Institution
Paris Descartes University
Government•Paris, France•
About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Immune system. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.
Topics: Population, Immune system, Cancer, Transplantation, Pregnancy
Papers published on a yearly basis
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TL;DR: Cellular stress responses primarily serve to rectify stress-associated damage, but these responses are also coupled with the generation of various signals that are transmitted to the cellular microenvironments or even across tissues, which generally supports the maintenance of systemic homeostasis but can also result in pathology.
Abstract: Mammalian cells respond to stress by activating mechanisms that support cellular functions and hence maintain microenvironmental and organismal homeostasis. Intracellular responses to stress, their regulation and their pathophysiological implications have been extensively studied. However, little is known about the signals that emanate from stressed cells to enable a coordinated adaptive response across tissues, organs and the whole organism. Considerable evidence has now accumulated indicating that the intracellular mechanisms that are activated in response to different stresses - which include the DNA damage response, the unfolded protein response, mitochondrial stress signalling and autophagy - as well as the mechanisms ensuring the proliferative inactivation or elimination of terminally damaged cells - such as cell senescence and regulated cell death - are all coupled with the generation of signals that elicit microenvironmental and/or systemic responses. These signals, which involve changes in the surface of stressed cells and/or the secretion of soluble factors or microvesicles, generally support systemic homeostasis but can also contribute to maladaptation and disease.
283 citations
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TL;DR: It is shown that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation, thereby triggering an immune response and perpetuating intestinal inflammation.
Abstract: Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA–gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA–gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD.
283 citations
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Radboud University Nijmegen1, Katholieke Universiteit Leuven2, University of Lausanne3, Karolinska University Hospital4, Carlos III Health Institute5, Florey Institute of Neuroscience and Mental Health6, University of Milan7, Paris Descartes University8, University of Oslo9, University of Alabama at Birmingham10, University of Münster11, University of Innsbruck12, University Hospital of South Manchester NHS Foundation Trust13, Universidade Federal de Ciências da Saúde de Porto Alegre14, University College London15, Hacettepe University16, University of Wisconsin-Madison17, Federal University of Rio de Janeiro18
TL;DR: Azole-resistant A. fumigatus was more frequently found than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.
Abstract: To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.
282 citations
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TL;DR: In this article, the authors obtained blood samples from Cambodian patients infected with P falciparum and treated with dihydroartemisinin-piperaquine, and patients were followed up for 42 days during the years 2009-15.
Abstract: BACKGROUND:
Western Cambodia is the epicentre of Plasmodium falciparum multidrug resistance and is facing high rates of dihydroartemisinin-piperaquine treatment failures. Genetic tools to detect the multidrug-resistant parasites are needed. Artemisinin resistance can be tracked using the K13 molecular marker, but no marker exists for piperaquine resistance. We aimed to identify genetic markers of piperaquine resistance and study their association with dihydroartemisinin-piperaquine treatment failures.
METHODS:
We obtained blood samples from Cambodian patients infected with P falciparum and treated with dihydroartemisinin-piperaquine. Patients were followed up for 42 days during the years 2009-15. We established in-vitro and ex-vivo susceptibility profiles for a subset using piperaquine survival assays. We determined whole-genome sequences by Illumina paired-reads sequencing, copy number variations by qPCR, RNA concentrations by qRT-PCR, and protein concentrations by immunoblotting. Fisher's exact and non-parametric Wilcoxon rank-sum tests were used to identify significant differences in single-nucleotide polymorphisms or copy number variants, respectively, for differential distribution between piperaquine-resistant and piperaquine-sensitive parasite lines.
FINDINGS:
Whole-genome exon sequence analysis of 31 culture-adapted parasite lines associated amplification of the plasmepsin 2-plasmepsin 3 gene cluster with in-vitro piperaquine resistance. Ex-vivo piperaquine survival assay profiles of 134 isolates correlated with plasmepsin 2 gene copy number. In 725 patients treated with dihydroartemisinin-piperaquine, multicopy plasmepsin 2 in the sample collected before treatment was associated with an adjusted hazard ratio (aHR) for treatment failure of 20·4 (95% CI 9·1-45·5, p<0·0001). Multicopy plasmepsin 2 predicted dihydroartemisinin-piperaquine failures with 0·94 (95% CI 0·88-0·98) sensitivity and 0·77 (0·74-0·81) specificity. Analysis of samples collected across the country from 2002 to 2015 showed that the geographical and temporal increase of the proportion of multicopy plasmepsin 2 parasites was highly correlated with increasing dihydroartemisinin-piperaquine treatment failure rates (r=0·89 [95% CI 0·77-0·95], p<0·0001, Spearman's coefficient of rank correlation). Dihydroartemisinin-piperaquine efficacy at day 42 fell below 90% when the proportion of multicopy plasmepsin 2 parasites exceeded 22%.
INTERPRETATION:
Piperaquine resistance in Cambodia is strongly associated with amplification of plasmepsin 2-3, encoding haemoglobin-digesting proteases, regardless of the location. Multicopy plasmepsin 2 constitutes a surrogate molecular marker to track piperaquine resistance. A molecular toolkit combining plasmepsin 2 with K13 and mdr1 monitoring should provide timely information for antimalarial treatment and containment policies
282 citations
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TL;DR: The protection observed challenges the paradigm whereby circulating antiviral antibodies are required for protection against HIV-1 infection and may serve in designing a human vaccine against HIV -1-AIDS.
282 citations
Authors
Showing all 21023 results
Name | H-index | Papers | Citations |
---|---|---|---|
Guido Kroemer | 236 | 1404 | 246571 |
Cyrus Cooper | 204 | 1869 | 206782 |
Jean-Laurent Casanova | 144 | 842 | 76173 |
Alain Fischer | 143 | 770 | 81680 |
Maxime Dougados | 134 | 1054 | 69979 |
Carlos López-Otín | 126 | 494 | 83933 |
Giuseppe Viale | 123 | 740 | 72799 |
Thierry Poynard | 119 | 668 | 64548 |
Lorenzo Galluzzi | 118 | 477 | 71436 |
Shahrokh F. Shariat | 118 | 1637 | 58900 |
Richard E. Tremblay | 116 | 685 | 45844 |
Olivier Hermine | 111 | 1026 | 43779 |
Yehezkel Ben-Ari | 110 | 459 | 44293 |
Loïc Guillevin | 108 | 800 | 51085 |
Gérard Socié | 107 | 920 | 44186 |