What drives an amyloid protein precursor from an amyloidogenic to a native-like aggregation pathway?

Conformational disorders such as Alzheimer’s, Parkinson’s, familial amyloidotic polyneuropathy and spongiform encephalopaties are a consequence of protein misfolding and aggregation predominantly in the form of amyloid fibrils. These pathologies represent a major health problem, which most probably will overwhelm the health systems of developed countries in the near future. Significant progress has been made recently to understanding the underlying mechanism of protein misfolding and aggregation. The current picture of protein aggregation is a phenomenon resulting from protein conformational fluctuations leading to misfolded intermediates prone to form non-native interactions with other intermediates, resulting in amyloid fibril formation. Fortunately just a small group of proteins are associated with human conformational disorders. The primary causes that lead this group of proteins to misfolding and aggregation are point mutations, protein over-expression and failure of protein quality-control system. Beside amyloid formation, there are other types of aggregation available to a misfold-disease-related polypeptide chain in the proteinfree energy landscape. Among them, native-like aggregation is becoming a widely studied topic of research.This aggregation type, simultaneously straightforward and ubiquitous, seems to be involved concurrently in the pathway of amyloid fibril formation and disruption. In this review, the pathways of misfold and aggregation of a protein are accessed along with the primary causes that turn a native soluble protein into amyloid fibrils or native-like aggregate. In addition, an insight into the biophysical and biochemical aspects fundamental to amyloid fibril formation and nativelike aggregation is provided. Finally some clues are presented about what makes a protein follow an amyloidogenic or native-like aggregation pathway.Conclusion: More laboratory data should be gathered about the structure, stability, dynamics and aggregation kinetics, in order to get a clearer picture of the biophysical mechanisms underlying native-like aggregation

A importância do estudo aprofundado da melodia na improvisação

Relatório de Estágio para a obtenção do grau de Mestre em Ensino da MúsicaEsta exposição é referente ao Relatório de Prática Educativa, no âmbito do Mestrado em Ensino da Música da Escola Superior de Música e Artes do Espectáculo (ESMAE) do Porto. Este deseja ser uma reflexão crítica sobre o ensino da música, práticas, métodos, metodologias, assim como dos seus presentes desafios, tem em conta a implementação de novas ofertas educativas na área do ensino da música e em particular do jazz no ensino artístico. Não obstante a reflexão sobre a Prática Educativa Supervisonada, descreve, ainda, um projeto de intervenção realizado no Conservatório de Música do Porto, e que contempla uma atividade realizada com e para os alunos do curso de Jazz do Conservatório de Música do Porto intitulada de “A Importância do Estudo Aprofundado da Melodia na Improvisação”. A minha intervenção consistiu em, através da análise da melodia de um tema, mais concretamente, através da redução melódica dos primeiros 8 compassos do tema All of Me com os alunos, perceber se havia influências musicais significativas nas improvisações dos mesmos. A metodologia foi a comparação entre as improvisações antes e depois da análise melódica e pequenos exercícios de improvisação à volta das notas resultantes da redução melódica baseando-se numa das componentes da análise schenkeriana. Pode-se concluir que a consciência auditiva das notas principais das melodias (Guide lines) é determinante no que respeita à capacidade de improvisar com sentido musical, uma vez que ajuda no desenvolvimento de linhas melódicas com uma relação próxima com o tema. As conclusões apontam para a ideia de que deve fazer parte da rotina de estudo dos alunos, uma análise das Guide lines das canções que interpretam.This exhibition refers to educational practice report, within the framework of the master's degree in Music Education at Escola Superior de Música e Artes do Espetáculo (ESMAE). It aims to be a critical reflection on the teaching of music, practices, methods, methodologies, as well as its present challenges and to take into account the implementation of new educational offerings in the area of the teaching of music and, in particular, of jazz in artistic education. Notwithstanding the reflection on the Overseen Educational Practice, it also describes an intervention project conducted at the Conservatório de Música do Porto, which includes an activity performed with and for the students of the Conservatório de Música do Porto entitled "The importance of the in-depth study of the melody in improvisation". My intervention was, through the analysis of the melody of a theme, more specifically, through the reduction of the melodic theme with students, to understand if there were significant musical influences in these improvisations. The methodology was the comparison between the improvisations before and after the melodic analysis and small improvisation exercises around the notes resulting from the melodic reduction based on the schenkerian analysis components. It can be concluded that the hearing conscience of the main notes of the melodies (Guide lines) is decisive in what concerns the ability to improvise with musical sense, since it helps in the development of melodic lines with a close relationship with the subject. The findings point to the idea that an analysis of the Guide lines of the songs being played must be part of the students’ study routine

Visual Memories of the marble industry: Using Cinema and Photography in Mining Heritage Studies

The introduction of new techniques and technological equipment into the Portuguese marble industry led to an exponential increase in production and, consequently, to profound environmental and landscape changes. The fact that the techniques had previously been adopted in other marble mining regions, like Wallonia (Belgium) and Carrara (Italy), confirms the standardization of the extraction and transformation process. However, despite using the same technology, each region’s local know-how and landscape features gave rise to different working contexts, many of which are not documented in written sources. Indeed, moving images and iconography prove to be a relevant source for studying local working techniques, machinery adaptations, or work distributions. Visual sources can be used to update previous studies and produce new ones, such as comparisons between quarrying techniques. Furthermore, these images prove to be a suitable and appealing educational instrument to show how technology has changed to allow firms to overcome market challenges and quarry vast mineral deposits

A Electricidade em Regiões do Interior: O Caso do Alentejo (Fins do Séc. XIX até à Década de 1950)

Nos vários países europeus a introdução electricidade não foi simultânea em todo o território, e em alguns casos verificou - se mesmo uma grande disparidade temporal entre as zonas que primeiro beneficiaram desta fonte de energia e aquelas que só m ais tarde vão dispor de energia eléctrica. Portugal foi um dos países em que se verificou uma grande diversidade na cronologia da electrificação das suas diferentes regiões. Se os principais centros urbanos beneficiaram da iluminação pública e privada através da electicidade a partir finais do século XIX, nas décadas de 60 e 70 do século XX ainda existiam amplas zonas do interior do país que aguardavam a electrificação

Neuroprotection or neurotoxicity of illicit drugs on Parkinson’s disease

Parkinson’s Disease (PD) is currently the most rapid growing neurodegenerative disease and over the past generation, its global burden has more than doubled. The onset of PD can arise due to environmental, sporadic or genetic factors. Nevertheless, most PD cases have an unknown etiology. Chemicals, such as the anthropogenic pollutant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amphetamine-type stimulants, have been associated with the onset of PD. Conversely, cannabinoids have been associated with the treatment of the symptoms’. PD and medical cannabis is currently under the spotlight, and research to find its benefits on PD is on-going worldwide. However, the described clinical applications and safety of pharmacotherapy with cannabis products are yet to be fully supported by scientific evidence. Furthermore, the novel psychoactive substances are currently a popular alternative to classical drugs of abuse, representing an unknown health hazard for young adults who may develop PD later in their lifetime. This review addresses the neurotoxic and neuroprotective impact of illicit substance consumption in PD, presenting clinical evidence and molecular and cellular mechanisms of this association. This research area is utterly important for contemporary society since illicit drugs’ legalization is under discussion which may have consequences both for the onset of PD and for the treatment of its symptoms.publishersversionpublishe

Assessing the content of a package of SGT-151 sold online

Abstract in proceedings of the Fourth International Congress of CiiEM: Health, Well-Being and Ageing in the 21st Century, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from 3–5 June 2019.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/publishedVersio

Circular dichroism of anthocyanidin 3-glucoside self-aggregates

“NOTICE: this is the author’s version of a work that was accepted for publication in Phytochemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Phytochemistry Volume 88, April 2013, Pages 92–98. DOI 10.1016/j.phytochem.2012.12.011 ."“NOTICE: this is the author’s version of a work that was accepted for publication in Phytochemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Phytochemistry Volume 88, April 2013, Pages 92–98. DOI 10.1016/j.phytochem.2012.12.011 .""Self-association constants for the flavylium cations of the six most common anthocyanidin 3-glucosides were determined by circular dichroism (CD) and UV–Vis spectroscopy. Along with previous 1H NMR results, all measurements were consistent with a monomer–dimer model. The CD spectra of the antho-cyanidin 3-glucosides were similar to the analogues 3,5-diglucosides. All dimers of the anthocyanidin 3-glucosides exhibited left-handed CD signals, with petunidin-3-glucoside and myrtillin having the most intense signals. In addition, the magnitude of the molar ellipticity, [h], was generally higher for the 3-glucosides than for the 3,5-diglucosides. For all six anthocyanins studied, the CD absorption spectra of their dimers showed evidence of the splitting of the monomer absorption into lower (J) and higher (H) energy bands. The angle and the distance between the dipolar moments of the two monomers comprising the dimer were obtained from the lower energy absorption band. While the angle was more or less similar in all six dimers, the separation distance between the monomer dipole moments differed dramatically. The intensity of the CD signal displayed a linear dependence with the inverse square of the dipole moment distances.

Toxicity of synthetic cannabinoids is increasing along with the regulatory measures taken for their control

Abstract in proceedings of the Fourth International Congress of CiiEM: Health, Well-Being and Ageing in the 21st Century, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from 3–5 June 2019.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/publishedVersio

2-Phenoxyethanol derivatization in ink dating determination

Abstract in proceedings of the Fourth International Congress of CiiEM: Health, Well-Being and Ageing in the 21st Century, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from 3–5 June 2019.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/publishedVersio

O Simbólico e o inconsciente na performance: uma análise sobre a filosofia de Nietzsche, em relação ao processo de criação do artista

Intitulada “O simbólico e o inconsciente na performance – Uma análise sobre a filosofia de Nietzsche em relação ao processo de criação do artista”, esta dissertação visa a uma perspectiva crítica sob os aspectos das condições do sujeito artista, que se utiliza do simbólico e do inconsciente, para se expressar através da performance, aliando-os à filosofia do referido autor alemão, a fim de se elucidar possíveis semelhanças e diferenças em que eles se deparam. O interesse por esses dois polos centrais investigativos de pesquisa, sendo ambos ainda bastante atuais, em que se buscam alternativas de descondicionamento do ser humano perante à sociedade, foi a questão da autonomia criativa do sujeito. Devido à presença de camadas da psique que oferecem conteúdos por vezes desconhecidos pela razão e que perpassam pelo corpo, o que estes poderiam auxiliar na reflexão e na autorreflexão sobre as inquietações pessoais e existenciais do artista-performer? O primeiro capítulo tem por intenção primeira, traçar uma panorâmica sobre as confluências de pensamento do objeto investigativo desta dissertação. Começa-se pela contextualização histórica da Grécia Antiga, visto que é relevante reconhecer as semelhanças de características comportamentais do homem ocidental daquela época, mais especificamente dos pré-socráticos, com a performance. Em ambos se encontram formas de reação, de enfrentamento e de respostas frente ao desconforto com o exterior que os afetaram e afetam em vida, e cuja afirmação da dor e do sofrimento propriciou a reconciliação de duas forças imanentes transformadoras, refletindo a própria arte, a própria vida: o dionisíaco e o apolíneo. Em seguida, para se obter uma melhor compreensão, busca-se registrar o elemento que assumirá grande proporção de veículo expressivo de pensamento, tanto para o filósofo como para a performance: o corpo como lugar da memória e do simbólico. A discussão a se apresentar nesse capítulo é dividida em subtópicos que interligam com os conteúdos do inconsciente. É nesse caminho do obscuro da psique que o território do simbólico entra como fator importante na performance, atribuindo assim o (re)conhecimento de valores a partir de novo solo que estejam em consonância com o corpo, com a vida, com a terra e com o outro. Procura-se por isso uma ligação direta de possibilidade ao retorno da subjetividade criativa do artista, refletida no processo de individuação junguiano. Por último, estabelece-se o capítulo em que as diretrizes são voltadas às diferentes fases do niilismo, no intuito de demonstrar as condições e transformações do sujeito, o da negação à superação do artista criador. Busca-se também aferir à metáfora nietzschiana das três metamorfoses do ser, como um projeto que propõe a transformação, a intensificação da vida e a superação do indivíduo, frente aos valores morais vigentes, através da primazia do criar sob o conhecimento e de suas ações, corroborando com a transitoriedade de tudo que vive.Entitled "The Symbolic and the Unconscious in Performance - An Analysis of Nietzsche's philosophy in relation to the artist's creation process", this dissertation aims at a critical perspective under the aspects of the conditions of the artist subject, which uses the symbolic and the unconscious, to express themselves through performance, linking them to the philosophy of the german author, in order to elucidate possible similarities and differences in which they come across. The interest in these two research centers, both of which are still quite current, in which alternatives are sought for the deconditioning of the human being before society, was the question of the creative autonomy of the subject. Due to the presence of layers of the psyche that offer content sometimes unknown by reason and that pass through the body, what could help in reflection and self-reflection on the personal and existential concerns of artist-performer? The first chapter of this dissertation intends first to draw a panorama under the confluences of thought of the investigative object of this dissertation. It begins with the historical contextualization of Ancient Greece, since it is relevant to recognize the similarities of behavioral characteristics of the western man of that time, specifically the pre-socratics ones, with performance. In both there are forms of reaction, confrontation and responses to the discomfort with the exterior that affected them in life, and whose affirmation of pain and suffering led to the reconciliation of two transforming immanent forces, reflecting art itself, life itself: the dionysian and the apollonian. Then, to obtain a better understanding, it is sought to record the element that will assume a great proportion of expressive vehicle of thought, both for the philosopher and for performance: the body as a place of memory and symbolic. The discussion to be presented also in this chapter is divided into subtopics that interconnect with the contents of the unconscious. It is in this obscure path of the psyche that the territory of the symbolic enters as an important factor in the performance, thus attributing the knowledge and recognition of values from new soil that are in harmony with the body, with life, with the earth and with the other. A direct connection of possibility is therefore sought for the return of the artist's creative subjectivity, reflected in the jungian process of individuation. Finally, the chapter is established in which the guidelines are directed to the different phases of nihilism, in order to demonstrate the conditions and transformations of the subject, that of the negation to the overcoming of the creative artist. It also seeks assess the Nietzschean metaphor of the three metamorphoses of being, as a project that proposes the transformation, intensification of life and the overcoming of the individual, in the face of prevailing moral values, through the primacy of creating under knowledge and its actions, corroborating the transience of all that lives