Ursolic acid inhibits the initiation, progression of prostate cancer and prolongs the survival of TRAMP mice by modulating pro-inflammatory pathways

10.1371/journal.pone.0032476PLoS ONE73

The Isotope Effect in d-Wave Superconductors

Based on recently proposed anti-ferromagnetic spin fluctuation exchange models for $d_{x^2-y^2}$-superconductors, we show that coupling to harmonic phonons {\it{cannot}} account for the observed isotope effect in the cuprate high-$T_c$ materials, whereas coupling to strongly anharmonic multiple-well lattice tunneling modes {\it{can}}. Our results thus point towards a strongly enhanced {\it{effective}} electron-phonon coupling and a possible break-down of Migdal-Eliashberg theory in the cuprates.Comment: 12 pages + 2 figures, Postscript files, all uuencoded Phys. Rev. Lett. (1995, to be published

Compressive and Flexural Strength of Concrete Containing Palm Oil Biomass Clinker with Hooked-End Steel Fibers

This research was carried out to investigate the effects of hooked-end steel fibers on compressive and flexural strength of concrete containing palm oil biomass clinker (POBC) as partial replacement of fine aggregates. The optimum percentage of POBC was taken as 10%, to replace natural sand on the basis of trial mixes. Due to the porous characteristic of POBC, hooked-end steel fibers were added to improve the flexural strength of concrete. For this research, the concrete mixture containing 10% of POBC with varying percentages of the hooked-end steel fibers i.e. 0.2%, 0.4% and 0.6% by weight was produced. Total 48 specimens were prepared, 24 concrete cubes for compressive strength and 24 prisms were prepared for flexural strength at 7 days and 28 days. Hence, it was evaluated that the reduction of workability in concrete with the addition of steel fibers. Furthermore, The maximum flexural strength were recorded as 2.54 MPa with 0.4% hooked-end steel fibers at 28days and maximum compressive strength of was recorded as 27.51 MPa with 0.6%  hooked-end steel fibers at 28days. It is concluded that the hooked-end steel fibers has good potentiality to enhance the compressive as well as flexural strength of concrete

Inhibition of STAT3 dimerization and acetylation by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo

10.1186/1476-4598-13-66Molecular Cancer131-MCOA

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Large-scale production of cellulose-binding domains : adsorption studies using CBD-FITC conjugates

A method for the gram-scale production of cellulose-binding domains (CBD) through the proteolytic digestion of a commercial nzymatic preparation (Celluclast) was developed. The CBD obtained, isolated from Trichoderma reesei cellobiohydrolase I, is highly pure and heavily glycosylated. The purified peptide has a molecular weight of 8.43 kDa, comprising the binding module, a part of the linker, and about 30% glycosidic moiety. Its properties may thus be different from recombinant ones expressed in bacteria. CBDfluorescein isothiocyanate conjugates were used to study the CBD-cellulose interaction. The presence of fluorescent peptides adsorbed on crystalline and amorphous cellulose fibers suggests that amorphous regions have a higher concentration of binding sites. The adsorption is reversible, but desorption is a very slow process.Fundação para a Ciência e a Tecnologia (FCT

A genome-wide association scan on estrogen receptor-negative breast cancer

Introduction: Breast cancer is a heterogeneous disease and may be characterized on the basis of whether estrogen receptors (ER) are expressed in the tumour cells. ER status of breast cancer is important clinically, and is used both as a prognostic indicator and treatment predictor. In this study, we focused on identifying genetic markers associated with ER-negative breast cancer risk.Methods: We conducted a genome-wide association analysis of 285,984 single nucleotide polymorphisms (SNPs) genotyped in 617 ER-negative breast cancer cases and 4,583 controls. We also conducted a genome-wide pathway analysis on the discovery dataset using permutation-based tests on pre-defined pathways. The extent of shared polygenic variation between ER-negative and ER-positive breast cancers was assessed by relating risk scores, derived using ER-positive breast cancer samples, to disease state in independent, ER-negative breast cancer cases.Results: Association with ER-negative breast cancer was not validated for any of the five most strongly associated SNPs followed up in independent studies (1,011 ER-negative breast cancer cases, 7,604 controls). However, an excess of small P-values for SNPs with known regulatory functions in cancer-related pathways was found (global P = 0.052). We found no evidence to suggest that ER-negative breast cancer share

Targeted NGS gene panel identifies mutations in RSPH1 causing primary ciliary dyskinesia and a common mechanism for ciliary central pair agenesis due to radial spoke defects.

Primary ciliary dyskinesia (PCD) is an inherited chronic respiratory obstructive disease with randomized body laterality and infertility, resulting from cilia and sperm dysmotility. PCD is characterized by clinical variability and extensive genetic heterogeneity, associated with different cilia ultrastructural defects and mutations identified in >20 genes. Next generation sequencing (NGS) technologies therefore present a promising approach for genetic diagnosis which is not yet in routine use. We developed a targeted panel-based NGS pipeline to identify mutations by sequencing of selected candidate genes in 70 genetically undefined PCD patients. This detected loss-of-function RSPH1 mutations in four individuals with isolated central pair (CP) agenesis and normal body laterality, from two unrelated families. Ultrastructural analysis in RSPH1-mutated cilia revealed transposition of peripheral outer microtubules into the 'empty' CP space, accompanied by a distinctive intermittent loss of the central pair microtubules. We find that mutations in RSPH1, RSPH4A and RSPH9, which all encode homologs of components of the 'head' structure of ciliary radial spoke complexes identified in Chlamydomonas, cause clinical phenotypes that appear to be indistinguishable except at the gene level. By high-resolution immunofluorescence we identified a loss of RSPH4A and RSPH9 along with RSPH1 from RSPH1-mutated cilia, suggesting RSPH1 mutations may result in loss of the entire spoke head structure. CP loss is seen in up to 28% of PCD cases, in whom laterality determination specified by CP-less embryonic node cilia remains undisturbed. We propose this defect could arise from instability or agenesis of the ciliary central microtubules due to loss of their normal radial spoke head tethering

Thrombocytogenesis by megakaryocyte; Interpretation by protoplatelet hypothesis

Serial transmission electron microscopy of human megakaryocytes (MKs) revealed their polyploidization and gradual maturation through consecutive transition in characteristics of various organelles and others. At the beginning of differentiation, MK with ploidy 32N, e.g., has 16 centrosomes in the cell center surrounded by 32N nucleus. Each bundle of microtubules (MTs) emanated from the respective centrosome supports and organizes 16 equally volumed cytoplasmic compartments which together compose one single 32N MK. During the differentiation, single centriole separated from the centriole pair, i.e., centrosome, migrates to the most periphery of the cell through MT bundle, corresponding to a half of the interphase array originated from one centrosome, supporting one “putative cytoplasmic compartment” (PCC). Platelet demarcation membrane (DM) is constructed on the boundary surface between neighbouring PCCs. Matured PCC, composing of a tandem array of platelet territories covered by a sheet of DM is designated as protoplatelet. Eventually, the rupture of MK results in release of platelets from protoplatelets