Signatures of natural selection in the adaptive immune system of primates

Tese de mestrado, Bioinformática e Biologia Computacional (Biologia Computacional), Universidade de Lisboa, Faculdade de Ciências, 2015O desenvolvimento de uma resposta imunitária adaptativa possibilitou aos vertebrados montar uma defesa mais eficaz em resposta a agentes patogénicos. O sistema imunitário adaptativo tem a capacidade de reconhecer e guardar memória de agentes patogénicos específicos, conferindo ao sistema um poder de resposta mais rápido e eficaz aquando de uma reinfecção. Com o sistema imunitário adaptativo surgem novas células, com o papel central na resposta imunitária. São exemplo dessas células, os linfócitos T e B, que produzem respectivamente os receptores das células T e B. Os receptores dos linfócitos T possuem grande capacidade de rearranjo das suas cadeias (α e β) e surgem de novo nos vertebrados mandibulados e em paralelo com o aparecimento dum novo órgão linfoide primário, o Timo. Este orgão é responsável pela maturação dos linfócitos T e tem a capacidade de eliminar linfócitos T autoreativos (isto é, que reconhecem o próprio).Dada a importância do sistema imunitário adaptativo nos vertebrados, foi objectivo do presente estudo a analise bioinformática de um conjunto de 38 genes intimamente ligados ao desenvolvimento do sistema imunitário adaptativo. Estes, estão compreendidos no “processo de desenvolvimento do timo” e “processo do sistema imunitário”, e foram analisados em busca de assinaturas de seleção positiva, através da aplicação de modelos estatísticos (PAML), que estimam pelo método de máxima verosimilhança, o rácio (ω) de mutações não sinónimas (dN) versus sinónimas (dS ) .No presente estudo, em genes ortólogos, de 11 espécies de primatas (incluindo Homo sapiens), encontraram-se sinais de seleção positiva em 7 genes que, após estudos complementares, foram reduzidos a 4 genes: CD4, IFNG, HOXA3 e PTCRA. O mapeamento dos aminoácidos selecionados positivamente, por inferência Bayesiana, nas suas estruturas terciárias ou quaternárias, revelou que os aminoácidos selecionados positivamente se encontravam predominantemente na região de superfície, da respectiva proteína. Isto leva à formulação da hipótese, de que a superfície da proteína poderá estar sujeita a menores pressões seletivas purificantes do que o seu interior. Neste cenário, uma mutação terá menor impacto na conformação tridimensional, aquando do enrolamento da estrutura primária. A ferramenta bioinformática SIFT, revelou que os aminoácidos selecionados positivamente surgem predominantemente em zonas putativamente menos conservadas. Os resultados do presente estudo, sugerem que os genomas tidos como completos apresentam ainda zonas com baixa qualidade, ou baixa cobertura, que irão beneficiar grandemente da integração de reads produzidas pelos sequenciadores de 4ª geração, como a tecnologia Nanopore.The emergence of an adaptive immune response has enabled vertebrates to respond more effectively to pathogenic infection. The adaptive immune system has the ability to recognize and memorize specific pathogens, allowing stronger responses each time the pathogen is encountered. In the adaptive immune system, T and B-lymphoid cells are central players, producing T-cell and B-cell receptors, respectively. The T-lymphoid cells arise a second time in vertebrates in the jawed lineage. These cells display a more random recombination process of the α and β chains of their receptors, which is followed by coevolution of a primary lymphoid organ (thymus), essential for the development T-lymphoid cells, allowing the elimination of self-reacting cells. Given the importance of the adaptive immune system in vertebrates, the present study aimed to analyze, from a bioinformatics perspective, a set of 38 genes annotated to “thymic development process” and “immune system process” GO terms. These genes were studied in order to find signatures of positive selection. To accomplish this, a statistical model (PAML) was applied to estimate the ratio (ω) of nonsynonymous (dN) versus synonymous substitutions (dS), through maximum likelihood. In the present study, in a set of orthologous genes, of 11 primate species (including Homo sapiens), signals of positive selection were found in 4 genes: CD4, IFNG, HOXA3 and PTCRA. The amino acids identified with positive selection, through Bayesian inference, were mapped to their tertiary and quaternary structures, revealing that these were predominantly located on the protein surface. This leads to the formulation of the hypothesis that the protein surface is under lower purifying selective pressure than its core, with the consequent reduction of impact on the protein folding. The positively selected amino acids were mainly in regions putatively non-damaging or less conserved as predicted by the SIFT tool. This study brings to light problems in the so called complete genomes, that still bear regions of low quality, or low coverage, which will greatly benefit from fourth generation sequencing technology, like Nanopore

Small RNA profiling in Pinus pinaster reveals the transcriptome of developing seeds and highlights differences between zygotic and somatic embryos

Regulation of seed development by small non-coding RNAs (sRNAs) is an important mechanism controlling a crucial phase of the life cycle of seed plants. In this work, sRNAs from seed tissues (zygotic embryos and megagametophytes) and from somatic embryos of Pinus pinaster were analysed to identify putative regulators of seed/embryo development in conifers. In total, sixteen sRNA libraries covering several developmental stages were sequenced. We show that embryos and megagametophytes express a large population of 21-nt sRNAs and that substantial amounts of 24-nt sRNAs were also detected, especially in somatic embryos. A total of 215 conserved miRNAs, one third of which are conifer-specific, and 212 high-confidence novel miRNAs were annotated. MIR159, MIR171 and MIR394 families were found in embryos, but were greatly reduced in megagametophytes. Other families, like MIR397 and MIR408, predominated in somatic embryos and megagametophytes, suggesting their expression in somatic embryos is associated with in vitro conditions. Analysis of the predicted miRNA targets suggests that miRNA functions are relevant in several processes including transporter activity at the cotyledon-forming stage, and sulfur metabolism across several developmental stages. An important resource for studying conifer embryogenesis is made available here, which may also provide insightful clues for improving clonal propagation via somatic embryogenesis.publishersversionpublishe

Desafios e avanços na personalização diagnóstica e terapêutica na era da inteligência artificial na saúde

The integration of artificial intelligence (AI) and machine learning (ML) in medicine represents a rapidly growing field, promising significant advances in diagnostic and treatment processes. Given this scenario, this integrative review seeks to consolidate and critically analyze the available scientific evidence on the application of these innovative technologies in medical practice. The methodology adopted for this integrative review involved a comprehensive search of the main databases, such as PubMed, Scielo and ScienceDirect, using the relevant descriptors, such as "Artificial Intelligence", "Machine Learning", "Clinical Diagnosis", "Machine Learning" and "Deep Learning". The careful selection of references included relevant studies that address the application of AI and ML in various domains of medicine, with a special focus on the references indicated in Vancouver in this abstract. The results of this review reveal a wide range of successful applications of AI and AM in medical diagnosis and treatment. Studies such as Wang et al. (2019) highlight the progress and challenges of using deep learning in medicine, while work by Erickson et al. (2017) highlights the effectiveness of ML in medical imaging, contributing to advances in clinical practice. Ethical approaches and future impacts on the actions of healthcare professionals, as discussed by Ahuja (2019) and Farhud and Zokaei (2021), emerge as crucial points in the integration of these technologies. The conclusion of this integrative review reinforces the significant transformation provided by the integration of AI and AM in medicine, offering faster and more accurate diagnoses, as well as outlining intrinsic ethical challenges. Patient privacy and ethical considerations become critical factors in this scenario. This comprehensive analysis highlights the continued need for responsible research and development, promoting advances that optimize clinical efficacy and ensure the trust of healthcare professionals and patients in the face of these transformative innovations.A integração de inteligência artificial (IA) e aprendizado de máquina (AM) na medicina representa um campo em rápido crescimento, prometendo avanços significativos nos processos de diagnóstico e tratamento. Diante desse cenário, a presente revisão integrativa busca consolidar e analisar criticamente as evidências científicas disponíveis sobre a aplicação dessas tecnologias inovadoras na prática médica. A metodologia adotada para esta revisão integrativa envolveu uma busca abrangente nas principais bases de dados, como PubMed, Scielo e Scopus, utilizando os descritores pertinentes, tais como "Inteligência Artificial", "Aprendizado de Máquina", "Diagnóstico Clínico", "Machine Learning" e "Deep Learning". A seleção criteriosa das referências incluiu estudos relevantes que abordam a aplicação de IA e AM em diversos domínios da medicina, com foco especial nas referências indicadas em Vancouver neste resumo. Os resultados desta revisão revelam uma ampla gama de aplicações bem-sucedidas de IA e AM em diagnósticos e tratamentos médicos. Estudos como o de Wang et al. (2019) destacam os progressos e desafios do uso de deep learning na medicina, enquanto trabalhos de Erickson et al. (2017) evidenciam a eficácia do AM em imagens médicas, contribuindo para avanços na prática clínica. Abordagens éticas e impactos futuros na atuação dos profissionais de saúde, conforme discutido por Ahuja (2019) e Farhud e Zokaei (2021), emergem como pontos cruciais na integração dessas tecnologias. A conclusão desta revisão integrativa reforça a transformação significativa proporcionada pela integração de IA e AM na medicina, oferecendo diagnósticos mais rápidos e precisos, bem como delineando desafios éticos intrínsecos. A privacidade do paciente e as considerações éticas tornam-se fatores críticos nesse cenário. Esta análise abrangente destaca a necessidade contínua de pesquisa e desenvolvimento responsável, promovendo avanços que otimizem a eficácia clínica e garantam a confiança dos profissionais de saúde e dos pacientes diante dessas inovações transformadoras

BrAPI-an application programming interface for plant breeding applications

Motivation: Modern genomic breeding methods rely heavily on very large amounts of phenotyping and genotyping data, presenting new challenges in effective data management and integration. Recently, the size and complexity of datasets have increased significantly, with the result that data are often stored on multiple systems. As analyses of interest increasingly require aggregation of datasets from diverse sources, data exchange between disparate systems becomes a challenge. Results: To facilitate interoperability among breeding applications, we present the public plant Breeding Application Programming Interface (BrAPI). BrAPI is a standardized web service API specification. The development of BrAPI is a collaborative, community-based initiative involving a growing global community of over a hundred participants representing several dozen institutions and companies. Development of such a standard is recognized as critical to a number of important large breeding system initiatives as a foundational technology. The focus of the first version of the API is on providing services for connecting systems and retrieving basic breeding data including germplasm, study, observation, and marker data. A number of BrAPI-enabled applications, termed BrAPPs, have been written, that take advantage of the emerging support of BrAPI by many databases

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

Educomunicação e suas áreas de intervenção: Novos paradigmas para o diálogo intercultural

oai:omp.abpeducom.org.br:publicationFormat/1O material aqui divulgado representa, em essência, a contribuição do VII Encontro Brasileiro de Educomunicação ao V Global MIL Week, da UNESCO, ocorrido na ECA/USP, entre 3 e 5 de novembro de 2016. Estamos diante de um conjunto de 104 papers executivos, com uma média de entre 7 e 10 páginas, cada um. Com este rico e abundante material, chegamos ao sétimo e-book publicado pela ABPEducom, em seus seis primeiros anos de existência. A especificidade desta obra é a de trazer as “Áreas de Intervenção” do campo da Educomunicação, colocando-as a serviço de uma meta essencial ao agir educomunicativo: o diálogo intercultural, trabalhado na linha do tema geral do evento internacional: Media and Information Literacy: New Paradigms for Intercultural Dialogue

Diminishing benefits of urban living for children and adolescents’ growth and development

AbstractOptimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.</jats:p

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining https://researchonline.ljmu.ac.uk/images/research_banner_face_lab_290.jpgunderweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity

Small RNA profiling in Pinus pinaster reveals the transcriptome of developing seeds and highlights differences between zygotic and somatic embryos

Regulation of seed development by small non-coding RNAs (sRNAs) is an important mechanism controlling a crucial phase of the life cycle of seed plants. In this work, sRNAs from seed tissues (zygotic embryos and megagametophytes) and from somatic embryos of Pinus pinaster were analysed to identify putative regulators of seed/embryo development in conifers. In total, sixteen sRNA libraries covering several developmental stages were sequenced. We show that embryos and megagametophytes express a large population of 21-nt sRNAs and that substantial amounts of 24-nt sRNAs were also detected, especially in somatic embryos. A total of 215 conserved miRNAs, one third of which are conifer-specific, and 212 high-confidence novel miRNAs were annotated. MIR159, MIR171 and MIR394 families were found in embryos, but were greatly reduced in megagametophytes. Other families, like MIR397 and MIR408, predominated in somatic embryos and megagametophytes, suggesting their expression in somatic embryos is associated with in vitro conditions. Analysis of the predicted miRNA targets suggests that miRNA functions are relevant in several processes including transporter activity at the cotyledon-forming stage, and sulfur metabolism across several developmental stages. An important resource for studying conifer embryogenesis is made available here, which may also provide insightful clues for improving clonal propagation via somatic embryogenesis.European Commission Seventh Framework Programme; Fundaçao para a Ciencia e a Tecnologia and GREEN-it.http://www.nature.com/sreppm2020BiochemistryGeneticsMicrobiology and Plant Patholog