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Antimicrobial peptides (AMPs) play essential roles in maintaining gut health and are associated with IBD. This study is to elucidate the effect of angiogenin (ANG), an intestine-secreted AMP, on gut microbiota and its relevance with IBD.
The effect of ANG on microbiota and its contribution to colitis were evaluated in different colitis models with co-housing and faecal microbiota transplantation. ANG-regulated bacteria were determined by 16S rDNA sequencing and their functions in colitis were analysed by bacterial colonisation. The species-specific antimicrobial activity of ANG and its underlying mechanism were further investigated with microbiological and biochemical methods. ANG level and the key bacteria were characterised in IBD faecal samples.
ANG regulated microbiota composition and inhibited intestinal inflammation. Specifically,
deficiency in mice led to a decrease in the protective gut commensal strains of Lachnospiraceae but an increase in the colitogenic strains of α-Proteobacteria. Direct binding of ANG to α-Proteobacteria resulted in lethal disruption of bacterial membrane integrity, and consequently promoted the growth of Lachnospiraceae, which otherwise was antagonised by α-Proteobacteria. Oral administration of ANG1 reversed the dysbiosis and attenuated the severity of colitis in
-deficient mice. The correlation among ANG, the identified bacteria and IBD status was established in patients.
These findings demonstrate a novel role of ANG in shaping gut microbe composition and thus maintaining gut health, suggesting that the ANG-microbiota axis could be developed as a potential preventive and/or therapeutic approach for dysbiosis-related gut diseases.
These findings demonstrate a novel role of ANG in shaping gut microbe composition and thus maintaining gut health, suggesting that the ANG-microbiota axis could be developed as a potential preventive and/or therapeutic approach for dysbiosis-related gut diseases.In meiosis, crossover (CO) formation between homologous chromosomes is essential for faithful segregation. However, misplaced meiotic recombination can have catastrophic consequences on genome stability. Within pericentromeres, COs are associated with meiotic chromosome missegregation. In organisms ranging from yeast to humans, pericentromeric COs are repressed. We previously identified a role for the kinetochore-associated Ctf19 complex (Ctf19c) in pericentromeric CO suppression. Here, we develop a dCas9/CRISPR-based system that allows ectopic targeting of Ctf19c-subunits. Using this approach, we query sufficiency in meiotic CO suppression, and identify Ctf19 as a mediator of kinetochore-associated CO control. The effect of Ctf19 is encoded in its NH2-terminal tail, and depends on residues important for the recruitment of the Scc2-Scc4 cohesin regulator. selleck compound This work provides insight into kinetochore-derived control of meiotic recombination. We establish an experimental platform to investigate and manipulate meiotic CO control. This platform can easily be adapted in order to investigate other aspects of chromosome biology.Gene expression is determined by a balance between RNA synthesis and RNA degradation. To elucidate the underlying regulatory mechanisms and principles of this, simultaneous measurements of RNA synthesis and degradation are required. Here, we report the development of "Dyrec-seq," which uses 4-thiouridine and 5-bromouridine to simultaneously quantify RNA synthesis and degradation rates. Dyrec-seq enabled the quantification of RNA synthesis and degradation rates of 4702 genes in HeLa cells. Functional enrichment analysis showed that the RNA synthesis and degradation rates of genes are actually determined by the genes' biological functions. A comparison of theoretical and experimental analyses revealed that the amount of RNA is determined by the ratio of RNA synthesis to degradation rates, whereas the rapidity of responses to external stimuli is determined only by the degradation rate. This study emphasizes that not only RNA synthesis but also RNA degradation is important in shaping gene expression patterns.
Women in the UK spend up to 30 years avoiding pregnancy, and effective use of contraception requires detailed information and support. Online forums offer opportunities to discuss contraception with few restrictions. Analysis of these discussions may generate learning on the information needs and preferences of their users. We analysed contraceptive discussions on forums to explore content, motivation for engaging, behaviours observed and outcomes reported.
We selected 50 threads across five English-speaking public forums, which contained more than 1000 contraceptive-specific threads. We generated a stratified sample of these threads (n=250) and then completed a qualitative thematic analysis.
Forum users seek urgent help, emotional support and the detailed accounts of others. The work of posting on forums is significant and includes framing the question to generate the desired response type, managing responses and assessing their value. Conversations were consistently framed in relation to healthcare and were important for preparing for, understanding and responding to consultations. Most of the technical information was accurate or corrected within the conversation. For most users this enquiry was part of a broader decision-making process and there was no evidence that users planned to make decisions based on forum discussions alone.
Our analysis has implications for healthcare organisations that offer or signpost to online information on contraception. It suggests that improvements in the online 'wrap around' information are needed to help decide when to consult, prepare for the consultation, understand the information given and manage post-consultation questions.
Our analysis has implications for healthcare organisations that offer or signpost to online information on contraception. It suggests that improvements in the online 'wrap around' information are needed to help decide when to consult, prepare for the consultation, understand the information given and manage post-consultation questions.