Hepatitis B vaccinations among Koreans: Results from 2005 Korea National Cancer Screening Survey

<p>Abstract</p> <p>Background</p> <p>Liver cancer is one of most commonly diagnosed cancers among Koreans. Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cancer. HBV infection can be prevented by effective screening and vaccination programs. The purpose of this study is to examine the status of HBV infection and the predictors associated with HBV vaccination.</p> <p>Methods</p> <p>The study population was derived from the 2005 Korea National Cancer Screening Survey (KNCSS). The KNCSS is an annual cross-sectional survey that uses a nationally-representative random sampling to investigate cancer screening rates. A total of 1,786 Koreans over 40 years of age participated in this study.</p> <p>Results</p> <p>Of all the participants, 5.9% reported HBV positive (HBsAg+, HBsAb-), 41.8% were HBV negative but protected (HBsAg-, HBsAb+), and 52.3% were unprotected (HBsAg-, HBsAb-). Among unprotected individuals (n = 934), 23.1% reported to have received the vaccination. About half of those who had vaccinations completed the 3-shot vaccine series. In multiple analyses, education, having private cancer insurance, alcohol use, having regular check-up, and doing regular exercise were associated with completed HBV vaccination.</p> <p>Conclusion</p> <p>This study result suggests that we need a liver cancer education program to increase HBV awareness and to increase the liver cancer prevention message among low educated populations.</p

Functional genomics reveals serine synthesis is essential in PHGDH-amplified breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation[superscript 1, 2]. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes[superscript 3]. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.Susan G. Komen Breast Cancer Foundation (Fellowship)Life Sciences Research Foundation (Fellowship)W. M. Keck FoundationDavid H. Koch Cancer Research FundAlexander and Margaret Stewart TrustNational Institutes of Health (U.S.) (Grant CA103866

Outer Membrane Vesicles as a Candidate Vaccine against Edwardsiellosis

Infection with Edwardsiella tarda, a Gram-negative bacterium, causes high morbidity and mortality in both marine and freshwater fish. Outer membrane vesicles (OMVs) released from Gram-negative bacteria are known to play important roles in bacterial pathogenesis and host immune responses, but no such roles for E. tarda OMVs have yet been described. In the present study, we investigated the proteomic composition of OMVs and the immunostimulatory effect of OMVs in a natural host, as well as the efficacy of OMVs when used as a vaccine against E. tarda infection. A total of 74 proteins, from diverse subcellular fractions, were identified in OMVs. These included a variety of important virulence factors, such as hemolysin, OmpA, porin, GAPDH, EseB, EseC, EseD, EvpC, EvpP, lipoprotein, flagellin, and fimbrial protein. When OMVs were administrated to olive flounder, significant induction of mRNAs encoding IL-1β, IL-6, TNFα, and IFNγ was observed, compared with the levels seen in fish injected with formalin-killed E. tarda. In a vaccine trial, olive flounder given OMVs were more effectively protected (p<0.0001) than were control fish. Investigation of OMVs may be useful not only for understanding the pathogenesis of E. tarda but also in development of an effective vaccine against edwardsiellosis

Resveratrol Inhibits Protein Translation in Hepatic Cells

Resveratrol is a plant-derived polyphenol that extends lifespan and healthspan in model organism. Despite extensive investigation, the biological processes mediating resveratrol's effects have yet to be elucidated. Because repression of translation shares many of resveratrol's beneficial effects, we hypothesized that resveratrol was a modulator of protein synthesis. We studied the effect of the drug on the H4-II-E rat hepatoma cell line. Initial studies showed that resveratrol inhibited global protein synthesis. Given the role of the mammalian Target of Rapamycin (mTOR) in regulating protein synthesis, we examined the effect of resveratrol on mTOR signaling. Resveratrol inhibited mTOR self-phosphorylation and the phosphorylation of mTOR targets S6K1 and eIF4E-BP1. It attenuated the formation of the translation initiation complex eIF4F and increased the phosphorylation of eIF2α. The latter event, also a mechanism for translation inhibition, was not recapitulated by mTOR inhibitors. The effects on mTOR signaling were independent of effects on AMP-activated kinase or AKT. We conclude that resveratrol is an inhibitor of global protein synthesis, and that this effect is mediated through modulation of mTOR-dependent and independent signaling

The First Stars

The first stars to form in the Universe -- the so-called Population III stars -- bring an end to the cosmological Dark Ages, and exert an important influence on the formation of subsequent generations of stars and on the assembly of the first galaxies. Developing an understanding of how and when the first Population III stars formed and what their properties were is an important goal of modern astrophysical research. In this review, I discuss our current understanding of the physical processes involved in the formation of Population III stars. I show how we can identify the mass scale of the first dark matter halos to host Population III star formation, and discuss how gas undergoes gravitational collapse within these halos, eventually reaching protostellar densities. I highlight some of the most important physical processes occurring during this collapse, and indicate the areas where our current understanding remains incomplete. Finally, I discuss in some detail the behaviour of the gas after the formation of the first Population III protostar. I discuss both the conventional picture, where the gas does not undergo further fragmentation and the final stellar mass is set by the interplay between protostellar accretion and protostellar feedback, and also the recently advanced picture in which the gas does fragment and where dynamical interactions between fragments have an important influence on the final distribution of stellar masses.Comment: 72 pages, 4 figures. Book chapter to appear in "The First Galaxies - Theoretical Predictions and Observational Clues", 2012 by Springer, eds. V. Bromm, B. Mobasher, T. Wiklin

High-Density Transcriptional Initiation Signals Underline Genomic Islands in Bacteria

Genomic islands (GIs), frequently associated with the pathogenicity of bacteria and having a substantial influence on bacterial evolution, are groups of “alien” elements which probably undergo special temporal–spatial regulation in the host genome. Are there particular hallmark transcriptional signals for these “exotic” regions? We here explore the potential transcriptional signals that underline the GIs beyond the conventional views on basic sequence composition, such as codon usage and GC property bias. It showed that there is a significant enrichment of the transcription start positions (TSPs) in the GI regions compared to the whole genome of Salmonella enterica and Escherichia coli. There was up to a four-fold increase for the 70% GIs, implying high-density TSPs profile can potentially differentiate the GI regions. Based on this feature, we developed a new sliding window method GIST, Genomic-island Identification by Signals of Transcription, to identify these regions. Subsequently, we compared the known GI-associated features of the GIs detected by GIST and by the existing method Islandviewer to those of the whole genome. Our method demonstrates high sensitivity in detecting GIs harboring genes with biased GI-like function, preferred subcellular localization, skewed GC property, shorter gene length and biased “non-optimal” codon usage. The special transcriptional signals discovered here may contribute to the coordinate expression regulation of foreign genes. Finally, by using GIST, we detected many interesting GIs in the 2011 German E. coli O104:H4 outbreak strain TY-2482, including the microcin H47 system and gene cluster ycgXEFZ-ymgABC that activates the production of biofilm matrix. The aforesaid findings highlight the power of GIST to predict GIs with distinct intrinsic features to the genome. The heterogeneity of cumulative TSPs profiles may not only be a better identity for “alien” regions, but also provide hints to the special evolutionary course and transcriptional regulation of GI regions

Search for Gravitational Waves from Intermediate Mass Binary Black Holes

We present the results of a weakly modeled burst search for gravitational waves from mergers of non-spinning intermediate mass black holes (IMBH) in the total mass range 100--450 solar masses and with the component mass ratios between 1:1 and 4:1. The search was conducted on data collected by the LIGO and Virgo detectors between November of 2005 and October of 2007. No plausible signals were observed by the search which constrains the astrophysical rates of the IMBH mergers as a function of the component masses. In the most efficiently detected bin centered on 88+88 solar masses, for non-spinning sources, the rate density upper limit is 0.13 per Mpc^3 per Myr at the 90% confidence level.Comment: 13 pages, 4 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=62326, see also the public announcement at http://www.ligo.org/science/Publication-S5IMBH

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