Melita insula : quam hodie Maltam vocant

Nimeketiedot nimiönkehyksissä

Mice expressing the E7 oncogene of HPV16 in epithelium show central tolerance, and evidence of peripheral anergising tolerance, to E7-encoded cytotoxic T-lymphocyte epitopes

In order to derive mice which expressed both the E7 open reading frame transgene of human papillomavirus type 16 in skin and MHC class 1 restriction elements for several E7-encoded cytotoxic T-lymphocyte (CTL) epitopes, K14.HPV16E7 mice which express E7 in basal keratinocytes were crossed to the F1 generation with A2.1 K-b transgenic mice which express the MHC binding cleft domains of human HLA A*0201, and murine H-2(b). F1 mice (denoted K14E7xA2.1) expressed E7 in the thymus at least as early as 2-5 days before birth. Immunisation of FVBxA2.1 control mice (transgenic for HLA A*0201 and H-2(b) but not for E7), with two HLA A*0201-restricted epitopes of E7 and one H-2(b)-restricted CTL epitope of E7, gave strong primary CTL responses recognising epitope-pulsed or constitutively E7-expressing syngeneic target cells. In contrast, in immunised K14E7xA2.1 mice, the CTL responses to the H-2(b) epitope and one of the HLA A*0201 CTL epitopes were strongly down-regulated, and to the other HLA A*0201 epitope, completely abolished, as demonstrated by percentage specific killing by bulk splenocyte cultures in cyrotoxicity assays, and by CTL precursor frequency analysis, In thymus-transplanted bone marrow radiation chimeras in which the immune system of K14E7xA2.1 mice was replaced by a FVBxA2.1 immune system, specific immunisation did not result in reemergence of strong E7-directed CTL responses. In agreement with these in vitro findings, specific immunisation failed to significantly alter the course of E7-associated tumour development in K14E7xA2.1 mice. These data are consistent with a model of central deletional CTL tolerance to E7-encoded epitopes recognised in the context of two distinct MHC class 1 restriction elements, and with the possibility of peripheral T-cell anergy maintained by expression of E7 in the skin. (C) 1998 Academic Press.

Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss

We used an exome-sequencing strategy and identified an allelic series of NOTCH2 mutations in Hajdu-Cheney syndrome, an autosomal dominant multisystem disorder characterized by severe and progressive bone loss. The Hajdu-Cheney syndrome mutations are predicted to lead to the premature truncation of NOTCH2 with either disruption or loss of the C-terminal proline-glutamate-serine-threonine-rich proteolytic recognition sequence, the absence of which has previously been shown to increase Notch signaling.

Relato de tres talleres del congreso.

Este artículo pertenece a una sección de la revista dedicada a innovación educativa, en este número, al Congreso Internacional de Formación Permanente del Profesorado

Processing coordinate subject-verb agreement in L1 and L2 Greek

The present study examines the processing of subject-verb (SV) number agreement with coordinate subjects in pre-verbal and post-verbal positions in Greek. Greek is a language with morphological number marked on nominal and verbal elements. Coordinate SV agreement, however, is special in Greek as it is sensitive to the coordinate subject's position: when pre-verbal, the verb is marked for plural while when post-verbal the verb can be in the singular. We conducted two experiments, an acceptability judgment task with adult monolinguals as a pre-study (Experiment 1) and a self-paced reading task as the main study (Experiment 2) in order to obtain acceptance as well as processing data. Forty adult monolingual speakers of Greek participated in Experiment 1 and a hundred and forty one in Experiment 2. Seventy one children participated in Experiment 2: 30 Albanian-Greek sequential bilingual children and 41 Greek monolingual children aged 10–12 years. The adult data in Experiment 1 establish the difference in acceptability between singular VPs in SV and VS constructions reaffirming our hypothesis. Meanwhile, the adult data in Experiment 2 show that plural verbs accelerate processing regardless of subject position. The child online data show that sequential bilingual children have longer reading times (RTs) compared to the age-matched monolingual control group. However, both child groups follow a similar processing pattern in both pre-verbal and post-verbal constructions showing longer RTs immediately after a singular verb when the subject was pre-verbal indicating a grammaticality effect. In the post-verbal coordinate subject sentences, both child groups showed longer RTs on the first subject following the plural verb due to the temporary number mismatch between the verb and the first subject. This effect was resolved in monolingual children but was still present at the end of the sentence for bilingual children indicating difficulties to reanalyze and integrate information. Taken together, these findings demonstrate that (a) 10–12 year-old sequential bilingual children are sensitive to number agreement in SV coordinate constructions parsing sentences in the same way as monolingual children even though their vocabulary abilities are lower than that of age-matched monolingual peers and (b) bilinguals are slower in processing overall.

Xenomelia: a social neuroscience view of altered bodily self-consciousness

Xenomelia, the "foreign limb syndrome," is characterized by the non-acceptance of one or more of one's own extremities and the resulting desire for elective limb amputation or paralysis. Formerly labeled "body integrity identity disorder" (BIID), the condition was originally considered a psychological or psychiatric disorder, but a brain-centered Zeitgeist and a rapidly growing interest in the neural underpinnings of bodily self-consciousness has shifted the focus toward dysfunctional central nervous system circuits. The present article outlays both mind-based and brain-based views highlighting their shortcomings. We propose that full insight into what should be conceived a "xenomelia spectrum disorder" will require interpretation of individual symptomatology in a social context. A proper social neuroscience of xenomelia respects the functional neuroanatomy of corporeal awareness, but also acknowledges the brain's plasticity in response to an individual's history, which is lived against a cultural background. This integrated view of xenomelia will promote the subfield of consciousness research concerned with the unity of body and self.

Relationship between genome and epigenome - challenges and requirements for future research

Understanding the links between genetic, epigenetic and non-genetic factors throughout the lifespan and across generations and their role in disease susceptibility and disease progression offer entirely new avenues and solutions to major problems in our society. To overcome the numerous challenges, we have come up with nine major conclusions to set the vision for future policies and research agendas at the European level.

4HPR-X radiation mechanisms of interactions in non-small cell lung cancer (NSCLC) cells in vitro

Lung cancer is the leading cause of cancer death. However, poor survival using conventional therapies fuel the search for more rational interventions. The objective of this study was to design and implement a 4HPR-radiation interaction model in NSCLC, employing a traditional clinical modality (radiation), a relatively new, therapeutically unexplored agent (4HPR) and rationally combining them based on molecular mechanistic findings pertaining to their interactions. To test the hypothesis that 4HPR sensitizes cells to radiation-induced cell death via G2+M accumulation, we designed a working model consisting of H522 adenocarcinoma cells (p53, K-ras mutated) derived from an NSCLC patient; 4HPR at concentrations up to 10 μM; and X radiation up to 6 Gy generated by a patient-dedicated Phillips RT-250 X ray unit at 250 KV, 15 mA, 1.85 Gy/min. We found that 4HPR produced time- and dose-dependent morphological changes, growth inhibition, and DNA damage-inducing enhancement of reactive oxygen species. A transient G2+M accumulation of cells maximal at 24 h of continuous 4HPR exposure was used for irradiation time scheduling. Our data demonstrated enhanced cell death (both apoptotic and necrotic) in irradiated cells pre-treated with 4HPR versus those with either stressor alone. 4HPR's effect of increased NSCLC cells' radioresponse was confirmed by clonogenic assay. To explore these practical findings from a molecular mechanistic perspective, we further investigated and showed that levels of cyclin B1 and p34cdc2 kinase—both components of the mitosis promoting factor (MPF) regulating the G2/M transition—did not change following 4HPR treatment. Likewise, cdc25C phosphatase was not altered. However, enhanced p34cdc2 phosphorylation on its Thr14Tyr15 residues—indicative of its inactivation and increased expression of MPF negative regulators chk1 and wee1 kinases—were supportive of explaining 4HPR-treated cells' accumulation. Hence, p34cdc2 phosphorylation, chk1, and wee1 warrant further evaluation as potential molecular targets for 4HPR-X radiation combination. In summary, we (1) demonstrated that 4HPR not only induces cell death by itself, but also increases NSCLC cells' subsequent radioresponse, indicative of potential clinical applicability, and (2) for the first time, shed light on deciphering 4HPR-X radiation molecular mechanisms of interaction, including the finding of 4HPR's role as a p34cdc2 inactivator via Thr14Tyr15 phosphorylation. ^

Megabenthic communities in the waters around Svalbard during POLARSTERN cruise ARK-VIII/2 (EPOS II)

Composition and distribution of megabenthic communities around Svalbard were investigated in June/July 1991 with 20 Agassiz trawl and 5 bottom trawl hauls in depths between 100 and 2100 m. About 370 species, ranging from sponges to fish, were identified in the catches. Species numbers per station ranged from 21 to 86. Brittle stars, such as Ophiacantha bidentata, Ophiura sarsi and Ophiocten sericeum, were most important in terms of constancy and relative abundance in the catches. Other prominent faunal elements were eunephthyid alcyonarians, bivalves, shrimps, sea stars and fish (Gadidae, Zoarcidae, Cottidae). Multivariate analyses of the species and environmental data sets showed that the spatial distribution of the megabenthos was characterized by a pronounced depth zonation: abyssal, bathyal, off-shore shelf and fjordic communities were discriminated. However, a gradient in sediment properties, especially the organic carbon content, seemed to superimpose on the bathymetric pattern. Both main factors are interpreted as proxies of the average food availability, which is, hence, suggested to have the strongest influence in structuring megabenthic communities off Svalbard.

Motricidad, ambiente propio y planetariedad

En este estudio se presenta un ensayo exploratorio acerca de los aspectos conceptuales de las relaciones entre motricidad, ambiente propio y planetariedad; conscientes de la necesidad de contar con un marco teórico que permita entender su complejidad para orientar estrategias de intervención pedagógica en las prácticas corporales y motrices en el ambiente. La posibilidad de indagar sobre los aspectos subjetivos-cualitativos de tales relaciones permite realizar un análisis crítico de los programas de los institutos de formación docente en Educación Física en donde el concepto de Naturaleza parece dominar en términos "biopolíticos", y la ausencia de procesos de construcción de la corporeidad y la motricidad en los sujetos a partir del contacto con el ambiente nos habla de la necesidad de recuperar la existencia del cuerpo en movimiento en la naturaleza, es decir la construcción de la corporeidad ligada al ambiente. Desde esta perspectiva, el presente estudio asume la forma de posible marco orientador teórico-práctico

El posicionamiento ideológico y la orientación política en jóvenes universitarios

Indagar por el significado de izquierda y derecha es interrogar por cuales son las creencias, valores y actitudes que se asocian a estas alternativas; es indagar por los programas políticos con los que los sujetos pueden identificarse y probablemente implicarse en participar (San Martín, 2006). La vinculación entre el binomio izquierda derecha y la identificación política, puede observarse como un conjunto más o menos coherente de creencias, valores y actitudes sobre el sistema social y político, y el rol que la persona desarrolla en cuanto ciudadano; en este sentido el sentido de este binomio compone la matriz para la identificación política de las personas, a partir de la relevancia que tiene para los sujetos pertenecer a un grupo cuya identificación con el mismo interviene en su comportamiento político. El aspecto ideológico de la cultura política conlleva la diferenciación de creencias y valores dentro de la sociedad; entonces, la configuración ideológica de un endogrupo serían las creencias y valores compartidos de actitudes políticas que muestran los miembros ese grupo; una ideología seria el modelo de actitudes comunes a un endogrupo desde la perspectiva de su disidencia políticamente destacable con otros patrones grupales. En un nivel específico diferenciaremos orientación política de configuración ideológica. Conceptualizamos la orientación política como la actitud de una persona hacia los aspectos de oposiciones (izquierda/derecha, progresista/conservador, democracia/autoritarismo, entre otros ejemplos) y polaridades generalizadas. En este trabajo operacionalizaremos la orientación política de los sujetos como su autoposicionamiento en una dimensión izquierda-derecha, siendo la más ampliamente usada en la investigación (Jost, 2005). Es decir, la orientación política se configuraría como una síntesis de la configuración ideológica, al organizar, de modo particular, las diversas actitudes políticas que comporten una multiplicidad ycomplejidad de dimensiones que no posee la orientación política (Jost, Christopher & Jaime, 2009). La muestra quedó conformada por 366 participantes, 274 mujeres y 62 varones, con edades comprendidas entre los 18 y los 54 años (M = 24,8; DT = 8); todos ellos estudiantes de la Facultad de Ciencias Sociales de la Universidad de Lomas de Zamora. Se aplico la Escala Conservador-Progresista (En asuntos de política la gente habla de conservadores y progresistas, ¿Dónde se situaría Ud. en esa escala?) y la Escala de orientación política (En asuntos de política la gente habla de izquierda y derecha, acorde con la siguiente escala de 1 a 5, siendo 1 de extrema derecha y 5 de extrema izquierda: ¿Dónde se situaría Ud.? ¿Dónde situaría a su padre? ¿Dónde situaría a su madre? ¿Dónde situaría a la mayoría de sus amigos?), adaptada y modificación a partir de Rodríguez, Sabucedo y Costa, 1993. Este estudio tenía como objetivo describir en los estudiantes de la Facultas de Ciencias Sociales de la Universidad de Lomas de Zamora, primero, el posicionamiento ideológico Conservador-Progresista, y la Orientación Política (Derecha Izquierda); y segundo, las asociaciones existentes entre la escala Conservador Progresista, y la escala Orientación Política. Los valores hallados muestran que prevalece un posicionamiento ideológico de centro- progresista y una orientación política de centro, coincidente con la percepción de orientación política de su endogrupo. Entre la escala Conservador-Progresista, y la escala Orientación Política hubo correlación moderada y positiva; pero en el estudio segmentado por sexo solo en las mujeres se asocian positiva y moderadamente la autoorientación política con la orientación política de su padre, madre y amigos

Motricidad, ambiente propio y planetariedad

En este estudio se presenta un ensayo exploratorio acerca de los aspectos conceptuales de las relaciones entre motricidad, ambiente propio y planetariedad; conscientes de la necesidad de contar con un marco teórico que permita entender su complejidad para orientar estrategias de intervención pedagógica en las prácticas corporales y motrices en el ambiente. La posibilidad de indagar sobre los aspectos subjetivos-cualitativos de tales relaciones permite realizar un análisis crítico de los programas de los institutos de formación docente en Educación Física en donde el concepto de Naturaleza parece dominar en términos "biopolíticos", y la ausencia de procesos de construcción de la corporeidad y la motricidad en los sujetos a partir del contacto con el ambiente nos habla de la necesidad de recuperar la existencia del cuerpo en movimiento en la naturaleza, es decir la construcción de la corporeidad ligada al ambiente. Desde esta perspectiva, el presente estudio asume la forma de posible marco orientador teórico-práctico