Evolution of Y chromosomes : lessons from mammals and amphibians

RÉSUMÉ : Le sexe des individus peut être déterminé par l'environnement ou la génétique. Lorsque la détermination du sexe est génétique, il y a dans le génome, la présence de chromosomes spécifiques qui détermineront le sexe. Dans cette thèse, j'ai étudié l'évolution des chromosomes sexuels et dans quel contexte des marqueurs sur ces chromosomes peuvent être utilisés. Pour explorer la formation du chromosome Y, nous avons étudié les caractéristiques des chromosomes sexuels chez la rainette verte, Hyla arborea. Dans un premier temps, nous avons utilisé un marqueur situé sur les chromosomes sexuels X et Y chez plusieurs espèces appartenant au groupe de la rainette verte. Cela nous a permis de révéler chez toutes ces espèces une hétérogamétie mâle. Dans un deuxième temps, nous avons tiré profit de deux autres marqueurs situés sur les chromosomes sexuels pour montrer que la recombinaison est supprimée chez les mâles mais pas chez les femelles. Pour expliquer la réduction de la variabilité sur le chromosome Y, il n'est pas nécessaire d'invoquer le balayage sélectif ou la sélection d'arrière-plan : le nombre de copies plus petit du chromosome Y dans le génome et l'absence de recombinaison suffisent à l'expliquer. Nous avons également analysé plus en détail la suppression de la recombinaison chez les mâles de H. arborea. Les modèles classiques de l'évolution des chromosomes sexuels supposent que la taille de la région non-recombinante augmente progressivement pendant l'évolution du chromosome Y, due à l'accumulation de changements structuraux. Dans cette étude, nous montrons un modèle différent, à savoir que la recombinaison est supprimée ou diminuée non seulement sur les chromosomes sexuels mais aussi sur les autosomes chez les mâles, dû à l'action de modificateurs généraux. En utilisant des marqueurs localisés sur le chromosome Y, ainsi que sur l'ADN mitochondrial et le chromosome X, nous avons étudié l'histoire évolutive de la musaraigne musette, Crocidura russula. Cette étude illustre que les analyses génétiques avec plusieurs types de marqueurs génétiques peuvent faciliter l'interprétation de l'histoire évolutive des espèces, mais que l'utilisation des marqueurs sur les chromosomes X et Y pour des études phylogéographiques est limitée par le peu de polymorphisme observé sur ces deux types de marqueurs. Le même jeu de données combiné avec des simulations a été employé pour comprendre les facteurs responsables de la faible variabilité sur le chromosome Y qui peut être expliqué, dans notre étude, par la démographie et les traits d'histoire de vie de C. russula. SUMMARY The sex of an individual is determined either by its environment or its genetics. Genetic sex determination relies on the presence of specific chromosomes that will determine the sex of their bearer. In this thesis, I studied the evolution of the sex chromosomes and the context in which markers on this type of chromosomes can be used. To explore the evolution of a Y chromosome, we studied the nascent sex chromosomes in the European tree frog Hyla arborea. First; we amplified a sex specific marker in several related species of European tree frog and found a homogeneous pattern of male heterogamety. Secondly, we used two additional sex-specific markers to show that recombination is suppressed in males but not in females. There is, therefore, no need to invoke background selection or selective sweeps to explain the reduced genetic variability on the Y chromosome, because the lower number of copies of the Y chromosomes per breeding pair and the absence of recombination are sufficient. To further analyze the suppression of recombination in male European. tree frogs, we constructed a microsatellite linkage map for this species. Classical models of sex-chromosome evolution assume that the non-recombining region expands progressively during the long-term evolution of the Y chromosome, owing to the accumulation of structural changes. Here we show a strikingly different pattern: recombination is suppressed or depressed both on sex chromosomes and autosomes in the heterogametic sex, presumably due to the action of general modifiers. We investigated the evolutionary history of the greater white-toothed shrew, Crocidura russula, using markers on both sex chromosomes and mtDNA. This study illustrates that multilocus genetic analyses facilitates the interpretation of a species' evolutionary history. It also demonstrates that phylogeographic inferences from X and Y chromosomal markers are restricted by the low levels of observed polymorphism. Combining this genetic study with simulations, we determined that the demography and the life-history traits of this species can alone be responsible for the low Y diversity. In conclusion, this thesis shows that sex chromosomes, in combination with autosomes or mtDNA, are necessary to understand the evolution of sex chromosomes and to precisely infer the population history of a species.

Similarities and convergence in G-7 cycles

This paper examines the properties of G-7 cycles using a multicountry Bayesian panelVAR model with time variations, unit specific dynamics and cross country interdependences.We demonstrate the presence of a significant world cycle and show that country specificindicators play a much smaller role. We detect differences across business cycle phasesbut, apart from an increase in synchronicity in the late 1990s, find little evidence of major structural changes. We also find no evidence of the existence of an Euro area specific cycle or of its emergence in the 1990s.

Sistemas da qualidade no ensino superior : contributos para modelos de melhoria da qualidade e responsabilidade social

A gestão das Instituições de Ensino Superior está a ser repensada num contexto de globalização tendo em conta a missão destas, a responsabilidade e a sua cultura (ou culturas), impondo-se novos modelos de gestão e governação. A Qualidade e a Responsabilidade Social do Ensino Superior constituem um tema pertinente e actual. As transformações estruturais que as sociedades atravessam aconselham e justificam da parte do Ensino Superior uma atitude consentânea com as necessidades daquelas. Os desafios que, as Instituições de Ensino Superior enfrentam, exigem novas perspectivas estratégicas e nova visão perante cenários de incerteza que surgem a nível mundial, desempenhando a liderança um papel fundamental na qualidade destas instituições. Neste sentido, lança-se no presente estudo, a seguinte questão: Que Modelos de Gestão e Governação contribuem para a melhoria da Qualidade no Ensino Superior? A metodologia utilizada para a realização deste estudo passa pelo delineamento de uma estratégia com cinco fases: elaboração de um plano ajustável à evolução do trabalho, levantamento do estado da arte de uma forma gradual, trabalho de pesquisa e criação, escrita da tese e análise crítica e reflexão. Para além de outros aspectos relevantes no domínio do Ensino Superior, foram estudados diversos modelos, Modelos de Excelência, modelos para implementação de Sistemas de Gestão da Qualidade, Gestão Ambiental, Gestão da Segurança e Saúde do Trabalho, Gestão de Risco; entre outros. Criaram-se diversos Indicadores de Responsabilidade Social neste contexto e foi feito um estudo piloto no âmbito da Responsabilidade Social em Instituições de Ensino Superior. Por último, destacaram-se as conclusões que decorrem do estudo piloto efectuado, bem como reflexões que surgem da investigação teórica realizada. O estudo piloto efectuado permitiu concluir, por exemplo, que existem indícios de algum alheamento no seio das Instituições às temáticas relacionadas com os princípios éticos e com a educação ambiental. Por outro lado, uma grande parte dos indivíduos inquiridos disseram não ter qualquer opinião quando confrontados com questões sobre Participação Social Responsável, Investigação Socialmente Útil e Gestão Social do Conhecimento. Conclui-se que as questões para as pessoas ainda são muito vagas, daí que, faça sentido o debate de todas estas questões, bem como estudos que contribuam para uma mudança de paradigma relativamente à educação, e em particular no Ensino Superior, com vista à qualidade, num sentido abrangente.

Sistemas da qualidade no ensino superior : contributos para modelos de melhoria da qualidade e responsabilidade social

The management of Higher Education Institutions is being rethought, with the mission and culture of the institutions changing due to globalization, resulting in new models of management and governance. The quality of Higher Education and its obligations to society are of current importance. The structural changes that the society has gone through requires a response in higher education that matches the changing needs of the society. Higher Education Institutions require new perspectives and a new strategic vision to cope with the uncertainty arising at a global scale, and this plays a role in their quality and whether they are leading institutions. Thus the following question arises: Which forms of management and governance contribute to the improvement of quality in higher education? The methodology for this study was designed with five stages: preparation of a plan of work within the thesis, the gradual progression to understanding the up-to-date understanding of Higher Education Research, generating research hypotheses and creating further understanding, writing the thesis with critical analysis and reflection. In addition to other relevant issues in higher education, different models were studied: Models of excellence, Models for implementation of Quality Management Systems, Environmental Management, Occupational Health and Safety Management, Risk Management, among others. Several indicators of Social Responsibility were created in this context and a pilot study was conducted in the area of Social Responsibility in Higher Education Institutions. Finally the conclusions resulting from the pilot study are presented and questions arising from the theoretical research are discussed. For example, the pilot study showed that there are indicators of a lack of understanding within the institutions to issues related to ethical and environmental education. Moreover, a large proportion of respondents said individuals have no opinion when confronted with questions on Responsible Social Involvement and Social Research and Social Management of Useful Knowledge. It is concluded that people have a vague awareness of these issues, so these concepts are new to them.

Sistemas da qualidade no ensino superior : contributos para modelos de melhoria da qualidade e responsabilidade social

The management of Higher Education Institutions is being rethought, with the mission and culture of the institutions changing due to globalization, resulting in new models of management and governance. The quality of Higher Education and its obligations to society are of current importance. The structural changes that the society has gone through requires a response in higher education that matches the changing needs of the society. Higher Education Institutions require new perspectives and a new strategic vision to cope with the uncertainty arising at a global scale, and this plays a role in their quality and whether they are leading institutions. Thus the following question arises: Which forms of management and governance contribute to the improvement of quality in higher education? The methodology for this study was designed with five stages: preparation of a plan of work within the thesis, the gradual progression to understanding the up-to-date understanding of Higher Education Research, generating research hypotheses and creating further understanding, writing the thesis with critical analysis and reflection. In addition to other relevant issues in higher education, different models were studied: Models of excellence, Models for implementation of Quality Management Systems, Environmental Management, Occupational Health and Safety Management, Risk Management, among others. Several indicators of Social Responsibility were created in this context and a pilot study was conducted in the area of Social Responsibility in Higher Education Institutions. Finally the conclusions resulting from the pilot study are presented and questions arising from the theoretical research are discussed. For example, the pilot study showed that there are indicators of a lack of understanding within the institutions to issues related to ethical and environmental education. Moreover, a large proportion of respondents said individuals have no opinion when confronted with questions on Responsible Social Involvement and Social Research and Social Management of Useful Knowledge. It is concluded that people have a vague awareness of these issues, so these concepts are new to them.

Sistemas da qualidade no ensino superior : contributos para modelos de melhoria da qualidade e responsabilidade social

The management of Higher Education Institutions is being rethought, with the mission and culture of the institutions changing due to globalization, resulting in new models of management and governance. The quality of Higher Education and its obligations to society are of current importance. The structural changes that the society has gone through requires a response in higher education that matches the changing needs of the society. Higher Education Institutions require new perspectives and a new strategic vision to cope with the uncertainty arising at a global scale, and this plays a role in their quality and whether they are leading institutions. Thus the following question arises: Which forms of management and governance contribute to the improvement of quality in higher education? The methodology for this study was designed with five stages: preparation of a plan of work within the thesis, the gradual progression to understanding the up-to-date understanding of Higher Education Research, generating research hypotheses and creating further understanding, writing the thesis with critical analysis and reflection. In addition to other relevant issues in higher education, different models were studied: Models of excellence, Models for implementation of Quality Management Systems, Environmental Management, Occupational Health and Safety Management, Risk Management, among others. Several indicators of Social Responsibility were created in this context and a pilot study was conducted in the area of Social Responsibility in Higher Education Institutions. Finally the conclusions resulting from the pilot study are presented and questions arising from the theoretical research are discussed. For example, the pilot study showed that there are indicators of a lack of understanding within the institutions to issues related to ethical and environmental education. Moreover, a large proportion of respondents said individuals have no opinion when confronted with questions on Responsible Social Involvement and Social Research and Social Management of Useful Knowledge. It is concluded that people have a vague awareness of these issues, so these concepts are new to them.

Potential impact of climate change on vegetation in the European Alps: a review

Based on conclusions drawn from general climatic impact assessment in mountain regions, the review synthesizes results relevant to the European Alps published mainly from 1994 onward in the fields of population genetics, ecophysiology, phenology, phytogeography, modeling, paleoecology and vegetation dynamics. Other important factors of global change interacting synergistically with climatic factors are also mentioned, such as atmospheric CO2 concentration, eutrophication, ozone or changes in land-use. Topics addressed are general species distribution and populations (persistence, acclimation, genetic variability, dispersal, fragmentation, plant/animal interaction, species richness, conservation), potential response of vegetation (ecotonal shift - area, physiography - changes in the composition, structural changes), phenology, growth and productivity, and landscape. In conclusion, the European Alps appear to have a natural inertia and thus to tolerate an increase of 1-2 K of mean air temperature as far as plant species and ecosystems are concerned in general. However, the impact of land-use is very likely to negate this buffer in many areas. For a change of the order of 3 K or more, profound changes may be expected.

Microinductive signal conditioning with resonant differential filters: high-sensitivity biodetection applications

Inductive-based devices integrated with Si technology for biodetection applications are characterized, using simple resonant differential filter configurations. This has allowed the corroboration of the viability of the proposed circuits, which are characterized by their very high simplicity, for microinductive signal conditioning in high-sensitivity sensor devices. The simulation of these simple circuits predicts sensitivities of the differential output voltage which can achieve values in the range of 0.1-1 V/nH, depending on the coil parameters. These very high-sensitivity values open the possibility for the experimental detection of extremely small inductance changes in the devices. For real microinductive devices, both series resistance and parasitic capacitive components contribute to the decrease of the differential circuit sensitivity. Nevertheless, measurements performed using micro-coils fabricated with relatively high series resistance and coupling parasitic effects have allowed detection of changes in the range of 2 nH. which are compatible with biodetection applications with estimated detection limits below the picomolarity range.

Genome-wide arrays in routine diagnostics of hematological malignancies.

Over the last three decades, cytogenetic analysis of malignancies has become an integral part of disease evaluation and prediction of prognosis or responsiveness to therapy. In most diagnostic laboratories, conventional karyotyping, in conjunction with targeted fluorescence in situ hybridization analysis, is routinely performed to detect recurrent aberrations with prognostic implications. However, the genetic complexity of cancer cells requires a sensitive genome-wide analysis, enabling the detection of small genomic changes in a mixed cell population, as well as of regions of homozygosity. The advent of comprehensive high-resolution genomic tools, such as molecular karyotyping using comparative genomic hybridization or single-nucleotide polymorphism microarrays, has overcome many of the limitations of traditional cytogenetic techniques and has been used to study complex genomic lesions in, for example, leukemia. The clinical impact of the genomic copy-number and copy-neutral alterations identified by microarray technologies is growing rapidly and genome-wide array analysis is evolving into a diagnostic tool, to better identify high-risk patients and predict patients' outcomes from their genomic profiles. Here, we review the added clinical value of an array-based genome-wide screen in leukemia, and discuss the technical challenges and an interpretation workflow in applying arrays in the acquired cytogenetic diagnostic setting.

Extending the Kuznets Curve

[cat] Les darreres dècades s’han caracteritzat per un intens augment de les desigualtats salarials a nivell mundial. Aquest article allarga la hipòtesi clàssica de la Corba de Kuznets per cobrir les economies post-industrials i tractar d’explicar aquest fenomen. Segons la hipòtesi de la Corba de Kuznets Allargada, les desigualtats salarials podrien evolucionar segons una corba en forma d’N. La U-inverida d’aquesta corba seria deguda al procés de canvi estructural que acompanya a un procés de industrialització. I l’extrem dret de la mateixa, associada al creixement explosiu de la formació de capital humà en les economies modernes i post-industrials. En aquest sentit, els principals candidats per explicar el recent augment de les desigualtats: el canvi tècnic esbiaixat a favor del treball qualificat, la globalització (comerç i migracions) i els factors institucionals, estarien ja incorporats en l’evolució de la composició de la força de treball en termes de qualificacions. La limitada evidència empírica sobre aquest tema, tendeix a donar suport a la Corba de Kuznets Allargada.

A Heterozygous Deletion Mutation in the Cardiac Sodium Channel Gene SCN5A with Loss- and Gain-of-Function Characteristics Manifests as Isolated Conduction Disease, without Signs of Brugada or Long QT Syndrome.

BACKGROUND: The SCN5A gene encodes for the α-subunit of the cardiac sodium channel NaV1.5, which is responsible for the rapid upstroke of the cardiac action potential. Mutations in this gene may lead to multiple life-threatening disorders of cardiac rhythm or are linked to structural cardiac defects. Here, we characterized a large family with a mutation in SCN5A presenting with an atrioventricular conduction disease and absence of Brugada syndrome. METHOD AND RESULTS: In a large family with a high incidence of sudden cardiac deaths, a heterozygous SCN5A mutation (p.1493delK) with an autosomal dominant inheritance has been identified. Mutation carriers were devoid of any cardiac structural changes. Typical ECG findings were an increased P-wave duration, an AV-block I° and a prolonged QRS duration with an intraventricular conduction delay and no signs for Brugada syndrome. HEK293 cells transfected with 1493delK showed strongly (5-fold) reduced Na(+) currents with altered inactivation kinetics compared to wild-type channels. Immunocytochemical staining demonstrated strongly decreased expression of SCN5A 1493delK in the sarcolemma consistent with an intracellular trafficking defect and thereby a loss-of-function. In addition, SCN5A 1493delK channels that reached cell membrane showed gain-of-function aspects (slowing of the fast inactivation, reduction in the relative fraction of channels that fast inactivate, hastening of the recovery from inactivation). CONCLUSION: In a large family, congregation of a heterozygous SCN5A gene mutation (p.1493delK) predisposes for conduction slowing without evidence for Brugada syndrome due to a predominantly trafficking defect that reduces Na(+) current and depolarization force.

Characterization of sustained BOLD activation in the rat barrel cortex and neurochemical consequences.

To date, only a couple of functional MR spectroscopy (fMRS) studies were conducted in rats. Due to the low temporal resolution of (1)H MRS techniques, prolonged stimulation paradigms are necessary for investigating the metabolic outcome in the rat brain during functional challenge. However, sustained activation of cortical areas is usually difficult to obtain due to neural adaptation. Anesthesia, habituation, high variability of the basal state metabolite concentrations as well as low concentrations of the metabolites of interest such as lactate (Lac), glucose (Glc) or γ-aminobutyric acid (GABA) and small expected changes of metabolite concentrations need to be addressed. In the present study, the rat barrel cortex was reliably and reproducibly activated through sustained trigeminal nerve (TGN) stimulation. In addition, TGN stimulation induced significant positive changes in lactate (+1.01μmol/g, p<0.008) and glutamate (+0.92μmol/g, p<0.02) and significant negative aspartate changes (-0.63μmol/g, p<0.004) using functional (1)H MRS at 9.4T in agreement with previous changes observed in human fMRS studies. Finally, for the first time, the dynamics of lactate, glucose, aspartate and glutamate concentrations during sustained somatosensory activation in rats using fMRS were assessed. These results allow demonstrating the feasibility of fMRS measurements during prolonged barrel cortex activation in rats.

Role of hemodynamic forces in the ex vivo arterialization of human saphenous veins.

BACKGROUND: Human saphenous vein grafts are one of the salvage bypass conduits when endovascular procedures are not feasible or fail. Understanding the remodeling process that venous grafts undergo during exposure to arterial conditions is crucial to improve their patency, which is often compromised by intimal hyperplasia. The precise role of hemodynamic forces such as shear stress and arterial pressure in this remodeling is not fully characterized. The aim of this study was to determine the involvement of arterial shear stress and pressure on vein wall remodeling and to unravel the underlying molecular mechanisms. METHODS: An ex vivo vein support system was modified for chronic (up to 1 week), pulsatile perfusion of human saphenous veins under controlled conditions that permitted the separate control of arterial shear stress and different arterial pressure (7 mm Hg or 70 mm Hg). RESULTS: Veins perfused for 7 days under high pressure (70 mm Hg) underwent significant development of a neointima compared with veins exposed to low pressure (7 mm Hg). These structural changes were associated with altered expression of several molecular markers. Exposure to an arterial shear stress under low pressure increased the expression of matrix metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 at the transcript, protein, and activity levels. This increase was enhanced by high pressure, which also increased TIMP-2 protein expression despite decreased levels of the cognate transcript. In contrast, the expression of plasminogen activator inhibitor-1 increased with shear stress but was not modified by pressure. Levels of the venous marker Eph-B4 were decreased under arterial shear stress, and levels of the arterial marker Ephrin-B2 were downregulated under high-pressure conditions. CONCLUSIONS: This model is a valuable tool to identify the role of hemodynamic forces and to decipher the molecular mechanisms leading to failure of human saphenous vein grafts. Under ex vivo conditions, arterial perfusion is sufficient to activate the remodeling of human veins, a change that is associated with the loss of specific vein markers. Elevation of pressure generates intimal hyperplasia, even though veins do not acquire arterial markers. CLINICAL RELEVANCE: The pathological remodeling of the venous wall, which leads to stenosis and ultimately graft failure, is the main limiting factor of human saphenous vein graft bypass. This remodeling is due to the hemodynamic adaptation of the vein to the arterial environment and cannot be prevented by conventional therapy. To develop a more targeted therapy, a better understanding of the molecular mechanisms involved in intimal hyperplasia is essential, which requires the development of ex vivo models of chronic perfusion of human veins.

Least limiting water range in assessing compaction in a Brazilian Cerrado latosol growing sugarcane

In the south-central region of Brazil, there is a trend toward reducing the sugarcane inter-harvest period and increasing traffic of heavy harvesting machinery on soil with high water content, which may intensify the compaction process. In this study, we assessed the structural changes of a distroferric Red Latosol (Oxisol) by monitoring soil water content as a function of the Least Limiting Water Range (LLWR) and quantified its effects on the crop yield and industrial quality of the first ratoon crop of sugarcane cultivars with different maturation cycles. Three cultivars (RB 83-5054, RB 84-5210 and RB 86-7515) were subjected to four levels of soil compaction brought about by a differing number of passes of a farm tractor (T0 = soil not trafficked, T2 = 2 passes, T10 = 10 passes, and T20 = 20 passes of the tractor in the same place) in a 3 × 4 factorial arrangement with three replications. The deleterious effects on the soil structure from the farm machinery traffic were limited to the surface layer (0-10 cm) of the inter-row area of the ratoon crop. The LLWR dropped to nearly zero after 20 tractor passes between the cane rows. We detected differences among the cultivars studied; cultivar RB 86-7515 stood out for its industrial processing quality, regardless of the level of soil compaction. Monitoring of soil moisture in the crop showed exposure to water stress conditions, although soil compaction did not affect the production variables of the sugarcane cultivars. We thus conclude that the absence of traffic on the plant row maintained suitable soil conditions for plant development and may have offset the harmful effects of soil compaction shown by the high values for bulk density between the rows of the sugarcane cultivars.

Is there histomorphological evidence of plantar metatarsal fat pad atrophy in patients with diabetes?

The etiology of diabetic foot ulceration remains incompletely understood. Among other factors such as foot deformity in the presence of neuropathy, plantar fat pad atrophy has been identified as a contributory factor in diabetic foot ulceration. An association between fat pad atrophy and diabetic foot ulceration has been documented by imaging and histomorphological analysis of the calcaneal fat pad. However, histomorphological analysis of the metatarsal fat pad has not been performed to date. The present study entailed 14 patients with diabetes and 14 nondiabetic controls and was aimed at documenting histomorphological evidence for presumed plantar metatarsal fat pad atrophy in patients with diabetes. Histological stains and computer-assisted planimetry were performed on samples of metatarsal fat obtained during forefoot surgery. The histomorphological and planimetric analyses of adipocyte cross-sectional area and nuclear density demonstrated no differences between patients with diabetes and control patients. Our findings demonstrate that systemic atrophy of the metatarsal fat pad is not present in the diabetic foot and may not explain the structural changes previously proposed by noninvasive imaging. Level of Clinical Evidence: 3.