Characterization of a plasminogen activator and its inhibitor in human mesangial cells

Characterization of a plasminogen activator and its inhibitor in human mesangial cells. In the course of some pathological and experimental nephropathies, intraglomerular fibrin deposits develop, possibly as a consequence of inefficient fibrinolysis. In vitro human glomeruli exhibit fibrinolytic activity due to the synthesis of plasminogen activators (PAs) such as, tissue-type PA (t-PA) and urokinase-type PA (u-PA). Immunofluorescence studies have previously shown that t-PA is localized in the capillary tufts and u-PA in the visceral epithelial cells. We have now investigated the fibrinolytic activity of cultured human mesangial cells. Inhibitory activity towards u-PA or t-PA but not plasmin was found in both conditioned medium and cellular extracts. Analysis of the conditioned medium by zymography revealed a single band of PA-activity (Mr: 110 to 120 kDa). Immunoneutralization with anti-t-PA and antiplasminogen activator inhibitor (PAI-1) IgG but not anti-u-PA or anti-PAI-2 removed this band. Reverse fibrin autography demonstrated the presence of PAI-1 in both cellular extracts and in conditioned medium. Western Blot analysis showed that two bands (50 kD and 120 kD) were recognized by the anti-PAI-1 antibody. By ELISA t-PA and PAI-1 antigens were found to increase progressively with time in the culture medium but not in cellular extracts. Both t-PA and PAI-1, but not u-PA and PAI-2, were also detected by immunofluorescence studies. Thus human glomerular mesangial cells synthesize and secrete t-PA and PAI-1 in vitro. PAI-1 is produced in excess, therefore t-PA is only found in the form of a complex with PAI-1

VITRUV - Science Cases

VITRUV is a second generation spectro-imager for the PRIMA enabled Very Large Telescope Interferometer. By combining simultaneously up to 8 telescopes VITRUV makes the VLTI up to 6 times more efficient. This operational gain allows two novel scientific methodologies: 1) massive surveys of sizes; 2) routine interferometric imaging. The science cases presented concentrate on the qualitatively new routine interferometric imaging methodology. The science cases are not exhaustive but complementary to the PRIMA reference mission. The focus is on: a) the close environment of young stars probing for the initial conditions of planet formation and disk evolution; b) the surfaces of stars tackling dynamos, activity, pulsation, mass-loss and evolution; c) revealing the origin of the extraordinary morphologies of Planetary Nebulae and related stars; d) studying the accretion-ejection structures of stellar black-holes (microquasars) in our galaxy; e) unveiling the different interacting components (torus, jets, BLRs) of Active Galactic Nuclei; and f) probing the environment of nearby supermassive black-holes and relativistic effects in the Galactic Center black-hole.Comment: 15 pages. The Power of Optical/IR Interferometry: Recent Scientific Results and 2nd Generation VLTI Instrumentation, Allemagne (2005) in pres

What's in a copy?

ABSTRACTI will answer the question “What’s in a copy?” by considering three sets of related issues: the importance of copies in academia; in cultural life; and in the economic world. In academia the current capability of making copies is challenging pedagogical practices and the trust of its members, plagiarism being the most immediate problem. The notion of authorship is also undergoing changes provoked by a proliferation of authors and new possibilities opened up by cyberspace. In cultural life, imitation and mimesis have long been fundamental engines of socialization. Our enhanced capacity of copying problematizes, with new intensity, the relationships between homogeneity and heterogeneity, between the genuine and the spurious. In the economic world, the digital era is threatening some of the fundamental tenets of capitalism, especially of its variant called the “knowledge society”, regarding the control of intellectual property rights. The gap between normativity and social practices is widening. The many dilemmas and tensions identified in the text are understood as symptoms of two major characteristics of the current times: hyperfetishism and hyperanimism. ________________________________________________________________________________ RESUMOResponderei à pergunta “O que existe em uma cópia?” considerando três conjuntos de questões relacionadas: a importância das cópias na academia, na vida cultural, no mundo econômico. Na academia a presente capacidade de fazer cópias está desafiando práticas pedagógicas e a confiança dos seus membros, o plágio sendo o problema mais imediato. A noção de autoria também está sofrendo mudanças provocadas por uma proliferação de autores e novas possibilidades abertas pelo ciberespaço. Na vida cultural, a imitação e a mimese de há muito são importantes motores de socialização. A nossa capacidade ampliada de fazer cópias problematiza, com nova intensidade, as relações entre homogeneidade e heterogeneidade, entre o genuíno e o espúrio. No mundo econômico, a era digital ameaça algumas das premissas fundamentais do capitalismo, especialmente da sua variante “sociedade do conhecimento”, no tocante aos direitos de propriedade intelectual. Cresce a distância entre normatividade e práticas sociais. Os muitos dilemas e tensões identificados no texto são compreendidos como sintomas de duas grandes características do presente: o hiperfetichismo e o hiperanimismo

SPICES: Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems

SPICES (Spectro-Polarimetric Imaging and Characterization of Exoplanetary Systems) is a five-year M-class mission proposed to ESA Cosmic Vision. Its purpose is to image and characterize long-period extrasolar planets and circumstellar disks in the visible (450 - 900 nm) at a spectral resolution of about 40 using both spectroscopy and polarimetry. By 2020/22, present and near-term instruments will have found several tens of planets that SPICES will be able to observe and study in detail. Equipped with a 1.5 m telescope, SPICES can preferentially access exoplanets located at several AUs (0.5-10 AU) from nearby stars ($<$25 pc) with masses ranging from a few Jupiter masses to Super Earths ($\sim$2 Earth radii, $\sim$10 M$_{\oplus}$) as well as circumstellar disks as faint as a few times the zodiacal light in the Solar System

Training of Instrumentalists and Development of New Technologies on SOFIA

This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal Survey (Astro2010)1 Committee on the State of the Profession to emphasize the potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to contribute to the training of instrumentalists and observers, and to related technology developments. This potential goes beyond the primary mission of SOFIA, which is to carry out unique, high priority astronomical research. SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable astronomical observations anywhere, any time, and at most wavelengths between 0.3 microns and 1.6 mm not accessible from ground-based observatories. These attributes, accruing from the mobility and flight altitude of SOFIA, guarantee a wealth of scientific return. Its instrument teams (nine in the first generation) and guest investigators will do suborbital astronomy in a shirt-sleeve environment. The project will invest $10M per year in science instrument development over a lifetime of 20 years. This, frequent flight opportunities, and operation that enables rapid changes of science instruments and hands-on in-flight access to the instruments, assure a unique and extensive potential - both for training young instrumentalists and for encouraging and deploying nascent technologies. Novel instruments covering optical, infrared, and submillimeter bands can be developed for and tested on SOFIA by their developers (including apprentices) for their own observations and for those of guest observers, to validate technologies and maximize observational effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on State of the Professio

The future of evapotranspiration : global requirements for ecosystem functioning, carbon and climate feedbacks, agricultural management, and water resources

The fate of the terrestrial biosphere is highly uncertain given recent and projected changes in climate. This is especially acute for impacts associated with changes in drought frequency and intensity on the distribution and timing of water availability. The development of effective adaptation strategies for these emerging threats to food and water security are compromised by limitations in our understanding of how natural and managed ecosystems are responding to changing hydrological and climatological regimes. This information gap is exacerbated by insufficient monitoring capabilities from local to global scales. Here, we describe how evapotranspiration (ET) represents the key variable in linking ecosystem functioning, carbon and climate feedbacks, agricultural management, and water resources, and highlight both the outstanding science and applications questions and the actions, especially from a space-based perspective, necessary to advance them

Multifocal Ectopic Purkinje-Related Premature Contractions: A New SCN5A-Related Cardiac Channelopathy.: MEPPC: a new SCN5A-related cardiac channelopathy

International audienceOBJECTIVES: The aim of this study was to describe a new familial cardiac phenotype and to elucidate the electrophysiological mechanism responsible for the disease. BACKGROUND: Mutations in several genes encoding ion channels, especially SCN5A, have emerged as the basis for a variety of inherited cardiac arrhythmias. METHODS: Three unrelated families comprising 21 individuals affected by multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by narrow junctional and rare sinus beats competing with numerous premature ventricular contractions with right and/or left bundle branch block patterns were identified. RESULTS: Dilated cardiomyopathy was identified in 6 patients, atrial arrhythmias were detected in 9 patients, and sudden death was reported in 5 individuals. Invasive electrophysiological studies demonstrated that premature ventricular complexes originated from the Purkinje tissue. Hydroquinidine treatment dramatically decreased the number of premature ventricular complexes. It normalized the contractile function in 2 patients. All the affected subjects carried the c.665G>A transition in the SCN5A gene. Patch-clamp studies of resulting p.Arg222Gln (R222Q) Nav1.5 revealed a net gain of function of the sodium channel, leading, in silico, to incomplete repolarization in Purkinje cells responsible for premature ventricular action potentials. In vitro and in silico studies recapitulated the normalization of the ventricular action potentials in the presence of quinidine. CONCLUSIONS: A new SCN5A-related cardiac syndrome, MEPPC, was identified. The SCN5A mutation leads to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular-Purkinje system. The MEPPC syndrome is responsive to hydroquinidine

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts