Post-translational modifications of lipid-activated nuclear receptors: Focus on metabolism

Post-translational modifications (PTM) occur to nearly all proteins, are catalysed by specific enzymes and are subjected to tight regulation. They have been shown to be a powerful means by which the function of proteins can be modified resulting in diverse effects. Technological advances such as the increased sensitivity of mass spectrometry-based techniques and availability of mutant animal models have enhanced our understanding of the complexities of their regulation and the effect they have on protein function. However, the role that PTMs have in a pathological context still remains unknown for the most part. PTMs enable the modulation of nuclear receptor function in a rapid and reversible manner in response to varied stimuli, thereby dramatically altering their activity in some cases. This review will focus on acetylation, phosphorylation, sumoylation and O-GlcNAcylation, which are the four most studied PTMs affecting lipid-regulated nuclear receptor biology, and the implications of such modifications on metabolic pathways under homeostatic and pathological situations. Moreover, we review recent studies on the modulation of PTMs as therapeutic targets for metabolic diseases

Comparative rainfall data analysis from two vertically pointing radars, an optical disdrometer, and a rain gauge

The authors present results of a comparative analysis of rainfall data from several ground-based instruments. The instruments include two vertically pointing Doppler radars, S-band and X-band, an optical disdrometer, and a tipping-bucket rain gauge. All instruments were collocated at the Iowa City Municipal Airport in Iowa City, Iowa, for a period of several months. The authors used the rainfall data derived from the four instruments to first study the temporal variability and scaling characteristics of rainfall and subsequently assess the instrumental effects on these derived properties. The results revealed obvious correspondence between the ground and remote sensors, which indicates the significance of the instrumental effect on the derived properties

On testing global optimization algorithms for space trajectory design

In this paper we discuss the procedures to test a global search algorithm applied to a space trajectory design problem. Then, we present some performance indexes that can be used to evaluate the effectiveness of global optimization algorithms. The performance indexes are then compared highlighting the actual significance of each one of them. A number of global optimization algorithms are tested on four typical space trajectory design problems. From the results of the proposed testing procedure we infer for each pair algorithm-problem the relation between the heuristics implemented in the solution algorithm and the main characteristics of the problem under investigation. From this analysis we derive a novel interpretation of some evolutionary heuristics, based on dynamical system theory and we significantly improve the performance of one of the tested algorithms

Statistical geometry in scalar turbulence

A general link between geometry and intermittency in passive scalar turbulence is established. Intermittency is qualitatively traced back to events where tracer particles stay for anomalousy long times in degenerate geometries characterized by strong clustering. The quantitative counterpart is the existence of special functions of particle configurations which are statistically invariant under the flow. These are the statistical integrals of motion controlling the scalar statistics at small scales and responsible for the breaking of scale invariance associated to intermittency.Comment: 4 pages, 5 figure

LXRα phosphorylation in cardiometabolic disease: insight from mouse models

Posttranslational modifications, such as phosphorylation, are a powerful means by which the activity and function of nuclear receptors such as LXRα can be altered. However, despite the established importance of nuclear receptors in maintaining metabolic homeostasis, our understanding of how phosphorylation affects metabolic diseases is limited. The physiological consequences of LXRα phosphorylation have, until recently, been studied only in vitro or nonspecifically in animal models by pharmacologically or genetically altering the enzymes enhancing or inhibiting these modifications. Here we review recent reports on the physiological consequences of modifying LXRα phosphorylation at serine 196 (S196) in cardiometabolic disease, including nonalcoholic fatty liver disease, atherosclerosis, and obesity. A unifying theme from these studies is that LXRα S196 phosphorylation rewires the LXR-modulated transcriptome, which in turn alters physiological response to environmental signals, and that this is largely distinct from the LXR-ligand–dependent action

Degenerate dispersive equations arising in the study of magma dynamics

An outstanding problem in Earth science is understanding the method of transport of magma in the Earth's mantle. Models for this process, transport in a viscously deformable porous media, give rise to scalar degenerate, dispersive, nonlinear wave equations. We establish a general local well-posedness for a physical class of data (roughly $H^1$) via fixed point methods. The strategy requires positive lower bounds on the solution. This is extended to global existence for a subset of possible nonlinearities by making use of certain conservation laws associated with the equations. Furthermore, we construct a Lyapunov energy functional, which is locally convex about the uniform state, and prove (global in time) nonlinear dynamic stability of the uniform state for any choice of nonlinearity. We compare the dynamics to that of other problems and discuss open questions concerning a larger range of nonlinearities, for which we conjecture global existence.Comment: 27 Pages, 7 figures are not present in this version. See http://www.columbia.edu/~grs2103/ for a PDF with figures. Submitted to Nonlinearit

Ontogeny of synaptophysin and synaptoporin in the central nervous system

The expression of the synaptic vesicle antigens synaptophysin (SY) and synaptoporin (SO) was studied in the rat striatum, which contains a nearly homogeneous population of GABAergic neurons. In situ hybridization revealed high levels of SY transcripts in the striatal anlage from embryonic day (E) 14 until birth. In contrast. SO hybridization signals were low, and no immunoreactive cell bodies were detected at these stages of development. At E 14, SY-immunoreactivity was restricted to perikarya. In later prenatal stages of development SY-immunoreactivity appeared in puncta (identified as terminals containing immunostained synaptic vesicles), fibers, thick fiber bundles and ‘patches’. In postnatal and adult animals, perikarya of striatal neurons exhibited immunoreaction for SO; ultrastructurally SO antigen was found in the Golgi apparatus and in multivesicular bodies. SO-positive boutons were rare in the striatum. In the neuropil, numerous presynaptic terminals positive for SY were observed. Our data indicate that the expression of synaptic vesicle proteins in GABAergic neurons of the striatum is developmentally regulated. Whereas SY is prevalent during embryonic development, SO is the major synaptic vesicle antigen expressed postnatally by striatal neurons which project to the globus pallidus and the substantia nigra. In contrast synapses of striatal afferents (predominantly from cortex, thalamus and substantia nigra) contain SY

Understanding the impact of legislation on 'reduction of disease risk' claims on food and drinks: The REDICLAIM project

The Nutrition and Health Claims Regulation (EC No. 1924/2006) has established a common framework for the regulation of nutrition and health claims used on foods across the European Union. This regulation aims to provide the European food industry opportunities for product innovation whilst protecting consumer interests with respect to controlling misleading advertising and promoting public health. However, in order to satisfy the approval of new health claims procedure particularly for new 'reduction of disease risk' claims [Article 14(1)(a) claims], significant research activity is required by industry to scientifically substantiate the claims they wish to make. There is a need to establish whether the implementation of this legislation is in fact driving product innovation and the development of healthy foods or whether it forms a barrier to such developments. The EU-funded REDICLAIM project is currently considering these issues. This article describes the project's preliminary results and outlines the further programme of work