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

Brain muscarinic cholinergic receptors in Huntington's disease

Muscarinic cholinergic receptors and choline acetyltransferase (ChAT) activity were studied in postmortem brain tissue from patients with Huntington's disease and matched control subjects. In comparison with controls, reductions in ChAT activity were found in the hippocampus, but not in the temporal cortex in Huntington's disease. Patients with Huntington's disease showed reduced densities of the total number of muscarinic receptors and of M-2 receptors in the hippocampus while the density of M-1 receptors was unaltered. Muscarinic receptor binding was unchanged in the temporal cortex. These results indicate a degeneration in Huntington's disease of the septo-hippocampal cholinergic pathway, but no impairment of the innominato-cortical cholinergic system

Chalcophile elements track the fate of sulfur at Kīlauea Volcano, Hawai'i

© 2020 Elsevier Ltd Chalcophile element concentrations in melt inclusions and matrix glasses may be used to investigate low pressure degassing processes, as well as sulfide saturation during crustal fractionation, and mantle melting. Erupted products from Kīlauea Volcano, Hawaiʻi, record three stages of sulfide saturation (in the mantle, crust, and within lava lakes), separated by episodes of sulfide resorption (i.e., sulfide undersaturation) during ascent through the thick Hawaiian lithosphere, and during syn-eruptive degassing. The presence of residual sulfides in the mantle source throughout the melting interval accounts for the high S concentrations of Kīlauean primary melts (1387–1600 ppm). Residual sulfides retain chalcophile elements during melting, decoupling the variability of these elements in high MgO melts from that of lithophile elements. Decompression associated with magma ascent through the thick Hawaiian lithosphere drives an increase in the sulfide concentration at sulfide saturation (SCSS2−), resulting in shallow storage reservoirs (∼1–5 km depth) being supplied with sulfide-undersaturated melts. A drop in temperature, coupled with major element changes during the fractionation of olivine, causes the SCSS2− to decrease. Combined with an increase in melt S contents during fractionation, this initiates a second stage of sulfide saturation at relatively high MgO contents (∼12 wt%). Syn-eruptive degassing of S drives the resorption of sulfides in contact with the carrier liquid. The covariance structure of Cu, MgO and Ni contents in melt inclusions and matrix glasses indicates that the dissolution of sulfides effectively liberates sulfide-hosted Cu and Ni back into the melt, rather than the vapour phase. The contrasting behaviour of Cu, Ni, Se and S during sulfide resorption indicates that the chalcophile element signature of the Kīlauean plume is largely controlled by silicate melt-vapour partitioning, rather than sulfide-vapour partitioning. The participation of dense sulfide liquids in shallow degassing processes may result from their direct attachment to buoyant vapour bubbles, or olivine crystals which were remobilized prior to eruption. Sulfide resorption obscures the textural and chemical record of sulfide saturation in matrix glasses, but not in melt inclusions, which are isolated from this late-stage release of chalcophile elements. The partitioning of S between the dissolving sulfide, melt and the vapour phase accounts for approximately 20% of the total S release into the atmosphere

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

Mathematical modelling of the interaction between cancer cells and an oncolytic virus: insights into the effects of treatment protocols

Oncolytic virotherapy is an experimental cancer treatment that uses genetically engineered viruses to target and kill cancer cells. One major limitation of this treatment is that virus particles are rapidly cleared by the immune system, preventing them from arriving at the tumour site. To improve virus survival and infectivity modified virus particles with the polymer polyethylene glycol (PEG) and the monoclonal antibody herceptin. While PEG modification appeared to improve plasma retention and initial infectivity it also increased the virus particle arrival time. We derive a mathematical model that describes the interaction between tumour cells and an oncolytic virus. We tune our model to represent the experimental data by Kim et al. (2011) and obtain optimised parameters. Our model provides a platform from which predictions may be made about the response of cancer growth to other treatment protocols beyond those in the experiments. Through model simulations we find that the treatment protocol affects the outcome dramatically. We quantify the effects of dosage strategy as a function of tumour cell replication and tumour carrying capacity on the outcome of oncolytic virotherapy as a treatment. The relative significance of the modification of the virus and the crucial role it plays in optimising treatment efficacy is explored.Comment: 15 pages, 6 figure

A novel magnet-based scratch method for standardisation of wound-healing assays

A novel magnetic scratch method achieves repeatability, reproducibility and geometric control greater than pipette scratch assays and closely approximating the precision of cell exclusion assays while inducing the cell injury inherently necessary for wound healing assays. The magnetic scratch is affordable, easily implemented and standardisable and thus may contribute toward better comparability of data generated in different studies and laboratories

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

Petrologic monitoring at Volcán de Fuego, Guatemala

Paroxysmal activity represents an end-member in the common range of activity at mafic arc volcanoes, characterised by rapid transitions across the effusive-explosive interface and thus posing significant challenges to hazard assessment. Conceptual models to explain changes in the frequency and magnitude of these paroxysmal events are based either on magma recharge or an increase in gas flux, largely framed in the context of two-phase flow. Gas- and magma-driven models are both viable mechanisms to explain the varying styles of paroxysmal behaviour observed in mafic systems; however, each has different implications for future activity. We present time series petrologic data for ash and lava samples collected at Volcán de Fuego, Guatemala, during paroxysmal eruptions between 2011 and 2018. We show that a step-change in glass composition occurred between 2015 and 2016, reflecting an increase in magma temperature and a reduction in pre-eruptive crystallisation, concurrent with an escalation in the frequency of paroxysmal activity. There was no change in the bulk or phase compositions during this period. To explain these observations, we propose that the increase in frequency of paroxysmal eruptions is modulated by the supply of exsolved volatiles from lower crustal degassing magmas, without invoking repeated transfer of new, primitive magma to a shallow reservoir. Protracted lava effusion, accompanied by more vigorous and more frequent Strombolian explosions and gas ‘chugging’, prior to the transition to sustained fountaining suggests that gas retention in crystal-rich magma may modulate the height of the magma column as gas supply increases. Slow decompression associated with effusion may determine the timing of effusive to explosive transitions in mafic arc systems more generally. A large paroxysmal eruption of Fuego on 3 June 2018, notable for the rapid escalation in eruptive intensity several hours into the eruption, produced ash with a range of textures and glass compositions consistent with magma evacuation over a range of depths and decompression rates. Given the protracted repose time between paroxysms before this event, we suggest that a shallow crystallised plug degraded, and ultimately failed, several hours into the eruption of 3 June 2018, triggering top-down decompression of magma in the conduit synchronous with the observed rapid acceleration in eruption rate. Ultimately, we propose that the frequency of paroxysms at Fuego is broadly proportional to the gas supply rate, while the range in glass compositions is related to the repose time prior to eruptive activity. Our data illustrate the potential of petrologic monitoring to distinguish between gas- and magma-driven paroxysm triggers and to anticipate future events, especially when interpreted in the context of geophysical observations and implemented within community-based ash collection initiatives

Brief intervention manual for personality disorders

This manual is designed to help services intervene early and better support young people and adults with personality disorders. It is particularly focused on clients in crisis, who have complex needs, by providing practical therapeutic techniques in the prevention and treatment of high-risk challenging behaviours. It describes a four session brief intervention that can act as the first step in a treatment journey for people with this disorder