Investigating the invasive and cytoprotective properties of the heme binding protein HRG-1 in cancer cells

This thesis investigates the mechanisms by which HRG-1 contributes to the invasive and cytoprotective signalling pathways in cancer cells through its effects on VATPase activity and heme transport. Plasma membrane-localised V-ATPase activity correlates with enhanced metastatic potential in cancer cells, which is attributed to extrusion of protons into the extracellular space and activation of pH-sensitive, extracellular matrix degrading-proteases. We found that HRG-1 is co-expressed with the V-ATPase at the plasma membrane of certain aggressive cancer cell types. Modulation of HRG-1 expression altered both the localisation and activity of the VATPase. We also found that HRG-1 enhances trafficking of essential transporters such as the glucose transporter (GLUT-1) in cancer cells, and increases glucose uptake, which is required for cancer cell growth, metabolism and V-ATPase assembly. Heme is potentially cytotoxic, owing to its iron moiety, and therefore the trafficking of heme is tightly controlled in cells. We hypothesised that HRG-1 is required for the transport of heme to intracellular compartments. Importantly, we found that HRG-1 interacts with the heme oxygenases that are necessary for heme catabolism. HRG-1 is also required for trafficking of both heme-bound and nonheme-bound receptors and suppression of HRG-1 results in perturbed receptor trafficking to the lysosome. Suppression of HRG-1 in HeLa cells increases toxic heme accumulation, reactive oxygen species accumulation, and DNA damage resulting in caspasedependent cell death. Mutation of essential heme binding residues in HRG-1 results in decreased heme binding to HRG-1. Interestingly, cells expressing heme-binding HRG-1 mutants exhibit decreased internalisation of the transferrin receptor compared to cells expressing wildtype HRG-1. These findings suggest that HRG- 1/heme trafficking contributes to a hitherto unappreciated aspect of receptormediated endocytosis. Overall, the findings of this thesis show that HRG-1-mediated regulation of intracellular and extracellular pH through V-ATPase activity is essential for a functioning endocytic pathway. This is critical for cells to acquire nutrients such as folate, iron and glucose and to mediate signalling in response to growth factor activation. Thus, HRG-1 facilitates enhanced metabolic activity of cancer cells to enable tumour growth and metastasis.

ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide.

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others(1), ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.

Social economy and economic crisis in the basque country abstract

This article examines the socio-economic evolution of the social economy sector in the Basque Country during the 2008-2014 period of economic crisis. Data have been obtained within a framework of collaboration between university, Basque Government and private sector of the social economy. The results suggest that such entities have evolved better, both in terms of number of enterprises and employment, than the general economy of the Basque Country, while the context of public policies aimed at social economy has worsened over the years. However, in economic terms (measured through the Gross Value Added generated), they have not been able to cope with the crisis in equal conditions to the general economy. The main contribution of this research lies in that, unlike similar studies, it discusses the evolution of the whole sector of the social economy, taking as reference a broad period of the current economic crisis.

El concepto de “posesión común originaria” en la doctrina kantiana de la propiedad

Los primeros parágrafos de la sección “El derecho privado” (§§ 1-17) de la Doctrina del derecho de Kant incluyen el conjunto de los elementos sistemáticos que conciernen a la justificación de los derechos relativos a la propiedad. El propósito central de este trabajo es analizar la función sistemática del concepto de “posesión común originaria” en la doctrina kantiana de la propiedad, con especial interés en el sentido novedoso que adquiere ese concepto —que pertenecía a la tradición del derecho natural— en su reformulación como un “concepto práctico de la razón, que contiene a priori, el principio según el cual tan solo los hombres pueden hacer uso del lugar sobre la tierra siguiendo leyes jurídicas” (RL, 262).

The determination of sinigrin in Brassica, and investigations into the use of allyl-isothiocyanate as a nematicide

The goal of this thesis was to study factors related to the development of Brassica juncea as a sustainable nematicide. Brassica juncea is characterized by the glycoside (glucosinolate) sinigrin. Various methods were developed for the determination of sinigrin in Brassica juncea tissue extracts. Sinigrin concentrations in plant tissues at various stages of growth were monitored. Sinigrin enzymatically breaks down into allylisothiocyanate (AITC). AITC is unstable in aqueous solution and degradation was studied in water and in soil. Finally, the toxicity of AITC against the root-lesion nematode (Pratylenchus penetrans) was determined. A method was developed to extract sinigrin from whole Brassica j uncea tissues. The optimal time of extraction wi th boiling phosphate buffer (0.7mM, pH=6.38) and methanol/water (70:30 v/v) solutions were both 25 minutes. Methanol/water extracted 13% greater amount of sinigrin than phosphate buffer solution. Degradation of sinigrin in boiling phosphate buffer solution (0.13%/minute) was similar to the loss of sinigrin during the extraction procedure. The loss of sinigrin from boiling methanol/water was estimated to be O.Ol%/minute. Brassica juncea extract clean up was accomplished by an ion-pair solid phase extraction (SPE) method. The recovery of sinigrin was 92.6% and coextractive impurities were not detected in the cleaned up extract. Several high performance liquid chromatography (HPLC) methods were developed for the determination of sinigrin. All the developed methods employed an isocratic mobile phase system wi th a low concentration of phosphate buffer solution, ammonium acetate solution or an ion-pair reagent solution. A step gradient system was also developed. The method involved preconditioning the analytical column with phosphate buffer solution and then switching the mobile phase to 100% water after sample injection.Sinigrin and benzyl-glucosinolate were both studied by HPLC particle beam negative chemical ionization mass spectrometry (HPLCPB- NCI-MS). Comparison of the mass spectra revealed the presence of fragments arising from the ~hioglucose moiety and glucosinolate side-chain. Variation in the slnlgrin concentration within Brassica juncea plants was studied (Domo and Cutlass cuItivars). The sinigrin concentration in the top three leaves was studied during growth of each cultivar. For Cutlass, the minimum (200~100~g/g) and maximum (1300~200~g/g) concentrations were observed at the third and seventh week after planting, respectively. For Domo, the minimum (190~70~g/g) and maximum (1100~400~g/g) concentrations were observed at the fourth and eighth week after planting, respectively. The highest sinigrin concentration was observed in flower tissues 2050±90~g/g and 2300±100~g/g for Cutlass and Domo cultivars, respectively. Physical properties of AITC were studied. The solubility of AITC in water was determined to be approximately 1290~g/ml at 24°C. An HPLC method was developed for the separation of degradation compounds from aqueous AITC sample solutions. Some of the degradation compounds identified have not been reported in the literature: allyl-thiourea, allyl-thiocyanate and diallyl-sulfide. In water, AITC degradation to' diallyl-thiourea was favored at basic pH (9.07) and degradation to diallyl-sulfide was favored at acidic pH (4 . 97). It wap necessary to amend the aqueous AITC sample solution with acetonitrile ?efore injection into the HPLC system. The acetonitrile amendment considerably improved AITC recovery and the reproducibility of the results. The half-life of aqueous AITC degradation at room temperature did not follow first-order kinetics. Beginning with a 1084~g/ml solution, the half-life was 633 hours. Wi th an ini tial AITC concentration of 335~g/ml the half-life was 865 hours. At 35°C the half-life AITC was 76+4 hours essentially independent of the iiisolution pH over the range of pH=4.97 to 9.07 (1000~g/ml). AITC degradation was also studied in soil at 35°C; after 24 hours approximately 75% of the initial AITC addition was unrecoverable by water extraction. The ECso of aqueous AITC against the root-lesion nematode (Pratylenchus penetrans) was determined to be approximately 20~g/ml at one hour exposure of the nematode to the test solution. The toxicological study was also performed with a myrosinase treated Brassica juncea extract. Myrosinase treatment of the Brassica juncea extract gave nearly quantitative conversion of sinigrin into AITC. The myrosinase treated extract was of the same efficacy as an aqueous AITC solution of equivalent concentration. The work of this thesis was focused upon understanding parameters relevant to the development of Brassica juncea as a sustainable nematicide. The broad range of experiments were undertaken in support of a research priority at Agriculture and Agri-Food Canada.

Which Legal Standards Should Apply To Web-logs? The present legal position of Internet journals in the European iuris prudence in the light of the European Parliament Committee’s on Culture and Education report and Polish Supreme Court decision

The article discusses the present status of weblogs and examines whether legal standards applicable to traditional press and media should be applied to that specific forum. The analysis is based on two key documents: the Draft Report on the concentration and pluralism in the media in European Union (2007/2253(INI)) of the European Parliament Committee on Culture and Education presented in March 2008 and a landmark decision of the Polish Supreme Court from July 26, 2007 (IV KK 174/07) in the light of present judicial tendency in other European countries. The first of the mentioned documents calls for the “clarification of the legal status of different categories of weblog authors and publishers as well as disclosure of interests and voluntary labelling of weblogs”. It emphasizes that the “undetermined and unindicated status of authors and publishers of weblogs causes uncertainties regarding impartiality, reliability, source protection, applicability of ethical codes and the assignment of liability in the event of lawsuits”. The position of the European Parliament, expressed in the document, raises serious questions on the limits of freedom of thought and speech on the Internet and on the degree of acceptable state control. A recent Polish Supreme Court decision, which caused quite a stir in the Polish Internet community, seems to head in the very direction recommended by the EP Culture Committee. In a case of two editors of a web journal (“czasopismo internetowe”) called “Szyciepoprzemysku”, available on-line, accused of publishing a journal without the proper registration, the Polish Supreme Court stated that “journals and periodicals do not lose the character of a press release due solely to the fact that they appear in the form of an  Internet transmission”, and that ‘’the publishing of press in an electronic form, available on the Internet, requires  registration”. The decision was most surprising, as prior lower courts decisions declined the possibility to register Internet periodicals. The accused were acquitted in the name of the constitutional principle of the rule of law (art. 7 of the Polish Constitution) and the ensuing obligation to protect the trust of a citizen to the state (a conviction in this case would break the collateral estoppel rule), however the decision quickly awoke media frenzy and raised the fear of a need to register all websites that were regularly updated. The spokesman of the Polish Supreme Court later explained that the sentence of the Court was not intended to cause a mass registration of all Internet “periodicals” and that neither weblogs nor Internet sites, that were regularly updated, needed registration. Such an interpretation of the Polish press law did not appear clear based only on the original text of the judgment and the decision as such still raises serious practical questions. The article aims to examine the status of Internet logs as press and seeks the compromise between the concerns expressed by European authorities and the freedom of thought and speech exercised on the Internet.

Iniciación al estudio universitario.

Manual de técnicas de estudio para universitarios que se estructura en cinco capítulos dedicados a la gestión del tiempo personal, al método personal de estudio, a las técnicas de búsqueda de información, a la realización y presentación de trabajos y a la preparación de exámenes..

Estudio sociológico de la escolarización a nivel de Educación Preescolar en Asturias.

Realizar una reflexión sociológica, investigando, a partir de la realidad de una provincia (Asturias), las principales situaciones y características que presente la escolarización de los niños en edad Preescolar (2 a 5 años). Clarificar la situación real de Asturias como ayuda para definir las líneas de acción en el futuro. Situación real de la escolarización de niños en edad Preescolar en la provincia de Asturias. Se analizan datos estadísticos sobre escolarización Preescolar, efectivos escolarizados en los últimos cinco cursos, tasas de escolarización, escolarización según el tipo de centro, edad y sexo y previsiones y escolarización, relación entre población escolarizada y prevista escolarizar, estimación de necesidades de profesorado. Datos de MEC y del INI. Estudios sociológicos. Investigaciones. Asturias mantiene una de las tasas más bajas de España en Educación Preescolar; esto es debido a una deficiente planificación de la política educativa en este nivel. Dada la situación en este momento de la escolarización Preescolar, se ve difícil el alcanzar los objetivos previstos por el III Plan de Desarrollo para 1980 a no ser que se duplique el número de puestos escolares en los siguientes cuatro años. La escolarización presenta acusados desequilibrios según el tipo de enseñanza, el tipo de centro y el tipo de comarca educativa dentro de la provincia. En los últimos cinco cursos la relación de centros estatales y privados se ha invertido a favor de los últimos. La administración debería reconsiderar la política de creación de centros a este nivel dadas las implicaciones educativas, sociales y asistenciales que presenta la educación de los niños comprendidos entre 2 y 5 años. Debería intensificarse la creación de unidades de jardines de infancia. Se propugna una política educativa realista que tienda a disminuir los desequilibrios internos. Se considera conveniente y urgente potenciar la formación de especialistas. Se propone, por último, la realización de una serie de investigaciones con el fin de extender al máximo la Educación Preescolar en esta región.

Portal de convivencia en Arag??n

P??gina web relacionada con la materia de convivencia. Se ofrece una plataforma para la divulgaci??n de los valores universales de la cultura de paz y a dar a conocer el importante trabajo que, en el ??mbito de la convivencia, desarrollan los centros docentes de Arag??n. Sirve como lugar de encuentro de la comunidad educativa, adem??s de posibilitar el intercambio de experiencias, el env??o de preguntas y sugerencias, la consulta de documentaci??n oficial, art??culos de prensa, herramientas de trabajo, novedades, enlaces de inter??s, etc..

Orientación : portal de educación orientativa de Aragón.

Página web del programa de orientación educativa, que incide especialmente en los alumnos para el conocimiento y valoración de sus propias aptitudes e intereses, en el desarrollo personal y de aprendizaje, y para que sea capaz de elegir y prepararse para la vida profesional. Su objetivo es servir de plataforma para la divulgación de experiencias e intercambio de materiales y recursos. Se publica información relacionada con la legislación vigente, actividades de formación, programas que se hayan llevado a cabo, bibliografía y enlaces de interés.

Caracterización de las concentraciones en aire de bioaerosoles cultivables y contables en sistemas de ventilación mecánica de edificaciones administrativas en la ciudad de Bogotá en el periodo 2012 2013

Un problema de salud ambiental relevante es la contaminación del aire generado por diferentes factores, uno de ellos es la carga microbiana. El estudio evidencia la presencia de estos contaminantes del aire como son los bioaerosoles cultivables y contables en las áreas de los edificios administrativos estudiados la cual podría afectar la calidad del aire interior. Se realizó un estudio observacional de corte transversal que permitió conocer y establecer las características de la carga microbiana presente relacionada con bioaerosoles cultivables y contables en los sistemas de ventilación mecánica en tres edificios administrativos de la ciudad de Bogotá en el periodo 2012 a 2013 y, la asociación o no entre variables de interés. Los bioaerosoles cultivables y contables encontrados con mayores porcentajes en las muestras tomadas fueron comunes a los tres edificios así: Aspergillus sp. se encontró en el 77,2% (61) de las muestras para el edifico uno, mientras que para el dos fue de 91% (30) de las muestras y para el edificio tres 100% (19) de las muestras tomadas; seguido por el género Penicillium sp. del cual se encontró 60,8% (48) de las muestras para el edificio uno, para el edificio dos 87,9% (29) de las muestras y para el edificio tres 94,7% (18) de las muestras. Otro género encontrado en porcentajes altos en los tres edificios fue el Cladosporium sp. , en el edificio uno 41,8% (33) de las muestras, mientras que para el edificio dos correspondió al 100% (33) de las muestra y finalmente para el edificio tres 84,2% (16) de las muestras analizadas. Los hallazgos se correlacionan con lo reportado por la literatura.

La gestión de lo público por los particulares en el estado contemporáneo: análisis de las alianzas público privadas (APP) en Colombia

El Estado como institución político-jurídica, así como las estructuras de poder y organización social, han sufrido grandes transformaciones en el mundo contemporáneo, producto de discusiones y tendencias como la globalización, la reconfiguración de la legitimidad de las instituciones burocráticas, el establecimiento de estándares, políticas y prácticas de calidad internacional, el impacto de las crisis de la hacienda pública, entre otros factores que influenciaron la creciente intervención de los particulares y sus mecanismos de regulación en la gestión de los asuntos públicos. El Estado Colombiano no ha sido ajeno a tales situaciones, y la creciente injerencia del sector privado en lo público, se ha visto representada en la expedición del régimen legal de las Asociaciones Público Privadas (Ley 1508 de 2012), en virtud del cual los particulares estructuran, ejecutan y desarrollan proyectos conjugando el ánimo de lucro con la promoción del interés general. De conformidad con lo anterior, el presente trabajo tiene como objetivo sistematizar y analizar las disposiciones legales y reglamentarias relacionadas con el régimen de las Asociaciones Público Privadas, así como abordar reflexiones sobre la transformación del Estado y el papel de los particulares en el ámbito de lo público.

La autonomía y descentralización del modelo federal venezolano. Una mutación del federalismo dual en el marco del ordenamiento latinoamericano

En la presente investigación se estudió la organización administrativa y territorial de la República Bolivariana de Venezuela, para poder identificar si se podían definir y catalogar a Venezuela como un Estado federal como manda su Constitución, o si por el contrario, podríamos estar hablando de una organización distinta llámese autonómica o unitaria, o simplemente un modelo federal diferente al dual influenciado por las diferentes formas de organización.

Iniciació al handbol.'Iniciación al balonmano'.

Introducción al tenis de mesa. Se expone el reglamento y las diferentes técnicas que comprenden este deporte.

Iniciación al tenis de mesa.

Aproximación al mundo del tenis de mesa. Se describen las técnicas y posiciones que ocupan los diferentes jugadores de este deporte.