RCAAP Repository

Este documento descreve detalhadamente todo o trabalho de estágio desenvolvido durante 9 meses na empresa GEDI (Gabinete de Estudos e Divulgação Informática, SA) pelo aluno Dan Mihai Ile, no âmbito do Mestrado em Engenharia Informática da Faculdade de Ciências da Universidade de Lisboa. Consta num projecto desenvolvido com objectivo de melhorar a qualidade, metodologia de desenvolvimento e utilização da framework SIAG tanto pelos utilizadores como pela equipa de desenvolvimento da mesma empresa. Pretende-se desenvolver um sistema que permita a criação de componentes de interface dinâmicos directamente no browser utilizando tecnologias como AJAX com interface web 2.0, GWT, web-services e sistema de mensagens para comunicação distribuída entre vários componentes da framework.

Central memory T cells (TCM) patrol lymph nodes, providing central immunosurveillance against known pathogens, but have not been described as conducting primary tissue immunosurveillance. We analyzed the expression of tissue-homing addressins in human TCM vs effector memory T cells (TEM) from the same donors. In humans, the majority of human TCM were tropic for either skin or gut, and the overall tissue tropism of TCM was comparable to that of TEM TCM were present in healthy, noninflamed human skin, lung, colon, and cervix, suggesting a role for TCM in the primary immunosurveillance of peripheral tissues. TCM also had potent effector functions; 80% of CD8+ TCM produced TC1/TC2/TC17/TC22 cytokines. TCM injected into human skin-grafted mice migrated into skin and induced inflammatory eruptions comparable to TEM-injected mice. In summary, human TCM express peripheral tissue-homing receptors at levels similar to their effector memory counterparts, are found in healthy human tissues, have impressive effector functions, and can act alone to induce skin inflammation in human engrafted mice. Our studies support a novel role for human TCM in primary immunosurveillance of peripheral tissues and highlight the important role of this long-lived cell type in tissue-based immune responses.

Campylobacter jejuni and Campylobacter coli are the most common cause of bacterial gastroenteritis worldwide. Additionally, C. jejuni is the most common bacterial etiological agent in the autoimmune Guillain-Barré syndrome (GBS). Ganglioside mimicry by C. jejuni lipooligosaccharide (LOS) is the triggering factor of the disease. LOS-associated genes involved in the synthesis and transfer of sialic acid (glycosyltranferases belonging to family GT-42) are essential in C. jejuni to synthesize ganglioside-like LOS. Despite being isolated from GBS patients, scarce genetic evidence supports C. coli role in the disease. In this study, through data mining and bioinformatics analysis, C. coli is shown to possess a larger GT-42 glycosyltransferase repertoire than C. jejuni. Although GT-42 glycosyltransferases are widely distributed in C. coli population, only a fraction of C. coli strains (1%) are very likely able to express ganglioside mimics. Even though the activity of C. coli specific GT-42 enzymes and their role in shaping the bacterial population are yet to be explored, evidence presented herein suggest that loss of function of some LOS-associated genes occurred during agriculture niche adaptation.

Micro-RNAs (miRNAs) are small non-coding RNAs that act as negative regulators of the genomic output. Their intrinsic importance within cell biology and human disease is well known. Their mechanism of action based on the base pairing binding to their cognate targets have helped the development not only of many computer applications for the prediction of miRNA target recognition but also of specific applications for functional assessment and analysis. Learning about miRNA function requires practical training in the use of specific computer and web-based applications that are complementary to wet-lab studies. In order to guide the learning process about miRNAs, we have created miRNAtools (http://mirnatools.eu), a web repository of miRNA tools and tutorials. This article compiles tools with which miRNAs and their regulatory action can be analyzed and that function to collect and organize information dispersed on the web. The miRNAtools website contains a collection of tutorials that can be used by students and tutors engaged in advanced training courses. The tutorials engage in analyses of the functions of selected miRNAs, starting with their nomenclature and genomic localization and finishing with their involvement in specific cellular functions.

Less is more: The efficacy of antibody-drug conjugates (ADCs) for cancer therapy is traditionally associated with cleavable linkers for payload release. Evidence now suggests that simpler constructs without cleavable moieties can afford more stable and effective ADCs.

Although yet poorly defined and often misused, the concept of functional mobility has been used in research studies as a more global and ecological outcome of patients’ health status. Functional mobility is a person’s physiological ability to move independently and safely in a variety of environments in order to accomplish functional activities or tasks and to participate in the activities of daily living, at home, work and in the community. Parkinson’s disease (PD) has a direct impact on patients’ motor control and on mobility in general. Even with optimal medical management, the progression of PD is associated with mounting impairments at different levels of body function, causing marked limitations in a wide variety of activities, as well as a severe disability and loss of autonomy. Despite this, for everyday functioning PD patients need to have a good functional mobility that allow them to get around effortlessly in a reasonable amount of time to access to the same environments as others. This paper reviewed the concept of functional mobility applied to PD. This was done through an International Classification of Functioning and Disability (ICF) perspective. Recommendations to address the known factors that contribute to a poor functional mobility were outlined while suggestions for clinical practice and research were made.

In the second edition of the Huntington’s Disease Clinical Trials Corner we list all currently registered and ongoing clinical trials, summarise the top-line results of the recently-announced IONIS-HTTRX trial (NCT02519036), expand on Wave Life Sciences’ PRECISION-HD1 (NCT03225833) and PRECISION-HD2 (NCT03225846), and cover one recently finished trial: the FIRST-HD deutetrabenazine trial (NCT01795859).

Four series of primaquine (PQ) derivatives were screened for antitubercular and antiplasmodial activity: amides 1a-k, ureas 2a-s, semicarbazides 3a-c and bis-ureas 4a-u. Antimycobacterial activity of PQ derivatives against Mycobacterium tuberculosis (MTB), M. avium complex (MAC) and M. avium subsp. paratuberculosis (MAP) were evaluated in vitro and compared with PQ and the standard antitubercular drugs. In general, the PQ derivatives showed higher potency than the parent compound. Most of the compounds of series 1 and 2 showed high activity against MAP, comparable or even higher than the relevant drug ciprofloxacin, and weak or no activity against MTB and MAC. bis-Trifluoromethylated cinnamamide 1k showed low cytotoxicity and high activity against all three Mycobacterium species and their activities were comparable or slightly higher than those of the reference drugs. PQ urea derivatives with hydroxyl, halogen and trifluoromethyl substituents on benzene ring 2f-p exerted very strong antimycobacterial activity towards all tested mycobacteria, stronger than PQ and the relevant standard drug(s). Unfortunately, these compounds had relatively high cytotoxicity, except bromo 2l and trifluoromethyl 2m, 2n derivatives. In general, meta-substituted derivatives were more active than analogues para-derivatives. Phenyl ureas were also more active than cycloalkyl or hydroxyalkyl ureas. Semicarbazide 3a showed similar activity as PQ, while the other two semicarbazides were inactive. Bis-urea derivatives 4 were generally less active than the urea derivatives sharing the same scaffold, differing only in the spacer type. Out of 21 evaluated bis-urea derivatives, only p-Cl/m-CF3 phenyl derivative 4p, benzhydryl derivatives 4t and 4u and bis-PQ derivative 4s showed high activity, higher than all three reference drugs. After comparison of activity and cytotoxicity, urea 2m and bis-urea 4u could be considered as the most promising agents. Antimalarial potential of PQ derivatives in vitro against the liver stage of P. berghei was evaluated as well. 3-(4-Chlorophenyl)-1-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]urea (4l) was the most active compound (IC50 = 42 nM; cytotoxicity/activity ratio >2000). Our results bring new insights into development of novel anti-TB and antimalarial compounds.

Genome engineering is a branch of modern biotechnology composed of a cohort of protocols designed to construct and modify a genotype with the main objective of giving rise to a desired phenotype. Conceptually, genome engineering is based on the so called genome editing technologies, a group of genetic techniques that allow either to delete or to insert genetic information in a particular genomic locus. Ten years ago, genome editing tools were limited to virus-driven integration and homologous DNA recombination. However, nowadays the uprising of programmable nucleases is rapidly changing this paradigm. There are two main families of modern tools for genome editing depending on the molecule that controls the specificity of the system and drives the editor machinery to its place of action. Enzymes such as Zn-finger and TALEN nucleases are protein-driven genome editors; while CRISPR system is a nucleic acid-guided editing system. Genome editing techniques are still not widely applied for the design of new compounds with pharmacological activity, but they are starting to be considered as promising tools for rational genome manipulation in biotechnology applications. In this review we will discuss the potential applications of programmable nucleases for the metabolic engineering of secondary metabolites with biological activity.

Introduction: Infections are a major cause of morbidity and mortality in systemic inflammatory rheumatic diseases and the management of infectious complications in patients under biological therapies deserves particular attention. Objective: Develop evidence-based recommendations for the management of infections in rheumatic patients receiving biological therapies. Methods: A search in PubMed (until 10 November 2014) and EMBASE (until 20 December 2014) databases was performed. Patients with systemic inflammatory rheumatic diseases treated with approved biologics in whom infections occurred were included. Search results were submitted to title and abstract selection, followed by detailed review of suitable studies. Information regarding presentation of the infectious complication, its diagnosis, treatment, and outcome, as well as maintenance or discontinuation of the biological agent was extracted and subsequently pooled according to the type of infection considered. Results of literature review were presented and critically reviewed in a dedicated meeting by a multidisciplinary panel. Recommendations were then formulated using the Delphi method. Finally, the level of agreement among rheumatologists was voted using an online survey. Results: Fifteen recommendations were issued. Nine general recommendations concerned the assessment of infectious risk before and while on biologics, the procedures in case of suspected infection and the management of biologics during infectious complications. Six specific recommendations were developed for respiratory, urinary, gastrointestinal, skin, osteoarticular and disseminated infections. Conclusion: These fifteen recommendations are intended to help rheumatologists in the management of infections in patients on biological therapy. They integrate an extensive literature review, expert opinion and inputs from Portuguese rheumatologists.

Introduction: Pancreas angiosarcoma is a very aggressive malignant neoplasm. The symptoms are nonspecific and it is usually diagnosed at an advanced stage, which confers a poor prognosis. Presentation of case: We present a 56-year-old woman with abdominal epigastric pain and nausea. The abdominal CT-scan showed a 7 cm mass within the head of the pancreas and the pathology and immunochemistry analysis were positive for pancreas angiosarcoma. Intra-operatively the tumor was irresectable. Discussion: Pancreas angiosarcoma is an extremely rare neoplasm with non-specific diagnosis. The histology has a wide range of presentations and immunohistochemistry is required. The surgery appears to be the only effective treatment. Conclusion: We report the seventh case of pancreas angiosarcoma in the English literature. Despite it's irresectability, the patient was asymptomatic two months after surgery, initiating chemotherapy with paclitaxel, with good tolerance.

Para mitigar os efeitos da perda e fragmentação dos habitats a rede Natura2000 tem-se tornado um importante aspecto de conservação sustentável, mas é também essencial implementar conexões funcionais entre Sítios. Os invertebrados podem actuar como importantes bioindicadores dos efeitos da fragmentação e os carabídeos são frequentemente utilizados neste contexto. As alterações climáticas podem ter um impacto significativo na biodiversidade, sendo importante perceber como as espécies vão responder a tais alterações. A modelação da distribuição potencial de espécies facilita a localização de habitats adequados e está no cerne da maioria das abordagens para a identificação de corredores ecológicos. Este estudo pretende modelar a distribuição de duas espécies de carabídeos, contribuir para um melhor conhecimento da distribuição e possíveis determinantes ecológicos das mesmas na área de estudo, analisar como os modelos de distribuição de espécies ajudam na definição de corredores ecológicos e perceber como as alterações climáticas podem afectar a distribuição das duas espécies e a persistência dos corredores ecológicos no futuro. Assim, foram recolhidos dados de presença nos Sítio Cabrela e Costa Sudoeste e na área entre ambos, para construir modelos preditivos de distribuição potencial e modelos para identificar corredores ecológicos. Os resultados destacam a importância de conhecer a distribuição de uma espécie para se poderem estimar corredores ecológicos relevantes. Só assim as medidas e esforços de gestão e conservação podem ser eficazes na preservação da conectividade. O cenário futuro B1 revelou as melhores previsões de distribuição potencial e persistência de corredores ecológicos para as duas espécies. A sobrevivência destas a longo prazo depende também da identificação de áreas que sejam importantes para a sua ocorrência e que permitam a sua dispersão. A aplicação de medidas de gestão e conservação nessas áreas é fundamental. Grândola revelou-se uma área de grande importância para a presença das espécies e para a conectividade entre os dois Sítios, funcionando ainda como um potencial refúgio para as espécies no futuro.

Esta Newsletter (NL) resulta de uma parceria entre o Instituto de Saúde Baseada na Evidência e a Cochrane Portugal, e tem como objectivo disponibilizar informação sobre áreas interessantes para a prática clínica, com base na melhor evidência científica. São incluídos estudos relevantes, criticamente avaliados pela sua validade, importância dos resultados e aplicabilidade prática, resumidos numa óptica de suporte à decisão. É dada prioridade a estudos de causalidade incluindo-se ainda, quando justificado, estudos qualitativos e metodológicos, assim como revisões científicas. O conteúdo da NL é da exclusiva responsabilidade do(s) seu(s) autor(es).

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The present volume is the outcome of a two-day International Workshop held at the School of Arts and Humanities in Lisbon on the subject “A terra sigillata sudgálica no Sudoeste da Península Ibérica: circulação e consumo | South Gaulish terra sigillata in Southwest Hispania: circulation and consumption”, organized by UNIARQ – Centre for Archaeology of the University of Lisbon (28th and 29th of September 2015). The first day was dedicated to presenting the data about the varying consumption patterns of south Gaulish sigillata in different sites in Lusitania – such as Coimbra, Ammaia, Lisbon, Mérida, Tróia and also in sites in the Algarve and Alentejo regions, as well as at Braga (in Tarraconensis) and Baelo Claudia and Seville, in the former province of Baetica. The papers presented provide an up-to-date overview of the import for this tableware both in urban and rural contexts. The second day was a practical session to enable the participants (archaeologists, researchers and students) to learn about how to consult, use and feed information into the “Samian Research database”.

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The digital research resource 'Samian Research' offers access to a quarter of a million recorded Samian (Terra Sigillata) stamps found within the Roman Empire and its barbarian borderlands. It comprises the main corpora 'Names on Terra Sigillata', 'Corpus Vasorum Arretinorum' and 'Gestempelte Südgallische Reliefsigillata' and thousands of new finds from various sites added after the printed publication of these books. The resource also offers tools for data exploration, generating dating curves for find-sites, weighted distribution maps and statistical tools to analyse the internal structures of Samian potteries.

Bracara Augusta, just like other nuclear cities of the Roman world, played an important role in the inter-provincial trade as an importer and redistributor centre of nourishing and manufactured goods. Regarding the supply of Gaulish terra sigillata, apart from some fragments from Montans and a Drag. 45 form fragment from Lezoux, the productions are from La Graufesenque.

The Augustan forum of Aeminium (Coimbra, Portugal) underwent a significant enlargement in the middle of the 1st century AD. The extension was built over a monumental cryptoporticus located on steep terrain. Archaeological campaigns carried out at this site more or less continuously since the 1990s have identified the construction levels associated to this extension. This text presents the collection of red gloss pottery (terra sigillata) from South Gaul gathered in these stratigraphic contexts. The study of them, together with other chronological indicators, has enabled the second stage of construction of the forum of Aeminium to be dated to the mid 1st century AD.