The haloacid operon of Burkholderia sp. MBA4 is catabolically repressed

Session: Biofilms - Keynotepublished_or_final_versio

Incremental prognostic value of global longitudinal strain in patients with type 2 diabetes mellitus

published_or_final_versio

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

BACKGROUND: Fibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross-sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases. METHODS AND RESULTS: Baseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow-up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow-up of 4 years. Baseline serum log-transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8-438.4] versus 151.1 pg/mL [75.6-274.6]; P<0.001). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10-2.19; P=0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors. CONCLUSIONS: We have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention.published_or_final_versio

Increased serum levels and epithelial expression of macrophage migration inhibitory factor in gastric cancer

This journal suppl. contain abstracts of the 8th Medical Research Conference, Medical Science Group, Queen Mary Hospital, Hong Kongpublished_or_final_versio

Development of interfering RNA agents to inhibit SARS-associated coronavirus infection and replication.

published_or_final_versio

Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance

Purpose: Chemoresistance is a major obstacle in cancer therapy. We found that fluorouracil (5-FU)-resistant esophageal squamous cell carcinoma cell lines, established through exposure to increasing concentrations of 5-FU, showed upregulation of Id1, IGF2, and E2F1. We hypothesized that these genes may play an important role in cancer chemoresistance. Experimental Design: In vitro and in vivo functional assays were performed to study the effects of Id1–E2F1–IGF2 signaling in chemoresistance. Quantitative real-time PCR, Western blotting, immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays were used to investigate the molecular mechanisms by which Id1 regulates E2F1 and by which E2F1 regulates IGF2. Clinical specimens, tumor tissue microarray, and Gene Expression Omnibus datasets were used to analyze the correlations between gene expressions and the relationships between expression profiles and patient survival outcomes. Results: Id1 conferred 5-FU chemoresistance through E2F1-dependent induction of thymidylate synthase expression in esophageal cancer cells and tumor xenografts. Mechanistically, Id1 protects E2F1 protein from degradation and increases its expression by binding competitively to Cdc20, whereas E2F1 mediates Id1-induced upregulation of IGF2 by binding directly to the IGF2 promoter and activating its transcription. The expression level of E2F1 was positively correlated with that of Id1 and IGF2 in human cancers. More importantly, concurrent high expression of Id1 and IGF2 was associated with unfavorable patient survival in multiple cancer types. Conclusions: Our findings define an intricate E2F1-dependent mechanism by which Id1 increases thymidylate synthase and IGF2 expressions to promote cancer chemoresistance. The Id1–E2F1–IGF2 regulatory axis has important implications for cancer prognosis and treatment. ©2015 AACR.postprin

An Exome-Chip Association Analysis in Chinese Subjects Reveals a Functional Missense Variant of GCKR That Regulates FGF21 Levels

Fibroblast growth factor 21 (FGF21) is increasingly recognized as an important metabolic regulator of glucose homeostasis. Here, we conducted an exome-chip association analysis by genotyping 5,169 Chinese individuals from a community-based cohort and two clinic-based cohorts. A custom Asian exome-chip was used to detect genetic determinants influencing circulating FGF21 levels. Single-variant association analysis interrogating 70,444 single nucleotide polymorphisms identified a novel locus, GCKR, significantly associated with circulating FGF21 levels at genome-wide significance. In the combined analysis, the common missense variant of GCKR, rs1260326 (p.Pro446Leu), showed an association with FGF21 levels after adjustment for age and sex (P = 1.61 × 10−12; β [SE] = 0.14 [0.02]), which remained significant on further adjustment for BMI (P = 3.01 × 10−14; β [SE] = 0.15 [0.02]). GCKR Leu446 may influence FGF21 expression via its ability to increase glucokinase (GCK) activity. This can lead to enhanced FGF21 expression via elevated fatty acid synthesis, consequent to the inhibition of carnitine/palmitoyl-transferase by malonyl-CoA, and via increased glucose-6-phosphate–mediated activation of the carbohydrate response element binding protein, known to regulate FGF21 gene expression. Our findings shed new light on the genetic regulation of FGF21 levels. Further investigations to dissect the relationship between GCKR and FGF21, with respect to the risk of metabolic diseases, are warranted.postprin

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

Neurobiology of social behavior abnormalities in autism and Williams syndrome

Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities

A Bayesian assessment of an approximate model for unconfined water flow in sloping layered porous media

The prediction of water table height in unconfined layered porous media is a difficult modelling problem that typically requires numerical simulation. This paper proposes an analytical model to approximate the exact solution based on a steady-state Dupuit–Forchheimer analysis. The key contribution in relation to a similar model in the literature relies in the ability of the proposed model to consider more than two layers with different thicknesses and slopes, so that the existing model becomes a special case of the proposed model herein. In addition, a model assessment methodology based on the Bayesian inverse problem is proposed to efficiently identify the values of the physical parameters for which the proposed model is accurate when compared against a reference model given by MODFLOW-NWT, the open-source finite-difference code by the U.S. Geological Survey. Based on numerical results for a representative case study, the ratio of vertical recharge rate to hydraulic conductivity emerges as a key parameter in terms of model accuracy so that, when appropriately bounded, both the proposed model and MODFLOW-NWT provide almost identical results