Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development

Establishment of the left-right axis is a fundamental process of vertebrate embryogenesis. Failure to develop left-right asymmetry leads to incorrect positioning and morphogenesis of numerous internal organs, and is proposed to underlie the etiology of several common cardiac malformations. The transcriptional modulator Cited2 is essential for embryonic development: Cited2-null embryos die during gestation with profound developmental abnormalities, including cardiac malformations, exencephaly and adrenal agenesis. Cited2 is also required for normal establishment of the left-right axis; we demonstrate that abnormal heart looping and right atrial and pulmonary isomerism are consistent features of the left-right-patterning defect. We show by gene expression analysis that Cited2 acts upstream of Nodal, Lefty2 and Pitx2 in the lateral mesoderm, and of Lefty1 in the presumptive floor plate. Although abnormal left-right patterning has a major impact on the cardiac phenotype in Cited2-null embryos, laterality defects are only observed in a proportion of these embryos. We have therefore used a combination of high-resolution imaging and three-dimensional (3D) modeling to systematically document the full spectrum of Cited2-associated cardiac defects. Previous studies have focused on the role of Cited2 in cardiac neural crest cell development, as Cited2 can bind the transcription factor Tfap2, and thus affect the expression of Erbb3 in neural crest cells. However, we have identified Cited2-associated cardiac defects that cannot be explained by laterality or neural crest abnormalities. In particular, muscular ventricular septal defects and reduced cell density in the atrioventricular (AV) endocardial cushions are evident in Cited2-null embryos. As we found that Cited2 expression tightly correlated with these sites, we believe that Cited2 plays a direct role in development of the AV canal and cardiac septa. We therefore propose that, in addition to the previously described reduction of cardiac neural crest cells, two other distinct mechanisms contribute to the spectrum of complex cardiac defects in Cited2-null mice; disruption of normal left-right patterning and direct loss of Cited2 expression in cardiac tissues.

Evaluation of the effects of Candidatus Liberibacter asiaticus on inoculated citrus plants using laser-induced breakdown spectroscopy (LIBS) and chemometrics tools

This study investigated the organic and inorganic constituents of healthy leaves and Candidatus Liberibacter asiaticus (CLas)-inoculated leaves of citrus plants. The bacteria CLas are one of the causal agents of citrus greening (or Huanglongbing) and its effect on citrus leaves was investigated using laser-induced breakdown spectroscopy (LIBS) combined with chemometrics. The information obtained from the LIBS spectra profiles with chemometrics analysis was promising for the construction of predictive models to identify healthy and infected plants. The major, macro- and microconstituents were relevant for differentiation of the sample conditions. The models were then applied to different inoculation times (from 1 to 8 months). The models were effective in the classification of 82-97% of the diseased samples with a 95% significance level. The novelty of this method was in the fingerprinting of healthy and diseased plants based on their organic and inorganic contents. (C) 2010 Elsevier B.V. All rights reserved.

Homicide mortality, socioeconomic development, and police violence in the city of Sao Paulo, Brazil

Objective. To analyze the association between police violence and homicide mortality rates taking into consideration the effect of contextual variables. Methods. This was an environmental, cross-sectional study that included the 96 census districts in the City of Sao Paulo. The association between the variables was analyzed using Spearman`s rank correlation and simple and multiple regression analysis. Results. Univariate analysis revealed a strong and significant association between homicide mortality coefficients and all the indicators of socioeconomic development and police violence. After controlling for potential confounding factors, the association between police violence and homicide mortality coefficients remained strong and significant. This significance was lost only after control for the size of the resident population. Conclusion. The results indicate that police action that violates basic human rights is not the right answer to urban violence. The combination of homicides from interpersonal violence and deaths from police violence results in negative socialization and promotes further violence.

INSTITUTIONAL DEVELOPMENT THROUGH POLICY-MAKING A Case Study of the Brazilian Central Bank

A number of contemporary studies rightly emphasize the notion that policy outcomes result from institutional determinants. But as a growing literature on institutional development notes, these institutions are themselves impermanent. Sometimes, in crisis moments, institutions are replaced wholesale. More frequently, institutions evolve gradually over time. Using the Brazilian Central Bank as a case study, this article illustrates that the policy-making process itself can be a central driver of gradual institutional development, with institutions evolving through the accumulation of policy choices made over many years and under different policymakers in response to contemporaneous events and unforeseeable economic and political challenges.

Achieving the millennium development goals for health - Cost effectiveness analysis of strategies for. maternal and neonatal health in developing countries

Objective To determine the costs and benefits of interventions for maternal and newborn health to assess the appropriateness of current strategies and guide future plans to attain the millennium development goals. Design Cost effectiveness analysis. Setting Two regions classified by the World Health Organization according to their epidemiological grouping: Afr-E, those countries in sub-Saharan Africa with very high adult and high child mortality, and Sear-D, comprising countries in South East Asia with high adult and high child mortality. Data sources Effectiveness data from several sources, including trials, observational studies, and expert opinion. For resource inputs, quantifies came from WHO guidelines, literature, and expert opinion, and prices from the WHO choosing interventions that are cost effective database. Main outcome measures Cost per disability adjusted life year (DALY) averted in year 2000 international dollars. Results The most cost effective mix of interventions was similar in Afr-E and Sear-D. These were the community based newborn care package, followed by antenatal care (tetanus toxoid, screening for pre-eclampsia, screening and treatment of asymptomatic bacteriuria and syphilis); skilled attendance at birth, offering first level maternal and neonatal care around childbirth; and emergency obstetric and neonatal care around and after birth. Screening and treatment of maternal syphilis, community based management of neonatal pneumonia, and steroids given during the antenatal period were relatively less cost effective in Sear-D. Scaling up all of the included interventions to 95% coverage would halve neonatal and maternal deaths. Conclusion Preventive interventions at the community level for newborn babies and at the primary care level for mothers and newborn babies are extremely cost effective, but the millennium development goals for maternal and child health will not be achieved without universal access to clinical services as well.

Achieving the millennium development goals for health - Time to reassess strategies for improving health in developing countries

Making best use of resources is vital in developing countries that are struggling to improve public health with limited funds. The WHO-CHOICE project has developed standardised methods to,evaluate the efficiency of a broad range of interventions. Ibis series starts by assessing die problems with strategies for meeting the millennium development goals. Subsequent articles describe the methods, apply them to maternal and neonatal health, child health, HIV and AIDS, tuberculosis, and malaria, and consider the implications for an overall health strategy. All appear on bmj.com this week.

Elevated expression of MeCP2 in cardiac and skeletal tissues is detrimental for normal development

MeCP2 plays a critical role in interpreting epigenetic signatures that command chromatin conformation and regulation of gene transcription. In spite of MeCP2`s ubiquitous expression, its functions have always been considered in the context of brain physiology. In this study, we demonstrate that alterations of the normal pattern of expression of MeCP2 in cardiac and skeletal tissues are detrimental for normal development. Overexpression of MeCP2 in the mouse heart leads to embryonic lethality with cardiac septum hypertrophy and dysregulated expression of MeCP2 in skeletal tissue produces severe malformations. We further show that MeCP2`s expression in the heart is developmentally regulated; further suggesting that it plays a key role in regulating transcriptional programs in non-neural tissues.

Eutectic modification and microstructure development in Al-Si alloys

Recent increasing applications for cast Al-Si alloys are particularly driven by the need for lightweighting components in the automotive sector. To improve mechanical properties, elements such as strontium, sodium and antimony can be added to modify the eutectic silicon from coarse and plate-like to fine and fibrous morphology. It is only recently being noticed that the morphological transformation resulting from eutectic modification is also accompanied by other, equally significant, but often unexpected changes. These changes can include a 10-fold increase in the eutectic grain size, redistribution of low-melting point phases and porosity as well as surface finish, consequently leading to variations in casting quality. This paper shows the state-of-the-art in understanding the mechanism of eutectic nucleation and growth in Al-Si alloys, inspecting samples, both quenched and uninterrupted, on the macro, micro and nano-scale. It shows that significant variations in eutectic nucleation and growth dynamics occur in AI-Si alloys as a function of the type and amount of modifier elements added. The key role of AIP particles in nucleating silicon is demonstrated. (c) 2005 Elsevier B.V. All rights reserved.

Late-season non-selective herbicide application reduces Lolium rigidum seed numbers, seed viability, and seedling fitness

Experiments were conducted to investigate the effect of Lolium rigidum (annual ryegrass) seed developmental stage and application rate of glyphosate and SpraySeed (paraquat 135 g/L+ diquat 115 g/L) on the number, germinability, and fitness of seeds produced. Glyphosate (450 g/L) was most effective when applied at a rate of 0.5-1 L/ha during heading and anthesis, reducing the number of filled seeds produced compared with unsprayed plants. Application post-anthesis, when seeds were at the milk to soft dough stage, was less effective. SpraySeed was most effective when applied post-anthesis, during the milk and early dough stages of seed development at a rate of 0.5-1L/ha, resulting in the production of few viable seeds. Although some filled seeds were produced, most of the seeds were dead. Application during anthesis or once the seeds reached soft dough stage was less effective. For both herbicides, those seeds that were capable of germinating were smaller and had slower radicle and coleoptile growth, resulting in slower early seedling growth and reduced biomass production within the first month of growth. Additionally, glyphosate application reduced the proportion of seeds exhibiting dormancy. The anticipated reduction in seed competitive ability and altered emergence timing resulting from late-season herbicide application, even when application timing is not optimal, could be exploited to reduce the likelihood of successful L. rigidum establishment in the following season.