Study of SUMO-2-interacting motifs in Kaposi's sarcoma-associated herpesvirus

Kaposi’s sarcoma-associated herpesvirus (KSHV) is one of the seven viruses able to cause cancer in humans. It displays a biphasic life cycle, in which the latent phase is regulated by the latency-associated nuclear antigen (LANA or kLANA), where the viral episome is maintained with limited gene expression inside the nucleus of the host B cell. During the lytic phase, viral gene products are systematically synthetized due to a time-controlled mechanism, which is activated by RTA (replication and transcription activator). SUMOylation is a reversible post-transcriptional modification involving SUMO (small ubiquitin-like modifier) proteins. A previous study in B lymphoma cells showed that kLANA contains a SUMO-interacting motif (LANASIM) that facilitates its own SUMOylation at lysine 1140. This motif also interacts with SUMO-2 modified transcription repressor KAP1, forming a transcriptional inhibitory complex along with Sin3A at the Rta gene promoter. LANASIM mutants led to loss of viral episome maintenance and lytic gene silencing. In this study, the aim was to assess the importance of LANASIM using an in vivo animal infection model. Considering the functional homology between murine herpesvirus-68 (MHV-68) mLANA and KSHV kLANA, LANASIM loss of function mutations were introduced into two MHV-68 chimeras. One where the mLANA coding sequence was replaced with the one from kLANA (v-kLANA SIM) and another where additionally the kLANA DNA binding domain was replaced with the one from mLANA (v-KM SIM)

Ventajas de la tintura por pulverización mediante la aplicación de pigmentos cromotrópicos.

Los pigmentos cromotrópicos o termocrómicos dan un buen resultado en la obtención de efectos especiales en el diseño textill si bien su elevado coste impide un uso más amplio. La aplicación mediante pulverización implica una significativa reducción de costes porque se necesita una cantidad inferior a la utilizada en los procesos de estampado tradicionales y también porque la no necesidad de preparar plantillas-tamiz hace que el tiempo requerido sea menor, adaptándose al propio tiempo, a las nuevas técnicas de gestión integrada en la cadena de abastecimiento, especialmente en lo que se refiere a respuesta rápida.Chromotropic or thermochromic pigments are a good way to obtain special effects in textile design, but its price is a impediment for a wider divulgation. The application by pulverization allo ws a significant reduction of costs because we need a smaller quantity than traditional printing processes, but also because as we don't need to prepare screens the time needed is reduced and is adapted to the new techniques of integrated management on the supplying chain of, namely the quick response.Les pigments chromotropiques ou thermotropiques donnent de bons résultats pour obtenir des effets spéciaux d'impression textile, mais leur coût élevé empeche de les utiliser plus sovent. L'application par pulvérisation implique une réduction significative des coûts. Il faut en effet des quantités moindres que les quantités utilisées avec des prix traditionnels d'impression et il n'est pas nécessaire de préparer des patrons-tamis, d'où un gain de temps et une meilleure adaptation aux nouvelles techniques de gestion intégrée dans la chaîne d'approvisionnement, notamment en ce qui concerne la réponse rapide.Peer Reviewe

Memory assist in ambient assisted living

Series : IFIP International Federation for Information ProcessingHuman collective set of experiences makes us who we are and help us delineate a path for our ongoing life. Ageing, however, progressively limits our ability to save, in our internal memory, these same experiences, or, at least, limits our capability to remember them. The capability to remember, intrinsic to our memory, is a very important one to us, as a human been, being this what deferent’s us from several other species. In this paper we present a memory assistant sub module of a bigger project, the VirtualECare, which ability will be to remember us, not our past experiences, but our routine day-to-day tasks and activities, in a somehow proactive manner, thus, allowing us to have some relaxation about them, and focus the remaining of our ability in most important facts

Perivascular adipose tissue as a relevant fat depot for cardiovascular risk in obesity

Obesity is associated with increased risk of premature death, morbidity, and mortality from several cardiovascular diseases (CVDs), including stroke, coronary heart disease (CHD), myocardial infarction, and congestive heart failure. However, this is not a straightforward relationship. Although several studies have substantiated that obesity confers an independent and additive risk of all-cause and cardiovascular death, there is significant variability in these associations, with some lean individuals developing diseases and others remaining healthy despite severe obesity, the so-called metabolically healthy obese. Part of this variability has been attributed to the heterogeneity in both the distribution of body fat and the intrinsic properties of adipose tissue depots, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, hormonal control, thermogenic ability, and vascularization. In obesity, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. The adventitial fat layer, also known as perivascular adipose tissue (PVAT), is of major importance. Similar to the visceral adipose tissue, PVAT has a pathophysiological role in CVDs. PVAT influences vascular homeostasis by releasing numerous vasoactive factors, cytokines, and adipokines, which can readily target the underlying smooth muscle cell layers, regulating the vascular tone, distribution of blood flow, as well as angiogenesis, inflammatory processes, and redox status. In this review, we summarize the current knowledge and discuss the role of PVAT within the scope of adipose tissue as a major contributing factor to obesity-associated cardiovascular risk. Relevant clinical studies documenting the relationship between PVAT dysfunction and CVD with a focus on potential mechanisms by which PVAT contributes to obesity-related CVDs are pointed out

Memory assistant in everyday living

Memory is one’s mental ability to store, to retain, and recall information, representing past and future, our dreams and/or expectations. However, as the human been ages, the capacity of remembering decreases as well the ability to pile up new memories, therefore affecting our quality-of-living and lowering our self- esteem. This configures a social and human dilemma. With the present work we intend to address some of these problems, in terms of a Personal Memory Assistant (PMA), in order to help the user to remember things and occurrences, making it in a proactive mode. It will also cater for some form of relaxation on the part of the user

Estudio de los efectos ototóxicos en 725 pacientes tratados con antimaláricos en el Hospital Central de Maputo (Mozambique)

Consultable des del TDXTítol obtingut de la portada digitalitzadaLos fármacos antimaláricos tienen capacidad ototóxica debido a las lesiones que pueden producir en la cóclea y/o en el vestíbulo. La lesión coclear se manifiesta frecuentemente por un cuadro de hipoacusia neurosensorial, que afecta inicialmente a las frecuencias altas; otros síntomas que aparecen con menor frecuencia son los zumbidos. La hipoacusia neurosensorial puede ser reversible o irreversible y se clasifica en diferentes grados: ligera, moderada, severa y profunda. La utilización en Mozambique de fármacos antimalaricos es obligatoria ya que es un país de malaria endémica. La incidencia de malaria es elevada, representando el 48% de todas las consultas externas de los servicios sanitarios del país, y afectando al 90,3% de la población que habita las zonas periféricas de la ciudad de Maputo. Los tratamientos antimaláricos utilizados en Mozambique se adaptan al Protocolo de Lucha Contra la Malaria establecido por el Ministerio de Salud en el año 2002 y a las indicaciones de la OMS. Sin embargo, sólo los pacientes que acuden a los centros sanitarios del país tienen control del tratamiento, mientras que otros pacientes pueden adquirir y automedicarse con fármacos que están disponibles en centros no sanitarios. En estos casos, no existe confirmación de laboratorio de la enfermedad ni control de las dosis, de la duración ni de posibles factores de riesgo de ototoxicidad (insuficiencia renal, insuficiencia hepática, infecciones crónicas, predisposición familiar y genética, tratamiento previo o simultáneo con otras drogas ototóxicas, patología coclear previa etc.). El estudio se realizó en 725 pacientes ingresados en el Hospital Central de Maputo (Mozambique) con un episodio de malaria severa, que fueron tratados con los fármacos antimaláricos establecidos en el Protocolo Nacional de Lucha contra la Malaria. 12 de estos pacientes fueron niños cuyas madres habían sido tratadas con fármacos antimaláricos durante el embarazo. Aunque a todos los pacientes se les programó una visita de control, sólo 96 de ellos acudieron a la misma. El análisis estadístico de los datos se realizó mediante el programa SPSS (versión 11.5). De los resultados obtenidos destacamos que el 78% de los pacientes presentaron una hipoacusia neurosensorial, siendo irreversible en el 7,6%. El grado de hipoacusia fue ligero en 47,9%, moderado en 33,8%, severo en 14,4% y profundo en 3,9%. La incidencia de hipoacusia y el grado de la misma fue mayor en los pacientes de sexo femenino y en los grupos de mayor edad. Los fármacos antimaláricos utilizados por los pacientes fueron la Quinina asociada a Fansidar® (37,7%), la Quinina (33,8%), la Artemisina asociada a Fansidar® (7,9 %), la Quinina asociada a Artemisina (6,6%), la Artemisina asociada a Fansidar® y a Quinina (5,4%), la Artemisina (2,6%), el Fansidar® (2,1%) y la Cloroquina sola o asociada a otros fármacos antimalaricos (4%). La mayor incidencia de hipoacusias la determinaron los tratamientos que incluían la Quinina mientras que los mayores grados, y las hipoacusias irreversibles, se relacionaron con el tratamiento con Cloroquina. En 251 pacientes (34,6%) se manifestaron además otros síntomas de ototoxicidad, como zumbidos, vértigos, nauseas y vómitos. Los síntomas asociados aparecieron más frecuentemente en los pacientes de los grupos de mayor edad. En 324 de los pacientes estudiados (44,7%) se observaron una serie de enfermedades asociadas, siendo la más frecuentes la anemia (20,7%), la trombocitopenia (17,7%) y las alteraciones del comportamiento (4,4%). Estas enfermedades asociadas fueron más frecuentes en los grupos de menor edad. Destacamos la relación positiva encontrada entre estas enfermedades y la presencia de hipoacusia, así cómo un menor grado de hipoacusia en los pacientes que manifestaron un cuadro de anemia. El estudio concluye que los fármacos antimaláricos utilizados actualmente en Mozambique tienen una alta incidencia de ototoxicidad, siendo necesaria su revisión.Antimalarials may cause ototoxicity due to the injuries that they may inflict upon the cochlea and/or the vestibule. Cochlear injuries frequently reveal sensoryneural hearing-loss, which initially takes place in the higher frequencies; feeling of fullness, roaring or ringing in the ears are less frequent symptoms that may also occur. Sensoryneural hearing-loss can be reversible or irreversible, and it presents a gradation at different levels: low, moderate, severe and profound. The use of antimalarial drugs in Mozambique is compulsory, since the incidence of endemic malaria is very high; it represents 48% of the total external consultations in the health services of the country, and affects 90.3% of the population living in the peripheral area of Maputo. The antimalarial treatment used in Mozambique adapts to the National Protocol of Prevention and Treatment of Malaria, as established by the Department of Health and the WHO in 2002. However, only those patients attending the health unities of the country stay in control to receive the appropriate treatment, while other patients may obtain antimalarials for self-treatment since there is medication available at those unities. In this case, no control is being exerted by the laboratories: no control of the dosage taken, nor of the duration or even of the possible ototoxic risks derived from it (namely, renal and hepatic insufficiency, chronic infections, genetic predisposition, previous or simultaneous treatment with other ototoxical drugs, previous cochlear pathology, etc.). This study was performed on 725 patients diagnosed with severe malaria and who had been taken into the Central Hospital of Maputo and treated with the antimalarials determined by the Protocol of Prevention and Treatment of Malaria. Twelve of these patients were children whose mothers had been medicated during pregnancy. A second control was programmed for all the patients, yet only 96 of them attended the meeting. The statistical analysis of the data was carried out with the SPSS program (version 11.5). The results showed that 78% of the patients were diagnosed with sensoryneural hearing-loss, which turned out to be irreversible in 7.6% of them. The level of hearing-loss was low in 47.9% of the cases, moderated in 33.8%, severe in 14.4% and profound in 3.9% of the cases. The incidence and level of hearing-loss was higher in female and elderly patients. The antimalarial drugs used for the treatment of these patients were as follows: Quinine associated with Fansidar® (37.7%), Quinine (33.8%), Artemisine associated with Fansidar® (7.9%), Quinine associated with Artemisine (6.6%), Artemisine associated with Quinine and Fansidar® (5.4%), Artemisine (2.6%), Fansidar® (2.1%) and Chloroquine (either associated with other antimalarials or not, 4%). The highest incidence of hearing-loss was caused by the treatment which included Quinine, while treatment with Chloroquine was associated to the most severe cases as well as the irreversible ones. In 251 patients (34.6%), other ototoxic symptoms were detected, such as the feeling of 'fullness' and ringing in the ear, vertigo, nausea and vomiting. The associated symptoms were more frequently in older patients. In 324 patients (44.7%,) a series of associated illnesses were observed, the most frequent being anaemia (20.7%), thrombocytopenia (17.7%) and major behaviour alterations (4.4%). These illnesses were also mostly frequent in the eldest patients. A positive connection between these illnesses and the presence of hearing-loss should be highlighted, as well as the lower level of hearing-loss in patients diagnosed with anaemia. The study concludes that the antimalarial drugs utilised nowadays in Mozambique are responsible of a high occurrence of ototoxicity, and that a close revision of their use is consequently necessary

Internship report: A guide to structured products – Reverse convertible on S&P500

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and EconomicsThe purpose of this report is to describe the main characteristics of structured products. These products can be divided in Capital Guaranteed products and Non Capital guaranteed products, having these two types of products different risk profiles and potential returns. In the final part of the report a Reverse Convertible on the S&P500 is created, which offers 8.57% return per year subject to a capital loss in case the underlying goes below 70% initial level, in one year

Política ambiental, municípios e cooperação intergovernamental no Brasil

The purpose of this paper is to explore the role of intergovernmental cooperation in federal environmental policies from the perspective of Brazilian local governments, considering Brazilian federal institutional framework. The analysis of the constitutional municipal agenda highlights that environmental defense activities provides the background for the analysis of selected examples of federal environmental policy. We conclude that federal success depends on a great extent on municipal support because they are in a unique position to combine the use of typical environmental strategies and instruments with policy instruments exclusive to municipalities.Neste artigo é realizada uma análise exploratória do papel das relações intergovernamentais nas iniciativas federais de defesa ambiental no Brasil do ponto de vista dos governos locais, na perspectiva federativa. A análise da agenda constitucional dos municípios fornece elementos para o exame de iniciativas do governo federal no campo ambiental por meio de exemplos selecionados. Conclui-se que seu êxito depende, em grande extensão, da adesão dos municípios, que têm uma condição única para combinar instrumentos típicos da institucionalidade ambiental com outros de seu uso exclusivo