A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P

The absence of the fragile X mental retardation protein (FMRP), encoded by the FMR1 gene, is responsible for pathologic manifestations in the Fragile X Syndrome, the most frequent cause of inherited mental retardation. FMRP is an RNA-binding protein associated with polysomes as part of a messenger ribonucleoprotein (mRNP) complex. Although its function is poorly understood, various observations suggest a role in local protein translation at neuronal dendrites and in dendritic spine maturation. We present here the identification of CYFIP1/2 (Cytoplasmic FMRP Interacting Proteins) as FMRP interactors. CYFIP1/2 share 88% amino acid sequence identity and represent the two members in humans of a highly conserved protein family. Remarkably, whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P/2P, CYFIP1 interacts exclusively with FMRP. FMRP–CYFIP interaction involves the domain of FMRP also mediating homo- and heteromerization, thus suggesting a competition between interaction among the FXR proteins and interaction with CYFIP. CYFIP1/2 are proteins of unknown function, but CYFIP1 has recently been shown to interact with the small GTPase Rac1, which is implicated in development and maintenance of neuronal structures. Consistent with FMRP and Rac1 localization in dendritic fine structures, CYFIP1/2 are present in synaptosomal extracts.

The joining (J) chain is present in invertebrates that do not express immunoglobulins.

Joining (J) chain is a component of polymeric, but not monomeric, immunoglobulin (Ig) molecules and may play a role in their polymerization and transport across epithelial cells. To date, study of the J chain has been confined to vertebrates that produce Ig and in which the J chain displays a considerable degree of structural homology. The role of the J chain in Ig polymerization has been questioned and, since the J chain can be expressed in lymphoid cells that do not produce Ig, it is possible that the J chain may have other functions. To explore this possibility, we have surveyed J-chain gene, mRNA, and protein expression by using reverse transcriptase-coupled PCR, Northern blot analysis, and immunoblot analysis in invertebrate species that do not produce Ig. We report that the J-chain gene is expressed in invertebrates (Mollusca, Annelida, Arthropoda, Echinodermata, and Holothuroidea), as well as in representative vertebrates (Mammalia, Teleostei, Amphibia). Furthermore, J-chain cDNA from the earthworm has a high degree of homology (68-76%) to human, mouse, and bovine J chains. Immunohistochemical studies reveal that the J chain is localized in the mucous cells of body surfaces, intestinal epithelial cells, and macrophage-like cells of the earthworm and slug. This study suggests that the J chain is a primitive polypeptide that arose before the evolution of Ig molecules and remains highly conserved in extent invertebrates and vertebrates.

cGMP mediates the vascular and platelet actions of nitric oxide: confirmation using an inhibitor of the soluble guanylyl cyclase.

The L-arginine:nitric oxide (NO) pathway is believed to exert many of its physiological effects via stimulation of the soluble guanylyl cyclase (SGC); however, the lack of a selective inhibitor of this enzyme has prevented conclusive demonstration of this mechanism of action. We have found that the compound 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) inhibits the elevation of cGMP induced by the NO donor S-nitroso-DL-penicillamine in human platelets and rat vascular smooth muscle (IC50 = 10-60 nM and <10 nM, respectively) and that this is accompanied by prevention of the platelet inhibitory and vasodilator actions of NO donors. ODQ also inhibited the antiaggregatory action of NO generated by the platelets but did not affect the action of prostacyclin or that of a cGMP mimetic. In addition, ODQ inhibited the vasodilator actions of endogenously released NO and of NO generated after induction of NO synthase in vascular preparations. It did not, however, affect the increase in vascular smooth muscle cGMP or the dilatation induced by atrial natriuretic factor. ODQ had no effect on NO synthase activity, nor did it react with NO. It did, however, potently (IC50 approximately 10 nM) inhibit the activity of the SGC in cytosol obtained from crude extract of rat aortic smooth muscle. Thus ODQ prevents the actions of NO on platelets and vascular smooth muscle through its potent inhibitory effect on the SGC.

Elongation factor 1 alpha concentration is highly correlated with the lysine content of maize endosperm.

Lysine is the most limiting essential amino acid in cereals, and for many years plant breeders have attempted to increase its concentration to improve the nutritional quality of these grains. The opaque2 mutation in maize doubles the lysine content in the endosperm, but the mechanism by which this occurs is unknown. We show that elongation factor 1 alpha (EF-1 alpha) is overexpressed in opaque2 endosperm compared with its normal counterpart and that there is a highly significant correlation between EF-1 alpha concentration and the total lysine content of the endosperm. This relationship is also true for two other cereals, sorghum and barley. It appears that genetic selection for genotypes with a high concentration of EF-1 alpha can significantly improve the nutritional quality of maize and other cereals.

Specific induction of cAMP in Langerhans cells by calcitonin gene-related peptide: relevance to functional effects.

Epidermal Langerhans cells (LC) are associated anatomically with epidermal nerves, and a product of these nerves, calcitonin gene-related peptide (CGRP), inhibits the antigen-presenting capacity of LC and macrophages. As the CGRP receptor appears to be coupled to Gs alpha protein, which in turn activates adenylate cyclase, the ability of CGRP to induce cAMP in LC was examined and correlated with functional effects. LC were isolated from murine epidermal cells using antibodies on magnetic microspheres. Exposure to CGRP induced a significant increase in cAMP content, which could be inhibited by coculture with a truncated form of CGRP [CGRP-(8-37)] that is a specific competitive inhibitor of CGRP. Substance P and calcitonin failed to induce cAMP in LC. Although culture in CGRP reduced the ability of murine epidermal cells enriched for LC content to present pigeon cytochrome c to a responsive clone or to present antigen for elicitation of delayed-type hypersensitivity in immune mice, culture in forskolin had little or no effect on antigen presentation despite increased cAMP content of LC as much or more than that induced by CGRP. The effect of CGRP on antigen presentation in these systems could be blocked with CGRP-(8-37). CGRP inhibited the induction of B7-2 by lipopolysaccharide on peritoneal macrophages and a LC line, whereas calcitonin did not. CGRP induces specific accumulation of cAMP in LC and inhibits LC antigen-presenting function by a receptor-mediated event. However, the induction of cAMP by itself does not account for inhibition of antigen presentation. Suppression of the expression of B7-2 may be one mechanism by which CGRP inhibits antigen presentation.

Detecção e caracterização moleculares de Picobirnavirus bovino na região centro-sul do Brasil

Picobirnavirus (PBV) pertencem à família Picobirnaviridae, divididos em duas espécies Human Picobirnavirus e Rabbit Picobirnavirus. São pequenos vírus constituídos de genoma bissegmentado de cadeia dupla de RNA (dsRNA), não envelopados, com capsídeo de simetria icosaédrica, sendo divididos em dois genogrupos, GI e GII. Já foram detectados em fezes humanas e de uma ampla gama de espécies animais, com ou sem sinais diarreicos, sendo considerados agentes emergentes e oportunistas, e seu potencial zoonótico foi sugerido. Entretanto, os estudos epidemiológicos e moleculares de PBV em bovinos são raros na literatura nacional e internacional. Devido à carência de dados a respeito de PBV em bovinos, o presente estudo foi realizado objetivando-se a detecção e caracterização moleculares de cepas de PVB bovinos dos genogrupos GI e GII em amostras fecais de bovinos com ou sem sintomatologia diarreica de diferentes idades e regiões do Brasil. O estudo foi conduzido a partir de 77 animais, obtendo-se 18 (23,3%) amostras positivas para GI, compreendendo animais provenientes dos estados de São Paulo, Minas Gerais e Goiás. Não foram detectadas amostras positivas para GII. A identidade nucleotídica das amostras obtidas apresentou média de 67,4% quando comparadas uma com as outras e de até 83,77% quando comparadas com amostras de PBV de referência. Na reconstrução filogenética, três amostras agruparam-se em clado de PVB humano e somente uma agrupou-se em clado de PVB bovino. Em síntese, os resultados obtidos indicam, de maneira inédita, a circulação de PVB bovino pertencente ao genogrupo GI em diferentes estados brasileiros, com perfis filogenéticos heterogêneos.

Filosofía de la pintura: cómo salvar a una clase del abismo

La pintura tiene mucho que aportar a la filosofía y más aún a la enseñanza de ésta, sobre todo si somos profesores de un grupo de educación secundaria que lo único que hace en nuestra asignatura es pintar y nosotros no queremos que la clase se convierta en una catástrofe. Hay estudiantes que desde muy pronto tienen clara cuál es su vocación y centran todo su esfuerzo únicamente en las asignaturas que consideran que tienen un vínculo más directo con ella. En este caso, nos encontramos con unos alumnos cuya única pasión es pintar y que consideran que asignaturas como filosofía nada tiene que ver con la que será su ocupación futura y, por ello, se pasan la clase muy concentrados en su lámina y sus rotuladores. En esta situación, la única salida es discutir acerca de qué relación existe entre pintura y filosofía y adaptar a un nivel de secundaria las ideas que nacen de esa reflexión para conseguir nuestro objetivo: que los alumnos estén motivados de tal forma que así aumenten su esfuerzo e implicación en el aula y que todo ello les ayude en su proceso de aprendizaje de manera efectiva y positiva. Y, lo más importante, que el cambio que efectúen no sea sólo momentáneo, sino que tenga una continuidad a largo plazo.

Determinantes principales de la función diastólica del ventrículo derecho

Cada vez más evidencia demuestra la importancia de la función sistólica y diastólica del ventrículo derecho en el ámbito clínico. Sin embargo, múltiples aspectos de las bases mecánicas de la diástole ventricular derecha siguen siendo desconocidos. La mayor parte del llenado ventricular derecho tiene lugar en las fases iniciales de la diástole y, al igual que en el ventrículo izquierdo, la relajación y el comportamiento pasivo de la cámara deben determinar la despresurización y el llenado rápido durante esta fase. Sin embargo, el papel de dichas propiedades nunca ha sido cuantificado en el ventrículo derecho. Recientemente se ha demostrado que la aplicación de métodos numéricos de optimización multidimensional al análisis de datos de presión y volumen permite caracterizar las propiedades diastólicas del ventrículo izquierdo de forma más completa, exacta, y reproducible que con los métodos convencionales. Dicha metodología permite medir no sólo la rigidez sino también la contribución de las fuerzas de retroceso elástico a la despresurización ventricular. El presente trabajo se diseñó con el fin de aplicar esta misma metodología al estudio de la diástole del ventrículo derecho. Por su disposición anatómica, la fisiología del ventrículo derecho está en parte condicionada por el fenómeno de interdependencia con el ventrículo izquierdo. Así, la geometría de la cámara puede modificar en parte las propiedades diastólicas. Por ello, otro objetivo de este estudio fue establecer el impacto de los cambios de la geometría septal sobre las propiedades pasivas del ventrículo derecho...

Detecção de Enterococcus resistentes a vancomicina em criações comerciais de ovinos e caprinos das regiões centro-leste e nordeste do Estado de São Paulo

As exigências das condições higiênico-sanitárias na produção de animais de interesse zootécnico vêm aumentando progressivamente dada à necessidade de aliar-se produtividade a produtos de alta qualidade para atender a mercados consumidores cada vez mais exigentes. Nesse sentido, a utilização de antimicrobianos, tanto na profilaxia como na terapêutica, permanece como estratégia de controle para vários microrganismos patogênicos, de importância não apenas para a produção animal como também para a saúde humana, ainda que restrições ao uso indiscriminado desses produtos têm se intensificado. Não obstante, o uso excessivo desses produtos está associado à seleção de microrganismos resistentes nas áreas de produção. Por outro lado, investigações sobre circulação de cepas resistentes em rebanhos animais, até então restritas a populações humanas, ainda permanecem limitadas no Brasil. Bactérias do gênero Enterococcus, integrantes usuais da microbiota gastrointestinal animal e humana, são indicadoras ambientais de contaminação fecal e tem-se tornado objeto de preocupação em saúde pública e veterinária dada a ocorrência de cepas resistentes à vancomicina (VRE). O presente trabalho teve como objetivo isolar, quantificar e caracterizar VRE presentes em amostras fecais de ovinos oriundos de pequenas propriedades das regiões centro-leste e nordeste do estado de São Paulo. Para tanto, 132 amostras fecais foram coletadas diretamente do reto dos animais ou do piso das instalações. As amostras foram semeadas em ágar m-Enterococcus e subcultivadas em Ágar Bile Esculina acrescido de 6 µg/mL de vancomicina (ABEV), para confirmação de Enterococcus spp e detecção de cepas resistentes. Procedeu-se igualmente a observação da morfologia, características tintoriais, bioquímicas e moleculares. O número máximo de Enterococcus spp. encontrado foi de 2,6 × 105 e 1,70 × 105 UFC/g de fezes do ambiente e dos animais, respectivamente. Na caracterização bioquímica espécies mais prevalentes foram: Enterococcus faecalis e Vagococcus fluvialis. No ABEV, houve crescimento de colônias VRE em 33 das 84 amostras de ovinos-caprinos e em 21 das 48 amostras ambientais, representando, respectivamente 46,7% e 29,3% das amostras analisadas. A análise por multiplex PCR das 54 cepas VRE obtidas indicaram que 23 (43%), 22 (41%), 2 (3,5%) e 2 (3,5%) foram positivas, respectivamente, para os genes vanC2/C3, vanC1, vanA e vanB, sendo que para 5,3% dos isolados nenhum produto foi amplificado, sugerindo a possível ocorrência de genes dos demais grupos van conhecidos entre os isolados. Os resultados obtidos indicam, de forma inédita no país, a circulação de VRE em propriedades produtoras de ovinos e caprinos, sem ocorrência de manifestações clínicas aparentes nos animais, porém com possíveis riscos à saúde dos produtores e profissionais envolvidos, bem como a eventuais consumidores.

Havana, Cuba, 1762 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: A plan of the Havana and its environs : with several posts and attacks made by the British forces under the command of the Earl of Albemarle and Sr. Geo. Pocock which was taken 13 Aug. 1762, Ths. Kitchin sculpt. engraver to H.R.H. the Duke of York. It was published by J. Boydell engraver in Cheapside & R. Willcock bookseller in Cornhill, Novr. 1st 1762. Scale [ca. 1:24,000]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'NAD 1927 Cuba Norte' coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map.This map shows features associated with the British Siege of Havana, 1762, such as roads, drainage, built-up areas and selected buildings, fortifications, lines of fire, troop placement, ship locations, ground cover, and more. Relief is shown by hachures; Depths are shown by soundings. Includes indexes for: References to the Moro -- Attack on the Moro -- References to the Town and Harbour -- Attack on the Town and Defences of that Side.This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Da queda de Tróia à fundação de Lisboa ou de como Gabriel Pereira de Castro espera ‘cantar de Ulisses, imitando a Homero’

No poema épico seiscentista Ulisseia ou Lisboa Edificada, Gabriel Pereira de Castro reescreve as aventuras de Ulisses, fazendo o navegador homérico aportar à costa lusitana e aí travar uma guerra pela fundação da cidade de Lisboa. Ainda que a estrutura geral desta epopeia portuguesa seja decalcada da epopeia vergiliana (a primeira metade corresponde à fase das viagens e a segunda metade corresponde à fase dos confrontos bélicos), rigorosamente a Ulisseia não representa senão “um novo episódio acrescentado à Odisseia de Homero” (Segurado e Campos 2004, Vol. II, 43). Neste trabalho, proponho-me fazer uma análise comparativa entre as jornadas de Ulisses na Ulisseia e as jornadas do facundo herói no modelo antigo, averiguando o modo como o trajecto marítimo de Tróia a Ítaca é alargado, nuns casos, e abreviado, noutros casos, mediante o engenho do autor português. São sobretudo os propósitos nacionalistas e a confluência de diferentes fontes antigas que justificam a maior parte dos desvios às aventuras marítimas do Ulisses odisseico.

Investment behaviour of EU arable crop farms in selected EU countries and the impact of policy reforms. Factor Markets Working Document No. 42, May 2013

This deliverable provides a comparative analysis, among selected EU member states, of the investment demand of a sample of specialised field crop farms for farm buildings, machinery and equipment as determined by different types and levels of Common Agricultural Policy support. It allows for the existence of uncertainty in the price of output farmers receive and for both long- and short-run determinants of investment levels, as well as for the presence of irregularities in the cost adjustment function due to the existence of threshold-type behaviours. The empirical estimation reveals that three investment regimes are consistently identified in Germany and Hungary, across asset and support types, and in France for machinery and equipment. More traditional disinvestment-investment type behaviours characterise investment in farm building in France and the UK, across support types, and Italy for both asset classes under coupled payments. The long-run dynamic adjustment of capital stocks is consistently and significantly estimated to be towards a – mostly non-stationary – lower level of capitalisation of the farm analysed. By contrast, the expected largely positive short-run effects of an increase in output prices are often not significant. The effect of CAP support on both types of investment is positive, although seldom significant, while the proxy for uncertainty employed fails to be significant yet, in most cases, has the expected effect of reducing the investment levels.

Simulation Results on the Impact of Changes in the Main EU Policy Tools on Farm Investment Behaviour. Factor Markets Working Document No. 56, June 2013

This paper completes the comparative analysis of the investment demand behaviour, of a sample of specialised arable crop farms, for farm buildings and machinery and equipment, as a function of the different types and levels of Common Agricultural Policy support, in selected European Union Member States. This contribution focuses on their quantitative interdependence calculating the relevant elasticity measures. In turn, they constitute the methodological tool to simulate the percentage expected change in average net investment levels associated to the implementation of the, recently proposed and currently under discussion, reductions in the Pillar I Direct Payments disbursed under the Common Agricultural Policy. Evidence suggests a statistically significant elastic and inelastic relationship between both types of subsidies and the investment levels for both asset classes in Germany and Italy, respectively. An elastic dependence of investment in farm buildings on decoupled subsidies exists in Hungary while changes in the level of coupled payments appear to translate into less than proportional changes in the demand for both farm buildings and machinery and equipment in France. Coupled payments appear to influence the UK demand for both asset classes in an elastic manner while decoupled support seems to induce a similar effect on investment in machinery and equipment. Since the currently discussed Common Agricultural Policy reform options imply, almost exclusively, a reduction in the level of support granted through Direct Payments, simulated effects were expected to reveal a worsening of the farm investment prospects for both asset types (i.e., a larger negative investment or a smaller positive one). The actual evidence largely respects this expectation with the sole exception of investment in machinery and equipment in France and Italy reaching smaller negative or larger positive levels irrespectively of the magnitude of the implemented cuts in Direct Payments.

Comparação de modelos estáticos, otimização dos determinantes da estrutura de capital das PME's portuguesas

Dissertação, Mestrado, Contabilidade e Fiscalidade, Instituto Politécnico de Santarém, Escola Superior de Gestão e Tecnologia, 2016