Glycogen synthase kinases 3α and 3β in cardiac myocytes: regulation and consequences of their inhibition

Inhibition of glycogen synthase kinase 3β (GSK3β) as a consequence of its phosphorylation by protein kinase B/Akt (PKB/Akt) has been implicated in cardiac myocyte hypertrophy in response to endothelin-1 or phenylephrine. We examined the regulation of GSK3α (which we show to constitute a significant proportion of the myocyte GSK3 pool) and GSK3β in cardiac myocytes. Although endothelin increases phosphorylation of GSK3 and decreases its activity, the response is less than that induced by insulin (which does not promote cardiac myocyte hypertrophy). GSK3 phosphorylation induced by endothelin requires signalling through the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade and not the PKB/Akt pathway, whereas the reverse is true for insulin. Cardiac myocyte hypertrophy involves changes in morphology, and in gene and protein expression. The potent GSK3 inhibitor 1-azakenpaullone increases myocyte area as a consequence of increased cell length whereas phenylephrine increases both length and width. Azakenpaullone or insulin promotes AP1 transcription factor binding to an AP1 consensus oligonucleotide, but this was significantly less than that induced by endothelin and derived principally from increased binding of JunB protein, the expression of which was increased. Azakenpaullone promotes significant changes in gene expression (assessed by Affymetrix microarrays), but the overall response is less than with endothelin and there is little overlap between the genes identified. Thus, although GSK3 may contribute to cardiac myocyte hypertrophy in some respects (and presumably plays an important role in myocyte metabolism), it does not appear to contribute as significantly to the response induced by endothelin as has been maintained.

‘The Making of the Book’: Roy Fisher, the Circle Press and the poetics of book art

Between 1972 and 2001, the English late-modernist poet Roy Fisher provided the text for nine separate artist's books produced by Ron King at the Circle Press. Taken together, as Andrew Lambirth has written, the Fisher-King collaborations represent a sustained investigation of the various ways in which text and image can be integrated, breaking the mould of the codex or folio edition, and turning the book into a sculptural object. From the three-dimensional pop-up designs of Bluebeard's Castle (1973), each representing a part of the edifice (the portcullis, the armoury and so on), to ‘alphabet books’ such as The Half-Year Letters (1983), held in an ingenious french-folded concertina which can be stretched to over a metre long or compacted to a pocketbook, the project of these art books is to complicate their own bibliographic codes, and rethink what a book can be. Their folds and reduplications give a material form to the processes by which meanings are produced: from the discovery, in Top Down, Bottom Up (1990), of how to draw on both sides of the page at the same time, to the developments of The Left-Handed Punch (1987) and Anansi Company (1992), where the book becomes first a four-dimensional theatre space, in which a new version of Punch and Judy is played out by twelve articulated puppets, and then a location for characters that are self-contained and removable, in the form of thirteen hand-made wire and card rod-puppets. Finally, in Tabernacle (2001), a seven-drawer black wooden cabinet that stands foursquare like a sculpture (and sells to galleries and collectors for over three thousand pounds), the conception of the book and the material history of print are fully undone and reconstituted. This paper analyses how the King-Fisher art books work out their radically material poetics of the book; how their emphasis on collaboration, between artist and poet, image and text, and also book and reader – the construction of meaning becoming a co-implicated process – continuously challenges hierarchies and fixities in our conception of authorship; and how they re-think the status of poetic text and the construction of the book as material object.

The effect of cues on young children’s abilities to discriminate among thoughts, feelings and behaviours

Objective: To determine if cues help young children discriminate among thoughts, feelings and behaviours. Participants: Ninety-six children aged 4–7 years from three schools in Norwich, UK. Design: Within each age band (4, 5, 6, 7), children were randomised to the cue or the no cue condition on a stratified basis ensuring that equal numbers of boys and girls from each school were in each of the eight cells (cue condition×age). Cues were glove puppets and post boxes. The effect of IQ was controlled. Measures: A discrimination task, in which children were asked to identify a thought, a feeling and a behaviour from each of six brief stories, and a brief IQ assessment were administered to children individually. Results: There was a significant effect of age and cue condition on performance; older children and those who were presented with the cue performed better. There were no gender differences and no interaction between cue condition and age. Conclusion: Many young children discriminated among thoughts, feelings and behaviours suggesting that they may be able to engage in this aspect of cognitive behaviour therapy. Simple cues (puppets and posting boxes) improved children’s performance and these may be useful therapeutic tools with young children.

Show de Mamulengos Heraldo Lins: construções e transformações de um espetáculo na cultura popular

The theater of puppets is one of the many expressions of popular culture which is marked by ongoing constructions and transformations in its symbolic representations as well as its characters and performances. In the city of Natal/RN, there is a manipulator called Heraldo Lins, an artist who operates such puppets, and has been performing his puppet since 1992. Lins has his own look at how he produces his performances and seeks to adjust his puppets to social and rentable contexts. Lins‟s performances are tailor-made in accordance with the request of his customers, as he makes up the passages and lines of his puppets according to his audience. This research aimed to study how the Heraldo Lins Mamulengos Show is built, especially its changes. We note that Lins chooses to dismantle the symbolic values of the tradition in the regular puppet theater once he adapts to modern patterns, placing himself between the traditional puppet theater and the cultural industry. The work in camp was made through a methodological focused in a participative observation and an audiovisual registry

Identification, characterization and expression analysis of hepcidin gene in sheep

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Statistics and kinetics of single-molecule electron transfer dynamics in complex environments: A simulation model study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Theory and practice of industrial policy: evidence from the Latin American experience

Includes bibliography

Uma novela infernal

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

An assessment of the economic impact of climate change on the Energy Sector in Trinidad and Tobago

The energy sector is a dominant one in Trinidad and Tobago and it plays an important role in the twin-island republic‟s economy. In 2008, the share of the energy sector in gross domestic product (GDP) amounted to approximately 48% while contributing 57% to total Government revenue. In that same year, the sector‟s share of merchandise exports was 88%, made up mainly of refined oil products including petroleum, liquefied natural gas (LNG), and natural gas liquids (Central Bank of Trinidad and Tobago, 2009). Trinidad and Tobago is the main exporter of oil in the Caribbean region and the main producer of liquefied natural gas in Latin America and the Caribbean. The role of the country‟s energy sector is, therefore, not limited to serving as the engine of growth for the national economy but also includes providing energy security for the small island developing States of the Caribbean. However, with its hydrocarbon-based economy, Trinidad and Tobago is ranked seventh in the world in terms of carbon dioxide (CO2) emissions per capita, producing an estimated 40 million tonnes of CO2 annually. Almost 90% of these CO2 emissions are attributed directly to the energy sector through petrochemical production (56%), power generation (30%) and flaring (3%). Trinidad and Tobago is a ratified signatory to the United Nations Framework Convention on Climate Change and the Kyoto Protocol. Although, as a non-Annex 1 country, Trinidad and Tobago is not required to cut its greenhouse gas emissions under the Protocol, it is currently finalizing a climate change policy document as well as a national energy policy with specific strategies to address climate change. The present study complements the climate change policy document by providing an economic analysis of the impact that climate change could have on the energy sector in Trinidad and Tobago under the Intergovernmental Panel on Climate Change alternative climate scenarios (A2 and B2) as compared to a baseline situation of no climate change. Results of analyses indicate that, in the short-run, climate change, represented by change in temperature, is not a significant determinant of domestic consumption of energy, electricity in particular, in Trinidad and Tobago. With energy prices subsidized domestically and fixed for years at a time, energy price does not play a role in determining electricity demand. Economic growth, as indicated by Gross Domestic Product (GDP), is the single major determinant of electricity consumption in the short-run. In the long-run, temperature, GDP, and patterns of electricity use, jointly determine electricity consumption. Variations in average annual temperature due to climate change for the A2 scenario are expected to lead to an increase in electricity consumption per capita, equivalent to an annual increase of 1.07% over the 2011 baseline value of electricity consumption per capita. Under the B2 scenario, the average annual increase in electricity consumption per capita over the 2011 baseline value is expected to be 1.01%. The estimated economic impact of climate change on electricity consumption for the period 2011-2050 is valued at US$ 142.88 million under the A2 scenario and US$ 134.83million under the B2 scenario. These economic impact estimates are equivalent to a loss of 0.737% of 2009 GDP under the A2 climate scenario and a loss of 0.695% of 2009 GDP under the B2 scenario. On the energy supply side, sea level rise and storm surges present significant risks to oil installations and infrastructure at the Petroleum Company of Trinidad and Tobago (PETROTRIN) Pointe-a-Pierre facilities (Singh and El Fouladi, 2006). However, data limitations do not permit the conduct of an economic analysis of the impact of projected sea level rise on oil and gas production.

Glutamatergic antagonism in the NTS decreases post-inspiratory drive and changes phrenic and sympathetic coupling during chemoreflex activation

For a better understanding of the processing at the nucleus tractus solitarius (NTS) level of the autonomic and respiratory responses to peripheral chemoreceptor activation, herein we evaluated the role of glutamatergic neurotransmission in the intermediate (iNTS) and caudal NTS (cNTS) on baseline respiratory parameters and on chemoreflex-evoked responses using the in situ working heart-brain stem preparation (WHBP). The activities of phrenic (PND), cervical vagus (cVNA), and thoracic sympathetic (tSNA) nerves were recorded before and after bilateral microinjections of kynurenic acid (Kyn, 5 nmol/20 nl) into iNTS, cNTS, or both simultaneously. In WHBP, baseline sympathetic discharge markedly correlated with phrenic bursts (inspiration). However, most of sympathoexcitation elicited by chemoreflex activation occurred during expiration. Kyn microinjected into iNTS or into cNTS decreased the postinspiratory component of cVNA and increased the duration and frequency of PND. Kyn into iNTS produced no changes in sympathoexcitatory and tachypneic responses to peripheral chemoreflex activation, whereas into cNTS, a reduction of the sympathoexcitation, but not of the tachypnea, was observed. The pattern of phrenic and sympathetic coupling during the chemoreflex activation was an inspiratory-related rather than an expiratory-related sympathoexcitation. Kyn simultaneously into iNTS and cNTS produced a greater decrease in postinspiratory component of cVNA and increase in frequency and duration of PND and abolished the respiratory and autonomic responses to chemoreflex activation. The data show that glutamatergic neurotransmission in the iNTS and cNTS plays a tonic role on the baseline respiratory rhythm, contributes to the postinspiratory activity, and is essential to expiratory-related sympathoexcitation observed during chemoreflex activation.

Floral nectar production and nectary structure of a bee-pollinated shrub from Neotropical savanna

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The abuse of intellectual property rights and regulations in China: a law and economic analysis

From the institutional point of view, the legal system of IPR (intellectual property right, hereafter, IPR) is one of incentive institutions of innovation and it plays very important role in the development of economy. According to the law, the owner of the IPR enjoy a kind of exclusive right to use his IP(intellectual property, hereafter, IP), in other words, he enjoys a kind of legal monopoly position in the market. How to well protect the IPR and at the same time to regulate the abuse of IPR is very interested topic in this knowledge-orientated market and it is the basic research question in this dissertation. In this paper, by way of comparing study and by way of law and economic analyses, and based on the Austrian Economics School’s theories, the writer claims that there is no any contradiction between the IPR and competition law. However, in this new economy (high-technology industries), there is really probability of the owner of IPR to abuse his dominant position. And with the characteristics of the new economy, such as, the high rates of innovation, “instant scalability”, network externality and lock-in effects, the IPR “will vest the dominant undertakings with the power not just to monopolize the market but to shift such power from one market to another, to create strong barriers to enter and, in so doing, granting the perpetuation of such dominance for quite a long time.”1 Therefore, in order to keep the order of market, to vitalize the competition and innovation, and to benefit the customer, in EU and US, it is common ways to apply the competition law to regulate the IPR abuse. In Austrian Economic School perspective, especially the Schumpeterian theories, the innovation/competition/monopoly and entrepreneurship are inter-correlated, therefore, we should apply the dynamic antitrust model based on the AES theories to analysis the relationship between the IPR and competition law. China is still a developing country with relative not so high ability of innovation. Therefore, at present, to protect the IPR and to make good use of the incentive mechanism of IPR legal system is the first important task for Chinese government to do. However, according to the investigation reports,2 based on their IPR advantage and capital advantage, some multinational companies really obtained the dominant or monopoly market position in some aspects of some industries, and there are some IPR abuses conducted by such multinational companies. And then, the Chinese government should be paying close attention to regulate any IPR abuse. However, how to effectively regulate the IPR abuse by way of competition law in Chinese situation, from the law and economic theories’ perspective, from the legislation perspective, and from the judicial practice perspective, there is a long way for China to go!

HIF1α regulates Mitochondrial biogenesis and Cellular senescence induced by Gamma Radiation

Cellular response to γ-rays is mediated by ATM-p53 axis. When p53 is phosphorylated, it can transactivate several genes to induce permanent cell cycle arrest (senescence) or apoptosis. Epithelial and mesenchymal cells are more resistant to radiation-induced apoptosis and respond mainly by activating senescence. Hence, tumor cells in a senescent state might remain as “dormant” malignant in fact through disruption of p53 function, cells may overcome growth arrest. Oncocytic features were acquired in the recurring neoplasia after radiation therapy in patient with colonrectal cancer. Oncocytic tumors are characterized by aberrant biogenesis and are mainly non-aggressive neoplasms. Their low proliferation degree can be explained by chronic destabilization of HIF1α, which presides to adaptation to hypoxia and also plays a pivotal role in hypoxia-related radio-resistance. The aim of the present thesis was to verify whether mitochondrial biogenesis can be induced following radiation treatment, in relation of HIF1α status and whether is predictive of a senescence response. In this study was demonstrate that mitochondrial biogenesis parameters like mitochondrial DNA copy number could be used for the prediction of hypoxic status of tissue after radiation treatment. γ-rays induce an increase of mitochondrial mass and function, in response to a genotoxic stress that pushes cells into senescence. Mitochondrial biogenesis is only indirectly regulated by p53, whose activation triggers a MDM2-mediated HIF1α degradation, leading to the release of PGC-1β inhibition by HIF1α. On the other hand, this protein blunts the mitochondrial response to γ-rays as well as the induction of p21-mediated cell senescence, indicating prevalence of the hypoxic over the genotoxic response. Finally in vivo, post-radiotherapy mtDNA copy number increase well correlates with lack of HIF1α increase in the tissue, concluding this may be a useful molecular tool to infer the trigger of a hypoxic response during radiotherapy, which may lead to failure of activation of senescence.

Private Publishing in Moscow and St. Petersburg: Historical Background, Present Situation and Trends"

This research was a complex study of the economic and socio-cultural aspects of the development of Russian private publishing in the second half of the19th and early 20th centuries, during the periods of 'war communism' and the New Economic Policy of 1917 to 1930, and during the reform of book publishing in 1986-1999. Conclusions about private book publishing in Moscow and St. Petersburg were extrapolated to Russia-wide problems of the development of this field. Svichenskaya sees her main achievement as having identified the economic and legal concepts behind the development of private book publishing over the period in question in the context of state and corporate regulation of publishing. Here the state was the main influence on its development and there was a paradox in the relations between the state authorities and private publishers, in that the latter constantly suffered from repression by the former but at the same time were dependent on state support. The research identified the administrative process of the liquidation of private publishing at the end of the 1920s and showed that its present flourishing is closely linked with the establishment of a preferential mode for the development of this sector. Private publishing now represents around 80% of domestic publishing, in terms both of the number of publishing houses and of the number of volumes published, and so plays the major role in satisfying the demand for books in Russia. Svichenskaya predicts that in the coming years private publishing will see a further concentration of growth and a tendency to monopolies and also the increasing specialisation of the publishing repertoire. She outlines a suggested concept of state management in publishing and ways to optimise this. In the transitional period of adaptation to the market regulation of publishing, these include a continuing degree of state protectionism, the creation of a favourable investment climate, privatisation of the printing companies with the aim of modernising these, and the development of coordinated corporate policies.

Genetic and pharmacologic manipulation of oxidative stress after neonatal hypoxia-ischemia

Oxidative stress is a critical component of the injury response to hypoxia-ischemia (HI) in the neonatal brain, and this response is unique and at times paradoxical to that seen in the mature brain. Previously, we showed that copper-zinc superoxide-dismutase (SOD1) over-expression is not beneficial to the neonatal mouse brain with HI injury, unlike the adult brain with ischemic injury. However, glutathione peroxidase 1 (GPx1) over-expression is protective to the neonatal mouse brain with HI injury. To further test the hypothesis that an adequate supply of GPx is critical to protection from HI injury, we crossed SOD1 over-expressing mice (hSOD-tg) with GPx1 over-expressing mice (hGPx-tg). Resulting litters contained wild-type (wt), hGPx-tg, hSOD-tg and hybrid hGPx-tg/hSOD-tg pups, which were subjected to HI at P7. Confirming previous results, the hGPx-tg mice had reduced injury compared to both Wt and hSOD-tg littermates. Neonatal mice over-expressing both GPx1 and SOD1 also had less injury compared to wt or hSOD-tg alone. A result of oxidative stress after neonatal HI is a decrease in the concentration of reduced (i.e. antioxidant-active) glutathione (GSH). In this study, we tested the effect of systemic administration of alpha-lipoic acid on levels of GSH in the cortex after HI. Although GSH levels were restored by 24h after HI, injury was not reduced compared to vehicle-treated mice. We also tested two other pharmacological approaches to reducing oxidative stress in hSOD-tg and wild-type littermates. Both the specific inhibitor of neuronal nitric oxide synthase, 7-nitroindazole (7NI), and the spin-trapping agent alpha-phenyl-tert-butyl-nitrone (PBN) did not reduce HI injury, however. Taken together, these results imply that H2O2 is a critical component of neonatal HI injury, and GPx1 plays an important role in the defense against this H2O2 and is thereby neuroprotective.