Vector-pathogen interactomics: connecting the dots

As carraças e doenças associadas a carraças têm um impacto negativo considerável na saúde humana e animal. Rhipicephalus bursa é uma carraça multihospedeiro hematófaga e é o principal vetor de Babesia ovis, um hemoparasita altamente patogénico em pequenos ruminantes, que pode levar a uma taxa de mortalidade de 30- 50% em animais suscetíveis e, indiretamente contribuir para um impacto socioeconómico negativo na sociedade humana. O controlo de carraças e doenças associadas depende principalmente do uso de fármacos, que apresentam grandes desvantagens, como a contaminação de alimentos e ambiente e o aumento da resistência, reforçando assim a necessidade de medidas alternativas, como a vacinação. Com base na premissa de que as glândulas salivares da carraça têm um papel crucial no comportamento hematófago e na transmissão de agentes patogénicos, o objetivo principal deste trabalho é aumentar o conhecimento sobre a interação R. bursa-B. ovis neste tecido, de forma a identificar novos candidatos a antigénios protetores para o desenvolvimento de vacinas. Assim sendo, os sialotranscritos e as sialoproteínas de R. bursa foram analisados em diferentes condições, para compreender melhor os processos de alimentação e infeção e contribuir para o desenvolvimento de novas vacinas anti-carraça e doenças associadas. A análise comparativa dos transcriptomas e proteomas revelou que a alimentação por sangue induz a produção de moléculas por parte da carraça, o que se traduziu no aumento da expressão genética e da síntese proteica. Além disso, os dados mostram que a combinação de estímulos (alimentação e infeção) influenciou positivamente a expressão genética, mas negativamente a tradução, podendo sugerir a manipulação de B. ovis no sialoma de R. bursa. Estes resultados aliados a diferentes metodologias como RNA de interferência (in vitro e in vivo) e vacinologia reversa, permitem explorar a maquinaria celular da carraça e identificar vários alvos como potenciais antigénios para vacinas. Os ensaios de silenciamento revelaram o impacto direto de algumas moléculas na sobrevivência da carraça e a sua fixação ao hospedeiro (como a putativa “Vitelogenin-3” e uma proteína do “cement”), enquanto que outros demonstraram um efeito duplo divergente na sobrevivência do vetor e do agente patogénico (como a “lachesin” e a “UB2N”). A análise imunoinformática dos dados anteriores de sequenciação permitiu a identificação de proteínas/peptídeos capazes de induzir, no hospedeiro vertebrado, uma resposta imunológica forte e robusta contra o vetor e o agente patogénico. Nesta análise, uma proteína membranar (proteína contendo domínios “Marvel”) e duas secretórias (uma “Evasin” e uma proteína contendo domínios de “Ricin”) foram selecionadas e promissores "immunological kernels" foram encontrados, contendo características ideais de uma vacina baseada em peptídeos, sem causar alergia e toxicidade. Além disso, a integração de diferentes análises ómicas de diferentes espécies de carraças foi usada como uma estratégia para pesquisar e caracterizar vias biológicas conservadas, a fim de selecionar novos alvos capazes de impactar uma ampla gama de espécies de carraças e bloquear a transmissão de vários agentes patogénicos transmitidos por estas. Deste estudo, destacou-se a via de biossíntese de folato, ao observar que durante a infeção da carraça, quer por bactéria quer por protozoário, a expressão de genes relacionados com esta via era aumentada. No entanto, ensaios de silenciamento numa linha celular de carraça mostraram que, a curto prazo, a redução da expressão de um gene relacionado ao folato (gch-I), não exorta alterações significativas nas células de carraça ou no comportamento do agente patogénico em termos de invasão ou multiplicação. Estudos aplicados e ensaios de vacinação precisam ser conduzidos para validar o potencial desses alvos promissores para o desenvolvimento de abordagens anti-carraça e de bloqueio de transmissão de doenças.health. Rhipicephalus bursa is a hematophagous multi-host tick and the main vector of Babesia ovis, a highly pathogenic hemoparasite in small ruminants, which leads to a 30-50 % of mortality rate in susceptible animals and, indirectly, to a negative socioeconomic impact in human society. Tick and disease control rely mainly in the use of chemotherapy and acaracides, which has major drawbacks including food and environment contamination and the increase of resistance, reinforcing the need for alternatives measures, such as vaccination. Based on the premise that tick salivary glands have a crucial role on hematophagous behaviour and on pathogen transmission, the main objective of this research was to increase the understanding on the Rhipicephalus bursa- Babesia ovis interaction in this organ, in order to find new protective antigen candidates for vaccine design. Thus, the R. bursa sialotranscripts and sialoproteins were screened under different conditions, to better understand the feeding and infection processes and contribute for the development of new anti-tick and tick-borne diseases. The comparative analyses of the transcriptomes and proteomes revealed that blood feeding induces the production of tick molecules, which was translated by the increased gene expression and protein synthesis. Moreover, the data unveiled that the combination of stimuli (feeding and infection) influenced positively gene expression but negatively translation, suggesting that B. ovis might manipulate R. bursa sialome. These results allied to interference RNA (in vitro and in vivo) and reverse vaccinology, allowed to explore the tick cellular machinery and pinpointed several targets as potential vaccine antigens. The silencing assays revealed the direct impact of some molecules in tick survival and attachment to the host (such as putative Vitellogenin-3 and a Cement protein), while others demonstrated a divergent dual-effect on both vector and parasite survival (such as Lachesin and UB2N). Immunoinformatic analysis of the previous sequencing data allowed the identification of proteins/peptides capable of elicit, in the vertebrate host, a strong and robust immune response against both vector and pathogen. In this experiment, one membrane-related (Marvel-containing protein) and two secreted (a Evasin and a ricin-containing protein) proteins were selected and promising “immunological kernels” were found to have ideal characteristics for an anti-tick peptide-based vaccine, without causing allergy and toxicity. Furthermore, the integration of different omics analyses from different tick species was used as a strategy to search and characterize conserved biological pathways in order to select new targets able to impact a wide range of tick vectors and block the transmission of several transmitted pathogens. From this study the folate biosynthesis pathway stood out by observing that during tick infection, by either bacteria or protozoan, the expression of genes related to this pathway were increased. However, silencing assays in a tick cell line demonstrate that, in a short term, the reduction of expression of a folate-related gene (gch-I), did not lead to significant changes in tick cells or pathogen behaviour of invasion or multiplication. Applied studies and vaccination trials need to be conducted to validate the potencial of these promising targets for the development of anti-tick and transmission blocking approaches

Confidence in the eye of the beholder : the influence of physical attractiveness on attitude confidence

Tese apresentada para cumprimento dos requisitos necessários à obtenção do grau de Doutor em Psicologia na área de especialização de Psicologia Social apresentada no ISPA - Instituto Universitário no ano de 2020.Physical attractiveness of a source influences attitudes regarding the attitudinal topic covered in a message. The present thesis aims to test if this attribute is also capable of influencing confidence on attitudes, i.e., the perceived amount of certainty on attitudes towards a topic. We review the literature suggesting the multiplicity of effects of this attribute on attitudes and attitude change, as it is with other persuasive variables, and built on the relevance to approach the influence on attitude confidence. Recent research suggest that judgments of confidence are sensitive to influence from the context, such as the influence of attributes of the source of a message. As it is with attitudes, we test if attitude confidence is sensitive to corrections processes based on the perceived relevance of the source of the message. In this thesis, we test if the influence of physical attractiveness might be dependent on the perception of this attribute as an unwanted source of bias. We start by approaching its impact, as a feature of the source of a message, on judgments of attitude confidence, and build on its relevance as a feature of the recipient of a message. In the first set of studies we demonstrated that the presence of an attractive source, when unrelated with the content of the message, decreases attitude confidence. We show that when asked to report attitude confidence, people seem to correct for the potential influence of physical attractiveness with consequential impact to attitude strength outcomes. In the second set of studies we clarified the role of perceiving the message as contradictory to individuals’ attitudes for the emergence of our effects. Finally, the third set of studies conceptualize the role of physical attractiveness as a self-evaluation from the recipient of the message. We show that this self-evaluation is informative to judgments of attitude confidence, providing an addition mechanism in which physical attractiveness in determining judgments of attitude confidence. We discuss how our findings integrate and expand what was previously known about the influence of physical attractiveness. We highlight the importance of studying features capable of decreasing attitude confidence, regardless of the influence on attitude change

Urinary incontinence: the impact on the quality of life

Quality of life (QoL) assessment represents an emerging focus in the health area since it use can complement clinical practice and optimize resources. Urinary incontinence is a common consequence in the oncologic pathology of the prostate that severely affects QoL.A descriptive, analytical and longitudinal study was conducted with the participation of oncological patients from the ambulatory urology department of an oncology hospital unit of the North of Portugal. The sample, obtained through convenience non-probabilistic sampling between October 2015 and July 2016, included 60 patients. The ICIQ-SF was used. The impact on QOL was classified as: zero (0), no impact; from 1 to 3, slight impact; 4 to 6, moderate; from 7 to 9, severe; and, of 10 or more, very serious. Urinary incontinence had a moderate impact on the perception of QoL of patients in M0 and M1. It was observed that as the symptoms decreased, the patients’ perception of QoL increased and M3 and M6 had a slight impact.info:eu-repo/semantics/publishedVersio

Movimentos europeus no século XVII:Nápoles, Inglaterra, Portugal e Catalunha

Nesta reflexão propomos, usando a sociologia histórica, entrar numa área de estudo, no mínimo, controversa ou problemática – o estudo das revoluções. Esta temática, assustadora devido à sua densidade, espelha as sociedades passada, presente e futura. Através de diretrizes simples e adequadas, centramos esta dissertação em quatro casos revolucionários aparentemente independentes entre si: Portugal, Espanha, Reino de Nápoles e Inglaterra. As reivindicações e alterações pós-revolucionárias destas rebeliões contextualizarão o assunto abordado, enquanto a duração dos efeitos – se são medidas a curto ou longo prazo – ajudarão a definir a sua eficácia. Nos quatro casos verificaremos que diversos fatores se alinham e repetem: as revoltas dos grupos inferiores; a ineficácia dos aparelhos definidos pelos governos vigentes; a tentativa de rutura do Estado por líderes reacionários. Iremos, também, refletir sobre toda a trajetória revolucionária, destacando diversas dimensões causais - democracia, guerra, centralidade política, posição popular, entre outras - e, através delas, ponderar a relação de concorrência entre os Estados e a tomada de medidas, por parte do governo, que afetarão todos os envolventes. Propomos, então, uma observação capaz de englobar a sociologia histórica, em todas as suas variantes, e de expandir a análise causal estrutural e não-estrutural, apontando a relevância do agente social, das mentalidades, da cultura, da religião, dos simbolismos.In this reflection we propose, using historical sociology, to enter a field of study that is, at least, controversial or problematic - the study of revolutions. This theme, frightening because of its density, mirrors past, present and future societies. Through simple and proper guidelines, we focus this dissertation on four revolutionary cases apparently independent of each other: Portugal, Spain, Kingdom of Naples and England. The post-revolutionary alterations and claims will provide the context for the object in study, while the duration of its effects – whether short-term or long-term measures – will help define its effectiveness. In these four cases we will find that several different factors align and repeat themselves: the revolts of the lower groups; the ineffectiveness of the apparatus defined by the existing governments; the attempt to break the state by reactionary leaders. We will also reflect on the whole revolutionary trajectory, highlighting various causal dimensions - democracy, war, political centrality, popular position, among others - and through them to ponder the relationship of competition between states and action by government, which will affect all involved. We propose, therefore, an observation capable of encompassing historical sociology, in all its variants, and of expanding structural and nonstructural causal analysis, pointing out the relevance of the social agent, mentalities, culture, religion, and symbolism

Papéis femininos: maternidade e cuidados na infância entre a sociedade micaelense do último quartel do Século XIX

Dissertação de Mestrado, História Insular e Atlântica (séculos XV-XX), 20 de setembro de 2023, Universidade dos Açores.Ao longo do século XIX, a afirmação dos ideais burgueses levou ao incremento e à consolidação do “culto da maternidade” assente no secular pressuposto de que o propósito de vida de uma mulher era ser esposa e mãe. Tais pressupostos ainda estavam bem presentes na sociedade portuguesa e açoriana, em particular, no último quartel da centúria de oitocentos. O debate sobre os predicados necessários para ser uma boa mãe versava sobre vários aspetos da maternidade, desde o parto, passando pela amamentação e pela educação das crianças. No conjunto de participantes deste debate encontramos os mais variados indivíduos, de ambos os sexos, tanto na esfera privada como na pública, nomeadamente no meio académico. Com este trabalho propomo-nos a analisar os vários aspetos desta realidade, relativamente à ilha de S. Miguel (Açores), bem como do debate em torno da mesma, considerando que se trata de questões ainda pouco estudadas pela historiografia açoriana.ABSTRACT: Throughout the 19th century, the affirmation of the bourgeois ideals led to the increase and the consolidation of the “cult of motherhood” based on the secular assumption that the greatest purpose of a woman was to be a mother and a wife. Such assumptions were still very present in Portuguese and Azorean society in the last quarter of the eight hundredth century. The debate about what it took to be a good mother addressed several aspects of motherhood, from birth to breastfeeding and the education of children. In the group of participants of the debate we found the most varied individuals, including both sexes, in both private and public spheres, namely the academic environment. With this work we propose to analyze the various aspects of that debate and reality

Optimization of fermentation conditions for the production of curcumin by engineered Escherichia coli

Curcumin is a plant secondary metabolite with outstanding therapeutic effects. Therefore, there is a great interest in developing new strategies to produce this high-value compound in a cheaper and environmentally friendly way. Curcumin heterologous production in E. coli using artificial biosynthetic pathways was previously demonstrated using synthetic biology approaches. However, the culturing conditions to produce this compound were not optimized and so far only a two-step fermentation involving the exchange of the culture medium allowed to obtain high concentrations of curcumin, which limits its production at an industrial scale. In this study, the culturing conditions to produce curcumin were evaluated and optimized. In addition, it was concluded that E. coli BL21 allows to produce higher concentrations compared to E. coli K-12 strains. Different IPTG concentrations, time of protein expression induction and substrate type and concentration were also evaluated. The highest curcumin production obtained was 959.3 µM (95.93% of percent yield), which was 3.1-fold higher than the highest concentration previously reported. This concentration was obtained using a two-stage fermentation with LB and M9. Moreover, TB demonstrated to be a very interesting alternative medium to produce curcumin since it also led to high concentrations (817.7 µM). The use of this single fermentation medium represents an advantage at industrial scale and although the final production is lower than the one obtained with the LB-M9 combination, it leads to a significantly higher curcumin production in the first 24 h of fermentation. This study allowed obtaining the highest concentrations of curcumin reported so far in a heterologous organism and is of interest for all of those working with the heterologous production of curcuminoids, other complex polyphenolic compounds or plant secondary metabolites.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of the UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01- 0145-FEDER-006684) and under the scope of the Project MultiBiorefinery-Multi-purpose strategies for broadband agro-forest and fisheries by-products valorization: a step forward for a truly integrated biorefinery (POCI-01-0145-FEDER-016403). The authors also acknowledge financial support from BioTecNorte operation (NORTE-01-0145-FEDER-000004), funded by the European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte and the post-doctoral grant (UMINHO/BPD/37/2015) to J.L.R. funded by FCT.info:eu-repo/semantics/publishedVersio

Amoxicillin Crystalluria: A Rare Side-Effect of a Commonly Prescribed Antibiotic

Although crystalluria is a frequent finding in the routine examination of urine, amoxicillin crystalluria is a rare event whose incidence remains unknown. Crystalluria caused by amoxicillin is very uncommon and may be asymptomatic or have severe renal implications. The authors describe the case of an 87-year-old female patient who presented with massive amoxicillin crystalluria due to poor hydration, low urinary pH and high intravenous amoxicillin dosage

Inconsistency Detection in Job Postings

The use of AI in recruitment is growing and there is AI software that reads jobs\u27 descriptions in order to select the best candidates for these jobs. However, it is not uncommon for these descriptions to contain inconsistencies such as contradictions and ambiguities, which confuses job candidates and fools the AI algorithm. In this paper, we present a model based on natural language processing (NLP), machine learning (ML), and rules to detect these inconsistencies in the description of language requirements and to alert the recruiter to them, before the job posting is published. We show that the use of an hybrid model based on ML techniques and a set of domain-specific rules to extract the language details from sentences achieves high performance in the detection of inconsistencies

Ganhos sinérgicos em fusões e aquisições: estudo de caso

Nos dias de hoje, o impacto das operações de fusões e aquisições nos processos de reestruturação organizacional tem-se sentido progressivamente na economia contemporânea, podendo ser encaradas como um dos principais meios de gerar ganho e riqueza nas empresas intervenientes. Mediante a extensa investigação desenvolvida sobre o tema constata-se que as fusões e aquisições podem ser consideradas como uma forma de planeamento empresarial que permite às organizações alcançar novas oportunidades de mercado, possibilitando inclusivamente uma diversificação ao nível dos seus negócios. Isto poderá levar a que as entidades consigam ganhar uma maior força e competição, cenário que na maioria dos casos não seria acessível operando de modo autónomo. Os ganhos resultantes dos processos de fusões e aquisições são o foco e o objetivo principal destas operações. Por esse motivo, o objetivo desta investigação empírica é o estudo dos ganhos sinérgicos obtidos com as operações de fusões. E, com o intuito de contribuir com melhores resultados, a técnica de investigação escolhida apoia-se num estudo de caso englobando a análise detalhada de dois processos de fusões por incorporação. O primeiro processo de fusão ocorre em 2016 entre as sociedades Sonae – Specialized, S.G.P.S., S.A. e Sonae MC – Modelo Continente, S.G.P.S., S.A., enquanto o segundo processo acontece em 2019 entre a Modelo Continente, S.G.P.S., S.A. e a Sonae MC, S.G.P.S., S.A.. Para tal, optamos pelo método de avaliação de empresas com recurso ao modelo quantitativo do fluxo de caixa descontado, onde o fluxo foi executado através do fluxo de caixa livre e os cash flows foram atualizados pelo custo médio ponderado de capital. Posto isto, determinamos a performance das entidades, isto é, quanto à determinação do valor de mercado que cada entidade regista antes e após os processos de fusão. Neste seguimento, para melhor análise relativamente ao desempenho e ao comportamento das entidades intervenientes recorremos à ajuda de indicadores económicos e financeiros, compreendendo a evolução destes indicadores. Os resultados alcançados demonstram que, comparando o valor apurado das empresas antes e pós fusão, é garantido um ganho extraordinário pós fusão, resultando na redução de custos, em especial através da otimização de processos e na melhoria da eficiência organizacional. Este estudo contribuiu para a compreensão dos ganhos sinérgicos em fusões e aquisições. E através da investigação realizada, o estudo desenvolvido possibilita identificar e quantificar os ganhos sinérgicos que as organizações alcançaram por meio das operações de fusão.Nowadays, the impact of mergers and acquisitions on organizational restructuring processes has been progressively felt in the contemporary economy and can be seen as one of the main ways of generating gain and wealth in the companies involved. Based on the extensive research carried out on the subject, it was possible to verify that mergers and acquisitions can be considered as a business planning strategy that allows organizations to reach new market opportunities and can also enable the diversification of their business portfolios. This could lead to entities being able to strengthen themselves and become more competitive, which in most cases would not be possible operating autonomously. The benefits obtained from mergers and acquisitions processes are the focus and main objective of these operations. For this reason, the objective of this empirical investigation is to study the synergistic gains obtained from merger operations. In order to contribute to better results through this research, the chosen research technique is based on a case study that includes a detailed analysis of two mergers by incorporation. The first merger takes place in 2016 between Sonae - Specialised, S.G.P.S., S.A. and Sonae MC - Modelo Continente, S.G.P.S., S.A., while the second takes place in 2019 between Modelo Continente, S.G.P.S., S.A. and Sonae MC, S.G.P.S., S.A.. For this purpose, we opted for the company valuation method using the quantitative discounted cash flow model, where the flow was determined through free cash flow and cash flows were updated by the weighted average cost of capital. Therefore, we determine the performance of entities based on the established estimation of the market value that each entity registers before and after the merger processes. Thereby we use the analysis of specific economic and financial indicators to understand their evolution and secure a better analysis regarding the performance and behavior of the entities involved. The results achieved reveal that comparing the value obtained by the companies before and after the merger, an extraordinary post-merger gain is guaranteed, that result in a cost reduction, especially through process optimization and improved organizational efficiency. This study contributed to the understanding of synergistic gains in mergers and acquisitions. The study developed based on the research carried out makes it possible both to identify and quantify the synergistic gains obtained by companies through merger operations