Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

Alci, Miguelzinho e Lazinho trouxeram espigas de milho, as primeiras colhidas no milharal de Ivo e Sueli, amigos e vizinhos, e Rosilene colocou na panela. Mais tarde, Alci, voltou com imensa abóbora que foi logo transformada em doce e ainda será quibebe e sopa, tudo em fogão de lenha. Neste recanto do sul de Minas, descoberto há cinco anos, conseguimos construir um pequeno refúgio. Marcia, arquiteta, decidiu que a casa teria grandes janelas e portas de vidro, abrindo para a floresta, (...) para vales e montanhas e, do lado direito, para a Pico do Papagaio, um dos símbolos de Minas Gerais. (shrink)

This article offers an interpretation of theories of management and organisation from the perspective of Hannah Arendt’s theory of free action. This endeavour will contribute to criticism and eventually improvement of the conceptual framework of management and organisation theory. We discuss conceptual tensions in this field, for instance with respect to the relationship between human action and the constraints of an organisation. To the extent that management and organisation theory are practiceoriented, such an analysis can help to understand tensions and (...) ambiguities in practice. Some of the optimism and high hopes found in the literature may have to be tempered as a consequence of a more adequate analysis of free action. The analysis therefore provides a critical point of view on the problems of managing freely acting people. (shrink)

In this paper I want to examine quantum teleportation from a point of view that is different from that normally considered. This will enable us to gain a new perspective into what is involved in the process of teleportation. It is clear that, at least in the case where particles are involved, it is not the particle that is transported, but rather the information contained in the wave function. This idea in itself is not new, but the central question that (...) requires clarification is the nature of this information. This paper provides a new insight into this question. (shrink)

In this article I argue that the value of epistemic justification cannot be adequately explained as being instrumental to truth. I intend to show that false belief, which is no means to truth, can nevertheless still be of epistemic value. This in turn will make a good prima facie case that justification is valuable for its own sake. If this is right, we will have also found reason to think that truth value monism is false: assuming that true belief does (...) have value, there is more of final epistemic value than mere true belief. (shrink)