Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone

SummaryGhrelin is a 28 amino acid, appetite-stimulating peptide hormone secreted by the food-deprived stomach. Serine-3 of ghrelin is acylated with an eight-carbon fatty acid, octanoate, which is required for its endocrine actions. Here, we identify GOAT (Ghrelin O-Acyltransferase), a polytopic membrane-bound enzyme that attaches octanoate to serine-3 of ghrelin. Analysis of the mouse genome revealed that GOAT belongs to a family of 16 hydrophobic membrane-bound acyltransferases that includes Porcupine, which attaches long-chain fatty acids to Wnt proteins. GOAT is the only member of this family that octanoylates ghrelin when coexpressed in cultured endocrine cell lines with prepro-ghrelin. GOAT activity requires catalytic asparagine and histidine residues that are conserved in this family. Consistent with its function, GOAT mRNA is largely restricted to stomach and intestine, the major ghrelin-secreting tissues. Identification of GOAT will facilitate the search for inhibitors that reduce appetite and diminish obesity in humans

Risk control of groundwater exploitation for Zhangye basin in the middle reaches of Heihe River basin, China

Regulation of the water table is a feasible and effective way to reduce the risk of groundwater exploitation. An index system of groundwater exploitation risk evaluation is developed. The groundwater numerical simulation model is established for Zhangye basin in the middle reaches of Heihe River basin, China. Based on the identification and validation, the model is used for numerical simulation and forecast of groundwater exploitation under the conditions of current and planned development. The results show that the increase of groundwater exploitation amount causes the falling of water table. The increase of groundwater exploitation is 7600 × 104 m3, which can displace the surface water amount of 10 100 × 104 m3. The annual river runoff can increase 7536 × 104 m3. It is beneficial to the let-down flow from Zhengyi Gorge cross-section, and also provides the basis for decision on risk control of groundwater exploitation

Efficiency of genomic selection using Bayesian multi-marker models for traits selected to reflect a wide range of heritabilities and frequencies of detected quantitative traits loci in mice

BACKGROUND: Genomic selection uses dense single nucleotide polymorphisms (SNP) markers to predict breeding values, as compared to conventional evaluations which estimate polygenic effects based on phenotypic records and pedigree information. The objective of this study was to compare polygenic, genomic and combined polygenic-genomic models, including mixture models (labelled according to the percentage of genotyped SNP markers considered to have a substantial effect, ranging from 2.5% to 100%). The data consisted of phenotypes and SNP genotypes (10,946 SNPs) of 2,188 mice. Various growth, behavioural and physiological traits were selected for the analysis to reflect a wide range of heritabilities (0.10 to 0.74) and numbers of detected quantitative traits loci (QTL) (1 to 20) affecting those traits. The analysis included estimation of variance components and cross-validation within and between families. RESULTS: Genomic selection showed a high predictive ability (PA) in comparison to traditional polygenic selection, especially for traits of moderate heritability and when cross-validation was between families. This occurred although the proportion of genomic variance of traits using genomic models was 22 to 33% smaller than using polygenic models. Using a 2.5% mixture genomic model, the proportion of genomic variance was 79% smaller relative to the polygenic model. Although the proportion of variance explained by the markers was reduced further when a smaller number of SNPs was assumed to have a substantial effect on the trait, PA of genomic selection for most traits was little affected. These low mixture percentages resulted in improved estimates of single SNP effects. Genomic models implemented for traits with fewer QTLs showed even lower PA than the polygenic models. CONCLUSIONS: Genomic selection generally performed better than traditional polygenic selection, especially in the context of between family cross-validation. Reducing the number of markers considered to affect the trait did not significantly change PA for most traits, particularly in the case of within family cross-validation, but increased the number of markers found to be associated with QTLs. The underlying number of QTLs affecting the trait has an effect on PA, with a smaller number of QTLs resulting in lower PA using the genomic model compared to the polygenic model

Postpartum depression in mothers and fathers: a structural equation model

open access articleBackground Post-partum depression (PPD) is a growing mental health concern worldwide. There is little evidence in the Chinese context of the relationship between paternal PPD and maternal PPD. Given the growing global concerns this relationship requires further exploration. Methods A survey was conducted with 950 total couples from March 2017 to December 2018. The study was conducted using a standardized questionnaire that included basic demographic information, information on the relationship between the mother-in-law and daughter-in-law, marital satisfaction (both maternal and paternal), and PPD symptoms. Structural Equation Modelling (SEM) analysis was used to explore the underlying mechanism for PPD symptoms in mothers and fathers. Results In 4.4% of the couples both the wife and the husband showed depressive symptoms. Maternal marital satisfaction showed a significant mediating effect on paternal PPD (B = -0.114, p < 0.01), and there was a direct effect of maternal PPD on paternal PPD (B = 0.31, p < 0.001). Conclusions This is the first study to investigate the possible correlation between maternal PPD, mother-in-law and daughter-in-law relationship satisfaction, maternal marital satisfaction, paternal marital satisfaction, and paternal PPD. It is important for future PPD interventions to target both maternal and paternal mental health, as well as the mechanisms identified that can lead to PPD

RETRACTED: Autoimmunity as the Consequence of a Spontaneous Mutation in Rasgrp1

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the Authors.The authors have agreed to retract the paper because of the falsification of the Western blot in Figure 6A. The figure shows a defect in Ras activation, labeled as RasGTP, following TCR engagement, in thymocytes isolated from a RasGRP1 lag mutant mouse strain. This data set is one of several that show signaling and functional deficiencies identified for cells with lost of function of RasGRP. The authors stand by the validity of the other figures, results and interpretation in this paper. This matter was investigated by the Massachusetts Institute of Technology and the Office of Research Integrity at the United States Department of Health & Human Services, which found the figure was falsified by Luk Van Parijs, who is solely responsible. The authors deeply regret any inconvenience resulting from the publication of this data

Methylation of the candidate biomarker TCF21 is very frequent across a spectrum of early-stage nonsmall cell lung cancers

The transcription factor TCF21 is involved in mesenchymal-to-epithelial differentiation and was shown to be aberrantly hypermethylated in lung and head and neck cancers. Because of its reported high frequency of hypermethylation in lung cancer, we sought to characterize the stages and types of non-small cell lung cancer (NSCLC) that are hypermethylated and to define the frequency of hypermethylation and associated “second hits”

Modality- and task-specific brain regions involved in Chinese lexical processing

fMRI was used to examine lexical processing in native adult Chinese speakers. A 2 task (semantics and phonology) x 2 modality (visual and auditory) within-subject design was adopted. The semantic task involved a meaning association judgment and the phonological task involved a rhyming judgment to two sequentially presented words. The overall effect across tasks and modalities was used to identify seven ROIs, including the left fusiform gyrus (FG), the left superior temporal gyrus (STG), the left ventral inferior frontal gyrus (VIFG), the left middle temporal gyrus (MTG), the left dorsal inferior frontal gyrus (DIFG), the left inferior parietal lobule (IPL), and the left middle frontal gyrus (MFG). ROI analyses revealed two modality-specific areas, FG for visual and STG for auditory, and three task-specific areas, IPL and DIFG for phonology and VIFG for semantics. Greater DIFG activation was associated with conflicting tonal information between words for the auditory rhyming task, suggesting this region&#39;s role in strategic phonological processing, and greater VIFG activation was correlated with lower association between words for both the auditory and the visual meaning task, suggesting this region&#39;s role in retrieval and selection of semantic representations. The modality- and task-specific effects in Chinese revealed by this study are similar to those found in alphabetical languages. Unlike English, we found that MFG was both modality- and task-specific, suggesting that MFG may be responsible for the visuospatial analysis of Chinese characters and orthography-to-phonology integration at a syllabic level

The Ubiquitin Peptidase UCHL1 Induces G0/G1 Cell Cycle Arrest and Apoptosis Through Stabilizing p53 and Is Frequently Silenced in Breast Cancer

Background: Breast cancer (BrCa) is a complex disease driven by aberrant gene alterations and environmental factors. Recent studies reveal that abnormal epigenetic gene regulation also plays an important role in its pathogenesis. Ubiquitin carboxyl- terminal esterase L1 (UCHL1) is a tumor suppressor silenced by promoter methylation in multiple cancers, but its role and alterations in breast tumorigenesis remain unclear. Methodology/Principal Findings: We found that UCHL1 was frequently downregulated or silenced in breast cancer cell lines and tumor tissues, but readily expressed in normal breast tissues and mammary epithelial cells. Promoter methylation of UCHL1 was detected in 9 of 10 breast cancer cell lines (90%) and 53 of 66 (80%) primary tumors, but rarely in normal breast tissues, which was statistically correlated with advanced clinical stage and progesterone receptor status. Pharmacologic demethylation reactivated UCHL1 expression along with concomitant promoter demethylation. Ectopic expression of UCHL1 significantly suppressed the colony formation and proliferation of breast tumor cells, through inducing G0/G1 cell cycle arrest and apoptosis. Subcellular localization study showed that UCHL1 increased cytoplasmic abundance of p53. We further found that UCHL1 induced p53 accumulation and reduced MDM2 protein level, and subsequently upregulated the expression of p21, as well as cleavage of caspase3 and PARP, but not in catalytic mutant UCHL1 C90Sexpressed cells