Browsing by Author "Ribeiro, Ana Luisa"
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- FGF23-klotho axis as predictive factors of fractures in type 2 diabetics with early chronic kidney diseasePublication . Ribeiro, Ana Luisa; Mendes, Filipa; Carias, Eduarda; Rato, Fátima; Santos, Nélio; Neves, Pedro Leão; Silva, Ana PaulaBackground: The aim of our study was to evaluate the relevance of FGF23-klotho axis in the predisposition for bone fractures in type 2 diabetic patients with early chronic kidney disease. Methods: In a prospective study we included 126 type 2 diabetic patients with CKD stages 2-3 (from 2010 to 2017). We used descriptive statistics, ANOVA and chi-square test. Our population was divided into two groups according to the occurrence of a bone fracture event or not, and the groups were compared considering several biological and laboratorial parameters. We employed a multiple regression model to identify risk factors for bone fracture events and hazard ratios (HR) were calculated using a backward stepwise likelihood ratio (LR) Cox regression. Results: Patients with a fracture event displayed higher levels of FGF-23, Phosphorus, PTH, TNF-alpha, OxLDL, HOMA-IR, calcium x phosphorus product and ACR and lower levels of Osteocalcin, alpha-Klotho, 25(OH)D3 and eGFR compared with patients without a fracture event (p < 0.001). The number of patients with a fracture event was higher than expected within inclining CKD stages (chi 2, p = 0.06). The occurrence of fracture and the levels of TNF-alpha, klotho, 25(OH)D3 and OxLDL were found to predict patient entry into RRT (p < 0.05). Age, osteocalcin, alpha-Klotho and FGF-23 independently influenced the occurrence of bone fracture (p < 0.05). Conclusions: alpha-Klotho and FGF-23 levels may have a good clinical use as biomarkers to predict the occurrence of fracture events. (C) 2019 Elsevier Inc. All rights reserved.
- Naa50/San-dependent N-terminal acetylation of Scc1 is potentially important for sister chromatid cohesionPublication . Ribeiro, Ana Luisa; Silva, Rui D.; Foyn, Havard; Tiago, Margarida N.; Rathore, Om; Arnesen, Thomas; Martinho, Rui GoncaloThe gene separation anxiety (san) encodes Naa50/San, a N-terminal acetyltransferase required for chromosome segregation during mitosis. Although highly conserved among higher eukaryotes, the mitotic function of this enzyme is still poorly understood. Naa50/San was originally proposed to be required for centromeric sister chromatid cohesion in Drosophila and human cells, yet, more recently, it was also suggested to be a negative regulator of microtubule polymerization through internal acetylation of beta Tubulin. We used genetic and biochemical approaches to clarify the function of Naa50/San during development. Our work suggests that Naa50/San is required during tissue proliferation for the correct interaction between the cohesin subunits Scc1 and Smc3. Our results also suggest a working model where Naa50/San N-terminally acetylates the nascent Scc1 polypeptide, and that this co-translational modification is subsequently required for the establishment and/or maintenance of sister chromatid cohesion.
