Craniofacial manifestations of Loeys Dietz syndrome : A case report and a review of the literature : Case report

症例報

Genetic Alterations in Gorlin Syndrome

Gorlin syndrome (GS) is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs). In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS) analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs) of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals), whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions

Discordance between hyposalivation and xerostomia

Individuals with an objective decrease in salivary flow (objective dry mouth) may not be aware of subjective dry mouth (xerostomia). However, no clear evidence exists to explain the discordance between subjective and objective dry mouth. Therefore, this cross-sectional study aimed to assess the prevalence of xerostomia and decreased salivary flow among community-dwelling elderly adults. In addition, this study assessed several potential demographic and health status determinants of the discrepancy between xerostomia and reduced salivary flow. The 215 participants in this study were community-dwelling older people aged 70 years and above who underwent dental health examinations between January-February 2019. Symptoms of xerostomia were collected in the form of a questionnaire. The unstimulated salivary flow rate (USFR) was measured by a dentist using visual inspection. The stimulated salivary flow rate (SSFR) was measured using the Saxon test. We identified 19.1% of participants as having mild-severe USFR decline with xerostomia and 19.1% as having mild-severe USFR decline without xerostomia. Additionally, 26.0% of participants had low SSFR and xerostomia, and 40.0% had low SSFR without xerostomia. Except for the age trend, no factors could be associated with the discordance between USFR measurement and xerostomia. Furthermore, no significant factors were associated with the discordance between the SSFR and xerostomia. However, females were significantly associated (OR = 2.608, 95% CI = 1.174–5.791) with low SSFR and xerostomia, as compared to males. Age was a factor that was also significantly associated (OR = 1.105, 95% CI = 1.010–1.209) with low SSFR and xerostomia. Our findings indicate that approximately 20% of the participants had low USFR without xerostomia, and 40% had low SSFR without xerostomia. This study showed that age, sex, and the number of medications may not be factors in the discrepancy between the subjective feeling of dry mouth and reduced salivary flow

Activin E Controls Energy Homeostasis in Both Brown and White Adipose Tissues as a Hepatokine

Brown adipocyte activation or beige adipocyte emergence in white adipose tissue (WAT) increases energy expenditure, leading to a reduction in body fat mass and improved glucose metabolism. We found that activin E functions as a hepatokine that enhances thermogenesis in response to cold exposure through beige adipocyte emergence in inguinal WAT (ingWAT). Hepatic activin E overexpression activated thermogenesis through Ucp1 upregulation in ingWAT and other adipose tissues including interscapular brown adipose tissue and mesenteric WAT. Hepatic activin E-transgenic mice exhibited improved insulin sensitivity. Inhibin βE gene silencing inhibited cold-induced Ucp1 induction in ingWAT. Furthermore, in vitro experiments suggested that activin E directly stimulated expression of Ucp1 and Fgf21, which was mediated by transforming growth factor-β or activin type I receptors. We uncovered a function of activin E to stimulate energy expenditure through brown and beige adipocyte activation, suggesting a possible preventive or therapeutic target for obesity

The 3rd DBCLS BioHackathon: improving life science data integration with Semantic Web technologies.

BACKGROUND: BioHackathon 2010 was the third in a series of meetings hosted by the Database Center for Life Sciences (DBCLS) in Tokyo, Japan. The overall goal of the BioHackathon series is to improve the quality and accessibility of life science research data on the Web by bringing together representatives from public databases, analytical tool providers, and cyber-infrastructure researchers to jointly tackle important challenges in the area of in silico biological research. RESULTS: The theme of BioHackathon 2010 was the 'Semantic Web', and all attendees gathered with the shared goal of producing Semantic Web data from their respective resources, and/or consuming or interacting those data using their tools and interfaces. We discussed on topics including guidelines for designing semantic data and interoperability of resources. We consequently developed tools and clients for analysis and visualization. CONCLUSION: We provide a meeting report from BioHackathon 2010, in which we describe the discussions, decisions, and breakthroughs made as we moved towards compliance with Semantic Web technologies - from source provider, through middleware, to the end-consumer.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed

Computational Prediction of Compound–Protein Interactions for Orphan Targets Using CGBVS

A variety of Artificial Intelligence (AI)-based (Machine Learning) techniques have been developed with regard to in silico prediction of Compound–Protein interactions (CPI)—one of which is a technique we refer to as chemical genomics-based virtual screening (CGBVS). Prediction calculations done via pairwise kernel-based support vector machine (SVM) is the main feature of CGBVS which gives high prediction accuracy, with simple implementation and easy handling. We studied whether the CGBVS technique can identify ligands for targets without ligand information (orphan targets) using data from G protein-coupled receptor (GPCR) families. As the validation method, we tested whether the ligand prediction was correct for a virtual orphan GPCR in which all ligand information for one selected target was omitted from the training data. We have specifically expressed the results of this study as applicability index and developed a method to determine whether CGBVS can be used to predict GPCR ligands. Validation results showed that the prediction accuracy of each GPCR differed greatly, but models using Multiple Sequence Alignment (MSA) as the protein descriptor performed well in terms of overall prediction accuracy. We also discovered that the effect of the type compound descriptors on the prediction accuracy was less significant than that of the type of protein descriptors used. Furthermore, we found that the accuracy of the ligand prediction depends on the amount of ligand information with regard to GPCRs related to the target. Additionally, the prediction accuracy tends to be high if a large amount of ligand information for related proteins is used in the training

Development of a new heat tolerance assay system for rice spikelet sterility

Abstract Background Reduction in rice yield caused by high temperature-induced spikelet sterility has been a serious concern in rice production. To date, several screening methods have been used, although their reproducibility is sometimes poor due to artifacts mainly caused by varietal differences in heading dates and panicle heights (i.e., the distance from the lamps). Methods We have developed a novel assay system for heat-induced spikelet sterility by using artificial rice paddies in phytotrons to conduct a highly reproducible assay throughout a year. Plants restricted to the main culm were treated under a series of heat conditions, and height uniformity of each plant was ensured by using height-adjustable pots. Results Results suggested that a 3-day heat treatment of 35 °C-day/29 °C-night cycles was the most suitable condition. Under the treatment, two distinct groups were identified among nine heat tolerant cultivars, with no varietal difference in panicle temperature, indicating that the system is capable of eliminating the varietal difference in panicle temperature. Conclusions It is concluded that the assay system would be a powerful tool for selecting heat tolerant varieties, as well as the analysis of genetic factors from various cultivars, eliminating potential artifacts