Transthyretin binding to A-Beta peptide – Impact on A-Beta fibrillogenesis and toxicity

AbstractIt has been suggested that transthyretin (TTR) is involved in preventing A-Beta fibrillization in Alzheimer’s disease (AD). Here, we characterized the TTR/A-Beta interaction by competition binding assays. TTR binds to different A-Beta peptide species: soluble (Kd, 28nM), oligomers and fibrils; diverse TTR variants bind differentially to A-Beta. Transmission electron microscopy (TEM) analysis demonstrated that TTR is capable of interfering with A-Beta fibrillization by both inhibiting and disrupting fibril formation. Co-incubation of the two molecules resulted in the abolishment of A-Beta toxicity. Our results confirmed TTR as an A-Beta ligand and indicated the inhibition/disruption of A-Beta fibrils as a possible mechanism underlying the protective role of TTR in AD

Familial amyloid polyneuropathy associated with TTRSer50Arg mutation in two Iberian families presenting a novel single base change in the mutant gene

Amyloid. 2007 Jun;14(2):147-52. Familial amyloid polyneuropathy associated with TTRSer50Arg mutation in two Iberian families presenting a novel single base change in the mutant gene. Munar-Qués M, Masjuan J, Coelho T, Moreira P, Viader-Farré C, Saraiva MJ. Grupo de Estudio de la PAF, Plaza Olivar 5, 07002 Palma de Mallorca, Majorca, Spain. [email protected] Abstract We present two families, from Spain and Portugal, with familial amyloid polyneuropathy (FAP) associated with the mutation TTRSer50Arg. This mutation was first described in two Japanese patients from independent families and later in a French-Italian patient and a Vietnamese family. The two families presented here, are the first to be diagnosed with this mutation in the Iberian Peninsula. In the patients of both families, FAP was very aggressive as they rapidly developed multiple symptoms with progressive deterioration; we emphasize the presence of severe orthostatic hypotension in the Spanish proband which confined him to a wheelchair. This proband was the first patient with this mutation to have undergone liver transplantation and results were encouraging. The mutation was detected in four patients and one disease-free relative by DNA sequencing of exon 3 and induced mutation restriction analysis. The most outstanding feature was the single base transversion A to C in codon 50 (CGT instead of AGT), whereas in both Japanese patients and the French-Italian patient it was T to G (AGG instead of AGT). To our knowledge only six FAP mutations with more than one single nucleotide mutation for the same codon have been reported to date. PMID: 17577688 [PubMed - indexed for MEDLINE

Zika virus infections imported from Brazil to Portugal, 2015

Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present.info:eu-repo/semantics/publishedVersio

Preservation of a highly perishable food, watermelon juice, at and above room temperature under mild pressure (hyperbaric storage) as an alternative to refrigeration

The feasibility of food preservation under pressure (hyperbaric storage) at and above room temperatures, as an alternative to refrigeration was evaluated. Preservation of a highly perishable food, watermelon juice, was studied at pressures of 25e150 MPa and temperatures ranging 20e37 C, being compared to refrigeration and storage at atmospheric pressure at the same temperatures. Hyperbaric storage at 75 MPa (20e37 C) revealed an inhibitory effect on microbial growth, with at least an equal performance compared to refrigeration. An additional inactivation effect was verified for storage at 100 and 150 MPa, with reduction of the initial microbial counts to 1.00 Log CFU/mL for enterobacteriaceae and yeasts and moulds, and from 4.43 ± 0.04 to 3.31 ± 0.04 and 2.99 ± 0.07 Log CFU/ mL, respectively, for total aerobic mesophiles (25 C). In general, pH, titratable acidity and total soluble solids did not show a clear variation trend with pressure and no considerable differences among storage conditions were verified. Cloudiness decreased for samples stored under pressure and browning degree was in general lower in samples stored under pressure compared to refrigeration. This work demonstrates the potentiality of hyperbaric storage as a new preservation methodology, at variable (uncontrolled) room temperature without energetic costs during storage, as an alternative to refrigeration

Welfare of rainbow trout at slaughter: integrating behavioural, physiological, proteomic and quality indicators and testing a novel fast-chill stunning method

A critical point in the life of a captive fish is the final stages of production, not only in welfare terms but also due to effects on meat quality, carcass appearance and derived economic impacts. The most common method to slaughter fish is by asphyxia either in ice-water or in the open air. In humane slaughter procedures, however, a stunning method needs to be implemented to render the fish immediately unconscious (within one second) until death. The objective of this research was to evaluate and compare the effectiveness and welfare effects of four types of stunning methods in rainbow trout (O. mykiss): cold shock by fast-chilling as a novel method, where the fish were immersed in liquid water at −8 °C, asphyxia (as the currently used method), electrical stunning, and anaesthesia with MS-222. We used a total of 176 trout (mean weight 524 ± 138 g), combining behavioural (individual swimming activity, equilibrium, opercular movement and eye-roll), physiological (heart rate and electrocardiogram amplitude) and circulating (plasma cortisol and osmolality) indicators with brain proteomic signatures. We also analysed the effects on fillet shelf-life and quality in each method (rigor mortis, water content, fillet colour, pH and ATP degradation). Anaesthesia effectively induced unconsciousness, with regular and strong heartbeat and low cortisol. Quality indicators were the best among all the methods assessed. Electric shock was found to be an effective and irreversible method for inducing unconsciousness, with strong heartbeat and large variation in cortisol response and quality indicators similar to anaesthesia. On the contrary, asphyxia presented indicators of poor welfare (e.g., long-lasting consciousness throughout the slaughter process, high cortisol levels), with very low flesh quality parameters. Fast-chilling also resulted in extreme signs of stress (intense mucus release, haemorrhage and no loss of consciousness), low ATP content and the worst proteomic signatures, along with an early onset and resolution of rigor mortis (6 and 48 h, respectively). Our results reinforce the idea that electric stunning is a promising humane method to stun farmed trout. In contrast, the fast-chilling method showed very poor results both in welfare and in quality, indicating that it is not a viable humane alternative to asphyxia. Moreover, the proteome analysis provided valuable insights into the brain mechanisms of rainbow trout at slaughter, offering potential fine-scale biomarkers of welfare.Provincia Autonoma di Trento; Fundação para a Ciência e a Tecnologiainfo:eu-repo/semantics/acceptedVersio

School dropout, problem behaviour and poor academic achievement : a longitudinal view of portuguese male offenders

This study examines school drop outs from the perspective of male adults themselves through interviews with offenders currently serving sentences. Participants were 10 Portuguese male inmates, between the ages of 19 and 46 years of age, incarcerated in two prison facilities of the Azores. Qualitative and interpretative methods were carried out using a semi-structured in-depth individual interview that was audiorecorded and conducted on the basis of a list of topics. Interview transcripts and thematic analysis were used in data treatment and analysis. The findings primarily indicate that poor academic achievement and emotional and behavioural difficulties of participants played a particular role in early school drop out. The trajectories these individuals followed within the education system presented problem behaviour, learning disabilities, and/or foster care interventions. While school drop out circumstances were apparently various, analysis showed that they were underpinned by three distinct sets of conditions generally not addressed by the education system. The analysis of the triggering factors and the maintenance dynamics of school drop outs indicated three distinct types: retention/absenteeism, life turning points and positive resolution. Implications for secondary prevention and screening practices are discussed.FCT (SFRH/ BD/ 44245/ 2008)CIEC - unidade de investigação 317 da FC

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02