173 research outputs found

    Genome Sequence and Transcriptome Analysis of the Radioresistant Bacterium Deinococcus gobiensis: Insights into the Extreme Environmental Adaptations

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    The desert is an excellent model for studying evolution under extreme environments. We present here the complete genome and ultraviolet (UV) radiation-induced transcriptome of Deinococcus gobiensis I-0, which was isolated from the cold Gobi desert and shows higher tolerance to gamma radiation and UV light than all other known microorganisms. Nearly half of the genes in the genome encode proteins of unknown function, suggesting that the extreme resistance phenotype may be attributed to unknown genes and pathways. D. gobiensis also contains a surprisingly large number of horizontally acquired genes and predicted mobile elements of different classes, which is indicative of adaptation to extreme environments through genomic plasticity. High-resolution RNA-Seq transcriptome analyses indicated that 30 regulatory proteins, including several well-known regulators and uncharacterized protein kinases, and 13 noncoding RNAs were induced immediately after UV irradiation. Particularly interesting is the UV irradiation induction of the phrB and recB genes involved in photoreactivation and recombinational repair, respectively. These proteins likely include key players in the immediate global transcriptional response to UV irradiation. Our results help to explain the exceptional ability of D. gobiensis to withstand environmental extremes of the Gobi desert, and highlight the metabolic features of this organism that have biotechnological potential

    20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action

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    We recently isolated 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD), a natural product from Panax notoginseng, and demonstrated its cytotoxicity against a variety of cancer cells. Here we report the effects of this compound in vitro and in vivo on human prostate cancer cells, LNCaP (androgen-dependent) and PC3 (androgen-independent), in comparison with three structurally related ginsenosides, ginsenoside Rh2, ginsenoside Rg3, and 20(S)-protopanaxadiol. Of the four test compounds, 25-OCH3-PPD was most potent. It decreased survival, inhibited proliferation, induced apoptosis, and led to G1 cell cycle arrest in both cell lines. It also decreased the levels of proteins associated with cell proliferation (MDM2, E2F1, cyclin D1, and cdks 2 and 4) and increased or activated pro-apoptotic proteins (cleaved PARP, cleaved caspase-3, -8, and -9). In LNCaP cells, 25-OCH3-PPD inhibited the expression of the androgen receptor and prostate-specific antigen. Moreover, 25-OCH3-PPD inhibited the growth of prostate cancer xenograft tumours. Combining 25-OCH3-PPD with conventional chemotherapeutic agents or with radiation led to potent antitumour effects; tumour regression was almost complete following administration of 25-OCH3-PPD and either taxotere or gemcitabine. 25-OCH3-PPD also demonstrated low toxicity to noncancer cells and no observable toxicity in animals. In conclusion, our preclinical data indicate that 25-OCH3-PPD is a potential therapeutic agent against both androgen-dependent and androgen-independent prostate cancer

    The prevalence of hyperuricemia in China: a meta-analysis

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    <p>Abstract</p> <p>Background</p> <p>The prevalence of hyperuricemia varied in different populations and it appeared to be increasing in the past decades. Recent studies suggest that hyperuricemia is an independent risk factor for cardiovascular disease. However, there has not yet been a systematic analysis of the prevalence of hyperuricemia in China.</p> <p>Methods</p> <p>Epidemiological investigations on hyperuricemia in China published in journals were identified manually and on-line by using CBMDISC, Chongqing VIP database and CNKI database. Those Reported in English journals were identified using MEDLINE database. Selected studies had to describe an original study defined by strict screening and diagnostic criteria. The fixed effects model or random effects model was employed according to statistical test for homogeneity.</p> <p>Results</p> <p>Fifty-nine studies were selected, the statistical information of which was collected for systematic analysis. The results showed that the pooled prevalence of hyperuricemia in male was 21.6% (95%CI: 18.9%-24.6%), but it was only 8.6% (95%CI: 8.2%-10.2%) in female. It was found that thirty years was the risk point age in male and it was fifty years in female.</p> <p>Conclusions</p> <p>The prevalence of hyperuricemia is different as the period of age and it increases after 30 years in male and 50 in female. Interventions are necessary to change the risk factors before the key age which is 30 years in male and 50 in female.</p

    Effect of FeO on the formation of spinel phases and chromium distribution in the CaO-SiO2-MgO-Al2O3-Cr2O3 system

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    Synthetic slag samples of the CaO-SiO2-MgO-Al2O3-Cr2O3 system were obtained to clarify the effect of FeO on the formation of spinel phases and Cr distribution. X-ray diffraction (XRD) and scanning electron microscopy (SEM) equipped with energy-dispersive spectroscopy (EDS), as well as the thermodynamic software FactSage 6.2, were used for sample characterization. The results show that the addition of FeO can decrease the viscosity of molten slag and the precipitation temperatures of melilite and merwinite. The solidus temperature significantly decreases from 1400 to 1250 degrees C with the increase of FeO content from 0wt% to 6wt%. The addition of FeO could enhance the content of Cr in spinel phases and reduce the content of Cr in soluble minerals, such as merwinite, melilite, and dicalcium silicate. Hence, the addition of FeO is conducive to decreasing Cr leaching.Validerad; 2013; 20130411 (andbra

    Pan-cancer analysis of whole genomes

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    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
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