A human infertility-associated KASH5 variant promotes mitochondrial localization

KASH5 is the most recently identified member of the KASH domain family of tail anchored, outer nuclear membrane (ONM) and endoplasmic reticulum (ER) proteins. During meiosis prophase I, KASH5 and SUN1 form a complex that spans the nuclear envelope and which links the telomeres of meiotic chromosomes to cytoplasmic dynein. This connection is essential for homologous chromosome dynamics and pairing. A recent study identified a variant in human KASH5 (L535Q) that correlated with male infertility associated with azoospermia. However, no molecular mechanism was described. Here, we report that this amino acid substitution, within the KASH5 transmembrane domain (TMD) has no predicted effects on secondary structure. However, the overall hydrophobicity of the L535Q TMD, is calculated to be lower than the wild-type KASH5, based on the GES (Goldman–Engelman–Steitz) amino acid hydrophobicity scale. This change in hydrophobicity profoundly affects the subcellular localization of KASH5. Through a series of amino acid substitution studies, we show that the L535Q substitution perturbs KASH5 localization to the ER and ONM and instead results in mistargeting to the mitochondria membrane. We suggest that this mislocalization accounts for the infertility and azoospermia phenotype in patients.Other Information Published in: Scientific Reports License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41598-021-89439-2</p

Reduced expression of PML predisposes to Paget's disease of bone by increasing osteoclast differentiation and bone resorption

Paget's disease of bone (PDB) is characterized by focal increases in bone remodelling. Genome-wide association studies identified a susceptibility locus for PDB tagged by rs5742915, which is located within the PML gene. Here, we have assessed the candidacy of PML as the predisposing gene for PDB at this locus. We found that the PDB-risk allele of rs5742915 was associated with lower PML expression and that PML expression in blood cells from individuals with PDB was lower than in controls. The differentiation, survival and resorptive activity of osteoclasts prepared from Pml-/- mice was increased compared with wild type. Furthermore, the inhibitory effect of IFN-γ on osteoclast formation from Pml-/- was significantly blunted compared with wild type. Bone nodule formation was also increased in osteoblasts from Pml-/- mice when compared with wild type. Although microCT analysis of trabecular bone showed no differences between Pml-/- mice and wild type, bone histomorphometry showed that Pml-/- mice had high bone turnover with increased indices of bone resorption and increased mineral apposition rate. These data indicate that reduced expression of PML predisposes an individual to PDB and identify PML as a novel regulator of bone metabolism. This article has an associated First Person interview with the first author of the paper

Vulnerable warriors: the atmospheric marketing of military and policing equipment before and after 9/11

In this article, we analyse changes in the circulation of advertisements of policing products at security expos between 1995 and 2013. While the initial aim of the research was to evidence shifts in terrorist frames in the marketing of policing equipment before and after 9/11, our findings instead suggested that what we are seeing is the rise of marketing to police as “vulnerable warriors”, law enforcement officers in need of military weapons both for their offensive capabilities and for the protection they can offer to a police force that is always under threat

The ocean sampling day consortium.

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

OceanSITES Innovation Report

Innovation and improvement report on the extension of capabilities to measure emerging EOVs including metagenomics across different observational platforms with links to MicroB3 best practice

Exploring the potential of civic engagement to strengthen mental health systems in Indonesia (IGNITE) : a study protocol

Background Indonesia has the highest rate of years of life lost to disability or early death from Schizophrenia than any other country in the world. More than 90% of people with mental illness do not get any treatment and tens of thousands of people with psychosis are illegally detained ('pasung') in the family home. Civic engagement, a core part of the recent World Health Organisation global strategy, has the potential to address some of these challenges through the development of person-centered models of care. The aim of the study is to develop a testable systems level, culturally appropriate, civic engagement framework for use in Jakarta and Bogor, Indonesia to strengthen local mental health services. Methods A mixed methods study underpinned by a realist approach will be undertaken across four phases in two study sites in Indonesia (Jakarta and Bogor). Phase 1 will explore the use of civic engagement across South East Asia by conducting a systematic review of existing evidence. By surveying 300 mental health professionals, phase 2 will identify the stakeholders, the sources of collaboration and the evidence used by professionals in decision making within local mental health systems and identify potential opportunities for civic engagement within the system. In order to explore the potential use of civic engagement within Indonesian mental health services and identify priorities for a culturally appropriate framework, phase 3 will undertake two focus groups with participants with experience of psychosis or caring for someone with psychosis (n = 20–30). Professionals and other key decision makers in a range of roles across the system at a national (n = 5) and local level (n = 10–15/site) will also take part in semi-structured interviews. Phase 4 will co-produce a civic engagement framework for use in Indonesia by synthesising evidence from phases 1–3 collaboratively with key stakeholders. Discussion Civic engagement is a potential way in which health services in low and middle income countries can address the burden of mental health conditions through the development of person-centred models of care. However, such approaches are underexplored in Indonesia. This study will work with local stakeholders to design a testable civic engagement framework for use in mental health services in Indonesia