Cardiac expression of ms1/STARS, a novel gene involved in cardiac development and disease, is regulated by GATA4.

Ms1/STARS is a novel muscle-specific actin-binding protein that specifically modulates the myocardin-related transcription factor (MRTF)-serum response factor (SRF) regulatory axis within striated muscle. This ms1/STARS-dependent regulatory axis is of central importance within the cardiac gene regulatory network and has been implicated in cardiac development and postnatal cardiac function/homeostasis. The dysregulation of ms1/STARS is associated with and causative of pathological cardiac phenotypes, including cardiac hypertrophy and cardiomyopathy. In order to gain an understanding of the mechanisms governing ms1/STARS expression in the heart, we have coupled a comparative genomic in silico analysis with reporter, gain-of-function, and loss-of-function approaches. Through this integrated analysis, we have identified three evolutionarily conserved regions (ECRs), α, SINA, and DINA, that act as cis-regulatory modules and confer differential cardiac cell-specific activity. Two of these ECRs, α and DINA, displayed distinct regulatory sensitivity to the core cardiac transcription factor GATA4. Overall, our results demonstrate that within embryonic, neonatal, and adult hearts, GATA4 represses ms1/STARS expression with the pathologically associated depletion of GATA4 (type 1/type 2 diabetic models), resulting in ms1/STARS upregulation. This GATA4-dependent repression of ms1/STARS expression has major implications for MRTF-SRF signaling in the context of cardiac development and disease.

What is the Causal Effect of Information and Learning about a Public Good on Willingness to Pay?

In this study we elicit agents’ prior information set regarding a public good, exogenously give information treatments to survey respondents and subsequently elicit willingness to pay for the good and posterior information sets. The design of this field experiment allows us to perform theoretically motivated hypothesis testing between different updating rules: non-informative updating, Bayesian updating, and incomplete updating. We find causal evidence that agents imperfectly update their information sets. We also field causal evidence that the amount of additional information provided to subjects relative to their pre-existing information levels can affect stated WTP in ways consistent overload from too much learning. This result raises important (though familiar) issues for the use of stated preference methods in policy analysis.

Effects of proallatotoxins (precocenes) on the development and reproduction of Rhodnius prolixus: some data

Proallatotoxins, and particularly preconcenes, are exceptionally promising models for studying Rhodnius prolixus physiology and for comparison with other natural compounds with anti-hormonal activities. Effects of preconcenes on feeding, development and reproduction of R. prolixus are being detailed. The precocenes reveal significant effects on feeding, moulting cycle (inducing precocious metamorphosis and ecdysial stasis), and reproduction of these insect. The mechanism of action of proallatotoxins was discussed based on the corpus allatum cytotoxic effect and on the ecdysteroid biosynthesis in prothoracic glands and ovaries. Further studies of these compounds on R. prolixus are need and will hopefully reveal other unesplored points regarding the action of the proallatotoxins on insects.

Development and Democratization

Current studies, mainly focused on the postwar period, are split on the impact of development on democracy. Examining panel data that runs from early nineteenth century (a time where hardly any democracy was in place) to the end of the twentieth century, I show income matters positively for democratization – both after controlling for country and time effects and instrumenting for income. Since the effect of time partly varies over time, with some historical periods that are more favorable to democracy than others, I investigate the domestic variables (a decreasing marginal effect of growth in already developed economies) and international factors (the strategies of great powers toward small countries) generating that result. I finally probe the underlying processes through which income shapes political institutions, showing that development produces key changes in the distribution and nature of wealth that, in turn, make democracy a stable political outcome.

South American monkeys in the development and testing of malarial vaccines - a review

South American Aoutus an d Saimiri monkeys, which are susceptible to infection with human malarias, have been used to develop models for the testing of huma malaria vaccines. Studies indicate that blood-stage and sporozoite vaccines can be tested in these monkeys using appropriate strains of parasites.

The Role of model uncertainty and learning in the U.S. postwar policy response to oil prices

This paper studies optimal monetary policy in a framework that explicitly accounts for policymakers' uncertainty about the channels of transmission of oil prices into the economy. More specfically, I examine the robust response to the real price of oil that US monetary authorities would have been recommended to implement in the period 1970 2009; had they used the approach proposed by Cogley and Sargent (2005b) to incorporate model uncertainty and learning into policy decisions. In this context, I investigate the extent to which regulator' changing beliefs over different models of the economy play a role in the policy selection process. The main conclusion of this work is that, in the specific environment under analysis, one of the underlying models dominates the optimal interest rate response to oil prices. This result persists even when alternative assumptions on the model's priors change the pattern of the relative posterior probabilities, and can thus be attributed to the presence of model uncertainty itself.

Development and selection of NKT cells.

NKT cells utilize a restricted alphabeta TCR repertoire that recognizes glycolipids in association with CD1d. The recent development of fluorescent CD1d tetramers loaded with the synthetic glycolipid alpha-galactosyl-ceramide has led to a clearer definition of NKT-cell subsets as well as important insights into their developmental origin. As many as four subsets may exist, differing in NK1.1 expression, TCR repertoire and dependence on CD1d and various glycolipids for development. Two different lineage-commitment models have been proposed, with most evidence favoring a byproduct of conventional-T-cell development.

Aggregate cultures of foetal rat liver cells: development and maintenance of liver gene expression.

Rotation-mediated aggregate cultures of foetal rat liver cells were prepared and grown in a chemically defined medium. Their capacity for cellular organisation and maturation was studied over a culture period of 3 wk by using both morphologic and biochemical criteria. It was found that within each aggregate, distinct liver cell types were present and attained their normal, differentiated phenotype. Parenchymal cells formed small acini with a central lumen. Within the first 2 wk in culture, albumin and ferritin mRNA levels were maintained, while the alpha-fetoprotein mRNA levels decreased, and tyrosine aminotransferase (TAT) gene expression increased. No significant response to glucocorticoids was observed in early cultures, whereas after 3 wk a marked increase in TAT mRNA levels was elicited by dexamethasone and glucagon (additive stimulatory effects). The results show that foetal rat liver cells cultured in a chemically defined medium are able to rearrange themselves into histotypic structures, and display a developmental pattern of gene expression comparable to that of perinatal rat liver in vivo. This culture system offers therefore a useful model to study the development and function of liver cells.

Acute pain in adults admitted to the emergency room: development and implementation of abbreviated guidelines.

AIM: Although acute pain is frequently reported by patients admitted to the emergency room, it is often insufficiently evaluated by physicians and is thus undertreated. With the aim of improving the care of adult patients with acute pain, we developed and implemented abbreviated clinical practice guidelines (CG) for the staff of nurses and physicians in our hospital's emergency room. METHODS: Our algorithm is based upon the practices described in the international literature and uses a simultaneous approach of treating acute pain in a rapid and efficacious manner along with diagnostic and therapeutic procedures. RESULTS: Pain was assessed using either a visual analogue scale (VAS) or a numerical rating scale (NRS) at ER admission and again during the hospital stay. Patients were treated with paracetamol and/or NSAID (VAS/NRS <4) or intravenous morphine (VAS/NRS > or =04). The algorithm also outlines a specific approach for patients with headaches to minimise the risks inherent to a non-specific treatment. In addition, our algorithm addresses the treatment of paroxysmal pain in patients with chronic pain as well as acute pain in drug addicts. It also outlines measures for pain prevention prior to minor diagnostic or therapeutic procedures. CONCLUSIONS: Based on published guidelines, an abbreviated clinical algorithm (AA) was developed and its simple format permitted a widespread implementation. In contrast to international guidelines, our algorithm favours giving nursing staff responsibility for decision making aspects of pain assessment and treatment in emergency room patients.

Development and testing of novel chloroplast microsatellite markers for Lolium perenne and other grasses (Poaceae) from de novo sequencing and in silico sequences

Twelve primers to amplify microsatellite markers from the chloroplast genome of Lolium perenne were designed and optimized using de novo sequencing and in silico sequences. With one exception, each locus was polymorphic with a range from two to nine alleles in L. perenne. The newly developed primer pairs cross-amplified in different species of Lolium and in 50 other grass species representing nine grass subfamilies.

Development and Consequences of Referendum Campaigns in Switzerland, 1981-1999

Since the early 1990s, new forms of referendum campaigns have emerged in the Swiss political arena. In this paper, we examine how referendum campaigns have transformed in Switzerland, focusing on a number of features: their intensity, duration and inclusiveness (i.e., the variety of actors involved). These features are assumed to change in the long run in response to societal changes and in the short run as a function of variations in elite support. We further argue that public knowledge of ballot issues depends on the characteristics of campaigns. To formally test our hypotheses, we draw on advertisement campaigns in six major Swiss newspapers in the four weeks preceding each ballot from 1981 to 1999 and develop a structural equation model. We indeed find that the duration of referendum campaigns has increased over time, while their inclusiveness has decreased. Most importantly, we find that pub­lic knowledge is strongly related to the characteristics of campaigns

Evolution of decision-making and learning under fluctuating social environments

The capacity to learn to associate sensory perceptions with appropriate motor actions underlies the success of many animal species, from insects to humans. The evolutionary significance of learning has long been a subject of interest for evolutionary biologists who emphasize the bene¬fit yielded by learning under changing environmental conditions, where it is required to flexibly switch from one behavior to another. However, two unsolved questions are particularly impor¬tant for improving our knowledge of the evolutionary advantages provided by learning, and are addressed in the present work. First, because it is possible to learn the wrong behavior when a task is too complex, the learning rules and their underlying psychological characteristics that generate truly adaptive behavior must be identified with greater precision, and must be linked to the specific ecological problems faced by each species. A framework for predicting behavior from the definition of a learning rule is developed here. Learning rules capture cognitive features such as the tendency to explore, or the ability to infer rewards associated to unchosen actions. It is shown that these features interact in a non-intuitive way to generate adaptive behavior in social interactions where individuals affect each other's fitness. Such behavioral predictions are used in an evolutionary model to demonstrate that, surprisingly, simple trial-and-error learn¬ing is not always outcompeted by more computationally demanding inference-based learning, when population members interact in pairwise social interactions. A second question in the evolution of learning is its link with and relative advantage compared to other simpler forms of phenotypic plasticity. After providing a conceptual clarification on the distinction between genetically determined vs. learned responses to environmental stimuli, a new factor in the evo¬lution of learning is proposed: environmental complexity. A simple mathematical model shows that a measure of environmental complexity, the number of possible stimuli in one's environ¬ment, is critical for the evolution of learning. In conclusion, this work opens roads for modeling interactions between evolving species and their environment in order to predict how natural se¬lection shapes animals' cognitive abilities. - La capacité d'apprendre à associer des sensations perceptives à des actions motrices appropriées est sous-jacente au succès évolutif de nombreuses espèces, depuis les insectes jusqu'aux êtres hu¬mains. L'importance évolutive de l'apprentissage est depuis longtemps un sujet d'intérêt pour les biologistes de l'évolution, et ces derniers mettent l'accent sur le bénéfice de l'apprentissage lorsque les conditions environnementales sont changeantes, car dans ce cas il est nécessaire de passer de manière flexible d'un comportement à l'autre. Cependant, deux questions non résolues sont importantes afin d'améliorer notre savoir quant aux avantages évolutifs procurés par l'apprentissage. Premièrement, puisqu'il est possible d'apprendre un comportement incorrect quand une tâche est trop complexe, les règles d'apprentissage qui permettent d'atteindre un com¬portement réellement adaptatif doivent être identifiées avec une plus grande précision, et doivent être mises en relation avec les problèmes écologiques spécifiques rencontrés par chaque espèce. Un cadre théorique ayant pour but de prédire le comportement à partir de la définition d'une règle d'apprentissage est développé ici. Il est démontré que les caractéristiques cognitives, telles que la tendance à explorer ou la capacité d'inférer les récompenses liées à des actions non ex¬périmentées, interagissent de manière non-intuitive dans les interactions sociales pour produire des comportements adaptatifs. Ces prédictions comportementales sont utilisées dans un modèle évolutif afin de démontrer que, de manière surprenante, l'apprentissage simple par essai-et-erreur n'est pas toujours battu par l'apprentissage basé sur l'inférence qui est pourtant plus exigeant en puissance de calcul, lorsque les membres d'une population interagissent socialement par pair. Une deuxième question quant à l'évolution de l'apprentissage concerne son lien et son avantage relatif vis-à-vis d'autres formes plus simples de plasticité phénotypique. Après avoir clarifié la distinction entre réponses aux stimuli génétiquement déterminées ou apprises, un nouveau fac¬teur favorisant l'évolution de l'apprentissage est proposé : la complexité environnementale. Un modèle mathématique permet de montrer qu'une mesure de la complexité environnementale - le nombre de stimuli rencontrés dans l'environnement - a un rôle fondamental pour l'évolution de l'apprentissage. En conclusion, ce travail ouvre de nombreuses perspectives quant à la mo¬délisation des interactions entre les espèces en évolution et leur environnement, dans le but de comprendre comment la sélection naturelle façonne les capacités cognitives des animaux.

Histoarchitecture of schistosomal granuloma development and involution: morphogenetic and biomechanical approaches

The authors present morphogenetic and biomechanical approaches on the concept of the Schistosoma mansoni granulomas, considering them as organoid structures that depend on cellular adhesion and sorting, forming rearrangement into hierarchical concentric layers, creating tension-dependent structures, aiming to acquire round form, since this is the minimal energy form, in which opposing forces pull in equally from all directions and are in balance. From the morphogenetic point of view, the granulomas function as little organs, presenting maturative and involutional stages in their development with final disappearance (pre-granulomatous stages, subdivided in: weakly and/or initial reactive and exudative; granulomatous stages: exudative-productive, productive and involutional). A model for the development of granulomas was suggested, according to the following stages: encapsulating, focal histolysis, fiber production, orientation and compacting and involution and desintegration. The authors concluded that schistosomal granuloma is not a tangled web of individual cells and fibers, but an organized structure composed by host and parasite components, which is not formed to attack the miracidia, but functions as an hybrid interface between two different phylogenetic beings.

Survival, development and growth of larvae of the blue swimmer crab, Portunus pelagicus, cultured under different photoperiod conditions

The blue swimmer crab is a commercially important species of the tropical Indo-Pacific regions that shows substantial potential as a candidate species for aquaculture. Optimization of larval rearing conditions, including photoperiod, is therefore important to establish a method for the intensive hatchery culture of this species. Newly hatched larvae of Portunuspelagicus in first zoeal stage (ZI) were reared under five photoperiod regimes 0L: 24D, 6L: 18D, 12L: 12D, 18L: 6D, and 24L: 0D (5 replicates per treatment) till they metamorphosed to megalopae (ranged from 8.5 ± 0.3 days (18L: 6D) to 10.8 ± 1.8 days (0L: 24D) at 29 ± 1 °C). Daily, larvae of each treatment were fed an identical diet of mixed rotifer and Artemia nauplii, and the survival and molt to successive stages was monitored. Newly hatched ZI larvae of P. pelagicus could successfully develop to the megalopal stage under all tested photoperiod conditions, but we detected significant differences in survival among treatments (p & 0.05). The constant darkness treatment (0L: 24D) had the lowest (19.2 ± 7.2%, mean ± S.E.) cumulative survival from ZI to the megalopal stage, while the 18L: 6D treatment achieved the highest survival (51.2 ± 23.6%). Similarly, the photoperiod significantly affected zoeal development. Constant darkness led to the longest cumulative zoeal duration (10.8 ± 1.8 days), whereas the 18L: 6D treatment rendered the shortest larval development (8.5 ± 0.3 days). In addition, larvae reared under constant darkness resulted in the smallest megalopae (carapace length = 1.44 ± 0.09 mm) and the lowest dry weight (0.536 ± 0.188 mg). In conclusion, photoperiod significantly affected the survival, development, and growth of P. pelagicus zoeal larvae. Constant darkness led to the lowest larval survival and developmental rate, while a photoperiod regime of 18L: 6D appeared to be the most suitable condition for the rearing of zoeal larvae of P. pelagicus.

Roles of canonical Wnt/TCF-1 signaling for hematopoiesis, lymphocyte development and function

Summary : The canonical Wnt signaling pathway plays key roles in the maintenance of self-renewing tissues, like the gut or the skin. In contrast, the role of this pathway in hematopoiesis remains poorly defined. Wnt ligands transmit signals through ß-catenin which activates gene transcription upon its association with Lymphoid Cell Enhancer/T Cell Factor (LEF/TCF). Currently, v-catenin is the only alternative factor known to transduce canonical Wnt signals. The ß-/γ-catenin bindiná domain in TCF-1 is required to partly rescue thymopoiesis and NK cell development in TCF-1-deficient mice. However, T cell development and hematopoiesis w-as normal in mice deficient of ß-catenin, or of γ-catenin. Surprisingly we found that hematopoiesis and thymopoiesis was also normal in the combined absence of ß- and γ-catenin. Reporter assays showed that double-deficient lymphocytes were still able to transduce canonical wnt signals. These data provided evidence that hematopoietic cells can transduce canonical Wnt signals in the combined absence of ß- and γ-catenin. There exist numerous TCF-1 isoforrns including those that harbor the N-terminal ß-/y-catenin binding domain or that contains a C-terminal CRARF domain whose role in vivo has not been previously tested. We found that the CRARF domain influences lymphocyte development in conjunction with the N-treminal ß-/γ-catenin binding. The presence of the two domains directs thymocytes to the CD8+ T cell lineage whereas NK cell development is abolished. Roles of the canonical Wnt/TCF-1 pathway for lymphocyte function have not been defined. We demonstrate that TCF-1 deficient CDBT T cells mount a normal primary response to viral infection but these T cells fail to expand upon restimulation. The failure of CD8+ T cells to respond to IL-2 during primary infection seems to account for this phenotype. Thus, TCF-1 is essential for programming functional CD8+ T cell memory. Collectively, these data provide significant new insights into the role of Wnt/TCF-1 pathway for lymphocyte development and function and suggest a novel mechanism of Wnt signal transuction in hematopoietic cells. Résumé : La voie de signalisation canonique Wnt joue un rôle prépondérant dans le renouvellement de tissus, comme l'intestin ou la peau. Son rôle dans l'hématopoïèse est quant à lui mal défini. Le ligand Wnt transmet le signal via la ß-catenin qui active la transcription de gènes cibles quand il est associé avec Lymphoid Cell Enhancer,~T Cell Factor (LEF/TCF). Actuellement, la γ-catenin est le seul autre facteur connu pouvant se substituer à la fonction de la ß-catenin. Un variant de TCF-1 contenant le domaine liant ß-/,~-catenin est capable de restaurer le développement des lymphocytes T et NK en l'absence de TCF-1. Cependant la thymopoïèse et l'hématopoïèse sont normales dans les souris déficientes pour la ß-catenin ou la γ-catenin. De façon surprenante, nous avons trouvé que l'hématopoïèse et le développement des lymphocytes sont normaux lors de l'absence combinée de ß-/γ-catenin. De plus, la transduction des signaux de la voie de signalisation Wnt est maintenue dans des lymphocytes déficients pour ß-/γ-catenin. Ces résultats démontrent que les cellules hématopoïétiques peuvent transmettre les signaux de la voie canonique Wnt lors de l'absence combinée de la ß et la γ -catenin. Il existe de nombreuses isofonnes de TCF-1, y compris certaines qui comprennent un domaine qui lie ß-/γ-catenin du côté N-terminus ou qui contiennent un domaine CRARF du côté C-terminus. Nous montrons ici que le domaine CRARF influence le développement des lymphocytes en conjonction avec le domaine liant ß-/γ-catenin. La présence des deux domaines dirige les thymocytes vers la lignée de cellules T CD8, alors que le développement des cellules NK est aboli. Au-delà de sa fonction sur le développement des lymphocytes, le rôle de la soie de signalisation canonique Wnt/TCF-1 lors d'une infection n'a pas été défini. Nous avons montré que les cellules T CD8, déficientes pour TCF-1, développent une réponse primaire normale à une infection virale, mais qu'elles ne s'accumulent pas après restimulation. L'incapacité des cellules TCD8 à répondre à l'IL-2 durant la réponse primaire peut expliquer ce phénotype. Ainsi; TCF-1 est essentiel pour la programmation de cellules T CD8 mémoires fonctionnelles. L'ensemble de ces résultats fournit de nouveaux aperçus du rôle de la voie de signalisation Wnt/TCF-1 pour le développement et la fonction des lymphocytes et suggèrent un nouveau mécanisme de transduction du signal Wnt dans les cellules hématopoïétiques.