Altered Oxygen Metabolism Associated to Neurogenesis of Induced Pluripotent Stem Cells Derived From a Schizophrenic Patient

Schizophrenia has been defined as a neurodevelopmental disease that causes changes in the process of thoughts, perceptions. and emotions, usually leading to a mental deterioration and affective blunting. Studies have shown altered cell respiration and oxidative stress response in schizophrenia; however, most of the knowledge has been acquired from postmortem brain analyses or from nonneural cells. Here we describe that neural cells, derived from induced pluripotent stem cells generated from skin fibroblasts of a schizophrenic patient, presented a twofold increase in extramitochondrial oxygen consumption as well as elevated levels of reactive oxygen species (ROS), when compared to controls. This difference in ROS levels was reverted by the mood stabilizer valproic acid. Our model shows evidence that metabolic changes occurring during neurogenesis are associated with schizophrenia, contributing to a better understanding of the development of the disease and highlighting potential targets for treatment and drug screening.

Using Prior Information from the Medical Literature in GWAS of Oral Cancer Identifies Novel Susceptibility Variant on Chromosome 4-the AdAPT Method

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)] = 2.5 x 10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/lld/gwas/service/config).

Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia

Background: Molecular alterations occur frequently in T-ALL and the potential impact of those abnormalities on outcome is still controversial. The current study aimed to test whether NOTCH1 mutations and additional molecular abnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases. Methods: T-ALL subtypes, status of SIL-TAL1 fusion, ectopic expression of TLX3, and mutations in FBXW7, KRAS, PTEN and NOTCH1 were assessed as overall survival (OS) and event-free survival (EFS) prognostic factors. OS and EFS were determined using the Kaplan-Meier method and compared using the log-rank test. Results: The frequencies of mutations were 43.5% for NOTCH1, while FBXW7, KRAS and PTEN exhibited frequencies of 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of NOTCH1 mutations and other molecular alterations was observed. In multivariate analysis no statistical association was revealed between NOTCH1 mutations and any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. SIL-TAL1 was identified as an adverse prognostic factor. NOTCH1 mutation status was not associated with outcome, while the presence of NOTCH1 complex mutations (indels) were associated with a longer overall survival (p = 0.031) than point mutations. Conclusion: NOTCH1 mutations alone or in combination with FBXW7 did not impact T-ALL prognosis. Nevertheless, complex NOTCH1 mutations appear to have a positive impact on OS and the SIL-TAL1 fusion was validated as a negative prognostic marker in our series of T-ALL.

Cambios en contextos de colonización: opciones económicas y transformaciones tecnológicas en el norte de Mendoza entre los siglos XV y XVII (Rca. Argentina)

[ES]Se analizan los cambios en las opciones económicas y la tecnología cerámica de la población indígena del norte de Mendoza (Centro Oeste Argentino), como consecuencia de la dominación inca y la colonia europea. Con base en la evidencia arqueológica y etnohistórica se reflexiona sobre estas transformaciones a luz del concepto de etnogénesis. Se concluye que los agentes de cambio -nuevos contextos de producción y consumo- influyeron de modo distinto: durante el incario y la colonia se mantuvieron prácticas ancestrales de subsistencia a la vez que se incorporaron nuevas; por el contrario, la producción cerámica cambió drásticamente en cada período de dominación. [EN] This paper analyses the changes in subsistence practices and ceramic technology in the local indigenous population of northern Mendoza (west central Argentina), which resulted from the Inca domination and the European colonization. Based on the archaeological and ethnohistorical evidence, we discuss these changes in relation to the concept of ethnogenesis. We conclude that agents of change -new contexts of production and consumption- affected this differently: during the Inca period and colony, ancestral subsistence practices were preserved, in addition to the new ones; on the contrary, ceramic production drastically changed in each period.

Analisi comparativa di un circuito low pressure e high pressure EGR per un motore diesel sottostante a normativa americana US LEV III ULEV 125

Questa tesi di laurea nasce dall’esperienza maturata presso la VM Motori S.p.A., ufficio CRM (Centro Ricerca Motori) di ingegneria, divisione del reparto R&D (Research and Development) situato a Cento di Ferrara. Durante tale esperienza sono state affrontate le problematiche inerenti al settore automotive riguardo la ricerca e lo sviluppo dei motori endotermici diesel. Dopo un approccio introduttivo, che definisce l’ambito lavorativo in cui opera VM Motori S.p.A. e l’oggetto della tesi, si passa alla definizione ed alla calibrazione di un circuito low pressure EGR di un propulsore diesel da 200HP@3800rpm di potenza e 500Nm@1600rpm di coppia per uso automobilistico, mediante l’ausilio dei software AδαMO, INCA, Controldesk Next Generation, DoE, DIAdem ed INDICOM, software per lo studio della calibrazione al banco sviluppo. Si analizzano gli aspetti che contraddistinguono la VM Motori S.p.A. dalle altre aziende specializzate nel settore automotive, facendo riferimento ai campi produttivi in cui si applica l’ingegneria meccanica ed analizzandone gli aspetti tecnici, metodici e gestionali. Da notare il ruolo fondamentale delle automotive nell’economia mondiale in riferimento alla produzione dei principali propulsori diesel, primarie fonti produttive della VM.

Ottimizzazione del consumo dei grassi durante esercizio fisico: studio di un test per il target mirato di allenamento individuale

Il primo studio ha verificato l'affidabilità del software Polimedicus e gli effetti indotti d'allenamento arobico all’intensità del FatMax. 16 soggetti sovrappeso, di circa 40-55anni, sono stati arruolati e sottoposti a un test incrementale fino a raggiungere un RER di 0,95, e da quel momento il carico è stato aumentato di 1 km/ h ogni minuto fino a esaurimento. Successivamente, è stato verificato se i valori estrapolati dal programma erano quelli che si possono verificare durante a un test a carico costante di 1ora. I soggetti dopo 8 settimane di allenamento hanno fatto un altro test incrementale. Il dati hanno mostrato che Polimedicus non è molto affidabile, soprattutto l'HR. Nel secondo studio è stato sviluppato un nuovo programma, Inca, ed i risultati sono stati confrontati con i dati ottenuti dal primo studio con Polimedicus. I risultati finali hanno mostrato che Inca è più affidabile. Nel terzo studio, abbiamo voluto verificare l'esattezza del calcolo del FatMax con Inca e il test FATmaxwork. 25 soggetti in sovrappeso, tra 40-55 anni, sono stati arruolati e sottoposti al FATmaxwork test. Successivamente, è stato verificato se i valori estrapolati da INCA erano quelli che possono verificarsi durante un carico di prova costante di un'ora. L'analisi ha mostrato una precisione del calcolo della FatMax durante il carico di lavoro. Conclusione: E’ emersa una certa difficoltà nel determinare questo parametro, sia per la variabilità inter-individuale che intra-individuale. In futuro bisognerà migliorare INCA per ottenere protocolli di allenamento ancora più validi.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10 ? ? ). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Climate and human impact during the past 2000 years as recorded in the Lagunas de Yala, Jujuy, northwestern Argentina

210Pb, 137Cs and 14C dated sediments of two late Holocene landslide lakes in the Provincial Park Lagunas de Yala (Laguna Rodeo, Laguna Comedero, 24°06′S, 65°30′W, 2100 m asl, northwestern Argentina) reveal a high-resolution multi-proxy data set of climate change and human impact for the past ca. 2000 years. Comparison of the lake sediment data set for the 20th century (sediment mass accumulation rates MARs, pollen spectra, nutrient and charcoal fluxes) with independent dendroecological data from the catchment (fire scars, tree growth) and long regional precipitation series (from 1934 onwards) show that (1) the lake sediment data set is internally highly consistent and compares well with independent data sets, (2) the chronology of the sediment is reliable, (3) large fires (1940s, 1983/1984–1989) as documented in the local fire scar frequency are recorded in the charcoal flux to the lake sediments and coincide with low wet-season precipitation rates (e.g., 1940s, 1983/1984) and/or high interannual precipitation variability (late 1940s), and (4) the regional increase in precipitation after 1970 is recorded in an increase in the MARs (L. Rodeo from 100 to 390 mg cm−2 yr−1) and in an increase in fern spores reflecting wet vegetation. The most significant change in MARs and nutrient fluxes (Corg and P) of the past 2000 years is observed with the transition from the Inca Empire to the Spanish Conquest around 1600 AD. Compared with the pre-17th century conditions, MARs increased by a factor of ca. 5 to >8 (to 800 +130, −280 mg cm−2 yr−1), PO4 fluxes increased by a factor of 7, and Corg fluxes by a factor of 10.5 for the time between 1640 and 1930 AD. 17th to 19th century MARs and nutrient fluxes also exceed 20th century values. Excess Pb deposition as indicated by a significant increase in Pb/Zr and Pb/Rb ratios in the sediments after the 1950s coincides with a rapid expansion of the regional mining industry. Excess Pb is interpreted as atmospheric deposition and direct human impact due to Pb smelting.

Pb pollution from leaded gasoline in South America in the context of a 2000-year metallurgical history

Exploitation of the extensive polymetallic deposits of the Andean Altiplano in South America since precolonial times has caused substantial emissions of neurotoxic lead (Pb) into the atmosphere; however, its historical significance compared to recent Pb pollution from leaded gasoline is not yet resolved. We present a comprehensive Pb emission history for the last two millennia for South America, based on a continuous, high-resolution, ice core record from Illimani glacier. Illimani is the highest mountain of the eastern Bolivian Andes and is located at the northeastern margin of the Andean Altiplano. The ice core Pb deposition history revealed enhanced Pb enrichment factors (EFs) due to metallurgical processing for silver production during periods of the Tiwanaku/Wari culture (AD 450–950), the Inca empires (AD 1450–1532), colonial times (AD 1532–1900), and tin production at the beginning of the 20th century. After the 1960s, Pb EFs increased by a factor of 3 compared to the emission level from metal production, which we attribute to gasoline-related Pb emissions. Our results show that anthropogenic Pb pollution levels from road traffic in South America exceed those of any historical metallurgy in the last two millennia, even in regions with exceptional high local metallurgical activity.

Psychosocial factors and musculoskeletal symptoms in a vulnerable working population in Nicaragua

This research is a secondary data analysis of the CUPID-INCA Nicaragua study, a cross-sectional study comparing psychosocial and physical factors on musculoskeletal symptoms among nurses, office workers and maquiladoras in Nicaragua. There were three objectives for this thesis. (1) To describe the study population according to their socio-demographic, psychosocial (i.e. work organization and health beliefs) and physical factors. (2) To estimate the prevalence of musculoskeletal disorders (MSDs) in the study population (nurses, office workers and maquilas). (3) To analyze and compare the trends of association between psychosocial factors and MSDs to that of physical factors and MSDs in the study population. Trends of association between MSDs and psychosocial factors were also compared between nurses, office workers and maquilas. ^ Majority of the total study population were females, middle aged, non smokers and had been on the job for more than five years. Prevalence rates of low back pain and upper extremity pain were 28% and 37% respectively in nurses, 17% and 34% in office workers and 18% and 31% in maquilas. Workers' health belief was significantly associated with MSDs in all three occupational groups. Psychosocial factors were not consistently associated more with MSDs than physical factors. Maquilas had more psychosocial factors statistically significantly associated with musculoskeletal symptoms than nurses and office workers. ^ The findings of this research suggest that both psychosocial and physical risk factors play a role on the prevalence of musculoskeletal symptoms in the three working populations in Nicaragua. Future research in this area should explore further, the risk of developing MSDs from workers' exposure to psychosocial factors as well as physical factors.^

La valoración de los espacios públicos con identidad local (frente a la globalización)

Se destacan los cambios del paisaje urbano, los que se plasman en el espacio público, los que fueron estructurantes de las ciudades: calles y plazas hoy en abandono ante el auge de los espacios públicos privados . Conceptualiza espacio y lugar para luego recorrer las características de los espacios públicos predominantes en cada período histórico de la humanidad. El siglo XX es analizado en detalle para determinar los factores que más han influido en la transformación; como las comunicaciones , que transmiten imágenes conocidas por todos, aunque logran una identidad más global que local. Se analizan los principales espacios públicos del Gran Mendoza, si han sido renovados o no, en asociación con el consumo y cultura de la imagen, su vinculación con las líneas estructurantes de la ciudad y espacios verdes más relevantes. Se tiene en cuenta el crecimiento poblacional y uso del suelo. A través de relevamiento y encuestas se detectan problemas que permiten determinar algunas áreas periféricas desvinculadas del tejido urbano de la metrópolis, motivo de diversas propuestas.

Una aproximación paisajística de Potrerillos

Se está creando un nuevo espacio. La construcción de la presa de Potrerillos implica muchos cambios en la localidad. Potrerillos le debe su identidad a la importancia que tiene su esencia, su origen, y su historia en la conformación de su estructura y sus propiedades formales particulares, elementos que deben considerarse a la hora de analizar la definición de su paisaje. Es importante que el ordenamiento territorial y un análisis apropiado del paisaje guarden relación. Que formen parte de la misma estrategia de desarrollo, en función de la valoración de los sitios no sólo a partir de su funcionalidad sino a través de su configuración paisajística. Se garantiza de esta forma un tipo de intervención que no solo contemple el óptimo funcionamiento de la localidad sino que mantenga y potencie sus características diferenciadoras, que son en definitiva el motivo por el cual se plantea el desarrollo y transformación del sitio.

Modelo de indicadores ambientales : observatorio ambiental

Los indicadores ambientales son una herramienta para efectuar el monitoreo de la biodiversidad a través de la recolección sistemática de datos obtenidos mediante mediciones u observaciones en series de tiempo y espacio. Se entiende por indicador ambiental a una variable o suma de variables que proporciona una información sintética sobre un fenómeno ambiental complejo que permite conocer y evaluar el estado y variación de la calidad ambiental. Para la caracterización y detección de indicadores ambientales del litoral de Río Negro se identifican y jerarquizan los conflictos o problemáticas del ambiente, a partir de lo cual se seleccionan las principales variables que componen el sistema de indicadores y por último, se recopilan los niveles de información existentes y los que requieren ser relevados e incorporados a bases de datos relacionales. Los requisitos que deben tener los indicadores seleccio nados son: ser medibles (cuali y cuantitativamente), compresibles, fáciles de usar e interrelacionar, tener dimensión espacial y temporal, ser objetivos sensibles a los cambios y permitir el diagnóstico y pronóstico en función de la detección de situaciones de alerta ambiental. Se realiza una aproximación a la selección de variables e indicadores con el fin de definir el modelo de datos y categorías de agrupamiento. El sistema de indicadores generados se agrupa en función de la disponibilidad de datos existentes y la posibilidad de recopilación para un correcto funcionamiento del prototipo del Observatorio. El modelo adoptado incorpora 3 subsistemas (ambiental, social y económico) interrelacionando con 3 nodos institucionales (que proveen y/o precisan estos datos para la toma de decisiones). Cada indicador se describe en una ficha metodológica, cuyo diseño es normalizado para un correcto funcionamiento del Observatorio. La implementación del modelo de indicadores exige contar con una infraestructura que permita la aplicación de mediciones, observaciones y registros y contar además, con personal idóneo para una correcta manipulación y análisis.

Seguridad humana : necesidad de innovar enfoques a partir del ordenamiento territorial

La inseguridad es uno de los mayores desafíos al que se enfrentan los gobernantes en América Latina. Este problema avanza desde una visión sectorial en los años ochenta hacia una visión transversal a partir de los noventa. Esto implica una evolución de su concepto; desde su consideración como una cuestión de seguridad de Estado de competencia policial y militar hacia la “seguridad humana", concepto multidimensional que contempla el desarrollo humano y la satisfacción de necesidades. En Argentina la inseguridad se agrava desde la crisis social y económica y es parte de la agenda política debido a los constantes reclamos de la sociedad. Sin embargo, con el transcurrir de los años se puede observar la imposibilidad de las gestiones gubernamentales de hacerle frente. Es por ello que en este trabajo se plantea la relación entre la seguridad humana y el Ordenamiento Territorial a través de la evaluación de la habitabilidad, enfoque que permite operacionalizar el concepto de seguridad de forma integradora y transversal. Para el desarrollo del trabajo se utiliza un caso de estudio: el piedemonte del Gran Mendoza. Se parte de la construcción de una metodología de análisis que permite espacializar los datos y de un sistema de variables e indicadores para medir la habitabilidad en términos de la seguridad humana.

Criterios de selección de terrenos para viviendas de interés social

El objetivo de la presente investigación es integrar criterios vinculados al hábitat en una herramienta de gestión que permita una mejor toma de decisión en cuanto a la selección de terrenos para viviendas de interés social; logrando así en un mediano y largo plazo una intervención más sostenible en el territorio. La localización de la vivienda social presenta un alto grado de complejidad para abordar su análisis debido a los diferentes actores y fuerzas que intervienen en la decisión de localización de los conjuntos habitacionales, esta multidimensionalidad está dada por lo social, lo económico – financiero, lo político – administrativo, lo legal – notarial y lo territorial - ambiental. La metodología utilizada es a través de un enfoque sistémico que permite contemplar las relaciones que se establecen entre los distintos elementos que conforman el sistema territorial. La Planilla de Evaluación de Impacto Territorial surge a partir de un proceso metodológico y se va ajustando con el tiempo a través de análisis de antecedentes, consulta a expertos, análisis bibliográfico y pruebas en territorio logrando una retroalimentación permanente. Esta herramienta se encuentra actualmente desarrollada y ha sido probada en numerosos terrenos priorizados por los Municipios ante el Instituto Provincial de la Vivienda de Mendoza para la obtención de créditos para la ejecución de conjuntos habitacionales de interés social. Los ejemplos presentados tratan de abarcar realidades territoriales diversas y a la vez típicas de las zonas más representativas del territorio: urbana consolidada, urbana a consolidar, centro de servicios y rural disperso.