Somatic expansion of the CAG repeat tract that causes Huntington’s disease (HD) is thought to contribute to the rate of disease pathogenesis. Therefore, factors influencing repeat expansion are potential therapeutic targets. Genes in the DNA mismatch repair pathway are critical drivers of somatic expansion in HD mouse models. Here, we have tested, using genetic and pharmacological approaches, the role of the endonuclease domain of the mismatch repair protein MLH3 in somatic CAG expansion in HD mice and patient cells. A point mutation in the MLH3 endonuclease domain completely eliminated CAG expansion in the brain and peripheral tissues of a HD knock-in mouse model (HttQ111). To test whether the MLH3 endonuclease could be manipulated pharmacologically, we delivered splice switching oligonucleotides in mice to redirect Mlh3 splicing to exclude the endonuclease domain. Splice redirection to an isoform lacking the endonuclease domain was associated with reduced CAG expansion. Finally, CAG expansion in HD patient-derived primary fibroblasts was also significantly reduced by redirecting MLH3 splicing to the endogenous endonuclease domain-lacking isoform. These data indicate the potential of targeting the MLH3 endonuclease domain to slow somatic CAG repeat expansion in HD, a therapeutic strategy that may be applicable across multiple repeat expansion disorders.Consumption of healthy and sustainable diets (HSD) provides opportunities to co-benefit human health and adapt to and mitigate climate change. Despite robust evidence and policy recommendations from authoritative groups to reorientate the food system to favour consumption of HSD there has been limited policy action. This study investigated potential barriers and enablers for successful HSD policies in Australia. A review of HSD policy recommendations and of current Australian policies was undertaken. Results from the reviews informed a Delphi study, which investigated Australian stakeholder opinions on the effectiveness of HSD policy recommendations and barriers and enablers to creating successful HSD policies. Nine participants completed two Delphi iterations. A lack of consensus was reached on the effectiveness of policy recommendations. Consensus was reached on the effect of five barriers and three enablers. Key barriers were the complex nature of the food system, competing interests of stakeholders, pressure from industry, government silos and lack of political will. Key enablers were building relationships with key stakeholders across multiple disciplines and sectors, understanding the policy making process and developing a clear and coherent solution. Most of the identified barriers fall under the broad category of lack of political will. Interrelationships between barriers are likely worsening the impact of inadequate political will. There is a need to act on the identified barriers and enablers to secure the HSD policies that are required. Interactions between barriers may present an opportunity to address them simultaneously.One of the best examples of sexual dimorphism is the development and function of the gonads, ovaries and testes, which produce sex-specific gametes, oocytes, and spermatids, respectively. The development of these specialized germ cells requires sex-matched somatic support cells. The sexual identity of somatic gonadal cells is specified during development and must be actively maintained during adulthood. We previously showed that the transcription factor Chinmo is required to ensure the male sexual identity of somatic support cells in the Drosophila melanogaster testis. Loss of chinmo from male somatic gonadal cells results in feminization they transform from squamous to epithelial-like cells that resemble somatic cells in the female gonad but fail to properly ensheath the male germline, causing infertility. Binimetinib molecular weight To identify potential target genes of Chinmo, we purified somatic cells deficient for chinmo from the adult Drosophila testis and performed next-generation sequencing to compare their transcriptome to that of control somatic cells. Bioinformatics revealed 304 and 1549 differentially upregulated and downregulated genes, respectively, upon loss of chinmo in early somatic cells. Using a combination of methods, we validated several differentially expressed genes. These data sets will be useful resources to the community.Necrophilous insects occupy an ecologically interesting niche because carrion is a highly desirable but ephemeral food source. Dung beetles (Coleoptera Scarabaeidae Scarabaeinae and Aphodiinae) within temperate regions are frequently found at carrion, but little is known about their attraction to this resource. Are dung beetles attracted to the carrion itself or are they indirectly attracted due to the exposed gastrointestinal contents? We investigated the association between dung beetles and carrion by examining the distribution of dung beetles on the cranial and caudal end of rat carcasses, delimiting a resource more attractive to necrophagous insects (cranial end) from a resource more attractive to coprophagous insects (caudal end). Dung beetle distribution on rat carcasses was compared with the distribution of carrion beetles (Coleoptera Silphidae), which serve as a null model of distribution patterns for a taxon known to directly target carrion. Results demonstrated that dung beetles show higher attraction to the cranial end of rat carrion. A similar distribution pattern was found in carrion beetles, suggesting that similar resources were targeted. When dung beetles were grouped by behavioral guilds, rollers and tunnelers also shared this pattern of greater abundance at the cranial end, but dwellers showed no discernible difference.A manually curated set of ohnolog families has been assembled, for seven species of bony vertebrates, that includes 255 four-member families and 631 three-member families, encompassing over 2,900 ohnologs. Across species, the patterns of chromosomes upon which the ohnologs reside fall into 17 distinct categories. These 17 paralogons reflect the 17 ancestral chromosomes that existed in our chordate ancestor immediately prior to the two rounds of whole-genome duplication (2R-WGD) that occurred around 600 Ma. Within each paralogon, it has now been possible to assign those pairs of ohnologs that diverged from each other at the first round of duplication, through analysis of the molecular phylogeny of four-member families. Comparison with another recent analysis has identified four apparently incorrect assignments of pairings following 2R, along with several omissions, in that study. By comparison of the patterns between paralogons, it has also been possible to identify nine chromosomal fusions that occurred between 1R and 2R, and three chromosomal fusions that occurred after 2R, that generated an ancestral bony-vertebrate karyotype comprising 47 chromosomes.