Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy

SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP (also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum. We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sj?gren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy. Identification of SIL1 mutations implicates Marinesco-Sj?gren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders.     

Interactions between amphetamine and reserpine in vitro

Resumen Se estudia en el conducto deferente aislado de rata la respuesta a la reserpina después de la estimulación del preparado con anfetamina. En estas condiciones, la reserpina produce una contracción que es proporcional a las concentraciones de anfetamina y reserpina utilizadas, y es máxima para una concentración de reserpina de 2,5×10^–5 g/ml, para ser luego decreciente cualquiera que sea la concentración de anfetamina que se haya empleado previamente. Se discuten los posibles mecanismos que regulan la respuesta a la reserpina después de la anfetamina.     

Twisting the Dollar? On the Consistency of Short‐Run and Long‐Run Exchange Rate Expectations

We examine consistency properties of the exchange rate expectation formation process of short‐run and long‐run forecasts in the dollar/euro and yen/dollar market. Applying nonlinear consistency restrictions we show that in a simple expectation formation structure short‐run forecasts are indeed inconsistent with long‐run predictions. Moreover, we establish a ‘twist’ in the dollar/euro expectation formation process, i.e. market participants expect bandwagon effects in the short run, while they have stabilizing expectations in their long‐run forecasts. Applying a panel probit analysis we find that this twisting behavior is more likely to occur in periods of excess exchange rate volatility. Copyright © 2011 John Wiley & Sons, Ltd.     

The evolution of X chromosome inactivation in mammals: the demise of Ohno’s hypothesis?

Ohno’s hypothesis states that dosage compensation in mammals evolved in two steps: a twofold hyperactivation of the X chromosome in both sexes to compensate for gene losses on the Y chromosome, and silencing of one X (X-chromosome inactivation, XCI) in females to restore optimal dosage. Recent tests of this hypothesis have returned contradictory results. In this review, we explain this ongoing controversy and argue that a novel view on dosage compensation evolution in mammals is starting to emerge. Ohno’s hypothesis may be true for a few, dosage-sensitive genes only. If so few genes are compensated, then why has XCI evolved as a chromosome-wide mechanism? This and several other questions raised by the new data in mammals are discussed, and future research directions are proposed.     

Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins

The isolation of extracellular vesicles (EVs) from blood is of great importance to understand the biological role of circulating EVs and to develop EVs as biomarkers of disease. Due to the concurrent presence of lipoprotein particles, however, blood is one of the most difficult body fluids to isolate EVs from. The aim of this study was to develop a robust method to isolate and characterise EVs from blood with minimal contamination by plasma proteins and lipoprotein particles. Plasma and serum were collected from healthy subjects, and EVs were isolated by size-exclusion chromatography (SEC), with most particles being present in fractions 8–12, while the bulk of the plasma proteins was present in fractions 11–28. Vesicle markers peaked in fractions 7–11; however, the same fractions also contained lipoprotein particles. The purity of EVs was improved by combining a density cushion with SEC to further separate lipoprotein particles from the vesicles, which reduced the contamination of lipoprotein particles by 100-fold. Using this novel isolation procedure, a total of 1187 proteins were identified in plasma EVs by mass spectrometry, of which several proteins are known as EV-associated proteins but have hitherto not been identified in the previous proteomic studies of plasma EVs. This study shows that SEC alone is unable to completely separate plasma EVs from lipoprotein particles. However, combining SEC with a density cushion significantly improved the separation of EVs from lipoproteins and allowed for a detailed analysis of the proteome of plasma EVs, thus making blood a viable source for EV biomarker discovery.     

The Liar-paradox in a Quantum Mechanical Perspective

In this paper we concentrate on the nature of the liar paradox asa cognitive entity; a consistently testable configuration of properties. We elaborate further on a quantum mechanical model (Aerts, Broekaert and Smets, 1999) that has been proposed to analyze the dynamics involved, and we focus on the interpretation and concomitant philosophical picture. Some conclusions we draw from our model favor an effective realistic interpretation of cognitive reality.     

Boltzmann's ergodic hypothesis

Summary Boltzmann's ergodic hypothesis is usually understood as the assumption that the trajectory of an isolated mechanical system runs through all states compatible with the total energy of the system. This understanding of Boltzmann stems from the Ehrenfests' review of the foundations of statistical mechanics in 1911. If Boltzmann's work is read with any attention, it becomes impossible to ascribe to him the claim that one single trajectory would fill the whole of state space. He admitted a continuous number of different possible mechanical trajectories. Ergodicity was formulated as the condition that only one integral of motion, the total energy, is preserved in time. The two reasons for this are external disturbing forces and collisions within the system. Boltzmann found it difficult to ascribe ergodic behavior to a single system where the theoretical dependence on initial conditions, though never observed, has to be admitted as possible. To circumvent the dependence, he invented the concept of a microcanonical ensemble.     

Asymmetries in conditional mean and variance: modelling stock returns by asMA‐asQGARCH

We propose a nonlinear time series model where both the conditional mean and the conditional variance are asymmetric functions of past information. The model is particularly useful for analysing financial time series where it has been noted that there is an asymmetric impact of good news and bad news on volatility (risk) transmission. We introduce a coherent framework for testing asymmetries in the conditional mean and the conditional variance, separately or jointly. To this end we derive both a Wald and a Lagrange multiplier test. Some of the new asymmetric model's moment properties are investigated. Detailed empirical results are given for the daily returns of the composite index of the New York Stock Exchange. There is strong evidence of asymmetry in both the conditional mean and the conditional variance functions. In a genuine out‐of‐sample forecasting experiment the performance of the best fitted asymmetric model, having asymmetries in both conditional mean and conditional variance, is compared with an asymmetric model for the conditional mean, and with no‐change forecasts. This is done both in terms of conditional mean forecasting as well as in terms of risk forecasting. Finally, the paper presents some evidence of asymmetries in the index stock returns of the Group of Seven (G7) industrialized countries. Copyright © 2004 John Wiley & Sons, Ltd.