Mosaic maternal ancestry in the Great Lakes region of East Africa

The Great Lakes lie within a region of East Africa with very high human genetic diversity, home of many ethno-linguistic groups usually assumed to be the product of a small number of major dispersals. However, our knowledge of these dispersals relies primarily on the inferences of historical, linguistics and oral traditions, with attempts to match up the archaeological evidence where possible. This is an obvious area to which archaeogenetics can contribute, yet Uganda, at the heart of these developments, has not been studied for mitochondrial DNA (mtDNA) variation. Here, we compare mtDNA lineages at this putative genetic crossroads across 409 representatives of the major language groups: Bantu speakers and Eastern and Western Nilotic speakers. We show that Uganda harbours one of the highest mtDNA diversities within and between linguistic groups, with the various groups significantly differentiated from each other. Despite an inferred linguistic origin in South Sudan, the data from the two Nilotic-speaking groups point to a much more complex history, involving not only possible dispersals from Sudan and the Horn but also large-scale assimilation of autochthonous lineages within East Africa and even Uganda itself. The Eastern Nilotic group also carries signals characteristic of West-Central Africa, primarily due to Bantu influence, whereas a much stronger signal in the Western Nilotic group suggests direct West-Central African ancestry. Bantu speakers share lineages with both Nilotic groups, and also harbour East African lineages not found in Western Nilotic speakers, likely due to assimilating indigenous populations since arriving in the region ~3000 years ago.

Evolving hallmarks in urothelial bladder cancer: unveiling potential biomarkers

Urothelial bladder carcinoma (UBC), the most frequent type (90%) of bladder cancer and the second most common malignancy of the urogenital region, is a relatively well understood type of cancer, with numerous studies concerning pathogenetic pathways, natural history and bladder tumor biology being reported. Despite this, it continues to remain a challenge in the oncology field, mostly due to its relapsing and progressive nature, and to the heterogeneity in the response to cisplatin-containing regimens. Although the formulae based on clinical staging and histopathological parameters are classically used as diagnostic and prognostic tools, they have proven insufficient to characterize the individual biological features and clinical behaviour of the tumours. Understanding the pathobiology of the disease can add important information to these classical criteria, and contribute to accurately predict outcome and individualize therapy for UBC patients. In this line of investigation, we found that tumour angiogenesis and lymphangiogenesis, the process of invasion and metastasis and the energy metabolism reprogramming/tumour microenvironment encompass several potential biomarkers that seem to infl bladder cancer aggressiveness and chemoresistance. We particularly highlight the roles of lymphovascular invasion, and of RKIP, CD147 and MCT1 immunoexpressions, as relevant prognostic and/or predictive biomarkers, and as promising areas of therapeutic intervention, eliciting for the development of additional studies that can validate and further explore these biomarkers.

The influence of kaolin application on key metabolic pathways associated with grape berry quality: a molecular and biochemical analysis

Dissertação de mestrado em Biologia Molecular, Biotecnologia e Bioempreendedorismo em Plantas

Early holocenic and historic mtDNA african signatures in the iberian peninsula: The andalusian region as a paradigm

Determining the timing, identity and direction of migrations in the Mediterranean Basin, the role of "migratory routes" in and among regions of Africa, Europe and Asia, and the effects of sex-specific behaviors of population movements have important implications for our understanding of the present human genetic diversity. A crucial component of the Mediterranean world is its westernmost region. Clear features of transcontinental ancient contacts between North African and Iberian populations surrounding the maritime region of Gibraltar Strait have been identified from archeological data. The attempt to discern origin and dates of migration between close geographically related regions has been a challenge in the field of uniparental-based population genetics. Mitochondrial DNA (mtDNA) studies have been focused on surveying the H1, H3 and V lineages when trying to ascertain north-south migrations, and U6 and L in the opposite direction, assuming that those lineages are good proxies for the ancestry of each side of the Mediterranean. To this end, in the present work we have screened entire mtDNA sequences belonging to U6, M1 and L haplogroups in Andalusians--from Huelva and Granada provinces--and Moroccan Berbers. We present here pioneer data and interpretations on the role of NW Africa and the Iberian Peninsula regarding the time of origin, number of founders and expansion directions of these specific markers. The estimated entrance of the North African U6 lineages into Iberia at 10 ky correlates well with other L African clades, indicating that U6 and some L lineages moved together from Africa to Iberia in the Early Holocene. Still, founder analysis highlights that the high sharing of lineages between North Africa and Iberia results from a complex process continued through time, impairing simplistic interpretations. In particular, our work supports the existence of an ancient, frequently denied, bridge connecting the Maghreb and Andalusia.

Nanotechnological approaches using curcumin and Withania somnifera: neuroprotection and antimicrobial activities

Tese de Doutoramento em Biologia de Plantas

Methylation at the CpG island shore region upregulates Nr3c1 promoter activity after early-life stress

Early-life stress (ELS) induces long-lasting changes in gene expression conferring an increased risk for the development of stress-related mental disorders. Glucocorticoid receptors (GR) mediate the negative feedback actions of glucocorticoids (GC) in the paraventricular nucleus (PVN) of the hypothalamus and anterior pituitary and therefore play a key role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the endocrine response to stress. We here show that ELS programs the expression of the GR gene (Nr3c1) by site-specific hypermethylation at the CpG island (CGI) shore in hypothalamic neurons that produce corticotropin-releasing hormone (Crh), thus preventing Crh upregulation under conditions of chronic stress. CpGs mapping to the Nr3c1 CGI shore region are dynamically regulated by ELS and underpin methylation-sensitive control of this region's insulation-like function via Ying Yang 1 (YY1) binding. Our results provide new insight into how a genomic element integrates experience-dependent epigenetic programming of the composite proximal Nr3c1 promoter, and assigns an insulating role to the CGI shore.

Promising blood-derived biomarkers for estimation of the postmortem interval

A precise estimation of the postmortem interval (PMI) is one of the most important topics in forensic pathology. However, the PMI estimation is based mainly on the visual observation of cadaverous pheno- mena (e.g. algor, livor and rigor mortis) and on alternative methods such as thanatochemistry that remain relatively imprecise. The aim of this in vitro study was to evaluate the kinetic alterations of several bio- chemical parameters (i.e. proteins, enzymes, substrates, electrolytes and lipids) during putrefaction of human blood. For this purpose, we performed kinetic biochemical analysis during a 264 hour period. The results showed a significant linear correlation between total and direct bilirubin, urea, uric acid, transferrin, immunoglobulin M (IgM), creatine kinase (CK), aspartate transaminase (AST), calcium and iron with the time of blood putrefaction. These parameters allowed us to develop two mathematical models that may have predictive values and become important complementary tools of traditional methods to achieve a more accurate PMI estimation

Development of Monoolein-based lipofection vectors for therapeutic siRNA delivery

Tese de Doutoramento em Biologia Molecular e Ambiental - Especialidade em Biologia Celular e Saúde

Diversity of non-clinical Acinetobacter species in a sub-saharan Africa region: evidence of carbapenem-hydrolysing class D-β-lactamase producers

[Excerpt] Although Acinetobacter baumannii has been the main agent for healthcare infections, recent reports suggest that some Acinetobacter environmental species should be considered as a potential cause of disease. In Angola, there are no previous data on its environmental reservoirs and resistance features. We aimed to unveil the occurrence and diversity of Acinetobacter species and the presence of resistance mechanisms in different non-clinical settings in Angola.

Experimental procedures for the identification of material properties of intervertebal disc - a contribution for the development of biomimetic substitutes for the nucleus pulposus

Tese de Doutoramento em Engenharia Mecânica.