bluuebunny/crossref_metadata_2025 huggingface dataset:
El vidrio romano del vertedero altoimperial de la calle Sacramento 38 (Cádiz): un acercamiento al instrumentum domesticum de la Gades romana
Authors: Retamosa Gámez José Alberto , Díaz Rodríguez José Juan , Portillo Sotelo José Luis , Bernal Casasola Darío , Martelo Fernández Marcos Antonio
Published: July 2022

Un vertedero periurbano con dos fases de uso datadas entre época tardorrepublicana y altoimperial ha sido documentado en los solares contiguos de las calles Sacramento 38 y Solano 1 (Cádiz), en relación con la ciudad hispanorromana de Gades. Entre el material mueble registrado, mayoritariamente de carácter cerámico, se advierte la presencia de vidrio elaborado mediante las técnicas de modelado y soplado al aire. El análisis morfológico, funcional y tipológico del vidrio aporta nueva información acerca del consumo de estos productos en el ámbito urbano y, en concreto, en el doméstico de la Gades romana.
Le prédicateur et le vicomte. La promotion du culte de saint Vincent Ferrier par Jean II de Rohan
Authors: Mens Diego
Published: July 2022

Jean II de Rohan est un personnage qui a été souvent au centre de controverses, notamment en raison de ses choix politiques entre duché de Bretagne et royaume de France. Toutefois, ce grand féodal breton a été également un constructeur important, un commanditaire éclairé et a joué un rôle important dans la promotion du culte de saint Vincent Ferrier en Bretagne, et notamment sur les terres du vicomte, soit près d’un cinquième du duché. À l’exception des Montfort et du culte de Saint-Yves, peu d’exemples ont été identifiés en Bretagne historique pour l’impulsion donnée au développement d’une dévotion par la noblesse, sur une telle échelle géographique et sur une durée aussi longue. C’est à partir de l’analyse du corpus actuel des représentations de saint Vincent Ferrier et de leur répartition que cet article s’attache à expliquer cette promotion et ses mécanismes, notamment au travers du parcours familial et politique du vicomte.
Un demi-succès ? La relance baroque du culte de saint Vincent Ferrier à Vannes (xviie-xviiie siècle)
Authors: Provost Georges
Published: July 2022

Le registre de la confrérie de saint Vincent Ferrier de Vannes révèle 709 membres enrôlés entre 1645 et 1781, avec une très forte présence des élites sociales de la ville. Est-ce un reflet exact de la popularité locale du saint dominicain ? Cette communication cherche à le préciser, en conjuguant deux échelles d’analyse : d’une part, l’ensemble du monde catholique, grâce aux registres d’indulgences romains qui permettent de prendre la mesure globale des confréries dédiées à saint Vincent Ferrier ; d’autre part, la ville de Vannes où la confrérie s’inscrit dans une dynamique plus large d’affirmation du culte de saint Vincent Ferrier : lors de sa fondation en 1645, son objectif est moins de relancer le culte, déjà porté par un large mouvement collectif, que de le pérenniser sous des formes partiellement nouvelles, en particulier à la date du 6 septembre qui devient la fête par excellence du saint patron de la cité.
Zygmunt Bauman
Authors: Chardel Pierre-Antoine
Published: July 2022

Zygmunt Bauman est une figure majeure de la sociologie européenne. Son œuvre est dominée par l’inquiétude provoquée par la succession des crises politiques, économiques, morales qui affectent nos sociétés contemporaines. Du Coût humain de la mondialisation à L’éthique a-t-elle une chance dans un monde de consommateurs ?, ses travaux portent un diagnostic corrosif sur notre époque sans se laisser enfermer dans des cadres théoriques trop univoques.Diversifiant les angles d’interprétation, engagé dans un constant dialogue avec une multitude d’auteurs, de Camus à Levinas, de Gramsci à Arendt, Bauman parvient à embrasser la complexité des phénomènes sociaux en couvrant des champs de réflexion a priori hétérogènes – de l’interrogation sur le statut de l’Holocauste dans l’histoire de la modernité industrielle à l’avènement du consumérisme dans nos sociétés devenues « liquides ». C’est cette exigence critique singulière que nous rend présent Pierre-Antoine Chardel dans cet essai, le premier en français consacré à ce penseur hors norme.
Identificar y reclutar al subalterno. Las filiaciones de policía (Buenos Aires, década de 1820)
Authors: Vaccaroni María Agustina
Published: July 2022

En este trabajo presentamos un tipo documental escasamente explorado, a saber las filiaciones hechas sobre soldados, cabos y celadores de policía por los comisarios de ciudad y campaña en Buenos Aires durante la década de 1820. Perseguimos, aquí, un doble objetivo: en primer lugar, dar cuenta de la existencia, el modo de conservación y las principales características de este tipo documental; en segundo lugar, abordar un análisis sobre las razones por las cuales los agentes vinculados al Departamento de Policía, instalado desde 1821 en Buenos Aires, hicieron uso de este registro escrito.Para ello, y luego de un apartado introductorio, dedicamos una sección de este artículo a la descripción de una serie de filiaciones contenidas en el fondo de Policía de la Sala X del Archivo General de la Nación (Argentina). En el siguiente apartado, abordamos su contexto de producción, marcado por la organización de Buenos Aires como entidad autónoma, y rastreamos, a partir de tres filiaciones y una nota de presentación de las mismas (hechas por el comisario Juan Bautista Perichon y enviadas al Departamento de Policía) que trascribimos como anexo, los problemas de reclutamiento que las configuraciones policiales experimentaron hacia mitad de la década de 1820. Las reflexiones finales sirven como puente para abrir posibilidades y caminos de exploración futuros.
“Nos perdimos en el monte al regreso”: los viajes del Dr. Salvador Bucca a Formosa en los años sesenta
Authors: Vidal Alejandra , Machuca Darío , Sánchez Julieta
Published: July 2022

Salvador Bucca fue Profesor Titular de Lingüística de la Facultad de Filosofía y Letras, Universidad de Buenos Aires, entre 1955 y 1983. Se formó en Italia y Estados Unidos. En calidad de docente y director del Centro de Estudios Lingüísticos, visitó en reiteradas ocasiones el nordeste argentino, para estudiar las lenguas de las comunidades locales. En este artículo nos enfocamos en sus viajes a la provincia de Formosa para realizar trabajo de campo en 1961, 1964 y 1968. En este sentido, señalamos la importancia de su figura en torno a la gestación de los primeros estudios sobre las lenguas indígenas chaqueñas. Este trabajo forma parte de un estudio más amplio de los documentos donados por la familia del Dr. Salvador Bucca al Archivo del Laboratorio de Documentación e Investigación en Lingüística y Antropología (DILA), tarea iniciada en 2019 por parte de un equipo de la Universidad Nacional de Formosa con la transcripción de los cuadernos de campo del Dr. Bucca. La fuente que presentamos corresponde a un extracto del Cuaderno N° 4, donde el lingüista describe su viaje a través de la predominantemente rural provincia de Formosa en el invierno de 1964. En este sentido, se destacan los problemas de movilidad y hospedaje, y la reticencia de algunos funcionarios y miembros de las fuerzas de seguridad a colaborar con la investigación. La contracara está representada por los misioneros de los distintos cultos cristianos que le facilitaron el contacto con sus informantes locales.
L’esthétique de la vulnérabilité. Auto-analyse et stratégies narratives dans La Trilogie de Copenhague de Tove Ditlevsen
Authors: Jelsbak Torben
Published: July 2022

Au cours des dix dernières années, l’œuvre de l’écrivaine et poétesse danoise Tove Ditlevsen (1917-1976) a connu un renouveau remarquable. Ses œuvres ont été massivement republiées et relues dans des éditions nouvelles en même temps que son héritage est repris par de jeunes écrivaines et par des acteurs des arts performatifs. En 2019, une collection regroupant ses trois ouvrages de mémoires tardives Enfance, Jeunesse et Dépendance (1967-1971) est sortie en anglais dans la collection de « Penguin Classics » sous le titre La Trilogie de Copenhague (The Copenhagen Trilogy). Aujourd’hui, l’ouvrage est vendu pour publication dans 31 pays. Plus de 40 ans après sa mort par suicide en 1976, Tove Ditlevsen fait l’objet d’une véritable percée internationale. Mais qu’est-ce qui explique la découverte et le succès soudain de l’écrivaine dans la culture littéraire de nos jours ? En quoi consiste la force d’attraction de son œuvre auprès des lecteurs contemporains ? Quels sont les sentiments qui sont attachés à son œuvre ? Pour aborder ces questions, le présent article propose une lecture de La Trilogie de Copenhague en examinant les stratégies narratives de l’œuvre ainsi que l’autoportrait qu’elle donne de sa créatrice.
Résoudre pauvreté et gaspillage alimentaire en réintroduisant le choix dans la consommation des ménages à faible budget ? Le cas d’une structure d’aide alimentaire privée à Stockholm
Authors: Boukhris-Ferré Yacine
Published: July 2022

Dans une banlieue de Stockholm, un supermarché « social et solidaire » propose de réintégrer les surplus alimentaires dans le circuit commercial. En les remettant en vente, ce supermarché réintroduit une forme de choix dans l’alimentation des ménages à petit budget qui constituent sa clientèle. Ces derniers, qui disposent d’une marge de manœuvre limitée, font « de nécessité vertu » et participent, par leur mode de consommation, à la lutte contre le gaspillage alimentaire. Cette solution, qui se développe en Suède et qui s’appuie presque entièrement sur le secteur privé, est intéressante à plus d’un titre, mais ne va pas sans soulever de nombreuses interrogations : assiste-t-on à une privatisation progressive des circuits fournissant l’aide alimentaire ?
OUI MOI JE SUIS SUR LE CHEMIN D’UNE HISTOIRE RADIEUSE - L’autoreprésentation dans la littérature de ghetto danoise
Authors: Helt Haarder Jon
Published: July 2022

Cet article trace l’histoire récente de l’autoreprésentation littéraire au Danemark, et ce qu’on appelle la littérature de ghetto danoise est comparée aux tendances-clés de cette histoire. À cet égard, l’article se focalise sur les auteurs danois Yahya Hassan et Morten Pape en tant qu’incarnations d’une tendance propre à chacun d’eux, respectivement l’autoreprésentation performativement authentique et l’autoreprésentation en quête de sincérité. Dans la continuité de cette distinction, je contextualise l’analyse à l’aide du concept d’état sociétal post-migratoire, et j’avance un argument en faveur de l’importance d’une perspective de classe sur cet état sociétal.
Linqing 麟慶 et les savoirs impériaux en Chine à la fin de la période impériale
Authors: Spicq Delphine
Published: July 2022

Cet article propose une réflexion sur les différents types de savoirs dans la Chine impériale tardive et analyse le rôle des élites lettrées et particulièrement des fonctionnaires dans la constitution, la reproduction et la circulation des savoirs, notamment des savoirs locaux ou vernaculaires au travers de l’exemple d’un haut fonctionnaire d’origine mandchoue spécialiste de conservation hydraulique et en charge de la gestion du grand canal. Au travers de l’analyse d’un des ouvrages de cet auteur, un manuel sur les outils et instruments utilisés pour la gestion des cours d’eau, cet article illustre la lente intégration des savoirs locaux et vernaculaires dans les corpus impériaux et le rôle des élites dans cette intégration et pose la question de la mise en pratique des nouveaux savoirs produits.
Application of Inquiry-Based Science Education, Anticipatory Learning Strategy, and Project-Based Learning Strategies in the Context of Environmental Problems of the Contemporary World
Authors: Piotrowska Iwona , Cichoń Małgorzata , Sypniewski Jakub , Abramowicz Dawid
Published: July 2022

The global challenges of melting ice caps, rising global ocean levels, increased methane release from permafrost, and restrictions on access to water resources are primarily associated with climate change. Geographical education is of particular importance in this regard. At all levels of education, it should therefore provide knowledge about the changes taking place, shape practical skills, and foster the acquisition of appropriate attitudes in caring for the state of individual components of the geographical environment. Thus, the mentioned problems of the modern world require the selection of appropriate educational strategies. The chapter presents three educational strategies: teaching through scientific inquiry (IBSE), anticipatory learning strategy (ALS), and teaching through project-based learning (PBL). A general characterization was made, and then a proposal for their application to geography education classes was prepared. Content contexts were proposed for the respective strategies: IBSE (global warming), ALS (ice sheet changes), and PBL (water resources and retention).
A Framework to Classify Clinical Data Using a Genetic Algorithm and Artificial Flora-Optimized Neural Network
Authors: Sreejith S.  , Nehemiah Khanna H. , Kannan A.
Published: July 2022

A new classification framework for a Clinical Decision Support System, utilizing a Genetic algorithm and an Artificial Flora Optimized Neural Network is presented in this paper. GAFON is an artificial neural network whose topology is optimized with Genetic Algorithm and the learnable parameters are optimized with Artificial Flora Optimization algorithm. Drop out technique is used in the topology optimization phase and weight regularization is used in the parameter optimization phase. The proposed method minimizes the co-adaptation problem, reduces over-fitting of training data and improves the generalization of a feed forward neural network. The classification framework developed has been tested for classifying both multi class and binary class clinical datasets. The proposed method attained accuracy values of 86.82% for Hepatitis C Virus (HCV) for Egyptian patients, 84.91% for Vertebral Column 95.65% for Statlog Heart Disease (SHD), SHD and 93.79% for Early Stage Diabetes Risk Prediction (ESDRP), all datasets obtained from UCI repository
An Entropy-View Secure Multiparty Computation Protocol Based on Semi-Honest Model
Authors: Luo Yun , Chen Yuling , Li Tao , Wang Yilei , Yang Yixian , Yu Xiaomei
Published: July 2022

Data interaction scenarios involving multiple parties in network communities have problems of trust, data security, and reliability of the parties, and secure multiparty computation(SMPC) can effectively solve these problems. To address the security and fairness issues of SMPC, this study considers that semi-honest participants can lead to deviations in the security and fairness of the protocol, and combines information entropy and mutual information to present an n-round information exchange protocol in which each participant broadcasts a relevant information value in each round without revealing other information. The uncertainty of the correct outcome value is blurred by the interaction information in each round, and each participant is not sure of the correct outcome value until the end of the protocol, which effectively prevents malicious behavior and ensures the correct execution of the protocol. Security and fairness analysis shows that our protocol guarantees the security and relative fairness of the output obtained by the participants after completing the protocol.
Role of C3a as a Novel Regulator of 25(OH)D3 to 1α,25-Dihydroxyvitamin D3 Metabolism in Upper Airway Epithelial Cells
Authors: Mulligan Jennifer K , Nord Dianna , Villanueva Maria V , Justice Jeb , Lobo Brian , Schlosser Rodney J , Atkinson Carl
Published: July 2022

In patients with chronic rhinosinusitis with nasal polyps, primary human sinonasal epithelial cell (HSNEC) 1α-hydroxylase levels are reduced, as is their ability to metabolize 25-hydroxycholecalciferol [25(OH)D3] to its active metabolite, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In this study, we sought to identify the factor responsible for the regulation of HSNEC metabolism of 25(OH)D3, focusing on C3 and C3a. Multiple inhaled irritants trigger the release of complement components, C3 and C3a, leading to suppression of 1α-hydroxylase levels in HSNECs. Recombinant C3a was able to decrease 1α-hydroxylase and impair 25(OH)D3 to 1,25(OH)2D3 metabolism, while addition of a C3a receptor antagonist restored conversion. Conversely, 1,25(OH)2D3 suppressed Aspergillus fumigatus–induced C3 and C3a levels in HSNEC supernatant. Given the ability of 1,25(OH)2D3 to modulate LL37 in other cell types, we examined its regulation in HSNECs and relationship to C3a. 1,25(OH)2D3 stimulated the secretion of LL37, whereas A. fumigatus and C3a suppressed it. Conversely, LL37 reduced the release of C3/C3a by HSNECs. Lastly, oral steroid use and in vitro dexamethasone application both failed to increase 1α-hydroxylase or reduce C3a levels. In summary, in this article, we describe for the first time a novel relationship between complement activation and local vitamin D metabolism in airway epithelial cells. The presence of elevated C3/C3a in patients with asthma and/or chronic rhinosinusitis with nasal polyps may account for their impaired HSNEC 25(OH)D3 to 1,25(OH)2D3 metabolism and explain why they receive limited therapeutic benefit from oral vitamin D3 supplementation.
Mouse Trophoblast Cells Can Provide IFN-Based Antiviral Protection to Embryonic Stem Cells via Paracrine Signaling
Authors: Fendereski Mona , Neupane Biswas , Nazneen Farzana , Bai Fengwei , Guo Yan-Lin
Published: July 2022

The blastocyst is the preimplantation stage embryo that consists of two major components: the inner cell mass (ICM) and the trophectoderm (TE). The ICM gives rise to the fetus and some extraembryonic tissues whereas the TE contributes to development of the placenta. Previous studies have demonstrated that both human and mouse embryonic stem cells (ESCs) derived from the ICM are deficient in expressing type I IFNs in response to viral infection. In this study, we investigated the IFN response in mouse trophoblast stem cells (TSCs) and their in vitro differentiated trophoblasts (TSC-TBs). In this study, we report that, unlike ESCs, TSCs have a functional IFN system. They can express type I IFNs in response to viral stimuli and express IFN-stimulated genes in response to type I IFNs. TSC-TBs have a further developed IFN system and acquired the ability to express specialized type III IFN-λ. Furthermore, TSCs and TSC-TBs can provide ESCs with antiviral activity against Chikungunya, West Nile, and Zika virus infection, as demonstrated with a novel coculture model that simulates the temporal and spatial relationship between the ICM and the TE in a blastocyst. Taken together, our data demonstrate that mouse ESCs can respond to type I IFNs and gain IFN-based antiviral protection from TSCs and TSC-TBs via paracrine signaling mechanisms even though they themselves are unable to express type I IFNs.
The Intracellular Interaction of Porcine β-Defensin 2 with VASH1 Alleviates Inflammation via Akt Signaling Pathway
Authors: Huang Chao , Sun Yufan , Qiu Xiuxiu , Huang Jing , Wang Antian , Zhang Qiuhong , Pang Siqi , Huang Qi , Zhou Rui , Li Lu
Published: July 2022

Defensins are a major class of antimicrobial peptides that facilitate the immune system to resist pathogen infection. To date, only β-defensins have been identified in pigs. In our previous studies, porcine β-defensin 2 (PBD-2) was shown to have both bactericidal activity and modulatory roles on inflammation. PBD-2 can interact with the cell surface TLR4 and interfere with the NF-κB signaling pathway to suppress the inflammatory response. In this study, the intracellular functions of PBD-2 were investigated. The fluorescently labeled PBD-2 could actively enter mouse macrophage cells. Proteomic analysis indicated that 37 proteins potentially interacted with PBD-2, among which vasohibin-1 (VASH1) was further tested. LPS, an inflammation inducer, suppressed the expression of VASH1, whereas PBD-2 inhibited this effect. PBD-2 inhibited LPS-induced activation of Akt, expression and release of the inflammatory mediators vascular endothelial growth factor and NO, and cell damage. A follow-up VASH1 knockdown assay validated the specificity of the above observations. In addition, PBD-2 inhibited LPS-induced NF-κB activation via Akt. The inhibition effects of PBD-2 on LPS triggered suppression of VASH1 and activation of Akt, and NF-κB and inflammatory cytokines were also confirmed using pig alveolar macrophage 3D4/21 cells. Therefore, the data indicate that PBD-2 interacts with intracellular VASH1, which inhibits the LPS-induced Akt/NF-κB signaling pathway, resulting in suppression of inflammatory responses. Together with our previous findings, we conclude that PBD-2 interacts with both the cell surface receptor (TLR4) and also with the intracellular receptor (VASH1) to control inflammation, thereby providing insights into the immunomodulatory roles of defensins.
IFN-λ Diminishes the Severity of Viral Bronchiolitis in Neonatal Mice by Limiting NADPH Oxidase–Induced PAD4-Independent NETosis
Authors: Sebina Ismail , Rashid Ridwan B , Sikder Md Al Amin , Rahman Muhammed Mahfuzur , Ahmed Tufael , Radford-Smith Daniel E , Kotenko Sergei V , Hill Geoffrey R , Bald Tobias , Phipps Simon
Published: July 2022

Infants with attenuated type III IFN (IFN-λ) responses are at increased risk of severe lower respiratory tract infection (sLRI). The IL-28Rα–chain and IL-10Rβ–chain form a heterodimeric receptor complex, necessary for IFN-λ signaling. Therefore, to better understand the immunopathogenic mechanisms through which an IFN-λlo microenvironment predisposes to a sLRI, we inoculated neonatal wild-type and IL-28R–deficient (IL-28R−/−) mice with pneumonia virus of mice, a rodent-specific pneumovirus. Infected IL-28R−/− neonates displayed an early, pronounced, and persistent neutrophilia that was associated with enhanced reactive oxygen species (ROS) production, NETosis, and mucus hypersecretion. Targeted deletion of the IL-28R in neutrophils was sufficient to increase neutrophil activation, ROS production, NET formation, and mucus production in the airways. Inhibition of protein-arginine deiminase type 4 (PAD4), a regulator of NETosis, had no effect on myeloperoxidase expression, citrullinated histones, and the magnitude of the inflammatory response in the lungs of infected IL-28R−/− mice. In contrast, inhibition of ROS production decreased NET formation, cellular inflammation, and mucus hypersecretion. These data suggest that IFN-λ signaling in neutrophils dampens ROS-induced NETosis, limiting the magnitude of the inflammatory response and mucus production. Therapeutics that promote IFN-λ signaling may confer protection against sLRI.
ICOS-Deficient Regulatory T Cells Can Prevent Spontaneous Autoimmunity but Are Impaired in Controlling Acute Inflammation
Authors: Chang Jinsam , Bouchard Antoine , Bouklouch Yasser , Panneton Vincent , Li Joanna , Diamantopoulos Nikoletta , Mohammaei Saba , Istomine Roman , Alvarez Fernando , Piccirillo Ciriaco A , Suh Woong-Kyung
Published: July 2022

ICOS is induced in activated T cells and its main role is to boost differentiation and function of effector T cells. ICOS is also constitutively expressed in a subpopulation of Foxp3+ regulatory T cells under steady-state condition. Studies using ICOS germline knockout mice or ICOS-blocking reagents suggested that ICOS has supportive roles in regulatory T (Treg) cell homeostasis, migration, and function. To avoid any compounding effects that may arise from ICOS-deficient non–Treg cells, we generated a conditional knockout system in which ICOS expression is selectively abrogated in Foxp3-expressing cells (ICOS FC mice). Compared to Foxp3-Cre control mice, ICOS FC mice showed a minor numerical deficit of steady-state Treg cells but did not show any signs of spontaneous autoimmunity, indicating that tissue-protective Treg populations do not heavily rely on ICOS costimulation. However, ICOS FC mice showed more severe inflammation in oxazolone-induced contact hypersensitivity, a model of atopic dermatitis. This correlated with elevated numbers of inflammatory T cells expressing IFN-γ and/or TNF-α in ICOS FC mice compared with the control group. In contrast, elimination of ICOS in all T cell compartments negated the differences, confirming that ICOS has a dual positive role in effector and Treg cells. Single-cell transcriptome analysis suggested that ICOS-deficient Treg cells fail to mature into T-bet+CXCR3+ “Th1-Treg” cells in the draining lymph node. Our results suggest that regimens that preferentially stimulate ICOS pathways in Treg cells might be beneficial for the treatment of Th1-driven inflammation.
Zbtb46 Controls Dendritic Cell Activation by Reprogramming Epigenetic Regulation of cd80/86 and cd40 Costimulatory Signals in a Zebrafish Model
Authors: Shao Tong , Ji Jian-fei , Zheng Jia-yu , Li Chen , Zhu Lv-yun , Fan Dong-Dong , Lin Ai-fu , Xiang Li-xin , Shao Jian-zhong
Published: July 2022

The establishment of an appropriate costimulatory phenotype is crucial for dendritic cells (DCs) to maintain a homeostatic state with optimal immune surveillance and immunogenic activities. The upregulation of CD80/86 and CD40 is a hallmark costimulatory phenotypic switch of DCs from a steady state to an activated one for T cell activation. However, knowledge of the regulatory mechanisms underlying this process remains limited. In this study, we identified a Zbtb46 homolog from a zebrafish model. Zbtb46 deficiency resulted in upregulated cd80/86 and cd40 expression in kidney marrow–derived DCs (KMDCs) of zebrafish, which was accompanied with a remarkable expansion of CD4+/CD8+ T cells and accumulation of KMDCs in spleen of naive fish. Zbtb46−/− splenic KMDCs exhibited strong stimulatory activity for CD4+ T cell activation. Chromatin immunoprecipitation-quantitative PCR and mass spectrometry assays showed that Zbtb46 was associated with promoters of cd80/86 and cd40 genes by binding to a 5′-TGACGT-3′ motif in resting KMDCs, wherein it helped establish a repressive histone epigenetic modification pattern (H3K4me0/H3K9me3/H3K27me3) by organizing Mdb3/organizing nucleosome remodeling and deacetylase and Hdac3/nuclear receptor corepressor 1 corepressor complexes through the recruitment of Hdac1/2 and Hdac3. On stimulation with infection signs, Zbtb46 disassociated from the promoters via E3 ubiquitin ligase Cullin1/Fbxw11-mediated degradation, and this reaction can be triggered by the TLR9 signaling pathway. Thereafter, cd80/86 and cd40 promoters underwent epigenetic reprogramming from the repressed histone modification pattern to an activated pattern (H3K4me3/H3K9ac/H3K27ac), leading to cd80/86 and cd40 expression and DC activation. These findings revealed the essential role of Zbtb46 in maintaining DC homeostasis by suppressing cd80/86 and cd40 expression through epigenetic mechanisms.
Age-Associated B Cell Features of the Murine High-Grade B Cell Lymphoma Bc.DLFL1 and Its Extranodal Expansion in Abdominal Adipose Tissues
Authors: Jia Xinkai , Bene Judit , Balázs Noémi , Szabó Katalin , Berta Gergely , Herczeg Róbert , Gyenesei Attila , Balogh Péter
Published: July 2022

Diffuse large B cell lymphoma comprises a heterogeneous group of B cell–derived tumors, with different degrees of aggressiveness, as defined by their cellular origin and tissue microenvironment. Using the spontaneous Bc.DLFL1 lymphoma originating from a BALB/c mouse as a diffuse large B cell lymphoma model, in this study we demonstrate that the lymphoma cells display surface phenotype, IgH V-region somatic mutations, transcription factor characteristics and in vivo location to splenic extrafollicular regions of age-associated B cells (ABCs), corresponding to T-bet+ and Blimp-1+/CD138− plasmablasts derivation. The expansion of lymphoma cells within lymphoid tissues took place in a close arrangement with CD11c+ dendritic cells, whereas the extranodal infiltration occurred selectively in the mesentery and omentum containing resident gp38/podoplanin+ fibroblastic reticular cells. Antagonizing BAFF-R activity by mBR3-Fc soluble receptor fusion protein led to a significant delay of disease progression. The extranodal expansion of Bc.DLFL1 lymphoma within the omental and mesenteric adipose tissues was coupled with a significant change of the tissue cytokine landscape, including both shared alterations and tissue-specific variations. Our findings indicate that while Bc.DLFL1 cells of ABC origin retain the positioning pattern within lymphoid tissues of their physiological counterpart, they also expand in non-lymphoid tissues in a BAFF-dependent manner, where they may alter the adipose tissue microenvironment to support their extranodal growth.
Heat Shock Protein 90’s Mechanistic Role in Contact Hypersensitivity
Authors: Kim Seong-Min , Studnitzer Bradley , Esser-Kahn Aaron
Published: July 2022

Despite the known dangers of contact allergens and their long-lasting use as models in immunology, their molecular mode of action largely remains unknown. In this study, we report that a contact allergen, 1-chloro-2,4-dinitrobenzene (DNCB), elicits contact hypersensitivity through binding the protein we identify. Starting from an unbiased sampling of proteomics, we found nine candidate proteins with unique DNCB-modified peptide fragments. More than half of these fragments belonged to heat shock protein 90 (HSP90), a common stress-response protein and a damage-associated molecular pattern, and showed the highest probability of incidence. Inhibition and short hairpin RNA knockdown of HSP90 in human monocyte cell line THP-1 suppressed the potency of DNCB by >80%. Next, we successfully reduced DNCB-induced contact hypersensitivity in HSP90-knockout mice, which confirmed our findings. Finally, we hypothesized that DNCB-modified HSP90 activates the immune cells through HSP90’s receptor, CD91. Pretreatment of CD91 in THP-1 cell lines and BALB/c mice attenuated the potency of DNCB, consistent with the result of HSP90-knockout mice. Altogether, our data show that DNCB-HSP90 binding plays a role in mediating DNCB-induced contact hypersensitivity, and the activation of CD91 by DNCB-modified HSP90 proteins could mediate this process.
KIR2DS2 Expression Identifies NK Cells With Enhanced Anticancer Activity
Authors: Blunt Matthew D , Vallejo Pulido Andres , Fisher Jack G , Graham Lara V , Doyle Amber D P , Fulton Rebecca , Carter Matthew J , Polak Marta , Johnson Peter W M , Cragg Mark S , Forconi Francesco , Khakoo Salim I
Published: July 2022

NK cells are promising cellular therapeutics against hematological and solid malignancies. Immunogenetic studies have identified that various activating killer cell Ig-like receptors (KIRs) are associated with cancer outcomes. Specifically, KIR2DS2 has been associated with reduced incidence of relapse following transplant in hematological malignancies and improved outcomes in solid tumors, but the mechanism remains obscure. Therefore, we investigated how KIR2DS2 expression impacts NK cell function. Using a novel flow cytometry panel, we show that human NK cells with high KIR2DS2 expression have enhanced spontaneous activation against malignant B cell lines, liver cancer cell lines, and primary chronic lymphocytic leukemia cells. Surface expression of CD16 was increased on KIR2DS2high NK cells, and, accordingly, KIR2DS2high NK cells had increased activation against lymphoma cells coated with the clinically relevant anti-CD20 Abs rituximab and obinutuzumab. Bulk RNA sequencing revealed that KIR2DS2high NK cells have upregulation of NK-mediated cytotoxicity, translation, and FCGR gene pathways. We developed a novel single-cell RNA-sequencing technique to identify KIR2DS2+ NK cells, and this confirmed that KIR2DS2 is associated with enhanced NK cell–mediated cytotoxicity. This study provides evidence that KIR2DS2 marks a population of NK cells primed for anticancer activity and indicates that KIR2DS2 is an attractive target for NK-based therapeutic strategies.
Activation-Induced Cytidine Deaminase Impacts the Primary Antibody Repertoire in Naive Mice
Authors: Bao Katherine , Zhang Juan , Scherl Alexis , Ziai James , Hadadianpour Azi , Xu Daqi , Dela Cruz Christopher , Liu John , Liang Yuxin , Tam Lucinda , Corzo Cesar A , Roose-Girma Merone , Warming Soren , Modrusan Zora , Lee Wyne P , Hoi Kam Hon , Zarrin Ali A
Published: July 2022

Genetic and environmental cues shape the evolution of the B cell Ig repertoire. Activation-induced cytidine deaminase (AID) is essential to generating Ig diversity through isotype class switching and somatic mutations, which then directly influence clonal selection. Impaired B cell development in AID-knockout mice has made it difficult to study Ig diversification in an aging repertoire. Therefore, in this report, we used a novel inducible AID-knockout mouse model and discovered that deleting AID in adult mice caused spontaneous germinal center formation. Deep sequencing of the IgH repertoire revealed that Ab diversification begins early in life and evolves over time. Our data suggest that activated B cells form germinal centers at steady state and facilitate continuous diversification of the B cell repertoire. In support, we identified shared B cell lineages that were class switched and showed age-dependent rates of mutation. Our data provide novel context to the genesis of the B cell repertoire that may benefit the understanding of autoimmunity and the strength of an immune response to infection.
TOLLIP Optimizes Dendritic Cell Maturation to Lipopolysaccharide and Mycobacterium tuberculosis
Authors: Venkatasubramanian Sambasivan , Pryor Robyn , Plumlee Courtney , Cohen Sarah B , Simmons Jason D , Warr Alexander J , Graustein Andrew D , Saha Aparajita , Hawn Thomas R , Urdahl Kevin B , Shah Javeed A
Published: July 2022

TOLLIP is a central regulator of multiple innate immune signaling pathways, including TLR2, TLR4, IL-1R, and STING. Human TOLLIP deficiency, regulated by single-nucleotide polymorphism rs5743854, is associated with increased tuberculosis risk and diminished frequency of bacillus Calmette–Guérin vaccine-specific CD4+ T cells in infants. How TOLLIP influences adaptive immune responses remains poorly understood. To understand the mechanistic relationship between TOLLIP and adaptive immune responses, we used human genetic and murine models to evaluate the role of TOLLIP in dendritic cell (DC) function. In healthy volunteers, TOLLIP single-nucleotide polymorphism rs5743854 G allele was associated with decreased TOLLIP mRNA and protein expression in DCs, along with LPS-induced IL-12 secretion in peripheral blood DCs. As in human cells, LPS-stimulated Tollip−/− bone marrow–derived murine DCs secreted less IL-12 and expressed less CD40. Tollip was required in lung and lymph node–resident DCs for optimal induction of MHC class II and CD40 expression during the first 28 d of Mycobacterium tuberculosis infection in mixed bone marrow chimeric mice. Tollip−/− mice developed fewer M. tuberculosis–specific CD4+ T cells after 28 d of infection and diminished responses to bacillus Calmette–Guérin vaccination. Furthermore, Tollip−/− DCs were unable to optimally induce T cell proliferation. Taken together, these data support a model where TOLLIP-deficient DCs undergo suboptimal maturation after M. tuberculosis infection, impairing T cell activation and contributing to tuberculosis susceptibility.
Innate and Innate-like Effector Lymphocytes in Health and Disease
Authors: Van Kaer Luc , Postoak J Luke , Song Wenqiang , Wu Lan
Published: July 2022

Lymphocytes can be functionally partitioned into subsets belonging to the innate or adaptive arms of the immune system. Subsets of innate and innate-like lymphocytes may or may not express Ag-specific receptors of the adaptive immune system, yet they are poised to respond with innate-like speed to pathogenic insults but lack the capacity to develop classical immunological memory. These lymphocyte subsets display a number of common properties that permit them to integrate danger and stress signals dispatched by innate sensor cells to facilitate the generation of specialized effector immune responses tailored toward specific pathogens or other insults. In this review, we discuss the functions of distinct subsets of innate and innate-like lymphocytes. A better understanding of the mechanisms by which these cells are activated in different contexts, their interactions with other immune cells, and their role in health and disease may inform the development of new or improved immunotherapies.
Acetylcholine, Fatty Acids, and Lipid Mediators Are Linked to COVID-19 Severity
Authors: Pérez Malena M , Pimentel Vinícius E , Fuzo Carlos A , da Silva-Neto Pedro V , Toro Diana M , Fraga-Silva Thais F C , Gardinassi Luiz G , Oliveira Camilla N S , Souza Camila O S , Torre-Neto Nicola T , de Carvalho Jonatan C S , De Leo Thais C , Nardini Viviani , Feitosa Marley R , Parra Rogerio S , da Rocha José J R , Feres Omar , Vilar Fernando C , Gaspar Gilberto G , Constant Leticia F , Ostini Fátima M , Degiovani Augusto M , Amorim Alessandro P , Viana Angelina L , Fernandes Ana P M , Maruyama Sandra R , Russo Elisa M S , Santos Isabel K F M , Bonato Vânia L D , Cardoso Cristina R B , Sorgi Carlos A , Dias-Baruffi Marcelo , Faccioli Lúcia H
Published: July 2022

Lipid and cholinergic mediators are inflammatory regulators, but their role in the immunopathology of COVID-19 is still unclear. Here, we used human blood and tracheal aspirate (TA) to investigate whether acetylcholine (Ach), fatty acids (FAs), and their derived lipid mediators (LMs) are associated with COVID-19 severity. First, we analyzed the perturbation profile induced by SARS-CoV-2 infection in the transcriptional profile of genes related to the ACh and FA/LM pathways. Blood and TA were used for metabolomic and lipidomic analyses and for quantification of leukocytes, cytokines, and ACh. Differential expression and coexpression gene network data revealed a unique transcriptional profile associated with ACh and FA/LM production, release, and cellular signaling. Transcriptomic data were corroborated by laboratory findings: SARS-CoV-2 infection increased plasma and TA levels of arachidonic acid, 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid, 11-hydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid, and ACh. TA samples also exhibited high levels of PGE2, thromboxane B2, 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid, and 6-trans-leukotriene B4. Bioinformatics and experimental approaches demonstrated robust correlation between transcriptional profile in Ach and FA/LM pathways and parameters of severe COVID-19. As expected, the increased neutrophil-to-lymphocyte ratio, neutrophil counts, and cytokine levels (IL-6, IL-10, IL-1β, and IL-8) correlated with worse clinical scores. Glucocorticoids protected severe and critical patients and correlated with reduced Ach levels in plasma and TA samples. We demonstrated that pulmonary and systemic hyperinflammation in severe COVID-19 are associated with high levels of Ach and FA/LM. Glucocorticoids favored the survival of patients with severe/critical disease, and this effect was associated with a reduction in ACh levels.
Monitoring Circulating CD207+CD1a+ Cells in Langerhans Cell Histiocytosis and Clinical Implications
Authors: Olexen Cinthia Mariel , Rosso Diego Alfredo , Nowak Wanda , Fortunati Daniela , Errasti Andrea Emilse , Carrera Silva Eugenio Antonio
Published: July 2022

Langerhans cell histiocytosis (LCH) is a disorder characterized by an abnormal accumulation of CD207+ and CD1a+ cells in almost any tissue. Currently, there is a lack of prognostic markers to follow up patients and track disease reactivation or treatment response. Putative myeloid precursors CD207+ and CD1a+ cells were previously identified circulating in the blood. Therefore, we aim to develop a sensitive tracing method to monitor circulating CD207+ and CD1a+ cells in a drop of blood sample of patients with LCH. A total of 202 blood samples from patients with LCH and 23 controls were tested using flow cytometry. A standardized cellular score was defined by quantifying CD207+ and CD1a+ expression in monocytes and dendritic cells, based on CD11b, CD14, CD11c, and CD1c subpopulations, resulting in a unique value for each sample. The scoring system was validated by a receiver operating characteristic curve showing a reliable discriminatory capacity (area under the curve of 0.849) with a threshold value of 14, defining the presence of circulating CD207+ and CD1a+ cells. Interestingly, a fraction of patients with no evident clinical manifestation at the time of sampling also showed presence of these cells (29.6%). We also found a differential expression of CD207 and CD1a depending on the organ involvement, and a positive correlation between the cellular score and plasma inflammatory markers such as soluble CD40L, soluble IL-2Ra, and CXCL12. In conclusion, the analysis of circulating CD207 and CD1a cells in a small blood sample will allow setting a cellular score with minimal invasiveness, helping with prognostic accuracy, detecting early reactivation, and follow-up.
Mechanical Effects of a Specific Neurodynamic Mobilization of the Superficial Fibular Nerve: A Cadaveric Study
Authors: Lavoie Felix-Antoine , St-Pierre Marc-Olivier , Paquin Jean-Philippe , Gilbert Kerry , Ellis Richard , Sobczak Stephane
Published: July 2022

Context

A specific neurodynamic mobilization for the superficial fibular nerve (SFN) has been suggested in the reference literature for manual therapists to evaluate nerve mechanosensitivity in patients. However, no authors of biomechanical studies have examined the ability of this technique to produce nerve strain. Therefore, the mechanical specificity of this technique is not yet established.

Objectives

To test whether this examination and treatment technique produced nerve strain in the fresh frozen cadaver and the contribution of each motion to total longitudinal strain.

Design

Controlled laboratory study.

Setting

Laboratory.

Main Outcome Measure(s)

A differential variable reluctance transducer was inserted in 10 SFNs from 6 fresh cadavers to measure strain during the mobilization. A specific sequence of plantar flexion, ankle inversion, straight-leg raise position, and 30° of hip adduction was applied to the lower limb. The mobilization was repeated at 0°, 30°, 60°, and 90° of the straight-leg raise position to measure the effect of hip-flexion position.

Results

Compared with a resting position, this neurodynamic mobilization produced a significant amount of strain in the SFN (7.93% ± 0.51%, P < .001). Plantar flexion (59.34% ± 25.82%) and ankle inversion (32.80% ± 21.41%) accounted for the biggest proportions of total strain during the mobilization. No difference was noted among different hip-flexion positions. Hip adduction did not significantly contribute to final strain (0.39% ± 10.42%, P > .05), although high variability among limbs existed.

Conclusions

Ankle motion should be considered the most important factor during neurodynamic assessment of the SFN for distal entrapment. These results suggest that this technique produces sufficient strain in the SFN and could therefore be evaluated in vivo for correlation with mechanosensitivity.
Single-Legged Triple-Hop Propulsion Strategies in Females With and Those Without a History of Anterior Cruciate Ligament Reconstruction
Authors: Mulligan Colin M.S. , Gibbs Emma R. , Huang Yu-Lun , Stutzenberger Lyndsay R. , Johnson Samuel T. , Norcross Marc F.
Published: July 2022

Context

The single-legged triple hop is a commonly used functional task after anterior cruciate ligament reconstruction (ACLR). Recently, researchers have suggested that individuals may use a compensatory propulsion strategy to mask underlying quadriceps dysfunction and achieve symmetric hop performance.

Objective

To evaluate the performance and propulsion strategies used by females with and those without ACLR during a single-legged triple hop.

Design

Cross-sectional study.

Setting

Laboratory.

Patients or Other Participants

A total of 38 females, 19 with ACLR (age = 19.21 ± 1.81 years, height = 1.64 ± 0.70 m, mass = 63.79 ± 7.59 kg) and 19 without ACLR (control group; age = 21.11 ± 3.28 years, height = 1.67 ± 0.73 m, mass = 67.28 ± 9.25 kg).

Main Outcome Measure(s)

Hop distance and limb symmetry index (LSI) were assessed during a single-legged triple hop for distance. Propulsion strategies were evaluated during the first and second hops of the single-legged triple hop. Separate 2-way analysis-of-variance models were used to examine the influence of ACLR, joint, and their interaction on mechanical joint work, moment impulse, and the relative joint contributions to total work and moment impulse in females with and those without a history of ACLR.

Results

Despite achieving a mean LSI of approximately 96%, the ACLR group produced less total work in the reconstructed than the uninvolved limb during single-legged triple-hop propulsion (first hop: t18 = −3.73, P = .002; second hop: t18 = −2.55, P = .02). During the first and second hops, the reconstructed knee generated 19.3% (t18 = −2.33, P = .03) and 27.3% (t18 = −4.47, P < .001) less work than the uninvolved knee. No differences were identified between the involved and uninvolved limbs of the ACLR group in moment impulse (first hop: t18 = −0.44, P = .67; second hop: t18 = −0.32; P = .76). Irrespective of limb or group, the ankle was the largest contributor to both work and moment during both the first and second hops (P < .001).

Conclusions

Clinicians should exercise caution when using a single-legged triple hop as a surrogate for restored lower extremity function in females post–ACLR. This recommendation is driven by the compelling findings that knee-joint deficits persisted in the reconstructed limb despite an LSI of approximately 96% and, regardless of previous injury status, single-legged triple-hop propulsion was predominantly driven by the ankle.
Affect as a predictor of occupational engagement, career adaptability and career decidedness
Authors: Hartung Paul J. , Taylor Jeannine M. , Taber Brian J.
Published: July 2022

Background: Cognition and reason have received substantial and inordinate attention relative to emotion and intuition in understanding and intervening to promote vocational behaviour and career development.Objectives: Towards redressing this situation, the present study examined positive affect (PA) and negative affect (NA) as proxies for emotion with regard to their relationship with three career decision-making (CDM) variables.Method: A total of 250 university students (183 women, 65 men; mean age = 23 years; 88% Caucasian) responded to measures of affect, occupational engagement, career adaptability and career decidedness.Results: The study results supported hypothesised positive interrelationships amongst the three CDM variables. As hypothesised, regression analysis indicated that PA positively predicted the three CDM variables. Contrary to expectations, NA also positively predicted occupational engagement and career decidedness, albeit to a lesser degree.Conclusion: The present results indicate that emotions, both positive and negative, seem to be linked to important vocational processes and should be considered in career theory and intervention.