A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum

A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20ka, 15ka, 10ka and 5ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse 1a. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorit. © 2014 The Authors

WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene

Telomere length (TL) regulation is an important factor in ageing, reproduction and cancer development. Genetic, hereditary and environmental factors regulating TL are currently widely investigated, however, their relative contribution to TL variability is still understudied. We have used whole genome sequencing data of 250 family trios from the Genome of the Netherlands project to perform computational measurement of TL and a series of regression and genome-wide association analyses to reveal TL inheritance patterns and associated genetic factors. Our results confirm that TL is a largely heritable trait, primarily with mother’s, and, to a lesser extent, with father’s TL having the strongest influence on the offspring. In this cohort, mother’s, but not father’s age at conception was positively linked to offspring TL. Age-related TL attrition of 40 bp/year had relatively small influence on TL variability. Finally, we have identified TL-associated variations in ribonuclease reductase catalytic subunit M1 (RRM1 gene), which is known to regulate telomere maintenance in yeast. We also highlight the importance of multivariate approach and the limitations of existing tools for the analysis of TL as a polygenic heritable quantitative trait

Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County, Minnesota

Circulation115151982-199

Surgical outcomes and strategy of hypertrophic obstructive cardiomyopathy

Objective: To evaluate the surgical clinical results of hypertrophic obstructive cardiomyopathy. Methods: We retrospectively collected data on 24 patients who underwent surgical management in the past ten years in two hospitals in China and Madras Medical Mission in India. Myomectomy was carried out on all patients. Among them 3 patients underwent mitral valve replacement; 2 patients underwent mitral valve repair (anterior mitral leaflet plication); 2 patients underwent aortic valve replacement; 1 patient underwent aortic valve repair; 2 patients underwent aortic root replacement; 1 patient underwent Bentall’s procedure and 1 patient underwent coronary artery bypass grafting because of a breached muscle bridge. Results: One patient died of post-operative heart failure. The mean follow-up time was 4.3 years. There was significant improvement in the symptomatic status. Sixteen patients were asymptomatic with good effort tolerance and only four patients had New York heart association (NYHA) Classes I~II due to associated valvular lesions. Conclusion: Our experience proved that symptomatic hypertrophic obstructive cardiomyopathy or non-symptomatic hypertrophic obstructive cardiomyopathy with combined heart disease is indication for surgery as surgical intervention could get better clinical results in this kind of patients compared with other non-surgical method because it beneficially reduces the systolic anterior motion (SAM) of the mitral valve leaflet, which could not be avoided by other non-surgical treatment

Genome-wide patterns and properties of de novo mutations in humans

Mutations create variation in the population, fuel evolution and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect. Here we analyze 11,020 de novo mutations from the whole genomes of 250 families. We show that de novo mutations in the offspring of older fathers are not only more numerous but also occur more frequently in early-replicating, genic regions. Functional regions exhibit higher mutation rates due to CpG dinucleotides and show signatures of transcription-coupled repair, whereas mutation clusters with a unique signature point to a new mutational mechanism. Mutation and recombination rates independently associate with nucleotide diversity, and regional variation in human-chimpanzee divergence is only partly explained by heterogeneity in mutation rate. Finally, we provide a genome-wide mutation rate map for medical and population genetics applications. Our results provide new insights and refine long-standing hypotheses about human mutagenesis