β-Lactams: chemical structure, mode of action and mechanisms of resistance

This synopsis summarizes the key chemical and bacteriological characteristics of β-lactams, penicillins, cephalosporins, carbanpenems, monobactams and others. Particular notice is given to first-generation to fifth-generation cephalosporins. This reviewalso summarizes the main resistancemechanism to antibiotics, focusing particular attention to those conferring resistance to broad-spectrum cephalosporins by means of production of emerging cephalosporinases (extended-spectrum β-lactamases and AmpC β-lactamases), target alteration (penicillin-binding proteins from methicillin-resistant Staphylococcus aureus) and membrane transporters that pump β-lactams out of the bacterial cell.

Wear resistance of TiAlSiN thin coatings

In the last decades TiAlN coatings deposited by PVD techniques have been extensively investigated but, nowadays, their potential development for tribological applications is relatively low. However, new coatings are emerging based on them, trying to improve wear behavior. TiAlSiN thin coatings are now investigated, analyzing if Si introduction increases the wear resistance of PVD films. Attending to the application, several wear test configurations has been recently used by some researchers. In this work, TiAlSiN thin coatings were produced by PVD Unbalanced Magnetron Sputtering technique and they were conveniently characterized using Scanning Electron Microscopy (SEM) provided with Energy Dispersive Spectroscopy (EDS), Atomic Force Microscopy (AFM), Electron Probe Micro-Analyzer (EPMA), Micro Hardness (MH) and Scratch Test Analysis. Properties as morphology, thickness, roughness, chemical composition and structure, hardness and film adhesion to the substrate were investigated. Concerning to wear characterization, two very different ways were chosen: micro-abrasion with ball-on-flat configuration and industrial non-standardized tests based on samples inserted in a feed channel of a selected plastic injection mould working with 30% (wt.) glass fiber reinforced polypropylene. TiAlSiN coatings with a small amount of about 5% (wt.) Si showed a similar wear behavior when compared with TiAlN reported performances, denoting that Si addition does not improve the wear performance of the TiAlN coatings in these wear test conditions.

Evolution of Drug Resistance: Insight on TEM -Lactamases Structure and Activity and Beta-Lactam Antibiotics

Extended-spectrum β-lactamases (ESBLs) prevalence was studied in the north of Portugal, among 193 clinical isolates belonging to citizens in a district in the boundaries between this country and Spain from a total of 7529 clinical strains. In the present study we recovered some members of Enterobacteriaceae family, producing ESBL enzymes, including Escherichia coli (67.9%), Klebsiella pneumoniae (30.6%), Klebsiella oxytoca (0.5%), Enterobacter aerogenes (0.5%), and Citrobacter freundii (0.5%). β-lactamases genes blaTEM, blaSHV, and blaCTX-M were screened by polymerase chain reaction (PCR) and sequencing approaches. TEM enzymes were among the most prevalent types (40.9%) followed by CTX-M (37.3%) and SHV (23.3%). Among our sample of 193 ESBL-producing strains 99.0% were resistant to the fourth-generation cephalosporin cefepime. Of the 193 isolates 81.3% presented transferable plasmids harboring genes. Clonal studies were performed by PCR for the enterobacterial repetitive intragenic consensus (ERIC) sequences. This study reports a high diversity of genetic patterns. Ten clusters were found for E. coli isolates and five clusters for K. pneumoniae strains by means of ERIC analysis. In conclusion, in this country, the most prevalent type is still the TEM-type, but CTX-M is growing rapidly.

Uma abordagem à incorporação de lenhinosulfonatos e materiais reciclados em misturas de SBR para produção sustentável de solas

Mestrado em Engenharia Química - Ramo Otimização Energética na Indústria Química

Teaching and learning with social software in higher education: content management systems integrated with Web-based applications as a key factor for success

The change of paradigm imposed by the Bologna process, in which the student will be responsible for their own learning, and the presence of a new generation of students with higher technological skills, represent a huge challenge for higher education institutions. The use of new Web Social concepts in teaching process, supported by applications commonly called Web 2.0, with which these new students feel at ease, can bring benefits in terms of motivation and the frequency and quality of students' involvement in academic activities. An e-learning platform with web-based applications as a complement can significantly contribute to the development of different skills in higher education students, covering areas which are usually in deficit.

Stability of the Transthyretin Molecule as a Key Factor in

Transthyretin (TTR) protects against A-Beta toxicity by binding the peptide thus inhibiting its aggregation. Previous work showed different TTR mutations interact differently with A-Beta, with increasing affinities correlating with decreasing amyloidogenecity of the TTR mutant; this did not impact on the levels of inhibition of A-Beta aggregation, as assessed by transmission electron microscopy. Our work aimed at probing differences in binding to A-Beta by WT, T119M and L55P TTR using quantitative assays, and at identifying factors affecting this interaction. We addressed the impact of such factors in TTR ability to degrade A-Beta. Using a dot blot approach with the anti-oligomeric antibody A11, we showed that A-Beta formed oligomers transiently, indicating aggregation and fibril formation, whereas in the presence of WT and T119M TTR the oligomers persisted longer, indicative that these variants avoided further aggregation into fibrils. In contrast, L55PTTR was not able to inhibit oligomerization or to prevent evolution to aggregates and fibrils. Furthermore, apoptosis assessment showed WT and T119M TTR were able to protect against A-Beta toxicity. Because the amyloidogenic potential of TTR is inversely correlated with its stability, the use of drugs able to stabilize TTR tetrameric fold could result in increased TTR/ABeta binding. Here we showed that iododiflunisal, 3-dinitrophenol, resveratrol, [2-(3,5-dichlorophenyl)amino] (DCPA) and [4- (3,5-difluorophenyl)] (DFPB) were able to increase TTR binding to A-Beta; however only DCPA and DFPB improved TTR proteolytic activity. Thyroxine, a TTR ligand, did not influence TTR/A-Beta interaction and A-Beta degradation by TTR, whereas RBP, another TTR ligand, not only obstructed the interaction but also inhibited TTR proteolytic activity. Our results showed differences between WT and T119M TTR, and L55PTTR mutant regarding their interaction with A-Beta and prompt the stability of TTR as a key factor in this interaction, which may be relevant in AD pathogenesis and for the design of therapeutic TTR-based therapies.

Evolution of Drug Resistance: Insight on TEM β-Lactamases Structure and Activity and β-Lactam Antibiotics

Since the discovery of the first penicillin bacterial resistance to β-lactam antibiotics has spread and evolved promoting new resistances to pathogens. The most common mechanism of resistance is the production of β-lactamases that have spread thorough nature and evolve to complex phenotypes like CMT type enzymes. New antibiotics have been introduced in clinical practice, and therefore it becomes necessary a concise summary about their molecular targets, specific use and other properties. β-lactamases are still a major medical concern and they have been extensively studied and described in the scientific literature. Several authors agree that Glu166 should be the general base and Ser70 should perform the nucleophilic attack to the carbon of the carbonyl group of the β-lactam ring. Nevertheless there still is controversy on their catalytic mechanism. TEMs evolve at incredible pace presenting more complex phenotypes due to their tolerance to mutations. These mutations lead to an increasing need of novel, stronger and more specific and stable antibiotics. The present review summarizes key structural, molecular and functional aspects of ESBL, IRT and CMT TEM β-lactamases properties and up to date diagrams of the TEM variants with defined phenotype. The activity and structural characteristics of several available TEMs in the NCBI-PDB are presented, as well as the relation of the various mutated residues and their specific properties and some previously proposed catalytic mechanisms.

Estudo da delaminação em compósitos

As excelentes propriedades mecânicas, associadas ao seu baixo peso, fazem com que os materiais compósitos sejam atualmente dos mais interessantes da nossa sociedade tecnológica. A crescente utilização destes materiais e a excelência dos resultados daí provenientes faz com que estes materiais sejam utilizados em estruturas complexas de responsabilidade, pelo que a sua maquinagem se torna necessária de forma a possibilitar a ligação entre peças. O processo de furação é o mais frequente. O processo de maquinagem de compósitos terá como base os métodos convencionais utilizados nos materiais metálicos. O processo deverá, no entanto, ser convenientemente adaptado, quer a nível de parâmetros, quer a nível de ferramentas a utilizar. As características dos materiais compósitos são bastante particulares pelo que, quando são sujeitos a maquinagem poderão apresentar defeitos tais como delaminação, fissuras intralaminares, arrancamento de fibras ou dano por sobreaquecimento. Para a detecção destes danos, por vezes a inspeção visual não é suficiente, sendo necessário recorrer a processos específicos de análise de danos. Existem já, alguns estudos, cujo âmbito foi a obtenção de furos de qualidade em compósitos, com minimização do dano, não se podendo comparar ainda com a informação existente, no que se refere à maquinagem de materiais metálicos ou ligas metálicas. Desta forma, existe ainda um longo caminho a percorrer, de forma a que o grau de confiança na utilização destes materiais se aproxime aos materiais metálicos. Este trabalho experimental desenvolvido nesta tese assentou essencialmente na furação de placas laminadas e posterior análise dos danos provocados por esta operação. Foi dada especial atenção à medição da delaminação causada pela furação e à resistência mecânica do material após ser maquinado. Os materiais utilizados, para desenvolver este trabalho experimental, foram placas compósitas de carbono/epóxido com duas orientações de fibras diferentes: unidireccionais e em “cross-ply”. Não se conseguiu muita informação, junto do fornecedor, das suas características pelo que se levaram a cabo ensaios que permitiram determinar o seu módulo de elasticidade. Relativamente á sua resistência â tração, como já foi referido, a grande resistência oferecida pelo material, associada às limitações da máquina de ensaios não permitiu chegar a valores conclusivos. Foram usadas três geometrias de ferramenta diferentes: helicoidal, Brad e Step. Os materiais utilizados nas ferramentas, foram o aço rápido (HSS) e o carboneto de tungsténio para as brocas helicoidais de 118º de ângulo de ponta e apenas o carboneto de tungsténio para as brocas Brad e Step. As ferramentas em diamante não foram consideradas neste trabalho, pois, embora sejam reconhecidas as suas boas características para a maquinagem de compósitos, o seu elevado custo não justifica a sua escolha, pelo menos num trabalho académico, como é o caso. As vantagens e desvantagens de cada geometria ou material utilizado foram avaliadas, tanto no que diz respeito à delaminação como á resistência mecânica dos provetes ensaiados. Para a determinação dos valores de delaminação, foi usada a técnica de Raio X. Algum conhecimento já existente relativamente a este processo permitiu definir alguns parâmetros (por exemplo: tempo de exposição das placas ao liquido contrastante), que tornaram acessível o procedimento de obtenção de imagens das placas furadas. Importando estas imagens para um software de desenho (no caso – AutoCad), foi possível medir as áreas delaminadas e chegar a valores para o fator de delaminação de cada furo efetuado. Terminado este processo, todas as placas foram sujeitas a ensaios de esmagamento, de forma a avaliar a forma como os parâmetros de maquinagem afectaram a resistência mecânica do material. De forma resumida, são objetivos deste trabalho: - Caracterizar as condições de corte em materiais compósitos, mais especificamente em fibras de carbono reforçado com matriz epóxida (PRFC); - Caracterização dos danos típicos provocados pela furação destes materiais; - Desenvolvimento de análise não destrutiva (RX) para avaliação dos danos provocados pela furação; - Conhecer modelos existentes com base na mecânica da fratura linear elástica (LEFM); - Definição de conjunto de parâmetros ideais de maquinagem com o fim de minimizar os danos resultantes da mesma, tendo em conta os resultados provenientes dos ensaios de força, da análise não destrutiva e da comparação com modelos de danos existentes e conhecidos.

Aerobic Exercise Does Not Predict Brain Derived Neurotrophic Factor And Cortisol Alterations in Depressed Patients

The pathophysiology of depression is related to neurobiological changes that occur in the monoamine system, hypothalamic-pituitary-adrenal axis, neurogenesis system and the neuroimmune system. In recent years, there has been a growing interest in the research of the effects of exercise on brain function, with a special focus on its effects on brainderived neurotrophic factor (BDNF), cortisol and other biomarkers. Thus, the aim of this study is to present a review investigating the acute and chronic effects of aerobic exercise on BDNF and cortisol levels in individuals with depression. It was not possible to establish an interaction between aerobic exercise and concentration of BDNF and cortisol, which may actually be the result of the divergence of methods, such as type of exercises, duration of the sessions, and prescribed intensity and frequency of sessions.