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Cancer has enormous costs for society with breast and prostate cancers accounting for the first and fifth cause of death among cancer patients. About 50% of the initially responsive breast cancers and almost all prostate cancers develop resistance to endocrine therapy, progressing towards a more aggressive, metastatic, and incurable disease. Thus, discovery of novel biomarkers to monitor patients’ response as well as new drug targets to surpass resistance are urgently needed. Cancer cells thrive under physiologic conditions that induce oxidative and proteotoxic stress, leading to protein misfolding and aggregation, which results in loss of proteostasis. To resolve proteotoxic stress, cells activate protein quality control mechanisms, being the Unfolded Protein Response (UPR) one of them. While it has been shown that specific UPR branches are activated in endocrine resistant breast and prostate cancer cells, there is nearly no knowledge about the specific proteins that aggregate, the biological processes they regulate, how protein aggregates affect cell survival and how this influences the acquisition of a resistant phenotype. Therefore, we proposed to identify and characterize the changes in signalling pathways regulating the proteostasis network leading to protein aggregation in endocrine-responsive vs resistant breast and prostate cancer cells. We characterized the aggregated proteome of breast cancer cell lines and identified a novel protein involved in acquired antiestrogen resistance – RNA-Splicing Ligase RtcB homolog (RTCB). We also explored the predictive value of RTCB and the endoplasmic reticulum chaperone BiP (BiP) in luminal breast cancer and evaluated the effect of antiestrogen therapy and metastasis on RTCB aggregation, aggresome formation and BiP expression. Our results show that RTCB aggregation status could be used as a potential predictive tool to evaluate the response of breast cancer patients to antiestrogen therapy. In addition, by combining three different strategies (analysis of publicly available datasets; systematic review and meta-analysis of immunohistochemistry (IHC) detection of BiP in human breast cancers; and IHC detection of BiP in our own cohorts) we confirmed the potential of BiP as an indicator of poor prognosis for breast cancer patients. We showed that castration resistant prostate cancer (CRPC) cells protect their proteome from flutamide-induced toxic aggresome accumulation through the activation of two distinct stress responses that work in concert. The antioxidative stress response is firstly activated to cope with reactive oxygen species (ROS) production. Secondly, UPR activation results in a transient inhibition of protein translation to avoid protein aggregation/ aggresome formation. We also identified Eukaryotic translation initiation factor 2-alpha kinase 3 (PERK) as a novel protein involved in acquired antiandrogen resistance in CRPC cells. Thus, with this work, we propose for the first time, that protein aggregation patterns could be indicative of the capacity of cells to maintain a healthy proteome in response to treatment, which provides a new perspective of proteostasis, where protein aggregation can be used to identify novel biomarkers and drug targets and should be considered as a novel approach to understand mechanisms of disease. As doenças oncológicas representam um enorme custo para a sociedade, sendo os cancros da mama e da próstata a primeira e a quinta causa de morte por cancro. Aproximadamente 50% dos cancros da mama e quase todos os cancros da próstata que inicialmente respondem à terapia endócrina desenvolvem resistência, progredindo para uma forma da doença que é mais agressiva, metastática e incurável. A descoberta de novos biomarcadores para monitorizar a resposta dos pacientes à terapia endócrina, bem como a descoberta de novos alvos terapêuticos que permitam ultrapassar o problema da resistência, são, portanto, uma necessidade urgente. As células cancerígenas proliferam sob condições fisiológicas que induzem stress oxidativo e proteotóxico. Estas condições levam à má formação de proteínas e à sua agregação, o que, consequentemente, pode resultar na perda de proteostase. De modo a resolverem o stress proteotóxico, as células ativam mecanismos de controlo de qualidade das proteínas, sendo um deles a Resposta a Proteínas Malformadas (UPR). Nos últimos anos tem sido demonstrado que ramos específicos da UPR são ativados nas células de cancro da mama e da próstata resistentes à terapia endócrina. No entanto, pouco se sabe acerca das proteínas que agregam, os processos biológicos que estas proteínas regulam, como é que os agregados de proteínas afetam a sobrevivência das células ou como é que este processo influencia a aquisição de um fenótipo de resistência. Assim sendo, o objetivo desta tese foi identificar e caracterizar as alterações nas vias de sinalização que regulam a rede de proteostase e que levam à agregação de proteínas em células de cancro da mama e da próstata resistentes vs sensíveis à terapia endócrina. Neste trabalho caracterizámos o proteoma agregado de linhas celulares de cancro da mama e identificámos uma nova proteína envolvida na aquisição da resistência a antiestrogénios – a Ligase de splicing de RNA homóloga de RtcB (RTCB). O valor preditivo da RTCB e da chaperona do reticulo endoplasmático BiP (BiP) foi também explorado em tumoures da mama com diferenciação luminal. Avaliou-se ainda o efeito da terapia com antiestrogénios e da metastização na agregação da RTCB, na formação de agressomas e na expressão de BiP nestes tumoures. Os nossos resultados mostram que o estado de agregação da RTCB poderá ser utilizado como uma potencial ferramenta preditiva para avaliar a resposta à terapia com antiestrogénios em pacientes com cancro da mama. Adicionalmente, ao combinar a utilização de três estratégias complementares (análise de bases de dados públicas; revisão sistemática e meta-análise da deteção imunohistoquímica (IHC) de BiP em casos de cancro da mama; e a deteção por IHC de BiP nas nossas próprias coortes) conseguimos confirmar que a deteção da expressão de BiP em pacientes com cancro da mama tem o potencial para ser utilizada como um indicador de mau prognóstico. Nesta tese demonstramos ainda que as células de cancro da próstata resistentes à castração (CRPC) protegem o seu proteoma da acumulação tóxica de agressomas induzida pela flutamida através da ativação de duas respostas de stress distintas. Primeiro, a resposta ao stress oxidativo é ativada de modo a eliminar as espécies reativas de oxigénio (ROS) produzidas pela terapia. Em seguida, a ativação da UPR resulta numa inibição temporária da tradução de modo a evitar a agregação de proteínas/ formação de agressomas. O factor 2-alfa cinase 3 de iniciação de tradução eucariótica (PERK) foi também identificado como uma nova proteína envolvida na aquisição da resistência ao antiandrogénio flutamida nas células CRPC. Assim sendo, nesta tese, propomos pela primeira vez, que os diferentes padrões de agregação de proteínas poderão ser indicativos da capacidade que as células têm para manter o seu proteoma saudável em resposta ao tratamento. A proteostase é analisada de uma nova perspetiva, onde se demonstra que os agregados de proteínas podem ser utilizados para identificar novos biomarcadores e novos alvos terapêuticos e deverão ser considerados como uma nova abordagem para compreender os mecanismos de diversas doenças. Programa Doutoral em Biomedicina

The Hero’s Journey framework has been used by prior scholars to conduct research in engineering and science education. This framework, when used for motif coding, can help identify and organize crucial aspects of a student’s narrative about their trajectory in engineering education. Following this coding technique with narrative smoothing provides a way to convey the story meaningfully and memorably. Our research team recently used this method to study a longitudinal set of interviews conducted with an Irish woman, and we herein extend the value of that work by analyzing the interview of a Kuwaiti woman studying at the same institution in Ireland. By using the Hero’s Journey framework to analyze these women’s stories, we distill core meanings and share findings that are significant for engineering educators. Their stories can help readers empathize with underrepresented students, and better understand the joys, challenges, and realities these students face. Our Kuwaiti protagonist chose to leave engineering, but the story she told can help break through existing cultural stereotypes and help us realize how much more there is to any student’s experience than first meets the eye.

We perform a systematic review of the literature on emotions in engineering education. The review is of the type meta-synthesis as described by Siddayway et al (2019) and aims to (1) provide an overview and critical appraisal of the existing literature on emotions in engineering education, and (2) outline directions for future research in this emerging field.

CONTEXT: There is today a broad consensus that emotions influence all forms of teaching and learning, and scholarship on Emotions in Engineering Education (EEE) is an emerging and rapidly growing field. However, this nascent research is currently very dispersed and not well consolidated. There is also a lack of knowledge about the state of the art, strengths, and limitations of the existing literature in the field, gaps, and future avenues for research. PURPOSE: We have conducted a scoping review of EEE research, aiming to provide a first overview of the EEE scholarship landscape. We report here on preliminary findings related to (1) the status of the field, (2) geographical representation of authors, and (3) emerging hot spots and blind spots in terms of research approaches, contexts, and topics. METHODS: The scoping review is part of a larger, systematic review of the EEE literature. Using an inclusive search strategy, we retrieved 2,175 items mentioning emotions and engineering education, including common synonyms. Through abstract screening and full text sifting, we identified 184 items that significantly focus on engineering education and emotion. From these items, we extracted and synthesized basic quantitative and qualitative information on publication outlets, author origins, keywords, research approaches, and research contexts. PRELIMINARY RESULTS: Surprised by the large number of EEE publications, we found that EEE is a rapidly expanding, but internationally dispersed field. Preliminary results also suggest a dominance of research on higher education, often exploring students’ academic emotions or emotional competences. Research on emotional intelligence and anxiety is particularly common while studies focusing on cultural and sociological aspects of EEE are largely absent. CONCLUSIONS: The EEE literature is expanding exponentially. However, the field is not well consolidated, and many blind spots remain to be explored in terms of research approaches, contexts, and foci. To accelerate the development of the field, we invite current and prospective EEE researchers to join our emerging, international community of EEE researchers.

There is today a broad consensus that emotions influence all forms of teaching and learning, and scholarship on Emotions in Engineering Education (EEE) is an emerging and rapidly growing field. However, this nascent research is currently very dispersed and not well consolidated. There is also a lack of knowledge about the state of the art, strengths, and limitations of the existing literature in the field, gaps, and future avenues for research. PURPOSE We have conducted a scoping review of EEE research, aiming to provide a first overview of the EEE scholarship landscape. We report here on preliminary findings related to (1) the status of the field, (2) geographical representation of authors, and (3) emerging hot spots and blind spots in terms of research approaches, contexts, and topics. METHODS The scoping review is part of a larger, systematic review of the EEE literature. Using an inclusive search strategy, we retrieved 2,175 items mentioning emotions and engineering education, including common synonyms. Through abstract screening and full text sifting, we identified 184 items that significantly focus on engineering education and emotion. From these items, we extracted and synthesized basic quantitative and qualitative information on publication outlets, author origins, keywords, research approaches, and research contexts. PRELIMINARY RESULTS Surprised by the large number of EEE publications, we found that EEE is a rapidly expanding, but internationally dispersed field. Preliminary results also suggest a dominance of research on higher education, often exploring students' academic emotions or emotional competences. Research on emotional intelligence and anxiety is particularly common while studies focusing on cultural and sociological aspects of EEE are largely absent. CONCLUSIONS The EEE literature is expanding exponentially. However, the field is not well consolidated, and many blind spots remain to be explored in terms of research approaches, contexts, and foci. To accelerate the development of the field, we invite current and prospective EEE researchers to join our emerging, international community of EEE researchers. CONTEXTThere is today a broad consensus that emotions influence all forms of teaching and learning, and scholarship on Emotions in Engineering Education (EEE) is an emerging and rapidly growing field. However, this nascent research is currently very dispersed and not well consolidated. There is also a lack of knowledge about the state of the art, strengths, and limitations of the existing literature in the field, gaps, and future avenues for research.PURPOSEWe have conducted a scoping review of EEE research, aiming to provide a first overview of the EEE scholarship landscape. We report here on preliminary findings related to (1) the status of the field, (2) geographical representation of authors, and (3) emerging hot spots and blind spots in terms of research approaches, contexts, and topics.METHODSThe scoping review is part of a larger, systematic review of the EEE literature. Using an inclusive search strategy, we retrieved 2,175 items mentioning emotions and engineering education, including common synonyms. Through abstract screening and full text sifting, we identified 184 items that significantly focus on engineering education and emotion. From these items, we extracted and synthesized basic quantitative and qualitative information on publication outlets, author origins, keywords, research approaches, and research contexts.PRELIMINARY RESULTSSurprised by the large number of EEE publications, we found that EEE is a rapidly expanding, but internationally dispersed field. Preliminary results also suggest a dominance of research on higher education, often exploring students’ academic emotions or emotional competences. Research on emotional intelligence and anxiety is particularly common while studies focusing on cultural and sociological aspects of EEE are largely absent.CONCLUSIONSThe EEE literature is expanding exponentially. However, the field is not well consolidated, and many blind spots remain to be explored in terms of research approaches, contexts, and foci. To accelerate the development of the field, we invite current and prospective EEE researchers to join our emerging, international community of EEE researchers.KEYWORDSEmotions, engineering education, systematic review, scoping review

info:eu-repo/semantics/publishedVersion

Tese de mestrado, Biologia Molecular e Genética, Universidade de Lisboa, Faculdade de Ciências, 2015 Submitted by Teresa Boa (tdboa@fc.ul.pt) on 2016-02-16T11:28:26Z No. of bitstreams: 1 ulfc116118_tm_Inês_Direito.pdf: 2684125 bytes, checksum: e43d47e12d184eeec7354356aeeaf40d (MD5) Made available in DSpace on 2016-02-16T11:28:35Z (GMT). No. of bitstreams: 1 ulfc116118_tm_Inês_Direito.pdf: 2684125 bytes, checksum: e43d47e12d184eeec7354356aeeaf40d (MD5) Previous issue date: 2015