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Activation of ataxia telangiectasia muted under experimental models and human Parkinson's disease

  • Pallas, Merce
  • Ferrer, Isidre
  • Jordan, Joaquin
  • Junyent, Felix
  • Verdaguer, Ester
  • Sureda, Francesc X
  • Folch, Jaume
  • de la Torre, Aurelio Vazquez
  • Gutierrez-Cuesta, Javier
  • Alvira, Daniel
  • Pizarro, Javier G
  • Camins, Antoni
In the present study we demonstrated that neurotoxin MPP(+)-induced DNA damage is followed by ataxia telangiectasia muted (ATM) activation either in cerebellar granule cells (CGC) or in B65 cell line. In CGC, the selective ATM inhibitor KU-55933 showed neuroprotective effects against MPP(+)-induced neuronal cell loss and apoptosis, lending support to the key role of ATM in experimental models of Parkinson's disease. Likewise, we showed that knockdown of ATM levels in neuroblastoma B65 cells using an ATM-specific siRNA attenuates the phosphorylation of retinoblastoma protein without affecting other cell-cycle proteins involved in the G(0)/G(1) cell-cycle phase. Moreover, we demonstrated DNA damage, in human brain samples of PD patients. These findings support a model in which MPP(+) leads to ATM activation with a subsequent DNA damage response and activation of pRb. Therefore, this study demonstrates a new link between DNA damage by MPP(+) and cell-cycle re-entry through retinoblastoma protein phosphorylation.

Triple-Class Virologic Failure in HIV-Infected Patients Undergoing Antiretroviral Therapy for Up to 10 Years

  • Phillips, Andrew N
  • Lundgren, Jens D
  • Chene, Genevieve
  • Kjaer, Jesper
  • Fabre-Colin, Celine
  • Paraskevis, Dimitrios
  • De Luca, Andrea
  • Paredes, Roger
  • Guenthard, Huldrych
  • Lo Caputo, Sergio
  • van Sighem, Ard
  • Pillay, Deenan
  • Perez-Hoyos, Santiago
  • Masip, Joan
  • Thorne, Claire
  • Warsawski, Josiane
  • Meyer, Laurence
  • Ramos, Jose
  • Duval, Xavier
  • Mussini, Cristina
  • Touloumi, Giota
  • Ghosn, Jade
  • Judd, Ali
  • Antinori, Andrea
  • Castagna, Antonella
  • De Wit, Stephane
  • Garcia, Federico
  • Staszewski, Schlomo
  • Masquelier, Bernard
  • Obel, Niels
  • Cozzi-Lepri, Alessandro
  • Podzamczer, Daniel
  • Mocroft, Amanda
  • Ledergerber, Bruno
  • Dorrucci, Maria
  • Teira, Ramon
  • Torti, Carlo
  • Reiss, Peter
  • Costagliola, Dominique
  • Lodwick, Rebecca
Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to approach that of the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades.We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed.Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF.The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from the start of a PI/r regimen after NNRTI failure provides a comparator for studies of response to second-line regimens in resource-limited settings.

Neumonía asociada a la ventilación mecánica

  • Jordi Rello Condomines
  • J. Vallés
  • Leonardo Lorente Ramos
  • E. Díaz

Environmental monitoring of metals, PCDD/Fs and PCBs as a complementary tool of biological surveillance to assess human health risks

  • Domingo J
  • Schuhmacher M
  • Nadal M
  • Mari M
  • Rovira J
The results of an environmental program around the municipal solid waste incinerator (MSWI) of Mataró (Catalonia, Spain), which was designed to assess the potential impact of the facility on the close environment and the health of the population living in the vicinity, are here reported. Metals, polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) were analyzed in soil and air samples collected in/around the facility. In soils, Mn and Zn showed the highest metal concentrations (ranges: 136-648 mg kg(-1) and 29.6-97.8 mg kg(-1), respectively), while total concentrations of PCDD/Fs and PCBs were 0.14-0.46 ng WHO-TEQ kg(-1) and 167-3340 ng kg(-1), respectively. In air, the highest metal levels corresponded to Cu (range: 26.9-52.9 ng m(-3)) and Mn (range: 6.92-19.3 ng m(-3)), while those of PCDD/Fs and PCBs ranged 0.008-0.015 pg WHO-TEQ m(-3) and 9.20-42.1 pg m(-3), respectively. Carcinogenic and non-carcinogenic risks derived of exposure to metals, PCDD/Fs and PCBs did not exceed the threshold values. Complementarily analyzed with the results obtained in the concurrent biomonitoring study and the stack emissions, data indicate that the MSWI of Mataró does not mean significant human health risks derived of emissions of metals, PCDD/Fs and PCBs.Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Determination of the Antioxidants' Ability to Scavenge Free Radicals Using Biosensors

  • Marty, Jean-Louis
  • Calas-Blanchard, Carole
  • Campas, Monica
  • Prieto-Simon, Beatriz
  • Cortina-Puig, Montserrat
Free radicals are highly reactive molecules generated during cellular metabolism. However, their overproduction results in oxidative stress, a deleterious process that can damage cell structures, including lipids and membranes, proteins and DNA. Antioxidants respond to this problem, scavenging free radicals. This chapter critically reviews the electrochemical biosensors developed for the evaluation of the antioxidant capacity of specific compounds. Due to the ability of these devices to perform simple, fast and reliable analysis, they are promising biotools for the assessment of antioxidant properties.

Assessing freshwater use impacts in LCA, part 2: case study of broccoli production in the UK and Spain

  • Clift, Roland
  • Anton, Assumpcio
  • Chenoweth, Jonathan
  • Orr, Stuart
  • Chapagain, Ashok
  • Mila i Canals, Llorenc
MilA i Canals et al. (Int J Life Cycle Ass 14(1):28-42, 2009) referred to as 'Part 1' in this paper) showed that impacts associated with use of freshwater must be treated more rigorously than is usual in life cycle assessment (LCA), going beyond the conventional consideration only of 'blue' water (i.e. irrigation and other abstractions), and suggested an operational method to include the impacts on freshwater ecosystems (freshwater ecosystem impact) and abiotic resource depletion (freshwater depletion). The inclusion of water-related impacts in LCA is of paramount importance, particularly for agricultural systems due to their large water consumption worldwide. A case study of UK consumption of broccoli grown in the UK and Spain is presented here to illustrate the method suggested in Part 1. Water footprint (WF) and life cycle impact assessment (LCIA) methods presented in Part 1 are applied to six different and synchronic supply chains providing broccoli during the British colder months (November-April); four of these chains refer to broccoli produced in Spain and the other two are based on frozen British produce. In addition, four UK-based supply chains delivering fresh broccoli from April to November are studied to provide a year-round perspective. Using WF accounting methods helps to provide a richer picture of the total water consumption associated with growing broccoli. Including the volumes of water consumed in the life cycle inventory (LCI), assessed following the WF approach (evaporative uses of irrigation water and soil moisture), shows that the total water consumption does not vary greatly between UK and Spanish broccoli production. However, when impact assessment indicators based on the water use per resource ratio are applied, water use in Spain is shown to b

Paired Subcutaneous and Visceral Adipose Tissue Aquaporin-7 Expression in Human Obesity and Type 2 Diabetes: Differences and Similarities between Depots

  • Vendrell, J
  • Wabitsch, M
  • Vilarrasa, N
  • Simon, I
  • Alcaide, M J
  • Ceperuelo-Mallafre, V
  • Escote, X
  • Miranda, M
Context: AQP7 is considered to be the sole adipose glycerol channel, and its regulation is crucial for glycemia control. Objectives: In this work, we aimed to further characterize AQP7 in human adipose tissue in obesity and type 2 diabetes (T2D): 1) to assess AQP7 expression levels in paired abdominal adipose tissue depots (sc and visceral); 2) to relate it with gene expression of genes involved in lipid metabolism; and 3) to confirm that AQP7 is mainly expressed in the adipocytes. Design: We conducted a transversal study of gene expression in paired samples of sc adipose tissue (SAT) and visceral adipose tissue (VAT). Patients: Caucasian lean and obese subjects (n = 62, matched for age and gender) and T2D subjects (n = 11, matched for age, gender, and BMI with their control group) participated in the study. Main Outcome Measure: We measured AQP7 expression levels in paired SAT and VAT. Results: We have proved the presence of AQP7 mRNA and protein in the adipocyte rather than the stromovascular fraction of adipose tissue (P = 0.001) and in mature adipocytes when differentiated in vitro. Increased AQP7 mRNA expression levels in VAT from T2D obese subjects (P < 0.05) were found. AQP7 transcript levels ratio of SAT vs. VAT changed with the presence of obesity and T2D. Interestingly, there were positive associations between AQP7 and both lipogenic and lipolytic genes in a similar manner in both adipose depots. Conclusions: Taken together, these data suggest a subtle regulation between adipose depots of the sole adipose aquaporin, AQP7, which is unbalanced in obesity and T2D. (J Clin Endocrinol Metab 95: 3470-3479, 2010)

Primeros resultados tafonómicos de las asociaciones fósiles de la Cova de Dalt del Tossal de la Font (Vilafamés, Castellón)

  • Eudald Carbonell i Roura
  • Francesc Gusi Jener
  • Carmen Rosa Olaria Puyoles
  • Francesc Burjachs i Casas
  • Isabel Expósito Barea
  • Carlos Lorenzo Merino
  • Lucía López-Polín
  • Maria Bennàsar Serra
  • Josep Maria Vergès Bosch
  • Jan van der Made
  • Josep Vallverdú Poch
  • Andreu Ollé Cañellas
  • Isabel Cáceres Cuello de Oro
  • Palmira Saladié i Ballesté

IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas

  • Campo, Elias
  • Jaffe, Elaine S
  • Taddesse-Heath, Lekidelu
  • Delabie, Jan
  • Martinez, Antonio
  • Colomo, Luis
  • Balague, Olga
  • Valera, Alexandra
Plasmablastic lymphoma (PBL) is an aggressive lymphoma characterized by a terminally differentiated B-cell phenotype that usually occurs in the immunocompromised or elderly patients. Although the clinical and pathologic characteristics of these tumors have been defined, the genetic alterations involved in their pathogenesis are not well known. In this study, we have investigated the chromosomal alterations of MYC, BCL2, BCL6, MALT1, PAX5, and IGH loci using fluorescence in situ hybridization in 42 PBL and 3 extracavitary primary effusion lymphomas. MYC rearrangements were identified in 20 of 41 (49%) PBL and the immunoglobulin (IG) genes were the partners in most tumors. MYC rearrangements were more common in Epstein-Barr virus (EBV)-positive (14 of 19, 74%) than EBV-negative (9 of 21, 43%) tumors (P<0.05). No rearrangements of BCL2, BCL6, MALT1, or PAX5 were detected in any PBL but gains of these loci were observed in 31% to 41% of the cases examined. Twelve of the 40 PBL in which 3 or more loci could be investigated had multiple simultaneous gains in 3 or more loci. No differences in the survival of the patients according to MYC were observed but the 4 patients with the longest survival (>50?mo) had no or low number of gains (<3). No rearrangements of any of these loci were seen in the primary effusion lymphomas. In conclusion, PBL are genetically characterized by frequent IG/MYC translocations and gains in multiple chromosomal loci. The oncogenic activation of MYC in these lymphomas may be an important pathogenetic element associated with EBV infection.

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