Formononetin, an isoflavone, relaxes rat isolated aorta through endothelium-dependent and endothelium-independent pathways

Author name used in this publication: Jian-Hong WuAuthor name used in this publication: Min-Yi WuAuthor name used in this publication: De-Jian GuoAuthor name used in this publication: Shi-Lin ChenAuthor name used in this publication: Alice L. S. AuAuthor name used in this publication: Christina C. W. Poon2010-2011 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos

The cornea is the outermost layer of the eye and is a vital component of focusing incoming light on the retina. Central corneal thickness (CCT) is now recognized to have a significant role in ocular health and is a risk factor for various ocular diseases, such as keratoconus and primary open angle glaucoma. Most previous genetic studies utilized European and Asian subjects to identify genetic loci associated with CCT. Minority populations, such as Latinos, may aid in identifying additional loci and improve our understanding of the genetic architecture of CCT. In this study, we conducted a genome-wide association study (GWAS) in Latinos, a traditionally understudied population in genetic research, to further identify loci contributing to CCT. Study participants were genotyped using either the Illumina OmniExpress BeadChip (~730K markers) or the Illumina Hispanic/SOL BeadChip (~2.5 million markers). All study participants were 40 years of age and older. We assessed the association between individual single nucleotide polymorphisms (SNPs) and CCT using linear regression, adjusting for age, gender and principal components of genetic ancestry. To expand genomic coverage and to interrogate additional SNPs, we imputed SNPs from the 1000 Genomes Project reference panels. We identified a novel SNP, rs10453441 (P=6.01E-09), in an intron of WNT7B that is associated with CCT. Furthermore, WNT7B is expressed in the human cornea. We also replicated 11 previously reported loci, including IBTK, RXRA-COL5A1, COL5A1, FOXO1, LRRK1 and ZNF469 (P < 1.25E-3). These findings provide further insight into the genetic architecture of CCT and illustrate that the use of minority groups in GWAS will help identify additional loci

Modelling the Genetic Risk in Age-Related Macular Degeneration

Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69–2.05) than patients aged 75 and above (1.45, 95% CI: 1.36–1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11–1131.96) for individuals in the highest category (GRS 3.44–5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS −0.05–1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

IMI - Myopia Genetics Report

The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary of current genetic findings and defines the direction where development is needed.We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes.To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression.The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed. This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth

IMI - Myopia Genetics Report

The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary of current genetic findings and defines the direction where development is needed. We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes. To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed. This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth

A pilot study on the effects of a Chinese herbal preparation on menopausal symptoms

This study was conducted to determine whether a particular Chinese medicinal preparation is effective in alleviating menopausal symptoms. Chinese women with menopausal symptoms were recruited to receive treatment for 3 months followed by 3 months without treatment. The severity of menopausal symptoms and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol levels were assessed at baseline, 3 and 6 months. Data from 97 women with a mean age of 52.3 years were analyzed. Sixty women (62%) were postmenopausal. The serum FSH level (interquartile range) was 58.0 (39.5-72.4) IU/l at baseline and rose significantly 3 months after treatment. The difference remained significant in the postmenopausal group while there was no significant difference in the perimenopausal women. The changes in serum LH and estradiol levels remained unchanged. The baseline menopausal symptom score was 8.9 ± 6.0. The menopausal symptom score improved markedly after treatment and remained at the same level at 6 months. All individual menopausal symptoms improved significantly after 3 months of treatment except dry eye. Most of these symptoms remained significantly improved at 6 months compared with the pre-treatment assessment. We observed that the Chinese medicinal preparation used in this study is effective in improving menopausal symptoms in healthy Chinese women. Further randomized controlled trial will be needed to confirm this observation. © 2006 Taylor & Francis.link_to_subscribed_fulltex

Quantifying the linkages and leakages of construction activities in an open economy using multiregional input-output analysis

202310 bcchAccepted ManuscriptRGCOthersWorks Branch of Development Bureau of Hong Kong SAR governmentPublishe

Association of dietary patterns and food groups intake with multimorbidity: A prospective cohort study

Background Although diet has been extensively studied in relation to individual chronic conditions, studies linking diet with multiple chronic conditions (multimorbidity) remained scarce. We aimed to undertake a comprehensive analysis evaluating associations of overall dietary patterns and specific food groups with long-term risk of multimorbidity. Methods The study included 348,290 participants from UK Biobank who completed eligible food frequency questionnaires (FFQ) and were not diagnosed with any of the 38 chronic or mental health conditions of interest at baseline (2006–2010). Dietary patterns were identified using exploratory factor analysis. Cox regression models were used to estimate corresponding hazard ratios (HRs) and 95% confidence intervals (CIs). Results The median follow-up was 8.01 years, and 50,837 (14.60%) participants developed multimorbidity. Among the three identified dietary patterns, the Western Pattern was associated with an increased risk of multimorbidity (HRQ5 vs Q1 = 1.06, 95% CI: 1.03–1.09), while inverse associations were observed for moderate adherence to the White Meat Pattern (HRQ3 vs Q1 = 0.97, 95% CI: 0.94–0.99) and highest adherence to the Prudent Pattern (HRQ5 vs Q1 = 0.92, 95% CI: 0.90–0.95). For specific food groups, more frequent intakes of processed meat and poultry were associated with higher risks of multimorbidity, whereas higher intake frequency of fish and more intakes of fruits and cereal were associated with decreased risks. Conclusion Dietary patterns and specific food groups are associated with the risk of multimorbidity. These findings suggest the importance of considering dietary interventions in the prevention and management of multimorbidity