Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C>T, rs2981745, located in the DMBT1 promoter; and DMBT1 c.124A>C, p.Thr42Pro, rs11523871(odds ratio [OR]=1.66, 95% confidence interval [CI]=1.21-2.29, P=0.0017; and OR=1.66; 95% CI=1.21-2.28, P=0.0016, respectively), based on 1,195 BRCA1/2 mutation-negative German breast cancer families and 1,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region are associated with increased breast cancer risk. In accordance with previous results, these data link decreased DMBT1 levels to breast cancer risk

Characterization of Multi-Functional Properties and Conformational Analysis of MutS2 from Thermotoga maritima MSB8

The MutS2 homologues have received attention because of their unusual activities that differ from those of MutS. In this work, we report on the functional characteristics and conformational diversities of Thermotoga maritima MutS2 (TmMutS2). Various biochemical features of the protein were demonstrated via diverse techniques such as scanning probe microscopy (SPM), ATPase assays, analytical ultracentrifugation, DNA binding assays, size chromatography, and limited proteolytic analysis. Dimeric TmMutS2 showed the temperature-dependent ATPase activity. The non-specific nicking endonuclease activities of TmMutS2 were inactivated in the presence of nonhydrolytic ATP (ADPnP) and enhanced by the addition of TmMutL. In addition, TmMutS2 suppressed the TmRecA-mediated DNA strand exchange reaction in a TmMutL-dependent manner. We also demonstrated that small-angle X-ray scattering (SAXS) analysis of dimeric TmMutS2 exhibited nucleotide- and DNA-dependent conformational transitions. Particularly, TmMutS2-ADPnP showed the most compressed form rather than apo-TmMutS2 and the TmMutS2-ADP complex, in accordance with the results of biochemical assays. In the case of the DNA-binding complexes, the stretched conformation appeared in the TmMutS2-four-way junction (FWJ)-DNA complex. Convergences of biochemical- and SAXS analysis provided abundant information for TmMutS2 and clarified ambiguous experimental results

Small intestinal mucosa expression of putative chaperone fls485

<p>Abstract</p> <p>Background</p> <p>Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. <it>fls485 </it>coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze <it>fls48</it>5 expression in human small intestinal mucosa.</p> <p>Methods</p> <p><it>fls485 </it>expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several <it>in situ </it>techniques and usage of newly synthesized mouse monoclonal antibodies.</p> <p>Results</p> <p>fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c.</p> <p>Conclusions</p> <p>Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.</p

Thermal stress analysis of a solid rocket motor nozzle throat insert using finite element method

271-277<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "times="" new="" roman";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:="" minor-latin;mso-bidi-font-family:"times="" roman";mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">A finite element formulation is developed for the analysis of axisymmetric, transient, anisotropic heat conduction problem with the temperature dependant thermo-physical material properties of a graphite throat nozzle for the solid rocket motor. A standard Galerkin method using linear triangular element is employed for the space discretization. The time integration is done using an implicit time marching scheme of the first order differential equation. The convective heat transfer coefficient is calculated using the Bartz correlation. A thermal stress analysis is also carried out on the graphite throat of the nozzle using finite element method with two degrees of freedom. The developed computer codes for this purpose are validated with known analytical solution and available ANSYS code.</span

Measurement of energy required to detach cotton fibres from seed -Some practical considerations

57-61<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "times="" new="" roman";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:="" minor-latin;mso-bidi-font-family:calibri;mso-bidi-theme-font:minor-latin;="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">While using the Shirley attachment strength tester, a commercially available instrument that measures the energy required to separate cotton fibres from the seed, it has been found that the process of fibre separation does not simulate the roller ginning process and that considerable fibre breakage occurs during the test, leading to high energy values. A partial modification of the experimental setup is suggested such that the process of fibre separation more closely resembles roller ginning. Also suggested is a testing procedure in which all the fibres on a seed, divided into five tufts, are tested one after another so that besides the average energy per fibre, the average energy per unit weight of fibres can be calculated without assuming arbitrary weightages for the micropylar, side and chalazal regions.</span

Effect of causticization and mercerization on the dyeing behaviour of rotor- and ring-spun cotton yarns

120-128<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "times="" new="" roman";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:="" minor-latin;mso-bidi-font-family:calibri;mso-bidi-theme-font:minor-latin;="" color:black;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" ar-sa"="">The dyeing behaviour of unmercerized, causticized and mercerized rotor- and ring-spun cotton yarns has been studied with a number of direct, vat and reactive dyes. The absorbance values for dye bath exhaustion and dye uptake for a fixed period of dyeing are reported<span style="font-size:11.0pt; line-height:115%;font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;="" mso-fareast-font-family:"times="" new="" roman";mso-fareast-theme-font:minor-fareast;="" mso-hansi-theme-font:minor-latin;mso-bidi-font-family:calibri;mso-bidi-theme-font:="" minor-latin;color:#151515;mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">. <span style="font-size:11.0pt;line-height: 115%;font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;="" mso-fareast-font-family:"times="" new="" roman";mso-fareast-theme-font:minor-fareast;="" mso-hansi-theme-font:minor-latin;mso-bidi-font-family:calibri;mso-bidi-theme-font:="" minor-latin;color:black;mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">The dye bath exhaustion and dye uptake have been found to be maximum for slack mercerized samples for all the dyes studied. The dye uptake is generally higher for the rotor-<span style="font-size:11.0pt; line-height:115%;font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;="" mso-fareast-font-family:"times="" new="" roman";mso-fareast-theme-font:minor-fareast;="" mso-hansi-theme-font:minor-latin;mso-bidi-font-family:calibri;mso-bidi-theme-font:="" minor-latin;color:#151515;mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">s<span style="font-size:11.0pt;line-height: 115%;font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;="" mso-fareast-font-family:"times="" new="" roman";mso-fareast-theme-font:minor-fareast;="" mso-hansi-theme-font:minor-latin;mso-bidi-font-family:calibri;mso-bidi-theme-font:="" minor-latin;color:black;mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">pun yarn when dyed with ring-spun yarn in a common hath.</span

Biomedical engineering curricula: Trends in Australia and abroad

his article provides an analysis of representative biomedical engineering curricula in Australia, the USA and the UK. The research was undertaken as part of an Australian Learning and Teaching Council project on Australian dual degrees