Altered muscarinic and nicotinic receptor densities in cortical and subcortical brain regions in Parkinson's disease

Muscarinic and nicotinic cholinergic receptors and choline acetyltransferase activity were studied in postmortem brain tissue from patients with histopathologically confirmed Parkinson's disease and matched control subjects. Using washed membrane homogenates from the frontal cortex, hippocampus, caudate nucleus, and putamen, saturation analysis of specific receptor binding was performed for the total number of muscarinic receptors with [3H]quinuclidinyl benzilate, for muscarinic M1 receptors with [3H]pirenzepine, for muscarinic M2 receptors with [3H]oxotremorine-M, and for nicotinic receptors with (-)-[3H]nicotine. In comparison with control tissues, choline acetyl-transferase activity was reduced in the frontal cortex and hippocampus and unchanged in the caudate nucleus and putamen of parkinsonian patients. In Parkinson's disease the maximal binding site density for [3H]quinuclidinyl benzilate was increased in the frontal cortex and unaltered in the hippocampus, caudate nucleus, and putamen. Specific [3H]pirenzepine binding was increased in the frontal cortex, unaltered in the hippocampus, and decreased in the caudate nucleus and putamen. In parkinsonian patients Bmax values for specific [3H]oxotremorine-M binding were reduced in the cortex and unchanged in the hippocampus and striatum compared with controls. Maximal (-)-[3H]nicotine binding was reduced in both the cortex and hippocampus and unaltered in both the caudate nucleus and putamen. Alterations of the equilibrium dissociation constant were not observed for any ligand in any of the brain areas examined. The present results suggest that both the innominatocortical and the septohippocampal cholinergic systems degenerate in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS

Terguride stimulates locomotor activity at 2 months but not 10 months after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets

The mixed dopamine (DA) agonist/antagonist terguride acts as a DA antagonist on normosensitive receptors but shows DA agonistic properties at supersensitive DA receptors. Such a compound could offer an alternative to the treatment of Parkinson's disease with indirect or direct DA agonists. The present study compares the actions of terguride, 4-12 mg/kg i.p., in naive common marmosets with its effects in animals rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 months or 10 months previously, in order to test its antiparkinsonian efficacy. Terguride reduced locomotor activity in naive common marmosets, similar to its effects in rodents and in line with the DA antagonistic activity of the compound. In marmosets treated with MPTP 2 months previously and exhibiting pronounced behavioural motor deficits, terguride stimulated locomotor activity, showing DA agonistic properties under these conditions. In contrast, the locomotor activity of animals that had recovered from MPTP treatment 10 months previously was not altered by terguride. It is concluded that terguride has anti-akinetic efficacy in this primate model of Parkinson's disease. In addition, terguride offers a unique opportunity to differentiate, pharmacologically, the extent of dopaminergic recovery from MPTP treatment in this primate species

Cumulate causes for the low contents of sulfide-loving elements in the continental crust

Despite the economic importance of chalcophile (sulfide-loving) and siderophile (metal-loving) elements (CSEs), it is unclear how they become enriched or depleted in the continental crust, compared with the oceanic crust. This is due in part to our limited understanding of the partitioning behaviour of the CSEs. Here I compile compositional data for mid-ocean ridge basalts and subduction-related volcanic rocks. I show that the mantle-derived melts that contribute to oceanic and continental crust formation rarely avoid sulfide saturation during cooling in the crust and, on average, subduction-zone magmas fractionate sulfide at the base of the continental crust prior to ascent. Differentiation of mantle-derived melts enriches lower crustal sulfide- and silicate-bearing cumulates in some CSEs compared with the upper crust. This storage predisposes the cumulate-hosted compatible CSEs (such as Cu and Au) to be recycled back into the mantle during subduction and delamination, resulting in their low contents in the bulk continental crust and potentially contributing to the scarcity of ore deposits in the upper continental crust. By contrast, differentiation causes the upper oceanic and continental crust to become enriched in incompatible CSEs (such as W) compared with the lower oceanic and continental crust. Consequently, incompatible CSEs are predisposed to become enriched in subduction-zone magmas that contribute to continental crust formation and are less susceptible to removal from the continental crust via delamination compared with the compatible CSEs

Quo Vadis Venomics? A Roadmap to Neglected Venomous Invertebrates

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0). The attached file is the published version of the article

Metodologia para diagnóstico e intervenção em edifícios correntes: habitação social no Porto e Recife

De acordo com o INE (2010), o parque de habitação social distribui-se por 246 Municípios, sendo constituído por cerca de 97 mil fogos e 22 mil edifícios. O município do Porto detém 12 682 fogos, correspondendo a 13% do total. Durante o ano de 2009 os municípios portugueses executaram obras de conservação em 2 252 edifícios (10,2% do total) e procederam à reabilitação de 6 636 fogos (6,8% do total). Este património municipal gerou, em 2009, uma receita média por fogo de 706 euros, entre rendas cobradas e fogos vendidos. Por seu lado a despesa média (incluindo os encargos fixos) ficou-se pelos 676 euros por fogo. Atendendo apenas a estas rubricas de receitas e despesas relacionadas com o parque de habitação social dos municípios, verifica-se a existência de um “défice” nas regiões do Norte de 12,7 milhões, o que demonstra o investimento em curso actualmente. O Município do Porto registou um défice superior a 1 000 euros por fogo (receita de 604 euros e despesa de 1 718 euros). A Habitação Social resulta de uma necessidade passada e presente de pensar nas pessoas, isto é, pensar numa política de valorização da qualidade de vida da população que passando muito pela habitação, não acaba nela. A política social da habitação dá início a um processo global de melhoria da qualidade de vida das pessoas, sendo necessário fazer coincidir a melhoria das condições de alojamento, com a melhoria das condições envolventes aos conjuntos habitacionais. Só com uma participação activa dos moradores é possível a sua identificação com o conjunto habitacional onde residem. A missão descrita é incompatível com habitação social em deficiente estado de conservação ou mesmo muito degradada, tal como se verifica em inúmeros países. Importa desta forma assegurar a reabilitação deste património construído e a sua posterior conservação. Nos últimos anos ocorreram desenvolvimentos muito significativos no que diz respeito à capacidade de utilizar técnicas experimentais (in situ ou em laboratório) e simulações em computador. Um aspecto relevante é que a engenharia “de conservação” deve ter uma abordagem e capacidade diferentes das usadas em construções novas. Frequentemente, os materiais e técnicas tradicionais são desconhecidos para os envolvidos. Também se verifica que a tendência das entidades reguladoras e dos projectistas para que os regulamentos actuais sejam cumpridos. Isto é muitas vezes inaceitável, visto que os regulamentos foram escritos tendo em mente outras formas de construção, pelo que a sua aplicação em materiais, tecnologias e formas tradicionais é excessivamente conservadora ou penalizadora. A necessidade de reconhecer a diferença entre o projecto moderno e a conservação também é relevante no contexto dos custos associados à contribuição da engenharia. O procedimento habitual de cálculo de honorários de engenharia, como uma percentagem do trabalho realizado, está claramente em oposição com as melhores práticas de conservação. Ser capaz de recomendar não tomar qualquer medida pode, na realidade, implicar mais estudos e mais custos reais do que uma recomendação para grandes intervenções. Os procedimentos das intervenções modernas exigem um levantamento cuidado da construção, bem como a compreensão da sua história, tendo em vista obter um diagnóstico claro, que requer muitas vezes técnicas de inspecção adequadas e experiência adquirida relevante, num processo muito semelhante à medicina Após reconstituir o historial do paciente (o edifício) e requerer exames (técnicas de inspecção e ensaios), é possível um diagnóstico. Este diagnóstico permite, se necessário, uma terapia adequada (projecto de intervenção) e o respectivo controlo de resultados (monitorização dos resultados). Tendo em vista demonstrar a abordagem metodológica necessária, no presente artigo serão apresentados casos de estudo em Portugal e Brasil, onde os autores estiveram envolvidos

Binge-watching: Video-on-demand, quality TV and mainstreaming fandom

This article explores the concept of the binge as viewing protocol associated with fan practices, industry practice and linked to ‘cult’ and ‘quality’ serialised content. Viewing binge-watching as an intersection of discourses of industry, audience and text, the concept is analysed here as shaped by a range of issues that dominate the contemporary media landscape. In this, factors like technological developments, fan discourses and practices being adopted as ‘mainstream’ media practice, changes in the discursive construction of ‘television’ and an emerging Video-on-Demand industry contribute to the construction of binge-watching as deliberate, self-scheduled alternative to ‘watching TV’

Acyl-chain elongation drives ketosynthase substrate selectivity in trans-acyltransferase polyketide synthases

Type I modular polyketide synthases (PKSs), responsible for the biosynthesis of many biologically active agents, possess a ketosynthase (KS) domain within each module to catalyze chain elongation. Acylation of the KS active site Cys residue is followed by transfer to malonyl-acyl carrier protein, yielding an extended β-ketoacyl chain. To date, the precise contribution of KS selectivity in controlling product fidelity has been unclear. We submitted six KS domains from the trans-acyl transferase PKSs to a mass spectrometry-basedelongation assay, and identified higher substrat selectivity in the elongating step than in preceding acylation. A close correspondence between observed KS selectivity and that predicted by phylogenetic analysis was seen. Our findings provide insights into the mechanism of KS selectivity in this important group of PKSs, can serve as guidance for engineering, and show that targeted mutagenesis can be used to expand the repertoire of acceptable substrates

Safety analysis of modern heritage masonry buildings : box-buildings in Recife, Brazil

Box-buildings are structural masonry buildings named as such because of their shape. There are around 5,000 of them in Recife, Brazil. This paper presents a safety analysis of one box-building that suffered collapse on December 2007. The research aims at quantifying the safety of this type of existing buildings and at better understanding their structural behavior to try to identify the reasons for the collapse. A finite element model was prepared and a set of nonlinear numerical analyses were performed. The results of the analyses show good agreement between the observed damage in the real building and the damage achieved numerically at the current condition (LF=1). The model thus seems to represent satisfactorily the real behavior of the building but the safety factor obtained seems too conservative and does not justify the collapse observed in reality. Since results show that the building should not have failed under normal working conditions, a collapse assessment about why the building fell is therefore provided and a sensitivity analysis was performed in order to understand the importance of the material parameters and their influence on the structural response of the building