The contribution of 700,000 ORF sequence tags to the definition of the human transcriptome

open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription-PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning.

O México como aliado dos EUA no projeto de integração das Américas

O artigo sugere que, nas duas últimas décadas, os governos mexicanos vêm adotando medidas políticas e econômicas amplamente afinadas com o modelo de integração econômica das Américas proposto pelos EUA. A adesão incondicional ao Nafta e o empenho para consolidar os projetos do Corredor Biológico Mesoamericano e do Plano Puebla-Panamá são exemplos fundamentais dessa estratégia.

Targeting Plasmodium ligands on mosquito salivary glands and midgut with a phage display peptide library

Despite vast efforts and expenditures in the past few decades, malaria continues to kill millions of persons every year, and new approaches for disease control are urgently needed. To complete its life cycle in the mosquito, Plasmodium, the causative agent of malaria, has to traverse the epithelia of the midgut and salivary glands. Although strong circumstantial evidence indicates that parasite interactions with the two organs are specific, hardly any information is available about the interacting molecules. By use of a phage display library, we identified a 12-aa peptide-salivary gland and midgut peptide 1 (SM1)-that binds to the distal lobes of the salivary gland and to the luminal side of the midgut epithelium, but not to the midgut surface facing the hemolymph or to ovaries. The coincidence of the tissues with which parasites and the SM1 peptide interact suggested that the parasite and peptide recognize the same surface ligand. In support of this hypothesis, the SM1 peptide strongly inhibited Plasmodium invasion of salivary gland and midgut epithelia. These experiments suggest a new strategy for the genetic manipulation of mosquito vectorial capacity.

The American empire in the new century: Hegemony or domination?

This chapter analyzes the current position of United States supremacy, in light of the debate on hegemony and domination that acquires greater relevance after the formulation of the 'Bush Doctrine', which is systematized in the document 'The National Security Strategy of the United States of America'. Our approach will emphasize the following aspects: establishment of a parallel between the transition from the 19th to the 20th centuries, from studies that point out the characteristics of imperialism at different times; an analysis of the current foreign policies of the United States, focusing on the debate between unilateralism and multilateralism, emphasizing the reactions caused by the intervention in Iraq; a critical argument about the approaches that highlight in the security agenda of the Bush administration an indicator of a loss of hegemony, which would impose open domination over the search for consensus. Copyright © 2005 SAGE Publications.

Economic survey of the United States, 1990

Incluye Bibliografía

Política internacional na revista Diretrizes (1938-1942)

Pós-graduação em História - FCLAS

O Brasil e a política estratégica dos Estados Unidos: o fim da Guerra Fria : hemisfério Ocidental, América Latina e as Relações Brasil-Estados Unidos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

As forças de operações especiais dos Estados Unidos e a intervenção no Afeganistão: um novo modo de guerra americano?

Pós-graduação em Relações Internacionais (UNESP - UNICAMP - PUC-SP) - FFC

An assessment of the economic impact of climate change on the Agriculture, Energy and Health sectors in Trinidad and Tobago

This report analyses the agriculture, energy, and health sectors in Trinidad and Tobago to assess the potential economic impacts of climate change on the sectors. The fundamental aim of this report is to assist with the development of strategies to deal with the potential impact of climate change on Trinidad and Tobago. It also has the potential to provide essential input for identifying and preparing policies and strategies to help advance the Caribbean subregion closer to solving problems associated with climate change and attaining individual and regional sustainable development goals. Some of the key anticipated impacts of climate change for the Caribbean include elevated air and sea-surface temperatures, sea-level rise, possible changes in extreme events and a reduction in freshwater resources. The economic impact of climate change on the three sectors was estimated for the A2 and B2 IPCC scenarios until 2050. An exploration of various adaptation strategies was also undertaken for each sector using standard evaluation techniques. The study of the impact of climate change on the agriculture sector focused on root crops, green vegetables and fisheries. For these sectors combined, the cumulative loss under the A2 scenario is calculated as approximately B$2.24 and approximately B$1.72 under the B2 scenario by 2050. This is equivalent to 1.37% and 1.05% of the 2008 GDP under the A2 and B2 scenarios, respectively. Given the potential for significant damage to the agriculture sector a large number of potential adaptation measures were considered. Out of these a short-list of 10 potential options were selected by applying 10 evaluation criteria. All of the adaptation strategies showed positive benefits. The analysis indicate that the options with the highest net benefits are: (1) Building on-farm water storage, (2) Mainstreaming climate change issues into agricultural management and (3) Using drip irrigation. Other attractive options include water harvesting. The policy decisions by governments should include these assessments, the omitted intangible benefits, as well as the provision of other social goals such as employment. The analysis of the energy sector has shown that the economic impact of climate change during 2011-2050 is similar under the A2 (US$142.88 million) and B2 (US$134.83 million) scenarios with A2 scenario having a slightly higher cost (0.737% of 2009 GDP) than the B2 scenario (0.695% of 2009 GDP) for the period. On the supply side, analyses indicate that Trinidad and Tobago’s energy sector will be susceptible to the climate change policies of major energy-importing countries (the United States of America and China), and especially to their renewable energy strategies. Implementation of foreign oil substitution policy by the United States of America will result in a decline in Trinidad and Tobago’s Liquefied Natural Gas (LNG) export (equivalent to 2.2% reduction in 2009 GDP) unless an alternative market is secured for the lost United States of America market. China, with its rapid economic growth and the highest population in the world, offers a potential replacement market for Trinidad and Tobago’s LNG export. In this context the A2 scenario will offer the best option for Trinidad and Tobago’s energy sector. The cost-benefit analysis undertaken on selected adaptation strategies reveal that the benefit-cost ratio of replacing electric water heaters with solar water heaters is the most cost-effective. It was also found that the introduction of Compact Fluorescent Light (CFL) and Variable Refrigerant Volume (VRV) air conditioners surpasses the projected cost of increased electricity consumption due to climate change, and provides an economic rationale for the adoption of these adaptation options even in a situation of increased electricity consumption occasioned by climate change. Finally, the conversion of motor fleets to Compressed Natural Gas (CNG) is a cost-effective adaptation option for the transport sector, although it has a high initial cost of implementation and the highest per capita among the four adaptation options evaluated. To investigate the effect of climate change on the health sector dengue fever, leptospirosis, food borne illnesses, and gastroenteritis were examined. The total number of new dengue cases for the period 2008 to 2050 was 204,786 for BAU, 153,725 for A2 and 131,890 for the B2 scenario. With regard to the results for leptospirosis, A2 and B2 seem to be following a similar path with total number of new cases in the A2 scenario being 9,727 and 9,218 cases under the B2 scenario. Although incidence levels in the BAU scenario coincided with those of A2 and B2 prior to 2020, they are somewhat lower post 2020. A similar picture emerges for the scenarios as they relate to food-borne illnesses and to gastroenteritis. Specifically for food-borne illnesses, the BAU scenario recorded 27,537 cases, the A2 recorded 28,568 cases and the B2 recorded 28,679 cases. The focus on the selected sources of morbidity in the health sector has highlighted the fact that the vulnerability of the country’s health sector to climate change does not depend solely on exogenously derived impacts, but also on the behaviour and practices among the population. It is clear that the vulnerability which became evident in the analysis of the impacts on dengue fever, leptospirosis and food-borne illnesses is not restricted solely to climate or other external factors. The most important adaptation strategy being recommended targets lifestyle, behaviour and attitude changes. The population needs to be encouraged to alter their behaviours and practices so as to minimise their exposure to harmful outcomes as it relates to the incidence of these diseases.

Riso e estratégias de poder: alianças atuais no governo das condutas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cocaine effects on mouse incentive-learning and human addiction are linked to alpha 2 subunit-containing GABA(A) receptors

Because GABA(A) receptors containing alpha 2 subunits are highly represented in areas of the brain, such as nucleus accumbens (NAcc), frontal cortex, and amygdala, regions intimately involved in signaling motivation and reward, we hypothesized that manipulations of this receptor subtype would influence processing of rewards. Voltage-clamp recordings from NAcc medium spiny neurons of mice with alpha 2 gene deletion showed reduced synaptic GABA(A) receptor-mediated responses. Behaviorally, the deletion abolished cocaine`s ability to potentiate behaviors conditioned to rewards (conditioned reinforcement), and to support behavioral sensitization. In mice with a point mutation in the benzodiazepine binding pocket of alpha 2-GABA(A) receptors (alpha 2H101R), GABAergic neurotransmission in medium spiny neurons was identical to that of WT (i.e., the mutation was silent), but importantly, receptor function was now facilitated by the atypical benzodiazepine Ro 15-4513 (ethyl 8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5-a] [1,4] benzodiazepine-3-carboxylate). In alpha 2H101R, but not WT mice, Ro 15-4513 administered directly into the NAcc-stimulated locomotor activity, and when given systemically and repeatedly, induced behavioral sensitization. These data indicate that activation of alpha 2-GABA(A) receptors (most likely in NAcc) is both necessary and sufficient for behavioral sensitization. Consistent with a role of these receptors in addiction, we found specific markers and haplotypes of the GABRA2 gene to be associated with human cocaine addiction.

Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development

Congenital heart disease (CHD) occurs in similar to 1% of newborns. CHD arises from many distinct etiologies, ranging from genetic or genomic variation to exposure to teratogens, which elicit diverse cell and molecular responses during cardiac development. To systematically explore the relationships between CHD risk factors and responses, we compiled and integrated comprehensive datasets from studies of CHD in humans and model organisms. We examined two alternative models of potential functional relationships between genes in these datasets: direct convergence, in which CHD risk factors significantly and directly impact the same genes and molecules and functional convergence, in which risk factors significantly impact different molecules that participate in a discrete heart development network. We observed no evidence for direct convergence. In contrast, we show that CHD risk factors functionally converge in protein networks driving the development of specific anatomical structures (e.g., outflow tract, ventricular septum, and atrial septum) that are malformed by CHD. This integrative analysis of CHD risk factors and responses suggests a complex pattern of functional interactions between genomic variation and environmental exposures that modulate critical biological systems during heart development.

Underground leaves of Philcoxia trap and digest nematodes

The recently described genus Philcoxia comprises three species restricted to well lit and low-nutrient soils in the Brazilian Cerrado. The morphological and habitat similarities of Philcoxia to those of some carnivorous plants, along with recent observations of nematodes over its subterranean leaves, prompted the suggestion that the genus is carnivorous. Here we report compelling evidence of carnivory in Philcoxia of the Plantaginaceae, a family in which no carnivorous members are otherwise known. We also document both a unique capturing strategy for carnivorous plants and a case of a plant that traps and digests nematodes with underground adhesive leaves. Our findings illustrate how much can still be discovered about the origin, distribution, and frequency of the carnivorous syndrome in angiosperms and, more generally, about the diversity of nutrient-acquisition mechanisms that have evolved in plants growing in severely nutrient-impoverished environments such as the Brazilian Cerrado, one of the world's 34 biodiversity hotspots.

Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy

Hypomagnesemia affects insulin resistance and is a risk factor for diabetes mellitus type 2 (DM2) and gestational diabetes mellitus (GDM). Two single nucleotide polymorphisms (SNPs) in the epithelial magnesium channel TRPM6 (V(1393)I, K(1584)E) were predicted to confer susceptibility for DM2. Here, we show using patch clamp analysis and total internal reflection fluorescence microscopy, that insulin stimulates TRPM6 activity via a phosphoinositide 3-kinase and Rac1-mediated elevation of cell surface expression of TRPM6. Interestingly, insulin failed to activate the genetic variants TRPM6(V(1393)I) and TRPM6(K(1584)E), which is likely due to the inability of the insulin signaling pathway to phosphorylate TRPM6(T(1391)) and TRPM6(S(1583)). Moreover, by measuring total glycosylated hemoglobin (TGH) in 997 pregnant women as a measure of glucose control, we demonstrate that TRPM6(V(1393)I) and TRPM6(K(1584)E) are associated with higher TGH and confer a higher likelihood of developing GDM. The impaired response of TRPM6(V(1393)I) and TRPM6(K(1584)E) to insulin represents a unique molecular pathway leading to GDM where the defect is located in TRPM6.

Structural basis for the sheddase function of human meprin β metalloproteinase at the plasma membrane

Ectodomain shedding at the cell surface is a major mechanism to regulate the extracellular and circulatory concentration or the activities of signaling proteins at the plasma membrane. Human meprin β is a 145-kDa disulfide-linked homodimeric multidomain type-I membrane metallopeptidase that sheds membrane-bound cytokines and growth factors, thereby contributing to inflammatory diseases, angiogenesis, and tumor progression. In addition, it cleaves amyloid precursor protein (APP) at the β-secretase site, giving rise to amyloidogenic peptides. We have solved the X-ray crystal structure of a major fragment of the meprin β ectoprotein, the first of a multidomain oligomeric transmembrane sheddase, and of its zymogen. The meprin β dimer displays a compact shape, whose catalytic domain undergoes major rearrangement upon activation, and reveals an exosite and a sugar-rich channel, both of which possibly engage in substrate binding. A plausible structure-derived working mechanism suggests that substrates such as APP are shed close to the plasma membrane surface following an "N-like" chain trace.