57 research outputs found

    Functional Divergence in the Genus Oenococcus as Predicted by Genome Sequencing of the Newly-Described Species, Oenococcus kitaharae

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    Oenococcus kitaharae is only the second member of the genus Oenococcus to be identified and is the closest relative of the industrially important wine bacterium Oenococcus oeni. To provide insight into this new species, the genome of the type strain of O. kitaharae, DSM 17330, was sequenced. Comparison of the sequenced genomes of both species show that the genome of O. kitaharae DSM 17330 contains many genes with predicted functions in cellular defence (bacteriocins, antimicrobials, restriction-modification systems and a CRISPR locus) which are lacking in O. oeni. The two genomes also appear to differentially encode several metabolic pathways associated with amino acid biosynthesis and carbohydrate utilization and which have direct phenotypic consequences. This would indicate that the two species have evolved different survival techniques to suit their particular environmental niches. O. oeni has adapted to survive in the harsh, but predictable, environment of wine that provides very few competitive species. However O. kitaharae appears to have adapted to a growth environment in which biological competition provides a significant selective pressure by accumulating biological defence molecules, such as bacteriocins and restriction-modification systems, throughout its genome

    Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

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    BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization

    Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

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    BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients

    Variation in the provision and practice of implant-based breast reconstruction in the UK: Results from the iBRA national practice questionnaire

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    Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored

    PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

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    Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T&gt;G and c.3113G&gt;A, CHEK2c.349A&gt;G, c.538C&gt;T, c.715G&gt;A, c.1036C&gt;T, c.1312G&gt;T, and c.1343T&gt;G and ATM c.7271T&gt;G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant.Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G&gt;A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T&gt;G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A&gt;G OR 2.26 (95% CI 1.29 to 3.95), c.1036C&gt;T OR 5.06 (95% CI 1.09 to 23.5) and c.538C&gt;T OR 1.33 (95% CI 1.05 to 1.67) (p≀0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T&gt;G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G&gt;T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants.Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.</p

    Evidence gaps and biodiversity threats facing the marine environment of the United Kingdom’s Overseas Territories

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    Understanding the evidence base and identifying threats to the marine environment is critical to ensure cost-effective management and to identify priorities for future research. The United Kingdom (UK) government is responsible for approximately 2% of the world’s oceans, most of which belongs to its 14 Overseas Territories (UKOTs). Containing biodiversity of global significance, and far in excess of the UK mainland’s domestic species, there has recently been a strong desire from many of the UKOTs, the UK Government, and NGOs to improve marine management in these places. Implementing evidence-based marine policy is, however, challenged by the disparate nature of scientific research in the UKOTs and knowledge gaps about the threats they face. Here, we address these issues by systematically searching for scientific literature which has examined UKOT marine biodiversity and by exploring publicly available spatial threat data. We find that UKOT marine biodiversity has received consistent, but largely low, levels of scientific interest, and there is considerable geographical and subject bias in research effort. Of particular concern is the lack of research focus on management or threats to biodiversity. The extent and intensity of threats vary amongst and within the UKOTs but unsurprisingly, climate change associated threats affect them all and direct human stressors are more prevalent in those with higher human populations. To meet global goals for effective conservation and management, there is an urgent need for additional and continued investment in research and management in the Overseas Territories, particularly those that have been of lesser focus

    THE EFFECTS OF HIGH-INTENSITY FUNCTIONAL TRAINING ON PERCEPTIONS OF EXERCISE IN MIDDLE-AGED FEMALES

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    Halle N. Brin1, Camilla L. Roy1, Baylie G. Sigmund1, Nathan D. Dicks2, Kathryn J. DeShaw3, Michael J. Carper1, Laura M. Covert-Miller1, Tanis J. Walch4, Allison M. Barry1. 1Pittsburg State University, Pittsburg, KS; 2Concordia College, Moorhead, MN; 3Loras College, Dubuque, IA; 4University of North Dakota, Grand Forks, ND The high prevalence of obesity and physical inactivity within the U.S. has become a public health crisis. PURPOSE: To examine the effects of High-Intensity Functional Training (HIFT) on the perceptions and beliefs towards exercise in an inactive sample of females. METHODS: Inactive, middle-aged females (n = 8) were recruited to participate in an 8-week supervised and verified intervention (2-weeks High-Intensity Interval Training (On-Ramp), followed by 6-weeks of HIFT) three days per week. Pre- and post-assessments included: body composition (percent body fat (%BF)), strength (1RM bench press (BP), 5RM deadlift (DL)), a stage-graded exercise treadmill test (O2max), and a Health Belief Model Scale for Exercise (HMBS-E). The HBMS-E was distributed weekly to assess changes in perceptions and beliefs towards exercise, consisting of 18 questions formatted into 5-point Likert scales. The HBMS-E questions were grouped into the five sub-categories: perceived objective barriers, perceived subjective barriers, self-efficacy, perceived severity, and cues to action. Comparisons between pre- and post-assessment of the physiological components as well as the HBMS-E categories were assessed using dependent t-tests. SPSS (v. 26) was used for statistical analysis. RESULTS: The participant demographics (age: 39.2 ± 7.7 yrs), performance, and HBMS-E data are reported as pre- to post-intervention, respectively. There was no significant difference in %BF (35.2 ± 6.6% to 34.3 ± 6.0%, p \u3e .05). There was a significant increase in 1RM BP (25.2 ± 10.1 kg to 35.7 ± 11.1 kg; p \u3c .001, d = 2.51; 5RM DL (36.2 ± 12.3 kg to 49.1 ± 9.8 kg; p = .001, d = 1.83); and O2max (23.4 ± 4.0 ml∙kg∙min-1 to 26.4 ± 4.1 ml∙kg∙min-1 ; p = .001, d = 1.81). There was a significant reduction in the HBMS-E sub-categories of objective barriers (3.5 ± 0.7 to 1.9 ± 0.6; p = .003; d = 1.58) and subjective barriers (2.7 ± 0.8 to 1.6 ± 0.5; p = .017, d = 1.09) and significant increase in self-efficacy (3.5 ± 1.4 to 4.6 ± 0.56; p = .016; d = 1.13). CONCLUSION: There is evidence to suggest HIFT has a positive influence on middle-aged females’ perceptions and beliefs of self-efficacy and barriers towards exercise. Additionally, the HIFT intervention had a significant impact on the physiological adaptions of strength in this population

    Intraspecific diversity of Oenococcus oeni strains determined by sequence analysis of target genes.

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    International audienceUsing molecular techniques and sequencing, we studied the intraspecific diversity of Oenococcus oeni, a lactic acid bacterium involved in red winemaking. A relationship between the phenotypic and genotypic characterization of 16 O. oeni strains isolated from wine with different levels of enological potential was shown. The study was based on the comparative genomic analysis by subtractive hybridization between two strains of O. oeni with opposite enological potential. The genomic sequences obtained from subtractive hybridization were amplified by polymerase chain reaction and sequenced for the 16 strains. A considerable diversity among strains of O. oeni was observed
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