Auswahl der wissenschaftlichen Literatur zum Thema „Interactions between tissues“

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Zeitschriftenartikel zum Thema "Interactions between tissues"

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Kawao, Naoyuki, und Hiroshi Kaji. „Interactions Between Muscle Tissues and Bone Metabolism“. Journal of Cellular Biochemistry 116, Nr. 5 (09.03.2015): 687–95. http://dx.doi.org/10.1002/jcb.25040.

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Tomas, Eva, Meghan Kelly, Xiaoqin Xiang, Tsu-Shuen Tsao, Charlotte Keller, Pernille Keller, Zhijun Luo et al. „Metabolic and hormonal interactions between muscle and adipose tissue“. Proceedings of the Nutrition Society 63, Nr. 2 (Mai 2004): 381–85. http://dx.doi.org/10.1079/pns2004356.

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From the perspective of a muscle physiologist, adipose tissue has long been perceived predominantly as a fuel reservoir that provides muscle and other tissues with NEFA when exogenous nutrients are insufficient for their energy needs. Recently, studies have established that adipose tissue is also an endocrine organ. Among the hormones it releases are adiponectin and leptin, both of which can activate AMP-activated protein kinase and increase fatty acid oxidation in skeletal muscle and probably other tissues. Deficiencies of leptin or leptin receptor, adiponectin and IL-6 are associated with obesity, insulin resistance and a propensity to type 2 diabetes. In addition, a lack of adiponectin has been linked to atherosclerosis. Whether this pathology reflects a deficient activation of AMP-activated protein kinase in peripheral tissues remains to be determined. Finally, recent studies have suggested that skeletal muscle may also function as an endocrine organ when it releases the cytokine IL-6 into the circulation during sustained exercise. Interestingly, one of the apparent effects of IL-6 is to stimulate lipolysis, causing the release of NEFA from the adipocyte. Thus, hormonal communications exist between the adipocyte and muscle that could enable them to talk to each other. The physiological relevance of this cross talk clearly warrants further study.
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Tsang, Anthony H., Johanna L. Barclay und Henrik Oster. „Interactions between endocrine and circadian systems“. Journal of Molecular Endocrinology 52, Nr. 1 (30.08.2013): R1—R16. http://dx.doi.org/10.1530/jme-13-0118.

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In most species, endogenous circadian clocks regulate 24-h rhythms of behavior and physiology. Clock disruption has been associated with decreased cognitive performance and increased propensity to develop obesity, diabetes, and cancer. Many hormonal factors show robust diurnal secretion rhythms, some of which are involved in mediating clock output from the brain to peripheral tissues. In this review, we describe the mechanisms of clock–hormone interaction in mammals, the contribution of different tissue oscillators to hormonal regulation, and how changes in circadian timing impinge on endocrine signalling and downstream processes. We further summarize recent findings suggesting that hormonal signals may feed back on circadian regulation and how this crosstalk interferes with physiological and metabolic homeostasis.
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Nammour, S., H. S. Loh, R. De Moor und C. P. Eduardo. „Interactions between Oral Tissues and External Light and Matters“. International Journal of Dentistry 2012 (2012): 1. http://dx.doi.org/10.1155/2012/726259.

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Nagase, T., T. Ito, M. Yanai, J. G. Martin und M. S. Ludwig. „Responsiveness of and interactions between airways and tissue in guinea pigs during induced constriction“. Journal of Applied Physiology 74, Nr. 6 (01.06.1993): 2848–54. http://dx.doi.org/10.1152/jappl.1993.74.6.2848.

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Mechanical interdependence between airways and tissues can modify the magnitude of induced bronchoconstriction. We questioned whether the guinea pig, an animal with abundant airway smooth muscle, would differ from other species in the relative responsiveness of and interactions between airways and tissues. Therefore we induced constriction with aerosolized methacholine (MCh) and partitioned responses into airway and tissue components. We measured tracheal and alveolar pressures using alveolar capsules in open-chest guinea pigs (n = 9) during mechanical ventilation [frequency = 1 Hz, tidal volume = 6 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) before and after administration of aerosols of MCh in progressively doubling concentrations (0.063–16 mg/ml). In separate animals (n = 10), measurements were made at 3–13 cmH2O PEEP. After aerosols of saline and MCh (0.125-32 mg/ml), measurements were repeated at 3, 7, and 11 cmH2O PEEP. At submaximal levels of constriction, the airways and lung tissues demonstrated similar responsiveness. Increasing PEEP increased RL and Rti and decreased Raw under baseline conditions. At low concentrations of MCh, increasing PEEP increased RL but decreased RL at the highest concentration. Increases in PEEP significantly increased Rti at all concentrations of MCh but decreased Raw only at 8 mg/ml of MCh. These observations demonstrate that, in guinea pigs, during submaximal constriction, airways and tissues behave similarly; moreover, airway-parenchymal interdependence is important in determining the level of bronchoconstriction.
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Wang, Congcong, Zihan Yi, Ye Jiao, Zhong Shen, Fei Yang und Shankuan Zhu. „Gut Microbiota and Adipose Tissue Microenvironment Interactions in Obesity“. Metabolites 13, Nr. 7 (05.07.2023): 821. http://dx.doi.org/10.3390/metabo13070821.

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Obesity is an increasingly serious global health problem. Some studies have revealed that the gut microbiota and its metabolites make important contributions to the onset of obesity. The gut microbiota is a dynamic ecosystem composed of diverse microbial communities with key regulatory functions in host metabolism and energy balance. Disruption of the gut microbiota can result in obesity, a chronic metabolic condition characterized by the excessive accumulation of adipose tissue. Host tissues (e.g., adipose, intestinal epithelial, and muscle tissues) can modulate the gut microbiota via microenvironmental interactions that involve hormone and cytokine secretion, changes in nutrient availability, and modifications of the gut environment. The interactions between host tissues and the gut microbiota are complex and bidirectional, with important effects on host health and obesity. This review provides a comprehensive summary of gut microbiota changes associated with obesity, the functional roles of gut microbiota-derived metabolites, and the importance of the complex interactions between the gut microbiota and target tissues in the pathogenesis of obesity. It places particular emphasis on the roles of adipose tissue microenvironment interactions in the onset of obesity.
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Rainbow, Roshni, Weiping Ren und Li Zeng. „Inflammation and Joint Tissue Interactions in OA: Implications for Potential Therapeutic Approaches“. Arthritis 2012 (18.06.2012): 1–8. http://dx.doi.org/10.1155/2012/741582.

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It is increasingly recognized that the pathogenesis of cartilage degradation in osteoarthritis (OA) is multifactorial and involves the interactions between cartilage and its surrounding tissues. These interactions regulate proinflammatory cytokine-mediated cartilage destruction, contributing to OA progression as well as cartilage repair. This review explores the pathogenesis of OA in the context of the multiple tissue types in the joint and discusses the implications of such complex tissue interaction in the development of anti-inflammatory therapeutics for the treatment of OA.
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Amponsah, N. T., E. E. Jones, H. J. Ridgway und M. V. Jaspers. „Microscopy of some interactions between Botryosphaeriaceae species and grapevine tissues“. Australasian Plant Pathology 41, Nr. 6 (05.08.2012): 665–73. http://dx.doi.org/10.1007/s13313-012-0159-x.

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Herrmann, Marietta, Klaus Engelke, Regina Ebert, Sigrid Müller-Deubert, Maximilian Rudert, Fani Ziouti, Franziska Jundt, Dieter Felsenberg und Franz Jakob. „Interactions between Muscle and Bone—Where Physics Meets Biology“. Biomolecules 10, Nr. 3 (10.03.2020): 432. http://dx.doi.org/10.3390/biom10030432.

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Muscle and bone interact via physical forces and secreted osteokines and myokines. Physical forces are generated through gravity, locomotion, exercise, and external devices. Cells sense mechanical strain via adhesion molecules and translate it into biochemical responses, modulating the basic mechanisms of cellular biology such as lineage commitment, tissue formation, and maturation. This may result in the initiation of bone formation, muscle hypertrophy, and the enhanced production of extracellular matrix constituents, adhesion molecules, and cytoskeletal elements. Bone and muscle mass, resistance to strain, and the stiffness of matrix, cells, and tissues are enhanced, influencing fracture resistance and muscle power. This propagates a dynamic and continuous reciprocity of physicochemical interaction. Secreted growth and differentiation factors are important effectors of mutual interaction. The acute effects of exercise induce the secretion of exosomes with cargo molecules that are capable of mediating the endocrine effects between muscle, bone, and the organism. Long-term changes induce adaptations of the respective tissue secretome that maintain adequate homeostatic conditions. Lessons from unloading, microgravity, and disuse teach us that gratuitous tissue is removed or reorganized while immobility and inflammation trigger muscle and bone marrow fatty infiltration and propagate degenerative diseases such as sarcopenia and osteoporosis. Ongoing research will certainly find new therapeutic targets for prevention and treatment.
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Elofsson, Hampus, Doroteya Raykova und Agata Zieba Wicher. „Abstract 6772: Powerful background reduction in fluorescent tissue stains with an improved proximity-based technology for detection of protein-protein interactions“. Cancer Research 83, Nr. 7_Supplement (04.04.2023): 6772. http://dx.doi.org/10.1158/1538-7445.am2023-6772.

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Abstract Immunofluorescent staining of tissues via in situ proximity ligation assay (isPLA) is now a well-established tool for highly sensitive detection of protein-protein interactions and their localization. It finds versatile applications in basic research, understanding of cellular processes, visualization of tissue architecture, and identification of biomarkers, among others. However, standard IF and isPLA techniques alike may suffer from high background. Tissues are particularly affected by background problems caused by autofluorescence and tissue infiltration of various cell types (e.g., immune, endothelial) where the fluorescently labelled oligos used for detection in isPLA may bind unspecifically. To address this, we developed a next generation isPLA-based technology for fluorescent detection of protein interactions in FFPE and fresh frozen human and mouse tissues, called NaveniFlex Tissue. In contrast to previously available protocols, it can visualize signal that would otherwise be obscured by background, thereby increasing sensitivity. Here, we compare the ability of NaveniFlex Tissue and similar commercial kits to detect the interaction between low abundance proteins Podocalyxin and Ezrin in the glomeruli of healthy kidney and in breast cancer, where co-expression is a prognostic marker for increased metastatic potential. While other kits generate high background which masks isPLA signal entirely, NaveniFlex Tissue dramatically reduces cell-based background and visualizes the interaction in its specific localization. Furthermore, in a TMA staining for the Mucin 16/Mesothelin interaction, our method successfully demonstrates strong and clear signal in stage III ovarian cancer. Moreover, it sensitively detects even low abundance interaction in a stage Ia tumor. In contrast, a different commercial kit detects significantly less interactions in the stage III tumor, while in the lower grade tumor it does not generate signals above background level. Therefore, NaveniFlex Tissue improves detection in tissues with varying disease progression, thus adding information and prognostic value to the staining. Taken together, our data illustrate that NaveniFlex Tissue outperforms current isPLA-based techniques by efficiently reducing background, which improves visualization of signal and signal-to-noise ratios in various healthy and diseased tissues. Citation Format: Hampus Elofsson, Doroteya Raykova, Agata Zieba Wicher. Powerful background reduction in fluorescent tissue stains with an improved proximity-based technology for detection of protein-protein interactions. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6772.
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Dissertationen zum Thema "Interactions between tissues"

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Dugan, Aisling Siobhan. „The interactions between BK virus and host cell receptors“. View abstract/electronic edition; access limited to Brown University users, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3318311.

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Floyd, Hayley. „Cobalt, chromium implant wear : investigating interactions between products and the local environment and presenting an approach for mapping tissues“. Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8366/.

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Modern cobalt-chromium (CoCr) alloy compositions, for hip implants, were developed to resist the issues of wear and corrosion; however they still succumb to degradation. While the literature is vast, there is still a lack of understanding of the variability in implant-metal derivatives generated, and the effect such products can have on biological components other than just cells. In this thesis the effect of Co ions on type I collagen (main component of the extracellular matrix) was investigated. The conformation of the triple-helix was maintained, however the time taken for fibril formation to complete increased with Co concentration. In addition, with increasing Co, the collagen matrix became more heterogeneous and cellular attachment and proliferation was reduced. It is likely that Co ions are interacting with a C-O (hydroxyl) group. An overlooked population of degradation products was also investigated. They were found to be highly dependent upon the local environment. Media composition resulted in changes to the morphology, while pH directed the initiation of precipitation. A pH < 5 resulted in no observed pellet. In addition, the presence of Co ions in the media resulted in a change of Cr speciation. Finally, an approach is presented for sub-micron (600nm) x-ray absorption near edge spectroscopy (XANES) mapping of ex vivo tissue. Sub-micron XANES maps contained at least 4 spectra, determined through principal component analysis and clustering. A 5x5 pixel region was averaged for comparison to the 3μm beam approach. Both spectra contained similar features representative of chromium phosphate suggesting that XANES with a micron-sized beam (standard approach) cannot represent the full chemical variability present within the tissue.
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Monnot, Pauline. „Rôle des interactions mécaniques entre tissus dans la mise en place du circuit olfactif du poisson-zèbre“. Electronic Thesis or Diss., Sorbonne université, 2021. http://www.theses.fr/2021SORUS113.

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Alors que les signaux biochimiques impliqués dans la croissance axonale et la migration neuronale sont largement étudiés, la contribution des signaux mécaniques dans la formation des circuits neuronaux reste peu explorée in vivo. Nous cherchons à étudier comment les forces mécaniques contribuent à la formation du circuit olfactif du poisson-zèbre. Ce circuit se développe durant la morphogénèse de la placode olfactive (PO), par le mouvement passif des corps cellulaires qui s’éloignent de l’extrémité de leurs axones. Mes travaux de thèse s’intéressent à la contribution mécanique de l’œil, qui se forme sous la PO par des mouvements d’évagination et d’invagination, à cette migration passive des neurones et à l’extension de leurs axones. L'analyse quantitative des mouvements cellulaires a tout d’abord révélé que les mouvements des cellules de la PO et de l’œil sont corrélés. Chez des embryons dans lesquels l’œil ne se développe pas, les mouvements des cellules de la PO sont affectés, ce qui produit des PO plus fines et des axones plus courts, et la tension mécanique dans la direction d’élongation des axones dans la PO est réduite. Enfin, la matrice extracellulaire s’accumule à l’interface oeil/PO et sa dégradation enzymatique réduit la corrélation entre les mouvements des cellules de la PO et de l’œil. Ces résultats suggèrent que l’œil en formation exerce des forces de traction sur la PO, transmises par la matrice, entrainant le mouvement des neurones et l’extension des axones. Ce travail apporte un éclairage nouveau sur le rôle des forces mécaniques échangées entre les neurones en développement et les tissus environnants dans la formation des circuits neuronaux in vivo
Whereas the biochemical signals guiding axon growth and neuronal migration are extensively studied, the contribution of mechanical cues in neuronal circuit formation is still poorly explored in vivo. We aim at investigating how mechanical forces influence the construction of the zebrafish olfactory circuit. This circuit forms during the morphogenesis of the olfactory placode (OP) by the passive displacement of neuronal cell bodies away from the tip of their axons. My PhD work focuses on the mechanical contribution of the adjacent eye tissue, which develops underneath the OP through extensive evagination and invagination movements, to this passive neuronal migration and to their associated axon elongation. Quantitative live cell imaging analysis during OP morphogenesis first revealed that OP and eye cells undergo correlated movements. In embryos lacking eyes, the movements of OP cell bodies are affected, resulting in thinner placodes and shorter axons, and the mechanical stress along the direction of axon elongation within the OP is reduced. Finally, extracellular matrix was observed to accumulate at the eye/OP interface, and its enzymatic degradation decreased the correlation between OP and eye cell movements. Altogether, these results suggest that the developing eye exerts traction forces on the OP through extracellular matrix, mediating proper neuronal movements and axon extension. This work sheds new light on the role of mechanical forces exchanged between developing neurons and surrounding tissues in the sculpting of neuronal circuits in vivo
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Hollville, Enzo. „Impact du type de surface sur la réponse à l’exercice : du muscle au mouvement Interactions between fascicles and tendinous tissues in gastrocnemius medialis and vastus lateralis during drop landing How surface properties affect fascicle-tendon interactions during drop landing? Muscle-tendon interactions in jumping: influence of surface properties“. Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCB018.

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Les propriétés des surfaces sportives peuvent impacter directement la performance et le risque de blessure en modulant la part d’énergie transmise à l'athlète lors de l'impact du pied sur la surface. Les pelouses naturelle et synthétique sont couramment utilisées sur les terrains de football et de rugby. Depuis quelques années, une nouvelle génération de pelouse dite naturelle renforcée a fait son apparition dans les clubs professionnels mais son influence sur la biomécanique du geste sportif est encore mal connue. Cette thèse vise à évaluer l'influence de trois types de surfaces (gazon naturel renforcée, gazon synthétique et tartan) sur les interactions muscle-tendon et les coordinations neuromusculaires des muscles gastrocnemius medialis (GM) et vastus lateralis (VL) lors de mouvements de réception uni et bilatérale ainsi que de saut. L’analyse des données échographiques dynamiques, de cinématique 2D et d’activité musculaire nous a permis de montrer que : i) les propriétés mécaniques des surfaces peuvent altérer les interactions entre les faisceaux musculaires et les tissus tendineux ainsi que l’amplitude d’activation musculaire ; ii) la pelouse naturelle renforcée semble avoir des propriétés plus optimales que la pelouse synthétique lors de sauts et réceptions ; iii) il existe des différences de comportement marquées entre le GM et VL qui dépendent du type de surface, du type de mouvement et de son intensité. Cela souligne l’importance de ne pas se limiter à l’étude des propriétés mécaniques des surface pour comprendre leur influence sur le mouvement sportif. Par ailleurs, l’étude des comportements musculo-tendineux in vivo en condition écologique permet de mieux comprendre les interactions complexes entre l’homme et la surface
Sports surface properties can substantially alter the overall performance and risk of injury. Surface mechanical properties influence the loading of the human musculoskeletal system by modulating the amount of foot-impact energy transmitted to the athlete. Natural grass and synthetic turf are commonly used pitches in football and rugby. More recently, reinforced natural grass technology has been used at the elite-level facilities, but its influence on player is not well defined. This thesis aimed at evaluating the influence of three different surfaces (reinforced natural grass, synthetic turf and athletic track) on the muscle-tendon interactions and neuromuscular coordination of gastrocnemius medialis (GM) and vastus lateralis (VL) muscles during landings and jumping tasks. Analysis of dynamic ultrasound imaging, 2D kinematics and electromyographic data showed that: i) surface mechanical properties influenced muscle-tendon interactions as well as the level of muscle activity; ii) the reinforced natural grass surface seems to optimize the muscular response during the movement and iii) GM and VL muscles displayed specific behaviors relative to the type of movement, its intensity and the type of surface. This emphasizes that the human response cannot be predicted by only analyzing the mechanical surface properties and highlights the important role of in vivo ecological testing to better understand player-surface interaction
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Shapero, Kayle Sarah. „Interactions between valvular cells: implications for heart valve tissue engineering“. Thesis, Boston University, 2013. https://hdl.handle.net/2144/11048.

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Thesis (Ph.D.)--Boston University
Approximately 1 in 1000 children are born with congenital cardiovascular defects yearly in the US, including many abnormalities in heart valves. Tissue engineered heart valves (TEHVs) offer a solution for replacement or repair of affected valves. However, its therapeutic application is limited, and in ovine models, no TEHV has performed satisfactorily in vivo for longer than twenty weeks, in part due to the absence of supporting data for selection of the appropriate cell type(s) to be incorporated into the construct. This partially owes to the lack of a full understanding of the cells that inhabit the valve, which includes valve interstitial cells (VICs) and valve endothelial cells (VECs), and on the molecular mechanism underlying their interactions that maintain valve homeostasis. During embryonic valve development, the vast majority of VICs are derived from VECs via endothelial to mesenchymal transformation (EMT). EMT in postnatal valves is rare but it has been implicated in diseased valves. Yet, relatively little is known about VECs and VICs in post-natal valves in terms of specialized features, and how VECs and VICs might influence each other. This lack of knowledge has made it difficult to determine what type of cells should be used to create a TEHV. In order to achieve the optimal construction of a tissue engineered heart valve we look to the native valve as our guide for proper valve structure and function. Examination of the native valve leaflets can contribute to our understanding of the proper cellular environment and how disruption of this environment affects the valves. Many common mitral valve pathologies including mitral valve prolapse are characterized by thickening of the valve spongiosa, the presence of activated myofibroblasts, and excessive remodeling of the extracellular matrix. By examining the cell-cell interactions in healthy native valves, and comparing this with observations from pathogenic valves, a greater understanding can be achieved and then applied to the field of TEHV. In this thesis we explored the cell dynamics of the heart valve as related to natural homeostasis, disease progression, and tissue engineering. Using an in vitro co-culture model we revealed a novel two-way communication between mitral valve endothelial and interstitial cells. We propose that this communication promotes a healthy valve phenotype and function by inhibiting EndMT and suppressing VIC activation. We made a similar observation in the aortic valve, where VEC-VIC communication may prevent the process of an EndMT mediated osteogenesis in the context of calcific aortic valve disease. We have also used the VEC-VIC co-culture model to identify possible candidate cell sources for a tissue engineered heart valve. And finally, we show that cells that populated a tissue engineered pulmonary valve leaflet, created using an acellular scaffold, are phenotypically and functionally similar to native valve cells. These studies contribute to an understanding of the dynamics of the cellular interactions between VECs and VICs, and provide a new framework for identifying and testing the functionality of appropriate cell sources for building a TEHV with the ability to grow with the child, maintain homeostasis, and prevent fibrosis and calcification.
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Carlsson, Karin. „Tissue Factor in Complex : Studies of interactions between blood coagulation proteins“. Doctoral thesis, Linköpings universitet, Biokemi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-63688.

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Many biological processes rely on specific protein-protein interactions, for example immune responses, cell signaling, transcription, and blood coagulation. Blood coagulation is initiated when a vessel wall is damaged, exposing tissue factor (TF) to the circulating factor VII/factor VIIa (FVII/FVIIa) which results in the formation of the TF:FVIIa complex and thereby the initiation of blood coagulation. One of the substrates for the TF:FVIIa complex is factor X (FX), which is activated to factor Xa (FXa), subsequently leading to a series of reactions resulting in clot formation. Tissue factor pathway inhibitor (TFPI) is the major physiological inhibitor of the sTF:FVIIa complex, involved in regulation of coagulation by forming the TF:FVIIa:FXa:TFPI complex. Occasionally, the blood coagulation mechanism malfunctions, resulting in conditions such as the inability to stop bleeding or thrombosis. The fact that TF is the main initiator of the coagulation makes this an interesting protein to study, in the hunt for means to interfere with players involved in the blood clotting process. Throughout the studies included in this thesis the site-directed labeling technique is utilized to attach spectroscopic probes to cysteines, introduced at specific positions by mutagenesis, in the protein of interest. These fluorescent or spin-probes are sensitive for changes in their immediate environment and can thus, for example be used to monitor protein-protein complex formation and conformational changes. No complete structure has been obtained as yet for the large complex involving sTF, FVIIa, FXa, and TFPI. Therefore, we introduced a fluorescent probe at specific positions in soluble tissue factor (sTF) and the changes in fluorescence emission were detected upon sTF:FVIIa:FXa:TFPI complex formation. From these measurements it was concluded that not only parts of the C-terminal domain of sTF (TF2), but also residues in the N-terminal domain (TF1) are involved in binding to FXa in the quaternary complex. In order to investigate conformational changes occurring in the extended interface between sTF and FVIIa upon binding of different inhibitors spectroscopic probes were introduced in sTF, in the vicinity of the interaction region. From the obtained data it was concluded that the exosite-binding inhibitor E-76 induces equivalent structural changes at the interface of sTF and the protease domain (PD) of FVIIa, as do the active-site inhibitors FFR and TFPI, i.e. makes the region around the active-site more compact. Binding of these inhibitors shows similar effects despite their differences in size, binding site, and inhibitory mechanism. In addition, the Ca2+ dependence of the formation of the sTF:FVIIa complex was studied. Association between sTF and FVIIa during Ca2+ titration begins by Ca2+ binding to the first EGF-like domain of FVIIa. However, Ca2+ saturation of the γ-carboxyglutamic acid-rich (Gla) domain of FVIIa is required for complete sTF:FVIIa complex formation, and we were also able to detect that a Gla domain with vacant Ca2+ sites hinders the docking to sTF. Finally, we investigated the structural changes of free inhibited FVIIa upon sTF and Ca2+ binding by FRET and quenching measurements. From this it was concluded that inhibited FVIIa does not seem to undergo large global structural changes upon binding to sTF, when taking the dynamics of free FVIIa into account. However, Ca2+ binding induces minor local conformational changes in the active-site region of the PD of inhibited FVIIa and subsequent binding of sTF causesfurther structural rearrangements in this area.
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Sim, Richard James. „Characterisation of the interaction between Neisseria meningitidis and the human host“. Thesis, University of Birmingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246497.

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Neisseria meningitidis is an important cause of septicaemia and meningitis, yet can be found colonising the nasopharynx of up to 20% of healthy individuals. The aim of my work was to provide detailed characterisation of the cellular location of meningococcal carriage and subsequently select suitable models to investigate the molecular and cellular basis of the mechanisms by which the bacterium interacts with the human upper respiratory tract. This is the fundamental microbial-host interaction underlying the commensalism of Neisseria meningitidis. A survey of meningococcal carriage in tonsillar tissue was undertaken using IHe techniques that detect PorA, a protein unique to Neisseria meningitidis. This showed that carriage rates are higher than those described with nasopharyngeal swabbing, and that the bacterium occupies a site deep to the epithelium in the carrier state. To identify genes that are required to reach sub-epithelial sites, air-interface organ culture models were used to screen bacteria subjected to signature tagged mutagenesis. Ten potentially colonisation deficient mutants were isolated and further analysed. This is the first time that such a screen has been undertaken in tissue of human origin. Additionally, homologues of two genes essential for intracellular survival in Legionella pneumophila (macrophage infectivity potentiator and an unknown virulence protein) were identified in Neisseria meningitidis and mutants containing specific genetic deletions constructed.
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Qui, Lin. „Interaction between vascular endothelial cells and surface textured biomaterials“. Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8854.

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A promising approach to overcome thrombus and neointima formation on vascular grafts is to create a functional, quiescent monolayer of endothelial cells on the surface of implants. Surface topography of these implants is proven to enhance cell attachment and to reduce the inflammation associated with a smooth surface. Photoembossing is a relatively new, simple, environment-friendly and cost-effective technique to create surface topographies, since there is no etching step or mould needed. In this study, photopolymer films are photoembossed through contact mask photoembossing, while fibres are photoembossed through holographic lithography. Surface relief textures of ridges and grooves with various pitch sizes and heights are successfully obtained through both methods. Furthermore, we introduce this technique to fabricate, for the first time, reproducible surface textures on electrospun fibres. Human umbilical vein endothelial cells (HUVECs) are used in the study. Three different systems are investigated: non-degradable PMMA-TPETA, semi-degradable PLGA-TPETA and fully degradable PLGA-PEGDA-DTT, for different applications and therapeutic requirements. Both non-degradable PMMA-TPETA photopolymer and semi-degradable PLGA-TPETA photopolymer are shown to improve biocompatibility compared to PMMA and PLGA, respectively. Photoembossed films made from these two photopolymers show significantly improved cell attachment and proliferation, IV with a water contact angle around 70º. It is shown that the pitch size of surface topographies affects cell adhesion and migration in the wound healing assay study. Interaction between HUVECs and fibres shows that cells grow from their initial locations at fibre crossings. Focal adhesions are seen to be more aggregated on the surface textured fibres, while those on the glass cover slips are more dispersed near the edge of the cell membrane. The appearance of F-actin in the cytoplasm is also seen to be influenced by the surface topography, where changes in the diameter of the fibre and its surface texture result in F-actin rearrangement. Our study shows that a surface textured, fully degradable, gel-like photopolymer PLGA-PEGDA-DTT has great potential to be further developed for tissue engineering applications.
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Aziz, Khalil Abdul. „Influence of GM-CSF and G-CSF on the mutual interactions between platelets and neutrophils“. Thesis, University of Liverpool, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241473.

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Hockey, Verity Irena. „Characterising the molecular interaction between tissue factor pathway inhibitor and protein S“. Thesis, Imperial College London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.530472.

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Bücher zum Thema "Interactions between tissues"

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Giuliani, Alessandra, und Alessia Cedola. Advanced High-Resolution Tomography in Regenerative Medicine: Three-Dimensional Exploration into the Interactions between Tissues, Cells, and Biomaterials. Springer, 2018.

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Jakob, Stephan M., und Jukka Takala. Oxygen transport in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0137.

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Adequate oxygen delivery is crucial for organ survival. The main determinants of oxygen delivery are cardiac output, haemoglobin concentration, and arterial oxygen saturation. The adequacy of oxygen delivery also depends on oxygen consumption, which may vary widely. Mixed venous oxygen saturation reflects the amount of oxygen not extracted by the tissues, and therefore provides useful information on the relationship between oxygen delivery and oxygen needs. If not in balance, tissue hypoxia may ensue and arterial lactate concentration increases. This occurs at higher oxygen delivery rates in acute compared with chronic diseases where metabolic adaptions often occur. Arterial and mixed venous oxygen saturation are related to each other. The influence of mixed venous saturation on arterial saturation increases with an increasing intrapulmonary shunt. This chapter discusses interactions between the components of oxygen transport and how they can be evaluated. Various methods for measuring tissue oxygenation and oxygen consumption are also presented, together with their limitations.
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Radermacher, Peter, und Claus-Martin Muth. Pathophysiology and management of depth-related disorders. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0351.

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Decompression illness comprises decompression sickness resulting from tissue inert gas super-saturation and pulmonary barotraumas due to alveolar or airway over-distension. Gas bubbles can cause vascular obstruction or tissue compression, resulting in tissue ischaemia and oedema. Interactions between the blood–gas interface and the endothelium will result in further tissue damage, and trigger an inflammatory cascade with capillary leakage and haemoconcentration. Decompression illness may mimic any other emergency pathology and any emergency coinciding with decompression is ‘due to’ decompression. Pulmonary barotrauma-induced arterial gas embolism and decompression sickness can be discriminated according to the onset of symptoms, with gas embolism predominantly developing within a few minutes after or even during decompression. Specific treatment consists of hyperbaric oxygen treatment, using several empirically-derived hyperbaric oxygen treatment schedules. Currently, there is no recognized pharmacological treatment, but fluid resuscitation is useful to counteract haemoconcentration and dehydration. Early treatment initiation is mandatory, and certain technical issues must be considered for the management of critically-ill patients in a hyperbaric chamber.
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Dettman, Robert, Juan Antonio Guadix, Elena Cano, Rita Carmona und Ramón Muñoz-Chápuli. The multiple functions of the proepicardial/epicardial cell lineage in heart development. Herausgegeben von José Maria Pérez-Pomares, Robert G. Kelly, Maurice van den Hoff, José Luis de la Pompa, David Sedmera, Cristina Basso und Deborah Henderson. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198757269.003.0020.

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The epicardium is the outer cell layer of the vertebrate heart. In recent years, both the embryonic and adult epicardium have revealed unsuspected peculiarities and functions, which are essential for cardiac development. In this chapter we review the current literature on the epicardium, and describe its evolutionary origin, the mechanisms leading to the induction of its extracardiac progenitor tissue, the proepicardium, and the way in which the proepicardium is transferred to the heart to form the epicardium. We also describe the epicardial epithelial–mesenchymal transition from which mesenchymal cells originate, and the developmental fate of these cells, which contribute to the vascular, interstitial, valvular, and adipose tissue. Finally, we review the molecular interactions established between the epicardium and the myocardium, which are key for myocardial development and can also play a role in cardiac homeostasis. This chapter highlights how the epicardium has become a major protagonist in cardiac biology.
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Parlato, Marianna, und Jean-Marc Cavaillon. Innate immunity and the inflammatory cascade. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0299.

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Inflammation results from a complex interaction between a large number of mediators able to induce each other and to favour the generation of other inflammatory molecules (e.g. free radicals, lipid mediators, and proteases). The perpetuation of inflammation by these cascades of mediators is favoured by their ability to induce coagulation, leukocyte recruitment, and cell and tissue alteration (apoptosis, necrosis, and barrier disruption). Other cascades of mediators occur to generate anti-inflammatory mediators favouring the healing process. A neuroendocrine loop and neuromediators from central and peripheral nervous system are also involved in the process, allowing a return to homeostasis.
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Vlachopoulos, Charalambos, und Nikolaos Ioakeimidis. Erectile dysfunction as a marker and predictor of cardiovascular disease. Herausgegeben von Charalambos Vlachopoulos. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0245.

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Erectile dysfunction (ED) is defined as the inability to obtain or maintain a penile erection to support satisfactory sexual performance. It is considered an early manifestation of generalized vascular disease and recognized as a marker of increased cardiovascular risk both acutely and chronically by predicting all-cause mortality, cardiovascular mortality, coronary events, stroke, and peripheral artery disease in men with and without known coronary artery disease. The link between ED and cardiovascular disease might reside in the interaction between androgen level, chronic inflammation, and cardiovascular risk factors that determine endothelial dysfunction and atherosclerosis both in the penile and coronary circulation. Because penile artery size is smaller compared with coronary arteries, the same degree of endothelial dysfunction and atherosclerotic burden causes a more significant reduction of blood flow in erectile tissues compared with that in coronary circulation. From a clinical standpoint, because ED may precede cardiovascular disease, it can be used as an early marker to identify men at higher risk of cardiovascular events. The average 3-year time period between the onset of ED symptoms and a cardiovascular event offers the opportunity for detailed cardiological assessment and intensive treatment of risk factors.
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Chinoy, Hector, und Robert G. Cooper. Polymyositis and dermatomyositis. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0124.

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Polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM) form part of the idiopathic inflammatory myopathies (IIM), a heterogeneous group of rare autoimmune diseases characterized by an acquired proximal muscle weakness, raised muscle enzymes (including creatine kinase), inflammatory cell infiltrates in muscle biopsy tissue, electrophysiological abnormalities, and presence of circulating myositis-specific/myositis-associated autoantibodies. The underlying aetiology of IIM is poorly understood, but likely involves interactions between environmental and genetic risk factors. Myositis may also manifest in association with other connective tissue disorders. The predominant clinical presentation of IIM is skeletal muscle weakness, but many extramuscular features can also occur. Access to good neuropathological support is essential in securing an accurate IIM diagnosis and excluding non-inflammatory myopathies, although IBM is often difficult to distinguish from PM. Antibody testing can help define IIM clinical subtypes, including cancer-associated myositis, predict prognosis, and help in optimizing treatment decisions. MRI can be invaluable for differentiating disease activity from damage, and detecting treatment-induced interval changes. Therapeutic effectiveness of new and existing treatments (where the evidence base remains poor) depends on making a prompt diagnosis and initiating early and appropriately aggressive treatment to prevent establishment of muscle damage. This chapter attempts to summarize the salient features of IIM and update the reader about currently used diagnostics and treatment paradigms in this rare and understudied disease.
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Eleftheriou, Despina, und Paul A. Brogan. Paediatric vasculitis. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0136.

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Systemic vasculitis is characterized by blood vessel inflammation which may lead to tissue injury from vascular stenosis, occlusion, aneurysm, and/or rupture. Apart from relatively common vasculitides such as Henoch-Schönlein purpura (HSP) and Kawasaki's disease (KD), most of the primary vasculitic syndromes are rare in childhood, but are associated with significant morbidity and mortality. New classification criteria for childhood vasculitis have recently been proposed and validated. The cause of most vasculitides is unknown, although it is likely that a complex interaction between environmental factors such as infections and inherited host responses trigger the disease and determine the vasculitis phenotype. Several genetic polymorphisms in vasculitis have now been described that may be relevant in terms of disease predisposition or development of disease complications. Treatment regimens continue to improve, with the use of different immunosuppressive medications and newer therapeutic approaches such as biologic agents. We provide an overview of paediatric vasculitides focusing on HSP, KD, and polyarteritis nodosa (PAN). Key differences (where relevant) between paediatric and adult vasculitis are highlighted. In addition we discuss new emerging challenges particularly in respect to the long-term cardiovascular morbidity for children with systemic vasculitis, and emphasize the importance of future international multicentre collaborative studies to further increase and standardize the scientific base of investigating and treating childhood vasculitis.
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Badimon, Lina, Felix C. Tanner, Giovanni G. Camici und Gemma Vilahur. Pathophysiology of thrombosis. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198755777.003.0018.

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Ischaemic heart disease and stroke are major causes of death and morbidity worldwide. Coronary and cerebrovascular events are mainly a consequence of a sudden thrombotic occlusion of the vessel lumen. Arterial thrombosis usually develops on top of a disrupted atherosclerotic plaque because of the exposure of thrombogenic material, such as collagen fibrils and tissue factor (TF), to the flowing blood. TF, either expressed by subendothelial cells, macrophage- and/or vascular smooth muscle-derived foam-cells in atherosclerotic plaques, is a key element in the initiation of thrombosis due to its ability to induce thrombin formation (a potent platelet agonist) and subsequent fibrin deposition at sites of vascular injury. Adhered platelets at the site of injury also play a crucial role in the pathophysiology of atherothrombosis. Platelet surface receptors (mainly glycoproteins) interact with vascular structures and/or Von Willebrand factor triggering platelet activation signalling events, including an increase in intracellular free Ca2+, exposure of a pro-coagulant surface, and secretion of platelet granule content. On top of this, interaction between soluble agonists and platelet G-coupled protein receptors further amplifies the platelet activation response favouring integrin alpha(IIb)beta(3) activation, an essential step for platelet aggregation. Blood-borne TF and microparticles have also been shown to contribute to thrombus formation and propagation. As thrombus evolves different circulating cells (red-blood cells and leukocytes, along with occasional undifferentiated cells) get recruited in a timely dependent manner to the growing thrombus and further entrapped by the formation of a fibrin mesh.
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Buchteile zum Thema "Interactions between tissues"

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Hendry, I. A., C. E. Hill und R. E. Bonyhady. „Interactions Between Developing Autonomic Neurons and their Target Tissues“. In Ciba Foundation Symposium 83 - Development of the Autonomic Nervous System, 194–212. Chichester, UK: John Wiley & Sons, Ltd., 2008. http://dx.doi.org/10.1002/9780470720653.ch10.

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Bertoluzza, A., P. Monti, R. Simoni und R. Caramazza. „Interface Interactions Between Hydrophilic Contact Lenses and Ocular Tissues“. In Interfaces in Medicine and Mechanics—2, 413–19. Dordrecht: Springer Netherlands, 1991. http://dx.doi.org/10.1007/978-94-011-3852-9_44.

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Ferlin, Kimberly M., David S. Kaplan und John P. Fisher. „Characterization of the Adhesive Interactions Between Cells and Biomaterials“. In Micro and Nanotechnologies in Engineering Stem Cells and Tissues, 159–82. Hoboken, New Jersey: John Wiley & Sons, Inc., 2013. http://dx.doi.org/10.1002/9781118574775.ch7.

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Roca, J., M. Hogan und P. D. Wagner. „Interactions Between Convective and Diffusive Components of O2 Transport to the Tissues“. In Update in Intensive Care and Emergency Medicine, 304–14. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-84209-2_26.

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Wiart, Joe, und Man Faï Wong. „Dosimetry of Interactions Between the Radioelectric Waves and Human Tissues - Hybrid Approach of the Metrology“. In Measurements using Optic and RF Waves, 229–48. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2013. http://dx.doi.org/10.1002/9781118586228.ch9.

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Edelstein-Keshet, Leah. „Pattern Formation Inside Living Cells“. In SEMA SIMAI Springer Series, 79–95. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-86236-7_5.

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AbstractWhile most of our tissues appear static, in fact, cell motion comprises an important facet of all life forms, whether in single or multicellular organisms. Amoeboid cells navigate their environment seeking nutrients, whereas collectively, streams of cells move past and through evolving tissue in the development of complex organisms. Cell motion is powered by dynamic changes in the structural proteins (actin) that make up the cytoskeleton, and regulated by a circuit of signaling proteins (GTPases) that control the cytoskeleton growth, disassembly, and active contraction. Interesting mathematical questions we have explored include (1) How do GTPases spontaneously redistribute inside a cell? How does this determine the emergent polarization and directed motion of a cell? (2) How does feedback between actin and these regulatory proteins create dynamic spatial patterns (such as waves) in the cell? (3) How do properties of single cells scale up to cell populations and multicellular tissues given interactions (adhesive, mechanical) between cells? Here I survey mathematical models studied in my group to address such questions. We use reaction-diffusion systems to model GTPase spatiotemporal phenomena in both detailed and toy models (for analytic clarity). We simulate single and multiple cells to visualize model predictions and study emergent patterns of behavior. Finally, we work with experimental biologists to address data-driven questions about specific cell types and conditions.
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Grote, J., G. Siegel, K. Zimmer und A. Adler. „The Interaction Between Oxygen and Vascular Wall“. In Oxygen Transport to Tissue XI, 575–81. Boston, MA: Springer US, 1989. http://dx.doi.org/10.1007/978-1-4684-5643-1_64.

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Majno, G. „Interactions Between Dead Cells and Living Tissue“. In Novartis Foundation Symposia, 87–105. Chichester, UK: John Wiley & Sons, Ltd., 2008. http://dx.doi.org/10.1002/9780470719336.ch5.

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Moreira, Sofia, Jaime A. Espina, Joana E. Saraiva und Elias H. Barriga. „A Toolbox to Study Tissue Mechanics In Vivo and Ex Vivo“. In Methods in Molecular Biology, 495–515. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2035-9_29.

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AbstractDuring vertebrate embryogenesis, tissues interact and influence each other’s development to shape an embryo. While communication by molecular components has been extensively explored, the role of mechanical interaction between tissues during embryogenesis is just starting to be revealed. Addressing mechanical involvement in morphogenesis has traditionally been challenging mainly due to the lack of proper tools to measure and modify mechanical environments of cells in vivo. We have recently used atomic force microscopy (AFM) to show that the migration of the Xenopus laevis cephalic neural crest cells is triggered by stiffening of the mesoderm, a tissue that neural crest cells use as a migratory substrate in vivo. Interestingly we showed that the activity of the planar cell polarity (PCP) pathway is required to mediate this novel mechanical interaction between two tissues. In this chapter, we share the toolbox that we developed to study the role of PCP signaling in mesoderm cell accumulation and stiffening (in vivo) as well as the impact of mesoderm stiffness in promoting neural crest cell polarity and migration (ex vivo). We believe that these tools can be of general use for investigators interested in addressing the role of mechanical inputs in vivo and ex vivo.
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Embery, G., R. J. Waddington und K. S. Last. „The Interaction between Connective Tissues and Implant Materials“. In Proceedings of the First International Conference on Interfaces in Medicine and Mechanics, 120–31. Dordrecht: Springer Netherlands, 1989. http://dx.doi.org/10.1007/978-94-011-7477-0_12.

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Konferenzberichte zum Thema "Interactions between tissues"

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Zhang, Lijuan, Spencer P. Lake, Victor K. Lai, Victor H. Barocas und Mark S. Shephard. „Elucidation of Microstructural Interactions Between Collagen and Non-Fibrillar Matrix in Soft Tissue Using a Coupled Fiber-Matrix Model“. In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80401.

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The mechanical properties of soft connective tissues are governed by their collagen fiber network and surrounding non-fibrillar matrix (e.g., proteoglycans, cells, elastin, etc.). In order to understand how healthy tissues function, and how properties change in injury and disease, it is necessary to quantify the mechanical response of both the collagen network and the non-fibrillar matrix (NFM), as well as the nature of the interaction between these tissue constituents. Using collagen-agarose co-gels as a simple experimental tissue analog system, we have demonstrated how NFM contributes to the mechanical and organizational properties of soft tissues in indentation and tension [1–2]. Furthermore, we used a network-based microscale model to examine how specific NFM properties alter the response of fiber-matrix composites under load [3]. This model fit our experimental data well and provided insight into the role of NFM in tensile mechanics. Since it was constructed according to the conventional approach of superposition of the two constituents (collagen network and NFM), however, the model could not specifically examine local interactions between collagen fibers and the surrounding NFM, which could be critical in assessing tissue damage or cell-matrix interactions. Therefore, we developed and evaluated a fiber-matrix modeling scheme to characterize the microstructural interactions between tissue constituents, as well as to quantify the role of individual tissue components in the behavior of soft tissues under tensile load. For validation, the new model (‘coupled’) was compared to our previous model (‘parallel’) and to experimental co-gel data.
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Frey, Christina R., Victor K. Lai und Victor H. Barocas. „Structural and Mechanical Differences Between Pure Collagen and Fibrin Gels and Partially Digested Co-Gels“. In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53675.

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Natural and bio-engineered tissues are often composed of multiple fiber networks (fibrin, collagen, elastin, etc.). The microstructure and interactions between components determine the macroscopic mechanical properties of the tissues. Examples of multi-fiber networks include skin (collagen and elastin) and thrombus during the wound healing process (collagen and fibrin). In addition, tissue engineers (eg. [1]) use fibrin as a scaffold to seed cells for tissue growth; over time, networks of collagen and fibrin coexist as the fibrin is degraded and replaced with cell-synthesized collagen. Our group has previously investigated the mechanical properties of single fiber networks of fibrin and collagen, but has shown that these do not obey the law of mixtures in a collagen-fibrin co-gel [2]. The goal of this project was to understand the interactions between the collagen and fibrin networks in a collagen-fibrin co-gel.
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Hyypio, Jeffrey D., Mohammad F. Hadi, Victor K. Lai und Victor H. Barocas. „A Microscale Collagen-Fibrin Interacting Network Model With Comparison to Experimental Results“. In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80656.

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Many native and bioengineered soft tissues are composed of two or more types of biopolymer networks that mechanically define and support the material [1]. Modeling the response of multi-network soft tissues to mechanical loading can be difficult due to the heterogeneous nature of these materials and the large strains (>1) involved. As tissues deform, the different biopolymer networks interact with one another and determine the overall stress-strain outcome for the tissue. Capturing this interaction could help improve the accuracy of a computer model to simulate the microscale behavior of soft tissues under load. We have developed a two-network model to reflect interactions between collagen and fibrin biopolymer networks loaded in uniaxial extension. The model can help improve our understanding of native and engineered tissue mechanics.
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Zhao, Ronghua, und Alan G. Casson. „Abstract 1098: Interactions between P53 and IGF2 in human esophageal adenocarcinoma tissues and cell lines“. In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-1098.

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Al-Safadi, Samer, und Parsaoran Hutapea. „An Analytical Model for Predicting the Deflection of Hollow Surgical Needle in Soft Tissue“. In ASME 2021 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2021. http://dx.doi.org/10.1115/imece2021-71532.

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Abstract Considerable research efforts have been devoted for studying the interaction between surgical needles and soft tissues which can be used to evaluate the deflection of a bevel-tip needle inside a tissue. The development of an analytical model to predict the steering behavior of the needle during needle-tissue interactions could improve the performance of many percutaneous needle-based procedures. In this study, Euler-Bernoulli beam elastic foundation theory was utilized to model the needle as a cantilever beam moving along its longitudinal axis and undergoing various external loads. The external loads are the result of the interaction between the tissue and the needle during insertion, they can be modeled as a concentrated tissue cutting force acting at the needle bevel, and needle-tissue interaction forces acting along the needle length and tangent to the needle shaft. The accuracy of the analytical predictions offered by the model are verified by comparing them to the experimental data. Due to the assumption of the elastic tissue material, the difference between the analytical model and the experimental results was between 15% to 33%. Current work is ongoing to consider tissue viscoelastic properties to improve the analytical prediction.
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Lai, Victor K., Allan M. Kerandi, Spencer P. Lake, Robert T. Tranquillo und Victor H. Barocas. „Collagen Network Architecture Varies Between Pure Collagen and Collagen-Fibrin Co-Gels“. In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80738.

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Naturally-occurring extracellular matrix (ECM) proteins, e.g. collagen I and fibrin, play an important role in tissues, conferring structural integrity and providing a biochemical environment for eliciting important cellular responses (e.g. migration). Tissue engineers use a variety of matrix polymers as initial scaffolds for seeding cells, sometimes in combination with one another (e.g. collagen-fibrin [1]). For example, our group fabricates arterial tissue equivalents (TEs) by seeding cells in a fibrin gel, which is gradually degraded over time and replaced by cell-produced collagen [2]. While the structure and mechanics of individual ECM proteins have been studied extensively, how multiple fibrillar networks interact to confer overall mechanical behavior remains poorly understood. Narrowing this gap in knowledge of scaffolds comprising multiple fibril networks is crucial in allowing for more rational design in tissue engineering, as cells react differently according to their mechanical environments. For collagen-fibrin networks in particular, early efforts in elucidating interactions between these two fibril networks in co-gels have proven inconclusive due to inconsistent findings from various groups. Recent modeling efforts by our group have shown that simple “series” and “parallel” type interactions provide bounds for the mechanical behavior of collagen-fibrin co-gels [3]. In addition, experiments on pure collagen and fibrin vs. their respective networks from collagen-fibrin co-gels after digestion showed slight differences in mechanical behavior [4]. These previous studies have focused on the composition-function relationship between collagen and fibrin. The objective of the current work is to explore how collagen network architecture changes in the presence of the fibrin network in collagen-fibrin co-gels, thereby providing an added dimension to our understanding of collagen-fibrin systems by elucidating structure-composition-function relationships between collagen and fibrin.
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Al-Safadi, Samer, und Parsaoran Hutapea. „Predicting Needle Deflection in Soft Tissue: a Computational Modeling Approach“. In ASME 2023 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2023. http://dx.doi.org/10.1115/imece2023-113833.

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Abstract This study explores the mechanical interactions between surgical needles and soft tissues during procedures like biopsies and brachytherapy. A key challenge is needle tip deflection, which can cause deviation from the intended target. The study aims to develop an analytical model that predicts needle tip deflection during insertion by combining principles from interfacial mechanics and soft tissue deformation. A modified version of the dynamic Euler-Bernoulli beam theory is employed to model needle insertion and predict needle tip deflection. The model’s predictions are then compared to experimental data obtained from needle insertions in real tissues. The research aims to deepen our understanding of needle-tissue interactions and develop a reliable model for predicting needle deflection, ultimately enhancing surgical robots and navigation systems for safer and more precise percutaneous procedures. Pig organs are used as a material data source for a viscoelastic model, simulating needle insertion into kidney-like environments and analyzing organ deformation. The modified Euler-Bernoulli beam theory considers the viscoelastic properties of the tissue. Deflection is then calculated and compared to experimental data, with analytical deflection measurements exhibiting a 5–10% difference compared to experimental results.
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Kim, Inki, Adam Gordon und Scarlett R. Miller. „Stochastic Event Detection in Needle-Tissue Interaction“. In ASME 2015 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2015. http://dx.doi.org/10.1115/detc2015-47384.

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Over the last decade, many dynamic models that express needle-force relationships under tissues of varying mechanical properties have been developed. While great progress has been made in the development of these high-fidelity models, they are only valid within certain boundary conditions limiting their match with reality. This gap in realism is aggravated by variability in human tissues, needles, and the modes of interaction with the tissue. In an effort to develop more realistic models, the current paper was developed to create and test an event (i.e. changes of variability) detection method based on the probability distribution of residues — difference between force models and measurements. To obtain force measurements, we repeated robotic-driven needle insertion into a simulated mannequin. Needle types and tissue thickness were varied in the measurements in order to add realistic variability. To obtain the force model, the measurement data was used as an input to a Grey-Box model. From the measurements and models, we estimated the probability distribution of residues. For validation, a Gaussian-Mixture Model (GMM) was used to confirm the stochastic model successfully distinguishes the residual distributions under different variability. We found that by examining the residual distributions it is possible to detect unexpected variability in needle-tissue interactions. The findings from this paper have implications for developing real-time event detection methods and simulating patient-variability in haptic applications.
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Ho, Patricia H., An M. Nguyen und Marc E. Levenston. „Osmotic Effects on the Dynamic Shear Properties of Meniscal Fibrocartilage“. In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192711.

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The meniscus plays an important role in many biomechanical functions of the knee, including shock absorption, load distribution, and joint lubrication. The ability to perform these functions is determined by the interactions of the major tissue constituents (water, proteoglycan, and collagen), although these interactions have not been as thoroughly studied in fibrocartilage as those in other soft tissues. In articular cartilage, electrochemical interactions between negatively charged glycosaminoglycan (GAG) side chains of proteoglycans and the interstitial fluid generate an osmotic swelling pressure that contributes to the compressive stiffness [1], and proteoglycan degradation dramatically decreases compressive and shear moduli [2]. Although the concentration of proteoglycan in the meniscus is substantially lower (<1%) than that in articular cartilage, aggrecan degradation also greatly decreases the compressive and shear moduli of meniscal fibrocartilage [3]. The proteoglycan distribution in meniscal fibrocartilage is macroscopically heterogeneous [4] and is concentrated in the secondary matrix surrounding the circumferential collagen bundles, and the extent to which osmotic interactions explain the influence on fibrocartilage material properties is unknown. Altering the osmotic strength of the bathing solution supplies a means to control osmotic interactions between the GAGs and the environment without degrading the tissue matrix. The objective of this study was to examine the effects of an altered osmotic environment on the dynamic shear modulus of meniscal tissue.
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Hatami-Marbini, Hamed, und Peter M. Pinsky. „Electrostatic Contribution of the Proteoglycans to the In-Plane Shear and Compressive Stiffness of Corneal Stroma“. In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19191.

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The extracellular matrix (ECM) is a fibrous structure embedded in an aqueous gel. The mechanical and electrostatic interactions of the ECM constituents, i.e. collagen fibers and proteoglycans (PGs), define the structure and mechanical response of connective tissues (CTs) such as cornea and articular cartilage. Proteoglycans are complex macromolecules consisting of linear chains of repeating gylcosaminoglycans (GAGs) which are covalently attached to a core protein. PGs can be as simple as decorin with a single GAG side chain or as complex as aggrecan with many GAGs. Decorin is the simplest small leucine-rich PG and is the main PG inside the corneal stroma. It has an arch shape and links non-covalently at its concave surface to the collagen fibrils. It has been shown that while collagen fibers inside the extracellular matrix resist the tensile forces, the negatively charged glycosaminoglycans and their interaction with water give compressive stiffness to the tissue. The role of PGs in biomechanical properties of the connective tissues has mainly been studied in order to explore the behavior of articular cartilage [1], which is a CT with large and highly negatively charged PGs, aggrecans. In order to explain the role of PGs in this tissue, it is commonly assumed that their contribution to the CT elasticity is because of both the repulsive forces between negatively charged GAGs and GAG interactions with free mobile charges in the ionic bath. The electrostatic contribution to the shear and compressive stiffness of cartilage is modeled by approximating GAGs as charged rods [1]. The Poisson-Boltzmann equation is used to compute the change in electrical potential and mobile ion distributions which are caused by the macroscopic deformation.
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Berichte der Organisationen zum Thema "Interactions between tissues"

1

Funkenstein, Bruria, und Shaojun (Jim) Du. Interactions Between the GH-IGF axis and Myostatin in Regulating Muscle Growth in Sparus aurata. United States Department of Agriculture, März 2009. http://dx.doi.org/10.32747/2009.7696530.bard.

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Growth rate of cultured fish from hatching to commercial size is a major factor in the success of aquaculture. The normal stimulus for muscle growth in growing fish is not well understood and understanding the regulation of muscle growth in fish is of particular importance for aquaculture. Fish meat constitutes mostly of skeletal muscles and provides high value proteins in most people's diet. Unlike mammals, fish continue to grow throughout their lives, although the size fish attain, as adults, is species specific. Evidence indicates that muscle growth is regulated positively and negatively by a variety of growth and transcription factors that control both muscle cell proliferation and differentiation. In particular, growth hormone (GH), fibroblast growth factors (FGFs), insulin-like growth factors (IGFs) and transforming growth factor-13 (TGF-13) play critical roles in myogenesis during animal growth. An important advance in our understanding of muscle growth was provided by the recent discovery of the crucial functions of myostatin (MSTN) in controlling muscle growth. MSTN is a member of the TGF-13 superfamily and functions as a negative regulator of skeletal muscle growth in mammals. Studies in mammals also provided evidence for possible interactions between GH, IGFs, MSTN and the musclespecific transcription factor My oD with regards to muscle development and growth. The goal of our project was to try to clarify the role of MSTNs in Sparus aurata muscle growth and in particular determine the possible interaction between the GH-IGFaxis and MSTN in regulating muscle growth in fish. The steps to achieve this goal included: i) Determining possible relationship between changes in the expression of growth-related genes, MSTN and MyoD in muscle from slow and fast growing sea bream progeny of full-sib families and that of growth rate; ii) Testing the possible effect of over-expressing GH, IGF-I and IGF-Il on the expression of MSTN and MyoD in skeletal muscle both in vivo and in vitro; iii) Studying the regulation of the two S. aurata MSTN promoters and investigating the possible role of MyoD in this regulation. The major findings of our research can be summarized as follows: 1) Two MSTN promoters (saMSTN-1 and saMSTN-2) were isolated and characterized from S. aurata and were found to direct reporter gene activity in A204 cells. Studies were initiated to decipher the regulation of fish MSTN expression in vitro using the cloned promoters; 2) The gene coding for saMSTN-2 was cloned. Both the promoter and the first intron were found to be polymorphic. The first intron zygosity appears to be associated with growth rate; 3) Full length cDNA coding for S. aurata growth differentiation factor-l I (GDF-II), a closely related growth factor to MSTN, was cloned from S. aurata brain, and the mature peptide (C-terminal) was found to be highly conserved throughout evolution. GDF-II transcript was detected by RT -PCR analysis throughout development in S. aurata embryos and larvae, suggesting that this mRNA is the product of the embryonic genome. Transcripts for GDF-Il were detected by RT-PCR in brain, eye and spleen with highest level found in brain; 4) A novel member of the TGF-Bsuperfamily was partially cloned from S. aurata. It is highly homologous to an unidentified protein (TGF-B-like) from Tetraodon nigroviridisand is expressed in various tissues, including muscle; 5) Recombinant S. aurata GH was produced in bacteria, refolded and purified and was used in in vitro and in vivo experiments. Generally, the results of gene expression in response to GH administration in vivo depended on the nutritional state (starvation or feeding) and the time at which the fish were sacrificed after GH administration. In vitro, recombinantsaGH activated signal transduction in two fish cell lines: RTHI49 and SAFI; 6) A fibroblastic-like cell line from S. aurata (SAF-I) was characterized for its gene expression and was found to be a suitable experimental system for studies on GH-IGF and MSTN interactions; 7) The gene of the muscle-specific transcription factor Myogenin was cloned from S. aurata, its expression and promoter activity were characterized; 8) Three genes important to myofibrillogenesis were cloned from zebrafish: SmyDl, Hsp90al and skNAC. Our data suggests the existence of an interaction between the GH-IGFaxis and MSTN. This project yielded a great number of experimental tools, both DNA constructs and in vitro systems that will enable further studies on the regulation of MSTN expression and on the interactions between members of the GHIGFaxis and MSTN in regulating muscle growth in S. aurata.
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2

Rafaeli, Ada, Russell Jurenka und Chris Sander. Molecular characterisation of PBAN-receptors: a basis for the development and screening of antagonists against Pheromone biosynthesis in moth pest species. United States Department of Agriculture, Januar 2008. http://dx.doi.org/10.32747/2008.7695862.bard.

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The original objectives of the approved proposal included: (a) The determination of species- and tissue-specificity of the PBAN-R; (b) the elucidation of the role of juvenile hormone in gene regulation of the PBAN-R; (c) the identificationof the ligand binding domains in the PBAN-R and (d) the development of efficient screening assays in order to screen potential antagonists that will block the PBAN-R. Background to the topic: Moths constitute one of the major groups of pest insects in agriculture and their reproductive behavior is dependent on chemical communication. Sex-pheromone blends are utilised by a variety of moth species to attract conspecific mates. In most of the moth species sex-pheromone biosynthesis is under circadian control by the neurohormone, PBAN (pheromone-biosynthesis-activating neuropeptide). In order to devise ideal strategies for mating disruption/prevention, we proposed to study the interactions between PBAN and its membrane-bound receptor in order to devise potential antagonists. Major conclusions: Within the framework of the planned objectives we have confirmed the similarities between the two Helicoverpa species: armigera and zea. Receptor sequences of the two Helicoverpa spp. are 98% identical with most changes taking place in the C-terminal. Our findings indicate that PBAN or PBAN-like receptors are also present in the neural tissues and may represent a neurotransmitter-like function for PBAN-like peptides. Surprisingly the gene encoding the PBAN-receptor was also present in the male homologous tissue, but it is absent at the protein level. The presence of the receptor (at the gene- and protein-levels), and the subsequent pheromonotropic activity are age-dependent and up-regulated by Juvenile Hormone in pharate females but down-regulated by Juvenile Hormone in adult females. Lower levels of pheromonotropic activity were observed when challenged with pyrokinin-like peptides than with HezPBAN as ligand. A model of the 3D structure of the receptor was created using the X-ray structure of rhodopsin as a template after sequence alignment of the HezPBAN-R with several other GPCRs and computer simulated docking with the model predicted putative binding sites. Using in silico mutagenesis the predicted docking model was validated with experimental data obtained from expressed chimera receptors in Sf9 cells created by exchanging between the three extracellular loops of the HezPBAN-R and the Drosophila Pyrokinin-R (CG9918). The chimera receptors also indicated that the 3ʳᵈ extracellular loop is important for recognition of PBAN or Diapause hormone ligands. Implications: The project has successfully completed all the objectives and we are now in a position to be able to design and screen potential antagonists for pheromone production. The successful docking simulation-experiments encourage the use of in silico experiments for initial (high-throughput) screening of potential antagonists. However, the differential responses between the expressed receptor (Sf9 cells) and the endogenous receptor (pheromone glands) emphasize the importance of assaying lead compounds using several alternative bioassays (at the cellular, tissue and organism levels). The surprising discovery of the presence of the gene encoding the PBAN-R in the male homologous tissue, but its absence at the protein level, launches opportunities for studying molecular regulation pathways and the evolution of these GPCRs. Overall this research will advance research towards the goal of finding antagonists for this important class of receptors that might encompass a variety of essential insect functions.
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Prusky, Dov, Lisa Vaillancourt und Robert Fluhr. Host Ammonification by Postharvest Pathogens and its Contribution to Fungal Colonization and Symptom Development. United States Department of Agriculture, Dezember 2006. http://dx.doi.org/10.32747/2006.7592640.bard.

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Postharvest decay of fruits and vegetables caused by pathogenic and saprophytic fungi significantly impairs the quality and quantity of fresh produce brought to market. Consequently, there is considerable interest in identifying factors that determine the susceptibility of these commodities to pathogen infection. Insidious postharvest decays remain quiescent during fruit growth and harvest, but activate during the postharvest period. A key response to the physiological changes occurring during fruit ripening is the initiation of ammonium secretion by the pathogen. Ammonium ions at the infection site (ammonification) have subsequent effects on both the pathogen and the host. An accompanying alkalinization process resulting from ammonia accumulation contributes to pathogenicity, since some important fungal virulence factors, (such as pectate lyase in Colletotrichum sp.), are significantly expressed only under alkaline conditions. In this proposal, investigated the mechanisms by which ammonification and alkalinization of infected tissues by the pathogen affect the host’s defense response to fungal attack, and instead increase compatibility during postharvest pathogen-host interactions. Our hypotheses were:1) that host signals, including ripening-related changes, induce secretion of ammonia by the pathogen; 2) that ammonia accumulation, and the resultant environmental alkalinization regulate the expression of fungal virulence genes that are essential for postharvest rot development; 3) that ammonification enhanced fungal colonization, by “suppression of host responses”, including production of reactive oxygen species, activation of superoxide, and polyphenol oxidase production. Our objectives were: to analyze: 1) factor(s) which activate the production and secretion of ammonia by the fungus; 2) fungal gene(s) that play role(s) in the ammonification process; 3) the relationship between ammonification and the activation of host defense response(s) during pathogen colonization; and 4) analyze hostgene expression in alkalinized regions of fruits attacked by hemibiotrophic fungi.
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Funkenstein, Bruria, und Cunming Duan. GH-IGF Axis in Sparus aurata: Possible Applications to Genetic Selection. United States Department of Agriculture, November 2000. http://dx.doi.org/10.32747/2000.7580665.bard.

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Many factors affect growth rate in fish: environmental, nutritional, genetics and endogenous (physiological) factors. Endogenous control of growth is very complex and many hormone systems are involved. Nevertheless, it is well accepted that growth hormone (GH) plays a major role in stimulating somatic growth. Although it is now clear that most, if not all, components of the GH-IGF axis exist in fish, we are still far from understanding how fish grow. In our project we used as the experimental system a marine fish, the gilthead sea bream (Sparus aurata), which inhabits lagoons along the Mediterranean and Atlantic coasts of Europe, and represents one of the most important fish species used in the mariculture industry in the Mediterranean region, including Israel. Production of Sparus is rapidly growing, however, in order for this production to stay competitive, the farming of this fish species has to intensify and become more efficient. One drawback, still, in Sparus extensive culture is that it grows relatively slow. In addition, it is now clear that growth and reproduction are physiological interrelated processes that affect each other. In particular sexual maturation (puberty) is known to be closely related to growth rate in fish as it is in mammals, indicating interactions between the somatotropic and gonadotropic axes. The goal of our project was to try to identify the rate-limiting components(s) in Sparus aurata GH-IGF system which might explain its slow growth by studying the ontogeny of growth-related genes: GH, GH receptor, IGF-I, IGF-II, IGF receptor, IGF-binding proteins (IGFBPs) and Pit-1 during early stages of development of Sparus aurata larvae from slow and fast growing lines. Our project was a continuation of a previous BARD project and could be divided into five major parts: i) obtaining additional tools to those obtained in the previous project that are necessary to carry out the developmental study; ii) the developmental expression of growth-related genes and their cellular localization; iii) tissue-specific expression and effect of GH on expression of growth-related genes; iv) possible relationship between GH gene structure, growth rate and genetic selection; v) the possible role of the IGF system in gonadal development. The major findings of our research can be summarized as follows: 1) The cDNAs (complete or partial) coding for Sparus IGFBP-2, GH receptor and Pit-1 were cloned. Sequence comparison reveals that the primary structure of IGFBP-2 protein is 43-49% identical to that of zebrafish and other vertebrates. Intensive efforts resulted in cloning a fragment of 138 nucleotides, coding for 46 amino acids in the proximal end of the intracellular domain of GH receptor. This is the first fish GH receptor cDNA that had been cloned to date. The cloned fragment will enable us to complete the GH - receptor cloning. 2) IGF-I, IGF-II, IGFBP-2, and IGF receptor transcripts were detected by RT-PCR method throughout development in unfertilized eggs, embryos, and larvae suggesting that these mRNAs are products of both the maternal and the embryonic genomes. Preliminary RT-PCR analysis suggest that GH receptor transcript is present in post-hatching larvae already on day 1. 3) IGF-1R transcripts were detected in all tissues tested by RT-PCR with highest levels in gill cartilage, skin, kidney, heart, pyloric caeca, and brain. Northern blot analysis detected IGF receptor only in gonads, brain and gill cartilage but not in muscle; GH increased slightly brain and gill cartilage IGF-1R mRNA levels. 4) IGFBP-2 transcript were detected only in liver and gonads, when analyzed by Northern blots; RT-PCR analysis revealed expression in all tissues studied, with the highest levels found in liver, skin, gonad and pyloric caeca. 5) Expression of IGF-I, IGF-II, IGF-1R and IGFBP-2 was analyzed during gonadal development. High levels of IGF-I and IGFBP-2 expression were found in bisexual young gonads, which decreased during gonadal development. Regardless of maturational stage, IGF-II levels were higher than those of IGF-L 6) The GH gene was cloned and its structure was characterized. It contains minisatellites of tandem repeats in the first and third introns that result in high level of genetic polymorphism. 7) Analysis of the presence of IGF-I and two types of IGF receptor by immunohistochemistry revealed tissue- and stage-specific expression during larval development. Immunohistochemistry also showed that IGF-I and its receptors are present in both testicular and ovarian cells. Although at this stage we are not able to pinpoint which is the rate-limiting step causing the slow growth of Sparus aurata, our project (together with the previous BARD) yielded a great number of experimental tools both DNA probes and antibodies that will enable further studies on the factors regulating growth in Sparus aurata. Our expression studies and cellular localization shed new light on the tissue and developmental expression of growth-related genes in fish.
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5

Cherlet, Tracy C., und Leigh C. Murphy. Interaction Between Estrogen Receptor-Beta and the Transforming Growth Factor-Beta Signaling Cascade in Human Breast Tissue. Fort Belvoir, VA: Defense Technical Information Center, Juli 2004. http://dx.doi.org/10.21236/ada430338.

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6

Matthews, Lisa, Guanming Wu, Robin Haw, Timothy Brunson, Nasim Sanati, Solomon Shorser, Deidre Beavers, Patrick Conley, Lincoln Stein und Peter D'Eustachio. Illuminating Dark Proteins using Reactome Pathways. Reactome, Oktober 2022. http://dx.doi.org/10.3180/poster/20221027matthews.

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Diseases are often the consequence of proteins or protein complexes that are non-functional or that function improperly. An active area of research has focused on the identification of molecules that can interact with defective proteins and restore their function. While 22% percent of human proteins are estimated to be druggable, less than fifteen percent are targeted by FDA-approved drugs, and the vast majority of untargeted proteins are understudied or so-called "dark" proteins. Elucidation of the function of these dark proteins, particularly those in commonly drug-targeted protein families, may offer therapeutic opportunities for many diseases. Reactome is the most comprehensive, open-access pathway knowledgebase covering 2585 pathways and including 14246 reactions, 11088 proteins, 13984 complexes, and 1093 drugs. Placing dark proteins in the context of Reactome pathways provides a framework of reference for these proteins facilitating the generation of hypotheses for experimental biologists to develop targeted experiments, unravel the potential functions of these proteins, and then design drugs to manipulate them. To this end, we have trained a random forest with 106 protein/gene pairwise features collected from multiple resources to predict functional interactions between dark proteins and proteins annotated in Reactome and then developed three scores to measure the interactions between dark proteins and Reactome pathways based on enrichment analysis and fuzzy logic simulations. Literature evidence via manual checking and systematic NLP-based analysis support predicted interacting pathways for dark proteins. To visualize dark proteins in the context of Reactome pathways, we have also developed a new website, idg.reactome.org, by extending the Reactome web application with new features illustrating these proteins together with tissue-specific protein and gene expression levels and drug interactions.
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Or, Etti, Tai-Ping Sun, Amnon Lichter und Avichai Perl. Characterization and Manipulation of the Primary Components in Gibberellin Signaling in the Grape Berry. United States Department of Agriculture, Januar 2010. http://dx.doi.org/10.32747/2010.7592649.bard.

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Seedless cultivars dominate the table grape industry. In these cultivars it is mandatory to apply gibberellin (GA) to stimulate berry development to a commercially acceptable size. These cultivars differ in their sensitivity to GA application, and it frequently results in adverse effects such as decreased bud fertility and increased fruit drop. Our long term goals are to (1) understand the molecular basis for the differential sensitivity and identify markers for selection of sensitive cultivars (2) to develop new strategies for targeted manipulation of the grape berry response to GA that will eliminate the need in GA application and the undesirable effects of GA on the vine, while maintaining its desirable effects on the berry. Both strategies are expected to reduce production cost and meet growing consumer demand for reduced use of chemicals. This approach relies on a comprehensive characterization of the central components in the GA signaling cascade in the berry. Several key components in the GA signaling pathway were identified in Arabidopsis and rice, including the GA receptors, GID1s, and a family of DELLA proteins that are the major negative regulators of the GA response. GA activates its response pathway by binding to GID1s, which then target DELLAs for degradation via interaction with SLY, a DELLA specific F-box protein. In grape, only one DELLA gene was characterized prior to this study, which plays a major role in inhibiting GA-promoted stem growth and GA-repressed floral induction but it does not regulate fruit growth. Therefore, we speculated that other DELLA family member(s) may control GA responses in berry, and their identification and manipulation may result in GA-independent berry growth. In the current study we isolated two additional VvDELLA family members, two VvGID1 genes and two VvSLY genes. Arabidopsis anti-AtRGA polyclonal antibodies recognized all three purified VvDELLA proteins, but its interaction with VvDELLA3 was weaker. Overexpression of the VvDELLAs, the VvGID1s, and the VvSLYs in the Arabidopsis mutants ga1-3/rga-24, gid1a-2/1c-2 and sly1-10, respectively, rescued the various mutant phenotypes. In vitro GAdependent physical interaction was shown between the VvDELLAs and the VvGID1s, and GAindependent interaction was shown between the VvDELLAs and VvSLYs. Interestingly, VvDELLA3 did not interact with VvGID1b. Together, the results indicate that the identified grape homologs serve as functional DELLA repressors, receptors and DELLA-interacting F-box proteins. Expression analyses revealed that (1) VvDELLA2 was expressed in all the analyzed tissues and was the most abundant (2) VvDELLA1 was low expressed in berries, confirming former study (3) Except in carpels and very young berries, VvDELLA3 levels were the lowest in most tissues. (4) Expression of both VvGID1s was detected in all the grape tissues, but VvGID1b transcript levels were significantly higher than VvGID1a. (5) In general, both VvDELLAs and VvGID1s transcripts levels increased as tissues aged. Unfertilized and recently fertilized carpels did not follow this trend, suggesting different regulatory mechanism of GA signaling in these stages. Characterization of the response to GA of various organs in three seedless cultivars revealed differential response of the berries and rachis. Interestingly, VvDELLA3 transcript levels in the GA-unresponsive berries of cv. Spring blush were significantly higher compared to their levels in the highly responsive berries of cv. Black finger. Assuming that VvDELLA2 and VvDELLA3 are regulating berry size, constructs carrying potential dominant mutations in each gene were created. Furthermore, constitutive silencing of these genes by mIR is underway, to reveal the effect of each gene on the berry phenotype.
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Davidson, Irit, Hsing-Jien Kung und Richard L. Witter. Molecular Interactions between Herpes and Retroviruses in Dually Infected Chickens and Turkeys. United States Department of Agriculture, Januar 2002. http://dx.doi.org/10.32747/2002.7575275.bard.

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Tumors in commercial poultry are caused mainly by infection with avian herpes and retroviruses, the herpesvirus Marek's disease virus (MDV) and the retroviruses, reticuloendotheliosis (REV), lymphoid leukosis, subgroups A-I and J (ALV and ALV-J) in chickens, or Iymphoprolipherative disease (LPDV) in turkeys. Infection with one virus aggravates the clinical outcome of birds that are already infected by another oncogenic virus. As these viruses do not interfere for infection, MDV and one or more retroviruses can infect the same flock, the same bird and the same cell. While infecting the same cell, herpes and retroviruses might interact in at least three ways: a) Integration of retrovirus genomes, or genomic fragments (mainly the LTR) into MDV;b) alteration of LTR-driven expression of retroviral genes by MDV immediate- early genes, and c) by herpesvirus induced cellular transcriptional factors. The first type of molecular interaction have been demonstrated to happen efficiently in vitro by Dr. Kung, in cases multiple infection of cell cultures with MDV and REV or MDV and ALV. Moreover, Dr. Witter showed that an in vitro-created recombinant, RM1, had altered in vitro replication and in vivo biological properties. A more comprehensive characterization of RM1 was carried out in the present project. We sought to highlight whether events of such integrations occur also in the bird, in vivo. For that, we had first to determine the prevalence of dually-infected individual birds in commercial flocks, as no systematic survey has been yet reported. Surprisingly, about 25% of the commercial flocks infected with avian oncogenic viruses had a multiple virus infection and 5% of the total samples ana lysed had multiple virus sequences. Then, we aimed to evaluate and characterize biologically and molecularly the resulting recombinants, if formed, and to analyse the factors that affect these events (virus strains, type and age of birds and time interval between the infection with both viruses). The perception of retrovirus insertions into herpesviruses in vivo is not banal, as the in vivo and in vitro systems differ in the viral-target cells, lymphocytes or fibroblasts, in the MDV-replicative type, transforming or productive, and the immune system presence. We realized that previous methods employed to study in vitro created recombinant viruses were not adequate for the study of samples taken directly from the bird. Therefore, the Hot Spot-combined PCR was developed based on the molecularly known RM1 virus. Also, the PFGE that was used for tissue cultured-MDV separation was inefficient for separating MDV from organs, but useful with feather tips as a source of bird original MDV. Much attention was dedicated now to feathers, because if a recombinant virus would be formed in vivo, its biological significance would be evident by horizontal dissemination through the feathers. Major findings were: a) not only in vitro, but also in vivo MDV and retrovirus co-infections lead to LTR integrations into MDV. That was shown by the detection of chimeric molecules. These appeared in low quantities and as quasispecies, thus interfering with sequence analysis of cloned gel-purified chimeric molecules. Mainly inserts were located in the repeat long MDV fragments. In field birds chimeric molecules were detected at a lower frequency (2.5%) than in experimentally infected birds (30-50%). These could be transmitted experimentally to another birds by inoculation with chimeric molecules containing blood. Several types of chimeric molecules were formed, and same types were detected in birds infected by a second round. To reproduce viral integrations, in vivo infection trials were done with field inoculate that contained both viruses, but the chimeric molecule yield was undetectable.
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9

Cucinotta, Francis A. Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling. Office of Scientific and Technical Information (OSTI), September 2016. http://dx.doi.org/10.2172/1335567.

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O'Neill, Peter, und Jennifer Anderson. Systems Biology Model of Interactions Between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFbeta and ATM Signaling. Office of Scientific and Technical Information (OSTI), Oktober 2014. http://dx.doi.org/10.2172/1158919.

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