193 research outputs found
Du passé faisons table d’hôte : Le mode d’entretien des zombi dans l’imaginaire haïtien et ses filiations historiques
Que la figure haïtienne du zombi soit assimilée à celle, historique, de l’esclave des temps coloniaux, c’est là un trait commun des études anthropologiques relatives à l’imaginaire dont elle est l’objet en Haïti. Asservis, aliénés, instrumentalisés, contraints à différents labeurs, le zombi et son homologue colonial se confondent en effet, sans pour autant qu’ait été jusque-là entrepris un repérage systématique des traits qui, de manière concrète et précise, permettraient de fonder cette coïncidence et de l’ancrer dans les représentations locales. S’attachant à la question particulière des modes d’entretien et d’exploitation respectifs des zombi et de leurs ascendants réels, cet article se propose donc d’examiner les éléments qui, dans les domaines du logement, de l’onomastique, du régime alimentaire, du mode de gestion funéraire de ces masses serviles, entreraient en résonance mutuelle. Cette confrontation de l’imaginaire et de l’histoire révèle alors la portée mémorielle de la figure du zombi, cette dernière rendant présent le passé collectif, évoquant en son langage l’épisode esclavagiste, mettant au présent le rapport fondateur de servitude suivant une forme de mémoire collective incarnée, incorporée, infraconsciente, distincte de l’habituelle reconstruction mémorielle de l’histoire basée sur des contenus de conscience.As the Haitian figure of the zombie has historically been compared to that of the slave in the colonial era, it is a feature shared with anthropological studies about its role in the Haitian imagination. Enslaved, alienated, exploited, forced into various tasks: in effect the zombie and his colonial counterpart merge, without as yet there having been engagement in a systematic locating of those traits which, in a concrete and precise manner, permit the justification of this coincidence and ground it in its local representations. Attaching to this the particular question of the modes of respectively maintaining and exploiting the zombie and its real ancestry, this article therefore proposes to examine the elements which, in the realms of housing, naming, the regimenting of foodways, and the manner of funerary management for this servile mass, worked in concert. This comparison of the imagined with the historical then shows the memorialising capacity of the figure of the zombie, the latter restoring for the present a collective past, evoking in its language the era of the slave society, placing in the present the founding narrative of servitude according to a pattern of collective memory incarnated, embodied, subconscious, distinguished by the habitual reconstruction of memory of a history based on the contents of conscience
Intramolecular Cyclization of N-phenyl N'(2-chloroethyl)ureas leads to Active N-phenyl-4,5-dihydrooxazol-2-amines Alkylating β-Tubulin Glu198 and Prohibitin Asp40
International audienceThe cyclization of anticancer drugs into active intermediates has been reported mainly for DNA alkylating molecules including nitrosoureas. We previously defined the original cytotoxic mechanism of anticancerous phenyl '(2-chloroethyl)ureas (CEUs) that involves their reactivity towards cellular proteins and not against DNA; two CEUs subsets have been shown to alkylate β-tubulin and prohibitin leading to inhibition of cell proliferation by G/M or G/S cell cycle arrest. In this study, we demonstrated that cyclic derivatives of CEUs, -phenyl-4,5-dihydrooxazol-2-amines (Oxas) are two to threefold more active than CEUs and share the same cytotoxic properties in B16F0 melanoma cells. Moreover, the CEU original covalent binding by an ester linkage on β-tubulin Glu198 and prohibitin Asp40 was maintained with Oxas. Surprisingly, we observed that Oxas were spontaneously formed from CEUs in the cell culture medium and were also detected within the cells. Our results suggest that the intramolecular cyclization of CEUs leads to active Oxas that should then be considered as the key intermediates for protein alkylation. These results could be useful for the design of new prodrugs for cancer chemotherapy
Immunophenotyping Reveals the Diversity of Human Dental Pulp Mesenchymal Stromal Cells In vivo and Their Evolution upon In vitro Amplification
International audienceMesenchymal stromal/stem cells (MSCs) from human dental pulp (DP) can be expanded in vitro for cell-based and regenerative dentistry therapeutic purposes. However, their heterogeneity may be a hurdle to the achievement of reproducible and predictable therapeutic outcomes. To get a better knowledge about this heterogeneity, we designed a flow cytometric strategy to analyze the phenotype of DP cells in vivo and upon in vitro expansion with stem cell markers. We focused on the CD31 − cell population to exclude endothelial and leukocytic cells. Results showed that the in vivo CD31 − DP cell population contained 1.4% of CD56 + , 1.5% of CD146 + , 2.4% of CD271 + and 6.3% of MSCA-1 + cells but very few Stro-1 + cells (≤1%). CD56 + , CD146 + , CD271 + , and MSCA-1 + cell subpopulations expressed various levels of these markers. CD146 + MSCA-1 + , CD271 + MSCA-1 + , and CD146 + CD271 + cells were the most abundant DP-MSC populations. Analysis of DP-MSCs expanded in vitro with a medicinal manufacturing approach showed that CD146 was expressed by about 50% of CD56 + , CD271 + , MSCA-1 + , and Stro-1 + cells, and MSCA-1 by 15-30% of CD56 + , CD146 + , CD271 + , and Stro-1 + cells. These ratios remained stable with passages. CD271 and Stro-1 were expressed by <1% of the expanded cell populations. Interestingly, the percentage of CD56 + cells strongly increased from P1 (25%) to P4 (80%) both in all sub-populations studied. CD146 + CD56 + , MSCA-1 + CD56 + , and CD146 + MSCA-1 + cells were the most abundant DP-MSCs at the end of P4. These results established that DP-MSCs constitute a heterogeneous mixture of cells in pulp tissue in vivo and in culture, and that their phenotype is modified upon in vitro expansion. Further studies are needed to determine whether co-expression of specific MSC markers confers DP cells specific properties that could be used for the regeneration of human tissues, including the dental pulp, with standardized cell-based medicinal products
Sequence Homology at the Breakpoint and Clinical Phenotype of Mitochondrial DNA Deletion Syndromes
Mitochondrial DNA (mtDNA) deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM), progressive external ophthalmoplegia (PEO), and Kearns-Sayre syndrome (KSS), to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH) followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients' age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (<6 years old) showed a diffused pattern of deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41). Only 15% (3/20) of the young patients (<6 years old) carry the 5 kb common deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17) exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier onset and more severe disease with multisystem involvement
Race, colonial history and national identity: Resident Evil 5 as a Japanese game
Resident Evil 5 is a zombie game made by Capcom featuring a White American protagonist and set in Africa. This paper argues that approaching this as a Japanese game reveals aspects of a Japanese racial and colonial social imaginary that are missed if this context of production is ignored. In terms of race, the game presents hybrid racial subjectivities that can be related to Japanese perspectives of Blackness and Whiteness where these terms are two poles of difference and identity through which an essentialised Japanese identity is constructed in what Iwabuchi calls “strategic hybridism” (Iwabuchi, 2002). In terms of colonialism, the game echoes structures of Japanese colonialism through which Japanese colonialism is obliquely memorialised and a “normal” Japanese global subjectivity can be performed
N-(4-iodophenyl)-N′-(2-chloroethyl)urea as a microtubule disrupter: in vitro and in vivo profiling of antitumoral activity on CT-26 murine colon carcinoma cell line cultured and grafted to mice
The antitumoral profile of the microtubule disrupter N-(4-iodophenyl)-N′-(2-chloroethyl)urea (ICEU) was characterised in vitro and in vivo using the CT-26 colon carcinoma cell line, on the basis of the drug uptake by the cells, the modifications of cell cycle, and β-tubulin and lipid membrane profiles. N-(4-iodophenyl)-N′-(2-chloroethyl)urea exhibited a rapid and dose-dependent uptake by CT-26 cells suggesting its passive diffusion through the membranes. Intraperitoneally injected ICEU biodistributed into the grafted CT-26 tumour, resulting thus in a significant tumour growth inhibition (TGI). N-(4-iodophenyl)-N′-(2-chloroethyl)urea was also observed to accumulate within colon tissue. Tumour growth inhibition was associated with a slight increase in the number of G2 tetraploid tumour cells in vivo, whereas G2 blockage was more obvious in vitro. The phenotype of β-tubulin alkylation that was clearly demonstrated in vitro was undetectable in vivo. Nuclear magnetic resonance analysis showed that cells blocked in G2 phase underwent apoptosis, as confirmed by an increase in the methylene group resonance of mobile lipids, parallel to sub-G1 accumulation of the cells. In vivo, a decrease of the signals of both the phospholipid precursors and the products of membrane degradation occurred concomitantly with TGI. This multi-analysis established, at least partly, the ICEU activity profile, in vitro and in vivo, providing additional data in favour of ICEU as a tubulin-interacting drug accumulating within the intestinal tract. This may provide a starting point for researches for future efficacious tubulin-interacting drugs for the treatment of colorectal cancers
Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.
RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Optimization of umbilical cord processing techniques and multiparametric immunophenotyping of umbilical cord Wharton's jelly mesenchymal stem cells for cell therapy applications
Avec environ 136,000,000 de naissances annuelles dans le monde, les cellules souches isolées à partir des tissus néonataux tels que le cordon ombilical présentent de nombreux avantages en terme d'accessibilité et de disponibilité. Le cordon ombilical contient un tissus de soutient présent en grande quantité et entourant les vaisseaux sanguin, la gelée de Wharton, qui a été démontrée dans plusieurs études comme très riche en cellules souches mésenchymateuses. Ces cellules souches multipotentes isolées à partir du cordon ombilical ont montré des capacité d'auto renouvellement et de différentiation en une variété de type cellulaire ayant un potentiel pour des applications en therapie cellulaire, pas uniquement en tant que cellules différenciés mais également grâce à d'importantes capacités immunomodulatrices et régulatrices de l'inflammation. Ce travail présente le développement de méthodes et d'outils permettant un traitement optimisé des échantillons de cordon ombilical et l'isolation d'explants de tissus de gelée de Wharton standardisés. Nous avons également étudié plusieurs méthodes améliorant l'isolation de MSC à partir de ces explants de tissus et développé un protocole de culture in‐vitro ne nécessitant pas l'ajout de sérum de veaux foetal ou la présence d'autres produits animaux dérivés dans le but de faciliter de futures applications cliniques. Nous avons développé un protocole de cytométrie en flux multiparamétrique dédié à l'analyse de l'expression de 27 antigènes et marqueur de surface présent sur les MSC de la gelée de Wharton et à l'étude des effets de diverses condition et événement durant la culture in‐vitro sur leur phénotype de surface. Le même protocole multiparamétrique a également été utilisé afin de comparer l'expression d'antigènes de surface des MSC isolés à partir de la gelée de Wharton et de la moelle osseuse, ou à des fibroblastes. Enfin, un protocole de différenciation ostéogénique a été appliqué avec succès aux MSC issues de la gelée de Wharton agrégées sur des granules d'hydroxyapatite fournissant ainsi un matériel autologue viable pour la réparation de manque osseux et spécialement développé pour la réparation de fente labio‐palatinesWith around 136,000,000 births per year worldwide stem cells isolated from neonatal tissues such as the umbilical cord have many advantages in term of access and availability. The umbilical cord contains a connective tissue present in large quantities surrounding the blood vessels, the Wharton’s jelly, demonstrated as a very rich source of Mesenchymal Stem Cells (MSCs). Those multipotent stem cells isolated from the umbilical cord have shown self‐renewal and differentiation capability into a range of cells inherent potential for cell therapy applications not only as differentiated cells but also thanks to potent capabilities for immunomodulation and regulation of inflammation. In this work we designed process and tools allowing efficient use of umbilical cord samples and the isolation of standardized Wharton's Jelly tissue explants. We studied techniques improving MSC isolation from tissue explants and developed an in‐vitro culture protocol, free of Foetal Bovine Serum (FBS) and other animal sourced products and thus more likely to be used in clinical settings. We developed a multiparametric flow cytometry protocol dedicated to phenotyping the surface expression of 27 different antigens present on Wharton's Jelly MSCs and to study the effect of several in‐vitro culture conditions and events on their surface phenotype. The multiparametric protocol was used to compare surface expression of MSCs isolated from Wharton's jelly, bone marrow and skin harvested fibroblasts. Finally, clinical development of human WJ‐MSC in a bone tissue differentiation protocol was evaluated for cleft palate repair, demonstrating the useful application of this tissue sourc
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