Evidence for classification of c.1852_1853AA > GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients. Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2(nd) generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

RCeveierwamide and ceramide 1-phosphate in health and disease

Sphingolipids are essential components of cell membranes, and many of them regulate vital cell functions. In particular, ceramide plays crucial roles in cell signaling processes. Two major actions of ceramides are the promotion of cell cycle arrest and the induction of apoptosis. Phosphorylation of ceramide produces ceramide 1-phosphate (C1P), which has opposite effects to ceramide. C1P is mitogenic and has prosurvival properties. In addition, C1P is an important mediator of inflammatory responses, an action that takes place through stimulation of cytosolic phospholipase A2, and the subsequent release of arachidonic acid and prostaglandin formation. All of the former actions are thought to be mediated by intracellularly generated C1P. However, the recent observation that C1P stimulates macrophage chemotaxis implicates specific plasma membrane receptors that are coupled to Gi proteins. Hence, it can be concluded that C1P has dual actions in cells, as it can act as an intracellular second messenger to promote cell survival, or as an extracellular receptor agonist to stimulate cell migration.

Effects of human chorionic gonadotropin (HCG), toad and Clarias pituitary hormogenates on spawning in the catfish: Clarias Lazera (C. and V.) and Clarias anguillaris (Linne)

Experiment on induced spawning of Clarias lazera and C. anguillaris using human chorionic gonadotropin (HCG) freshly prepared toad and Clarias pituitary hormogenates were carried out. Clarias pituitary hormogenates induced spawning in C. lazera and C. anguillaris at dosage levels of 0.27-0.46 mg/150 g body weight or 2 glands/fish of equivalent weights. HCG induced spawning in C. anguillaris at 500 i.u/500 g body weight but failed in C. lazera. Toad pituitary was not successful at even a higher dosage level of 0.60 mg/150 g body weight. The implications of these results are discussed. Spawning occurred in the HCG (and Clarias pituitary treated females in less than 12 hours after injection and subsequent examination of ovaries of the spawned fish showed incomplete spawning. Furthermore, fertilization occurred, following spawning in the piscine pituitary hormone treated male and female fish but failed in the HCG (treated pair. A mean fertilization rate of 50-90% was recorded. Possible explanations of these observations are advanced. The hatching time of 24-48 hours and a mean hatching rate of 75-90% were recorded. A high larval mortality of up to 95% was observed in the post yolk-sac stag after 8 days. The need for the development of appropriate larval food for Clarias species in culture practice is stressed

Induced spawning of African cat fish Clarias lazera (C. and V.) using acetone dried carp pituitary extract, deoxy-corticosterone acetate and human chorionic gonadotropin

A study was conducted to determine the efficacy of carp pituitary extract, deoxycorticosterone acetate, and human chorionic gonadotropin in inducing spawning in Clarias lazera . Results indicate deoxycorticosterone acetate to be more potent than pituitary extract, although the difference is not significant

[Reseña] F. Petrarca, De viris illustribus, I, II, IV (eds. S. Ferrone, C. Malta, P. de Capua), Firenze, Le Lettere, 2006-2007

[ES] Un real decreto de 1904, emitido con motivo de la celebración del VI Centenario del nacimiento de Petrarca (1304-1374), creó la Commissione per l’Edizione Nazionale delle Opere di Francesco Petrarca. Después de un siglo en el que los estudios petrarquescos han experimentado un florecimiento espectacular, con varias revistas y colecciones dedicadas exclusivamente a Petrarca y con una deslumbrante nómina de especialistas, han visto la luz siete de los veinte volúmenes previstos inicialmente.

Lead accumulation by hammerhead shark, Sphyrna couardi (C.) off Lagos coast, Nigeria

Levels of concentration of lead in the hammerhead shark, Sphyrna couardi, off the Lagos Coast of Nigeria were investigated. The standard length of the specimens examined ranged from 31.4cm to 47.2cm while the weights ranged from 451.5 to 1,667g. The lead concentration ranged from 0.11 degree kg/G to 0.38 degree kg/G. The mean lead concentration was 0.56 degree kg/G (dry weight). The gill has the highest lead concentration. There was no linear correlation between the length and weight and the amount of lead concentrated

Development And Characterization Of Composite Ni-Cr-C-Caf2 Laser Cladding On Gamma-Tial Intermetallic Alloy

A process of laser cladding Ni-CF-C-CaF2 mixed powders to form a multifunctional composite coatingd on gamma-TiAl substrate was carried out. The microstructure of the coating was examined using XRD, SEM and EDS. The coating has a unique microstructure consisting of primary dendrite or short-stick TiC and block Al4C3 carbides reinforcement as well as fine isolated spherical CaF2 solid lubrication particles uniformly dispersed in the NiCrAlTi (gamma) matrix. The average microhardness of the composite coatings is approximately HV 650 and it is 2-factor greater than that of the TiAl substrate. (C) 2008 Elsevier B.V. All rights reserved.

Length-weight relationship and organ indices of pond raised and wild population of C. gariepinus (Burchell 1822) pisces-Claridae

Samples of C. gariepinus collected from the wild and cultured populations in Plateau and Niger States of Nigeria were analyzed for length-weight relationship and organ indices (Gonadosomatic index (GSI), hepatosomatic index (HSI), renalsomatic index (RSI) and somatic fat deposit index (PDI). High correlation and linear relationship between body length and body weight was observed in all sample population (P<0.05). A significant difference was observed between the GSI of males and females of both wild and cultured population and also between females of the wild and cultured population,(P < 0.05).There was no significant difference in HSI, CSI RSI and PDI of all the sample populations (P < 0.05).The importance of length-weight relationship and organ indices in fish production are discussed

The LIN-3 gene of the nematode C. elegans is the vulval-inducing signal

The development of the vulva of the nematode Caenorhabditis elegans is induced by a signal from the anchor cell of the somatic gonad. Activity of the gene lin-3 is required for the Vulval Precursor Cells (VPCs) to assume vulval fates. It is shown here that lin-3 encodes the vulval-inducing signal.

lin-3 was molecularly cloned by transposon-tagging and shown to encode a nematode member ofthe Epidermal Growth Factor (EGF) family. Genetic epistasis experiments indicate that lin-3 acts upstream of let-23, which encodes a homologue of the EGF-Receptor.

lin-3 transgenes that contain multiple copies of wild-type lin-3 genomic DNA clones confer a dominant multivulva phenotype in which up to all six of the VPCs assume vulval fates. The properties of these trans genes suggest that lin-3 can act in the anchor cell to induce vulval fates. Ablation of the gonadal precursors, which prevents the development of the AC, strongly reduces the ability of lin-3 transgenes to stimulate vulval development. A lin-3 recorder transgene that retains the ability to stimulate vulval development is expressed specifically in the anchor cell at the time of vulval induction.

Expression of an obligate secreted form of the EGF domain of Lin-S from a heterologous promoter is sufficient to induce vulval fates in the absence of the normal source of the inductive signal. This result suggests that Lin-S may act as a secreted factor, and that Lin-S may be the sole vulval-inducing signal made by the anchor cell.

lin-3 transgenes can cause adjacent VPCs to assume the 1° vulval fate and thus can override the action of the lateral signal mediated by lin-12 that normally prevents adjacent 1° fates. This indicates that the production of Lin-3 by the anchor cell must be limited to allow the VPCs to assume the proper pattern of fates of so 3° 3° 2° 1° 2° 3°.

Ejercicio f??sico para supervivientes del c??ncer tras mastectom??a

El c??ncer es una enfermedad que produce alta mortalidad, y el c??ncer de mama es un c??ncer espec??fico que se da especialmente en las mujeres y que les produce una disminuci??n de la calidad de vida y en caso de que sufran una mastectom??a, una disminuci??n de la movilidad del hombro. Por ello es importante que las mujeres realicen un programa ejercicio aer??bico y fuerza as?? como un programa de ejercicios para recuperar esa movilidad del hombro afectado.Espa??ol.