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1

Burais, Noël, Laurent Nicolas, Ronan Perrussel, Riccardo Scorretti und Nicolas Siauve. „Modélisation des interactions entre les champs électromagnétiques et les tissus biologiques“. Revue internationale de génie électrique 8, Nr. 5-6 (30.12.2005): 679–701. http://dx.doi.org/10.3166/rige.8.679-701.

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2

Debroas, Guilhaume, Guillaume Hoeffel, Ana Reynders und Sophie Ugolini. „Interactions neuro-immunes dans la peau“. médecine/sciences 34, Nr. 5 (Mai 2018): 432–38. http://dx.doi.org/10.1051/medsci/20183405016.

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Lors d’une infection, notre capacité à éliminer les pathogènes dépend essentiellement de notre système immunitaire. Des études récentes révèlent cependant un rôle du système nerveux dans la régulation des processus infectieux et inflammatoires. Des interactions fonctionnelles bidirectionnelles s’établissent entre systèmes nerveux et immunitaire pour préserver l’intégrité des tissus. La peau constitue l’une des premières lignes de défense contre les menaces extérieures et présente un système neuro-immun particulièrement développé. En cas de lésion cutanée, des neurones impliqués dans la perception douloureuse sont activés et modulent la fonction et le recrutement des cellules immunitaires au sein du tissu. Nous illustrons ici l’importance de ces régulations neuro-immunes à travers différents exemples de pathologies cutanées.
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BONNET, M., I. LOUVEAU, I. CASSAR-MALEK, L. LEFAUCHEUR und P. Y. RESCAN. „Comprendre le développement des muscles et des tissus adipeux : un préalable pour maîtriser les qualités des carcasses et des produits des animaux d’élevage“. INRA Productions Animales 28, Nr. 2 (13.01.2020): 137–50. http://dx.doi.org/10.20870/productions-animales.2015.28.2.3021.

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Les qualités des carcasses et des viandes/chairs des espèces d’intérêt agronomique (mammifères, espèces aviaires et poissons) dépendent en grande partie des caractéristiques et des proportions relatives des différents compartiments tissulaires, principalement les fibres et le tissu conjonctif musculaires et les tissus adipeux. Dans cette revue, nous décrivons la mise en place de ces trois compartiments au cours du développement embryonnaire et foetal, ainsi que leur croissance après la naissance ou l’éclosion. Les fibres musculaires et le tissu conjonctif des muscles du tronc sont issus de domaines embryonnaires distincts de ceux à l’origine des muscles des membres et de la tête. L’origine embryonnaire des adipocytes blancs reste à établir, mais est vraisemblablement multiple et dépendante de la localisation anatomique des tissus adipeux. La croissance post-embryonnaire des muscles et des tissus adipeux implique la prolifération puis la différenciation de cellules progénitrices non-embryonnaires. Le nombre total de fibres musculaires est fixé aux deux tiers ou aux quatre cinquièmes de la gestation chez le bovin et le porc respectivement, et dès la naissance chez les volailles alors qu’il augmente encore après l’éclosion chez certains poissons. Le nombre d’adipocytes augmente durant la croissance foetale et dans une moindre mesure après la naissance. Des interactions entre tissus au cours de la croissance, auparavant suggérées, sont maintenant démontrées par l’identification de protéines sécrétées par les cellules musculaires et adipeuses qui participent au dialogue entre tissus.
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LEBRET, B., L. LEFAUCHEUR und J. MOUROT. „La qualité de la viande de porc. Influence des facteurs d’élevage non génétiques sur les caractéristiques du tissu musculaire“. INRAE Productions Animales 12, Nr. 1 (23.02.1999): 11–28. http://dx.doi.org/10.20870/productions-animales.1999.12.1.3851.

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Les interactions entre le type génétique, les conditions d’élevage et les conditions d’abattage des animaux déterminent la qualité de la fraction maigre des viandes de porc. L’influence du type génétique, en particulier la présence des gènes majeurs Hal et RN-, ainsi que les conditions d’abattage ont des conséquences importantes et maintenant bien établies sur la qualité. Une fois ces facteurs maîtrisés, l’amélioration de la qualité des viandes nécessite la prise en compte de l’influence des facteurs d’élevage non génétiques sur les propriétés des tissus maigres, ce qui constitue l’objectif de la présente revue. Cet article présente les caractéristiques du tissu musculaire, en particulier les fibres musculaires, les lipides intramusculaires et le tissu conjonctif, puis les relations entre ces caractéristiques et les composantes organoleptique, technologique, nutritionnelle et hygiénique de la qualité. Nous décrivons ensuite les effets de différents facteurs d’élevage : âge et poids à l’abattage, type sexuel, niveau et nature de la ration alimentaire, promoteurs de croissance, température ambiante, activité physique et système d’élevage, sur les propriétés des muscles et leur incidence sur la qualité des viandes. Si certaines relations sont bien établies, comme l’effet favorable, jusqu’à 3 % environ, du taux de lipides intramusculaires sur la qualité sensorielle, l’influence des propriétés des fibres (type contractile et métabolique, diamètre) sur la qualité des viandes est moins claire. La détermination des caractéristiques musculaires favorables aux différentes composantes de la qualité, ainsi qu’une meilleure connaissance des mécanismes de différenciation et de développement des tissus conduisant à ces caractéristiques sont nécessaires, afin de pouvoir répondre aux besoins variés des transformateurs et consommateurs
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CHILLIARD, Y., und A. OLLIER. „Alimentation lipidique et métabolisme du tissu adipeux chez les ruminants. Comparaison avec le porc et les rongeurs“. INRAE Productions Animales 7, Nr. 4 (27.09.1994): 293–308. http://dx.doi.org/10.20870/productions-animales.1994.7.4.4176.

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Les effets de la supplémentation en lipides des rations pour vaches laitières sont récapitulés, en particulier pour ce qui concerne l’efficacité énergétique, la production laitière, le bilan énergétique et les variations de poids vif et d’état corporel. La supplémentation lipidique ne modifie pas le gain de poids vif ou d’état corporel après le pic de lactation mais tend à accroître la perte de poids vif en début de lactation, malgré l’accroissement du bilan énergétique calculé. La supplémentation lipidique tend à accroître le dépôt des lipides corporels chez le ruminant en croissance. Elle diminue la synthèse de novo d’acides gras dans les tissus adipeux, sans changer l’activité de la lipoprotéine lipase ni la capacité d’estérification totale des acides gras in vitro. La libération basale d’acides gras libres par le tissu adipeux in vitro, et les réponses lipolytiques beta- adrénergiques, sont accrues par les acides gras polyinsaturés protégés. La supplémentation en lipides accroît le dépôt des lipides corporels chez le porc en croissance lorsqu’il est dans un environnement chaud ou à la neutralité thermique. Chez la truie en lactation, elle accroît l’ingestion d’énergie et la sécrétion des lipides du lait, tout en diminuant la perte de poids vif. La supplémentation lipidique diminue la synthèse de novo d’acides gras et la libération basale de glycérol par le tissu adipeux de porc, et tend à accroître les réponses lipolytiques beta-adrénergiques simultanément à un accroissement de la fluidité membranaire et à une diminution de l’activité de la phosphodiestérase. Les lipides corporels sont accrus chez les rongeurs qui reçoivent des régimes enrichis en lipides, mais de façon moins marquée avec les lipides riches en acides gras polyinsaturés. L’activité de la lipoprotéine lipase du tissu adipeux est diminuée. La synthèse d’acides gras dans le foie est fortement diminuée par les acides gras polyinsaturés, et de façon moindre dans les tissus adipeux. La réponse beta-adrénergique de la lipolyse des tissus adipeux est diminuée, l’estérification est augmentée, et une résistance à l’insuline apparaît, en particulier avec les acides gras saturés. Il existe d’importantes interactions entre la supplémentation des rations en lipides, l’espèce animale et l’état physiologique. Les acides gras ingérés sont orientés prioritairement vers la mamelle pendant la lactation, ce qui explique la faible réponse des tissus adipeux, en particulier chez les ruminants où la supplémentation en lipides n’augmente que faiblement l’ingestion d’énergie.
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Piecq, Andrée. „Les pratiques médicales au 21e siècle“. Acta Europeana Systemica 7 (11.07.2020): 153–62. http://dx.doi.org/10.14428/aes.v7i1.56703.

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En ce 21e siècle notre conception du monde est modifiée par l’explosion des nouvelles technologies qu’elles soient du domaine de la communication, de l’intelligence artificielle ou encore en neurochirurgie ... Vers quels paradigmes allons-nous ? Quels risques courons-nous ? En effet : « Sciences sans conscience n’est que ruine de l’âme » (Rabelais). Cet article tente, à travers l’observation de l’évolution de la médecine de démontrer que : « nouveaux paradigmes et réflexions éthiques » doivent évoluer ensemble. La médecine du XXIe siècle ne se contente plus des connaissances traditionnelles de l’art de guérir et de soigner. Elle se doit de s’approprier les évolutions scientifiques et les techniques ainsi que les modifications des interactions entre les professionnels, les patients, les scientifiques et les techniciens. Elle se situe à l’interface multidisciplinaire et transdisciplinaire de l’évolution des sciences et des techniques (les nanotechnologies, les biotechniques, les technologies de l'Information, les sciences cognitives, le clonage, les microchirurgies, les greffes d’organes et de tissus, la procréation assistée, la télémédecine, l'imagerie et la biologie moléculaire ...). Tout cela suscite l’apparition de nouveaux paradigmes.Cet article va soulever certains points à analyser en profondeur. Il part de l’observation des pratiques médicales et les déclinent en 3 niveaux logiques : 1. Le niveau micro : la pratique del’art de guérir et de soigner en ajoutant les nouvelles technologies, 2. Le niveau méso : l’amélioration des caractéristiques physiques et mentales des êtres humains. 3. Le niveau macro qui ajoute au niveau méso : la suppression des handicaps, de la souffrance, de maladie, de la vieillesse et la mort. A partir de ces 3 niveaux, des questions se posent sur 1. des finalités, 2. des règles (mythiques et phénoménologiques) qui les régissent, 3. des frontières à transgresser ou pas, 4. des Interactions entre les professionnels les chercheurs. Les concepts systémiques utilisés pour appréhender ces 3 niveaux sont : la finalité, le contexte, les frontières, les règles, et certains éléments de la communication tel que les interactions. Une proposition de réponse à ces questions va émerger de cette l’analyse systémique.
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Baujat, G. „Interactions entre activité physique, tissu musculaire et tissu osseux“. Perfectionnement en Pédiatrie 5, Nr. 3 (Januar 2023): 3S24–3S28. http://dx.doi.org/10.1016/s2588-932x(23)00032-3.

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8

Confavreux, Cyrille B. „Interactions entre tissu osseux et métabolisme énergétique“. Revue du Rhumatisme 77, Nr. 4 (Juli 2010): 323–25. http://dx.doi.org/10.1016/j.rhum.2010.03.017.

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9

Altieri, Anthony, Grace V. Visser und Matthew B. Buechler. „Enter the Matrix: Fibroblast-immune interactions shape ECM deposition in health and disease.“ F1000Research 13 (19.02.2024): 119. http://dx.doi.org/10.12688/f1000research.143506.1.

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Fibroblasts, non-hematopoietic cells of mesenchymal origin, are tissue architects which regulate the topography of tissues, dictate tissue resident cell types, and drive fibrotic disease. Fibroblasts regulate the composition of the extracellular matrix (ECM), a 3-dimensional network of macromolecules that comprise the acellular milieu of tissues. Fibroblasts can directly and indirectly regulate immune responses by secreting ECM and ECM-bound molecules to shape tissue structure and influence organ function. In this review, we will highlight recent studies which elucidate the mechanisms by which fibroblast-derived ECM factors (e.g., collagens, fibrillar proteins) regulate ECM architecture and subsequent immune responses, with a focus on macrophages. As examples of fibroblast-derived ECM proteins, we examine Collagen Triple Helix Repeat Containing 1 (CTHRC1) and Transforming Growth Factor-β-inducible protein (TGFBI), also known as BIGH3. We address the need for investigation into how diverse fibroblast populations coordinate immune responses by modulating ECM, including the fibroblast-ECM-immune axis and the precise molecular mediators and pathways which regulate these processes. Finally, we will outline how novel research identifying key regulators of ECM deposition is critical for therapeutic development for fibrotic diseases and cancer.
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Kubota, Marie, und Takao Hashiguchi. „Unique Tropism and Entry Mechanism of Mumps Virus“. Viruses 13, Nr. 9 (01.09.2021): 1746. http://dx.doi.org/10.3390/v13091746.

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Mumps virus (MuV) is an important human pathogen that causes parotitis, orchitis, oophoritis, meningitis, encephalitis, and sensorineural hearing loss. Although mumps is a vaccine-preventable disease, sporadic outbreaks have occurred worldwide, even in highly vaccinated populations. MuV not only causes systemic infection but also has a unique tropism to glandular tissues and the central nervous system. In general, tropism can be defined by multiple factors in the viral life cycle, including its entry, interaction with host factors, and host-cell immune responses. Although the underlying mechanisms of MuV tropism remain to be fully understood, recent studies on virus–host interactions have provided insights into viral pathogenesis. This review was aimed at summarizing the entry process of MuV by focusing on the glycan receptors, particularly the recently identified receptors with a trisaccharide core motif, and their interactions with the viral attachment proteins. Here, we describe the receptor structures, their distribution in the human body, and the recently identified host factors for MuV and analyze their relationship with MuV tropism.
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De Moraes, Consuelo M., W. J. Lewis und James H. Tumlinson. „Examining plant-parasitoid interactions in tritrophic systems“. Anais da Sociedade Entomológica do Brasil 29, Nr. 2 (Juni 2000): 189–203. http://dx.doi.org/10.1590/s0301-80592000000200001.

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The demonstration that parasitoids are attracted to volatile compounds released by plants in response to herbivore feeding has generated a great deal of interest over the past ten years. The release of volatile signals by plants occurs not only in response to tissue damage but is also specifically initiated by exposure to herbivore salivary secretions. Although some volatile compounds are stored in plant tissues and immediately released when damage occurs, others are induced by herbivore feeding and released not only from damaged tissue but also from undamaged leaves. Thus, damage localized to only a few leaves results in a systemic response and the release of volatiles from the entire plant. New evidence suggests that, in addition to being highly detectable and reliable indicators of herbivore presence, herbivore-induced plant volatiles may convey herbivore-specific information that allows parasitoids to discriminate even closely-related herbivore species at long range. Here we give an overview of the recent developments in the investigation of plant-parasitoid interactions.
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Martin-Martin, Ines, Thiago Luiz Alves E. Silva, Adeline E. Williams, Joel Vega-Rodriguez und Eric Calvo. „A Simple Method for Immunohistochemistry and Imaging of Mosquito Salivary Glands“. Cold Spring Harbor Protocols 2022, Nr. 10 (05.08.2022): pdb.prot107990. http://dx.doi.org/10.1101/pdb.prot107990.

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Immunohistochemistry is a valuable technique that provides information on protein localization and interactions in tissues. Mosquito salivary gland immunohistochemistry requires the meticulous dissection of a delicate tissue. The integrity of the salivary glands must be closely monitored throughout the entire process to prevent structural damage and loss of saliva. This protocol describes a series of simple steps to perform salivary gland immunohistochemistry including tissue dissection, permeabilization, immunostaining, mounting, and imaging by confocal microscopy.
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Chanda, Arnab, Subhodip Chatterjee und Vivek Gupta. „Soft composite based hyperelastic model for anisotropic tissue characterization“. Journal of Composite Materials 54, Nr. 28 (23.06.2020): 4525–34. http://dx.doi.org/10.1177/0021998320935560.

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Soft tissues are complex anisotropic composite systems comprising of multiple differently oriented layers of fiber embedded within a soft matrix. To date, soft tissues have been mainly characterized using simplified linear elastic material models, isotropic viscoelastic and hyperelastic models, and transversely isotropic models. In such models, the effect of fiber volume fraction (FVF), fiber orientation, and fiber-matrix interactions are missing, inhibiting accurate characterization of anisotropic tissue properties. The current work addresses this literature gap with the development of a novel soft composite based material framework to model tissue anisotropy. In this model, the fiber and matrix are considered as separate hyperelastic materials, and fiber-matrix interaction is modeled using multiplicative decomposition of the deformation gradient. The effect of the individual contribution of the fibers and matrix are introduced into the numerical framework for a single soft composite layer, and fiber orientation effects are incorporated into the strain energy functions. Also, strain energy formulations are developed for multiple soft composite layers with varying fiber orientations and contributions, describing the biomechanical behavior of an entire anisotropic tissue block. Stress-strain relationships were derived from the strain energy equations for a uniaxial mechanical test condition. To validate the model parameters, experimental models of soft composites tested under uniaxial tension were characterized using the novel anisotropic hyperelastic model (R2 = 0.983). To date, such a robust anisotropic hyperelastic composite framework has not been developed, which would be indispensable for experimental characterization of tissues and for improving the fidelity of computational biological models in future.
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Shatunova, Polina O., Anatoly S. Bykov, Oksana A. Svitich und Vitaly V. Zverev. „Angiotensin-converting enzyme 2. Approaches to pathogenetic therapy of COVID-19“. Journal of microbiology, epidemiology and immunobiology 97, Nr. 4 (02.09.2020): 339–45. http://dx.doi.org/10.36233/0372-9311-2020-97-4-6.

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The SARS-CoV-2 virus is a pathogen causing the coronavirus infection that culminated in a worldwide pandemic in 2020. It belongs to β-coronaviruses and has high genetic similarity to the SARS-CoV virus that is responsible for an outbreak of severe acute respiratory syndrome in 2002–2003. The analysis of molecular interactions shows that SARS-CoV-2 has higher virulence due to lower binding free energy in interaction with the angiotensin-converting enzyme 2 (ACE2), which is used by the virus to enter the host cell. At the time of the global coronavirus pandemic, the thorough study of ACE2 as a key component of the disease pathogenesis comes to the fore. The detailed study of the enzyme, which is a receptor located on the surface of different tissues and which normally catalyzes the conversion of angiotensin II to angiotensin (1–7), led to diverging conclusions. Being non-tissue specific, the receptor is abundantly present in the heart, kidneys, small intestine, testes, thyroid, and adipose tissue. Besides regulating blood pressure, it suppresses inflammation, mainly in the lung tissue, participates in amino acid transport and maintains the activity of the gut microbiome. With all its essential positive functions, the role of ACE2 is highly ambiguous, specifically in coronavirus infection. The influence on the renin-angiotensin system can be seen as a promising therapeutic route in treatment of coronavirus infection. The preliminary data on using of ACE2 inhibitors, soluble forms of ACE2, and angiotensin II receptor blockers demonstrate their effectiveness and, consequently, improvement in symptoms and prognoses for patients with coronavirus infection. The review presents information about ACE2 distribution in human tissues, explores its interaction with SARS-CoV-2, provides a theoretical basis for medications involving ACE2 metabolic pathways and for using them in treatment of coronavirus infection and its prevention.
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Raff, Rudolf A., und Elizabeth C. Raff. „The Role of Biology in the Fossilization of Embryos and Other Soft-Bodied Organisms: Microbial Biofilms and Lagerstätten“. Paleontological Society Papers 20 (Oktober 2014): 83–100. http://dx.doi.org/10.1017/s1089332600002813.

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Soft-tissue fossils are among the most striking and informative remains of extinct organisms. Although relatively rare, they are diverse, ranging from single microbial cells to nuclei and chromosomes; algae; metazoan embryos and larvae; flowers; complete, small, soft-bodied metazoans, metazoan tissues; integumentary structures such as melanosomes; skin texture, vertebrate feathers and hair, insect wings with color patterns, and sometimes even the entire bodies of large animals. The susceptibility of newly dead soft tissues to physical destruction, consumption, and microbial decay makes their preservation unlikely under most taphonomic conditions. In addition, their vulnerability to rapid autolysis, bioturbation, and destructive physical processes requires that rapid biological events must occur as the critical first steps of fossilization. An understanding of the processes by which biological remains enter the fossil record is important in inferring what non-microbial and microbial processes were operative in Lagerstätten. Paleontologists have recognized that microbial biofilms often accompany soft-tissue fossils, and have suggested that bacteria play an active role in soft tissue fossilization, but that role must be determined experimentally with living bacteria and dead tissue.Marine embryos and marine bacteria are used to investigate the processes that mediate early steps in soft-tissue preservation because they offer simple systems for laboratory investigation of the roles of autolysis-blocking environments, microbial interactions, biofilm formation, and authigenic mineralization in taphonomy. Understanding microbially mediated preservation of embryos may supply new insights into a more general biology of fossilization.
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Cheng, Laurence E., Brandon M. Sullivan, Lizett E. Retana, Christopher D. C. Allen, Hong-Erh Liang und Richard M. Locksley. „IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function“. Journal of Experimental Medicine 212, Nr. 4 (16.03.2015): 513–24. http://dx.doi.org/10.1084/jem.20141671.

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Vertebrate immunity has evolved a modular architecture in response to perturbations. Allergic inflammation represents such a module, with signature features of antigen-specific IgE and tissue eosinophilia, although the cellular and molecular circuitry coupling these responses remains unclear. Here, we use genetic and imaging approaches in models of IgE-dependent eosinophilic dermatitis to demonstrate a requisite role for basophils. After antigenic inflammation, basophils initiate transmigration like other granulocytes but, upon activation via their high-affinity IgE receptor, alter their migratory kinetics to persist at the endothelium. Prolonged basophil–endothelial interactions, in part dependent on activation of focal adhesion kinases, promote delivery of basophil-derived IL-4 to the endothelium and subsequent induction of endothelial vascular cell adhesion molecule-1 (VCAM-1), which is required for eosinophil accumulation. Thus, basophils are gatekeepers that link adaptive immunity with innate effector programs by altering access to tissue sites by activation-induced interactions with the endothelium.
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Hiraiwa, Tetsuya, Fu-Lai Wen, Tatsuo Shibata und Erina Kuranaga. „Mathematical Modeling of Tissue Folding and Asymmetric Tissue Flow during Epithelial Morphogenesis“. Symmetry 11, Nr. 1 (19.01.2019): 113. http://dx.doi.org/10.3390/sym11010113.

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Recent studies have revealed that intrinsic, individual cell behavior can provide the driving force for deforming a two-dimensional cell sheet to a three-dimensional tissue without the need for external regulatory elements. However, whether intrinsic, individual cell behavior could actually generate the force to induce tissue deformation was unclear, because there was no experimental method with which to verify it in vivo. In such cases, mathematical modeling can be effective for verifying whether a locally generated force can propagate through an entire tissue and induce deformation. Moreover, the mathematical model sometimes provides potential mechanistic insight beyond the information obtained from biological experimental results. Here, we present two examples of modeling tissue morphogenesis driven by cell deformation or cell interaction. In the first example, a mathematical study on tissue-autonomous folding based on a two-dimensional vertex model revealed that active modulations of cell mechanics along the basal–lateral surface, in addition to the apical side, can induce tissue-fold formation. In the second example, by applying a two-dimensional vertex model in an apical plane, a novel mechanism of tissue flow caused by asymmetric cell interactions was discovered, which explained the mechanics behind the collective cellular movement observed during epithelial morphogenesis.
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Blanc, Nathalie. „L’inter-agir professionnel entre terrain et recherche en éducation“. Diversité 177, Nr. 1 (2014): 109–14. http://dx.doi.org/10.3406/diver.2014.8361.

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L’analyse de corpus vidéo, l’écriture du mémoire professionnel, le stage de pratique accompagnée en mobilité internationale et la création d’espaces de rencontre entre sphère de recherche et sphère professionnelle sont des dispositifs qui peuvent contribuer à tisser des liens entre terrain et théorie dans la formation. Notre contribution propose un regard original sur les interactions prometteuses entre terrain, recherche et formation.
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Mallol, Christophe Serra. „Entre local et global : l’alimentation polynésienne“. Anthropologie et Sociétés 37, Nr. 2 (15.08.2013): 137–53. http://dx.doi.org/10.7202/1017909ar.

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Les interactions entre influences globales, mondialisées et de type occidental, et traditions locales différenciées forment le tissu de l’expérience humaine contemporaine. La généralisation de la circulation des capitaux, des biens, des idées et des hommes, ainsi que la prise de conscience de leur interconnexion, sont constitutifs du processus de globalisation, notamment dans le domaine de l’alimentation. Lieu privilégié de rencontre du global et du local, une anthropologie de l’alimentation polynésienne permet la mise en évidence d’un processus d’adaptation du local au global, une forme de « glocalisation alimentaire ». Appliquée aux Îles de la Société et à Rapa (Polynésie française), elle met en évidence la complexité mouvante des interrelations qui lient les hommes entre eux, à leurs traditions et à des influences exogènes. La prise de conscience par les acteurs sociaux de nouvelles formes de modèles normatifs possibles permet de dépasser les modèles alimentaires parfois vécus comme imposés, entre résistance, adaptation et création hybride.
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Devaprasad, Abhinandan, und Aridaman Pandit. „Enrichment of SARS-CoV-2 Entry Factors and Interacting Intracellular Genes in Tissue and Circulating Immune Cells“. Viruses 13, Nr. 9 (02.09.2021): 1757. http://dx.doi.org/10.3390/v13091757.

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SARS-CoV-2 uses ACE2 and TMPRSS2 to gain entry into the cell. However, recent studies have shown that SARS-CoV-2 may use additional host factors that are required for the viral lifecycle. Here we used publicly available datasets, CoV-associated genes, and machine learning algorithms to explore the SARS-CoV-2 interaction landscape in different tissues. We found that in general a small fraction of cells express ACE2 in the different tissues, including nasal, bronchi, and lungs. We show that a small fraction of immune cells (including T cells, macrophages, dendritic cells) found in tissues also express ACE2. We show that healthy circulating immune cells do not express ACE2 and TMPRSS2. However, a small fraction of circulating immune cells (including dendritic cells, monocytes, T cells) in the PBMC of COVID-19 patients express ACE2 and TMPRSS2. Additionally, we found that a large spectrum of cells (in tissues and circulation) in both healthy and COVID-19-positive patients were significantly enriched for SARS-CoV-2 factors, such as those associated with RHOA and RAB GTPases, mRNA translation proteins, COPI- and COPII-mediated transport, and integrins. Thus, we propose that further research is needed to explore if SARS-CoV-2 can directly infect tissue and circulating immune cells to better understand the virus’ mechanism of action.
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Enkerli, K., C. W. Mims und M. G. Hahn. „Ultrastructure of compatible and incompatible interactions of soybean roots infected with the plant pathogenic oomycete Phytophthora sojae“. Canadian Journal of Botany 75, Nr. 9 (01.09.1997): 1493–508. http://dx.doi.org/10.1139/b97-864.

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Compatible and incompatible interactions of two soybean isolines containing either Rps1a or Rps1b resistance genes with races 2 and 8 of Phytophthora sojae were examined by light and electron microscopy. Phytophthora sojae race 2 is virulent on Rps1b plants and avirulent on Rps1a plants. Race 8 shows the reverse reaction; it is avirulent on Rps1b plants, but virulent on Rps1a plants. All combinations of races and cultivars were examined at times ranging from 30 min to 20 h postinoculation. Zoospore encystment, germination, and infection occurred within 30 min in all interactions. No evidence of appressorium formation was found. Wall appositions in epidermal cells adjacent to hyphae were very frequent by 30 min postinoculation. Differences between compatible and incompatible interactions became evident as early as 4 h postinoculation. The major difference appeared to relate to timing of host responses, which lead to two different types of relationships. In compatible interactions, P. sojae exhibited a short biotrophic phase with the establishment of many haustoria without triggering visible plant responses in cortical cells until approximately 10 h postinoculation. By 15 h postinoculation, almost the entire root was necrotic, wall appositions were abundant, and vascular tissue was colonized. The incompatible interaction was characterized by a nearly complete absence of haustoria, rapid host cell necrosis, and formation of many wall appositions by 4 h postinoculation. The pathogen rarely penetrated beyond the endodermis of the resistant host and colonization of vascular tissue was rare. Overall there were clear ultrastructural differences between compatible and incompatible interactions of soybean with P. sojae. These data support a strong correlation of resistance with host cell death, formation of wall appositions, and absence of root stele colonization. Key words: Phytophthora sojae, Glycine max, host–pathogen interaction, ultrastructure.
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Bodea, Ioana Maria, Giorgiana Mihaela Cătunescu, Teodor Florian Stroe, Sonia Alexandra Dîrlea und Florin Ioan Beteg. „Applications of bacterial-synthesized cellulose in veterinary medicine – a review“. Acta Veterinaria Brno 88, Nr. 4 (2019): 451–71. http://dx.doi.org/10.2754/avb201988040451.

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Tissue engineering promotes tissue regeneration through biomaterials that have excellent properties and have the potential to replace tissues. Many studies show that bacterial cellulose (BC) might ensure tissue regeneration and substitution, being used for the bioengineering of hard, cartilaginous and soft tissues. Bacterial cellulose is extensively used as wound dressing material and results show that BC is a promising tissue scaffold (bone, cardiovascular, urinary tissue). It can be combined with polymeric and non-polymeric compounds to acquire antimicrobial, cell-adhesion and proliferation properties. To ensure proper tissue regeneration, the material has to be: biocompatible, with minimum tissue reaction and biodegradability; bio-absorbable, to promote tissue development, cellular interaction and grow; resistant to support the weight of the newly formed tissue. Its versatile structure, physical and biochemical properties can be adjusted by adapting the bacteria culturing conditions. The main biomedical applications seem to be as hard (bone, dental), fibrocartilaginous (meniscal) and soft tissue (skin, cardiovascular, urinary) substituents. This paper reviews the current state of knowledge, challenges and future applications of BC and its biomedical potential in veterinary medicine. It was focused on the main uses in regeneration and scaffold tissue replacement and, although BC showed promising results, there is a lack of successful results of BC use in clinical practice. Most studies were performed only at experimental level and further research is needed for BC to enter clinical veterinary practice.
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Johnson, Louise A., und David G. Jackson. „Hyaluronan and Its Receptors: Key Mediators of Immune Cell Entry and Trafficking in the Lymphatic System“. Cells 10, Nr. 8 (12.08.2021): 2061. http://dx.doi.org/10.3390/cells10082061.

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Entry to the afferent lymphatics marks the first committed step for immune cell migration from tissues to draining lymph nodes both for the generation of immune responses and for timely resolution of tissue inflammation. This critical process occurs primarily at specialised discontinuous junctions in initial lymphatic capillaries, directed by chemokines released from lymphatic endothelium and orchestrated by adhesion between lymphatic receptors and their immune cell ligands. Prominent amongst the latter is the large glycosaminoglycan hyaluronan (HA) that can form a bulky glycocalyx on the surface of certain tissue-migrating leucocytes and whose engagement with its key lymphatic receptor LYVE-1 mediates docking and entry of dendritic cells to afferent lymphatics. Here we outline the latest insights into the molecular mechanisms by which the HA glycocalyx together with LYVE-1 and the related leucocyte receptor CD44 co-operate in immune cell entry, and how the process is facilitated by the unusual character of LYVE-1 • HA-binding interactions. In addition, we describe how pro-inflammatory breakdown products of HA may also contribute to lymphatic entry by transducing signals through LYVE-1 for lymphangiogenesis and increased junctional permeability. Lastly, we outline some future perspectives and highlight the LYVE-1 • HA axis as a potential target for immunotherapy.
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Borrmann, Helene, und Filipa Rijo-Ferreira. „Crosstalk between circadian clocks and pathogen niche“. PLOS Pathogens 20, Nr. 5 (09.05.2024): e1012157. http://dx.doi.org/10.1371/journal.ppat.1012157.

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Circadian rhythms are intrinsic 24-hour oscillations found in nearly all life forms. They orchestrate key physiological and behavioral processes, allowing anticipation and response to daily environmental changes. These rhythms manifest across entire organisms, in various organs, and through intricate molecular feedback loops that govern cellular oscillations. Recent studies describe circadian regulation of pathogens, including parasites, bacteria, viruses, and fungi, some of which have their own circadian rhythms while others are influenced by the rhythmic environment of hosts. Pathogens target specific tissues and organs within the host to optimize their replication. Diverse cellular compositions and the interplay among various cell types create unique microenvironments in different tissues, and distinctive organs have unique circadian biology. Hence, residing pathogens are exposed to cyclic conditions, which can profoundly impact host–pathogen interactions. This review explores the influence of circadian rhythms and mammalian tissue-specific interactions on the dynamics of pathogen–host relationships. Overall, this demonstrates the intricate interplay between the body’s internal timekeeping system and its susceptibility to pathogens, which has implications for the future of infectious disease research and treatment.
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Woods, Amber, Nithya Srivinasan und Victor Engelhard. „Effector TCD8 use different homing receptor/ligand interactions to enter subcutaneous and intraperitoneal B16 melanoma tumors (TUM7P.1022)“. Journal of Immunology 194, Nr. 1_Supplement (01.05.2015): 142.11. http://dx.doi.org/10.4049/jimmunol.194.supp.142.11.

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Abstract Immunotherapies have the potential to control cancer, but are currently only effective in patients with a preexisting TCD8 infiltrate. TCD8 infiltration into tissues relies on interactions between homing receptors on TCD8 and ligands on the vasculature. However, those required for entry into tumors are incompletely characterized. Using B16 melanoma expressing the strong antigen ovalbumin, the homing receptor ligands VCAM-1 and E-selectin were more highly expressed on SC tumor vasculature, while MadCAM-1 was expressed more highly on IP tumor vasculature. B16 parental tumors and tumors grown in Rag1KO animals expressed negligible levels of VCAM-1 and MadCAM-1, suggesting that activated adaptive immune cells that previously infiltrated the tumor drove their expression. Our previous work showed that anatomical site of TCD8 priming results in differential expression of α4β1, α4β7, and E-Selectin Ligand (ESL) on effectors. We showed that α4β1+ effectors enter SC and IP tumors via interaction with VCAM-1, while ESL+ effectors preferentially enter SC tumors via interaction with E-Selectin. Unexpectedly, α4β7 and MadCAM-1 did not mediate entry into IP tumors, apparently because MadCAM-1 was not expressed on the luminal surface. Our results suggest that the commonly used SC vaccination route generates effectors that may not home efficiently to visceral metastases. Vaccination targeting non-skin draining LN may generate effectors that infiltrate visceral metastases more efficiently.
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Olivier, Alain. „La relation entre le Striga hermonthica et ses hôtes: une synthèse“. Canadian Journal of Botany 74, Nr. 7 (01.07.1996): 1119–37. http://dx.doi.org/10.1139/b96-137.

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The parasitic weed Striga hermonthica causes considerable yield losses in maize, pearl millet, and sorghum in Africa. The extent of the damage caused to crops is related to their close interaction with the parasite. The S. hermonthica seed germinates in response to germination stimulants exuded by cereal roots. The rootlet extremity then turns into a haustorium that attaches itself to the host root and penetrates its tissue. In this manner, a connection is established between the vascular systems of both plants, allowing absorption of water, minerals, and organic compounds that are essential for the parasite's development. S. hermonthica also affects the host's metabolism and photosynthesis. No effective control method against the parasite is available for the African peasants. The utilization of germination stimulants and herbicides, the rotation practice, and intercropping as well as biological control and varietal selection have given disappointing results so far. A better understanding of host resistance mechanisms is necessary to develop new methods for the control of the parasite. Keywords: Striga hermonthica, germination, haustorium, host–parasite interaction, control methods, resistance.
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Dubreuil, J. Daniel, Giuseppe Del Giudice und Rino Rappuoli. „Helicobacter pylori Interactions with Host Serum and Extracellular Matrix Proteins: Potential Role in the Infectious Process“. Microbiology and Molecular Biology Reviews 66, Nr. 4 (Dezember 2002): 617–29. http://dx.doi.org/10.1128/mmbr.66.4.617-629.2002.

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SUMMARY Helicobacter pylori, a gram-negative spiral-shaped bacterium, specifically colonizes the stomachs of humans. Once established in this harsh ecological niche, it remains there virtually for the entire life of the host. To date, numerous virulence factors responsible for gastric colonization, survival, and tissue damage have been described for this bacterium. Nevertheless, a critical feature of H. pylori is its ability to establish a long-lasting infection. In fact, although good humoral (against many bacterial proteins) and cellular responses are observed, most infected persons are unable to eradicate the infection. A large body of evidence has shown that the interaction between H. pylori and the host is very complex. In addition to the effect of virulence factors on colonization and persistence, binding of specialized bacterial proteins, known as receptins, to certain host molecules (ligands) could explain the success of H. pylori as a chronically persisting pathogen. Some of the reported interactions are of high affinity, as revealed by their calculated dissociation constant. This review examines the binding of host proteins (serum and extracellular matrix proteins) to H. pylori and considers the significance of these interactions in the infectious process. A more thorough understanding of the kinetics of these receptin interactions could provide a new approach to preventing deeper tissue invasion in H. pylori infections and could represent an alternative to antibiotic treatment.
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Pihan-le bars, F., F. Bonnet, O. Loréal, A. Le Loupp, M. Ropert, X. Prieur, K. Bach, B. Fromenty und B. Cariou. „P219 Interactions entre fer et adiponectine dans le tissu adipeux : un rôle dans les complications métaboliques de l’obésité ?“ Diabetes & Metabolism 40 (März 2014): A80. http://dx.doi.org/10.1016/s1262-3636(14)72510-8.

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Vily, J., M. Soty, M. Raffin und G. Mithieux. „La néoglucogenèse intestinale contrôle une interaction humorale entre le tissu adipeux blanc et les cellules β-pancréatiques“. Annales d'Endocrinologie 78, Nr. 4 (September 2017): 230. http://dx.doi.org/10.1016/j.ando.2017.07.057.

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Labroussaa, Fabien, Nathalie Arricau-Bouvery, Marie-Pierre Dubrana und Colette Saillard. „Entry of Spiroplasma citri into Circulifer haematoceps Cells Involves Interaction between Spiroplasma Phosphoglycerate Kinase and Leafhopper Actin“. Applied and Environmental Microbiology 76, Nr. 6 (29.01.2010): 1879–86. http://dx.doi.org/10.1128/aem.02384-09.

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ABSTRACT Transmission of the phytopathogenic mollicutes, spiroplasmas, and phytoplasmas by their insect vectors mainly depends on their ability to pass through gut cells, to multiply in various tissues, and to traverse the salivary gland cells. The passage of these different barriers suggests molecular interactions between the plant mollicute and the insect vector that regulate transmission. In the present study, we focused on the interaction between Spiroplasma citri and its leafhopper vector, Circulifer haematoceps. An in vitro protein overlay assay identified five significant binding activities between S. citri proteins and insect host proteins from salivary glands. One insect protein involved in one binding activity was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as actin. Confocal microscopy observations of infected salivary glands revealed that spiroplasmas colocated with the host actin filaments. An S. citri actin-binding protein of 44 kDa was isolated by affinity chromatography and identified by LC-MS/MS as phosphoglycerate kinase (PGK). To investigate the role of the PGK-actin interaction, we performed competitive binding and internalization assays on leafhopper cultured cell lines (Ciha-1) in which His6-tagged PGK from S. citri or purified PGK from Saccharomyces cerevisiae was added prior to the addition of S. citri inoculum. The results suggested that exogenous PGK has no effect on spiroplasmal attachment to leafhopper cell surfaces but inhibits S. citri internalization, demonstrating that the process leading to internalization of S. citri in eukaryotic cells requires the presence of PGK. PGK, regardless of origin, reduced the entry of spiroplasmas into Ciha-1 cells in a dose-dependent manner.
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Patyal, Baldev. „Dosimetry Aspects of Proton Therapy“. Technology in Cancer Research & Treatment 6, Nr. 4_suppl (August 2007): 17–23. http://dx.doi.org/10.1177/15330346070060s403.

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High-energy photons and high-energy protons are very different in the ways they interact with matter. These differences lead to distinct advantages of protons over photons for treatment of cancer. Some aspects of proton interactions with tissue that make this modality superior for treating cancer are: (i) Initially, the protons lose energy very slowly as they enter the body; this results in a low entrance dose and low doses to the normal tissues proximal to the tumor. (ii) Near the end of range, protons lose energy very rapidly and deposit all their energy over a very small volume before they come to rest. This is the Bragg peak, a property that results in delivery of the maximum dose to the tumor. (iii) Beyond the Bragg peak, the energy deposited by the protons is zero; no dose is received by normal tissues distal to the tumor. Therefore, protons deliver their maximum dose to the tumor, a low dose to normal structures proximal to the tumor, and no dose to the normal structures beyond the tumor, ideal properties of a radiation modality to treat cancer. One distinct advantage of protons over photons is the ease with which the tumor target can be irradiated conformably to a high dose, and at the same time the normal structures in the vicinity of the tumor can be protected conformably from that high dose. Given the same dose to the tumor via photons and protons, protons inherently deliver less integral dose and, thus, lead to fewer normal-tissue complications. In addition, proton interactions also offer distinct radiobiological advantages over photons. Superior physical and radiobiological proton interactions lead naturally to the concepts of dose escalation and hypofractionation. The superiority of treatment delivery with protons as contrasted with photons is demonstrated by treatment plans.
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Gardiner, Juliet C. „Tissue-Specific Tumorigenesis in Multiple Endocrine Neoplasia Type I“. Journal of the Endocrine Society 5, Supplement_1 (01.05.2021): A557. http://dx.doi.org/10.1210/jendso/bvab048.1135.

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Abstract While a germline heterozygous mutation in the MEN1 gene predisposes tumor formation in the endocrine pancreas, parathyroid glands and anterior pituitary, this tissue-specific tumorigenesis is not dependent on MEN1 mutations alone. In fact, a homozygous deletion of Men1 in the entire pancreas of a mouse results in tumor formation only in the endocrine pancreas, not in the exocrine pancreas, suggesting an endocrine tissue-specific mechanism. The MEN1 gene encodes the menin protein, which interacts with chromatin associated protein complexes, therefore engaging in epigenetic control mechanisms. Recognizing menin’s participation in epigenetic regulation led to an investigation of whether the pathogenesis of MEN1 syndrome may be related to epigenetic changes in the affected endocrine tissues. Indeed, MEN1-associated endocrine cell types exhibit various menin-dependent epigenetic mechanisms. In fact, a significant increase in methylated DNA loci was observed in MEN1 human parathyroid tumors when compared to human parathyroid adenomas and carcinomas without known MEN1 mutations. Subsequent studies revealed that loss of menin results in increased activity of DNA methyltransferase 1 (Dnmt1). Our studies have shown that Dnmt1 is transcriptionally regulated by the menin-interacting protein Rbbp5. While menin normally functions to suppress Rbbp5 activity, loss of menin activates Rbbp5, thus upregulating Dnmt1 expression, causing global DNA hypermethylation and subsequent tumorigenesis in MEN1-target endocrine tissues. In order to assess the behavior of Rbbp5 in both MEN1-target tissues and non-target tissues, Rbbp5 protein expression was analyzed in both MEN1-target tissues (endocrine pancreas, anterior pituitary, parathyroid) and non-MEN1-target tissues (kidney, lung, liver, brain, heart) of wild-type (WT) mice. We confirmed that Rbbp5 protein expression is ubiquitous throughout all of these WT mouse tissues. Since Rbbp5 is a transcriptional activator responsible for enhanced Dnmt1 gene expression, and the loss of menin causes Dnmt1 overexpression solely in MEN1-target tissues, we assessed whether Rbbp5 binds preferentially in a tissue-specific manner to the Dnmt1 promoter. We determined the presence of Rbbp5 on the Dnmt1 promoter in MEN1-target tissues (WT mouse endocrine pancreas, normal human parathyroid, WT mouse pituitary) and the absence of Rbbp5 on the Dnmt1 promoter in non-MEN1-target tissues (WT mouse liver, WT mouse kidney, WT mouse lung). These results confirmed that Rbbp5 does exhibit MEN1-target-tissue-specific occupancy at the Dnmt1 promoter. This endocrine-specific localization of Rbbp5 to the Dnmt1 promoter suggests the presence of additional tissue-specific factors (with tissue-specific expression or interactions/activity) that must be validated and tested further.
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Nemanichvili, Nikoloz, Alinda Berends, Richard Wubbolts, Andrea Gröne, Jolianne Rijks, Robert de Vries und Monique Verheije. „Tissue Microarrays to Visualize Influenza D Attachment to Host Receptors in the Respiratory Tract of Farm Animals“. Viruses 13, Nr. 4 (31.03.2021): 586. http://dx.doi.org/10.3390/v13040586.

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The trimeric hemagglutinin-esterase fusion protein (HEF) of influenza D virus (IDV) binds 9-O-acetylated sialic acid receptors, which are expressed in various host species. While cattle are the main reservoir for IDV, the viral genome has also been detected in domestic pigs. In addition, antibodies against IDV have been detected in other farm animals such as sheep, goats, and horses, and even in farmers working with IDV positive animals. Viruses belonging to various IDV clades circulate, but little is known about their differences in host and tissue tropism. Here we used recombinantly produced HEF proteins (HEF S57A) from the major clades D/Oklahoma (D/OK) and D/Oklahoma/660 (D/660) to study their host and tissue tropism and receptor interactions. To this end, we developed tissue microarrays (TMA) composed of respiratory tissues from various farm animals including cattle, domestic pigs, sheep, goats, and horses. Protein histochemical staining of farm animal respiratory tissue-microarrays with HEF proteins showed that cattle have receptors present over the entire respiratory tract while receptors are only present in the nasal and pharyngeal epithelium of pigs, sheep, goats, and horses. No differences in tropism for tissues and animals were observed between clades, while hemagglutination assays showed that D/OK has a 2-fold higher binding affinity than D/660 for receptors on red blood cells. The removal of O-acetylation from receptors via saponification treatment confirmed that receptor-binding of both clades was dependent on O-acetylated sialic acids.
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Cheng, Yang-Ran, Xinglin Li, Xuesen Zhao und Hanxin Lin. „Cell Entry of Animal Coronaviruses“. Viruses 13, Nr. 10 (01.10.2021): 1977. http://dx.doi.org/10.3390/v13101977.

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Coronaviruses (CoVs) are a group of enveloped positive-sense RNA viruses and can cause deadly diseases in animals and humans. Cell entry is the first and essential step of successful virus infection and can be divided into two ongoing steps: cell binding and membrane fusion. Over the past two decades, stimulated by the global outbreak of SARS-CoV and pandemic of SARS-CoV-2, numerous efforts have been made in the CoV research. As a result, significant progress has been achieved in our understanding of the cell entry process. Here, we review the current knowledge of this essential process, including the viral and host components involved in cell binding and membrane fusion, molecular mechanisms of their interactions, and the sites of virus entry. We highlight the recent findings of host restriction factors that inhibit CoVs entry. This knowledge not only enhances our understanding of the cell entry process, pathogenesis, tissue tropism, host range, and interspecies-transmission of CoVs but also provides a theoretical basis to design effective preventive and therapeutic strategies to control CoVs infection.
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Jäger, Jens, Sebastian Marwitz, Jana Tiefenau, Janine Rasch, Olga Shevchuk, Christian Kugler, Torsten Goldmann und Michael Steinert. „Human Lung Tissue Explants Reveal Novel Interactions during Legionella pneumophila Infections“. Infection and Immunity 82, Nr. 1 (28.10.2013): 275–85. http://dx.doi.org/10.1128/iai.00703-13.

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ABSTRACTHistological and clinical investigations describe late stages of Legionnaires' disease but cannot characterize early events of human infection. Cellular or rodent infection models lack the complexity of tissue or have nonhuman backgrounds. Therefore, we developed and applied a novel model forLegionella pneumophilainfection comprising living human lung tissue. We stimulated lung explants withL. pneumophilastrains and outer membrane vesicles (OMVs) to analyze tissue damage, bacterial replication, and localization as well as the transcriptional response of infected tissue. Interestingly, we found that extracellular adhesion ofL. pneumophilato the entire alveolar lining precedes bacterial invasion and replication in recruited macrophages. In contrast, OMVs predominantly bound to alveolar macrophages. Specific damage to septa and epithelia increased over 48 h and was stronger in wild-type-infected and OMV-treated samples than in samples infected with the replication-deficient, type IVB secretion-deficient DotA−strain. Transcriptome analysis of lung tissue explants revealed a differential regulation of 2,499 genes after infection. The transcriptional response included the upregulation of uteroglobin and the downregulation of the macrophage receptor with collagenous structure (MARCO). Immunohistochemistry confirmed the downregulation of MARCO at sites of pathogen-induced tissue destruction. Neither host factor has ever been described in the context ofL. pneumophilainfections. This work demonstrates that the tissue explant model reproduces realistic features of Legionnaires' disease and reveals new functions for bacterial OMVs during infection. Our model allows us to characterize early steps of human infection which otherwise are not feasible for investigations.
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Frybortova, Veronika, Stefan Satka, Lenka Jourova, Iveta Zapletalova, Martin Srejber, Philippe Briolotti, Martine Daujat-Chavanieu et al. „On the Possible Effect of Phytic Acid (Myo-Inositol Hexaphosphoric Acid, IP6) on Cytochromes P450 and Systems of Xenobiotic Metabolism in Different Hepatic Models“. International Journal of Molecular Sciences 25, Nr. 7 (23.03.2024): 3610. http://dx.doi.org/10.3390/ijms25073610.

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As compounds of natural origin enter human body, it is necessary to investigate their possible interactions with the metabolism of drugs and xenobiotics in general, namely with the cytochrome P450 (CYP) system. Phytic acid (myo-inositol hexaphosphoric acid, IP6) is mainly present in plants but is also an endogenous compound present in mammalian cells and tissues. It has been shown to exhibit protective effect in many pathological conditions. For this paper, its interaction with CYPs was studied using human liver microsomes, primary human hepatocytes, the HepG2 cell line, and molecular docking. Docking experiments and absorption spectra demonstrated the weak ability of IP6 to interact in the heme active site of CYP1A. Molecular docking suggested that IP6 preferentially binds to the protein surface, whereas binding to the active site of CYP1A2 was found to be less probable. Subsequently, we investigated the ability of IP6 to modulate the metabolism of xenobiotics for both the mRNA expression and enzymatic activity of CYP1A enzymes. Our findings revealed that IP6 can slightly modulate the mRNA levels and enzyme activity of CYP1A. However, thanks to the relatively weak interactions of IP6 with CYPs, the chances of the mechanisms of clinically important drug–drug interactions involving IP6 are low.
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Wilson, Ashley Lauren, Amber N. Woods und Victor H. Engelhard. „Immunosuppression limits CD8+ T cell entry into subcutaneous B16 melanoma“. Journal of Immunology 196, Nr. 1_Supplement (01.05.2016): 212.6. http://dx.doi.org/10.4049/jimmunol.196.supp.212.6.

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Abstract Interactions between homing receptors (HR) and ligands on the vasculature facilitate effector CD8 T cell entry into tissues. HR ligand expression on normal inflamed tissue vasculature is induced by the local release of pro-inflammatory cytokines. In tumors, however, it is likely that expression of HR ligands on tumor vasculature is suboptimal due to immunosuppression. We hypothesized that disruption of immunosuppression would increase HR ligand expression on tumor vasculature, and consequently, enhance CD8 T cell entry. B16-F1 melanoma tumor-bearing mice were treated with blocking antibodies against CTLA-4 or PD-1. HR ligand expression on tumor vasculature and CD8 T cell representation were assessed. We found that CTLA-4 or PD-1 blockade significantly increased intravascular CXCL9 expression in subcutaneous B16-F1 tumors. Unlike PD-1 blockade, CTLA-4 blockade was associated with increased E-selectin expression on tumor vasculature, which we have shown to be important for CD8 T cell entry into subcutaneous tumors. CTLA-4 blockade also enhanced CD8 T cell representation and reduced tumor size. We observed a very low percentage of PD-1+ CD8 T cells in B16-F1 tumors, which may account for the limited efficacy of PD-1 blockade. Interestingly, the percentage of intratumoral PD-1+ CD8 T cells increased post-treatment with anti-CTLA-4. Our data suggest that CTLA-4 blockade may act to enhance T cell priming in the lymph node to increase the number of CD8 T cell effectors available to infiltrate tumors. It is also possible that CTLA-4 blockade may act on CTLA-4+ intratumoral Tregs, thereby promoting reactivation of tumor-resident CD8 T cell effectors that secrete pro-inflammatory cytokines that upregulate HR ligands on tumor vasculature.
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Piña-Vázquez, Carolina, Magda Reyes-López, Guillermo Ortíz-Estrada, Mireya de la Garza und Jesús Serrano-Luna. „Host-Parasite Interaction: Parasite-Derived and -Induced Proteases That Degrade Human Extracellular Matrix“. Journal of Parasitology Research 2012 (2012): 1–24. http://dx.doi.org/10.1155/2012/748206.

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Parasitic protozoa are among the most important pathogens worldwide. Diseases such as malaria, leishmaniasis, amoebiasis, giardiasis, trichomoniasis, and trypanosomiasis affect millions of people. Humans are constantly threatened by infections caused by these pathogens. Parasites engage a plethora of surface and secreted molecules to attach to and enter mammalian cells. The secretion of lytic enzymes by parasites into host organs mediates critical interactions because of the invasion and destruction of interstitial tissues, enabling parasite migration to other sites within the hosts. Extracellular matrix is a complex, cross-linked structure that holds cells together in an organized assembly and that forms the basement membrane lining (basal lamina). The extracellular matrix represents a major barrier to parasites. Therefore, the evolution of mechanisms for connective-tissue degradation may be of great importance for parasite survival. Recent advances have been achieved in our understanding of the biochemistry and molecular biology of proteases from parasitic protozoa. The focus of this paper is to discuss the role of protozoan parasitic proteases in the degradation of host ECM proteins and the participation of these molecules as virulence factors. We divide the paper into two sections, extracellular and intracellular protozoa.
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Rondelli, Cola, Koutsioubas, Alongi, Ferruti, Ranucci und Brocca. „Mucin Thin Layers: A Model for Mucus-Covered Tissues“. International Journal of Molecular Sciences 20, Nr. 15 (29.07.2019): 3712. http://dx.doi.org/10.3390/ijms20153712.

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The fate of macromolecules of biological or pharmacological interest that enter the mucus barrier is a current field of investigation. Studies of the interaction between the main constituent of mucus, mucins, and molecules involved in topical transmucoidal drug or gene delivery is a prerequisite for nanomedicine design. We studied the interaction of mucin with the bio-inspired arginine-derived amphoteric polymer d,l-ARGO7 by applying complementary techniques. Small angle X-ray scattering in bulk unveiled the formation of hundreds of nanometer-sized clusters, phase separated from the mucin mesh. Quartz microbalance with dissipation and neutron reflectometry measurements on thin mucin layers deposited on silica supports highlighted the occurrence of polymer interaction with mucin on the molecular scale. Rinsing procedures on both experimental set ups showed that interaction induces alteration of the deposited hydrogel. We succeeded in building up a new significant model for epithelial tissues covered by mucus, obtaining the deposition of a mucin layer 20 Å thick on the top of a glycolipid enriched phospholipid single membrane, suitable to be investigated by neutron reflectometry. The model is applicable to unveil the cross structural details of mucus-covered epithelia in interaction with macromolecules within the Å discreteness.
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Carvalho, Duarte Nuno, Flávia C. M. Lobo, Luísa C. Rodrigues, Emanuel M. Fernandes, David S. Williams, Andrew Mearns-Spragg, Carmen G. Sotelo et al. „Advanced Polymeric Membranes as Biomaterials Based on Marine Sources Envisaging the Regeneration of Human Tissues“. Gels 9, Nr. 3 (20.03.2023): 247. http://dx.doi.org/10.3390/gels9030247.

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The self-repair capacity of human tissue is limited, motivating the arising of tissue engineering (TE) in building temporary scaffolds that envisage the regeneration of human tissues, including articular cartilage. However, despite the large number of preclinical data available, current therapies are not yet capable of fully restoring the entire healthy structure and function on this tissue when significantly damaged. For this reason, new biomaterial approaches are needed, and the present work proposes the development and characterization of innovative polymeric membranes formed by blending marine origin polymers, in a chemical free cross-linking approach, as biomaterials for tissue regeneration. The results confirmed the production of polyelectrolyte complexes molded as membranes, with structural stability resulting from natural intermolecular interactions between the marine biopolymers collagen, chitosan and fucoidan. Furthermore, the polymeric membranes presented adequate swelling ability without compromising cohesiveness (between 300 and 600%), appropriate surface properties, revealing mechanical properties similar to native articular cartilage. From the different formulations studied, the ones performing better were the ones produced with 3 % shark collagen, 3% chitosan and 10% fucoidan, as well as with 5% jellyfish collagen, 3% shark collagen, 3% chitosan and 10% fucoidan. Overall, the novel marine polymeric membranes demonstrated to have promising chemical, and physical properties for tissue engineering approaches, namely as thin biomaterial that can be applied over the damaged articular cartilage aiming its regeneration.
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41

Muravyov, A. V., P. V. Mikhailov und I. A. Tikhomirova. „Microcirculation and Hemorheology: points of interaction“. Regional blood circulation and microcirculation 16, Nr. 2 (30.06.2017): 90–100. http://dx.doi.org/10.24884/1682-6655-2017-16-2-90-100.

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Transport of respiratory gases and the entire spectrum of substances for the metabolism of cells is carried out by coordinated work of circulation and blood. The review considers the main theoretical and experimental studies on microcirculation and hemorheology with an emphasis on the mechanisms of their interrelation and on the influence of individual hemorheological characteristics on the regulation of microvascular tissue perfusion. The analysis of the leading microrheological characteristics of erythrocytes - deformability is performed, the signal molecular mechanisms associated with the change of this cell parameter are shown. Data on the role of erythrocytes in the regulation of arteriolar tonus and functional density of capillaries are given. The mechanism of this regulation by exocytosis with erythrocytes adenosine triphosphate (ATP) and its stimulation of nitric oxide synthesis by endothelial cells is discussed. The review performed a comprehensive analysis of the participation of major hemorheological characteristics in the regulation of microvascular perfusion, including the role of the optimal viscosity of whole blood and the viscosity of plasma for effective tissue perfusion and oxygenation.
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Maginnis, Melissa, Colleen L. Mayberry, Kashif Mehmood, Matthew Parent und Samuel Hess. „Characterization of JC Polyomavirus Entry by Serotonin Receptors“. Proceedings 50, Nr. 1 (17.06.2020): 73. http://dx.doi.org/10.3390/proceedings2020050073.

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JC polyomavirus (JCPyV) causes a lifelong persistent infection in the kidney in the majority of the population. In severely immunocompromised individuals, JCPyV can become reactivated, spread in the central nervous system, and infect glial cells, astrocytes, and oligodendrocytes which are necessary for myelin production. The viral infection and cytolytic destruction of glial cells leads to the development of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML), for which there are currently no approved treatment options. In order to develop effective antiviral therapies, it is essential to define the virus–host cell interactions that drive infection and the virus–receptor interactions that are major regulators of tissue tropism and viral disease outcomes. Following attachment to sialic acid receptors, JCPyV requires the serotonin 5-hydroxytryptamine (5-HT2) receptors to mediate internalization. However, the mechanism by which JCPyV utilizes 5-HT2 receptors to invade host cells is poorly understood. Using super-resolution fluorescence photoactivation localization microscopy (FPALM), we have determined that JCPyV localizes with 5-HT2 receptors at timepoints consistent with viral entry. Furthermore, we have determined that the 5-HT2 receptor-associated scaffolding proteins beta-arrestin, adaptor protein complex 2 (AP2) and dynamin are required for viral internalization through a clathrin-mediated endocytosis pathway. Additionally, we have identified a beta-arrestin-binding motif in the intracellular loop of the 5-HT2A receptor that is critical for JCPyV entry and infection. These findings highlight the importance of viral receptors in regulating viral infection and illuminate potential targets for antiviral treatment.
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Zaeck, Luca, Madlin Potratz, Antonia Klein, Conrad M. Freuling, Thomas Müller und Stefan Finke. „High-Resolution 3D Imaging of Virus Infections in Solvent-Cleared Organs: Novel Insights into Virus Replication and Tropism In Vivo“. Proceedings 50, Nr. 1 (17.06.2020): 75. http://dx.doi.org/10.3390/proceedings2020050075.

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The visualization of infection processes in relevant tissues and organs using microscopy methods reveals a unique link between the distribution, tropism, and abundance of pathogens and the physiological structure of the respective organ. To dissect virus replication and the host reaction in vivo at both a global and a single-cell level, conventional 2D imaging approaches can only provide limited insight. However, pathological studies of infected organ material are still mostly restricted to the immunostaining of thin sections from paraffin-embedded or frozen samples. While the 3D analysis of large tissue volumes is possible via laborious serial sectioning, a variety of problems and artifacts remain. Modern immunostaining-compatible tissue clearing techniques allow for the seamless 3D visualization of infection sites in optically cleared thick tissues sections or even entire organs. Benefiting from pure optical slicing, this approach enables the acquisition of multicolor high-volume 3D image stacks for coherent qualitative and quantitative analyses of the infection and its surrounding cellular environment. Here, we demonstrate the utility and power of this methodology by visualizing virus infections in different target tissues. For instance, we reconstructed the cellular context of rabies virus infection sites in mouse brain tissue, allowing a thorough investigation and quantitative analysis of rabies virus cell tropism. The systematic comparison of different rabies viruses with varying pathogenicity revealed a remarkable difference for highly virulent street rabies viruses and attenuated lab strains. While the virus protein expression was readily detectable at a comparable level in both neurons and non-neuronal glial cells from brains of mice infected with street rabies viruses, it was virtually absent in glial cells of lab strain-infected mice. These data provide novel and detailed insights into the pathogenesis of virus infections and substantially contribute to an improved understanding of virus–host interactions in vivo.
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Kuznetsov, Andrey V., Raimund Margreiter, Michael J. Ausserlechner und Judith Hagenbuchner. „The Complex Interplay between Mitochondria, ROS and Entire Cellular Metabolism“. Antioxidants 11, Nr. 10 (08.10.2022): 1995. http://dx.doi.org/10.3390/antiox11101995.

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Besides their main function for energy production in form of ATP in processes of oxidative phosphorylation (OxPhos), mitochondria perform many other important cellular functions and participate in various physiological processes that are congregated. For example, mitochondria are considered to be one of the main sources of reactive oxygen species (ROS) and therefore they actively participate in the regulation of cellular redox and ROS signaling. These organelles also play a crucial role in Ca2+ signaling and homeostasis. The mitochondrial OxPhos and their cellular functions are strongly cell/tissue specific and can be heterogeneous even within the same cell, due to the existence of mitochondrial subpopulations with distinct functional and structural properties. However, the interplay between different functions of mitochondria is not fully understood. The mitochondrial functions may change as a response to the changes in the cellular metabolism (signaling in). On the other hand, several factors and feedback signals from mitochondria may influence the entire cell physiology (signaling out). Numerous interactions between mitochondria and the rest of cell, various cytoskeletal proteins, endoplasmic reticulum (ER) and other cellular elements have been demonstrated, and these interactions could actively participate in the regulation of mitochondrial and cellular metabolism. This review highlights the important role of the interplay between mitochondrial and entire cell physiology, including signaling from and to mitochondria.
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LaBarge, Wesley, Andrés Morales, Daniëlle Pretorius, Asher Kahn-Krell, Ramaswamy Kannappan und Jianyi Zhang. „Scaffold-Free Bioprinter Utilizing Layer-By-Layer Printing of Cellular Spheroids“. Micromachines 10, Nr. 9 (29.08.2019): 570. http://dx.doi.org/10.3390/mi10090570.

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Free from the limitations posed by exogenous scaffolds or extracellular matrix-based materials, scaffold-free engineered tissues have immense clinical potential. Biomaterials may produce adverse responses, interfere with cell–cell interaction, or affect the extracellular matrix integrity of cells. The scaffold-free Kenzan method can generate complex tissues using spheroids on an array of needles but could be inefficient in terms of time, as it moves and places only a single spheroid at a time. We aimed to design and construct a novel scaffold-free bioprinter that can print an entire layer of spheroids at once, effectively reducing the printing time. The bioprinter was designed using computer-aided design software and constructed from machined, 3D printed, and commercially available parts. The printing efficiency and the operating precision were examined using Zirconia and alginate beads, which mimic spheroids. In less than a minute, the printer could efficiently pick and transfer the beads to the printing surface and assemble them onto the 4 × 4 needles. The average overlap coefficient between layers was measured and found to be 0.997. As a proof of concept using human induced pluripotent stem cell-derived spheroids, we confirmed the ability of the bioprinter to place cellular spheroids onto the needles efficiently to print an entire layer of tissue. This novel layer-by-layer, scaffold-free bioprinter is efficient and precise in operation and can be easily scaled to print large tissues.
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Sharer, J. Daniel, Jack F. Shern, Hillary Van Valkenburgh, Douglas C. Wallace und Richard A. Kahn. „ARL2 and BART Enter Mitochondria and Bind the Adenine Nucleotide Transporter“. Molecular Biology of the Cell 13, Nr. 1 (Januar 2002): 71–83. http://dx.doi.org/10.1091/mbc.01-05-0245.

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The ADP-ribosylation factor-like 2 (ARL2) GTPase and its binding partner binder of ARL2 (BART) are ubiquitously expressed in rodent and human tissues and are most abundant in brain. Both ARL2 and BART are predominantly cytosolic, but a pool of each was found associated with mitochondria in a protease-resistant form. ARL2 was found to lack covalent N-myristoylation, present on all other members of the ARF family, thereby preserving the N-terminal amphipathic α-helix as a potential mitochondrial import sequence. An overlay assay was developed to identify binding partners for the BART·ARL2·GTP complex and revealed a specific interaction with a protein in bovine brain mitochondria. Purification and partial microsequencing identified the protein as an adenine nucleotide transporter (ANT). The overlay assay was performed on mitochondria isolated from five different tissues from either wild-type or transgenic mice deleted for ANT1. Results confirmed that ANT1 is the predominant binding partner for the BART·ARL2·GTP complex and that the structurally homologous ANT2 protein does not bind the complex. Cardiac and skeletal muscle mitochondria fromant1 − /ant1 − mice had increased levels of ARL2, relative to that seen in mitochondria from wild-type animals. We conclude that the amount of ARL2 in mitochondria is subject to regulation via an ANT1-sensitive pathway in muscle tissues.
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Després, Merlin, und Simon Gaudin. „Le monoxyde d’azote: Une arme du système immunitaire pour brouiller les communications entre bactéries“. médecine/sciences 36, Nr. 11 (November 2020): 1074–77. http://dx.doi.org/10.1051/medsci/2020214.

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Le dossier thématique suivant a été rédigé par les étudiantes et étudiants de Master 1 de Biologie de l’École Normale Supérieure de Lyon à l’issue de l’UE Microbiologie Moléculaire et Structurale (2019-2020). Le Master de Biologie de l’ENS de Lyon, cohabilité par l’université Claude Bernard Lyon 1, accueille chaque année environ 50 étudiants en M1 et en M2 et propose une formation de haut niveau à la recherche en biosciences. Chaque étudiant y construit son parcours à la carte, en choisissant ses options parmi un large panel de modules, favorisant ainsi une approche pluridisciplinaire des sciences du vivant, et ce en relation étroite avec les laboratoires de recherche du tissu local, national et international. En participant à diverses activités scientifiques connexes aux UE de leur formation, les étudiants préparent également l’obtention du Diplôme de l’ENS de Lyon, qui valide leur scolarité à l’ENS. La rédaction du présent dossier, qui vise à transmettre de façon claire les messages issus d’une sélection d’articles scientifiques publiés récemment dans le domaine de la microbiologie, constitue l’une de ces activités connexes proposées aux étudiants. Les bactéries peuvent vivre en communautés dont la structure est régulée par de nombreuses interactions abiotiques et biotiques. Les interactions biotiques reposent sur des communications inter-bactériennes qui participent à la mise en place de relations de collaboration, de compétition ou de prédation. Ces communautés bactériennes peuvent en outre être en interaction avec des hôtes animaux, dans le cas des bactéries du microbiote ou des bactéries pathogènes par exemple, ou avec des virus parasites, les bactériophages. Le présent dossier illustre quelques aspects nouveaux de cette communication bactérienne, et de la façon dont les interactions bactéries/hôte ou bactéries/phages peuvent impacter cette communication. Deux nouvelles s’attardent sur des découvertes récentes autour du quorum sensing, une modalité de communication bactérienne permettant l’expression coordonnée des gènes à l’échelle de la population, en fonction de la densité de la population. La nouvelle intitulée « Le monoxyde d’azote : une arme du système immunitaire pour brouiller les communications entre bactéries » illustre comment le quorum sensing chez Staphylococcus aureus, une bactérie opportuniste, peut être affecté par un médiateur du système immunitaire de la souris. La nouvelle intitulée « Un bactériophage exploite le système de communication de son hôte bactérien pour entrer en cycle lytique » montre une stratégie étonnante par laquelle le phage VP882 décrypte des signaux issus du quorum sensing de la bactérie qu’il infecte pour réguler son propre cycle de réplication. Au-delà du quorum sensing, deux nouvelles décrivent de nouvelles modalités de communication inter-bactérienne. La nouvelle intitulée « Les nanotubes bactériens, acteurs de la compétition entre Bacillus subtilis et Bacillus megaterium » met en lumière le rôle des nanotubes, des structures de communication intercellulaire insoupçonnées jusque récemment chez les bactéries. La nouvelle intitulée « La bactérie Vibrio cholerae lyse les bactéries environnantes et assimile leur ADN qu’elle intègre dans son propre génome » illustre comment un système de sécrétion, qui permet l’injection d’effecteurs bactériens dans des cellules cibles, peut être exploité pour faciliter les transferts horizontaux de gènes chez les bactéries. Enfin, pour élargir la réflexion au monde des virus eucaryotes, deux nouvelles montrent comment l’infection virale peut interférer avec la communication entre cellules eucaryotes, sur l’exemple de la communication s’effectuant par l’intermédiaire de vésicules extracellulaires. La nouvelle intitulée « La sécrétion de vésicules extracellulaires par les plaquettes activées à l’origine de la létalité de la dengue ? » discute des mécanismes par lesquels le virus de la dengue déclenche la sécrétion de vésicules extracellulaires par les plaquettes, et des conséquences que cela peut avoir sur l’inflammation et le déclenchement de chocs hémorragiques. La nouvelle intitulée « Le coccolithovirus et Emiliania huxleyi : le détournement viral des vésicules extracellulaires » montre enfin comment ce virus d’algue unicellulaire exploite la communication intercellulaire de son hôte pour augmenter son pouvoir de diffusion au sein de la population, et des conséquences écologiques et géochimiques que cela peut entraîner à grande échelle.
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Jakovija, Arnolda, und Tatyana Chtanova. „Neutrophil Interactions with the Lymphatic System“. Cells 10, Nr. 8 (17.08.2021): 2106. http://dx.doi.org/10.3390/cells10082106.

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The lymphatic system is a complex network of lymphatic vessels and lymph nodes designed to balance fluid homeostasis and facilitate host immune defence. Neutrophils are rapidly recruited to sites of inflammation to provide the first line of protection against microbial infections. The traditional view of neutrophils as short-lived cells, whose role is restricted to providing sterilizing immunity at sites of infection, is rapidly evolving to include additional functions at the interface between the innate and adaptive immune systems. Neutrophils travel via the lymphatics from the site of inflammation to transport antigens to lymph nodes. They can also enter lymph nodes from the blood by crossing high endothelial venules. Neutrophil functions in draining lymph nodes include pathogen control and modulation of adaptive immunity. Another facet of neutrophil interactions with the lymphatic system is their ability to promote lymphangiogenesis in draining lymph nodes and inflamed tissues. In this review, we discuss the significance of neutrophil migration to secondary lymphoid organs and within the lymphatic vasculature and highlight emerging evidence of the neutrophils’ role in lymphangiogenesis.
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Shah, Shreyas N., und Falguni Patel. „Erupting Compound Odontome - A Case Report“. Journal of Evolution of Medical and Dental Sciences 10, Nr. 18 (03.05.2021): 1361–64. http://dx.doi.org/10.14260/jemds/2021/287.

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Odontomas are asymptomatic, benign odontogenic tumours comprised of dental tissue. Most of the cases usually get detected on routine radiographic evaluation. Odontoma can be classified according to morphology in two different variants, compound odontoma showing anatomic similarity or miniature version of the tooth and complex odontoma having irregular masses with different type of dental tissues. Early detection of such type of silent lesion is mandatory to rule out certain silent but aggressive pathologies. Here, we present a case of erupting compound odontoma of maxillary area in 15-year-old male patient. Development of tooth is a result of complicated interaction between ectodermal and ecto mesenchymal tissue. Sometimes the remnants of such tissues are left behind in the jaw after development and eruption of tooth, which can become a source of development of odontogenic lesions later on.1 As revealed by World Health Organization (WHO), Odontogenic tumours can be classified in three different categories according to their histopathological form.2 1. Odontogenic tumours which develop from odontogenic epithelium without involvement of odontogenic ectomesenchyme, 2. Odontogenic tumours which develop from odontogenic epithelium with involvement of odontogenic ectomesenchyme, with or without formation of dental hard tissue and 3. Odontogenic tumours which develop from odontogenic ectomesenchyme with or without involvement of odontogenic epithelium.2 For such lesions “Odontoma” word was initially given by Paul Broca in 1866, who revealed the term as tumour occurred by the overgrowth of entire dental tissue. The growth of absolutely differentiated epithelial cells as functional ameloblast and mesenchymal cells as functional odontoblast can give rise to a different developmental anomaly coined as Odontomas.3 According to their behaviour and composition, odontomas can be considered as malformations or hamartomas rather than a true neoplasm. 4,5,6 In 2005, World Health Organization (WHO) classified two variants of odontomas, 1. Compound odontomas, which typically appears as unilocular lesions containing multiple radiopaque, tiny tooth like structures commonly known as denticles; and 2. Complex odontomas, which is comprised of an irregular mass of soft and hard dental tissues.
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Yun, Sang-Im, und Young-Min Lee. „Early Events in Japanese Encephalitis Virus Infection: Viral Entry“. Pathogens 7, Nr. 3 (13.08.2018): 68. http://dx.doi.org/10.3390/pathogens7030068.

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Japanese encephalitis virus (JEV), a mosquito-borne zoonotic flavivirus, is an enveloped positive-strand RNA virus that can cause a spectrum of clinical manifestations, ranging from mild febrile illness to severe neuroinvasive disease. Today, several killed and live vaccines are available in different parts of the globe for use in humans to prevent JEV-induced diseases, yet no antivirals are available to treat JEV-associated diseases. Despite the progress made in vaccine research and development, JEV is still a major public health problem in southern, eastern, and southeastern Asia, as well as northern Oceania, with the potential to become an emerging global pathogen. In viral replication, the entry of JEV into the cell is the first step in a cascade of complex interactions between the virus and target cells that is required for the initiation, dissemination, and maintenance of infection. Because this step determines cell/tissue tropism and pathogenesis, it is a promising target for antiviral therapy. JEV entry is mediated by the viral glycoprotein E, which binds virions to the cell surface (attachment), delivers them to endosomes (endocytosis), and catalyzes the fusion between the viral and endosomal membranes (membrane fusion), followed by the release of the viral genome into the cytoplasm (uncoating). In this multistep process, a collection of host factors are involved. In this review, we summarize the current knowledge on the viral and cellular components involved in JEV entry into host cells, with an emphasis on the initial virus-host cell interactions on the cell surface.
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