Vibrationally induced inversion of photoelectron forward-backward asymmetry in chiral molecule photoionization by circularly polarized light

Electron–nuclei coupling accompanying excitation and relaxation processes is a fascinating phenomenon in molecular dynamics. A striking and unexpected example of such coupling is presented here in the context of photoelectron circular dichroism measurements on randomly oriented, chiral methyloxirane molecules, unaffected by any continuum resonance. Here, we report that the forward-backward asymmetry in the electron angular distribution, with respect to the photon axis, which is associated with photoelectron circular dichroism can surprisingly reverse direction according to the ion vibrational mode excited. This vibrational dependence represents a clear breakdown of the usual Franck–Condon assumption, ascribed to the enhanced sensitivity of photoelectron circular dichroism (compared with other observables like cross-sections or the conventional anisotropy parameter-β) to the scattering phase off the chiral molecular potential, inducing a dependence on the nuclear geometry sampled in the photoionization process. Important consequences for the interpretation of such dichroism measurements within analytical contexts are discussed

Determinants of exercise peak arterial blood pressure, circulatory power, and exercise cardiac power in a population based sample of Finnish male and female aged 30 to 47 years: the Cardiovascular Risk in Young Finns Study

Background Novel parameters derived from peak maximal oxygen uptake (VO2) and exercise arterial blood pressure, such as peak circulatory power (CP) and exercise cardiac power (ECP), can be used in the risk assessment of cardiovascular disease and stroke. However, the determinants of these factors are poorly characterized in the general population. Methods We assessed peak arterial blood pressure, CP and ECP with standardized cardiopulmonary exercise test (CPET) on 281 female and 257 male participants of the Cardiovascular Risk in Young Finns Study. The subjects were aged 30–47 years. Peak VO2 as well as systolic and diastolic arterial blood pressures were measured to calculate peak mean arterial pressure, CP and ECP. These parameters were assessed for correlation with sex, age, height, weight, waist-to-hip ratio, smoking, physical activity index (PAI), fasting insulin and glucose levels as well as the use of antihypertensive treatment. Results Sex, age and weight explained 36% of the variation in peak systolic blood pressure, and these factors in combination with height and the use of antihypertensive treatment explained 13% of the variation in peak diastolic blood pressure. Sex, height, weight, waist-to-hip ratio, PAI and smoking explained 49% − 52% of the variation in peak CP. Sex, age, height, weight, waist-to-hip ratio, PAI, smoking and insulin levels explained 21% − 49% of variation in ECP. Conclusions Subject demographics and lifestyle-related factors should be taken into account when exercise blood pressure response, CP and ECP are used to evaluate patients’ cardiac function in CPET.BioMed Central open acces

Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands

Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Exome sequencing of a single cohort of 2,871 CHD probands including 2,645 parent- offspring trios implicated rare transmitted mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ~5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ~11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ~3% of isolated CHD patients and ~28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance and 19 genes not previously implicated in CHD had > 70% probability of being disease-related; DNMs in ~440 genes are inferred to contribute to CHD. There was striking overlap between genes with damaging DNMs in probands with CHD and autism

Insights into the evolution of mammalian telomerase: Platypus TERT shares similarities with genes of birds and other reptiles and localizes on sex chromosomes

Background The TERT gene encodes the catalytic subunit of the telomerase complex and is responsible for maintaining telomere length. Vertebrate telomerase has been studied in eutherian mammals, fish, and the chicken, but less attention has been paid to other vertebrates. The platypus occupies an important evolutionary position, providing unique insight into the evolution of mammalian genes. We report the cloning of a platypus TERT (OanTERT) ortholog, and provide a comparison with genes of other vertebrates. Results The OanTERT encodes a protein with a high sequence similarity to marsupial TERT and avian TERT. Like the TERT of sauropsids and marsupials, as well as that of sharks and echinoderms, OanTERT contains extended variable linkers in the N-terminal region suggesting that they were present already in basal vertebrates and lost independently in rayfinned fish and eutherian mammals. Several alternatively spliced OanTERT variants structurally similar to avian TERT variants were identified. Telomerase activity is expressed in all platypus tissues like that of cold-blooded animals and murine rodents. OanTERT was localized on pseudoautosomal regions of sex chromosomes X3/Y2, expanding the homology between human chromosome 5 and platypus sex chromosomes. Synteny analysis suggests that TERT co-localized with sex-linked genes in the last common mammalian ancestor. Interestingly, female platypuses express higher levels of telomerase in heart and liver tissues than do males. Conclusions OanTERT shares many features with TERT of the reptilian outgroup, suggesting that OanTERT represents the ancestral mammalian TERT. Features specific to TERT of eutherian mammals have, therefore, evolved more recently after the divergence of monotremes.Radmila Hrdličková, Jiří Nehyba, Shu Ly Lim, Frank Grützner, Henry R Bose J

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons