Arquitectas: (Des)construindo Percursos

A presente Dissertação de Mestrado, Arquitectas: (Des)construindo Percursos, propõe uma reflexão sobre o legado das mulheres na Arquitectura e a conjuntura das parcerias entre géneros diferentes, tanto a nível nacional como internacional. Os percursos das arquitectas iniciam-se, ainda que tardiamente, graças ao gradual acesso à esfera académica em arquitectura e devido, sobretudo, às significativas alterações sociais ocorridas ao longo dos séculos. Não obstante, as contribuições femininas permanecem silenciadas, tanto as do passado como as da contemporaneidade, quer a título individual quer em parcerias sendo, geralmente, posicionadas para um segundo plano em relação ao elemento masculino da dupla. Desta forma, torna-se fundamental descortinar o protagonismo feminino e a (in)visibilidade dos seus percursos para que se possa (re) construir a representatividade, a natureza e os limites da própria disciplina. Este trabalho surge assim, na tentativa de reformular uma Arquitectura que visa incluir as perspectivas das arquitectas, expondo os cenários públicos, profissionais e educacionais vividos. Para a concretização final desta reflexão preconiza-se a análise dos percursos das arquitectas, Joana Vasconcelos e Fátima Fernandes, de forma a contribuir para a sua visibilidade e reconhecimento na Arquitectura Portuguesa.This Master Dissertation, The Female Architects: (Des)constructing Paths, requires a reflection about women´s legacy in Architecture and the work partnerships between both genders, nationally and internationally. Women jouney in Architecture started late, due to the slow acess to the gender at superior studies and, it´s directly linked with major social accomplishments made through the centuries. Even though womens work in architecture came a long way, their insight is still very invisible, like we saw happening the past. Working by themselves or in partnerships, they are still a background figure, even in partnerships the central figure is the male. It urges, to envelop womens main role and (in)visibility of their work so that it can be (re) built in terms of the representativity, nature and limits of the architecture itself. This work is an attempt to reformulate an architecture so that it includes the womens architects vision, in public life, professional and educational cenaries. As a final reflection we showcase the work of two portuguese architects Joana Vasconcelos e Fátima Fernandes as a contribution to their visibility and acknowledgment in Portuguese Architecture

Blaming Bill Gates AGAIN! Misuse, overuse and misunderstanding of performance data in sport

Recently in Sport, Education and Society, Williams and Manley (2014) argued against the heavy reliance on technology in professional Rugby Union and elite sport in general. In summary, technology is presented as an elitist, ‘gold standard’ villain that management and coaches use to exert control and by which players lose autonomy, identity, motivation, social interactions and expertise. In this article we suggest that the sociological interpretations and implications offered by Williams and Manley may be somewhat limited when viewed in isolation. In doing so, we identify some core methodological issues in Williams and Manley’s study and critically consider important arguments for utilising technology; notably, to inform coach decision making and generate player empowerment. Secondly, we present a different, yet perhaps equally concerning, practice-oriented interpretation of the same results but from alternative coaching and expertise literature. Accordingly, we suggest that Williams and Manley have perhaps raised their alarm prematurely, inappropriately and on somewhat shaky foundations. We also hope to stimulate others to consider contrary positions, or at least to think about this topic in greater detail. More specifically, we encourage coaches and academics to think carefully about what technology is employed, how and why, and then the means by which these decisions are discussed with and, preferably, sold to players. Certainly, technology can significantly enhance coach decision making and practice, while also helping players to optimise their focus, empowerment and independence in knowing how to achieve their personal and collective goals

Osteoarthritis:Mechanistic Insights, Senescence, and Novel Therapeutic Opportunities

Osteoarthritis (OA) is the most common joint disease. In the last years, the research community has focused on understanding the molecular mechanisms that led to the pathogenesis of the disease, trying to identify different molecular and clinical phenotypes along with the discovery of new therapeutic opportunities. Different types of cell-to-cell communication mechanisms have been proposed to contribute to OA progression, including mechanisms mediated by connexin43 (Cx43) channels or by small extracellular vesicles. Furthermore, changes in the chondrocyte phenotype such as cellular senescence have been proposed as new contributors of the OA progression, changing the paradigm of the disease. The use of different drugs able to restore chondrocyte phenotype, to reduce cellular senescence and senescence-associated secretory phenotype components, and to modulate ion channel activity or Cx43 appears to be promising therapeutic strategies for the different types of OA. In this review, we aim to summarize the current knowledge in OA phenotypes related with aging and tissue damage and the new therapeutic opportunities currently available

A neutralizing IL-11 antibody reduces vessel hyperplasia in a mouse carotid artery wire injury model

Vascular restenosis remains a major problem in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). Neointimal hyperplasia, defined by post-procedure proliferation and migration of vascular smooth muscle cells (VSMCs) is a key underlying pathology. Here we investigated the role of Interleukin 11 (IL-11) in a mouse model of injury-related plaque development. Apoe−/− mice were fed a hyperlipidaemic diet and subjected to carotid wire injury of the right carotid. Mice were injected with an anti-IL11 antibody (X203), IgG control antibody or buffer. We performed ultrasound analysis to assess vessel wall thickness and blood velocity. Using histology and immunofluorescence approaches, we determined the effects of IL-11 inhibition on VSMC and macrophages phenotypes and fibrosis. Treatment of mice with carotid wire injury using X203 significantly reduced post-endothelial injury vessel wall thickness, and injury-related plaque, when compared to control. Immunofluorescence staining of the injury-related plaque showed that X203 treatment did not reduce macrophage numbers, but reduced the number of VSMCs and lowered matrix metalloproteinase 2 (MMP2) levels and collagen content in comparison to control. X203 treatment was associated with a significant increase in smooth muscle protein 22α (SM22α) positive cells in injury-related plaque compared to control, suggesting preservation of the contractile VSMC phenotype. Interestingly, X203 also reduced the collagen content of uninjured carotid arteries as compared to IgG, showing an additional effect on hyperlipidemia-induced arterial remodeling in the absence of mechanical injury. Therapeutic inhibition of IL-11 reduced vessel wall thickness, attenuated neointimal hyperplasia, and has favorable effects on vascular remodeling following wire-induced endothelial injury. This suggests IL-11 inhibition as a potential novel therapeutic approach to reduce arterial stenosis following revascularization in CAD and PAD patients

Recruitment of RNA molecules by connexin RNA-binding motifs: Implication in RNA and DNA transport through microvesicles and exosomes

Connexins (Cxs) are integral membrane proteins that form high-conductance plasma membrane channels, allowing communication from cell to cell (via gap junctions) and from cells to the extracellular environment (via hemichannels). Initially described for their role in joining excitable cells (nerve and muscle), gap junctions (GJs) are found between virtually all cells in solid tissues and are essential for functional coordination by enabling the direct transfer of small signalling molecules, metabolites, ions, and electrical signals from cell to cell. Several studies have revealed diverse channel-independent functions of Cxs, which include the control of cell growth and tumourigenicity. Connexin43 (Cx43) is the most widespread Cx in the human body. The myriad roles of Cx43 and its implication in the development of disorders such as cancer, inflammation, osteoarthritis and Alzheimer's disease have given rise to many novel questions. Several RNA- and DNA-binding motifs were predicted in the Cx43 and Cx26 sequences using different computational methods. This review provides insights into new, ground-breaking functions of Cxs, highlighting important areas for future work such as transfer of genetic information through extracellular vesicles. We discuss the implication of potential RNA- and DNA-binding domains in the Cx43 and Cx26 sequences in the cellular communication and control of signalling pathwaysThis work was supported in part through funding from the Society for Research on Bone and Mineral Metabolism - Grant number FEIOMM2016 (to M.D.M.), by grant PRECIPITA-2015-000139 from the FECYT-Ministry of Economy and Competitiveness (to M.D.M), by grants PI13/00591 and PI16/00035 from the Health Institute “Carlos III” (ISCIII, Spain) and co-financed by the European Regional Development Fund, “A way of making Europe” from the European Union (to M.D.M.), by a grant from Xunta de Galicia (pre-doctoral fellowship) to M.V.-E., and by a grant from the Ministry of Education, Culture and Sports, Spain (FPU grant to M.R.-C.M.)S

Understanding the process of psychological development in youth athletes attending an intensive wrestling camp

This study used a grounded theory methodology to understand if and how psychological development in youth athletes was facilitated by an ‘intensive’ summer wrestling camp experience. The theoretical sampling approach involved 10 athlete participants of the camp, nine parents of athletes, the director of the camp, and four camp staff members, who took part in a series of interviews before, during, and after the camp. Two researchers were also embedded in the camp and attended all sessions, took detailed notes, collected camp materials, and conducted observations. Following a grounded theory analysis approach, a model is presented that outlines how youth participants’ developed psychological qualities from the coach created hallenges and adversity that were systematically designed to facilitate sport performance enhancement and life skills. Variations emerged in psychological antecedents and characteristics, how the challenging wrestling camp environment was interpreted and experienced, and how learning was transferred to sport and life domains outside of the wrestling camp. This study provided insight into a unique youth sport context that was able to simultaneously develop psychological qualities to be used as sport performance enhancement and life skills

DNA replication stress restricts ribosomal DNA copy number

Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number

Senolytic Activity of Small Molecular Polyphenols from Olive Restores Chondrocyte Redifferentiation and Promotes a Pro-Regenerative Environment in Osteoarthritis

[Abstract] Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43 and cellular senescence for tissue engineering and regenerative medicine strategies for OA treatment. Oleuropein regulates Cx43 promoter activity and enhances the propensity of hMSCs to differentiate into chondrocytes and bone cells, reducing adipogenesis. This small molecule reduce Cx43 levels and decrease Twist-1 activity in osteoarthritic chondrocytes (OACs), leading to redifferentiation, restoring the synthesis of cartilage ECM components (Col2A1 and proteoglycans), and reducing the inflammatory and catabolic factors mediated by NF-kB (IL-1ß, IL-6, COX-2 and MMP-3), in addition to lowering cellular senescence in OACs, synovial and bone cells. Our in vitro results demonstrate the use of olive-derived polyphenols, such as oleuropein, as potentially effective therapeutic agents to improve chondrogenesis of hMSCs, to induce chondrocyte re-differentiation in OACs and clearing out senescent cells in joint tissues in order to prevent or stop the progression of the disease.Xunta de Galicia; IN607B 2017/21Xunta de Galicia; ED481A-2015/188Xunta de Galicia; IN606B-2019/004Xunta de Galicia; IN606B-2017/014This work was supported in part through funding from the Spanish Foundation for Research on Bone and Mineral Metabolism (FEIOMM), grant PRECIPITA-2015-000139 from the FECYT-Ministry of Economy and Competitiveness (to M.D.M.), grant PI16/00035 and PI19/00145 from the Health Institute ‘Carlos III’ (ISCIII, Spain), the European Regional Development Fund, ‘A way of making Europe’ from the European Union (to M.D.M.) and a grant from Xunta de Galicia IN607B 2017/21 (to M.D.M.). M.V.-E. was funded with a predoctoral (ED481A-2015/188) and a postdoctoral fellowship (IN606B-2019/004) from Xunta de Galicia. P.C.-F. was funded with a postdoctoral fellowship (IN606B-2017/014) from Xunta de Galicia