that looks at the virome as a target for tailored treatments, blocking the early phases of chronic inflammation and possibly leading to better disease management.
Project description:The first GSSM of V. vinifera was reconstructed (MODEL2408120001). Tissue-specific models for stem, leaf, and berry of the Cabernet Sauvignon cultivar were generated from the original model, through the integration of RNA-Seq data. These models have been merged into diel multi-tissue models to study the interactions between tissues at light and dark phases.
Project description:Necrotizing enterocolitis (NEC) is a severe intestinal disorder connected to a gut microbiota dysbiosis. Approximately 7-8% of very low birth weight (VLBW) infants are diagnosed with NEC with mortality rates reaching 20-50%. Fecal virome transfer (FVT) is an approach where the bacteria-free fecal fraction from a healthy donor is administered to a patient with a GM dysbiosis. FVT contains e.g. bacteriophages, eukaryotic viruses, and metabolites. Oral administered FVT from healthy milk-fed term pigs shows promising potential in preventing NEC in the preterm piglet model. However, efficacy and safety are inconsistent between experiments. In the current study, we aim to explore methods of creating reproducible FVT-like treatments and test if these act preventive against NEC and possess minimal side effects in the preterm piglet model. Using cesarean-delivered, formula-fed preterm pigs, we compare the NEC preventive effect of native donor fecal virome (nFV) with: 1) a defined bacteriophage cocktail targeting NEC-associated bacteria; and 2) a chemostat fecal virome propagation with lactose as the major carbohydrate source (cFV), and 3) chemostat fecal virome propagation with lactose and milk oligosaccharides (cFV-OS). All methods will be compared to control treatment with SM buffer (SM).
Project description:Tissue-specific methylation patterns suggest a role for CpG island methylation in differentiation and cell-type-specific gene regulation. We have profiled CpG island methylation in different cells of the immune cell lineage to investigate this role. MBD-affinity purification combined with next generation sequencing was used to analyse CpG island methylation in dendritic cells, B cells, Th1, Th2 and naïve T cells. ChIP-seq was carried out to determine RNA polymerase II binding sites in these cell types and this was compared to the methylation profiles obtained. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ Abstract: We have profiled CpG island methylation in various immune system cell types and related this to gene expression in these cells.
Project description:Xylella fastidiosa (Xf) is a Gram-negative bacterial plant pathogen responsible for severe diseases in a variety of economically important crops. A critical aspect of its virulence is the production of extracellular vesicles (EVs). In this study, we discovered that DNA-binding proteins and non-ribosomal RNA-binding proteins are abundant in the corona of Xf-EVs. DNA-seq revealed enrichment of three genomic islands (GIS) in EVs, which carry molecular signatures indicative of horizontal gene transfer (HGT). The most abundant GI encodes five homologous small RNAs designated sXFs. RNA sequencing revealed a distinct pattern of non-coding RNAs enriched in EVs, including four island-encoded sXFs. One of the sXF’s stem-loops contains motifs for binding the RNA chaperone Hfq, which is also abundant in EVs. Predicted target analysis suggests that sXFs play a role in regulation of natural competence in bacteria. Additionally, sXF plant target prediction identifies a coiled-coil nucleotide-binding domain leucine-rich repeat receptor (CNL) immune gene that is downregulated following Xf infection and Xf-EV treatment. We propose a model where Xf releases nucleic acid carrying EVs with two functions: one to deliver RNA-related cargo that regulates gene expression in both bacterial and plant cells, and another to deliver DNA-related cargo for the genetic transfer of genomic islands. We highlight island-encoded sXFs as potential virulence factors and vesiduction as a mechanism of horizontal gene transfer of sXFs in Xf. Taken together, our data on Xf-EV cargoes provide a molecular framework for understanding the virulence of Xf.
2025-05-27 | PXD056167 | Pride
Project description:Virome analysis of sugarcane using RNA-seq