Nanoclustering as a dominant feature of plasma membrane organization

Early studies have revealed that some mammalian plasma membrane proteins exist in small nanoclusters. The advent of super-resolution microscopy has corroborated and extended this picture, and led to the suggestion that many, if not most, membrane proteins are clustered at the plasma membrane at nanoscale lengths. In this Commentary, we present selected examples of glycosylphosphatidyl-anchored proteins, Ras family members and several immune receptors that provide evidence for nanoclustering. We advocate the view that nanoclustering is an important part of the hierarchical organization of proteins in the plasma membrane. According to this emerging picture, nanoclusters can be organized on the mesoscale to form microdomains that are capable of supporting cell adhesion, pathogen binding and immune cell-cell recognition amongst other functions. Yet, a number of outstanding issues concerning nanoclusters remain open, including the details of their molecular composition, biogenesis, size, stability, function and regulation. Notions about these details are put forth and suggestions are made about nanocluster function and why this general feature of protein nanoclustering appears to be so prevalent.Postprint (published version

Forest road planning, construction and maintenance to improve forest fire fighting: A review

Forest roads play a key-role in fire fighting activities. In fact, all ground-based activities are strictly related to the presence of forest roads as access to fire edge. In spite of this important role, forest roads are often planned and built without considering their use in fire fighting, and this also occurs in literature, where few studies are dedicated to the importance of forest roads in fire fighting. A well-developed and well-maintained forest road network is the answer to different needs in fire management. The objective of this review is to clarify basic principles for obtaining efficient road network also for fire fighting, collecting, defining and resuming the main roles, the most important aspects and the reported experiences to be taken into account in forest road network planning and maintenance in fire-prone areas. The most important themes treated are related to: i) the analysis of the functions of forest roads in fire prevention and suppression; ii) the importance of forest road planning and building also considering their importance for protecting forests against fires: iii) the construction and maintenance characteristics to be considered for building and maintaining an efficient forest road network against fires; iv) the importance of fire prevention and the related role of forest roads. Special attention has been dedicated to maintenance activities, because a not well-maintained forest road is a not efficient forest road, and it represents a useless economic and environmental cost

Collective effects in spin-crossover chains with exchange interaction

The collective properties of spin-crossover chains are studied. Spin-crossover compounds contain ions with a low-spin ground state and low lying high-spin excited states and are of interest for molecular memory applications. Some of them naturally form one-dimensional chains. Elastic interaction and Ising exchange interaction are taken into account. The transfer-matrix approach is used to calculate the partition function, the fraction of ions in the high-spin state, the magnetization, susceptibility, etc., exactly. The high-spin-low-spin degree of freedom leads to collective effects not present in simple spin chains. The ground-state phase diagram is mapped out and compared to the case with Heisenberg exchange interaction. The various phases give rise to characteristic behavior at nonzero temperatures, including sharp crossovers between low- and high-temperature regimes. A Curie-Weiss law for the susceptibility is derived and the paramagnetic Curie temperature is calculated. Possible experiments to determine the exchange coupling are discussed.Comment: 9 pages, 13 color figures, published versio

Deuteron photo-disintegration with polarised photons in the energy range 30 - 50 MeV

The reaction d(\vec\gamma,np) has been studied using the tagged and polarised LADON gamma ray beam at an energy 30 - 50 MeV to investigate the existence of narrow dibaryonic resonances recently suggested from the experimental measurements in a different laboratory. The beam was obtained by Compton back-scattering of laser light on the electrons of the storage ring ADONE. Photo-neutron yields were measured at five neutron angle \vartheta_n = 22, 55.5, 90, 125 and 157 degrees in the center of mass system.Our results do not support the existence of such resonances.Comment: 16 pages, Latex, 22 figures, 1 table. Nucl. Phys. A to appea

Association of metabolic syndrome and change in Unified Parkinson\u27s Disease Rating Scale scores.

OBJECTIVE: To explore the association between metabolic syndrome and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT). METHODS: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome. RESULTS: Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p \u3c 0.0001), were more likely to be male (75.3% vs 57.0%; p \u3c 0.0001), and had a higher mean uric acid level (men 5.7 [1.3] vs 5.3 [1.1] mg/dL, women 4.9 [1.3] vs 3.9 [0.9] mg/dL, p \u3c 0.0001). Participants with metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS (p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS (p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores. CONCLUSIONS: Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding. CLINICALTRIALSGOV IDENTIFIER: NCT00449865

Cardioplegia and angiotensin II receptor antagonists modulate signal transducers and activators of transcription activation in neonatal rat myocytes.

A crescente necessidade de informação para a tomada de decisões dos gestores do setor do transporte urbano de passageiros obriga a desenvolver sistemas para o cálculo, análise e controle de custos que permitam conhecer de forma acurada os mecanismos de formação dos seus preços internos. Nesse contexto, a medida do rendimento adquire um interesse especial quando é comparada a parâmetros e padrões significativos, que permitam aplicar técnicas de benchmarking para melhorar a gestão econômica do serviço. Com esses fins, entende-se que a geração de medidas representativas de padrões coletivos de comportamento constitui-se em uma ferramenta útil para orientar a ação de gestores e administradores públicos. E, como conseqüência, nós apresentamos à Asociación de Empresas de Transporte Urbano Colectivo (ATUC), na Espanha, um projeto para a criação de um Observatório de Custos que possa constituir-se em um importante ponto de referência para as empresas de transporte urbano de passageiros. Palavras-chave: Custos. Financiamento. Transporte urbano de passageiros. * Trabalho apresentado no XIII Congresso Brasileiro de Custos, realizado em Belo Horizonte – MG, no período de 30 de outubro a 01 de novembro 2006.The possibility of providing more complete and detailed data about passenger transport enterprises management justifies the development of analysis and cost control systems that provide precise and rigorous knowledge about internal price formation mechanisms. In this framework, measurement of performance is especially relevant when compared with some other significant reference parameters that allow the use of benchmarking in order to improve the economic management of the service. To this end, we consider it especially useful for the ATUC (Asociación de Empresas de Transporte Urbano Colectivo, i.e., the Association of Collective Urban Transport Companies) to provide a service that establishes measures which represent actual behaviour patterns, that enhances the knowledge of the reality of the sector and that generates a spirit of self-improvement in their associates. We presented a project to ATUC proposing the establishment of a Costs Observatory that can become a significant reference point for passenger transport companies. Key words: Costs. Funding. Urban Passenger Transport.Las crecientes necesidades de información para la gestión y la toma de decisiones de los agentes que operan en el sector del transporte urbano de pasajeros, obliga a desarrollar sistemas para el cálculo, análisis y control de costes que permitan un conocimiento riguroso de los mecanismos de formación de sus precios internos. En dicho marco, la medida del rendimiento adquiere especial interés cuando entra en comparación con parámetros y estándares significativos, que permitan aplicar técnicas de benchmarking para mejorar la gestión económica del servicio. A tales efectos, entendemos que la generación de medidas representativas de patrones colectivos de comportamiento, constituye una herramienta de gran utilidad para orientar la acción de gestores y administradores públicos. Y, en consecuencia, en España, y en el seno de la Asociación de Empresas de Transporte Urbano Colectivo (ATUC), estamos desarrollando un proyecto para la creación de un Observatorio de Costes que pueda constituirse en significativo punto de referencia para las empresas de transporte urbano de viajeros. Palabras clave: Costes. Financiación.Transporte urbano de viajeros

Cardioplegia and angiotensin II receptor antagonists modulate signal transducers and activators of transcription activation in neonatal rat myocytes.

Previous investigations have shown that the signal transducers and activators of transcription (STATs) signaling pathway play an important role in the modulation of apoptosis after ischemia and reperfusion. The mechanism for this enhanced cardioprotection is unknown, but we believe that alterations STATs may play a role. To investigate this hypothesis, we examined the effects of angiotension II type 1 (AT1) and angiotension II type 2 (AT2) receptor antagonist added to cardioplegia on the downstream response of different STATs, connected with proinflammatory pathways (STAT2, STAT5) and prohypertrophic and antiapoptotic pathways (STAT3). Isolated, nonworking hearts (n = 3 per group) from neonatal rats were perfused aerobically (4°C) for 20 min in the Langendorff mode with the modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 1), the MSTH2 cardioplegic solution + AT1 receptor antagonist (Group 2), and MSTH2 cardioplegic solution + AT2 receptor antagonist (Group 3). Thus, myocytes were isolated by enzymatic digestion, and STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 8-12 s for all groups. Total cardioplegia delivery volume was about 300 mL for the 20 min. Perfusion with the MSTH2 cardioplegic solution supplemented with AT1 receptor antagonist (Group 2) induced a significant reduction in STAT2 and STAT5 tyrosine phosphorylation (-58 and -63%, respectively, vs. Group 1, P < 0.05). Conversely, STAT2 and STAT5 activation were unaffected by perfusion with the MSTH2 cardioplegic solution supplemented with AT2 receptor antagonist (Group 3). The decreased activation of STAT2 and STAT5 observed in Group 2 was accompanied by reduction of interleukin-1β (-57% in Group 2 vs. Group 1, P < 0.05). There were no significant differences in STAT3 phosphorylation among all groups. Only the addition of AT1 receptor antagonist to MSTH2 cardioplegia significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by tyrosine phosphorylation of STAT3. AT1 receptor antagonist added to cardioplegia represents an additional modality for enhancing myocardial protection during cardiac surgery and could contribute to optimize the ischemia tolerance of the pediatric heart

Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases.

The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated α-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated α-synuclein in SNCA gene multiplication or aggregated β-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death. These 3 conceptual frameworks of protein aggregation (pathogenic, epiphenomenon, protective) are difficult to resolve because of the inability to probe brain tissue in real time. Whereas animal models, in which neither PD nor AD occur in natural states, consistently support a pathogenic role of protein aggregation, indirect evidence from human studies does not. We hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress. Future precision medicine efforts for molecular targeting of neurodegenerative diseases may require analyses not anchored on current clinicopathologic criteria but instead on biological signals generated from large deeply phenotyped aging populations or from smaller but well-defined genetic-molecular cohorts