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Novel assays to assess the prevalence and neutralizing potential of anti-IdeS antibodies in healthy humans
No full textInternational audienceBackground: The IgG-degrading enzyme IdeS (imlifidase) is a cysteine protease produced by Streptococcus pyogenes. It specifically hydrolyzes human IgG, cleaving the molecule to separate the F(ab’)2 fragment from the Fc region, thereby promoting IgG catabolism. The therapeutic form of IdeS (Idefirix®) is currently approved for use in patients undergoing kidney transplantation to eliminate donor-specific IgG, and in patients with Goodpasture syndrome to remove pathogenic anti-glomerular basement membrane antibodies. IgG antibodies directed against IdeS have been previously reported in both healthy individuals and kidney transplant recipients. However, the occurrence and potential clinical significance of anti-IdeS IgA antibodies and IdeS neutralizing antibodies have not been thoroughly investigated.Methods: In this study, we developed semi-quantitative enzyme-linked immunosorbent assays, synthesized a specific IdeS substrate, and validated a quantitative neutralization assay to detect and quantify anti-IdeS IgG, IgA, and IdeS neutralizing antibodies in healthy human plasma and serum samples.Results: We demonstrate the presence of anti-IdeS IgG capable of neutralizing IdeS enzymatic activity in therapeutic preparations of pooled normal human IgG (IVIg). Anti-IdeS IgG and IgA antibodies were detected in the plasma and serum of over 85% of 136 healthy individuals. However, clinically significant levels of IdeS-neutralizing activity were found in only ~1% of the individuals tested. IdeS-neutralizing activity was mediated exclusively by IgG, not IgA, and did not systematically correlate with levels of anti-IdeS IgG.Conclusions: Anti-IdeS IgG and IgA are highly prevalent in the normal population. This may relate to repeated infection by S. pyogenes. However, we found a low prevalence of clinically relevant levels of IdeS neutralizing antibodies. These findings highlight the need for a prospective clinical trial to assess IdeS-binding and IdeS-neutralizing antibody levels in kidney transplant recipients. Our novel functional IdeS neutralization assay offers a predictive tool to guide personalized medicine and determine patient eligibility for IdeS-based desensitization protocols
Bas les masques ! GAMM—Une Taxonomie des Mécanismes d'Attributs Manquants dans les Graphes
No full textInternational audienceExploring missing data in attributed graphs introduces unique challenges beyond those found in tabular datasets. In this work, we extend the taxonomy for missing data mechanisms to attributed graphs by proposing GAMM (Graph Attributes Missing Mechanisms), a framework that systematically links missingness probability to both node attributes and the underlying graph structure. Our taxonomy enriches the conventional definitions of masking mechanisms by introducing graph-specific dependencies. We empirically demonstrate that state-of-the-art imputation methods, while effective on traditional masks, significantly struggle when confronted with these more realistic graph-aware missingness scenarios
Em busca das estruturas fundamentais da vida humana: Entrevista com Bernard Lahire
No full textThis interview with Bernard Lahire addresses his theoretical framework on the fundamental structures of human societies, proposing an expansion of sociology to the 'social sciences of the living'. Identifying trans-historical regularities in social life, he analyses domination, hierarchy, cooperation and cultural transmission, articulating biological and social factors without determinism. He discusses epistemological implications, overcoming classical dichotomies, the limits of social change, and the ambivalent role of science
CCASL: Counterexamples to comparative analysis of scientific literature—Application to polymers
No full textInternational audienceThe exponential growth of scientific publications has made the exploration and comparative analysis of scientific literature increasingly complex. For instance, identifying pairs of publications that diverge on widely accepted concepts within a domain is extremely difficult, if not impossible, at a large scale. Our work aims to automatically detect such discrepancies using recent artificial intelligence techniques. Given a particular scientific domain, we propose to capture domain knowledge through the definition of arbitrary functions expressed as relaxed functional dependencies (RFDs), and then focus on the large-scale analysis of tables in the publications related to these RFDs. In this context, we propose a four-step method called Counterexamples to Comparative Analysis of Scientific Literature (CCASL), which consists of the following steps: (1) Modeling the domain knowledge with functions expressed as RFDs, (2) Acquiring a corpus of related publications, (3) Analyzing all tables in the PDF documents and producing a consolidated table, (4) Detecting counterexamples of the RFDs in the consolidated table and conducting a comparative analysis of the pairs of papers containing the detected counterexamples. We have applied CCASL to a subfield of polymer research by identifying an arbitrary function relating the storage modulus, the polymer structure, and the glass transition temperature. Based on this function, we implemented the four steps of CCASL for largescale bibliographic confrontation in polymer science, which enabled us to detect several counterexamples. After detailed analysis, these counterexamples were found to originate from two main sources: typographical errors and methodological inconsistencies. The latter led to an update of the initial arbitrary function, specifying that it is valid only for fully reacted mixtures
Contre-je : genre et énonciations minoritaires en littérature
No full textDire je : un acte simple et banal pour les écrivain·es ? Depuis la poésie lyrique dans l’Antiquité jusqu’à l’egotrip dans le rap contemporain en passant par le récit de témoignage ou l’autofiction, la première personne s’affirme dans toute la littérature, où elle a acquis ses lettres de noblesse de longue date. En cultivant l’idée de génie créateur, la critique a participé à sacraliser le pouvoir que l’on accorde à ce pronom : partir « des mouvements de sa vie intime » afin d’illustrer « les sentiments vrais de la nature humaine » serait, comme l’affirme Friedrich Hegel, le propre du poète accompli. Cette fable, héritière des Lumières, répond à l’idée que l’homme de lettres puisse, par la communauté de cœur qu’il forme avec ses semblables, s’exprimer au nom du genre humain. Mais près d’un demi-siècle d’études de genre et postcoloniales a dénoncé ces prétentions du moi à tendre à l’universel : « Inclure, parler pour, intégrer toute position marginale ou exclue d’un discours donné, c’est affirmer que ce discours particulier ne rencontre nulle part de limites, qu’il est capable de domestiquer tous les signes de la différence et qu’il le fera », déclare Judith Butler. S’énoncer contre je, ou contre un autre je que celui qui parlerait non pas pour les autres mais pour la majorité : tel est le projet des auteur·trices, chanteur·euses ou performeur·euses présenté·es dans ce n°42 de la revue Sextant. En empruntant leurs outils à l’analyse littéraire, à la linguistique du discours et aux études féministes et subalternes, les contributions se proposent d’explorer comment ces artistes interrogent les conditions d’énonciation d’un je minoritaire qui, depuis les marges de genre, de classe et de race d’où il·elles s’expriment, leur permet de s’affirmer sujets de leur existence
Skin thermal dynamics and hypothalamic thermosensitivity dissociate REM sleep and cataplexy in narcolepsy
No full textInternational audienceNarcolepsy is caused by hypothalamic hypocretin/orexin loss and characterized by cataplexy, a unique brain state triggered by emotion. Cataplexy shares features with rapid eye movement (REM) sleep, including muscle atonia and wake-like electroencephalographic activity. REM sleep is characterized by thermoregulatory suspension and, when the need for thermoregulatory responses is reduced as during ambient thermoneutral warming, melanin-concentrating hormone (MCH) neurons play a critical role in favoring REM sleep expression. However, it remains unknown whether REM sleep and cataplexy share thermomodulatory mechanisms. Here, we demonstrate that reduced skin temperatures and a widening of the distal-to-proximal skin temperature gradient precede cataplexy in both patients with narcolepsy and hypocretin-knockout (Hcrt-KO) narcoleptic mice. To test a causal role for skin temperature in cataplexy modulation, thermoneutral manipulation of skin temperature in Hcrt-KO mice revealed that skin cooling promoted cataplexy, whereas skin warming increased REM sleep. Fiber photometry showed that, at constant ambient temperatures (23°C), cataplexy and REM sleep were associated with increased MCH neuron activity. Skin cooling, however, reduced the MCH calcium imaging dynamics associated with cataplexy. Moreover, MCH optogenetic or chemogenetic manipulation recapitulated these effects, with MCH silencing favoring cataplexy and MCH activation driving REM sleep. Last, using the skin warming condition, we combined cFos staining and retrograde labeling and identified activated monosynaptic inputs from known thermoregulatory hubs such as the median preoptic nucleus, dorsomedial hypothalamus, and the parabrachial nucleus to MCH neurons. These findings unveil an unexplored role for skin thermal dynamics and hypothalamic MCH thermosensitivity in dissociating cataplexy and REM sleep
Écologiser les pratiques pédagogiques en école d’ingénieurs : vers une écologisation radicale ?
No full textInternational audienceDans ce chapitre, nous proposons quelques repères théoriques permettant de soutenir le développement de l’écologisation dans les écoles d’ingénieurs. Nous comprenons cette écologisation « radicale » comme une démarche de rupture avec le positivisme naturaliste qui fonde les sciences et techniques modernes. Cette critique nous conduit à mettre en valeur la pédagogie de l’enquête, en ce qu’elle permet de faire ressortir la multiplicité des acteurs ainsi que celle de leurs pratiques, usages et interdépendances. À partir de notre expérience d’enseignants en humanités dans le module « Enjeux de la transition écologique de l’INSA Lyon », nous montrons l’intérêt de cette écologisation radicale et ses difficultés à exister par rapport à l’approche dominante des enjeux écologiques héritée des modernes. Cette réflexion sur nos pratiques pédagogiques nous pousse enfin à faire émerger plusieurs axes de questionnement vis-à-vis du potentiel transformateur de l’écologisation par l'enquête
Interictal epileptiform discharges are involved in momentary lapses of attention in children with epilepsy
No full textInternational audienceAbstract Objective Attention impairments are common in children with epilepsy and widely impact their quality of life. Interictal epileptiform discharges (IEDs) may induce subtle dysfunctions of various cognitive processes, but data regarding the impact of IEDs on sustained attention remain limited. The objective of the present study was to evaluate the impact of IEDs on continuous undivided attention in children with epilepsy, controlling for the number of treatments, type of epilepsy, frequency of seizures in the past year, age at onset, and comorbid attention disorder. Methods Using a computerized sustained attention test synchronized with the electroencephalogram in 61 children with diverse epilepsy syndromes, reaction time (RT), errors, attention stability over time, and the event‐related potential (ERP) in Pz (related to attentional engagement) were collected. The cumulative impact of IEDs was evaluated using multivariate models controlling for epilepsy‐related factors. The transient impact of IEDs was assessed by comparing responses in trials with and without IEDs. Results IEDs were associated with attention fluctuations independently from other epilepsy‐related factors. In terms of cumulative impact, a higher IED rate was associated with a poorer sustained attention performance over the entire task. In terms of transient impact, trials disrupted by IEDs were characterized by longer RT and a lower amplitude of the ERP extending over a long time window that included attentional processing (P300). Significance These results suggest that IEDs may negatively impact sustained attention, independently of other epilepsy‐related features. These findings support the hypothesis that IEDs could contribute to subtle attentional deficits and serve as potential biomarkers of abnormal brain function