92 research outputs found

    Translating and Mapping the Many Voices in the Work of Niki Marangou

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    This article examines the work of Niki Marangou, a Greek-language author from Cyprus. Her many stories and anecdotes, whether in poetry or prose, bring in a perspective of cultural geography as they open up places to a spatial imaginary on the crossroad of cartography and testimony. Conceptual tools developed in the field of contemporary Translation Studies may be used to articulate fresh and interesting views on the historical, cultural, political, and ideological contexts of her work, and show the cross-cultural literary dynamic in which her writing emerges

    0232 : Small, medium but not large arteries are involved in digital ulcers associated with systemic sclerosis

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    BackgroundDigital ulcers (DU) are a burden in systemic sclerosis (SSc). Microangiopathy is a cardinal feature of SSc that plays a critical role in the development of DU. However, whether injury of medium or large vessels also contributes to DU in SSc is unknown.MethodsTo measure concomitantly in SSc patients with and without active DU i) the Augmentation Index of the reflected wave (Aix_75) by radial applanation tonometry, an index of small and medium arterial function, II) the aortic pulse wave velocity (PWV), a marker of large vessel injury (aortic stiffness).Results63 consecutive SSc patients were included (49 females, aged 57±12 years, disease duration 9.7±7.1 years), including 10 (15.9%) with active DU.Patients with active DU versus those without had increased Aix_75 (35% [28-38] versus 28% [20-34], p=0.041) whereas no difference existed in PWV (7,0m/s [6.7-10.1] versus 7,6m/s [6.8-8.7], p=0.887), in systolic, diastolic, as well as aortic pulse pressure (p=0.126, 0.592, and 0.161 respectively).By multivariate analysis, DU remained independently associated with Aix_75 (p=0.020).Using Aix_75 as a longitudinal variable, and when compared to patients in the low tertile, patients having Aix_75 in the highest tertile had ten-fold more DU (OR=10.23; 95% CI 1.12 to 93.34, p=0.039).ConclusionThe presence of DU is independently associated with Aix_75 whereas there is no relation with PWV. These data suggest that small and medium arteries are involved in the occurrence of DU whether large vessel stiffness does not contribute. Whether Aix_75 is predictive of further DU remained to be studied

    Body mass index influences the response to infliximab in ankylosing spondylitis

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    INTRODUCTION: The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients. METHODS: In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID) were dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression. RESULTS: Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50 (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95% CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)), criteria. According to the three WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and 16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50 (63.2%, 51.5%, and 34.6%; P = 0.06). CONCLUSIONS: This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics, and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response

    JAK inhibition in Aicardi-GoutiĂšres syndrome: a monocentric multidisciplinary real-world approach study

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    International audienceThe paradigm type I interferonopathy Aicardi-GoutiĂšres syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of type I interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements in cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level of the neurological system has been less conclusive. Here, we report our real-word approach study of JAK1/2 inhibition in 11 patients with AGS, providing extensive assessments of clinical and radiological status; interferon signaling, including in cerebrospinal fluid (CSF); and drug concentrations in blood and CSF. Over a median follow-up of 17 months, we observed a clear benefit of JAK1/2 inhibition on certain systemic features of AGS, and reproduced results reported using the AGS neurologic severity scale. In contrast, there was no change in other scales assessing neurological status; using the caregiver scale, only patient comfort, but no other domain of everyday-life care, was improved. Serious bacterial infections occurred in 4 out of the 11 patients. Overall, our data lead us to conclude that other approaches to treatment are urgently required for the neurologic features of AGS. We suggest that earlier diagnosis and adequate central nervous system penetration likely remain the major factors determining the efficacy of therapy in preventing irreversible brain damage, implying the importance of early and rapid genetic testing and the consideration of intrathecal drug delivery

    The Evolution of Primate Short-Term Memory.

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    Short-term memory is implicated in a range of cognitive abilities and is critical for understanding primate cognitive evolution. To investigate the effects of phylogeny, ecology and sociality on short-term memory, we tested the largest and most diverse primate sample to date (421 non-human primates across 41 species) in an experimental delayed-response task. Our results confirm previous findings that longer delays decrease memory performance across species and taxa. Our analyses demonstrate a considerable contribution of phylogeny over ecological and social factors on the distribution of short-term memory performance in primates; closely related species had more similar short-term memory abilities. Overall, individuals in the branch of Hominoidea performed better compared to Cercopithecoidea, who in turn performed above Platyrrhini and Strepsirrhini. Interdependencies between phylogeny and socioecology of a given species presented an obstacle to disentangling the effects of each of these factors on the evolution of short-term memory capacity. However, this study offers an important step forward in understanding the interspecies and individual variation in short-term memory ability by providing the first phylogenetic reconstruction of this trait’s evolutionary history. The dataset constitutes a unique resource for studying the evolution of primate cognition and the role of short-term memory in other cognitive abilities.info:eu-repo/semantics/publishedVersio

    Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

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    Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

    Type I interferon-mediated autoinflammation due to DNase II deficiency

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    Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity. We record increased interferon alpha protein levels using digital ELISA, enhanced interferon signaling by RNA-Seq analysis and constitutive upregulation of phosphorylated STAT1 and STAT3 in patient lymphocytes and monocytes. A hematological disease transcriptomic signature and increased numbers of erythroblasts are recorded in patient peripheral blood, suggesting that interferon might have a particular effect on hematopoiesis. These data define a type I interferonopathy due to DNase II deficiency in humans

    The Evolution of Primate Short-Term Memory

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    Short-term memory is implicated in a range of cognitive abilities and is critical for understanding primate cognitive evolution. To investigate the effects of phylogeny, ecology and sociality on short-term memory, we tested the largest and most diverse primate sample to date (421 non-human primates across 41 species) in an experimental delayed-response task. Our results confirm previous findings that longer delays decrease memory performance across species and taxa. Our analyses demonstrate a considerable contribution of phylogeny over ecological and social factors on the distribution of short-term memory performance in primates; closely related species had more similar short-term memory abilities. Overall, individuals in the branch of Hominoidea performed better compared to Cercopithecoidea, who in turn performed above Platyrrhini and Strepsirrhini. Interdependencies between phylogeny and socioecology of a given species presented an obstacle to disentangling the effects of each of these factors on the evolution of short-term memory capacity. However, this study offers an important step forward in understanding the interspecies and individual variation in short-term memory ability by providing the first phylogenetic reconstruction of this trait’s evolutionary history. The dataset constitutes a unique resource for studying the evolution of primate cognition and the role of short-term memory in other cognitive abilities

    Research and characterization of vaccine antigens against Campylobacter by reverse vaccinology

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    Les campylobactĂ©rioses sont les infections intestinales bactĂ©riennes d’origine alimentaire les plus frĂ©quemment rapportĂ©es au sein de l’Union EuropĂ©enne et sont principalement associĂ©es Ă  la consommation de viande de volailles. Une diminution de la colonisation intestinale des volailles par Campylobacter de 2 Ă  3 log10 UCF/g permettrait de rĂ©duire l’incidence des cas humains de 76 Ă  100 %. La vaccination aviaire constitue un moyen de lutte potentiel mais, malgrĂ© de nombreuses Ă©tudes, aucun vaccin commercial n’est actuellement disponible. L’objectif de ce projet a Ă©tĂ© d’identifier de nouveaux antigĂšnes vaccinaux contre Campylobacter en appliquant la stratĂ©gie de la vaccinologie inverse et d’évaluer leurs pouvoirs immunogĂšne et protecteur contre la colonisation intestinale des volailles. Sur la base de leur localisation subcellulaire, leur antigĂ©nicitĂ©, leur densitĂ© en Ă©pitopes B et leur homologie de sĂ©quence avec l’ensemble des souches de C. jejuni et C. coli, quatorze antigĂšnes ont Ă©tĂ© sĂ©lectionnĂ©s. Six d’entre eux ont Ă©tĂ© produits et testĂ©s in vivo en appliquant un protocole vaccinal optimisĂ©. Quatre antigĂšnes ont montrĂ© des diminutions significatives de la charge intestinale des oiseaux de 2 Ă  4,2 log10 UFC/g associĂ©es Ă  l’induction de rĂ©ponses humorales spĂ©cifiques. L’immunogĂ©nicitĂ© de ces candidats vaccins et l’efficacitĂ© protectrice de deux antigĂšnes ont Ă©tĂ© observĂ©es Ă  nouveau. Ces premiers rĂ©sultats montrent l’intĂ©rĂȘt et la fiabilitĂ© de la vaccinologie inverse. L’évaluation du potentiel vaccinal de ces nouveaux antigĂšnes doit ĂȘtre poursuivie et approfondie lors de futures expĂ©rimentations.Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis reported in the European Union and is mainly associated to consumption of poultry meat. Reducing the intestinal colonization of broilers by Campylobacter from 2 to 3 log10 CFU/g could decrease human cases incidence by 76 to 100%. Vaccination of poultry could be a potential strategy but despite many studies, no efficient vaccine is available yet. The aim of this project was to identify new vaccine antigens against Campylobacter using the reverse vaccinology strategy and to assess their immune and protective powers against the avian intestinal colonization. Based on their sub-cellular localization, immunogenicity, B-epitopes density and their sequence conservation among C. jejuni and C. coli strains, fourteen antigens were selected. Six out of them were produced and in vivo tested according to an optimized avian vaccine protocol. Four antigens showed intestinal load decreases from 2 to 4.2 log10 CFU/g correlated with the induction of specific humoral responses. Vaccine candidates’ immunogenicity and the protective efficiency of two antigens were observed again. These first results highlight the interest and reliability of the reverse vaccinology. The assessment of these new antigens vaccine potential needs to be continued and deepened in next experiments
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