Genomic map of the past: Reconstructing the demographic history of wood ant species and their hybrids

Tese de mestrado, Biologia Evolutiva e do Desenvolvimento, Universidade de Lisboa, Faculdade de Ciências, 2020Hybridization is a process known to occur in various animal and plant taxa, leading to the combination of genetic material from previously isolated gene pools. While hybridization can lead to favourable outcomes, such as adaptive introgression, reconstructing speciation and hybridization histories is essential to better understand such outcomes. In Southern Finland, the distributions of the wood ant species Formica polyctena and F. aquilonia overlap and these species interbreed, producing viable and stable hybrid offspring. Whether these hybrid populations have a single origin or were formed through independent hybridization events remained an open question. In this project, we used genome-wide polymorphism data to study speciation and hybridization between F. polyctena and F. aquilonia. We characterized the genetic diversity and differentiation of populations of F. polyctena and F. aquilonia sampled across Europe, and hybrid populations from Finland. We modelled the demographic history of parental species and inferred their relationship with hybrid populations using the site frequency spectrum. To reconstruct the speciation history between F. polyctena and F. aquilonia, we considered alternative models of divergence, with and without gene flow. Across comparisons with different pairs of populations, we found that divergence between these species started in the Pleistocene, with continuous asymmetric gene flow from F. aquilonia into F. polyctena. The genomic patterns consistent with asymmetric migration could not be explained by gene flow from unsampled species, more closely related to F. polyctena or F. aquilonia. To reconstruct the hybridization history in Finland, we tested alternative secondary contact and admixture scenarios. Our results confirm that the three Finnish populations studied likely arose due to hybridization between F. polyctena and F. aquilonia. Our estimates indicate a higher contribution from F. polyctena into all hybrids (0.55 to 0.65 depending on the population), and strongly suggest that the two genetic lineages in Långholmen, the most extensively studied population of F. polyctena x F. aquilonia hybrids, share the same origin. It is, however, unclear whether this is the case for the remaining hybrid populations. This is the first study modelling the demographic history to elucidate the speciation of rufa group species. This allows us to provide insight into speciation with gene flow in eusocial haplodiploid organisms. Our findings concerning admixture between F. polyctena and F. aquilonia expand on the current knowledge on hybridization in the rufa group and will be useful to interpret the observed patterns of variation in F. polyctena x F. aquilonia hybrid genomes

THE ADOLESCENT AND THE CHRONIC ILLNESS: AN ADOLESCENT WITH KLIPPEL-TRENAUNAY SYNDROME

Introdução: A relação do adolescente com a doença cró- nica é complexa e causa desequilíbrios no seu desenvolvimento biopsicossocial. A adolescência constitui uma fase crítica de mudança que pode afectar e ser afectada pela doença, independentemente da sua especificidade. Caso Clínico: Adolescente de 16 anos do sexo masculino, portador de síndrome de Klippel-Trenaunay, que apresenta sintomatologia do foro depressivo e ansioso, alteração de atitudes e comportamentos face à doença e dificuldade na adesão terapêutica, relacionados com o processo de integração e gestão da sua doença, com impacto físico, psíquico e social. Conclusão: As alterações desenvolvimentais da adolescência colocam desafios acrescidos à gestão da doença crónica. Por isso, impõe-se aos serviços de saúde a compreensão do seu impacto global - com especial atenção à percepção da qualidade de vida e bem-estar - e a criação de espaço para que este possa ser abordado e minimizado

Exploring the evolutionary link between biofilms and spores formation in spore-formers

Bacteria are often thought as single cell organisms, however they can develop into morphologically complex multicellular communities composed of different subpopulations of specialized cell types. Biofilm is an example, in which bacteria organize for protection from harmful conditions in the host and to create nutrient-rich areas. In the last years biofilm have been show to comprise an important aspect of microbial persistence in the human gut. Endospore-formers, although thought not to be major constituents of the microbiota in the human intestine, cause several intestinal diseases, usually associated with antibiotic use. Whether these bacteria persist in the intestine in biofilms or as endospores is not totally elucidated since both, biofilms and endospores, are able to resist to antimicrobial agents. Most likely sporulation and biofilm formation are tightly linked processes. For some endosporeformers, spore differentiation is induced by a sub-population of cells within the biofilm. In this work we tackled the link between bacterial biofilms and endosporulation in Bacillus subtilis. We showed that endospores produced in biofilms have higher resistance to UV radiation. We revealed that a gene, remA, conserved among endosporeformers and essential for biofilm formation is expressed during sporulation. remA is expressed in the forespore soon after asymmetric division and in the mother cell after engulfment completion. GerE represses remA expression in the mother cell at late stages of sporulation. Consequently, we found components of the biofilm matrix, TasA and BslA, on the coat of endospores produced in biofilms. We suggest that components of the biofilm matrix may be part of mature endospores. We hypothesize that some of the structural proteins that confer integrity to the matrix biofilm, as TasA, may have a role as a scaffold for the assembly of the endospore surface layers.A percepção instalada é a de que as bactérias são organismos unicelulares. No entanto, estes organismos são capazes de se organizarem em comunidades multicelulares complexas compostas de subpopulações de células diferenciadas. Os biofilmes são um exemplo deste tipo de organização. Os biofilmes conferem protecção contra as condições desfavoráveis encontradas no hospedeiro, ao mesmo tempo que criam nichos ricos em nutrientes facilitando a implantação da população. Nos últimos anos foi demonstrado que a persistência microbiana no trato gastrointestinal humano se deve em larga medida à formação de biofilmes. Algumas bactérias que podem ser encontradas no trato gastrointestinal humano são ainda capazes de diferenciar um tipo celular altamente resistente a insultos químicos e físicos, o esporo. Nestes casos, não é claro se são os biofilmes ou os endoesporos os principais responsáveis pela persistência destes organismos, já que ambos são resistentes aos antibióticos. Neste trabalho exploramos a ligação genética entre a formação de biofilmes e a esporulação em Bacillus subtilis. Mostramos que os endoesporos produzidos em biofilmes exibem maior resistência aos UV. Mostramos que um gene, remA, conservado em bactérias formadoras de endoesporos e essencial para a formação de biofilmes é expresso durante a esporulação. remA é expresso no pré-esporo após a divisão assimétrica e na célula mãe após o envolvimento do pré-esporo. GerE reprime a expressão de remA na célula mãe em estádios tardios de desenvolvimento. Consequentemente, encontramos componentes da matriz do biofilme no manto de endoesporos maduros. Algumas das proteínas estruturais que conferem integridade à matriz do biofilme, como TasA, poderão servir como base para a montagem das camadas superficiais do esporo

Prevalência da disfagia sarcopénica na população geriátrica

Introduction: Oropharyngeal Dysphagia (OD) and sarcopenia have been recognized as geriatric syndromes and have shown a higher prevalence in institutionalized elderly, being associated with increased socioeconomic burdens. Prevalence of Sarcopenic Dysphagia (SOD) seems to increase with the average age of population. Objectives: To investigate the presence of sarcopenia and risk of OD in a geriatric population and to analyse the relationship between the factors associated with SOD. Methodology: Cross-sectional study conducted in two nursing homes in Tomar. The OD was screened using The Gugging Swallowing Screen (GUSS). Sarcopenia was assessed according to the criteria defined by the European Working Group on Sarcopenia in Older People. The nutritional status was screened using the Mini Nutritional Assessment - Short Form (MNA-SF), and independence in daily living activities (ADL) was assessed using the Barthel Index (BI). The sample was divided into 4 groups, based on the diagnosis: G1 - Without pathology; G2 - Only being at risk of having OD; G3 - Only with sarcopenia; G4 - With probable SOD. Comparisons were made between the different groups, univariate analyses were performed to find the predictors for each group, and finally, a correlational study between the different scales used. Results: We studied 36 elderly people (23 women; 13 men; age 88.0 ± 5.6), 55.6% were at risk for DO, 52.8% had sarcopenia and 36.1% were probable SOD. Literacy was lower (p<.05) in women. The prevalence of malnutrition based on MNA-SF was 19.4%. The most elderly were independent in ADL (91.7%). The results of the univariate analysis of individuals in different groups showed that the SARC-F questionnaire was a significant predictor (OR=9.0; CI95%=1,285-63,025) for the risk of having SOD. Conclusions: The prevalence of OD risk and sarcopenia has increased with age and with the risk of malnutrition or malnourishment. We have observed that female gender, low educational level and score ≥4 on the SARC-F screening test are associated with higher odds of being at risk for OD, sarcopenia, and even probable SOD. We found that the use of badly adjusted artificial teeth increases odds for sarcopenia by 50%, and that this condition was a significant predictor (p<.05) of risk for OD. Based on the results, we suggested including a Speech and Language Therapist in the multidisciplinary geriatric teams in order to improve the prevention of OD, sarcopenia and SOD, avoiding its consequences.Enquadramento: A disfagia orofaríngea (DO) e a sarcopenia têm sido reconhecidas como síndromes geriátricas e têm apresentado maior prevalência em idosos institucionalizados, estando associadas a elevados encargos socioeconómicos. A prevalência da Disfagia Sarcopénica (DOS) parece aumentar com a idade média da população. Objetivos: Investigar a presença de sarcopenia e risco de ter DO, numa população geriátrica e analisar a relação existente entre os fatores associados à DOS. Métodos: Estudo transversal realizado em duas Estruturas Residenciais para idosos (ERPI), em Tomar. A DO foi rastreada usando o Gugging Swallowing Test (GUSS). A sarcopenia foi diagnosticada com base nas orientações do Grupo de Trabalho Europeu sobre Sarcopenia em Idosos. O estado nutricional foi examinado usando o Mini Nutritional Assessment-Short Form (MNA-SF), e a independência nas atividades de vida diária (AVDs) foi avaliada usando o Indice de Barthel (IB). Dividiu-se a amostra em 4 grupos, com base no diagnóstico: G1: sem patologia; G2: apenas com risco de DO; G3: apenas com sarcopenia; G4: com provável DOS. Realizaram-se comparações entre os diferentes grupos, análises univaridas para encontrar os preditores para cada um dos grupos, e por fim, um estudo correlacional entre as diferentes escalas utilizadas. Resultados: Estudaram-se 36 idosos (23 mulheres; 13 homens; média de idade 88.0±5.6), 55.6% apresentaram risco de ter DO, 52.8% apresentaram sarcopenia e 36.1% apresentaram provável DOS. O nível de alfabetização foi menor (p<.05) nas mulheres. A prevalência de malnutrição com base no MNA-SF foi de 19.4%. A maioria dos idosos era independente nas AVDs (91.7%). Os resultados da análise univariada dos indivíduos nos diferentes grupos mostraram que o questionário SARC-F foi um preditor significativo (OR=9.0; IC95%=1.285-63.025) para o risco de ter DOS. Conclusão: A prevalência de DO e sarcopenia aumentou com a idade e com o risco de malnutrição ou desnutrição. Observámos que o género feminino, o baixo nível educacional e a pontuação ≥4 no teste de rastreio SARC-F, estão associados a maiores probabilidades de sarcopenia, bem como de maior risco de DO e DOS. Vimos ainda que a utilização de próteses dentárias mal ajustadas, aumenta em 50% a probabilidade de ocorrência de sarcopenia, e que esta condição foi um preditor significativo (p<.05) de risco de DO. Com base nos resultados, sugere-se a inclusão do Terapeuta da Fala nas equipas multidisciplinares das ERPI, a fim de melhorar a prevenção de DO, sarcopenia e DOS, evitando as consequências das mesmas.Mestrado em Terapia da Fal

The Emergent Power of Human Cellular vs Mouse Models in Translational Hair Research

Different animal models have been used for hair research and regeneration studies based on the similarities between animal and human skins. Primary knowledge on hair follicle (HF) biology has arisen from research using mouse models baring spontaneous or genetically engineered mutations. These studies have been crucial for the discovery of genes underlying human hair cycle control and hair loss disorders. Yet, researchers have become increasingly aware that there are distinct architectural and cellular features between the mouse and human HFs, which might limit the translation of findings in the mouse models. Thus, it is enticing to reason that the spotlight on mouse models and the unwillingness to adapt to the human archetype have been hampering the emergence of the long-awaited human hair loss cure. Here, we provide an overview of the major limitations of the mainstream mouse models for human hair loss research, and we underpin a future course of action using human cell bioengineered models and the emergent artificial intelligence.This work was supported by FEDER (Fundo Europeu de Desenvolvimento Regional) funds through COMPETE 2020 (POCI, Programa Operacional Competividade e Internacionalização) and Portugal 2020 in the framework of the project 70201-SI I&DT EMPRESAS EM COPROMOÇÃO. E.L. was supported by CEECIND/00654/2020 grant from FCT—Fundação para a Ciência e a Tecnologia, I.P

A CHILD WITH NARCOLEPSY

Introdução: A Narcolepsia é uma doença crónica caracterizada por ataques de sono, sonolência diurna excessiva e fragmentação do sono noturno. Pode associar-se a cataplexia e a outros fenómenos do sono REM (paralisia do sono e alucinações hipnagógicas e hipnopômpicas). Caso clínico: Um menino de 10 anos foi enviado à consulta de Pedopsiquiatria por alterações do comportamento, irritabilidade, adormecimento fácil e distração, sendo interpretado como uma “criança mal-educada”. Após avaliação clínica e estudo concluiu-se que apresentava narcolepsia com cataplexia. Discussão/conclusão: Os doente com narcolepsia confrontam-se com vários problemas devido à própria doença que, se não tratada ou tratada ineficazmente, provoca sintomas perturbadores ou embaraçosos, influenciando a sua qualidade de vida. O objetivo deste trabalho é chamar a atenção para este problema uma vez que é uma situação rara e por isso também muitas vezes desconhecida pelo público em geral e até pelos profissionais de saúde.Introduction: Narcolepsy is a chronic disease characterized by sleep attacks, excessive daytime sleepiness and nocturnal sleep fragmentation. It can be associated cataplexy and other disturbance of REM sleep (sleep paralysis and hypnagogic hallucinations and hypnopompic). Case report: A 10-year old boy was referred to Pedopsychiatry because of behavioural disturbance, irritability, sleepiness and distraction, being interpreted as an “ill-mannered child.” After clinical evaluation and comprehensive laboratory studies we concluded that he presented narcolepsy with cataplexy. Discussion/conclusion: Patients with narcolepsy face several problems due to the disease which, if left untreated or ineffectively treated, cause embarrassing or distressing symptoms, affecting their quality of life. The purpose of this paper is to draw attention to this problem since it is a rare condition and therefore seldom not recognized by the general public or even by health professionals

Cross-sectional study to investigate the presence of sarcopenic dysphagia in a Portuguese geriatric population

Oropharyngeal Dysphagia (OD) and sarcopenia have been recognized as geriatric syndromes and have shown a higher prevalence in institutionalized elderly, being associated with increased socioeconomic burdens. The objectives were to investigate the presence of sarcopenia and risk of OD in a geriatric population and to analyse the relationship between the factors associated with Sarcopenic Dysphagia (SOD). We have observed that female gender, low educational level and score ≥4 on the SARC-F screening test are associated with higher odds of being at risk for OD, sarcopenia, and even probable SOD. Based on the results, we suggested including a Speech and Language Therapist in the multidisciplinary geriatric teams in order to improve the prevention of OD, sarcopenia and SOD, avoiding its consequences.publishe

Sporulation Strategies and Potential Role of the Exosporium in Survival and Persistence of Clostridium botulinum

Clostridium botulinum produces the botulinum neurotoxin that causes botulism, a rare but potentially lethal paralysis. Endospores play an important role in the survival, transmission, and pathogenesis of C. botulinum. C. botulinum strains are very diverse, both genetically and ecologically. Group I strains are terrestrial, mesophilic, and produce highly heat-resistant spores, while Group II strains can be terrestrial (type B) or aquatic (type E) and are generally psychrotrophic and produce spores of moderate heat resistance. Group III strains are either terrestrial or aquatic, mesophilic or slightly thermophilic, and the heat resistance properties of their spores are poorly characterized. Here, we analyzed the sporulation dynamics in population, spore morphology, and other spore properties of 10 C. botulinum strains belonging to Groups I–III. We propose two distinct sporulation strategies used by C. botulinum Groups I–III strains, report their spore properties, and suggest a putative role for the exosporium in conferring high heat resistance. Strains within each physiological group produced spores with similar characteristics, likely reflecting adaptation to respective environmental habitats. Our work provides new information on the spores and on the population and single-cell level strategies in the sporulation of C. botulinum

Sporulation Strategies and Potential Role of the Exosporium in Survival and Persistence of Clostridium botulinum

Clostridium botulinum produces the botulinum neurotoxin that causes botulism, a rare but potentially lethal paralysis. Endospores play an important role in the survival, transmission, and pathogenesis of C. botulinum. C. botulinum strains are very diverse, both genetically and ecologically. Group I strains are terrestrial, mesophilic, and produce highly heat-resistant spores, while Group II strains can be terrestrial (type B) or aquatic (type E) and are generally psychrotrophic and produce spores of moderate heat resistance. Group III strains are either terrestrial or aquatic, mesophilic or slightly thermophilic, and the heat resistance properties of their spores are poorly characterized. Here, we analyzed the sporulation dynamics in population, spore morphology, and other spore properties of 10 C. botulinum strains belonging to Groups I–III. We propose two distinct sporulation strategies used by C. botulinum Groups I–III strains, report their spore properties, and suggest a putative role for the exosporium in conferring high heat resistance. Strains within each physiological group produced spores with similar characteristics, likely reflecting adaptation to respective environmental habitats. Our work provides new information on the spores and on the population and single-cell level strategies in the sporulation of C. botulinum

Sporulation Strategies and Potential Role of the Exosporium in Survival and Persistence of Clostridium botulinum

Clostridium botulinum produces the botulinum neurotoxin that causes botulism, a rare but potentially lethal paralysis. Endospores play an important role in the survival, transmission, and pathogenesis of C. botulinum. C. botulinum strains are very diverse, both genetically and ecologically. Group I strains are terrestrial, mesophilic, and produce highly heat-resistant spores, while Group II strains can be terrestrial (type B) or aquatic (type E) and are generally psychrotrophic and produce spores of moderate heat resistance. Group III strains are either terrestrial or aquatic, mesophilic or slightly thermophilic, and the heat resistance properties of their spores are poorly characterized. Here, we analyzed the sporulation dynamics in population, spore morphology, and other spore properties of 10 C. botulinum strains belonging to Groups I-III. We propose two distinct sporulation strategies used by C. botulinum Groups I-III strains, report their spore properties, and suggest a putative role for the exosporium in conferring high heat resistance. Strains within each physiological group produced spores with similar characteristics, likely reflecting adaptation to respective environmental habitats. Our work provides new information on the spores and on the population and single-cell level strategies in the sporulation of C. botulinum.Peer reviewe