Restoration of XAF1 expression inhibits gastric and colonic tumorigenesis in vivo

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

Ethnic and sex differences in the incidence of hospitalized acute myocardial infarction: British Columbia, Canada 1995-2002

<p>Abstract</p> <p>Background</p> <p>As populations in Western countries continue to change in their ethnic composition, there is a need for regular surveillance of diseases that have previously shown some health disparities. Earlier data have already demonstrated high rates of cardiovascular mortality among South Asians and relatively lower rates among people of Chinese descent. The aim of this study was to describe the differences in the incidence of hospitalized acute myocardial infarction (AMI) among the three largest ethnic groups in British Columbia (BC), Canada.</p> <p>Methods</p> <p>Using hospital administrative data, we identified all patients with incident AMI in BC between April 1, 1995, and March 31, 2002. Census data from 2001 provided the denominator for the entire BC population. Ethnicity was determined using validated surname analysis and applied to the census and hospital administrative datasets. Direct age standardization was used to compare incidence rates.</p> <p>Results</p> <p>A total of 34,848 AMI cases were identified. Among men, South Asians had the highest age standardized rate of AMI hospitalization at 4.97/1000 population/year, followed by Whites at 3.29, and then Chinese at 0.98. Young South Asian men, in particular, showed incidence rates that were double that of young Whites and ten times that of young Chinese men. South Asian women also had the highest age-standardized rate of AMI hospitalization at 2.35/1000 population/year, followed by White women (1.53) and Chinese women (0.49).</p> <p>Conclusions</p> <p>South Asians continue to have a higher incidence of hospitalized AMI while incidence rates among Chinese remain low. Ethnic differences are most notable among younger men.</p

Effect of hypoxia-inducible factor-1α on transcription of survivin in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Survivin is a structurally and functionally unique member of the inhibitor of apoptosis protein (IAP) family. It plays an important role, not only in regulating mitosis but also in inhibiting apoptosis. The current literature contains few reports on the transcriptional regulation of survivin expression in lung cancer.</p> <p>Methods</p> <p>In this study, we investigated the effect of hypoxia-inducible factor-1α (HIF-1α) on the transcriptional activity of the survivin promoter in non-small cell lung cancer (NSCLC). Immunohistochemical staining was used to detect the expression of survivin and HIF-1α in the lung tissue of 120 patients with non-small cell lung cancer (NSCLC) and 40 patients with benign pulmonary disease. We also performed experiments with the lung adenocarcinoma cell line A549 cells, which were cultured under hypoxic conditions. The expression of survivin and HIF-1α was detected by real-time RT-PCR and Western blotting. In the survivin promoter the putative binding-site for HIF-1α, is -19 bp~-16 bp upstream of TSS. We performed site-directed mutagenesis of this binding site, and used luciferase reporter plasmids to determine the relative activity of the survivin promoter in A549 cells. We also studied the effect of HIF-1α on the expression of survivin by dsRNA targeting of HIF-1α mRNA.</p> <p>Results</p> <p>HIF-1α (58.33%) and survivin (81.60%) were both over-expressed in NSCLC and their expressions correlated with one another. They were also expressed in A549 cells under normal and hypoxic conditions, with a significant increase under hypoxic conditions. Site directed mutagenesis of the putative binding site for HIF-1α in the survivin promoter significantly decreased the activity of the survivin promoter in A549 cells. Inhibition of HIF-1α by RNAi decreased the expression of survivin in A549 cell lines.</p> <p>Conclusion</p> <p>Our results indicate that the binding of HIF-1α to the survivin promoter increases transcription of the survivin gene. Thus, HIF-1α is an important transcriptional regulator of survivin expression</p

Synthesis of Monodisperse Nanocrystals via Microreaction: Open-to-Air Synthesis with Oleylamine as a Coligand

Microreaction provides a controllable tool to synthesize CdSe nanocrystals (NCs) in an accelerated fashion. However, the surface traps created during the fast growth usually result in low photoluminescence (PL) efficiency for the formed products. Herein, the reproducible synthesis of highly luminescent CdSe NCs directly in open air was reported, with a microreactor as the controllable reaction tool. Spectra investigation elucidated that applying OLA both in Se and Cd stock solutions could advantageously promote the diffusion between the two precursors, resulting in narrow full-width-at-half maximum (FWHM) of PL (26 nm). Meanwhile, the addition of OLA in the source solution was demonstrated helpful to improve the reactivity of Cd monomer. In this case, the focus of size distribution was accomplished during the early reaction stage. Furthermore, if the volume percentage (vol.%) of OLA in the precursors exceeded a threshold of 37.5%, the resulted CdSe NCs demonstrated long-term fixing of size distribution up to 300 s. The observed phenomena facilitated the preparation of a size series of monodisperse CdSe NCs merely by the variation of residence time. With the volume percentage of OLA as 37.5% in the source solution, a 78 nm tuning of PL spectra (from 507 to 585) was obtained through the variation of residence time from 2 s to 160 s, while maintaining narrow FMWH of PL (26–31 nm) and high QY of PL (35–55%)

Respiratory syncytial virus infection induces higher Toll-like receptor-3 expression and TNF-α production than human metapneumovirus infection

published_or_final_versio

Comparative Proteomic Analysis of the PhoP Regulon in Salmonella enterica Serovar Typhi Versus Typhimurium

Background: S. Typhi, a human-restricted Salmonella enterica serovar, causes a systemic intracellular infection in humans (typhoid fever). In comparison, S. Typhimurium causes gastroenteritis in humans, but causes a systemic typhoidal illness in mice. The PhoP regulon is a well studied two component (PhoP/Q) coordinately regulated network of genes whose expression is required for intracellular survival of S. enterica. Methodology/Principal Findings: Using high performance liquid chromatography mass spectrometry (HPLC-MS/MS), we examined the protein expression profiles of three sequenced S. enterica strains: S. Typhimurium LT2, S. Typhi CT18, and S. Typhi Ty2 in PhoP-inducing and non-inducing conditions in vitro and compared these results to profiles of $phoP^−/Q^−$ mutants derived from S. Typhimurium LT2 and S. Typhi Ty2. Our analysis identified 53 proteins in S. Typhimurium LT2 and 56 proteins in S. Typhi that were regulated in a PhoP-dependent manner. As expected, many proteins identified in S. Typhi demonstrated concordant differential expression with a homologous protein in S. Typhimurium. However, three proteins (HlyE, STY1499, and CdtB) had no homolog in S. Typhimurium. HlyE is a pore-forming toxin. STY1499 encodes a stably expressed protein of unknown function transcribed in the same operon as HlyE. CdtB is a cytolethal distending toxin associated with DNA damage, cell cycle arrest, and cellular distension. Gene expression studies confirmed up-regulation of mRNA of HlyE, STY1499, and CdtB in S. Typhi in PhoP-inducing conditions. Conclusions/Significance: This study is the first protein expression study of the PhoP virulence associated regulon using strains of Salmonella mutant in PhoP, has identified three Typhi-unique proteins (CdtB, HlyE and STY1499) that are not present in the genome of the wide host-range Typhimurium, and includes the first protein expression profiling of a live attenuated bacterial vaccine studied in humans (Ty800)

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe