Assessment of WASH infrastructure in schools in Central Sulawesi, Indonesia using structured observations and principal interviews

Adequate water, sanitation, and hygiene(WASH) facilities in schools are vital, especially for girls. This study addresses a gap in assessing the adequacy of WASH facilities' repair at schools affected by natural hazards. Central Sulawesi was used as a case study where principal interviews were conducted at 26 schools, and structured observations were made at 18 schools, 3 years after the earthquake in September 2018. Of the 26 principals, 10 reported no damage to the toilets from the events of September 2018. Among those who reported damage, a third felt that the fixes insufficiently met basic needs and that they did not deliver WASH services as well as they used to. Structured observations revealed that most toilets lacked soap, open water reserves were placed next to non-flush latrines, posing a high potential for vector-breeding, and there were inadequate facilities for menstrual hygiene management, including no bins. Recommendations include ensuring a supply of soaps, adding lids to water storage containers for hygiene, and providing sanitary napkins and lidded bins. It was noted that private schools provided a better level of WASH service than state schools, and state schools in more hazardous zones did not take long to recover and offer lower-quality WASH facilities

A structured review of emotional barriers to WASH provision for schoolgirls post-disaster

Pubescent girls face unique emotional barriers to returning to school after a disaster concerning water, sanitation and hygiene (WASH). This paper explores themes of WASH, gender violence, the lack of dignity and sense of shame arising from inadequate WASH facilities for girls in disaster settings. We conducted a structured literature review of 126 sources to investigate the emotional constraints facing pubescent girls concerning WASH in schools in Indonesia, a region prone to frequent disasters. Findings are synthesised into four major themes: psychological experiences of WASH, challenges faced by girls in schools, barriers to inclusive WASH provision and how to create a holistic approach to WASH. Key conclusions include the need for interdisciplinary research, cross sectoral collaboration, more evidence and research in Indonesia, especially regarding menstrual hygiene management, improved toilet design to reduce the physical barriers linked to emotional barriers and inclusive design for those with disabilities.</p

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

SUMO ylated PRC 1 controls histone H3.3 deposition and genome integrity of embryonic heterochromatin

Chromatin integrity is essential for cellular homeostasis. Polycombgroup proteins modulate chromatin states and transcriptionallyrepress developmental genes to maintain cell identity. They alsorepress repetitive sequences such as major satellites and consti-tute an alternative state of pericentromeric constitutive hete-rochromatin at paternal chromosomes (pat-PCH) in mouse pre-implantation embryos. Remarkably, pat-PCH contains the histoneH3.3 variant, which is absent from canonical PCH at maternal chro-mosomes, which is marked by histone H3 lysine 9 trimethylation(H3K9me3), HP1, and ATRX proteins. Here, we show that SUMO2-modified CBX2-containing Polycomb Repressive Complex 1 (PRC1)recruits the H3.3-specific chaperone DAXX to pat-PCH, enablingH3.3 incorporation at these loci. Deficiency of Daxx or PRC1 compo-nents Ring1 and Rnf2 abrogates H3.3 incorporation, induces chro-matin decompaction and breakage at PCH of exclusively paternalchromosomes, and causes their mis-segregation. Complementationassays show that DAXX-mediated H3.3 deposition is required forchromosome stability in early embryos. DAXX also regulates repres-sion of PRC1 target genes during oogenesis and early embryogene-sis. The study identifies a novel critical role for Polycomb inensuring heterochromatin integrity and chromosome stability inmouse early development

Assessment of WASH infrastructure in schools in Central Sulawesi, Indonesia using structured observations and principal interviews

Adequate water, sanitation, and hygiene (WASH) facilities in schools are vital, especially for girls. This study addresses a gap in assessing the adequacy of WASH facilities' repair at schools affected by natural hazards. Central Sulawesi was used as a case study where principal interviews were conducted at 26 schools, and structured observations were made at 18 schools, 3 years after the earthquake in September 2018. Ten of 26 principals reported no damage to the toilets from the events of September 2018. Among those who did, a third felt that the fixes insufficiently met basic needs and that they did not deliver WASH services as well as they used to. Not all WASH inadequacy stemmed from the earthquake. Structured observations revealed that most toilets lacked soap, open water reserves were placed next to non-flush latrines, posing a high potential for vector-breeding, and there were inadequate facilities for menstrual hygiene management, including no bins. Recommendations include ensuring a supply of soap, adding lids to water storage containers, and providing sanitary napkins and lidded bins. Observations suggested that private schools provided a better level of WASH service than state schools, and schools in more hazardous zones did not take longer to recover. HIGHLIGHTS Structured observations and interviews with school principals were used to assess WASH facilities, 3 years after the 2018 earthquake in Central Sulawesi, Indonesia.; Coping mechanisms for damage to main pipelines include storing water in buckets in toilets.; State schools lagged behind private schools in WASH facilities.; Inadequate menstrual hygiene management in schools.

The RNase III Enzyme DROSHA Is Essential for MicroRNA Production and Spermatogenesis

Background: miRNA biogenesis requires two RNase III enzymes, DROSHA and DICER. Results: Lack of DROSHA in the male germ line leads to deficiency in miRNA production and male infertility. Conclusion: DROSHA and DICER have both common and unique functions in male germ cell development. Significance: This study reveals an essential role of DROSHA, DICER, and DROSHA-/DICER-dependent small noncoding RNAs spermatogenesis. DROSHA is a nuclear RNase III enzyme responsible for cleaving primary microRNAs (miRNAs) into precursor miRNAs and thus is essential for the biogenesis of canonical miRNAs. DICER is a cytoplasmic RNase III enzyme that not only cleaves precursor miRNAs to produce mature miRNAs but also dissects naturally formed/synthetic double-stranded RNAs to generate small interfering RNAs (siRNAs). To investigate the role of canonical miRNA and/or endogenous siRNA production in spermatogenesis, we generated Drosha or Dicer conditional knock-out (cKO) mouse lines by inactivating Drosha or Dicer exclusively in spermatogenic cells in postnatal testes using the Cre-loxp strategy. Both Drosha and Dicer cKO males were infertile due to disrupted spermatogenesis characterized by depletion of spermatocytes and spermatids leading to oligoteratozoospermia or azoospermia. The developmental course of spermatogenic disruptions was similar at morphological levels between Drosha and Dicer cKO males, but Drosha cKO testes appeared to be more severe in spermatogenic disruptions than Dicer cKO testes. Microarray analyses revealed transcriptomic differences between Drosha - and Dicer -null pachytene spermatocytes or round spermatids. Although levels of sex-linked mRNAs were mildly elevated, meiotic sex chromosome inactivation appeared to have occurred normally. Our data demonstrate that unlike DICER, which is required for the biogenesis of several small RNA species, DROSHA is essential mainly for the canonical miRNA production, and DROSHA-mediated miRNA production is essential for normal spermatogenesis and male fertility

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research