Identification of CT46/HORMAD1, an immunogenic cancer/testis antigen encoding a putative meiosis-related protein.

Transcripts with ESTs derived exclusively or predominantly from testis, and not from other normal tissues, are likely to be products of genes with testis-restricted expression, and are thus potential cancer/testis (CT) antigen genes. A list of 371 genes with such characteristics was compiled by analyzing publicly available EST databases. RT-PCR analysis of normal and tumor tissues was performed to validate an initial selection of 20 of these genes. Several new CT and CT-like genes were identified. One of these, CT46/HORMAD1, is expressed strongly in testis and weakly in placenta; the highest level of expression in other tissues is <1% of testicular expression. The CT46/HORMAD1 gene was expressed in 31% (34/109) of the carcinomas examined, with 11% (12/109) showing expression levels >10% of the testicular level of expression. CT46/HORMAD1 is a single-copy gene on chromosome 1q21.3, encoding a putative protein of 394 aa. Conserved protein domain analysis identified a HORMA domain involved in chromatin binding. The CT46/HORMAD1 protein was found to be homologous to the prototype HORMA domain-containing protein, Hop1, a yeast meiosis-specific protein, as well as to asy1, a meiotic synaptic mutant protein in Arabidopsis thaliana.

Development and validation of a clinical prediction rule for chest wall syndrome in primary care

Le "Chest wall syndrome" (CWS) est défini comme étant une source bénigne de douleurs thoraciques, localisées sur la paroi thoracique antérieure et provoquées par une affection musculosquelettique. Le CWS représente la cause la plus fréquente de douleurs thoraciques en médecine de premier recours. Le but de cette étude est de développer et valider un score de prédiction clinique pour le CWS. Une revue de la littérature a d'abord été effectuée, d'une part pour savoir si un tel score existait déjà, et d'autre part pour retrouver les variables décrites comme étant prédictives d'un CWS. Le travail d'analyse statistique a été effectué avec les données issues d'une cohorte clinique multicentrique de patients qui avaient consulté en médecine de premier recours en Suisse romande avec une douleur thoracique (59 cabinets, 672 patients). Un diagnostic définitif avait été posé à 12 mois de suivi. Les variables pertinentes ont été sélectionnées par analyses bivariées, et le score de prédiction clinique a été développé par régression logistique multivariée. Une validation externe de ce score a été faite en utilisant les données d'une cohorte allemande (n= 1212). Les analyses bivariées ont permis d'identifier 6 variables caractérisant le CWS : douleur thoracique (ni rétrosternale ni oppressive), douleur en lancées, douleur bien localisée, absence d'antécédent de maladie coronarienne, absence d'inquiétude du médecin et douleur reproductible à la palpation. Cette dernière variable compte pour 2 points dans le score, les autres comptent pour 1 point chacune; le score total s'étend donc de 0 à 7 points. Dans la cohorte de dérivation, l'aire sous la courbe sensibilité/spécificité (courbe ROC) est de 0.80 (95% de l'intervalle de confiance : 0.76-0.83). Avec un seuil diagnostic de > 6 points, le score présente 89% de spécificité et 45% de sensibilité. Parmi tous les patients qui présentaient un CWS (n = 284), 71% (n = 201) avaient une douleur reproductible à la palpation et 45% (n= 127) sont correctement diagnostiqués par le score. Pour une partie (n = 43) de ces patients souffrant de CWS et correctement classifiés, 65 investigations complémentaires (30 électrocardiogrammes, 16 radiographies du thorax, 10 analyses de laboratoire, 8 consultations spécialisées, et une tomodensitométrie thoracique) avaient été réalisées pour parvenir au diagnostic. Parmi les faux positifs (n = 41), on compte trois angors stables (1.8% de tous les positifs). Les résultats de la validation externe sont les suivants : une aire sous la courbe ROC de 0.76 (95% de l'intervalle de confiance : 0.73-0.79) avec une sensibilité de 22% et une spécificité de 93%. Ce score de prédiction clinique pour le CWS constitue un complément utile à son diagnostic, habituellement obtenu par exclusion. En effet, pour les 127 patients présentant un CWS et correctement classifiés par notre score, 65 investigations complémentaires auraient pu être évitées. Par ailleurs, la présence d'une douleur thoracique reproductible à la palpation, bien qu'étant sa plus importante caractéristique, n'est pas pathognomonique du CWS.

The promoter of the gene encoding 3',5'-cyclic adenosine monophosphate (cAMP) response element binding protein contains cAMP response elements: evidence for positive autoregulation of gene transcription.

The transcriptional transactivational activities of the phosphoprotein cAMP-response element-binding protein (CREB) are activated by the cAMP-dependent protein kinase A signaling pathway. Dimers of CREB bind to the palindromic DNA element 5'-TGACGTCA-3' (or similar motifs) called cAMP-responsive enhancers (CREs) found in the control regions of many genes, and activate transcription in response to phosphorylation of CREB by protein kinase A. Earlier we reported on the cyclical expression of the CREB gene in the Sertoli cells of the rat testis that occurred concomitant with the FSH-induced rise in cellular cAMP levels and suggested that transcription of the CREB gene may be autoregulated by cAMP-dependent transcriptional proteins. We now report the structure of the 5'-flanking sequence of the human CREB gene containing promoter activity. The promoter has a high content of guanosines and cytosines and lacks canonical TATA and CCAAT boxes typically found in the promoters of genes in eukaryotes. Notably, the promoter contains three CREs and transcriptional activities of a promoter-luciferase reporter plasmid transfected to placental JEG-3 cells are increased 3- to 5-fold over basal activities in response to either cAMP or 12-O-tetradecanoyl phorbol-14-acetate, and give 6- to 7-fold responses when both agents are added. The CREs bind recombinant CREB and endogenous CREB or CREB-like proteins contained in placental JEG-3 cells and also confer cAMP-inducible transcriptional activation to a heterologous minimal promoter. Our studies suggest that the expression of the CREB gene is positively autoregulated in trans.

Michael's Game ou le jeu des hypothèses

Basé sur les psychothérapies cognitives des psychoses, Michael's Game est un jeu de cartes qui propose à des patients de s'entraîner au raisonnement par hypothèses. Après une présentation théorique du jeu (cadre, déroulement, bénéfices attendus pour les patients...) les auteurs illustrent avec des réactions d'un groupe de patients.

On the dimension of the core of the assignment game

The set of optimal matchings in the assignment matrix allows to define a reflexive and symmetric binary relation on each side of the market, the equal-partner binary relation. The number of equivalence classes of the transitive closure of the equal-partner binary relation determines the dimension of the core of the assignment game. This result provides an easy procedure to determine the dimension of the core directly from the entries of the assignment matrix and shows that the dimension of the core is not as much determined by the number of optimal matchings as by their relative position in the assignment matrix.

Single-valued solutions for the Böhm-Bawerk horse market game

Single-valued solutions for the case of two-sided market games without product differentiation, also known as Böhm-Bawerk horse market games, are analyzed. The nucleolus is proved to coincide with the tau-value, and is thus the midpoint of the core. Moreover a characterization of this setof games in terms of the assignment matrix is provided.

A mutation in the gene encoding the vaccinia virus 37,000-M(r) protein confers resistance to an inhibitor of virus envelopment and release.

Plaque formation in vaccinia virus is inhibited by the compound N1-isonicotinoyl-N2-3-methyl-4-chlorobenzoylhydrazine (IMCBH). We have isolated a mutant virus that forms wild-type plaques in the presence of the drug. Comparison of wild-type and mutant virus showed that both viruses produced similar amounts of infectious intracellular naked virus in the presence of the drug. In contrast to the mutant, no extracellular enveloped virus was obtained from IMCBH-treated cells infected with wild-type virus. Marker rescue experiments were used to map the mutation conferring IMCBH resistance to the mutant virus. The map position coincided with that of the gene encoding the viral envelope antigen of M(r) 37,000. Sequence analysis of both wild-type and mutant genes showed a single nucleotide change (G to T) in the mutant gene. In the deduced amino acid sequence, the mutation changes the codon for an acidic Asp residue in the wild-type gene to one for a polar noncharged Tyr residue in the mutant.

An axiomatization of the nucleolus of the assignment game

[cat] En el domini dels jocs bilaterals d’assignació, es presenta una axiomàtica del nucleolus com l´unica solució que compleix les propietats de consistència respecte del joc derivat definit per Owen (1992) i monotonia de les queixes dels sectors respecte de la seva cardinalitat. Com a conseqüència obtenim una caracterització geomètrica del nucleolus mitjançant una propietat de bisecció més forta que la que satisfan els punts del kernel (Maschler et al, 1979).

A note on the coincidence between Stackelberg and Nash equilibria in a differential game between government and firms

[cat] A Navas i Marín Solano es va demostrar la coincidència entre els equilibris de Nash i de Stackelberg per a una versi´o modificada del joc diferencial proposat por Lancaster (1973). Amb l’objectiu d’obtenir una solució interior, es van imposar restriccions importants sobre el valors dels paràmetres del model. En aquest treball estenem aquest resultat, en el límit en que la taxa de descompte és igual a zero, eliminant les restriccions i considerant totes les solucions possibles.

Activation of PPAR delta Regulates Ywhae (Encoding 14-3-3 epsilon Protein), a Gene Required for Ventricular Morphogenesis

Cardiac ventricular morphogenesis is a key developmental stage during which the ventricles grow considerably in size, but the transcriptional pathways controlling this process remains poorly understood. 14-3-3_ is a member of a conserved protein family that regulates a wide range of processes such as transcription, apoptosis and proliferation by binding to the phospho-serine/threonine residues of its target proteins. We found that deletion of the Ywhae gene (encoding 14-3-3_) in mice leads to abnormal ventricular morphogenesis and an embryonic cardiomyopathy (Cieslik KA et al, Circ. Res. 2008, abstract). Interestingly, we recently showed in cultured cells that the Ywhae gene is regulated directly by peroxisome proliferator-activated receptor _ (PPAR_) (Brunelli L et al, Circ. Res. 2007), a ligand-inducible nuclear receptor that controls energy metabolism and development. Postnatal cardiac-specific deletion of the Ppard gene in mice causes a lethal dilated cardiomyopathy, but it is still unknown whether PPAR_ regulates genes involved in heart development. We hypothesized that the expression of the Ywhae gene is responsive to PPAR_ during heart development. We confirmed that PPAR_ is expressed in the heart during development, and found higher expression at E10.5 compared to later gestational ages. We showed by immunofluorescence that a PPAR_ agonist (50 _M L-165,041 for 24 hr) upregulates 14-3-3_ in primary cardiomyocytes. We showed that when P19CL6 cells are driven towards cardiomyocyte lineage by dimethyl sulfoxide (DMSO), 14-3-3_ levels increase 4-fold, while L-165,041 treatment increases levels by an additional 50%. Based on previous work in mice (Leibowitz MD et al, FEBS Lett. 2000; Letavernier E et al, J. Am. Soc. Nephrol. 2005), we tested the response of Ywhae to PPAR_ in vivo . We fed 30 mg/kg/day L-165,041 to 14-3-3__/_ adult pregnant mice for 3 days starting at E9.5 and assessed Ywhae mRNA levels in embryonic hearts at E12.5. Baseline mRNA levels in Ywhae_/_ hearts were double that of Ywhae_/ hearts, while L-165,041 upregulated Ywhae mRNA levels in both Ywhae_/_ and Ywhae_/ hearts by 65%. These results indicate that Ywhae responds to PPAR_ in vivo, and suggest that PPAR_ regulates Ywhae during ventricular morphogenesis.

Game story, une histoire des jeux vidéo

Compte rendu de l'exposition « Game Story. Une histoire du jeu vidéo » qui s'est tenue au Grand Palais à Paris du 10 novembre 2011 au 9 janvier 2012, envisagée à partir du champ de l'histoire et de la théorie du cinéma en termes de discours historique sur un « nouveau média » ainsi que dans une optique intermédiale.

The assignment game: core bounds for mixed-pair coalitions

In the assignment game framework, we try to identify those assignment matrices in which no entry can be increased without changing the coreof the game. These games will be called buyer¿seller exact games and satisfy the condition that each mixed¿pair coalition attains the corresponding matrix entry in the core of the game. For a given assignment game, a unique buyerseller exact assignment game with the same core is proved to exist. In order to identify this matrix and to provide a characterization of those assignment games which are buyer¿seller exact in terms of the assignment matrix, attainable upper and lower core bounds for the mixed¿pair coalitions are found. As a consequence, an open question posed in Quint (1991) regarding a canonical representation of a ¿45o¿lattice¿ by means of the core of an assignment game can now be answered

The extreme core allocations of the assignment game

Although assignment games are hardly ever convex, in this paper a characterization of their set or extreme points of the core is provided, which is also valid for the class of convex games. For each ordering in the player set, a payoff vector is defined where each player receives his marginal contribution to a certain reduced game played by his predecessors. We prove that the whole set of reduced marginal worth vectors, which for convex games coincide with the usual marginal worth vectors, is the set of extreme points of the core of the assignment game