Phenotype-driven identification of epithelial signalling clusters

In metazoans, epithelial architecture provides a context that dynamically modulates most if not all epithelial cell responses to intrinsic and extrinsic signals, including growth or survival signalling and transforming oncogene action. Three-dimensional ( 3D) epithelial culture systems provide tractable models to interrogate the function of human genetic determinants in establishment of context-dependency. We performed an arrayed genetic shRNA screen in mammary epithelial 3D cultures to identify new determinants of epithelial architecture, finding that the key phenotype impacting shRNAs altered not only the data population average but even more noticeably the population distribution. The broad distributions were attributable to sporadic gene silencing actions by shRNA in unselected populations. We employed Maximum Mean Discrepancy concept to capture similar population distribution patterns and demonstrate here the feasibility of the test in identifying an impact of shRNA in populations of 3D structures. Integration of the clustered morphometric data with protein-protein interactions data enabled hypothesis generation of novel biological pathways underlying similar 3D phenotype alterations. The results present a new strategy for 3D phenotype-driven pathway analysis, which is expected to accelerate discovery of context-dependent gene functions in epithelial biology and tumorigenesis.Peer reviewe

Histórias de vida : um instrumento de pesquisa ao serviço da inclusão social

Intervenção social. - ISSN 0874-1611. - N. 49/50 (2017). - p. 67-83.Neste artigo pretende-se debater as virtualidades das histórias de vida, enquanto instrumento de pesquisa, tomando como exemplo uma investigação já concluída. Uma investigação cujo principal objetivo foi o de analisar um projeto de intervenção que se propôs inverter trajetórias de desinvestimento na qualificação escolar de jovens cuja socialização ocorreu em contextos fortemente restritivos de oportunidades. Partindo das reflexões produzidas na referida investigação, procurar-se-á discutir como se pode tirar partido das histórias de vida não só para aprofundar a compreensão dos processos sociais que empurram numerosos jovens para as margens da sociedade, mas também para neles desencadear a tomada de consciência de que podem distanciar-se, em alguma medida, dos seus habitus2 originais e, de certo modo, provocar a alteração do seu “destino” social

Study protocol of the YP Face IT feasibility study: Comparing an online psychosocial intervention versus treatment as usual for adolescents distressed by appearance-altering conditions/injuries

© Published by the BMJ Publishing Group Limited. Introduction A significant number of adolescents suffer extensive and enduring difficulties such as social anxiety, body image dissatisfaction, low self-esteem and bullying as a result of conditions or injuries that affect their appearance (eg, craniofacial and skin conditions, treatment side effects and scarring). Evidence-based psychosocial interventions to meet their specific needs are currently lacking. YP Face IT, developed by the UK's Centre for Appearance Research in collaboration with clinical experts and young people, is an innovative online psychosocial intervention designed to offer this group immediate support, advice and coping strategies. It has been endorsed by young people, their parents/carers, GPs, clinical psychologists and health professionals working with those affected by appearance-related conditions. Methods and analysis Young people aged 12-17 with an appearance-altering condition/injury that self-identify as experiencing appearance-related distress, teasing or bullying will be invited to participate via GP practices and UK charities. Consenting participants will be randomised to the intervention (YP Face IT) or the treatment as usual (TAU) control group. Outcome measures will be completed by young people and their parents/carers at baseline, 13, 26 and 52â €..weeks. Primary outcome measures will be the Body Esteem Scale and the Social Anxiety Scale for Adolescents. Participants will complete other health-related outcome measures and resource use questionnaires for health economic analysis. We will assess recruitment rates, acceptability of the YP Face IT programme, adherence and retention to treatment, questionnaire completion rates, variation of TAU in Primary Care and the feasibility of GP practice staff supervising young people's use of YP Face IT. Ethics and dissemination This feasibility trial protocol (V.1, 3 March 2014), received a favourable ethical opinion from the NRES Committee South West-Frenchay (reference number 14/SW/0058). Findings will be disseminated through academic peer-reviewed publications, conferences and to participating GP practices and charities supporting those with conditions affecting appearance

O conforto em contexto de urgência: a experiência da família da pessoa em situação crítica

Background: When facing a critical illness, patients and their families need comfort. Objective: To understand how families of critically ill patients experience comfort in emergency settings. Methodology: This exploratory descriptive mixed-method study uses semi-structured interviews in a non-probability convenience sample of ten family members of critically ill patients in emergency services. Results: Comfort was described as a state/perception of security, with emphasis on psychospiritual and physical dimensions. Comfort-promoting factors were related to nurses’ positive attitudes/interactions and technical-scientific and relational skills, with emphasis on the psychospiritual dimension. Suggestions for comfort promotion focused on the development of relational and communication skills. Conclusion: Comfort is associated with the situation/circumstance experienced and is transitory. In emergency services, comfort emerges as a dimension that nurses can adjust by harmonizing interests and performing specific actions that empower the families of critically ill patients.Enquadramento: Perante a vivência de uma doença crítica, o conforto enquanto necessidade acontece tanto na pessoa que vivencia a doença, como nos seus familiares. Objetivo: Compreender a experiência do conforto da família da pessoa em situação crítica (PSC) em contexto de urgência. Metodologia: Estudo exploratório descritivo misto recorrendo-se à entrevista semi-estruturada, numa amostragem não probabilística acidental de 10 familiares da pessoa em situação crítica num serviço de urgência. Resultados: O significado de conforto expressou-se por um estado/perceção de segurança destacando-se a dimensão psico-espiritual e física. Os fatores promotores de conforto relacionaram-se com atitudes/interações positivas, competências técnico-científicas e relacionais dos enfermeiros, com enfoque na dimensão psico-espiritual. As sugestões para um cuidado confortador centraram-se no desenvolvimento de competências relacionais e de comunicação. Conclusão: A perceção de conforto relaciona-se com a situação/circunstância vivida e assume um carácter transitório. No serviço de urgência, o conforto surge como uma dimensão que o enfermeiro pode ajustar, compatibilizando interesses e realizando determinadas atividades promotoras da capacitação da família da PSC.info:eu-repo/semantics/publishedVersio

Experiências e conceções de felicidade em adultos utilizadores e não utilizadores de redes sociais

Com o crescente uso das redes sociais, a atenção tem sido cada vez mais voltada para este tema. A importância de como estas podem ser ou não, no seio cultural contemporâneo, importantes agentes de reforço de visibilidade para uma imposição social evidente – o ser feliz. Nesta investigação realizou-se um estudo fenomenológico com o objetivo de descrever e interpretar a experiência de felicidade associado ao uso de redes socias. Deste modo, este estudo contou com a participação de dez adultos com idades compreendidas entre os 40 anos a 70 anos, usuários e não usuários de redes sociais. Com recurso à aplicação de uma entrevista semiestruturada e um questionário sociodemográfico obtiveram-se como principais resultados a heterogeneidade entre usuários e não usuários de redes socais relativamente ao interesse ou não pelas mesmas; a ambivalência das óticas dos participantes relativas à perceção da relação das redes sociais com a felicidade; as diferentes experiências de felicidade em adultos que usam ou não usam as redes sociais. Assim, a pertinência deste estudo permite comparar como os indivíduos de uma mesma geração se comportam quando se é ou não usuário de redes sociais; é de igual modo, essencial promover e sensibilizar para a importância da felicidade e de se ser, verdadeiramente, feliz; evitar comparações ou vivermos numa felicidade ilusória que nos é transmitida pelas redes sociais.With the increasing use of social networks, attention has been increasingly focused on this topic. The importance of how these may or may not be, in the contemporary cultural environment, important agents of visibility reinforcement for an evident social imposition – being happy. In this investigation, a phenomenological study was carried out with the objective of describing and interpreting the experience of happiness associated with the use of social networks. Thus, this study had the participation of ten adults aged between 40 and 70 years, users and non-users of social networks. Using a semi-structured interview and a sociodemographic questionnaire, the main results were the heterogeneity between users and non-users of social networks in terms of interest or not in them; the ambivalence of the participants' perspectives regarding the perception of the relationship between social networks and happiness; the different experiences of happiness in adults who use or do not use social networks. Thus, the relevance of this study makes it possible to compare how individuals of the same generation behave when one is or is not a user of social networks; it is also essential to promote and raise awareness of the importance of happiness and of being truly happy; avoid comparisons or live in an illusory happiness that is transmitted to us by social networks

A transformação do Convento de São Paulo/ Fábrica Sofal de Vila Viçosa em Centro cultural

Dissertação de Mestrado para a obtenção do grau de Mestre em Arquitectura de Interiores, apresentada na Faculdade de Arquitectura da Universidade Técnica de Lisboa

Tumor Suppressor Functions of Epithelial Integrity Genes in Breast Cancer

Epithelial integrity defines the well-established positioning and communication of the epithelial cells within the tissue architecture, which is necessary for the epithelium to flawlessly perform its functions. Loss of tissue integrity is a hallmark of practically all advanced solid cancers. Tissue integrity can be lost by altered cell-cell, cell-matrix connections, and/or mislocalization of the proteins responsible for the establishment of cell polarity. It has been postulated that the abnormal proliferative behavior observed in cancer cells is not only a consequence but also requires loss of epithelial integrity. Early studies in Caenorhabditis elegans and Drosophila melanogaster have found evidence of the tumor suppression role of polarity regulating genes. In vertebrates, the role of polarity genes in cancer development is less clear, with only few polarity genes convincingly linked to tumorigenesis in animal cancer models. The general aim of the study was to clarify the role of epithelial integrity regulating genes in breast cancer development. The study primarily focused on cell cycle and epithelial architecture alterations induced by the shRNA-mediated silencing of putative epithelial integrity regulating genes. The targeted genes were selected based on available Drosophila genes knowledgebases. By exploiting the advantages of the three-dimensional (3D) cell cultures, which mimic the natural cell–cell and cell–extracellular matrix interactions, combined with genes knockdown and MYC oncogene activation, the study was able to identify novel putative tumor suppressor functions of genes regulating epithelial integrity. Specifically, the study unraveled a PARD6G tumor suppressor function linked to the modulation of the AKT signaling pathway, critical for cancer development. This study also exposed an unexpected synthetic lethality between loss of RHOA (small GTPase) and active MYC. The performed experiments indicate that the observed apoptosis is a consequence of an altered glutamine metabolism, important for the survival of cell with active MYC. Furthermore, a novel statistical framework was developed to efficiently analyze phenotypic data resulting from genetic screens performed in 3D cultures. Finally, the genetic profiling of patients’ derived breast cancer samples resulted in the identification of a genetic signature for tumors with disseminated tumor cells (DTC). Amongst this genetic signature, low RAI-2 expression was also correlated to patients’ poor prognosis. Further in vitro studies exposed a RAI-2 link to epithelial integrity regulation. In conclusion, this study successfully identified novel human epithelial integrity regulators in breast cancer, thereby opening potential therapeutic avenues for MYC-driven tumors and revealing a novel biomarker for early metastasis in breast cancer.Epiteelisolujen tarkkasti määritelty sijainti ja niiden keskinäinen kommunikaatio kudosrakenteen sisällä on seurausta epiteelin sisäisestä eheydestä, jonka säilyminen on välttämätöntä, jotta epiteelikudos voi suorittaa virheettä sille ominaiset toiminnot. Epiteelikudoksen rakenteellisen eheyden menetys on tunnusmerkki miltei kaikissa pitkälle edenneissä kiinteissä syövissä. Eheyden katoaminen saattaa olla seurausta solujen välisten yhteyksien, tai solujen ja niiden ekstrasellulaarimatriisin eli soluväliaineen yhteyksien muutoksista, ja/tai solun polariteetin määräävien proteiinien väärästä sijannista. On ehdotettu, että syöpäsolujen epänormaali proliferaatio ei ole ainoastaan seurausta, mutta myös vaatii epiteelikudoksen eheyden puuttumista. Solujen polariisuutta säätelevien geenien on osoitettu toimivan kasvainten kasvua estävästi Caenorhabditis elegans- ja Drosophila melanogaster-mallieläimillä tehdyillä varhaisissa tutkimuksissa. Selkärankaisilla solupolariteettin vaikuttavien geenien osallisuus syövän kehitykseen on heikommin tunnettu, ja vain muutama polariteettigeeni on yhdistetty eläinsyöpämalleissa vakuuttavasti kasvainten syntyyn. Väitöskirjan pääasiallinen tavoite oli selvittää epiteelin eheyttä säätelevien geenien roolia rintasyövän kehityksessä. Työssä keskityttiin etenkin näiden geenien shRNA-välitteisen hiljentämisen seurauksena solusyklissä ja epiteelikudoksen rakenteessa tapahtuviin muutoksiin. Kohdegeenit valittiin saatavilla olevien Drosophila-geeni-tietokantojen perusteella. Hyödyntämällä kolmiulotteisia (3D) soluviljelmiä, jotka jäljittelevät solujen ja niiden ekstrasellulaarimatriisin välisiä interaktioita, yhdistettynä kohdegeenien hiljentämisen ja MYC-onkogeenin aktivaatioon, tutkimuksessa kyettiin tunnistamaan epiteelin eheyttä sääteleviin geeneihin liittyviä ennestään tuntemattomia oletettuja tuumorisupressorifunktioita. Erityisesti tutkimuksessa osoitettiin PARDG6-tuumorisupressorifunktio, joka liittyy syövän kehitykselle kriittisen AKT-signalointireitin modulaatioon. Tutkimus myös osoitti odottamattoman synteettisen letaalisuus-yhteyden RHOA:n (pieni GTPaasi, GTP:tä hajoittava proteiini) ja MYC:n välillä. Kokeiden perusteella voidaan olettaa, että niissä havaittu apoptoosi on seurausta muuttuneesta glutamiini-metaboliasta, joka on tärkeää sellaisten solujen selviytymiselle, joilla on aktiivinen MYC. Lisäksi tutkimuksessa kehitettiin uusi statistinen analyysijärjestelmä, jotta kyettiin analysoimaan tehokkaammin 3D-viljelmmillä tehdyistä geneettisistä seulonnoista saatu fenotyyppinen data. Rintasyöpäpotilaiden kasvain-näytteiden tutkiminen mahdollisti erillisen geneettisen profiilin identifioinnin kasvaimille, joista on kulkeutunut kasvainsoluja muihin kudoksiin (disseminated tumor cells, DTC). Tämän geneettisen profiilin sisällä alhainen RAI-2 ekspressio korreloi potilaan huonon ennusteen kanssa. Lisäksi in vitro havaittin, että RAI-2 oallistuu epiteelin eheyden säätelyyn. Yhteenvetona tässä tutkimuksessa tunnistettiin rintasyövässä onnistuneesti uusia ihmisen epiteelikudoksen eheyden säätelijöitä, luoden samalla potentiaalisia hoitokeinoja MYC:n säätelemille kasvaimille, sekä löydettiin uusi biomarkkeri varhaisvaiheen metastaasille rintasyövässä

Planeamento e reabilitação urbana no âmbito de autarquia local

Mestrado em Engenharia CivilO presente relatório sintetiza as atividades realizadas durante os oito meses de estágio curricular, realizado no âmbito do Mestrado Integrado em Engenharia Civil. O estágio desenvolveu-se na Divisão de Planeamento, Gestão Urbanística e Requalificação Urbana, da Câmara Municipal de Albergaria-a-Velha, distrito de Aveiro. A realização do estágio teve como principal objetivo a análise, a experiência e o desenvolvimento de conhecimentos na área da reabilitação urbana e gestão urbanística. Estas são consideradas áreas cruciais nos dias de hoje, principalmente em Portugal, apesar da preferência pela construção nova em detrimento da reabilitação de construções existentes. A degradação do parque habitacional em Portugal é uma realidade que persiste ao longo do tempo, adquirindo grande relevo nas grandes áreas urbanas. Para além de demonstrar todo o trabalho realizado durante o estágio curricular, um outro objetivo foi evidenciar a importância da realização do mesmo integrado no plano curricular. A importância na expansão de competências não adquiridas na parte letiva, a oportunidade de contactar com o mercado de trabalho em contexto de formação/aprendizagem apresentam-se como pontos de partida para a carreira profissional. No decurso da execução das tarefas propostas, houve um acompanhamento permanente pelos elementos da Divisão, nomeadamente pelo chefe da equipa, bem como total disponibilidade na assistência e colaboração.This report summarizes the activities carried out during the eight-month traineeship held in the Master’s Degree in Civil Engineering. The internship was developed in the Planning, Urban Management and Urban Renewal Division of the Municipality of Albergaria-a-Velha, Aveiro district. The realization of the internship had as main objective the analysis, the experience and the development of knowledge in the field of urban regeneration and urban management. These are areas considered crucial nowadays, especially in Portugal, despite the preference for new construction at the expense of rehabilitation of existing buildings. The degradation of the housing stock in Portugal is a reality that persists over time, acquiring great importance in large urban areas. In addition to showing all the work done during the internship, another objective was to demonstrate the importance of holding the same integrated into the curriculum. The importance of expanding skills not acquired in the degree plan, the opportunity to contact with the labor market in the context of training/learning are presented as starting points for a professional career. During the implementation of the proposed tasks, there was a permanent monitoring of the elements of the Division, including the team leader, and full availability on assistance and cooperation