Heparin-induced lipoprotein precipitation apheresis in dyslipidemic patients: A multiparametric assessment

Low-density lipoprotein (LDL) apheresis (LA) selectively eliminates lipoproteins containing apolipoprotein B 100 (ApoB100) on patients affected by severe dyslipidemia. In addition to lowering lipids, LA is thought to exert pleiotropic effects altering a number of other compounds associated with atherosclerosis, such as pro- and anti-inflammatory cytokines or pro-thrombotic factors

Materiais didáticos no ensino e aprendizagem da matemática

O relatório final de estágio apresenta-se no âmbito do Mestrado em Educação Pré-Escolar e Ensino do 1.º Ciclo do Ensino Básico. Este inclui uma reflexão crítica relativamente às unidades curriculares de Prática de Ensino Supervisionada (II e III), em contexto de estágio, no 1.º Ciclo do Ensino Básico e na Educação Pré-Escolar. O relatório contempla ainda uma investigação cuja temática se centra na área da Matemática. Para a realização da primeira parte do relatório, foram utilizados diversos materiais construídos e implementados ao longo das PES II e III, bem como autores de referência, de forma a fundamentar o texto. Relativamente à segunda parte do relatório final de estágio foi realizada uma investigação de caráter qualitativo, que teve como principal objetivo perceber de que forma a utilização de materiais didáticos, em aulas do 1.º Ciclo do Ensino Básico, influencia a aprendizagem da Matemática, num tópico muito particular: números racionais. Desta forma, foi realizado um teste diagnóstico de forma a perceber o conteúdo em que os alunos sentiam mais dificuldades. Posteriormente, foram desenvolvidas três tarefas diferentes, utilizando materiais didáticos distintos e, foi ainda realizada uma entrevista semiestruturada aos três participantes do estudo. A análise dos dados recolhidos permitiu concluir, com alguma segurança, que a utilização de materiais didáticos, em conteúdos matemáticos, é benéfica para os alunos, pois revelam maior envolvimento nas tarefas propostas e uma melhor compreensão dos conteúdos abordados.The final apprenticeship report is related to the scope of the Masters Degree of Pre-schooling and Teaching the 1st Cycle of Basic School. It includes a critical reflection in relation to the curricular units of Supervised Teaching Practice (II and III), in the context of apprenticeship, in the 1st Cycle of Basic School and in Pre-school Education. The report also contemplates research whose theme concentrates on the fields of mathematics. For the first part of the report several different materials were used, which had been built and implemented along STP II and III, as well as authors of reference, so as to support the text. In relation to the second part of the apprenticeship final report, a qualitative research was carried out, which main purpose was to understand to which extent the use of didactic materials in the 1st cycle of Basic School classes influences the learning of mathematics, in a very particular topic: rational numbers. This way, a diagnosis was performed for a better understanding of the contents in which learners feel the most difficulties. Later on three tasks were developed, by using different didactic materials, and a semi-structured interview was held to the three participants in the study. The analysis of the collected data allowed to conclude, with some certainty, that the use of didactic materials in mathematical contents is beneficial for learners, because they reveal a greater involvement in the proposed tasks and a better understanding of the addressed contents

Amyloid-Associated Nucleic Acid Hybridisation

Nucleic acids promote amyloid formation in diseases including Alzheimer's and Creutzfeldt-Jakob disease. However, it remains unclear whether the close interactions between amyloid and nucleic acid allow nucleic acid secondary structure to play a role in modulating amyloid structure and function. Here we have used a simplified system of short basic peptides with alternating hydrophobic and hydrophilic amino acid residues to study nucleic acid - amyloid interactions. Employing biophysical techniques including X-ray fibre diffraction, circular dichroism spectroscopy and electron microscopy we show that the polymerized charges of nucleic acids concentrate and enhance the formation of amyloid from short basic peptides, many of which would not otherwise form fibres. In turn, the amyloid component binds nucleic acids and promotes their hybridisation at concentrations below their solution Kd, as shown by time-resolved FRET studies. The self-reinforcing interactions between peptides and nucleic acids lead to the formation of amyloid nucleic acid (ANA) fibres whose properties are distinct from their component polymers. In addition to their importance in disease and potential in engineering, ANA fibres formed from prebiotically-produced peptides and nucleic acids may have played a role in early evolution, constituting the first entities subject to Darwinian evolution

Fluorescence Quantum Yield of Thioflavin T in Rigid Isotropic Solution and Incorporated into the Amyloid Fibrils

In this work, the fluorescence of thioflavin T (ThT) was studied in a wide range of viscosity and temperature. It was shown that ThT fluorescence quantum yield varies from 0.0001 in water at room temperature to 0.28 in rigid isotropic solution (T/η→0). The deviation of the fluorescence quantum yield from unity in rigid isotropic solution suggests that fluorescence quantum yield depends not only on the ultra-fast oscillation of ThT fragments relative to each other in an excited state as was suggested earlier, but also depends on the molecular configuration in the ground state. This means that the fluorescence quantum yield of the dye incorporated into amyloid fibrils must depend on its conformation, which, in turn, depends on the ThT environment. Therefore, the fluorescence quantum yield of ThT incorporated into amyloid fibrils can differ from that in the rigid isotropic solution. In particular, the fluorescence quantum yield of ThT incorporated into insulin fibrils was determined to be 0.43. Consequently, the ThT fluorescence quantum yield could be used to characterize the peculiarities of the fibrillar structure, which opens some new possibilities in the ThT use for structural characterization of the amyloid fibrils

The spin label amino acid TOAC and its uses in studies of peptides: chemical, physicochemical, spectroscopic, and conformational aspects

We review work on the paramagnetic amino acid 2,2,6,6-tetramethyl-N-oxyl-4-amino-4-carboxylic acid, TOAC, and its applications in studies of peptides and peptide synthesis. TOAC was the first spin label probe incorporated in peptides by means of a peptide bond. In view of the rigid character of this cyclic molecule and its attachment to the peptide backbone via a peptide bond, TOAC incorporation has been very useful to analyze backbone dynamics and peptide secondary structure. Many of these studies were performed making use of EPR spectroscopy, but other physical techniques, such as X-ray crystallography, CD, fluorescence, NMR, and FT-IR, have been employed. The use of double-labeled synthetic peptides has allowed the investigation of their secondary structure. A large number of studies have focused on the interaction of peptides, both synthetic and biologically active, with membranes. In the latter case, work has been reported on ligands and fragments of GPCR, host defense peptides, phospholamban, and β-amyloid. EPR studies of macroscopically aligned samples have provided information on the orientation of peptides in membranes. More recent studies have focused on peptide–protein and peptide–nucleic acid interactions. Moreover, TOAC has been shown to be a valuable probe for paramagnetic relaxation enhancement NMR studies of the interaction of labeled peptides with proteins. The growth of the number of TOAC-related publications suggests that this unnatural amino acid will find increasing applications in the future

Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response

<p>Abstract</p> <p>Background</p> <p>Ciguatoxins (CTXs) are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO) and molecular pathway enrichment of the gene expression data.</p> <p>Results</p> <p>A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p < 0.0001) with microarray results.</p> <p>Conclusions</p> <p>Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against neuroinflammation. Pathologic activity of the complement/coagulation cascade has been shown in patients suffering from a chronic form of ciguatera poisoning and is of particular interest in this model. Anti-inflammatory processes were at work not only in the brain but were also seen in whole blood and liver of these animals, creating a systemic anti-inflammatory environment to protect against the initial cellular damage caused by the toxin.</p