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University of Technology of Compiègne, France

Dhakal R.,National Reference Center for the Study and Diagnosis of Toxoplasmosis | Gajurel K.,Stanford University | Pomares C.,National Reference Center for the Study and Diagnosis of Toxoplasmosis | Pomares C.,Stanford University | And 6 more authors.
Journal of Clinical Microbiology | Year: 2015

A positive Toxoplasma immunoglobulinM(IgM) result is often interpreted as a marker of an acute infection. However, IgM can persist for several years, and Toxoplasma commercial IgM diagnostic test kits can yield a number of false-positive results. For these reasons, a chronic Toxoplasma infection can be erroneously classified as an acute infection, resulting in serious adverse consequences, especially in pregnant women, leading to emotional distress and unnecessary interventions, including termination of pregnancy. Interpretation of Toxoplasma serology at a reference laboratory can help differentiate a recently acquired infection from a chronic infection. Serological test results for 451 patients with positive Toxoplasma IgM and IgG test results obtained at nonreference laboratories (NRLs) that were referred to Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL) to determine whether the patient was acutely or chronically infected were retrospectively reviewed. PAMF-TSL results established that of the 451 patients, 335 (74%) had a chronic infection, 100 (22%) had an acute infection, and 7 (2%) were not infected, and for 9 (2%), results were indeterminate. Positive Toxoplasma IgM and IgG test results obtained at NRLs cannot accurately distinguish between acute and chronic infections. To do so, testing at reference laboratories is required, as mandated in 1997 in a letter from the Food and Drug Administration (FDA) to clinicians and laboratories in the United States. Copyright © 2015, American Society for Microbiology. All Rights Reserved. Source


Hu Q.,University of California at San Diego | Tanasa B.,University of California at San Diego | Tanasa B.,Scripps Research Institute | Trabucchi M.,University of California at San Diego | And 7 more authors.
Nature Structural and Molecular Biology | Year: 2012

Although liganded nuclear receptors have been established to regulate RNA polymerase II (Pol II)-dependent transcription units, their role in regulating Pol III-transcribed DNA repeats remains largely unknown. Here we report that ∼2-3% of the ∼100,000-200,000 total human DR2 Alu repeats located in proximity to activated Pol II transcription units are activated by the retinoic acid receptor (RAR) in human embryonic stem cells to generate Pol III-dependent RNAs. These transcripts are processed, initially in a DICER-dependent fashion, into small RNAs (∼28-65 nt) referred to as repeat-induced RNAs that cause the degradation of a subset of crucial stem-cell mRNAs, including Nanog mRNA, which modulate exit from the proliferative stem-cell state. This regulation requires AGO3-dependent accumulation of processed DR2 Alu transcripts and the subsequent recruitment of AGO3-associated decapping complexes to the target mRNA. In this way, the RAR-dependent and Pol III-dependent DR2 Alu transcriptional events in stem cells functionally complement the Pol II-dependent neuronal transcriptional program. © 2012 Nature America, Inc. All rights reserved. Source


Berthou F.,French Institute of Health and Medical Research | Berthou F.,Center Mediterraneen Of Medecine Moleculaire | Ceppo F.,French Institute of Health and Medical Research | Ceppo F.,Center Mediterraneen Of Medecine Moleculaire | And 11 more authors.
Molecular Endocrinology | Year: 2015

Bioactive lipid mediators such as prostaglandin E2 (PGE2) have emerged as potent regulator of obese adipocyte inflammation and functions. PGE2 is produced by cyclooxygenases (COXs) from arachidonic acid, but inflammatory signaling pathways controlling COX-2 expression and PGE2 production in adipocytes remain ill-defined. Here, we demonstrated that the MAP kinase kinase kinase tumor progression locus 2 (Tpl2) controls COX-2 expression and PGE2 secretion in adipocytes in response to different inflammatory mediators. We found that pharmacological- or small interfering RNA-mediated Tpl2 inhibition in 3T3-L1 adipocytes decreased by 50% COX-2 induction in response to IL-1β, TNF- α, or a mix of the 2 cytokines. PGE2 secretion induced by the cytokine mix was also markedly blunted. At the molecular level, nuclear factor κB was required for Tpl2-induced COX-2 expression in response to IL-1β but was inhibitory for the TNF-α or cytokine mix response. In a coculture between adipocytes and macrophages, COX-2 was mainly increased in adipocytes and pharmacological inhibition of Tpl2 or its silencing in adipocytes markedly reduced COX-2 expression and PGE2 secretion. Further, Tpl2 inhibition in adipocytes reduces by 60% COX-2 expression induced by a conditioned medium from lipopolysaccharide (LPS)-treated macrophages. Importantly, LPS was less efficient to induce COX-2 mRNA in adipose tissue explants of Tpl2 null mice compared with wild-type and Tpl2 null mice displayed low COX-2 mRNA induction in adipose tissue in response to LPS injection. Collectively, these data established that activation of Tpl2 by inflammatory stimuli in adipocytes and adipose tissue contributes to increase COX-2 expression and production of PGE2 that could participate in the modulation of adipose tissue inflammation during obesity. © 2015 by the Endocrine Society. Source


Bost F.,Center Mediterraneen Of Medecine Moleculaire | Bost F.,University of Nice Sophia Antipolis | Ben-Sahra I.,Center Mediterraneen Of Medecine Moleculaire | Ben-Sahra I.,University of Nice Sophia Antipolis | And 3 more authors.
Cancer Prevention Research | Year: 2012

Several experimental and epidemiologic studies have shown that the antidiabetes drug metformin has antitumor properties. The report by Algire and colleagues in this issue of the journal (beginning on page 536) shows for the first time that metformin reduces mutagenesis induced by reactive oxygen species. This report offers new perspectives on metformin in cancer prevention and provides a new mechanism for the reduction of cancer risk in diabetic patients treated with this drug. ©2012 AACR. Source


Jager J.,Center Mediterraneen Of Medecine Moleculaire | Jager J.,University of Nice Sophia Antipolis | Corcelle V.,Center Mediterraneen Of Medecine Moleculaire | Corcelle V.,University of Nice Sophia Antipolis | And 15 more authors.
Diabetologia | Year: 2011

Aims/hypothesis: Extracellular signal-regulated kinase (ERK) activity is increased in adipose tissue in obesity and type 2 diabetes mellitus and strong evidences suggests that it is implicated in the downregulation of insulin signalling and action in the insulin-resistant state. To determine the role of ERK1 in obesity-associated insulin resistance in vivo, we inactivated Erk1 (also known as Mapk3) in obese leptin-deficient mice (ob/ob). Methods: Mice of genotype ob/ob-Erk1-/- were obtained by crossing Erk1-/- mice with ob/ob mice. Glucose tolerance and insulin sensitivity were studied in 12-week-old mice. Tissue-specific insulin sensitivity, insulin signalling, liver steatosis and adipose tissue inflammation were determined. Results While ob/ob-Erk1-/- and ob/ob mice exhibited comparable body weight and adiposity, ob/ob-Erk1-/- mice did not develop hyperglycaemia and their glucose tolerance was improved. Hyperinsulinaemic-euglycaemic clamp studies demonstrated an increase in whole-body insulin sensitivity in the ob/ob-Erk1-/- mice associated with an increase in both insulin-stimulated glucose disposal in skeletal muscles and adipose tissue insulin sensitivity. This occurred in parallel with improved insulin signalling in both tissues. The ob/ob-Erk1-/- mice were also partially protected against hepatic steatosis with a strong reduction in acetyl-CoA carboxylase level. These metabolic improvements were associated with reduced expression of mRNA encoding inflammatory cytokine and T lymphocyte markers in the adipose tissue. Conclusions/interpretation: Our results demonstrate that the targeting of ERK1 could partially protect obese mice against insulin resistance and liver steatosis by decreasing adipose tissue inflammation and by increasing muscle glucose uptake. Our results indicate that deregulation of the ERK1 pathway could be an important component in obesity-associated metabolic disorders. © Springer-Verlag 2010. Source

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