S100B chaperone multimers suppress the formation of oligomers during Aβ42 aggregation

Extracellular aggregation of the amyloid-β 1–42 (Aβ42) peptide is a major hallmark of Alzheimer’s disease (AD), with recent data suggesting that Aβ intermediate oligomers (AβO) are more cytotoxic than mature amyloid fibrils. Understanding how chaperones harness such amyloid oligomers is critical toward establishing the mechanisms underlying regulation of proteostasis in the diseased brain. This includes S100B, an extracellular signaling Ca2+-binding protein which is increased in AD as a response to neuronal damage and whose holdase-type chaperone activity was recently unveiled. Driven by this evidence, we here investigate how different S100B chaperone multimers influence the formation of oligomers during Aβ42 fibrillation. Resorting to kinetic analysis coupled with simulation of AβO influx distributions, we establish that supra-stoichiometric ratios of dimeric S100B-Ca2+ drastically decrease Aβ42 oligomerization rate by 95% and AβO levels by 70% due to preferential inhibition of surface-catalyzed secondary nucleation, with a concomitant redirection of aggregation toward elongation. We also determined that sub-molar ratios of tetrameric apo-S100B decrease Aβ42 oligomerization influx down to 10%, while precluding both secondary nucleation and, more discreetly, fibril elongation. Coincidently, the mechanistic predictions comply with the independent screening of AβO using a combination of the thioflavin-T and X-34 fluorophores. Altogether, our findings illustrate that different S100B multimers act as complementary suppressors of Aβ42 oligomerization and aggregation, further underpinning their potential neuroprotective role in AD

The update of semantic memories in amnestic mild cognitive impairment

It is still controversial to what extent neocortical consolidated memories are susceptible of change by processes of reconsolidation and transformation throughout experience, and whether the medial temporal lobes are necessary for this update of semantic consolidated memories, as they are for episodic remembering. We hypothesize that patients with amnestic mild cognitive impairment (aMCI) who have deficits in episodic memory may also have difficulties in updating information on added new features of objects. Sixteen participants with aMCI and 20 healthy control participants performed a semantic word-to-picture task, in which they were asked to identify as belonging to a given semantic category NEW objects, that have incorporated novel features, as well as OLD items, semantically and visually SIMILAR items and UNRELATED items. Patients with aMCI made a greater percentage of errors than healthy controls. Participants globally made greater percentages of errors in difficult types of items, namely NEW and SIMILAR, as compared to easier ones, OLD and UNRELATED. Importantly, an item by diagnostic group interaction effect was observed, and post hoc analysis showed that patients with aMCI made a higher percentage of errors than controls in NEW items only. In conclusion, patients with aMCI had a particular difficulty in identifying the NEW items of the word-to-picture task as compared to the control participants, supporting the concept of a flexible and dynamic conceptual knowledge system, involving the update of semantic memories and the integration of new attributes in a constant transformation process, which is impaired in these patients.Fundação para a Ciência e Tecnologia - FCTinfo:eu-repo/semantics/publishedVersio

Energy and exergy analysis of a biomass based ceramic plant

The manufacture of relatively low commercial value ceramic products for construction is an energy intensive industry. It is important to improve and optimize the energy equation of the plant operation while simultaneously introducing renewable primary energy sources for the heat supply. The present paper concerns the analysis of the energy usage in a brick plant. This unit operates continuously on a 3 shift schedule. The overall annual production of five types of bricks is over 62 kton and the main energy consumption unit is the furnace. For this unit, the thermal load is supplied mainly by biomass coupled with fuel oil (80%–20% split, respectively) which yield a maximum temperature of 950 °C. The process is controlled by adjusting the air mixing in the kiln. A secondary furnace provides the heat for a rotating dryer for biomass drying which is supplied to the main furnace. The fuel is a mixture of various sources and its characteristics were determined by means of an elemental analysis, ash content and the measurement of the heat value. Measurements of mass fluxes along with the operating temperature on critical elements of the plant and chemical composition of the flue gases were used to calculate the energy balances to the plant. Because of the diversity of the product mix the production was normalized using the mass/surface area ratio of the various types of bricks. From the results, the energy intensity is 44 kg of oil equivalent per ton. The exergy analysis of the plant shows that most of the energy degradation occurs in the kiln. The analysis also enabled to assess the influence of the replacing fossil fuel by biomass on the increase of exergy efficiency of the plant.This work was financed by FCT, under the Strategic Project UID/SEM/04077/2013. The authors acknowledge the contribution of Amaro de Macedo S.A., for providing access to the plant

Influence of exposure to cold thermal environment on core and skin temperatures

Exposure to extreme cold triggers in humans various of physiological responses, which is necessary to control is necessary when it comes to occupational exposure. The objective of the present study was to analyze the evolution of core temperature, mean skin temperature during exposure to extreme cold (-20 degrees C), with the usual protection for this type of exposure. From a total of 12 healthy individuals using a climatic chamber, intra-abdominal temperature and skin temperature were measured during and after the exposure period. The results demonstrate a decrease in core temperature and mean skin temperature at the initial moments of the test, from an increase to the end of exposure. The choice of individual protective equipment with the appropriate thermal insulation as well as the protection of the extremities is fundamental in order to guarantee the safety and the comfort of the exposed individuals. Further studies should be conducted using larger samples with a greater diversity of individual factors

Salvia elegans: uma fonte natural de compostos antioxidantes

A espécie Salvia elegans é um arbusto que pertence ao género Salvia, família das Lamiaceae. Várias espécies do mesmo género têm vindo a ser cultivadas para uso na culinária e em medicina tradicional [1]. Devido ao seu cheiro característico, a S. elegans é vulgarmente conhecida por salva ananás e utilizada como condimento ou aromatizante em alimentos. No México esta espécie é popularmente conhecida como “mirto” e tem sido usada na medicina tradicional para tratar afeções do sistema nervoso central [2, 3]. Apesar disso, as suas propriedades biológicas não estão ainda estudadas. Neste trabalho pretende-se clarificar a capacidade antioxidante da espécie S. elegans, bem como proceder à identificação dos seus principais constituintes fenólicos, uma vez que vulgarmente estes compostos se encontram associados a esta propriedade [4]. Para tal, as partes aéreas da planta S. elegans foram extraídas com água quente [5] e o teor de compostos fenólicos totais no extrato foi determinado por uma adaptação do método colorimétrico de Folin-Ciocalteu [6]. A identificação dos compostos fenólicos foi efetuada por análise de cromatografia líquida de alta resolução (HPLC-DAD), acoplada à técnica de espectrometria de massa com ionização por electrospray (ESI-MSn), em modo negativo. Ainda, a capacidade antioxidante do extrato aquoso de S. elegans foi testada através dos testes de captação de radicais livres DPPH•, e do teste do poder redutor. De acordo com o método de Folin-Ciocalteu, os compostos fenólicos no extrato aquoso de S. elegans totalizam 201±46 μg EAG/ mg de extrato. O extrato é particularmente rico em ácido rosmarínico e contém ainda quantidades moderadas de outros derivados do ácido cafeico. Para além disto, o extrato de S. elegans possui uma boa capacidade antioxidante demonstrada pelos métodos de DPPH• e poder redutor. Os resultados obtidos neste estudo permitem sugerir que S. elegans possui grande potencial para ser aplicada como agente antioxidante. Futuramente, pretende-se esclarecer a contribuição individual dos principais constituintes fenólicos do extrato de S. elegans na atividade antioxidante do mesmo

Genomic profiling by DNA amplification of laser capture microdissected tissues and array CGH.

Comparative genomic hybridization by means of BAC microarrays (array CGH) allows high-resolution profiling of copy-number aberrations in tumor DNA. However, specific genetic lesions associated with small but clinically relevant tumor areas may pass undetected due to intra-tumor heterogeneity and/or the presence of contaminating normal cells. Here, we show that the combination of laser capture microdissection, phi29 DNA polymerase-mediated isothermal genomic DNA amplification, and array CGH allows genomic profiling of very limited numbers of cells. Moreover, by means of simple statistical models, we were able to bypass the exclusion of amplification distortions and variability prone areas, and to detect tumor-specific chromosomal gains and losses. We applied this new combined experimental and analytical approach to the genomic profiling of colorectal adenomatous polyps and demonstrated our ability to accurately detect single copy gains and losses affecting either whole chromosomes or small genomic regions from as little as 2 ng of DNA or 1000 microdissected cells

Neuropsychological profile of amyloid-positive versus amyloid-negative amnestic Mild Cognitive Impairment

Patients diagnosed with amnestic mild cognitive impairment (aMCI) are at high risk of progressing to dementia. It became possible, through the use of biomarkers, to diagnose those patients with aMCI who have Alzheimer's disease. However, it is presently unfeasible that all patients undergo biomarker testing. Since neuropsychological testing is required to make a formal diagnosis of aMCI, it would be interesting if it could be used to predict the amyloid status of patients with aMCI.Fundação para a Ciência e Tecnologia - FCTinfo:eu-repo/semantics/publishedVersio

Spintronic devices for biomedical applications

Spintronic devices have been proposed over the past decade for various biomedical applications. These include static or dynamic biomolecular recognition platforms ( DNA-cDNA, antibody-antigen, phage-bacteria, ), cytometer and cell separation devices and lateral bio assay platforms , microelectrode based devices for neuroelectronic applications, and hybrid sensor arrays for imaging applications [1]. The biomolecular recognition platforms include a magnetoresistive sensor array, a set of biomolecular probes ( surface immobilized or in solution) , biological targets labeled with particular magnetic micro beads or magnetic nanoparticles, and arraying architectures and microfluidics used to increase sensitivity and favour probe-target interaction. The platforms also incorporate the proper signal conditioning and processing electronics. Results will be shown for cell free DNA detection as a cancer marker indicator, and for cell detection using phage markers. For neuroelectronic applications, magnetoresistive sensors were fabricated onto Si microelectrode arrays. Experiments probe either extra cellular currents measured in mouse hypocampus slices, or spinal medulla signals probed directly with implanted magnetoresistive electrodes. For deep brain simulation and detection, sensors and electrodes are being fabricated into flexible polyimide probes. Separation between straight electrical contributions and magnetic signals is discussed. For imaging applications ( magneto cardiography) efforts continue to reach pT level detectivity at 1Hz, using hybrid MEMS/magnetoresistive sensor devices. Two architectures will be presented leading to larger DC field mechanical modulation, and therefore increased sensitivity

Score CTo-aBCDE : um novo score preditor de sucesso nas CTOs

© 2020 Sociedade Portuguesa de Cardiologia. Published by Elsevier España, S.L.U. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Introduction: Patient selection for percutaneous coronary intervention (PCI) in chronic total occlusions (CTOs) is crucial to procedural success. Our aim was to identify independent predictors of success in CTO PCI in order to create an accurate score. Methods: In a single-center observational registry of CTO PCI, demographic and clinical data and anatomical characteristics of coronary lesions were recorded. Linear and logistic regression analysis were used to identify predictors of success. A score to predict success was created and its accuracy was measured by receiver operating curve analysis. Results: A total of 377 interventions were performed (334 patients, age 68±11 years, 75% male). The success rate was 65% per patient and 60% per procedure. Predictors of success in univariate analysis were absence of active smoking (OR 2.02, 95% CI 1.243-3.29; p=0.005), presence of tapered stump (OR 5.2, 95% CI 2.7-10.2; p8 with high probability (95%). Conclusion: In our sample only anatomical characteristics were predictors of success. The creation of a score to predict success, with good accuracy, may enable selection of cases that can be treated by any operator, those in which a dedicated operator will be desirable, and those with an extremely low probability of success, which should be considered individually for conservative management, surgical revascularization or PCI by a team experienced in CTO.info:eu-repo/semantics/publishedVersio