RCAAP Repository

Pancreatic cancer (PCA) is one of the most lethal malignancies worldwide with a 5-year survival rate of 9%. Despite the advances in the field, the need for an earlier detection and effective therapies is paramount. PCA high heterogeneity suggests that epigenetic alterations play a key role in tumour development. However, only few epigenetic biomarkers or therapeutic targets have been identified so far. Here we explored the potential of distinct DNA methylation signatures as biomarkers for early detection and prognosis of PCA. PI3K/AKT-related genes differentially expressed in PCA were identified using the Pancreatic Expression Database (n = 153). Methylation data from PCA patients was obtained from The Cancer Genome Atlas (n = 183), crossed with clinical data to evaluate the biomarker potential of the epigenetic signatures identified and validated in independent cohorts. The majority of selected genes presented higher expression and hypomethylation in tumour tissue. The methylation signatures of specific genes in the PI3K/AKT pathway could distinguish normal from malignant tissue at initial disease stages with AUC > 0.8, revealing their potential as PCA diagnostic tools. ITGA4, SFN, ITGA2, and PIK3R1 methylation levels could be independent prognostic indicators of patients' survival. Methylation status of SFN and PIK3R1 were also associated with disease recurrence. Our study reveals that the methylation levels of PIK3/AKT genes involved in PCA could be used to diagnose and predict patients' clinical outcome with high sensitivity and specificity. These results provide new evidence of the potential of epigenetic alterations as biomarkers for disease screening and management and highlight possible therapeutic targets.

X-inactive-specific transcript (Xist) is a long non-coding RNA (lncRNA) essential for X-chromosome inactivation (XCI) in female placental mammals. Thirty years after its discovery, it is still puzzling how this lncRNA triggers major structural and transcriptional changes leading to the stable silencing of an entire chromosome. Recently, a series of studies in mouse cells have uncovered domains of functional specialization within Xist mapping to conserved tandem repeat regions, known as Repeats A-to-F. These functional domains interact with various RNA binding proteins (RBPs) and fold into distinct RNA structures to execute specific tasks in a synergistic and coordinated manner during the inactivation process. This modular organization of Xist is mostly conserved in humans, but recent data point towards differences regarding functional specialization of the tandem repeats between the two species. In this review, we summarize the recent progress on understanding the role of Xist repetitive blocks and their involvement in the molecular mechanisms underlying XCI. We also discuss these findings in the light of the similarities and differences between mouse and human Xist.

An intriguing and remarkable feature of African trypanosomes is their antigenic variation system, mediated by the variant surface glycoprotein (VSG) family and fundamental to both immune evasion and disease epidemiology within host populations. Recent studies have revealed that the VSG repertoire has a complex evolutionary history. Sequence diversity, genomic organization, and expression patterns are species-specific, which may explain other variations in parasite virulence and disease pathology. Evidence also shows that we may be underestimating the extent to what VSGs are repurposed beyond their roles as variant antigens, establishing a need to examine VSG functionality more deeply. Here, we review sequence variation within the VSG gene family, and highlight the many opportunities to explore their likely diverse contributions to parasite survival.

Tomados na sua especificidade, os fenômenos educativos referem-se a uma acção que se insere num contexto e evolui num determinado sentido, compreendendo uma materialidade, uma materialização e uma substantivação; uma relação de comunicação, alteridade e transmissão entre agentes e sujeitos; uma projecção e uma apropriação. Abordarei estas questões no quadro paradigmático, complexo e multidimensional, das instituições educativas, focalizado enquanto objecto que se constitui como uma totalidade em organização e em evolução. Adoptarei um registo teórico-prático, procurando referências arquivísticas, hermenêuticas e discursivas neste quadro investigativo específico da histórica das instituições escolares e das práticas educativas.

We report the case of a patient with symptoms of myelopathy following acute SARS-CoV-2 infection. MRI documented a longitudinally extensive transverse myelitis and further investigation was unremarkable with the exception of positivity for MOG-IgG in serum. This report extends the spectrum of post-COVID-19 neurological syndromes, and documents a very significant improvement to long-term oral corticosteroid therapy in this setting. Further prospective studies are needed to establish the risk of recurrence in this subset of patients.

Interleukin-7 receptor α (encoded by IL7R) is essential for lymphoid development. Whether acute lymphoblastic leukemia (ALL)-related IL7R gain-of-function mutations can trigger leukemogenesis remains unclear. Here, we demonstrate that lymphoid-restricted mutant IL7R, expressed at physiological levels in conditional knock-in mice, establishes a pre-leukemic stage in which B-cell precursors display self-renewal ability, initiating leukemia resembling PAX5 P80R or Ph-like human B-ALL. Full transformation associates with transcriptional upregulation of oncogenes such as Myc or Bcl2, downregulation of tumor suppressors such as Ikzf1 or Arid2, and major IL-7R signaling upregulation (involving JAK/STAT5 and PI3K/mTOR), required for leukemia cell viability. Accordingly, maximal signaling drives full penetrance and early leukemia onset in homozygous IL7R mutant animals. Notably, we identify 2 transcriptional subgroups in mouse and human Ph-like ALL, and show that dactolisib and sphingosine-kinase inhibitors are potential treatment avenues for IL-7R-related cases. Our model, a resource to explore the pathophysiology and therapeutic vulnerabilities of B-ALL, demonstrates that IL7R can initiate this malignancy.

Active commuting to and from school (ACS) is a strategy to enhance physical activity levels in youths. To promote ACS, it is important to understand the factors that lead to this behaviour. With this in mind, an adaptation of the Basic Psychological Needs in Exercise Scale for ACS was developed, named the Basic Psychological Need Satisfaction in Active Commuting to and from School (BPNS-ACS) scale. This study aimed to translate and evaluate the psychometric properties of the BPNS-ACS scale in young Portuguese students. A cross-sectional study was designed. A total of 338 students (212 girls, 126 boys), aged between 11 and 19 years old from 31 Portuguese cities participated in this study. To provide validity evidence based on the questionnaire's internal structure, confirmatory factor analyses were performed to test the three dimensions of the BNPS-ACS scale. The results of the confirmatory factor analysis indicated an acceptable fit to the data. The internal consistency of the measures was accepted as the composite reliability values ranged from 0.78 to 0.94. The evaluation of psychometric properties provided evidence of the adequacy of this questionnaire among Portuguese youth aged 11 to 19 years old.

A pergunta contida no título deste livro sugere um pressuposto tácito e uma resposta implícita. O pres - suposto consiste em admitir que o capitalismo, en - quanto sistema económico, social, político e cultural, teve uma época em que demonstrou o seu carácter progressivo. A resposta remete para um enunciado de dúvida de que o capitalismo possa continuar a ser progressivo, ao mesmo tempo que convida o leitor a acreditar que algo pode e deve ser feito para que de novo o venha a ser

Through the drawing tool, Cristiana Silva elaborates a set of registers where shelooks for and explores issues of identity as well as inherent moments, these being fragmented to a unique identity that in turn is dispersed from the initial image captured. By recording several moments of his daily and intimate life, as in an archival manner as well as safeguarding something that is in itself immaterial to safeguard, she revives it again and reinterprets it through constructive processes of drawing, transferring it, that abstratic and incapable of replacing to an a Another platform, another support, another purpose. Through Drawing, as well as her skills and characteristics acquired to date, Cristiana, simultaneously explores not only the divergences of innumerable errors that occur in the moment, and therefore, develop through it different means of dialogue, plastic exploration, communication process and continuation among themselves, among others, as well as self-recognition of inherent successive moments, frozen in an memory attachment. Drawing is not only a means of communication but also a source of self-discovery, as a unit, as a tool for communication and thinking. Thus, in this way, the Project started in 2015, during the course of the BA, at the Faculty of Licenciatura de Belas Artes, where it has been extended to date. It is a project that continues in continuity with its identity, which in turn was still very new at the time, where it is possible to see a growth, not only in its practical exploration but also as being, character, person.

A posição privilegiada que o artista detinha permitia-lhe registar, através da sua prática, a complexidade da sociedade em que se inseria. Ao longo do final do século XIX e no início do século XX, à semelhança de períodos anteriores, a produção artística demonstrou interesse no modo como o género feminino vivia. A presente dissertação aborda esse fascínio provocado pela figura da mulher, analisando a diversificação de espaços por ela ocupados e representados pela produção artística. Mediante a defesa de uma arte que se pretendia moderna, adequando-se à sociedade na qual era produzida, os artistas serviram-se da sua prática para reflectir acerca das questões que demarcavam o seu tempo. E, nesse sentido, as questões relacionadas com a vivência do género feminino não foram excepção. Através de abordagens mais ou menos idealizadas, consoante a escolha efectuada pelo artista, as obras deste período testemunham a complexidade da vivência do género feminino, constituindo-se, assim, como o nosso objecto de estudo. Conforme veremos, as actividades desempenhadas pelas mulheres representadas nas obras de arte que escolhemos analisar, o modo como elas são representadas e até mesmo os espaços nos quais são retratadas, poderão ilustrar um modelo de mulher ideal. Caracterizando assim um cânone de beleza, de vivência, que limitava as actividades desempenhadas pelas mulheres àquelas que eram consideradas como adequadas à sua condição como: a leitura, a escrita, o consumo de bens de luxo. Todos estes aspectos são registados na obra de arte. Esta padronização da vivência do género feminino foi, contudo, contornada por alguns artistas, designadamente pelos seus pares, conforme teremos oportunidade de observar. O nosso estudo percorre, assim, o período entre 1880 e 1930, observando a evolução da condição feminina na obra de arte.

This paper aims to discuss the original sense of the myth of Narcissus, pointing out its relation with ritual and cult in Ancient Greece.

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Trata-se de um projecto de pintura e instalação pictural no qual o autor explora situações artísticas e espaciais que confrontam o espectador com gestos e procedimentos simultaneamente pertencentes ao domínio da pintura, do vídeo e do cinema, tendo como disrupção comum o glitch criativo, ou seja, uma modalidade de acaso expressivo e tecnológico cujas primeiras manifestações, segundo o próprio, derivam do elemento pictural, embora, com dispositivos e instrumentos diferentes dos outros media mencionados. Pelos motivos apresentados, algumas das peças instaladas aludem a Stan Brakhage, outras a Jennifer West ou a Takeshi Murata, outras ainda, aludem às conquistas ‘involuntárias’ de Protogenes para a pintura e para a arte em geral, em plena Grécia Antiga, resultado da angústia e dos impasses experienciados na realização de uma pintura pelo pintor de Rodes.

Seguindo a imprensa para avaliar a recepção da cultura de protesto em Portugal, o presente estudo centra-se na ideia de que os fenómenos contraculturais que decorreram no nosso país em finais da década de 60 foram manifestações que, tendo tido origem no estrangeiro, chegaram a Portugal com uma força que nem um regime que se opunha a valores democráticos podia travar. Para além disso, pretende-se estabelecer pontos de contacto entre os movimentos congéneres nos EUA, em França, no Reino Unido e em Portugal, país que vivia os anos finais de uma ditadura. Dado que este estudo se baseia na imprensa nacional, importa, não apenas clarificar conceitos como os de «cultura», «contracultura» e «cultura de protesto», mas também tentar interpretar o papel que teve a imprensa periódica na disseminação da cultura (de protesto) no Portugal dessa época. Neste sentido, não se pode deixar de dar relevância às novas (ou velhas) políticas que Marcelo Caetano adoptou para o país e para a imprensa. Se a censura continuou a existir após o afastamento político de Salazar, é necessário explicar de que forma jornalistas, escritores e intelectuais de diferentes áreas foram conseguindo protestar num país que, embora estivesse a passar por um processo de acentuado crescimento económico (como acontecia com muitos dos países democráticos ocidentais), não garantia as liberdades individuais de expressão.

Após apresentar, contextualizar e caracterizar os Cadernos de um Barbeiro, refiro-me à importância ao mérito do labor historiográfico de Ernesto Português. Faço uso de três conceitos-chave, que defino e aplico: sociabilidade escrita; ego-escrita; memória colectiva.

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Background: Individuals recovering from COVID-19 are known to have antibodies against the Spike and other structural proteins. Antibodies against Spike have been shown to display viral neutralization. However, not all antibodies against Spike have neutralizing ability although they may be cross-reactive. There is a need for easy-to-use SARS-CoV-2 neutralizing assays for the determination of virus-neutralizing activity in sera of individuals. Here we describe a PCR-based micro-neutralization assay that can be used to evaluate the viral neutralization titers of serum from SARS-CoV-2 infected individuals. Methods: The SARS-CoV-2 strain used was isolated from a nasopharyngeal specimen of a COVID-19 case. The limiting dilution method was used to obtain a 50% tissue culture infective dose (TCID50) of Vero cells. For the micro-neutralization assay, 19 serum samples, with positive IgG titers against Spike Receptor-Binding Domain (RBD) were tested. After 24 hours, infected cells were inspected for the presence of a cytopathic effect, lysed and RNA RT-PCR conducted for SARS-CoV-2. PCR target Ct values were used to calculate percent neutralization/inhibition of SARS-CoV-2. Results: Out of 19 samples, 13 samples gave 100% neutralization at all dilutions, 1 sample showed neutralization at the first dilution, 4 samples showed neutralization at lower dilutions, while one sample did not demonstrate any neutralization. The RBD ODs and neutralization potential percentages were found to be positively correlated. Conclusion: We describe a rapid RT-PCR-based SARS-CoV-2 microneutralization assay for the detection of neutralizing antibodies. This can effectively be used to test the antiviral activity of serum antibodies for the investigation of both disease-driven and vaccine-induced responses.

School archives cause a profound concern regarding the safe-keeping and preservation of documents which are fundamental tools for the history of a school and for the construc‑ tion of educational memory. Their importance has come to be recognized and has led to considering their preservation, conditions of installations, the correct organization of the documents and access to the information therein. The school archives are a repository of sources of information directly related to the functioning of educational institutions, which confers upon them a growing importance in the new paths of research in educa‑ tion. This places these institutions in a centralised position as regards understanding ed‑ ucational phenomena and the socialisation processes of the younger generations. In this paper we intend to reflect about: the role of school archives in educational institutions; the documents, their nature and the potentials for research in education; school archives from an interdisciplinary perspective; the archives, school culture and the construction of educational memory.

Pulmonary rehabilitation is based on a thorough patient assessment, including peripheral oxygen saturation (SpO2) and heart rate (HR) at rest and on exertion. To understand whether exercise-field tests identify patients who desaturate (SpO2 < 90%) during physical activities, this study compared the six-minute walk test (6MWT) and daily-life telemonitoring. Cross-sectional study including 100 patients referred for pulmonary rehabilitation. The 6MWT was performed in hospital with continuous assessment of SpO2, HR, walked distance and calculated metabolic equivalent of tasks (METs). Patients were also evaluated in real-life by SMARTREAB telemonitoring, a combined oximetry-accelerometery with remote continuous assessment of SpO2, HR and METs. SMARTREAB telemonitoring identified 24% more desaturators compared with the 6MWT. Moreover, there were significant mean differences between 6MWT and SMARTREAB in lowest SpO2 of 7.2 ± 8.4% (P < 0.0005), in peak HR of - 9.3 ± 15.5% (P < 0.0005) and also in activity intensity of - 0.3 ± 0.8 METs (P < 0.0005). The 6MWT underestimates the proportion of patients with exercise-induced oxygen desaturation compared to real-life telemonitoring. These results help defining oximetry-guided interventions, such as telemedicine algorithms, oxygen therapy titration and regular physical activity assessment in pulmonary rehabilitation.