No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis

STUDY QUESTION Is there a contribution of the minor allele at the KRAS single nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to endometriosis risk? SUMMARY ANSWER We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS. WHAT IS KNOWN ALREADY The rs61764370 SNP in the 3' untranslated region of the KRAS gene is predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA, and was recently reported to be at a high frequency (31%) in 132 women of varying ancestry with endometriosis compared with frequencies in a database of population controls (up to 7.6% depending on ancestry), suggesting a strong effect of this KRAS SNP in the aetiology of endometriosis. STUDY DESIGN, SIZE AND DURATION This was a case-control study with a total of 11 206 subjects. The study was performed between February 2012 and July 2012. PARTICIPANTS/MATERIALS, SETTINGAND METHODS We first investigated a possible association between common markers in KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry. Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the study were highly correlated with this variant. The rs61764370 and two SNPs highly correlated with rs61764370 were then genotyped in 933 endometriosis cases and 952 controls using the Sequenom MassARRAY platform. MAIN RESULTS AND THE ROLE OF CHANCE There was no evidence for an association between rs61764370 and endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals: 0.88-1.36). We also found no evidence for an association between the highly correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in cases and controls were of 0.087-0.091 similar to the population frequency reported previously for this variant in controls. Analyses of endometriosis cases with revised American Fertility Society stage III/IV disease also showed no evidence for an association between these SNPs and endometriosis risk. LIMITATIONS AND REASONS FOR CAUTION The GWA and genotyped data sets were not independent since individuals and cases from some families overlap. Controls in our GWA study were not screened for endometriosis. WIDER IMPLICATIONS OF THE FINDINGS The key SNP, rs61764370, was genotyped in a subset of samples. Our results do not support the suggestion that carrying the minor allele at rs61764370 contributes to a significant number of endometriosis cases and rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk. STUDY FUNDING/COMPETING INTEREST(S) The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.

Herman Sommerfeld (center) with other reserve soldiers in military uniform Portraits Men

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Herman Sommerfeld (center) with other soldiers in military uniform Portraits Men

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Herman Sommerfeld (fifth from right) with other soldier recruits; Döberitz, Germany Portraits Men

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Enhancing development outcomes for smallholder farmers through closer collaboration between ACIAR’s landcare and other projects

Improving development outcomes for smallholder farmers through closer collaboration between landcare and other ACIAR projects.

Dr. William Levison (seated, far left) with other U.S. Army medial doctors and nurses with Christmas Tree in background Portraits Groups

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Leopold Landsberger with other unidentified soldiers standing inside and around a hot air balloon at Verdun, France.

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Arrival of Ludwig Marum and other socialist leaders from Baden (Karlsruhe) to the concentration camp Kislau.

Includes l-r: Hermann Stenz, Adam Remmele, Erwin Sammet, Ludwig Marum, Gustav Heller, Sally Gruenebaum and August Furrer

Deportation of Ludwig Marum and other socialist leaders from Baden (Karlsruhe) to the concentration camp Kislau.

Typed caption on verso: Schaufahrt durch Karlsruhe, 16 May 1933 auf der Kaiserstrasse mit dem Blick auf die Fahrbahn: ganz hinten allein: Ludwig Marum dann: Erwin Sammet u. Hermann Stenz verdeckt: Sally Gruenebaum u. August Furrer vorne: Gustav Heller u. Adam Remmele

The other country: A father's journey with autism

The memoir The Other Country and the essay Inspiration is Power examine i) contemporary experiences of autism and ii) the representation of autism disorder in scientific and autobiographical writing. The Other Country is a memoir of four years in the life of its author Michael Whelan, and his family, in the care of his son, Charlie. In February 1998, Charlie was diagnosed with autism, and in that moment Michael and his family's lives changed. The memoir describes in four parts a four-year journey through a father?s experiences: - Part 1, Welcome to Holland, the family's feelings of fear, grief and dislocation following diagnosis; - Part 2, Look at Me, the chaotic process of research and treatment, and intense early intervention programs; - Part 3, The Enchanted Cottage, the slow process of recovery that the family went through, and; - Part 4, The Long Way Home, the transformation of Charlie, Michael and his family and notions of home and normalcy. The title, The Other Country, in this context refers to the largely invisible parallel society inhabited by anyone who lives outside the mainstream. The accompanying critical essay, Inspiration is Power, examines the influence of the discourses of biomedical science and parental pathology on the representation and understanding of autism. Specifically, among autism narratives, the medical voice has an overwhelming authority and power in characterizing autistic disorder and experience for the lay reader. This discourse contests the moral authority of parental autobiographical writing, which, by contrast, characterizes autism as a personalized invading other and thief of their child. Through a critique of specific aspects of identity, narrative, evidence and authority, the essay suggests a register of rhetorical moves that may be employed to influence, and consequently empower, the reader of autism narratives.

Immunological cross-reactivity of mycobacterial topoisomerase I and divergence from other bacteria

Mycobacterium smegmatis topoisomerase I exhibits several distinctive characteristics among all topoisomerases. The enzyme is devoid of Zn2+fingers found typically in other bacterial type I topoisomerases and binds DNA in a site-specific manner. Using polyclonal antibodies, we demonstrate the high degree of relatedness of the enzyme across mycobacteria but not other bacteria. This absence of cross-reactivity from other bacteria indicates that mycobacterial topoisomerase I has diverged from Escherichia coli and other bacteria. We have investigated further the immunological properties of the enzyme by raising a panel of monoclonal antibodies that recognises different antigenically active regions of the enzyme and binds it with widely varied affinity. Inhibition of a C-terminal domain-specific antibody binding by enzyme-specific and non-specific oligonucleotides suggests the possibility of using these monoclonal antibodies to probe the structure, function and in vivo role of the enzyme.

A checklist of plant pathogenic and other microfungi in the rainforests of the wet tropics of northern Queensland

Microfungi that cause disease or are associated with diseased plants in the wet tropics of northern Queensland are listed. A total of 206 host-pathogen combinations on 148 host species has been compiled from the results of plant disease surveys in the Wet Tropics World Heritage Area in 1992 and 1993, from herbarium records and from previously published host-pathogen combinations.

Fritz Gottschalk family with other children on the beach; Norderney, Germany.

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