Polymorphisms in Toll-like receptor 4 ( TLR4 ) are associated with protection against leprosy

Accumulating evidence suggests that polymorphisms in Toll-like receptors (TLRs) influence the pathogenesis of mycobacterial infections, including leprosy, a disease whose manifestations depend on host immune responses. Polymorphisms in TLR2 are associated with an increased risk of reversal reaction, but not susceptibility to leprosy itself. We examined whether polymorphisms in TLR4 are associated with susceptibility to leprosy in a cohort of 441 Ethiopian leprosy patients and 197 healthy controls. We found that two single nucleotide polymorphisms (SNPs) in TLR4 (896G>A [D299G] and 1196C>T [T399I]) were associated with a protective effect against the disease. The 896GG, GA and AA genotypes were found in 91.7, 7.8 and 0.5% of leprosy cases versus 79.9, 19.1 and 1.0% of controls, respectively (odds ratio [OR] = 0.34, 95% confidence interval [CI] 0.20-0.57, P < 0.001, additive model). Similarly, the 1196CC, CT and TT genotypes were found in 98.1, 1.9 and 0% of leprosy cases versus 91.8, 7.7 and 0.5% of controls, respectively (OR = 0.16, 95% CI 0.06--.40, P < 0.001, dominant model). We found that Mycobacterium leprae stimulation of monocytes partially inhibited their subsequent response to lipopolysaccharide (LPS) stimulation. Our data suggest that TLR4 polymorphisms are associated with susceptibility to leprosy and that this effect may be mediated at the cellular level by the modulation of TLR4 signalling by M. lepra

Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.

BACKGROUND: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. METHODS: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. RESULTS: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. CONCLUSIONS: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Aprovechamiento de barros procedentes de central de áridos para la elaboración de piezas cerámicas porosas

Aggregates (gravel and sand) are, after water, the Earth’s second most used natural resource, representing about 50% of all consumed mineral resources. Aggregate production generates a large quantity of waste from the aggregate washing process. This waste is made up of suspended solids – sludge – which has a great environmental impact. It is deposited in huge troughs because of the impossibility of discharging it directly into rivers. Many plants have incorporated decanters and filter presses to separate the solid from the liquid fraction. This paper evaluates the possibility of exploiting the solid fraction (i.e. sludge) in the manufacture of fired clay bricks. The added value of these bricks is, on the one hand, the exploitation of sludge as a currently useless waste product, and on the other, the use of this sludge to enhance the physical and mechanical properties of conventional fired clay bricks.Los áridos son la segunda materia prima más consumida en la Tierra después del agua, representando alrededor del 50% de todos los recursos minerales consumidos. El proceso de elaboración de estos áridos genera una gran cantidad de residuos procedentes de su lavado. Se trata de partículas sólidas en suspensión – lodos – de gran impacto ambiental, que se depositan en grandes charcas ante la imposibilidad de verterlos directamente al rio. Muchas empresas han incorporado decantadores y filtros de prensa para separar la fracción solida de la líquida. El presente trabajo evalúa la posibilidad de utilizar la fracción sólida, es decir el barro, para la fabricación de piezas cerámicas. El valor añadido de estas piezas es por un lado el aprovechamiento del barro como producto residual, que en estos momentos es desechable, y por otro, conseguir que este barro mejore las propiedades físico-mecánicas de la cerámica convencional

Prostate cancer and Hedgehog signalling pathway

[Abstract] The Hedgehog (Hh) family of intercellular signalling proteins have come to be recognised as key mediators in many fundamental processes in embryonic development. Their activities are central to the growth, patterning and morphogenesis of many different regions within the bodies of vertebrates. In some contexts, Hh signals act as morphogens in the dose-dependent induction of distinct cell fates within a target field, in others as mitogens in the regulation of cell proliferation or as inducing factors controlling the form of a developing organ. These diverse functions of Hh proteins raise many intriguing questions about their mode of action. Various studies have now demonstrated the function of Hh signalling in the control of cell proliferation, especially for stem cells and stem-like progenitors. Abnormal activation of the Hh pathway has been demonstrated in a variety of human tumours. Hh pathway activity in these tumours is required for cancer cell proliferation and tumour growth. Recent studies have uncovered the role for Hh signalling in advanced prostate cancer and demonstrated that autocrine signalling by tumour cells is required for proliferation, viability and invasive behaviour. Thus, Hh signalling represents a novel pathway in prostate cancer that offers opportunities for prognostic biomarker development, drug targeting and therapeutic response monitoring

Training for innovation in Spain

The capacity for innovation of an organisation largely depends on its ability to acquire and develop new knowledge. Training is particularly important in this process, as it allows employees to constantly acquire new competences. This study provides a preliminary picture of the situation of training for innovation in Spain, and identifies the characteristics of companies offering training for innovation. Results show that 35.3% of Spanish companies undertake innovation processes and 22.3% offer training related to these innovation processes. For the 82% of these companies training helped the innovation process, so training is an important tool for innovative changes

Comuniquem amb la veu i les imatges dels centres educatius la innovació que promou el programa agenda 21 escolar de Barcelona

A l’acte de cloenda del curs 07/08 de l’Agenda 21Escolar de Barcelona s’ha presentat una nova eina de comunicació en forma de curtmetratge. Com a conclusió destaquem que, donat el seu nou format i enfoc, ha estat útil per mostrar als centres educatius un grapat d'experiències reals a partir d’un eix que vertebra les idees més innovadores, que motiva als centres que inicien per primer cop la seva A21E i que ens serveix per donar noves idees a les comissions coordinadores. A l’equip, ens ha permès crear espais de reflexió per identificar aquells aspectes que es consideren més importants del Programa i/o que cal reforçar. El procés de recollida d’experiències, les converses i les reflexions amb el professorat i l’alumnat durant el procés de gravació també ens ha permès avaluar l’assoliment dels objectius del Programa

Development of an Enriched Lubi-Lubi (Ficus pseudopalma) Noodles

This research is focused on the development and acceptability of an enriched lubi-lubi (Ficus pseudopalma) noodle utilizing its puree as indigenous ingredients. Noodles were developed and enriched using lubi-lubi leaves. The level of acceptability was determined to find out the degree of acceptance of the noodles among consumers. Experimental method was used by extracting the puree of lubi-lubi leaves and used as flavor and packed/stored in polyethylene bag. Of the three trials conducted the enriched lubi-lubi noodles with ingredients of 250 g of Lubi-lubi leaves puree, 325 g APF, 10 g salt, 150g eggs and 2 g vegetable oil, 187.5 water was rated much acceptable. Based on acceptability level, trial 2 was rated as much acceptable as to taste and color and acceptable as to texture and odor. Sensory evaluation was done by the panelist using standard score sheets. Acceptability factors such as color, texture, flavor and odor were included among the choices. Results were obtained across prepared products, indicating the evident taste and aroma of lubi-lubi leaves through varied degree depending upon the quantity of puree used. The researchers observed correct mixing methods or techniques used flavorings and other materials that nicely blended with lubi-lubi puree as suggested by evaluators; the accepted ones were then standardized. The researchers concluded that lubi-lubi leaves are potential flavoring in the preparation of enriched lubi-lubi noodles and accepted among consumers

Traçando mapas: a teoria histórico-cultural e as contribuições para a pesquisa com crianças e suas espacialidades

Este texto busca fazer uma reflexão sobre as pesquisas sistematizadas no campo da infância, tendo como enfoque principal as estratégias de pesquisas “com crianças”. O recorte ao qual nos dedicamos são as relações que as crianças estabelecem com o meio, tendo como foco principal as suas espacialidades. A partir das contribuições de pesquisas que se aportam em estratégias de natureza qualitativas e fundamentadas nos aportes da teoria históricas cultural, elege-se o conceito de vivência (perejivanie) como mote em torno do qual nossos trabalhos são desenvolvidos. Para isso, traça-se, inicialmente, a origem da pesquisa com base em paradigmas positivistas e evidenciam-se alguns caminhos que buscaram romper com essa perspectiva: os postulados etnográficos de Malinovky e Boas; o Interacionismo simbólico, cujo precursor é George Herbert Mead; a Etnometodologia de Harold Garfinkel; as contribuições de Marx e os princípios estabelecidos por Vigotski e seus colaboradores.</p