OR05-3 Mir-21 Contributes to Cytokine-Induced Beta Cell Dysfunction via Inhibition of mRNAs Regulating Beta Cell Identity

A hallmark of diabetes is the loss of physical or functional β cell mass. Alterations in β cell microRNA (miRNA) profiles have been described in diabetes. MiRNAs have also been shown to serve as important regulators of β cell development and function, implicating them in β cell dysfunction during diabetes development. Our lab has previously demonstrated that β cell microRNA 21 (miR-21) is increased in models of diabetes. However, a comprehensive analysis of the β cell effects of miR-21 remain poorly defined, and the effects of miR-21 on in vivo glucose homeostasis have never been explored. To this end, we performed a comprehensive in silico analysis of bioinformatics databases to identify potential β cell targets of miR-21, which yielded multiple targets in the Transforming Growth Factor Beta 2 (Tgfb2) and Fibroblast Growth Factor Receptor 3 (Fgfr3) pathways associated with regulation of differentiation. We hypothesize that β cell miR-21 plays a critical role in inhibiting β cell function and inducing loss of β cell identity. To validate targets in vitro, we developed a model whereby miR-21 is upregulated using a dose dependent lentiviral Tetracycline-on system in INS1 cells. Overexpression of miR-21 led to a reduction in expression levels of several members of the Tgfb2 and Fgfr3 pathways as well as multiple transcription factors associated with β cell function and identity, and an increase in aldehyde dehydrogenase transcripts, consistent with β cell dedifferentiation. To verify direct interactions between miR-21 and candidate target mRNAs, a biotin pulldown experiment was performed using a 3’ biotinylated mature miR-21 construct and a 3’ biotinylated cel-miR-67 control construct. Several mRNAs associated with β cell identity were enriched in the pulldown, indicating a direct interaction with miR-21. Lineage tracing was performed within an in vivo zebrafish model of β cell specific oxidative stress in which β cells expressed a nuclear GFP signal. Whole body knock down of miR-21 by morpholino microinjection showed a protective effect in stressed β cells and rescued against a dedifferentiated phenotype. To test the effect of miR-21 on glucose tolerance in vivo, inducible β cell specific knockout (βmiR-21KO) and overexpression (βmiR-21) mice were generated by crossing Ins1tm1(CreERT2)Thor mice with miR-21 floxed mice and miR-21-CAG-Z-EGFP mice, respectively. When compared to littermate controls, intraperitoneal glucose tolerance tests (IPGTT) exhibited hyperglycemia in βmiR-21 mice and euglycemia in βmiR-21KO mice. Metabolic studies, including glucose stimulated insulin secretion (GSIS) and insulin tolerance tests (ITT) are ongoing in our mouse models. Our results implicate miR-21 as a regulator of β cell dedifferentiation during diabetes development

Towards Integrated Socio-Cultural Space in “Fareej Old Al-Hitmi” Neighborhood in Doha

In the face of rapid urban development, population growth, and socio-cultural changes, most historic districts in the Gulf are experiencing difficulties in making the necessary adaptation and adjustments to the present needs and changes. On the one hand, most of these districts are suffering from decay and dilapidation. On the other hand, many of them are being erased and replaced by new business districts. Consequently, historic districts are being neglected and are losing their identity. Doha, the capital of the state of Qatar, is experiencing a rapid growth in its economy and population, resulting in the transformation of its built environment. This transformation is characterized by multiple construction projects and the abandonment of old historic neighborhoods. The aim of this thesis is to examine the impact of this rapid urban development on the socio-cultural spaces in Doha’s historic neighborhoods, focusing on ‘Fareej Old Al-Hitmi’. This is an old neighborhood in Doha that contains the rich history of the Al-Hitmi family, and which has a coherent fabric with authentic old houses of different characters and types. Old Al-Hitmi neighborhood is one of the spaces that is currently being neglected and is losing its cultural identity. The main objective deals with the evaluation of the current socio-cultural spaces within the study area, and examining different methods to enhance the social interaction and connectivity between the neighborhood users. To achieve the aim of this research study, a mixed methods approach involving a combination of both quantitative and qualitative analyses were adopted and developed. (1) Theoretical study, by reviewing different topics and disciplines (2) Applied and analytical study, through site observation, field notes and photographs (3) Structured questioners and interviews with planners and design professionals from the Ministry of Municipality and Environment (MME), Qatar Museum Authority (QMA), Engineering consultant companies and Qatar Rail (QR). As an outcome, this research study attempts to develop an approach to enhance the socio-cultural spaces, and promote social interaction and engagement in urban life through a set of recommendations and design guidelines

How Can the Government Utilize Elites & Celebrities to manage Global Public Opinion on Egypt? An Exploratory Study of Mo Salah & Egypt

With Egypt’s latest global reputation index, nation brand, and soft power indices scoring low, such rankings have left room for finding new ways of enhancing Egypt’s global public opinion and reputation. This study showcases an untapped potential for enhancing a nation’s reputation and public opinion. This untapped potential lies in the power of elite commentary and celebrity activity. Such commentary and activity influence public opinion of the celebrity but also subsequently affect the public opinion of their country-of-origin nations. With a global phenomenon such as football player Mo Salah, it has always been suggested that his performance positively affected Egypt\u27s public opinion. Such a hypothesis has been suggested by Egyptians but has never been tested. This study is testing existing hypotheses through the commentary of the elites and how public opinion is shaped through such commentary around Mo Salah. This developed public opinion about Mo Salah assessed how the public opinion of Egypt could be affected too. As a result, elite commentary leading to public opinion on Mo Salah indeed enhanced the public opinion of Egypt. It led to an awareness of 35 times more in 2022 in the UK than before his joining Liverpool F.C. The sentiment of how public opinion through the lens of elites’ social media commentary and celebrity activity, was the main measurement of the impact on the public opinion of Egypt. The study showed that elite commentary on Mo Salah is highly significant in the development of public opinion about Mo Salah. There has been also a significant correlation between the public opinion on Mo Salah and the public opinion on Egypt accordingly. Subsequently, the study develops policy recommendations around how social media, elite commentary, and public opinion/reputation activities could be developed for enhancing the public opinion of Egypt. The policy recommendation based on such a finding is the development of the Egyptian Council of Public Opinion & Nation Branding. Such initiation of this council has its core around integrating the elite’s commentary around events in Egypt. Another recommendation is for nurturing more talents like Mo Salah locally and globally, ensuring their exposure through the lens of the elites on social media, media outlets, and beyond

The influence of intangible resources on the performance of Waqf project collaboration: mediating effect of sustainability and moderating role of collaborative effort / Siti Sara Ibrahim

The waqf institution has contributed significantly to sustainable socioeconomic growth. Despite its remarkable significance in this industry, waqf institution is still confronted with several industrial challenges, and one of them is the underperformance of waqf properties development that is caused by the lack of resources as well as an integrative approach. Resources management through cross-sector collaboration practices between the State Islamic Religious Councils (SIRCs) and their partners has been suggested for a better performance of waqf properties development. However, the claim was not supported empirically within the academic literature. In response to this issue, this thesis has examined the influence of intangible resources namely commitment, trust, networking and urgency on the performance of waqf project collaborations through the integration of the Resources Based View (RBV) theory and Stakeholder Salience theory. This thesis has also assessed the mediating effect of sustainability with regard to the relationship between commitment, trust, networking and urgency on the performance of waqf project collaborations. Finally, the present thesis has evaluated the moderating role of collaborative effort in strengthening the relationship between sustainability and performance which was argued to be inconsistent in previous literatures. A quantitative approach was conducted using a set of questionnaires that were distributed among the SIRCs and their partners based on the available waqf project collaborations. The research model was further analysed using the Partial Least Square-Structural Equation Modelling (PLS-SEM) technique. Based on the research questions, three core findings have been derived as follows: 1) commitment, trust, and urgency significantly influenced the performance of waqf project collaborations in Malaysia; on the other hand, networking was insignificant to the performance of waqf project collaborations; 2) as a mediating variable, sustainability partially mediated the relationship between trust, networking and urgency with performance. Contrastingly, commitment demonstrated an insignificant influence when tested indirectly through sustainability as a mediating variable; it was concluded to be a standalone influence on the performance of waqf project collaborations, and 3) as a moderating variable, collaborative effort played a significant role in strengthening the relationship between sustainability and performance in this study. This thesis contributes the relevant empirical evidence which indicates that intangible resources do play a significant role in influencing the performance of waqf properties development through cross-sector collaboration practices between the SIRCs and their partners. The research framework of this thesis has been registered for Intellectual Property Rights (IPR) to maximize excludability and increased innovativeness. Industry practitioners are encouraged to adopt this research framework in developing a model that can provides a comprehensive guideline on the importance of resources management. This implementation is crucial to enhance the performance of existing waqf properties development in the industry. Consequently, the significant role of waqf on the development of sustainable socioeconomic growth will be further enhanced

Novel applications of vaporized hydrogen peroxide on contaminated materials and surfaces

Tese de Mestrado, Microbiologia Aplicada, 2021, Universidade de Lisboa, Faculdade de CiênciasIn the first stages of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the global demand for personal protective equipment (PPE) could not be met solely by the limited capacities of expanding PPE production and therefore several coordinated efforts were focused on the re-use of various items. While prior decontamination was paramount to the re-use of surgical masks or respirators, little information existed on effective decontamination of these typically single-use-only products. The main goals of this project are the optimization of the decontamination process of FFP3 (filtering facepiece 3) masks using vaporized hydrogen peroxide (VHP) and the evaluation of this technology as a suitable decontamination method for materials, surfaces and laboratory equipment. For a better understanding of the decontamination properties of the VHP releaser equipment, Geobacillus stearothermophilus spore-discs were used as biological indicators (BI) and submitted to Most Probable Number tests. Decontamination conditions were optimized to achieved the minimum spore-log reduction for a successful decontamination. Among other conditions, it was found that the temperature inside the decontamination chamber should rise above 38ºC.To accomplish the first goal, experiments regarding exposure to VHP were first performed on the chamber materials used to build the decontamination chamber (rubber, PVC – polyvinyl chloride – and PVC with fire retardant) in order to assess their compatibility with HP (hydrogen peroxide) and ensure that they would not compromise VHP decontamination tests. Subsequently, multiple decontamination experiments were executed in the presence of FFP3 masks until bio-decontamination was achieved. The results obtained showed that the masks presence compromised the diffusion of HP and therefore an extra source of ventilation and heat needed to be added to the experiments in order to obtain successful bio-decontaminations. To achieve the final goal, different materials and surfaces were artificially contaminated with bacterial DNA and then subjected to VHP decontamination experiments. After interpretation of real-time PCR data, it was concluded that the tests attained satisfactory results. All materials reached decontamination rates above 98%, however, some surfaces struggled to surpass the 85% threshold. It was hypothesized that the HP was reacting with the materials of those surfaces and compromising decontamination. Overall, the satisfactory results obtained throughout this thesis experiments suggests that DNA decontamination resorting to VHP technology is not only possible but indeed effective.Um novo coronavírus denominado SARS-CoV-2 (síndrome respiratória aguda grave - coronavírus 2) surgiu em Wuhan, China, em dezembro de 2019 e rapidamente deu origem a uma pandemia global. Dado que a transmissão deste vírus ocorre principalmente por meio de gotículas respiratórias, a sua disseminação sucedeu-se rapidamente, o que gerou uma procura global feroz por equipamentos de proteção individual (EPI) como máscaras cirúrgicas e máscaras FFP2 (ou N95) descartáveis. Esta procura sem precedentes resultou numa rápida escassez destes EPI, ultrapassando a capacidade de produção dos mesmos. Devido à extrema necessidade do uso destes EPI, profissionais de saúde por todo o mundo recorreram à reutilização de máscaras adotando estratégias de descontaminação que não garantiam ser eficazes na prevenção contra o vírus e que arriscavam comprometer a integridade das máscaras. Enquanto se aguardava pela produção de novos equipamentos de proteção, esforços coordenados focaram-se na procura de métodos eficazes de descontaminação de EPI e outros produtos. Os principais objetivos deste projeto são a otimização do processo de descontaminação de máscaras FFP3 (máscara de proteção respiratória) recorrendo ao uso de vapor de peróxido de hidrogénio (VPH) e a avaliação desta tecnologia como método adequado de descontaminação de materiais, superfícies e equipamento de laboratório. O peróxido de hidrogénio (PH) é um oxidante potente que atua contra bactérias, vírus, fungos e esporos altamente resistentes. O PH por si só tem uma capacidade oxidante relativamente fraca, sendo o principal mecanismo de atuação a oxidação de grupos tiol das proteínas. No entanto, ao decompor-se, forma radical hidroxilo, uma espécie oxidante muito potente capaz de oxidar proteínas, lípidos e ácidos nucleicos, impedindo o funcionamento correto dos mesmos, inibindo assim o processo de infeção e replicação de microrganismos. Os produtos finais de decomposição do PH são a água e o oxigénio, tornando o PH não tóxico para o ambiente ou potencialmente cancerígeno para o ser humano, ao contrário de outros desinfetantes regularmente usados como o formaldeído e o óxido de etileno. Para uma melhor compreensão das propriedades de descontaminação dos equipamentos utilizados para libertação de VPH e avaliação da eficácia dos mesmos como dispositivos adequados para descontaminação, indicadores biológicos (IB) foram utilizados como medidores de eficácia microbicida. Os IB escolhidos para este efeito foram discos com esporos da bactéria Geobacillus stearothermophilus, que vários estudos provam ser os mais resistentes à inativação por VPH. Estes IB foram submetidos a testes de contagem do número mais provável de esporos e os seus resultados ajudaram a compreender a capacidade de descontaminação do VPH libertado pelos equipamentos de descontaminação. Segundo as experiências realizadas, uma redução de 3-log no número de esporos presentes no IB é possível quando a temperatura dentro da câmara ultrapassa os 38ºC, sendo esta a redução mínima para se considerar que ocorreu descontaminação. Caso as temperaturas no interior da câmara atinjam valores acima dos 43ºC, ocorre inativação total dos esporos. Partindo destes ensaios, foi igualmente calculado o D-value (tempo de redução decimal), por ser um fator chave na determinação do momento e das condições necessárias para se dar início à descontaminação, tendo sido determinado o valor de 4,07 minutos, sendo este valor similar aos obtidos em estudos que utilizaram metodologia análoga. Antes de iniciar as experiências relacionadas com a otimização do processo de descontaminação, foram realizadas experiências preliminares de exposição a VPH, com os materiais com que é construída a câmara de descontaminação, de forma a compreender a sua capacidade de adsorção do PH e garantir que estes não comprometeriam posteriores testes de descontaminação. Estes ensaios foram realizados com o auxílio de um sistema de descontaminação que liberta VPH dentro de uma câmara de pequenas dimensões, na qual foram depositados os materiais a ser testados (borracha, PVC - policloreto de vinilo - e vidro). De forma a calcular a capacidade de adsorção de PH de cada material, a câmara era aberta ao fim de cada ciclo de descontaminação de forma a permitir a expulsão de todo o VPH e, quando os valores de concentração de PH atingissem valores próximos de zero, a câmara era fechada. Se a concentração de PH começasse a subir, significaria que o material a ser testado estava a libertar PH que tinha adsorvido. Apesar de se ter observado subidas da concentração de PH após o encerramento da câmara, nenhum material provocou uma subida significativa de PH, tendo o PVC sido o material que, em média, mais PH libertou, provocando uma subida na concentração de 13 ppm. Após uma melhor compreensão das propriedades de descontaminação dos equipamentos utilizados para libertação de VPH e da capacidade de adsorção de materiais que poderiam comprometer subsequentes experiências, estavam criadas as condições para iniciar os ensaios relacionados com o primeiro objetivo deste projeto. De forma a determinar as condições necessárias para atingir descontaminação, várias experiências foram realizadas na presença de máscaras FFP3, previamente usadas. Para tal, IB foram colocados no lado interno das máscaras de maneira a testar se o VPH a penetrar através das fibras e inativar eficazmente os esporos do indicador. Caso se verifique inativação dos esporos, assume-se que as condições criadas durante o ensaio foram suficientes para as subsequentes experiências de descontaminação. Após a realização de seis testes, concluiu-se que a presença das máscaras comprometia a difusão de PH e, por isso, foi necessária a adição de um pequeno ventilador no interior da câmara de luvas. Este contribuiu para o aumento da temperatura e ventilação, fatores estes que provaram ser cruciais para o sucesso da descontaminação. Para alcançar o segundo objetivo, diferentes materiais e superfícies foram contaminados artificialmente com DNA de Bacillus cereus e sujeitos a experiências de descontaminação via VPH. Primeiramente, foram inoculados tubos de centrífuga e pontas de pipeta. Estes materiais são tipicamente de pequenas dimensões, o que poderia dificultar a penetração do VPH e comprometer a descontaminação das áreas contaminadas, especialmente nas pontas. Como nenhum teste semelhante tinha sido anteriormente realizado com este equipamento de dispersão de VPH, não existiam dados que suportassem a capacidade de descontaminação destes materiais. Cada material foi submetido a três ensaios de descontaminação independentes, nos quais os materiais foram colocados em cada canto da câmara de luvas e no centro da mesma. Os resultados obtidos demonstram que o VPH conseguiu descontaminar com sucesso a grande maioria dos materiais, atingindo percentagens de descontaminação acima dos 98% em ambos os materiais, tendo alcançado os 100% em alguns tubos de centrífuga. No entanto, todas as experiências revelaram um decréscimo na descontaminação dos materiais localizados no canto inferior esquerdo da câmara, podendo este acontecimento ser resultado da ventilação criada dentro da mesma que, possivelmente, estaria a comprometer o fluxo de PH naquela região. A interpretação destes resultados foi feita com base nos dados obtidos por PCR em tempo real. Para os testes de descontaminação de superfícies, pequenos quadrados de PVC, borracha e vidro foram inoculados com o mesmo DNA bacteriano e submetidos a ciclos de descontaminação com a mesma metodologia aplicada aos materiais. Dado o facto de as áreas contaminadas estarem completamente expostas ao VPH, assumia-se que os níveis de descontaminação iriam atingir valores superiores aos dos materiais. Todavia, a interpretação dos dados obtidos por RT-PCR revelou resultados muito inconsistentes. As superfícies de vidro, obtiveram percentagens de descontaminação acima dos 98% na maioria dos cantos onde tinham sido colocados, à exceção das amostras posicionadas no canto inferior esquerdo, como esperado dado os resultados já referidos para os materiais. Por sua vez, os níveis de descontaminação das superfícies de borracha e PVC alcançaram valores de 90% e 83%, respetivamente. Foi colocada a hipótese do VPH estar a reagir com esses materiais e, consequentemente, comprometer a sua capacidade de descontaminação. Estudos mais aprofundados deverão ser realizados para confirmar esta hipótese. Em suma, os objetivos desta dissertação de mestrado foram alcançados e proporcionaram uma visão importante da tecnologia de VPH como método de descontaminação

The Portrayal Of The State Of Qatar In The Media: An Analytical Study Of The Newspapers Of The Gulf Blockading Countries (From 24 May 2017 To 21 September 2017) Of The Gulf Crisis 2017–2018

This research study investigates the ways in which the State of Qatar was portrayed in some of the Arabic-language newspapers of the three Gulf blockading countries. The main question addressed concerns the main characteristics of the portrayal of the State of Qatar in the media of the Gulf blockading countries during the Gulf Crisis of 2017. This study has adopted a quantitative content analysis. A total of 996 news stories were collected from the three newspapers, which consist of news reports, opinion articles, political caricatures, interviews, graphics, and so on. The selected newspapers were Al-Ittihad newspaper (UAE), Al-Watan newspaper (Bahrain) and Al-Jazirah newspaper (KSA). The duration of this study is from 24 May 2017 to 21 September 2017, that is the first five months of the Gulf Crisis of 2017–2018. The collected data were divided into two main categories within which to analyze the portrayal of the State of Qatar in the selected newspapers: (1) What was said about Qatar; and (2) How it was said. The results of this study show that the image of the State of Qatar has been distorted by the three selected newspapers, and that the distortion has appeared in the majority of the contents of news stories and the specific frames within the political caricatures. Accordingly, the newspapers have portrayed the State of Qatar as the ‘financier of terrorism’ that poses a threat to the Gulf region. This study reviews some literature that discusses the power and the performance of the media during political conflicts. Moreover, the study is theoretically linked with the Framing Theory that provided a grounded understanding of the media in the Gulf blockading countries. The portrayal of Qatar in the media has been extensively addressed in the media, talk shows, conferences and opinion articles. However, there is a scarcity of academic studies which focus on the media portrayal of a GCC member in the media of other GCC countries during the Gulf Crisis 2017–2018. Therefore, this study will shed light on the framing of Qatar in the media, and it will potentially contribute to the enrichment of research studies on the ‘media framing’ of the Arabian Gulf

Investigating the Efficacy of Radiofrequency Renal Artery Denervation: From Bench to Bedside

Hypertension is a prevalent condition affecting one third of the adult population worldwide. Medications alone have failed to control the blood pressure (BP) in a large proportion of the hypertensive population. Therefore, renal artery denervation (RAD) was developed for the management of resistant hypertension. However, its efficacy was found to be inconsistent in clinical trials. Delivery of effective ablation that results in sufficient nerve injury is one important criterion for a successful procedure. This thesis focuses on evaluation of various commercially available RAD devices and understanding their unique properties and limitations. Using an in-house built renal artery phantom model, we demonstrated that single electrode Symplicity Flex produced larger lesions, in depth and width compared to multi-electrode EnligHTN when both systems were used under identical experimental conditions, and with optimal vessel wall contact. Clinically, in a small cohort of patients who underwent RAD using either systems, we found no significant difference in office BP reduction between the two systems and both groups had a significant reduction in office BP, which persisted up to 4 years. When the new generation multi-electrode Symplicity Spyral and multi-electrode EnligHTN systems were assessed in the same model, EnligHTN lesions were larger in depth. However, lesion depth of the new generation devices was reduced by 30-40% compared to older generation devices. In a phantom model of branch renal artery, Symplicity Spyral produced lesion that were of similar size and with bigger circumferential coverage compared to main vessel phantom model. No overheating at the electrode-tissue interface occurred during branch ablation. Overall, this thesis broadens our knowledge in the field of RAD with respect to information regarding properties and limitation of different RAD systems and it aids in refining the procedure in order to achieve the best clinical outcome

TRAUMATIC BRAIN INJURY LEADS TO ABERRANT MIGRATION OF ADULT-BORN NEURONS IN THE HIPPOCAMPUS

poster abstractTraumatic brain injury (TBI) is the leading cause of death in children and young adults, leading to substantial cognitive impairment, motor dysfunction and epilepsy. There is no effective treatment for these dis-orders. The discovery of neural stem/progenitor cells (NSCs) in the adult brain raises a potentially promising strategy for repairing CNS in-jury.Our previous study showed that TBI promotes NSC proliferation in an attempt to initiate innate repair and/or plasticity mechanisms. However, the spontaneously post-traumatic recovery of hippocampal-related cognitive and memory functions is very limited. Better under-standing of neurogenesis following TBI may provide additional inter-vention to further enhance neurogenesis for successfully repairing the damaged brain following TBI. Although newborn neurons generated from NSCs are continuously added to the brain throughout our life, they must migrate from their birthplace to their appropriate destina-tion to develop into mature neurons. When we tracked the migration of newly generated neurons in the adult hippocampus after TBI, we found that a large percentage of immature neurons migrate pass their normal stopping site at the inner granular cell layer, and misplace in the outer granular cell layer of the hippocampal dentate gyrus. The aberrant migration of adult-born neurons in the hippocampus occurs 3 days after TBI, and lasts for 10 weeks, resulting in a great number of newly generated neurons misplaced in the outer granular layer in the hippocampus. The newborn neurons at the displaced position will not be able to make correct connections with their appropriate targets, and may even make wrong connections with inappropriate nearby tar-gets in the pre-existing neural network. Abnormal migration can cause several diseases including epilepsy. These results suggest that stimu-lation of endogenous adult neural stem cells following TBI might offer new avenues for cell-based therapy. Additional intervention is required to further enhance successful neurogenesis for repairing the damaged brain