Stricklandforrest9251

In recent years, genome-wide association studies have shed light on the genetics of early growth and its links with later-life health outcomes. Large-scale datasets and meta-analyses, combined with recently developed analytical methods, have enabled dissection of the maternal and fetal genetic contributions to variation in birth weight. Additionally, longitudinal approaches have shown differences between the genetic contributions to infant, childhood and adult adiposity. In contrast, studies of adult height loci have shown strong associations with early body length and childhood height. Early growth-associated loci provide useful tools for causal analyses Mendelian randomization (MR) studies have provided evidence that early BMI and height are causally related to a number of adult health outcomes. read more We advise caution in the design and interpretation of MR studies of birth weight investigating effects of fetal growth on later-life cardiometabolic disease because birth weight is only a crude indicator of fetal growth, and the choice of genetic instrument (maternal or fetal) will greatly influence the interpretation of the results. Most genetic studies of early growth have to date centered on European-ancestry participants and outcomes measured at a single time-point, so key priorities for future studies of early growth genetics are aggregation of large samples of diverse ancestries and longitudinal studies of growth trajectories.Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disorder. However, studies providing PAH-related gene expression profiles are scarce. To identify hub genes involved in PAH, we investigate two microarray data sets from gene expression omnibus (GEO). A total of 150 differentially expressed genes (DEGs) were identified by limma package. Enriched Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included mitotic nuclear division, ATPase activity, and Herpes simplex virus one infection. Ten hub genes from three significant modules were ascertained by Cytoscape (CytoHubba). Gene set enrichment analysis (GSEA) plots showed that transcription elongation factor complex was the most significantly enriched gene set positively correlated with the PAH group. At the same time, solute proton symporter activity was the most significantly enriched gene set positively correlated with the control group. Correlation analysis between hub genes suggested that SMC4, TOP2A, SMC2, KIF11, KIF23, ANLN, ARHGAP11A, SMC3, SMC6 and RAD50 may involve in the pathogenesis of PAH. Then, the miRNA-target genes regulation network was performed to unveil the underlying complex association among them. Finally, RNA extracted from monocrotaline (MCT)-induced Rat-PAH model lung artery tissues were to conduct quantitative real-time PCR (qRT-PCR) to validate these hub genes. In conclusion, our study offers new evidence for the underlying molecular mechanisms of PAH as well as attractive targets for diagnosis and treatment of PAH.ANKS6 is a ciliary protein that localizes to the proximal compartment of the primary cilium, where it regulates signaling. Mutations in the ANKS6 gene cause multiorgan ciliopathies in humans, which include laterality defects of the visceral organs, renal cysts as part of nephronophthisis and congenital hepatic fibrosis (CHF) in the liver. Although CHF together with liver ductal plate malformations are common features of several human ciliopathy syndromes, including nephronophthisis-related ciliopathies, the mechanism by which mutations in ciliary genes lead to bile duct developmental abnormalities is not understood. Here, we generated a knockout mouse model of Anks6 and show that ANKS6 function is required for bile duct morphogenesis and cholangiocyte differentiation. The loss of Anks6 causes ciliary abnormalities, ductal plate remodeling defects and periportal fibrosis in the liver. Our expression studies and biochemical analyses show that biliary abnormalities in Anks6-deficient livers result from the dysregulation of YAP transcriptional activity in the bile duct-lining epithelial cells. Mechanistically, our studies suggest, that ANKS6 antagonizes Hippo signaling in the liver during bile duct development by binding to Hippo pathway effector proteins YAP1, TAZ and TEAD4 and promoting their transcriptional activity. Together, this study reveals a novel function for ANKS6 in regulating Hippo signaling during organogenesis and provides mechanistic insights into the regulatory network controlling bile duct differentiation and morphogenesis during liver development.

We have shown that ingesting a large bolus (70g) of the fungal-derived, whole food mycoprotein robustly stimulates muscle protein synthesis (MPS) rates.

The aim of this study was to determine if a lower dose (35g) of mycoprotein enriched with branched-chain amino acids (BCAAs) stimulates MPS to the same extent as 70g of mycoprotein in resistance-trained young men.

Nineteen men [aged 22±1y, BMI (kg/m2) 25±1] took part in a randomized, double-blind, parallel-group study. Participants received primed, continuous infusions of l-[ring-2H5]phenylalanine and ingested either 70g mycoprotein (31.5g protein; MYCO; n=10) or 35g BCAA-enriched mycoprotein (18.7g protein matched on BCAA content; ENR; n=9) following a bout of unilateral resistance exercise. Blood and bilateral quadriceps muscle samples were obtained before exercise and protein ingestion and during a 4-h postprandial period to assess MPS in rested and exercised muscle. Two- and 3-factor ANOVAs were used to detect differences in plasma amino acid kinetito a lesser extent compared with the ingestion of a BCAA-matched 70-g mycoprotein bolus in healthy young men. This trial was registered at clinicaltrials.gov as 660065600.

Human milk contains a diverse community of bacteria believed to play a role in breast health and inoculation of the infant's gastrointestinal tract. The role of maternal nutrition and infant feeding practices on the human milk microbiota remains poorly understood.

Our aim was to explore the associations between maternal diet (delivery to 3 mo postpartum), infant feeding practices, and the microbial composition and predicted function in milk from women with varied metabolic status.

This was an exploratory analysis of a previously completed prospective cohort study of women with varying degrees of gestational glucose intolerance (NCT01405547). Milk samples (n=93 mothers) were collected at 3 mo postpartum. Maternal dietary information (validated food-frequency questionnaire) and infant feeding practices (human milk exclusivity, frequency of direct breastfeeding per day) were collected. V4-16S ribosomal RNA gene sequencing (Illumina MiSeq) was conducted to determine microbiota composition.

Intake of polyunsaturated fat [β estimate (SE) 0.