University of Coimbra

About: University of Coimbra is a education organization based out in Coimbra, Portugal. It is known for research contribution in the topics: Population & Context (language use). The organization has 14318 authors who have published 43067 publications receiving 994733 citations. The organization is also known as: UC & Universidade dos Estudos Gerais.

Distinct DNA methylomes of newborns and centenarians

Abstract: Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine—phosphate—guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level.

Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3 -mutant mice

Abstract: Obsessive-compulsive disorder (OCD) is an anxiety-spectrum disorder characterized by persistent intrusive thoughts (obsessions) and repetitive actions (compulsions). Dysfunction of cortico-striato-thalamo-cortical circuitry is implicated in OCD, although the underlying pathogenic mechanisms are unknown. SAP90/PSD95-associated protein 3 (SAPAP3; also known as DLGAP3) is a postsynaptic scaffolding protein at excitatory synapses that is highly expressed in the striatum. Here we show that mice with genetic deletion of Sapap3 exhibit increased anxiety and compulsive grooming behaviour leading to facial hair loss and skin lesions; both behaviours are alleviated by a selective serotonin reuptake inhibitor. Electrophysiological, structural and biochemical studies of Sapap3-mutant mice reveal defects in cortico-striatal synapses. Furthermore, lentiviral-mediated selective expression of Sapap3 in the striatum rescues the synaptic and behavioural defects of Sapap3-mutant mice. These findings demonstrate a critical role for SAPAP3 at cortico-striatal synapses and emphasize the importance of cortico-striatal circuitry in OCD-like behaviours.

Proton Structure from the Measurement of 2S-2P Transition Frequencies of Muonic Hydrogen

Abstract: Accurate knowledge of the charge and Zemach radii of the proton is essential, not only for understanding its structure but also as input for tests of bound-state quantum electrodynamics and its predictions for the energy levels of hydrogen. These radii may be extracted from the laser spectroscopy of muonic hydrogen (μp, that is, a proton orbited by a muon). We measured the 2 S 1 / 2 F = 0 - 2 P 3 / 2 F = 1 transition frequency in μp to be 54611.16(1.05) gigahertz (numbers in parentheses indicate one standard deviation of uncertainty) and reevaluated the 2 S 1 / 2 F = 1 - 2 P 3 / 2 F = 2 transition frequency, yielding 49881.35(65) gigahertz. From the measurements, we determined the Zemach radius, rZ = 1.082(37) femtometers, and the magnetic radius, rM = 0.87(6) femtometer, of the proton. We also extracted the charge radius, rE = 0.84087(39) femtometer, with an order of magnitude more precision than the 2010-CODATA value and at 7σ variance with respect to it, thus reinforcing the proton radius puzzle.

Global exchange and accumulation of non-native plants

Abstract: All around the globe, humans have greatly altered the abiotic and biotic environment with ever-increasing speed. One defining feature of the Anthropocene epoch is the erosion of biogeographical barriers by human-mediated dispersal of species into new regions, where they can naturalize and cause ecological, economic and social damage. So far, no comprehensive analysis of the global accumulation and exchange of alien plant species between continents has been performed, primarily because of a lack of data. Here we bridge this knowledge gap by using a unique global database on the occurrences of naturalized alien plant species in 481 mainland and 362 island regions. In total, 13,168 plant species, corresponding to 3.9% of the extant global vascular flora, or approximately the size of the native European flora, have become naturalized somewhere on the globe as a result of human activity. North America has accumulated the largest number of naturalized species, whereas the Pacific Islands show the fastest increase in species numbers with respect to their land area. Continents in the Northern Hemisphere have been the major donors of naturalized alien species to all other continents. Our results quantify for the first time the extent of plant naturalizations worldwide, and illustrate the urgent need for globally integrated efforts to control, manage and understand the spread of alien species.

MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells

Abstract: In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor/interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of TAB2, an important signal transduction molecule. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.