Tissue-Specific Transcriptomes Reveal Gene Expression Trajectories in Two Maturing Skin Epithelial Layers in Zebrafish Embryos.

Epithelial cells are the building blocks of many organs, including skin. The vertebrate skin initially consists of two epithelial layers, the outer periderm and inner basal cell layers, which have distinct properties, functions, and fates. The embryonic periderm ultimately disappears during development, whereas basal cells proliferate to form the mature, stratified epidermis. Although much is known about mechanisms of homeostasis in mature skin, relatively little is known about the two cell types in pre-stratification skin. To define the similarities and distinctions between periderm and basal skin epithelial cells, we purified them from zebrafish at early development stages and deeply profiled their gene expression. These analyses identified groups of genes whose tissue enrichment changed at each stage, defining gene flow dynamics of maturing vertebrate epithelia. At each of 52 and 72 hr post-fertilization (hpf), more than 60% of genes enriched in skin cells were similarly expressed in both layers, indicating that they were common epithelial genes, but many others were enriched in one layer or the other. Both expected and novel genes were enriched in periderm and basal cell layers. Genes encoding extracellular matrix, junctional, cytoskeletal, and signaling proteins were prominent among those distinguishing the two epithelial cell types. In situ hybridization and BAC transgenes confirmed our expression data and provided new tools to study zebrafish skin. Collectively, these data provide a resource for studying common and distinguishing features of maturing epithelia

Fetal and childhood growth patterns associated with bone mass in school-age children: The generation R study

Low birth weight is associated with lower bone accrual in children and peak bone mass in adults. We assessed how different patterns of longitudinal fetal and early childhood growth influence bone properties at school age. In 5431 children participating in a population-based prospective cohort study, we measured fetal growth by ultrasound at 20 and 30 weeks gestation, and childhood growth at birth, 1, 2, 3, and 4 years of age. We analy

DETECCIÓN DE COUMARINAS EN Asparagus officinalis L. (LILIACEAE)

Se investigó la presencia de coumarinas en raíces, tallos, flores, frutos y semillas de cinco variedades de Asparagus officinalis L. “esparrago” (Mary Washington, UC-72, UC-157, UC-66, y UC-800), provenientes de los alrededores de la ciudad de Trujillo, Perú. Las técnicas fotoquímicas utilizadas fueron: Extracción con etanol en un Soxhlet y detección de coumarinas mediante fluorescencia con luz ultravioleta y reacción colorida. Resultaron ser positivas las muestras de frutos y semillas de todas las variedades; tanto al ser irradiada con luz ultravioleta a una longitud de onda de 366 nm, como para la reacción colorida, en donde se observó desaparición de la coloración amarilla al hacerlas reaccionar con HCL. Actualmente se las identifica y purifica.Palabras clave: Fotoquímica, coumarinas, Asparagus officinalis L.ABSTRACTThe presence of coumarins in roots, stems, flowers, fruits and seeds of five varieties of Asparagus officinalis L. " asparagus" (Mary Washington , UC -72 , UC -157 , UC - 66 and UC- 800) was investigated, from around the city of Trujillo, Peru. Photochemical techniques used were: Extraction with ethanol in a Soxhlet apparatus and coumarins detection by fluorescence with ultraviolet light and colorful reaction. The samples of fruits and seeds of all varieties found to be positives; both when irradiated with ultraviolet light at a wavelength of 366 nm, as for colorful reaction, wherein disappearance of yellow coloration was observed to make them react with HCL. Currently coumarins are  identified and purified.Keywords: Phytochemistry, coumarins, Asparagus officinalis L

Defining type 2 diabetes polygenic risk scores through colocalization and network-based clustering of metabolic trait genetic associations

Background: Type 2 diabetes (T2D) is a heterogeneous and polygenic disease. Previous studies have leveraged the highly polygenic and pleiotropic nature of T2D variants to partition the heterogeneity of T2D, in order to stratify patient risk and gain mechanistic insight. We expanded on these approaches by performing colocalization across GWAS traits while assessing the causality and directionality of genetic associations. Methods: We applied colocalization between T2D and 20 related metabolic traits, across 243 loci, to obtain inferences of shared casual variants. Network-based unsupervised hierarchical clustering was performed on variant-trait associations. Partitioned polygenic risk scores (PRSs) were generated for each cluster using T2D summary statistics and validated in 21,742 individuals with T2D from 3 cohorts. Inferences of directionality and causality were obtained by applying Mendelian randomization Steiger’s Z-test and further validated in a pediatric cohort without diabetes (aged 9–12 years old, n = 3866). Results: We identified 146 T2D loci that colocalized with at least one metabolic trait locus. T2D variants within these loci were grouped into 5 clusters. The clusters corresponded to the following pathways: obesity, lipodystrophic insulin resistance, liver and lipid metabolism, hepatic glucose metabolism, and beta-cell dysfunction. We observed heterogeneity in associations between PRSs and metabolic measures across clusters. For instance, the lipodystrophic insulin resistance (Beta − 0.08 SD, 95% CI [− 0.10–0.07], p = 6.50 × 10−32) and beta-cell dysfunction (Beta − 0.10 SD, 95% CI [− 0.12, − 0.08], p = 1.46 × 10−47) PRSs were associated to lower BMI. Mendelian randomization Steiger analysis indicated that increased T2D risk in these pathways was causally associated to lower BMI. However, the obesity PRS was conversely associated with increased BMI (Beta 0.08 SD, 95% CI 0.06–0.10, p = 8.0 × 10−33). Analyses within a pediatric cohort supported this finding. Additionally, the lipodystrophic insulin resistance PRS was associated with a higher odds of chronic kidney disease (OR 1.29, 95% CI 1.02–1.62, p = 0.03). Conclusions: We successfully partitioned T2D genetic variants into phenotypic pathways using a colocalization first approach. Partitioned PRSs were associated to unique metabolic and clinical outcomes indicating successful partitioning of disease heterogeneity. Our work expands on previous approaches by providing stronger inferences of shared causal variants, causality, and directionality of GWAS variant-trait associations.</p

Defining type 2 diabetes polygenic risk scores through colocalization and network-based clustering of metabolic trait genetic associations

Background: Type 2 diabetes (T2D) is a heterogeneous and polygenic disease. Previous studies have leveraged the highly polygenic and pleiotropic nature of T2D variants to partition the heterogeneity of T2D, in order to stratify patient risk and gain mechanistic insight. We expanded on these approaches by performing colocalization across GWAS traits while assessing the causality and directionality of genetic associations. Methods: We applied colocalization between T2D and 20 related metabolic traits, across 243 loci, to obtain inferences of shared casual variants. Network-based unsupervised hierarchical clustering was performed on variant-trait associations. Partitioned polygenic risk scores (PRSs) were generated for each cluster using T2D summary statistics and validated in 21,742 individuals with T2D from 3 cohorts. Inferences of directionality and causality were obtained by applying Mendelian randomization Steiger’s Z-test and further validated in a pediatric cohort without diabetes (aged 9–12 years old, n = 3866). Results: We identified 146 T2D loci that colocalized with at least one metabolic trait locus. T2D variants within these loci were grouped into 5 clusters. The clusters corresponded to the following pathways: obesity, lipodystrophic insulin resistance, liver and lipid metabolism, hepatic glucose metabolism, and beta-cell dysfunction. We observed heterogeneity in associations between PRSs and metabolic measures across clusters. For instance, the lipodystrophic insulin resistance (Beta − 0.08 SD, 95% CI [− 0.10–0.07], p = 6.50 × 10−32) and beta-cell dysfunction (Beta − 0.10 SD, 95% CI [− 0.12, − 0.08], p = 1.46 × 10−47) PRSs were associated to lower BMI. Mendelian randomization Steiger analysis indicated that increased T2D risk in these pathways was causally associated to lower BMI. However, the obesity PRS was conversely associated with increased BMI (Beta 0.08 SD, 95% CI 0.06–0.10, p = 8.0 × 10−33). Analyses within a pediatric cohort supported this finding. Additionally, the lipodystrophic insulin resistance PRS was associated with a higher odds of chronic kidney disease (OR 1.29, 95% CI 1.02–1.62, p = 0.03). Conclusions: We successfully partitioned T2D genetic variants into phenotypic pathways using a colocalization first approach. Partitioned PRSs were associated to unique metabolic and clinical outcomes indicating successful partitioning of disease heterogeneity. Our work expands on previous approaches by providing stronger inferences of shared causal variants, causality, and directionality of GWAS variant-trait associations.</p

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

astroplan: An Open Source Observation Planning Package in Python

We present astroplan - an open source, open development, Astropy affiliated package for ground-based observation planning and scheduling in Python. astroplan is designed to provide efficient access to common observational quantities such as celestial rise, set, and meridian transit times and simple transformations from sky coordinates to altitude-azimuth coordinates without requiring a detailed understanding of astropy's implementation of coordinate systems. astroplan provides convenience functions to generate common observational plots such as airmass and parallactic angle as a function of time, along with basic sky (finder) charts. Users can determine whether or not a target is observable given a variety of observing constraints, such as airmass limits, time ranges, Moon illumination/separation ranges, and more. A selection of observation schedulers are included which divide observing time among a list of targets, given observing constraints on those targets. Contributions to the source code from the community are welcome

TOI 540 b: A Planet Smaller than Earth Orbiting a Nearby Rapidly Rotating Low-mass Star

We present the discovery of TOI 540 b, a hot planet slightly smaller than Earth orbiting the low-mass star 2MASS J05051443-4756154. The planet has an orbital period of $P = 1.239149$ days ($\pm$ 170 ms) and a radius of $r = 0.903 \pm 0.052 R_{\rm Earth}$, and is likely terrestrial based on the observed mass-radius distribution of small exoplanets at similar insolations. The star is 14.008 pc away and we estimate its mass and radius to be $M = 0.159 \pm 0.014 M_{\rm Sun}$ and $R = 0.1895 \pm 0.0079 R_{\rm Sun}$, respectively. The star is distinctive in its very short rotational period of $P_{\rm rot} = 17.4264 +/- 0.0094$ hours and correspondingly small Rossby number of 0.007 as well as its high X-ray-to-bolometric luminosity ratio of $L_X / L_{\rm bol} = 0.0028$ based on a serendipitous XMM-Newton detection during a slew operation. This is consistent with the X-ray emission being observed at a maximum value of $L_X / L_{\rm bol} \simeq 10^{-3}$ as predicted for the most rapidly rotating M dwarfs. TOI 540 b may be an alluring target to study atmospheric erosion due to the strong stellar X-ray emission. It is also among the most accessible targets for transmission and emission spectroscopy and eclipse photometry with JWST, and may permit Doppler tomography with high-resolution spectroscopy during transit. This discovery is based on precise photometric data from TESS and ground-based follow-up observations by the MEarth team.Comment: 18 pages, 7 figures. Accepted for publication in The Astronomical Journa