Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy

The increased prevalence of type 2 diabetes mellitus (T2DM) and life expectancy of diabetic patients fosters the worldwide prevalence of retinopathy and nephropathy, two major microvascular complications that have been difficult to treat with contemporary glucose-lowering medications. The gut microbiota (GM) has become a lively field research in the last years; there is a growing recognition that altered intestinal microbiota composition and function can directly impact the phenomenon of ageing and age-related disorders. In fact, human GM, envisaged as a potential source of novel therapeutics, strongly modulates host immunity and metabolism. It is now clear that gut dysbiosis and their products (e.g. p-cresyl sulfate, trimethylamine?N?oxide) dictate a secretory associated senescence phenotype and chronic low-grade inflammation, features shared in the physiological process of ageing (“inflammaging”) as well as in T2DM (“metaflammation”) and in its microvascular complications. This review provides an in-depth look on the crosstalk between GM, host immunity and metabolism. Further, it characterizes human GM signatures of elderly and T2DM patients. Finally, a comprehensive scrutiny of recent molecular findings (e.g. epigenetic changes) underlying causal relationships between GM dysbiosis and diabetic retinopathy/nephropathy complications is pinpointed, with the ultimate goal to unravel potential pathophysiological mechanisms that may be explored, in a near future, as personalized disease-modifying therapeutic approaches.     

A picture of tuberculosis in young Portuguese people in the early 20th century: a multidisciplinary study of the skeletal and historical evidence

The aim of this study was to examine the evidence, and consider the differential diagnosis, for tuberculosis (TB) in juvenile individuals from early 20th century documented skeletons. There are 66 male and female juvenile individuals in the Coimbra Identified Skeletal Collection (CISC) with an age at death ranging from 7-21 years. The individuals died between 1904-1936 in different areas of Coimbra, Portugal. Eighteen of these individuals died from TB affecting different parts of the body. Thirteen (72.2%) showed skeletal lesions that may be related to this infection. Of the 48 individuals with a non-tuberculous cause of death, only 2 (4.2%) had skeletal changes that could be attributed to TB. The distribution of skeletal manifestations caused by the types of TB under study, based on macroscopic and radiological findings, is described and discussed. In addition, the medical records from 6 tuberculous individuals who died in Coimbra University Hospital (CUH) were analysed, and the information, including their diet and access to treatment, is presented. This work, based on data arising before antibiotics became available for treatment, can contribute to the future diagnosis of TB in non-documented skeletal material, and will facilitate a more reliable diagnosis of TB in juvenile individuals.     

Dental caries in a Portuguese identified skeletal sample from the late 19th and early 20th centuries

Dental caries was investigated in 600 adult dentitions belonging to the identified osteological collections of the Museum of Anthropology, University of Coimbra, Portugal (late 19th/early 20th centuries). The main advantage of this sample compared to an archaeological source is the presence of known demographic parameters such as age, sex, and occupation. The aim of this study is to investigate the issues involved in comparing caries data derived from archaeological death assemblages with statistics compiled from clinical studies of the living. When only the upper dentition was considered, higher rates were observed in females than in males. No differences were found between sexes for lower teeth. In both sexes, both the percentage of carious teeth and the severity of lesions were found to increase with age, demonstrating that caries activity continued throughout life. The slight decrease observed for the age group 70–79 years is probably due to the increased antemortem tooth loss in the elderly. Caries was most common at contact areas (32.9%) and rarest at smooth crown surfaces (6.5%). Root surface caries was graphed in relation to the exposure of roots, and it was confirmed that the degree of root exposure was not strongly related to the frequency of carious lesions on the exposed root surface, although both increased with age. Molars were attacked more frequently by caries as a whole than premolars, canines or incisors. The results are similar to studies of recent living populations with a limited access to professional dental care. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.     

Geochemical Modifications in a Calcic Cambisol by the Impact of an Old Foundry (Coimbra,Central Portugal)

A great number of potentially toxic elements are introduced into soils by numerous anthropogenic activities, such as the foundry industry and may have negative consequences on the environment and subsequently on human health. This paper reports the characterization of soil samples collected at the facilities of an old foundry, already demolished, that operated during the last century in an industrial area in the Center of Portugal, Coimbra. The mineralogy, physicochemical parameters, and geochemistry of the soil foundry's area, were studied and compared with regional soil parameters to understand the impact of the foundry's activity on the soil. The enrichment and degree of contamination in the factory soil were also assessed, according to public guidelines. Foundry soil was found to exhibit higher average contents of Al₂O₃, Fe₂O₃(t), SiO₂, TiO₂, Zr, Sr, Rb, Pb, Zn, Cu, V, Nb, and Bi, than the corresponding regional baseline values. Specifically, the soil in the foundry area is polluted with Cu, Pb, and Zn. PCA analysis allowed to distinguish the natural soil from the foundry contaminated soil and the contribution of the spent sands and iron slags in the modification of the geochemistry of the regional soil. The contaminants and pollutants are not uniformly distributed as they show the higher concentrations in places of local storage, disposal, and finishing of materials used in the foundry.     

Acetylation as a major determinant to microtubule-dependent autophagy: Relevance to Alzheimer's and Parkinson disease pathology

Protein post-translational modifications (PTMs) that potentiate protein aggregation have been implicated in several neurological disorders, including Alzheimer's (AD) and Parkinson's disease (PD). In fact, Tau and alpha-synuclein (ASYN) undergo several PTMs potentiating their aggregation and neurotoxicity.Recent data posits a role for acetylation in Tau and ASYN aggregation. Herein we aimed to clarify the role of Sirtuin-2 (SIRT2) and HDAC6 tubulin deacetylases as well as p300 acetyltransferase in AD and PD neurodegeneration. We used transmitochondrial cybrids that recapitulate pathogenic alterations observed in sporadic PD and AD patient brains and ASYN and Tau cellular models.We confirmed that Tau protein and ASYN are microtubules (MTs)-associated proteins (MAPs). Moreover, our results suggest that α-tubulin acetylation induced by SIRT2 inhibition is functionally associated with the improvement of MT dynamic determined by decreased Tau phosphorylation and by increased Tau/tubulin and ASYN/tubulin binding. Our data provide a strong evidence for a functional role of tubulin and MAPs acetylation on autophagic vesicular traffic and cargo clearance. Additionally, we showed that an accumulation of ASYN oligomers imbalance mitochondrial dynamics, which further compromise autophagy. We also demonstrated that an increase in Tau acetylation is associated with Tau phosphorylation. We found that p300, HDAC6 and SIRT2 influences Tau phosphorylation and autophagic flux in AD. In addition, we demonstrated that p300 and HDAC6 modulate Tau and Tubulin acetylation.Overall, our data disclose the role of Tau and ASYN modifications through acetylation in AD and PD pathology, respectively. Moreover, this study indicates that MTs can be a promising therapeutic target in the field of neurodegenerative disorders in which intracellular transport is altered.     

The Krantz collections of palaeontology held at the University of Coimbra (Portugal): a century of teaching and museum activities

The University of Coimbra holds a large repository of palaeontological collections bought from European mineral dealers, during the late nineteenth and early twentieth centuries. Among these specimens currently available at the Science Museum stand out three collections acquired from the Krantz house, between 1890 and 1913, for the Section of Mineralogy and Geology of the Natural History Museum. Their taxonomic diversity is high, as well as their geographic and stratigraphic wide-range origins, representing many classical locations and sedimentary formations of the European geology, and overseas countries. These collections have been used since long for teaching in practical classes of Natural Sciences at the University, using hands-on procedures. Together with other contemporary Krantz collections, known by several Iberian institutions, reveal an important heritage with both scientific and historical relevance that should be preserved, studied and reviewed from a scientific point of view.     

The three oralTori in the Coimbra population (Portugal) at the beginning of the XXth century A.D.

The remarkable anthropological series formed by E. Tamagnini at the Universidade de Coimbra consists of the exhumed human remains from “La Conchada” cemetery, in Coimbra (Northern Portugal). From this collection, only those individuals coming from the different districts of Coimbra, where they also lived and died, were selected for study. The resulting series was made of by 483 individuals: 234 women and 249 men. The personal data sheets indicate that these people died between 1910 and 1938; their professions, age at death and its cause are also noted. They can be considered as a relatively homogeneous group of low socioeconomical level. The study of the three oraltori demonstrated the high frequencies of all of them, the absence of sexual dimorphism and only a few statistically significant differences between some of the age classes considered. The possible etiological factors (genetical and/or environmental) are also discussed.