Von Willebrand Factor multimerization and the polarity of secretory pathways in endothelial cells

The Von Willebrand factor (VWF) synthesised and secreted by endothelial cells is central to haemostasis and thrombosis, providing a multifunctional adhesive platform that brings together components needed for these processes. VWF secretion can occur from both apical and basolateral sides of endothelial cells, and from constitutive, basal and regulated secretory pathways, the latter two via Weibel-Palade bodies (WPB). Although the amount and structure of VWF is crucial to its function, the extent of VWF release, multimerization and polarity of the three secretory pathways have only been addressed separately and with conflicting results. We set out to clarify these relationships using polarized Human Umbilical Vein Endothelial Cells (HUVECs) grown on Transwell membranes. We found that regulated secretion of Ultra large (UL) molecular weight VWF predominantly occurred apically, consistent with a role in localised platelet capture in the vessel lumen. We found that constitutive secretion of low molecular weight (LMW) VWF is targeted basolaterally, toward the subendothelial matrix, using the adaptor protein complex 1 (AP-1), where it may provide the bulk of collagen bound subendothelial VWF. We also found that basally-secreted VWF is composed of UL-VWF, released continuously from WPBs in the absence of stimuli, and occurs predominantly apically, suggesting this could be the main source of circulating plasma VWF. Together, we provide a unified dataset reporting the amount and multimeric state of VWF secreted from the constitutive, basal and regulated pathways in polarized HUVECs, and have established a new role for AP-1 in the basolateral constitutive secretion of VWF

Genetic analysis of self-associating immunoglobulin G rheumatoid factors from two rheumatoid synovia implicates an antigen-driven response.

Although much has been learned about the molecular basis of immunoglobulin M (IgM) rheumatoid factors (RFs) in healthy individuals and in patients with mixed cryoglobulinemia and rheumatoid arthritis, little is known about the genetic origins of the potentially pathogenic IgG RFs in the inflamed rheumatoid synovia of patients. Recently, we generated from unmanipulated synovium B cells several hybridomas that secreted self-associating IgG RFs. To delineate the genetic origins of such potentially pathogenic RFs, we adapted the anchored polymerase chain reaction to rapidly clone and characterize the expressed Ig V genes for the L1 and the D1 IgG RFs. Then, we identified the germline counterparts of the expressed L1 IgG RF V genes. The results showed that the L1 heavy chain was encoded by a Vh gene that is expressed preferentially during early ontogenic development, and that is probably located within 240 kb upstream of the Jh locus. The overlap between this RF Vh gene and the restricted fetal antibody repertoire is reminiscent of the natural antibody-associated Vh genes, and suggests that at least part of the "potential pathogenic" IgG RFs in rheumatoid synovium may derive from the "physiological" natural antibody repertoire in a normal immune system. Indeed, the corresponding germline Vh gene for L1 encodes the heavy chain of an IgM RF found in a 19-wk-old fetal spleen. Furthermore, the comparisons of the expressed RF V genes and their germline counterparts reveal that the L1 heavy and light chain variable regions had, respectively, 16 and 7 somatic mutations, which resulted in eight and four amino acid changes. Strikingly, all eight mutations in the complementarity determining regions of the V gene-encoded regions were replacement changes, while only 6 of 11 mutations in the framework regions caused amino acid changes. Combined with L1's high binding affinity toward the Fc fragment, these results suggest strongly that the L1 IgG RF must have been driven by the Fc antigen

Resumos apresentados.

bitstream/CPAC-2009/27819/1/doc_152.pdfEditores: Evie dos Santos de Sousa, Fábio Gelape Faleiro

First Record of Culex (Culex) brethesi (Dyar) (Diptera: Culicidae) in Rio Grande do Sul State, Brazil

This is the first record of Culex (Culex) brethesi (Dyar) in Rio Grande do Sul state, Brazil. The species was identified from specimens collected in a sand bar vegetation with the aid of a Nasci's trap, during an expedition for surveillance of the West Nile Virus in July of 2006, in the city of Mostardas, Rio Grande do Sul, Brazil.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Técnico e Científico (CNPq

Effect of cadmium on the morphology and anatomy of Salvinia auriculata

This study aimed to evaluate the morphological and anatomical changes of Salvinia auriculata exposed to different concentrations 0, 2.5, 5, 7.5 and 10 μM of cadmium (Cd) and its effect on plant growth. The experiment was conducted in the laboratory of Plant Anatomy of the IF Goiano/Rio Verde Campus, Goiás. Cd free samples of S. auriculata, was obtained from the Aquários Plantados  company, located in Belo Horizonte. The material was grown hydroponically for 20 days and after the experimental period, the leaf samples were fixed, including in historesin, cut to 5 μm thick thick, stained with toluidine blue and the images were obtained in an optical microscope. The toxic effects of Cd on S. auriculata was observed at lowest concentration with the appearance of chlorotic and necrotic spots. Microscopic analysis showed increased height and width of the aerenchyma gaps, mesophyll and a reduction in abaxial surface epidermal cells, due to increased doses of this metal. It was observed that S. auriculata is a plant sensitive to Cd, and thus indicated for environmental monitoring.Key words: Ecological, aquatic species, pollution

Dark spinor models in gravitation and cosmology

We introduce and carefully define an entire class of field theories based on non-standard spinors. Their dominant interaction is via the gravitational field which makes them naturally dark; we refer to them as Dark Spinors. We provide a critical analysis of previous proposals for dark spinors noting that they violate Lorentz invariance. As a working assumption we restrict our analysis to non-standard spinors which preserve Lorentz invariance, whilst being non-local and explicitly construct such a theory. We construct the complete energy-momentum tensor and derive its components explicitly by assuming a specific projection operator. It is natural to next consider dark spinors in a cosmological setting. We find various interesting solutions where the spinor field leads to slow roll and fast roll de Sitter solutions. We also analyse models where the spinor is coupled conformally to gravity, and consider the perturbations and stability of the spinor.Comment: 43 pages. Several new sections and details added. JHEP in prin

Valorização do trabalho humano: uma diretriz constitucional esquecida em meio à crise econômica e às consequentes propostas flexibilizantes

RESUMO: A flexibilização dos direitos trabalhistas é assunto em evidência na realidade econômica de nosso país, mormente em meio ao cenário de crise econômica que vivenciamos. O objetivo deste trabalho é refletir sobre a compatibilidade entre o raciocínio econômico, que entoa as atuais propostas de relativização da legislação trabalhista, e as balizas jurídicas conformadoras da Ordem Econômica constitucional, em especial o valor social do trabalho humano.  Por meio de pesquisa bibliográfica e análise normativa constitucional e infraconstitucional, será realizada, primeiramente, uma digressão sobre a evolução do ordenamento jurídico protetivo trabalhista e das propostas flexibilizantes que o acompanham na história.  Uma vez observado o histórico atrito entre os interesses empresariais e a proteção social trabalhista, o trabalho se ocupará em aprofundar as principais características que notabilizam esse antagonismo entre racionalidades econômica e laboral-protetiva. A partir daí, aclaradas as premissas atinentes aos diferentes pontos de vista que envolvem o tema e partindo para a apreciação em um plano constitucional mais abstrato, axiológico, o texto seguirá no sentido de perquirir, à luz de uma leitura moral (dworkiniana) do problema constitucional, o modo como o ponto de vista patrimonialista típico das categorias econômicas deverá se compatibilizar com a realização dos fins sociais atinentes à valorização do trabalho humano.  Ao final, proporemos que, no atual contexto democrático de direito, os interesses empresariais de flexibilização da tutela trabalhista, apesar de atuarem legitimamente mediante uma racionalidade econômica no sentido de minimizar custos e maximizar riquezas, devem ser limitados pelas diretrizes constitucionais que, a partir de um robusto aparato normativo de proteção da pessoa humana, evidenciam a predileção pela tutela do trabalhador frente aos interesses mercantis, sob pena de nos distanciarmos a passos largos do ideal de justiça e equidade.PALAVRAS-CHAVE: Direito Constitucional do Trabalho. Flexibilização. Racionalidade econômica. Valor social do trabalho. ABSTRACT: The flexibilization of labor rights is an issue in the economic reality of our country, especially in the context of the economic crisis we are experiencing. The objective of this work is to reflect on the compatibility between the economic reasoning, linked with the current proposals for relativization of labor legislation, and the legal frameworks from Constitutional Economic Order, especially the social value of human labor. Through a bibliographical research and constitutional and infraconstitutional normative analysis, a digression will be made first on the evolution of the labor protection legal system and the flexibilizing proposals in history. Once the historical friction between corporate interests and labor social protection is observed, this work will focus on deepening the main characteristics that distinguish this antagonism between economic and labor-protection rationalities. Clarifying the premises concerning the different points of view that involve the theme and starting for the appreciation in a more abstract, axiological constitutional plan, the text will follow in order to investigate how the patrimonialist viewpoint of the economic categories should be compatible with the social purposes related to the valorization of human work, based on a moral (Dworkinian) interpretation of the constitutional problem. In the end, we will propose that, in the current democratic context of law, the business interests in flexibilization of labor protection, although acting legitimately through economic rationality to minimize costs and maximize wealth, should be limited by the constitutional guidelines that, from a robust normative apparatus of human protection, evidences the predilection for the protection of the worker against the mercantile interests, otherwise we would distance ourselves from the ideal of justice and equity.KEYWORDS: Constitutional Labor Law. Flexibilization. Economic rationality. Social value of labor. Submetido em: 31-03-2017Aprovado em: 14-07-201

Probable detection of starlight reflected from the giant exoplanet orbiting tau Bootis

Giant planets orbiting stars other than the Sun are clearly detectable through precise radial-velocity measurements of the orbital reflex motion of the parent star. In the four years since the discovery of the companion to the star 51 Peg, similar low-amplitude ``Doppler star wobbles'' have revealed the presence of some 20 planets orbiting nearby solar-type stars. Several of these newly-discovered planets are very close to their parent stars, in orbits with periods of only a few days. Being an indirect technique, however, the reflex-velocity method has little to say about the sizes or compositions of the planets, and can only place lower limits on their masses. Here we report the use of high-resolution optical spectroscopy to achieve a probable detection of the Doppler-shifted signature of starlight reflected from one of these objects, the giant exoplanet orbiting the star tau Bootis. Our data give the planet's orbital inclination i=29 degrees, indicating that its mass is some 8 times that of Jupiter, and suggest strongly that the planet has the size and reflectivity expected for a gas-giant planet.Comment: 15 pages, 4 figures. (Fig 1 and equation for epsilon on p1 para 2 revised; changed from double to single spacing

Evaluation of two lead malaria transmission blocking vaccine candidate antibodies in natural parasite-vector combinations.

Transmission blocking vaccines (TBV) which aim to control malaria by inhibiting human-to-mosquito transmission show considerable promise though their utility against naturally circulating parasites remains unknown. The efficacy of two lead candidates targeting Pfs25 and Pfs230 antigens to prevent onwards transmission of naturally occurring parasites to a local mosquito strain is assessed using direct membrane feeding assays and murine antibodies in Burkina Faso. The transmission blocking activity of both candidates depends on the level of parasite exposure (as assessed by the mean number of oocysts in control mosquitoes) and antibody titers. A mathematical framework is devised to allow the efficacy of different candidates to be directly compared and determine the minimal antibody titers required to halt transmission in different settings. The increased efficacy with diminishing parasite exposure indicates that the efficacy of vaccines targeting either Pfs25 or Pfs230 may increase as malaria transmission declines. This has important implications for late-stage candidate selection and assessing how they can support the drive for malaria elimination

The Initial Mass Function in the Galactic Center

The Galactic Center contains the most massive young clusters in the Galaxy and serves as the closest example of a massive starburst region. Our recent results suggest that the Galactic Center environment produces massive clusters with relatively flat initial mass functions, as might be expected on theoretical grounds. I will discuss these recent results, along with evidence for star formation in the immediate vicinity of the super massive black hole at the Galactic Center. The results of this work might be useful in extrapolating to other galactic centers with similar conditions, as well as other starburst regions