Porównawcza analiza udziału pokrewnych kinaz MAPK (MKK1, MKK2, MKK4 i MKK5) Arabidopsis thaliana w odpowiedzi na stres suszy

Wydział Biologii: Instytut Biologii Molekularnej i Biotechnologii

Early-type stars observed in the ESO UVES Paranal Observatory Project - I. Interstellar NaIUV, TiII and CaIIKobservations

We present an analysis of interstellar NaI (lambda(air) = 3302.37 and 3302.98 angstrom), TiII (lambda(air) = 3383.76 angstrom) and CaII K (lambda(air) = 3933.66 angstrom) absorption features for 74 sightlines towards O- and B-type stars in the Galactic disc. The data were obtained from the Ultraviolet and Visual Echelle Spectrograph Paranal Observatory Project, at a spectral resolution of 3.75 km s(-1) and with mean signal-to-noise ratios per pixel of 260, 300 and 430 for the NaI, TiII and CaII observations, respectively. Interstellar features were detected in all but one of the TiII sightlines and all of the CaII sightlines. The dependence of the column density of these three species with distance, height relative to the Galactic plane, HI column density, reddening and depletion relative to the solar abundance has been investigated. We also examine the accuracy of using the NaI column density as an indicator of that for HI. In general, we find similar strong correlations for both Ti and Ca, and weaker correlations for Na. Our results confirm the general belief that Ti and Ca occur in the same regions of the interstellar medium ( ISM) and also that the TiII/CaII ratio is constant over all parameters. We hence conclude that the absorption properties of Ti and Ca are essentially constant under the general ISM conditions of the Galactic disc.

RNA polymerase I-specific subunits promote polymerase clustering to enhance the rRNA gene transcription cycle.

RNA polymerase I (Pol I) produces large ribosomal RNAs (rRNAs). In this study, we show that the Rpa49 and Rpa34 Pol I subunits, which do not have counterparts in Pol II and Pol III complexes, are functionally conserved using heterospecific complementation of the human and Schizosaccharomyces pombe orthologues in Saccharomyces cerevisiae. Deletion of RPA49 leads to the disappearance of nucleolar structure, but nucleolar assembly can be restored by decreasing ribosomal gene copy number from 190 to 25. Statistical analysis of Miller spreads in the absence of Rpa49 demonstrates a fourfold decrease in Pol I loading rate per gene and decreased contact between adjacent Pol I complexes. Therefore, the Rpa34 and Rpa49 Pol I–specific subunits are essential for nucleolar assembly and for the high polymerase loading rate associated with frequent contact between adjacent enzymes. Together our data suggest that localized rRNA production results in spatially constrained rRNA production, which is instrumental for nucleolar assembly.

A Novel Multilocus Sequence Typing Scheme for the Opportunistic Pathogen Propionibacterium acnes and Characterisation of Type I Cell Surface-Associated Antigens.

We have developed a novel Multilocus Sequence Typing Scheme (MLST) and database (http://pubmlst.org/pacnes/) for Propionibacterium acnes based on the analysis of seven core housekeeping genes. The scheme, which was validated against previously described antibody, single locus and Random Amplification of Polymorphic DNA (RAPD) typing methods, displayed excellent resolution and differentiated 123 isolates into 37 sequence types (ST). An overall clonal population structure was detected with six eBURST groups representing the major clades I, II and III, along with two singletons. Two highly successful and global clonal lineages, ST6 (type IA) and ST10 (type IB1), representing 65% of this current MLST isolate collection were identified. The ST6 clone and closely related single locus variants (SLV), which comprise a large clonal complex CC6, dominated isolates from patients with acne, and were also significantly associated with ophthalmic infections. Our data therefore supports an association between acne and P. acnes strains from the type IA cluster and highlights the role of a widely disseminated clonal genotype in this condition. Characterisation of type I cell surface-associated antigens that are not detected in ST10 or strains of type II and III identified two dermatan-sulphate-binding proteins with putative phase/antigenic variation signatures. We propose that the expression of these proteins by type IA organisms contributes to their role in the pathophysiology of acne and helps explain the recurrent nature of the disease. The MLST scheme and database described in this study should provide a valuable platform for future epidemiological and evolutionary studies of P. acnes.

O burlesco e o satírico na obra de Marcial e Juvenal

A presente dissertação assenta na análise comparativa da obra de Marcial e Juvenal e tem como principais objectivos evidenciar a natureza burlesca e satírica que lhes assiste, assim como a (a)temporalidade e o alcance pedagógico-didáctico que as suas palavras comportam. Neste sentido, a análise tomou como matéria a abordagem que ambos fazem de temáticas comuns, no âmbito da representação da sociedade imperial do século I d.C. O trabalho divide-se em duas partes: I. Contexto e Condicionalismos; II. A vida quotidiana em Roma. A primeira subdividida em dois capítulos: 1. O espírito burlesco e o espírito satírico; 2. Apologia pro opere suo, e a segunda em quatro: 3. Modus vivendi Romani: prazeres e distracções em Roma; 4. (A)masculinidade Romana; 5. A condição feminina e o seu lugar em Roma; 6. Clientelismo e patronato sob o olhar de Marcial e Juvenal. Depois de uma contextualização dos termos burlesco e satírico, fundamentalmente alicerçada no primitivo espírito romano, procedeu-se à abordagem dos condicionalismos culturais, sócio-políticos e bibliográficos que melhor contribuem para a compreensão das principais diferenças/semelhanças entre a natureza, as intenções, as estratégias discursivas e a projecção das obras em causa. Na segunda parte, a análise comparativa da representação que os autores fazem da vida quotidiana em Roma focou essencialmente quatro aspectos, abordados em capítulos distintos, conforme supra-enunciado: no primeiro, a visão global que os autores projectam de Roma, através da representação dos principais divertimentos e distracções que ocupam e agradam aos Romanos; no segundo, a moralidade/falsidade que assiste aos comportamentos masculinos; no terceiro, a invectiva à mulher e ao lugar que esta ocupa nas relações sociais, afectivas e sexuais; no quarto, a instituição patronatoclientelismo e os valores sociais e morais que a revestem. A partir desta análise atestam-se as afinidades e o alcance de um fim semelhante nas obras de Marcial e Juvenal, não obstante a natureza e as diferenças estruturais que lhes assistem. Desta dissertação constam também uma Introdução e uma Conclusão, uma Bibliografia, bem como um Índice geral e um Index auctorum et locorum latinorum.

Estimating the net contribution of interleukin-28B variation to spontaneous hepatitis C virus clearance.

The identification of associations between interleukin-28B (IL-28B) variants and the spontaneous clearance of hepatitis C virus (HCV) raises the issues of causality and the net contribution of host genetics to the trait. To estimate more precisely the net effect of IL-28B genetic variation on HCV clearance, we optimized genotyping and compared the host contributions in multiple- and single-source cohorts to control for viral and demographic effects. The analysis included individuals with chronic or spontaneously cleared HCV infections from a multiple-source cohort (n = 389) and a single-source cohort (n = 71). We performed detailed genotyping in the coding region of IL-28B and searched for copy number variations to identify the genetic variant or haplotype carrying the strongest association with viral clearance. This analysis was used to compare the effects of IL-28B variation in the two cohorts. Haplotypes characterized by carriage of the major alleles at IL-28B single-nucleotide polymorphisms (SNPs) were highly overrepresented in individuals with spontaneous clearance versus those with chronic HCV infections (66.1% versus 38.6%, P = 6 × 10(-9) ). The odds ratios for clearance were 2.1 [95% confidence interval (CI) = 1.6-3.0] and 3.9 (95% CI = 1.5-10.2) in the multiple- and single-source cohorts, respectively. Protective haplotypes were in perfect linkage (r(2) = 1.0) with a nonsynonymous coding variant (rs8103142). Copy number variants were not detected. We identified IL-28B haplotypes highly predictive of spontaneous HCV clearance. The high linkage disequilibrium between IL-28B SNPs indicates that association studies need to be complemented by functional experiments to identify single causal variants. The point estimate for the genetic effect was higher in the single-source cohort, which was used to effectively control for viral diversity, sex, and coinfections and, therefore, offered a precise estimate of the net host genetic contribution.

Stereoselective synthesis of 5-substituted pyrrolo[1,2-c]imidazol-3-ones. Access to aldosterone synthase inhibitors and chiral precatalysts

Compounds containing the pyrrolidine moiety are key substructures of compounds with biological activity and organocatalysts. In particular, annulated chiral pyrrolidines with alpha stereogenic centers have aldostereone synthase inhibition activity. In addition, 5-substituted pyrroloimidazol(in)ium salts precursors to N-heterocyclic carbene (NHC) precatalysts are rare due to a lack of convenient synthetic routes to access them. In this thesis is described a rapid synthesis of NHC precursors and a possible route to 5-substituted pyrroloimidazole biologically active compounds. The method involves the preparation of chiral saturated and achiral unsaturated pyrrolo[I,2- c]imidazol-3-ones from N-Cbz-protected t-Butyl proline carboxamide. The resulting starting materials may be used to prepare the target chiral annulated imidazol(in)ium products by a two-step sequence involving first stereoselective lithiation-substitution, followed by POCh induced salt formation.

Synthèse de 4-désoxy hexopyrannoses, C-disaccharides et C-glycosides biologiquement actifs

Les glucides constituent la classe de molécules organiques la plus abondante et ceux-ci jouent des rôles cruciaux dans divers processus biologiques. De part leur importance médicinale, la préparation des désoxy-sucres, des C-glycosides et des C-disaccharides est devenue un sujet de pointe en synthèse organique. De façon générale, cette thèse décrit une nouvelle synthèse de novo des 4-désoxy hexopyrannoses en plus de la préparation de C-glycosides biologiquement actifs. De plus, une attention particulière a été portée à la préparation de novo de 4-désoxy-C-disaccharides. Dans un premier temps, le catalyseur de Cr(III) de Jacobsen et un complexe binaphtol/titane ont été utilisés pour réaliser des hétéro-Diels-Alder énantiosélectives. Les dihydropyrannes ainsi générés ont été transformés en 4-désoxy hexopyrannoses présents dans la nature. De cette façon, un dérivé de l’acide ézoaminuroïque, un précurseur de la désosamine et de la néosidomycine, a été préparé suivant cette approche de novo. De plus, à titre comparatif, la néosidomycine a également été fabriquée selon une approche chiron, à partir du méthyl alpha-D-mannopyrannoside. Finalement, une évaluation biologique préliminaire de la néosidomycine a été effectuée sur une la concanavaline-A (Chapitre 2). Dans un deuxième temps, une allylation stéréosélective sur un aldéhyde lié via des liens C-C à une unité mannoside a permis de générer un alcool homoallylique. Cette dernière fonctionnalité a été transformée en 4-désoxy hexopyrannose de configuration D ou L. De cette façon, la préparation de pseudo 4-désoxy-C-disaccharides, de 4-désoxy-C-disaccharides et de pseudo 4-désoxy aza-C-disaccharides a facilement été réalisée. Les rapports diastéréoisomériques de la réaction d’allylation ont été déterminés en plus de la configuration absolue des nouveaux centres stéréogéniques formés. La transformation des alcools homoallyliques en pyrannes poly hydroxylés ou en lactames poly hydroxylés a été réalisée, en plus de la déprotection de certains membres de cette famille pour une évaluation biologique préliminaire sur la concanavaline-A (Chapitre 3). Finalement, la synthèse de C-glycosides biologiquement actifs a été réalisée selon deux volets: i) préparation de 3-C-mannopyrannosyl coumarines et ii) synthèse de C-galactosides, inhibiteurs de la lectine PA-IL. Pour ce faire, le couplage de Heck a été utilisé à partir d’un ester alpha,bêta-insaturé, attaché à une unité glycosidique via des liens C-C, pour générer un dérivé glycosyl cinnamate de méthyle. Cependant, lorsque le 2-iodophénol est utilisé comme partenaire de Heck, la coumarine correspondante a été isolée. Les dérivés C-galactopyrannosyl cinnamates de méthyle représentent de bons inhibiteurs monovalents de la PA-IL avec un Kd aussi bas que 37 micro M (Chapitre 4).

Àlgebra moderna: conjunts, relacions i aplicacions

Oferim als estudiants universitaris i als lectors interessats aquesta guia didàctica de la matemàtica universitària com a fruit dels nostres anys de docència de les matemàtiques a la Universitat. El resultat final ha esdevingut una col·lecció de setze petits volums agrupats en els dos mòduls d'Àlgebra Lineal i de Càlcul Infinitesimal. El primer volum de la col•lecció, s’inicia amb les nocions primàries del conjunt, element i pertinença que constitueixen el pilar bàsic del llenguatge matemàtic. Tot seguit tractem el tema de les relacions binàries entre els elements d’un conjunt, destacant-hi entre elles les relacions d’equivalència que, com veurem en el proper volum, permetran la fonamentació de les diferents classes de nombres. Finalment, es tracten les aplicacions entre conjunts, un concepte que es desenvoluparà plenament en l’estudi del Càlcul Funcional

Càlcul funcional: topologia, successions i continuïtat

Oferim als estudiants universitaris i als lectors interessats aquesta guia didàctica de la matemàtica universitària com a fruit dels nostres anys de docència de les matemàtiques a la Universitat. El resultat final ha esdevingut una col·lecció de setze petits volums agrupats en els dos mòduls d'Àlgebra Lineal i de Càlcul Infinitesimal. El present volum s’inicia amb un estudi de les nocions de la topologia de Rn , que creiem necessari per analitzar amb un mínim de rigor el concepte de continuïtat d’una funció, que tractem en aquest mateix volum, i el concepte de derivabilitat que analitzem en el volum següent. Així mateix, es realitza un estudi de les successions i sèries numèriques, noció que emprarem també per definir el límit d’una funció en un punt. Malgrat que incloem les definicions rigoroses d’alguns conceptes, hem volgut fugir deliberadament de l’excessiu rigor per donar prioritat a les idees intuïtives que ens poden ajudar a entendre la pràctica dels conceptes

Les Compravendes al detall i a crèdit en el món artesà: El cas dels especiers i els candelers: El cas dels especiers i els candelers

Estudi de com el crèdit va tenir un paper molt important en les compravendes al detall en els gremis dels especiers (o apotecaris) i cerers a la Barcelona baixmedieval. Es pretén extrapolar les conclusions per aquests dos col•lectius a altres grups socioprofessionals similars. Es parteix de la teoria que aquest paper del crèdit va ser ben diferent que el desenvolupat en les pràctiques mercantils, banc��ries i rendistes

Les Ordinacions de mercaderies encamerades o falsificades: evolució del control municipal sobre la qualitat de les espècies i les drogues (segles XIV-XV)

Aproximació al funcionament de la mostassafia barcelonina medieval, i a la creació d’un dret municipal encarregat de regular la vida ciutadana. Aquesta aproximació es fa a partir d’un aspecte relativament simple: el control de la qualitat de les espècies i les drogues. L’anàlisi de les ordinacions de mercaderies encamerades serveix per veure com els consellers aprofitaren la creació de la figura del mostassaf i l’establiment de les seves àmplies atribucions normatives per controlar l’activitat mercantil barcelonina

Ordinacions, privilegis i oficis: la regulació de l'art de l'especieria (s. XIV-XV)

L’estudi de l’evolució de la regulació de l’art de l’especieria o apotecaria a Barcelona permet copsar com les arts i els oficis no solament s’aprofitaren en benefici propi de la cessió del "ius statuendi" al govern municipal, sinó que, quan ho van considerar convenient, van acudir al rei per tal que consolidés per via de privilegi la seva posició de força en el seu camp professional