CREB3 subfamily transcription factors are not created equal: Recent insights from global analyses and animal models

<p>Abstract</p> <p>The CREB3 subfamily of membrane-bound bZIP transcription factors has five members in mammals known as CREB3 and CREB3L1-L4. One current model suggests that CREB3 subfamily transcription factors are similar to ATF6 in regulated intramembrane proteolysis and transcriptional activation. Particularly, they were all thought to be proteolytically activated in response to endoplasmic reticulum (ER) stress to stimulate genes that are involved in unfolded protein response (UPR). Although the physiological inducers of their proteolytic activation remain to be identified, recent findings from microarray analyses, RNAi screens and gene knockouts not only demonstrated their critical roles in regulating development, metabolism, secretion, survival and tumorigenesis, but also revealed cell type-specific patterns in the activation of their target genes. Members of the CREB3 subfamily show differential activity despite their structural similarity. The spectrum of their biological function expands beyond ER stress and UPR. Further analyses are required to elucidate the mechanism of their proteolytic activation and the molecular basis of their target recognition.</p

Chiral microstructures (spirals) fabrication by holographic lithography

We present an optical interference model to create chiral microstructures (spirals) and its realization in photoresist using holographic lithography. The model is based on the interference of six equally-spaced circumpolar linear polarized side beams and a circular polarized central beam. The pitch and separation of the spirals can be varied by changing the angle between the side beams and the central beam. The realization of the model is carried out using the 325 nm line of a He-Cd laser and spirals of sub-micron size are fabricated in photoresist.Comment: 6 page

The regulation of the residential property market in Hong Kong : a study of government strategies and tools

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Identification of a novel distal regulatory element of the human Neuroglobin gene by the chromosome conformation capture approach

Neuroglobin (NGB) is predominantly expressed in the brain and retina. Studies suggest that NGB exerts protective effects to neuronal cells and is implicated in reducing the severity of stroke and Alzheimer's disease. However, little is known about the mechanisms which regulate the cell type-specific expression of the gene. In this study, we hypothesized that distal regulatory elements (DREs) are involved in optimal expression of the NGB gene. By chromosome conformation capture we identified two novel DREs located -70 kb upstream and +100 kb downstream from the NGB gene. ENCODE database showed the presence of DNaseI hypersensitive and transcription factors binding sites in these regions. Further analyses using luciferase reporters and chromatin immunoprecipitation suggested that the -70 kb region upstream of the NGB gene contained a neuronalspecific enhancer and GATA transcription factor binding sites. Knockdown of GATA-2 caused NGB expression to drop dramatically, indicating GATA-2 as an essential transcription factor for the activation of NGB expression. The crucial role of the DRE in NGB expression activation was further confirmed by the drop in NGB level after CRISPR-mediated deletion of the DRE. Taken together, we show that the NGB gene is regulated by a cell type-specific loop formed between its promoter and the novel DRE

The incidence and risk of developing a second primary esophageal cancer in patients with oral and pharyngeal carcinoma: a population-based study in Taiwan over a 25 year period

<p>Abstract</p> <p>Background</p> <p>The incidence of oral and pharyngeal (including oral cavity, oropharynx and hypopharynx) carcinoma increases rapidly in Asia and South Pacific because of betel quid chewing. Thus far, large-scale epidemiological studies are not available yet to stratify these patients by their risks of developing a second primary cancer in the digestive tract including esophagus, stomach, colon, and rectum.</p> <p>Methods</p> <p>A population-based study was conducted using the database from the Taiwan National Cancer Registry for the period 1979-2003. We quantified standardized incidence ratios (SIRs) and cumulative incidence of second primary cancers among 33,787 patients with initial diagnoses of oral and pharyngeal carcinoma.</p> <p>Results</p> <p>Among these four digestive tract organs, the esophagus was the only site of second cancer with excess risk in patients with oral and pharyngeal carcinoma. The incidence and risk of developing a second primary esophageal cancer differed by the site of the primary index tumor, most frequently seen in hypopharyngeal cancer (71/4,218 = 1.68%, SIR = 22.76, 95% CI 17.77-28.70), followed by oropharyngeal cancer (30/3,403 = 0.88%, SIR = 14.29, 95% CI 9.64-20.39) and the least in oral cavity cancer (99/26,166 = 0.38%, SIR = 5.57, 95% CI 4.53-6.78). In addition, the risk was extraordinarily high for patients with a follow-up interval ≤ 1 year and those with first primary cancer diagnosed at age ≤50. These patients may justify more close surveillance.</p> <p>Conclusion</p> <p>The present study represents the first population-based study in Asia attempting to stratify the patients of oral and pharyngeal carcinoma by their risk of developing a second esophageal cancer. It helps identify patients at high risk and tailor the application of intense follow-up surveillance to the estimated risk in each individual case.</p

Serum 25-hydroxyvitamin D concentrations and cardiometabolic risk factors in adolescents and young adults

Evidence associating serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiometabolic risk factors is inconsistent and studies have largely been conducted in adult populations. We examined the prospective associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the West Australian Pregnancy Cohort (Raine) Study. Serum 25(OH)D concentrations, BMI, homoeostasis model assessment for insulin resistance (HOMA-IR), TAG, HDL-cholesterol and systolic blood pressure (SBP) were measured at the 17-year (n 1015) and 20-year (n 1117) follow-ups. Hierarchical linear mixed models with maximum likelihood estimation were used to investigate associations between serum 25(OH)D concentrations and cardiometabolic risk factors, accounting for potential confounders. In males and females, respectively, mean serum 25(OH)D concentrations were 73·6 (sd 28·2) and 75·4 (sd 25·9) nmol/l at 17 years and 70·0 (sd 24·2) and 74·3 (sd 26·2) nmol/l at 20 years. Deseasonalised serum 25(OH)D3 concentrations were inversely associated with BMI (coefficient -0·01; 95 % CI -0·03, -0·003; P=0·014). No change over time was detected in the association for males; for females, the inverse association was stronger at 20 years compared with 17 years. Serum 25(OH)D concentrations were inversely associated with log-HOMA-IR (coefficient -0·002; 95 % CI -0·003, -0·001; P<0·001) and positively associated with log-TAG in females (coefficient 0·002; 95 % CI 0·0008, 0·004; P=0·003). These associations did not vary over time. There were no significant associations between serum 25(OH)D concentrations and HDL-cholesterol or SBP. Clinical trials in those with insufficient vitamin D status may be warranted to determine any beneficial effect of vitamin D supplementation on insulin resistance, while monitoring for any deleterious effect on TAG