77 research outputs found

    G-Quadruplex Aptamer Beacon for Detection of Prostate Cancer Biomarker

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    The prostate is the major male reproductive gland involved in male fertility and plays an important role in triggering of molecular pathways relevant to fertility success. Unfortunately, in Portugal prostate cancer is the most common cancer type among men, being asymptomatic in earlier stages. Thus, is important early detection of disease. NCL is a multifunctional protein involved in multiple biological processes under both physiological and pathological processes and can have several cellular localizations. Cell surface protein overexpression was found restricted to cancer cells, namely in prostate cancer cells. Thus, we can consider NCL as a potential biomarker for cancer diagnosis and a target for cancer treatment. The AS1411 is an aptamer capable to recognise and binds specifically NCL and have a therapeutic effect on cancer cells through of induction of antiproliferative activity. Beyond its therapeutic use, AS1411 can be used in imaging and diagnostic, particularly on aptasensors development. One of the most relevant characteristics of this aptamer is the ability to fold in a G4 conformation, a secondary structure of nucleic acids. G4 structure confers stabilization to sequence and availability to bind NCL. Thus, in this work is presented the first approach of use AS1411 aptamer to prostate cancer diagnosis, namely through the design of molecular beacon (MB) designated by AS1411N5. Initially, biophysical characterization of AS1411-N5 was done by circular dichroism, nuclear magnetic resonance or fluorometric spectroscopies. Additionally, it was performed microfluidic experiments, to detect NCL using AS1411-N5 in biological samples. The results demonstrated that the proposed AS1411-N5 adopt a G4 structure and it is capable to bind with specificity and selectivity NCL, even in plasma of human patients with prostate cancer.A próstata é a maior glândula reprodutiva masculina e tem um papel importante nas vias moleculares relevantes para o sucesso da fertilização. Infelizmente, em Portugal o cancro da próstata é o cancro mais comum entre os homens, sendo assintomático em estadios iniciais. Assim é imperativo a deteção precoce da doença. A nucleolina (NCL) é uma proteína multifuncional envolvida em múltiplos processos biológicos sob condições fisiológicas e patológicas, podendo ter várias localizações celulares. A sobre-expressão da proteína na superfície das células é apenas encontrada em células cancerosas, nomeadamente as do cancro da próstata. Assim a NCL pode ser considerada como um potencial biomarcador para o diagnóstico e tratamento do cancro da próstata. O AS411 é um aptamero capaz de reconhecer e ligar especificamente a esta proteína, e de ter um efeito terapêutico nas células cancerosas ao induzir atividade antiproliferativa. Além do uso terapêutico, a sequência pode ser utilizada na imagiologia e diagnóstico, particularmente através do desenvolvimento de aptasensores. Uma das características mais relevantes do aptamero AS1411 é a capacidade de adotar a configuração de G-quadruplex (G4), uma estrutura secundária dos ácidos nucleicos. As estruturas G4 conferem estabilização à sequência e capacidade de ligar à NCL quando adota esta estrutura. Assim, neste trabalho é apresentada uma primeira abordagem do uso do AS1411 no diagnóstico do cancro da próstata, nomeadamente através da construção de uma sonda a partir da sequência deste aptamero designado por AS1411N5. Inicialmente foi efetuada a caracterização biofísica do AS1411-N5 a nível da estrutura e interação com o alvo, recorrendo às espectroscopias dicroísmo circular e ressonância magnética nuclear, e ensaios fluorométricos. Adicionalmente foram efetuadas experiências de microfluídica, para o uso do AS1411N5 como sonda de deteção da NCL. Estes resultados demonstraram, que o AS1411-N5adota a estrutura G4 e é capaz de ligar especificamente e com seletividade com a NCL, mesmo em amostras biológicas

    Dream West

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    A industria do entretenimento tem como grande objectivo promover momentos de lazer e distracção as pessoas. O seu crescimento nos últimos anos e as boas perspectivas para o futuro tornam-no num sector atractivo e com elevado potencial. Um estudo recente revela que a música está cada vez mais presente no público português, destacando-se os festivais de verão e os concertos. Uma análise ao sector permitiu concluir que existe espaço para mais uma entidade. O investimento em capital fixo é reduzido pois a grande fatia do investimento durante o ano é destinado a fornecimentos e serviços externos. No primeiro ano definiu-se um cenário conservador com resultado liquido negativo, mas no segundo e terceiros anos o cenário é o oposto com as vendas a atingirem os 15,5 milhões de Euros no ano 3. Conclui-se que o projecto é viável, apesar de uma conjuntura económica desfavorável, pois o VAL apurado é de aproximadamente 141 mil Euros. Aconselha-se portanto o investimento numa zona com elevado potencial turístico, mas que necessita de algum dinamismo.The entertainment industry has the aim of promoting leisure. Its growth in recent years and the prospects for the future make it an attractive sector and with high potential. A recent study shows that music is increasingly present in the Portuguese public, especially the summer festivals and concerts. An analysis of the sector concluded that there is room for another entity. Investment in fixed capital is reduced because the large share of investment over the years is for supplies and services. In the first year set up a conservative scenario with negative net profit, but in the second and third year the scenario is the opposite with sales reaching 15.5 million Euros in year 3. It’s concluded that the project is viable, despite an unfavorable economic environment, A because the NPV calculated is approximately 141 thousand Euros. It is advisable therefore the investment in an area with high tourism potential, but needs some momentum

    Low temperature degradation - ageing of a zirconia dental implant

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    This work compares the topographical aspect of the surface and its chemical composition of a zirconia dental implant before and after artificial ageing. Two implants commercialized were analysed, both made from zirconia: Straumann ZLA Pure (TM) Ceramic. The chemical tests performed allowed to identify the elements of the implants' surface and the topographical test was used to observe the surface of the implants before and after ageing. Both tests provide information about the alterations occur on the surface of the implant after ageing.info:eu-repo/semantics/publishedVersio

    Estádios de maturação de frutos de pinhão manso visando maior rendimento no teor de óleo

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    A planta de pinhão manso encontra-se entre as culturas com grande potencial energético, devido à grande concentração de óleo nas suas sementes, e seu alto poder calorífico. Entretanto, a maturação desuniforme é um problema na colheita, principalmente levando em consideração o melhor momento para se colher os frutos visando maior rendimento de óleo. Neste sentido, este trabalho teve como objetivo avaliar quais características dos frutos de pinhão manso indicam a melhor época para colheita visando maior rendimento de teor de óleo nas sementes. Para tal, coletaram-se em 2013 e 2014 frutos de pinhão-manso em diferentes estádios de maturação: frutos verdes escuros (VE), frutos amarelos (AM), frutos marrom-amarelados (MA) e frutos marrons na planta (MP). Destes, avaliou-se, tanto das sementes como dos frutos, o comprimento, largura, espessura e a massa seca. Dos frutos avaliou-se ainda a porcentagem de umidade, e das sementes avaliou-se o teor de óleo. Tanto em 2013 como em 2014, para as variáveis relacionadas com dimensões (comprimento, largura e espessura), tanto nos frutos como nas sementes, as maiores médias foram obtidas pelos frutos verdes. Em contrapartida, tanto para os frutos como para as sementes, observou-se que os frutos mais maduros apresentam maior matéria seca onde obteve-se médias de 60,28% e 92,52 em 2013 e 62,79% e 80,31% em 2014 respectivamente para MA e MP. Já quanto ao teor de óleo os estádios de maturação mais adequados à colheita de pinhão manso encontram-se imediatamente após o amarelecimento dos frutos, quando os mesmos apresentam quantidade de óleo mais elevada

    Reirradiação em paciente com cancro da mama tratada por linfoma de Hodgkin

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    The long-term survival of the Hodgkin’s lymphoma patients treated at an early age with chemoradiotherapy is raising awareness for the late effects of this treatment. Radio-induced breast cancer is one of the described risks and occurs almost exclusively after a period of 10 years. Well-established risk factors include the diagnosis in the 10-16 age group, the use of extended-field radiation therapy and an increase in radiation dose. Conservative breast surgery with adjuvant radiotherapy is feasible, but dose-reduction techniques to organs at risk should be considered, given the previous irradiation. We report a clinical case of a secondary breast cancer in a patient who underwent chemoradiotherapy, with mantle field radiation therapy, for supradiaphragmatic Hodgkin’s lymphoma at youth. After multidisciplinary discussion and given the patient’s willingness to preserve the breast, she was treated with conservative breast surgery and adjuvant radiotherapy.A sobrevida longa das pacientes com linfoma de Hodgkin submetidas a quimioradioterapia numa idade precoce tem evidenciado os efeitos tardios deste tratamento. O desenvolvimento de cancro da mama radio-induzido é um dos riscos descritos, ocorrendo quase exclusivamente após um intervalo de 10 anos do tratamento. A idade ao diagnóstico entre os 10-16 anos, a radioterapia de campo amplo e um aumento da dose prescrita são os fatores de risco estabelecidos. A cirurgia conservadora da mama com radioterapia adjuvante é exequível, mas, dada a irradiação prévia, devem ser equacionadas estratégias de redução de dose nos órgãos de risco. Apresenta-se o caso de cancro da mama secundário numa paciente submetida em jovem a quimioradioterapia, com técnica de irradiação em manto, por linfoma de Hodgkin supradiafragmático. Após discussão multidisciplinar e dada a vontade da paciente em preservar a mama, foi tratada com cirurgia conservadora e radioterapia adjuvante

    The silent extinction of freshwater mussels in Portugal

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    Freshwater mussels are one of the most threatened animal groups in the world. In the European Union, threatened and protected mussel species are not adequately monitored, while species considered to be common and widespread receive even less attention. This is particularly worrying in the Mediterranean region, where species endemism is high and freshwater habitats are severely affected by water scarcity. In the absence of hard data on population trends, we report here a long-term comparison of freshwater mussel assemblages at 132 sites covering 15 different hydrological basins in Portugal. This study reveals a widespread decline of 60 % in the number of sites and 67 % in the overall abundance of freshwater mussels across Portugal over the last 20 years, indicating that all species are rapidly declining and threatened with extinction. These results show that current legislation and conservation measures are largely ineffective and highlight the importance of updating the Habitats Directive to enforce standard monitoring protocols for threatened species in the European Union and to extend monitoring to other freshwater species thought to be common and widespread. Efficient water management, restrictions on irrigation expansion in important biodiversity areas, mitigation of hydrological changes and loss of aquatic habitat connectivity caused by physical alterations are urgently needed to reverse these declining population trends. For the severely endangered species Margaritifera margaritifera, Potomida littoralis, and Unio tumidiformis, where populations are now critically low, more urgent action is needed, such as ex-situ conservation, protection of remaining populations and large-scale habitat restoration.We would like to thank Jake Dimon, José Tourais, Filipe Rolo, and Elza Fonseca for their help in the surveys. This research was developed under the project EdgeOmics - Freshwater Bivalves at the edge: Adaptation genomics under climate-change scenarios (PTDC/CTA-AMB/3065/2020) funded by the Portuguese Foundation for Science and Technology (FCT) through national funds. FCT also funded MLL under contract 2020.03608.CEECIND, EF under contract CEECINST/00027/2021/CP2789/CT0003, AGS under the grants SFRH/BD/137935/2018 and COVID/DB/152933/2022, and JGN under the grant 2020.04637. BD. The baseline survey was funded by the project “Documentos Estruturantes” (POA 1.100021) of the Instituto da Conservaçã da Natureza

    Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity

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    © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.This project was supported by the “Fundação para a Ciência e Tecnologia”, program “Research 4 Covid-19 Apoio especial a projetos de implementação rápida para soluções inovadoras de resposta à pandemia de COVID-19”. It was also partially supported by each institution.info:eu-repo/semantics/publishedVersio

    Pervasive gaps in Amazonian ecological research

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    Pervasive gaps in Amazonian ecological research

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    Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio
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