The mechanism of activation of the adenovirus type 2 protease

The adenovirus codes for a protease which is essential for virion infectivity. This protease requires the presence of a peptide cofactor in order to develop optimal activity. This peptide, GVQSLBCRRRCF, originates from the C-terminal of a viral protein, pVI, and some evidence regarding its specificity came from observations showing that neither of the peptides GVQSLKRRRAF or KRRRCF was able to activate the protease, indicating that both the cysteine and the N-terminal were important in the activation process. However, the mechanism by which the peptide activates the protease has never been elucidated. In this project, several factors contributing to the activation mechanism of the human adenovirus type 2 protease were studied, such as the peptide N-terminal length and composition, the environment close to the cysteine and the distance between the N-terminal and the cysteine, in view of assessing the relevance of each of these parameters in the activation process and proposing a mechanism of activation. Based on the above studies, attempts of protease inhibition were also performed based on the activation process rather than on the blocking of the active site, and the relevance of these results was related with the proposed activation mechanism. An attempt to clone an avian adenovirus protease was also performed, in order to try and compare the activation processes between the two proteases

Capacitor recruitment fusion methodology: a case study

The Project entitled Methodology for Recruitment Capacitor: a case study (Fusion Resourcing - A case study) emerged from a need of the firm Innovagency SA that operates in the technological field and in the digital communication field. This need is associated with the difficulty of recruiting programmers with specific technical knowledge and skills related to the most sophisticated technology platforms, currently used on the web. It presents the design and implementation of a synergetic fusion, recruitment, selection, and training and integration solution supported by a "Trainee Academy" called "i9.station". Based on the results obtained, the interest and potential of this fusion approach it is approve. Both in terms of recruitment effectiveness and the effectiveness of the selection process associated with training, as well as in the speed and strength of both competency acquisition and process of socio-professional and technical integration in the firm and in the work teams, proving, above all, an investment capable of generating generous positive returns

Evolution of outpatient antibiotic use in mainland Portugal 2000-2009

Introduction: In the latest years, the increasing resistance to antibiotics has become a serious public health issue. The resistance to antimicrobial agents is multifactorial although several studies have shown that the large use of antibiotics for therapeutical and prophylactic purposes, and particularly their misuse, is one factor that contributes most to this problem. Aim: To assess the evolution of antibiotic consumption in Portugal, Health Regions and Districts of Portugal, from 2000 to 2009. Material and Methods: Descriptive observational study using as source of information a database of outpatient antibiotic prescription provided by Infarmed, National Authority of Medicines and Health Products. Antibiotic consumption is estimated up from medical prescription, and expressed in DDD/1000 inhabitants/day (DHD). Results: From 2000 to 2009 antibiotic total consumption varied between 24,12 DHD and 22,03 DHD, which means a decrease by 8,65%. The use of tetracyclines (J01A), cephalosporins (J01D), sulphonamides (J01E), quinolones (J01M) and other antibacterials (J01B, J01G and J01X) decreased during the aforesaid time period. By contrast, there was an increase in the use of the combination penicilin and beta-lactamases inhibitor, and macrolides (J01F). Between 2000 and 2009 there was a significant decrease in the use of outpatient cephalosporins ( - 43,50%). Most notable is the large reduction of the use of cephalosporins between 2000 and 2009 (-43.50%) and also the decrease in the consumption of quinolones (-15.31%). Conclusion: Although there has been a decrease in the use of antibiotics in Portugal, their consumption is still high. The current study provides information that may be useful to regional Health Authorities in order to develop educational activities, for the population or health professionals, which can promote the rational use of antibiotics.info:eu-repo/semantics/publishedVersio

Em busca de marcadores sensoriais por entre a composição do vinho tinto: um estudo nacional inovador

The objective of this work was to verify the signaling/profiling potential of wine compounds and the physicochemical and bioclimatic winerelated measurements on a nationwide sensory scale of red wine typicality. Color tonality evolved from violet-purple in cooler northern regions to ruby-garnet in hotter southern regions. Acidity and astringency were enhanced from south to north. Conversely, alcohol and viscosity progressed southward. Bitterness was primarily affected by inland-coastal influence. The regional differentiation of astringency and bitterness introduced an orthogonal reading (N north- S south vs. E inland-W coastal, respectively), rather than a linear one, these findings adding novelty to sensory research. Additionally, several Portuguese-related studies were reviewed, and their findings were correlated with six sensory measures. Bioclimatic indexes, pH and the total phenol index were considered the strongest profilers in a nationwide assessment on red wine typicality. The ratio of the oligomeric/polymeric composition of tannins, as well as total anthocyanins, was also to be considered to be a valid sensory profiler. Several nationwide tendencies and correlations between sensory evaluations and wine chemistry may represent interesting findings and challenge unexplored ways for new researc

Aqueous and Methanolic Extracts of Caulerpa mexicana Suppress Cell Migration and Ear Edema Induced by Inflammatory Agents

The regulation of the inflammatory response is essential to maintaining homeostasis. Several studies have investigated new drugs that may contribute to avoiding or minimizing excessive inflammatory process. The aim of this study was to evaluate the effect of extracts of green algae Caulerpa mexicana on models inflammation. In mice, the inflammatory peritonitis model is induced by zymosan. Previous treatment of mice with aqueous and methanolic extracts of C. mexicana was able to suppress the cell migration to the peritoneal cavity, in a time-dependent but not in a dose-dependent manner. The treatment of mice with C. mexicana extracts also decreased the xylene-induced ear edema, exerting strong inhibitory leukocyte migration elicited by zymosan into the air pouch. We concluded that administration of the extracts resulted in a reduction of cell migration to different sites as well as a decrease in edema formation induced by chemical irritants. This study demonstrates for the first time the anti-inflammatory effect of aqueous and methanolic extracts from the green marine algae Caulerpa mexicana

Comparison of Listeria monocytogenes Exoproteomes from biofilm and planktonic state:Lmo2504, a protein associated with biofilms

The food-borne pathogen Listeria monocytogenes is the causative agent of the severe human and animal disease listeriosis. The persistence of this bacterium in food processing environments is mainly attributed to its ability to form biofilms. The search for proteins associated with biofilm formation is an issue of great interest, with most studies targeting the whole bacterial proteome. Nevertheless, exoproteins constitute an important class of molecules participating in various physiological processes, such as cell signaling, pathogenesis, and matrix remodeling. The aim of this work was to quantify differences in protein abundance between exoproteomes from a biofilm and from the planktonic state. For this, two field strains previously evaluated to be good biofilm producers (3119 and J311) were used, and a procedure for the recovery of biofilm exoproteins was optimized. Proteins were resolved by two-dimensional difference gel electrophoresis and identified by electrospray ionization-tandem mass spectrometry. One of the proteins identified in higher abundance in the biofilm exoproteomes of both strains was the putative cell wall binding protein Lmo2504. A mutant strain with deletion of the gene for Lmo2504 was produced (3119Δlmo2504), and its biofilm-forming ability was compared to that of the wild type using the crystal violet and the ruthenium red assays as well as scanning electron microscopy. The results confirmed the involvement of Lmo2504 in biofilm formation, as strain 3119Δlmo2504 showed a significantly (P < 0.05) lower biofilm-forming ability than the wild type. The identification of additional exoproteins associated with biofilm formation may lead to new strategies for controlling this pathogen in food processing facilities

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM