Germline DLST variants promote epigenetic modifications in pheochromocytoma-paraganglioma

Context: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors in which altered central metabolism appears to be a major driver of tumorigenesis, and many PPGL genes encode proteins involved in the tricarboxylic acid (TCA) cycle.Objective/design: While about 40% of PPGL cases carry a variant in a known gene, many cases remain unexplained. In patients with unexplained PPGL showing clear evidence of a familial burden or multiple tumors, we aimed to identify causative factors using genetic analysis of patient DNA and functional analyses of identified DNA variants in patient tumor material and engineered cell lines.Patients and Setting: Patients with a likely familial cancer burden of pheochromocytomas and/or paragangliomas and under investigation in a clinical genetic and clinical research setting in university hospitals.Results: While investigating unexplained PPGL cases, we identified a novel variant, c.1151C>T, p.(Pro384Leu), in exon 14 of the gene encoding dihydrolipoamide S-succinyltransferase (DLST), a component of the multi-enzyme complex 2-oxoglutarate dehydrogenase. Targeted sequence analysis of further unexplained cases identified a patient carrying a tumor with compound heterozygous variants in DLST, consisting of a germline variant, c.1121G>A, p.(Gly374Glu), together with a somatic missense variant identified in tumor DNA, c.1147A>G, p.(Thr383Ala), both located in exon 14. Using a range of in silico and functional assays we show that these variants are predicted to be pathogenic, profoundly impact enzyme activity, and result in DNA hypermethylation.Conclusions: The identification and functional analysis of these DLST variants further validates DLST as an additional PPGL gene involved in the TCA cycle.MTG

Back to the future : using long-term observational and paleo-proxy reconstructions to improve model projections of Antarctic climate

Quantitative estimates of future Antarctic climate change are derived from numerical global climate models. Evaluation of the reliability of climate model projections involves many lines of evidence on past performance combined with knowledge of the processes that need to be represented. Routine model evaluation is mainly based on the modern observational period, which started with the establishment of a network of Antarctic weather stations in 1957/58. This period is too short to evaluate many fundamental aspects of the Antarctic and Southern Ocean climate system, such as decadal-to-century time-scale climate variability and trends. To help address this gap, we present a new evaluation of potential ways in which long-term observational and paleo-proxy reconstructions may be used, with a particular focus on improving projections. A wide range of data sources and time periods is included, ranging from ship observations of the early 20th century to ice core records spanning hundreds to hundreds of thousands of years to sediment records dating back 34 million years. We conclude that paleo-proxy records and long-term observational datasets are an underused resource in terms of strategies for improving Antarctic climate projections for the 21st century and beyond. We identify priorities and suggest next steps to addressing this

Large-Eddy Simulations of Magnetohydrodynamic Turbulence in Heliophysics and Astrophysics

We live in an age in which high-performance computing is transforming the way we do science. Previously intractable problems are now becoming accessible by means of increasingly realistic numerical simulations. One of the most enduring and most challenging of these problems is turbulence. Yet, despite these advances, the extreme parameter regimes encountered in space physics and astrophysics (as in atmospheric and oceanic physics) still preclude direct numerical simulation. Numerical models must take a Large Eddy Simulation (LES) approach, explicitly computing only a fraction of the active dynamical scales. The success of such an approach hinges on how well the model can represent the subgrid-scales (SGS) that are not explicitly resolved. In addition to the parameter regime, heliophysical and astrophysical applications must also face an equally daunting challenge: magnetism. The presence of magnetic fields in a turbulent, electrically conducting fluid flow can dramatically alter the coupling between large and small scales, with potentially profound implications for LES/SGS modeling. In this review article, we summarize the state of the art in LES modeling of turbulent magnetohydrodynamic (MHD) ows. After discussing the nature of MHD turbulence and the small-scale processes that give rise to energy dissipation, plasma heating, and magnetic reconnection, we consider how these processes may best be captured within an LES/SGS framework. We then consider several special applications in heliophysics and astrophysics, assessing triumphs, challenges,and future directions

Strategies for Controlled Placement of Nanoscale Building Blocks

The capability of placing individual nanoscale building blocks on exact substrate locations in a controlled manner is one of the key requirements to realize future electronic, optical, and magnetic devices and sensors that are composed of such blocks. This article reviews some important advances in the strategies for controlled placement of nanoscale building blocks. In particular, we will overview template assisted placement that utilizes physical, molecular, or electrostatic templates, DNA-programmed assembly, placement using dielectrophoresis, approaches for non-close-packed assembly of spherical particles, and recent development of focused placement schemes including electrostatic funneling, focused placement via molecular gradient patterns, electrodynamic focusing of charged aerosols, and others

Composition of woody species in a dynamic forest-woodland-savannah mosaic in Uganda: implications for conservation and management

Forest¿woodland¿savannah mosaics are a common feature in the East African landscape. For the conservation of the woody species that occur in such landscapes, the species patterns and the factors that maintain it need to be understood. We studied the woody species distribution in a forest¿woodland¿savannah mosaic in Budongo Forest Reserve, Uganda. The existing vegetation gradients were analyzed using data from a total of 591 plots of 400 or 500 m2 each. Remotely sensed data was used to explore current vegetation cover and the gradients there in for the whole area. A clear species gradient exists in the study area ranging from forest, where there is least disturbance, to wooded grassland, where frequent fire disturbance occurs. Most species are not limited to a specific part of the gradient although many show a maximum abundance at some point along the gradient. Fire and accessibility to the protected area were closely related to variation in species composition along the ordination axis with species like Cynometra alexandri and Uvariopsis congensis occurring at one end of the gradient and Combretum guenzi and Lonchocarpus laxiflorus at the other. The vegetation cover classes identified in the area differed in diversity, density and, especially, basal area. All vegetation cover classes, except open woodland, had indicator species. Diospyros abyssinica, Uvariopsis congensis, Holoptelea grandis and all Celtis species were the indicator species for the forest class, Terminalia velutina and Albizia grandbracteata for closed woodland, Grewia mollis and Combretum mole for very open woodland and Lonchocarpus laxiflorus, Grewia bicolor and Combretum guenzi for the wooded grassland class. Eleven of the species occurred in all cover classes and most of the species that occurred in more than one vegetation cover class showed peak abundance in a specific cover class. Species composition in the study area changes gradually from forest to savannah. Along the gradient, the cover classes are distinguishable in terms of species composition and vegetation structure. These classes are, however, interrelated in species composition. For conservation of the full range of the species within this East African landscape, the mosaic has to be managed as an integrated whole. Burning should be varied over the area with the forest not being burnt at all and the wooded grassland burnt regularly. The different vegetation types that occur between these two extremes should be maintained using a varied fire regim

Effect of traditional food processing methods on the nutritional value of yams in Cameroon

Meeting: Root Crops Symposium, 1st, 8-12 Sept. 1980, Ibadan, NGIn IDL-271

Influence des transformations technologiques traditionnelles sur la valeur nutritive de l'igname au Cameroun

Réunion: Symposium triennal sur les plantes-racines de la Société internationale pour les plantes-racines tropicales - Direction Afrique, 8-12 sept. 1980, Ibadan, NGDans IDL-471

Langual : un langage international pour la description structuree des aliments

National audienc

Description de la typicité des vins et boissons alcoolisées par le système international de codification LANGUAL

National audienc

Etude experimentale de la ramification de la pousse de l'annee du noyer

National audienc