The mechanisms of inflammation in gout and pseudogout (CPP-induced arthritis).

Recent advances have stimulated new interest in the area of crystal arthritis, as microcrystals can be considered to be endogenous "danger signals" and are potent stimulators of immune as well as non-immune cells. The best known microcrystals include urate (MSU), and calcium pyrophosphate (CPP) crystals, associated with gout and pseudogout, respectively. Acute inflammation is the hallmark of the acute tissue reaction to crystals in both gout and pseudogout. The mechanisms leading to joint inflammation in these diseases involve first crystal formation and subsequent coating with serum proteins. Crystals can then interact with plasma cell membrane, either directly or via membrane receptors, leading to NLRP3 activation, proteolytic cleavage and maturation of pro-interleukin-1β (pro-IL1β) and secretion of mature IL1β. Once released, this cytokine orchestrates a series of events leading to endothelial cell activation and neutrophil recruitment. Ultimately, gout resolution involves several mechanisms including monocyte differentiation into macrophage, clearance of apoptotic neutrophils by macrophages, production of Transforming Growth Factor (TGF-β) and modification of protein coating on the crystal surface. This review will examine these different steps.

A proline-rich TGF-beta-responsive transcriptional activator interacts with histone H3.

The molecular mechanisms involved in the regulation of gene expression by transforming growth factor-beta (TGF-beta) have been analyzed. We show that TGF-beta specifically induces the activity of the proline-rich trans-activation domain of CTF-1, a member of the CTF/NF-I family of transcription factors. A TGF-beta-responsive domain (TRD) in the proline-rich transcriptional activation sequence of CTF-1 was shown to mediate TGF-beta induction in NIH-3T3 cells. Mutagenesis studies indicated that this domain is not the primary target of regulatory phosphorylations, suggesting that the growth factor may regulate a CTF-1-interacting protein. A two-hybrid screening assay identified a nucleosome component, histone H3, as a specific CTF-1-interacting protein in yeast. Furthermore, the CTF-1 trans-activation domain was shown to interact with histone H3 in both transiently and stably transfected mammalian cells. This interaction requires the TRD, and it appears to be upregulated by TGF-beta in vivo. Moreover, point mutations in the TRD that inhibit TGF-beta induction also reduce interaction with histone H3. In vitro, the trans-activation domain of CTF-1 specifically contacts histone H3 and oligomers of histones H3 and H4, and full-length CTF-1 was shown to alter the interaction of reconstituted nucleosomal cores with DNA. Thus, the growth factor-regulated trans-activation domain of CTF-1 can interact with chromatin components through histone H3. These findings suggest that such interactions may regulate chromatin dynamics in response to growth factor signaling.

Multiple imputations applied to the DREAM3 phosphoproteomics challenge: a winning strategy.

DREAM is an initiative that allows researchers to assess how well their methods or approaches can describe and predict networks of interacting molecules [1]. Each year, recently acquired datasets are released to predictors ahead of publication. Researchers typically have about three months to predict the masked data or network of interactions, using any predictive method. Predictions are assessed prior to an annual conference where the best predictions are unveiled and discussed. Here we present the strategy we used to make a winning prediction for the DREAM3 phosphoproteomics challenge. We used Amelia II, a multiple imputation software method developed by Gary King, James Honaker and Matthew Blackwell[2] in the context of social sciences to predict the 476 out of 4624 measurements that had been masked for the challenge. To chose the best possible multiple imputation parameters to apply for the challenge, we evaluated how transforming the data and varying the imputation parameters affected the ability to predict additionally masked data. We discuss the accuracy of our findings and show that multiple imputations applied to this dataset is a powerful method to accurately estimate the missing data. We postulate that multiple imputations methods might become an integral part of experimental design as a mean to achieve cost savings in experimental design or to increase the quantity of samples that could be handled for a given cost.

Creació d'una eina en Java que a partir d'OWL i JESS generi SCORM

Aquest projecte consisteix en generar un programa escrit en llenguatge Java, que utilitzant un motor d'inferència a través d'una llibreria anomenada JESS, pugui llegir un document en format OWL que és una representació de l'ontologia (representació del coneixement) sobre una assignatura, transformant-lo al format de triples que és capaç d'interpretar JESS.

Cytokine profile associated with human chronic schistosomiasis mansoni

This study objective was to evaluate the cytokines associated with early events of hepatic fibrosis in schistosomiasis mansoni. Hepatic fibrosis was classified by ultrasonography in 94 patients. Immunological evaluation was performed by measurement of secreted cytokines (interleukin IL-5, IL-10, IL-13, interferon-gamma, tumor necrosis factor-alpha and transforming growth factors-beta) in peripherl blood mononuclear cells stimulated by Schistosoma mansoni antigens. Significantly, higher levels of IL-5, IL-10 and IL-13 were found in supernatants of SEA-stimulated PBMC from subjects with degree III hepatic fibrosis as compared to patients with degree I or II fibrosis, Significant increases in IL-5 and IL-13 levels were also observed in some of the subjects who remained untreated for one year following initial assessment and developed more serious fibrosis during this period. The data suggests a role for type 2 cytokines in early stages of hepatic fibrosis in human schistosomiasis mansoni.

Substance use behaviours of young people with a moderate learning disability: a longitudinal analysis.

Substance use behaviors of young people attending a special school are reported over a 4-year period from the age of 12-16 years. The article investigated these behaviors by surveying a cohort of young people with a statement for moderate learning disabilities annually during the last 4 years of compulsory schooling. The findings show that these young people consistently reported lower levels of tobacco, alcohol, and cannabis use compared with those attending mainstream school. No other illicit drug use was reported. The potential implications of these findings are discussed in relation to the context and timing of targeted substance education and prevention initiatives for young people with moderate learning disability attending a special school.This resource was contributed by The National Documentation Centre on Drug Use.

Generació de codi amb WebRatio

L'objectiu d'aquest PFC és la implementació d'una eina que s'encarregui de transformar un model de dades en un model de navegació complet i correcte. Per fer-ho, el programa WebRatio suporta completament el llenguatge WebML i s'utilitzarà com a dissenyador dels models de dades i també com a eina per comprovar els models de navegació generats.

Report of the Advisory Group on Post Primary Teacher Education

The occasion of this report on Teacher Education is timely. The teaching profession is now confronted with major challenges. Schooling has changed very radically in the recent past. Other review exercises of the education system have taken place and it is a time when a new legislative framework, better accommodated to the diversity of the range of duties and responsibilities of the teacher and school, is emerging. It is anticipated that the Report will stimulate debate, secure a new platform for development and provide for a framework for teacher education models which is better disposed towards the well being of the profession and the service to society it wishes to provide.

The involvement of tetA and tetE tetracycline resistance genes in plasmid and chromosomal resistance of Aeromonas in Brazilian strains

This study analyzed the involvement of tetA and tetE genes in the tetracycline resistance of 16 strains of genus Aeromonas, isolated from clinical and food sources. Polymerase chain reactions revealed that 37.5% of the samples were positive for tetA, and also 37.5% were tetE positive. One isolate was positive for both genes. Only the isolate A. caviae 5.2 had its resistance associated to the presence of a plasmid, pSS2. The molecular characterization of pSS2 involved the construction of its restriction map and the determination of its size. The digestion of pSS2 with HindIII originated two fragments (A and B) that were cloned separately into the pUC18 vector. The tetA gene was shown to be located on the HindIII-A fragment by PCR. After transforming a tetracycline-sensitive strain with pSS2, the transformants expressed the resistance phenotype and harbored a plasmid whose size was identical to that of pSS2. The results confirmed the association between pSS2 and the tetracycline resistance phenotype, and suggest a feasible dissemination of tetA and tetE among strains of Aeromonas. This study suggests the spreading tetA and tetE genes in Aeromonas in Brazil and describes a resistance plasmid that probably contributes to the dissemination of the resistance.

La Intervenció psicopedagògica en el marc de les UEC : elements que afavoreixen un bon assessorament i una bona resposta educativa.

S'ha aprofundit en el camp de l'atenció a la diversitat que reben, i que poden rebre, els adolescents que fracassen en l'escolaritat reglada. Es fa un estudi de 4 unitats d'escolarització compartida i unes pràctiques a la Unitat Mèdico-Educativa de Sant Boi. Es plantegen alternatives per tal d'afavorir l'assessorament d'aquest centre i per a donar una bona resposta educativa a aquests alumnes en edat crítica.

Pla d'actuació amb alumnes nouvinguts : assessorament a un centre per l'elaboració del Pla d'acollida

L'escola ha de potenciar la convivència i la cohesió comunitària, així com també l'equitat d'accés i adquisició de recursos, i el pla d'acollida del centre ha de ser una eina que ajudi els nouvinguts a acabar l'etapa d'escolarització obligatòria amb les destreses, coneixements i possibilitats que els permetin viure en un territori com a subjectes actius, autònoms i responsables.

El Pla d'Acollida de Centre : una proposta intercultural del tractament a la diversitat

El projecte recull un treball d'assessorament en centres de primària pel que fa a l'elaboració del pla d'acollida. L'assessorament tenia una doble finalitat: dotar el centre d'una eina que el permetés sistematitzar-la i dotar de coherència i continuïtat els dubtes o angoixes que aquesta situació provocava. La base teòrica és doble: l'enfocament constructivista de l'assessorament psicopedagògic i la perspectiva de l'interculturalisme, atès el vessant socialitzador, interactiu i harmonitzador del PdA i la consideració social i sistèmica dels dos referents. La metodologia utilitzada ha estat qualitativa: la investigació-acció, ja que és un assessorament orientat cap a l'acció i basat en la pràctica, amb la finalitat de capacitar els docents en la millora d'aquesta pràctica. Recull aspectes organitzatius -matriculació, adscripció al curs, acollida i relació entre la família i el centre, llengua, recursos interns i suports externs- i coordinacions i estratègies d'aula -acollida, organització i funcionament de la classe, planificació de l'escolarització i activitats. Van quedar pendents de realitzar els aspectes referents al currículum i a la cooperació amb l'entorn.

Analysis of interaction of cloned human and/or sheep fetal hemoglobin gamma-chain and LPS in augmenting induction of inflammatory cytokine production in vivo and in vitro.

We have reported earlier that purified preparations of sheep fetal hemoglobin, but not adult hemoglobin, in concert with non-stimulatory doses of lipopolysaccharide (LPS) (lipid A), act cooperatively to regulate in vitro production of a number of cytokines, including TNFalpha, TGFbeta and IL-6 from murine and human leukocytes. Following in vivo treatment of mice with the same combination of hemoglobin and LPS, harvested spleen or peritoneal cells showed a similar augmented capacity to release these cytokines into culture supernatants. We report below that genetically cloned gamma-chain of human or sheep fetal hemoglobin, but not cloned alpha- or beta-chains, can produce this cooperative effect, as indeed can HPLC purified, heme-free, gamma-chains derived from cord blood fetal hemoglobin, and that purified haptoglobin completely abolishes the cooperative interaction.

OER as a Model for Enhanced Teaching and Learning

This article presents preliminary findings from a research study conducted by the Institute for the Study of Knowledge Management in Education on the role of open educational resources (OER) in transforming pedagogy. Based on a study of art and humanities teachers participating in an OER training network, the study reveals how exposure to OER resources and tools support collaboration among teachers, as well as new conversations about teaching practices. These findings have implications for engaging teachers in adopting new OER use practices, and for how OER can be integrated as a model for innovation in teaching and in resource development.

Risk factors associated with human papillomavirus infection in two populations from Rio de Janeiro, Brazil

We investigated human papillomavirus (HPV) infection in two female populations from diverse socio-economic strata from the state of Rio de Janeiro and we also investigated the possible co-factors related to infection and the progression to cancer. In Group I, the reference group of this study, 10.7% of the patients presented HPV infection, as detected by generic PCR, while in Group II (low socio-demographic conditions) HPV was detected in 31.1% of the samples. HPV16 was the most prevalent virus type found in both Groups I and II (5.3% and 10%, respectively), followed by HPV 18 (1.3% and 4.7%, respectively). Although only a small sample was analysed, we detected differences among the groups regarding the rates of HPV infection, HPV types, age, ethnicity, familial income, schooling, marital status, parity, tobacco smoking and oral contraceptive use. For Group I, the Papanicolaou test was the most powerful independent factor associated with HPV status, followed by an age of under 30 years old, the number of sexual partners and black ethnicity. Our data are in agreement with the co-factors that are typically described for the developed world. For Group II, the Pap test was also the most relevant variable that was analysed, but the history of other sexually transmitted diseases and the use of alcohol were additional factors that were implicated in infection. These findings point out the need for the development of general and specific strategies for HPV screening of all Brazilian women.