Phenotypic impact of deregulated expression of class I histone deacetylases in urothelial cell carcinoma of the bladder

Deregulated expression of histone deacetylases (HDACs) has been implicated in tumorigenesis. Herein, we investigated class I HDACs expression in bladder urothelial cell carcinoma (BUCC), its prognostic value and biological significance. Significantly increased transcript levels of all HDACs were found in BUCC compared to 20 normal mucosas, and these were higher in lower grade and stage tumors. Increased HDAC3 levels were associated with improved patient survival. SiRNA experiments showed decrease cell viability and motility, and increased apoptosis. We concluded that class I HDACs play an important role in bladder carcinogenesis through deregulation of proliferation, migration and apoptosis, constituting putative therapeutic targets

Diversity and characterisation of coagulasenegative staphylococci isolated from healthy individuals in Portugal

In the past few years the interest in coagulase-negative staphylococci (CoNS) has significantly increased in human medicine. CoNS are common commensal colonisers of the human skin, although now also recognised as major nosocomial pathogens. Over the last decades, several studies have been carried out in order to understand the pathogenicity mechanisms of CoNS. The well known determinants in the pathogenesis of CoNS infections are their ability to form biofilms and an exceptional resistance to several antibiotics. Nevertheless, there is a lack of studies regarding the commensal lifestyle of these microorganisms. Additionally, it is now hypothesised that commensal bacteria might be a reservoir of pathogenic determinants. Therefore, the work described throughout this thesis was aimed to perform a phenotypic and genotypic characterisation of different CoNS species isolated from healthy Portuguese individuals. A total of 61 CoNS isolates, comprising 7 different species, were obtained and characterised at the level of biofilm formation and antibiotic susceptibility profiles. According to the results, biofilm formation ability and presence of biofilm-associated genes were commonly found features, highlighting their pivotal role in the colonising lifestyle of CoNS. This study also addressed the correlation between phenotypic and genotypic characteristics of biofilm formation, corroborating and raising questions about the importance of some genes in this process. Moreover, it was observed a great proportion of isolates with decreased susceptibility and multiple resistances to some important antibiotics. A significant association between antibiotic resistance and biofilm formation was also demonstrated, and some hypotheses about the nature of such association were provided. Lastly, the expression patterns of two biofilm-associated genes at two distinct biofilm developmental stages were determined, confirming their importance in the accumulative stage of biofilm formation. Overall, the results presented in this thesis indicate that staphylococcal skin flora might be an important reservoir of potentially pathogenic bacteria and, simultaneously, bring to light new perceptions about the molecular basis of staphylococcal biofilm formation, and the nature of the association between antibiotic resistance and biofilm formation.

La médecine indigène comme instrument normatif social: l’exemple du corps malade navajo

La médecine traditionnelle indigène peut parfois se poser comme un instrument normatif désignant le malade comme celui qui transgresse l‘ordre établi par les ancêtres sacrés et permet à la maladie d‘advenir. Un tiers malveillant ou un sorcier peuvent également être les causes du désordre physiologique et moral du corps social communautaire. L‘étiologie navajo repose sur deux phénomènes : l‘existence de sociosomas (troubles liés à une mauvaise relation à l‘entourage) et de mouvements d‘exclusion ou d‘inclusion du corps étranger, de la conduite déviante. L‘étude de la figure du malade dans les mythes soulignera l‘aspect normatif des thérapeutiques navajo. Enfin, une réflexion sur la justification idéologique de l‘intégration des pratiques ancestrales au protocole de soin montrera dans quelle mesure la collaboration entre praticiens traditionnels et personnels de santé contribue à stigmatiser le malade comme l‘épitome de toutes les déviances : par rapport à la tradition mais aussi au modèle social dominant.

Alcipe, Nathercia e Tirse: Considerações sobre as luzes no feminino no Portugal de setecentos

O presente artigo desenvolve-se em torno de três damas esclarecidas da sociedade portuguesa de setecentos: D. Leonor de Almeida (1750-1839), ou Alcipe; D. Catarina de Lencastre (1749-1824), ou Nathercia; e D. Teresa de Mello Breyner (1739-1798?), ou Tirse. Sabendo que o século XVIII foi um período marcado por mudança e controvérsia, pela emergência de novos paradigmas, pelo reequacionamento de estruturas mentais e tradições seculares – ainda que em Portugal se experimentasse uma certa resistência às teorias filosóficas emergentes – a questão que lançamos e procuramos analisar é: qual o reflexo destas transformações no universo feminino? Assim, partindo dos três exemplos referidos e a eles tornando, pretendemos problematizar três questões centrais no discurso iluminista – educação, leituras e viagens – observando como estas matérias, assaz discutidas e teorizadas ao longo do século XVIII, se repercutiram na formação feminina em solo português e, por outro lado, analisar o modesto mas expressivo papel que as referidas damas assumiram na propagação da cultura das luzes em Portugal.

Transgenerational Inheritance of Paternal Neurobehavioral Phenotypes: Stress, Addiction, Ageing and Metabolism

Epigenetic modulation is found to get involved in multiple neurobehavioral processes. It is believed that different types of environmental stimuli could alter the epigenome of the whole brain or related neural circuits, subsequently contributing to the long-lasting neural plasticity of certain behavioral phenotypes. While the maternal influence on the health of offsprings has been long recognized, recent findings highlight an alternative way for neurobehavioral phenotypes to be passed on to the next generation, i.e., through the male germ line. In this review, we focus specifically on the transgenerational modulation induced by environmental stress, drugs of abuse, and other physical or mental changes (e.g., ageing, metabolism, fear) in fathers, and recapitulate the underlying mechanisms potentially mediating the alterations in epigenome or gene expression of offsprings. Together, these findings suggest that the inheritance of phenotypic traits through male germ-line epigenome may represent the unique manner of adaptation during evolution. Hence, more attention should be paid to the paternal health, given its equivalently important role in affecting neurobehaviors of descendants.