Domain matching epitaxy of ferrimagnetic CoFe2O4 thin films on Sc2O3/Si(111)

This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics.Ferrimagnetic spinel CoFe2O4 (CFO) films are integrated with Si(111) using Sc2O3 buffer layers. The huge lattice mismatch (17%) between CFO and Sc2O3 is accommodated by domain matching, and CFO grows epitaxially with (111) out-of-plane orientation and coexistence of A- and B-type in-plane crystal variants. CFO films have low roughness of 4 Å and saturation magnetization of about 300 emu/cm3. These properties make CFO films on Sc2O3-buffered Si(111) comparable to those grown on oxide single crystals and thus extend the possibilities of using spinel oxides in electronic devices

Genome-Wide Association Analysis Identifies Ancestry-Specific Genetic Variation Associated With Acute Response to Metformin and Glipizide in SUGAR-MGH

AIMS/HYPOTHESIS: Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes. METHODS: One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping Array. Imputation was performed with the TOPMed reference panel. Multiple linear regression using an additive model tested for association between genetic variants and primary endpoints of drug response. In a more focused analysis, we evaluated the influence of 804 unique type 2 diabetes- and glycaemic trait-associated variants on SUGAR-MGH outcomes and performed colocalisation analyses to identify shared genetic signals. RESULTS: Five genome-wide significant variants were associated with metformin or glipizide response. The strongest association was between an African ancestry-specific variant (minor allele frequency [MAF CONCLUSIONS/INTERPRETATION: We present a well-phenotyped, densely genotyped, multi-ancestry resource to study gene-drug interactions, uncover novel variation associated with response to common glucose-lowering medications and provide insight into mechanisms of action of type 2 diabetes-related variation. DATA AVAILABILITY: The complete summary statistics from this study are available at the Common Metabolic Diseases Knowledge Portal ( https://hugeamp.org ) and the GWAS Catalog ( www.ebi.ac.uk/gwas/ , accession IDs: GCST90269867 to GCST90269899)

An unbiased assessment of the role of imprinted genes in an intergenerational model of developmental programming.

Environmental factors during early life are critical for the later metabolic health of the individual and of future progeny. In our obesogenic environment, it is of great socioeconomic importance to investigate the mechanisms that contribute to the risk of metabolic ill health. Imprinted genes, a class of functionally mono-allelic genes critical for early growth and metabolic axis development, have been proposed to be uniquely susceptible to environmental change. Furthermore, it has also been suggested that perturbation of the epigenetic reprogramming of imprinting control regions (ICRs) may play a role in phenotypic heritability following early life insults. Alternatively, the presence of multiple layers of epigenetic regulation may in fact protect imprinted genes from such perturbation. Unbiased investigation of these alternative hypotheses requires assessment of imprinted gene expression in the context of the response of the whole transcriptome to environmental assault. We therefore analyse the role of imprinted genes in multiple tissues in two affected generations of an established murine model of the developmental origins of health and disease using microarrays and quantitative RT-PCR. We demonstrate that, despite the functional mono-allelicism of imprinted genes and their unique mechanisms of epigenetic dosage control, imprinted genes as a class are neither more susceptible nor protected from expression perturbation induced by maternal undernutrition in either the F1 or the F2 generation compared to other genes. Nor do we find any evidence that the epigenetic reprogramming of ICRs in the germline is susceptible to nutritional restriction. However, we propose that those imprinted genes that are affected may play important roles in the foetal response to undernutrition and potentially its long-term sequelae. We suggest that recently described instances of dosage regulation by relaxation of imprinting are rare and likely to be highly regulated

International consensus guideline for reporting transmission electron microscopy results in the diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria)

Primary Ciliary Dyskinesia (PCD) is a heterogeneous genetic condition. European and North American diagnostic guidelines recommend transmission electron microscopy (TEM) as one of a combination of tests to confirm a diagnosis. However, there is no definition of what constitutes a defect or consensus on reporting terminology. The aim of this project was to provide an internationally agreed ultrastructural classification for PCD diagnosis by TEM. A consensus guideline was developed by PCD electron microscopy experts representing 18 centres in 14 countries. An initial meeting and discussion were followed by a Delphi consensus process. The agreed guideline was then tested, modified and retested through exchange of samples and electron micrographs between the 18 diagnostic centres. The final guideline a) Provides agreed terminology and a definition of class 1 defects which are diagnostic for PCD; b) Identifies class 2 defects which can indicate a diagnosis of PCD in combination with other supporting evidence; c) Describes features which should be included in a ciliary ultrastructure report to assist multidisciplinary diagnosis of PCD d) Defines adequacy of a diagnostic sample. This tested and externally validated statement provides a clear guideline for the diagnosis of PCD by TEM which can be used to standardise diagnosis internationally.</p

A Common Genetic Origin for Early Farmers from Mediterranean Cardial and Central European LBK Cultures

The spread of farming out of the Balkans and into the rest of Europe followed two distinct routes: An initial expansión represented by the Impressa and Cardial traditions, which followed the Northern Mediterranean coastline; and another expansion represented by the LBK (Linearbandkeramik) tradition, which followed the Danube River into Central Europe. Although genomic data now exist from samples representing the second migration, such data have yet to be successfully generated from the initial Mediterranean migration. To address this, we generated the complete genome of a 7,400-yearold Cardial individual (CB13) from Cova Bonica in Vallirana (Barcelona), as well as partial nuclear data from five others excavated from different sites in Spain and Portugal. CB13 clusters with all previously sequenced early European farmers and modern-day Sardinians. Furthermore, our analyses suggest that both Cardial and LBK peoples derived from a common ancient population located in or around the Balkan Peninsula. The Iberian Cardial genome also carries a discernible huntergatherer genetic signature that likely was not acquired by admixture with local Iberian foragers. Our results indicate that retrieving ancient genomes from similarly warm Mediterranean environments such as the Near East is technically feasible

Expression of the Splicing Factor Gene SFRS10 Is Reduced in Human Obesity and Contributes to Enhanced Lipogenesis

SummaryAlternative mRNA splicing provides transcript diversity and may contribute to human disease. We demonstrate that expression of several genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. We evaluated a representative splicing factor, SFRS10, downregulated in both obese human liver and muscle and in high-fat-fed mice, and determined metabolic impact of reduced expression. SFRS10-specific siRNA induces lipogenesis and lipid accumulation in hepatocytes. Moreover, Sfrs10 heterozygous mice have increased hepatic lipogenic gene expression, VLDL secretion, and plasma triglycerides. We demonstrate that LPIN1, a key regulator of lipid metabolism, is a splicing target of SFRS10; reduced SFRS10 favors the lipogenic β isoform of LPIN1. Importantly, LPIN1β-specific siRNA abolished lipogenic effects of decreased SFRS10 expression. Together, our results indicate that reduced expression of SFRS10, as observed in tissues from obese humans, alters LPIN1 splicing, induces lipogenesis, and therefore contributes to metabolic phenotypes associated with obesity

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Global wetland contribution to 2000-2012 atmospheric methane growth rate dynamics

Increasing atmospheric methane (CH4) concentrations have contributed to approximately 20% of anthropogenic climate change. Despite the importance of CH4 as a greenhouse gas, its atmospheric growth rate and dynamics over the past two decades, which include a stabilization period (1999–2006), followed by renewed growth starting in 2007, remain poorly understood. We provide an updated estimate of CH4 emissions from wetlands, the largest natural global CH4 source, for 2000–2012 using an ensemble of biogeochemical models constrained with remote sensing surface inundation and inventory-based wetland area data. Between 2000–2012, boreal wetland CH4 emissions increased by 1.2 Tg yr−1 (−0.2–3.5 Tg yr−1), tropical emissions decreased by 0.9 Tg yr−1 (−3.2−1.1 Tg yr−1), yet globally, emissions remained unchanged at 184 ± 22 Tg yr−1. Changing air temperature was responsible for increasing high-latitude emissions whereas declines in low-latitude wetland area decreased tropical emissions; both dynamics are consistent with features of predicted centennial-scale climate change impacts on wetland CH4 emissions. Despite uncertainties in wetland area mapping, our study shows that global wetland CH4 emissions have not contributed significantly to the period of renewed atmospheric CH4 growth, and is consistent with findings from studies that indicate some combination of increasing fossil fuel and agriculture-related CH4 emissions, and a decrease in the atmospheric oxidative sink