Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Functionalised inherently conducting polymers as low biofouling materials

Diatoms are a major component of microbial biofouling layers that develop on man-made surfaces placed in aquatic environments, resulting in significant economic and environmental impacts. This paper describes surface functionalisation of the inherently conducting polymers (ICPs) polypyrrole (PPy) and polyaniline (PANI) with poly(ethylene glycol) (PEG) and their efficacy as fouling resistant materials. Their ability to resist interactions with the model protein bovine serum albumin (BSA) was tested using a quartz crystal microbalance with dissipation monitoring (QCM-D). The capacity of the ICP-PEG materials to prevent settlement and colonisation of the fouling diatom Amphora coffeaeformis (Cleve) was also assayed. Variations were demonstrated in the dopants used during ICP polymerisation, along with the PEG molecular weight, and the ICP-PEG reaction conditions, all playing a role in guiding the eventual fouling resistant properties of the materials. Optimised ICP-PEG materials resulted in a significant reduction in BSA adsorption, and \u3e 98% reduction in diatom adhesion

X-ray structure, thermodynamics, elastic properties and MDsimulations of cardiolipin/dimyristoylphosphatidylcholine mixedmembranes

tCardiolipins (CLs) are important biologically for their unique role in biomembranes that couple phos-phorylation and electron transport like bacterial plasma membranes, chromatophores, chloroplasts andmitochondria. CLs are often tightly coupled to proteins involved in oxidative phosphorylation. The firststep in understanding the interaction of CL with proteins is to obtain the pure CL structure, and the struc-ture of mixtures of CL with other lipids. In this work we use a variety of techniques to characterize the fluidphase structure, material properties and thermodynamics of mixtures of dimyristoylphosphatidylcholine(DMPC) with tetramyristoylcardiolipin (TMCL), both with 14-carbon chains, at several mole percentages.X-ray diffuse scattering was used to determine structure, including bilayer thickness and area/lipid, thebending modulus, KC, and SXray, a measure of chain orientational order. Our results reveal that TMCL thick-ens DMPC bilayers at all mole percentages, with a total increase of ∼6˚A in pure TMCL, and increases ALfrom 64˚ A2(DMPC at 35◦C) to 109˚A2(TMCL at 50◦C). KCincreases by ∼50%, indicating that TMCL stiffensDMPC membranes. TMCL also orders DMPC chains by a factor of ∼2 for pure TMCL. Coarse grain moleculardynamics simulations confirm the experimental thickening of 2˚A for 20 mol% TMCL and locate the TMCLheadgroups near the glycerol-carbonyl region of DMPC; i.e., they are sequestered below the DMPC phos-phocholine headgroup. Our results suggest that TMCL plays a role similar to cholesterol in that it thickensand stiffens DMPC membranes, orders chains, and is positioned under the umbrella of the PC headgroup.CL may be necessary for hydrophobic matching to inner mitochondrial membrane proteins. Differentialscanning calorimetry, SXrayand CGMD simulations all suggest that TMCL does not form domains withinthe DMPC bilayers. We also determined the gel phase structure of TMCL, which surprisingly displaysdiffuse X-ray scattering, like a fluid phase lipid. AL= 40.8˚ A2for the ½TMCL gel phase, smaller than theDMPC gel phase with AL= 47.2˚ A2, but similar to ALof DLPE = 41˚ A2, consistent with untilted chains in gelphase TMCL