The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature.

Long non-coding RNAs (lncRNAs) are deregulated in several tumors, although their role in acute myeloid leukemia (AML) is mostly unknown.We have examined the expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241 AML patients. We have correlated HOTAIRM1 expression with a miRNA expression profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215 intermediate-risk AML (IR-AML) patients.The lowest expression level was observed in acute promyelocytic leukemia (P < 0.001) and the highest in t(6;9) AML (P = 0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently associated with shorter overall survival (OR:2.04;P = 0.001), shorter leukemia-free survival (OR:2.56; P < 0.001) and a higher cumulative incidence of relapse (OR:1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic value within the favorable molecular subgroup (OR: 3.43; P = 0.009). Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover, HOTAIRM1 expression was associated with a specific 33-microRNA signature that included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and has previously been reported to have an independent prognostic value in AML. miR-196b and HOTAIRM1 in combination as a prognostic factor can classify patients as high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P = 0.004).Determination of HOTAIRM1 level at diagnosis provided relevant prognostic information in IR-AML and allowed refinement of risk stratification based on common molecular markers. The prognostic information provided by HOTAIRM1 was strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1 correlated with a 33-miRNA signature.

Rolandus Passagerii, Summa artis notariae (3-76v).

Abbaye Saint-Maur-des-Fossés ; cf. B. de Montfaucon, Bibliotheca bibliothecarum, II, 1739, p. 1141-1143 : "96. 1117. Summa artis Notariae per M. Rollandinum. / Summa M. Thomae de Capua" — Abbaye de Saint Germain des Prés, Paris. Ex-libris : F. 3 : "Sti Germani a Pratis".

The polymorphic nature of HIV type 1 env V4 affects the patterns of potential N-glycosylation sites in proviral DNA at the intrahost level.

We have previously shown that env V4 from HIV-1 plasma RNA is highly heterogeneous within a single patient, due to indel-associated polymorphism. In this study, we have analyzed the variability of V4 in proviral DNA from unfractionated PBMC and sorted T and non-T cell populations within individual patients. Our data show that the degree of sequence variability and length polymorphism in V4 from HIV provirus is even higher than we previously reported in plasma. The data also show that the sequence of V4 depends largely on the experimental approach chosen. We could observe no clear trend for compartmentalization of V4 variants in specific cell types. Of interest is the fact that some variants that had been found to be predominant in plasma were not detected in any of the cell subsets analyzed. Consistently with our observations in plasma, V3 was found to be relatively conserved at both interpatient and intrapatient level. Our data show that V4 polymorphism involving insertions and deletions in addition to point mutations results in changes in the patterns of sequons in HIV-1 proviral DNA as well as in plasma RNA. These rearrangements may result in the coexistence, within the same individual, of a swarm of different V4 regions, each characterized by a different carbohydrate surface shield. Further studies are needed to investigate the mechanism responsible for the variability observed in V4 and its role in HIV pathogenesis.

Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports.

Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5β-androstane-3α,17β-diol and 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol as best biomarkers for DHT administration and DHEA/E, 16α-hydroxydehydroepiandrosterone/E, 7β-hydroxydehydroepiandrosterone/E and 5β-androstane-3α,17β-diol/5α-androstane-3α,17β-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained. The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids.

Rehabilitació de Cal Racó

El treball consisteix en una proposta de rehabilitació d'una casa entre mitgeres situada al poble de Llardecans, analitzant les seves lesions i adaptant-la a la normativa vigent. El treball s'organitza de la manera següent: aixecament de plànols, descripció i anàlisis de l'estat actual, estudi patològic, intervenció de les lesions i proposta de reforma.

Estudio de los futuros estándares HTML5 y CSS3 : propuesta de actualización del sitio www.mpiua.net

Este trabajo se divide en dos partes. Por un lado, el estudio de los futuros estándares HTML 5 y CSS 3 (donde vemos las nuevas propiedades y capacidades que estas tecnologías proporcionan) y por otro la propuesta de actualización del sitio web www.mpiua.net utilizando los citados estándares

ScheUDLe generador d'horaris

La idea d'aquest projecte, neix de la complexitat per a la confecció d'horaris i distribució de professors en centres docents amb una gran quantitat de cursos, professors i assignatures. Amb scheUDLe es pretén simplificar aquesta tasca al màxim i reduir el gran treball que suposa quadrar hores i assignatures.

Implantació d'un sistema per a la gestió de projectes amb Microsoft Dymanics AX 2009

Implantació del mòdul de projectes que incorpora l'estàndard de l'ERP Microsoft Dynamics AX 2009 segons requeriments que planteja la guia Project Management Body of Knowledge per la gestió de projectes.

Unitat per a la detecció de complicacions cròniques en pacients amb Diabetis Mellitus

Des de l’estudi UKPDS s’accepta que el 50% de pacients diabètics presenten alguna complicació crònica al moment del diagnòstic. L’objectiu del treball és determinar la prevalença i incidència de complicacions cròniques de la diabetis. Van participar 460 pacients realitzant un cribatge de les complicacions cròniques micro i macrovasculars en una única visita. La prevalença de complicacions cròniques va ser del 57% i la incidència d’un 35.4%. Els pacients diagnosticats d’alguna complicació nova eren més hipertensos, dislipèmics, i presentaven una edat més avançada i un índex de massa corporal (IMC) més elevat comparat amb els pacients amb complicacions ja diagnosticades prèviament.

Conflicto de intereses: agencias de rating, reguladores, países y empresas

Les agencies de qualificació de riscos son una peça fonamental en el engranatge del sistema financer internacional. Arreu de la crisi financera es detecten conflictes d’interès entre aquestes i la resta de agents econòmics, generat per un canvi en el model de cobro. El document explica com s’ha generat aquest problema, la resposta del mercat i de les pròpies agencies de rating i exposa també les noves propostes regulatòries per a corregir-lo.

MicroRNA-122 modulates the rhythmic expression profile of the circadian deadenylase Nocturnin in mouse liver.

Nocturnin is a circadian clock-regulated deadenylase thought to control mRNA expression post-transcriptionally through poly(A) tail removal. The expression of Nocturnin is robustly rhythmic in liver at both the mRNA and protein levels, and mice lacking Nocturnin are resistant to diet-induced obesity and hepatic steatosis. Here we report that Nocturnin expression is regulated by microRNA-122 (miR-122), a liver specific miRNA. We found that the 3'-untranslated region (3'-UTR) of Nocturnin mRNA harbors one putative recognition site for miR-122, and this site is conserved among mammals. Using a luciferase reporter construct with wild-type or mutant Nocturnin 3'-UTR sequence, we demonstrated that overexpression of miR-122 can down-regulate luciferase activity levels and that this effect is dependent on the presence of the putative miR-122 recognition site. Additionally, the use of an antisense oligonucleotide to knock down miR-122 in vivo resulted in significant up-regulation of both Nocturnin mRNA and protein expression in mouse liver during the night, resulting in Nocturnin rhythms with increased amplitude. Together, these data demonstrate that the normal rhythmic profile of Nocturnin expression in liver is shaped in part by miR-122. Previous studies have implicated Nocturnin and miR-122 as important post-transcriptional regulators of both lipid metabolism and circadian clock controlled gene expression in the liver. Therefore, the demonstration that miR-122 plays a role in regulating Nocturnin expression suggests that this may be an important intersection between hepatic metabolic and circadian control.

Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210.

BACKGROUND: Establishing the genetic basis of phenotypes such as skeletal dysplasia in model organisms can provide insights into biologic processes and their role in human disease. METHODS: We screened mutagenized mice and observed a neonatal lethal skeletal dysplasia with an autosomal recessive pattern of inheritance. Through genetic mapping and positional cloning, we identified the causative mutation. RESULTS: Affected mice had a nonsense mutation in the thyroid hormone receptor interactor 11 gene (Trip11), which encodes the Golgi microtubule-associated protein 210 (GMAP-210); the affected mice lacked this protein. Golgi architecture was disturbed in multiple tissues, including cartilage. Skeletal development was severely impaired, with chondrocytes showing swelling and stress in the endoplasmic reticulum, abnormal cellular differentiation, and increased cell death. Golgi-mediated glycosylation events were altered in fibroblasts and chondrocytes lacking GMAP-210, and these chondrocytes had intracellular accumulation of perlecan, an extracellular matrix protein, but not of type II collagen or aggrecan, two other extracellular matrix proteins. The similarities between the skeletal and cellular phenotypes in these mice and those in patients with achondrogenesis type 1A, a neonatal lethal form of skeletal dysplasia in humans, suggested that achondrogenesis type 1A may be caused by GMAP-210 deficiency. Sequence analysis revealed loss-of-function mutations in the 10 unrelated patients with achondrogenesis type 1A whom we studied. CONCLUSIONS: GMAP-210 is required for the efficient glycosylation and cellular transport of multiple proteins. The identification of a mutation affecting GMAP-210 in mice, and then in humans, as the cause of a lethal skeletal dysplasia underscores the value of screening for abnormal phenotypes in model organisms and identifying the causative mutations.

Estudi de la connectivitat de l’illa de Menorca

Com a objectius generals: Analitzar la connectivitat ecològica a nivell paisatgístic de Menorca a partir d’una diagnosi que permeti determinar els espais d’interès connector i els punts crítics. Desenvolupar un pla d’acció amb propostes per millorar la connectivitat actual. Objectius específics: Aplicar una metodologia capaç de parametritzar els diferents conceptes relacionats amb la connectivitat ecològica i que sigui aplicable en la planificació territorial. Identificar els espais i elements d’interès per a la correcta circulació dels fluxos ecològics (flora i fauna) i socials, clau pel manteniment del paisatge i de la connectivitat funcional, definint connectors fluvials, espais naturals protegits, matrius (forestal, agrícola i urbana), unitats paisatgístiques, patrimoni arquitectònic i arqueològic, senders i camins ramaders, etc. que permetin determinar Espais o Elements d’Interès Estratègic per a la Connectivitat (EIEC). Definir els punts clau per a la connectivitat i identificar els punts crítics, on les barreres i els elements de fragmentació (carreteres, torrents, sòl urbà, etc.) intercepten els EIEC