Divergent Gene Expression Following Duplication of Meiotic Genes in the Stick Insect Clitarchus hookeri

evab060Some animal groups, such as stick insects (Phasmatodea), have repeatedly evolved alternative reproductive strategies, including parthenogenesis. Genomic studies have found modification of the genes underlying meiosis exists in some of these animals. Here we examine the evolution of copy number, evolutionary rate, and gene expression in candidate meiotic genes of the New Zealand geographic parthenogenetic stick insect Clitarchus hookeri. We characterized 101 genes from a de novo transcriptome assembly from female and male gonads that have homology with meiotic genes from other arthropods. For each gene we determined copy number, the pattern of gene duplication relative to other arthropod orthologs, and the potential for meiosis-specific expression. There are five genes duplicated in C hookers; including one also duplicated in the stick insect Timema cristinae, that are not or are uncommonly duplicated in other arthropods. These included two sister chromatid cohesion associated genes (SA2 and SCC2), a recombination gene (HOPI), an RNA-silencing gene (AGO2) and a cell-cycle regulation gene (WEE1). Interestingly, WEE1 and SA2 are also duplicated in the cyclical parthenogenetic aphid Acyrthosiphon pisum and Daphnia duplex, respectively, indicating possible roles in the evolution of reproductive mode. Three of these genes (SA2, SCC2, and WEE1) have one copy displaying gonad-specific expression. All genes, with the exception of WEE1, have significantly different nonsynonymous/synonymous ratios between the gene duplicates, indicative of a shift in evolutionary constraints following duplication. These results suggest that stick insects may have evolved genes with novel functions in gamete production by gene duplication.Peer reviewe

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Hormone therapy in relation to survival from large bowel cancer.

Epidemiologic studies of hormone therapy (HT) and colorectal cancer incidence consistently show an inverse association; however, few studies have considered prediagnostic use of HT on mortality among colorectal cancer patients. We evaluated the relationship of HT and survival among a population-based cohort of women with large bowel cancer. Cases (n = 1,297) were newly diagnosed with invasive cancer of the colon or rectum, aged 40-74 years at diagnosis, who were identified by Wisconsin's statewide registry (1988-1991; 1997-2001) for two case-control studies. Information on HT use and other colorectal cancer risk factors was collected by standardized interview. There were 507 deaths (274 of these attributable to colorectal cancer) over 8.4 years of follow-up through December 2005. Hormone use was not associated with colorectal cancer mortality (adjusted hazard rate ratio = 1.09, confidence interval = 0.81-1.47). Colorectal cancer specific mortality was not associated with HT when considered separately by preparation type. Stage did not modify this relationship. Long-term HT was weakly positively associated with increased mortality after diagnosis of proximal colon, but not distal colon cancer. Because we detected no differences in survival among users of HT compared to non-users, the results suggest that HT use may affect only the incidence of some colorectal tumors

Recent Work on the Design and Construction of Air Inflated Structures

AbstractOver the last few years our practice has been responsible for the structural design of a number of lightweight structures that achieve their structural stability by inflating elements of fabric structure. The paper will explain the design rationale of key examples; describing the structural forms, methods of analysis and design, and the detailing, materials, and methods of fabrication. The largest and most complex of these structures to date is a demountable stage set structure for the Cirque du Soleil “Toruk: First Flight” show, comprising two 15 metre high and 20 metre wide structures. The stage set structures form ‘trees’ on which acrobats climb and perform. Each structure incorporates a high level access gantry with acrobat suspension and counterweight systems, as well as a secondary inflatable skin cladding. The entire primary structure and cladding system is constructed from inflated fabric elements using internal pressures ranging from 0.5 KN/m2 up to 90 KN/m2, and are deflated down to less than 5% of their erected volume for transport between venues. Other examples of our work described will include temporary pavilions with clear spans of up to 25 metres, using a combination of air tight and air permeable elements. Also a range of wide span structures that we describe as “semi-permanent” that are capable of resisting full environmental wind and snow loading, and that are fully demountable but that can also be erected for extended periods of time in a single location

Bone mineral density and the subsequent risk of cancer in the NHANES I follow-up cohort

BACKGROUD: Bone mineral density (BMD) is a marker of long-term estrogen exposure. BMD measurement has been used in this context to investigate the association of estrogen with breast cancer risk in three cohorts. In order to assess further BMD as a predictor of estrogen related cancer risk, the association of BMD with colorectal and corpus uteri cancer was investigated in the NHANES I Epidemiologic Followup Study (NHEFS) cohort along with breast cancer and prostate cancer. METHODS: Participants were members of the NHEFS cohort who had BMD measurement in 1974–1975. Age, race, and BMI adjusted rate ratios and 95% confidence intervals were calculated for incidence of cancers of the corpus uterus, breast, colorectum, prostate, and of osteoporosis and hip fracture related to baseline BMD. RESULTS: Data were available for 6046 individuals. One hundred cases of breast cancer, 94 prostate cancers, 115 colorectal cancers, 29 uterine cancers, 110 cases of hip fracture and 103 cases of osteoporosis were reported between 1974 and 1993. Hip fracture and osteoporosis were both significantly inversely associated with BMD. Uterine cancer was positively associated (p = 0.005, test for linear trend) and colorectal cancer negatively associated (p = 0.03) with BMD. No association was found between elevated BMD and incidence of breast cancer (p = 0.74) or prostate cancer (p = 0.37) in the overall cohort, although a weak association was seen between BMD and subsequent breast cancer incidence when BMD was measured in post-menopausal women (p = 0.04). CONCLUSION: The findings related to cancers of the uterus and colorectum as well as the weak association of BMD with breast cancer strengthen the use of BMD as a marker of estrogen exposure and cancer risk

Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer

Objective: To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2). Design: We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-Analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-Analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as â € positive' and â € less-credible positive' were further validated in three large GWAS consortia conducted in populations of European origin. Results: We initially identified 18 independent variants at 16 loci that were classified as â € positive' polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as â € less-credible positive' SNPs; 72.2% of the â € positive' SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to â € less-credible' positive (reducing the â € positive' variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-Analyses found no evidence to support their associations with CRC risk. Conclusion: The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility.</p

An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

Abstract: It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article