NLRC5 deficiency impairs MHC class I-dependent lymphocyte killing by cytotoxic T cells

Purpose/Objective: NLRs are intracellular proteins involved in sensing pathogen- and danger-associated molecular patterns, thereby initiating inflammatory responses or cell death. The function of the family member NLRC5 remains a matter of debate, particularly with respect to NF-jB activation, type I IFN, and MHC class I expression. Materials and methods: To study the function of this NLR in vivo, we generated Nlrc5-deficient mice. Results: We found that NLRC5 deletion led to a mild reduction in MHC class I expression on DCs and an intermediate decrease on B cells, while MHC class I levels were dramatically lowered on T, NKT, and NK cells. Nlrc5-/- lymphocytes showed decreased H-2 gene transcript abundance and, accordingly, NLRC5 was sufficient to drive MHC class I expression in a human lymphoid cell line. Moreover, endogenous NLRC5 localized to the nucleus and occupied the proximal promoter region of H-2 genes. Notably, cytotoxic T cell-mediated elimination of Nlrc5-/- lymphocytes was markedly reduced. In addition, we observed low NLRC5 expression in several murine and human lymphoid-derived tumor cell lines. Conclusions: We found that NLRC5 acts as a key transcriptional regulator of MHC class I genes, in particular in lymphocytes. Loss of NLRC5 expression represents an advantage for evading CD8+ T cellmediated elimination by downmodulation of MHCI levels * a mechanism transformed cells may take advantage of. Therefore, our data support an essential role for NLRs in directing not only innate, but also adaptive immune responses (Staehli F et al. J Immunol 2012).

On the q=1/2 non-extensive maximum entropy distribution

A detailed mathematical analysis on the q = 1/2 non-extensive maximum entropydistribution of Tsallis' is undertaken. The analysis is based upon the splitting of such adistribution into two orthogonal components. One of the components corresponds to theminimum norm solution of the problem posed by the fulfillment of the a priori conditionson the given expectation values. The remaining component takes care of the normalizationconstraint and is the projection of a constant onto the Null space of the "expectation-values-transformation"

Coneixement lingüístic i matemàtic d'escolars de nivel sociocultural baix en programes d'immersió = Linguistic and mathematic knowledge in pupils of low sociocultural level in immersiom programmes

This piece of research compares knowledge of Catalan, Castilian and mathematics, as well as the attitudes to these two languages, of a sample of non-Catalan speaking pupils of low sociocultural level in their fourth year of primary school. Some of the pupils had followed an immersion programme in Catalan, whereas others had approached Catalan through their habitual language (Castilian). The findings show that not only did the immersion pupils obtain significantly better results in L2 (Catalan), but their mother tongue (Castilian) competence was undiminished and their performance on the mathematics test was superior to that of the other group. Moreover, the findings indicate that in pupils starting out from less favourable conditions (a low sociocultural level and a low I.Q.) the effect of the educational approach variable is greater than in other cases

Stultitia atheismi, psalmo XIV: v. I. innixa

Invocatio: Q.F.S.F.Q.

Estudo randômico da correção cirúrgica do prolapso uterino através de tela sintética de polipropileno tipo I comparando histerectomia versus preservação uterina

OBJETIVO: Comparar os resultados anatômicos pós-operatórios de pacientes portadoras de prolapso uterino tratadas utilizando tela de polipropileno para correção dos defeitos do assoalho pélvico, comparando histerectomia vaginal com a preservação do útero. MÉTODO: Estudo randomizado com 31 mulheres portadoras de prolapso uterino estádio III ou IV (POP-Q) divididas em dois grupos: Grupo HV- 15 mulheres submetidas à histerectomia vaginal e reconstrução da anatomia do assoalho pélvico com tela de polipropileno tipo I (Nazca R-Promedon) e Grupo HP- 16 mulheres mulheres submetidas à reconstrução da anatomia do assoalho pélvico com tela de polipropileno tipo I (Nazca R-Promedon) preservando o útero. Raça, urgência miccional, constipação intestinal, dor sacral, sangramento e tempo de operação foram os parâmetros analisados. RESULTADOS: O tempo de seguimento médio foi de nove meses. Não se observou diferença entre os grupos nas complicações funcionais. O tempo cirúrgico foi 120 minutos para grupo HV versus 58.9 minutos para grupo HP ( p < 0.001 ) e o volume de perda sanguínea intraoperatória foi 120 mL no grupo HV versus 20 mL para grupo HP ( p < 0.001*). A taxa de sucesso objetivo foi 86.67% para grupo HV e 75% para grupo HP (p = 0,667). A taxa de erosão de tela foi 20% (3/15) de extrusão no grupo HV versus 18,75% (3/16) no grupo HP (p = 1,000). CONCLUSÃO: A correção cirúrgica do assoalho pélvico com telas nas portadoras de prolapso uterino apresentaram similaridade quer sendo ela feita com histeropexia quer com histerectomia. Contudo, o tempo cirúrgico e o volume da perda sanguínea foram significantemente maiores no grupo com histerectromia (HV). Operações vaginais com telas são procedimentos efetivos para a correção do prolapso.

De unctione omnia docente, I Joh. II: 27

Invokaatio: Q.B.V.J.D.T.O.M.

Études de type structure fonction des mutations causant l’ataxie épisodique de type I sur les canaux potassiques dépendants du voltage

Les ataxies épisodiques (EA) d’origine génétique sont un groupe de maladies possédant un phénotype et génotype hétérogènes, mais ont en commun la caractéristique d’un dysfonctionnement cérébelleux intermittent. Les EA de type 1 et 2 sont les plus largement reconnues des ataxies épisodiques autosomiques dominantes et sont causées par un dysfonctionnement des canaux ioniques voltage-dépendants dans les neurones. La présente étude se concentrera sur les mutations causant l'EA-1, retrouvées dans le senseur de voltage (VSD) de Kv1.1, un canal très proche de la famille des canaux Shaker. Nous avons caractérisé les propriétés électrophysiologiques de six mutations différentes à la position F244 et partiellement celles des mutations T284 A/M, R297 K/Q/A/H, I320T, L375F, L399I et S412 C/I dans la séquence du Shaker grâce à la technique du ‘’cut open voltage clamp’’ (COVC). Les mutations de la position F244 situées sur le S1 du canal Shaker sont caractérisées par un décalement des courbes QV et GV vers des potentiels dépolarisants et modifient le couplage fonctionnel entre le domaine VSD et le pore. Un courant de fuite est observé durant la phase d'activation des courants transitoires et peut être éliminé par l'application du 4-AP (4-aminopyridine) ou la réinsertion de l'inactivation de type N mais pas par le TEA (tétraéthylamonium). Dans le but de mieux comprendre les mécanismes moléculaires responsables de la stabilisation d’un état intermédiaire, nous avons étudié séparément la neutralisation des trois premières charges positives du S4 (R1Q, R2Q et R3Q). Il en est ressorti l’existence d’une interaction entre R2 et F244. Une seconde interface entre S1 et le pore proche de la surface extracellulaire agissant comme un second point d'ancrage et responsable des courants de fuite a été mis en lumière. Les résultats suggèrent une anomalie du fonctionnement du VSD empêchant la repolarisation normale de la membrane des cellules nerveuses affectées à la suite d'un potentiel d'action.

Eduard Bonet i Guinó: el científic com a filòsof

Entrevista a Eduard Bonet i Guinó

Carles Cuadras i les probabilitats multivariants

Entrevista a Carles Cuadras Avellana

Josep Carreras Barnés i l'evolució dels enzims

Entrevista a Josep Carreras Barnés

L'ensenyança de les matemàtiques i les ciències segons Baldiri Reixac

L'ensenyament de les matemàtiques i les ciències segons Baldiri Reixac. Baldiri Reixac enfoca l'ensenyament de les ciéncies i de les matemátiques sota l'óptica de l'experiència quotidiana. Vol relacionar l'explicació, freqüentmenc abstracta per la naturalesa propia del tema que exposa, amb les coses que els nois veuen, coneixen, senten i amb les que viuen

Ramon Carbó i la semblança molecular quàntica

Entrevista en Ramon Carbó-Dorca sobre la semblança molecular quantica

Enric Canadell i la química teòrica

Entrevista a Enric Canadell, fisicoquímic gironí