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Complement
Kinds of Complement Terms modified by Complement Selected AbstractsComplement C5a regulates IL-17 by affecting the crosstalk between DC and ,, T cells in CLP-induced sepsisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2010Ruonan Xu Abstract Complement 5a (C5a) and Interleukin-17 (IL-17) are two important inflammatory mediators in sepsis. Here we studied the mechanisms underlying regulation of IL-17 by anaphylatoxin C5a. We found that C5a blockade increased the survival rate of mice following cecal ligation and puncture (CLP)-induced sepsis and decreased IL-17 expression in vivo. IL-17 was secreted mainly by ,, T cells in this model. Importantly, our data suggest that C5a participates in the regulation of IL-17 secretion by ,, T cells. Dendritic cells (DC) were found to act as a "bridge" between C5a and ,, T cells in a mechanism involving IL-6 and transforming growth factor , (TGF-,). These results imply that C5a affects the crosstalk between DC and ,, T cells during sepsis development, and this may result in a large production of inflammatory mediators such as IL-17. [source] Cross-linking tumor cells with effector cells via CD55 with a bispecific mAb induces ,-glucan-dependent CR3-dependent cellular cytotoxicityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2006Abstract Complement (C) regulatory proteins decrease the effectiveness of immunotherapeutic anti-cancer antibodies. Bispecific mAb (bi-mAb) that target a tumor antigen and simultaneously inhibit a C regulator increase the effectiveness of such a therapy. Here we investigated the mechanism by which bi-mAb increase tumor cell lysis. Apart from C-dependent cytotoxicity, C activation can lead to complement receptor 3 (CR3)-dependent cellular cytotoxicity (CR3-DCC) by CR3-positive effector cells in the presence of ,-glucan. Here we show that an anti-Ep-CAM*anti-CD55 bi-mAb induced more than threefold higher CR3-DCC (71%) of human colorectal cancer cells compared with anti-Ep-CAM alone (20%). This CR3-DCC was dependent on the binding of the anti-CD55 arm of tumor-bound anti-Ep-CAM*anti-CD55 bi-mAb to effector cell CD55, CR3 priming by ,-glucan and the presence of iC3b on the target cell. Comparable lysis could be obtained in the absence of iC3b, when CR3 and CD55 were cross-linked on the effector cells, suggesting cooperation between CD55 and CR3 in signal transduction. Tumor cells with low antigen expression were effectively lysed via this mechanism in contrast to direct C-dependent cytotoxicity. These data imply that the effectiveness of mAb immunotherapy can be improved using anti-tumor antigen*anti-CD55 bi-mAb and ,-glucan, thereby initiating CR3-DCC as an additional effector mechanism that is efficient for eradication of tumor cells with lower antigen expression. [source] C-type lectin-independent interaction of complement opsonized HIV with monocyte-derived dendritic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2005Monika Pruenster Abstract HIV directly activates the complement cascade and is, therefore, opsonized with C3-cleavage products in vivo. This cloud of C3 fragments on the viral surface may impair the interaction of the HIV envelope glycoproteins gp120/gp41 with C-type lectins expressed on immature dendritic cells (iDC). Therefore, we determined the accessibility of gp120 after opsonization and compared the interaction of DC with non-opsonized or complement-opsonized HIV. The recognition of native gp120 was drastically impaired when the virus was covered by complement. Independent of opsonization, similar amounts of HIV bound to DC. The interaction of iDC and the infection of DC-PBL co-cultures with non-opsonized virus was significantly reduced by mannan and antibodies which inhibit the ICAM-1-CR3 interaction. The binding of opsonized virus to iDC was reduced by an anti-CR3-antibody, which interferes with the binding of C3 fragments, but was not affected by mannan. Complement enhanced the HIV infection of DC and DC-PBL co-cultures significantly. Mannan did not inhibit the complement-dependent enhancement of infection. Thus, non-opsonized and opsonized HIV interacted with iDC, although the binding mechanisms seemed to differ. As HIV is opsonized in vivo, the C-type lectin-independent interaction of opsonized viruses with iDC has to be taken into account. [source] Complement and its implications in cardiac ischemia/reperfusion: strategies to inhibit complementFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2001Tiphaine Monsinjon Although reperfusion of the ischemic myocardium is an absolute necessity to salvage tissue from eventual death, it is also associated with pathologic changes that represent either an acceleration of processes initiated during ischemia or new pathophysiological changes that were initiated after reperfusion. This so-called ,reperfusion injury' is accompanied by a marked inflammatory reaction, which contributes to tissue injury. In addition to the well known role of oxygen free radicals and white blood cells, activation of the complement system probably represents one of the major contributors of the inflammatory reaction upon reperfusion. The complement may be activated through three different pathways: the classical, the alternative, and the lectin pathway. During reperfusion, complement may be activated by exposure to intracellular components such as mitochondrial membranes or intermediate filaments. Two elements of the activated complement contribute directly or indirectly to damages: anaphylatoxins (C3a and C5a) and the membrane attack complex (MAC). C5a, the most potent chemotactic anaphylatoxin, may attract neutrophils to the site of inflammation, leading to superoxide production, while MAC is deposited over endothelial cells and smooth vessel cells, leading to cell injury. Experimental evidence suggests that tissue salvage may be achieved by inhibition of the complement pathway. As the complement is composed of a cascade of proteins, it provides numerous sites for pharmacological interventions during acute myocardial infarction. Although various strategies aimed at modulating the complement system have been tested, the ideal approach probably consists of maintaining the activity of C3 (a central protein of the complement cascade) and inhibiting the later events implicated in ischemia/reperfusion and also in targeting inhibition in a tissue-specific manner. [source] Astrocyte-specific expression of a soluble form of the murine complement control protein Crry confers demyelination protection in the cuprizone modelGLIA, Issue 14 2007Dustin T. Briggs Abstract Complement has been implicated as a potential effector mechanism in neurodegeneration; yet the precise role of complement in this process remains elusive. In this report, we have utilized the cuprizone model of demyelination-remyelination to examine the contribution of complement to disease. C1q deposition was observed in the corpus callosum of C57BL/6 mice during demyelination, suggesting complement activation by apoptotic oligodendrocyte debris. Simultaneously, these mice lost expression of the rodent complement regulatory protein, Crry. A soluble CNS-specific form of the Crry protein (sCrry) expressed in a transgenic mouse under the control of an astrocyte-specific promoter was induced in the corpus callosum during cuprizone treatment. Expression of this protein completely protected the mice from demyelination. Interestingly, sCrry mice had low levels of demyelination at later times when control mice were remyelinating. Although the sCrry transgenic mice had lower levels of demyelination, there was no decrease in overall cellularity, however there were decreased numbers of microglia in the sCrry mice relative to controls. Strikingly, sCrry mice had early recovery of mature oligodendrocytes, although they later disappeared. TUNEL staining suggested that production of the sCrry protein in the transgenic mice protected from a late apoptosis event at 3 weeks of cuprizone treatment. Our data suggest complement provides some protection of mature oligodendrocytes during cuprizone treatment but may be critical for subsequent remyelination events. These data suggest that temporal restriction of complement inhibition may be required in some disease settings. © 2007 Wiley-Liss, Inc. [source] Complement: a critical test of its biological importanceIMMUNOLOGICAL REVIEWS, Issue 1 2000Bela Z. Schmidt First page of article [source] Vertical Social Differentiation in Athens: Alternative or Complement to Community Segregation?INTERNATIONAL JOURNAL OF URBAN AND REGIONAL RESEARCH, Issue 4 2001Thomas Maloutas Vertical social differentiation is presented in the recent literature as an important element of reduced segregation in South European cities, and the supporting evidence originates mainly from Athens. The authors of this article question the claim about the common form and function of vertical social differentiation across South Europe, as well as its opposition to community segregation, and try to reveal the specificity of the processes leading to its formation in Athens. Since the mid-1970s, the dominant process of urban growth in Athens has been middle-class suburbanization. This process has reinforced community segregation and, at the same time, has triggered a filtering-down process in wide areas around the CBD, formerly occupied by upper and mainly intermediate professional categories. Interclass vertical segregation has subsequently appeared in these areas, where intermediate professional categories and lower middle-class households are now predominant. The fact that these areas do not represent a real choice for any of their resident groups shows that this vertical cohabitation has been the unintended consequence of changing segregation patterns, and hardly the outcome or the corollary of a growing process of sociospatial homogenization. Dans les textes récents, la différenciation sociale verticale est présentée comme un facteur important dans la réduction de la ségrégation urbaine en Europe du Sud, les éléments probants provenant essentiellement d'Athènes. Cet article conteste l'idée que la différenciation sociale verticale ait une forme ou une fonction commune en Europe méridionale, et qu'elle entrave la ségrégation horizontale; de plus, il tente d'exposer la spécificité des processus qui conduisent à sa formation à Athènes. Depuis le milieu des années 1970, l'expansion urbaine de la capitale grecque se caractérise par l'implantation en banlieue des classes supérieurs et moyennes. Ce processus a renforcé la ségrégation dans les quartiers et, parallèlement, a déclenché un processus de filtrage vers le bas dans de vastes zones entourant l'hypercentre, précédemment occupées par des catégories de professionnels libéraux supérieures et surtout moyennes. Une ségrégation verticale interclasse est ensuite apparue dans ces quartiers, des catégories de libéraux moyennes et des ménages de la petite bourgeoisie y prédominant désormais. Or, quel que soit le groupe de résidents, ces zones ne représentent pas un choix réel; cette cohabitation verticale est donc bien la conséquence imprévue de la modification des schémas de ségrégation, plutôt que le résultat ou le corollaire d'une homogénéisation socio-spatiale accentuée. [source] Complement of peritumoral and subareolar injection in breast cancer sentinel lymph node biopsyJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2009Masakuni Noguchi MD Abstract Background The optimal site for injection of mapping tracers is controversial in sentinel lymph node (SLN) biopsy for breast cancer. We evaluated whether a combination of peritumoral (PT) injection and subareolar (SA) injection can improve the identification rate of SLN biopsy and decrease the false-negative rate. Methods Two hundred one patients underwent SLN biopsy with PT injection of radioisotope and SA injection of blue dye. Results The overall identification rate for blue and/or hot lymph nodes was 99.5%; the identification rate of blue-dyed lymph nodes was 98.0% and that of hot lymph nodes was 97.0%. However, no concordance between the hot node and the blue node was found in 17 patients (8.5%). Among SLN-positive 51 patients, 4 patients had blue-only positive SLN and 7 had hot-only positive SLN. Consequently, the false-negative rates were at least 7.8% for PT injection and 13.7% for SA injection, while axillary lymph node dissection was not performed in SLN-negative patients. However, a combination of both injections significantly decreased the false-negative rate. Conclusions The success of SLN mapping is optimized not only by using dye and isotope in combination but also by using PT and SA injections in combination. J. Surg. Oncol. 2009;100:100,105. © 2009 Wiley-Liss, Inc. [source] Complement 3 deficiency impairs early pregnancy in miceMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 7 2009Wang-Ngai Chow Human oviductal cells produce complement-3 (C3) and its derivative, iC3b. These molecules are important in immune responses. Our recent study suggested that iC3b also possessed embryotrophic activity and it stimulates the blastulation and hatching rates of in vitro cultured mouse embryos. The objective is to study the impact of C3 deficiency on early pregnancy in vivo using homozygous C3-deficient (C3KO) and wild-type (C3WT) mice. C3 protein was undetectable in the reproductive tissues of C3KO mice. Deficiency in C3 is associated with significantly longer estrous cycle (P,=,0.037). No significant difference was found in the ovulation rate, total cell count in blastocysts and implantation rate between the wild-type and the C3KO mice, though C3KO mice tended to have lower values in the latter two parameters. On day 15 of pregnancy, C3KO mice had fewer conceptus (P,<,0.001) and higher resorption rate (P,<,0.001) than that of C3WT mice. The fetal and placental weights (P,<,0.001) were lower in the C3KO mice. The placenta of C3KO mice had smaller spongiotrophoblast (P,=,0.001) and labyrinth (P,=,0.037). Deficiency in C3 is associated with mild impairment in early pregnancy including longer estrous cycle and higher resorption rates after implantation. The impairment may be related to compromised placental development leading to under-developed fetuses. Mol. Reprod. Dev. 76: 647,655, 2009. © 2009 Wiley-Liss, Inc. [source] Complement and fungal pathogens: an updateMYCOSES, Issue 6 2008Cornelia Speth Summary Fungal infections are a serious complication in immunocompromised patients such as human immunodeficiency virus-infected individuals, patients with organ transplantations or with haematological neoplasia. The lethality of opportunistic fungal infection is high despite a growing arsenal of antimycotic drugs, implying the urgent need for supportive immunological therapies to strengthen the current inefficient antimicrobial defences of the immunocompromised host. Therefore, increasing effort has been directed to investigating the interplay between fungi and the host immunity and thus to find starting points for additional therapeutic approaches. In this article, we review the actual state of the art concerning the role of complement in the pathogenesis of fungal infections. Important aspects include the activation of the complement system by the fungal pathogen, the efficiency of the complement-associated antimicrobial functions and the arsenal of immune evasion strategies applied by the fungi. The twin functions of complement as an interactive player of the innate immunity and at the same time as a modulator of the adaptive immunity make this defence weapon a particularly interesting therapeutic candidate to mobilise a more effective immune response and to strengthen in one fell swoop a broad spectrum of different immune reactions. However, we also mention the ,Yin-Yang' nature of the complement system in fungal infections, as growing evidence assigns to complement a contributory part in the pathogenesis of fungus-induced allergic manifestations. [source] Complement in renal diseaseNEPHROLOGY, Issue 6 2001John A Charlesworth [source] ORIGINAL ARTICLE: Activation of the Alternative Pathway of Complement is a Feature of Pre-Term Parturition but not of Spontaneous Labor at TermAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Edi Vaisbuch Citation Vaisbuch E, Romero R, Erez O, Mazaki-Tovi S, Kusanovic JP, Soto E, Dong Z, Chaiworapongsa T, Kim SK, Ogge G, Pacora P, Yeo L, Hassan SS. Activation of the alternative pathway of complement is a feature of pre-term parturition but not of spontaneous labor at term. Am J Reprod Immunol 2010; 63: 318,330 Problem, Plasma concentrations of fragment Bb (FBb) are a marker for activation of the alternative pathway of the complement system. High concentrations of FBb in maternal blood, as early as the first trimester, are associated with subsequent spontaneous pre-term delivery <34 weeks of gestation. The aim of this study was to determine whether spontaneous pre-term labor (PTL) with intact membranes, intra-amniotic infection/inflammation (IAI) or labor at term are associated with alterations in circulating maternal FBb concentrations. Method of study, This cross-sectional study included women in the following groups: (i) non-pregnant (n = 40); (ii) normal pregnancy (gestational age range 20,36, 6/7 weeks, n = 63); (iii) women at term not in labor (n = 70); (iv) women at term in spontaneous labor (n = 59); (v) patients with an episode of PTL who delivered at term (n = 62); (vi) PTL without IAI who delivered pre-term (n = 30); and (vii) PTL with IAI who delivered pre-term (n = 67). Maternal plasma FBb concentrations were determined by ELISA. Results, (i) Among patients with PTL, those who had a pre-term delivery either with IAI (1.21 ,g/mL, IQR 0.77,2.16) or without IAI (1.13 ,g/mL, IQR 0.92,2.08) had a higher median maternal plasma FBb concentration than those who delivered at term (0.86 ,g/mL, IQR 0.64,1.57; P = 0.007 and P = 0.026, respectively); (ii) there was no difference in the median plasma FBb concentration between patients with and without IAI who delivered pre-term (P = 0.9); (iii) in contrast, spontaneous labor at term was not associated with a significant change in the maternal plasma FBb concentration (P = 0.8); (iv) maternal plasma concentration of FBb did not differ significantly between normal pregnant women and the non-pregnant controls (P = 0.8) and were not correlated with advancing gestational age (r = ,0.28, P = 0.8). Conclusion, (i) Pre-term parturition is associated with activation of the alternative complement pathway in maternal circulation; (ii) such activation is not detectable in spontaneous labor at term; (iii) IAI does not explain the activation of the alternative pathway of complement in PTL. Collectively, these observations suggest that pre-term and term labors have fundamental differences in the regulation of innate immunity. [source] Correlation of Donor-Specific Antibodies, Complement and Its Regulators with Graft Dysfunction in Cardiac Antibody-Mediated RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009C. D. Tan Antibody-mediated rejection (AMR) is an immunopathologic process in which activation of complement often results in allograft injury. This study correlates C4d and C3d with HLA serology and graft function as diagnostic criteria for AMR. Immunofluorescence staining for C4d and C3d was performed on 1511 biopsies from 330 patients as part of routine diagnostic work-up of rejection. Donor-specific antibodies were detected in 95% of those with C4d+C3d+ biopsies versus 35% in the C4d+C3d, group (p = 0.002). Allograft dysfunction was present in 84% in the C4d+ C3d+ group versus 5% in the C4d+C3d, group (p < 0.0001). Combined C4d and C3d positivity had a sensitivity of 100% and specificity of 99% for the pathologic diagnosis of AMR and a mortality of 37%. Since activation of complement does not always result in allograft dysfunction, we correlated the expression pattern of the complement regulators CD55 and CD59 in patients with and without complement deposition. The proportion of patients with CD55 and/or CD59 staining was highest in C4d+C3d, patients without allograft dysfunction (p = 0.03). We conclude that a panel of C4d and C3d is diagnostically more useful than C4d alone in the evaluation of AMR. CD55 and CD59 may play a protective role in patients with evidence of complement activation. [source] Novel complement inhibitor limits severity of experimentally myasthenia gravis,ANNALS OF NEUROLOGY, Issue 1 2009Jindrich Soltys DVM Objective Complement mediated injury of the neuromuscular junction is considered a primary disease mechanism in human myasthenia gravis and animal models of experimentally acquired myasthenia gravis (EAMG). We utilized active and passive models of EAMG to investigate the efficacy of a novel C5 complement inhibitor rEV576, recombinantly produced protein derived from tick saliva, in moderating disease severity. Methods Standardized disease severity assessment, serum complement hemolytic activity, serum cytotoxicity, acetylcholine receptor (AChR) antibody concentration, IgG subclassification, and C9 deposition at the neuromuscular junction were used to assess the effect of complement inhibition on EAMG induced by administration of AChR antibody or immunization with purified AChR. Results Administration of rEV576 in passive transfer EAMG limited disease severity as evidenced by 100% survival rate and a low disease severity score. In active EAMG, rats with severe and mild EAMG were protected from worsening of disease and had limited weight loss. Serum complement activity (CH50) in severe and mild EAMG was reduced to undetectable levels during treatment, and C9 deposition at the neuromuscular junction was reduced. Treatment with rEV576 resulted in reduction of toxicity of serum from severe and mild EAMG rats. Levels of total AChR IgG, and IgG2a antibodies were similar, but unexpectedly, the concentration of complement fixing IgG1 antibodies was lower in a group of rEV576-treated animals, suggesting an effect of rEV576 on cellular immunity. Interpretation Inhibition of complement significantly reduced weakness in two models of EAMG. C5 inhibition could prove to be of significant therapeutic value in human myasthenia gravis. Ann Neurol 2009;65:67,75 [source] Homogeneity of active demyelinating lesions in established multiple sclerosisANNALS OF NEUROLOGY, Issue 1 2008Esther C. W. Breij PhD Objective Four different patterns of demyelination have been described in active demyelinating lesions of multiple sclerosis (MS) patients that were biopsied shortly after disease onset. These patterns were suggested to represent heterogeneity of the underlying pathogenesis. The aim of this study was to determine whether lesion heterogeneity also exists in an unselected collection of autopsy material from patients with established MS. Methods All MS brain tissue available in the VU Medical Center was assessed for the presence of active demyelinating lesions using magnetic resonance imaging,guided sampling and immunohistochemistry. Tissue blocks containing active demyelinating lesions were evaluated for the presence of complement and antibody deposition, oligodendrocyte apoptosis, differential loss of myelin proteins, and hypoxia-like damage using histology, immunohistochemistry, and confocal microscopy. Blocks with active demyelinating lesions were compared with blocks with active (nondemyelinating) and inactive lesions. Results Complement and antibodies were consistently associated with macrophages in areas of active demyelination. Preferential loss of myelin proteins, extensive hypoxia-like damage, and oligodendrocyte apoptosis were absent or rare. This pattern was observed in all tissue blocks containing active demyelinating lesions; lesion heterogeneity between patients was not found. Interpretation The immunopathological appearance of active demyelinating lesions in established MS is uniform. Initial heterogeneity of demyelinating lesions in the earliest phase of MS lesion formation may disappear over time as different pathways converge in one general mechanism of demyelination. Consistent presence of complement, antibodies, and Fc, receptors in phagocytic macrophages suggests that antibody- and complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in established MS. Ann Neurol 2008;63:16,25 [source] Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 7 2009Michael G. Barnes Objective To identify differences in peripheral blood gene expression between patients with different subclasses of juvenile idiopathic arthritis (JIA) and healthy controls in a multicenter study of patients with recent-onset JIA prior to treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. Methods Peripheral blood mononuclear cells (PBMCs) from 59 healthy children and 136 patients with JIA (28 with enthesitis-related arthritis [ERA], 42 with persistent oligoarthritis, 45 with rheumatoid factor [RF],negative polyarthritis, and 21 with systemic disease) were isolated from whole blood. Poly(A) RNA was labeled using a commercial RNA amplification and labeling system (NuGEN Ovation), and gene expression profiles were obtained using commercial expression microarrays (Affymetrix HG-U133 Plus 2.0). Results A total of 9,501 differentially expressed probe sets were identified among the JIA subtypes and controls (by analysis of variance; false discovery rate 5%). Specifically, 193, 1,036, 873, and 7,595 probe sets were different in PBMCs from the controls compared with those from the ERA, persistent oligoarthritis, RF-negative polyarthritis, and systemic JIA patients, respectively. In patients with persistent oligoarthritis, RF-negative polyarthritis, and systemic JIA subtypes, up-regulation of genes associated with interleukin-10 (IL-10) signaling was prominent. A hemoglobin cluster was identified that was underexpressed in ERA patients but overexpressed in systemic JIA patients. The influence of JAK/STAT, ERK/MAPK, IL-2, and B cell receptor signaling pathways was evident in patients with persistent oligoarthritis. In systemic JIA, up-regulation of innate immune pathways, including IL-6, Toll-like receptor/IL-1 receptor, and peroxisome proliferator,activated receptor signaling, were noted, along with down-regulation of gene networks related to natural killer cells and T cells. Complement and coagulation pathways were up-regulated in systemic JIA, with a subset of these genes being differentially expressed in other subtypes as well. Conclusion Expression analysis identified differentially expressed genes in PBMCs obtained early in the disease from patients with different subtypes of JIA and in healthy controls, providing evidence of immunobiologic differences between these forms of childhood arthritis. [source] Complement driven innate immune response to malaria: fuelling severe malarial diseasesCELLULAR MICROBIOLOGY, Issue 8 2010Karlee L. Silver Summary Severe malaria remains a major cause of global mortality. The innate immune response to infection is a key determinant of malaria severity and outcome. The complement system plays a key role in initiating and augmenting innate immune responses, including inflammation, endothelial activation, opsonization and coagulation, processes which have been implicated in malaria pathogenesis. In this review, we discuss the evidence supporting a role for excessive complement activation in the pathogenesis of severe malaria. [source] Insights into Sequence,Activity Relationships amongst Baeyer,Villiger Monooxygenases as Revealed by the Intragenomic Complement of Enzymes from Rhodococcus jostii RHA1CHEMBIOCHEM, Issue 7 2009Claudia Szolkowy Abstract TheRhodococcus jostiiRHA1 genome encodes a number of enzymes that can be exploited as biocatalysts. Study of the substrate spectrum and enantioselectivity of Baeyer,Villiger monooxygenases from R. jostii allowed the identification of short amino acid sequences specific to groups displaying certain catalytic characteristics. The gel illustrates the substrate acceptance spectra and selectivities of the different proteins. Microbial genome sequences are providing a wealth of information on new enzymes that have considerable potential as biocatalysts. The recently sequenced genome of Rhodococcus jostii RHA1, for example, has revealed an impressive array of catabolic enzymes, including many putative Baeyer,Villiger monooxygenases (BVMOs). We have cloned 23 target BVMO sequences from the genome of R. jostii RHA1 and heterologously expressed 13 of these as soluble proteins to unearth new substrate specificities and selectivities. Whole-cell biocatalysts expressing the genes were screened against seven different test substrates. Each of these catalysts displayed activity toward at least three ketones. We observed a remarkable diversity of both regio- and enantioselectivity among the BVMOs from R. jostii RHA1 for the transformation of two chiral substrates, with some enzymes displaying high enantioselectivity for the isomers of 2-methylcyclopentanone. With the notable exception of the product of gene ro03437, named MO14, the biocatalysts' sequences correlated well with their respective activities and selectivities. This correlation allowed the identification of sequence motifs specific to subgroups of the BVMOs from R. jostii and other organisms. Overall, the data improve predictive models of BVMO activity from sequence and suggest new avenues to pursue in engineering these enzymes. [source] Cobalt-Catalyzed Trimethylsilylmethylmagnesium-Promoted Radical Alkenylation of Alkyl Halides: A Complement to the Heck Reaction.CHEMINFORM, Issue 43 2006Walter Affo Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Cobalt-Catalyzed Trimethylsilylmethylmagnesium-Promoted Radical Alkenylation of Alkyl Halides: A Complement to the Heck Reaction.CHEMINFORM, Issue 43 2006Walter Affo Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] The AMD-associated complement factor H (CFH) polymorphism Y402H results in decreased CFH localisation to Bruch's membraneACTA OPHTHALMOLOGICA, Issue 2009PN BISHOP Purpose CFH down-regulates the alternative pathway of the complement system by binding to polyanionic structures on host cells/tissues and inactivating surface associated C3b. Recently, the Y402H polymorphism in CFH has been shown to be a major risk factor for AMD. Here we investigated the functional consequences of the Y402H polymorphism by testing the hypothesis that the resultant amino acid substitution alters CFH binding to macular tissue Methods The 402H and 402Y forms of full-length CFH and recombinant CFH fragments (composed of CCP6-8) were labelled with different fluorophores (402Y with AlexFluor-488 and 402H with AlexaFluor-594). These were simultaneously incubated with frozen sections of human macular tissue from donor eyes and the relative binding of the two forms was investigated. In some experiments the tissue sections were digested with glycosidic enzymes prior to incubation with the fluorescently-labelled proteins. Results Whilst the 402H and 402Y variants showed similar levels of binding to the RPE, there was a marked reduction in binding of the 402H form to Bruch's membrane. The binding of both forms to Bruch's membrane was dependent upon interactions with heparan sulfates, and to a lesser extent dermatan sulfates. Conclusion Complement mediated damage is important in the pathogenesis of AMD and the relative failure of the 402H form of CFH to localise to Bruch's membrane may result in over activation of the complement system at the retinal pigment epithelium/Bruch's membrane interface. [source] Knightly Complements: The Malcontent and the Matter of WitENGLISH LITERARY RENAISSANCE, Issue 2 2010Ian Munro This essay uses John Marston's play The Malcontent to explore the social understanding and cultural practice of wit in the early modern period. Through the interactions between its various versions, The Malcontent charts the linguistic, stylistic, and cultural boundaries of early modern wit as both intrinsic class marker and promiscuous commodity. This duality of wit helps the play negotiate the complexities of its own theatrical genealogy that not only inform the larger context of wit in the period, but also inflect, in significant ways, the play's modern reception. (I.M.) [source] Revisiting Oligopolistic Reaction: Are Decisions on Foreign Direct Investment Strategic Complements?JOURNAL OF ECONOMICS & MANAGEMENT STRATEGY, Issue 3 2002Keith Head Knickerbocker (1973) introduced the notion of oligopolistic reaction to explain why firms follow rivals into foreign markets. We develop a model that incorporates central features of Knickerbocker's story,oligopoly, uncertainty, and risk aversion,to establish the conditions required to generate follow-the-leader behavior. We find that rival foreign investment will make risk-neutral firms less inclined to move abroad once its rivals have done so. We show that Knickerbocker's prediction relies on risk aversion and derive an expression for the minimum amount of risk aversion needed to generate oligopolistic reaction. [source] On the Hicks,Allen Definition of Complements and Substitutes with Discrete Changes in PricesMETROECONOMICA, Issue 1 2002Christian E. Weber For discrete price changes, compensated cross-price effects for two goods need not be equal if the household consumes three or more goods. In this paper I ask whether compensated cross-price effects must have the same sign even if they differ in magnitude. I show that with three or more goods, the answer to this question is ,no'. For discrete price changes, with more than two goods, the signs of the compensated cross-price effects for two goods can differ depending on which price changes. Hence, the Hicks,Allen definition of complements and substitutes can also differ depending on which price changes. [source] Cannabis, Alcohol and Cigarettes: Substitutes or Complements?THE ECONOMIC RECORD, Issue 236 2001Lisa Cameron This paper uses individual level data from the National Drug Strategy Household Surveys to estimate the price responsiveness of participation in cannabis, alcohol and cigarette use. In addition to own price effects, we estimate cross price effects and the impact of decriminalizing cannabis use. We find that participation is responsive to own prices. There is some evidence that cannabis is a substitute for alcohol and a complement to cigarettes, and that alcohol and cigarettes are complements. The liberalization of cannabis laws in South Australia may have led to a temporary increase in cannabis use among the over-30 age group. [source] Stabilisation of RNA Bulges by Oligonucleotide Complements Containing an Adenosine AnalogueCHEMBIOCHEM, Issue 11 2003Annemieke Madder Abstract Incorporation of 2,-deoxy-2,- , -(1-naphthylmethyl)tubercidin into an oligodeoxyribonucleotide mostly has little or a slightly negative effect on the Tmvalues of complexes with DNA complements. With the same naphthylmethyl-substituted nucleoside at the 3,-end of a 2,-O-methyloligoribonucleotide, however, a stabilisation of 1,2,°C in the corresponding complexes with both DNA and RNA is observed. When the target sequence is an RNA fragment forming a two- or three-nucleotide bulge, complexes with (naphthylmethyl)tubercidin-modified oligodeoxyribonucleotides, as well as with the corresponding 2,-O-methyloligoribonucleotides, give stabilisations of 1,2,°C for the three-nucleotide bulge and of almost 4,°C for the two-nucleotide bulge. This stabilisation is specific to RNA, since the corresponding complexes with the DNA fragments do not display this effect. Thus, the (naphthylmethyl)tubercidin-containing oligonucleotides are the first reported oligonucleotide modifications that specifically stabilise bulged RNA. [source] ADAM17 activity during human neutrophil activation and apoptosisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2006Bruce Walcheck Dr. Abstract Substrates of the metalloprotease ADAM17 (also known as TNF-, converting enzyme or TACE) undergo ectodomain shedding and include various inflammatory modulators. Though polymorphonuclear leukocytes contribute significantly to inflammation, direct analyses of ADAM17 on human neutrophils are very limited. In addition, the current understanding of the processes regulating ADAM17 activity primarily relate to its rapid activation. Therefore, to extend insights into the mechanisms of ADAM17 activity, we examined its surface expression and the shedding of its substrates during extended periods of neutrophil activation and apoptosis. Contrary to studies with immortalized hematopoietic cell lines, we report that surface expression of ADAM17 is maintained by human neutrophils activated with formyl peptides or by FcR/complement receptor-mediated phagocytosis. Interestingly, bacterial phagocytosis resulted in a significant increase in ADAM17 expression several hours after pathogen engulfment. We provide novel evidence that ADAM17 surface expression is also maintained during spontaneous and anti-Fas-induced neutrophil apoptosis. The well-validated ADAM17 substrates L-selectin and proTNF-, were shed efficiently by neutrophils under each of the conditions tested. Our data thus indicate prolonged ADAM17 expression during neutrophil effector functions. The implications of this may be a role by ADAM17 in both the induction and down-regulation of neutrophil activity. [source] Strategies for Meeting EU End-of-Life Vehicle Reuse/Recovery TargetsJOURNAL OF INDUSTRIAL ECOLOGY, Issue 4 2006Paulo Ferrão Summary Disposal of end-of-life vehicles (ELVs) is a relatively new focus of the European policy community. Technical requirements for car design and minimum reuse and recovery rates for end-of-life vehicles are the subject of a recent European Union directive on ELVs. This directive is expected to induce changes in the infrastructure required for ELV processing, and presents a substantial challenge to maintaining such an infrastructure as economically viable. This paper assesses current and emerging ELV recycling technologies, in order to provide guidelines for the development of future ELV recycling strategies. Emphasis is given to technologies dedicated to automobile shredder residue (ASR) recovery, as an alternative/complement to more labor-intensive dismantling activities. The ultimate goal is to develop a vision of the type of ASR processing technology that could emerge in the future. The analysis is based on a model developed to simulate ELV processing infrastructures, and shredding data are taken from full-scale experiments. The results obtained show that ASR mechanical separation and recycling technologies may enable more extensive recycling and contribute to achieving European Union recycling targets, and can thus be considered as far more promising than technologies based on energy recovery. [source] BetweenIT: An Interactive Tool for Tight InbetweeningCOMPUTER GRAPHICS FORUM, Issue 2 2010Brian Whited Abstract The generation of inbetween frames that interpolate a given set of key frames is a major component in the production of a 2D feature animation. Our objective is to considerably reduce the cost of the inbetweening phase by offering an intuitive and effective interactive environment that automates inbetweening when possible while allowing the artist to guide, complement, or override the results. Tight inbetweens, which interpolate similar key frames, are particularly time-consuming and tedious to draw. Therefore, we focus on automating these high-precision and expensive portions of the process. We have designed a set of user-guided semi-automatic techniques that fit well with current practice and minimize the number of required artist-gestures. We present a novel technique for stroke interpolation from only two keys which combines a stroke motion constructed from logarithmic spiral vertex trajectories with a stroke deformation based on curvature averaging and twisting warps. We discuss our system in the context of a feature animation production environment and evaluate our approach with real production data. [source] Manifold Homotopy via the Flow ComplexCOMPUTER GRAPHICS FORUM, Issue 5 2009Bardia Sadri Abstract It is known that the critical points of the distance function induced by a dense sample P of a submanifold , of ,n are distributed into two groups, one lying close to , itself, called the shallow, and the other close to medial axis of ,, called deep critical points. We prove that under (uniform) sampling assumption, the union of stable manifolds of the shallow critical points have the same homotopy type as , itself and the union of the stable manifolds of the deep critical points have the homotopy type of the complement of ,. The separation of critical points under uniform sampling entails a separation in terms of distance of critical points to the sample. This means that if a given sample is dense enough with respect to two or more submanifolds of ,n, the homotopy types of all such submanifolds together with those of their complements are captured as unions of stable manifolds of shallow versus those of deep critical points, in a filtration of the flow complex based on the distance of critical points to the sample. This results in an algorithm for homotopic manifold reconstruction when the target dimension is unknown. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||