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Triggering
Terms modified by Triggering Selected AbstractsTriggering Creativity in Teams: An Exploratory InvestigationCREATIVITY AND INNOVATION MANAGEMENT, Issue 1 2002Sven F. Kyle“n Triggering, developing and maintaining creativity in teams is critical to the economic performance of the firm. This article presents an exploratory action research effort in a health care organization that focused on interaction patterns amongst team members, creativity and performance. The results indicate that the teams' inquiry and dialogue into their interaction patterns have the potential of influencing creativity. Team interaction patterns were found to influence team performance. Directions for future research are discussed. [source] Treatment with oxidizing agents damages the inner membrane of spores of Bacillus subtilis and sensitizes spores to subsequent stressJOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2004D.E. Cortezzo Abstract Aims:, To determine if treatment of Bacillus subtilis spores with a variety of oxidizing agents causes damage to the spore's inner membrane. Methods and Results:, Spores of B. subtilis were killed 80,99% with wet heat or a variety of oxidizing agents, including betadine, chlorine dioxide, cumene hydroperoxide, hydrogen peroxide, OxoneTM, ozone, sodium hypochlorite and t-butylhydroperoxide, and the agents neutralized and/or removed. Survivors of spores pretreated with oxidizing agents exhibited increased sensitivity to killing by a normally minimal lethal heat treatment, while spores pretreated with wet heat did not. In addition, spores treated with wet heat or the oxidizing agents, except sodium hypochlorite, were more sensitive to high NaCl in plating media than were untreated spores. The core region of spores treated with at least two oxidizing agents was also penetrated much more readily by methylamine than was the core of untreated spores, and spores treated with oxidizing agents but not wet heat germinated faster with dodecylamine than did untreated spores. Spores of strains with very different levels of unsaturated fatty acids in their inner membrane exhibited essentially identical resistance to oxidizing agents. Conclusions:, Treatment of spores with oxidizing agents has been suggested to cause damage to the spore's inner membrane, a membrane whose integrity is essential for spore viability. The sensitization of spores to killing by heat and to high salt after pretreatment with oxidizing agents is consistent with and supports this suggestion. Presumably mild pretreatment with oxidizing agents causes some damage to the spore's inner membrane. While this damage may not be lethal under normal conditions, the damaged inner membrane may be less able to maintain its integrity, when dormant spores are exposed to high temperature or when germinated spores are faced with osmotic stress. Triggering of spore germination by dodecylamine likely involves action by this agent on the spore's inner membrane allowing release of the spore core's depot of dipicolinic acid. Presumably dodecylamine more readily alters the permeability of a damaged inner membrane and thus more readily triggers germination of spores pretreated with oxidizing agents. Damage to the inner spore membrane by oxidizing agents is also consistent with the more rapid penetration of methylamine into the core of treated spores, as the inner membrane is likely the crucial permeability barrier to methylamine entry into the spore core. As spores of strains with very different levels of unsaturated fatty acids in their inner membrane exhibited essentially identical resistance to oxidizing agents, it is not through oxidation of unsaturated fatty acids that oxidizing agents kill and/or damage spores. Perhaps these agents work by causing oxidative damage to key proteins in the spore's inner membrane. Significance and Impact of the Study:, The more rapid heat killing and germination with dodecylamine, the greater permeability of the spore core and the osmotic stress sensitivity in outgrowth of spores pretreated with oxidizing agents is consistent with such agents causing damage to the spore's inner membrane, even if this damage is not lethal under normal conditions. It may be possible to take advantage of this phenomenon to devise improved, less costly regimens for spore inactivation. [source] Drug-induced apoptosis in osteosarcoma cell lines is mediated by caspase activation independent of CD95-receptor/ligand interactionJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2000J. Fellenberg Osteosarcoma is one of the most common primary malignant tumors of bone. Treatment of this tumor with systemic chemotherapy dramatically improves the prognosis, although the molecular mechanisms involved in the drug action are poorly understood. In chemosensitive leukaemic T cells and certain solid tumors. cytotoxic drugs mediate the induction of apoptosis by activation of the CD95/APO-1/Fas system. Triggering of the corresponding signaling pathway may involve CD95-receptor/ligand interaction, activation of caspases, or alterations in mitochondrial function. The purpose of our study was to determine if similar mechanisms are involved in the chemosensitivity of osteosarcomas. We found that cytotoxic drugs induce characteristic biochemical and morphological alterations related to apoptosis in osteosarcoma cell lines, including activation of caspases and disturbance of mitochondrial function. However, drug treatment did not result in activation of CD95-receptor or CD95-ligand mRNA. In addition, drug-induced apoptosis was blocked by caspase inhibitors but not by inhibition of CD95-ligand action, indicating a CD95-receptor/ligand-independent mechanism in osteosarcoma cell lines. [source] Triggering of dendritic cell apoptosis by xanthohumolMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue S2 2010Nguyen Thi Xuan Abstract Xanthohumol, a flavonoid from beer with anticancer activity is known to trigger apoptosis in a variety of tumor cells. Xanthohumol further has anti-inflammatory activity. However, little is known about the effect of xanthohumol on survival and function of immune cells. The present study thus addressed the effect of xanthohumol on dendritic cells (DCs), key players in the regulation of innate and adaptive immunity. To this end, mouse bone marrow-derived DCs were treated with xanthohumol with subsequent assessment of enzymatic activity of acid sphingomyelinase (Asm), ceramide formation determined with anti-ceramide antibodies in FACS and immunohistochemical analysis, caspase activity utilizing FITC conjugated anti-active caspase 8 or caspase 3 antibodies in FACS and by Western blotting, DNA fragmentation by determining the percentage of cells in the sub-G1 phase and cell membrane scrambling by annexin V binding in FACS analysis. As a result, xanthohumol stimulated Asm, enhanced ceramide formation, activated caspases 8 and 3, triggered DNA fragmentation and led to cell membrane scrambling, all effects virtually absent in DCs from gene targeted mice lacking functional Asm or in wild-type cells treated with sphingomyelinase inhibitor amitriptyline. In conclusion, xanthohumol stimulated Asm leading to caspase activation and apoptosis of bone marrow-derived DCs. [source] Emotional Stress Triggers Symptoms in Hypertrophic Cardiomyopathy: A Survey of the Hypertrophic Cardiomyopathy AssociationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 9 2010RACHEL LAMPERT M.D. Background:,Symptoms are among the most important factors impacting quality of life (QOL) in hypertrophic cardiomyopathy (HCM) patients, and reflect a poor prognosis. Whether emotional stress can trigger symptoms of chest pain, dyspnea, palpitations, and lightheadedness has not been described. Methods:,Members of the Hypertrophic Cardiomyopathy Association (HCMA) received an electronic link via e-mail to an ongoing online survey, also accessed via links on the HCMA message-board and homepage. Between May 2007 and November 2008, there were 1,297 respondents. The survey queried demographic and self-reported clinical information, and types and triggers of symptoms. Respondents reported physical and emotional QOL on a 1,10 Likert scale. Results:,Symptoms reported included chest pain (49%), dyspnea (70%), palpitations (61%), and syncope/lightheadedness (59%). The most common symptom trigger was exertion, 64% describing symptoms while climbing stairs or hills. Forty-nine percent described experiencing symptoms during emotional stress. Those reporting chest pain were more likely to report emotion triggering (60%) than those reporting palpitations, syncope/lightheadedness, or dyspnea (50,54% each). Both physical and emotional QOL were significantly decreased in those describing emotion-triggered symptoms. Women were more likely than men to report symptoms overall, as well as emotion-triggered symptoms (50% vs 35%, P < 0.001) and exertion-triggered symptoms (79% vs 58%, P < 0.001). After controlling for presence of symptoms, both emotion- and exertion-triggered symptoms remained significantly more common in women. Conclusions:,Triggering of symptoms by emotion is common in individuals with HCM. Further studies will determine pathways linking emotional stressors with chest pain, dyspnea, palpitations, and lightheadedness in these patients. (PACE 2010; 33:1047,1053) [source] Cloud-resolving model simulations of multiply-banded frontal cloudsTHE QUARTERLY JOURNAL OF THE ROYAL METEOROLOGICAL SOCIETY, Issue 611 2005M. Pizzamei Abstract An idealized two-dimensional cloud-resolving model is used to investigate the formation and temporal evolution of multiply-banded clouds in frontal zones. Radar observations often show both upright and slantwise convection in the circulations associated with such bands. The aim is to examine the interaction between upright and slantwise convection and to determine the mechanisms leading to multiple banding. A warm bubble is used to initiate convection in the frontal zone, which has an initial thermodynamic profile based on observations. Further triggering occurs and banded clouds evolve. The initially upright plumes become tilted due to the so-called ,M adjustment process (upscale development). Observed multiple bands in frontal zones are frequently attributed to the release of conditional symmetric instability (CSI). However, in these simulations, there is no evidence of the release of CSI despite the fragmentation of slantwise bands into multiple layers in the mid-troposphere. Successive triggering of upright convection is instead associated with a spreading cold pool driven by evaporative cooling in the slanted downdraughts. Triggering can occur on both the warm- and cold-air sides of the frontal zone, and is sensitive to the microphysical parametrization used. Copyright © 2005 Royal Meteorological Society. [source] Triggering of systolic arterial pressure alarms using statistics-based versus threshold alarms,ANAESTHESIA, Issue 2 2009C. W. Connor Summary Threshold systolic arterial pressure alarms often use pre-operative values as a guide for intra-operative values. Recently, two systems (normalisation and principal component analysis) have been described that use the ,current' systolic arterial pressure and the change in systolic arterial pressure over a preceding time interval to generate an alarm based on units of standard deviation. Normalisation and principal component analysis techniques should prioritise alarms for clinically significant changes and hence reduce overall activation of alarms. Our aim was to measure the change in alarm activation using these techniques compared with standard threshold alarms. Systolic blood pressure data, collected from 10 patients (a total of 2177 min at 100 Hz), were cleaned and submitted to analysis using threshold alarms, normalisation and principal component analysis. With the threshold alarms set at 100 mmHg (low) and 140 mmHg (high), and a 5-min window, the alarms were activated for 557 min; using statistics-based thresholds the alarms were activated for 169 min (normalisation) and 155 min (principal component analysis), a reduction of approximately 70,72%. [source] Triggering of Guanosine Self-Assembly by Light,ANGEWANDTE CHEMIE, Issue 21 2010Stefano Lena Dr. Licht bestimmt die Struktur: Eine photochemisch aktive Einheit macht die Selbstorganisation eines lipophilen Guanosinderivats mit Licht steuerbar: Die Bildung von G-Quartetten lässt sich ein- und ausschalten (siehe Schema). [source] Triggering of proteinase-activated receptor 4 leads to joint pain and inflammation in miceARTHRITIS & RHEUMATISM, Issue 3 2009Jason J. McDougall Objective To investigate the role of proteinase-activated receptor 4 (PAR-4) in mediating joint inflammation and pain in mice. Methods Knee joint blood flow, edema, and pain sensitivity (as induced by thermal and mechanical stimuli) were assessed in C57BL/6 mice following intraarticular injection of either the selective PAR-4 agonist AYPGKF-NH2 or the inactive control peptide YAPGKF-NH2. The mechanism of action of AYPGKF-NH2 was examined by pretreatment of each mouse with either the PAR-4 antagonist pepducin P4pal-10 or the bradykinin antagonist HOE 140. Finally, the role of PAR-4 in mediating joint inflammation was tested by pretreating mice with acutely inflamed knees with pepducin P4pal-10. Results PAR-4 activation caused a long-lasting increase in joint blood flow and edema formation, which was not seen following injection of the control peptide. The PAR-4,activating peptide was also found to be pronociceptive in the joint, where it enhanced sensitivity to a noxious thermal stimulus and caused mechanical allodynia and hyperalgesia. The proinflammatory and pronociceptive effects of AYPGKF-NH2 could be inhibited by pepducin P4pal-10 and HOE 140. Finally, pepducin P4pal-10 ameliorated the clinical and physiologic signs of acute joint inflammation. Conclusion This study demonstrates that local activation of PAR-4 leads to proinflammatory changes in the knee joint that are dependent on the kallikrein,kinin system. We also show for the first time that PARs are involved in the modulation of joint pain, with PAR-4 being pronociceptive in this tissue. Thus, blockade of articular PAR-4 may be a useful means of controlling joint inflammation and pain. [source] A link between endoplasmic reticulum stress-induced , -cell apoptosis and the group VIA Ca2+ -independent phospholipase A2 (iPLA2,)DIABETES OBESITY & METABOLISM, Issue 2010X. Lei Endoplasmic reticulum (ER) stress is becoming recognized as an important contributing factor in various diseases, including diabetes mellitus. Prolonged ER stress can cause , -cell apoptosis; however, the underlying mechanism(s) that contribute to this process are not well understood. Early reports suggested that arachidonic acid metabolites and a Ca2+ -independent phospholipase A2 (iPLA2) activity play a role in , -cell apoptosis. The PLA2 family of enzymes catalyse the hydrolysis of the sn -2 substituent (i.e. arachidonic acid) of membrane phospholipids. In light of our findings that the pancreatic islet , -cells are enriched in arachidonate-containing phospholipids and express the group VIA iPLA2,, we considered the possibility that iPLA2, participates in ER stress-induced , -cell apoptosis. Our work revealed a novel mechanism, involving ceramide generation and triggering of mitochondrial abnormalities, by which iPLA2, participates in the , -cell apoptosis process. Here, we review our evidence linking ER stress, , -cell apoptosis and iPLA2,. Continued studies in this area will increase our understanding of the contribution of iPLA2, to the evolution of diabetes mellitus and will further our knowledge of factors that influence , -cell health in diabetes mellitus and identify potential targets for future therapeutic interventions to prevent , -cell death. [source] Content and distribution of arsenic in soils, sediments and groundwater environments of the southern Pampa region, ArgentinaENVIRONMENTAL TOXICOLOGY, Issue 6 2006M. del C. Blanco Abstract The health of a large rural population in the southern Pampa (Argentina) is at risk owing to newly detected areas where As-groundwater exceeds 0.01 mg/L standard (WHO (1995) Guidelines for drinking water quality, 2nd edition. pp 43,45). Currently, devitrification of volcanic glass is invoked to interpret the origin of arsenic in the aquifers hosted in a sequence of pampean loess (Plio-Pleistocene) juxtaposed with postpampean loess (Holocene). Our data suggest that arsenic is not specifically associated with volcanic glass and that other minerals contribute to As-release into groundwater. The goals were (1) to understand As-groundwater spatial variability, (2) to explore soils/sediments/water relationships and to identify the probable As-provenance. Comparable As concentrations of the light and the heavy sand fractions suggest that though detrital glass is a major light constituent, other existing primary minerals are As-bearers that contribute to As-release into groundwater. Grouping of materials according to their As-content indicated spatial variability in the sedimentary distribution pattern leading to differences in the frequencies of occurrence of As-bearing minerals. Phreatic waters were Ca + Mg bicarbonate and devoid of As in the intake areas (Ventania System) and Na-carbonate but As-rich towards the discharge (Atlantic coast and local depressions). As-groundwater reflects a patchy distribution within the pampean landscape. A correspondence between As-high groundwater, EC >1 dSm, CO3H,, alkaline pH and a longer water residence time do exist triggering As extraction from the loess sand fraction and desorption from charged fine particles which lead to As-toxicity towards groundwater discharge. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 561,574, 2006. [source] The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll -pathway activation functionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010Alexey A. Matskevich Abstract The Drosophila Toll -signaling pathway controls the systemic antifungal host response. Gram-negative binding protein 3 (GNBP3), a member of the ,-glucan recognition protein family senses fungal infections and activates this pathway. A second detection system perceives the activity of proteolytic fungal virulence factors and redundantly activates Toll. GNBP3hades mutant flies succumb more rapidly to Candida albicans and to entomopathogenic fungal infections than WT flies, despite normal triggering of the Toll pathway via the virulence detection system. These observations suggest that GNBP3 triggers antifungal defenses that are not dependent on activation of the Toll pathway. Here, we show that GNBP3 agglutinates fungal cells. Furthermore, it can activate melanization in a Toll -independent manner. Melanization is likely to be an essential defense against some fungal infections given that the entomopathogenic fungus Beauveria bassiana inhibits the activity of the main melanization enzymes, the phenol oxidases. Finally, we show that GNBP3 assembles "attack complexes", which comprise phenoloxidase and the necrotic serpin. We propose that Drosophila GNBP3 targets fungi immediately at the inception of the infection by bringing effector molecules in direct contact with the invading microorganisms. [source] MAPK3 deficiency drives autoimmunity via DC armingEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010Ivo Bendix Abstract DC are professional APC that instruct T cells during the inflammatory course of EAE. We have previously shown that MAPK3 (Erk1) is important for the induction of T-cell anergy. Our goal was to determine the influence of MAPK3 on the capacity of DC to arm T-cell responses in autoimmunity. We report that DC from Mapk3,/, mice have a significantly higher membrane expression of CD86 and MHC-II and , when loaded with the myelin oligodendrocyte glycoprotein , show a superior capacity to prime naļve T cells towards an inflammatory phenotype than Mapk3+/+ DC. Nonetheless and as previously described, Mapk3,/, mice were only slightly but not significantly more susceptible to myelin oligodendrocyte glycoprotein-induced EAE than WT littermate mice. However, Mapk3+/+ mice engrafted with Mapk3,/, BM (KO,WT) developed a severe form of EAE, in direct contrast to WT,KO mice, which were even less sick than control WT,WT mice. An infiltration of DC and accumulation of Th17 cells was also observed in the CNS of KO,WT mice. Therefore, triggering of MAPK3 in the periphery might be a therapeutic option for the treatment of neuroinflammation since absence of this kinase in the immune system leads to severe EAE. [source] DNA methylation controls Foxp3 gene expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Julia Abstract Compelling evidence suggests that Foxp3-expressing CD25+CD4+ regulatory T cells (Treg) are generated within the thymus as a separate lineage. However, Foxp3+CD4+ Treg can also be generated de novo in a TGF-,-dependent process from naive T cells by TCR triggering. Recently, we have shown that naturally occurring, but not in vitro TGF-,-induced Foxp3+ Treg display stable Foxp3 expression that was associated with selective demethylation of an evolutionarily conserved element within the Foxp3 locus named TSDR (Treg-specific demethylated region). Here, we report that inhibition of DNA methylation by azacytidine, even in absence of exogenous TGF-,, not only promoted de novo induction of Foxp3 expression during priming, but also conferred stability of Foxp3 expression upon restimulation. Most notably, such stable Foxp3 expression was found only for cells displaying enhanced TSDR demethylation. In contrast, in vitro TSDR methylation diminished its transcriptional activity. Foxp3+ Treg generated in vivo by DEC-205-mediated targeting of agonist ligands to dendritic cells showed long-term survival in the absence of the inducing antigen and exhibited efficient TSDR demethylation. Together, our data suggest that TSDR is an important methylation-sensitive element regulating Foxp3 expression and demonstrate that epigenetic imprinting in this region is critical for establishment of a stable Treg lineage. Supporting Information for this article is available at www.wiley-vch.de/contents/jc_2040/2008/38105_s.pdf [source] Fc, receptor I activation induces leukocyte recruitment and promotes aggravation of glomerulonephritis through the FcR, adaptorEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2007Yutaka Kanamaru Abstract Myeloid cells bear Fc receptors (FcR) that mediate inflammatory signaling through the ITAM-containing FcR, adaptor. They express FcR,-associated Fc,RI, which modulate either activating or inhibitory signaling depending on the type of ligand interaction. The role of Fc,RI, in disease progression remains unknown, notably in IgA nephropathy (IgAN), one of major causes of end-stage renal disease, in which large amounts of circulating IgA-immune complexes (IC) may mediate receptor activation. To analyze the involvement of Fc,RI activation in glomerulonephritis (GN), we generated Tg mice expressing a mutated, signaling-incompetent, human Fc,RIR209L that cannot associate with FcR,. Like Fc,RIwt -Tg mice, they developed mesangial IgA deposits but not macrophage infiltration. Fc,RI activation in Fc,RIwt, but not in Fc,RIR209L, Tg mice resulted in marked inflammation with severe proteinuria and leukocyte infiltration in spontaneous IgAN or anti-glomerular basement membrane Ab-induced GN models. Receptor triggering of syngenically transferred Fc,RIwt Tg macrophages into non-Tg animals induced their recruitment into injured kidneys during GN development. Fc,RIwt cross-linking on macrophages activated MAP kinases and production of TNF-, and MCP-1. Moreover, IgA-IC from IgAN patients activated Fc,RI and induced TNF-, production. Thus, Fc,RI activation mediates GN progression by initiating a cytokine/chemokine cascade that promotes leukocyte recruitment and kidney damage. [source] Increased natural cytotoxicity receptor expression and relevant IL-10 production in NK cells from chronically infected viremic HCV patientsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2007Andrea De Maria M. D. Abstract Hepatitis C virus (HCV) readily establishes high-level lifelong persistent infection in the majority of immunocompetent adults with failure of HCV-specific CD8+ CTL to clear viral replication. Virus-induced conditioning of innate immune responses is a possible mechanism that may contribute to the impairment of virus-specific CD8+ CTL responses. Here, we analyzed whether triggering of NK cell receptor expression and function is affected during chronic viremic HCV infection. Flow cytometric analysis of purified resting peripheral NK cells showed no evidence of NK cell activation, while analysis of natural cytotoxicity receptors (NCR) showed that NK cells from HCV-infected patients had selective increased expression of NKp30 and NKp46. NK cells had corresponding conserved cytotoxic activity against all targets with the exception of HepG2 hepatoma cells. Freshly separated NK cells from HCV patients showed significant production of IL-10 and normal concentrations of IFN-, upon cell-mediated triggering. Thus, increased expression of NKp30 during HCV infection with increased IL-10 production could contribute, once NK cells localize in the liver, to a NK-DC crosstalk leading to skewing of subsequent adaptive immune responses and lack of virus control. [source] Modulation of 2B4 (CD244) activity and regulated SAP expression in human NK cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007Johanna Endt Abstract The adapter protein SAP is important for the signal transduction of the family of SLAM-related receptors (SRR), which have important immune-modulating functions. The importance of SAP and SRR for a functional immune reaction becomes obvious in patients suffering from X-linked lymphoproliferative disease, which is characterized by non-functional SAP. Here we investigate the regulation of SAP expression in human NK cells. We demonstrate that SAP mRNA expression and protein levels are low in freshly isolated resting NK cells. IL-2 stimulation leads to an up-regulation of SAP expression, which can be enhanced by IL-12, the stimulation of TLR3 by polyinosinic-polycytidylic acid (poly(I:C))and to a lesser extent by IFN-,. EAT-2, a SAP-related adapter protein, is already detectable in resting NK cells and does not change its expression after IL-2 stimulation. The regulation of SAP has functional consequences for the stimulation of NK cell cytotoxicity by 2B4. In resting NK cells, 2B4 stimulation can only enhance NK cell lysis when co-triggered with other activating NK cell receptors. In IL-2-activated NK cells with high SAP expression the triggering of 2B4 alone is sufficient to induce NK cell cytotoxicity, demonstrating a correlation between the regulated SAP expression and the function of 2B4. [source] Notch ligands Delta-like1, Delta-like4 and Jagged1 differentially regulate activation of peripheral T helper cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2005Sascha Rutz Abstract The Notch pathway is involved in cell differentiation processes in various organs and at several developmental stages. The importance of Notch for early T lymphocyte development is well established. Recently, Notch has been implicated in directing naive T helper cell differentiation towards the Th1, Th2 or regulatory T cell lineages. However, the molecular events underlying these processes are poorly understood. We show that the Notch ligands Delta-like1, Delta-like4 and Jagged1 differentially affect early T cell activation and proliferation following T cell receptor cross-linking. Delta-like1 and Jagged1 induce a dose-dependent inhibition of early activation markers CD69 and CD25, as well as inhibition of proliferation after anti-CD3 stimulation of purified CD4+ T cells. Similarly, the rapid activation of transcription factors NF-AT, AP-1 and NF-,B is suppressed. In contrast, triggering of Notch by Delta-like4 enhances T cell activation and proliferation. The observed effects are dependent on simultaneous cross-linking of TCR and Notch but independent of ,-secretase-mediated cleavage of Notch. These data suggest direct interference between Notch and early TCR signal transduction events, independent of the classical Notch pathway via release of the Notch intracellular domain. A Notch-mediated alteration of TCR signaling strength may contribute to the recently described modulation of naļve T cell differentiation by Notch ligands. [source] Apoptosis via the B cell antigen receptor requires Bax translocation and involves mitochondrial depolarization, cytochrome C release, and caspase-9 activationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2004Eric Eldering Abstract Various routes to apoptosis can be active during B cell development. In a model system of mature B cells, differences in caspase-3 processing have suggested that antigen receptor (BCR)-mediated apoptosis may involve a zVAD-insensitive initiator protease(s). In search of the events leading to caspase-3 activation, we now establish that both CD95- and BCR-mediated apoptosis depend on Bax activation and cytochrome C (cytC) release. Nevertheless, the timing and caspase-dependence of mitochondrial membrane depolarization differed considerably after CD95- or BCR-triggering. To delineate events subsequent to cytC release, we compared apoptosis induced via BCR triggering and via direct mitochondrial depolarization by CCCP. In both cases, partial processing of caspase-3 was observed in the presence of zVAD. By expression in 293 cells we addressed the potential of candidate initiator caspases to function in the presence of zVAD, and found that caspase-9 efficiently processed caspase-3, while caspase-2 or ,8 were inactive. Finally, retroviral expression of dominant-negative caspase-9 inhibited both CD95- and BCR-mediated apoptosis. In conclusion, we obtained no evidence for involvement of a BCR-specific protease. Instead, our data show for the first time that the BCR-signal causes Bax translocation, followed by mitochondrial depolarization, and cytC release. Subsequent caspase-9 activation can solely account for events further downstream. [source] Governments and unpopular social policy reform: Biting the bullet or steering clear?EUROPEAN JOURNAL OF POLITICAL RESEARCH, Issue 1 2009BARBARA VIS This article shows that there exists substantial cross-cabinet variation in the degree to which governments take unpopular measures and argues that current studies cannot adequately explain this variation. Using insights from prospect theory, a psychological theory of choice under risk, this study hypothesises that governments only engage in unpopular reform if they face a deteriorating socio-economic situation, a falling political position, or both. If not, they shy away from the risk of reform. A fuzzy-set Qualitative Comparative Analysis (fs/QCA) of the social policy reform activities pursued by German, Dutch, Danish and British cabinets between 1979 and 2005 identifies a deteriorating socio-economic situation as necessary for unpopular reform. It is only sufficient for triggering reform, however, if the political position is also deteriorating and/or the cabinet is of rightist composition. This study's findings further the scholarly debate on the politics of welfare state reform by offering a micro-foundation that helps one to understand what induces political actors aspiring to be re-elected to engage in electorally risky unpopular reform. [source] High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphomaGENES, CHROMOSOMES AND CANCER, Issue 1 2003Anke van den Berg In a search for genes specifically expressed in Reed,Sternberg (RS) cells of Hodgkin lymphoma (HL), we applied the serial analysis of gene expression (SAGE) technique on the HL-derived cell line DEV. Genes highly expressed in DEV were subjected to an RT-PCR analysis to confirm the SAGE results. For one of the genes, a high expression was observed in DEV and other HL-derived cell lines but not in non-Hodgkin lymphoma (NHL),derived cell lines and normal controls, suggesting an HL-specific expression. This gene corresponds to the human BIC gene, a member of the noncoding mRNA-like molecules. RNA in situ hybridization (ISH) indicated an exclusive nucleolar localization of BIC transcripts in all RS cells in 91% of HL cases, including nodular lymphocyte predominance (NLP) HL and classical HL. Analyses of normal human tissues revealed BIC transcripts in only a small number of CD20-positive B-cells in lymph node and tonsil tissue, albeit at a much lower level compared to that of RS cells. BIC RT-PCR in the Burkitt lymphoma,derived cell line Ramos demonstrated a significant up-regulation upon cross-linking of the B-cell receptor (BcR). I,B,-mediated blocking of NF-,B translocation in Ramos did not effect the up-regulation of BIC expression upon BcR triggering, suggesting that activation of NF-,B is not involved in regulation of BIC expression. In summary, our data show that expression of BIC is specific for RS cells of HL. In normal tissue, BIC is expressed weakly in a minority of germinal center B cells. Expression of BIC can be modified/influenced by BcR triggering, indicating that BIC might play a role in the selection of B cells. © 2003 Wiley-Liss, Inc. [source] The role of static stress transfer in mining induced seismic events occurrence, a case study of the Rudna mine in the Legnica-Glogow Copper District in PolandGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 2 2010B. Orlecka-Sikora SUMMARY Seismicity accompanying mining exploitation results from changes in the stress field in the rock mass near the mining excavations caused by human activity. Many studies of the temporal and spatial distribution of mining induced seismicity have provided evidence for interrelations among events. Although a variety of techniques have been applied to quantify the interdependences of mining induced seismic events, the physical mechanism of interactions has not been unequivocally identified. Based on the premise that one possible cause of interactions among seismic events can be static stress transfer, we have verified statistically the role of Coulomb stress transfer in the generation process of mining induced seismicity using a series of seismic events that occurred in the Rudna mine in the Legnica-G,ogów Copper District in Poland. We quantify the triggering and inhibiting effect by the proportion of events in the series, whose locations are consistent with the stress increased and stress decreased zones, respectively. We have found that more than 60 per cent of the analysed seismic events occurred in areas where stress was enhanced due to the occurrence of previous events. The statistical significance of these results is tested by comparing them with the same proportions obtained for 2000 random permutations of the original series of events. The test has indicated that the locations in positive stress changes areas are preferred statistically significantly when the stress changes exceed 0.05 bar. This result turns out to be robust to the errors of the nodal planes determination. [source] Fault interactions and subduction tectonics: a re-examination of the Weber, New Zealand, earthquake sequence of 1990GEOPHYSICAL JOURNAL INTERNATIONAL, Issue 3 2003Russell Robinson SUMMARY Two moderate magnitude (Mw= 6.2 and 6.4) earthquakes in the Hikurangi subduction margin, North Island, New Zealand, occurred 3 months apart in 1990. The epicentres are nearly coincident, but the first (Weber 1, primarily normal faulting) occurred within the subducting Pacific Plate (depth about 28 km) and the second (Weber 2, a mix of thrusting and right-lateral motion) occurred within the overlying Australian Plate (depth about 13 km), the plate interface in between. The plate interface is interpreted to be locked trenchward (SE) from about the position of these events, with a transition to aseismic slip further down-dip to the NW. Several stress interaction questions are examined. First, to see whether Weber 1 triggered Weber 2, a range of possible mainshock parameters are used to calculate induced changes in the static Coulomb failure stress (,CFS). In most cases the results are consistent with triggering. Secondly, previous work showed that the rate of aftershock occurrence for Weber 1 decreased markedly about 35 days before Weber 2, recovering afterwards. To see whether aseismic pre-slip on the Weber 2 fault, as predicted by rate and state friction, could be the cause of the decrease, the same fault parameters have been used in reverse. The results are ambiguous, some fault parameters giving results consistent with the hypothesis and others not. The amount of pre-slip required for significant inhibition, however, is about equal to that in the mainshock and distributed over the entire fault plane. Thirdly, observations of episodic, aseismic slip down-dip from locked sections of other plate interfaces are becoming more common. Could such slip have triggered both Weber events? The induced changes in CFS for such slip are uniformly positive on the Weber 1 fault plane, and mostly positive on the Weber 2 fault plane, so the answer is yes. Although there is no independent evidence for aseismic slip prior to the Weber sequence, this case shows that such slip may trigger events on other nearby faults, besides loading the locked section of the plate interface. Static stress triggering considerations are thus likely to be important in subduction environments. [source] Fluid-induced seismicity: Pressure diffusion and hydraulic fracturingGEOPHYSICAL PROSPECTING, Issue 2 2009S.A. Shapiro ABSTRACT Borehole fluid injections are common for the development of hydrocarbon and geothermic reservoirs. Often they induce numerous microearthquakes. Spatio-temporal dynamics of such induced microseismic clouds can be used to characterize reservoirs. However, a fluid-induced seismicity can be caused by a wide range of processes. Here we show that linear pore pressure relaxation and a hydraulic fracturing are two asymptotic end members of a set of non-linear diffusional phenomena responsible for seismicity triggering. To account for the whole range of processes we propose a rather general non-linear diffusional equation describing the pore pressure evolution. This equation takes into account a possibly strong enhancement of the medium permeability. Both linear pore pressure relaxation and hydraulic fracturing can be obtained as special limiting cases of this equation. From this equation we derive the triggering front of fluid induced seismicity, which is valid in the general case of non-linear pore pressure diffusion. We demonstrate corresponding seismicity signatures on different case studies. [source] Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangementHEPATOLOGY, Issue 1 2003Agustķn Albillos Intestinal bacterial overgrowth and translocation, both common in cirrhosis with ascites, may lead to the activation of monocytes and lymphocytes, increased levels of proinflammatory cytokines, and enhanced synthesis of nitric oxide present in cirrhosis. Bacterial endotoxin promotes the synthesis of lipopolysaccharide (LPS)-binding protein (LBP), and forms a LPS-LBP complex that binds to CD14. This study was designed to evaluate LBP levels and their correlation to the immune response and the hemodynamic status in cirrhotic patients. Plasma LBP, endotoxin, soluble CD14 (sCD14), cytokines, renin, nitrites, and systemic vascular resistance were determined before and 4 weeks after norfloxacin or placebo in 102 cirrhotic patients and 30 controls. LBP was elevated in 42% of ascitic cirrhotic patients (15.7 ± 0.7 versus 6.06 ± 0.5 ,g/mL, P < .01). In 60% of high LBP patients, endotoxin was within normal range. Among ascitic patients, those with high LBP showed greater (P < .05) levels of sCD14, tumor necrosis factor , (TNF-,), interleukin 6 (IL-6), nitrites + nitrates (NOx)/creatinine, and renin, and lower vascular resistance. In the cirrhotic patients with high LBP, norfloxacin normalized (P < .01) LBP (from 16.6 ± 0.5 to 5.82 ± 0.8 , g/mL) and sCD14; reduced the level of cytokines, NOx/creatinine, and renin; and increased vascular resistance; but lacked effect in patients with normal LBP. Portal pressure was unchanged after norfloxacin in another group of 18 cirrhotic patients with high and 19 with normal LBP. In conclusion, the subset of ascitic cirrhotic patients with marked immune and hemodynamic derangement is identified by increased LBP levels. Amelioration of these abnormalities by norfloxacin suggests the involvement of enteric bacteria or their products in the triggering of the process. [source] Regulated transcription of the immediate-early gene Zif268: Mechanisms and gene dosage-dependent function in synaptic plasticity and memory formationHIPPOCAMPUS, Issue 5 2002Bruno Bozon Abstract The immediate-early gene Zif268 is a member of the Egr family of inducible transcription factors. Data from gene expression studies have suggested that this gene may play a critical role in initial triggering of the genetic machinery that has long been considered a necessary mechanism for maintenance of the later phases of LTP and also for the consolidation or stabilization of long-lasting memories. Until recently, however, the data supporting this assumption have been based primarily on circumstantial evidence, with no direct evidence to suggest that Zif268 is required for long-lasting synaptic plasticity and memory. In this report, we review our own data using Zif268 mutant mice; we show that although the early phase of dentate gyrus LTP is normal in these mice, the later phases are not present, and the ability of the mice to maintain learned information over a 24-h period is deficient. In addition, we present new information showing a task-dependent gene dosage effect in Zif268 heterozygous mice. We show that spatial learning is particularly sensitive to reduced levels of Zif268, as one-half of the complement of Zif268 in heterozygous mice is insufficient to maintain spatial long-term memories. Hippocampus 2002;12:570,577. © 2002 Wiley-Liss, Inc. [source] Liver failure following partial hepatectomyHPB, Issue 3 2006Thomas S. Helling Abstract While major liver resections have become increasingly safe due to better understanding of anatomy and refinement of operative techniques, liver failure following partial hepatectomy still occurs from time to time and remains incompletely understood. Observationally, certain high-risk circumstances exist, namely, massive resection with small liver remnants, preexisting liver disease, and advancing age, where liver failure is more likely to happen. Upon review of available clinical and experimental studies, an interplay of factors such as impaired regeneration, oxidative stress, preferential triggering of apoptotic pathways, decreased oxygen availability, heightened energy-dependent metabolic demands, and energy-consuming inflammatory stimuli work to produce failing hepatocellular functions. [source] The triggering of debris flow due to channel-bed failure in some alpine headwater basins of the Dolomites: analyses of critical runoffHYDROLOGICAL PROCESSES, Issue 13 2008C. Gregoretti Abstract The debris deposits at the bottom of very steep natural channels and streams in high mountain areas can be mobilized by runoff, triggering a water,sediment mixture flow known as debris flow. The routing of debris flow through human settlements can cause damage to civil structures and loss of human lives. The prediction of such an event, or the runoff discharge that triggers it, assumes an interest in risk analyses and the planning of defence measures. The object of this study is to find a method to determine the critical runoff value that triggers debris flow as a result of channel-bed failure. Historical and rainfall data on 30 debris flows that occurred in six watersheds of the Dolomites (north-eastern Italian Alps) were collected from different sources. Field investigations at the six sites, together with the hydrologic response to the rainfalls that triggered the events, were performed to obtain a realistic scenario of the formation of the debris flow there occurred. Field observations include a survey along the channel of the triggering reach of debris flow, with measurements of the channel slope and cross-section and sampling of debris deposits for grain size distribution. Simulated runoff discharge values based on the rainfall recorded by pluviometers were then compared with values obtained through experimental criteria on the initiation and formation of debris flow by bed failure. The results are discussed to provide a plausible physical-based method for the prediction of the triggering of debris flow by channel-bed failure. Copyright © 2007 John Wiley & Sons, Ltd. [source] Rainfall-induced landslides and debris flowsHYDROLOGICAL PROCESSES, Issue 4 2008Giovanni B. Crosta Abstract In this preface we introduce the special issue on rainfall-induced landslides and debris flows. The topic is of high interest for many practical and scientific reasons. In fact, rainfall is the most relevant factor for the triggering of both shallow and deep-seated landslides, and rainfall analysis is the most frequently adopted approach for forecasting the occurrence of such phenomena. The six papers of the special issue cover most of the key issues relative to rainfall-induced landslides. Starting from the analysis of these contributions, we identify and discuss, in this paper, several main topics that deserve further research in the field of rainfall-induced landslide, such as the uncertainty of the data, the quality of geotechnical analysis, the validation of the models, and the applicability of results in the framework of natural hazards. Copyright © 2007 John Wiley & Sons, Ltd. [source] Human natural killer cell receptors and co-receptorsIMMUNOLOGICAL REVIEWS, Issue 1 2001Roberto Biassoni Summary: In the absence of sufficient signaling by their HLA class I-specific inhibitory receptors, human natural killer (NK) cells become activated and display potent cytotoxicity against cells that are either HLA class I negative or deficient. This indicates that the NK receptors responsible for the induction of cytotoxicity recognize ligands on target cells different from HLA class I molecules. On this basis, the process of NK-cell triggering can be considered as a mainly non-MHC-restricted mechanism. The recent identification of a group of NK-specific triggering surface molecules has allowed a first series of pioneering studies on the functional/molecular characteristics of such receptors. The first three members of a receptor family that has been termed natural cytotoxicity receptors (NCR) are represented by NKp46, NKp44 and NKp30. These receptors are strictly confined to NK cells, and their engagement induces a strong activation of NK-mediated cytolysis. A direct correlation exists between the surface density of NCR and the ability of NK cells to kill various target cells. Importantly, mAb-mediated blocking of these receptors has been shown to suppress cytotoxicity against most NK-susceptible target cells. However, the process of NK-cell triggering during target cell lysis may also depend on the concerted action of NCR and other triggering receptors, such as NKG2D, or surface molecules, including 2B4 and NKp80, that appear to function as co-receptors rather than as true receptors. Notably, a dysfunction of 2B4 has been associated with a severe form of immunodeficiency termed X-linked lymphoproliferative disease. Future studies will clarify whether also the altered expression and/or function of other NK-triggering molecules may represent a possible cause of immunological disorders. This work was supported by grants awarded by Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.), Istituto Superiore di Sanitą (I.S.S.), Ministero della Sanitą, and Ministero dell'Universitą e della Ricerca Scientifica e Tecnologica (M.U.R.S.T.) and Consiglio Nazionale delle Ricerche, Progetto Finalizzato Biotecnologie. The financial support of Telethon-Italy (grant no. E.0892) is gratefully acknowledged. [source] | ||||||||||||||||||||||||||||||||||||||||||||||||||||