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L’œuvre collective de Dulac est ambitieuse théoriquement car elle propose un syncrétisme entre divers points de vue sur le social : réalisme et constructivisme, déterminismes des structures sociales et liberté des choix individuels. Elle est ici mise en miroir des positions de Lahire sur les structures fondamentales des sociétés et de Boullier sur les propagations. La discussion porte sur quatre enjeux importants de la scientificité des sciences sociales : la prise en compte des équipements de l’activité scientifique et des Science and Technology Studies et notamment l’absence des méthodes numériques ; la question du réductionnisme et le souci du Tout ; la place de l’action et la distribution d’agentivité ; le « modèle bilantiel » du social. Toutes ces questions sont parfois clairement tranchées, parfois plus contradictoires ou ambiguës comme il se doit dans un travail collectif. Elles ne prennent en compte ni l’économie, ni la psychologie, trop individualistes selon Dulac, ni la biologie, hors du champ du social. Oser traiter les questions clés du statut théorique du « social » constitue une œuvre salutaire et exigeante.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major health concerns due to their increasing incidence and high mortality. They are interconnected syndromes; AKI without recovery evolves into acute kidney disease (AKD), which can indicate an AKI-to-CKD transition. Both AKI and CKD are associated with a risk of long-term cardiovascular complications, but whether vascular and cardiac dysfunctions can occur as early as the AKD period has not been studied extensively. In a mouse model of kidney injury (KI) with non-recovery, we performed vasoreactivity and echocardiography analyses on days 15 (D15) and 45 (D45) after KI. We determined the concentrations of two major gut-derived protein-bound uremic toxins known to induce cardiovascular toxicity—indoxyl sulfate (IS) and para-cresyl sulfate (PCS)—and the levels of inflammation and contraction markers on D7, D15, and D45. Mice with KI showed acute tubular and interstitial kidney lesions on D7 and D15 and chronic glomerulosclerosis on D45. They showed significant impairment of aorta relaxation and systolic-diastolic heart function, both on D15 and D45. Such dysfunction was associated with downregulation of the expression of two contractile proteins, αSMA and SERCA2a, with a more pronounced effect on D15 than on D45. KI was also followed by a rapid increase in IS and PCS serum concentrations and the expression induction of pro-inflammatory cytokines and endothelial adhesion molecules in serum and cardiovascular tissues. Therefore, these results highlight that AKD leads to early cardiac and vascular dysfunctions. How these dysfunctions could be managed to prevent cardiovascular events deserves further study.

Background/Objectives: Delays in bone healing and complications of remodeling constitute a major medical problem—particularly in older adults and patients with comorbidities. Current therapeutic approaches are based on strategies that promote bone regeneration. We recently identified a disaccharide compound (DP2) that enhances in vitro mineralization in human osteoblast cells via the early activation of Runx2 and the induction of osteoblast differentiation. Methods: First, a calcium quantification assay was performed to assess mineralization in MC3T3-E1 cells. Next, microcomputed tomography and histological analyses were used to examine in vivo bone repair in a rat 5 mm cranial defect model following the implantation of DP2 coupled to a micro/macroporous biphasic CaP ceramic (MBCP+) or collagen scaffold. Results: Here, we demonstrated that DP2 induced osteogenic differentiation and significantly elevated calcium matrix deposition in the murine preosteoblast cell line MC3T3-E1. We found that treatment with DP2 coupled to MBCP+ repaired the calvarial defect on post-implantation day 91. It significantly increased bone mineral density starting on day 29 post-treatment. In addition, DP2 did not induce ectopic bone formation. Conclusions: Taken as a whole, these results show that DP2 is a promising candidate treatment for delayed bone healing.

Les inventaires et les listes sont un outil de gouvernement extrêmement répandu, mais dont les enjeux et les processus d’élaboration sont globalement méconnus. Ces artéfacts en apparence neutres et apolitiques, souvent décrits comme des « choses ennuyeuses », constituent en réalité des entrées particulièrement riches pour analyser les rapports de force dans la mise en œuvre de politiques sanitaires et environnementales. Nous nous intéressons ici à deux systèmes de classement : la liste des « substances soumises à autorisation » créée dans le cadre du règlement européen REACH, qui regroupe des substances toxiques destinées à être retirées du marché, et la catégorisation des antibiotiques vétérinaires de l’Agence européenne des médicaments, qui vise à préserver des molécules indispensables en médecine humaine. Des dispositions dérogatoires, des non-dits et des angles morts permettent à ces listes d’afficher un objectif de changement tout en ménageant les activités des industries et des professionnels de ces secteurs. Ce faisant, elles font preuve d’une certaine souplesse : elles soulignent l’urgence d’agir en régulant certains usages problématiques mais évitent de prononcer des interdictions fermes.

Toxicoepigenetics examines the health effects of environmental exposure associated with, or mediated by, changes in the epigenome. Despite high expectations, toxicoepigenomic data and methods have yet to become significantly utilized in chemical risk assessment. This article draws on a social science framework to highlight hitherto overlooked structural barriers to the incorporation of toxicoepigenetics in risk assessment and to propose ways forward. The present barriers stem not only from the lack of maturity of the field but also from differences in constraints and standards between the data produced by toxicoepigenetics and the regulatory science data that risk assessment processes require. Criteria and strategies that frame the validation of knowledge used for regulatory purposes limit the application of basic research in toxicoepigenetics toward risk assessment. First, the need in regulatory toxicology for standardized methods that form a consensus between regulatory agencies, basic research, and the industry conflicts with the wealth of heterogeneous data in toxicoepigenetics. Second, molecular epigenetic data do not readily translate into typical toxicological endpoints. Third, toxicoepigenetics investigates new forms of toxicity, in particular low-dose and long-term effects, that do not align well with the traditional framework of regulatory toxicology. We propose that increasing the usefulness of epigenetic data for risk assessment will require deliberate efforts on the part of the toxicoepigenetics community in 4 areas: fostering the understanding of epigenetics among risk assessors, developing knowledge infrastructure to demonstrate applicability, facilitating the normalization and exchange of data, and opening the field to other stakeholders.

While “cooperation” has been widely understood as a notion that allows us to better understand the dynamics of scientific research within citizen science practices in the field of social sciences and humanities (SSH), the concept of cooperation has not been precisely defined in the citizen science literature, nor measured quantitatively for digital platforms. This article adopts a conceptual approach to define cooperation and its key features, based on a systematic literature review. This approach allowed us to design 21 features of cooperation and build indicators that enable us to measure these features between citizen scientists. These 21 features of cooperation allow us to account for the plurality of citizen scientists’ meanings and practices in SSH. The indicators, which we refer to as “cooperation analytics,” can be deployed in a digital platform to provide direct and constant feedback to the actors themselves while their project is still under development. These analytics can serve as a tool for reflexivity, that is, to reflect on the assumptions that we make when producing knowledge, where cooperation is considered as a learning process under continuous revision and not as a criterion for conformity. Ultimately, cooperation analytics contribute to establishing new conventions for an enhanced citizen science, and to providing accountability and robustness in knowledge production and policymaking.

In 2019, the Swiss canton of Vaud launched a new digital education format for all levels, from kindergarten to high school, that closely combines IT and social sciences. In this experience report, we present the model that inspired it, the conceptual references to which it is linked, many examples of its implementation and the conditions under which it was carried out. The model is pluralistic in that it combines several pedagogical aims: understanding algorithms as a principle of modularity in problem processing, understanding the historical and contemporary socio-technical environments in which they are deployed, engaging in delegation decisions to machines at various levels, engaging in ethical self-regulation of these choices. Within this framework, a variant of the model focusing on ecological issues is presented.

Bone fracture healing is a complex biological process involving four phases coordinated over time: hematoma formation, granulation tissue formation, bony callus formation, and bone remodelling. Bone fractures represent a significant health problem, particularly among the elderly population and patients with comorbidities. Therapeutic strategies proposed to treat such fractures include the use of autografts, allografts, and tissue engineering strategies. It has been shown that bone morphogenetic protein 2 (BMP-2) has a therapeutic potential to enhance fracture healing. Despite the clinical efficacy of BMP-2 in osteoinduction and bone repair, adverse side effects and complications have been reported. Therefore, in this in vitro study, we propose the use of a disaccharide compound (DP2) to improve the mineralisation process. We first evaluated the effect of DP2 on primary human osteoblasts (HOb), and then investigated the mechanisms involved. Our findings showed that (i) DP2 improved osteoblast differentiation by inducing alkaline phosphatase activity, osteopontin, and osteocalcin expression; (ii) DP2 induced earlier in vitro mineralisation in HOb cells compared to BMP-2 mainly by earlier activation of Runx2; and (iii) DP2 is internalized in HOb cells and activates the protein kinase C signalling pathway. Consequently, DP2 is a potential therapeutical candidate molecule for bone fracture repair.

Understanding diagenetic reactions in accreted sediments is critical for establishing the balance of fluid sources and sinks in accretionary prisms, which is in turn important for assessing the fluid pressure field and the ability for faults to host seismic slip. For this reason, we studied diagenetic reactions in deformation bands (shear zones and veins) within deep mud sediments from the Nankai accretionary prism (SW Japan) drilled at site C0001 during IODP Expedition 315, by means of microscopic observation, X-ray diffraction, and major- and trace-element analyses. Deformation bands are not only more compacted than the host sediment but are also enriched in framboidal pyrite, as observed under microscopy and confirmed by chalcophile-element enrichments (Fe, S, Cu, As, Sb, Pb). In tandem, one shear zone sample displays a destabilization of smectite or illite–smectite mixed layers and a slight crystallization of illite relative to its sediment matrix, and another sample shows correlated increases in B and Li in shear zones and veins compared to the host sediment, both effects suggesting a transformation of smectite into illite in deformation bands. The two diagenetic reactions of sulfide precipitation and smectite-to-illite transformation are explained by a combined action of sulfate-reducing and methanogen bacteria, which strongly suggests an increased activity of anaerobic microbial communities localized in deformation bands. This local bacterial proliferation was possibly enhanced by the liberation of hydrogen from strained phyllosilicates. We suggest that the proliferation of anoxic bacteria, boosted by deformation, may contribute to the pore water freshening observed at depth in accretionary prisms. Deformation-enhanced metabolic reactions may also explain the illitization observed in major faults of accretionary prisms. Care is therefore needed before interpreting illitization, and other diagenetic reactions as well, as evidence of shear heating, as these might be biogenic instead of thermogenic.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major health concerns due to their increasing incidence and high mortality. They are interconnected syndromes; AKI without recovery evolves into acute kidney disease (AKD), which can indicate an AKI-to-CKD transition. Both AKI and CKD are associated with a risk of long-term cardiovascular complications, but whether vascular and cardiac dysfunctions can occur as early as the AKD period has not been studied extensively. In a mouse model of kidney injury (KI) with non-recovery, we performed vasoreactivity and echocardiography analyses on days 15 (D15) and 45 (D45) after KI. We determined the concentrations of two major gut-derived protein-bound uremic toxins known to induce cardiovascular toxicity—indoxyl sulfate (IS) and para-cresyl sulfate (PCS)—and the levels of inflammation and contraction markers on D7, D15, and D45. Mice with KI showed acute tubular and interstitial kidney lesions on D7 and D15 and chronic glomerulosclerosis on D45. They showed significant impairment of aorta relaxation and systolic-diastolic heart function, both on D15 and D45. Such dysfunction was associated with downregulation of the expression of two contractile proteins, αSMA and SERCA2a, with a more pronounced effect on D15 than on D45. KI was also followed by a rapid increase in IS and PCS serum concentrations and the expression induction of pro-inflammatory cytokines and endothelial adhesion molecules in serum and cardiovascular tissues. Therefore, these results highlight that AKD leads to early cardiac and vascular dysfunctions. How these dysfunctions could be managed to prevent cardiovascular events deserves further study. [ABSTRACT FROM AUTHOR]

Abstract Chronic kidney disease (CKD) worsens ischemic stroke severity in both patients and animals. In mice, these poorer functional outcomes are associated with decreased brain activity of AMP-activated protein kinase (AMPK), a molecule that recently emerged as a potential therapeutic target for ischemic stroke. The antidiabetic drug metformin, a well-known activator of AMPK, has improved stroke outcomes in diabetic patients with normal renal function. We investigated whether chronic metformin pre-conditioning can rescue AMPK activity and prevent stroke damage in non-diabetic mice with CKD. Eight-week-old female C57BL/6J mice were assigned to CKD or SHAM groups. CKD was induced through right kidney cortical electrocautery, followed by left total nephrectomy. Mice were then allocated to receive metformin (200 mg/kg/day) or vehicle for 5 weeks until stroke induction by transient middle cerebral artery occlusion (tMCAO). The infarct volumes were lower in CKD mice exposed to metformin than in vehicle-treated CKD mice 24 h after tMCAO. Metformin pre-conditioning of CKD mice improved their neurological score, grip strength, and prehensile abilities. It also enhanced AMPK activation, reduced apoptosis, increased neuron survival and decreased microglia/macrophage M1 signature gene expression as well as CKD-induced activation of the canonical NF-κB pathway in the ischemic lesions of CKD mice.

Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that is endemic in a number of regions across the world. There are an estimated 5–10 million people infected worldwide. Japan is currently the only country with a national antenatal screening programme in place. HTLV-1 is primarily transmitted sexually in adulthood, however it can be transmitted from mother-to-child perinatally. This can occur transplacentally, during the birth process or via breastmilk. If HTLV-1 is transmitted perinatally then the lifetime risk of adult T cell leukemia/lymphoma rises from 5 to 20%, therefore prevention of mother-to-child transmission of HTLV-1 is a public health priority. There are reliable immunological and molecular tests available for HTLV-1 diagnosis during pregnancy and screening should be considered on a country by country basis. Further research on best management is needed particularly for pregnancies in women with high HTLV-1 viral load. A first step would be to establish an international registry of cases and to monitor outcomes for neonates and mothers. We have summarized key risk factors for mother-to-child transmission of HTLV-1 and subsequently propose a pragmatic guideline for management of mothers and infants in pregnancy and the perinatal period to reduce the risk of transmission. This is clinically relevant in order to reduce mother-to-child transmission of HTLV-1 and it's complications.

Abstract Introduction Chronic infection with human T‐cell lymphotropic virus type‐1 (HTLV‐1) may result in aggressive adult T‐cell leukaemia/lymphoma (ATL) in 4‐6% carriers. The majority of this risk arises in carriers infected during infancy, and so each infant has ∼25% lifetime risk. Other risk factors include a family history of ATL. Antenatal HTLV‐1 screening is not undertaken in the UK. Methods Here we describe four cases of ATL diagnosed during pregnancy and describe strategies to minimise HTLV‐1 transmission to neonates. Results/conclusion These cases highlight undiagnosed HTLV‐1 in pregnancy which allows ongoing mother to child vertical transmission and risk of future ATL. We recommend the UK National Screening Committee incorporate HTLV‐1 serology into antenatal screening.

Abstract Background The bactericidal activity of an antimicrobial drug is generally assessed by in vitro bacterial time-kill experiments which do not include any components of the immune system, even though the innate immunity, the primary host defence, is probably able to kill a large proportion of pathogenic bacteria in immunocompetent patients. We developed an in vitro tripartite model to investigate the joint action of C57Bl/6 murine bone-marrow-derived macrophages and cephalexin on the killing of Staphylococcus aureus. Results By assessing the bactericidal effects on four bacterial inoculum sizes, we showed that macrophages can cooperate with cephalexin on inoculum sizes lower than 106 CFU/mL and conversely, protect S. aureus from cephalexin killing activity at the highest inoculum size. Cell analysis by flow cytometry revealed that macrophages were rapidly overwhelmed when exposed to large inoculums. Increasing the initial inoculum size from 105 to 107 CFU/mL increased macrophage death and decreased their ability to kill bacteria from six hours after exposure to bacteria. The addition of cephalexin at 16-fold MIC to 105 and 106 CFU/mL inoculums allowed the macrophages to survive and to maintain their bactericidal activity as if they were exposed to a small bacterial inoculum. However, with the highest inoculum size of 107 CFU/mL, the final bacterial counts in the supernatant were higher with macrophages plus cephalexin than with cephalexin alone. Conclusions These results suggest that if the bacterial population at the infectious site is low, as potentially encountered in the early stage of infection or at the end of an antimicrobial treatment, the observed cooperation between macrophages and cephalexin could facilitate its control.

Les agences réglementaires sont aujourd’hui au cœur des politiques de protection des populations et de l’environnement, en France comme en Europe. À chaque fois que les effets sanitaires d’un produit font l’objet d’une controverse publique (bisphénol A, benfluorex, glyphosate), ces agences sont mises en accusation : leurs procédures de gestion des conflits d’intérêts et leurs politiques de transparence seraient insuffisantes. Les débats qui ont récemment entouré les évaluations divergentes du Centre international de recherche sur le cancer (CIRC) et de l’Autorité européenne de sécurité des aliments (EFSA) sur la cancérogénicité du glyphosate suggèrent cependant une situation plus complexe. Plutôt qu’un problème de « conflit d’intérêts », les critiques formulées à l’égard de l’EFSA sont liées au fait que les questions qui lui sont posées, les protocoles sur lesquels elle s’appuie, et les données qu’elle utilise, le sont dans un contexte bien particulier : celui de l’évaluation réglementaire de produits en vue de leur commercialisation.

Background: Vascular calcification (VC) is a cardiovascular complication associated with a high mortality rate among patients with diseases such as atherosclerosis and chronic kidney disease. During VC, vascular smooth muscle cells (VSMCs) undergo an osteogenic switch and secrete a heterogeneous population of extracellular vesicles (EVs). Recent studies have shown involvement of EVs in the inflammation and oxidative stress observed in VC. We aimed to decipher the role and mechanism of action of macrophage-derived EVs in the propagation of inflammation and oxidative stress on VSMCs during VC.Methods: The macrophage murine cell line RAW 264.7 treated with lipopolysaccharide (LPS-EK) was used as a cellular model for inflammatory and oxidative stress. EVs secreted by these macrophages were collected by ultracentrifugation and characterized by transmission electron microscopy, cryo-electron microscopy, nanoparticle tracking analysis, and the analysis of acetylcholinesterase activity, as well as that of CD9 and CD81 protein expression by western blotting. These EVs were added to a murine VSMC cell line (MOVAS-1) under calcifying conditions (4 mM Pi—7 or 14 days) and calcification assessed by the o-cresolphthalein calcium assay. EV protein content was analyzed in a proteomic study and EV cytokine content assessed using an MSD multiplex immunoassay.Results: LPS-EK significantly decreased macrophage EV biogenesis. A 24-h treatment of VSMCs with these EVs induced both inflammatory and oxidative responses. LPS-EK-treated macrophage-derived EVs were enriched for pro-inflammatory cytokines and CAD, PAI-1, and Saa3 proteins, three molecules involved in inflammation, oxidative stress, and VC. Under calcifying conditions, these EVs significantly increase the calcification of VSMCs by increasing osteogenic markers and decreasing contractile marker expression.Conclusion: Our results show that EVs derived from LPS-EK–treated-macrophages are able to induce pro-inflammatory and pro-oxidative responses in surrounding cells, such as VSMCs, thus aggravating the VC process.

Pour Dominique Boullier, mieux que d’autres notion telles que « milieu », « monde » ou « espace », la notion de « territoire » est pertinente parce qu’elle permet d’intégrer « les deux faces de l’expérience spatiale qui comporte un mouvement d’appropriation ». Elle permet alors de déployer une anthropologie de l’appropriation qui regarde Internet non comme un habit, un habité, un habitat ou un habitacle, mais comme tout cela à la fois, condensé dans la notion d’« habitèle ». Cette approche théorique est déterminante dans le regard critique que Dominique Boullier porte ici sur les transformations qu’a connu Internet ces 10 dernières années : en poussant à l’extrême l’analyse proposée par celui-ci on peut dire que les enjeux de ce territoire numérique, de cet habitèle, en ont oublié l’habitant lui-même. Il est question de montée en puissance des plateformes, de « disparition de l’internet en tant qu’espace mondial », d’enjeux économiques des métriques d’audience devenues métriques d’activités, d’impact de la monétisation des engagements sur la création de monopoles, de polarisation… Les luttes dont Internet est l’objet portent en effet moins vers la conquête d’un « bien commun » comme d’exigences de transparence qui permettent à tous d’apprendre, que vers un rééquilibrage des seules mannes financières dont il est porteur : « Toute la décennie 2010 a été celle du Far-West, de la prédation de traces, de la fraude fiscale, des achats des concurrents sans limites, des abus de positions dominantes, et de l’augmentation de l’opacité des algorithmes et de leur puissance prédictive supposée grâce au Machine Learning ».

BackgroundObesity is a major public health problem of our time as a risk factor for cardiometabolic disease and the available pharmacological tools needed to tackle the obesity pandemic are insufficient. Neurotensin (NTS) is a 13 amino acid peptide, which is derived from a larger precursor hormone called proneurotensin or Long Form NTS (LF NTS). NTS modulates neuro-transmitter release in the central system nervous, and facilitates intestinal fat absorption in the gastrointestinal tract. Mice lacking LF NTS are protected from high fat diet (HFD) induced obesity, hepatic steatosis and glucose intolerance. In humans, increased levels of LF NTS strongly and independently predict the development of obesity, diabetes mellitus, cardiovascular disease and mortality. With the perspective to develop therapeutic tools to neutralize LF NTS, we developed a monoclonal antibody, specifically inhibiting the function of the LF NTS (LF NTS mAb). This antibody was tested for the effects on body weight, metabolic parameters and behavior in mice made obese by high-fat diet.MethodsC57bl/6j mice were subjected to high-fat diet (HFD) until they reached an obesity state, then food was switched to chow. Mice were treated with either PBS (control therapy) or LF NTS mAb at the dose of 5 mg/kg once a week (i.v.). Mice weight, plasma biochemical analysis, fat and muscle size and distribution and behavioral tests were performed during the losing weight period and the stabilization period.ResultsObese mice treated with the LF NTS mAb lost weight significantly faster than the control treated group. LF NTS mAb treatment also resulted in smaller fat depots, increased fecal cholesterol excretion, reduced liver fat and larger muscle fiber size. Moreover, mice on active therapy were also less stressed, more curious and more active, providing a possible explanation to their weight loss.ConclusionOur results demonstrate that in mice subjected to HFD-induced obesity, a blockade of LF NTS with a monoclonal antibody results in reduced body weight, adipocyte volume and increased muscle fiber size, possibly explained by beneficial effects on behavior. The underlying mechanisms as well as any future role of LF NTS mAb as an anti-obesity agent warrants further studies.

Simple Summary: Pulmonary neuroendocrine neoplasms (NENs) are a challenging type of lung cancer due to their varied clinical features and aggressive behavior. This study aimed to find specific metabolomic profiles in the blood of patients with different subtypes of lung NENs, which could help in early diagnosis. By analyzing 153 metabolites in the plasma of 120 NEN patients and comparing them with healthy individuals and patients with other lung cancers, we identified specific metabolic changes. These findings could lead to new biomarkers for early detection and better management of lung NENs, ultimately improving patient outcomes. Background/Objectives: Pulmonary neuroendocrine neoplasms (NENs) account for 20% of malignant lung tumors. Their management is challenging due to their diverse clinical features and aggressive nature. Currently, metabolomics offers a range of potential cancer biomarkers for diagnosis, monitoring tumor progression, and assessing therapeutic response. However, a specific metabolomic profile for early diagnosis of lung NENs has yet to be identified. This study aims to identify specific metabolomic profiles that can serve as biomarkers for early diagnosis of lung NENs. Methods: We measured 153 metabolites using liquid chromatography combined with mass spectrometry (LC-MS) in the plasma of 120 NEN patients and compared them with those of 71 healthy individuals. Additionally, we compared these profiles with those of 466 patients with non-small-cell lung cancers (NSCLCs) to ensure clinical relevance. Results: We identified 21 metabolites with consistently altered plasma concentrations in NENs. Compared to healthy controls, 18 metabolites were specific to carcinoid tumors, 5 to small-cell lung carcinomas (SCLCs), and 10 to large-cell neuroendocrine carcinomas (LCNECs). These findings revealed alterations in various metabolic pathways, such as fatty acid biosynthesis and beta-oxidation, the Warburg effect, and the citric acid cycle. Conclusions: Our study identified biomarker metabolites in the plasma of patients with each subtype of lung NENs and demonstrated significant alterations in several metabolic pathways. These metabolomic profiles could potentially serve as biomarkers for early diagnosis and better management of lung NENs. [ABSTRACT FROM AUTHOR]