Phenyl Saligenin Phosphate Induced Caspase-3 and c-Jun N-Terminal Kinase Activation in Cardiomyocyte-Like Cells

At present, little is known about the effect(s) of organophosphorous compounds (OPs) on cardiomyocytes. In this study we have investigated the effects of phenyl saligenin phosphate (PSP), two organophosphorothioate insecticides (diazinon and chlorpyrifos) and their acutely toxic metabolites (diazoxon and chlorpyrifos oxon) on mitotic and differentiated H9c2 cardiomyoblasts. OP-induced cytotoxicity was assessed by monitoring MTT reduction, LDH release and caspase-3 activity. Cytotoxicity was not observed with diazinon, diazoxon or chlorpyrifos oxon (48 h exposure; 200 μM). Chlorpyrifos-induced cytotoxicity was only evident at concentrations >100 μM. In marked contrast, PSP displayed pronounced cytotoxicity towards mitotic and differentiated H9c2 cells. PSP triggered the activation of JNK1/2, but not ERK1/2, p38 MAPK or PKB, suggesting a role for this pro-apoptotic protein kinase in PSP-induced cell death. The JNK1/2 inhibitor SP 600125 attenuated PSP-induced caspase-3 and JNK1/2 activation, confirming the role of JNK1/2 in PSP-induced cytotoxicity. Fluorescently labelled PSP (dansylated PSP) was used to identify novel PSP binding proteins. Dansylated PSP displayed cytotoxicity towards differentiated H9c2 cells. 2D-gel electrophoresis profiles of cells treated with dansylated PSP (25 μM) were used to identify proteins fluorescently labelled with dansylated PSP. Proteomic analysis identified tropomyosin, heat shock protein β-1 and nucleolar protein 58 as novel protein targets for PSP. In summary, PSP triggers cytotoxicity in differentiated H9c2 cardiomyoblasts via JNK1/2-mediated activation of caspase-3. Further studies are required to investigate whether the identified novel protein targets of PSP play a role in the cytotoxicity of this OP, which is usually associated with the development of OP-induced delayed neuropathy

Towards a unified theory of Sobolev inequalities

We discuss our work on pointwise inequalities for the gradient which are connected with the isoperimetric profile associated to a given geometry. We show how they can be used to unify certain aspects of the theory of Sobolev inequalities. In particular, we discuss our recent papers on fractional order inequalities, Coulhon type inequalities, transference and dimensionless inequalities and our forthcoming work on sharp higher order Sobolev inequalities that can be obtained by iteration.Comment: 39 pages, made some changes to section 1

Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review

There is mounting evidence that pulmonary arterial hypertension (PAH), asthma and chronic obstructive pulmonary disease (COPD) share important pathological features, including inflammation, smooth muscle contraction and remodeling. No existing drug provides the combined potential advantages of reducing vascular- and bronchial-constriction, and anti-inflammation. Vasoactive intestinal peptide (VIP) is widely expressed throughout the cardiopulmonary system and exerts a variety of biological actions, including potent vascular and airway dilatory actions, potent anti-inflammatory actions, improving blood circulation to the heart and lung, and modulation of airway secretions. VIP has emerged as a promising drug candidate for the treatment of cardiopulmonary disorders such as PAH, asthma, and COPD. Clinical application of VIP has been limited in the past for a number of reasons, including its short plasma half-life and difficulty in administration routes. The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of PAH, asthma, and COPD. This article reviews the physiological significance of VIP in cardiopulmonary system and the therapeutic potential of VIP-based agents in the treatment of pulmonary diseases

Basaltic Dyke with Specific Volcanogenic Structures and its geomorphic evolution: Unique Geoheritage of the Faroe Islands (North Atlantic Ocean)

Volcanic landforms resulting from Cenozoic volcanism represent the most peculiar features of global geodiversity and provide eminent narratives for geoeducation. Among them, however, relict volcanic forms and site-specific landforms in remote areas have received less attention. In this paper, we provide the first description of unique volcanogenic features (hereinafter referred to as pseudo-hieroglyphs) developed on a summit rock wall at the Sandfelli ridge near the village of Gjógv in the N Eysturoy Island (Faroe Islands). The geomorphic evolution of the ridge and rock wall during the Quaternary is described and detailed petrographic analyses of the volcanogenic features are provided. Based on observed petrographical features, we interpret the pseudo-hieroglyphs to probably represent unique examples of chaotic horizontal columnar jointing. Following the geomorphological and petrographic examination of the study site, we analyse current Faroese legislation aiming at nature conservation and use this case to discuss broader implications of geoheritage conservation and geotourism in distant regions.Vulkanická krajina vzniklá kenozoickým vulkanismem představuje nejpodivnější rysy globální geodiversity a poskytuje vynikající příběhy pro geovzdělávání. Méně pozornosti se však dostává reliktním vulkanickým formám a lokálním tvarům reliéfu v odlehlých oblastech. V tomto článku přinášíme první popis unikátních vulkanogenních tvarů (dále jen "pseudo-hieroglyfy"), které se vyvíjely na skalní stěně vrcholu na hřbetě Sandfelli u vesnice Gjógv v severní části ostrova Eysturoy (Faerské ostrovy). Je popsán geomorfologický vývoj hřbetu a skalní stěny během kvartéru a jsou uvedeny podrobné petrografické analýzy vulkanogenních vlastností. Na základě pozorovaných petrografických rysů interpretujeme pseudo-hieroglyfy, které pravděpodobně představují jedinečné příklady chaotické horizontální sloupcovité odlučnosti. Po geomorfologickém a petrografickém studiu zájmové lokality analyzujeme současnou faerskou legislativu zaměřenou na ochranu přírody a užíváme tohoto příkladu k diskusi širších důsledků zachování a geoturistiky geografického dědictví ve vzdálených regionech

Crise de abastecimento de água em São Paulo e falta de planejamento estratégico

Embora a crise no abastecimento de água na Região Metropolitana de São Paulo (RMSP) tenha se manifestado de maneira mais intensa no verão de 2013-2014, ela revela um problema crônico que vem afetando toda a Região nos últimos dez anos. Esse problema foi gerado pela falta de um planejamento estratégico que considere questões climatológicas que podem indicar, com meses de antecedência, problemas de recomposição dos níveis dos mananciais, permitindo que ações sejam empreendidas com razoável antecedência, reduzindo os impactos para a população. Este estudo mostra como é possível utilizar informações climáticas na gestão estratégica do sistema de abastecimento da RMSP.Though the crisis in the water supplying system in the Metropolitan Region of São Paulo (RMSP) was more intensively felt in the 2013-2014 summer, it reveals a chronic problem that has been affecting the whole RMSP for the past ten years. This problem is originated from the lack of a strategic planning that takes into consideration climate issues that could, months before, foresee problems to restore the levels of water resources, allowing measures to be implemented within a reasonable anticipation, therefore reducing the impacts on the population. This study shows how it is possible to use climate information in the strategic management of the water supply in the RMSP