Galaxy interactions I. Major and minor mergers

Aims. We study galaxy pair samples selected from the Sloan Digital Sky Survey (SDSS-DR7) and we perform an analysis of minor and major mergers with the aim of investigating the dependence of galaxy properties on interactions. Methods. We build a galaxy pair catalog requiring r(p) < 25 kpc h(-1) and Delta V < 350 km s(-1) within redshift z < 0.1. By visual inspection of SDSS images we remove false identifications and we classify the interactions into three categories: pairs undergoing merging, M; pairs with evident tidal features, T; and non disturbed, N. We also divide the pair sample into minor and major interactions according to the luminosity ratio of the galaxy members. We study star formation activity through colors, the 4000 angstrom break, and star formation rates. Results. We find that similar to 10% of the pairs are classified as M. These systems show an excess of young stellar populations as inferred from the D-n(4000) spectral index, colors, and star formation rates of the member galaxies, an effect which we argue is directly related to the ongoing merging process. We find similar to 30% of the pairs exhibiting tidal features (T pairs) with member galaxies showing evidence of old stellar populations. This can be associated either to the disruptive effect of some tidal interactions, or to the longer time-scale of morphological disturbance with respect to the bursts of the tidal induced star formation. Regardless of the color distribution, we find a prominent blue peak in the strongest mergers, while pairs with tidal signs under a minor merger show a strong red peak. Therefore, our results show that galaxy interactions are important in driving the evolution of galaxy bimodality. By adding stellar masses and star formation rates of the two members of the pairs, we explore the global efficiency of star formation of the pairs as a whole. We find that, at a given total stellar mass, major mergers are significantly more efficient (a factor approximate to 2) in forming new stars, with respect to both minor mergers or a control sample of non-interacting galaxies. We conclude that the characteristics of the interactions and the ratio of luminosity galaxy pair members involved in a merger are important parameters in setting galaxy properties.

No-pole condition in Landau gauge: Properties of the Gribov ghost form factor and a constraint on the 2d gluon propagator

We study general properties of the Landau-gauge Gribov ghost form factor sigma(p(2)) for SU(N-c) Yang-Mills theories in the d-dimensional case. We find a qualitatively different behavior for d = 3, 4 with respect to the d = 2 case. In particular, considering any (sufficiently regular) gluon propagator D(p(2)) and the one-loop-corrected ghost propagator, we prove in the 2d case that the function sigma(p(2)) blows up in the infrared limit p -> 0 as -D(0) ln(p(2)). Thus, for d = 2, the no-pole condition sigma(p(2)) < 1 (for p(2) > 0) can be satisfied only if the gluon propagator vanishes at zero momentum, that is, D(0) = 0. On the contrary, in d = 3 and 4, sigma(p(2)) is finite also if D(0) > 0. The same results are obtained by evaluating the ghost propagator G(p(2)) explicitly at one loop, using fitting forms for D(p(2)) that describe well the numerical data of the gluon propagator in two, three and four space-time dimensions in the SU(2) case. These evaluations also show that, if one considers the coupling constant g(2) as a free parameter, the ghost propagator admits a one-parameter family of behaviors (labeled by g(2)), in agreement with previous works by Boucaud et al. In this case the condition sigma(0) <= 1 implies g(2) <= g(c)(2), where g(c)(2) is a "critical" value. Moreover, a freelike ghost propagator in the infrared limit is obtained for any value of g(2) smaller than g(c)(2), while for g(2) = g(c)(2) one finds an infrared-enhanced ghost propagator. Finally, we analyze the Dyson-Schwinger equation for sigma(p(2)) and show that, for infrared-finite ghost-gluon vertices, one can bound the ghost form factor sigma(p(2)). Using these bounds we find again that only in the d = 2 case does one need to impose D(0) = 0 in order to satisfy the no-pole condition. The d = 2 result is also supported by an analysis of the Dyson-Schwinger equation using a spectral representation for the ghost propagator. Thus, if the no-pole condition is imposed, solving the d = 2 Dyson-Schwinger equations cannot lead to a massive behavior for the gluon propagator. These results apply to any Gribov copy inside the so-called first Gribov horizon; i.e., the 2d result D(0) = 0 is not affected by Gribov noise. These findings are also in agreement with lattice data.

PTEN Directly Activates the Actin Depolymerization Factor Cofilin-1 During PGE(2)-Mediated Inhibition of Phagocytosis of Fungi

Macrophage ingestion of the yeast Candida albicans requires its recognition by multiple receptors and the activation of diverse signaling programs. Synthesis of the lipid mediator prostaglandin E-2 (PGE(2)) and generation of cyclic adenosine monophosphate (cAMP) also accompany this process. Here, we characterized the mechanisms underlying PGE(2)-mediated inhibition of phagocytosis and filamentous actin (F-actin) polymerization in response to ingestion of C. albicans by alveolar macrophages. PGE(2) suppressed phagocytosis and F-actin formation through the PGE(2) receptors EP2 and EP4, cAMP, and activation of types I and II protein kinase A. Dephosphorylation and activation of the actin depolymerizing factor cofilin-1 were necessary for these inhibitory effects of PGE(2). PGE(2)-dependent activation of cofilin-1 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated. Because enhanced production of PGE(2) accompanies many immunosuppressed states, the PTEN-dependent pathway described here may contribute to impaired antifungal defenses.

Colibacillosis in lambs is associated to type I heat-stable enterotoxin in a farm in Sao Paulo State, Brazil

Twenty seven (48.2%) culture supernatants of 56 Escherichia coli isolated from diarrheic lamb feces (7 to 10 days old) in Sao Paulo State, Brazil, presented positive results to suckling mice assay (fluid accumulation) but none caused cytopathic effects on Vero and CHO cells, indicating that these strains did not produced LT or VT toxins. PCR assays showed that these 27 E. coli strains harbored estA, that codifies for STa, but not for stx1, stx2 or cnf genes. The positive STa strains were checked for genes that codify for F41, F17 and K99 fimbriae, wich are considered colonization factors in ETEC. Only F17 was detect in two samples (7.4%). Twelve of 27 STa positive carried hlyA gene and presented hemolytic activity in blood Agar. Presence of rotavirus was not detected among the diarrheic feces. These data suggests that STa must be an important diarrheagenic factor to small ruminants in Sao Paulo State.

A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial

Abstract Background Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. Methods/design This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. Discussion The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. Clinical trials registration number ClinicalTrials.gov: NCT00971165

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems

Methods We conducted a phase I, multicenter, randomized, double-blind, placebo-controlled, multi-arm (10) parallel study involving healthy adults to evaluate the safety and immunogenicity of influenza A (H1N1) 2009 non-adjuvanted and adjuvanted candidate vaccines. Subjects received two intramuscular injections of one of the candidate vaccines administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay before and 21 days after each vaccination. The three co-primary immunogenicity end points were the proportion of seroprotection >70%, seroconversion >40%, and the factor increase in the geometric mean titer >2.5. Results A total of 266 participants were enrolled into the study. No deaths or serious adverse events were reported. The most commonly solicited local and systemic adverse events were injection-site pain and headache, respectively. Only three subjects (1.1%) reported severe injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent candidate vaccines that met the three requirements to evaluate influenza protection, after a single dose, were identified: 15 μg of hemagglutinin antigen without adjuvant; 7.5 μg of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 μg of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 μg of hemagglutinin antigen with aluminum hydroxide and squalene. Conclusions Adjuvant systems can be safely used in influenza vaccines, including the adjuvant monophosphoryl lipid A (MPL) derived from Bordetella pertussis with squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and aluminum hydroxide.

Evaluación de la hiperbilirrubinemia como factor de riesgo de hipoacusia neurosensorial en el programa de screening universal de hipoacusia infantil del Complejo Hospitalario Universitario Universitario Insular Materno Infantil de Gran Canaria ente los años 2007 al 2011

Programa de doctorado: Avances en Traumatología, Medicina del Deporte y Cuidados de Heridas.

Il ruolo delle idee e del loro cambiamento nei processi di policy making universitario nel mondo anglosassone dagli anni ottanta ad oggi. I casi di Inghilterra e Nuova Zelanda in prospettiva comparata

THE TITLE OF MY THESIS IS THE ROLE OF THE IDEAS AND THEIR CHANGE IN HIGHER EDUCATION POLICY-MAKING PROCESSES FROM THE EIGHTIES TO PRESENT-DAY: THE CASES OF ENGLAND AND NEW ZEALAND IN COMPARATIVE PERSPECTIVE UNDER A THEORETICAL POINT OF VIEW, THE AIM OF MY WORK IS TO CARRY OUT A RESEARCH MODELLED ON THE CONSTRUCTIVIST THEORY. IT FOCUSES ON THE ANALYSIS OF THE IMPACT OF IDEAS ON THE PROCESSES OF POLICY MAKING BY MEANS OF EPISTEMIC COMMUNITIES, THINK TANKS AND VARIOUS SOCIOECONOMIC CONTEXTS THAT MAY HAVE PLAYED A KEY ROLE IN THE CONSTRUCTION OF THE DIFFERENT PATHS. FROM MY POINT OF VIEW IDEAS CONSTITUTE A PRIORITY RESEARCH FIELD WHICH IS WORTH ANALYSING SINCE THEIR ROLE IN POLICY MAKING PROCESSES HAS BEEN TRADITIONALLY RATHER UNEXPLORED. IN THIS CONTEXT AND WITH THE AIM OF DEVELOPING A RESEARCH STRAND BASED ON THE ROLE OF IDEAS, I INTEND TO CARRY ON MY STUDY UNDER THE PERSPECTIVE OF CHANGE. DEPENDING ON THE DATA AND INFORMATION THAT I COLLECTED I EVALUATED THE WEIGHT OF EACH OF THESE VARIABLES AND MAYBE OTHERS SUCH AS THE INSTITUTIONS AND THE INDIVIDUAL INTERESTS, WHICH MAY HAVE INFLUENCED THE FORMATION OF THE POLICY MAKING PROCESSES. UNDER THIS LIGHT, I PLANNED TO ADOPT THE QUALITATIVE METHODOLOGY OF RESEARCH WHICH I BELIEVE TO BE VERY EFFECTIVE AGAINST THE MORE DIFFICULT AND POSSIBLY REDUCTIVE APPLICATION OF QUANTITIVE DATA SETS. I RECKON THEREFORE THAT THE MOST APPROPRIATE TOOLS FOR INFORMATION PROCESSING INCLUDE CONTENT ANALYSIS, AND IN-DEPTH INTERVIEWS TO PERSONALITIES OF THE POLITICAL PANORAMA (ÉLITE OR NOT) WHO HAVE PARTICIPATED IN THE PROCESS OF HIGHER EDUCATION REFORM FROM THE EIGHTIES TO PRESENT-DAY. THE TWO CASES TAKEN INTO CONSIDERATION SURELY SET AN EXAMPLE OF RADICAL REFORM PROCESSES WHICH HAVE OCCURRED IN QUITE DIFFERENT CONTEXTS DETERMINED BY THE SOCIOECONOMIC CHARACTERISTICS AND THE TRAITS OF THE ÉLITE. IN NEW ZEALAND THE DESCRIBED PROCESS HAS TAKEN PLACE WITH A STEADY PACE AND A GOOD GRADE OF CONSEQUANTIALITY, IN LINE WTH THE REFORMS IN OTHER STATE DIVISIONS DRIVEN BY THE IDEAS OF THE NEW PUBLIC MANAGEMENT. CONTRARILY IN ENGLAND THE REFORMATIVE ACTION OF MARGARET THATCHER HAS ACQUIRED A VERY RADICAL CONNOTATION AS IT HAS BROUGHT INTO THE AMBIT OF HIGHER EDUCATION POLICY CONCEPTS LIKE EFFICIENCY, EXCELLENCE, RATIONALIZATION THAT WOULD CONTRAST WITH THE GENERALISTIC AND MASS-ORIENTED IDEAS THAT WERE FASHIONABLE DURING THE SEVENTIES. THE MISSION I INTEND TO ACCOMPLISH THORUGHOUT MY RESEARCH IS TO INVESTIGATE AND ANALYSE INTO MORE DEPTH THE DIFFERENCES THAT SEEM TO EMERGE FROM TWO CONTEXTS WHICH MOST OF THE LITERATURE REGARDS AS A SINGLE MODEL: THE ANGLO-SAXON MODEL. UNDER THIS LIGHT, THE DENSE ANALYSIS OF POLICY PROCESSES ALLOWED TO BRING OUT BOTH THE CONTROVERSIAL AND CONTRASTING ASPECTS OF THE TWO REALITIES COMPARED, AND THE ROLE AND WEIGHT OF VARIABLES SUCH AS IDEAS (MAIN VARIABLE), INSTITUTIONAL SETTINGS AND INDIVIDUAL INTERESTS ACTING IN EACH CONTEXT. THE CASES I MEAN TO ATTEND PRESENT PECULIAR ASPECTS WORTH DEVELOPING AN IN-DEPTH ANALYSIS, AN OUTLINE OF WHICH WILL BE PROVIDED IN THIS ABSTRACT. ENGLAND THE CONSERVATIVE GOVERNMENT, SINCE 1981, INTRODUCED RADICAL CHANGES IN THE SECTOR OF HIGHER EDUCATION: FIRST CUTTING DOWN ON STATE FUNDINGS AND THEN WITH THE CREATION OF AN INSTITUTION FOR THE PLANNING AND LEADERSHIP OF THE POLYTECHNICS (NON-UNIVERSITY SECTOR). AFTERWARDS THE SCHOOL REFORM BY MARGARET THATCHER IN 1988 RAISED TO A GREAT STIR ALL OVER EUROPE DUE TO BOTH ITS CONSIDERABLE INNOVATIVE IMPRINT AND THE STRONG ATTACK AGAINST THE PEDAGOGY OF THE ‘ACTIVE’ SCHOOLING AND PROGRESSIVE EDUCATION, UNTIL THEN RECOGNIZED AS A MERIT OF THE BRITISH PUBLIC SCHOOL. IN THE AMBIT OF UNIVERSITY EDUCATION THIS REFORM, TOGETHER WITH SIMILAR MEASURES BROUGHT IN DURING 1992, PUT INTO PRACTICE THE CONSERVATIVE PRINCIPLES THROUGH A SERIES OF ACTIONS THAT INCLUDED: THE SUPPRESSION OF THE IRREMOVABILITY PRINCIPLE FOR UNIVERSITY TEACHERS; THE INTRODUCTION OF STUDENT LOANS FOR LOW-INCOME STUDENTS AND THE CANCELLATION OF THE CLEAR DISTINCTION BETWEEN UNIVERSITIES AND POLYTECHNICS. THE POLICIES OF THE LABOUR MAJORITY OF MR BLAIR DID NOT QUITE DIVERGE FROM THE CONSERVATIVES’ POSITION. IN 2003 BLAIR’S CABINET RISKED TO BECOME A MINORITY RIGHT ON THE OCCASION OF AN IMPORTANT UNIVERSITY REFORM PROPOSAL. THIS PROPOSAL WOULD FORESEE THE AUTONOMY FOR THE UNIVERSITIES TO RAISE UP TO 3.000 POUNDS THE ENROLMENT FEES FOR STUDENTS (WHILE FORMERLY THE CEILING WAS 1.125 POUNDS). BLAIR HAD TO FACE INTERNAL OPPOSITION WITHIN HIS OWN PARTY IN RELATION TO A MEASURE THAT, ACCORDING TO THE 150 MPS PROMOTERS OF AN ADVERSE MOTION, HAD NOT BEEN INCLUDED IN THE ELECTORAL PROGRAMME AND WOULD RISK CREATING INCOME-BASED DISCRIMINATION AMONG STUDENTS. AS A MATTER OF FACT THE BILL FOCUSED ON THE INTRODUCTION OF VERY LOW-INTEREST STUDENT LOANS TO BE SETTLED ONLY WHEN THE STUDENT WOULD HAVE FOUND A REMUNERATED OCCUPATION (A SYSTEM ALREADY PROVIDED FOR BY THE AUSTRALIAN LEGISLATION). NEW ZEALAND CONTRARILY TO MANY OTHER COUNTRIES, NEW ZEALAND HAS ADOPTED A VERY WIDE VISION OF THE TERTIARY EDUCATION. IT INCLUDES IN FACT THE FULL EDUCATIONAL PROGRAMME THAT IS INTERNATIONALLY RECOGNIZED AS THE POST-SECONDARY EDUCATION. SHOULD WE SPOTLIGHT A PECULIARITY OF THE NEW ZEALAND TERTIARY EDUCATION POLICY THEN IT WOULD BE ‘CHANGE’. LOOKING AT THE REFORM HISTORY RELATED TO THE TERTIARY EDUCATION SYSTEM, WE CAN CLEARLY IDENTIFY FOUR ‘SUB-PERIODS’ FROM THE EIGHTIES TO PRESENT-DAY: 1. BEFORE THE 80S’: AN ELITARIAN SYSTEM CHARACTERIZED BY LOW PARTICIPATION RATES. 2. BETWEEN MID AND LATE 80S’: A TREND TOWARDS THE ENLARGEMENT OF PARTICIPATION ASSOCIATED TO A GREATER COMPETITION. 3. 1990-1999: A FUTHER STEP TOWARDS A COMPETITIVE MODEL BASED ON THE MARKET-ORIENTED SYSTEM. 4. FROM 2000 TO TODAY: A CONTINUOUS EVOLUTION TOWARDS A MORE COMPETITIVE MODEL BASED ON THE MARKET-ORIENTED SYSTEM TOGETHER WITH A GROWING ATTENTION TO STATE CONTROL FOR SOCIAL AND ECONOMIC DEVELOPMENT OF THE NATION. AT PRESENT THE GOVERNMENT OF NEW ZEALAND OPERATES TO STRENGHTHEN THIS PROCESS, PRIMARILY IN RELATION TO THE ROLE OF TERTIARY EDUCATION AS A STEADY FACTOR OF NATIONAL WALFARE, WHERE PROFESSIONAL DEVELOPMENT CONTRIBUTES ACTIVELY TO THE GROWTH OF THE NATIONAL ECONOMIC SYSTEM5. THE CASES OF ENGLAND AND NEW ZEALAND ARE THE FOCUS OF AN IN-DEPTH INVESTIGATION THAT STARTS FROM AN ANALYSIS OF THE POLICIES OF EACH NATION AND DEVELOP INTO A COMPARATIVE STUDY. AT THIS POINT I ATTEMPT TO DRAW SOME PRELIMINARY IMPRESSIONS ON THE FACTS ESSENTIALLY DECRIBED ABOVE. THE UNIVERSITY POLICIES IN ENGLAND AND NEW ZEALAND HAVE BOTH UNDERGONE A SIGNIFICANT REFORMATORY PROCESS SINCE THE EARLY EIGHTIES; IN BOTH CONTEXTS THE IMPORTANCE OF IDEAS THAT CONSTITUTED THE BASE OF POLITICS UNTIL 1980 WAS QUITE RELEVANT. GENERALLY SPEAKING, IN BOTH CASES THE PRE-REFORM POLICIES WERE INSPIRED BY EGALITARIANISM AND EXPANSION OF THE STUDENT POPULATION WHILE THOSE BROUGHT IN BY THE REFORM WOULD PURSUE EFFICIENCY, QUALITY AND COMPETITIVENESS. UNDOUBTEDLY, IN LINE WITH THIS GENERAL TENDENCY THAT REFLECTS THE HYPOTHESIS PROPOSED, THE TWO UNIVERSITY SYSTEMS PRESENT SEVERAL DIFFERENCES. THE UNIVERSITY SYSTEM IN NEW ZEALAND PROCEEDED STEADILY TOWARDS THE IMPLEMENTATION OF A MANAGERIAL CONCEPTION OF TERTIARY EDUCATION, ESPECIALLY FROM 1996 ONWARDS, IN ACCORDANCE WITH THE REFORMATORY PROCESS OF THE WHOLE PUBLIC SECTOR. IN THE UNITED KINGDOM, AS IN THE REST OF EUROPE, THE NEW APPROACH TO UNIVERSITY POLICY-MAKING HAD TO CONFRONT A DEEP-ROOTED TRADITION OF PROGRESSIVE EDUCATION AND THE IDEA OF EDUCATION EXPANSION THAT IN FACT DOMINATED UNTIL THE EIGHTIES. FROM THIS VIEW POINT THE GOVERNING ACTION OF MARGARET THATCHER GAVE RISE TO A RADICAL CHANGE THAT REVOLUTIONIZED THE OBJECTIVES AND KEY VALUES OF THE WHOLE EDUCATIONAL SYSTEM, IN PARTICULAR IN THE HIGHER EDUCATION SECTOR. IDEAS AS EFFICIENCY, EXCELLENCE AND CONTROL OF THE PERFORMANCE BECAME DECISIVE. THE LABOUR CABINETS OF BLAIR DEVELOPED IN THE WAKE OF CONSERVATIVE REFORMS. THIS APPEARS TO BE A FOCAL POINT OF THIS STUDY THAT OBSERVES HOW ALSO IN NEW ZEALAND THE REFORMING PROCESS OCCURRED TRANSVERSELY DURING PROGRESSIVE AND CONSERVATIVE ADMINISTRATIONS. THE PRELIMINARY IMPRESSION IS THEREFORE THAT IDEAS DEEPLY MARK THE REFORMATIVE PROCESSES: THE AIM OF MY RESEARCH IS TO VERIFY TO WHICH EXTENT THIS STATEMENT IS TRUE. IN ORDER TO BUILD A COMPREHENSIVE ANALYLIS, FURTHER SIGNIFICANT FACTORS WILL HAVE TO BE INVESTIGATED: THE WAY IDEAS ARE PERCEIVED AND IMPLEMENTED BY THE DIFFERENT POLITICAL ELITES; HOW THE VARIOUS SOCIOECONOMIC CONTEXTS INFLUENCE THE REFORMATIVE PROCESS; HOW THE INSTITUTIONAL STRUCTURES CONDITION THE POLICY-MAKING PROCESSES; WHETHER INDIVIDUAL INTERESTS PLAY A ROLE AND, IF YES, TO WHICH EXTENT.

Studio della trasduzione del Segnale Nucleare Inositide-Dipendente: identificazione di eEF1A2 come nuovo Fosfosubstrato di PKC βI

Introduction Phospholipase Cb1 (PLC-β1) is a key player in the regulation of nuclear inositol lipid signaling and of a wide range of cellular functions, such as proliferation and differentiation (1,2,3). PLCb1 signaling depends on the cleavage of phosphatidylinositol 4,5-bisphosphate and the formation of the second messengers diacylglycerol and Inositol tris-phosphate which activate canonical protein kinase C (cPKC) isoforms. Here we describe a proteomic approach to find out a potential effector of nuclear PLC-b1 dependent signaling during insulin stimulated myogenic differentiation. Methods Nuclear lysates obtained from insulin induced C2C12 myoblasts were immunoprecipitated with anti-phospho-substrate cPKC antibody. Proteins, stained with Comassie blue, were excised, digested and subsequently analysed in LC-MS/MS. For peptide sequence searching, the mass spectra were processed and analyzed using the Mascot MS/MS ion search program with the NCBI database. Western blotting, GST-pull down and co-immunoprecipitation were performed to study the interaction between eEF1A2 and cPKCs. Site direct mutagenesis was performed to confirm the phosphorylated motif recognized by the antibody. Immunofluorescence analysis, GFP-tagged eEF1A2 vector and subcellular fractionation were performed to study nuclear localization and relative distribution of eEF1A2. Results We have previously shown that PLC-β1 is greatly increased at the nuclear level during insulin-induced myoblasts differentiation and that this nuclear localization is essential for induction of differentiation. Thus, nuclear proteins of insulin stimulated C2C12 myoblasts, were immunoprecipitated with an anti-phospho-substrate cPKC antibody. After Electrophoretic gel separation of proteins immunoprecipitated, several molecules were identified by LC-MS/MS. Among these most relevant and unexpected was eukaryotic elongation factor 1 alpha 2 (eEF1A2). We found that eEF1A2 is phosphorylated by PKCb1 and that these two molecules coimmunolocalized at the nucleolar level. eEF1A2 could be phosphorylated in many sites among which both threonine and serine residues. By site direct mutagenesis we demonstrated that it is the serine residue of the motif recognized by the antibody that is specifically phosphorylated by PKCb1. The silencing of PLCb1 gives rise to a reduction of expression and phosphorylation levels of eEF1A2 indicating this molecule as a target of nuclear PLCb1 regulatory network during myoblasts differentiation.

Identification of the N-Linked Glycosylation Sites of the Transcription Factor Rest and Effect of Glycosylation on DNA Binding and Transcriptional Activity

REST is a zinc-finger transcription factor implicated in several processes such as maintenance of embryonic stem cell pluripotency and regulation of mitotic fidelity in non-neuronal cells [Chong et al., 1995]. The gene encodes for a 116-kDa protein that acts as a molecular platform for co-repressors recruitment and promotes modifications of DNA and histones [Ballas, 2005]. REST showed different apparent molecular weights, consistent with the possible presence of post-translational modifications [Lee et al., 2000]. Among these the most common is glycosylation, the covalent attachment of carbohydrates during or after protein synthesis [Apweiler et al., 1999] My thesis has ascertained, for the first time, the presence of glycan chians in the transcription factor REST. Through enzymatic deglycosylation and MS, oligosaccharide composition of glycan chains was evaluated: a complex mixture of glycans, composed of N-acetylgalactosamine, galactose and mannose, was observed thus confirming the presence of O- and N-linked glycan chains. Glycosylation site mapping was done using a 18O-labeling method and MS/MS and twelve potential N-glycosylation sites were identified. The most probable glycosylation target residues were mutated through site-directed mutagenesis and REST mutants were expressed in different cell lines. Variations in the protein molecular weight and mutant REST ability to bind the RE-1 sequence were analyzed. Gene reporter assays showed that, altogether, removal of N-linked glycan chains causes loss of transcriptional repressor function, except for mutant N59 which showed a slight residual repressor activity in presence of IGF-I. Taken togheter these results demonstrate the presence of complex glycan chians in the transcription factor REST: I have depicted their composition, started defining their position on the protein backbone and identified their possible role in the transcription factor functioning. Considering the crucial role of glycosylation and transcription factors activity in the aetiology of many diseases, any further knowledge could find important and interesting pharmacological application.

Espressione del vascular endothelium growth factor (VEGF) nella micosi fungoide

La micosi fungoide (MF) è un linfoma a cellule T primitivo della cute usualmente indolente negli stadi iniziali, ma con prognosi decisamente peggiore nelle fasi avanzate, ove attualmente non sono presenti strategie terapeutiche tali da indurre remissioni durature. Recenti osservazioni indicano che alti livelli di espressione del vascular endothelial growth factor (VEGF) nelle cellule della MF sembrano correlare con una prognosi peggiore. Nel presente studio, sono state vagliate le eventuali differenze di espressione di VEGF nella MF e nei linfociti T normali. In primo luogo sono stati raffrontati 63 casi di MF con 20 campioni corrispondenti alle diverse sottopopolazioni di linfociti T normali, per stabilire quale fra questi esprimesse maggiori livelli di VEGF. Tale esperimento ha dimostrato che il gene è notevolmente più espresso nella MF. Si è provveduto a stabilire se tale dato sia da correlarsi ad un fenomeno patologico o fisiologico. Quindi sono state eseguite indagini di gene expression profiling (GEP) allo scopo di vagliare i livelli di VEGF nella popolazione linfocitaria T normale (CD4+, CD8+, HLA-DR+ e HLA-DR-): da ciò è risultato che i linfociti T attivati esprimono maggiormente VEGF e che il loro GEP è globalmente paragonabile a quello della MF. Pertanto, i linfociti T attivati sono stati considerati la controparte normale delle cellule della MF. Successivamente si è confrontata l’espressione quantitativa di VEGF nei linfociti T attivati e nelle cellule della MF, evidenziando come questa sia maggiore nella popolazione neoplastica indipendentemente dallo stadio della malattia. Le indagini immunoistochimiche condotte su 18 casi di MF, hanno confermato quanto evidenziato attraverso il GEP. Concludendo, la ricerca ha dimostrato per la prima volta l’espressione di VEGF negli elementi della MF. Ciò porta a supporre che la de-regolazione genica della via di VEGF sia correlata nella patogenesi della MF e che tale molecola possa considerarsi un potenziale bersaglio terapeutico.

L'Orientamento politico come fattore di differenziazione delle politiche pubbliche locali: I casi di Modena e Verona

La tesi ha per oggetto lo studio delle politiche pubbliche locali ed in particolare delle politiche sociali che dal 2011 sono diventate politiche esclusivamente territoriali. L’obiettivo è quello di verificare se il differente orientamento politico delle amministrazioni genera politiche differenti. Per verificare le ipotesi si sono scelti 2 Comuni simili sul piano delle variabili socio-economiche, ma guidati da giunte con orientamento politico differente: il Comune di Modena a guida Partito Democratico e il Comune di Verona con un sindaco leghista a capo di una giunta di centro-destra. Nella prima parte vengono esposti ed analizzati i principali paradigmi di studio delle politiche (rational choice, paradigma marxista, economia del benessere, corporativismo e pluralismo, neo-istituzionalismo e paradigma relazionale) e viene presentato il paradigma che verrà utilizzato per l’analisi delle politiche (paradigma relazionale). Per la parte empirica si è proceduto attraverso interviste in profondità effettuate ai due Assessori alle Politiche sociali e ai due Dirigenti comunali dei Comuni e a 18 organizzazioni di Terzo settore impegnate nella costruzione delle politiche e selezionate attraverso la metodologia “a palla di neve”. Sono analizzate le disposizioni normative in materia di politica sociale, sia per la legislazione regionale che per quella comunale. L’analisi dei dati ha verificato l’ipotesi di ricerca nel senso che l’orientamento politico produce politiche differenti per quanto riguarda il rapporto tra Pubblica Amministrazione e Terzo settore. Per Modena si può parlare di una scelta di esternalizzazione dei servizi che si accompagna ad un processo di internalizzazione dei servizi tramite le ASP; a Verona almeno per alcuni settori delle politiche (disabilità e anziani) sono stati realizzati processi di sussidiarietà e di governance. Per la fase di programmazione l’orientamento politico ha meno influenza e la programmazione mostra caratteristiche di tipo “top-down”.

Studio numerico e sperimentale delle miscele di aggregati per i conglomerati bituminosi

I crescenti volumi di traffico che interessano le pavimentazioni stradali causano sollecitazioni tensionali di notevole entità che provocano danni permanenti alla sovrastruttura. Tali danni ne riducono la vita utile e comportano elevati costi di manutenzione. Il conglomerato bituminoso è un materiale multifase composto da inerti, bitume e vuoti d'aria. Le proprietà fisiche e le prestazioni della miscela dipendono dalle caratteristiche dell'aggregato, del legante e dalla loro interazione. L’approccio tradizionalmente utilizzato per la modellazione numerica del conglomerato bituminoso si basa su uno studio macroscopico della sua risposta meccanica attraverso modelli costitutivi al continuo che, per loro natura, non considerano la mutua interazione tra le fasi eterogenee che lo compongono ed utilizzano schematizzazioni omogenee equivalenti. Nell’ottica di un’evoluzione di tali metodologie è necessario superare questa semplificazione, considerando il carattere discreto del sistema ed adottando un approccio di tipo microscopico, che consenta di rappresentare i reali processi fisico-meccanici dai quali dipende la risposta macroscopica d’insieme. Nel presente lavoro, dopo una rassegna generale dei principali metodi numerici tradizionalmente impiegati per lo studio del conglomerato bituminoso, viene approfondita la teoria degli Elementi Discreti Particellari (DEM-P), che schematizza il materiale granulare come un insieme di particelle indipendenti che interagiscono tra loro nei punti di reciproco contatto secondo appropriate leggi costitutive. Viene valutata l’influenza della forma e delle dimensioni dell’aggregato sulle caratteristiche macroscopiche (tensione deviatorica massima) e microscopiche (forze di contatto normali e tangenziali, numero di contatti, indice dei vuoti, porosità, addensamento, angolo di attrito interno) della miscela. Ciò è reso possibile dal confronto tra risultati numerici e sperimentali di test triassiali condotti su provini costituiti da tre diverse miscele formate da sfere ed elementi di forma generica.