Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB.

Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia characterized by aggressive osteolysis, particularly affecting the carpal and tarsal bones, and is frequently associated with progressive renal failure. Using exome capture and next-generation sequencing in five unrelated simplex cases of MCTO, we identified previously unreported missense mutations clustering within a 51 base pair region of the single exon of MAFB, validated by Sanger sequencing. A further six unrelated simplex cases with MCTO were also heterozygous for previously unreported mutations within this same region, as were affected members of two families with autosomal-dominant MCTO. MAFB encodes a transcription factor that negatively regulates RANKL-induced osteoclastogenesis and is essential for normal renal development. Identification of this gene paves the way for development of novel therapeutic approaches for this crippling disease and provides insight into normal bone and kidney development.

Effects of bisoprolol fumarate on left ventricular size, function, and exercise capacity in patients with heart failure: analysis with magnetic resonance myocardial tagging.

BACKGROUND: Recent data suggest that beta-blockers can be beneficial in subgroups of patients with chronic heart failure (CHF). For metoprolol and carvedilol, an increase in ejection fraction has been shown and favorable effects on the myocardial remodeling process have been reported in some studies. We examined the effects of bisoprolol fumarate on exercise capacity and left ventricular volume with magnetic resonance imaging (MRI) and applied a novel high-resolution MRI tagging technique to determine myocardial rotation and relaxation velocity. METHODS: Twenty-eight patients (mean age, 57 +/- 11 years; mean ejection fraction, 26 +/- 6%) were randomized to bisoprolol fumarate (n = 13) or to placebo therapy (n = 15). The dosage of the drugs was titrated to match that of the the Cardiac Insufficiency Bisoprolol Study protocol. Hemodynamic and gas exchange responses to exercise, MRI measurements of left ventricular end-systolic and end-diastolic volumes and ejection fraction, and left ventricular rotation and relaxation velocities were measured before the administration of the drug and 6 and 12 months later. RESULTS: After 1 year, heart rate was reduced in the bisoprolol fumarate group both at rest (81 +/- 12 before therapy versus 61 +/- 11 after therapy; P <.01) and peak exercise (144 +/- 20 before therapy versus 127 +/- 17 after therapy; P <.01), which indicated a reduction in sympathetic drive. No differences were observed in heart rate responses in the placebo group. No differences were observed within or between groups in peak oxygen uptake, although work rate achieved was higher (117.9 +/- 36 watts versus 146.1 +/- 33 watts; P <.05) and exercise time tended to be higher (9.1 +/- 1.7 minutes versus 11.4 +/- 2.8 minutes; P =.06) in the bisoprolol fumarate group. A trend for a reduction in left ventricular end-diastolic volume (-54 mL) and left ventricular end-systolic volume (-62 mL) in the bisoprolol fumarate group occurred after 1 year. Ejection fraction was higher in the bisoprolol fumarate group (25.0 +/- 7 versus 36.2 +/- 9%; P <.05), and the placebo group remained unchanged. Most changes in volume and ejection fraction occurred during the latter 6 months of treatment. With myocardial tagging, insignificant reductions in left ventricular rotation velocity were observed in both groups, whereas relaxation velocity was reduced only after bisoprolol fumarate therapy (by 39%; P <.05). CONCLUSION: One year of bisoprolol fumarate therapy resulted in an improvement in exercise capacity, showed trends for reductions in end-diastolic and end-systolic volumes, increased ejection fraction, and significantly reduced relaxation velocity. Although these results generally confirm the beneficial effects of beta-blockade in patients with chronic heart failure, they show differential effects on systolic and diastolic function.

Desempenho de sementes de sapoti (Achras sapota L.) submetidas a diferentes tratamentos pré-germinativos

O sapotizeiro (Achras sapota L.) é cultivado principalmente para a produção de frutos, encontrando-se entre os mais apreciados pela população das áreas onde cresce. Sua propagação pode dar-se através de enxertia ou diretamente por sementes, dando origem aos chamados pés-francos. Considerando o fato de que muitas das espécies florestais e frutíferas apresentam o fenômeno de dormência, e diante da necessidade de se intensificar estudos que melhor expliquem tal processo, o objetivo deste trabalho foi avaliar a eficiência de diferentes tratamentos pré-germinativos em sementes de sapoti, visando a acelerar e uniformizar a germinação de suas sementes. O ensaio foi conduzido em casa de vegetação do Departamento de Fitotecnia, CCA/UFPB, Areia-PB, sendo utilizados os seguintes tratamentos: imersão em água a 60°C por 1, 2 e 3 minutos; corte lateral (ao embrião) com e sem embebição em água por 24 horas; corte distal (ao embrião) com e sem embebição em água por 24 horas; corte lateral+distal (ao embrião) com e sem embebição em água por 24 horas e a testemunha (ausência de tratamento). Efetuados os tratamentos, foi realizada a semeadura em bandejas contendo areia lavada e autoclavada, utilizando-se de quatro repetições de 25 sementes. As características avaliadas foram: percentagem e índice de velocidade de emergência, comprimento de raiz e de hipocótilo e peso de matéria seca de planta. O delineamento experimental foi o Inteiramente Casualizado, e os contrastes entre as médias foram realizados através do teste de Duncan, ao nível de 5% de probabilidade. As sementes de sapoti exibiram maior emergência (81%) e índice de velocidade de emergência (0,58) quando submetidas ao corte lateral, sem embebição. O corte das sementes seguido de embebição por 24 horas não foi eficiente para acelerar a emergência e o índice de velocidade de emergência de plântulas de sapoti. A imersão em água a 60°C, independentemente do tempo utilizado, não deve ser recomendada como tratamento pré-germinativo para sementes de sapoti.

Specific targeting of pro-death NMDA receptor signals with differing reliance on the NR2B PDZ ligand.

NMDA receptors (NMDARs) mediate ischemic brain damage, for which interactions between the C termini of NR2 subunits and PDZ domain proteins within the NMDAR signaling complex (NSC) are emerging therapeutic targets. However, expression of NMDARs in a non-neuronal context, lacking many NSC components, can still induce cell death. Moreover, it is unclear whether targeting the NSC will impair NMDAR-dependent prosurvival and plasticity signaling. We show that the NMDAR can promote death signaling independently of the NR2 PDZ ligand, when expressed in non-neuronal cells lacking PSD-95 and neuronal nitric oxide synthase (nNOS), key PDZ proteins that mediate neuronal NMDAR excitotoxicity. However, in a non-neuronal context, the NMDAR promotes cell death solely via c-Jun N-terminal protein kinase (JNK), whereas NMDAR-dependent cortical neuronal death is promoted by both JNK and p38. NMDAR-dependent pro-death signaling via p38 relies on neuronal context, although death signaling by JNK, triggered by mitochondrial reactive oxygen species production, does not. NMDAR-dependent p38 activation in neurons is triggered by submembranous Ca(2+), and is disrupted by NOS inhibitors and also a peptide mimicking the NR2B PDZ ligand (TAT-NR2B9c). TAT-NR2B9c reduced excitotoxic neuronal death and p38-mediated ischemic damage, without impairing an NMDAR-dependent plasticity model or prosurvival signaling to CREB or Akt. TAT-NR2B9c did not inhibit JNK activation, and synergized with JNK inhibitors to ameliorate severe excitotoxic neuronal loss in vitro and ischemic cortical damage in vivo. Thus, NMDAR-activated signals comprise pro-death pathways with differing requirements for PDZ protein interactions. These signals are amenable to selective inhibition, while sparing synaptic plasticity and prosurvival signaling.

Artificial evolution on network structures : how time and space influence dynamics

Abstract The main objective of this work is to show how the choice of the temporal dimension and of the spatial structure of the population influences an artificial evolutionary process. In the field of Artificial Evolution we can observe a common trend in synchronously evolv¬ing panmictic populations, i.e., populations in which any individual can be recombined with any other individual. Already in the '90s, the works of Spiessens and Manderick, Sarma and De Jong, and Gorges-Schleuter have pointed out that, if a population is struc¬tured according to a mono- or bi-dimensional regular lattice, the evolutionary process shows a different dynamic with respect to the panmictic case. In particular, Sarma and De Jong have studied the selection pressure (i.e., the diffusion of a best individual when the only selection operator is active) induced by a regular bi-dimensional structure of the population, proposing a logistic modeling of the selection pressure curves. This model supposes that the diffusion of a best individual in a population follows an exponential law. We show that such a model is inadequate to describe the process, since the growth speed must be quadratic or sub-quadratic in the case of a bi-dimensional regular lattice. New linear and sub-quadratic models are proposed for modeling the selection pressure curves in, respectively, mono- and bi-dimensional regu¬lar structures. These models are extended to describe the process when asynchronous evolutions are employed. Different dynamics of the populations imply different search strategies of the resulting algorithm, when the evolutionary process is used to solve optimisation problems. A benchmark of both discrete and continuous test problems is used to study the search characteristics of the different topologies and updates of the populations. In the last decade, the pioneering studies of Watts and Strogatz have shown that most real networks, both in the biological and sociological worlds as well as in man-made structures, have mathematical properties that set them apart from regular and random structures. In particular, they introduced the concepts of small-world graphs, and they showed that this new family of structures has interesting computing capabilities. Populations structured according to these new topologies are proposed, and their evolutionary dynamics are studied and modeled. We also propose asynchronous evolutions for these structures, and the resulting evolutionary behaviors are investigated. Many man-made networks have grown, and are still growing incrementally, and explanations have been proposed for their actual shape, such as Albert and Barabasi's preferential attachment growth rule. However, many actual networks seem to have undergone some kind of Darwinian variation and selection. Thus, how these networks might have come to be selected is an interesting yet unanswered question. In the last part of this work, we show how a simple evolutionary algorithm can enable the emrgence o these kinds of structures for two prototypical problems of the automata networks world, the majority classification and the synchronisation problems. Synopsis L'objectif principal de ce travail est de montrer l'influence du choix de la dimension temporelle et de la structure spatiale d'une population sur un processus évolutionnaire artificiel. Dans le domaine de l'Evolution Artificielle on peut observer une tendence à évoluer d'une façon synchrone des populations panmictiques, où chaque individu peut être récombiné avec tout autre individu dans la population. Déjà dans les année '90, Spiessens et Manderick, Sarma et De Jong, et Gorges-Schleuter ont observé que, si une population possède une structure régulière mono- ou bi-dimensionnelle, le processus évolutionnaire montre une dynamique différente de celle d'une population panmictique. En particulier, Sarma et De Jong ont étudié la pression de sélection (c-à-d la diffusion d'un individu optimal quand seul l'opérateur de sélection est actif) induite par une structure régulière bi-dimensionnelle de la population, proposant une modélisation logistique des courbes de pression de sélection. Ce modèle suppose que la diffusion d'un individu optimal suit une loi exponentielle. On montre que ce modèle est inadéquat pour décrire ce phénomène, étant donné que la vitesse de croissance doit obéir à une loi quadratique ou sous-quadratique dans le cas d'une structure régulière bi-dimensionnelle. De nouveaux modèles linéaires et sous-quadratique sont proposés pour des structures mono- et bi-dimensionnelles. Ces modèles sont étendus pour décrire des processus évolutionnaires asynchrones. Différentes dynamiques de la population impliquent strategies différentes de recherche de l'algorithme résultant lorsque le processus évolutionnaire est utilisé pour résoudre des problèmes d'optimisation. Un ensemble de problèmes discrets et continus est utilisé pour étudier les charactéristiques de recherche des différentes topologies et mises à jour des populations. Ces dernières années, les études de Watts et Strogatz ont montré que beaucoup de réseaux, aussi bien dans les mondes biologiques et sociologiques que dans les structures produites par l'homme, ont des propriétés mathématiques qui les séparent à la fois des structures régulières et des structures aléatoires. En particulier, ils ont introduit la notion de graphe sm,all-world et ont montré que cette nouvelle famille de structures possède des intéressantes propriétés dynamiques. Des populations ayant ces nouvelles topologies sont proposés, et leurs dynamiques évolutionnaires sont étudiées et modélisées. Pour des populations ayant ces structures, des méthodes d'évolution asynchrone sont proposées, et la dynamique résultante est étudiée. Beaucoup de réseaux produits par l'homme se sont formés d'une façon incrémentale, et des explications pour leur forme actuelle ont été proposées, comme le preferential attachment de Albert et Barabàsi. Toutefois, beaucoup de réseaux existants doivent être le produit d'un processus de variation et sélection darwiniennes. Ainsi, la façon dont ces structures ont pu être sélectionnées est une question intéressante restée sans réponse. Dans la dernière partie de ce travail, on montre comment un simple processus évolutif artificiel permet à ce type de topologies d'émerger dans le cas de deux problèmes prototypiques des réseaux d'automates, les tâches de densité et de synchronisation.

Influência da cobertura vegetal do solo na qualidade dos frutos de videira 'Niagara Rosada'

Devido ao aumento no custo de produção com a utilização de cobertura morta com capim nas ruas da videira 'Niagara Rosada' e à dificuldade para sua aquisição, objetivou-se a possibilidade de substituí-la por plantas de cobertura intercalares. Em experimentos realizados em Indaiatuba e Jundiaí-SP, de 1999-2000 a 2003-2004, instalaram-se seis tratamentos nas entrelinhas, em blocos ao acaso e quatro repetições, constando de área no limpo; vegetação espontânea roçada; cobertura com capim seco de Brachiaria decumbens; cobertura verde de aveia preta (Avena strigosa); cobertura verde de chícharo (Lathyrus sativus); cobertura verde de tremoço (Lupinus albus), de março a outubro, seguidas de cobertura verde de mucuna anã (Mucuna deeringiana) de outubro a março. Determinaram-se massa, comprimento e largura do cacho, engaço e bagas, número total de bagas por cacho e diâmetro do pedicelo de bagas, comparando-se os valores médios pelo teste de Duncan ao nível de 5%. Na média dos anos, os resultados com a cobertura verde foram similares ou mais favoráveis que os da cobertura com braquiária seca, podendo-se substituí-la por coberturas vegetais intercalares com gramínea e leguminosas, o ano todo, sem interferência negativa na qualidade comercial dos frutos.

Absorção radicular e foliar de 65Zn e sua redistribuição em laranjeiras

O objetivo deste trabalho foi avaliar a contribuição do Zn aplicado nas folhas e no solo para os órgãos desenvolvidos após a aplicação. Plantas de laranjeiras 'Valência' (Citrus sinensis (L.) Osbeck) enxertadas em citrumeleiro 'Swingle'(Citrus paradisi Macfad. cv. Duncan x Poncirus trifoliata (L.) Raf.) foram utilizadas para os dois experimentos conduzidos em casa de vegetação. No primeiro experimento, laranjeiras com 5 anos, conduzidas em substrato, foram pulverizadas com 80 ml de solução com 65ZnCl2 na concentração de 0,25 g L-1 Zn, durante o florescimento. No segundo experimento, foram transplantadas mudas e laranjeiras com 5 anos, para vasos com solo arenoso. As mudas receberam aplicação de 65ZnSO4.7H2O no plantio, e as laranjeiras, com 5 anos em cobertura. Após a emissão de novos fluxos de crescimento, o material vegetal foi colhido, seco e submetido à extração nitroperclórico. No extrato, foi determinado o Zn total e o 65Zn em cintilador sólido. A adubação foliar aumentou o teor de Zn nas folhas que receberam a aplicação. O Zn aplicado no solo, tanto em plantio como em cobertura, aumentou os teores de Zn nos órgãos que nasceram após a aplicação.

Evaluation of substrates on the emergence of "araticum-de-terra-fria" (Annona emarginata (Schltdl.) H. Rainer) Seedlings

Choosing a substrate is the determinant factor for the seedling producer; thus, the aim of this study was to evaluate the effect of different types of substrates on the emergence of "araticum-de-terra-fria" (Annona emarginata (Schltdl.) H. Rainer) seedlings. The experiment was carried out in a greenhouse and the experimental design was in randomized blocks, with three treatments and five replicates of 72 seeds per plot. The treatments consisted of the following substrates: coconut fiber, vermiculite and Plantmax® Citrus. The number of emerged seedlings was weekly counted for 105 days. Data regarding seedling height were obtained, and the emergence velocity index and mean time, besides total emergence percentage and that over time were calculated. Results from total mean emergence percentage, seedling height, emergence velocity index (EVI), and mean emergence time (MET) were subjected to analysis of variance and means were compared by the Tukey's test at 5% significance. The curves concerning the emergence percentage over time were fit by the logistic growth equation for each treatment and the means of each parameter (A, B, C) were compared by the Duncan's test at 5% significance. The substrates vermiculite led to the highest values of emergence percentage differing from the PlantMax® Citrus, but not of the coconut fiber, however the vermiculite promoted seedling height in a shorter time; therefore, this substrate is recommended for the initial development of "araticum-de-terra-fria" (Annona emarginata (Schltdl.) H. Rainer) seedlings.

Concepcions i raonaments en l'ús de sistemes de referència galileans

Durant la darrera dècada s'han multiplicat les investigacions sobre les idees que tenen els nens i els estudiants en general de diversos aspectes que s'estudien a les classes de Ciències i de !'impacte que les classes de Ciències fan 'Sobre aquestes idees ( Driver i Erickson, 1983, Gilbert i Watts, 1983, Osborne i Freyberg, 1985, etc. )...

Produtividade da videira 'Niagara Rosada' em cultivo intercalar com adubos verdes

Devido ao aumento no custo de produção com a utilização de cobertura morta com capim nas ruas da videira 'Niagara Rosada' e à dificuldade para sua aquisição, objetivou-se a possibilidade de substituí-la por plantas de cobertura de solo nas entrelinhas da videira. Em experimentos realizados em cinco safras, em Indaiatuba, numa entrelinha, e em três em Jundiaí, em duas entrelinhas-SP, no período de 1999/2000 a 2003/2004, conduziram-se seis tratamentos nas entrelinhas, em blocos ao acaso e com quatro repetições, constando de área no limpo; vegetação espontânea roçada; cobertura com capim seco de Brachiaria decumbens (testemunha); coberturas de aveia-preta (Avena strigosa), chícharo (Lathyrus sativus) ou de tremoço-branco (Lupinus albus), de março a outubro, seguidas de mucuna-anã (Mucuna deeringiana) de outubro a março. Determinaram-se número de cachos planta-1, produtividade de frutos (kg planta-1) e massa do cacho de uva (g), comparando-se os valores médios pelo teste de Duncan, ao nível de 5%. Nas análises conjuntas por local, constataram-se mais diferenças significativas entre safras do que propriamente entre os tratamentos ou na interação safra x tratamentos, sobretudo em Indaiatuba. Os valores foram significativamente sempre superiores em 2001/2002 para produtividade e massa de cacho nos dois locais e, para número de cachos, em 1999/2000, em Indaiatuba, e em 2000/2001, em Jundiaí. Houve efeito dos tratamentos de cobertura nas três safras apenas em Jundiaí, com resultados similares ou até superiores das coberturas vegetais em relação à cobertura com capim seco, com destaque, particularmente, da cobertura com tremoço seguida de mucuna-anã. Independentemente do número de entrelinhas cultivadas, pode-se substituir a cobertura tradicional de capim por coberturas vegetais intercalares com gramínea e leguminosas, o ano todo, sem interferência negativa na produtividade quantitativa da videira.

Bacteris per fer electricitat

LA CIVILITZACIÓ TECNOLÒGICA en què vivim consumeix molta energia. Es calcula que cada dia cada un de nosaltres gasta directament o indirectament uns 10.000 watts de potèncial"equivalent a 100 làmpades de filament de 100 watts cadascuna, en activitats tan diverses com transport, calefacció, il·luminació, refrigeració, subministrament d"aigua, indústria, generació d"aliments, eliminació de deixalles, reciclatge, etc.

Prototypical Arthropod Gene Content and Genome Organisation in the Centipede Strigamia maritima

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.