Academic literature on the topic 'Non- essential activator'
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Journal articles on the topic "Non- essential activator"
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Noriega, Guillermo O., Adela A. Juknat, and Alcira M. del C. Batlle. "Non-Essential Activation of Rat Liver Porphobilinogen-Deaminase by Folic Acid." Zeitschrift für Naturforschung C 47, no. 5-6 (June 1, 1992): 416–19. http://dx.doi.org/10.1515/znc-1992-0616.
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This report demonstrates the ability of folic acid to activate rat liver porphobilinogen-deaminase (PBG -D). Lineweaver-Burk analysis revealed an increase in Vmax (38%) without affecting the Km. In the concentration range assayed, secondary replots of 1/Δslope and 1/Δintersect versus 1/[folic acid] yielded straight lines, indicating the binding of a single molecule of activator to the enzyme PBG-D , with a KA = 1.66 mᴍ. Results presented here show that folic acid acts as a non-essential activator (α = 1; β = 1.6). The activating effect of folic acid has been observed employing the 35-70% ammonium sulphate precipitated fraction, desalted by dialysis or gel filtration, whereas no action was detected when other partially purified PBG -D preparations were utilized as the enzyme source, suggesting either the presence of sites saturated for the activator, or the existence of a different structural protein conformation, or both.
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Das-Panja, Kaberi, Vidya Jonnalagadda, and Sobhanaditya Jonnalagadda. "Orthophosphate is a non-essential activator of Vigna radiata flavokinase." IUBMB Life 47, no. 4 (April 1999): 547–54. http://dx.doi.org/10.1080/15216549900201583.
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Cassels, R., R. Fears, and R. A. Smith. "The interaction of streptokinase.plasminogen activator complex, tissue-type plasminogen activator, urokinase and their acylated derivatives with fibrin and cyanogen bromide digest of fibrinogen. Relationship to fibrinolytic potency in vitro." Biochemical Journal 247, no. 2 (October 15, 1987): 395–400. http://dx.doi.org/10.1042/bj2470395.
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The effects of purified soluble fibrin and of fibrinogen fragments (fibrin mimic) on the activation of Lys-plasminogen (i.e. plasminogen residues 77-790) to plasmin by streptokinase.plasminogen activator complex and by tissue-type plasminogen activator were studied. Dissociation constants of both activators were estimated to lie in the range 90-160 nM (fibrin) and 16-60 nM (CNBr-cleavage fragments of fibrinogen). The kinetic mechanism for both types of activator comprised non-essential enzyme activation via a Rapid Equilibrium Ordered Bireactant sequence. In order to relate the fibrin affinity of plasminogen activators to their fibrinolytic potency, the rate of lysis of supported human plasma clots formed in the presence of unmodified or active-centre-acylated precursors of plasminogen activators was studied as a function of the concentration of enzyme derivative. The concentrations of unmodified enzyme giving 50% lysis/h in this assay were 0.9, 2.0 and 11.0 nM for tissue-type plasminogen activator, streptokinase.plasmin(ogen) and urokinase respectively. However, the potencies of active-centre-acylated derivatives of these enzymes suggested that acylated-tissue plasminogen activator and streptokinase.plasminogen complexes of comparable hydrolytic stability were of comparable potency. Both types of acyl-enzyme were significantly more potent than acyl-urokinases.
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Speijer, Han, José W. P. Govers-Riemslag, Robert F. A. Zwaal, and Jan Rosing. "Platelet Procoagulant Properties Studied with Snake Venom Prothrombin Activators." Thrombosis and Haemostasis 57, no. 03 (1987): 349–55. http://dx.doi.org/10.1055/s-0038-1651132.
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SummaryPurified snake venom prothrombin activators were used to probe the procoagulant properties of platelet membranes. Human platelets were able to stimulate prothrombin activation by the venom activators from Oxyuranus scutellatus and Notechis scutatus, while the prothrombin activator from Echis carinatus was not affected by the presence of platelets. The prothrombinconverting activity of platelets was further studied with the venom activator from Oxyuranus scutellatus and with the factor Xa-Va complex as prothrombin activating enzymes. Stimulation of platelets with collagen, collagen plus thrombin or with the Ca-ionophore A23187 resulted in a considerable increase of platelet prothrombin converting activity probed with the factor Xa-Va complex as well as with the prothrombin activator from Oxyuranus scutellatus. The stimulatory effect of activated platelets on the rates of prothrombin activation by Oxyuranus scutellatus was similar to that determined for factor Xa-Va-catalyzed prothrombin activation. Compared to non-stimulated platelets, platelets stimulated with thrombin plus collagen exposed 20-times more procoagulant sites for as well the factor Xa-Va complex, as for the venom activator from Oxyuranus scutellatus. The actual number of procoagulant sites per platelet determined with the factor Xa-Va complex was in close agreement with the number of sites determined with the venom activator. Also the time course of appearance of procoagulant activity during platelet stimulation by collagen plus thrombin was comparable for both activator complexes. Phospholipase A2 treatment of stimulated platelets resulted in an almost complete loss of their ability to stimulate prothrombin activation by the enzyme from Oxyuranus scutellatus or by factor Xa-Va complex. The findings presented in this paper suggest: a) that the factor Xa-Va complex and the prothrombin activator from Oxyuranus scutellatus recognize the same procoagulant sites on both stimulated and unstimulated platelets and b) that negatively-charged phospholipids are essential components of these procoagulant sites.
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Gai, Lili, Yuting Zhu, Chun Zhang, and Xianfang Meng. "Targeting Canonical and Non-Canonical STAT Signaling Pathways in Renal Diseases." Cells 10, no. 7 (June 27, 2021): 1610. http://dx.doi.org/10.3390/cells10071610.
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Signal transducer and activator of transcription (STAT) plays an essential role in the inflammatory reaction and immune response of numerous renal diseases. STATs can transmit the signals of cytokines, chemokines, and growth factors from the cell membrane to the nucleus. In the canonical STAT signaling pathways, upon binding with their cognate receptors, cytokines lead to a caspase of Janus kinases (JAKs) and STATs tyrosine phosphorylation and activation. Besides receptor-associated tyrosine kinases JAKs, receptors with intrinsic tyrosine kinase activities, G-protein coupled receptors, and non-receptor tyrosine kinases can also activate STATs through tyrosine phosphorylation or, alternatively, other post-translational modifications. Activated STATs translocate into the nucleus and mediate the transcription of specific genes, thus mediating the progression of various renal diseases. Non-canonical STAT pathways consist of preassembled receptor complexes, preformed STAT dimers, unphosphorylated STATs (U-STATs), and non-canonical functions including mitochondria modulation, microtubule regulation and heterochromatin stabilization. Most studies targeting STAT signaling pathways have focused on canonical pathways, but research extending into non-canonical STAT pathways would provide novel strategies for treating renal diseases. In this review, we will introduce both canonical and non-canonical STAT pathways and their roles in a variety of renal diseases.
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Qiu, Yi, Min Guo, Suming Huang, and Roland Stein. "Insulin Gene Transcription Is Mediated by Interactions between the p300 Coactivator and PDX-1, BETA2, and E47." Molecular and Cellular Biology 22, no. 2 (January 15, 2002): 412–20. http://dx.doi.org/10.1128/mcb.22.2.412-420.2002.
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ABSTRACT Pancreatic β-cell-type-specific expression of the insulin gene requires both ubiquitous and cell-enriched activators, which are organized within the enhancer region into a network of protein-protein and protein-DNA interactions to promote transcriptional synergy. Protein-protein-mediated communication between DNA-bound activators and the RNA polymerase II transcriptional machinery is inhibited by the adenovirus E1A protein as a result of E1A’s binding to the p300 coactivator. E1A disrupts signaling between the non-DNA-binding p300 protein and the basic helix-loop-helix DNA-binding factors of insulin’s E-element activator (i.e., the islet-enriched BETA2 and generally distributed E47 proteins), as well as a distinct but unidentified enhancer factor. In the present report, we show that E1A binding to p300 prevents activation by insulin’s β-cell-enriched PDX-1 activator. p300 interacts directly with the N-terminal region of the PDX-1 homeodomain protein, which contains conserved amino acid sequences essential for activation. The unique combination of PDX-1, BETA2, E47, and p300 was shown to promote synergistic activation from a transfected insulin enhancer-driven reporter construct in non-β cells, a process inhibited by E1A. In addition, E1A inhibited the level of PDX-1 and BETA2 complex formation in β cells. These results indicate that E1A inhibits insulin gene transcription by preventing communication between the p300 coactivator and key DNA-bound activators, like PDX-1 and BETA2:E47.
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Geletu, Mulu, Zaid Taha, Patrick T. Gunning, and Leda Raptis. "PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication." Cancers 11, no. 2 (February 1, 2019): 167. http://dx.doi.org/10.3390/cancers11020167.
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Gap junctional, intercellular communication (GJIC) is interrupted in cells transformed by oncogenes such as activated Src. The Src effector, Ras, is required for this effect, so that Ras inhibition restores GJIC in Src-transformed cells. Interestingly, the inhibition of the Src effector phosphatidyl-inositol-3 kinase (PI3k) or Signal Transducer and Activator of Transcription-3 (Stat3) pathways does not restore GJIC. In the contrary, inhibition of PI3k or Stat3 in non-transformed rodent fibroblasts or epithelial cells or certain human lung carcinoma lines with extensive GJIC inhibits communication, while mutational activation of PI3k or Stat3 increases GJIC. Therefore, it appears that oncogenes such as activated Src have a dual role upon GJIC; acting as inhibitors of communication through the Ras pathway, and as activators through activation of PI3k or Stat3. In the presence of high Src activity the inhibitory functions prevail so that the net effect is gap junction closure. PI3k and Stat3 constitute potent survival signals, so that their inhibition in non-transformed cells triggers apoptosis which, in turn, has been independently demonstrated to suppress GJIC. The interruption of gap junctional communication would confine the apoptotic event to single cells and this might be essential for the maintenance of tissue integrity. We hypothesize that the GJIC activation by PI3k or Stat3 may be linked to their survival function.
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Wang, Xinjiang, Junru Wang, and Xuejun Jiang. "MdmX Protein Is Essential for Mdm2 Protein-mediated p53 Polyubiquitination." Journal of Biological Chemistry 286, no. 27 (May 13, 2011): 23725–34. http://dx.doi.org/10.1074/jbc.m110.213868.
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Genetic evidence has implicated both Mdm2 and MdmX as essential in negative regulation of p53. However, the exact role of MdmX in this Mdm2-dependent protein degradation is not well understood. Most, if not all, previous Mdm2 studies used GST-Mdm2 fusion proteins in the in vitro assays. Here, we show that the p53 polyubiquitination activity of GST-Mdm2 is conferred by the GST tag and non-GST-tagged Mdm2 only catalyzes monoubiquitination of p53 even at extremely high concentrations. We further demonstrate that MdmX is a potent activator of Mdm2, facilitating dose-dependent p53 polyubiquitination. This activation process requires the RING domains of both MdmX and Mdm2 proteins. The polyubiquitination activity of Mdm2/MdmX is Mdm2-dependent. Unlike Mdm2 or MdmX overexpression alone, co-overexpression of MdmX and Mdm2 consistently triggered p53 degradation in cells. Moreover, cellular polyubiquitination of p53 was only observable in the cytoplasm where both Mdm2 and MdmX are readily detectable. Importantly, RNAi knockdown of MdmX increased levels of endogenous p53 accompanied by reduced p53 polyubiquitination. In conclusion, our work has resolved a major confusion in the field derived from using GST-Mdm2 and demonstrated that MdmX is the cellular activator that converts Mdm2 from a monoubiquitination E3 ligase to a polyubiquitination E3 ligase toward p53. Together, our findings provide a biochemical basis for the requirement of both Mdm2 and MdmX in the dynamic regulation of p53 stability.
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Peluso, Heather, Julie A. Caffrey, and Stephen M. Milner. "4G/4G PAI-1 gene variant in a patient with non-healing ulcers." Journal of Epidemiological Research 2, no. 1 (November 11, 2015): 91. http://dx.doi.org/10.5430/jer.v2n1p91.
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Plasminogen activator inhibitor is a serine protease inhibitor from the serpin gene family that modulates fibrin clot breakdown.PAI-1 irreversibly inhibits tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) from activatingplasminogen. PAI-1 also inhibits integrin-vitronectin and vitronectin-vitronectin interactions that are essential for cell migration,adhesion, and angiogenesis. We describe a patient, who developed chronic non-healing ulcers after minimal trauma to severalareas of his body. Genetic testing revealed the 4G/4G homozygous genotype for the polymorphism in the promoter regionof the PAI-1 gene. Increased PAI-1 activity prevents the breakdown of the fibrin clot and cell migration to remodel damagedtissue. A combination of poor clot fibrinolysis and cell recruitment to the site of injury may explain our patient’s non-healingulcers following minor traumatic injury. Early treatment with excision and skin grafting may benefit patients presenting withnon-healing ulcers and the homozygous 4G/4G PAI-1 variant. To our knowledge, there have been no reports in the literatureassociating PAI-1 overexpression and chronic non-healing wounds.
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Liu, Yudan, Meghan Harding, Andrea Pittman, Jules Dore, Jörg Striessnig, Anjali Rajadhyaksha, and Xihua Chen. "Cav1.2 and Cav1.3 L-type calcium channels regulate dopaminergic firing activity in the mouse ventral tegmental area." Journal of Neurophysiology 112, no. 5 (September 1, 2014): 1119–30. http://dx.doi.org/10.1152/jn.00757.2013.
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Dopaminergic projections from the ventral tegmental area (VTA) constitute the mesolimbocortical system that underlies addiction and psychosis primarily as a result of increased dopaminergic transmission. Dopamine release is spike dependent. L-type calcium channels (LTCCs) play an important role in regulating firing activities, but the contribution of specific subtypes remains unclear. This article describes different functions of Cav1.2 and Cav1.3 subtypes in regulating firing properties with two transgenic mouse strains. For basal firing, Cav1.3-deficient (Cav1.3−/−) mice had a lower basal firing frequency. The dihydropyridine (DHP) channel blocker nifedipine reduced single-spike firing in mice expressing DHP-insensitive Cav1.2 channels (Cav1.2DHP−/− mice), confirming the significant contribution from the Cav1.3 subtype in basal firing. Moreover, the DHP channel activator ( S)-(−)-Bay K8644 and the non-DHP channel activator FPL 64176 converted firing patterns from single spiking to bursting in Cav1.2DHP−/− mice. Nifedipine inhibited burst firing induced by both activators, suggesting that Cav1.3 also serves an essential role in burst firing. However, FPL 64176 also induced bursting in Cav1.3−/− mice. These results indicate that the Cav1.3 subtype is crucial to regulation of basal single-spike firing, while activation of both Cav1.2 and Cav1.3 can support burst firing of VTA neurons.
Dissertations / Theses on the topic "Non- essential activator"
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Soualmia, Feryel. "Modulateurs synthétiques de la kallikréine 6, protéase à sérine impliquée dans les maladies neurodégénératives : identification, mécanisme d’action et validation de concept." Electronic Thesis or Diss., Paris 6, 2016. http://www.theses.fr/2016PA066755.
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La kallikréine humaine 6 (hK6) ou neurosine est la protéase à sérine la plus abondante du système nerveux central (SNC). Sa dualité de fonction dans les processus neurodégénératifs font d’elle une cible privilégiée pour la conception de modulateurs pharmacologiques de son activité. Cependant, il existe aujourd’hui très peu de composés répondant à cette attente. Aussi, le principal objectif de ces travaux de thèse a consisté à identifier des inhibiteurs et activateurs organiques de faible poids moléculaire (<500 Da) de la hK6, compatibles avec un développement clinique. L’étude de la hK6 sous ses différents aspects a permis d’établir son profil catalytique et dynamique et de mettre en évidence son rôle anti-agrégatif de l’α-synucléine endogène. L’exploration de diverses chimiothèques regroupant près de 1 200 molécules a permis d’identifier des molécules touches (hits) qui ont fait l’objet d’études mécanistiques approfondies. Des évaluations par modélisation moléculaire ont également été réalisées afin d’établir les bases structurales de la modulation et un profil de sélectivité de ces molécules vis-à-vis d’autres protéases à sérine concurrentes a pu être établi. Pour la première fois, un modulateur bimodal ainsi qu’un activateur, tous deux hautement sélectifs de la hK6, ont été identifiés et un modèle de régulation allostérique a pu être proposé. Plusieurs inhibiteurs originaux possédant un bon profil de sélectivité vis-à-vis de la hK6 ont également été sélectionnés. Ces molécules ne présentent pas d’effet cytotoxique sur des cultures primaires de neurones. Les composés identifiés au cours de cette thèse constituent ainsi une excellente base pour le développement d’agents pharmacologiques à visée neuroprotectrice et anti-inflammatoire et ouvre la voie à l’exploration de nouveaux sites allostériques au sein de cette enzyme et des protéases à sérine tryptiquesThe human kallikrein 6 (hK6) or neurosin is the most abundant serine protease of the central nervous system (CNS). Its dual implication in neurodegenerative processes makes it an emerging target for the design of pharmacological modulators of its activity. Yet today there are only very few compounds that meet this expectation. Thus, the main aim of these thesis was to identify organic low molecular weight (<500 Da) inhibitors and activators of hK6 compatible with clinical development. The study ofhK6 through various aspects has established its catalytic and dynamic profile and highlights its anti-aggregative role of endogenous α-synuclein. Exploring the diverse libraries comprising nearly 1 200molecules led to the identification of key compounds (hits) that have been subjected to extensive mechanistic studies. Assessments by molecular modeling were also carried out to establish the structural basis for activity modulation and selectivity profiling toward competing serine proteases has also been established. For the first time, a bimodal modulator as well as an activator, both highly selective to hK6, were identified and an allosteric regulatory model was proposed. Several original inhibitors having a good selectivity profile toward hK6 were also selected. Furthermore, these molecules do not exhibit any cytotoxic effect on primary neuronal cultures. The compounds identified in this thesis provide an excellent basis for the development of pharmacological agents with neuroprotective and anti-inflammatory properties and pave the way for the exploration of new allosteric sites in hK6 and tryptic serine proteases in general
Books on the topic "Non- essential activator"
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Voll, Reinhard E., and Barbara M. Bröker. Innate vs acquired immunity. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0048.
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The innate and the adaptive immune system efficiently cooperate to protect us from infections. The ancient innate immune system, dating back to the first multicellular organisms, utilizes phagocytic cells, soluble antimicrobial peptides, and the complement system for an immediate line of defence against pathogens. Using a limited number of germline-encoded pattern recognition receptors including the Toll-like, RIG-1-like, and NOD-like receptors, the innate immune system recognizes so-called pathogen-associated molecular patterns (PAMPs). PAMPs are specific for groups of related microorganisms and represent highly conserved, mostly non-protein molecules essential for the pathogens' life cycles. Hence, escape mutants strongly reduce the pathogen's fitness. An important task of the innate immune system is to distinguish between harmless antigens and potentially dangerous pathogens. Ideally, innate immune cells should activate the adaptive immune cells only in the case of invading pathogens. The evolutionarily rather new adaptive immune system, which can be found in jawed fish and higher vertebrates, needs several days to mount an efficient response upon its first encounter with a certain pathogen. As soon as antigen-specific lymphocyte clones have been expanded, they powerfully fight the pathogen. Importantly, memory lymphocytes can often protect us from reinfections. During the development of T and B lymphocytes, many millions of different receptors are generated by somatic recombination and hypermutation of gene segments making up the antigen receptors. This process carries the inherent risk of autoimmunity, causing most inflammatory rheumatic diseases. In contrast, inadequate activation of the innate immune system, especially activation of the inflammasomes, may cause autoinflammatory syndromes.
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Jones, Michael, Norman Qureshi, and Kim Rajappan. Atrial flutter. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0117.
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Atrial flutter is the term given to one of the four types of supraventricular tachycardia; in it, atrial activation occurs as a consequence of a continuous ‘short circuit’: a defined and fixed anatomical route, resulting in a fairly uniform atrial rate, and uniform atrial flutter waves on the ECG. The ventricles are not a part of this arrhythmia circuit, and ventricular activation is variable, dependent on atrioventricular (AV) nodal conduction. Given that the atrial rate is essentially uniform (e.g. 300 min−1), ventricular activation tends to be regular (i.e. 150 min−1, 100 min−1, 75 min−1, etc., if the atrial rate is 300 mins−1), or regularly irregular if changes are occurring in the fraction of conducted impulses to the ventricles. When AV nodal conduction permits only 4:1 conduction or less, atrial flutter is usually obvious, but when ventricular rates are higher (150 min−1 or more) the flutter waves can be obscured by the QRS complexes, making diagnosis more difficult. Atrial flutter is of two types, typical and atypical. Typical atrial flutter is a right atrial tachycardia, with electrical activation proceeding around the tricuspid valve annulus. This arrhythmia is dependent on a zone of slow electrical conduction through the cavotricuspid isthmus (the tissue lying between the origin of the inferior vena cava and the posterior tricuspid valve). The resulting circuit can be either anticlockwise (activation proceeds up the inter-atrial septum, across the atrial roof, down the free wall, and then through the cavotricuspid isthmus to the basal septum) or clockwise (down the inter-atrial septum and around the circuit in the opposite direction). Anticlockwise typical atrial flutter is more common. Atypical atrial flutter refers to all other atrial flutters, and this includes other right atrial flutters (e.g. pericristal flutter), left atrial flutters, post-ablation or post-surgical flutters, and pulmonary vein flutters. The feature common to all types of flutter and which differentiates flutter from other types of supraventricular tachycardia is the presence of a macro-re-entrant anatomical circuit around which the electrical impulse travels continuously and repeatedly, thereby generating the flutter. Even though typical atrial flutter has a fairly obvious and specific appearance on the ECG, atypical flutters do not, and often it is only possible to differentiate atypical flutter from atrial tachycardias by invasive electrophysiology studies, as the ECG alone may be insufficient.
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Baildam, Eileen. Juvenile idiopathic arthritis. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0116.
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Juvenile idiopathic arthritis (JIA) is defined as arthritis lasting for 6 weeks or more presenting in childhood at any age up to 17 years. Arthritis is diagnosed clinically by the presence of joint pain, stiffness, and swelling with inflammation limiting the range of individual joint movement. There are subtypes that tend to follow distinct courses and with phenotypes that vary widely from a serious systemic inflammatory disorder of systemic JIA to single-joint monoarthritis. The differential diagnosis of JIA is wide and the best chance of long-term remission is where treatment is started as early as possible. However, there is often delay in diagnosis in childhood and there is no single reliable diagnostic test so pattern recognition is fundamental. There are associated disorders such as silent uveitis that must be screened for and managed as part of essential multidisciplinary care. Systemic JIA is complicated by potentially life-threatening macrophage activation syndrome that is often underdiagnosed but where the diagnosis is based on easy clinical tests and where awareness is vital. This chapter covers descriptions of the classification criteria for chronic arthritis in children, clinical presentations and likely course for the various subtypes.
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Sullivan MD, PhD, Mark. From Patient to Agent. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780195386585.001.0001.
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In the 21st century, the primary challenge for health care is chronic illness. To meet this challenge, we need to think anew about the role of the patient in health and health care. There have been widespread calls for patient-centered care, but this model of care does not question deeply enough the goals of health care, the nature of the clinical problem, and the definition of health itself. We must instead pursue patient-centered health, which is a health perceived and produced by patients. We should not only respect, but promote patient autonomy as an essential component of this health. Objective health measures cannot capture the burden of chronic illness, so we need to draw on the patient's perspective to help define the clinical problem. We require a new definition of health as the capacity for meaningful action. It is recognized that patients play a central role in chronic illness care, but the concept of health behavior retards innovation. We seek not just an activated patient, but an autonomous patient who sets and pursues her own vital goals. To fully enlist patients, we must bridge the gap between impersonal disease processes and personal processes. This requires understanding how the roots of patient autonomy lie in the biological autonomy that allows organisms to carve their biological niche. It is time for us to recognize the patient as the primary customer for health care and the primary producer of health. Patient agency is both the primary means and primary end of health care.
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Whitworth, Caroline, and Stewart Fleming. Malignant hypertension. Edited by Neil Turner. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0216.
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Malignant hypertension (MH) is recognized clinically by elevated blood pressure together with retinal haemorrhages or exudates with or without papilloedema (grades III or IV hypertensive retinopathy); and may constitute a hypertensive emergency or crisis when complicated by evidence of end-organ damage including microangiopathic haemolysis, encephalopathy, left ventricular failure, and renal failure. Though reversible, it remains a significant cause of end-stage renal failure, and of cardiovascular and cerebrovascular morbidity and mortality in developing countries.MH can complicate pre-existing hypertension arising from diverse aetiologies, but most commonly develops from essential hypertension. The absolute level of blood pressure appears not to be critical to the development of MH, but the rate of rise of blood pressure may well be relevant in the pathogenesis. The pathogenesis of this transformation remains unclear.The pathological hallmark of MH is the presence of fibrinoid necrosis (medial vascular smooth muscle cell necrosis and fibrin deposition within the intima) involving the resistance arterioles in many organs. Fibrinoid necrosis is not specific to MH and this appearance is seen in other conditions causing a thrombotic microangiopathy such as haemolytic uraemic syndrome, scleroderma renal crisis, antiphospholipid syndrome, and acute vascular rejection post transplant. MH can both cause a thrombotic microangiopathy (TMA) but can also complicate underlying conditions associated with TMA.The pathophysiological factors that interact to generate and sustain this condition remain poorly understood. Risk factors include Afro-Caribbean race, smoking history, younger age of onset of hypertension, previous pregnancy, and untreated hypertension associated with non-compliance or cessation of antihypertensive therapy.Evidence from clinical studies and animal models point to a central role for the intrarenal renin–angiotensin system (RAS) in MH; there is good evidence for renal vasoconstriction and activation of the renal paracrine RAS potentiating MH once established; however, there may also be a role in the predisposition of MH suggested by presence of increased risk conferred by an ACE gene polymorphism in humans and polymorphisms for both ACE and AT1 receptor in an animal model of spontaneous MH. Other vasoactive mediators such as the endothelin and the inflammatory response may be important contributing to and increasing endothelial damage. There have been no randomized controlled trials to define the best treatment approach, but progressive lowering of pressures over days is considered safest unless made more urgent by critical clinical state. It seems logical to introduce ACE inhibition cautiously and early, but in view of the risk of rapid pressure lowering some recommend delay.
Book chapters on the topic "Non- essential activator"
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Danisi, Carmelo, Moira Dustin, Nuno Ferreira, and Nina Held. "The Decision-Making Procedure." In IMISCOE Research Series, 179–258. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-69441-8_6.
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AbstractWhereas in Chap. 10.1007/978-3-030-69441-8_5 we analysed pre-departure, journey and arrival experiences of SOGI claimants, we now turn our attention to the decision-making procedure. Whether they apply for asylum on arrival or later on, the initial screening is usually followed by a substantive interview. This is the essential moment when SOGI claimants have the opportunity to present their case. If the application is then refused, a judicial process is normally activated to appeal against the initial negative decision.
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Nakanishi, Tomoko M. "Element-Specific Distribution in a Plant." In Novel Plant Imaging and Analysis, 75–107. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-33-4992-6_3.
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AbstractFor the first stage of the study of the elements, the distribution of the element within the plant tissue was presented employing neutron activation analysis (NAA). Since NAA allows nondestructive analysis of the elements in the sample, this is the only method to measure the absolute amount of elements in the sample.The results showed that the element-specific profile varied throughout the whole plant, and this distribution tendency remained similar throughout development. There were many junctions of element-specific concentrations between the tissues, suggesting barriers to the movement of the elements. Generally, heavy elements tended to accumulate in roots, except for Mn and Cr. Of the elements measured, Ca and Mg showed changes in concentration with the circadian rhythm. Since the amount of the element in a plant reflects the features of the soil where the plant grows, multielement analysis of the plant could specify the site of the agricultural products produced.Before addressing the development of a real-time RI imaging system (RRIS), the production of RIs for essential elements for plant nutrition, 28Mg and 42K, is presented. The reason why concentrating on RIs is because when we examine the history of plant research, physiological research on the elements without available radioisotopes has not been well developed. For example, the boron (B) transporter was recently found and the study of B in plants is far behind compared to the other elements.Therefore, we developed a preparation method for elements whose available RIs were not previously employed in plant research, 28Mg and 42K. They are the radioisotopes we prepared and a root absorption study using 28Mg as a tracer is presented as an example. It was found that the orientation of Mg transfer was different according to the site of the root where Mg was absorbed. The specific role of Mg has not yet been clarified by florescent imaging because the overwhelming amount of Ca makes it difficult to distinguish Mg and Ca.
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Pavelkic, Vesna, Tanja Brdaric, and Kristina Gopcevic. "Aluminium - Non-Essential Activator of Pepsin: Kinetics and Thermodynamics." In Medicinal Chemistry and Drug Design. InTech, 2012. http://dx.doi.org/10.5772/35081.
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Schober, Andreas, Saffiyeh Saboor Maleki, and Maliheh Nazari-Jahantigh. "Regulatory Non-coding RNAs in Atherosclerosis." In Handbook of Experimental Pharmacology. Berlin, Heidelberg: Springer Berlin Heidelberg, 2020. http://dx.doi.org/10.1007/164_2020_423.
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AbstractRegulatory RNAs like microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) control vascular and immune cells’ phenotype and thus play a crucial role in atherosclerosis. Moreover, the mutual interactions between miRNAs and lncRNAs link both types of regulatory RNAs in a functional network that affects lesion formation. In this review, we deduce novel concepts of atherosclerosis from the analysis of the current data on regulatory RNAs’ role in endothelial cells (ECs) and macrophages. In contrast to arterial ECs, which adopt a stable phenotype by adaptation to high shear stress, macrophages are highly plastic and quickly change their activation status. At predilection sites of atherosclerosis, such as arterial bifurcations, ECs are exposed to disturbed laminar flow, which generates a dysadaptive stress response mediated by miRNAs. Whereas the highly abundant miR-126-5p promotes regenerative proliferation of dysadapted ECs, miR-103-3p stimulates inflammatory activation and impairs endothelial regeneration by aberrant proliferation and micronuclei formation. In macrophages, miRNAs are essential in regulating energy and lipid metabolism, which affects inflammatory activation and foam cell formation.Moreover, lipopolysaccharide-induced miR-155 and miR-146 shape inflammatory macrophage activation through their oppositional effects on NF-kB. Most lncRNAs are not conserved between species, except a small group of very long lncRNAs, such as MALAT1, which blocks numerous miRNAs by providing non-functional binding sites. In summary, regulatory RNAs’ roles are highly context-dependent, and therapeutic approaches that target specific functional interactions of miRNAs appear promising against cardiovascular diseases.
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Mabe, Michael R. "The Library as Lifeboat." In Advances in Library and Information Science, 494–515. IGI Global, 2016. http://dx.doi.org/10.4018/978-1-4666-8624-3.ch021.
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According to Hurricane Katrina: Lessons Learned (2006), emergency management professionals realized first-hand that preplanning and coordination is essential when mounting an effective reaction to natural disasters. This chapter describes how leaders in Chesterfield County, VA learned similar lessons in 2001 during Hurricane Irene. In comparison to Katrina the amount of damage caused by Irene was minimal but the impact on county leaders was severe. Based on lessons learned during Irene and an unexpected wind storm nine months later, Chesterfield County leaders now include the Chesterfield County Public (CCPL) in their official disaster relief plans. When activated, CCPL will serve as an information hub, double as a daytime relief shelter and participate in mass feeding if necessary. Selected library branches are available to be used as overnight relief shelters for mass care when the activation of a standard sized shelter facility is not warranted. These changes have made a notable difference.
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Mabe, Michael R. "The Library as Lifeboat." In Emergency and Disaster Management, 1513–35. IGI Global, 2019. http://dx.doi.org/10.4018/978-1-5225-6195-8.ch071.
Full textAbstract:
According to Hurricane Katrina: Lessons Learned (2006), emergency management professionals realized first-hand that preplanning and coordination is essential when mounting an effective reaction to natural disasters. This chapter describes how leaders in Chesterfield County, VA learned similar lessons in 2001 during Hurricane Irene. In comparison to Katrina the amount of damage caused by Irene was minimal but the impact on county leaders was severe. Based on lessons learned during Irene and an unexpected wind storm nine months later, Chesterfield County leaders now include the Chesterfield County Public (CCPL) in their official disaster relief plans. When activated, CCPL will serve as an information hub, double as a daytime relief shelter and participate in mass feeding if necessary. Selected library branches are available to be used as overnight relief shelters for mass care when the activation of a standard sized shelter facility is not warranted. These changes have made a notable difference.
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Voll, Reinhard E., and Barbara M. Bröker. "Innate vs acquired immunity." In Oxford Textbook of Rheumatology, 356–64. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0048_update_001.
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The innate and the adaptive immune system efficiently cooperate to protect us from infections. The ancient innate immune system, dating back to the first multicellular organisms, utilizes phagocytic cells, soluble antimicrobial peptides, and the complement system for an immediate line of defence against pathogens. Using a limited number of germline-encoded pattern recognition receptors including the Toll-like, RIG-1-like, and NOD-like receptors, the innate immune system recognizes so-called pathogen-associated molecular patterns (PAMPs). PAMPs are specific for groups of related microorganisms and represent highly conserved, mostly non-protein molecules essential for the pathogens’ life cycles. Hence, escape mutants strongly reduce the pathogen’s fitness. An important task of the innate immune system is to distinguish between harmless antigens and potentially dangerous pathogens. Ideally, innate immune cells should activate the adaptive immune cells only in the case of invading pathogens. The evolutionarily rather new adaptive immune system, which can be found in jawed fish and higher vertebrates, needs several days to mount an efficient response upon its first encounter with a certain pathogen. As soon as antigen-specific lymphocyte clones have been expanded, they powerfully fight the pathogen. Importantly, memory lymphocytes can often protect us from reinfections. During the development of T and B lymphocytes, many millions of different receptors are generated by somatic recombination and hypermutation of gene segments making up the antigen receptors. This process carries the inherent risk of autoimmunity, causing most inflammatory rheumatic diseases. In contrast, inadequate activation of the innate immune system, especially activation of the inflammasomes, may cause autoinflammatory syndromes.
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Ježek, Petr, Blanka Holendová, Martin Jabůrek, Jan Tauber, Andrea Dlasková, and Lydie Plecitá-Hlavatá. "Redox Signaling is Essential for Insulin Secretion." In Type 2 Diabetes [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.94312.
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In this review, we place redox signaling in pancreatic β-cells to the context with signaling pathways leading to insulin secretion, acting for example upon the action of incretins (GLP-1, GIP) and the metabotropic receptor GPR40. Besides a brief description of ion channel participation in depolarization/repolarization of the plasma membrane, we emphasize a prominent role of the elevated glucose level in pancreatic β-cells during glucose-stimulated insulin secretion (GSIS). We focus on our recent findings, which revealed that for GSIS, not only elevated ATP synthesis is required, but also fundamental redox signaling originating from the NADPH oxidase 4- (NOX4-) mediated H2O2 production. We hypothesized that the closing of the ATP-sensitive K+ channel (KATP) is only possible when both ATP plus H2O2 are elevated in INS-1E cells. KATP alone or with synergic channels provides an element of logical sum, integrating both metabolic plus redox homeostasis. This is also valid for other secretagogues, such as branched chain ketoacids (BCKAs); and partly for fatty acids (FAs). Branched chain aminoacids, leucine, valine and isoleucine, after being converted to BCKAs are metabolized by a series of reactions resembling β-oxidation of FAs. This increases superoxide formation in mitochondria, including its portion elevated due to the function of electron transfer flavoprotein ubiquinone oxidoreductase (ETF:QOR). After superoxide conversion to H2O2 the oxidation of BCKAs provides the mitochondrial redox signaling extending up to the plasma membrane to induce its depolarization together with the elevated ATP. In contrast, experimental FA-stimulated insulin secretion in the presence of non-stimulating glucose concentrations is predominantly mediated by GPR40, for which intramitochondrial redox signaling activates phospholipase iPLA2γ, cleaving free FAs from mitochondrial membranes, which diffuse to the plasma membrane and largely amplify the GPR40 response. These events are concomitant to the insulin release due to the metabolic component. Hypothetically, redox signaling may proceed by simple H2O2 diffusion or via an SH-relay enabled by peroxiredoxins to target proteins. However, these aspects have yet to be elucidated.
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Taofeek Popoola, Lekan, and Alhaji Shehu Grema. "Adsorption of Heavy Metals from Industrial Wastewater using Nanoparticles from Agro Wastes." In Nanopores [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.98241.
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Effluents from essential industries have been characterized with heavy metals which are non-biodegradable in nature and also detrimental to health when accumulated in body tissues over long exposure. Adsorption was proved as the best efficient process amongst others to remove these heavy metals from industrial wastewater due to its excellent features. Activated carbons from nanoparticles of agricultural wastes such as pods, shells, husks, peels, shafts and many prepared via calcination process at high temperature can be used as active adsorbent for the industrial wastewater treatment involving heavy metals removal. This chapter discusses heavy metals in industrial wastewater effluents and potential agro wastes from which nanoparticles of activated carbon for industrial wastewater purification could be generated. The transformation of agro wastes nanoparticles into activated carbons via calcination and their applications for heavy metals removal from industrial wastewater via adsorption were examined. Various characterization techniques to study the effects of calcination on structural, morphological and textural properties of activated carbon prepared from agro waste nanoparticles were also discussed. Various isotherm, kinetics, mechanistic and thermodynamics models to investigate the adsorptive nature of the process were presented. Error functions and algorithms for both the linear and non-linear isotherm models regression to affirm their fitness for prediction were presented. Lastly, proposed adsorption mechanisms of heavy metals removal from industrial wastewater using activated carbons from nanoparticles of agro wastes were presented.
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Enciso-Pablo, Óscar, Karina Angélica Méndez-Reséndiz, Tamara Rosenbaum, and Sara Luz Morales-Lázaro. "Nociceptive TRP Channels and Sex Steroids." In Reproductive Hormones. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.95552.
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Proteins belonging to Transient Receptor Potential (TRP) family are nonselective cation channels that play an essential role in mammalian physiology, functioning as transducers of several environmental signals including those of chemical, thermal and mechanical natures. A subgroup of these receptors is expressed in sensory neurons where they are activated by noxious stimuli and are key players of pain responses in the organism. Some TRP channels are molecular targets for the classical and non-classical effects of sex steroids. This chapter will describe the close relationship between nociceptive TRP channels and sex steroids as well as their impact on nociception and pain-related responses.
Conference papers on the topic "Non- essential activator"
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Lambers, J. W. J., M. Cammenga, B. Konig, H. Pannekoek, and J. A. van Mourik. "ACTIVATION OF HUMAN ENDOTHELIAL TYPE PLASMINOGEN ACTIVATOR INHIBITOR (PAI-1) BY NEGATIVELY CHARGED PHOSPHOLIPIDS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642807.
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The endothelial cell type plasminogen activator inhibitor (PAI-1) may exist in an active, latent form that can be converted into an active form upon exposure to denaturants such as sodium dodecyl sulphate (SDS), guanidine-HCl or urea. Here we show that latent PAI-1 can be activated with lipid vesicles, consisting of the negatively charged phospholipids phosphatidylserine (PS) or phosphatidylinositol (PI). The presence of a net negative charge on the phospholipid headgroup is essential for activation. Incubation with lipid vesicles, consisting of the zwitterionic phospholipids phosphatidylcholine (PC) and phosphatidylethanol-amine (PE), does not result in activation of the inhibitor. In the presence of PS vesicles, the capacity of PAI-1 to inhibit tissue type plasminogen activator (t-PA) is 50-fold higher than that of the untreated protein. For comparison, the activity of PAI-1 was enhanced 25-fold by treatment of the protein with SDS. PS induces activation of the inhibitor at much lower concentrations than SDS. For example, to achieve 50% inhibition of t-PA with a more than 100-fold excess of PAI-1, 0.25 nmoles of PS are required, whereas L.60 nmoles of SDS are necessary to reach half maximal inactivation of t-PA. Activation of PAI-1 by PS can be reversed by the addition of Ca2+-ions, suggesting that Ca2+-ions interfere with the interaction of PAI-1 with the negatively charged lipid surface, thus preventing its activation. The lipid-induced activation of PAI-1 points to a possibly important role of phospholipids in fibrinolysis; regulation of the fibrinolytic activity in blood plasma may ultimately be determined by the extent to which these phospholipids activate the inhibitor of t-PA.This study was supported by the Netherlands Thrombosis Foundation.
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D'Angelo, A., F. Gilardoni, V. Toschi, C. Ciminiello, E. A. Sinico, and S. Viganò D'Angelo. "REDUCED PROTEIN S ANTICOAGULANT ACTIVITY IN ESSENTIAL MIXED CRYOGLOBULINEMIA." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644293.
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Protein S (PS) is found in two forms in plasma, as free PS, which functions as a cofactor for activated protein C, and in e-quimolar complex with C4b-binding protein (C4b-bp), an inhibitor of the complement system. The Kd of the PS-C4b-bp interaction is one order of magnitude lower than the plasma concentration of the two proteins; thus 55-60% of total PS circulates in the bound form. Evidence has been provided that in vitro complement activation does not affect the equilibrium between PS and C4b-bp; however in patients with systemic lupus erythematosus and low C4 levels, a shift from free to bound PS has been observed. To further evaluate the relationship between complement activation and PS distribution we have measured PS and C4b-bp levels in 21 patients with essential mixed cryoglobulinemia (EMC), an autoimmune disorder characterized by cryo-precitable circulating immunocomplexes and associated with vasculitis and thrombotic episodes. EMC patients had cryocrit rangin from 1 to 66% and greatly reduced complement components (Clq: 45%, C3: 71%, C4: 15% of normal). Mean PS activity was significantly reduced inpatients as compared to the control population consisting of 20 age-and sex-matched blood donors (69%, p< 0.001). Free PS was similar in patients and controls, but total PS was lower in EMC patients (82%, p<0.05). Seven EMC patients had C4b-bp levels be low 60%. Thus, reduction of PS activity in patients with EMC is not due to reduced free PS. Cultured endothelial cells synthesize and release PS with reduced specif ic activity. In EMC patients very high levels of von Willebrand factor (313%, p< 0.001) a protein released from endothelial cells, but not of ceruplasmin, another acute phase reactant protein, were observed.In vivo release of PS from en dothelial cells might contribute to reduced PS specific activity in EMC.
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Thorsen, Terje, and Holm Holmsen. "PLATELET ACTIVATION AND AGGREGATION BY GAS BOBBLES IN VITRO." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643759.
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After diving, in decompression sickness and after extra-corporeal circulation in membrane oxygenators, there is often a reductionin the number of circulating platelets. Gas bubbles seem to be the common denominator for these quite different conditions, and it is assumed that gas bubbles activate the platelets although by unknown mechanisms. We have used gas bubbles as a platelet agonist in an aggregometer-like apparatus. The bubbles produced platelet aggregation similar to that caused by "classical" agonists,e.g.,ADP, epinephrine etc. The gas-liquidinterface was essential for this aggregation,and the bubble diameter, rather than thetype of gas or the total number of bubbles, determined the potency of this agonist. Electron microscopical studies revealed that singleplatelets and platelet aggregates with numerous, short pseudopods adhered to the bubble wall. The platelet aggregation caused bygas bubbles was abolished by metabolic blockers (2-deoxyglucose and antimycin A), EGTA,phosphodiesterase inhibitors (theophylline, caffeine, papaverine, dipyridamole), adenylate cyclase activators (PGE1 adenosine, AMP), or a combination of low concentrationsof phosphodiesterase inhibitors and adenylate activators. Theophylline which is regardedas a weak inhibitor of platelet activation in general, was an especially potent inhibitor of gas bubble-induced platelet aggregationwhereas cyclooxygenase inhibitors (acetyl salicylic acid, indomethacin), adrenoreceptor blocker (yohimbine), guanylate cyclase activators (azide, jiitroprusside) and trifluoperazine had little or no effect. Bubble-induced,aggregation is thus similar to theprimary,and not the secondary, aggregation caused byclassical agonists. However, the ineffectiveness of guanylate cyclase activators distinguishes bubble-induced aggegation from "classical" primary aggregation.
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Scott, Cheryl F., John L. Brash, Pauline ten Hove, Peter Wojciechowaki, and Robert W. Colman. "PLASMA-ARTIFICIAL SURFACE INTERACTIONS; ROLE OF CONTACT AND FIBRINOLYTIC SYSTEMS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642919.
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The transient adsorption of fibrinogen (Fg) to artificial surfaces (Vroman Effect) is modulated principally by the procofactor, high molecular weight kininogen (HK). We investigated which form of HK was responsible for Fg displacement and also whether other proteins participated in the Vroman Effect. Experiments were performed at 23°C with a 5 min surface exposure to various concentrations of either normal plasma or plasma deficient in specific proteins to which 125I Fg had been added. Typically, Fg adsorption reached a maximum at 1% plasma and decreased at higher plasma concentrations. On all surfaces tested, Fg displacement was greatly reduced in HK-deficient plasma. Normal plasma,when exposed to the contact system activator, dextran sulfate, prior to its interaction with glass, displayed Fg displacement similar to untreated HK-deficient plasma.However, if Factor Xl-deficient plasma was incubated with dextran sulfate prior to exposure to glass, the Fg displacement pattern resembled normal, untreated plasma. These results suggest that the inactive cofactor form of HK (HMWKi) generated by Factor XIa (formed during extensive contact activation) does not displace Fg. Furthermore, Fg displacement was also reduced in untreated Factor Xll-deficient plasma exposed to glass, suggesting that the active cofactor form of HK (HMWKa) generated by exposure to kallikrein (during Factor Xll-dependent contact activation) may be the active participant in the Vroman Effect. The cofactor function of HK and its ability to displace Fg, therefore, appear to parallel. We also found that plasminogen or plasminogen activators were minimally involved in the Vroman Effect. Fg adsorption to glass in plasminogen-depleted HK-deficent plasma resembled Fg adsorption in a single protein system since more Fg was adsorbed and desorption failed to occur. A synergism may therefore exist between plasminogen and HK in the Vroman Effect. A better understanding of the mechanism of blood-artificial surface interaction is essential for the design of less thrombogenic biomaterials.
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Cao, Mingnan, Limei Guo, Juan Li, Chun Liu, Yiguo Zhang, Siwang Yu, and Tony A.-N. Kong. "Abstract 4556: Activation of sonic hedgehog signaling is essential for non-alcoholic steatohepatitis induced by liver-specific disruption of Nrf1." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-4556.
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Kanamori, Y., I. Yada, I. Yuasa, M. Kusagawa, and K. Deguchi. "PHYSIOLOGICAL ROLE OF THE ENHANCED FIBRINOLYTIC ACTIVITY DURING CARDIOPULMONARY BYPASS IN OPEN HEART SURGERY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644658.
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Fibrinolytic activity is reportedly increased during cardiopulmonary bypass( CPB ), and this increase has been considered to be related to the bleeding complications in open heart surgery. The purpose of this study was to clarify the nature of the fibrinolytic activity duringCPB. Twenty patients with valve replacement or aortocoronary bypass surgery were examined. The following parameters were determined: fibrinogen, plasminogen, fibrinopeptide A( FPA ), fibrinopeptide B β 15-42 ( FPB β15-42 ), and tissue-type plasminogen activator ( t-PA ). For further characterization of the fibrinolytic activity, the fibrin plate method was used. Intrinsic fibrinolytic activity was determined by the assay of the fibrinolytic activity of the kaolin activatedeuglobulin. Extrinsic fibrinolyticactivity was estimated by the assayof Cl-inactivator resistant fibrinolytic activity as well as t-PA. Fibrinogen and plasminogen did not decrease except at the beginning of CPB. FPA was increased significantly during CPB. FPB3 15-42 was also increased to four times the preoperative value at 2 hrs of CPB. The intrinsic fibrinolytic system was activatedonly a short time after the startof CPB. The Cl-inactivator resistant fibrinolytic activity was activated gradually during CPB, reached a maximum level 1 hr after the start of CPB, and returned to the preoperative level within 1 hr after the end of CPB. The changes on t-PA paralleled the course of the Cl-inactivator resistant fibrinolytic activity, indicating that enhanced fibrinolytic activity during CPB is predominantly of extrinsic origin caused by t-PA. We conclude that thrombin activity continues during CPB despite the use of heparin, and thatthe enhanced fibrinolytic activity during CPB is essential because t-PA activates plasminogen predominantly at the sites where fibrin is formed, resulting in the dissolution of the microthrombi formed during CPB.
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Wyler, B., and K. J. Clemetson. "THE ROLE OF GPIb IN PLATELET ACTIVATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642922.
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Platelet membrane glycoprotein lb (GPIb) is known to contain a receptor for von Willebrand factor (vWf) and for thrombin. The role of GPIb in platelet activation was investigated by comparing the effect of removal of the binding sites by specific proteolysis with that of blocking them using specific antibodies. Specific removal of the 45 kDa outer part of GPIb by treatment of platelets with human leukocyte elastase caused loss of platelet agglutination response to von Willebrand factor (vWf) but also a weaker activation by thrombin similar to that found with Bernard-Soulier syndrome platelets which lack GPIb. Removal of the major part of the external region of the GPIba chain, including the 45 kDa domain, by calcium activated protease or by chymotrypsin, produced similar effects. The 45 kDa region of GPIba was purified by tryptic cleavage of isolated glycocalicin followed by gel filtration. Antibodies to this fragment were produced in rabbits and showed high specificity and affinity for the 45 kDa polypeptide. Fab fragments of IgG prepared from this anti serum affect platelet response to vWf and thrombin in a dose-dependent way. In both protease-treated and antibody-treated platelets the reduced response to thrombin, but not to vWf could be overcome by increasing the dose of thrombin. In contrast to removal of the 45 kDa domain, antibody treatment affected not only the platelet response to vWf and thrombin but also to collagen, ADP, PAF and arachidonic acid. Only the response to the calcium ionophore A23,187 was unaltered.Though not the essential receptor GPIb is clearly involved in platelet response to thrombin. A possible mechanism could involve a conformational change in the cytoplasmic/inter-membranous part of GPIb induced by binding of thrombin to the 45 kDa domain. Binding of antibodies might affect platelet activation by other agonists via a general down regulation effect. These results support the two receptor models for thrombin activation of platelets as proposed for other cell -types. In platelets the first receptor appears to be GPIb but the second receptor has not yet been identified.
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Johannessen, M., F. E. Nielsen, K. Pingel, and L. C. Petersen. "FIBRINOLYTIC EFFECT OF ONE-CHAIN TTSSUE-TYPE PLASMINOGEN ACTIVATOR." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644406.
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The fibrinolytic properties of authentic one- and two-chain recombinant tPA were compared to those of a plasmin resistant one-chain tPA analogue, tPA-Gly275, which is point mutated in Arg275 of the activation site. The proteins were characterised by reversed phase HPLC, reduced SDS-PAGE, and their concentrations determined by the BCA (modified Lowry) method. When equivalent conc. of these enzymes were tested for fibrinolytic activity by means of clot lysis and fibrin plate lysis methods, the values found for two-chain tPA were consistently 50% higher than one-chain tPA forms. The time course for plasmin catalysed one-chain tPA cleavage during fibrin clot lysis was determined by means of 125I-tPA. The cleavage is not instantaneous, and one-chain tPA may account for a considerable fraction of the total amount of plasmin formed. This is confirmed by similar experiments with 125I-tPA-Gly275, which is essentially intact one-chain tPA at the time of fibrin clot lysis. The effect of tPA activation site cleavage was also studied using plasmin coupled to sepharose beads. Plasmin sepharose was removed at different time intervals, and tPA was tested for amidolytic activity with > Glu-Gly-Arg-pNA and fibrinolytic activity as measured by fibrin clot lysis time as well as by fibrin plate methods. The results indicate that in the presence of fibrin, plasminogen can be activated by one-chain tPA at a considerable rate. On the other hand, the fact that the fibrinolytic activity measured by conventional assays is lower with one-chain tPA than with two-chain tPA should be considered when of these methods are used for standardization.
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Lande, K., I. O. S. S. E. Kieldsen, A. Westheim, I. Aakesson, I. Hlermann, I. Eide, and K. GiesdaL. "PATIENTS WITH MILD ESSENTIAL HYPERTENSION HAVE INCREASED PLATELET SIZE AND RELEASE REACTION ANO SHOW INCREASED RECEPTOR RESPONSE TO INFUSED ADRENALINE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644261.
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Hypertensive (n = 35) and normotensive {n = 44) men all 42 years old were studied. The hypertensive (HT) had larger venous platelets than the normotensive (HT) (7.46 ± 0.10 vs 7.12 ± 0.09 10-15 1, p = 0.01). Plasma concentration of |3-thromboglobulin (BTG) was increased in arterial blood in hypertensive (40 ± 8 vs 21 ± 2 ug/1, p=0.02) while the venous values were similar in the two groups. Despite similar sampling procedure, the normotensive subjects had markedly higher BTGconcentration in venous compared to arterial blood (p≺0.01) at variance from thehypertensive where the arteriovenous difference in plasma BTG concentration was not present. Adrenaline was infused to 13 hypertensive and 12 normotensive subjects with dose gradually increasing to 0.04 pg/kg/min. Forearm blood flow was measured by strain gauge technique and relative forearm resistance calculated as mean blood pressure divided by flow. Twelve normotensive subjects (control group) received saline infusion.Change in forearm resistance reflectsβ2- activation of smooth vascular cells, change in platelet count reflects splenic liberation of platelets in response to adrenergic stimulation while change in BTG may reflect platelet release upon stimulation of α2 -receptors. Thus, middle aged men with essential hypertension show increased sensitivity to adrenaline infusion in vascular smooth muscle, spleen and platelets.
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Lember, Erki, Karin Pachel, and Enn Loigu. "Adsorption of Diclofenac, Sulfamethoxazole and Levofloxacin with Powdered Activated Carbon." In Environmental Engineering. VGTU Technika, 2017. http://dx.doi.org/10.3846/enviro.2017.082.
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The presence of pharmaceutical residues in the receiving waterbodies of wastewater treatment plants (WWTP) and in the environment has become a global concern. We can now say for certain that, having metabolised in our bodies, partially modified or unmodified pharmaceuticals will reach WWTP. However, WWTP are not designed for the removal of such com-pounds. Only a small fraction of pharmaceuticals decompose during biological treatment or are adsorbed in sediment. There-fore, it is essential to find a treatment process that is capable of removing pharmaceutical residues. The aim of the present study was to research the removal of three pharmaceuticals found in the environment, namely diclofenac (DCF), sulfamethoxazole (SMX) and levofloxacin (LFX), through the use of powdered activated carbon (PAC). To this end, adsorption tests were con-ducted where the adsorption capacity was estimated according to the adsorbent dose and the residence time of the process. LFX had the highest adsorption rate: the removal effectiveness was 77% in a residence time of 5 minutes and in 60 minutes a stable indicator was achieved whereby 94% of LFX had become adsorbed. The worst adsorption property was observed for SMX, as 68% of SMX was adsorbed in a residence time of 60 minutes. According to the conducted tests, the Freundlich adsorption isotherms and constants characterising the adsorption were found where the DCF K was 23.8, the SMX K was 34.3 and the LFX K was 106.1. This test demonstrated that the pharmaceuticals selected for the experiment could easily be subjected to adsorption processes and could be removed by means of PAC.
Reports on the topic "Non- essential activator"
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Prusky, Dov, Nancy P. Keller, and Amir Sherman. global regulation of mycotoxin accumulation during pathogenicity of Penicillium expansum in postharvest fruits. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7600012.bard.
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Background to the topic- Penicilliumas a postharvest pathogen and producer of the mycotoxin PAT. Penicilliumspp. are destructive phytopathogens, capable of causing decay in many deciduous fruits, during postharvest handling and storage; and the resulting losses can amount to 10% of the stored produce and the accumulation of large amounts of the mycotoxinpatulin. The overall goal of this proposal is to identify critical host and pathogen factors that modulate P. expansummycotoxin genes and pathways which are required for PAT production and virulence. Our preliminary results indicated that gluconic acid are strongly affecting patulin accumulation during colonization. P. expansumacidifies apple fruit tissue during colonization in part through secretion of gluconic acid (GLA). Several publications suggested that GLA accumulation is an essential factor in P. expansumpathogenicity. Furthermore, down regulation of GOX2 significantly reduced PAT accumulation and pathogenicity. PAT is a polyketide and its biosynthesis pathway includes a 15-gene cluster. LaeA is a global regulator of mycotoxin synthesis. It is now known that patulin synthesis might be subjected to LaeA and sometimes by environmental sensing global regulatory factors including the carbon catabolite repressor CreA as well as the pH regulator factor PacC and nitrogen regulator AreA. The mechanisms by which LaeA regulates patulin synthesis was not fully known and was part of our work. Furthermore, the regulatory system that controls gene expression in accordance with ambient pH was also included in our work. PacC protein is in an inactive conformation and is unable to bind to the promoter sites of the target genes; however, under alkaline growth conditions activated PacC acts as both an activator of alkaline-expressed genes and a repressor of acid-expressed genes. The aims of the project- This project aims to provide new insights on the roles of LaeA and PacC and their signaling pathways that lead to GLA and PAT biosynthesis and pathogenicity on the host. Specifically, our specific aims were: i) To elucidate the mechanism of pH-controlled regulation of GLA and PAT, and their contribution to pathogenesis of P. expansum. We are interested to understanding how pH and/or GLA impact/s under PacC regulation affect PAT production and pathogenesis. ii) To characterize the role of LaeA, the global regulator of mycotoxin production, and its effect on PAT and PacC activity. iii) To identify the signaling pathways leading to GLA and PAT synthesis. Using state- of-the-art RNAseq technologies, we will interrogate the transcriptomes of laeAand pacCmutants, to identify the common signaling pathways regulating synthesis of both GLA and PAT. Major conclusions, solutions, achievements- In our first Aim our results demonstrated that ammonia secreted at the leading edge of the fungal colony induced transcript activation of the global pH modulator PacC and PAT accumulation in the presence of GLA. We assessed these parameters by: (i) direct exogenous treatment of P. expansumgrowing on solid medium; (ii) direct exogenous treatment on colonized apple tissue; (iii) growth under self-ammonia production conditions with limited carbon; and (iv) analysis of the transcriptional response to ammonia of the PAT biosynthesis cluster. Ammonia induced PAT accumulation concurrently with the transcript activation of pacCand PAT biosynthesis cluster genes, indicating the regulatory effect of ammonia on pacCtranscript expression under acidic conditions. Transcriptomic analysis of pH regulated processes showed that important genes and BARD Report - Project 4773 Page 2 of 10 functionalities of P. expansumwere controlled by environmental pH. The differential expression patterns of genes belonging to the same gene family suggest that genes were selectively activated according to their optimal environmental conditions to enable the fungus to cope with varying conditions and to make optimal use of available enzymes. Concerning the second and third Aims, we demonstrated that LaeA regulates several secondary metabolite genes, including the PAT gene cluster and concomitant PAT synthesis invitro. Virulence studies of ΔlaeAmutants of two geographically distant P. expansumisolates (Pe-21 from Israel and Pe-T01 from China) showed differential reduction in disease severity in freshly harvested fruit ranging from no reduction for Ch-Pe-T01 strains in immature fruit to 15–25% reduction for both strains in mature fruit, with the ΔlaeAstrains of Is-Pe-21 always showing a greater loss in virulence. Results suggest the importance of LaeA regulation of PAT and other secondary metabolites on pathogenicity. Our work also characterized for the first time the role of sucrose, a key nutritional factor present in apple fruit, as a negative regulator of laeAexpression and consequent PAT production in vitro. This is the first report of sugar regulation of laeAexpression, suggesting that its expression may be subject to catabolite repression by CreA. Some, but not all of the 54 secondary metabolite backbone genes in the P. expansumgenome, including the PAT polyketide backbone gene, were found to be regulated by LaeA. Together, these findings enable for the first time a straight analysis of a host factor that potentially activates laeAand subsequent PAT synthesis.
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Makhachashvili, Rusudan K., Svetlana I. Kovpik, Anna O. Bakhtina, and Ekaterina O. Shmeltser. Technology of presentation of literature on the Emoji Maker platform: pedagogical function of graphic mimesis. [б. в.], July 2020. http://dx.doi.org/10.31812/123456789/3864.
Full textAbstract:
The article deals with the technology of visualizing fictional text (poetry) with the help of emoji symbols in the Emoji Maker platform that not only activates students’ thinking, but also develops creative attention, makes it possible to reproduce the meaning of poetry in a succinct way. The application of this technology has yielded the significance of introducing a computer being emoji in the study and mastering of literature is absolutely logical: an emoji, phenomenologically, logically and eidologically installed in the digital continuum, is separated from the natural language provided by (ethno)logy, and is implicitly embedded into (cosmo)logy. The technology application object is the text of the twentieth century Cuban poet José Ángel Buesa. The choice of poetry was dictated by the appeal to the most important function of emoji – the expression of feelings, emotions, and mood. It has been discovered that sensuality can reconstructed with the help of this type of meta-linguistic digital continuum. It is noted that during the emoji design in the Emoji Maker program, due to the technical limitations of the platform, it is possible to phenomenologize one’s own essential-empirical reconstruction of the lyrical image. Creating the image of the lyrical protagonist sign, it was sensible to apply knowledge in linguistics, philosophy of language, psychology, psycholinguistics, literary criticism. By constructing the sign, a special emphasis was placed on the facial emogram, which also plays an essential role in the transmission of a wide range of emotions, moods, feelings of the lyrical protagonist. Consequently, the Emoji Maker digital platform allowed to create a new model of digital presentation of fiction, especially considering the psychophysiological characteristics of the lyrical protagonist. Thus, the interpreting reader, using a specific digital toolkit – a visual iconic sign (smile) – reproduces the polylaterial metalinguistic multimodality of the sign meaning in fiction. The effectiveness of this approach is verified by the poly-functional emoji ousia, tested on texts of fiction.
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Lers, Amnon, and Pamela J. Green. LX Senescence-Induced Ribonuclease in Tomato: Function and Regulation. United States Department of Agriculture, September 2003. http://dx.doi.org/10.32747/2003.7586455.bard.
Full textAbstract:
Natural leaf senescence, which occurs even when growth conditions are near optimal, has a negative influence on yield. Postharvest induced senescence contributes to the losses of quality in flowers, foliage, and vegetables. Strategies designed to control the senescence process in crop plants could therefore have great applied significance. However, the successful design of such strategies requires a better insight into the senescence machinery and control in higher plants. A main feature of senescence is the hydrolysis of macromolecules by hydrolases of various types such as ribonucleases (RNases) and proteases. Previously we had identified and characterized the tomato LX RNase gene demonstrating its transcript to be highly and specifically induced during senescence. This reported study was focused on LX but also had broadened our research to other senescence-associated nucleic acids degrading enzymes to learn about their function and the regulation of their encoding genes. Beside tomato we used parsley and Arabidopsis for the study of: the bi-functional nuclease which has a role in senescence. The study of different senescence- associated nucleases in few plant systems will allow a more general view on function and regulation of these enzymes in senescence. The specific original proposed objectives included: 1. Study the consequences of alterations in LX RNase level on tomato leaf senescence and general development; 2. Analyze stimuli which may participate in senescence-specific activation of the LX gene; 3. Clone the senescence-associated BFNI nuclease gene homologue from tomato. 4. Further characterize the sequences required for senescence-specific gene expression. Homozygous transgenic plants in which LX gene was either inhibited or over-expressed were generated. In both of these LX mutated plants no major phenotypic consequences were observed, which may suggests that LX is not essential for plant growth under optimal growth conditions. Lack of any abnormalities in the LX over-expressing lines suggests that special system exist to allow function of the RNase only when needed. Detailed analyses of growth under stress and consequences to RNA metabolism are underway. We have analyzed LX expression on the protein level demonstrating that it is involved also in petal senescing. Our results suggest that LX is responding to complex regulation involving developmental, organ dependent factors and responds differently to hormonal or environmental stimuli in the different plant organs. The cloned 1.4 kb promoter was cloned and its analysis revealed that probably not all required elements for senescence induction are included. Biochemical analysis of senescence-associated be-functional nucleases in the different plants, tomato, parsley and Arabidopsis, suggests they belong to a sub-class within the type I plant nucleases. The parsley PcNUC1/2 nuclease protein was purified from senescing leaves its and activity was studied in vitro revealing endo-, double strand, nucleolytic activity and exo-nucleolytic activity. Its encoding gene was cloned and found to be induced on the mRNA level. The promoter of the related Arabidopsis BFNI nuclease was shown in both tomato and Arabidopsis to be able and direct senescence-specific expression suggesting that, at least part, the gene is regulated on the transcriptional level and that the mechanism for this senescence-specific regulation is conserved between different plants. Few plants in which the BFNI gene is mutated were identified which are subjected now to detailed analysis. Our results suggest that the senescence-related nucleic acid degrading enzymes share similarities in both function and regulation between different plants and possibly have important functions in processes un-related to senescence. Still, the function of these enzymes, at least in some cases is not essential to plant development under optimal growth conditions. We are now at the stage which permits in depth investigation of the specific functions and mode of molecular regulation of senescence-associated nucleases with the aid of the research tools developed. The isolated senescence-specific promoter, shown to be active in heterologous plant system, could be utilized in agricultural-related biotechnological applications for retardation of senescence.
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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.
Full textAbstract:
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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Sionov, Edward, Nancy Keller, and Shiri Barad-Kotler. Mechanisms governing the global regulation of mycotoxin production and pathogenicity by Penicillium expansum in postharvest fruits. United States Department of Agriculture, January 2017. http://dx.doi.org/10.32747/2017.7604292.bard.
Full textAbstract:
The original objectives of the study, as defined in the approved proposal, are: To characterize the relationship of CreA and LaeA in regulation of P T production To understand how PacC modulates P. expansumpathogenicity on apples To examine if other secondary metabolites are involved in virulence or P. expansumfitness To identify the signaling pathways leading to PAT synthesis Penicilliumexpansum, the causal agent of blue mould rot, is a critical health concern because of the production of the mycotoxinpatulin (PAT) in colonized apple fruit tissue. Although PAT is produced by many Penicilliumspecies, the factors activating its biosynthesis were not clear. This research focused on host and fungal mechanisms of activation of LaeA (the global regulator of secondary metabolism), PacC (the global pH modulator) and CreA (the global carbon catabolite regulator) on PAT synthesis with intention to establish P. expansumas the model system for understanding mycotoxin synthesis in fruits. The overall goal of this proposal is to identify critical host and pathogen factors that mechanistically modulate P. expansumgenes and pathways to control activation of PAT production and virulence in host. Several fungal factors have been correlated with disease development in apples, including the production of PAT, acidification of apple tissue by the fungus, sugar content and the global regulator of secondary metabolism and development, LaeA. An increase in sucrose molarity in the culture medium from 15 to 175 mM negatively regulated laeAexpression and PAT accumulation, but, conversely, increased creAexpression, leading to the hypothesis that CreA could be involved in P. expansumPAT biosynthesis and virulence, possibly through the negative regulation of LaeA. We found evidence for CreAtranscriptional regulation of laeA, but this was not correlated with PAT production either in vitro or in vivo, thus suggesting that CreA regulation of PAT is independent of LaeA. Our finding that sucrose, a key ingredient of apple fruit, regulates PAT synthesis, probably through suppression of laeAexpression, suggests a potential interaction between CreA and LaeA, which may offer control therapies for future study. We have also identified that in addition to PAT gene cluster, CreA regulates other secondary metabolite clusters, including citrinin, andrastin, roquefortine and communesins, during pathogenesis or during normal fungal growth. Following creation of P. expansumpacCknockout strain, we investigated the involvement of the global pH regulator PacC in fungal pathogenicity. We demonstrated that disruption of the pH signaling transcription factor PacC significantly decreased the virulence of P. expansumon deciduous fruits. This phenotype is associated with an impairment in fungal growth, decreased accumulation of gluconic acid and reduced synthesis of pectolytic enzymes. We showed that glucose oxidase- encoding gene, which is essential for gluconic acid production and acidification during fruit colonization, was significantly down regulated in the ΔPepacCmutant, suggesting that gox is PacC- responsive gene. We have provided evidence that deletion of goxgene in P. expansumled to a reduction in virulence toward apple fruits, further indicating that GOX is a virulence factor of P. expansum, and its expression is regulated by PacC. It is also clear from the present data that PacC in P. expansumis a key factor for the biosynthesis of secondary metabolites, such as PAT. On the basis of RNA-sequencing (RNA-seq) analysis and physiological experimentation, the P. expansumΔlaeA, ΔcreAand ΔpacCmutants were unable to successfully colonize apples for a multitude of potential mechanisms including, on the pathogen side, a decreased ability to produce proteolytic enzymes and to acidify the environment and impaired carbon/nitrogen metabolism and, on the host side, an increase in the oxidative defence pathways. Our study defines these global regulatory factors and their downstream signalling pathways as promising targets for the development of strategies to fight against this post-harvest pathogen.
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Sessa, Guido, and Gregory Martin. A functional genomics approach to dissect resistance of tomato to bacterial spot disease. United States Department of Agriculture, January 2004. http://dx.doi.org/10.32747/2004.7695876.bard.
Full textAbstract:
The research problem. Bacterial spot disease in tomato is of great economic importance worldwide and it is particularly severe in warm and moist areas affecting yield and quality of tomato fruits. Causal agent of spot disease is the Gram-negative bacterium Xanthomonas campestris pv. vesicatoria (Xcv), which can be a contaminant on tomato seeds, or survive in plant debris and in association with certain weeds. Despite the economic significance of spot disease, plant protection against Xcvby cultural practices and chemical control have so far proven unsuccessful. In addition, breeding for resistance to bacterial spot in tomato has been undermined by the genetic complexity of the available sources of resistance and by the multiple races of the pathogen. Genetic resistance to specific Xcvraces have been identified in tomato lines that develop a hypersensitive response and additional defense responses upon bacterial challenge. Central goals of this research were: 1. To identify plant genes involved in signaling and defense responses that result in the onset of resistance. 2. To characterize molecular properties and mode of action of bacterial proteins, which function as avirulence or virulence factors during the interaction between Xcvand resistant or susceptible tomato plants, respectively. Our main achievements during this research program are in three major areas: 1. Identification of differentially expressed genes during the resistance response of tomato to Xcvrace T3. A combination of suppression subtractive hybridization and microarray analysis identified a large set of tomato genes that are induced or repressed during the response of resistant plants to avirulent XcvT3 bacteria. These genes were grouped in clusters based on coordinate expression kinetics, and classified into over 20 functional classes. Among them we identified genes that are directly modulated by expression of the type III effector protein AvrXv3 and genes that are induced also during the tomato resistance response to Pseudomonas syringae pv. tomato. 2. Characterization of molecular and biochemical properties of the tomato LeMPK3MAP kinase. A detailed molecular and biochemical analysis was performed for LeMPK3 MAP kinase, which was among the genes induced by XcvT3 in resistant tomato plants. LeMPK3 was induced at the mRNA level by different pathogens, elicitors, and wounding, but not by defense-related plant hormones. Moreover, an induction of LeMPK3 kinase activity was observed in resistant tomato plants upon Xcvinfection. LeMPK3 was biochemically defined as a dual-specificity MAP kinase, and extensively characterized in vitro in terms of kinase activity, sites and mechanism of autophosphorylation, divalent cation preference, Kₘand Vₘₐₓ values for ATP. 3. Characteriztion of molecular properties of the Xcveffector protein AvrRxv. The avirulence gene avrRxvis involved in the genetic interaction that determines tomato resistance to Xcvrace T1. We found that AvrRxv functions inside the plant cell, localizes to the cytoplasm, and is sufficient to confer avirulence to virulent Xcvstrains. In addition, we showed that the AvrRxv cysteine protease catalytic core is essential for host recognition. Finally, insights into cellular processes activated by AvrRxv expression in resistant plants were obtained by microarray analysis of 8,600 tomato genes. Scientific and agricultural significance: The findings of these activities depict a comprehensive and detailed picture of cellular processes taking place during the onset of tomato resistance to Xcv. In this research, a large pool of genes, which may be involved in the control and execution of plant defense responses, was identified and the stage is set for the dissection of signaling pathways specifically triggered by Xcv.
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Coplin, David L., Shulamit Manulis, and Isaac Barash. roles Hrp-dependent effector proteins and hrp gene regulation as determinants of virulence and host-specificity in Erwinia stewartii and E. herbicola pvs. gypsophilae and betae. United States Department of Agriculture, June 2005. http://dx.doi.org/10.32747/2005.7587216.bard.
Full textAbstract:
Gram-negative plant pathogenic bacteria employ specialized type-III secretion systems (TTSS) to deliver an arsenal of pathogenicity proteins directly into host cells. These secretion systems are encoded by hrp genes (for hypersensitive response and pathogenicity) and the effector proteins by so-called dsp or avr genes. The functions of effectors are to enable bacterial multiplication by damaging host cells and/or by blocking host defenses. We characterized essential hrp gene clusters in the Stewart's Wilt of maize pathogen, Pantoea stewartii subsp. stewartii (Pnss; formerly Erwinia stewartii) and the gall-forming bacterium, Pantoea agglomerans (formerly Erwinia herbicola) pvs. gypsophilae (Pag) and betae (Pab). We proposed that the virulence and host specificity of these pathogens is a function of a) the perception of specific host signals resulting in bacterial hrp gene expression and b) the action of specialized signal proteins (i.e. Hrp effectors) delivered into the plant cell. The specific objectives of the proposal were: 1) How is the expression of the hrp and effector genes regulated in response to host cell contact and the apoplastic environment? 2) What additional effector proteins are involved in pathogenicity? 3) Do the presently known Pantoea effector proteins enter host cells? 4) What host proteins interact with these effectors? We characterized the components of the hrp regulatory cascade (HrpXY ->7 HrpS ->7 HrpL ->7 hrp promoters), showed that they are conserved in both Pnss and Fag, and discovered that the regulation of the hrpS promoter (hrpSp) may be a key point in integrating apoplastic signals. We also analyzed the promoters recognized by HrpL and demonstrated the relationship between their composition and efficiency. Moreover, we showed that promoter strength can influence disease expression. In Pnss, we found that the HrpXY two-component signal system may sense the metabolic status of the bacterium and is required for full hrp gene expression in planta. In both species, acyl-homoserine lactone-mediated quorum sensing may also regulate epiphytic fitness and/or pathogenicity. A common Hrp effector protein, DspE/WtsE, is conserved and required for virulence of both species. When introduced into corn cells, Pnss WtsE protein caused water-soaked lesions. In other plants, it either caused cell death or acted as an Avr determinant. Using a yeast- two-hybrid system, WtsE was shown to interact with a number of maize signal transduction proteins that are likely to have roles in either programmed cell death or disease resistance. In Pag and Pab, we have characterized the effector proteins HsvG, HsvB and PthG. HsvG and HsvB are homologous proteins that determine host specificity of Pag and Pab on gypsophila and beet, respectively. Both possess a transcriptional activation domain that functions in yeast. PthG was found to act as an Avr determinant on multiple beet species, but was required for virulence on gypsophila. In addition, we demonstrated that PthG acts within the host cell. Additional effector genes have been characterized on the pathogenicity plasmid, pPATHₚₐg, in Pag. A screen for HrpL- regulated genes in Pnsspointed up 18 candidate effector proteins and four of these were required for full virulence. It is now well established that the virulence of Gram-negative plant pathogenic bacteria is governed by Hrp-dependent effector proteins. However; the mode of action of many effectors is still unresolved. This BARD supported research will significantly contribute to the understanding of how Hrp effectors operate in Pantoea spp. and how they control host specificity and affect symptom production. This may lead to novel approaches for genetically engineering plants resistant to a wide range of bacterial pathogens by inactivating the Hrp effectors with "plantabodies" or modifying their receptors, thereby blocking the induction of the susceptible response. Alternatively, innovative technologies could be used to interfere with the Hrp regulatory cascade by blocking a critical step or mimicking plant or quorum sensing signals.