RNA-based gene duplication sheds new light on mammalian sex chromosome evolution

ABSTRACT : Gene duplication is a fundamental source of raw material for the origin of genetic novelty. It has been assumed for a long time that DNA-based gene duplication was the only source of new genes. Recently however, RNA-based gene duplication (retroposition) was shown in multiple organisms to contribute significantly to their genetic diversity. This mechanism produces intronless gene copies (retrocopies) that are inserted in random genomic position, independent of the position of the parental source genes. In human, mouse and fruit fly, it was demonstrated that the X-linked genes spawned an excess of functional retroposed gene copies (retrogenes). In human and mouse, the X chromosome also recruited an excess of retrogenes. Here we further characterized these interesting biases related to the X chromosome in mammals. Firstly, we have confirmed presence of the aforementioned biases in dog and opossum genome. Then based on the expression profile of retrogenes during various spermatogenetic stages, we have provided solid evidence that meiotic sex chromosome inactivation (MSCI) is responsible for an excess of retrogenes stemming from the X chromosome. Moreover, we showed that the X-linked genes started to export an excess of retrogenes just after the split of eutherian and marsupial mammalian lineages. This suggests that MSCI has originated around this time as well. More fundamentally, as MSCI reflects the spread of recombination barrier between the X and Y chromosomes during their evolution, our observation allowed us to re-estimate the age of mammalian sex chromosomes. Previous estimates suggested that they emerged in the common ancestor of all mammals (before the split of monotreme lineage); whereas, here we showed that they originated around the split of marsupial and eutherian lineages, after the divergence of monotremes. Thus, the therian (marsupial and eutherian) sex chromosomes are younger than previously thought. Thereafter, we have characterized the bias related to the recruitment of genes to the X chromosome. Sexually antagonistic forces are most likely driving this pattern. Using our limited retrogenes expression data, it is difficult to determine the exact nature of these forces but some conclusions have been made. Lastly, we looked at the history of this biased recruitment: it commenced around the split of marsupial and eutherian lineages (akin to the biased export of genes out of the X). In fact, the sexually antagonistic forces are predicted to appear just around that time as well. Thereby, the history of the recruitment of genes to the X, provides an indirect evidence that these forces are responsible for this bias.

Biological monitoring of exposure to solvents using the chemical itself in urine: application to toluene

Objective Biomonitoring of solvents using the unchanged substance in urine as exposure indicator is still relatively scarce due to some discrepancies between the results reported in the literature. Based on the assessment of toluene exposure, the aim of this work was to evaluate the effects of some steps likely to bias the results and to measure urinary toluene both in volunteers experimentally exposed and in workers of rotogravure factories. Methods Static headspace was used for toluene analysis. o-Cresol was also measured for comparison. Urine collection, storage and conservation conditions were studied to evaluate possible loss or contamination of toluene in controlled situations applied to six volunteers in an exposure chamber according to four scenarios with exposure at stable levels from 10 to 50 ppm. Kinetics of elimination of toluene were determined over 24 h. A field study was then carried out in a total of 29 workers from two rotogravure printing facilities. Results Potential contamination during urine collection in the field is confirmed to be a real problem but technical precautions for sampling, storage and analysis can be easily followed to control the situation. In the volunteers at rest, urinary toluene showed a rapid increase after 2 h with a steady level after about 3 h. At 47.1 ppm the mean cumulated excretion was about 0.005% of the amount of the toluene ventilated. Correlation between the toluene levels in air and in end of exposure urinary sample was excellent (r = 0.965). In the field study, the median personal exposure to toluene was 32 ppm (range 3.6-148). According to the correlations between environmental and biological monitoring data, the post-shift urinary toluene (r = 0.921) and o-cresol (r = 0.873) concentrations were, respectively, 75.6 mu g/l and 0.76 mg/g creatinine for 50 ppm toluene personal exposure. The corresponding urinary toluene concentration before the next shift was 11 mu g/l (r = 0.883). Conclusion Urinary toluene was shown once more time a very interesting surrogate to o-cresol and could be recommended as a biomarker of choice for solvent exposure. [Authors]

Paper money and national distress: William Huskisson and the early theories of credit, speculation and crises

This paper examines the explanation of commercial crises offered by William Huskisson in 1810 in the wake of the debate on the Bullion Report. Huskisson argued that the suspension of convertibility made it possible to extend issues of paper currency beyond its proper limits. Such an expansion, being in the interest of all parties concerned, would actually take place and stimulate excessive speculations, which would eventually prove unsustainable and bring generalized ruin and distress. Although some elements of this explanations were not new (having been anticipated by writers sucha as James Currie in 1793, William Roscoe in 1793, William Anderson in 1797 and an anonymous in 1796), Huskisson's explanation is more systematic and better organized, and his emphasis on the endogenous character of the crisis and on the instability of the dynamics of trade and credit makes it an interesting foreshadower of the theories of crises that were advanced half a century later.

Congenital Myasthenic Syndromes with COLQ mutations: Long term follow-up

Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous inherited disorders characterized by impaired neuromuscular transmission. Mutations in the acetylcholinesterase (AChE) collagenlike tail subunit gene (ColQ) cause recessive forms of synaptic CMS with end plate AChE deficiency. We report the time course of clinical manifestations in 15 COLQ-mutated patients followed from 1987 to 2010. All patients suffered from a muscle weakness with onset at birth or in childhood. Ocular and bulbar signs were found in 60% of the patients and delayed pupillary light response in 20% of our patients. EMG study demonstrated a decrement on repetitive nerve stimulation and repetitive compound muscle action potential in all patients. Clinical symptoms strongly fluctuated daily, weekly, monthly or even yearly. Severe relapses were characterized by a general motor weakness associated with pain which resolved spontaneously after a few months whereas the relapses with these symptoms and bulbar signs could last up to several years. Genetic analyses identified 16 different mutations including 9 novel ones. There was no genotype-phenotype correlation. Our study confirms the predominance of oculobulbar signs and the frequency of respiratory distress in COLQrelated CMS. At the end of the follow up of 23 years, interesting findings were (i) the spontaneous reversibility of severe relapses, some of them lasting for up to 5 years (ii) the good prognosis of COLQ-related CMS, since at the end of the follow-up 80% of patients were ambulant and 87% of patients had no respiratory trouble (iii) the efficacy of Ephedrine and, to a lesser extend, of 3-4 DAP. The triggering factors of relapses were esterase inhibitors, effort, puberty, pregnancy and delivery highlighting the importance of hormonal factors in CMS. In conclusion, patients diagnosed with unknown congenital myopathy should undergo an electrophysiological study of neuromuscular junction to identify ColQ-related CMS.

Paleoparasitology and the antiquity of human host-parasite relationships

Paleoparasitology may be developed as a new tool to parasite evolution studies. DNA sequences dated thousand years ago, recovered from archaeological material, means the possibility to study parasite-host relationship coevolution through time. Together with tracing parasite-host dispersion throughout the continents, paleoparasitology points to the interesting field of evolution at the molecular level. In this paper a brief history of paleoparasitology is traced, pointing to the new perspectives opened by the recent techniques introduced.

R&D cooperation between Spanish firms and scientific partners: what is the role of tertiary education?

This paper explores the factors that determine firm’s R&D cooperation with different partners, paying special attention on the role of tertiary education (degree and PhDs level) in facilitating the connection between the firms and the to scientific bodies (technology centres, public research centres and universities). Here, we attempt to answer two questions. First, are innovative firms that carry out internal and external R&D activities more likely to cooperate on R&D projects with other partners? Second, do Spanish innovative firms with a high participation of researchers with degrees or PhDs tend to cooperate more with scientific partners? To answer both questions we apply a three-dimensional approach on a firm level Panel Data with a sample of 4.998 manufacturing and services Spanish firms. First, we run a complementary test between external R&D acquisition and skilled research workers and find that firms which carry out external R&D activities obtain a greater return on R&D cooperation when they have skilled workers in R&D, especially in high-tech manufactures and KIS services. Second, we carry out a 2-step tobit model to estimate, in the first stage, the determinants that explain whether Spanish innovative firms cooperate or not; and in the second stage the factors that affect the choice of partners. And third, we apply an ordered probit model to test the marginal effects of explanatory variables on the different partners. Here we contrast some of the most interesting empirical hypotheses of previous studies, and which emphasize the role of employees with degrees and PhDs in facilitating cooperative R&D between firms and scientific partners. JEL classification: O31, O33, O38. Key words: Determinants R&D cooperation, industry-university flows, PhD research workers.

Impacte de la variabilitat climàtica ràpida de l'últim període glacial sobre la vegetació del sud-est de Nord Amèrica

Projecte de recerca elaborat a partir d’una estada a UMR-CNRS - Géologie et Océanographie, França, entre 2007 i 2009. Els canvis climàtics ràpids de l’últim període glacial (cicles Dansgaard/Oeschger i Heinrich Stadials-HS), han estat documentats en testimonis marins, de gel i dipòsits continentals, generalment de l’hemisferi nord. Mentre que la majoria dels estudis paleoclimàtics i paleoceanogràfics de l’Atlàntic Nord sobre l’últim període glacial s’han centrat en la part nord i est, les latituds mitjanes de la part occidental han estat menys estudiades. Particularment, els canvis de la vegetació de l’est de Nord Amèrica durant l’últim glacial es coneixen molt poc degut a la manca de seqüències pol.líniques llargues en aquesta regió. Només dues seqüències de pol.len del llac Tulane (Florida) mostren canvis de la vegetació significatius i interessants durant l’últim glacial, que suggereixen HS càlids i humits, que contrasta amb el que s’observa a l’altre costat de l’Atlàntic Nord. El treball realitzat al UMR-CNRS 5805 EPOC, Université Bordeaux 1, EPHE, des del 23 d’abril 2007 al 22 d’abril 2009, gràcies a la beca Beatriu de Pinós, implica una reconstrucció a alta resolució dels canvis de la vegetació a partir de l’anàlisi d’un testimoni marí, localitzat a l’oest de l’Atlàntic Nord subtropical (MD99-2203, 34º58’N, 75º12’W), durant l’Estadi Isotòpic Marí 3 (MIS 3). Les dades pal.linològiques del testimoni mostren una alternança entre Picea i Quercus. En general, les associacions pol.líniques indiquen que les variacions de la vegetació segueixen un patró bosc boreal/temperat durant l’últim glacial. El model d’edat preliminar basat en edats radiomètriques suggereix un augment del bosc temperat acompanyat d’una reducció del boreal entre el H4 i el H3. La comparació amb registres pol.línics marins d’alta resolució de la regió est subtropical, a latituds similars, mostren, per primer cop, que els canvis en les formacions forestals associats als canvis climàtics ràpids de l’últim glacial van ser menys intensos al sud-est de Nord Amèrica que a la Península Ibèrica.

Elaboració de membranes de fibra buida modificades amb nanopartícules metàl·liques per aplicacions catalítiques

Investigación producida a partir de una estancia en la Université Paul Sabatier, Toulouse III - CNRS, entre 2007 y 2009. Durante los últimos años la investigación centrada en nuevos materiales de tamaño nanoscòpico (nanopartículas, quantum dots, nanotubos de carbono,...) ha experimentado un crecimiento considerable debido a las especiales propiedades de los "nanoobjetos" con respecto a magnetismo, catálisis, conductividad eléctrica, etc ... Sin embargo, hoy en día todavía existen pocas aplicaciones de las nanopartículas en temas medioambientales. Uno de los motivos de esta situación es la posible toxicidad de los nanoobjetos, pero existe también una dificultad tecnológica dado que las nanopartículas tienden a agregarse y es muy difícil manipularlas sin que pierdan sus propiedades especiales. Así, aunque la preparación de materiales catalíticos nanoestructurados es muy interesante, es necesario definir nuevas estrategias para prepararlos. Este proyecto de investigación tiene como objetivo principal la preparación de nuevas membranas catalíticas con nanopartículas metálicas en el interior para aplicaciones de tratamiento de agua. La innovación principal de este proyecto consiste en que las nanopartículas no son introducidas en la matriz polimérica una vez preformadas sino que se hacen crecer en el interior de la matriz polimérica mediante una síntesis intermatricial. El único requisito es que la matriz polimérica contenga grupos funcionales capaces de interaccionar con los precursores de las nanopartículas. Una vez finalizado el proyecto se puede afirmar que se han logrado parte de los objetivos planteados inicialmente. Concreamente ha quedado demostrado que se pueden sintetizar nanopartículas metálicas de metales nobles (platino y paladio) en membranas de fibra hueca de micro- y ultrafiltración siguiendo dos metodologías diferentes: modificación fotoquímica de polímeros y deposición de multicapas de polielectrolitos. Los nuevos materiales son efectivos en la catálisis de reducción de un compuesto modelo (4-nitrofenol con borohidruro de sodio) y, en general, los resultados han sido satisfactorios. Sin embargo, se ha puesto de manifiesto que el uso de un reactivo que genera hidrógeno gas en contacto con la solución acuosa dificulta enormemente la implementación de la reacción catalítica al ser el medio de la membrana una matriz porosa. Así, como conclusión principal se puede decir que se han encontrado las limitaciones de esta aproximación y se sugieren dos posibilidades de continuidad: la utilización de las membranas sintetizadas en contactores gas-líquido o bien el estudio y optimización del sistema de membrana en configuración de membranas planas, un objetivo más asequible dada su menor complejidad. Esta investigación se ha realizado en el seno del “Laboratoire de Génie Chimique” de Toulouse y del Departamento de Química de la Michigan State University y ha sido posible gracias a un proyecto financiado por la “Agence National pour la Recherce” y al programa PERMEANT entre el CNRS y la NSF.

Comparison between computational alanine scanning and per-residue binding free energy decomposition for protein-protein association using MM-GBSA: application to the TCR-p-MHC complex.

Recognition by the T-cell receptor (TCR) of immunogenic peptides (p) presented by Class I major histocompatibility complexes (MHC) is the key event in the immune response against virus-infected cells or tumor cells. A study of the 2C TCR/SIYR/H-2K(b) system using a computational alanine scanning and a much faster binding free energy decomposition based on the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) method is presented. The results show that the TCR-p-MHC binding free energy decomposition using this approach and including entropic terms provides a detailed and reliable description of the interactions between the molecules at an atomistic level. Comparison of the decomposition results with experimentally determined activity differences for alanine mutants yields a correlation of 0.67 when the entropy is neglected and 0.72 when the entropy is taken into account. Similarly, comparison of experimental activities with variations in binding free energies determined by computational alanine scanning yields correlations of 0.72 and 0.74 when the entropy is neglected or taken into account, respectively. Some key interactions for the TCR-p-MHC binding are analyzed and some possible side chains replacements are proposed in the context of TCR protein engineering. In addition, a comparison of the two theoretical approaches for estimating the role of each side chain in the complexation is given, and a new ad hoc approach to decompose the vibrational entropy term into atomic contributions, the linear decomposition of the vibrational entropy (LDVE), is introduced. The latter allows the rapid calculation of the entropic contribution of interesting side chains to the binding. This new method is based on the idea that the most important contributions to the vibrational entropy of a molecule originate from residues that contribute most to the vibrational amplitude of the normal modes. The LDVE approach is shown to provide results very similar to those of the exact but highly computationally demanding method.

Creació i transmissió de coneixement als clústers empresarials: un model de simulació

Projecte de recerca elaborat a partir d’una estada a l’Snider Entrepreneurial Research Center de la Wharton School de la University of Pennsilvanya y, EUA entre juliol i desembre del 2007. L’objectiu d’aquest projecte és estudiar la relació entre les estratègies de gestió del coneixement i les tecnologies de la informació i la comunicació (TIC) en l’evolució de les poblacions d’organitzacions i els seus efectes en els patrons industrials d’aglomeració espacial. Per a això s’adopta una aproximació fonamentada en la utilització d'un model basats en agents per a obtenir hipòtesis significatives i provables sobre l’evolució de les poblacions d’organitzacions al si de clústers geogràfics. El model de simulació incorpora les perspectives i supòsits d’un marc conceptual, l’Espai de la Informació o I-Space. Això permet una conceptualització basada en la informació de l’entorn econòmic que té en compte les seves dimensions espacials i temporals. Mitjançant els paràmetres del model es dóna la possibilitat d’assignar estratègies específiques de gestió del coneixement als diversos agents i de localitzar-los en una posició de l’espai físic. La simulació mostra com l'adopció d'estratègies diverses pel que fa a la gestió del coneixement influeix en l'evolució de les organitzacions i de la seva localització espacial, i que aquesta evolució es veu modificada pel desenvolupament de les TIC. A través de la modelització de dos casos ben coneguts de clústers geogràfics d’alta tecnologia, com són Silicon Valley a Califòrnia i la Route 128 als voltants de Boston, s’estudia la interrelació entre les estratègies de gestió del coneixement adoptades per les empreses i la seva tria de localització espacial, i també com això és afectat per l’evolució de les tecnologies de la informació i de la comunicació (TIC). Els resultats obtinguts generen una sèrie d’hipòtesis de rica potencialitat sobre l’impacte del desenvolupament de les TIC en la dinàmica d’aquests clusters geogràfics. Concretament, es troba que la estructuració del coneixement i l’aglomeració espacial co-evolucionen i que aquesta coevolució es veu significativament alterada pel desenvolupament de les TIC.

Plasma ionized magnesium during acute hyperventilation in humans.

1. Respiratory alkalosis accompanies the clinical syndrome of tetany, precipitates cardiac arrhythmias and predisposes to coronary vasoconstriction. Magnesium plays a critical role in the maintenance of membrane function, and magnesium depletion is often associated with cardiac arrhythmias or vasoconstriction. 2. As technology for detecting circulating ionized magnesium (the most interesting form with respect to physiological and biological properties) is now available in the form of new magnesium-selective electrodes, the effect of respiratory alkalosis induced by voluntary overbreathing for 30 min on circulating ionized magnesium was studied in eight healthy subjects. 3. The total plasma magnesium concentration was not modified by hyperventilation. On the contrary, hyperventilation was associated with a significant reduction in the ionized magnesium concentration of 0.05 (0.02-0.15) mmol/l (median and range) and in the free magnesium fraction of 0.06 (0.01-0.19). During hyperventilation the relative intravascular magnesium mass, calculated from changes in total plasma magnesium concentration and haematocrit, decreased significantly. 4. It is concluded that acute overbreathing reduces the circulating ionized magnesium concentration and the intravascular magnesium mass. It is therefore conceivable that extracellular magnesium deficiency is at least a subsidiary cause of the syndrome of tetany and the cardiac complications that are precipitated by hyperventilation.

Araucnephia iberaensis n. sp., a Neotropical Black Fly with a Peculiar Distribution (Diptera-Simuliidae)

Araucnephia Wygodzinsky & Coscarón is a Neotropical black fly genus in which only one species from Central Chile is known. Another species has now been found in Corrientes province on the eastern side of the Iberá tropical swamps of Argentina, on the western border of the mountainous region of southern Brazil. This new species, A. iberaensis, is herein described and illustrated and information on its bionomics is recorded. It is an interesting species because previous to its discovery no black fly genus or subgenus from Central Chile region has been found in tropical areas, because these two regions are separated by the Monte and Pampas realms. Similarly, no Brazilian genus or subgenus has crossed the Andes mountains to Chile. A comparison with other Neotropical, Nearctic, Ethiopian (Afrotropical) and Australian Prosimuliini (sensu Crosskey & Howard) showed Araucnephia to be a valid taxon most closely related to Araucnephioides (sympatric in Chile). Araucnephia also shows great affinities with Lutzsimulium from Southeast Brazil and Argentina and Paracnephia from South Africa.

In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruzi

Cytotoxicity assays of 24 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivatives were performed. The 17 compounds with higher anti-epimastigote activity and lower cytotoxicity were, thereafter, screened against amastigote of Trypanosoma cruzi. Out of these 17 derivatives S-2d was selected to be assayed in vivo, because of its remarkable trypanocidal properties. To determine toxicity against J774 macrophages, a method based on quantification of cell damage, after 24 h, was used. Cell respiration, an indicator of cell viability, was assessed by the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to formazan. Anti-amastigote activity was estimated after 48 h by microscopic counts of May Grünwald-Giemsa-stained monolayers. Nifurtimox and benznidazole were used as reference drugs. For the in vivo experiences, mice were infected with 10(4) blood trypomastigotes and then treated during 15 days with S-2d or nifurtimox by oral route. All of the compounds were highly toxic at 100 µg/ml for macrophages and a few of them maintained this cytotoxicity even at 10 µg/ml. Of the derivatives assayed against amastigotes 3k and S-2d showed an interesting activity, that was held even at 1µg/ml. It is demonstrated that the high anti-epimastigote activity previously reported is mainly due to the non-specific toxicity of these compounds. In vivo assays assessed a reduction of parasitemia after administration of S-2d to infected mice.

Zuckerman's reivsed alternative five-factor model: Validation of the Zuckerman-Kuhlman-Aluja Personality Questionnaire in four French-speaking countries

The aim of this study was to analyze the replicability of Zuckerman's revised Alternative Five-factor model in a French-speaking context by validating the Zuckerman-Kuhlman-Aluja Personality Questionnaire (ZKA-PQ) simultaneously in 4 French-speaking countries. The total sample was made up of 1,497 subjects from Belgium, Canada, France, and Switzerland. The internal consistencies for all countries were generally similar to those found for the normative U.S. and Spanish samples. A factor analysis confirmed that the normative structure replicated well and was stable within this French-speaking context. Moreover, multigroup confirmatory factor analyses have shown that the ZKA-PQ reaches scalar invariance across these 4 countries. Mean scores were slightly different for women and men, with women scoring higher on Neuroticism but lower on Sensation Seeking. Globally, mean score differences across countries were small. Overall, the ZKA-PQ seems an interesting alternative to assess both lower and higher order personality traits for applied or research purposes.

Efectes no intencionats de transgens i optimització de la producció de pèptids antimicrobians d'ús fitosanitari en plantes-biofactoria

Actualment s’està duent a terme el projecte de tesi consistent en estudiar la producció de pèptids antimicrobians d'ús fitosanitari en plantes-biofactoria. Durant aquest període de la tesi doctoral he realitzat la transformació (mitjançant Agrobacterium tumefaciens) de plantes d’arròs per a la síntesi massiva d’una sèrie de pèptids antimicrobians, BP188, BP183, BP183TAG, BP215, BP173 i BP178. Es tracta d’una sèrie de derivats de BP100 que presenta unes propietats fitosanitàries molt interessants: elevada activitat contra bacteris d’interès fitosanitari, toxicitat reduïda i estabilitat moderada. El treball que he realitzat per dur a terme aquesta tasca ha requerit inicialment realitzar els clonatges necessaris per a les transformacions; per a continuació realitzar les transformacions de calls d’arròs varietat Sènia, seleccionar les cèl•lules transformades, regenerar plantes transgèniques i analitzar-ne la presència del transgén.