Initial State Interactions for K−K^--Proton Radiative Capture

The effects of the initial state interactions on the $K^--p$ radiative capture branching ratios are examined and found to be quite sizable. A general coupled-channel formalism for both strong and electromagnetic channels using a particle basis is presented, and applied to all the low energy $K^--p$ data with the exception of the {\it 1s} atomic level shift. Satisfactory fits are obtained using vertex coupling constants for the electromagnetic channels that are close to their expected SU(3) values.Comment: 16 pages, uses revte

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

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

Purpose: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors. Methods: A total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study. Results: None of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_297

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

Identification by gas chromatography-mass spectrometry of the volatile organic compounds emitted from the wood-rotting fungi Serpula lacrymans and Coniophora puteana, and from Pinus sylvestris timber

Volatile organic compounds (VOCs) emitted by two wood-rotting basidiomycete fungi, Serpula lacrymans (dry rot fungus) and Coniophora puteana (cellar fungus), and the timber of Pinus sylvestris (Scots pine), were identified. Several volatile collection techniques were employed including dichloromethane solvent extraction, solid-phase microextraction (SPME) and thermal desorption of VOCs entrained on Tenax GR. In addition, a new method of solid sample injection (SSI) is described which utilises a low injector temperature and an all-glass deactivated injector liner designed to minimise both the formation of pyrolysis products and analyte degradation. All the volatile compounds collected were analysed using electron impact capillary gas chromatography-mass spectrometry (GC-MS) on HP-5. HP-Innowax and β-cyclodextrin columns. SSI and Tenax thermal desorption were found to be the most effective extraction methods. A total of 19 VOCs were observed from S. lacrymans grown on glass slides and pine, 15 from C. puteana grown on glass slides and 12 from P. sylvestris timber. S. lacrymaux was found to emit, in low abundance, six unique VOCs, of which 2-methylbutanal was the greatest. The major volatile compound emitted by S. lacrymans was 1-octen-3-ol, which was also found in lower abundance from C. puteana. Six VOCs, including diethylene glycol and 4-methyl methylbenzoate, were found to be unique to C. puteana, all in medium abundance. From P. sylvestris, the major volatiles identified were S-α-pinene and 3-carene

The competition between halogen bonds (Br???O) and C–H???O hydrogen bonds: the structure of the acetone–bromine complex revisited

A combination of single-crystal X-ray (at 110 and 200 K) and high-resolution neutron powder diffraction (110 K only) using perdeuterated samples has been used to re-determine the crystal structure of the well-known acetone-Br-2 complex. The results indicate a significant interaction between the carbonyl oxygen and the nearest Br atom leading to a marked elongation of the molecular Br-Br bond. In the earlier widely cited crystal structure, no such elongation was reported. Furthermore, the new structure indicates the presence of additional weaker C-H???O and C-H???Br interactions. In this simple complex, in which the halogen bonding is strong compared to the hydrogen bonding (C-H???O), the former interaction is found to occur close (similar to 12 degrees) to the plane of the carbonyl group, with the C-H???Br complementing the stronger halogen bond

Gas chromatography-mass spectrometry analyses of volatile organic compounds from potato tubers inoculated with Phytophthora infestans or Fusarium coeruleum

Volatile organic compounds (VOCs) collected from potato tubers inoculated with Phytophthora infestans (late blight), Fusarium coeruleum (dry rot) or sterilized distilled water (as a control) were analysed using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID). A total of 52 volatiles were identified by GC-MS in the headspaces above P. infestans- and F. coeruleum-inoculated tubers after incubation for 42 days in the dark at 10°C. Of these VOCs, the six most abundant were common to both pathogens. These were benzothiazole (highest abundance), 2-ethyl-1-hexanol (second highest abundance), and at approximately equal third abundance, hexanal, 2-methylpropanoic acid-2,2-dimethyl-1-(2-hydroxy-1-methylethyl)-propyl ester, 2-methylpropanoic acid-3-hydroxy-2,4,4-trimethyl-pentyl ester and phenol. In addition, styrene also occurred at approximately equal third abundance in the headspace of F. coeruleum-inoculated tubers, but at lower abundance in the headspace of P. infestans-inoculated tubers. Some VOCs were specific to each pathogen. Butanal, 3-methylbutanal, undecane and verbenone were found at low levels only in the headspace of tubers inoculated with P. infestans, while 2-pentylfuran and copaene were found only in the headspace of tubers inoculated with F. coeruleum. Additionally GC-FID analysis identified ethanol and 2-propanol in the liquid exudate from both P. infestans- and F. coeruleum-inoculated tubers after incubation for 35 days, and in the headspace after incubation for 42 days. These data provide key information for developing a sensor-based early warning system for the detection of postharvest diseases in stored potato tubers

Performance of new criteria for right ventricular hypertrophy and myocardial infarction in patients with pulmonary hypertension due to cor pulmonale and mitral stenosis

Historically, electrocardiographic criteria for right ventricular (RV) hypertrophy has achieved high specificity but low sensitivity. Recently, however, Butler-Leggett et al, have introduced three criteria that attained a 66% sensitivity in a population with RV hypertrophy due to mitral stenosis while maintaining a 95% specificity in an extensive normal control group. Electrocardiographic diagnosis of RV hypertrophy is principally dependent on changes in the QRS complex that may be masked or mimicked by myocardial infarction (MI). This dilemma has been confirmed by documentation of the low specificity of both the Selvester QRS scoring system for MI size estimation (>3 points) and its screening subset (>0 points) in a pure mitral stenosis population. This study introduces the population characterized by RV hypertrophy due to cor pulmonale, which has a mean pulmonary arterial systolic pressure that is higher than the mean for the mitral stenosis population and consequently suggests more severe RV hypertrophy. When compared, the Butler-Leggett criteria for RV hypertrophy are more sensitive in the new population than in the mitral stenosis population (89% versus 60%) and the Selvester QRS scoring system is less specific (12% versus 60%). Three sequential steps are suggested for electrocardiographic analysis: (1) diagnosis of RV hypertrophy using the Butler-Leggett criteria, (2) diagnosis of MI using the Selvester screening criteria in those patients with step 1 negative, and (3) estimation of MI size using the complete Selvester scoring system in patients with step 1 negative and step 2 positive