Maternal underweight and obesity and risk of orofacial clefts in a large international consortium of population-based studies

Background: Evidence on association of maternal pre-pregnancy weight with risk of orofacial clefts is inconsistent

Inheritance analysis and identification of SNP markers associated with ZYMV resistance in Cucurbita pepo

[EN] Cucurbit crops are economically important worldwide. One of the most serious threats to cucurbit production is Zucchini yellow mosaic virus (ZYMV). Several resistant accessions were identified in Cucurbita moschata and their resistance was introgressed into Cucurbita pepo. However, the mode of inheritance of ZYMV resistance in C. pepo presents a great challenge to attempts at introgressing resistance into elite germplasm. The main goal of this work was to analyze the inheritance of ZYMV resistance and to identify markers associated with genes conferring resistance. An Illumina GoldenGate assay allowed us to assess polymorphism among nine squash genotypes and to discover six polymorphic single-nucleotide polymorphisms (SNPs) between two near-isogenic lines, "True French" (susceptible to ZYMV) and Accession 381e (resistant to ZYMV). Two F-2 and three BC1 populations obtained from crossing the ZYMV-resistant Accession 381e with two susceptible ones, the zucchini True French and the cocozelle "San Pasquale," were assayed for ZYMV resistance. Molecular analysis revealed an approximately 90% association between SNP1 and resistance, which was confirmed using High Resolution Melt (HRM) and a CAPS marker. Co-segregation up to 72% in populations segregating for resistance was observed for two other SNP markers that could be potentially linked to genes involved in resistance expression. A functional prediction of proteins involved in the resistance response was performed on genome scaffolds containing the three SNPs of interest. Indeed, 16 full-length pathogen recognition genes (PRGs) were identified around the three SNP markers. In particular, we discovered that two nucleotide-binding site leucine-rich repeat (NBS-LRR) protein-encoding genes were located near the SNP1 marker. The investigation of ZYMV resistance in squash populations and the genomic analysis performed in this work could be useful for better directing the introgression of disease resistance into elite C. pepo germplasm.This work was supported by the Ministry of University and Research (GenHORT project).Capuozzo, C.; Formisano, G.; Iovieno, P.; Andolfo, G.; Tomassoli, L.; Barbella, M.; Picó Sirvent, MB.... (2017). Inheritance analysis and identification of SNP markers associated with ZYMV resistance in Cucurbita pepo. Molecular Breeding. 37(8). https://doi.org/10.1007/s11032-017-0698-5S378Addinsoft (2007) XLSTAT, Analyse de données et statistique avec MS Excel. Addinsoft, NYAndolfo G, Ercolano MR (2015) Plant innate immunity multicomponent model. Front Plant Sci 6:987Andolfo G, Sanseverino W, Rombauts S et al (2013) Overview of tomato (Solanum lycopersicum) candidate pathogen recognition genes reveals important Solanum R locus dynamics. 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Molecular Signatures of Prostate Stem Cells Reveal Novel Signaling Pathways and Provide Insights into Prostate Cancer

BACKGROUND:The global gene expression profiles of adult and fetal murine prostate stem cells were determined to define common and unique regulators whose misexpression might play a role in the development of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS:A distinctive core of transcriptional regulators common to both fetal and adult primitive prostate cells was identified as well as molecules that are exclusive to each population. Elements common to fetal and adult prostate stem cells include expression profiles of Wnt, Shh and other pathways identified in stem cells of other organs, signatures of the aryl-hydrocarbon receptor, and up-regulation of components of the aldehyde dehydrogenase/retinoic acid receptor axis. There is also a significant lipid metabolism signature, marked by overexpression of lipid metabolizing enzymes and the presence of the binding motif for Srebp1. The fetal stem cell population, characterized by more rapid proliferation and self-renewal, expresses regulators of the cell cycle, such as E2f, Nfy, Tead2 and Ap2, at elevated levels, while adult stem cells show a signature in which TGF-beta has a prominent role. Finally, comparison of the signatures of primitive prostate cells with previously described profiles of human prostate tumors identified stem cell molecules and pathways with deregulated expression in prostate tumors including chromatin modifiers and the oncogene, Erg. CONCLUSIONS/SIGNIFICANCE:Our data indicate that adult prostate stem or progenitor cells may acquire characteristics of self-renewing primitive fetal prostate cells during oncogenesis and suggest that aberrant activation of components of prostate stem cell pathways may contribute to the development of prostate tumors

A single-point modeling approach for the intercomparison and evaluation of ozone dry deposition across chemical transport models (Activity 2 of AQMEII4)

A primary sink of air pollutants and their precursors is dry deposition. Dry deposition estimates differ across chemical transport models, yet an understanding of the model spread is incomplete. Here, we introduce Activity 2 of the Air Quality Model Evaluation International Initiative Phase 4 (AQMEII4). We examine 18 dry deposition schemes from regional and global chemical transport models as well as standalone models used for impact assessments or process understanding. We configure the schemes as single-point models at eight Northern Hemisphere locations with observed ozone fluxes. Single-point models are driven by a common set of site-specific meteorological and environmental conditions. Five of eight sites have at least 3 years and up to 12 years of ozone fluxes. The interquartile range across models in multiyear mean ozone deposition velocities ranges from a factor of 1.2 to 1.9 annually across sites and tends to be highest during winter compared with summer. No model is within 50 % of observed multiyear averages across all sites and seasons, but some models perform well for some sites and seasons. For the first time, we demonstrate how contributions from depositional pathways vary across models. Models can disagree with respect to relative contributions from the pathways, even when they predict similar deposition velocities, or agree with respect to the relative contributions but predict different deposition velocities. Both stomatal and nonstomatal uptake contribute to the large model spread across sites. Our findings are the beginning of results from AQMEII4 Activity 2, which brings scientists who model air quality and dry deposition together with scientists who measure ozone fluxes to evaluate and improve dry deposition schemes in the chemical transport models used for research, planning, and regulatory purposes

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

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

Climate control of terrestrial carbon exchange across biomes and continents

Peer reviewe

Breeding Biology of the Black-Backed Lesser Goldfinch in Ponderosa Pine Forests on the Colorado Front Range

Volume: 114Start Page: 192End Page: 19