Autosomal Recessive Dilated Cardiomyopathy due to DOLK Mutations Results from Abnormal Dystroglycan O-Mannosylation

Genetic causes for autosomal recessive forms of dilated cardiomyopathy (DCM) are only rarely identified, although they are thought to contribute considerably to sudden cardiac death and heart failure, especially in young children. Here, we describe 11 young patients (5–13 years) with a predominant presentation of dilated cardiomyopathy (DCM). Metabolic investigations showed deficient protein N-glycosylation, leading to a diagnosis of Congenital Disorders of Glycosylation (CDG). Homozygosity mapping in the consanguineous families showed a locus with two known genes in the N-glycosylation pathway. In all individuals, pathogenic mutations were identified in DOLK, encoding the dolichol kinase responsible for formation of dolichol-phosphate. Enzyme analysis in patients' fibroblasts confirmed a dolichol kinase deficiency in all families. In comparison with the generally multisystem presentation in CDG, the nonsyndromic DCM in several individuals was remarkable. Investigation of other dolichol-phosphate dependent glycosylation pathways in biopsied heart tissue indicated reduced O-mannosylation of alpha-dystroglycan with concomitant functional loss of its laminin-binding capacity, which has been linked to DCM. We thus identified a combined deficiency of protein N-glycosylation and alpha-dystroglycan O-mannosylation in patients with nonsyndromic DCM due to autosomal recessive DOLK mutations

VISIONS:the VISTA Star Formation Atlas I. Survey overview

VISIONS is an ESO public survey of five nearby (d < 500 pc) star-forming molecular cloud complexes that are canonically associated with the constellations of Chamaeleon, Corona Australis, Lupus, Ophiuchus, and Orion. The survey was carried out with the Visible and Infrared Survey Telescope for Astronomy (VISTA), using the VISTA Infrared Camera (VIRCAM), and collected data in the near-infrared passbands J (1.25 μm), H (1.65 μm), and KS (2.15 μm). With a total on-sky exposure time of 49.4h VISIONS covers an area of 650 deg2, it is designed to build an infrared legacy archive with a structure and content similar to the Two Micron All Sky Survey (2MASS) for the screened star-forming regions. Taking place between April 2017 and March 2022, the observations yielded approximately 1.15 million images, which comprise 19 TB of raw data. The observations undertaken within the survey are grouped into three different subsurveys. First, the wide subsurvey comprises shallow, large-scale observations and it has revisited the star-forming complexes six times over the course of its execution. Second, the deep subsurvey of dedicated high-sensitivity observations has collected data on areas with the largest amounts of dust extinction. Third, the control subsurvey includes observations of areas of low-to-negligible dust extinction. Using this strategy, the VISIONS observation program offers multi-epoch position measurements, with the ability to access deeply embedded objects, and it provides a baseline for statistical comparisons and sample completeness – all at the same time. In particular, VISIONS is designed to measure the proper motions of point sources, with a precision of 1 mas yr−1 or better, when complemented with data from the VISTA Hemisphere Survey (VHS). In this way, VISIONS can provide proper motions of complete ensembles of embedded and low-mass objects, including sources inaccessible to the optical ESA Gaia mission. VISIONS will enable the community to address a variety of research topics from a more informed perspective, including the 3D distribution and motion of embedded stars and the nearby interstellar medium, the identification and characterization of young stellar objects, the formation and evolution of embedded stellar clusters and their initial mass function, as well as the characteristics of interstellar dust and the reddening law

VISIONS:the VISTA Star Formation Atlas I. Survey overview

VISIONS is an ESO public survey of five nearby (d < 500 pc) star-forming molecular cloud complexes that are canonically associated with the constellations of Chamaeleon, Corona Australis, Lupus, Ophiuchus, and Orion. The survey was carried out with the Visible and Infrared Survey Telescope for Astronomy (VISTA), using the VISTA Infrared Camera (VIRCAM), and collected data in the near-infrared passbands J (1.25 μm), H (1.65 μm), and KS (2.15 μm). With a total on-sky exposure time of 49.4h VISIONS covers an area of 650 deg2, it is designed to build an infrared legacy archive with a structure and content similar to the Two Micron All Sky Survey (2MASS) for the screened star-forming regions. Taking place between April 2017 and March 2022, the observations yielded approximately 1.15 million images, which comprise 19 TB of raw data. The observations undertaken within the survey are grouped into three different subsurveys. First, the wide subsurvey comprises shallow, large-scale observations and it has revisited the star-forming complexes six times over the course of its execution. Second, the deep subsurvey of dedicated high-sensitivity observations has collected data on areas with the largest amounts of dust extinction. Third, the control subsurvey includes observations of areas of low-to-negligible dust extinction. Using this strategy, the VISIONS observation program offers multi-epoch position measurements, with the ability to access deeply embedded objects, and it provides a baseline for statistical comparisons and sample completeness – all at the same time. In particular, VISIONS is designed to measure the proper motions of point sources, with a precision of 1 mas yr−1 or better, when complemented with data from the VISTA Hemisphere Survey (VHS). In this way, VISIONS can provide proper motions of complete ensembles of embedded and low-mass objects, including sources inaccessible to the optical ESA Gaia mission. VISIONS will enable the community to address a variety of research topics from a more informed perspective, including the 3D distribution and motion of embedded stars and the nearby interstellar medium, the identification and characterization of young stellar objects, the formation and evolution of embedded stellar clusters and their initial mass function, as well as the characteristics of interstellar dust and the reddening law

VISIONS: The VISTA Star Formation Atlas -- I. Survey overview

© The Authors 2023. Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0).VISIONS is an ESO public survey of five nearby (d < 500 pc) star-forming molecular cloud complexes that are canonically associated with the constellations of Chamaeleon, Corona Australis, Lupus, Ophiuchus, and Orion. The survey was carried out with VISTA, using VIRCAM, and collected data in the near-infrared passbands J, H, and Ks. With a total on-sky exposure time of 49.4 h VISIONS covers an area of 650 deg$^2$, and it was designed to build an infrared legacy archive similar to that of 2MASS. Taking place between April 2017 and March 2022, the observations yielded approximately 1.15 million images, which comprise 19 TB of raw data. The observations are grouped into three different subsurveys: The wide subsurvey comprises shallow, large-scale observations and has visited the star-forming complexes six times over the course of its execution. The deep subsurvey of dedicated high-sensitivity observations has collected data on the areas with the largest amounts of dust extinction. The control subsurvey includes observations of areas of low-to-negligible dust extinction. Using this strategy, the VISIONS survey offers multi-epoch position measurements, is able to access deeply embedded objects, and provides a baseline for statistical comparisons and sample completeness. In particular, VISIONS is designed to measure the proper motions of point sources with a precision of 1 mas/yr or better, when complemented with data from VHS. Hence, VISIONS can provide proper motions for sources inaccessible to Gaia. VISIONS will enable addressing a range of topics, including the 3D distribution and motion of embedded stars and the nearby interstellar medium, the identification and characterization of young stellar objects, the formation and evolution of embedded stellar clusters and their initial mass function, as well as the characteristics of interstellar dust and the reddening law.Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reelin Together with ApoER2 Regulates Interneuron Migration in the Olfactory Bulb

One pathway regulating the migration of neurons during development of the mammalian cortex involves the extracellular matrix protein Reelin. Reelin and components of its signaling cascade, the lipoprotein receptors ApoER2 and Vldlr and the intracellular adapter protein Dab1 are pivotal for a correct layer formation during corticogenesis. The olfactory bulb (OB) as a phylogenetically old cortical region is known to be a prominent site of Reelin expression. Although some aspects of Reelin function in the OB have been described, the influence of Reelin on OB layer formation has so far been poorly analyzed. Here we studied animals deficient for either Reelin, Vldlr, ApoER2 or Dab1 as well as double-null mutants. We performed organotypic migration assays, immunohistochemical marker analysis and BrdU incorporation studies to elucidate roles for the different components of the Reelin signaling cascade in OB neuroblast migration and layer formation. We identified ApoER2 as being the main receptor responsible for Reelin mediated detachment of neuroblasts and correct migration of early generated interneurons within the OB, a prerequisite for correct OB laminatio