Occurrence of poly(alpha2,8-deaminoneuraminic acid) in mammalian tissues: widespread and developmentally regulated but highly selective expression on glycoproteins.

In tissues of higher organisms homopolymers of alpha2,8-linked N-acetylneuraminic acid can be found as a posttranslational modification on selected proteins. We report here the discovery of homopolymers of alpha2,8-linked deaminoneuraminic acid [poly(alpha2,8-KDN)] in various tissues derived from all three germ layers in vertebrates including mammals. The monoclonal antibody kdn8kdn in conjunction with a bacterial KDNase permitted the detection of poly(alpha2,8-KDN) by immunohistochemistry and immunoblotting. Further evidence for the existence of poly(alpha2,8-KDN) was obtained by gas/liquid chromatography. The poly(alpha2,8-KDN) glycan was detectable in all tissues studied with the exception of mucus-producing cells present in various organs, the extracellular matrix, and basement membranes. However, in certain organs such as muscle, kidney, lung, and brain its expression was developmentally regulated. Despite its widespread tissue distribution, the poly(alpha2,8-KDN) glycan was detected on a single 150-kDa glycoprotein except for a single >350-kDa glycoprotein in kidney, which makes it most distinctive among polysialic acids. The ubiquitous yet selective expression may be indicative of a general function of the poly(alpha2,8-KDN)-bearing glycoproteins.

Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys.

The selective activation of the prefrontal cortical dopamine system by mild stress can be mimicked by anxiogenic beta-carbolines such as FG7142. To investigate the functional relevance of elevated levels of dopamine turnover in the prefrontal cortex, the current study examined the effects of FG7142 on the performance of spatial working memory tasks in the rat and monkey. FG7142 selectively increased prefrontal cortical dopamine turnover in rats and significantly impaired performance on spatial working memory tasks in both rats and monkeys. Spatial discrimination, a task with similar motor and motivational demands (rats), or delayed response performance following zero-second delays (monkeys) was unaffected by FG7142. Further, biochemical analysis in rats revealed a significant positive correlation between dopamine turnover in the prefrontal cortex and cognitive impairment on the delayed alternation task. The cognitive deficits in both rats and monkeys were prevented by pretreatment with the benzodiazepine receptor antagonist, RO15-1788, which blocked the increase in dopamine turnover and by the dopamine receptor antagonists, haloperidol, clozapine, and SCH23390. These findings indicate that excessive dopamine activity in the prefrontal cortex is detrimental to cognitive functions mediated by the prefrontal cortex.

Longevity and the genetic determination of collagen glycoxidation kinetics in mammalian senescence.

A fundamental question in the basic biology of aging is whether there is a universal aging process. If indeed such a process exists, one would expect that it develops at a higher rate in short- versus long-lived species. We have quantitated pentosidine, a marker of glycoxidative stress in skin collagen from eight mammalian species as a function of age. A curvilinear increase was modeled for all species, and the rate of increase correlated inversely with maximum life-span. Dietary restriction, a potent intervention associated with increased life-span, markedly inhibited glycoxidation rate in the rodent. On the assumption that collagen turnover rate is primarily influenced by the crosslinking due to glycoxidation, these results suggest that there is a progressive age-related deterioration of the process that controls the collagen glycoxidation rate. Thus, the ability to withstand damage due to glycoxidation and the Maillard reaction may be under genetic control.

Grb-IR: a SH2-domain-containing protein that binds to the insulin receptor and inhibits its function.

To identify potential signaling molecules involved in mediating insulin-induced biological responses, a yeast two-hybrid screen was performed with the cytoplasmic domain of the human insulin receptor (IR) as bait to trap high-affinity interacting proteins encoded by human liver or HeLa cDNA libraries. A SH2-domain-containing protein was identified that binds with high affinity in vitro to the autophosphorylated IR. The mRNA for this protein was found by Northern blot analyses to be highest in skeletal muscle and was also detected in fat by PCR. To study the role of this protein in insulin signaling, a full-length cDNA encoding this protein (called Grb-IR) was isolated and stably expressed in Chinese hamster ovary cells overexpressing the human IR. Insulin treatment of these cells resulted in the in situ formation of a complex of the IR and the 60-kDa Grb-IR. Although almost 75% of the Grb-IR protein was bound to the IR, it was only weakly tyrosine-phosphorylated. The formation of this complex appeared to inhibit the insulin-induced increase in tyrosine phosphorylation of two endogenous substrates, a 60-kDa GTPase-activating-protein-associated protein and, to a lesser extent, IR substrate 1. The subsequent association of this latter protein with phosphatidylinositol 3-kinase also appeared to be inhibited. These findings raise the possibility that Grb-IR is a SH2-domain-containing protein that directly complexes with the IR and serves to inhibit signaling or redirect the IR signaling pathway.

Platelet-derived growth factor stimulates the secretion of hyaluronic acid by proliferating human vascular smooth muscle cells.

Total glycans from the cell layer and the culture medium of human vascular smooth muscle cells (VSMC) that had been cultivated in the presence of platelet-derived growth factor (PDGF) were isolated and purified by gel filtration after Pronase and DNase digestion and alkaliborohydride treatment. Measurements of the content of neutral hexoses and uronic acids revealed that PDGF stimulates total glycan synthesis by proliferating VSMC in a linear fashion from 24 h to 72 h of incubation. In contrast, total glycan synthesis by human fibroblasts, epithelial cells, or endothelial cells was not affected by PDGF, indicating cell-type specificity. Chemical, biochemical, and enzymological characterization of the total glycans synthesized by VSMC showed that PDGF stimulates the secretion of a 340-kDa glycan molecule in a time-dependent manner from 24 h to 72 h. This molecule is highly acidic, shares a common structure with hyaluronic acid, and exhibits a potent antiproliferative activity on VSMC. These results suggest that VSMC in response to PDGF are capable of controlling their own growth and migration by the synthesis of a specific form of hyaluronic acid with antiproliferative potency, which may be involved in the regulation of the local inflammatory responses associated with atherosclerosis.

Phospholipase D is present on Golgi-enriched membranes and its activation by ADP ribosylation factor is sensitive to brefeldin A.

ADP ribosylation factor (ARF) is a small guanosine triphosphate (GTP)-binding protein that regulates the binding of coat proteins to membranes and is required for several stages of vesicular transport. ARF also stimulates phospholipase D (PLD) activity, which can alter the lipid content of membranes by conversion of phospholipids into phosphatidic acid. Abundant PLD activity was found in Golgi-enriched membranes from several cell lines. Golgi PLD activity was greatly stimulated by ARF and GTP analogs and this stimulation could be inhibited by brefeldin A (BFA), a drug that blocks binding of ARF to Golgi membranes. Furthermore, in Golgi membranes from BFA-resistant PtK1 cells, basal PLD activity was high and not stimulated by exogenous ARF or GTP analogs. Thus, ARF activates PLD on the Golgi complex, suggesting a possible link between transport events and the underlying architecture of the lipid bilayer.

Evolution of the chalcone synthase gene family in the genus Ipomoea.

The evolution of the chalcone synthase [CHS; malonyl-CoA:4-coumaroyl-CoA malonyltransferase (cyclizing), EC 2.3.1.74] multigene family in the genus Ipomoea is explored. Thirteen CHS genes from seven Ipomoea species (family Convolvulaceae) were sequenced--three from genomic clones and the remainder from PCR amplification with primers designed from the 5' flanking region and the end of the 3' coding region of Ipomoea purpurea Roth. Analysis of the data indicates a duplication of CHS that predates the divergence of the Ipomoea species in this study. The Ipomoea CHS genes are among the most rapidly evolving of the CHS genes sequenced to date. The CHS genes in this study are most closely related to the Petunia CHS-B gene, which is also rapidly evolving and highly divergent from the rest of the Petunia CHS sequences.

Distinct functions of SR proteins in recruitment of U1 small nuclear ribonucleoprotein to alternative 5' splice sites.

Alternative splicing of precursor messenger RNAs (pre-mRNAs) is an important mechanism for the regulation of gene expression. The members of the SR protein family of pre-mRNA splicing factors have distinct functions in promoting alternative splice site usage. Here we show that SR proteins are required for the first step of spliceosome assembly, interaction of the U1 small nuclear ribonucleoprotein complex (U1 snRNP) with the 5' splice site of the pre-mRNA. Further, we find that individual SR proteins have distinct abilities to promote interaction of U1 snRNP with alternative 5' splice junctions. These results suggest that SR proteins direct 5' splice site selection by regulation of U1 snRNP assembly onto the pre-mRNA.

Valor de marca-país: uma investigação empírica em diferentes modelos operacionais e relações com imagem de país e percepção de cultura

Atualmente, os valores intangíveis são cada vez mais importantes no processo gerencial de empresas e governos, implicando a necessidade de informações mais precisas. Dentre os ativos intangíveis mais importantes encontram-se as marcas. É por meio das marcas que os consumidores escolhem e memorizam suas compras, e assim destinam seu dinheiro para algo que possa solucionar problemas em suas vidas. Marcas são formas de empresas e países conseguirem se diferenciar no mercado competitivo globalizado, e estas últimas são denominadas marca-país. A marca-país é fonte de conhecimento e associações no mercado, e torna o país mais ou menos atraente para os estrangeiros. Para se medir o valor de uma marca-país (country brand equity) utilizamse métodos específicos. Essa métrica perceptual é uma construção de valores baseados na marca-país, como conhecimento, associações, imagem, qualidade percebida e lealdade. Este trabalho visa compor um modelo de mensuração de country brand equity aplicável à realidade brasileira. Para tanto foram apresentados diversos modelos de avaliação de marcas e marca-país, por serem complementares, e testados empiricamente. Os dois principais modelos utilizados neste trabalho foram o modelo de valor de marca de Yoo, Donthu e Lee (2000), e o modelo de valor de marca-país de Pappu e Quester (2010). Como o construto de valor de marca-país é derivado de dimensões formativas que o compõem, foram somadas nessa equação as dimensões de imagem baseada na personalidade (AAKER, 1997) e percepção de cultura (NEWMAN; NOLLEN, 1996; HOFSTEDE; BOND, 1984). Todas as variáveis e composições de dimensões foram avaliadas quanto à sua confiabilidade, linearidade, normalidade, heterocedasticidade, multicolinearidade, correlações, formação de fatores e, por fim, avaliadas em regressões e modelos de equações estruturais. Foram criados dezesseis (16) modelos iniciais, nos quais se avaliou o poder de explicação dos construtos com a variável dependente proposta por Zeugner-Roth, Diamantopoulos e Montesinos (2008). Verificou-se pouca variabilidade entre os modelos. Em seguida, foram elaborados mais oito (8) modelos com a proxy de valor de marca-país pela reputação de marca-país, proposta por Kang e Yang (2010), na qual se pôde observar que os modelos com maior número de dimensões se mostraram melhores para explicar a variável dependente. Além disso, verificou-se a importância das dimensões de imagem e percepção de cultura nesses construtos. Por fim, esta tese apresenta modelos mais consistentes de avaliação de marca-país.

Strasbourg, France, 1823 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan de Strasbourg : avec tous les établissmens publics renfermés dans l'enceinte des fortifications, réduit par Ch. Rothé sur le plan général dressé en 1821 par Mr. N. J. Villot, architecte de la ville ; dessiné et écrit sur pierre par Clément Senefelder. It was published by la lithographie de F. G. Levrault, imprimeur du Roi in 1823. Scale [1:3,126]. Covers Strasbourg, France. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'European Datum 1950 UTM Zone 32N' 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 such as roads, drainage, built-up areas and selected buildings, fortification, ground cover, and more. 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.

Saint Petersburg, Russia, 1776 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Novoi plan stolichnago goroda i krieposti Sanktpeterburga original'noi chertezh sego plana nakhoditsia v arkhivie glavnoi Politsii, Grid: Kh. M. Rot. = Nouveau plan de la ville et de la forteresse de St. Pétersbourg, exécuté exactement d'après l'original qui se trouve dans les Archives de la Police, par C. M. Roth. It was published by C.M. Roth in 1776. Scale [ca. 1:20,000]. Covers Saint Petersburg, Russia. Map in Russian, French, and German. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'Pulkovo 1995 Gauss Kruger Zone 6N' 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 such as roads, drainage, built-up areas and selected buildings, fortification, ground cover, and more. Includes indexes. 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.

Neueste Karte der Koenigreiche Bosnien Servien Croatien und Slavonien: samt den angrœnzenden Provinzen Temeswar, Dalmatien, Herzegowina, Ragusa, Steyermark, Kærthen, Krain, Friaul, Gradiska, und Istrien, einem grossen Theil von Ungarn, Siebenbürgen, Walachei, Bulgarien, Albanien, Macedonien, und einem Stück des Kirchenstaats und K.reichs Neapel

nach den besten Originalzeichnungen Charten und Beschriebungen entworfen von Herrn Carl Schütz ; gestochen von C. Schütz und F. Müller.

Death Threat Letters: Allegories of American Authorship in the Age of Terrorism

This dissertation examines novels that use terrorism to allegorize the threatened position of the literary author in contemporary culture. Allegory is a term that has been differently understood over time, but which has consistently been used by writers to articulate and construct their roles as authors. In the novels I look at, the terrorist challenge to authorship results in multiple deployments of allegory, each differently illustrating the way that allegory is used and authorship constructed in the contemporary American novel. Don DeLillo’s Mao II (1991), first puts terrorists and authors in an oppositional pairing. The terrorist’s ability to traffic in spectacle is presented as indicative of the author’s fading importance in contemporary culture and it is one way that terrorism allegorizes threats to authorship. In Philip Roth’s Operation Shylock (1993), the allegorical pairing is between the text of the novel and outside texts – newspaper reports, legal cases, etc. – that the novel references and adapts in order to bolster its own narrative authority. Richard Powers’s Plowing the Dark (1999) pairs the story of an imprisoned hostage, craving a single book, with employees of a tech firm who are creating interactive, virtual reality artworks. Focusing on the reader’s experience, Powers’s novel posits a form of authorship that the reader can take into consideration, but which does not seek to control the experience of the text. Finally, I look at two of Paul Auster’s twenty-first century novels, Travels in the Scriptorium (2007) and Man in the Dark (2008), to suggest that the relationship between representations of authors and terrorists changed after 9/11. Auster’s author-figures forward an ethics of authorship whereby novels can use narrative to buffer readers against the portrayal of violent acts in a culture that is suffused with traumatizing imagery.

Carbon leakage: an overview. CEPS Special Report No. 79, 6 December 2013

Carbon leakage is central to the discussion on climate policy, given the confluence of issues that are currently being debated, including the 2030 Energy and Climate Framework and the review of the EU carbon leakage list by 2014. Carbon leakage is the result of asymmetrical carbon policies, especially carbon pricing, and the resulting carbon cost, which affects the international competitive position of some EU industry and could displace production and/or investment, and the emissions of the activities displaced. This paper identifies the difference between carbon price and carbon cost to leakage exposed industry as one of two fundamental issues to be understood and addressed; lack of visibility on future climate policies and anti-leakage provisions is the other key issue. While this is a global issue, most of the experience has been accumulated in the EU. Carbon leakage is only one of the factors that could affect the competitive position of sectors, but it is difficult to attribute the impact of carbon costs versus other variables such as energy costs, labour, etc. Studies have predicted the risk of a significant amount of production leakage in a number of energy-intensive industries. To address the danger, they were included in the EU ETS carbon leakage list, which gave them access to free allowances. However, a limited number of studies undertaken after the end of the second trading period (2012) show little evidence of production leakage and asks the question whether the issue has not been blown out of proportion. The paper argues that the past may not be a good representation of the future, as it was heavily influenced by a high level of free allocation, the exceptional economic downturn, CO2 prices significantly below what was anticipated, as well as the potential for changes in some fundamental variables such as the shrinking pool of allowances available for free allocation. It emphasises the need for a well-informed debate in the EU on measures to address carbon leakage post-2020, underpinned by a number of options, and objective criteria to evaluate those options. It emphasises that the debate should cover both investment and production leakage, caused by both direct and indirect carbon costs.

The Europe 2020 Strategy: Can it maintain the EU’s competitiveness in the world? CEPS Paperbacks. September 2012

Launched in March 2010 by the European Commission, the Europe 2020 strategy aims at achieving “smart, sustainable and inclusive” growth. This growth is intended to be driven by three sets of engines: knowledge and innovation, a greener and more efficient use of resources and higher employment combined with social and territorial cohesion. This CEPS report takes an in-depth look at the Europe 2020 strategy and the goals it sets for the EU, with the aim of shedding light on the question of whether the strategy will succeed in fostering the global competitiveness of the European Union. While finding that the Europe 2020 strategy identifies the right key indicators for its targets, the authors advise that it should be revised in several important respects and conclude with relevant policy steps to foster the future capability of European economies and their prosperity.