Identification, characterization and antigenicity of the Plasmodium vivax rhoptry neck protein 1 (PvRON1)

Background: Plasmodium vivax malaria remains a major health problem in tropical and sub-tropical regions worldwide. Several rhoptry proteins which are important for interaction with and/or invasion of red blood cells, such as PfRONs, Pf92, Pf38, Pf12 and Pf34, have been described during the last few years and are being considered as potential anti-malarial vaccine candidates. This study describes the identification and characterization of the P. vivax rhoptry neck protein 1 (PvRON1) and examine its antigenicity in natural P. vivax infections. Methods: The PvRON1 encoding gene, which is homologous to that encoding the P. falciparum apical sushi protein (ASP) according to the plasmoDB database, was selected as our study target. The pvron1 gene transcription was evaluated by RT-PCR using RNA obtained from the P. vivax VCG-1 strain. Two peptides derived from the deduced P. vivax Sal-I PvRON1 sequence were synthesized and inoculated in rabbits for obtaining anti-PvRON1 antibodies which were used to confirm the protein expression in VCG-1 strain schizonts along with its association with detergent-resistant microdomains (DRMs) by Western blot, and its localization by immunofluorescence assays. The antigenicity of the PvRON1 protein was assessed using human sera from individuals previously exposed to P. vivax malaria by ELISA. Results: In the P. vivax VCG-1 strain, RON1 is a 764 amino acid-long protein. In silico analysis has revealed that PvRON1 shares essential characteristics with different antigens involved in invasion, such as the presence of a secretory signal, a GPI-anchor sequence and a putative sushi domain. The PvRON1 protein is expressed in parasite's schizont stage, localized in rhoptry necks and it is associated with DRMs. Recombinant protein recognition by human sera indicates that this antigen can trigger an immune response during a natural infection with P. vivax. Conclusions: This study shows the identification and characterization of the P. vivax rhoptry neck protein 1 in the VCG-1 strain. Taking into account that PvRON1 shares several important characteristics with other Plasmodium antigens that play a functional role during RBC invasion and, as shown here, it is antigenic, it could be considered as a good vaccine candidate. Further studies aimed at assessing its immunogenicity and protection-inducing ability in the Aotus monkey model are thus recommended.

Plasmodium vivax lineages: geographical distribution, tandem repeat polymorphism, and phylogenetic relationship

Background: Multi-drug resistance and severe/ complicated cases are the emerging phenotypes of vivax malaria, which may deteriorate current anti-malarial control measures. The emergence of these phenotypes could be associated with either of the two Plasmodium vivax lineages. The two lineages had been categorized as Old World and New World, based on geographical sub-division and genetic and phenotypical markers. This study revisited the lineage hypothesis of P. vivax by typing the distribution of lineages among global isolates and evaluated their genetic relatedness using a panel of new mini-satellite markers. Methods: 18S SSU rRNA S-type gene was amplified from 420 Plasmodium vivax field isolates collected from different geographical regions of India, Thailand and Colombia as well as four strains each of P. vivax originating from Nicaragua, Panama, Thailand (Pak Chang), and Vietnam (ONG). A mini-satellite marker panel was then developed to understand the population genetic parameters and tested on a sample subset of both lineages. Results: 18S SSU rRNA S-type gene typing revealed the distribution of both lineages (Old World and New World) in all geographical regions. However, distribution of Plasmodium vivax lineages was highly variable in every geographical region. The lack of geographical sub-division between lineages suggests that both lineages are globally distributed. Ten mini-satellites were scanned from the P. vivax genome sequence; these tandem repeats were located in eight of the chromosomes. Mini-satellites revealed substantial allelic diversity (7-21, AE = 14.6 +/- 2.0) and heterozygosity (He = 0.697-0.924, AE = 0.857 +/- 0.033) per locus. Mini-satellite comparison between the two lineages revealed high but similar pattern of genetic diversity, allele frequency, and high degree of allele sharing. A Neighbour-Joining phylogenetic tree derived from genetic distance data obtained from ten mini-satellites also placed both lineages together in every cluster. Conclusions: The global lineage distribution, lack of genetic distance, similar pattern of genetic diversity, and allele sharing strongly suggested that both lineages are a single species and thus new emerging phenotypes associated with vivax malaria could not be clearly classified as belonging to a particular lineage on basis of their geographical origin.

Liderazgo e inteligencia emocional en personas que desempeñan jefaturas en empresas de Bogotá

El objetivo investigativo fue describir el estilo de liderazgo, el desempeño en competencias de liderazgo eficaz y el nivel de habilidades de la inteligencia emocional de jefes que trabajan en tres empresas ubicadas en la ciudad de Bogotá. Los resultados muestran que los líderes tienden a autoevaluarse con un mayor número de conductas de liderazgo transformacional que de liderazgo transaccional, a diferencia de sus seguidores que los evalúan más como líderes transaccionales. Existe bajo dominio de competencias personales y sociales de la inteligencia emocional, teniendo impacto en el estilo de liderazgo y en las variables de consecuencias organizacionales.

Inmunoterapia en pacientes con cáncer de pulmón de células no pequeñas versus terapia convencional. Revisión sistemática

RESUMEN Antecedentes y Justificación: El cáncer de pulmón es la principal causa de muerte relacionada con Cáncer en el mundo. El cáncer pulmonar de células no pequeñas (Non-Small-cell lung cancer NSCLC) representa el 85% de todos los cánceres de pulmón y en un 40% es diagnosticado tardíamente y con los tratamientos disponibles actualmente (cirugía, radioterapia y quimioterapia) presenta una supervivencia a 5 años entre el 10 y el 15%. En los últimos años han surgido nuevos tratamientos basados en la inmunoterapia que prometen mejorar la supervivencia de estos pacientes. Objetivo: Determinar la eficacia de la inmunoterapia en el tratamiento del cáncer de pulmón de células no pequeñas (NSCLC) con el fin de integrar la información disponible para su posterior uso en la clínica. Metodología: Se realizó búsqueda exhaustiva de la literatura disponible del 1 de Enero de 2003 al 31 de Diciembre de 2013. Se examinaron las siguientes bases de datos: Pubmed, Scielo, Medline, Lilacs, EMBASE, Bandolier, peDRO y Cochrane. Se utilizaron los términos MeSH de búsqueda: immunotherapy, NSCLC, clinical trials. Resultados: de 163 referencias identificadas en las bases de datos, 12 fueron seleccionadas para la revisión. Se identificaron 11 estrategias inmunoterapéuticas que fueron complementarias al uso de quimioterapia, radioterapia o ambas. No se encontró diferencia significativa entre la supervivencia global de los grupos de intervención y controles con excepción de 1 artículo. La mayoría de efectos secundarios fueron de leves a moderados y no hubo diferencias significativas entre los grupos. Discusión: no se evidenció un aumento significativo de la supervivencia global con la utilización de inmunoterapias, a excepción de la que emplea células asesinas inducidas por citocinas junto a células dendríticas. Sin embargo es necesario esperar resultados de estudios fase III en curso.

La Imagen de ciencia desvelada por los libros de texto en las representaciones icónicas de célula

El libro de texto como tal viene siendo una representación externa, temática relevante en el campo de la enseñanza de las ciencias desde la historia hasta el mundo de hoy, y es definida según Greca (2000) citado en Henao (2006) como cualquier notación signo o conjunto de símbolos que representan algo del mundo exterior. Existen dos tipos de representaciones, las externas que a su vez se dividen en lingüísticas e icónicas y las internas, pero, de acuerdo a los asuntos que son objeto de estudio en este trabajo, solo se tendrán presente las primeras

Aplicações do marketing na cultura: estratégias de captação e fidelização de públicos: o caso do cinema-Teatro Joaquim d'Almeida (Montijo)

RESUMO: O presente trabalho salienta a importância da aplicação do Marketing às instituições culturais, nomeadamente como veículo de captação e fidelização de públicos. Nesse sentido, foi estudado o Cinema-Teatro Joaquim d’Almeida, no Montijo, tendo sido realizada uma análise mais geral da programação, comunicação e públicos desde a sua reabertura em 2005 como equipamento cultural municipal e uma análise mais aprofundada da última temporada do mesmo, correspondente ao ano de 2009-2010. Pretende-se assim com este trabalho salientar a importância da aplicação do marketing à cultura através da investigação do objecto de estudo supracitado e consequente análise e sugestão de estratégias para melhoria da relação entre a referida instituição e os seus públicos. O marketing revela-se assim essencial para a construção desse relacionamento, satisfazendo cada vez mais os consumidores e simultaneamente beneficiando a instituição. ABSTRACT: This thesis intends to point out the importance of the use of marketing in cultural institutions, particularly as a medium of audiences’ attraction and loyalty building. In that sense, we studied Cinema-Teatro Joaquim d’Almeida, in Montijo. We proceeded at a general analysis of the programming, communication and audiences since it opened to public as a municipal cultural infrastructure. We proceeded at a more detailed analysis of the last season, in the year 2009-2010. Then it was elaborated a theoretical investigation about Portugal’s cultural environment and the general applications of marketing at culture and services. Later we continued the analysis of the case study, regarding the documentation supplied by this cultural institution. It was also developed a marketing research about the audiences of the Theater in order to understand their general opinion about its offers and services. With this procedure, we intended to suggest a set of marketing strategies to improve the relationship between the institution and its audiences, in order to delight even more the consumers and simultaneously to benefit the institution.

La mediación como requisito previo para descongestionar a la justicia ordinaria en cuestiones de interés público

Los problemas por los que atraviesa la Función Judicial en el país debido a la acumulación de procesos, despacho lento de las causas y otras dificultades, hacen que los usuarios no tengan confianza en la Administración de Justicia. Además en nuestro país todavía existen zonas geográficas y poblacionales aisladas de los servicios públicos y por ende del acceso a la justicia siendo necesaria su incorporación dentro de una justicia más inclusiva. Se busca entonces a través de los métodos alternos de solución de controversias, y en especial de la mediación, hacer que las personas sean sus propios jueces y que decidan sus conflictos de una manera amigable y pacífica, más aún en asuntos de interés público, de manera que se fomente una cultura de paz y en una cultura social que ha girado alrededor del litigio. Para lograr comprender el alcance de este trabajo, es necesario de dar un impulso a la mediación con un cambio en la mentalidad en los agentes de justicia ya que el conflicto no es malo por sí mismo, sino que constituye una importante fuente de dinamismo social, que acaba en el lugar común, decisivo, según el cual no importan los conflictos sino la forma de resolverlos. La investigación pretende a partir de la experiencia Argentina, EE UU y de otros países que acogieron a la mediación como requisito previo, plantear una propuesta de reforma a la actual Ley de Arbitraje y Mediación, la cual se sustentará además en los criterios de los 100 estudiantes y profesores de la Facultad de Derecho de tres diferentes universidades, así como se contó con el apoyo mediante las entrevistas a los Directores y Subdirectores de Centros de Mediación de la ciudad de Quito. El presente trabajo aborda además como tema de estudio la conciliación en el Derecho Administrativo con enfoque en la Contratación Pública por ser un tema de evidente interés público y de vital importancia en nuestros días.

No impact of malaria infection or immunisation on the expression of the immune GTPase GIMAP1 at the protein or mRNA levels (Article no. 53)

GIMAP (GTPase of the immunity-associated protein family) proteins are a family of putative GTPases believed to be regulators of cell death in lymphomyeloid cells. GIMAP1 was the first reported member of this gene family, identified as a gene up-regulated at the RNA level in the spleens of mice infected with the malarial parasite, Plasmodium chabaudi. Methods A monoclonal antibody against mouse GIMAP1 was developed and was used to analyse the expression of the endogenous protein in tissues of normal mice and in defined sub-populations of cells prepared from lymphoid tissues using flow cytometry. It was also used to assess the expression of GIMAP1 protein after infection and/or immunization of mice with P. chabaudi. Real-time PCR analysis was employed to measure the expression of GIMAP1 for comparison with the protein level analysis. Results GIMAP1 protein expression was detected in all lineages of lymphocytes (T, B, NK), in F4/80+ splenic macrophages and in some lymphoid cell lines. Additional evidence is presented suggesting that the strong expression by mature B cells of GIMAP1 and other GIMAP genes and proteins seen in mice may be a species-dependent characteristic. Unexpectedly, no increase was found in the expression of GIMAP1 in P. chabaudi infected mice at either the mRNA or protein level, and this remained so despite applying a number of variations to the protocol. Conclusion The model of up-regulation of GIMAP1 in response to infection/immunization with P. chabaudi is not a robustly reproducible experimental system. The GIMAP1 protein is widely expressed in lymphoid cells, with an interesting increase in expression in the later stages of B cell development. Alternative approaches will be required to define the functional role of this GTPase in immune cells.

The severity of malarial anaemia in Plasmodium chabaudi infections of BALB/c mice is determined independently of the number of circulating parasites

Background: Severe malarial anaemia is a major complication of malaria infection and is multifactorial resulting from loss of circulating red blood cells (RBCs) from parasite replication, as well as immune-mediated mechanisms. An understanding of the causes of severe malarial anaemia is necessary to develop and implement new therapeutic strategies to tackle this syndrome of malaria infection. Methods: Using analysis of variance, this work investigated whether parasite-destruction of RBCs always accounts for the severity of malarial anaemia during infections of the rodent malaria model Plasmodium chabaudi in mice of a BALB/c background. Differences in anaemia between two different clones of P. chabaudi were also examined. Results: Circulating parasite numbers were not correlated with the severity of anaemia in either BALB/c mice or under more severe conditions of anaemia in BALB/c RAG2 deficient mice (lacking T and B cells). Mice infected with P. chabaudi clone CB suffered more severe anaemia than mice infected with clone AS, but this was not correlated with the number of parasites in the circulation. Instead, the peak percentage of parasitized RBCs was higher in CB-infected animals than in AS-infected animals, and was correlated with the severity of anaemia, suggesting that the availability of uninfected RBCs was impaired in CB-infected animals. Conclusion: This work shows that parasite numbers are a more relevant measure of parasite levels in P. chabaudi infection than % parasitaemia, a measure that does not take anaemia into account. The lack of correlation between parasite numbers and the drop in circulating RBCs in this experimental model of malaria support a role for the host response in the impairment or destruction of uninfected RBC in P. chabaudi infections, and thus development of acute anaemia in this malaria model.

Real-time multi-model decadal climate predictions

We present the first climate prediction of the coming decade made with multiple models, initialized with prior observations. This prediction accrues from an international activity to exchange decadal predictions in near real-time, in order to assess differences and similarities, provide a consensus view to prevent over-confidence in forecasts from any single model, and establish current collective capability. We stress that the forecast is experimental, since the skill of the multi-model system is as yet unknown. Nevertheless, the forecast systems used here are based on models that have undergone rigorous evaluation and individually have been evaluated for forecast skill. Moreover, it is important to publish forecasts to enable open evaluation, and to provide a focus on climate change in the coming decade. Initialized forecasts of the year 2011 agree well with observations, with a pattern correlation of 0.62 compared to 0.31 for uninitialized projections. In particular, the forecast correctly predicted La Niña in the Pacific, and warm conditions in the north Atlantic and USA. A similar pattern is predicted for 2012 but with a weaker La Niña. Indices of Atlantic multi-decadal variability and Pacific decadal variability show no signal beyond climatology after 2015, while temperature in the Niño3 region is predicted to warm slightly by about 0.5 °C over the coming decade. However, uncertainties are large for individual years and initialization has little impact beyond the first 4 years in most regions. Relative to uninitialized forecasts, initialized forecasts are significantly warmer in the north Atlantic sub-polar gyre and cooler in the north Pacific throughout the decade. They are also significantly cooler in the global average and over most land and ocean regions out to several years ahead. However, in the absence of volcanic eruptions, global temperature is predicted to continue to rise, with each year from 2013 onwards having a 50 % chance of exceeding the current observed record. Verification of these forecasts will provide an important opportunity to test the performance of models and our understanding and knowledge of the drivers of climate change.

Coordinated Cluster/Double Star observations of dayside reconnection signatures

The recent launch of the equatorial spacecraft of the Double Star mission, TC-1, has provided an unprecedented opportunity to monitor the southern hemisphere dayside magnetopause boundary layer in conjunction with northern hemisphere observations by the quartet of Cluster spacecraft. We present first results of one such situation where, on 6 April 2004, both Cluster and the Double Star TC-1 spacecraft were on outbound transits through the dawnside magnetosphere. The observations are consistent with ongoing reconnection on the dayside magnetopause, resulting in a series of flux transfer events (FTEs) seen both at Cluster and TC-1, which appear to lie north and south of the reconnection line, respectively. In fact, the observed polarity and motion of each FTE signature advocates the existence of an active reconnection region consistently located between the positions of Cluster and TC-1, with Cluster observing northward moving FTEs with +/− polarity, whereas TC-1 sees −/+ polarity FTEs. This assertion is further supported by the application of a model designed to track flux tube motion for the prevailing interplanetary conditions. The results from this model show, in addition, that the low-latitude FTE dynamics are sensitive to changes in convected upstream conditions. In particular, changing the interplanetary magnetic field (IMF) clock angle in the model suggests that TC-1 should miss the resulting FTEs more often than Cluster and this is borne out by the observations.

Attityd till att fullfölja nuvarande studier - En applikation av The Theory of Planned Behavior

För att förutsäga och förklara människors beteenden och intentioner har ”attityd” länge varit ett centralt begrepp inom socialpsykologin. En vanlig teori och modell för ändamålet är ”theory of planned behavior” (TpB), vilken säger att en individs beteende styrs av dess intention, som i sin tur är en funktion av den personliga attityden, det sociala trycket och den upplevda kontrollen att kunna genomföra aktuellt beteende. Syftet med föreliggande studie var att undersöka attityden och intentionen till att fullfölja nuvarande studier och göra en applikation av TpB-modellen via en Internetenkät riktad till studenter på Högskolan Dalarna (N = 1292). Hypotesen att ”den upplevda kontrollen” är den viktigaste direkta variabeln för intentionen kunde godtas, vilket kan antagas bero på beteendets karaktär. Diskussion förs också kring intentionens eventuella omvandling till verkligt beteende.

Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania : an open label prospective study

Background: Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home. Methods: An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. Results: A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p <= 0.046). Conclusions: Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

A interação entre professor/tutor e aluno nas modalidades presencial e a distância do curso IPGN-SEBRAE

O presente trabalho trata da influência da Internet como tecnologia que está transformando a forma como as pessoas se relacionam, indo influenciar decisivamente nos modelos de ensino-aprendizagem. O trabalho pretende contribuir com o SEBRAE (Serviço de Apoio às micro e pequenas empresas) na avaliação de um de seus programas de Educação a Distância: o curso Iniciando Um Pequeno Grande Negócio – IPGN para conhecer como é feita a interação entre professores e tutores e alunos, considerando as duas modalidades distintas do curso, a presencial e a distância. Desta forma, este trabalho tem o objetivo geral de identificar a percepção de professores e tutores quanto ao processo de interação com alunos do curso IPGN e auxiliar na apresentação de alguns fatores que vão atuar na motivação e na retenção do alunos do referido curso. Para isso, foram realizadas entrevistas com seis tutores virtuais contratados para prestar consultoria a distância aos alunos inscritos e com seis professores que ministram as aulas do mesmo curso no modelo presencial.