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Bacillus subtilis is considered a soil organism for which endospore formation provides a means to ensure long-term survival in the environment. We have addressed here the question of what happens to a spore when ingested. Spores displaying on their surface a heterologous antigen, tetanus toxin fragment C (TTFC), were shown to generate anti-TTFC responses not to the antigen contained in the primary oral inoculum but to those displayed on spores that had germinated and then resporulated. We then used reverse transcription-PCR to determine expression of vegetative genes and sporulation-specific genes in the mouse gut following oral dosing with spores. Significant levels of germination and sporulation were documented. Using natural isolates of B. subtilis that could form biofilms, we showed that these strains could persist in the mouse gut for significantly longer than the laboratory strain. Moreover, these isolates could grow and sporulate anaerobically and exhibited a novel phenomenon of being able to form spores in almost half the time required for the laboratory isolate. This suggests that spores are not transient passengers of the gastrointestinal tract but have adapted to carry out their entire lifecycle within this environment. This is the first report showing an intestinal life cycle of B. subtilis and suggests that other Bacillus species could also be members of the gut microflora.

This study evaluated the experience of implementing water safety plans (WSPs) in Vietnam. WSPs were introduced in Vietnam by the World Health Organization (WHO) in collaboration with the Ministry of Construction in 2006 and have been a mandatory requirement for municipal water supplies since 2012. Using a mixed-methods approach, we collected data on the perceived benefits and challenges of WSP implementation from 23 provincial water companies between August and November 2021. Potential public health benefits of improved water quality were a key motivation; 87% of the water utilities were also motivated by the risk of climate change and prepared response plans to climate-related extreme events as part of WSPs. A decrease in E. coli and an improvement in disinfectant residual in treated water were reported by 61 and 83% of the water supplies, respectively. Sixty-five percent of the water supplies also reported improved revenue and cost recovery. Key barriers to WSP implementation were a lack of WSP guidance suitable for the local context (87%) and insufficient funds for WSP implementation (43%). Our study highlights the need for improved support and capacity building along with locally suited guidance on WSP implementation and audit. HIGHLIGHTS Increasing water pollution, emerging climate change, process of equitization, and expansion of service areas are important impacts on water safety plan (WSP).; WSP has led to tangible benefits. The WSP is a useful vehicle for climate change adaptations, improve resilience.; The commitment from Government and from water utilities is strong.; The critical financial barriers, training needs, and support in WSP need to be addressed.;

Pancreatic islets are composed of alpha-, beta-, as well as delta-cells and appropriate regulation of glucose homeostasis relies on auto- and paracrine cellular communication. Here, the authors study the role of delta-cell filopodia in this context by employing optogenetic and calcium imaging approaches.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Bone toxicities are common among paediatric patients treated for acute lymphoblastic leukaemia (ALL) with potentially major negative impact on patients' quality of life. To identify the underlying genetic contributors, we conducted a genome-wide association study (GWAS) and a transcriptome-wide association study (TWAS) in 260 patients of European-descent from the DFCI 05-001 ALL trial, with validation in 101 patients of European-descent from the DFCI 11-001 ALL trial. We identified a significant association between rs844882 on chromosome 20 and bone toxicities in the DFCI 05-001 trial (p = 1.7 × 10 -8 ). In DFCI 11-001 trial, we observed a consistent trend of this variant with fracture. The variant was an eQTL for two nearby genes, CD93 and THBD. In TWAS, genetically predicted ACAD9 expression was associated with an increased risk of bone toxicities, which was confirmed by meta-analysis of the two cohorts (meta-p = 2.4 × 10 -6 ). In addition, a polygenic risk score of heel quantitative ultrasound speed of sound was associated with fracture risk in both cohorts (meta-p = 2.3 × 10 -3 ). Our findings highlight the genetic influence on treatment-related bone toxicities in this patient population. The genes we identified in our study provide new biological insights into the development of bone adverse events related to ALL treatment., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Noroviruses are a leading cause of epidemic and sporadic acute gastroenteritis worldwide. The development of sensitive molecular diagnostic techniques has revolutionized our understanding of norovirus epidemiology over the past two decades, but norovirus strain types associated with sporadic gastroenteritis remain poorly described. Therefore, we conducted a systematic review of studies performed after 2000 to clarify the genotypic distribution of noroviruses in children (≤18 years of age) with sporadic acute gastroenteritis. Genogroup GII norovirus was the most prevalent, accounting for 96% of all sporadic infections. GII.4 was the most prevalent genotype, accounting for 70% of the capsid genotypes and 60% of the polymerase genotypes, followed by the capsid genotype GII.3 (16%) and the polymerase genotype GII.b (14%). The most common ORF1/ORF2 inter-genotype recombinants were GII.b, GII.12, and GII.4 polymerase genotypes combined with the capsid genotype GII.3, accounting for 19% of all genotyped strains. The distribution of GII.4 variants over the last decade was dominated by successive circulation of GII.4/2002, GII.4/2004, GII.4/2006b, and GII.4/2008 with GII.4/2006b continuing to date. Genotypes GII.4 and GII.3 have predominated in children during the past decade; this is most notable in the global emergence of GII.4 variant noroviruses. As the burden of rotavirus disease decreases following the introduction of childhood immunization programs, the relative importance of norovirus in the etiology of acute childhood gastroenteritis will likely increase. In order for a successful norovirus vaccine to be developed, it should provide immunity against strains with capsid genotypes GII.4 and GII.3., (Copyright © 2012 Elsevier B.V. All rights reserved.)