Ancestral roles of eukaryotic frataxin: mitochondrial frataxin function and heterologous expression of hydrogenosomal Trichomonas homologs in trypanosomes.

Frataxin is a small conserved mitochondrial protein; in humans, mutations affecting frataxin expression or function result in Friedreich's ataxia. Much of the current understanding of frataxin function comes from informative studies with yeast models, but considerable debates remain with regard to the primary functions of this ubiquitous protein. We exploit the tractable reverse genetics of Trypanosoma brucei in order to specifically consider the importance of frataxin in an early branching lineage. Using inducible RNAi, we show that frataxin is essential in T. brucei and that its loss results in reduced activity of the marker Fe-S cluster-containing enzyme aconitase in both the mitochondrion and cytosol. Activities of mitochondrial succinate dehydrogenase and fumarase also decreased, but the concentration of reactive oxygen species increased. Trypanosomes lacking frataxin also exhibited a low mitochondrial membrane potential and reduced oxygen consumption. Crucially, however, iron did not accumulate in frataxin-depleted mitochondria, and as T. brucei frataxin does not form large complexes, it suggests that it plays no role in iron storage. Interestingly, RNAi phenotypes were ameliorated by expression of frataxin homologues from hydrogenosomes of another divergent protist Trichomonas vaginalis. Collectively, the data suggest trypanosome frataxin functions primarily only in Fe-S cluster biogenesis and protection from reactive oxygen species

'Small European states in world markets' revisited The questioning of compensation policies in the light of the Swiss case

'Fifteen years ago, Katzenstein convincingly emphasized the specific features of small European states to cope with their external environment: international liberalization, domestic compensation and flexible adjustment to fluctuations of international markets through democratic corporatist institutions. Thus, small countries should be expected to be less vulnerable to the current trend of economic globalization, as they have previously been exposed to international competition, at least in product markets. Like other small European countries, Switzerland also developed some kind of compensation policies, which were quite different from the policies of other small European states, and favored mainly economic sectors producing for domestic markets. In the 1990's, the liberalization of domestic markets, in response to increasing external pressures, was one of the most important issues in Swiss politics. External pressures, and the changing political preferences of the export-oriented sectors, also triggered important changes in other social and economic policy domains. While much attention has been paid to the recent changes in Scandinavian countries, especially Sweden, the Swiss 'liberal-conservative model' also faced important changes in the recent period. In the paper, the author highlights in which ways the processes of globalization and 'europeanization' affect social and economic policies, which can be considered compensation policies. He analyses three main fields (labor market regulations, social policies and domestic regulations favouring domestic economic sectors) where changes occurred in the recent period.' (author's abstract)'Vor fuenfzehn Jahren hat Katzenstein die spezifischen Anpassungsmerkmale kleiner europaeischer Staaten an ihre internationale Umgebung ueberzeugend gezeigt: internationale Liberalisierung, innere Kompensation und flexible Anpassung an internationale Maerkte durch korporatistische Institutionen. Dank ihrer fruehen Integration in die Weltmaerkte muessten kleine Staaten im jetzigen Globalisierungsprozess weniger verwundbar sein. Wie andere kleine europaeische Staaten hat auch die Schweiz einige Kompensationspolitiken entwickelt. Diese unterschieden sich aber sehr von den Politiken anderer europaeischer Staaten und konzentrierten sich haupsaechlich auf den Schutz des Binnenmarkts. Waehrend der 90er Jahre war die Liberalisierung des Binnenmarkts als Antwort auf steigenden internationalen Druck eines der wichtigsten Themen der schweizerischen Politik. Aeusserer Druck und die Aenderung der politischen Praeferenzen der exportorientierten Sektoren haben auch wichtige Reformen in anderen Bereichen der Sozial- und Wirtschaftspolitik ausgeloest. Waehrend viel ueber Reformen in den skandinavischen Laender, besonders in Schweden, geschrieben wurde, hat auch das schweizerische 'liberal-konservative' Modell viele Reformen erlebt. In dem Papier wird gezeigt, wie sich die Globalisierungs- und Europaeisierungsprozesse auf die Sozial- und Wirtschaftspolitik, die man als Kompensationspolitiken bezeichnen kann, auswirken. Drei Bereiche, wo Reformen stattgefunden haben, wurden analysiert: Arbeitsmarktregulierungen, Sozialpolitik und protektionistische Regulierungen des Binnenmarkts.' (Autorenreferat)German title: Kleine europaeische Staaten im Weltmarkt: Globalisierung und schweizerische KompensationspolitikAvailable from UuStB Koeln(38)-20001102808 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Copy Number Variations Found in Patients with a Corpus Callosum Abnormality and Intellectual Disability

International audienceOBJECTIVE:To evaluate the role that chromosomal micro-rearrangements play in patients with both corpus callosum abnormality and intellectual disability, we analyzed copy number variations (CNVs) in patients with corpus callosum abnormality/intellectual disability STUDY DESIGN: We screened 149 patients with corpus callosum abnormality/intellectual disability using Illumina SNP arrays.RESULTS:In 20 patients (13%), we have identified at least 1 CNV that likely contributes to corpus callosum abnormality/intellectual disability phenotype. We confirmed that the most common rearrangement in corpus callosum abnormality/intellectual disability is inverted duplication with terminal deletion of the 8p chromosome (3.2%). In addition to the identification of known recurrent CNVs, such as deletions 6qter, 18q21 (including TCF4), 1q43q44, 17p13.3, 14q12, 3q13, 3p26, and 3q26 (including SOX2), our analysis allowed us to refine the 2 known critical regions associated with 8q21.1 deletion and 19p13.1 duplication relevant for corpus callosum abnormality; report a novel 10p12 deletion including ZEB1 recently implicated in corpus callosum abnormality with corneal dystrophy; and) report a novel pathogenic 7q36 duplication encompassing SHH. In addition, 66 variants of unknown significance were identified in 57 patients encompassed candidate genes.CONCLUSIONS:Our results confirm the relevance of using microarray analysis as first line test in patients with corpus callosum abnormality/intellectual disability.Copyright © 2017 Elsevier Inc. All rights reserved