Fumarate Analogs Act as Allosteric Inhibitors of the Human Mitochondrial NAD(P)+-Dependent Malic Enzyme

Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P)-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P)-ME_R67A/R91A and m-NAD(P)-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P)-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P)-ME enzyme activity

Predicting Exchange Rates in Asia: New Insights on the Accuracy of Survey Forecasts

This paper evaluates aggregated survey forecasts with forecast horizons of 3, 12, and 24 months for the exchange rates of the Chinese yuan, the Hong Kong dollar, the Japanese yen, and the Singapore dollar vis-à-vis the US dollar using common forecast accuracy measures. Additionally, the rationality of the exchange rate predictions are assessed utilizing tests for unbiasedness and efficiency. All investigated forecasts are irrational in the sense that the predictions are biased. However, these results are inconsistent with an alternative measure of rationality based on methods of applied time series analysis. Investigating the order of integration of the time series and using cointegration analysis, empirical evidence supports the conclusion that the majority of forecasts are rational. Regarding forerunning properties of the predictions, the results are less convincing, with shorter term forecasts for the tightly managed USD/CNY FX regime being one exception. As one important evaluation result, it can be concluded, that the currency regime matters for the quality of exchange rate forecasts

Nanomaterials in the Environment: Behavior, Fate, Bioavailability, and Effects-An Updated Review.

This review covers developments in studies of nanomaterials (NMs) in the environment, since the much-cited review of Klaine et al. (2008). It discusses novel insights on fate and behavior, metrology, transformations, bioavailability, toxicity mechanisms and environmental impacts, with a focus on terrestrial and aquatic systems. Overall the findings were that: i) despite the substantial developments, there remain critical gaps, in large part due to the lack of analytical, modelling and field capabilities and in part due to the breadth and complexity of the area; ii) a key knowledge gap is the lack of data on environmental concentrations and dosimetry generally; iii) there is substantial evidence that there are nano-specific effects (different from both ions and larger particles) in the environment in terms of fate, bioavailability and toxicity, but this is not consistent for all NMs, species and all relevant processes; iv) a paradigm is emerging that NMs are less toxic than equivalent dissolved materials but more toxic than the corresponding bulk materials; v) translation of incompletely understood science into regulation and policy continues to be challenging. There is a developing consensus that NMs may pose a relatively low environmental risk, however, with the uncertainty and lack of data in many areas, definitive conclusions cannot be drawn. In addition, this emerging consensus will likely change rapidly with qualitative changes in the technology and increased future discharges. This article is protected by copyright. All rights reserved

The third dimension in urban geography; the urban volume approach

A new methodology is presented that measures density in urban systems. By combining highly detailed height measurements with, amongst others, topographical data we are able to quantify urban volume. This new approach is demonstrated in two separate case studies that relate to the temporal and spatial dimension of the urban environment, respectively. In the first study the growth of the city of Amsterdam over the past century is studied. The urban-volume indicator is used to visualise and quantify the urban extension and intensification process. To critically analyse the spatiotemporal development of Amsterdam the self-organising-map approach is applied. Special attention is given to highlighting any signs of recent polynuclear development. The second case study compares the building-height frequency and spatial distribution of high-density zones in the four major Dutch cities. Additionally, the presence of built-up areas and the actual urban-volume values are explained simultaneously using a Heckman selection model. © 2009 Pion Ltd and its Licensors