Hatching and larval export of the intertidal crab Neohelice granulata in Mar Chiquita coastal lagoon, Argentina

Synchronization in the events of the reproductive cycle in female Neohelice granulata Dana, 1851 were studied from samples taken weekly and biweekly from September to December 2006 in the Laguna Mar Chiquita. The timing and larval hatching and synchronicity were inferred from numbers of ovigerous females and observing the stages of embryonic development. Synchronization in larval hatching also was observed in females in experiments in dark for a period of 48 hours, at three different salinities (10, 23 and 33 ppm). In addition plankton sampling were performed in order to study larval exportation at the field and its link to the tidal and light/dark cycles. We found that ovigerous females of N. granulata have a marked synchronization in embryonic development which results in that most of berried females are close to hatching within a period of maximum tidal range (days). Within this period, there is a synchronization of hatching at a time scale of hours, governed by environmental conditions. The salinity range used in this study (10-32‰) did not affect hatching synchronicity neither time to hatch. Hatching was synchronized according to endogenous rhythms governed mainly by the tidal cycle and secondarily by the breadth of it. It is also conditioned by the light-dark cycle through an exogenous cycle, so that the hatchings would occur mostly at night high tides.

Chaotic dynamics in credit constrained emerging economies

This paper analyzes the role of financial development as a source of endogenous instability in small open economies. By assuming that firms face credit constraints, our model displays a complex dynamic behavior for intermediate values of the parameter representing the level of financial development of the economy. The basic implication of our model is that economies experiencing a process of financial development are more unstable than both very underdeveloped and very developed economies. Our instability concept means that small shocks have a persistent effect on the long run behavior of the model and also that economies can exhibit cycles with a very high period or even chaotic dynamic patterns.

The behavior of money velocity in low and high inflation countries

This paper presents a general equilibrium model of money demand where the velocity of money changes in response to endogenous fluctuations in the interest rate. The parameter space can be divided into two subsets: one where velocity is constant as in standard cash-in-advance models, and another one where velocity fluctuates as in Baumol (1952). The model provides an explanation of why, for a sample of 79 countries, the correlation between the velocity of money and the inflation rate appears to be low, unlike common wisdom would suggest. The reason is the diverse transaction technologies available in different economies.

Mergers, investment decisions and internal organisation

We analyse the effects of investment decisions and firms' internal organisation on the efficiency and stability of horizontal mergers. In our framework economies of scale are endogenous and there might be internal conflict within merged firms. We show that often stable mergers do not lead to more efficiency and may even lead to efficiency losses. These mergers lead to lower total welfare, suggesting that a regulator should be careful in assuming that possible efficiency gains of a merger will be effiectively realised. Moreover, the paper offers a possible explanation for merger failures.

Sequential formation of coalitions through bilateral agreements

We study a sequential protocol of endogenous coalition formation based on a process of bilateral agreements among the players. We apply the game to a Cournot environment with linear demand and constant average costs. We show that the final outcome of any Subgame Perfect Equilibrium of the game is the grand coalition, provided the initial number of firms is high enough and they are sufficiently patient.

The role of central bank operating procedures in an economy with productive government spending

The choice of either the rate of monetary growth or the nominal interest rate as the instrument controlled by monetary authorities has both positive and normative implications for economic performance. We reexamine some of the issues related to the choice of the monetary policy instrument in a dynamic general equilibrium model exhibiting endogenous growth in which a fraction of productive government spending is financed by means of issuing currency. When we evaluate the performance of the two monetary instruments attending to the fluctuations of endogenous variables, we find that the inflation rate is less volatile under nominal interest rate targeting. Concerning the fluctuations of consumption and of the growth rate, both monetary policy instruments lead to statistically equivalent volatilities. Finally, we show that none of these two targeting procedures displays unambiguously higher welfare levels.

Financial intermediation in a model of growth through creative destruction

This paper presents an endogenous growth model in which the research activity is financed by intermediaries that are able to reduce the incidence of researcher's moral hazard. It is shown that financial activity is growth promoting because it increases research productivity. It is also found that a subsidy to the financial sector may have larger growth effects than a direct subsidy to research. Moreover, due to the presence of moral hazard, increasing the subsidy rate to R\&D may reduce the growth rate. I show that there exists a negative relation between the financing of innovation and the process of capital accumulation. Concerning welfare, the presence of two externalities of opposite sign steaming from financial activity may cause that the no-tax equilibrium provides an inefficient level of financial services. Thus, policies oriented to balance the effects of the two externalities will be welfare improving.

On the stability of cooperation structures

Qin [J. Eco. Th., 1996] recently showed that in a game of endogenous formation of cooperation structure, if the underlying TU-game is superadditive, then the full cooperation structure is stable. In this note, we characterize the class of games that ensure the stability of the full cooperation structure, and show that this class is much larger than that of superadditive TU-games.

Entrepreneurship, management services and economic growth

We model the joint production of entrepreneurs and workers where the former provide both entrepreneurial (strategic) and managerial (coordination, motivation) services, and management services are shared with individual workers in an output maximizing way. The static equilibrium of the model determines the endogenous share of entrepreneurs in the economy in a given moment of time. The time dynamics of the solution implies that a given growth rate in quality of entrepreneurial services contributes to productivity growth proportionally to the share of entrepreneurs at the start of the period and improvement in quality of entrepreneurial services is convergence enhancing. Model predictions are tested with data from OECD countries in the period 1970-2002. We find that improvements in quality of entrepreneurial services over time explain up to 100% of observed average productivity growth in these countries.

A Multisectorial model of prices: the SAM approach

Social Accounting Matrices (SAM) are normally used to analyse the income generation process. They are also useful, however, for analysing the cost transmission and price formation mechanisms. For price contributions, Roland-Holst and Sancho (1995) used the SAM structure to analyse the price and cost linkages through a representation of the interdependence between activities, households and factors. This paper is a further analysis of the cost transmission mechanisms, in which I add the capital account to the endogenous components of the Roland-Holst and Sancho approach. By doing this I reflect the responses of prices to the exogenous shocks in savings and investment. I also present an additive decomposition of the global price effects into categories of interdependence that isolates the impact on price levels of shocks in the capital account. I use a 1994 Social Accounting Matrix to make an empirical application of the Catalan economy. Keywords: social accounting matrix, cost linkages, price transmission, capital account. JEL Classification: C63, C69, D59.

Evolution of sarcoma 180 in mice treated with hyperchlorinated water

Mice treated with hyperchlorinated water (50 ppm of chlorine) and control mice, drinking tap water (1-3 ppm of chlorine) were inoculated with 2.5 x 10 [raised to the power of 6] sarcoma 180 cells, by intraperitoneal route. Tumor evolution was measured by enumeration of tumor cells in peritoneal cavity and by evaluation of weight gain at different time intervals after tumor implantation. In mice treated with excessive amounts of chlorine there was enhancement of tumor growth demonstrated by: (a) shorter incubation period and increased weight gain (ascites formation) after tumor implantation; (b) increased number of tumor cells in the peritoneal cavity 2, 3 and 4 days after tumor challenge. The number of peritoneal cells exsudated after tumor implantation was lower in mice treated with hyperchlorinated water than in controls. The tumor enhancement observed after excessive chlorine ingestion would be due to: (a) reduction of the number of peritoneal macrophages that migrate to the peritoneal cavity and (b) reduction of the tumoricidal capacity of peritonela macrophages induced by the direct effect of chlorine or by the reduction of the amount of endogenous endotoxins due to the bactericidal effect of chlorine.

Improving the risk concept: a revision of Arrow-Pratt theory in the context of controlled dynamic stochastic environments

In the literature on risk, one generally assume that uncertainty is uniformly distributed over the entire working horizon, when the absolute risk-aversion index is negative and constant. From this perspective, the risk is totally exogenous, and thus independent of endogenous risks. The classic procedure is "myopic" with regard to potential changes in the future behavior of the agent due to inherent random fluctuations of the system. The agent's attitude to risk is rigid. Although often criticized, the most widely used hypothesis for the analysis of economic behavior is risk-neutrality. This borderline case must be envisaged with prudence in a dynamic stochastic context. The traditional measures of risk-aversion are generally too weak for making comparisons between risky situations, given the dynamic �complexity of the environment. This can be highlighted in concrete problems in finance and insurance, context for which the Arrow-Pratt measures (in the small) give ambiguous.

IFN stimulated gene expression in the liver is a better predictor of treatment response in chronic hepatitis c than the IL28b (IFN lambda 3) genotype

Background: Therapy of chronic hepatitis C (CHC) with pegIFNa/ribavirin achieves sustained virologic response (SVR) in ~55%. Pre-activation of the endogenous interferon system in the liver is associated non-response (NR). Recently, genome-wide association studies described associations of allelic variants near the IL28B (IFNλ3) gene with treatment response and with spontaneous clearance of the virus. We investigated if the IL28B genotype determines the constitutive expression of IFN stimulated genes (ISGs) in the liver of patients with CHC. Methods: We genotyped 93 patients with CHC for 3 IL28B single nucleotide polymorphisms (SNPs, rs12979860, rs8099917, rs12980275), extracted RNA from their liver biopsies and quantified the expression of IL28B and of 8 previously identified classifier genes which discriminate between SVR and NR (IFI44L, RSAD2, ISG15, IFI22, LAMP3, OAS3, LGALS3BP and HTATIP2). Decision tree ensembles in the form of a random forest classifier were used to calculate the relative predictive power of these different variables in a multivariate analysis. Results: The minor IL28B allele (bad risk for treatment response) was significantly associated with increased expression of ISGs, and, unexpectedly, with decreased expression of IL28B. Stratification of the patients into SVR and NR revealed that ISG expression was conditionally independent from the IL28B genotype, i.e. there was an increased expression of ISGs in NR compared to SVR irrespective of the IL28B genotype. The random forest feature score (RFFS) identified IFI27 (RFFS = 2.93), RSAD2 (1.88) and HTATIP2 (1.50) expression and the HCV genotype (1.62) as the strongest predictors of treatment response. ROC curves of the IL28B SNPs showed an AUC of 0.66 with an error rate (ERR) of 0.38. A classifier with the 3 best classifying genes showed an excellent test performance with an AUC of 0.94 and ERR of 0.15. The addition of IL28B genotype information did not improve the predictive power of the 3-gene classifier. Conclusions: IL28B genotype and hepatic ISG expression are conditionally independent predictors of treatment response in CHC. There is no direct link between altered IFNλ3 expression and pre-activation of the endogenous system in the liver. Hepatic ISG expression is by far the better predictor for treatment response than IL28B genotype.

Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity.

AIMS: Aldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. METHODS AND RESULTS: C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. CONCLUSION: Obesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.

Coevolution of restriction factors and retroviruses

Les virus exploitent la machinerie cellulaire de l'hôte pour se répliquer. Ils doivent s'adapter pour infecter la cellule hôte de manière optimale tout en échappant à la vigilance du système de défense de l'hôte. Ainsi l'hôte et les virus se livrent à de constantes batailles évolutives. Mon travail de thèse a porté sur l'étude des signatures évolutives de facteurs de l'hôte agissant comme des 'facteurs de restriction' en bloquant la réplication rétrovirale chez les primates. Plus spécifiquement, mon travail a visé à utiliser des données évolutives pour renseigner les analyses fonctionnelles et la biologie. Nous avons étudié le facteur anti-VIH-1 nommé TRIM5a (i) chez les prosimiens pour mieux comprendre son rôle dans le contrôle d'un lentivirus endogène, (ii) dans son activité contre d'autres anciennes infections représentées par des rétrovirus endogènes humains et (iii) en tant que protéine capable de générer des mutants de la capside. Premièrement nous nous sommes intéressés à TRIM5a chez deux espèces de lémuriens dont Microcebus murinus qui porte le lentivirus endogène PSIV dans son génome depuis plusieurs millions d'années,. Nous avons observé que TRIM5a chez M. murinus a un spectre d'activité antivirale réduit à l'opposé de TRIM5a chez le Lemur catta - non porteur du PSIV endogène - qui bloque une large variété de rétrovirus dont le PSIV. De ce fait TRIM5a aurait pu contribuer à protéger certaines espèces de lémuriens vis-à-vis d'anciennes infections par le PSIV. A l'inverse du PSIV, des virus dérivés des rétrovirus endogènes humains HERV-K and HERV-H se sont révélés largement résistants à l'inhibition par TRIM5a. Ces données illustrent une absence de protection par TRIM5a face à d'autres anciennes infections rétrovirales. Puis, pour évaluer l'impact de la protéine TRIM5a humaine sur le VIH-1, nous avons testé l'effet de mutations des résidues sous sélection positive dans la capside du VIH-1 sur l'inhibition par TRIM5a. Nos résultats montrent que TRIM5a ne jouerait pas un rôle significatif dans l'évolution de la capside du VIH-1. Enfin notre travail a porté sur le facteur anti-VIH-1 SAMHD1 récemment découvert, que nous avons séquencé chez 25 espèces de primates. L'analyse évolutive des sites sous sélection positive et des expériences fonctionnelles ont permis d'identifier le domaine de SAMHD1 interagissant avec la protéine lentivirale Vpx. De même que d'autres protéines virales contrecarrent les facteurs de restriction en les menant à la dégradation, nous avons observé que Vpx induit la dégradation de SAMHD1 de manière spécifique à l'espèce. Ces découvertes contribuent à comprendre comment les facteurs de restriction et les virus co-évoluent pour se neutraliser l'un l'autre. - Viruses hijack the host cellular machinery to replicate. They adapt to infect optimally host cells while escaping host defense systems. Viruses and the host coevolve in an evolutionary struggle. My thesis work has been devoted to study the evolutionary signatures of host factors acting as restriction factors that block retroviral replication in primates. Specifically, my work aimed at using evolutionary data to inform functional analyses and biology. We studied the anti-HIV-1 factor TRIM5a (i) in prosimians to better understand its possible role in the control of an endogenous lentivirus, (ii) in its activity against other ancient infections - as represented by HERVs, and (iii) as a protein capable of generating escape mutants in the viral capsid. First, my work focused on two lemur species, one of which was the gray mouse lemur that carries the endogenous lentivirus PSIV integrated in its genome for several million years. TRIM5a from gray mouse lemur exhibited a limited antiviral spectrum as opposed to TRIM5a from ring-tailed lemur - not a host of PSIV - that is able to block diverse retroviruses notably PSIV. These results support the possible contribution of TRIM5a in protecting lemur species from ancient infection by PSIV. In contrast, chimeric viruses derived from two human endogenous retroviruses were broadly resistant to TRIM5a-mediated restriction, suggesting TRIM5a lack of activity against other types of ancient infections. To evaluate the recent impact of human TRIM5a on HIV-1 evolution, we tested whether variants at positively selected sites in the HIV-1 capsid affected the ability of human TRIM5a alleles to restrict HIV-1. Our results indicate that TRIM5a does not play a significant role in the evolution of HIV1 capsid. At last, our work concentrated on the newly discovered anti-HIV-1 restriction factor SAMHD1. We determined its coding sequence in a panel of 25 species of primates. Evolutionary analyses of positively selected sites in SAMHD1 domains and functional assays identified the domain of SAMHD1 interacting with the lentiviral protein Vpx. Similar to other viral countermeasures targeting cellular restriction factors, Vpx was responsible of the degradation of SAMHD1 orthologs in a species-specific manner. These findings contributed to understanding how restriction factors and viruses evolve to counteract each other.