Sobre una inscripció ibèrica suspecta: MNAT 664

L'objectiu d'aquest treball és reivindicar l'autenticitat d'una inscripció ibèrica conservada al MNAT des de temps antic i condemnada sense causa justificada.

La epigrafía ibérica en la obra de Joan Maluquer

Los trabajos de Joan Maluquer de Motes dedicados directamente a las lenguas y epigrafías paleohispánicas son relativamente poco numerosos, sobre todo si se ponen en comparación con la abundancia de su producción científica en otros dominios. Además, muy raras veces entran de lleno en el ámbito de la lingüística, aspecto poco menos que fundamental cuando se trata, como es el caso, de lenguas in descifradas o de conocimiento muy deficiente. Y, pese a lo dicho, más de treinta años después de publicada la Epigrafía prelatina de la Península Ibérica, pocas contribuciones a los estudios paleohispánicos pueden considerarse tan lúcidas para su tiempo y, lo que es más importante, tan vigentes todavía en el nuestro.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.

Endoplasmic reticulum stress promotes inflammation through activation of the NLRP3 inflammasome

SummaryMulticellular organisms have evolved an immune system in order to cope with the constant threats they are facing. Foreign pathogens or endogenous danger signals released by injured or dying host cells can be readily detected through a set of germline- encoded pattern-recognition receptors. The NOD-like receptors are a cytoplasmic family of pattern-recognition receptors that have recently attracted considerable attention due to their ability to form inflammasomes, which are molecular complexes responsible for the activation of caspase-1 and the subsequent processing of the pro¬inflammatory cytokines IL-IB and 11-18 into their mature, bioactive form.In this study, we describe a novel pro-inflammatory signaling pathway, whereby the endoplasmic reticulum promotes inflammation through activation of the NLRP3 inflammasome. This was shown to be independent of the classical endoplasmic reticulum stress response pathway constituted by the effectors IREla, PERK and ATF6a. In keeping with other known NLRP3 activators, generation of reactive oxygen species and potassium efflux were required. We also provide evidence that calcium signaling is critical to this pathway, and possibly integrates signaling triggered by various NLRP3 inflammasome activators. Moreover, the mitochondrial channel VDAC1 was instrumental in mediating this response. We thus propose that the endoplasmic reticulum acts as an integrator of stress and is able to activate the mitochondria in a calcium-dependent manner in order to promote NLRP3 inflammasome activation in response to a wide range of activators.Given the role played by inflammation in the pathogenesis of atherosclerosis, we decided to investigate a possible role for the NLRP3 inflammasome in the progression of the disease. Using an ApoE mouse model, we find that deficiency in the NLRP3 inflammasome components NLRP3, ASC or Caspase-1 does not impair atherosclerosis progression, nor does it impact plaque stability. While previous studies have clearly shown a role for the interleukin-1 family of ligands in atherosclerosis, our results suggest that its contribution might be more complex than previously appreciated, and further research is thus warranted in this field.RésuméLes organismes multicellulaires ont développé un système immunitaire pour faire face aux menaces qui les entourent. Des pathogènes étrangers ou des signaux de danger relâchés par des cellules de l'hôte en détresse peuvent être rapidement détectés via un assemblage de récepteurs spécifiques qui sont présents dès la naissance. Certains membres de la famille de récepteurs NOD ont récemment attiré beaucoup d'attention au vu de leur capacité à former des inflammasomes, complexes moléculaires responsables de l'activation de la easpase-1 et de la maturation des cytokines pro-inflammatoires IL- 1β et IL-18 en leur forme bioactive.Dans cette étude, nous décrivons une nouvelle voie de signalisation pro-inflammatoire, par laquelle le réticulum endoplasmique induit l'inflammation via l'activation de l'inflammasome NLRP3. Cette voie est indépendante de la voie classique de réponse au stress du réticulum endoplasmique, qui comprend les effecteurs IRE1, PERK et ATF6. Comme pour d'autres activateurs de NLRP3, la génération de radicaux libres d'oxygène ainsi que Γ efflux de potassium sont requis. Nous montrons également que le calcium joue un rôle critique dans cette voie, et intègre possiblement la signalisation provoquée par divers activateurs de l'inflammasome NLRP3. De plus, le canal mitochondrial VDAC1 est essentiel dans cette réponse. Nous proposons donc que le réticulum endoplasmique agit comme un intégrateur de stress, activant la mitochondrie d'une façon calcium-dépendante pour promouvoir l'activation de l'inflammasome NLRP3 en réponse à divers activateurs.Au vu du rôle joué par l'inflammation dans la pathogenèse de l'athérosclérose, nous avons étudié un possible rôle pour l'inflammasome NLRP3 dans la progression de la maladie. Dans un modèle de souris ApoE, l'absence des composants de l'inflammasome NLRP3 que sont NLRP3, ASC et Caspase-1 n'influence pas la progression des plaques ni leur stabilité. Alors que d'autres études ont démontré un rôle pour les membres de la famille de l'interleukine-1 dans l'athérosclérose, nos résultats suggèrent que leur contribution pourrait être plus complexe que précédemment apprécié, et d'autres recherches dans ce domaine sont donc nécessaires.

Graus de resistência à brusone e produtividade de cultivares melhoradas de arroz de terras altas

O objetivo deste trabalho foi estudar o nível de resistência à brusone nas folhas e panículas e seu efeito sobre a produtividade de 12 cultivares de arroz, em experimento de campo, durante três anos consecutivos. O grau de resistência das cultivares à brusone nas folhas e panículas foi determinado utilizando-se o critério de área sob curva de progresso e severidade de brusone nas panículas dez dias antes de colheita, respectivamente. As cultivares Progresso, Cuiabana, Caiapó, Carajás e Araguaia, em ordem decrescente, foram as mais resistentes à brusone nas folhas. As cultivares Carajás e Progresso apresentaram severidades da brusone, nas panículas, menores do que as demais cultivares em dois anos. A produtividade das cultivares nos três anos de avaliações, que variou de 83 kg/ha na IAC 201 a 3.617 kg/ha na Rio Paraguai, é explicada principalmente pela severidade da brusone nas panículas, já que as correlações foram negativas e significativas. As raças de Pyricularia grisea, IB-9, IB-41, IB-13 e IC-27, provenientes de 13 cultivares, apresentaram interações diferenciais. Os resultados permitiram concluir que o grau de resistência de algumas cultivares é inadequado e necessita de outras medidas de controle.

Comportamento de somaclones de arroz derivados de híbridos da geração F1 para resistência à brusone

A indução de variabilidade genética em relação à resistência à brusone, utilizando cultura de tecidos como material, constitui uma das alternativas para a obtenção de novas fontes de genes de resistência. O objetivo deste estudo foi aumentar a freqüência de variantes usando como explante panículas imaturas da geração F1 de cruzamentos envolvendo fontes altamente suscetíveis e moderadamente resistentes à brusone como parentais. Somaclones de arroz derivados de plantas F1 dos cruzamentos Bluebelle/Araguaia e Maratelli/Basmati-370 foram avaliados, nas gerações avançadas, quanto à resistência à brusone e a algumas características agronômicas. Nos testes de inoculações em casa de vegetação, todos os somaclones, de ambos os cruzamentos, na geração R4, apresentaram alto grau de resistência aos patótipos IB-1 e IB-9. Alguns dos somaclones mantiveram-se resistentes na geração R5, em avaliações realizadas com alta pressão de brusone. No campo, os somaclones R5 e R6 mostraram alta freqüência de variação quanto à resistência à doença, altura da planta, produtividade, peso e tipo de grãos. Dois somaclones derivados do cruzamento Bluebelle/Araguaia e 31 somaclones derivados do cruzamento Maratelli/Basmati-370 foram identificados como novas fontes de resistência à brusone, e podem ser utilizados no programa de melhoramento de arroz irrigado.

Mécanismes moléculaires de l'homodimérisation de la protéine Scaffold IB1 et son implication dans la sécrétion d'insuline

RÉSUMÉ Les kinases activées par des mitogènes (MAPKs) constituent une importante famille d'enzymes conservée dans l'évolution. Elles forment un réseau de signalisation qui permet à la cellule de réguler spécifiquement divers processus impliqués dans la différenciation, la survie ou l'apoptose. Les kinases formant le module MAPK sont typiquement disposées en cascades de trois partenaires qui s'activent séquentiellement par phosphorylation. Le module minimum est constitué d'une MAPK kinase kinase (MAPKKK), d'une MAPK kinase (MAPKK) et d'une MAPK. Une fois activée, la MAPK phosphoryle différents substrats tels que des facteurs de transcription ou d'autres protéines. Chez les mammifères, trois groupes principaux de MAPKs ont été identifiés. Il s'agit du groupe des kinases régulées par des signaux extracellulaires du type «mitogènes » (ERK), ainsi que des groupes p38 et cJun NH2-terminal kinase (JNK), ou SAPK pour stress activated protein kinase, plutôt activées par des stimuli de type «stress ». De nombreuses études ont impliqué JNK dans la régulation de différents processus physiologiques et pathologiques, comme le diabète, les arthrites rhumatoïdes, l'athérosclérose, l'attaque cérébrale, les maladies de Parkinson et d'Alzheimer. JNK, en particulier joue un rôle dans la mort des cellules sécrétrices d'insuline induite par l'interleukine (IL)-1 β, lors du développement du diabète de type 1. IB1 est une protéine scaffold (échafaud) qui participe à l'organisation du module de JNK. IB1 est fortement exprimée dans les neurones et les cellules β du pancréas. Elle a été impliquée dans la survie des cellules, la régulation de l'expression du transporteur du glucose de type 2 (Glut-2) et dans le processus de sécrétion d'insuline glucose-dépendante. IBl est caractérisée par plusieurs domaines d'interaction protéine-protéine : un domaine de liaison à JNK (JBD), un domaine homologue au domaine 3 de Src (SH3) et un domaine d'interaction avec des tyrosines phosphorylées (PID). Des partenaires d'IB1, incluant les membres de la familles des kinases de lignée mélangée (MLKs), la MAPKK MKK7, la phosphatase 7 des MAPKs (MKP-7) ainsi que la chaîne légère de la kinésine, ont été isolés. Tous ces facteurs, sauf les MLKs et MKK7 interagissent avec le domaine PID ou l'extrême partie C-terminale d'IBl (la chaîne légère de la kinésine). Comme d'autres protéines scaffolds déjà décrites, IBl et un autre membre de la famille, IB2, sont capables d'homo- et d'hétérodimériser. L'interaction a lieu par l'intermédiaire de leur région C-terminale, contenant les domaines SH3 et PID. Mais ni le mécanisme moléculaire, ni la fonction de la dimérisation n'ont été caractérisés. Le domaine SH3 joue un rôle central lors de l'assemblage de complexes de macromolécules impliquées dans la signalisation intracellulaire. Il reconnaît de préférence des ligands contenant un motif riche en proline de type PxxP et s'y lie. Jusqu'à maintenant, tous les ligands isolés se liant à un domaine SH3 sont linéaires. Bien que le domaine SH3 soit un domaine important de la transmission des signaux, aucun partenaire interagissant spécifiquement avec le domaine SH3 d'IB1 n'a été identifié. Nous avons démontré qu'IBl homodimérisait par un nouveau set unique d'interaction domaine SH3 - domaine SH3. Les études de cristallisation ont démontré que l'interface recouvrait une région généralement impliquée dans la reconnaissance classique d'un motif riche en proline de type PxxP, bien que le domaine SH3 d'IB1 ne contienne aucun motif PxxP. L'homodimère d'IB1 semble extrêmement stable. Il peut cependant être déstabilisé par trois mutations ponctuelles dirigées contre des résidus clés impliqués dans la dimérisation. Chaque mutation réduit l'activation basale de JNK dépendante d'IB 1 dans des cellules 293T. La déstabilisation de la dimérisation induite par la sur-expression du domaine SH3, provoque une diminution de la sécrétion d'insuline glucose dépendant. SUMMARY Mitogen activated kinases (MAPK) are an important and conserved enzyme family. They form a signaling network required to specifically regulate process involved in cell differentiation, proliferation or death. A MAPK module is typically organized in a threekinase cascade which are activated by sequential phosphorylation. The MAPK kinase kinase (MAPKKK), the MAPK kinase (MAPKK) and the MAPK constitute the minimal module. Once activated, the MAPK phosphorylates its targets like transcription factors or other proteins. In mammals, three major groups of MAPKs have been identified : the group of extra-cellular regulated kinase (ERK) which is activated by mitogens and the group of p38 and cJun NH2-terminal kinase (JNK) or SAPK for stress activated protein kinase, which are activated by stresses. Many studies implicated JNK in many physiological or pathological process regulations, like diabetes, rheumatoid arthritis, arteriosclerosis, strokes or Parkinson and Alzheimer disease. In particular, JNK plays a crucial role in pancreatic β cell death induced by Interleukin (IL)-1 β in type 1 diabetes. Islet-brain 1 (IB 1) is a scaffold protein that interacts with components of the JNK signal-transduction pathway. IB 1 is expressed at high levels in neurons and in pancreatic β-cells, where it has been implicated in cell survival, in regulating expression of the glucose transporter type 2 (Glut-2) and in glucose-induced insulin secretion. It contains several protein-protein interaction domains, including a JNK-binding domain (JBD), a Src homology 3 domain (SH3) and a phosphotyrosine interaction domain (PID). Proteins that have been shown to associate with IB 1 include members of the Mixed lineage kinase family (MLKs), the MAPKK MKK7, the MAPK phosphatase-7 MKP7, as well as several other ligands including kinesin light chain, LDL receptor related family members and the amyloid precursor protein APP. All these factors, except MLK3 and MKK7 have been shown to interact with the PID domain or the extreme C-terminal part (Kinesin light chain) of IB 1. As some scaffold already described, IB 1 and another member of the family, IB2, have previously been shown to engage in oligomerization through their respective C-terminal regions that include the SH3 and PID domains. But neither the molecular mechanisms nor the function of dimerization have yet been characterized. SH3 domains are central in the assembly of macromolecular complexes involved in many intracellular signaling pathways. SH3 domains are usually characterized by their preferred recognition of and association with canonical PxxP motif. In all these cases, a single linear sequence is sufficient for binding to the SH3 domain. However, although SH3 domains are important elements of signal transduction, no protein that interacts specifically with the SH3 domain of IB 1 has been identified so far. Here, we show that IB 1 homodimerizes through a navel and unique set of SH3-SH3 interactions. X-ray crystallography studies indicate that the dieter interface covers a region usually engaged in PxxP-mediated ligand recognition, even though the IB 1 SH3 domain lacks this motif. The highly stable IB 1 homodimer can be significantly destabilized in vitro by individual point-mutations directed against key residues involved in dimerization. Each mutation reduces IB 1-dependent basal JNK activity in 293T cells. Impaired dimerization induced by over-expression of the SH3 domain also results in a significant reduction in glucose-dependent insulin secretion in pancreatic β-cells.

Resistance spectra of six elite breeding lines of upland rice to Pyricularia grisea

The objective of this work was to evaluate the resistance spectra of six elite breeding lines of rice, developed for improved yield and grain quality, in inoculation tests in the greenhouse and in the field. Forty-six isolates of Pyricularia grisea collected from the cultivar Primavera, 31 from the cultivar Maravilha and 19 from six elite breeding lines, totaling 96 were utilized for inoculations. Out of 11 international and 15 Brazilian pathotypes, IC-1, IB-9, and BD-16, respectively, were identified as most frequent isolates collected from the cultivar Primavera. The isolates retrieved from Maravilha belong to four international and 11 Brazilian pathotypes, the predominant ones being IB-9 and IB-49 and BB-1 and BB-21, respectively. Lines CNAs 8711 and CNAs 8983 showed resistant reaction to all test isolates from Maravilha, while CNAs 8983 was susceptible to three isolates of Primavera pertaining to the pathotype IC-1. A majority of isolates exhibiting compatible reaction to Primavera were incompatible to Maravilha and vice-versa.Field assessment of rice blast utilizing the area under disease progress curve as a criterion for measuring disease severity showed significant differences among the six breeding lines. The isolates of P. grisea exhibiting differential reaction on breeding lines can be utilized in pyramiding resistance genes in new upland rice cultivars.

La Corona immarcescible : pintures de l'antiguitat tardana de la necròpolis alta d'Oxirinc (Mínia, Egipte)

La primera publicació de l’Institut enceta la Sèrie Documenta, que respon a la voluntat de promoure i editar estudis que donin a conèixer i emmarquin científicament nous elements de la cultura material de l’antiguitat clàssica.Aquest llibre estudia un conjunt de pintura mural dels segles V o VI que decorava les parets d’una casa funerària, convertida després en oratori, i que fou descoberta a la necròpolis alta de l’antiga ciutat d’Oxirinc (Mínia, Egipte). El cicle pictòric presenta una sobrietat simbolista que evoluciona després en una iconografia rica en figures i colors.Tot això, completat per la gens menyspreable qualitat artística de les representacions pictòriques, fa d’aquest conjunt una peça arqueològica molt singular.L’estudi inclou un primer capítol a càrrec del Dr. Josep Padró, de la Universitat de Barcelona, Maite Mascort i Hassan Ibrahim Amer, on es sintetitzen els treballs arqueològics i històrics realitzats, des de l’any 1992, a l’antiga Oxirin. Tot seguit, la Dra. Eva Subías, investigadora de la Universitat Rovira i Virgili i col·laboradora de l’Institut des del primer moment, ens ofereix l’estudi històricoartístic del cicle mural. Finalment, Concepció Piedrafita ens dóna la lectura i traducció dels textos grecs presents en les pintures.L’obra inclou una presentació a càrrec de Josep Guitart, director de l’Institut Català d’Arqueologia Clàssica i una traducció dels textos al francès.

Adenosine A1 receptor activation is arrhythmogenic in the developing heart through NADPH oxidase/ERK- and PLC/PKC-dependent mechanisms.

Whether adenosine, a crucial regulator of the developing cardiovascular system, can provoke arrhythmias in the embryonic/fetal heart remains controversial. Here, we aimed to establish a mechanistic basis of how an adenosinergic stimulation alters function of the developing heart. Spontaneously beating hearts or dissected atria and ventricle obtained from 4-day-old chick embryos were exposed to adenosine or specific agonists of the receptors A(1)AR (CCPA), A(2A)AR (CGS-21680) and A(3)AR (IB-MECA). Expression of the receptors was determined by quantitative PCR. The functional consequences of blockade of NADPH oxidase, extracellular signal-regulated kinase (ERK), phospholipase C (PLC), protein kinase C (PKC) and L-type calcium channel (LCC) in combination with adenosine or CCPA, were investigated in vitro by electrocardiography. Furthermore, the time-course of ERK phosphorylation was determined by western blotting. Expression of A(1)AR, A(2A)AR and A(2B)AR was higher in atria than in ventricle while A(3)AR was equally expressed. Adenosine (100μM) triggered transient atrial ectopy and second degree atrio-ventricular blocks (AVB) whereas CCPA induced mainly Mobitz type I AVB. Atrial rhythm and atrio-ventricular propagation fully recovered after 60min. These arrhythmias were prevented by the specific A(1)AR antagonist DPCPX. Adenosine and CCPA transiently increased ERK phosphorylation and induced arrhythmias in isolated atria but not in ventricle. By contrast, A(2A)AR and A(3)AR agonists had no effect. Interestingly, the proarrhythmic effect of A(1)AR stimulation was markedly reduced by inhibition of NADPH oxidase, ERK, PLC, PKC or LCC. Moreover, NADPH oxidase inhibition or antioxidant MPG prevented both A(1)AR-mediated arrhythmias and ERK phosphorylation. These results suggest that pacemaking and conduction disturbances are induced via A(1)AR through concomitant stimulation of NADPH oxidase and PLC, followed by downstream activation of ERK and PKC with LCC as possible target.

Infrainguinal bypass for peripheral arterial occlusive disease: when arms save legs.

OBJECTIVES: Determine if arm veins are good conduits for infrainguinal revascularisation and should be used when good quality saphenous vein is not available. DESIGN: Retrospective study. MATERIALS AND METHODS: We evaluated a consecutive series of infrainguinal bypass (IB) using arm vein conduits from March 2001 to December 2006.We selected arm vein by preoperative ultrasound mapping to identify suitable veins. We measured vein diameter and assessed vein wall quality. We followed patients with systematic duplex imaging at 1 week, 1, 3, 6 and 12 months, and annually thereafter. We treated significative stenoses found during the follow-up. RESULTS: We performed 56 infrainguinal revascularisation using arm vein conduits in 56 patients. Primary patency rates at 1, 2 and 3 years were 65%, 51% and 47%. Primary assisted patencies at 1, 2 and 3 years were 96%, 96% and 82%. Secondary patency rates at 1, 2 and 3 years were 92%, 88% and 88%. The three-year limb salvage rate was 88%. CONCLUSIONS: We conclude that infrainguinal bypass using arm vein for conduits gives good patency rates, if selected by a preoperative US mapping to use the best autogenous conduit available.