Why Reform Europe's Universities?

Based on a survey of European universities, this policy brief states that despite the good performance of some countries, Europe as a whole trails the US by a wide margin. The reason is two-fold. First, Europe invests too little in higher education. Second, European universities suffer from poor governance, insufficient autonomy and often perverse incentives. If Europe is to be a leader in the global knowledge economy, comprehensive reform of higher education is the order of the day. Most countries should invest an extra one percent in higher education each year, and universities should be given more autonomy in budgets, hiring and remuneration.

Higher aspirations: an agenda for reforming European universities

Since the introduction of the Shanghai ranking of the worldâ??s universities it has been clear that European universities are underperforming. This blueprint discusses the potential explanations and points at different reform priorities for higher education in Europe.

Études structurales d’interactions protéine/protéine impliquées dans l’érythropoïèse

Le développement hématopoïétique est régulé par l’action combinée de facteurs de transcription lignée spécifiques et de la machinerie transcriptionnelle de base, permettant ainsi l’expression de gènes en temps et lieu appropriés. Les travaux présentés dans cette thèse portent sur l’étude structurale et fonctionnelle d’interactions décisives pour la régulation de l’expression de gènes et impliquant des domaines de transactivation (TAD). En effet, les interactions faisant intervenir les TAD d’activateurs permettent de réguler l’activation de la transcription de façon spécifique. La première étude présentée dans cette thèse relate l'identification et la caractérisation d'une nouvelle interaction entre deux facteurs de transcription : le facteur hématopoïétique GATA-1 et la protéine suppresseur de tumeur p53. En combinant des études in vitro par titrage calorimétrique en condition isotherme (ITC) et par spectroscopie RMN et des études in vivo, nous avons identifié et caractérisé cette nouvelle interaction. Il s'avère que le TAD de p53 et le domaine de liaison à l’ADN de GATA-1 sont les domaines minimaux requis pour la formation de ce complexe. L'inhibition de la voie p53 par GATA-1 s’est avérée être la conséquence majeure de cette interaction, permettant ainsi le maintien en vie des précurseurs érythrocytaires via l’inhibition de l’apoptose. Un deuxième type d’interaction a fait l’objet d’études : l’interaction entre divers TAD et la machinerie transcriptionnelle de base, plus spécifiquement avec le Facteur général de Transcription IIH (TFIIH). La structure des complexes constitués par la sous-unité Tfb1/p62 du facteur TFIIH en interaction avec le TAD viral de VP16 d’une part, et avec le TAD humain du facteur érythrocytaire « Erythroid Krüppel-like factor» (EKLF) d’autre part, ont été résolues par spectroscopie RMN. La structure du complexe Tfb1/VP16 a révélée que le mode de liaison de VP16 à Tfb1 est similaire au mode de liaison du TAD de p53 avec le même partenaire. En effet, les TAD de VP16 et de p53 forment tous deux une hélice α de 9 résidus en interaction avec Tfb1. En dépit de partager avec p53 et VP16 le même site de liaison sur Tfb1/p62, la structure RMN du complexe EKLF/Tfb1 démontre que le mode d’interaction de ce TAD se distingue du mode de liaison canonique des activeurs transcriptionnels. Etonnamment, EKLF adopte un mécanisme de liaison semblable au mécanisme de liaison du facteur général de transcription TFIIEα avec p62, leurs conformations demeurent étendues en interaction avec Tfb1/p62. En se basant sur nos données structurales, nous avons identifié un résidu dans le TAD d'EKLF décisif pour la formation du complexe EKLF/p62 : le Trp73. La mutation de cet acide aminé perturbe son interaction avec Tfb1PH/p62PH et réduit significativement l'activité transcriptionnelle d'EKLF dans les érythrocytes.Hematopoietic development is regulated through a combinatorial interplay between lineage-specific activators and the general transcription machinery that enables cell-specific patterns of gene expression. This thesis reports structural and functional studies of interactions involving the transcativation domains (TAD) of activators proteins and their role in hematopoietic development. Interactions between the TAD of activators and their partners play an important role in the transcriptional regulation of all genes including those regulating hematopoiesis. The first section reports the identification and characterization of a novel interaction between the erythroid transcription factor GATA-1 and the tumor suppressor protein p53. Using a combination of isothermal titration calorimetry (ITC), NMR spectroscopy and in vivo studies, we identified and characterized the direct interaction between these two important transcription factors in an attempt to determine the role of this interaction in erythroid development. Based on our results, the TAD of p53 directly interacts with the DNA-binding domain of GATA-1 in a cell-type specific manner. Through this interaction, GATA-1 inhibits activation of select p53-regulated genes and we postulate that the inhibition of p53-dependent apoptotic pathways is essential for survival of erythroid precursor cells. In the second section, we report on the interactions between two acidic TADs and the general transcription factor IIH (TFIIH). The structure of the complexes formed by the Tfb1/p62 subunit of TFIIH (Tfb1PH/p62PH) and the acidic TAD of Herpes Simplex viral protein 16 (VP16) and the Erythroid Krüppel-like factor (EKLF) were determined by NMR spectroscopy. The structure of the Tfb1PH/VP16 complex demonstrated that a viral TAD has the ability to mimic the actions of the TAD from the human p53 with Tfb1PH/p62PH. The TADs of both VP16 and p53 adopt a 9-residue α-helix in complex with Tfb1PH/p62PH. Interestingly, the NMR structure of the EKLF/Tfb1PH complex demonstrated that despite sharing a common binding site with p53 and VP16 on Tfb1PH, the EKLF/Tfb1PH binding interface is distinctly different from the binding interfaces we previously observed with p53/Tfb1PH and VP16/Tfb1PH complexes. Surprisingly, EKLF adopted a similar binding mechanism as the general transcription factor TFIIEα in interaction with p62PH as both interact in an extended conformation. Moreover, based on our structural data, we have identified Trp73 as a key residue within the TAD of EKLF that is required for the formation of the EKLF/Tfb1PH complex. Mutations of Trp73 disrupted the binding to Tfb1PH/p62PH and significantly reduced the transcriptional activity of EKLF in red blood cells

The Governance and Performance of Research Universities: Evidence from Europe and the U.S.

We investigate how university governance affects research output, measured by patenting and international university research rankings. For both European and U.S. universities, we generate several measures of autonomy, governance, and competition for research funding. We show that university autonomy and competition are positively correlated with university output, both among European countries and among U.S. public universities. We then identity a (political) source of exogenous shocks to funding of U.S. universities. We demonstrate that, when a state's universities receive a positive funding shock, they produce more patents if they are more autonomous and face more competition from private research universities. Finally, we show that during periods when merit-based competitions for federal research funding have been most prominent, universities produce more patents when they receive an exogenous funding shock, suggesting that routine participation in such competitions hones research skill.

Modern sedimentation patterns and human impacts on the Barcelona continental shelf (NE Spain)

Seafloor sediments were collected from the Barcelona continental shelf, NE Spain, to determine the textural characteristics and sedimentary processes related to different depositional systems and human pressures. The Barcelona continental shelf is principally influenced by the discharge of the Llobregat and Besòs rivers, and also by anthropogenic modifications Duch as the diversion of the Llobregat River or the enlargement of the Port of Barcelona. Sedimentological, physical and biogeochemical properties of 14 sediment cores and grabs indicate the presence of three distinct depositional environments linked to river-influenced, marine-influenced and mixed sedimentation. Sedimentological results have been used to groundtruth available backscatter data. The river-influenced environment, mainly associated to the Llobregat River input, does not reach the shelf edge as the prevailing oceanographic currents deflect sediments south-westward. Riverine sediments are fine-grained, with abundant plant debris, micas and relatively high organic carbon content. The associated sedimentary features are the Holocene prodelta and two modern mud patches. The marine-influenced environment extends north-easterly over the middle and outer shelf and on the upper continental slope. The sediments are coarser grained with abundant bioclasts and lower organic carbon content. Mixed sedimentation is present between the river- and marine-influenced areas. In addition, 210Pb, 226Ra and 137Cs radiometric analyses were used to estimate accumulation rates as well as to identify sites with disturbed sedimentation. Relatively high sediment accumulation rates (up to 0.70-1.03 g•cm-2•yr-1 equivalent to 6.4-10 mm•yr-1) are estimated on the Llobregat prodelta while moderate rates 0.21-0.46 g•cm-2•yr-1 or 1.6-3.6 mm•yr-1) are found between the Besòs and the Llobregat outlets. Two sediment cores show a sharp change from river-influenced to marine-dominated conditions that occurred in the mid- 1960s. This is interpreted as a significant regression (~2.5 km in 40 years) of the river-influenced domain that may be associated to the extension of the Port of Barcelona and the canalization of the Besòs River, amongst other reasons. Other important human impacts observed in the Barcelona continental shelf are (i) sediment mixing by dredging, ship anchoring and trawling; and (ii) possible organic pollution associated to river and sewage discharges

The murine orthologue of the Golgi-localized TPTE protein provides clues to the evolutionary history of the human TPTE gene family

Abstract.: The human TPTE gene encodes a testis-specific protein that contains four potential transmembrane domains and a protein tyrosine phosphatase motif, and shows homology to the tumor suppressor PTEN/MMAC1. Chromosomal mapping revealed multiple copies of the TPTE gene present on the acrocentric chromosomes 13, 15, 21 and 22, and the Y chromosome. Zooblot analysis suggests that mice may possess only one copy of TPTE. In the present study, we report the isolation and initial characterization of the full-length cDNA of the mouse homologue Tpte. At least three different mRNA transcripts (Tpte.a, b, c) are produced via alternative splicing, encoding predicted proteins that would contain four potential transmembrane domains and a protein tyrosine phosphatase motif. Transfection of a 5′EGFP-TPTE fusion protein in Hela cells revealed an intracellular localization within the Golgi apparatus. Tpte was mapped by radiation hybrid to a region of mouse chromosome 8 that shows conserved synteny with human 13q14.2-q21 between NEK3 and SGT1. This region of the human genome was found to contain a partial, highly diverged copy of TPTE that is likely to represent the ancestral copy from which the other copies of TPTE arose through duplication events. The Y chromosome copy of TPTE is a pseudogene and is not therefore involved in the testis expression of this gene famil

Backbone resonance assignments of the monomeric DUF59 domain of human Fam96a

Proteins containing a domain of unknown function 59 (DUF59) appear to have a variety of physiological functions, ranging from iron-sulfur cluster assembly to DNA repair. DUF59 proteins have been found in bacteria, archaea and eukaryotes, however Fam96a and Fam96b are the only mammalian proteins predicted to contain a DUF59 domain. Fam96a is an 18 kDa protein comprised primarily of a DUF59 domain (residues 31-157) and an N-terminal signal peptide (residues 1-27). Interestingly, the DUF59 domain of Fam96a exists as monomeric and dimeric forms in solution, and X-ray crystallography studies of both forms unexpectedly revealed two different domain-swapped dimer structures. Here we report the backbone resonance assignments and secondary structure of the monomeric form of the 127 residue DUF59 domain of human Fam96a. This study provides the basis for further understanding the structural variability exhibited by Fam96a and the mechanism for domain swapping

1H-NMR, 1H-NMR T2-edited, and 2D-NMR in bipolar disorder metabolic profiling

CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThe objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. Methods. Metabolomic profiling, employing 1H-NMR, 1H-NMR T2-edit51CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informação2014/18938-