Academic literature on the topic 'Cellular control mechanisms'

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Journal articles on the topic "Cellular control mechanisms"

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Reynolds, Noah M., Beth A. Lazazzera, and Michael Ibba. "Cellular mechanisms that control mistranslation." Nature Reviews Microbiology 8, no. 12 (November 16, 2010): 849–56. http://dx.doi.org/10.1038/nrmicro2472.

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Roath, Stuart. "Cellular Proteases and Control Mechanisms." Blood Coagulation & Fibrinolysis 2, no. 4 (August 1991): 575. http://dx.doi.org/10.1097/00001721-199108000-00010.

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Keeling, Jacob, Leonidas Tsiokas, and Dipak Maskey. "Cellular Mechanisms of Ciliary Length Control." Cells 5, no. 1 (January 29, 2016): 6. http://dx.doi.org/10.3390/cells5010006.

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Erne, P., E. Carafoli, C. van Breemen, and F. R. Bühler. "Update on Cellular Calcium Control Mechanisms." Journal of Cardiovascular Pharmacology 12, Supplement (1988): 1. http://dx.doi.org/10.1097/00005344-198800125-00001.

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Erne, P., E. Carafoli, C. van Breemen, and F. R. Bühler. "Update on Cellular Calcium Control Mechanisms." Journal of Cardiovascular Pharmacology 12 (1988): 1. http://dx.doi.org/10.1097/00005344-198806125-00001.

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Berridge, Michael J. "Calcium signal transduction and cellular control mechanisms." Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1742, no. 1-3 (December 2004): 3–7. http://dx.doi.org/10.1016/j.bbamcr.2004.08.012.

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Deaton, Lewis E., and Sidney K. Pierce. "Introduction: Cellular volume regulation—mechanisms and control." Journal of Experimental Zoology 268, no. 2 (February 1, 1994): 77–79. http://dx.doi.org/10.1002/jez.1402680202.

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Andrews, Norma W., Patricia E. Almeida, and Matthias Corrotte. "Damage control: cellular mechanisms of plasma membrane repair." Trends in Cell Biology 24, no. 12 (December 2014): 734–42. http://dx.doi.org/10.1016/j.tcb.2014.07.008.

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Outeiro, Tiago Fleming, and Julie Tetzlaff. "Mechanisms of Disease II: Cellular Protein Quality Control." Seminars in Pediatric Neurology 14, no. 1 (March 2007): 15–25. http://dx.doi.org/10.1016/j.spen.2006.11.005.

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Billmann, GE. "Cellular Mechanisms for Ventricular Fibrillation." Physiology 7, no. 6 (December 1, 1992): 254–59. http://dx.doi.org/10.1152/physiologyonline.1992.7.6.254.

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Alterations in cardiac autonomic control cause changes in cytosolic second messenger concentrations. This may represent the cellular mechanism for malignant arrhythmias. In particular, cytosolic calcium elevations can alter cardiac impulse generation (oscillatory afterdepolarization) and impulse conduction (nonuniform repolarization), which alone or in combination could trigger ventricular fibrillation.
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Dissertations / Theses on the topic "Cellular control mechanisms"

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Chirasani, Sridhar Reddy. "Cellular and molecular mechanisms of glioma growth control." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2009. http://dx.doi.org/10.18452/16032.

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Im ersten Teil meiner Arbeit habe ich den molekularen Mechanismus beschrieben, mit dem endogene neuronale Vorläuferzellen antitumorigen gegen Gliomstammzellen wirken. Unsere Forschungsgruppe hat in bereits veröffentlichten Arbeiten gezeigt, dass neuronale Vorläuferzellen zu experimentellen Gehirntumoren migrieren und Tumorzelltod induzieren können. In der nun vorliegenden Arbeit zeige ich, dass die neuronalen Vorläuferzellen nicht nur benefiziell gegen die Hauptpopulation der Tumorzellen wirken, sondern darüber hinaus auch die kleinere Population der sehr aggressiven Tumorstammzellen – mittels Sekretion von BMP7 – supprimieren. Insgesamt zeigt meine Arbeit, dass neuronale Vorläuferzellen die Pathogenität der Gliomstammzellen unterdrücken. Im zweiten Teil meiner Arbeit habe ich einen zellautonomen Mechanismus untersucht, der Gliomzellen in vitro und in vivo vermehrt expandieren lässt. Meine Ergebnisse zeigen, dass die Familie der ets-Transkriptionsfaktoren Gliomzellen zur Proliferation anregen, indem sie die Expresion eines Eisentransporters (dem Transferrin-Rezeptor-1) induzieren und damit die intrazelluläre Akkumulation von Eisenionen begünstigen. Die Veränderung des Redox-Gleichgewichts in den Gliomzellen regt die Tumore zu verstärkter Sekretion von Glutamat an. Dadurch werden die Gliome sehr zytotoxisch und induzieren Zelltod in den Zellen des tumorumgebenden Parenchyms. Das untergegangene Nervengewebe schafft damit den Platz, den der Tumor zur Expansion braucht. Insgesamt zeigt meine Arbeit, dass die ets1-induzierte CD71 Expression nicht nur das Tumorwachstum befördert, sondern auch den Platz zum Tumorwachstum schafft.
In my first part,Gliomas cells with stem-like properties (GSCs) control tumor growth and recurrence. Here, I showed that endogenous neural precursor cells (NPCs) perform an anti-tumor response by specifically targeting GSCs: In vitro, NPCs predominantly expressed BMP7; BMP7 was constitutively released from neurospheres and induced canonical BMP-signaling in GSCs. Exposure of human and murine GSCs to neurosphere-derived BMP7 increased GSC differentiation, attenuated GSC-marker expression, GSC self-renewal and the ability for tumor initiation.This anti-tumor response of NPCs protect the brain from gliomas by releasing BMP7, which acts as a paracrine tumor suppressor that represses proliferation, self-renewal and tumor-initiation of GSCs. In the 2nd part, Transferrin receptors (TfR) are overexpressed in brain tumors, but the pathological relevance has not been fully explored. Here, I showed that TfR is an important downstream effector of ets transcription factors that promotes glioma proliferation and increases glioma-evoked neuronal death. TfR mediates iron accumulation and reactive oxygen formation and thereby enhanced proliferation in clonal human glioma lines. TfR-induced oxidant accumulation modified cellular signaling by inactivating a protein tyrosine phosphatase (low-molecular-weight protein tyrosine phosphatase), activating mitogen-activated protein kinase and Akt and by inactivating p21/cdkn1a and pRB. Inactivation of these cell cycle regulators facilitated S-phase entry. Besides its effect on proliferation, TfR also boosted glutamate release, which caused NMDA mediated reduction of neuron cell mass. Overall my results indicate that TfR promotes glioma progression by two mechanisms, an increase in proliferation rate and glutamate production, the latter mechanism providing space for the progressing tumor mass.
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Bulmer, J. Todd. "Cellular responses to the anti-cancer drug, cisplatin /." *McMaster only, 2001.

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Harding, Angus Silas. "A biochemical analysis of the MAP kinase pathway in mammalian cells /." A biochemical analysis of the MAP kinase pathway in mammalian cellsRead the abstract of the thesis, 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17885.pdf.

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Yu, Lu. "Multiple signaling pathways cooperate to activate skeletal muscle differentiation /." View abstract or full-text, 2005. http://library.ust.hk/cgi/db/thesis.pl?BICH%202005%20YU.

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Martinez-Zaguilan, Raul. "The role of intracellular pH and calcium in the regulation of cellular functions." Diss., The University of Arizona, 1992. http://hdl.handle.net/10150/185889.

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Upon cell stimulation with hormones and other mitogens, a variety of biochemical and physiological responses occur within the first few minutes, including turnover of inositol phospholipids, activation of a number of kinases, and changes in intracellular pH (pHⁱⁿ) and calcium ([Ca²⁺]ⁱⁿ). Changes in both pHⁱⁿ and [Ca²⁺](in) are prominent and play a major role in the signal transduction mechanism leading to the physiological response, i.e. secretion, neurotransmission, proliferation and differentiation. The intracellular pH changes that follow mitogenic activation are complex and may reflect several different H⁺ transporting mechanisms. There are at least three main systems involved in the regulation of pHⁱⁿ in eukaryotic cells: (a) the mitogen stimulated Na⁺/H⁺ exchange, which electroneutrally raises pHⁱⁿ and can be inhibited by amiloride and its derivatives; (b) a variety of HCO₃⁻-based mechanisms which can alkalinize or acidify the cytosol, and can be inhibited by stilbene disulfonate derivatives; (c) and a plasma membrane H⁺-ATPase, which represents the least understood mechanism of pHⁱⁿ regulation. Under non-pathological conditions, pHⁱⁿ regulation is generally achieved by Na⁺/H⁺ exchange and HCO₃⁻-based mechanisms. Missexpression of a H⁺-ATPase in the plasma membrane can lead to a chronically high pHⁱⁿ in some tumor cells and might contribute to carcinogenesis. Chapter I explains the dissertation format and the relationship of the manuscripts included in three appendices. This chapter also indicates my contribution to each of these manuscripts. Chapter II is a summary of the most important findings in these manuscripts. Appendix I deals with the role of Na⁺/H⁺ exchange and Cl⁻/HCO₃⁻ exchange in the regulation of pHⁱⁿ. Appendix II deals with the role of H⁺-ATPase in the maintenance of a chronically high pHⁱⁿ and its possible involvement in tumorigenesis. Appendix III describes a technique to simultaneously measure pHⁱⁿ and [Ca²⁺]ⁱⁿ by fIuorescence spectroscopy. This appendix also describes the application to study the role of pHⁱⁿ and Ca²⁺ in the regulation of cell growth and progesterone secretion.
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Tang, Ho Lam. "The subcellular localization of actin, cofilin and cell-death-inducing DFF45-like effector (CIDE)-A and -B upon apoptosis /." View abstract or full-text, 2006. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202006%20TANG.

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Daniels, Brodie Belinda. "The effect of human soluble FceRII on the RPMI 8866 B-Lymphoblastoid and the U937 Monocyte cell lines." Thesis, University of Port Elizabeth, 2003. http://hdl.handle.net/10948/322.

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Due to the diverse functions of Fc eRII, such as its roles in cellular adhesion, growth and differentiation of B and T lymphocytes, rescue of B cells from apoptosis and release of cytotoxic mediators, it is clear why it is believed to be a central molecule in allergic response. Because of its important role in the regulation of IgE production, FceRII may be the primary cause of certain allergic conditions. This study attempted to express and purify a recombinant human soluble FceRII to test its effect on a B-lymphoblastoid (RPMI 8866) and a monocytic (U937) cell line. The protein was expressed in Escherichia coli inclusion bodies, before being refolded and purified in a single gel chromatography step. This pure protein was then tested for biological activity by testing its IgE binding func tion. Once proven functional, it was used to test its effect on the cell lines at three concentrations for its apoptotic rescue properties and its cytokine effects. The recombinant protein did not seem to have any significant effect on the apoptotic rescue of either cell line. While the recombinant sFceRII appeared to have a slight effect on the stimulation of IL-1ß and TNFa in the RPMI 8866 cells, there was no apparent effect on the production of NF?B. In U937 cells, the protein did not seem to have any effect on the stimulation of IL-1ß, TNFa or NF?B. However, the cytokine effects of the recombinant protein were tested on isolated PBMCs from a healthy individual and a hyper-IgE syndrome patient. The recombinant protein was able to stimulate the production of cytokines in both individuals’ PBMCs, proving that it has the same effect as the natural protein. The upregulation of these cytokines indicates that the recombinant protein is able to stimulate the immune system. Therefore, this recombinant soluble FceRII protein could possibly be used for immune therapy.
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Buschmann, Mary McVey. "Laminin-332-Mediated Proliferation Control: Mechanisms Regulating Formation of the Epithelium." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275661166.

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Mei, Hua. "The role of G[alpha]z during muscle differentiation /." View abstract or full-text, 2006. http://library.ust.hk/cgi/db/thesis.pl?BICH%202006%20MEI.

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Chan, Siu Chiu. "Regulation of cidea protein stability by the ubiquitin-mediated proteasomal degradation pathway and characterization of Cidea's interacting proteins /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202007%20CHANS.

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Books on the topic "Cellular control mechanisms"

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R, Pfeiffer Douglas, McMillin-Wood Jeanie B, and Little Steve, eds. Cellular Ca²⁺ regulation. New York: Plenum Press, 1988.

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1933-, Eguchi Gorō, Okada T. S, and Saxén Lauri, eds. Regulatory mechanism in developmental processes: Proceedings of the 3rd Symposium of the International Prize for Biology : National Institute for Basic Biology, Okazaki, 27-28 November 1987. Amsterdam: Elsevier, 1988.

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Ralph, Lydic, and Baghdoyan Helen A, eds. Handbook of behavioral state control: Cellular and molecular mechanisms. Boca Raton: CRC Press, 1999.

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1961-, Pagano M., ed. Cell cycle control. Berlin: Springer, 1998.

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Christoph, Lüttgau Hans, ed. Membrane control of cellular activity. Stuttgart: Fischer, 1986.

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Keränen, Sirkka, and Jussi Jäntti. Regulatory mechanisms of intracellular membrane transport. Berlan: Springer-Verlag, 2004.

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R, Whittenbury, ed. Homeostatic mechanisms in micro-organisms. Claverton Down, Bath: Published by Bath University Press for the Society for Applied Bacteriology on behalf of the Federation of European Microbiological Societies, 1988.

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NATO Advanced Study Instiute on Cellular and Molecular Control of Direct Cell Interactions in Developing Systems (1984 Banyuls-sur-Mer, France). Cellular and molecular control of direct cell interactions. New York: Plenum Press, 1985.

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1933-, Kuo J. F., ed. Phospholipids and cellular regulation. Boca Raton, Fla: CRC Press, 1985.

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Todorov, I. N. Mechanisms of cell stability: Subcellular and molecular aspects. New York: Nova Science Publishers, 1994.

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Book chapters on the topic "Cellular control mechanisms"

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Simpson, Paul C., Ken-ichi Kariya, Larry R. Karns, Carlin S. Long, and Joel S. Karliner. "Adrenergic hormones and control of cardiac myocyte growth." In Molecular Mechanisms of Cellular Growth, 35–43. Boston, MA: Springer US, 1991. http://dx.doi.org/10.1007/978-1-4615-3886-8_5.

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Olson, Eric N., Thomas J. Brennan, Tushar Chakraborty, Tse-Chang Cheng, Peter Cserjesi, Diane Edmondson, Guy James, and Li Li. "Molecular control of myogenesis: antagonism between growth and differentiation." In Molecular Mechanisms of Cellular Growth, 7–13. Boston, MA: Springer US, 1991. http://dx.doi.org/10.1007/978-1-4615-3886-8_1.

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de Lanerolle, Primal. "Cellular Control Mechanisms in Airway Smooth Muscle." In Airway Smooth Muscle in Health and Disease, 99–125. Boston, MA: Springer US, 1989. http://dx.doi.org/10.1007/978-1-4613-0779-2_6.

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Busse, R., A. Lückhoff, and A. Mülsch. "Cellular mechanisms controlling EDRF/NO formation in endothelial cells." In Endothelial Mechanisms of Vasomotor Control, 7–16. Heidelberg: Steinkopff, 1991. http://dx.doi.org/10.1007/978-3-642-72461-9_2.

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Schnapp, Andreas, Horst Rosenbauer, and Ingrid Grummt. "Trans-acting factors involved in species- specificity and control of mouse ribosomal gene transcription." In Molecular Mechanisms of Cellular Growth, 137–47. Boston, MA: Springer US, 1991. http://dx.doi.org/10.1007/978-1-4615-3886-8_17.

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Fuchs, Franklin. "The Frank -Starling Relationship: Cellular and Molecular Mechanisms." In Molecular Control Mechanisms in Striated Muscle Contraction, 379–415. Dordrecht: Springer Netherlands, 2002. http://dx.doi.org/10.1007/978-94-015-9926-9_11.

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Truman, D. E. S. "The Evolution of Control Mechanisms in Cellular Differentiation." In Coordinated Regulation of Gene Expression, 299–310. Boston, MA: Springer US, 1986. http://dx.doi.org/10.1007/978-1-4613-2245-0_28.

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Bee, James A., and Klaus von der Mark. "Mechanisms of Embryonic Limb Bud Intercellular Adhesion : Kinetic Analyses and Characterization of the Molecular Mechanism." In Cellular and Molecular Control of Direct Cell Interactions, 219–35. Boston, MA: Springer US, 1985. http://dx.doi.org/10.1007/978-1-4684-5092-7_11.

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Flemström, Gunnar, Bengt Säfsten, and Lars Knutson. "Role of Dopamine in Control of Duodenal Mucosal Bicarbonate Secretion." In Molecular and Cellular Mechanisms of H+ Transport, 483–90. Berlin, Heidelberg: Springer Berlin Heidelberg, 1994. http://dx.doi.org/10.1007/978-3-642-79301-1_55.

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Isenberg, Gerrit. "Smooth Muscle: Control of [Ca2+]c by the Membrane Potential." In Molecular and Cellular Mechanisms of Cardiovascular Regulation, 149–67. Tokyo: Springer Japan, 1996. http://dx.doi.org/10.1007/978-4-431-65952-5_12.

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Conference papers on the topic "Cellular control mechanisms"

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Ueda, Jun, Thomas Secord, and H. Harry Asada. "Piezoelectric Cellular Actuators Using Nested Rhombus Multilayer Mechanisms." In ASME 2008 Dynamic Systems and Control Conference. ASMEDC, 2008. http://dx.doi.org/10.1115/dscc2008-2128.

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Piezoelectric ceramic material, such as Lead Zirconate Titanate (PZT), has large stress and bandwidth, but its extremely small strain, i.e. only 0.1%, has been a major bottleneck for broad applications. We have proposed a “nested rhombus” multi-layer mechanism for PZT actuators, which increases strain exponentially through its hierarchical cellular structure, for over 20% effective strain. To drive a large load, however, care must be taken in the design of the strain amplification structure. Through kinematic and static analysis this paper addresses how the output force and displacement are attenuated by the joint stiffness and beam compliance involved in the strain amplification mechanism. An insightful lumped parameter model is developed to quantify the performance degradation and facilitate design tradeoffs. A prototype nested PZT cellular actuator that weighs only 15 g has produced 21% effective strain (2.49 mm displacement from 12 mm actuator length) and 1.7 N blocking force.
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Lopez-Aguilera, Elena, and Jordi Casademont. "Transmit power control mechanisms in IEEE 802.11 cellular networks." In Proceeding of the 2006 international conference. New York, New York, USA: ACM Press, 2006. http://dx.doi.org/10.1145/1143549.1143695.

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Mayalu, Michaëlle N., and H. Harry Asada. "Integrated Mechanistic-Empirical Modeling of Cellular Response Based on Intracellular Signaling Dynamics." In ASME 2013 Dynamic Systems and Control Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/dscc2013-3806.

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A hybrid modeling framework integrating a highly specific mechanistic model with highly abstract empirical model is presented. With the growing interest in the scientific and medical community for identification of therapeutic targets in treatment of disease, it is necessary to develop predictive models that can describe cellular behavior in response to environmental cues. Intracellular signaling pathways form complex networks that regulate cellular response in both health and disease. Mechanistic (or white-box) models of biochemical networks are often unable to explain comprehensive cellular response due to lack of knowledge and/or intractable complexity (especially in events distal from the cell membrane). Empirical (or black-box) models may provide a less than accurate representation of cellular response due to data deficiency and/or loss of mechanistic detail. In the proposed framework, we use a mechanistic model to capture early signaling events and apply the resulting generated internal signals (along with external inputs) to a downstream empirical sub-model. The key construct in the approach is the treatment of a cell’s biochemical network as an encoder that creates a functional internal representation of external environmental cues. The signals derived from this representation are then used to inform downstream behaviors. Using this idea, we are able to create a comprehensive framework that describes important mechanisms with sufficient detail, while representing complex or unknown mechanisms in a more abstract form. The model is verified using published biological data describing T-Cells in immune response.
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Tien, Joe, John L. Tan, Celeste M. Nelson, and Christopher S. Chen. "Building Cellular Microenvironments to Control Capillary Endothelial Cell Proliferation, Death, and Differentiation." In ASME 2001 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2001. http://dx.doi.org/10.1115/imece2001/bed-23154.

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Abstract The dynamic binding interactions between cell surface receptors and local bioactive ligands serves as the principal mechanism by which cells survey their microenvironment and accordingly modulate their behaviors, such as proliferation, differentiation, migration, and suicide. Using conventional and non-conventional microfabrication approaches to engineer well-defined cellular microenvironments, we are examining how cells recognize and respond to adhesive interactions with the insoluble extracellular matrix (ECM). We will discuss our approaches to control the architecture and geometry of the adhesive interactions, as well as our resulting progress in identifying and elucidating the mechanisms by which cells sense the physical, chemical, and structural information carried within the ECM. By developing these approaches to engineering cell-surface interactions, we hope to improve the interconnect between artificial surfaces and living cells.
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Schultz, Joshua A., and Jun Ueda. "Analysis of Antagonist Stiffness for Nested Compliant Mechanisms in Agonist-Antagonist Arrangements." In ASME 2011 Dynamic Systems and Control Conference and Bath/ASME Symposium on Fluid Power and Motion Control. ASMEDC, 2011. http://dx.doi.org/10.1115/dscc2011-5953.

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Members of the animal kingdom produce motion by muscle contraction. Biological muscle can be viewed as a unidirectional actuator. To achieve bidirectional motion, each muscle has a corresponding antagonist muscle whose contraction produces motion in the opposite direction. This gives biological systems the unique ability to modulate the stiffness of a joint, which is important when interacting with the environment. Certain bio-inspired robotic systems incorporate antagonistic pairs in an attempt to produce similar desirable properties. The cellular actuator employs nested compliant mechanisms to produce human-scale motion from piezoelectric stack actuators, which on their own have a small displacement. The expression for the stiffness of the actuator composed of these mechanisms takes the form of a continued fraction, which results from the nested structure. In this way, the stiffness can be easily approximated to a desired degree of accuracy by considering only the outermost mechanisms.
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Jumanov, I. I., R. A. Safarov, and O. I. Djumanov. "Error Control of Identification and Filtering of Micro-Object Images." In III All-Russian Scientific Conference with International Participation "Science, technology, society: Environmental engineering for sustainable development of territories". Krasnoyarsk Science and Technology City Hall, 2022. http://dx.doi.org/10.47813/nto.3.2022.6.109-124.

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Researched and developed scientifically and methodologically foundations for optimal identification of micro-objects using traditional and Gaussian filtering, median filter, filters based on fast Fourier transform, wavelet transforms, shift transforms, mechanisms using geometric, specific features, statistical, dynamic properties of image information. Mechanisms for optimizing the identification of micro-objects are proposed that have advantages in reducing the complexity and laboriousness of analyzing the structure and processing information, identifying and segmentation of the image contour, using the dynamics of growth, visual differentiation, extracting internal features and properties, approximation, smoothing, and interpretation of objects. A mechanism has been investigated and implemented that performs the following functions: aligns histology slices; finds contours of objects, a set of levels, thresholds, combines segmentation, conducts registrations, forms a search graph, performs approximations based on a wavelet, shear, and other transformations, determines parameters, performs color coding and color visualization of micro-objects. The implementations of algorithms and software modules of the software complex for identification, recognition and classification of micro-objects, in particular, cellular elements of the inflammatory series (fibroblasts, fibrocytes) of lung disease, have been tested. The signs of chronic inflammation were assessed - the presence of giant cells. A software package for visualization, recognition, classification of images of pollen grains has been developed, the implementations of which have been tested taking into account the conditions of a priori insufficiency, parametric uncertainty and nonstationarity of processes.
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Farahat, Waleed A., and H. Harry Asada. "Control of Eukaryotic Cell Migration Through Modulation of Extracellular Chemoattractant Gradients." In ASME 2010 Dynamic Systems and Control Conference. ASMEDC, 2010. http://dx.doi.org/10.1115/dscc2010-4190.

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Cell migration is fundamental to a wide range of biological and physiological functions including: wound healing, immune defense, cancer metastasis, as well as the formation and development of biological structures such as vascular and neural networks. In these diverse processes, cell migration is influenced by a broad set of external mechanical and biochemical cues, particularly the presence of (time dependent) spatial gradients of soluble chemoattractants in the extracellular domain. Many biological models have been proposed to explain the mechanisms leading to the migratory response of cells as a function of these external cues. Based on such models, here we propose approaches to controlling the chemotactic response of eukaryotic cells by modulating their micro-environments in vitro (for example, using a microfluidic chemotaxis chamber). By explicitly modeling i) chemoattractant-receptor binding kinetics, ii) diffusion dynamics in the extracellular domain, and iii) the chemotactic response of cells, models for the migration processes arise. Based on those models, optimal control formulations are derived. We present simulation results, and suggest experimental approaches to controlling cellular motility in vitro, which can be used as a basis for cellular manipulation and control.
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Nathan, Ashwin S., Brendon M. Baker, and Robert L. Mauck. "Cytoskeletal Control of Mesenchymal Stem Cell Nuclear Deformation on Nanofibrous Scaffolds." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206855.

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Nanofibrous scaffolds hold great potential for tissue engineering as they recapitulate the mechanical and topographic features of fibrous tissues on both the macroscopic and microscopic level [1,2]. When seeded with cells capable of fibrous extracellular matrix (ECM) production such as mesenchymal stem cells (MSCs), the new matrix is deposited in accordance with the underlying topography, and scaffolds develop improved mechanical properties with time in free swelling culture [6]. While promising, the free swelling conditions employed in evaluating in vitro construct maturation have thus far remained insufficient in achieving native-level properties. As most fibrous tissues are subjected to loading in vivo, mechanical conditioning is considered critical in directing tissue development and subsequent homeostasis with normal use. Mechanical signals are translated from the ECM to the nucleus via the cytoskeleton, with signals culminating in the control of biosynthetic activity based upon external loading conditions. Various bioreactor systems have been developed to mimic these in vivo conditions towards enhancing the maturation of engineered constructs, with most focusing on dynamic tensile deformation [3,4]. Towards gaining further insight into the means by which mechanical cues inspire alterations in cellular behavior, this study developed methods for evaluating cell and sub-cellular deformation of MSCs seeded on randomly-oriented and aligned nanofibrous scaffolds. Using a device that enables visualization of cells seeded on nanofibrous scaffolds undergoing static tensile deformation, we examined the effect of applied strain rate on cell adhesion to scaffolds, as well as changes in nuclear shape in the context of viable actin and microtubule sub-cellular networks with applied strain. These data provide new insight into fundamental mechanisms of MSC mechanoregulation on nanofibrous scaffolds, and offer constraints for long-term bioreactor studies.
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Baker, Brendon M., Britta Trappmann, Iris L. Kim, Jason A. Burdick, and Christopher S. Chen. "Engineered Fibrillar Microenvironments With Controllable Architecture and Mechanics for Studying Cellular Stiffness Sensing." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14804.

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The mechanical properties of the extracellular matrix (ECM) have emerged as fundamental players in numerous basic cellular functions such as spreading, migration, proliferation and differentiation, thus impacting many biological processes including embryonic development, adult tissue homeostasis, and disease pathogenesis such as fibrosis and cancer [1,2,3]. Synthetic matrices have been crucial to studying the effect of mechanics on cell behavior, as they allow for precise control of mechanical properties over a wide stiffness range, unachievable in vivo or in many naturally derived material systems. Seminal work employing polyacrylamide hydrogels of varying stiffness to direct the differentiation of human mesenchymal stem cells concluded that the bulk modulus, a measure of the material’s resistance to uniform deformation, is a defining parameter influencing cell function [4]. While much current effort aims to shed light on the molecular mechanisms governing stiffness sensing, existing knowledge is limited by the dissimilarity between the simple hydrogel surfaces employed in these studies and the topographically and mechanically more complex ECM cells routinely reside within in vivo. In contrast to the flat expanse of cell adhesive ligand and linear elastic, continuum behavior of typical gel systems, within the body, cell-scale mechanics and ligand availability are entwined, as both are defined by the presence and organization of the proteins that compose the surrounding ECM. The structure of native ECMs vary but largely are fibrillar, given that collagen comprises approximately 25% of the human body by mass. Thus, there remains a significant need for engineered fibrillar materials that afford precise and independent control of architectural features and resulting mechanical properties for application in cell biology. In this work, we establish a novel material system towards this end.
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Ramakrishnan, Subramanian, and Manish Kumar. "Synthesis and Analysis of Control Laws for Swarm of Mobile Robots Emulating Ant Foraging Behavior." In ASME 2010 Dynamic Systems and Control Conference. ASMEDC, 2010. http://dx.doi.org/10.1115/dscc2010-4244.

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Ant foraging behavior has inspired research in a number of areas including distributed problem solving such as optimization and task allocation and mobile robot navigation. In the area of swarm robotic systems, ant foraging behavior has been largely modeled via behavior based techniques and analyzed using cellular automata. Development of continuous time models for ant foraging can potentially provide insights into new mechanisms and behaviors used by ants that provide self-organizing capabilities to the ant colony. This paper presents a distributed control law in continuous time that combines gradient following for pheromone concentration as well as food scent with random motion seen in ants. The paper also provides a continuous time model for pheromone laying in a 2D environment and carries out a preliminary numerical stability analysis of the solutions. Extensive simulation studies confirm emergent behaviors seen in ant systems such as trail formation and convergence to single food site. In addition, the paper examines the effect of randomness on robustness of convergence to a single food site.
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Reports on the topic "Cellular control mechanisms"

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Kumar, Aishani, Thendral Yalini, and Sunil Kumar C. Unlocking Cellular Control: The Promise of PROTACs in Disease Intervention. Science Reviews - Biology, May 2024. http://dx.doi.org/10.57098/scirevs.biology.3.2.1.

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The discovery of proteolysis-targeting chimeras (PROTACs) is among the most exciting and promising avenues in cancer therapy. These fascinating compounds signify a paradigm shift from traditional approaches to medication development, offering a new idea that leverages the complexities of biological mechanisms to accomplish highly focused degradation of particular proteins implicated in pathological processes. This novel strategy has the potential to address a number of drawbacks with conventional therapy techniques, such as the development of drug resistance and unexpected adverse effects resulting from interactions that are not intended. The fundamental attraction of PROTACs is their distinct mode of action, which is based on controlling the cell's own machinery for protein degradation. This orchestrated degradation translates to a substantial reduction in the levels of disease-driving proteins, often leading to the disruption of critical pathways involved in cancer growth and progression. The in-depth principles underlying PROTAC technology are thoroughly explored in this review study, which also provides insight into the complex chemical mechanisms that enable these chimeric molecules to specifically degrade certain proteins while leaving others intact. Showcasing the potential of PROTACs as a revolutionary force in targeted cancer therapy, and focusing on its application in prostate and breast cancer especially, the article draws from a comprehensive compilation of preclinical and clinical studies, advancements, and breakthroughs in the field. The methods used to create and refine PROTACs for various cancer types will be examined throughout the review, along with the subtleties of the ligand and linker choices that are crucial to their effectiveness and selectivity. The difficulties and possibilities of transferring this ground-breaking technology from the lab to clinical practice will also be thoroughly examined, with an emphasis on issues like bioavailability, administration strategies, and potential resistance mechanisms. Through the integration of perspectives from various studies, the objective is to present a thorough but succinct review of the state of ongoing PROTAC research, emphasizing both, noteworthy advancements and the important issues that still need to be resolved. In the end, our investigation into PROTACs aims to shed light on how they can change the face of cancer therapy by providing a preview of a day when targeted protein degradation of disease-causing proteins would lead the way in novel therapeutic approaches.
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Lillehoj, Hyun, Dan Heller, and Mark Jenkins. Cellular and molecular identification of Eimeria Acervulina Merozoite Antigens eliciting protective immunity. United States Department of Agriculture, November 1992. http://dx.doi.org/10.32747/1992.7561056.bard.

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Coccidiosis, ubiquitous diseases of poultry, seriously impair the growth and feed utilization of livestock and poultry. Coccidiosis causes over $600 million annual losses world-wide and no vaccine is currently available. The goal of this study was to investigate the cellular and molecular mechanisms controlling protective immune responses to coccidia parasites in order to develop immunological control strategy against coccidiosis. The major findings of this study were: 1) cell-mediated immunity plays a major role in protection against coccidiosis, 2) when different genetic lines showing different levels of disease susceptibility were compared, higher T-cell response was seen in the strains of chickens showing higher disease resistance, 3) early interferon secretion was observed in more coccidia-resistant chicken strains, 4) both sporozoite and merozoite antigens were able to induce interferon production, and 5) chicken monoclonal antibodies which detect immunogenic coccidia proteins have been developed. This study provided a good background work for future studies toward the development of recombinant coccidial vaccine. Availability of chicken monoclonal antibodies which detect immunogenic coccidia proteins will enhance our ability to identify potential coccidial vaccine antigens.
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Chejanovsky, Nor, and Bruce A. Webb. Potentiation of pest control by insect immunosuppression. United States Department of Agriculture, July 2004. http://dx.doi.org/10.32747/2004.7587236.bard.

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Our original aims were to elucidate the mechanisms through which the immunosuppressive insect virus, the Campoletis sonorensis polydnavirus (CsV) promotes replication of a well-characterized pathogenic virus, the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) in hosts that are mildly or non-permissive to virus replication. According to the BARD panels criticism we modified our short-term goals (see below). Thus, in this feasibility study (one-year funding) we aimed to show that: 1. S. littoralis larvae mount an immune response against a baculovirus infection. 2. Immunosuppression of an insect pest improves the ability of a viral pathogen (a baculovirus) to infect the pest. 3. S. littoralis cells constitute an efficient tool to study some aspects of the anti- viral immune response. We achieved the above objectives by: 1. Finding melanized viral foci upon following the baculoviral infection in S . littoralis larvae infected with a polyhedra - positive AcMNPV recombinant that expressed the GFP gene under the control of the Drosophila heat shock promoter. 2. Studying the effect of AcMNPV-infection in S . littoralis immunosuppressed by parasitation with the Braconidae wasp Chelonus inanitus that bears the CiV polydna virus, that resulted in higher susceptibility of S. littoralis to AcMNPV- infection. 3. Proving that S. littoralis hemocytes resist AcMNPV -infection. 4. Defining SL2 as a granulocyte-like cell line and demonstrating that as littoralis hemocytic cell line undergoes apoptosis upon AcMNPV -infection. 5. Showing that some of the recombinant AcMNPV expressing the immuno-suppressive polydna virus CsV- vankyrin genes inhibit baculoviral-induced lysis of SL2 cells. This information paves the way to elucidate the mechanisms through which the immuno- suppressive polydna insect viruses promote replication of pathogenic baculoviruses in lepidopteran hosts that are mildly or non-permissive to virus- replication by: - Assessing the extent to which and the mechanisms whereby the immunosuppressive viruses, CiV and CsV or their genes enhance AcMNPV replication in polydnavirus- immunosuppressed H. zea and S. littoralis insects and S. littoralis cells. - Identifying CiV and CsV genes involved in the above immunosuppression (e.g. inhibiting cellular encapsulation and disrupting humoral immunity). This study will provide insight to the molecular mechanisms of viral pathogenesis and improve our understanding of insect immunity. This knowledge is of fundamental importance to controlling insect vectored diseases of humans, animals and plants and essential to developing novel means for pest control (including baculoviruses) that strategically weaken insect defenses to improve pathogen (i.e. biocontrol agent) infection and virulence.
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Chejanovsky, Nor, and Bruce A. Webb. Potentiation of Pest Control by Insect Immunosuppression. United States Department of Agriculture, January 2010. http://dx.doi.org/10.32747/2010.7592113.bard.

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The restricted host range of many baculoviruses, highly pathogenic to Lepidoptera and non-pathogenic to mammals, limits their use to single or few closely related Lepidopteran species and is an obstacle to extending their implementation for pest control. The insect immune response is a major determinant of the ability of an insect pathogen to efficiently multiply and propagate. We have developed an original model system to study the Lepidopteran antiviral immune response based on Spodoptera littoralis resistance to AcMNPV (Autographa californica multiple nucleopolyhedrovirus) infection and the fascinating immunosuppressive activity of polydnaviruses .Our aim is to elucidate the mechanisms through which the immunosuppressive insect polydnaviruses promote replication of pathogenic baculoviruses in lepidopteran hosts that are mildly or non-permissive to virus- replication. In this study we : 1- Assessed the extent to which and the mechanisms whereby the immunosuppressive Campoletis sonorensis polydnavirus (CsV) or its genes enhanced replication of a well-characterized pathogenic baculovirus AcMNPV, in polydnavirus-immunosuppressedH. zea and S. littoralis insects and S. littoralis cells, hosts that are mildly or non-permissive to AcMNPV. 2- Identified CsV genes involved in the above immunosuppression (e.g. inhibiting cellular encapsulation and disrupting humoral immunity). We showed that: 1. S. littoralis larvae mount an immune response against a baculovirus infection. 2. Immunosuppression of an insect pest improves the ability of a viral pathogen, the baculovirus AcMNPV, to infect the pest. 3. For the first time two PDV-specific genes of the vankyrin and cystein rich-motif families involved in immunosuppression of the host, namely Pvank1 and Hv1.1 respectively, enhanced the efficacy of an insect pathogen toward a semipermissive pest. 4. Pvank1 inhibits apoptosis of Spodopteran cells elucidating one functional aspect of PDVvankyrins. 5. That Pvank-1 and Hv1.1 do not show cooperative effect in S. littoralis when co-expressed during AcMNPV infection. Our results pave the way to developing novel means for pest control, including baculoviruses, that rely upon suppressing host immune systems by strategically weakening insect defenses to improve pathogen (i.e. biocontrol agent) infection and virulence. Also, we expect that the above result will help to develop systems for enhanced insect control that may ultimately help to reduce transmission of insect vectored diseases of humans, animals and plants as well as provide mechanisms for suppression of insect populations that damage crop plants by direct feeding.
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Eldar, Avigdor, and Donald L. Evans. Streptococcus iniae Infections in Trout and Tilapia: Host-Pathogen Interactions, the Immune Response Toward the Pathogen and Vaccine Formulation. United States Department of Agriculture, December 2000. http://dx.doi.org/10.32747/2000.7575286.bard.

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In Israel and in the U.S., Streptococcus iniae is responsible for considerable losses in various fish species. Poor understanding of its virulence factors and limited know-how-to of vaccine formulation and administration are the main reasons for the limited efficacy of vaccines. Our strategy was that in order to Improve control measures, both aspects should be equally addressed. Our proposal included the following objectives: (i) construction of host-pathogen interaction models; (ii) characterization of virulence factors and immunodominant antigens, with assessment of their relative importance in terms of protection and (iii) genetic identification of virulence factors and genes, with evaluation of the protective effect of recombinant proteins. We have shown that two different serotypes are involved. Their capsular polysaccharides (CPS) were characterized, and proved to play an important role in immune evasion and in other consequences of the infection. This is an innovative finding in fish bacteriology and resembles what, in other fields, has become apparent in the recent years: S. iniae alters surface antigens. By so doing, the pathogen escapes immune destruction. Immunological assays (agar-gel immunodiffusion and antibody titers) confirmed that only limited cross recognition between the two types occurs and that capsular polysaccharides are immunodominant. Vaccination with purified CPS (as an acellular vaccine) results in protection. In vitro and ex-vivo models have allowed us to unravel additional insights of the host-pathogen interactions. S. iniae 173 (type II) produced DNA fragmentation of TMB-8 cells characteristic of cellular necrosis; the same isolate also prevented the development of apoptosis in NCC. This was determined by finding reduced expression of phosphotidylserine (PS) on the outer membrane leaflet of NCC. NCC treated with this isolate had very high levels of cellular necrosis compared to all other isolates. This cellular pathology was confirmed by observing reduced DNA laddering in these same treated cells. Transmission EM also showed characteristic necrotic cellular changes in treated cells. To determine if the (in vitro) PCD/apoptosis protective effects of #173 correlated with any in vivo activity, tilapia were injected IV with #173 and #164 (an Israeli type I strain). Following injection, purified NCC were tested (in vitro) for cytotoxicity against HL-60 target cells. Four significant observations were made : (i) fish injected with #173 had 100-400% increased cytotoxicity compared to #164 (ii) in vivo activation occurred within 5 minutes of injection; (iii) activation occurred only within the peripheral blood compartment; and (iv) the isolate that protected NCC from apoptosis in vitro caused in vivo activation of cytotoxicity. The levels of in vivo cytotoxicity responses are associated with certain pathogens (pathogen associated molecular patterns/PAMP) and with the tissue of origin of NCC. NCC from different tissue (i.e. PBL, anterior kidney, spleen) exist in different states of differentiation. Random amplified polymorphic DNA (RAPD) analysis revealed the "adaptation" of the bacterium to the vaccinated environment, suggesting a "Darwinian-like" evolution of any bacterium. Due to the selective pressure which has occurred in the vaccinated environment, type II strains, able to evade the protective response elicited by the vaccine, have evolved from type I strains. The increased virulence through the appropriation of a novel antigenic composition conforms with pathogenic mechanisms described for other streptococci. Vaccine efficacy was improved: water-in-oil formulations were found effective in inducing protection that lasted for a period of (at least) 6 months. Protection was evaluated by functional tests - the protective effect, and immunological parameters - elicitation of T- and B-cells proliferation. Vaccinated fish were found to be resistant to the disease for (at least) six months; protection was accompanied by activation of the cellular and the humoral branches.
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Philosoph-Hadas, Sonia, Peter Kaufman, Shimon Meir, and Abraham Halevy. Signal Transduction Pathway of Hormonal Action in Control and Regulation of the Gravitropic Response of Cut Flowering Stems during Storage and Transport. United States Department of Agriculture, October 1999. http://dx.doi.org/10.32747/1999.7695838.bard.

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Original objectives: The basic goal of the present project was to increase our understanding of the cellular mechanisms operating during the gravitropic response of cut flowers, for solving their bending problem without affecting flower quality. Thus, several elements operating at the 3 levels o the gravity-induced signal transduction pathway, were proposed to be examined in snapdragon stems according to the following research goals: 1) Signaling: characterize the signal transduction pathway leading to the gravitropic response, regarding the involvement of [Ca2+]cyt as a mediator of IAA movement and sensitivity to auxin. 2) Transduction by plant hormones: a) Examine the involvement of auxin in the gravitropic response of flower stems with regard to: possible participation of auxin binding protein (ABP), auxin redistribution, auxin mechanism of action (activation of H+-ATPase) mediation by changes in [Ca2+]cyt and possible regulation of auxin-induced Ca2+ action b: calmodulin-activated or Ca2+-activated protein kinases (PK). b) Examine the involvement of ethylene in the gravitropic response of flower stems with regard to auxin-induced ethylene production and sensitivity of the tissue to ethylene. 3) Response: examine the effect of gravistimulation on invertase (associated with growth and elongation) activity and invertase gene expression. 4) Commercial practice: develop practical and simple treatments to prevent bending of cut flowers grown for export. Revisions: 1) Model systems: in addition to snapdragon (Antirrhinum majus L.), 3 other model shoe systems, consisting of oat (Avena sativa) pulvini, Ornithogalun 'Nova' cut flowers and Arabidopsis thaliana inflorescence, were targeted to confirm a more general mechanism for shoot gravitropism. 2 Research topics: the involvement of ABP, auxin action, PK and invertase in the gravitropic response of snapdragon stems could not be demonstrated. Alternatively, the involvement in the gravity signaling cascade of several other physiological mediators apart of [Ca2+]cyt such as: IP3, protein phosphorylation and actin cytoskeleton, was shown. Additional topics introduced: starch statolith reorientation, differential expression of early auxin responsive genes, and differential shoot growth. Background to the topic: The gravitropic bending response of flowering shoots occurring upon their horizontal placement during shipment exhibits a major horticultural problem. In spite of extensive studies in various aboveground organs, the gravitropic response was hardly investigated in flowering shoots. Being a complex multistep process that requires the participation of various cellular components acting in succession or in parallel, analysis of the negative gravitropic response of shoot includes investigation of signal transduction elements and various regulatory physiological mediators. Major achievements: 1) A correlative role for starch statoliths as gravireceptors in flowering shoot was initially established. 2) Differentially phosphorylated proteins and IP3 levels across the oat shoe pulvini, as well as a differential appearance of 2 early auxin-responsive genes in snapdragon stems were all detected within 5-30 minutes following gravistimulation. 3) Unlike in roots, involvement of actin cytoskeleton in early events of the gravitropic response of snapdragon shoots was established. 4) An asymmetric IAA distribution, followed by an asymmetric ethylene production across snapdragon stems was found following gravistimulation. 5) The gravity-induced differential growth in shoots of snapdragon was derived from initial shrinkage of the upper stem side and a subsequent elongation o the lower stem side. 6) Shoot bending could be successfully inhibited by Ca2+ antagonists (that serve as a basis for practical treatments), kinase and phosphatase inhibitors and actin-cytoskeleton modulators. All these agents did not affect vertical growth. The essential characterization of these key events and their sequence led us to the conclusion that blocking gravity perception may be the most powerful means to inhibit bending without hampering shoot and flower growth after harvest. Implications, scientific and agriculture: The innovative results of this project have provided some new insight in the basic understanding of gravitropism in flower stalks, that partially filled the gap in our knowledge, and established useful means for its control. Additionally, our analysis has advanced the understanding of important and fundamental physiological processes involved, thereby leading to new ideas for agriculture. Gravitropism has an important impact on agriculture, particularly for controlling the bending of various important agricultural products with economic value. So far, no safe control of the undesired bending problem of flower stalks has been established. Our results show for the first time that shoot bending of cut flowers can be inhibited without adverse effects by controlling the gravity perception step with Ca2+ antagonists and cytoskeleton modulators. Such a practical benefit resulting from this project is of great economic value for the floriculture industry.
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Epel, Bernard, and Roger Beachy. Mechanisms of intra- and intercellular targeting and movement of tobacco mosaic virus. United States Department of Agriculture, November 2005. http://dx.doi.org/10.32747/2005.7695874.bard.

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To cause disease, plant viruses must replicate and spread locally and systemically within the host. Cell-to-cell virus spread is mediated by virus-encoded movement proteins (MPs), which modify the structure and function of plasmodesmata (Pd), trans-wall co-axial membranous tunnels that interconnect the cytoplasm of neighboring cells. Tobacco mosaic virus (TMV) employ a single MP for cell- cell spread and for which CP is not required. The PIs, Beachy (USA) and Epel (Israel) and co-workers, developed new tools and approaches for study of the mechanism of spread of TMV that lead to a partial identification and molecular characterization of the cellular machinery involved in the trafficking process. Original research objectives: Based on our data and those of others, we proposed a working model of plant viral spread. Our model stated that MPᵀᴹⱽ, an integral ER membrane protein with its C-terminus exposed to the cytoplasm (Reichel and Beachy, 1998), alters the Pd SEL, causes the Pd cytoplasmic annulus to dilate (Wolf et al., 1989), allowing ER to glide through Pd and that this gliding is cytoskeleton mediated. The model claimed that in absence of MP, the ER in Pd (the desmotubule) is stationary, i.e. does not move through the Pd. Based on this model we designed a series of experiments to test the following questions: -Does MP potentiate ER movement through the Pd? - In the presence of MP, is there communication between adjacent cells via ER lumen? -Does MP potentiate the movement of cytoskeletal elements cell to cell? -Is MP required for cell-to-cell movement of ER membranes between cells in sink tissue? -Is the binding in situ of MP to RNA specific to vRNA sequences or is it nonspecific as measured in vitro? And if specific: -What sequences of RNA are involved in binding to MP? And finally, what host proteins are associated with MP during intracellular targeting to various subcellular targets and what if any post-translational modifications occur to MP, other than phosphorylation (Kawakami et al., 1999)? Major conclusions, solutions and achievements. A new quantitative tool was developed to measure the "coefficient of conductivity" of Pd to cytoplasmic soluble proteins. Employing this tool, we measured changes in Pd conductivity in epidermal cells of sink and source leaves of wild-type and transgenic Nicotiana benthamiana (N. benthamiana) plants expressing MPᵀᴹⱽ incubated both in dark and light and at 16 and 25 ᵒC (Liarzi and Epel, 2005 (appendix 1). To test our model we measured the effect of the presence of MP on cell-to-cell spread of a cytoplasmic fluorescent probe, of two ER intrinsic membrane protein-probes and two ER lumen protein-probes fused to GFP. The effect of a mutant virus that is incapable of cell-to-cell spread on the spread of these probes was also determined. Our data shows that MP reduces SEL for cytoplasmic molecules, dilates the desmotubule allowing cell-cell diffusion of proteins via the desmotubule lumen and reduces the rate of spread of the ER membrane probes. Replicase was shown to enhance cell-cell spread. The data are not in support of the proposed model and have led us to propose a new model for virus cell-cell spread: this model proposes that MP, an integral ER membrane protein, forms a MP:vRNAER complex and that this ER-membrane complex diffuses in the lipid milieu of the ER into the desmotubule (the ER within the Pd), and spreads cell to cell by simple diffusion in the ER/desmotubule membrane; the driving force for spread is the chemical potential gradient between an infected cell and contingent non-infected neighbors. Our data also suggests that the virus replicase has a function in altering the Pd conductivity. Transgenic plant lines that express the MP gene of the Cg tobamovirus fused to YFP under the control the ecdysone receptor and methoxyfenocide ligand were generated by the Beachy group and the expression pattern and the timing and targeting patterns were determined. A vector expressing this MPs was also developed for use by the Epel lab . The transgenic lines are being used to identify and isolate host genes that are required for cell-to-cell movement of TMV/tobamoviruses. This line is now being grown and to be employed in proteomic studies which will commence November 2005. T-DNA insertion mutagenesis is being developed to identify and isolate host genes required for cell-to-cell movement of TMV.
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Evans, Donald L., Avigdor Eldar, Liliana Jaso-Friedmann, and Herve Bercovier. Streptococcus Iniae Infection in Trout and Tilapia: Host-Pathogen Interactions, the Immune Response Towards the Pathogen and Vaccine Formulation. United States Department of Agriculture, February 2005. http://dx.doi.org/10.32747/2005.7586538.bard.

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The objectives of the BARD proposal were to determine the mechanisms of nonspecific cytotoxic cells (NCC) that are necessary to provide heightened innate resistance to infection and to identify the antigenic determinants in Streptococcus iniae that are best suited for vaccine development. Our central hypothesis was that anti-bacterial immunity in trout and tilapia can only be acquired by combining "innate" NCC responses with antibody responses to polysaccharide antigens. These Objectives were accomplished by experiments delineated by the following Specific Aims: Specific aim (SA) #1 (USA) "Clone and Identify the Apoptosis Regulatory Genes in NCC"; Specific aim #2 (USA)"Identify Regulatory Factors that Control NCC Responses to S. iniae"; Specific aim #3 (Israel) "Characterize the Biological Properties of the S. iniae Capsular Polysaccharide"; and Specific aim #4 (Israel) "Development of an Acellular Vaccine". Our model of S. iniae pathogenesis encompassed two approaches, identify apoptosis regulatory genes and proteins in tilapia that affected NCC activities (USA group) and determine the participation of S.iniae capsular polysaccharides as potential immunogens for the development of an acellular vaccine (Israel group). We previously established that it was possible to immunize tilapia and trout against experimental S. difficile/iniaeinfections. However these studies indicated that antibody responses in protected fish were short lived (3-4 months). Thus available vaccines were useful for short-term protection only. To address the issues of regulation of pathogenesis and immunogens of S. iniae, we have emphasized the role of the innate immune response regarding activation of NCC and mechanisms of invasiveness. Considerable progress was made toward accomplishing SA #1. We have cloned the cDNA of the following tilapia genes: cellular apoptosis susceptibility (CAS/AF547173»; tumor necrosis factor alpha (TNF / A Y 428948); and nascent polypeptide-associated complex alpha polypeptide (NACA/ A Y168640). Similar attempts were made to sequence the tilapia FasLgene/cDNA, however these experiments were not successful. Aim #2 was to "Identify Regulatory Factors that Control NCC Responses to S. iniae." To accomplish this, a new membrane receptor has been identified that may control innate responses (including apoptosis) of NCC to S. iniae. The receptor is a membrane protein on teleost NCC. This protein (NCC cationic antimicrobial protein-1/ncamp-1/AAQ99138) has been sequenced and the cDNA cloned (A Y324398). In recombinant form, ncamp-l kills S. iniae in vitro. Specific aim 3 ("Characterize the Biological Properties of the S.iniae Capsular Polysaccharide") utilized an in- vitro model using rainbow trout primary skin epithelial cell mono layers. These experiments demonstrated colonization into epithelial cells followed by a rapid decline of viable intracellular bacteria and translocation out of the cell. This pathogenesis model suggested that the bacterium escapes the endosome and translocates through the rainbow trout skin barrier to further invade and infect the host. Specific aim #4 ("Development of an Acellular Vaccine") was not specifically addressed. These studies demonstrated that several different apoptotic regulatory genes/proteins are expressed by tilapia NCC. These are the first studies demonstrating that such factors exist in tilapia. Because tilapia NCC bind to and are activated by S. iniae bacterial DNA, we predict that the apoptotic regulatory activity of S. iniae previously demonstrated by our group may be associated with innate antibacterial responses in tilapia.
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Wang, X. F., and M. Schuldiner. Systems biology approaches to dissect virus-host interactions to develop crops with broad-spectrum virus resistance. Israel: United States-Israel Binational Agricultural Research and Development Fund, 2020. http://dx.doi.org/10.32747/2020.8134163.bard.

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More than 60% of plant viruses are positive-strand RNA viruses that cause billion-dollar losses annually and pose a major threat to stable agricultural production, including cucumber mosaic virus (CMV) that infects numerous vegetables and ornamental trees. A highly conserved feature among these viruses is that they form viral replication complexes (VRCs) to multiply their genomes by hijacking host proteins and remodeling host intracellular membranes. As a conserved and indispensable process, VRC assembly also represents an excellent target for the development of antiviral strategies that can be used to control a wide-range of viruses. Using CMV and a model virus, brome mosaic virus (BMV), and relying on genomic tools and tailor-made large-scale resources specific for the project, our original objectives were to: 1) Identify host proteins that are required for viral replication complex assembly. 2) Dissect host requirements that determine viral host range. 3) Provide proof-of-concept evidence of a viral control strategy by blocking the viral replication complex-localized phospholipid synthesis. We expect to provide new ways and new concepts to control multiple viruses by targeting a conserved feature among positive-strand RNA viruses based on our results. Our work is going according to the expected timeline and we are progressing well on all aims. For Objective 1, among ~6,000 yeast genes, we have identified 96 hits that were possibly play critical roles in viral replication. These hits are involved in cellular pathways of 1) Phospholipid synthesis; 2) Membrane-shaping; 3) Sterol synthesis and transport; 4) Protein transport; 5) Protein modification, among many others. We are pursuing several genes involved in lipid metabolism and transport because cellular membranes are primarily composed of lipids and lipid compositional changes affect VRC formation and functions. For Objective 2, we have found that CPR5 proteins from monocotyledon plants promoted BMV replication while those from dicotyledon plants inhibited it, providing direct evidence that CPR5 protein determines the host range of BMV. We are currently examining the mechanisms by which dicot CPR5 genes inhibit BMV replication and expressing the dicot CPR5 genes in monocot plants to control BMV infection. For Objective 3, we have demonstrated that substitutions in a host gene involved in lipid synthesis, CHO2, prevented the VRC formation by directing BMV replication protein 1a (BMV 1a), which remodels the nuclear membrane to form VRCs, away from the nuclear membrane, and thus, no VRCs were formed. This has been reported in Journal of Biological Chemistry. Based on the results from Objective 3, we have extended our plan to demonstrate that an amphipathic alpha-helix in BMV 1a is necessary and sufficient to target BMV 1a to the nuclear membrane. We further found that the counterparts of the BMV 1a helix from a group of viruses in the alphavirus-like superfamily, such as CMV, hepatitis E virus, and Rubella virus, are sufficient to target VRCs to the designated membranes, revealing a conserved feature among the superfamily. A joint manuscript describing these exciting results and authored by the two labs will be submitted shortly. We have also successfully set up systems in tomato plants: 1) to efficiently knock down gene expression via virus-induced gene silencing so we could test effects of lacking a host gene(s) on CMV replication; 2) to overexpress any gene transiently from a mild virus (potato virus X) so we could test effects of the overexpressed gene(s) on CMV replication. In summary, we have made promising progress in all three Objectives. We have identified multiple new host proteins that are involved in VRC formation and may serve as good targets to develop antiviral strategies; have confirmed that CPR5 from dicot plants inhibited viral infection and are generating BMV-resistance rice and wheat crops by overexpressing dicot CPR5 genes; have demonstrated to block viral replication by preventing viral replication protein from targeting to the designated organelle membranes for the VRC formation and this concept can be further employed for virus control. We are grateful to BARD funding and are excited to carry on this project in collaboration.
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10

Philosoph-Hadas, Sonia, Peter B. Kaufman, Shimon Meir, and Abraham H. Halevy. Inhibition of the Gravitropic Shoot Bending in Stored Cut Flowers Through Control of Their Graviperception: Involvement of the Cytoskeleton and Cytosolic Calcium. United States Department of Agriculture, December 2005. http://dx.doi.org/10.32747/2005.7586533.bard.

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Original objectives: The basic goal of the present project was to study the mechanism involved in shoot graviperception and early transduction, in order to determine the sequence of events operating in this process. This will enable to control the entire process of gravity-induced differential growth without affecting vertical growth processes essential for development. Thus, several new postulated interactions, operating at the perception and early transduction stages of the signaling cascade leading to auxin-mediated bending, were proposed to be examined in snapdragon spikes and oat shoot pulvini, according to the following research goals: 1) Establish the role of amyloplasts as gravireceptors in shoots; 2) Investigate gravity-induced changes in the integrity of shoot actin cytoskeleton (CK); 3) Study the cellular interactions among actin CK, statoliths and cell membranes (endoplasmic reticulum - ER, plasma membrane - PM) during shoot graviperception; 4) Examine mediation of graviperception by modulations of cytosolic calcium - [Ca2+]cyt, and other second messengers (protein phosphorylation, inositol 1,4,5-trisphosphate - IP3). Revisions: 1) Model system: in addition to snapdragon (Antirrhinum majus L.) spikes and oat (Avena sativa) shoot pulvini, the model system of maize (Zea mays) primary roots was targeted to confirm a more general mechanism for graviperception. 2) Research topic: brassinolide, which were not included in the original plan, were examined for their regulatory role in gravity perception and signal transduction in roots, in relation to auxin and ethylene. Background to the topic: The negative gravitropic response of shoots is a complex multi-step process that requires the participation of various cellular components acting in succession or in parallel. Most of the long-lasting studies regarding the link between graviperception and cellular components were focused mainly on roots, and there are relatively few reports on shoot graviperception. Our previous project has successfully characterized several key events occurring during shoot bending of cut flowers and oat pulvini, including amyloplast displacement, hormonal interactions and differential growth analysis. Based on this evidence, the present project has focused on studying the initial graviperception process in flowering stems and cereal shoots. Major conclusions and achievements: 1) The actin and not the microtubule (MT) CK is involved in the graviperception of snapdragon shoots. 2) Gravisensing, exhibited by amyloplast displacement, and early transduction events (auxin redistribution) in the gravitropic response of snapdragon spikes are mediated by the acto-myosin complex. 3) MTs are involved in stem directional growth, which occurs during gravitropism of cut snapdragon spikes, but they are not necessary for the gravity-induced differential growth. 4) The role of amyloplasts as gravisensors in the shoot endodermis was demonstrated for both plant systems. 5) A gravity-induced increase in IP.
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