43 research outputs found

    Gene-Expression Signatures Can Distinguish Gastric Cancer Grades and Stages

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    Microarray gene-expression data of 54 paired gastric cancer and adjacent noncancerous gastric tissues were analyzed, with the aim to establish gene signatures for cancer grades (well-, moderately-, poorly- or un-differentiated) and stages (I, II, III and IV), which have been determined by pathologists. Our statistical analysis led to the identification of a number of gene combinations whose expression patterns serve well as signatures of different grades and different stages of gastric cancer. A 19-gene signature was found to have discerning power between high- and low-grade gastric cancers in general, with overall classification accuracy at 79.6%. An expanded 198-gene panel allows the stratification of cancers into four grades and control, giving rise to an overall classification agreement of 74.2% between each grade designated by the pathologists and our prediction. Two signatures for cancer staging, consisting of 10 genes and 9 genes, respectively, provide high classification accuracies at 90.0% and 84.0%, among early-, advanced-stage cancer and control. Functional and pathway analyses on these signature genes reveal the significant relevance of the derived signatures to cancer grades and progression. To the best of our knowledge, this represents the first study on identification of genes whose expression patterns can serve as markers for cancer grades and stages

    Analysis of Hypoxia and Hypoxia-Like States through Metabolite Profiling

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    In diverse organisms, adaptation to low oxygen (hypoxia) is mediated through complex gene expression changes that can, in part, be mimicked by exposure to metals such as cobalt. Although much is known about the transcriptional response to hypoxia and cobalt, little is known about the all-important cell metabolism effects that trigger these responses.Herein we use a low molecular weight metabolome profiling approach to identify classes of metabolites in yeast cells that are altered as a consequence of hypoxia or cobalt exposures. Key findings on metabolites were followed-up by measuring expression of relevant proteins and enzyme activities. We find that both hypoxia and cobalt result in a loss of essential sterols and unsaturated fatty acids, but the basis for these changes are disparate. While hypoxia can affect a variety of enzymatic steps requiring oxygen and heme, cobalt specifically interferes with diiron-oxo enzymatic steps for sterol synthesis and fatty acid desaturation. In addition to diiron-oxo enzymes, cobalt but not hypoxia results in loss of labile 4Fe-4S dehydratases in the mitochondria, but has no effect on homologous 4Fe-4S dehydratases in the cytosol. Most striking, hypoxia but not cobalt affected cellular pools of amino acids. Amino acids such as aromatics were elevated whereas leucine and methionine, essential to the strain used here, dramatically decreased due to hypoxia induced down-regulation of amino acid permeases.These studies underscore the notion that cobalt targets a specific class of iron proteins and provide the first evidence for hypoxia effects on amino acid regulation. This research illustrates the power of metabolite profiling for uncovering new adaptations to environmental stress

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    Inactivation of bacteria using ultraviolet irradiation in a recirculating salmonid culture system

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    AbstractThe objective of this research was to determine the ultraviolet (UV) irradiation dosages required to inactivate bacteria in a commercial-scale recirculating salmonid culture system. Research was conducted in the commercial-scale recirculating system used for Arctic char growout at the Conservation Fund Freshwater Institute (Shepherdstown, West Virginia). This recirculating system uses a UV channel unit to treat 100% of the 4750L/min recirculating water flow with an approximately 100–120mWs/cm2 UV irradiation dose. However, a second UV irradiation unit was operated at a constant intensity to treat a side-stream flow of water pumped from the commercial-scale recirculating system's low head oxygenator (LHO) sump. The side-stream water flow ranged from 0.15–3.8% (i.e., 7–180L/min) of the entire recirculating flow so as to regulate the water retention time (i.e., from 3–70s) within the UV irradiation unit and thus produce a range of UV irradiation doses (mWs/cm2). UV irradiation doses of approximately 75, 150, 300, 500, 980, and 1800mWs/cm2 were applied to determine the dose required to inactivate total heterotrophic bacteria and total coliform bacteria. Total heterotrophic bacteria counts and total coliform bacteria counts were measured immediately before and immediately after the side-stream UV irradiation unit. Total heterotrophic bacteria in the recirculating system required a UV dosage in excess of 1800mWs/cm2 to achieve a not quite 2 LOG10 reduction (i.e., a 98.0±0.4% reduction). In contrast, total coliform bacteria were more susceptible to UV inactivation and complete inactivation of coliform bacteria was consistently achieved at the lowest UV dose applied, i.e., at approximately 77mWs/cm2. These results suggest that: (1) the UV dose required to inactivate total heterotrophic bacteria—and thus disinfect a recirculating water flow—was nearly 60 times greater than the 30mWs/cm2 dose typically recommended in aquaculture and (2) inactivating 100% of bacteria in a given flow can be difficult, even at excessive UV doses, because UV irradiation cannot always penetrate particulate matter to reach embedded bacteria. We present a hypothesis that the recirculating system provided a selection process that favors bacteria that embed within particulate matter or that form bacterial aggregates that provides shading from some of the UV irradiation, because the bacteria in the recirculating water were exposed to approximately 100–120mWs/cm2 of UV irradiation every 30min
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