Browsing by Issue Date, starting with "2017-09-08"
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- Widening the spectrum of deletions and molecular mechanisms underlying alpha-thalassemiaPublication . Ferrão, José; Silva, Marisa; Gonçalves, Lúcia; Gomes, Susana; Loureiro, Pedro; Coelho, Andreia; Miranda, Armandina; Seuanes, Filomena; Reis, Ana Batalha; Pina, Francisca; Maia, Raquel; Kjollerstrom, Paula; Monteiro, Estela; Lacerda, João F.; Lavinha, João; Gonçalves, João; Faustino, PaulaInherited deletions of α-globin genes and/or their upstream regulatory elements (MCSs) give rise to α-thalassemia, an autosomal recessive microcytic hypochromic anemia. In this study, Multiplex Ligation-dependent Probe Amplification performed with commercial and synthetic engineered probes, Gap-PCR, and DNA sequencing were used to characterize lesions in the subtelomeric region of the short arm of chromosome 16, possibly explaining the α-thalassemia/HbH disease phenotype in ten patients. We have found six different deletions, in heterozygosity, ranging from approximately 3.3 to 323 kb, two of them not previously described. The deletions fall into two categories: one includes deletions which totally remove the α-globin gene cluster, whereas the other includes deletions removing only the distal regulatory elements and keeping the α-globin genes structurally intact. An indel was observed in one patient involving the loss of the MCS-R2 and the insertion of 39 bp originated from a complex rearrangement spanning the deletion breakpoints. Finally, in another case no α-globin gene cluster deletion was found and the patient revealed to be a very unusual case of acquired alpha-thalassemia-myelodysplastic syndrome. This study further illustrates the diversity of genomic lesions and underlying molecular mechanisms leading to α-thalassemia.
- Regulation of glucose transporters by protein kinases in cancer cellsPublication . Henriques, Andreia; Matos, Paulo; Jordan, PeterBackground: Cancer cells require increased glucose supply to sustain proliferation. One mechanism involves increased expression of glucose transporter (GLUT) genes. But insulin has revealed that protein phosphorylation is another key mechanism in glucose uptake regulation: insulin binding to responsive cells triggers a signalling cascade with phosphorylation of TBC1D4, a negative regulator of endosomal GLUT trafficking, so that more transporters are inserted into the plasma membrane. Previous work from the host lab has identified the family of WNK protein kinases and shown that WNK1 can also phosphorylate TBC1D4 and promote GLUT translocation to the cell surface. Our objective is to understand the contribution of WNK1 to glucose uptake in colorectal cancer cells.
- Stimulation of RAC1/PAK1 signalling upregulates DNA damage repair genes via the BCL6/STAT5-switchPublication . Barros, Patrícia; Amaral, Andreia; Abrantes, Leonor; Oliveira, Tiago; Louro, Henriqueta; Silva, Maria João; Jordan, Peter; Gama-Carvalho, Margarida; Matos, PauloColorectal cancer is one of the most prevalent types of cancer worldwide. The GTPase RAC1 and its effector PAK1 have been found overexpressed or hyperactivated in colorectal cancers, particularly those with more aggressive and invasive features, leading to unfavourable clinical prognosis, often resulting from chemoresistance.
- Using directed acyclic graphs to ajust for confounding in influenza vaccine effectiveness studiesPublication . Machado, Ausenda; Kislaya, Irina; Gómez, Verónica; Sousa-Uva, Mafalda; Rodrigues, Ana Paula; Nunes, BaltazarThe annual estimation of the Influenza Vaccine Effectiveness (IVE) requires the implementation of observational studies that are prone to potential bias. Significance testing or change-in-point estimate approaches have been commonly used to selectect covariates for models adjustment in IVE studies. In EuroEVA, the test-negative study Portuguese component of the IMOVE network, for the past 8 seasons the potential confounders were identified if they changed crude OR estimate. The set of variables changed every season and some model adjustment issues were raised. This study aimed evaluating the use of causal directed acyclic graph (DAG) approach for IVE studies to allow adjustment with a more consistent and stable set of variables. We used data from EuroEVA study from seasons 2011-12 to 2015-16. The set of collected variables included sociodemographic (sex, education, cohabitants), health status (immunocompromising, non-immunocompromising conditions), health behaviour (smoking), severity (hospitalizations), previous vaccination, functional status (help to bath), health seeking behaviour (nr of GP consultations), target group for vaccination (health professional or caregiver), time in the influenza season. Three steps were done to build the theoretical model of causal relation between influenza vaccination and medically attended influenza: 1) literature review; 2) development of DAG using DAGitty software; 3) adjustment of logistic regression model using minimum sufficient set of covariates to adjust for confounding (testing for conditional independencies). DAGitty proposed three different models, where the variables age, both health conditions, being health professional and time in the season were common to all models. Other additional variables included were smoking and education (model 1), nr of GP visits (model 2) and sex (model 3). IVE were 58% (95%CI:41%-70%), 57% (95%CI: 40%-70%) and 58% (95%CI:40%-70%) for model 1, 2 and 3 respectively. The minimum variable set to adjust for confounding included six variables. Both IVE adjusted estimates and confidence intervals were similar between the three proposed models. DAG resulted in a good framework to study analysis and leaded to more stable set of variables that allows inter season comparison. However, it should be noted that two important variable were not included (previous infection and vaccination). Also, DAG needs to be updated if changes occur in the vaccination programme or individuals behaviour towards the vaccine and infection.
- Teores de vitamina C em alimentos destinados a lactentes e crianças jovens: serão adequados?Publication . Silva, M.A.; Albuquerque, T.G.; Oliveira, M.B.P.P.; Costa, H.S.Apresentaçao oral sobre se os teores de vitamina C em alimentos destinados a lactentes e crianças jovens são os adequados.