High occurrence of hepatitis E virus in samples from wastewater treatment plants in Switzerland and comparison with other enteric viruses.

Hepatitis E virus (HEV) is responsible for many enterically transmitted viral hepatitides around the world. It is currently one of the waterborne diseases of global concern. In industrialized countries, HEV appears to be more common than previously thought, even if it is rarely virulent. In Switzerland, seroprevalence studies revealed that HEV is endemic, but no information was available on its environmental spread. The aim of this study was to investigate -using qPCR- the occurrence and concentration of HEV and three other viruses (norovirus genogroup II, human adenovirus-40 and porcine adenovirus) in influents and effluents of 31 wastewater treatment plants (WWTPs) in Switzerland. Low concentrations of HEV were detected in 40 out of 124 WWTP influent samples, showing that HEV is commonly present in this region. The frequency of HEV occurrence was higher in summer than in winter. No HEV was detected in WWTP effluent samples, which indicates a low risk of environmental contamination. HEV occurrence and concentrations were lower than those of norovirus and adenovirus. The autochthonous HEV genotype 3 was found in all positive samples, but a strain of the non-endemic and highly pathogenic HEV genotype I was isolated in one sample, highlighting the possibility of environmental circulation of this genotype. A porcine fecal marker (porcine adenovirus) was not detected in HEV positive samples, indicating that swine are not the direct source of HEV present in wastewater. Further investigations will be necessary to determine the reservoirs and the routes of dissemination of HEV.

Destruction of conditional insulinoma cell lines in NOD mice: a role for autoimmunity.

AIMS/HYPOTHESIS: betaTC-tet (H2(k)) is a conditional insulinoma cell line derived from transgenic mice expressing a tetracycline-regulated oncogene. Transgenic expression of several proteins implicated in the apoptotic pathways increase the resistance of betaTC-tet cells in vitro. We tested in vivo the sensitivity of the cells to rejection and the protective effect of genetic alterations in NOD mice. METHODS: betaTC-tet cells and genetically engineered lines expressing Bcl-2 (CDM3D), a dominant negative mutant of MyD88 or SOCS-1 were transplanted in diabetic female NOD mice or in male NOD mice with diabetes induced by high-dose streptozotocin. Survival of functional cell grafts in NOD-scid mice was also analyzed after transfer of splenocytes from diabetic NOD mice. Autoreactive T-cell hybridomas and splenocytes from diabetic NOD mice were stimulated by betaTC-tet cells. RESULTS: betaTC-tet cells and genetically engineered cell lines were all similarly rejected in diabetic NOD mice and in NOD-scid mice after splenocyte transfer. In 3- to 6-week-old male NOD mice treated with high-dose streptozotocin, the cells temporarily survived, in contrast with C57BL/6 mice treated with high-dose streptozotocin (indefinite survival) and untreated 3- to 6-week-old male NOD mice (rejection). The protective effect of high-dose streptozotocin was lost in older male NOD mice. betaTC-tet cells did not stimulate autoreactive T-cell hybridomas, but induced IL-2 secretion by splenocytes from diabetic NOD mice. CONCLUSION/INTERPRETATION: The autoimmune process seems to play an important role in the destruction of betaTC-tet cells in NOD mice. Genetic manipulations intended at increasing the resistance of beta cells were inefficient. Similar approaches should be tested in vivo as well as in vitro. High dose streptozotocin influences immune rejection and should be used with caution.

Aplicación de CPAP vs. BIPAP en pacientes con edema agudo de pulmón

Estudi clínic, prospectiu, randomizat, on d'un total de 59 pacients foren asignats a dos grups de soport ventilatori (CPAP (30) o BIPAP (29)). L' objectiu primari analizat fou la necessitat de IOT. Com objetius secundaris s'estudiaren la milloria de parámetres clínics, gasomètrics, el temps de soport ventilatori i d' estància en UCI, la supervivència a l' alta d' UCI i als 28 dies. No vam trobar diferències en cap dels paràmetres excepte en la pO2/FiO2 després de la primera hora (146,94CPAP vs 198,49BIPAP p=0.037).

HLA photoaffinity labeling reveals overlapping binding of homologous melanoma-associated gene peptides by HLA-A1, HLA-A29, and HLA-B44.

Melanoma-associated genes (MAGEs) encode tumor-specific antigens that can be recognized by CD8+ cytotoxic T lymphocytes. To investigate the interaction of the HLA-A1-restricted MAGE-1 peptide 161-169 (EADPT-GHSY) with HLA class I molecules, photoreactive derivatives were prepared by single amino acid substitution with N beta-[iodo-4-azidosalicyloyl]-L-2,3-diaminopropionic acid. These derivatives were tested for their ability to bind to, and to photoaffinity-label, HLA-A1 on C1R.A1 cells. Only the derivatives containing the photoreactive amino acid in position 1 or 7 fulfilled both criteria. Testing the former derivative on 14 lymphoid cell lines expressing over 44 different HLA class I molecules indicated that it efficiently photoaffinity-labeled not only HLA-A1, but possibility also HLA-A29 and HLA-B44. MAGE peptide binding by HLA-A29 and HLA-B44 was confirmed by photoaffinity labeling with photoreactive MAGE-3 peptide derivatives on C1R.A29 and C1R.B44 cells, respectively. The different photoaffinity labeling systems were used to access the ability of the homologous peptides derived from MAGE-1, -2, -3, -4a, -4b, -6, and -12 to bind to HLA-A1, HLA-A29, and HLA-B44. All but the MAGE-2 and MAGE-12 nonapeptides efficiently inhibited photoaffinity labeling of HLA-A1, which is in agreement with the known HLA-A1 peptide-binding motif (acidic residue in P3 and C-terminal tyrosine). In contrast, photoaffinity labeling of HLA-A29 was efficiently inhibited by these as well as by the MAGE-3 and MAGE-6 nonapeptides. Finally, the HLA-B44 photoaffinity labeling, unlike the HLA-A1 and HLA-A29 labeling, was inhibited more efficiently by the corresponding MAGE decapeptides, which is consistent with the reported HLA-B44 peptide-binding motif (glutamic acid in P2, and C-terminal tyrosine or phenylalanine). The overlapping binding of homologous MAGE peptides by HLA-A1, A29, and B44 is based on different binding principles and may have implications for immunotherapy of MAGE-positive tumors.

Positive control of swarming, rhamnolipid synthesis, and lipase production by the posttranscriptional RsmA/RsmZ system in Pseudomonas aeruginosa PAO1.

In Pseudomonas aeruginosa, the small RNA-binding, regulatory protein RsmA is a negative control element in the formation of several extracellular products (e.g., pyocyanin, hydrogen cyanide, PA-IL lectin) as well as in the production of N-acylhomoserine lactone quorum-sensing signal molecules. RsmA was found to control positively the ability to swarm and to produce extracellular rhamnolipids and lipase, i.e., functions contributing to niche colonization by P. aeruginosa. An rsmA null mutant was entirely devoid of swarming but produced detectable amounts of rhamnolipids, suggesting that factors in addition to rhamnolipids influence the swarming ability of P. aeruginosa. A small regulatory RNA, rsmZ, which antagonized the effects of RsmA, was identified in P. aeruginosa. Expression of the rsmZ gene was dependent on both the global regulator GacA and RsmA, increased with cell density, and was subject to negative autoregulation. Overexpression of rsmZ and a null mutation in rsmA resulted in quantitatively similar, negative or positive effects on target genes, in agreement with a model that postulates titration of RsmA protein by RsmZ RNA.

Impacto de la rotación cíclica de antibióticos sobre la etiología de las neumonías nosocomiales por gramnegativos en una unidad de cuidados intensivos (uci)

La rotació cíclica d'antibiòtics (RCA) consisteix a restringir de forma determinada i establerta un antibiòtic o classe d'antibiòtics durant un determinat període de temps, per a tornar a reintroduir-lo posteriorment. D'aquesta manera es pretén evitar l'aparició de resistències bacterianes derivades d'un ús continuat del mateix. En aquest treball, proposem la RCA com una estratègia per al control d'infeccions per gèrmens multirresistents i veure la seva influència en els gèrmens més freqüents que intervenen en les pneumònies nosocomials (NN). A través del registre ENVIN es van recollir les dades de tots els pacients ingressats a la UCI de l'Hospital Universitari la Fe durant dotze mesos consecutius. Es van dividir en 4 cicles de 3 mesos de durada cadascun d'ells. En el primer cicle es va restringir ampicilina/sulbactam, amikacina, cefalosporines i vancomicina; en el segon cicle carbapenems, amikacina i linezolid; en el tercer cicle tigeciclina, quinolones, tobramicina i linezolid i al quart i últim cicle, piperacilina/tazobactam, tobramicina i teicoplanina. Es va comparar amb els tres mesos previs al inici del treball, al qual l'ús d'antibiòtics va ser lliure. El temps global de l'estudi va ser de 15 mesos. El percentatge d'aïllaments d´Acinetobacter spp en el període basal va ser del 46,15% (n=6), de Pseudomonas aeruginosa 15,38% (n=2) i d'Escherichia coli 7, 69% (n=1). Al final de l'estudi els gèrmens aïllats van ser en un 8,57% (n=3) Acinetobacter spp i en un 37,14% (n=13) Pseudomonas aeruginosa.

La responsabilidad patrimonial de la Administración Pública Urbanística

En la memoria del trabajo se detallan las tareas realizadas durante los cuatro años en los que he sido beneficiaria de la beca FI, que me permitió incorporarme en el área de Derecho Administrativo de la Universidad de Girona, bajo la dirección del Dr. Joan M. Trayter Jiménez, para la elaboración del proyecto de investigación "La responsabilidad patrimonial de la Administración Púbica Urbanística", que una vez terminado dará lugar a la Tesis Doctoral. Durante el primer año realizé y superé los cursos del programa de Doctorado “Globalización y Derecho: el Derecho Europeo como referencia”; que me permitió obtener la renovación de la Beca FI, para la elaboración y defensa en el año posterior de la tesina titulada "La responsabilidad patrimonial de la Administración Pública por cambio de la ordenación territorial o urbanística”; con la consiguiente obtención del Diploma de Estudios Avanzados en Derecho. En líneas generales, puedo destacar -además de la investigación en la elaboración de la Tesis-, la realización de dos estancias de investigación en la University of Oxford, bajo la tutorización del Prof. Paul Craig, del St. John's College; gracias a la concesión de una beca por parte del "Institut d'Estudis Autonòmics de Catalunya" y otra, por la Generalitat de Catalunya, dirigida a estancias de investigación en el extrangero. También diversas publicaciones traducidas en la participación en dos libros, un artículo, una recensión y una comunicación; así como la asistencia a distintos Congresos de Derecho Administrativo y seminarios, la realización de distintos cursos entre ellos un Posgrado de Derecho Urbanístico en la UdG y la docencia realizada. Asimismo he devenido miembro de los proyectos de investigación del grupo de investigación del Área; importantes por formar parte del Plan Nacional I+D, financiados por el Ministerio de Educación y Ciencia.

Manual del aplicador de CO2 en cultivos hortícolas

Este manual se ha solicitado como parte del encargo que Iberdrola realizó al IRTA dentro del proyecto SOST-CO2, financiado por el programa CENIT (Consorcios Estratégicos Nacionales en Investigación Técnica), que forma parte del Programa Ingenio 2010, un proyecto del Gobierno español para incrementar la inversión en I+D, tanto pública como privada, con el objetivo de alcanzar en 2010 el 2% del PIB. El proyecto SOST-CO2 tiene como objetivo abordar el ciclo de vida completo del CO2, desde su captura en las fuentes de emisión pasando por su transporte, su almacenamiento y su valorización a gran escala. Se pretende enlazar la captura del CO2 con su posterior revalorización, buscando así una alternativa sostenible al mero confinamiento geológico de las emisiones. En el contexto del proyecto SOST-CO2, Iberdrola se planteó la utilización directa en horticultura intensiva de gases de combustión procedentes de sus plantas de ciclo combinado que utilizan gas natural como combustible, dado su contenido enriquecido en CO2, y encargó al IRTA su estudio. El objetivo general era, a parte de una importante fijación de carbono por parte de los cultivos, un elevado nivel de sostenibilidad ambiental por reducción de los inputs energéticos empleados en la climatización de los invernaderos y en la depuración de los gases. El trabajo se desarrolló a lo largo de cuatro años (2008-2011) en diversos escenarios experimentales. De las diferentes facetas que abarcó este trabajo, se presentan aquí las más directamente relacionadas con el principal resultado del estudio, es decir, la adecuación de los gases de combustión mencionados para obtener una mejora en la producción y rendimiento por su aplicación en horticultura intensiva.

Genome-wide association analysis identifies 20 loci that influence adult height.

Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.

Differential requirement for CD4 help in the development of an antigen-specific CD8+ T cell response depending on the route of immunization.

Previous studies in our laboratory have shown that DBA/2 mice injected i.p. with syngeneic P815 tumor cells transfected with the HLA-CW3 gene (P815-CW3) showed a dramatic expansion of activated CD8+CD62L- T cells expressing exclusively the Vbeta10 segment. We have used this model to study the regulatory mechanisms involved in the development of the CW3-specific CD8+ response, with respect to different routes of immunization. Whereas both intradermal (i.d.) and i.p. immunization of DBA/2 mice with P815-CW3 cells led to a strong expansion of CD8+CD62L-Vbeta10+ cells, only the i.d. route allowed this expansion after immunization with P815 cells transfected with a minigene coding for the antigenic epitope CW3 170-179 (P815 miniCW3). Furthermore, depletion of CD4+ T cells in vivo completely abolished the specific response of CD8+CD62L-Vbeta10+ cells and prevented the rejection of P815-CW3 tumor cells injected i.p., whereas it did not affect CD8S+CD62L-Vbeta10+ cell expansion after i.d. immunization with either P815-CW3 or P815 miniCW3. Finally, the CW3-specific CD8+ memory response was identical whether or not CD4+ T cells were depleted during the primary response. Collectively, these results suggest that the CD8+ T cell response to P815-CW3 tumor cells injected i.p. is strictly dependent upon recognition of a helper epitope by CD4+ T cells, whereas no such requirement is observed for i.d. injection.

Disseny d'un sistema d'informació per als nouvinguts estrangers a Olot : 'EL SINO'

Treball que té com a objectiu desenvolupar i aplicar un sistema d'informació integrat al servei d'atenció al públic nouvingut d'origen estranger a la ciutat d'Olot. El sistema s'ha dissenyat en tres grans apartats: en el primer es presenta una diagnosi de les necessitats informatives; el segon correspon pròpiament al disseny del sistema d'informació amb l'elaboració d'un observatori estadístic de la immigració a Olot, d'unes fitxes descriptives de tràmits administratius i d'unes fitxes de serveis locals, i el tercer apartat és el disseny d'un sistema informàtic per a la gestió de tota la informació amb la creació d'un lloc web i el disseny conceptual d'un sistema de gestió de base de dades.

Factors Supporting Cysteine Tolerance and Sulfite Production in Candida albicans.

The amino acid cysteine has long been known to be toxic at elevated levels for bacteria, fungi, and humans. However, mechanisms of cysteine tolerance in microbes remain largely obscure. Here we show that the human pathogenic yeast Candida albicans excretes sulfite when confronted with increasing cysteine concentrations. Mutant construction and phenotypic analysis revealed that sulfite formation from cysteine in C. albicans relies on cysteine dioxygenase Cdg1, an enzyme with similar functions in humans. Environmental cysteine induced not only the expression of the CDG1 gene in C. albicans, but also the expression of SSU1, encoding a putative sulfite efflux pump. Accordingly, the deletion of SSU1 resulted in enhanced sensitivity of the fungal cells to both cysteine and sulfite. To study the regulation of sulfite/cysteine tolerance in more detail, we screened a C. albicans library of transcription factor mutants in the presence of sulfite. This approach and subsequent independent mutant analysis identified the zinc cluster transcription factor Zcf2 to govern sulfite/cysteine tolerance, as well as cysteine-inducible SSU1 and CDG1 gene expression. cdg1Δ and ssu1Δ mutants displayed reduced hypha formation in the presence of cysteine, indicating a possible role of the newly proposed mechanisms of cysteine tolerance and sulfite secretion in the pathogenicity of C. albicans. Moreover, cdg1Δ mutants induced delayed mortality in a mouse model of disseminated infection. Since sulfite is toxic and a potent reducing agent, its production by C. albicans suggests diverse roles during host adaptation and pathogenicity.

Sistema per protegir la privadesa dels usuaris dels motors de cerca d'Internet

Actualment seria impensable la existència d'una xarxa d'informació com Internet sense la existència dels motors de cerca. Gràcies a ells, qualsevol usuari tenim al nostre abast la possibilitat d'obtenir informació sobre qualsevol tema només enviant una consulta des dels nostres ordinadors i rebent una resposta en qüestió de segons. Entre els usuaris dels cercadors d'Internet és molt habitual que les consultes facin referència a la empresa on treballem, la ciutat on vivim, els llocs que visitem, o inclús sobre problemes que tenim o malalties que patim amb l'objectiu de trobar opinions, consells o solucions. En resum, els usuaris, a través de les nostres consultes, proporcionem a diari als motors de cerca informació sobre nosaltres mateixos i sobre la nostra identitat que, juntament amb la adreça IP de la màquina des d'on fem les nostres consultes, ens fa perdre l'anonimat dins dels seus sistemes. Sobre aquesta problemàtica és del que tracta el present Projecte de Final de Carrera. En ell s'ha implementat una solució de la proposta especificada per Alexandre Viejo i Jordi Castellà-Roca en la seva publicació "Using social networks to disort users' profiles generated by web search engines", en la qual es documenten una sèrie de protocols de seguretat i d'algorismes de protecció i distribució que garanteixen la privacitat de la identitat dels usuaris dins dels motors de cerca aprofitant per aquest fi la relació existent entre aquests usuaris a través de les xarxes socials.

Performance of an ICU ventilator and two turbin-based ventilators dedicated to non invasive ventilation (NIV) in simulated high inspiratory effort and rate: a NIV-bench-study.

INTRODUCTION. The role of turbine-based NIV ventilators (TBV) versus ICU ventilators with NIV mode activated (ICUV) to deliver NIV in case of severe respiratory failure remains debated. OBJECTIVES. To compare the response time and pressurization capacity of TBV and ICUV during simulated NIV with normal and increased respiratory demand, in condition of normal and obstructive respiratory mechanics. METHODS. In a two-chamber lung model, a ventilator simulated normal (P0.1 = 2 mbar, respiratory rate RR = 15/min) or increased (P0.1 = 6 mbar, RR = 25/min) respiratory demand. NIV was simulated by connecting the lung model (compliance 100 ml/mbar; resistance 5 or 20 l/mbar) to a dummy head equipped with a naso-buccal mask. Connections allowed intentional leaks (29 ± 5 % of insufflated volume). Ventilators to test: Servo-i (Maquet), V60 and Vision (Philips Respironics) were connected via a standard circuit to the mask. Applied pressure support levels (PSL) were 7 mbar for normal and 14 mbar for increased demand. Airway pressure and flow were measured in the ventilator circuit and in the simulated airway. Ventilator performance was assessed by determining trigger delay (Td, ms), pressure time product at 300 ms (PTP300, mbar s) and inspiratory tidal volume (VT, ml) and compared by three-way ANOVA for the effect of inspiratory effort, resistance and the ventilator. Differences between ventilators for each condition were tested by oneway ANOVA and contrast (JMP 8.0.1, p\0.05). RESULTS. Inspiratory demand and resistance had a significant effect throughout all comparisons. Ventilator data figure in Table 1 (normal demand) and 2 (increased demand): (a) different from Servo-i, (b) different from V60.CONCLUSION. In this NIV bench study, with leaks, trigger delay was shorter for TBV with normal respiratory demand. By contrast, it was shorter for ICUV when respiratory demand was high. ICUV afforded better pressurization (PTP 300) with increased demand and PSL, particularly with increased resistance. TBV provided a higher inspiratory VT (i.e., downstream from the leaks) with normal demand, and a significantly (although minimally) lower VT with increased demand and PSL.