Treatment with benznidazole in association with immunosuppressive drugs in mice chronically infected with Trypanosoma cruzi: investigation into the possible development of neoplasias

Benznidazole is recommended in Brazil for the treatment of Trypanosoma cruzi infection in acute and early chronic phases of Chagas' disease. Observations by others have indicated a higher incidence of neoplasias in immunosuppressed patients, presenting Chagas' disease reactivation, submitted to treatment with benznidazole. In the present study, we investigated whether there is a potentiation in the generation of lymphomas in chronically infected mice, treated with immunosuppressive drugs and benznidazole. For this, 142 Swiss mice chronically infected with the 21 SF strain of T. cruzi and 72 normal Swiss mice were used. Both infected and normal mice were divided into experimental groups and submitted to one of the following treatment regimens: benznidazole alone; immunosuppressive drugs (azathioprine, betamethasone and cyclosporin); a combination of immunosuppressive drugs and benznidazole; and untreated controls. In the infected group treated with benznidazole, one mouse developed a non-Hodgkin's lymphoma. This finding has been interpreted as a spontaneous tumor of mice. The study of the chronically infected mice treated with the combination of immunosuppressive drugs and benznidazole demonstrated an absence of lymphomas or other neoplasias. These findings support the indication of benznidazole, as the drug of choice, for immunosuppressed patients that develop a reactivation of Chagas' disease.

Some Notes on the Reception of Josquin and of Northern Idioms in Portuguese Music and Culture

Although Josquin is by far the best-represented foreign composer in Gonçalo de Baena's Arte novamente inventada pera aprender a tanger (Lisbon, 1540), his music is undeniably under-represented both in the extant sixteenth-century Portuguese manuscripts containing Franco-Flemish polyphony and in volumes imported from the Netherlands such as Coimbra MM 2 and VienNB 1783. Josquin’s reputation made him, along with Ockeghem, a symbol in Portuguese humanistic culture, but up to at least the late 1530s his name seems to have been much better known than his music. Nevertheless, possible allusions to specific works by Josquin can be found in early- and mid-sixteenth-century Portuguese polyphony. By the 1520s, the general technical and stylistic characteristics of his and the following generation of northerners had begun to permeate locally produced polyphony. This eventually replaced the late-fifteenth- and early-sixteenth-century pan-consonant and homorythmic style associated with the Aragonese and the so-called Spanish court repertory.

The implementation of an Enterprise Geographical Information System to support Cadastre and Expropriation activities.

The processes of mobilization of land for infrastructures of public and private domain are developed according to proper legal frameworks and systematically confronted with the impoverished national situation as regards the cadastral identification and regularization, which leads to big inefficiencies, sometimes with very negative impact to the overall effectiveness. This project report describes Ferbritas Cadastre Information System (FBSIC) project and tools, which in conjunction with other applications, allow managing the entire life-cycle of Land Acquisition and Cadastre, including support to field activities with the integration of information collected in the field, the development of multi-criteria analysis information, monitoring all information in the exploration stage, and the automated generation of outputs. The benefits are evident at the level of operational efficiency, including tools that enable process integration and standardization of procedures, facilitate analysis and quality control and maximize performance in the acquisition, maintenance and management of registration information and expropriation (expropriation projects). Therefore, the implemented system achieves levels of robustness, comprehensiveness, openness, scalability and reliability suitable for a structural platform. The resultant solution, FBSIC, is a fit-for-purpose cadastre information system rooted in the field of railway infrastructures. FBSIC integrating nature of allows: to accomplish present needs and scale to meet future services; to collect, maintain, manage and share all information in one common platform, and transform it into knowledge; to relate with other platforms; to increase accuracy and productivity of business processes related with land property management.

Phage display as a tool for development of novel therapeutics for breast cancer

Phage display technology is a powerful platform for the generation of highly specific human monoclonal antibodies (Abs) with potential use in clinical applications. Moreover, this technique has also proven to be a reliable approach in identifying and validating new cancer-related targets. For scientific or medical applications, different types of Ab libraries can be constructed. The use of Fab Immune libraries allows the production of high quality and affinity antigen-specific Abs. In this work, two immune human phage display IgG Fab libraries were generated from the Ab repertoire of 16 breast cancer patients, in order to obtain a tool for the development of new therapeutic Abs for breast cancer, a condition that has great impact worldwide. The generated libraries are estimated to contain more than 108 independent clones and a diversity over 90%. Libraries validation was pursued by selection against BSA, a foreign and highly immunogenic protein, and HER2, a well established cancer target. Preliminary results suggested that phage pools with affinity for these antigens were selected and enriched. Individual clones were isolated, however, it was not possible to obtain enough data to further characterize them. Selection against the DLL1 protein was also performed, once it is a known ligand of the Notch pathway, whose deregulation is associated to breast cancer, making it an interesting target for the generation of function-blocking Abs. Selection resulted in the isolation of a clone with low affinity and Fab expression levels. The validation process was not completed and further effort will have to be put in this task in the future. Although immune libraries concept implies limited applicability, the library reported here has a wide range of use possibilities, since it was not restrained to a single antigen but instead thought to be used against any breast cancer associated target, thus being a valuable tool.

Co-infection and risk factors of tuberculosis in a Mexican HIV+ population

INTRODUCTION: The situation of tuberculosis (TB) is being modified by the human immunodeficiency virus (HIV), which is increasing the occurrence of new cases and the generation of drug resistant strains, affecting not only the people infected with HIV, but also their close contacts and the general population, conforming a serious public health concern. However, the magnitudes of the factors associated to this co-infection differ considerably in relation to the population groups and geographical areas. METHODS: In order to evaluate the prevalence and risk factors for the co-infection of tuberculosis (TB) in a population with human immunodeficiency virus (HIV+) in the Southeast of Mexico, we made the analysis of clinical and epidemiological variables and the diagnosis of tuberculosis by isolation of mycobacteria from respiratory samples. RESULTS: From the 147 HIV+ individuals analyzed, 12 were culture positive; this shows a prevalence of 8% for the co-infection. The only variable found with statistical significance for the co-infection was the number of CD4-T < 200 cells/mm³, OR 13 (95%, CI 2-106 vs 12-109). CONCLUSIONS: To our knowledge this is the first report describing the factors associated with tuberculosis co -infection with HIV in a population from Southern Mexico. The low number of CD4 T-cells was the only variable associated with the TB co-infection and the rest of the variables provide scenarios that require specific and particular interventions for this population group.

An integrated approach to Physcomitrella patens transcriptomics reveals importantclues of the evolutionary development of plant organs and sexual reproduction

Land plant evolution required the generation of a new body plan that could resist the harsher and fluctuating environmental conditions found outside of aquatic environments. Unraveling the genetic basis of plant developmental innovations is not only revealing in terms of an evolutionary point of view, but it is also important for understanding the emergence of agronomically important traits. Comparative genetic studies between basal and modern land plants, both at the genome and trancriptome levels, can help in the generation of hypotheses related to the genetic basis of plant evolutionary development.(...)

“What matters?”: The case of sustainability reporting in Spain and Portugal

This project explores the case of Sustainability Reporting in Spain and Portugal and the recently launched new generation of Global Reporting Initiative Guidelines. The sample of the study is composed of companies included in the “GRI Report list 1999-2015”. In particular 2013 onwards 51 companies that published their G4 Report are taken into consideration. An indirect study is conducted based on the content of the sustainability reports of companies that implemented the Global Report Initiatives (GRI) reporting guidelines in order to identify focus areas of sustainability reporting in Spain and Portugal, analyzing trends and patterns relevant for observation. The project also promotes a discussion of the usability of the G4 guidelines and the adoption of materiality definition.

Detection of immunogenic proteins from Anopheles sundaicussalivary glands in the human serum

AbstractINTRODUCTION:The saliva of mosquitoes has an important role in the transmission of several diseases, including malaria, and contains substances with vasomodulating and immunomodulating effects to counteract the host physiological mechanisms and enhance pathogen transmission. As immunomodulatory components, salivary gland proteins can induce the generation of specific IgG antibodies in the host, which can be used as specific biomarkers of exposure to Anopheles sundaicus . The objective of this study was to identify immunogenic proteins from the salivary glands of Anopheles sundaicus by reaction with sera from individuals living in malaria-endemic areas who are thus exposed to Anopheles mosquitoes.METHODS:IgG antibodies targeting salivary gland proteins in serum samples from individuals living in malaria-endemic areas were measured by enzyme-linked immunosorbent assay (ELISA). Sera from healthy individuals living in non-endemic areas were used as negative controls. Determination of the presence of salivary gland immunogenic proteins was carried out by western blotting.RESULTS:Sixteen bands appeared in sodium dodecyl sulfate polyacrylamide gel electrophoresis, with molecule weights ranging from 22 to 144kDa. Among the exposed individuals, IgG responses to salivary gland proteins were variable. Protein bands with molecular weights of 46, 41, 33, and 31kDa were the most immunogenic. These immunogenic proteins were consistently recognized by pooled serum and individual samples from people living in malaria-endemic areas but not by negative controls.CONCLUSIONS:These results support the potential use of immunogenic proteins from the salivary glands of Anopheles as candidate markers of bite exposure or in malaria vaccines.

Towards modification of Medicago truncatula epigenome: genome editing with engineered nucleases

Periodic drought is the primary limitation of plant growth and crop yield. The rise of water demand caused by the increase in world population and climate change, leads to one of the biggest challenges of modern agriculture: to increase food and feed production. De novo DNA methylation is a process regulated by small interfering RNA (siRNAs), which play a role in plant response and adaptation to abiotic stress. In the particular case of water deficit, growing evidences suggest a link between the siRNA pathways and drought response in the model legume Medicago truncatula. As a first step to understand the role of DNA methylation under water stress, we have set up several bioinformatics and molecular methodologies allowing the design of Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 systems and the assembly of TALENs (transcription activator-like effector nucleases), to target both dicer-like 3 (MtDCL3) and RNA-Dependent RNA polymerase (MtRDR2), enzymes of the RNA-directed DNA methylation pathway. TALENs efficiency was evaluated prior to plant transformation by a yeast-based assay using two different strategies to test TALENs activity: Polyacrylamide gel electrophoresis (PAGE) and Single strand conformation polymorphisms (SSCP). In this assay, yeast cells triple transformation emerged as good and rapid alternative to laborious yeast mating strategies. PAGE analysis might be a valuable tool to test TALENs efficacy in vivo if we could increase TALENs activity. SSCP-based approach proved to be ineffective due to the generation of several false positives. TALENs and CRISPR/Cas9 system constructed and designed in this work will in the future certainly enable the successful disruption of DCL3 and RDR2 genes and shed the light on the relationship between plant stress resistance and epigenetic regulation mediated by siRNAs in M.truncatula.

Optimization of production of anti-cancer vaccines based on dendritic cells

Cancer remains as one of the top killing diseases in first world countries. It’s not a single, but a set of various diseases for which different treatment approaches have been taken over the years. Cancer immunotherapy comes as a “new” breath on cancer treatment, taking use of the patients’ immune system to induce anti-cancer responses. Dendritic Cell (DC) vaccines use the extraordinary capacity of DCs’ antigen presentation so that specific T cell responses may be generated against cancer. In this work, we report the ex vivo generation of DCs from precursors isolated from clinical-grade cryopreserved umbilical cord blood (UCB) samples. After the thawing protocol for cryopreserved samples was optimized, the generation of DCs from CD14+ monocytes, i.e., moDCs, or CD34+ hematopoietic stem cells (HSCs), i.e, CD34-derived DCs, was followed and their phenotype and function evaluated. Functional testing included the ability to respond to maturation stimuli (including enzymatic removal of surface sialic acids), Ovalbumin-FITC endocytic capacity, cytokine secretion and T cell priming ability. In order to evaluate the feasibility of using DCs derived from UCB precursors to induce immune responses, they were compared to peripheral blood (PB) moDCs. We observed an increased endocytosis capacity after moDCs were differentiated from monocyte precursors, but almost 10-fold lower than that of PB moDCs. Maturation markers were absent, low levels of inflammatory cytokines were seen and T cell stimulatory capacity was reduced. Sialidase enzymatic treatment was able to mature these cells, diminishing endocytosis and promoting higher T cell stimulation. CD34-derived DCs showed higher capacity for both maturation and endocytic capacity than moDCs. Although much more information was acquired from moDCs than from CD34-derived DCs, we conclude the last as probably the best suited for generating an immune response against cancer, but of course much more research has to be performed.

Revolution in Crisis: The Ruptures of Revolution and Ruptured Revolutions Through the Ruptures of Artistic Practice

This article proposes an investigation of the history and memory of the Carnation Revolution through the lens of contemporary art. Drawing upon the argument according to which history and memory are investigated by visual artists by means other, but no less relevant, than those of professional historians, this article will argue for the importance of attending to the visual, auditory, textual, object- and research-based ways in which artists from several generations and geographies have been unearthing the repressed histories and memories of the Carnation Revolution in Portugal and of anticolonial struggles, decolonization and post-independence nation-building in Mozambique, Guinea-Bissau and Angola. The discussion focuses on several works by Ângela Ferreira, but attention will also be paid to precursors in imaging the Revolution, such as Ana Hatherly, and to a younger generation of artists such as Filipa César, Kiluanji Kia Henda and Daniel Barroca.

The relationship between the education level of successor's and the firm performance in German publicly listed family firms- an empirical analysis

The purpose of this thesis is to investigate how far the education level of the second or third generation of publicly traded German family firms affects the post-succession firm performance. By conducting a correlational and regression design, the aim is to examine how several variables influence the performance of family firms. Performance measures, for example ROA and Tobin’s q and variables, like Education level and succession periods, examine analytically that a positive succession trend will occur. However, with the used model, only a less rigid model shows empirical evidence.

Development of foam one-part geopolymers with enhanced thermal insulation performance and low carbon dioxide emissions

Buildings are responsible for more than 40% of the energy consumption and greenhouse gas emissions. Thus, increasing building energy efficiency is one the most cost-effective ways to reduce emissions. The use of thermal insulation materials could constitute the most effective way of reducing heat losses in buildings by minimising heat energy needs. These materials have a thermal conductivity factor, k (W/m.K) lower than 0.065 while other insulation materials such as aerated concrete can go up to 0.11. Current insulation materials are associated with negative impacts in terms of toxicity. Polystyrene, for example contains anti-oxidant additives and ignition retardants. In addition, its production involves the generation of benzene and chlorofluorocarbons. Polyurethane is obtained from isocyanates, which are widely known for their tragic association with the Bhopal disaster. Besides current insulation materials releases toxic fumes when subjected to fire. This paper presents experimental results on one-part geopolymers. It also includes global warming potential assessment and cost analysis. The results show that only the use of aluminium powder allows the production mixtures with a high compressive strength however its high cost means they are commercially useless when facing the competition of commercial cellular concrete. The results also show that one-part geopolymer mixtures based on 26%OPC +58.3%FA +8%CS +7.7%CH and 3.5% hydrogen peroxide constitute a promising cost efficient (67 euro/m3), thermal insulation solution for floor heating systems with low global warming potential of 443 KgCO2eq/m3.

Development of innovative hybrid sandwich panel slabs: Experimental results

The authors appreciate the collaboration of the following labs: Civitest for developing DHCC materials, PIEP for conducting VARTM process (Eng. Luis Oliveira) and Department of Civil Engineering of Minho University to perform the tests (Mr. Antonio Matos and Eng. Marco Jorge).

Blast loading of masonry infills: testing and simulation

This work intends to present a newly developed test setup for dynamic out-of-plane loading using underWater Blast Wave Generators (WBWG) as loading source. Underwater blasting operations have been, during the last decades, subject of research and development of maritime blasting operations (including torpedo studies), aquarium tests for the measurement of blasting energy of industrial explosives and confined underwater blast wave generators. WBWG allow a wide range for the produced blast impulse and surface area distribution. It also avoids the generation of high velocity fragments and reduces atmospheric sound wave. A first objective of this work is to study the behavior of masonry infill walls subjected to blast loading. Three different masonry walls are to be studied, namely unreinforced masonry infill walls and two different reinforcement solutions. These solutions have been studied previously for seismic action mitigation. Subsequently, the walls will be simulated using an explicit finite element code for validation and parametric studies. Finally, a tool to help designers to make informed decisions on the use of infills under blast loading will be presented.