The JAK/STAT3 Pathway Is a Common Inducer of Astrocyte Reactivity in Alzheimer's and Huntington's Diseases.

Astrocyte reactivity is a hallmark of neurodegenerative diseases (ND), but its effects on disease outcomes remain highly debated. Elucidation of the signaling cascades inducing reactivity in astrocytes during ND would help characterize the function of these cells and identify novel molecular targets to modulate disease progression. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway is associated with reactive astrocytes in models of acute injury, but it is unknown whether this pathway is directly responsible for astrocyte reactivity in progressive pathological conditions such as ND. In this study, we examined whether the JAK/STAT3 pathway promotes astrocyte reactivity in several animal models of ND. The JAK/STAT3 pathway was activated in reactive astrocytes in two transgenic mouse models of Alzheimer's disease and in a mouse and a nonhuman primate lentiviral vector-based model of Huntington's disease (HD). To determine whether this cascade was instrumental for astrocyte reactivity, we used a lentiviral vector that specifically targets astrocytes in vivo to overexpress the endogenous inhibitor of the JAK/STAT3 pathway [suppressor of cytokine signaling 3 (SOCS3)]. SOCS3 significantly inhibited this pathway in astrocytes, prevented astrocyte reactivity, and decreased microglial activation in models of both diseases. Inhibition of the JAK/STAT3 pathway within reactive astrocytes also increased the number of huntingtin aggregates, a neuropathological hallmark of HD, but did not influence neuronal death. Our data demonstrate that the JAK/STAT3 pathway is a common mediator of astrocyte reactivity that is highly conserved between disease states, species, and brain regions. This universal signaling cascade represents a potent target to study the role of reactive astrocytes in ND.

Análisis de la esperanza de vida libre de discapacidad a lo largo de la biografía: de la madurez a la vejez

Objetivo: determinar en qué etapas del curso de vida previo a los setenta años se acortan las expectativas de vida en salud. Método: análisis longitudinal retrospectivo. La población a estudio es una cohorte de 1286 individuos de entre 70 y 74 años de edad que viven en áreas metropolitanas no institucionalizados. La discapacidad se mide mediante el desarrollo de las actividades instrumentales de la vida diaria (AIVD) y las actividades básicas de la vida diaria (ABVD). Se calculan las esperanzas de vida libre de discapacidad y la probabilidades de supervivencia mediante Kaplan-Meier Resultados: La incidencia de discapacidad básica se incrementó a partir del tramo de 50 a 54 años acelerándose progresivamente hasta los 65-69 años donde la probabilidad de padecer discapacidad instrumental fue ligeramente superior en hombres que en mujeres (0,23 en hombres versus 0,19 en mujeres). La supervivencia sin discapacidad de las mujeres fue peor que la de los hombres tanto para cualquier tipo de discapacidad (LogRank = 5,80; p = 0,016) como para la discapacidad básica (LogRank = 4,315; p = 0,038). Conclusiones: se pone de manifiesto el importante peso que para la autonomía de la población masculina de estas edades tiene la falta de habilidad instrumental para cuestiones domésticas. Además, las mujeres ostentan un peor pronóstico de supervivencia sin discapacidad tanto para cualquier tipo de discapacidad como para la discapacidad básica. Para ambos sexos, desde los 40 hasta los 60 años de edad, hay un ligero descenso de la supervivencia sin discapacidad. A partir de esta edad, el descenso se acelera notablemente.

Protective effects of social networks on disability among older adults in Spain

The loss of autonomy at advanced ages is not only associated with ageing, but also with the characteristics of the physical and social environment. Recent investigations have shown that social networks, social engagement and participation act like predictors of disability among the elderly. The aim of this study is to determine whether social networks are related to the development and progression of disability in the early years of old age. The source of data is the first wave of the survey "Processes of Vulnerability among Spanish Elderly", carried out in 2005 to a sample of 1 244 individuals. The population object of study is the cohort aged 70 to 74 years in metropolitan areas (Madrid and Barcelona) and not institutionalized. Disability is measured by the development of basic activities of daily life (ADL), and instrumental activities of daily life (IADL). The structural aspects of the social relationships are measured through the diversity of social networks and participation. We used the social network index (SNI). For each point over the SNI, the risk of developing any type of disability decreased by 49% (HR = 0.51, 95%CI = 0.31-0.82). The SNI was a decisive factor in all forecasting models constructed with some hazard ratios (HR) that ranged from 0.29 (95%CI = 0.14-0.59) in the first model to 0.43 (95%CI 0.20-0.90) in the full model. The results of the present study showed a strong association between an active social life, emotional support provided by friends and confidents and disability. These findings suggest a protective effect of social networks on disability. Also, these results indicate that some family and emotional ties have a significant effect on both the prevalence and the incidence of disability.

El método BAPNE y su repercusión en las capacidades cognitivas

Los ejercicios de percusión corporal propuestos por el método BAPNE pretenden estimular a través del juego nuestras dimensiones corporal, emocional y cognitiva. Ello requiere, en primer lugar, focalizar la atención para el aprendizaje y coordinación de todas las actividades involucradas (canto, movimiento, percusión extremidades superiores e inferiores) lo cual demanda una buena disposición de nuestras funciones cognitivas. El movimiento es vital para nuestra salud, y la música está íntimamente relacionada con el movimiento. Es conocido que incluso en estados de escucha pasiva de música, el área cerebral que planifica los mecanismos necesarios para los movimientos está activa, aunque externamente no lo manifestemos. Se ha constatado la existencia de conexiones neuronales entre las áreas auditiva y motora, y de ahí nuestra tendencia a imitar con movimientos corporales la música que percibimos y escuchamos. Por otra parte, son conocidos muchos de los beneficios terapéuticos que las actividades musicales pueden aportarnos en todas sus modalidades, desde el aprendizaje hasta la interpretación (ya sea vocal o instrumental) pasando por la simple escucha activa o pasiva. Todo pa rece indicar, pues, que el movimiento es básico para nuestra salud y que la música, íntimamente ligada a él, es una fuente placentera y agradable para experimentarlo.

Quaternary active tectonic structures in the offshore Bajo Segura basin (SE Iberian Peninsula Mediterranean Sea).

The Bajo Segura fault zone (BSFZ) is the northern terminal splay of the Eastern Betic shear zone (EBSZ), a large left-lateral strike-slip fault system of sigmoid geometry stretching more than 450 km from Alicante to Almería. The BSFZ extends from the onshore Bajo Segura basin further into the Mediterranean Sea and shows a moderate instrumental seismic activity characterized by small earthquakes. Nevertheless, the zone was affected by large historical earthquakes of which the largest was the 1829 Torrevieja earthquake (IEMS98 X). The onshore area of the BSFZ is marked by active transpressive structures (faults and folds), whereas the offshore area has been scarcely explored from the tectonic point of view. During the EVENT-SHELF cruise, a total of 10 high-resolution single-channel seismic sparker profiles were obtained along and across the offshore Bajo Segura basin. Analysis of these profiles resulted in (a) the identification of 6 Quaternary seismo-stratigraphic units bounded by five horizons corresponding to regional erosional surfaces related to global sea level lowstands; and (b) the mapping of the active sub-seafloor structures and their correlation with those described onshore. Moreover, the results suggest that the Bajo Segura blind thrust fault or the Torrevieja left-lateral strike-slip fault, with prolongation offshore, could be considered as the source of the 1829 Torrevieja earthquake. These data improve our understanding of present deformation along the BSFZ and provide new insights into the seismic hazard in the area.

Päällystetyn graafisen kartongin hajuominaisuudet

Diplomityön tavoitteena oli selvittää elintarvikepakkauksiin soveltuvan graafisen kartongin potentiaalinen hajun aiheuttaja. Lisäksi tavoitteena oli vähentää päällystetyn tasakoosteisen (SBS) kolmikerroskartongin hajutasoa keskittyen päällystyspastakomponentteihin sekä massaosaston jälkeen annosteltaviin kemikaaleihin. Kirjallisuusosassa tarkasteltiin eri kartonkilajeja, päällystyspastoja ja sen sisältämiä komponentteja, pääpainon ollessa kuitenkin kartongin hajuominaisuuksiin vaikuttavien tekijöiden selvittämisessä. Lisäksi luotiin katsaus kartonkien aistinvaraisiin ja instrumentaalisiin määritysmenetelmiin. Instrumentaalisista määritysmenetelmistä käsiteltiin headspace –kaasukromatografia (HSGC) sekä korkeanerotuskyvyn nestekromatografia yhdistettynä massaspektrometriin (HPLC/MS). Kokeellisen osan alussa kartoitettiin päällystyskemikaalien sekä liima- ja retentioaineiden haihtuvat yhdisteet HSGC- ja HPLC/MS –tekniikoiden avulla. Kaasukromatografisesti analysoidut kokonaishaihtuvien tasot eivät poikenneet normaaleista tasoista, joten jouduttiin siirtymään HPLC/MS –menetelmään. HPLC/MS –tekniikalla on päästy tutkimaan herkästi haihtuvien typpiyhdisteiden amiinipitoisuuksia. Kemikaalimittausten perusteella vaihdettiin potentiaaliset hajua aiheuttavat kemikaalit, kovete ja synteettinen paksuntaja, markkinoilla oleviin vaihtoehtoisiin kemikaaleihin ja suoritettiin pilot -koeajo sekä tehdasmittakaavaiset koeajot. Työssä perehdyttiin myös varastoinnin aiheuttamiin vaikutuksiin eri kartonkilaatujen aistinvaraisissa ominaisuuksissa. Päällystyspastan kemikaaleista suuren hajukuorman aiheuttavat kovete, dispergointiaine, päällystyspigmentit ja lateksit sekä synteettinen paksuntaja. Kovetteen annostelumäärä päällystyspastoihin on alhainen, mutta sen sisältämä ammoniakkipitoisuus on kuitenkin huomattavan suuri. Kovete ohjaakin lopputuotteen ammoniakkipitoisuutta. Merkittävän metyyliamiinikuorman sisältää dispergointiaine. Sen vaikutus lopputuotteeseen voidaan olettaa vähäiseksi johtuen kemikaalin pienestä määrästä pastassa. Päällystyspigmenttien ja lateksien korkea metyyliamiinikuorma voi puolestaan aiheuttaa lopputuotteeseen huomattavan hajukuorman johtuen niiden suurista annostelumääristä. Eri synteettisille paksuntajille tehtyjen tutkimusten mukaan niiden hajukuormat olivat hyvin samankaltaisia ja vaikutus lopputuotteen kokonaishajutasoon jäi pieneksi. Aistinvaraisesti tarkasteltuna eri kartonkilaaduille saadaan eri hajutasoja. Elintarvikepakkauksiin soveltuvan graafisen kartongin hajutasot olivat korkeita muihin kartonkilaatuihin nähden niin tuoreena kuin varastoinnin jälkeen. Erityisesti tuoreen kartonkinäytteen metyyliamiinipitoisuus ylitti hajukynnyksen. Käytetty lateksi, kovete ja synteettinen paksuntaja näyttävät muodostavan niin tiiviin hajua koteloivan päällystekerroksen kartongin pinnalle, että hajua vapautuu pitkällä aikavälillä. Myös varastointi tiiviinä pakkauksena estää amiinien haihtumisen. Tutkimusten mukaan ammoniakkivapaalla PZC –kovetteella saadaan alennettua graafisen kartongin ammoniakkikuormaa huomattavasti. Tämä on vaikuttamassa myös lopputuotteen hajutasoon, jota on mahdollisuus alentaa käyttämällä ammoniakkivapaata kovetetta.

Population Size and Civil Conflict Risk: Is There A Causal Link?

[spa] La estimación del impacto del tamaño de la populación sobre la probabilidad de conflicto civil se complica por el sesgo de endogeneidad y las variables omitidas. Este artículo trata el problema de causalidad utilizando métodos de variables instrumentales en un panel de 37 países del África Sub-sahariana en el período 1981-2004. Encontramos que un aumento de la población en un 1% aumenta la probabilidad de conflicto civil por un 5.2%.

Les odeurs répugnantes des démons : une preuve de leur présence corporelle au sabbat ?

The present article examines the meaning and function of olfactory remnants, often repugnant, linked to demons in the context of late medieval witchcraft and demonology. This reflection is developed within the framework of a «make believe» logic sustained by the doctrinal, theological, narrative and judiciary constructions of the witches' Sabbath. Incorporated within the order of sensory perception, references to the fetid smell of demons - who are by nature devoid of odour because they are pure spirits - constitute further proofs bearing witness to demonic presence, and thus testifying to the ignominy of the crime of witchcraft and to the guiltiness of the accused. According to those who attacked demon worshippers, the devil truly revealed himself physically; human beings were able to touch, hear, see and smell him. Sensory faculties were therefore perceived as being instrumental in corroborating the existence and reality of the Sabbath and the presence of the devil in bodily form. These considerations bring us to examine the olfactory fields associated with the devil's odour: odour of corpses, hell, sin, deviance, but also of defilement, impurity, corruption and excrements. These fetid odours are embedded in a logic of moral, spiritual and religious inversion of positive odours, such as the «sweet fragrance» of the saints, the «pure odour» of Christ or the «soft perfume» of virtue.

El levantamiento del mapa topográfico a escala 1:50.000 en Cataluña (1912-1932)

El primer levantamiento topográfico a gran escala del territorio catalán, efectuado con carácter sistemático, completo y uniforme, fue realizado entre 1912 y 1932. Este artículo estudia la organización del citado levantamiento, que formaba parte de la ejecución del Mapa topográfico de España a escala 1:50.000, y que en Cataluña fue llevado a término por el Instituto Geográfico y Estadístico y el Depósito de la Guerra. Se analiza el desarrollo de las labores topográficas, y se describe el personal y el instrumental empleado en las mismas. Una de las novedades de los trabajos topográficos conducidos en Cataluña fue la introducción de la fotogrametría terrestre en las zonas de montaña.

The conditions for the reproduction of the SAGUAPAC water cooperative in the city of Santa Cruz de la Sierra, Bolivia : discourse analysis

The SAGUAPAC cooperative in the city of Santa Cruz de la Sierra (Eastern Bolivia) is regularly presented as an example of cooperative successes regarding water supply and sanitation. Its efficiency, both economic and technical, is widely considered as the main reason for its attractiveness. However, without denying its importance, we show, through a discourse analysis from and about SAGUAPAC in local media, that moral and non-instrumental factors are crucial in the reproduction of the cooperative. These factors create attachment and affection toward the cooperative, through a storytelling using a four-dimensional rhetoric (mythification, identification, emotionalisation and personification). This storytelling technique, internalized in the local media discourse and materializing the so-called new spirit of capitalism, exploits the affects and instrumentalisation of local myths and legends, as well as the 'camba' ethnic identity. In that, it tends to retain SAGUAPAC members and to canvass new ones, by providing them with recognition in their quality of local community members. However, the mobilisation of social norms and power hierarchies might end up reinforcing the social exclusion of Andean non-camba immigrants, inspite of an a priori inclusive and democratic organisation.

DESENVOLVIMENTO DE GELEIA DE UMBU-CAJÁ CONVENCIONAL E DIETÉTICA

RESUMO O objetivo deste estudo foi desenvolver e caracterizar geleias de umbu-cajá, convencional (com sacarose) e dietética (com xilitol), a partir dos genótipos Suprema e Preciosa. As formulações foram elaboradas com a proporção 1:1, de polpa mais açúcar ou polpa mais xilitol, com 0,5% de pectina e teor final de sólidos solúveis entre 62 e 65 °Brix. As geleias foram analisadas em relação às suas características físico-químicas (pH, acidez titulável, sólidos solúveis, açúcares totais, umidade e cor instrumental) e sensoriais (teste de aceitação, preferência e intenção de compra). O teste de aceitação foi realizado por 73 consumidores, por meio de escala hedônica de 9 pontos, avaliando-se os atributos cor, aroma, sabor e textura. As geleias elaboradas com sacarose apresentaram características físico-químicas semelhantes às geleias dietéticas, exceto os teores de açúcares totais que foram inferiores no produto dietético. A geleia convencional, elaborada com o genótipo Suprema, foi preferida para os atributos aroma, sabor e textura, enquanto a geleia convencional, elaborada com o genótipo Preciosa, foi preferida para os atributos cor, aroma e textura. As geleias dietéticas, elaboradas com os dois genótipos, foram as menos preferidas, mas apresentaram índices de aceitação acima de 60%, o que demonstra o potencial dessas geleias para atender públicos específicos.

Meeting report of the European mouse complex genetics network SYSGENET.

The second scientific meeting of the European systems genetics network for the study of complex genetic human disease using genetic reference populations (SYSGENET) took place at the Center for Cooperative Research in Biosciences in Bilbao, Spain, December 10-12, 2012. SYSGENET is funded by the European Cooperation in the Field of Scientific and Technological Research (COST) and represents a network of scientists in Europe that use mouse genetic reference populations (GRPs) to identify complex genetic factors influencing disease phenotypes (Schughart, Mamm Genome 21:331-336, 2010). About 50 researchers working in the field of systems genetics attended the meeting, which consisted of 27 oral presentations, a poster session, and a management committee meeting. Participants exchanged results, set up future collaborations, and shared phenotyping and data analysis methodologies. This meeting was particularly instrumental for conveying the current status of the US, Israeli, and Australian Collaborative Cross (CC) mouse GRP. The CC is an open source project initiated nearly a decade ago by members of the Complex Trait Consortium to aid the mapping of multigenetic traits (Threadgill, Mamm Genome 13:175-178, 2002). In addition, representatives of the International Mouse Phenotyping Consortium were invited to exchange ongoing activities between the knockout and complex genetics communities and to discuss and explore potential fields for future interactions.

Correlação clínico-radiológica na artéria carótida interna aberrante: relato de caso

A artéria carótida interna aberrante é uma anomalia na embriogênese da porção vertical da artéria carótida interna, caracterizada pela projeção desta artéria no ouvido médio, adjacente ao promontório coclear. Os autores relatam um caso no qual a tomografia computadorizada contrastada e a angiorressonância foram decisivas, caracterizando adequadamente a anomalia e evitando intervenção instrumental ou cirúrgica, que poderia ter conseqüências fatais.

Estimating 750 years of temperature variations and uncertainties in the Pyrenees by tree-ring reconstructions and climate simulations.

Past temperature variations are usually inferred from proxy data or estimated using general circulation models. Comparisons between climate estimations derived from proxy records and from model simulations help to better understand mechanisms driving climate variations, and also offer the possibility to identify deficiencies in both approaches. This paper presents regional temperature reconstructions based on tree-ring maximum density series in the Pyrenees, and compares them with the output of global simulations for this region and with regional climate model simulations conducted for the target region. An ensemble of 24 reconstructions of May-to-September regional mean temperature was derived from 22 maximum density tree-ring site chronologies distributed over the larger Pyrenees area. Four different tree-ring series standardization procedures were applied, combining two detrending methods: 300-yr spline and the regional curve standardization (RCS). Additionally, different methodological variants for the regional chronology were generated by using three different aggregation methods. Calibration verification trials were performed in split periods and using two methods: regression and a simple variance matching. The resulting set of temperature reconstructions was compared with climate simulations performed with global (ECHO-G) and regional (MM5) climate models. The 24 variants of May-to-September temperature reconstructions reveal a generally coherent pattern of inter-annual to multi-centennial temperature variations in the Pyrenees region for the last 750 yr. However, some reconstructions display a marked positive trend for the entire length of the reconstruction, pointing out that the application of the RCS method to a suboptimal set of samples may lead to unreliable results. Climate model simulations agree with the tree-ring based reconstructions at multi-decadal time scales, suggesting solar variability and volcanism as the main factors controlling preindustrial mean temperature variations in the Pyrenees. Nevertheless, the comparison also highlights differences with the reconstructions, mainly in the amplitude of past temperature variations and in the 20th century trends. Neither proxy-based reconstructions nor model simulations are able to perfectly track the temperature variations of the instrumental record, suggesting that both approximations still need further improvements.

Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study.

BACKGROUND: Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue. AIMS: To investigate whether higher BMI increases the risk of major depression. METHOD: Two instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case-control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI. RESULTS: Linear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient -0.03, 95% CI -0.18 to 0.13, P = 0.73; GRS: coefficient -0.02, 95% CI -0.11 to 0.07, P = 0.62). CONCLUSIONS: Our instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.