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HIV-1 Infection and the PPAR-Dependent Control of Adipose Tissue Physiology
Marta Giralt,Pere Domingo,Francesc Villarroya
PPAR Research , 2009, DOI: 10.1155/2009/607902
Abstract: PPAR is a ligand-dependent master transcription factor controlling adipocyte differentiation as well as multiple biological processes taking place in other cells present in adipose tissue depots such as macrophages. Recent research indicates that HIV-1 infection-related events may alter adipose tissue biology through several mechanisms involving PPAR, ranging from direct effects of HIV-1-encoded proteins on adipocytes to the promotion of a proinflammatory environment that interferes with PPAR actions. This effect of HIV-1 on adipose tissue cells can occur even in the absence of direct infection of adipocytes, as soluble HIV-1-encoded proteins such as Vpr may enter cells and inhibit PPAR action. Moreover, repression of PPAR actions may relieve inhibitory pathways of HIV-1 gene transcription, thus enhancing HIV-1 effects in infected cells. HIV-1 infection-mediated interference of PPAR-dependent pathways in adipocytes and other cells inside adipose depots such as macrophages is likely to create an altered local environment that, after antiretroviral treatment, leads to lipodystrophy in HIV-1-infected and HAART-treated patients.
Aulas 2.0 y uso de las TIC en la práctica docente Classroom 2.0 Experiences and Building on the Use of ICT in Teaching
María Domingo Coscollola,Pere Marquès Graells
Comunicar , 2011, DOI: 10.3916/c37-2011-03-09
Abstract: Asumiendo la importancia de las nuevas tecnologías en las aulas, pretendemos impulsar la integración de las tecnologías de la información y de la comunicación (TIC) en la práctica docente desde una investigación colaborativa donde se aplican metodologías cercanas a la investigación-acción y participan 21 centros de educación primaria y secundaria de Espa a. En los seminarios de esta investigación, el profesorado participante recibe progresivamente una formación didáctica y tecnológica orientada hacia la experimentación y la reflexión de las posibilidades de uso de un ordenador por alumno, en el aula, y de la pizarra digital o pizarra digital interactiva (PDI). Después del primer periodo de la investigación, aportamos ideas significativas que han guiado la formación impartida y avanzamos información de la experimentación del profesorado en sus aulas denominadas aulas 2.0 por estar dotadas de una PDI y de ordenadores con acceso a Internet. Concretamente, de esta experimentación, aportamos resultados relevantes sobre la intensidad de uso de la PDI y de los ordenadores, las actividades habituales realizadas con estos recursos tecnológicos, sus ventajas e inconvenientes destacables al utilizarlos y sus incidencias de uso en los aprendizajes de los estudiantes. En las conclusiones, se analizan y se valoran los resultados, apuntando posibles criterios de actuación para ir avanzando en la práctica docente del siglo XXI y en la inclusión de las TIC en las aulas. Recognising the importance of new technology in the classroom, our aim is to promote the integration of information and communication technology (ICT) in teaching practice from a collaborative research in which action research style methods are applied involving 21 primary and secondary schools in Spain. In these research seminars, the participating teachers receive a progressive educational and technological training orientated towards the experiment and reflect on the possibilities of using a computer per student in the classroom and a digital whiteboard or interactive whiteboard (IWB). After the first period of research, we bring to the table significant ideas that have guided the training and put forward findings on the testing of teachers in their classrooms denoted classrooms 2.0 for being equipped with an IWB and computers with Internet access. In specific, from this experiment, we provide relevant results on the intensity of use of IWBs and computers, the usual activities conducted with these technological resources, their advantages and disadvantages found from use and their impact on student le
Impaired expression of mitochondrial and adipogenic genes in adipose tissue from a patient with acquired partial lipodystrophy (Barraquer-Simons syndrome): a case report
Jordi P Guallar, Ricardo Rojas-Garcia, Elena Garcia-Arumi, Joan C Domingo, Eduardo Gallardo, Antoni L Andreu, Pere Domingo, Isabel Illa, Marta Giralt, Francesc Villarroya
Journal of Medical Case Reports , 2008, DOI: 10.1186/1752-1947-2-284
Abstract: This is a case report of a 44-year-old woman with acquired partial lipodystrophy. To obtain insight into the molecular basis of lipoatrophy in acquired partial lipodystrophy, we examined gene expression in adipose tissue from this patient newly diagnosed with acquired partial lipodystrophy. A biopsy of subcutaneous adipose tissue was obtained from the patient, and DNA and RNA were extracted in order to evaluate mitochondrial DNA abundance and mRNA expression levels.The expression of marker genes of adipogenesis and adipocyte metabolism, including the master regulator PPARγ, was down-regulated in subcutaneous adipose tissue from this patient. Adiponectin mRNA expression was also reduced but leptin mRNA levels were unaltered. Markers of local inflammatory status were unaltered. Expression of genes related to mitochondrial function was reduced despite unaltered levels of mitochondrial DNA. It is concluded that adipogenic and mitochondrial gene expression is impaired in adipose tissue in this patient with acquired partial lipodystrophy.Acquired partial lipodystrophy (APL) or Barraquer-Simons syndrome is a rare form of progressive lipodystrophy (OMIM 60879). Patients show a progressive and symmetrical lipoatrophy of subcutaneous adipose tissue starting from the face and spreading to the upper part of the body. Other alterations, such as nephropathy or central nervous system abnormalities, are often, but not always, present [1]. Patients without any associated anomalies or medical complications have also been reported [2]. Women are more often affected than men and most of the reported cases appear to be sporadic [3]. However, the appearance of similarly affected relatives in the families of several patients has suggested autosomal dominant inheritance [1,4]. Recently, through a study of 35 cases and extensive review of the literature, Garg and collaborators established a major diagnostic criterion for APL as being gradual onset of bilaterally symmetrical loss of subcutan
Thymidine Kinase 2 Deficiency-Induced Mitochondrial DNA Depletion Causes Abnormal Development of Adipose Tissues and Adipokine Levels in Mice
Joan Villarroya, Beatriz Dorado, Maya R. Vilà, Elena Garcia-Arumí, Pere Domingo, Marta Giralt, Michio Hirano, Francesc Villarroya
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0029691
Abstract: Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues.
Polymorphisms of Pyrimidine Pathway Enzymes Encoding Genes and HLA-B*40∶01 Carriage in Stavudine-Associated Lipodystrophy in HIV-Infected Patients
Pere Domingo, Maria Gracia Mateo, Alain Pruvost, Ferran Torres, Juliana Salazar, Maria del Mar Gutierrez, M a Carmen Cabeza , Joan Carles Domingo, Irene Fernandez, Francesc Villarroya, Francesc Vidal, Montserrat Baiget, Oscar de la Calle-Martín
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0067035
Abstract: Purpose To assess in a cohort of Caucasian patients exposed to stavudine (d4T) the association of polymorphisms in pyrimidine pathway enzymes and HLA-B*40:01 carriage with HIV/Highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). Methods Three-hundred and thirty-six patients, 187 with HALS and 149 without HALS, and 72 uninfected subjects were recruited. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Polymorphisms in the thymidylate synthase (TS) and methylene-tetrahydrofolate reductase (MTHFR) genes were determined by direct sequencing, HLA-B genotyping by PCR-SSOr Luminex Technology, and intracellular levels of stavudine triphosphate (d4T-TP) by a LC-MS/MS assay method. Results HALS was associated with the presence of a low expression TS genotype polymorphism (64.7% vs. 42.9%, OR = 2.43; 95%CI: 1.53–3.88, P<0.0001). MTHFR gene polymorphisms and HLA-B*40:01 carriage were not associated with HALS or d4T-TP intracellular levels. Low and high expression TS polymorphisms had different d4T-TP intracellular levels (25.60 vs. 13.60 fmol/106 cells, P<0.0001). Independent factors associated with HALS were(OR [95%CI]: (a) Combined TS and MTHFR genotypes (p = 0.006, reference category (ref.): ‘A+A’; OR for ‘A+B’ vs. ref.: 1.39 [0.69–2.80]; OR for ‘B+A’ vs. ref.: 2.16 [1.22–3.83]; OR for ‘B+B’ vs. ref.: 3.13, 95%CI: 1.54–6.35), (b) maximum viral load ≥5 log10 (OR: 2.55, 95%CI: 1.56–4.14, P = 0.001), (c) use of EFV (1.10 [1.00–1.21], P = 0.008, per year of use). Conclusion HALS is associated with combined low-expression TS and MTHFR associated with high activity polymorphisms but not with HLA-B*40:01 carriage in Caucasian patients with long-term exposure to stavudine.
Association of Thymidylate Synthase Polymorphisms with Acute Pancreatitis and/or Peripheral Neuropathy in HIV-Infected Patients on Stavudine-Based Therapy
Pere Domingo, Maria del Carmen Cabeza, Ferran Torres, Juliana Salazar, Maria del Mar Gutierrez, Maria Gracia Mateo, Esteban Martínez, Joan Carles Domingo, Irene Fernandez, Francesc Villarroya, Esteban Ribera, Francesc Vidal, Montserrat Baiget
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057347
Abstract: Background Low expression thymidylate synthase (TS) polymorphism has been associated with increased stavudine triphosphate intracellular (d4T-TP) levels and the lipodystrophy syndrome. The use of d4T has been associated with acute pancreatitis and peripheral neuropathy. However, no relationship has ever been proved between TS polymorphisms and pancreatitis and/or peripheral neuropathy. Methods We performed a case-control study to assess the relationship of TS and methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms with acute pancreatitis and/or peripheral neuropathy in patients exposed to d4T. Student’s t test, Pearson’s correlations, one-way ANOVA with Bonferroni correction and stepwise logistic regression analyses were done. Results Forty-three cases and 129 controls were studied. Eight patients (18.6%) had acute pancreatitis, and 35 (81.4%) had peripheral neuropathy. Prior AIDS was more frequent in cases than in controls (OR = 2.36; 95%CI 1.10–5.07, P = 0.0247). L7ow expression TS and MTHFR genotype associated with increased activity were more frequent in patients with acute pancreatitis and/or peripheral neuropathy than in controls (72.1% vs. 46.5%, OR = 2.97; 95%CI: 1.33–6.90, P = 0.0062, and 79.1% vs. 56.6%, OR = 2.90, 95%CI: 1.23–7.41, P = 0.0142, respectively). Independent positive or negative predictors for the development of d4T-associated pancreatitis and/or peripheral neuropathy were: combined TS and MTHFR genotypes (reference: A+A; P = 0.002; ORA+B = 0.34 [95%CI: 0.08 to 1.44], ORB+A = 3.38 [95%CI: 1.33 to 8.57], ORB+B = 1.13 [95%CI: 0.34 to 3.71]), nadir CD4 cell count >200 cells/mm3 (OR = 0.38; 95%CI: 0.17–0.86, P = 0.021), and HALS (OR = 0.39 95%CI: 0.18–0.85, P = 0.018). Conclusions Low expression TS plus a MTHFR genotype associated with increased activity is associated with the development of peripheral neuropathy in d4T-exposed patients.
Effects of Switching from Stavudine to Raltegravir on Subcutaneous Adipose Tissue in HIV-Infected Patients with HIV/HAART-Associated Lipodystrophy Syndrome (HALS). A Clinical and Molecular Study
Pere Domingo, María del Mar Gutierrez, José Miguel Gallego-Escuredo, Ferran Torres, Gracia María Mateo, Joan Villarroya, Ignacio de los Santos, Joan Carles Domingo, Francesc Villarroya, Luis Del Rio, Vicente Estrada, Marta Giralt
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089088
Abstract: HIV-1/HAART-associated lipodystrophy syndrome (HALS) has been associated with exposure to stavudine (d4T) through mitochondrial dysfunction. We performed a 48-week study to assess the effects of switching from d4T to raltegravir (RAL) on metabolic and fat molecular parameters of patients with HALS. Forty-two patients with HALS and a median exposure to d4T > 7 years were switched to RAL and followed for 48 weeks. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat measured by DEXA were obtained at baseline and week 48. mtDNA and gene transcripts for PPAR gamma, adiponectin, cytochrome b, Cox IV, TNF alpha, MCP-1 and CD68 were assessed in paired subcutaneous fat tissue biopsies. Lipid parameters, fasting glucose, insulin, and HOMA-IR did not change significantly. Whole body fat (P = 0.0027) and limb fat mass (P<0.0001) increased from baseline. Trunk/limb fat ratio (P = 0.0022), fat mass ratio (P = 0.0020), fat mass index (P = 0.0011) and percent leg fat normalized to BMI (P<0.0001) improved after 48 weeks. Relative abundance of mtDNA, expression of PPAR gamma, adiponectin, Cyt b, and MCP-1 genes increased, whereas Cox IV, TNF alpha, and CD68 did not change significantly from baseline. Switching from d4T to RAL in patients with HALS is associated with an increase in limb fat mass and an improvement in markers of adipocyte differentiation and mitochondrial function in SAT.
A Rational Approach to the Resonance Region
Masjuan, Pere
High Energy Physics - Phenomenology , 2008, DOI: 10.1016/j.nuclphysbps.2008.12.035
Abstract: Resonance Saturation in QCD can be understood in the large-Nc limit from the mathematical theory of Pade Approximants to meromorphic functions.
Notas de campo : la llamada recibió respuesta
Godoy Pere
Gaceta Sanitaria , 2003,
Security Contents: Politico-Military or Multidimensional?
Pere Vilanova
Revista CIDOB d'Afers Internacionals , 1997,
Abstract: The description of security problems has dramatically changed since the end of the bipolar system, and there are difficulties in building new concepts to comprehend a new and not yet defined international system. In the bipolar world, based on the North-South and East-West axes, security was described as systemic stability built upon deterrence and the defense of the statu quo. After the end of the Cold War, a new concept of multidimensional security was formulated. It lay emphasis on political, social (economic development) andinternational (peaceful international relations) democracy and the rule of law, putting aside too rapidly the military dimension. Vilanova argues that what have been identified as sources of new threats –narcotrafficking, ecology, migration, terrorism and fundamentalism– are not really new. There is a need to formulate political responses to these risks factors by means of public policies and intergovernmental and supranational action.
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