Dynamics of Gray Matter Loss in Alzheimer's Disease

We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer's disease (AD). The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions, sparing sensorimotor cortices. The shifting deficits were asymmetric (left hemisphere >right hemisphere) and correlated with progressively declining cognitive status ( p 15% loss). The maps distinguished different phases of AD and differentiated AD from normal aging. Local gray matter loss rates (5.3 +/- 2.3% per year in AD v 0.9 +/- 0.9% per year in controls) were faster in the left hemisphere ( p < 0.029) than the right. Transient barriers to disease progression appeared at limbic/frontal boundaries. This degenerative sequence, observed in vivo as it developed, provides the first quantitative, dynamic visualization of cortical atrophic rates in normal elderly populations and in those with dementia.

The trans-membrane protein p25 forms highly specialized domains that regulate membrane composition and dynamics

Trans-membrane proteins of the p24 family are abundant, oligomeric proteins predominantly found in cis-Golgi membranes. They are not easily studied in vivo and their functions are controversial. We found that p25 can be targeted to the plasma membrane after inactivation of its canonical KKXX motif (KK to SS, p25SS), and that p25SS causes the co-transport of other p24 proteins beyond the Golgi complex, indicating that wild-type p25 plays a crucial role in retaining p24 proteins in cis-Golgi membranes. We then made use of these observations to study the intrinsic properties of these proteins, when present in a different membrane context. At the cell surface, the p25SS mutant segregates away from both the transferrin receptor and markers of lipid rafts, which are enriched in cholesterol and glycosphingolipids. This suggests that p25SS localizes to, or contributes to form, specialized membrane domains, presumably corresponding to oligomers of p25SS and other p24 proteins. Once at the cell surface, p25SS is endocytosed, together with other p24 proteins, and eventually accumulates in late endosomes, where it remains confined to well-defined membrane regions visible by electron microscopy. We find that this p25SS accumulation causes a concomitant accumulation of cholesterol in late endosomes, and an inhibition of their motility - two processes that are functionally linked. Yet, the p25SS-rich regions themselves seem to-exclude not only Lamp1 but also accumulated cholesterol. One may envision that p25SS accumulation, by excluding cholesterol from oligomers, eventually overloads neighboring late endosomal membranes with cholesterol beyond their capacity (see Discussion). In any case, our data show that p25 and presumably other p24 proteins are endowed with the intrinsic capacity to form highly specialized domains that control membrane composition and dynamics. We propose that p25 and other p24 proteins control the fidelity of membrane transport by maintaining cholesterol-poor membranes in the Golgi complex.

GRIP domain-mediated targeting of two new coiled-coil proteins, GCC88 and GCC185, to subcompartments of the trans-Golgi network

The GRIP domain is a targeting sequence found in a family of coiled-coil peripheral Golgi proteins. Previously we demonstrated that the GRIP domain of p230/golgin245 is specifically recruited to tubulovesicular structures of the traps-Golgi network (TGN). Here we have characterized two novel Golgi proteins with functional GRIP domains, designated GCC88 and GCC185. GCC88 cDNA encodes a protein of 88 kDa, and GCC185 cDNA encodes a protein of 185 kDa. Both molecules are brefeldin A-sensitive peripheral membrane proteins and are predicted to have extensive coiled-coil regions with the GRIP domain at the C terminus. By immunofluorescence and immunoelectron microscopy GCC88 and GCC185, and the GRIP protein golgin97, are all localized to the TGN of Hela cells. Overexpression of full-length GCC88 leads to the formation of large electron dense structures that extend from the traps-Golgi. These de novo structures contain GCC88 and co-stain for the TGN markers syntaxin 6 and TGN38 but not for alpha2,6-sialyltransferase, beta-COP, or cis-Golgi GM130. The formation of these abnormal structures requires the N-terminal domain of GCC88. TGN38, which recycles between the TGN and plasma membrane, was transported into and out of the GCC88 decorated structures. These data introduce two new GRIP domain proteins and implicate a role for GCC88 in the organization of a specific TGN subcompartment involved with membrane transport.

GAIP participates in budding of membrane carriers at the trans-Golgi network

Galpha interacting protein (GAIP) is a regulator of G protein signaling protein that associates dynamically with vesicles and has been implicated in membrane trafficking, although its specific role is not yet known. Using an in vitro budding assay, we show that GAIP is recruited to a specific population of trans-Golgi network-derived vesicles and that these are distinct from coatomer or clathrin-coated vesicles. A truncation mutant (NT-GAIP) encoding only the N-terminal half of GAIP is recruited to trans -Golgi network membranes during the formation of vesicle carriers. Overexpression of NT-GAIP induces the formation of long, coated tubules, which are stabilized by microtubules. Results from the budding assay and from imaging in live cells show that these tubules remain attached to the Golgi stack rather than being released as carrier vesicles. NT-GAIP expression blocks membrane budding and results in the accumulation of tubular carrier intermediates. NT-GAIP-decorated tubules are competent to load vesicular stomatitis virus protein G-green fluorescent protein as post-Golgi, exocytic cargo and in cells expressing NT-GAIP there is reduced surface delivery of vesicular stomatitis virus protein G-green fluorescent protein. We conclude that GAIP functions as an essential part of the membrane budding machinery for a subset of post-Golgi exocytic carriers derived from the trans-Golgi network.

Influence of hysteresis on tidal capillary fringe dynamics in a well-sorted sand

Nielsen and Perrochet [Adv. Water Resour. 23 (2000) 503] presented experimental data for cyclic water movement in the vadose zone above an oscillating watertable. The response of the watertable to cyclic forcing was characterised by the ratios of the forcing head to watertable amplitudes and their associated phase lag. They found that their non-hysteretic Richards' equation model failed to represent the observed behaviour of these parameters. This paper explores the effect on the simulated capillary fringe dynamics (in terms of these parameters) of including varying degrees of hysteresis in the moisture retention curve used in a numerical model of their experiment. It is clear that hysteresis can indeed account for observed discrepancies between simulation and experiment and that the effect of hysteresis varies with the frequency of oscillation. The use of a single-valued mean retention curve, as advocated by some authors, fails to provide a match between the simulated and observed behaviour of the Nielsen and Perrochet parameters, but is shown to be adequate for predicting time-averaged soil moisture profiles. (C) 2003 Elsevier Ltd. All rights reserved.

A reduced load approximation accounting for link interactions in a loss network

This paper is concerned with evaluating the performance of loss networks. Accurate determination of loss network performance can assist in the design and dimen- sioning of telecommunications networks. However, exact determination can be difficult and generally cannot be done in reasonable time. For these reasons there is much interest in developing fast and accurate approximations. We develop a reduced load approximation that improves on the famous Erlang fixed point approximation (EFPA) in a variety of circumstances. We illustrate our results with reference to a range of networks for which the EFPA may be expected to perform badly.

Genotype and environment effects on dynamics of harvest index during grain filling in sorghum

An approach based on a linear rate of increase in harvest index (141) with time after anthesis has been used as a simple means-to predict grain growth and yield in many crop simulation models. When applied to diverse situations, however, this approach has been found to introduce significant error in grain yield predictions. Accordingly, this study was undertaken to examine the stability of the HI approach for yield prediction in sorghum [Sorghum bicolor (L.) Moench]. Four field experiments were conducted under nonlimiting water. and N conditions. The experiments were sown at times that ensured a broad range in temperature and radiation conditions. Treatments consisted of two population densities and three genotypes varying in maturity. Frequent sequential harvests were used to monitor crop growth, yield, and the dynamics of 111. Experiments varied greatly in yield and final HI. There was also a tendency for lower HI with later maturity. Harvest index dynamics also varied among experiments and, to a lesser extent, among treatments within experiments. The variation was associated mostly with the linear rate of increase in HI and timing of cessation of that increase. The average rate of HI increase was 0.0198 d(-1), but this was reduced considerably (0.0147) in one experiment that matured in cool conditions. The variations found in IN dynamics could be largely explained by differences in assimilation during grain filling and remobilization of preanthesis assimilate. We concluded that this level of variation in HI dynamics limited the general applicability of the HI approach in yield prediction and suggested a potential alternative for testing.

SPAnDX: a process-based population dynamics model to explore management and climate change impacts on an invasive alien plant, Acacia nilotica

This paper describes a process-based metapopulation dynamics and phenology model of prickly acacia, Acacia nilotica, an invasive alien species in Australia. The model, SPAnDX, describes the interactions between riparian and upland sub-populations of A. nilotica within livestock paddocks, including the effects of extrinsic factors such as temperature, soil moisture availability and atmospheric concentrations of carbon dioxide. The model includes the effects of management events such as changing the livestock species or stocking rate, applying fire, and herbicide application. The predicted population behaviour of A. nilotica was sensitive to climate. Using 35 years daily weather datasets for five representative sites spanning the range of conditions that A. nilotica is found in Australia, the model predicted biomass levels that closely accord with expected values at each site. SPAnDX can be used as a decision-support tool in integrated weed management, and to explore the sensitivity of cultural management practices to climate change throughout the range of A. nilotica. The cohort-based DYMEX modelling package used to build and run SPAnDX provided several advantages over more traditional population modelling approaches (e.g. an appropriate specific formalism (discrete time, cohort-based, process-oriented), user-friendly graphical environment, extensible library of reusable components, and useful and flexible input/output support framework). (C) 2003 Published by Elsevier Science B.V.

Effect of pore-network connectivity on multicomponent adsorption of large molecules

The effect of pore-network connectivity on binary liquid-phase adsorption equilibria using the ideal adsorbed solution theory (LAST) was studied. The liquid-phase binary adsorption experiments used ethyl propionate, ethyl butyrate, and ethyl isovalerate as the adsorbates and commercial activated carbons Filtrasorb-400 and Norit ROW 0.8 as adsorbents. As the single-component isotherm, a modified Dubinin-Radushkevich equation was used. A comparison with experimental data shows that incorporating the connectivity of the pore network and considering percolation processes associated with different molecular sizes of the adsorptives in the mixture, as well as their different corresponding accessibility, can improve the prediction of binary adsorption equilibria using the LAST Selectivity of adsorption for the larger molecule in binary systems increases with an increase in the pore-network coordination number, as well with an increase in the mean pore width and in the spread of the pore-size distribution.

Mulheres mães vítimas de violência : impactos, vivências e constituição da rede de apoio sócio afetiva

A violência está presente a nível nacional e mundial no cotidiano de muitas famílias e se configura como um fenômeno de múltiplas determinações, podendo estar presente no cenário público e privado. Diante dos diversos tipos de violência presentes no espaço social, encontra-se a violência praticada pelo homem contra sua companheira. O presente estudo, com enfoque qualitativo, objetivou de maneira geral investigar de que forma o Centro de Referência Especializado da Assistência Social – Proteção e Atendimento Especializado a Famílias e Indivíduos (CREAS PAEFI “Adulto”) do município de Colatina, compõe a rede de apoio social e afetiva de mulheres/mães vítimas de violência física e/ou psicológica por parte de seus maridos/companheiros na percepção dos profissionais atuantes no serviço e, também, na percepção das próprias mulheres vítimas de violência usuárias do serviço. Para tanto, participaram da pesquisa 10 mulheres/mães usuárias do CREAS PAEFI “Adulto” do município de Colatina/ES, com faixa etária variando de 34 a 45 anos, que sofreram violência física e/ou psicológica por parte de seus maridos/companheiros e que possuíam pelo menos um filho. Também participaram da pesquisa 6 profissionais, com faixa etária variando de 25 a 38 anos, que faziam parte da equipe técnica do serviço. Os dados foram coletados por meio de entrevistas semi estruturadas realizadas individualmente em sala cedida pelo CREAS PAEFI “Adulto”. Para a organização dos dados utilizou-se a Análise de Conteúdo, sendo estes organizados em eixos temáticos e discutidos com base na Teoria Bioecológica do Desenvolvimento Humano de Urie Bronfenbrenner. Como resultados principais, pode-se notar que as interações estabelecidas entre os profissionais e as mulheres vítimas de violência usuárias do CREAS favoreceram processos proximais que promoveram mudanças positivas nas características pessoais das mulheres e reforçaram as relações que elas possuíam com suas famílias, principalmente com os filhos. Também foi verificado no macrossistema, que os papéis sociais estabelecidos pela sociedade para o homem e para a mulher estavam presentes nos discursos das usuárias do serviço, os quais naturalizavam a mulher como responsável pelos filhos, casa e marido, e o homem como o provedor da casa. A maternidade foi considerada por todas as usuárias como um fator importante em suas vidas e causou mudanças na dinâmica familiar com o companheiro.Verificou-se o comprometimento e envolvimento dos profissionais no atendimento às mulheres que se mostraram interessadas e engajadas com o atendimento e que tinham o objetivo de reconstruir suas vidas. A articulação do CREAS com a rede de atendimento à mulher vítima de violência no município de Colatina foi considerada satisfatória, principalmente levando em consideração o fato de que a cidade é pequena, o que facilita o contato entre os serviços. Algumas mulheres expuseram outras fontes de apoio que atuaram concomitantemente ao CREAS como, os amigos e a religião (Deus). Conclui-se que o CREAS PAEFI foi um serviço integrante da rede de apoio sócio afetiva das mulheres vítimas de violência que participaram do estudo, atuando como um microssistema significativo que favoreceu o desenvolvimento das mulheres frente à situação de violência vivenciada

Currículo e educação especial : as ações da escola a partir dos diálogos cotidianos

O estudo teve como objetivo investigar as ações constituídas por uma escola pública de Ensino Fundamental para o envolvimento de alunos com deficiência e com transtornos globais do desenvolvimento no currículo escolar. Contou com as contribuições teóricas de Boaventura de Sousa Santos, Michel de Certeau e Philippe Meirieu para uma discussão sociológica, filosófica e pedagógica das situações desencadeadas pela pesquisa. No campo do currículo, aproximou-se das teorizações de Silva, Moreira, Apple e Sacristán, dentre outros, por serem teóricos que analisam o trabalho com o conhecimento no contexto escolar. Já no campo da Educação Especial, dialogou com as produções de pesquisadores que postulam pela ideia de que o processo de inclusão escolar pressupõe acesso à escola, bem como permanência e a garantia do direito de apropriação dos conhecimentos socialmente produzidos. Como aporte teórico-metodológico, apoiou-se nos pressupostos da pesquisa-ação colaborativo-crítica que advoga pela possibilidade de, por meio da pesquisa científica, produzir conhecimento sobre a realidade social, promover mudanças nas situações desafiadoras e envolver os sujeitos pesquisados em processos de formação continuada em contexto. O trabalho de pesquisa foi realizado em uma escola de Ensino Fundamental, pertencente à Rede Pública Municipal de Ensino de Vila Velha/ES, envolvendo professores, pedagogos, dirigente escolar, responsáveis pelos discentes e alunos matriculados do 1º ao 6º ano do Ensino Fundamental. O processo de produção de dados se efetivou no período de julho de 2010 a julho de 2011. O pesquisador esteve três vezes por semana no campo de pesquisa, participando das intervenções em sala de aula, dos espaços para planejamento e formação continuada e também de momentos informais na entrada, recreio e saída dos alunos. Para o desenvolvimento do estudo, trabalhou-se com três frentes correlacionadas: a observação participante e a escuta dos discursos produzidos por alunos, professores, equipe técnico-pedagógica e responsáveis pelos discentes sobre o envolvimento dos estudantes com indicativos à Educação Especial no currículo escolar; a constituição de espaços de formação continuada, tomando os dados produzidos na primeira etapa do estudo como elementos de sustentação da dinâmica formativa; o acompanhamento das ações praticadas pela escola para envolvimento das necessidades educacionais dos alunos com indicativos à Educação Especial no currículo escolar, a partir das reflexões desencadeadas nos espaços de formação continuada. Como resultados, a pesquisa aponta a necessidade de advogar pela constituição de currículos escolares mais abertos para contemplar as necessidades de aprendizagem de alunos com comprometimentos físicos, psíquicos, intelectuais ou sensoriais. Esta pesquisa se distancia de lógicas que defendem a flexibilização curricular como um esvaziamento do currículo em nome das condições existenciais dos alunos. Entende que, entre o currículo escolar e a produção de conhecimentos pelos alunos com indicativos à Educação Especial, há uma pluralidade de situações que precisam ser problematizadas pela escola: a leitura produzida sobre a aprendizagem dos alunos; a falta de conhecimento sobre a sexualidade humana; os desafios presentes na relação família e escola; e os pressupostos da normalidade/anormalidade. Esses fatores podem se configurar como elementos que impedem que os alunos obtenham sucesso em sua jornada educativa, porém, em contrapartida, podem ser utilizados como questões a subsidiar espaços de formação continuada. O estudo aponta que, por meio de atitudes colaborativas e críticas entre os profissionais da escola, é possível articular ações que garantam o direito de aprender do estudante com deficiência e com transtornos globais do desenvolvimento na escola de ensino comum.

A network society communicative model for optimizing the Refugee Status Determination (RSD) procedures

This article recommends a new way to improve Refugee Status Determination (RSD) procedures by proposing a network society communicative model based on active involvement and dialogue among all implementing partners. This model, named after proposals from Castells, Habermas, Apel, Chimni, and Betts, would be mediated by the United Nations High Commissioner for Refugees (UNHCR), whose role would be modeled after that of the International Committee of the Red Cross (ICRC) practice.

An outline of military technological dynamics as restraints for acquisition, international cooperation and domestic technological development

The expectation that technological returns from defense expenditure through acquisition, international cooperation and domestic research would further national development underappreciates the different technological dynamic of the armed services. This paper outlines the technological dynamic the stems from fighting in the air, at sea and on land, exemplifying consequences for the case of acquisition.

The international implications of the Chinese model of development in the Global South: Asian Consensus as a network power

This paper analyzes People's Republic of China (PRC) economic and political ascendance in the 21st century focusing on the evolution of the sui generis economic development model and its significances of the evolution of relationship between China and the developing countries in the peripheral "Global South." The objective of this article is to analyze the relationship between China and the Global South (Africa and South America) in the 21st century, characterized as a new Center-periphery global network power based on trade and investment that we call as "Asian Consensus."