Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas

To evaluate the use of alphavirus vectors for tumor treatment we have constructed and compared two Semliki Forest virus (SFV) vectors expressing different levels of IL-12. SFV-IL-12 expresses both IL-12 subunits from a single subgenomic promoter, while in SFV-enhIL-12 each IL-12 subunit is expressed from an independent subgenomic promoter fused to the SFV capsid translation enhancer. This latter strategy provided an eightfold increase of IL-12 expression. We chose the poorly immunogenic MC38 colon adenocarcinoma model to evaluate the therapeutic potential of SFV vectors. A single intratumoral injection of 10(8) viral particles of SFV-IL-12 or SFV-enh-IL-12 induced>or=80% complete tumor regressions with long-term tumor-free survival. However, lower doses of SFV-enhIL-12 were more efficient than SFV-IL-12 in inducing antitumoral responses, indicating a positive correlation between the IL-12 expression level and the therapeutic effect. Moreover, repeated intratumoral injections of suboptimal doses of SFV-enhIL-12 increased the antitumoral response. In all cases SFV vectors were more efficient at eliminating tumors than a first-generation adenovirus vector expressing IL-12. In addition, the antitumoral effect of SFV vectors was only moderately affected by preimmunization of animals with high doses of SFV vectors. This antitumoral effect was produced, at least partially, by a potent CTL-mediated immune response

Anàlisi espacio-temporal de la línia de costa i del foredune del sistema dunar de Sa Canova d’Artà (Mallorca)

[cat] Els sistemes platja-duna, són una de les morfologies sedimentàries més abundants a les Illes Balears. Aquests es troben composats per diferents subsistemes, els quals presenten diferents nivells de dinamisme. Des d’aquest punt de vista, la foredune és el sector més dinàmic de la part emergida del sistema i en la qual la vegetació té un paper clau per al desenvolupament de la resta del sistema. Tots i cada un dels sistemes existents a la comunitat autònoma i a la resta del món disposa d’una condicions/característiques que el fan peculiar i diferent a la resta; a part de les pròpies condicions físiques intrínseques al propi medi, a dia d’avui els sistemes han de fer front a tota una sèrie de pressions d’origen antròpic, destacant especialment l’activitat turística en el cas Balear. El cas d’estudi, és Sa Canova, situada al terme municipal d’Artà (NE de l’illa de Mallorca); aquest sistema tampoc n’és una excepció, al llarg del període d’estudi (1956-2012), ha sofert variacions, tant d’origen natural, com antròpic, les quals han tingut com a conseqüència el sistema dunar actualment existent.[eng] The beach-dune systems, are one of the most abundant sedimentary morphologies in the Balearic Islands. These are composed of different subsystems, which present different levels of dynamism. From this point of view, Foredune is the most dynamic sector of the emerging part of the system and in which vegetation plays a key role for the development of the rest of the system. Each and every one of the existing systems in the autonomous community and the rest of the world has conditions / characteristics that make it peculiar and different from the rest; Apart from the intrinsic physical conditions inherent in their own environment, today, systems have to deal with a whole series of pressures of anthropogenic origin, with special emphasis on tourism in the Balearic Islands. The case study is Sa Canova, located in the municipality of Artà (NE of the island of Mallorca); This system is not an exception either, during the period of study (1956-2012), it has undergone variations, both of natural origin and anthropic, which have resulted in the current dune system

Integrated stratigraphy and 40Ar/39Ar chronology of the Early to Middle Miocene Upper Freshwater Molasse in eastern Bavaria (Germany)

A detailed integrated stratigraphic study was carried out on middle Miocene fluvial successions of the Upper Freshwater Molasse (OSM) from the North Alpine Foreland Basin, in eastern Bavaria, Germany. The biostratigraphic investigations yielded six new localities thereby refining the OSM biostratigraphy for units C to E (sensu; Heissig, Actes du Congres BiochroM'1997) and further improving biostratigraphic correlations between the different sections throughout eastern Bavaria. Radioisotopic ages of 14.55 ± 0.19 and 14.88 ± 0.11 Ma have been obtained for glass shards from the main bentonite horizon and the Ries impactite: two important stratigraphic marker beds used for confirming our magnetostratigraphic calibration to the Astronomical Tuned Neogene Time Scale (ATNTS04; Lourens et al. in Geologic Time Scale 2004, Cambridge University Press, 2004). Paleomagnetic analysis was performed using alternating field (AF) and thermal (TH) demagnetization methods. The AF method revealed both normal and reverse polarities but proofs to yield unreliable ChRM directions for the Puttenhausen section. Using the biostratigraphic information and radioisotopic ages, the magnetostratigraphic records of the different sections are tentatively correlated to the Astronomical Tuned Neogene Time Scale (ATNTS04; Lourens et al. in Geologic Time Scale 2004, Cambridge University Press, 2004). This correlation implies that the main bentonite horizon coincides to chron C5ADn, which is corroborated by its radioisotopic age of 14.55 Ma, whereas the new fossil locality Furth 460, belonging to OSM unit E, probably correlates to chron C5Bn.1r. The latter correlation agrees well with the Swiss Molasse locality Frohberg. Correlations of the older sections are not straightforward. The Brock horizon, which comprises limestone ejecta from the Ries impact, possibly correlates to C5ADr (14.581 ± 14.784 Ma), implying that, although within error, the radioisotopic age of 14.88 ± 0.11 Ma is somewhat too old. The fossil localities in Puttenhausen, belonging to the older part of OSM unit C, probably coincide with chron C5Cn.2n or older, which is older than the correlations established for the Swiss Molasse. © Springer-Verlag 2007

Learning and assessment about competences in Social Sciences university students

[EN] On the new European Higher Education Area the students exercise their academic and professional competences. From the formative approach, the learning develops the acquisition of basic competences such as team work, the creative and entrepreneur capacity or communicate and relationship capacity. This paper studies in the learning and assessment of competences in Social Sciences university students through instruments mediational that allow theirs to reflect on the skills needed to profession. The sample includes 273 university students belonging to the Faculty of Social Sciences of the Pablo Olavide University of Seville. Through a group task based on problem-based learning (PBL), they used the team notebook to mediate for regulation of team and the rubric in the end presentation task. The group interaction self-report (GIS) was use for evaluate basic competences acquired in the task by students. The results show a great disposition of the students to participate in research teams exercising professional competences through the mediational instruments. In open tasks the mediational instruments allow students to manage their relationships and acquire competencies that are fundamental to profession.[ES] En el nuevo Espacio Europeo de Educación Superior el alumnado ejercita sus competencias académicas y profesionales. Desde este en-foque formativo, el aprendizaje desarrolla la adquisición de competencias genéricas como el trabajo en equipo, la capacidad creativa y emprendedora o la capacidad comunicativa y relacional. Este trabajo profundiza en el aprendizaje y evaluación de competencias en el alumnado universitario de Ciencias Sociales a través de instrumentos mediadores que permiten al mismo, reflexionar sobre las habilidades necesarias para fomentar las competencias orientadas hacia la profesión. La muestra incluye 273 estudiantes universitarios pertenecientes a la Facultad de Ciencias Sociales de la Universidad Pablo Olavide de Sevilla. A través de una tarea grupal de Aprendizaje Basado en Problemas (ABP), utilizaron el cuaderno de equipo como instrumento de mediación en la gestión de grupo y una rúbrica en la exposición final de la tarea. El Autoinforme de Interacciones de Grupo (AIG) fue utilizado como instrumento para valorar las competencias genéricas adquiridas por el alumnado. Los resultados muestran una gran disposición del alum-nado en participar en equipos de investigación ejercitando competencias profesionales a través de los instrumentos mediadores. En tareas abiertas los instrumentos mediadores permiten al alumnado gestionar sus relaciones y adquirir competencias que son fundamentales para la profesión.Prieto García, J.; Alarcón Rubio, D.; Fernández Portero, C. (2018). Aprendizaje y evaluación de competencias en el alumnado universitario de Ciencias Sociales. 193-210. doi:10.4995/redu.2018.894119321

Characterization of a possible nosocomial aspergillosis outbreak

ObjectiveTo study the epidemiologic aspects of a suspected outbreak of nosocomial invasive aspergillosis.MethodsSixteen Aspergillus fumigatus strains were isolated from bronchoalveolar washings or sputa of 10 patients during a 9-month period. Furthermore, two environmental samples, isolated in a microbiological screening of the hospital, were also available for analysis. Random amplified polymorphic DNA analysis (RAPD) was carried out.ResultsThe analysis performed by RAPD clearly demonstrated substantial genetic variation among the isolates. Both of the two different primers selected for RAPD analysis (R-108 and AP12h) were able to demonstrate that the strains isolated from all patients infected with the same fungal species and the environmental samples were genotypically distinct. The results by RAPD typing demonstrated that this technique could detect variability among isolates of Aspergillus fumigatus from different patients and even from the same patient.ConclusionsRAPD genotyping proved that the outbreak of invasive aspergillosis consisted of a series of events, non-related, and probably not coming from the same source within the hospital. This type of analysis is an easy, quick and highly discriminatory technique that may help in planning epidemiologic studies of aspergillosis

First results on ongrowing of hatchery reared Atlantic bluefin tuna, Thunnus thynnus, kept in sea cages

Bluefin tuna (ABFT) fingerlings born in captivity were raised during 15 months in sea cages. ABFT were fed with raw fish, and they grew during this period from 4 gr to 8 kg. Mortality rate was great, mainly during the first three months. This is the first experience of ongrowing ABFT born in captivity.EU (SELFDOTT), Caladeros del Mediterráneo, S.A. Instituto Español de Oceanografí

A web-based system for statistical shape analysis in temporomandibular joint osteoarthritis

This study presents a web-system repository: Data Storage for Computation and Integration (DSCI) for Osteoarthritis of the temporomandibular joint (TMJ OA). This environment aims to maintain and allow contributions to the database from multi-clinical centers and compute novel statistics for disease classification. For this purpose, imaging datasets stored in the DSCI consisted of three-dimensional (3D) surface meshes of condyles from CBCT, clinical markers and biological markers in healthy and TMJ OA subjects. A clusterpost package was included in the web platform to be able to execute the jobs in remote computing grids. The DSCI application allowed runs of statistical packages, such as the Multivariate Functional Shape Data Analysis to compute global correlations between covariates and the morphological variability, as well as local p-values in the 3D condylar morphology. In conclusion, the DSCI allows interactive advanced statistical tools for non-statistical experts

Shape variation analyzer: A classifier for temporomandibular joint damaged by osteoarthritis

We developed a deep learning neural network, the Shape Variation Analyzer (SVA), that allows disease staging of bony changes in temporomandibular joint (TMJ) osteoarthritis (OA). The sample was composed of 259 TMJ CBCT scans for the training set and 34 for the testing dataset. The 3D meshes had been previously classified in 6 groups by 2 expert clinicians. We improved the robustness of the training data using data augmentation, SMOTE, to alleviate over-fitting and to balance classes. We combined geometrical features and a shape descriptor, heat kernel signature, to describe every shape. The results were compared to nine different supervised machine learning algorithms. The deep learning neural network was the most accurate for classification of TMJ OA. In conclusion, SVA is a 3D Slicer extension that classifies pathology of the temporomandibular joint osteoarthritis cases based on 3D morphology

RNA-seq and Tn-seq reveal fitness determinants of vancomycin-resistant Enterococcus faecium during growth in human serum

BACKGROUND: The Gram-positive bacterium Enterococcus faecium is a commensal of the human gastrointestinal tract and a frequent cause of bloodstream infections in hospitalized patients. The mechanisms by which E. faecium can survive and grow in blood during an infection have not yet been characterized. Here, we identify genes that contribute to growth of E. faecium in human serum through transcriptome profiling (RNA-seq) and a high-throughput transposon mutant library sequencing approach (Tn-seq). RESULTS: We first sequenced the genome of E. faecium E745, a vancomycin-resistant clinical isolate, using a combination of short- and long read sequencing, revealing a 2,765,010 nt chromosome and 6 plasmids, with sizes ranging between 9.3 kbp and 223.7 kbp. We then compared the transcriptome of E. faecium E745 during exponential growth in rich medium and in human serum by RNA-seq. This analysis revealed that 27.8% of genes on the E. faecium E745 genome were differentially expressed in these two conditions. A gene cluster with a role in purine biosynthesis was among the most upregulated genes in E. faecium E745 upon growth in serum. The E. faecium E745 transposon mutant library was then used to identify genes that were specifically required for growth of E. faecium in serum. Genes involved in de novo nucleotide biosynthesis (including pyrK_2, pyrF, purD, purH) and a gene encoding a phosphotransferase system subunit (manY_2) were thus identified to be contributing to E. faecium growth in human serum. Transposon mutants in pyrK_2, pyrF, purD, purH and manY_2 were isolated from the library and their impaired growth in human serum was confirmed. In addition, the pyrK_2 and manY_2 mutants were tested for their virulence in an intravenous zebrafish infection model and exhibited significantly attenuated virulence compared to E. faecium E745. CONCLUSIONS: Genes involved in carbohydrate metabolism and nucleotide biosynthesis of E. faecium are essential for growth in human serum and contribute to the pathogenesis of this organism. These genes may serve as targets for the development of novel anti-infectives for the treatment of E. faecium bloodstream infections