Genetic analysis of Pitx2 in left -right asymmetry and cardiovascular development

Pitx2, a paired-related homeobox gene that is mutated in human Rieger Syndrome, plays a key role in transferring the early asymmetric signals to individual organs. Pitx2 encodes three isoforms, Pitx2a, Pitx2b and Pitx2c. I found that Pitx2c was the Pitx2 isoform for regulating left-right asymmetry in heart, lung and the predominant isoform in guts. Previous studies suggested that the generation of left-right asymmetry within individual organs is an all or none, random event. Phenotypic analysis of various Pitx2 allelic combinations, that encode graded levels of Pitx2c, reveals an organ-intrinsic mechanism for regulating left-right asymmetric morphogenesis based on differential response to Pitx2c levels. The heart needs low Pitx2c levels, while the lungs and duodenum require higher doses of Pitx2c. In addition, the duodenal rotation is under strict control of Pitx2c activity. Left-right asymmetry development for aortic arch arteries involves complex vascular remodeling. Left-sided expression of Pitx2c in these developing vessels implied its potential function in this process. In order to determine if Pitx2c also can regulate the left-right asymmetry of the aortic arch arteries, a Pitx2c-specific loss of function mutation is generated. Although in wild type mice, the direction of the aortic arch is always oriented toward the left side, the directions of the aortic arches in the mutants were randomized, showing that Pitx2c also determined the left-right asymmetry of these vessels. I have further showed that the cardiac neural crest wasn't involved in this vascular remodeling process. In addition, all mutant embryos had Double Outlet Right Ventricle (DORV), a common congenital heart disease. This study provided insight into the mechanism of Pitx2c-mediated late stages of left-right asymmetry development and identified the roles of Pitx2c in regulation of aortic arch remodeling and heart development. ^

Economic voting and electoral volatility in Turkish provinces

Two groups of questions were addressed in this paper: (1) Is voter punishment of the incumbent the primary factor in electoral volatility? Are there any other types of vote swings that underlie volatility? (2) In general, does a decline in economic growth destabilize voter behavior? If so, what kinds of vote swings does an economic downturn tend to generate? Provincial-level panel data analysis yielded the following results: (1) Changes in volatility is primarily due to vote swings from the incumbent to the opposition and also to and from left-wing and right-wing parties. (2) Lower economic growth increases electoral volatility. Economic decline induces vote swings not only from the government to the opposition but also from left-wing to right-wing parties. This is probably because right-wing parties seem more concerned with economic issues and are thus more popular than left-wing parties with lower-income voters.

Common variants in left/right asymmetry genes and pathways are associated with relative hand skill

Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10-9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development. © 2013 Brandler et al.

Spatial patterns in the brood combs of Nannotrigona testaceicornis (Hymenoptera: Meliponinae): male clusters

Genetic models of sex and caste determination in eusocial stingless bees suggest specific patterns of male, worker and gyne cell distribution in the brood comb. Conflict between queen and laying workers over male parentage and center-periphery gradients of conditions, such as food and temperature, could also contribute to non-random spatial configuration. We converted the positions of the hexagonal cells in a brood comb to Cartesian coordinates, labeled by sex or caste of the individuals inside. To detect and locate clustered patterns, the mapped brood combs were evaluated by indexes of dispersion (MMC, mean distance of cells of a given category from their centroid) and eccentricity (DMB, distance between this centroid and the overall brood comb centroid) that we developed. After randomizing the labels and recalculating the indexes, we calculated probabilities that the original values had been generated by chance. We created sets of binary brood combs in which males were aggregated, regularly or randomly distributed among females. These stylized maps were used to describe the power of MMC and DMB, and they were applied to evaluate the male distribution in the sampled Nannotrigona testaceicornis brood combs. MMC was very sensitive to slight deviations from a perfectly rounded clump; DMB detected any asymmetry in the location of these compact to fuzzy clusters. Six of the 82 brood combs of N. testaceicornis that we analyzed had more than nine males, distributed according to variations in spatial patterns, as indicated by the two indexes.

Thermal Transport and Strong Mass Renormalization in NiCl(2)-4SC(NH(2))(2)

Several quantum paramagnets exhibit magnetic-field-induced quantum phase transitions to an anti-ferromagnetic state that exists for H(c1) <= H <= H(c2). For some of these compounds, there is a significant asymmetry between the low-and high-field transitions. We present specific heat and thermal conductivity measurements in NiCl(2)-4SC(NH(2))(2), together with calculations which show that the asymmetry is caused by a strong mass renormalization due to quantum fluctuations for H <= H(c1) that are absent for H >= H(c2). We argue that the enigmatic lack of asymmetry in thermal conductivity is due to a concomitant renormalization of the impurity scattering.

Attenuation of perceptual asymmetries in patients with early-onset schizophrenia: Evidence in favour of reduced hemispheric differentiation in schizophrenia?

Lateral biases in visual perception have been demonstrated in normal individuals and in patients with unilateral brain lesions. It has been suggested that the absence of structural and functional asymmetries in schizophrenia could be due to a failure in lateralisation that may be most pronounced in those patients whose illness onset is at an early age. Here we examined lateral biases in patients with schizophrenia of an early onset (N = 21) and a late onset.(N = 19), and their respective age-matched control groups, using the greyscales task, a sensitive measure of asymmetries in visual processing. The stimuli consisted of two rectangles, one above the other, shaded in opposite directions and matched overall for darkness. Participants judged which of the two rectangles looked darker overall. Previous studies using this task in healthy participants have reported a reliable bias, such that the rectangle with the darker end on the left is selected preferentially. Whereas the late-onset patients in this study exhibited a perceptual bias of similar direction and magnitude to that of controls, this was not the case for the early-onset patients, who exhibited significantly less bias than their control group. The reduced perceptual bias seen in the early-onset group, but not the late-onset group, suggests an attenuation of right hemisphere mechanisms dedicated to processing vistiospatial information. The attenuated perceptual asymmetry in the early-onset group only may be consistent with the view that (i) an earlier illness onset reflects a greater loss of hemispheric differentiation and (ii) reduced functional asymmetries in the early-onset group are a manifestation of a failure to allocate functions to one or the other hemisphere.

Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Context Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulatioin in BD. Objective: To use tract-based spatial statistics (TBSS) to examine VVM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design: Cross-sectional, case-control, whole-brain DTI using TBSS. Setting: University research institute. Participants: Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type 1 (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures: Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results: Subjects with BD vs controls had significantly greater FA (t > 3.0, P <=.05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P <=.05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P <.01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P <.01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions: To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

Are wing size, wing shape and asymmetry related to field fitness of Trichogramma egg parasitoids?

The effects of wing shape, wing size, and fluctuating asymmetry in these measures oil the field fitness of T. nr. brassicae and T. pretiosum were investigated. Trichogramma wasps mass-reared on eggs of the factitious host Sitotroga cerealella were released in tomato paddocks and those females ovipositing on Helicoverpo spp. eggs were recaptured. Comparisons of the recaptured group with a sample from the release population were used to assess fitness. Wing data were obtained by positioning landmarks on mounted forewings. Size was then measured as the centroid size computed from landmark distances, while Procrustes analysis followed by principal component analysis was used to assess wing shape. Similar findings were obtained for both Trichogramma species: fitness of wasps was strongly related to wing size and some shape dimensions, but not to the asymmetries of these measures. Wasps which performed well in the field had larger wings and a different wing shape compared to wasps from the mass reared population. Both size and the shape dimensions were linearly associated with fitness although there was also some evidence for non-linear selection on shape. The results suggest that wing shape and wing size are reliable predictors of field fitness for these Trichogramma wasps.

Is stock market volatility persistent? A fractionally integrated approach

This paper seeks to study the persistence in the G7’s stock market volatility, which is carried out using the GARCH, IGARCH and FIGARCH models. The data set consists of the daily returns of the S&P/TSX 60, CAC 40, DAX 30, MIB 30, NIKKEI 225, FTSE 100 and S&P 500 indexes over the period 1999-2009. The results evidences long memory in volatility, which is more pronounced in Germany, Italy and France. On the other hand, Japan appears as the country where this phenomenon is less obvious; nevertheless, the persistence prevails but with minor intensity.

Os efeitos das variações das taxas de juro na volatilidade dos mercados bolsistas

Mestrado em Controlo de Gestão e dos Negócios

Evolution of the gene regulatory network controlling flower dorsoventral asymmetry

Tese de Doutoramento em Biologia de Plantas.

Split sex ratios in the social Hymenoptera: a meta-analysis

The study of sex allocation in social Hymenoptera (ants, bees, and wasps) provides an excellent opportunity for testing kin-selection theory and studying conflict resolution. A queen-worker conflict over sex allocation is expected because workers are more related to sisters than to brothers, whereas queens are equally related to daughters and sons. If workers fully control sex allocation, split sex ratio theory predicts that colonies with relatively high or low relatedness asymmetry (the relatedness of workers to females divided by the relatedness of workers to males) should specialize in females or males, respectively. We performed a meta-analysis to assess the magnitude of adaptive sex allocation biasing by workers and degree of support for split sex ratio theory in the social Hymenoptera. Overall, variation in relatedness asymmetry (due to mate number or queen replacement) and variation in queen number (which also affects relatedness asymmetry in some conditions) explained 20.9% and 5% of the variance in sex allocation among colonies, respectively. These results show that workers often bias colony sex allocation in their favor as predicted by split sex ratio theory, even if their control is incomplete and a large part of the variation among colonies has other causes. The explanatory power of split sex ratio theory was close to that of local mate competition and local resource competition in the few species of social Hymenoptera where these factors apply. Hence, three of the most successful theories explaining quantitative variation in sex allocation are based on kin selection.

Three essays in international finance

Executive Summary The first essay of this dissertation investigates whether greater exchange rate uncertainty (i.e., variation over time in the exchange rate) fosters or depresses the foreign investment of multinational firms. In addition to the direct capital financing it supplies, foreign investment can be a source of valuable technology and know-how, which can have substantial positive effects on a host country's economic growth. Thus, it is critically important for policy makers and central bankers, among others, to understand how multinationals base their investment decisions on the characteristics of foreign exchange markets. In this essay, I first develop a theoretical framework to improve our knowledge regarding how the aggregate level of foreign investment responds to exchange rate uncertainty when an economy consists of many firms, each of which is making decisions. The analysis predicts a U-shaped effect of exchange rate uncertainty on the total level of foreign investment of the economy. That is, the effect is negative for low levels of uncertainty and positive for higher levels of uncertainty. This pattern emerges because the relationship between exchange rate volatility and 'the probability of investment is negative for firms with low productivity at home (i.e., firms that find it profitable to invest abroad) and the relationship is positive for firms with high productivity at home (i.e., firms that prefer exporting their product). This finding stands in sharp contrast to predictions in the existing literature that consider a single firm's decision to invest in a unique project. The main contribution of this research is to show that the aggregation over many firms produces a U-shaped pattern between exchange rate uncertainty and the probability of investment. Using data from industrialized countries for the period of 1982-2002, this essay offers a comprehensive empirical analysis that provides evidence in support of the theoretical prediction. In the second essay, I aim to explain the time variation in sovereign credit risk, which captures the risk that a government may be unable to repay its debt. The importance of correctly evaluating such a risk is illustrated by the central role of sovereign debt in previous international lending crises. In addition, sovereign debt is the largest asset class in emerging markets. In this essay, I provide a pricing formula for the evaluation of sovereign credit risk in which the decision to default on sovereign debt is made by the government. The pricing formula explains the variation across time in daily credit spreads - a widely used measure of credit risk - to a degree not offered by existing theoretical and empirical models. I use information on a country's stock market to compute the prevailing sovereign credit spread in that country. The pricing formula explains a substantial fraction of the time variation in daily credit spread changes for Brazil, Mexico, Peru, and Russia for the 1998-2008 period, particularly during the recent subprime crisis. I also show that when a government incentive to default is allowed to depend on current economic conditions, one can best explain the level of credit spreads, especially during the recent period of financial distress. In the third essay, I show that the risk of sovereign default abroad can produce adverse consequences for the U.S. equity market through a decrease in returns and an increase in volatility. The risk of sovereign default, which is no longer limited to emerging economies, has recently become a major concern for financial markets. While sovereign debt plays an increasing role in today's financial environment, the effects of sovereign credit risk on the U.S. financial markets have been largely ignored in the literature. In this essay, I develop a theoretical framework that explores how the risk of sovereign default abroad helps explain the level and the volatility of U.S. equity returns. The intuition for this effect is that negative economic shocks deteriorate the fiscal situation of foreign governments, thereby increasing the risk of a sovereign default that would trigger a local contraction in economic growth. The increased risk of an economic slowdown abroad amplifies the direct effect of these shocks on the level and the volatility of equity returns in the U.S. through two channels. The first channel involves a decrease in the future earnings of U.S. exporters resulting from unfavorable adjustments to the exchange rate. The second channel involves investors' incentives to rebalance their portfolios toward safer assets, which depresses U.S. equity prices. An empirical estimation of the model with monthly data for the 1994-2008 period provides evidence that the risk of sovereign default abroad generates a strong leverage effect during economic downturns, which helps to substantially explain the level and the volatility of U.S. equity returns.

Two-sided learning in new keynesian models: dynamics, (lack of) convergence and the value of information

This paper investigates the role of learning by private agents and the central bank (two-sided learning) in a New Keynesian framework in which both sides of the economy have asymmetric and imperfect knowledge about the true data generating process. We assume that all agents employ the data that they observe (which may be distinct for different sets of agents) to form beliefs about unknown aspects of the true model of the economy, use their beliefs to decide on actions, and revise these beliefs through a statistical learning algorithm as new information becomes available. We study the short-run dynamics of our model and derive its policy recommendations, particularly with respect to central bank communications. We demonstrate that two-sided learning can generate substantial increases in volatility and persistence, and alter the behavior of the variables in the model in a signifficant way. Our simulations do not converge to a symmetric rational expectations equilibrium and we highlight one source that invalidates the convergence results of Marcet and Sargent (1989). Finally, we identify a novel aspect of central bank communication in models of learning: communication can be harmful if the central bank's model is substantially mis-specified

Perfusion abnormalities in hemimegalencephaly

INTRODUCTION: Cerebrovascular changes are rarely discussed in patients with hemimegalencephaly. These alterations have previously been associated with epileptical activity. CASE: We report the case of a 36-week gestation neonate presenting with total right hemimegalencephaly, as demonstrated by a magnetic resonance imaging (MRI) performed in the first days of life. Perfusion-weighted imaging displayed a clear hypervascularization of the right hemisphere. Diffusion-tensor imaging showed an arrangement of white matter fibers concentrically around the ventricle on the right hemisphere. AngioMRI showed an obvious asymmetry in the size of the middle cerebral arteries, with the right middle cerebral artery being prominent. The baby was free of clinical seizures during his first week of life. An electroencephalogram at that time displayed an asymmetric background activity, but no electrical seizures. CONCLUSION: Perfusion anomalies in hemimegalencephaly may not necessarily be related to epileptical activity, but may be related to vessel alterations.