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Transcriptional control of the Cryptosporidium life cycle

The parasite Cryptosporidium is a leading agent of diarrhoeal disease in young children, and a cause and consequence of chronic malnutrition1,2. There are no vaccines and only limited treatment options3. The parasite infects enterocytes, in which it engages in asexual and sexual replication4, both of which are essential to continued infection and transmission. However, their molecular mechanisms remain largely unclear5. Here we use single-cell RNA sequencing to reveal the gene expression programme of the entire Cryptosporidium parvum life cycle in culture and in infected animals. Diverging from the prevailing model6, we find support for only three intracellular stages: asexual type-I meronts, male gamonts and female gametes. We reveal a highly organized program for the assembly of components at each stage. Dissecting the underlying regulatory network, we identify the transcription factor Myb-M as the earliest determinant of male fate, in an organism that lacks genetic sex dete

United statesChlamydomonas reinhardtiiMuris genGlobal enteric multicenter studyWkly repCell host microbeHost microbeCryptosporidium murisPlant biolTrends plant sciAcids res

Necroptosis blockade prevents lung injury in severe influenza

Severe influenza A virus (IAV) infections can result in hyper-inflammation, lung injury and acute respiratory distress syndrome1–5 (ARDS), for which there are no effective pharmacological therapies. Necroptosis is an attractive entry point for therapeutic intervention in ARDS and related inflammatory conditions because it drives pathogenic lung inflammation and lethality during severe IAV infection6–8 and can potentially be targeted by receptor interacting protein kinase 3 (RIPK3) inhibitors. Here we show that a newly developed RIPK3 inhibitor, UH15-38, potently and selectively blocked IAV-triggered necroptosis in alveolar epithelial cells in vivo. UH15-38 ameliorated lung inflammation and prevented mortality following infection with laboratory-adapted and pandemic strains of IAV, without compromising antiviral adaptive immune responses or impeding viral clearance. UH15-38 displayed robust therapeutic efficacy even when administered late in the course of infection, suggesti

United statesAmerican thoracic societyScare medHost microbeMicrobes infectTissue resDeath disCell proteomicsCancer resCell physiolDeath differ

Group 3 innate lymphoid cells in intestinal health and disease

Group 3 innate lymphoid cells in intestinal health and disease
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C groupUs national library of medicineMed centralCell resStem cellHost microbeBowel disAllergy asthma repCrohns colitisOptions oncol

Dengue - The Lancet

Dengue - The Lancet
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Sri lankaUbon ratchathaniBasse normandieJapan generalRio de janeiroEstado do rioMaricopa countyUnited statesPan american health organizationDistrict of columbiaKrung thep mahanakhonRepublic ofFrance generalNew delhiKamphaeng phetHaute normandie

Host genetic regulation of human gut microbial structural variation

Although the impact of host genetics on gut microbial diversity and the abundance of specific taxa is well established1–6, little is known about how host genetics regulates the genetic diversity of gut microorganisms. Here we conducted a meta-analysis of associations between human genetic variation and gut microbial structural variation in 9,015 individuals from four Dutch cohorts. Strikingly, the presence rate of a structural variation segment in Faecalibacterium prausnitzii that harbours an N-acetylgalactosamine (GalNAc) utilization gene cluster is higher in individuals who secrete the type A oligosaccharide antigen terminating in GalNAc, a feature that is jointly determined by human ABO and FUT2 genotypes, and we could replicate this association in a Tanzanian cohort. In vitro experiments demonstrated that GalNAc can be used as the sole carbohydrate source for F. prausnitzii strains that carry the GalNAc-metabolizing pathway. Further in silico and in vitro studies demonstrated

Mecklenburg vorpommernUnited kingdomThe netherlandsHmp research network consortiumGenome of the netherlands consortiumDutch microbiomeHost microbeAcids resHuman microbiomeResearch networkIntegrative human microbiomeCategorical data analysis