Increased mRNA expression levels of ERCC1, OGG1 and RAI in colorectal adenomas and carcinomas

BACKGROUND: The majority of colorectal cancer (CRC) cases develop through the adenoma-carcinoma pathway. If an increase in DNA repair expression is detected in both early adenomas and carcinomas it may indicate that low repair capacity in the normal mucosa is a risk factor for adenoma formation. METHODS: We have examined mRNA expression of two DNA repair genes, ERCC1 and OGG1 as well as the putative apoptosis controlling gene RAI, in normal tissues and lesions from 36 cases with adenomas (mild/moderat n = 21 and severe n = 15, dysplasia) and 9 with carcinomas. RESULTS: Comparing expression levels of ERCC1, OGG1 and RAI between normal tissue and all lesions combined yielded higher expression levels in lesions, 3.3-fold higher (P = 0.005), 5.6-fold higher(P < 3·10(-5)) and 7.7-fold higher (P = 0.0005), respectively. The levels of ERCC1, OGG1 and RAI expressions when comparing lesions, did not differ between adenomas and CRC cases, P = 0.836, P = 0.341 and P = 0.909, respectively. When comparing expression levels in normal tissue, the levels for OGG1 and RAI from CRC cases were significantly lower compared to the cases with adenomas, P = 0.012 and P = 0.011, respectively. CONCLUSION: Our results suggest that increased expression of defense genes is an early event in the progression of colorectal adenomas to carcinomas

Human Endometrial CD98 Is Essential for Blastocyst Adhesion

BACKGROUND: Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. METHODS AND PRINCIPAL FINDINGS: Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-β-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate. CONCLUSIONS: These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window

Manipulation of CD98 expression affects both trophoblast cell fusion and amino acid transport activity during syncytialization of human placental BeWo cells

The physiological importance of CD98 surface antigen in regulating placental trophoblast cell fusion and amino acid transport activity has been studied in parallel in a cell model of syncytialization (the cytotrophoblast cell line BeWo following increased intracellular cAMP by forskolin treatment) using antisense oligonucleotides. CD98 protein abundance (determined by Western blot) was decreased by 50 % following antisense oligonucleotide transfection. Transfection with antisense oligonucleotide altered the responses of BeWo to forskolin. Cell fusion (determined by a quantitative flow cytometry assay) was inhibited by 57 %, and both human chorionic gonadotropin secretion and L-leucine influx through system L were suppressed. These findings show that CD98 is involved in the process of cell fusion necessary for syncytiotrophoblast formation and that during this physiologically important event, amino acid transport activity is also regulated through expression of this membrane protein

Incompressible SPH simulation of solitary wave propagation on permeable beaches

Wave propagation on uniformly sloped beaches is a canonical coastal engineering topic that has been studied extensively in the past few decades. However, most of these studies treat beaches as solid boundaries even though they are often made of porous materials, such as sediment and vegetation. Permeable beaches struck by tsunami-like waves have not been adequately investigated. It is expected that the degree of permeability plays a crucial role in mitigating the impact of the wave. This study examines solitary wave run-ups on sandy beaches using an incompressible smoothed particle hydrodynamics (ISPH) model. The permeability of the beach is considered to be directly related to the diameter of its constituent sand particles. To obtain a satisfactory pressure field, which cannot be achieved using the original ISPH algorithm, the source term of the Poisson pressure equation has been modified based on a higher-order source-term expression. Flows within the porous medium are computed in the same framework as those outside the porous medium. In the current model, no transition zone is needed at the boundary of the porous structure. The wave-attenuation effect of the porous medium is discussed, with a particular focus on the relationship between the run-up height and grainsize.This work was supported by the Royal Academy of Engineering UK-China Urban Flooding Research Impact Programme (Grant No. UUFRIP\100051), the Ministry of Education and State Administration of Foreign Experts Affairs 111 Project (Grant No. B17015) and the Cambridge Tier-2 system operated by the University of Cambridge Research Computing Service (http://www.hpc.cam.ac.uk) funded by EPSRC Tier-2 capital (Grant No. EP/P020259/1)