Falk Submission
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB38337 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:THE HUMAN BRAIN MICROBIOME IN HEALTH AND PARKINSONS’s DISEASE MUCH ADO ABOUT NOTHING
| PRJEB38246 | ENA
Project description:Much ado about nothing? - Off-target amplification can lead to false positive bacterial brain microbiome detection in healthy and Parkinson's disease individuals
| PRJEB42409 | ENA
Project description:Dysregulation of adenosine (Ado) homeostasis has been observed in both rodent models and human patients of Huntington’s disease (HD). However, the underlying mechanisms of Ado signaling in HD pathogenesis is still unclear. In this study we examined influence of Ado signaling on Drosophila HD model. We further examined the transcription profile of AdoR mutants by microarray analysis to identified a downstream target of AdoR signaling, which mediates the AdoR effects on HD pathology. Our findings have important implications for the crosstalk between Ado signaling and pathogenic effects of HD as well as other human diseases associated with polyglutamine aggregation.
2020-10-17 | E-MTAB-8704 | biostudies-arrayexpress
Project description:Dysregulation of adenosine (Ado) homeostasis has been observed in both rodent models and human patients of Huntington’s disease (HD). However, the underlying mechanisms of Ado signaling in HD pathogenesis is still unclear. In this study we examined influence of Ado signaling on Drosophila HD model. We further compared the transcription profiles of AdoR and ENT2 mutants by microarray analysis to identify a downstream target of AdoR signaling, which mediates the AdoR effects on HD pathology. Our findings have important implications for the crosstalk between Ado signaling and pathogenic effects of HD as well as other human diseases associated with polyglutamine aggregation.
2020-10-17 | E-MTAB-8699 | biostudies-arrayexpress
Project description:The human microbiome and human health and disease
| PRJNA46305 | ENA
Project description:The human gut is colonized by trillions of microorganisms that influence human health and disease through the metabolism of xenobiotics, including therapeutic drugs and antibiotics. The diversity and metabolic potential of the human gut microbiome have been extensively characterized, but it remains unclear which microorganisms are active and which perturbations can influence this activity. Here, we use flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the human gut contains distinctive subsets of active and damaged microorganisms, primarily composed of Firmicutes, which display marked temporal variation. Short-term exposure to a panel of xenobiotics resulted in significant changes in the physiology and gene expression of this active microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding novel candidate proteins for antibiotic resistance, drug metabolism, and stress response. These results demonstrate the power of moving beyond DNA-based measurements of microbial communities to better understand their physiology and metabolism. RNA-Seq analysis of the human gut microbiome during exposure to antibiotics and therapeutic drugs.
2012-10-30 | E-GEOD-38151 | biostudies-arrayexpress
Project description:Many safe and effective drugs have unknown targets, limiting opportunities to extend their use to other disease states with overlapping etiologies. Here, we have elucidated the mechanism of action of the direct vasodilator, hydralazine (HYZ), which has been used for more than seven decades and remains on the World Health Organization's List of Essential Medicines as a treatment for preeclampsia and hypertensive crisis. Using our chemoproteomic drug de-orphanization approach, we identify a key enzyme mediator of targeted protein degradation, 2-aminoethanethiol dioxygenase (ADO), as a selective HYZ target. The structure of the ADO•HYZ complex shows that the drug chelates the enzyme's metal cofactor in the course of alkylating one of its ligands. The resultant inactivation stabilizes regulators of G-protein signaling (RGS4/5) that are normally marked for degradation by ADO. This activity explains the drug's impact on blood vessel tension, and it comports with prior associations of insufficient RGS levels with both clinical preeclampsia and analogous symptoms in mice. The established importance of ADO in glioblastoma motivated evaluation of the efficacy of HYZ against such cells, revealing that a single dose induces prolonged senescence. The results identify ADO as a novel pharmacological target for both diseases and connect it to a known drug, opening avenues for the rational tailoring of HYZ to create new pharmaceuticals.
2025-10-24 | PXD067316 | Pride
Project description:Metabolites produced by human gut microbiome have a profound influence on brain health with increasing associations to Parkinson’s disease pathology that lack a mechanistic insight. Using Caenorhabditis elegans model expressing human α-synuclein, we systematically tested key microbial fermentation products and identified succinate as a potent driver of pathology. As succinate administration was found to alter major PD associated pathological end-points, we further investigated the changes at transcriptional level by performing the whole worm transcriptome profiling of the wild-type strain. Through differentially expressed genes (DEGs), we examined the extent of physiological impact exerted by an exogenously administered metabolite and tried to comprehend the mechanism through which succinate generates a proteotoxic environment that promotes aggregation of alpha-synuclein in a transgenic C. elegans strain expressing human alpha-synuclein. It also helped us to identify the molecular pathways that result in mitochondrial dysfunction and substantiate our findings.
2026-04-21 | E-MTAB-15794 | biostudies-arrayexpress
Project description:Off-target amplification can lead to false positive human brain microbiome detection. 16s rRNA amplicon samples from brain tissue of healthy and Parkinson's disease patients.
| EGAD00001006553 | EGA
Project description:Differences in microbiome variability of carnivores and herbivores
| PRJEB43842 | ENA