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Sample records for complete complement c4

  1. Juvenile elastic arteries after 28 years of renal replacement therapy in a patient with complete complement C4 deficiency

    PubMed Central

    2012-01-01

    Background Complement activation products are present in atherosclerotic plaques. Recently, binding of complement to elastin and collagen in the aortic wall has been demonstrated, suggesting a role of complement in the development aortic stiffness and atherosclerosis. The definitive role of complement in atherosclerosis and arteriosclerosis, however, remains unclear. Case presentation We here describe a patient with hereditary complete deficiency of complement C4 suffering from Henoch-Schoenlein purpura and on renal replacement therapy for twenty-eight years. The patient had the full range of risk factors for vascular damage such as hypertension, volume overload, hyperphosphatemia and hyperparathyroidism. Despite that, his carotid artery intima media thickness was below the normal range and his pulse wave velocity was normal. In contrast, the patient’s coronary and peripheral muscular arteries were heavily calcified. Conclusion This case supports the hypothesis that complement plays an important role in the development of stiffness of elastic arteries. We speculate that inability to activate complement by the classical or lectin pathways protected the patient from atherosclerosis, arteriosclerosis, stiffening and calcification of the aorta and carotid arteries. Inhibition of complement activation may be a potential target for prophylactic and therapeutic interventions. PMID:23199021

  2. Complement components C2, C3, and C4 (C4A and C4B) and BF polymorphisms in populations of the Indian subcontinent.

    PubMed

    Ad'hiah, A H; Papiha, S S

    1996-10-01

    Genetic polymorphisms of the complement components (five loci: C2, C3, C4A, C4B, and BF) have been investigated in the Telugu-speaking Hindu population of Hyderabad, Andhra Pradesh, India, and the Bangali-speaking Muslim population of Dacca, Bangladesh. The available data are compared to understand the genetic variation of complement components in populations of the Indian subcontinent. The C3*F and BF*F alleles show wide frequency variations in different ethnic groups of India. The range of variation in the C3*F allele is intermediate between European whites and southeast Asian populations, whereas the BF*F allele places the Indian frequencies between European whites and African blacks. This is the first population study to investigate the C2 and C4 (C4A and C4B) polymorphisms in two distinct groups of the Indian subcontinent. For the C2 polymorphism only the C2*B variant allele was observed, and its frequency was slightly higher than in European populations. In both populations the C4A and C4B loci were highly polymorphic, with a high frequency of the null alleles C4A*QO and C4B*QO, which may account for the greater susceptibility to certain autoimmune diseases in populations of South Asia.

  3. Comparison of a fluorometric method with radial immunodiffusion assays for determination of complement components C3 and C4.

    PubMed Central

    Koelle, M; Bartholomew, W R

    1982-01-01

    Measurements of patient serum complement components C3 and C4 are useful indicators of complement consumption in immune complex diseases. A fluorometric quantitative immunofluorescence system was evaluated in terms of measuring these complement components, and the results were compared with those of radial immunodiffusion assays. For comparison of the two systems, 232 patient sera were evaluated for C3, and 202 specimens were tested for C4. Analysis of the data by linear regression indicated a proportional difference between the methods. C3 and C4 concentrations measured by the fluorometric method were lower than those measured by radial immunodiffusion, especially concentrations exceeding the normal ranges. In detecting lower concentrations (less than 120 mg/dl for C3 and less than 25 mg/dl for C4), the two methods showed better agreement. Each assay system was reproducible and could be used to evaluate changes that occur in concentrations of complement components during therapeutic treatment. However, the ease in processing a large volume of specimens and the short time needed to complete the assay are advantages that make the fluorometric method more suitable than radial immunodiffusion for use in a large clinical laboratory. PMID:6811611

  4. Comparison of a fluorometric method with radial immunodiffusion assays for determination of complement components C3 and C4.

    PubMed

    Koelle, M; Bartholomew, W R

    1982-08-01

    Measurements of patient serum complement components C3 and C4 are useful indicators of complement consumption in immune complex diseases. A fluorometric quantitative immunofluorescence system was evaluated in terms of measuring these complement components, and the results were compared with those of radial immunodiffusion assays. For comparison of the two systems, 232 patient sera were evaluated for C3, and 202 specimens were tested for C4. Analysis of the data by linear regression indicated a proportional difference between the methods. C3 and C4 concentrations measured by the fluorometric method were lower than those measured by radial immunodiffusion, especially concentrations exceeding the normal ranges. In detecting lower concentrations (less than 120 mg/dl for C3 and less than 25 mg/dl for C4), the two methods showed better agreement. Each assay system was reproducible and could be used to evaluate changes that occur in concentrations of complement components during therapeutic treatment. However, the ease in processing a large volume of specimens and the short time needed to complete the assay are advantages that make the fluorometric method more suitable than radial immunodiffusion for use in a large clinical laboratory.

  5. Pasteurella pneumotropica Evades the Human Complement System by Acquisition of the Complement Regulators Factor H and C4BP

    PubMed Central

    Sahagún-Ruiz, Alfredo; Granados Martinez, Adriana Patricia; Breda, Leandro Carvalho Dantas; Fraga, Tatiana Rodrigues; Castiblanco Valencia, Mónica Marcela; Barbosa, Angela Silva; Isaac, Lourdes

    2014-01-01

    Pasteurella pneumotropica is an opportunist Gram negative bacterium responsible for rodent pasteurellosis that affects upper respiratory, reproductive and digestive tracts of mammals. In animal care facilities the presence of P. pneumotropica causes severe to lethal infection in immunodeficient mice, being also a potential source for human contamination. Indeed, occupational exposure is one of the main causes of human infection by P. pneumotropica. The clinical presentation of the disease includes subcutaneous abscesses, respiratory tract colonization and systemic infections. Given the ability of P. pneumotropica to fully disseminate in the organism, it is quite relevant to study the role of the complement system to control the infection as well as the possible evasion mechanisms involved in bacterial survival. Here, we show for the first time that P. pneumotropica is able to survive the bactericidal activity of the human complement system. We observed that host regulatory complement C4BP and Factor H bind to the surface of P. pneumotropica, controlling the activation pathways regulating the formation and maintenance of C3-convertases. These results show that P. pneumotropica has evolved mechanisms to evade the human complement system that may increase the efficiency by which this pathogen is able to gain access to and colonize inner tissues where it may cause severe infections. PMID:25347183

  6. Phenotyping of human complement component C4, a class-III HLA antigen.

    PubMed Central

    Sim, E; Cross, S J

    1986-01-01

    The plasma complement protein C4 is encoded at two highly polymorphic loci, A and B, within the class-III region of the major histocompatibility complex. At least 34 different polymorphic variants of human C4 have been identified, including non-expressed or 'null' alleles. The main method of identification of C4 polymorphic allotypes is separation on the basis of charge by agarose-gel electrophoresis of plasma. On staining by immunofixation with anti-C4 antibodies, each C4 type gives three major bands, but, since individuals can have up to five allotypes, the overlapping banding pattern is difficult to interpret. We show that digestion of plasma samples with carboxypeptidase B, which removes C-terminal basic amino acids, before electrophoresis, produces a single, sharp, distinct band for each allotype and allows identification of the biochemical basis of the multiple banding pattern previously observed in C4 phenotype determination. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:3103606

  7. Evolutionary analysis of two complement C4 genes: Ancient duplication and conservation during jawed vertebrate evolution.

    PubMed

    Nonaka, Mayumi I; Terado, Tokio; Kimura, Hiroshi; Nonaka, Masaru

    2017-03-01

    The complement C4 is a thioester-containing protein, and a histidine (H) residue catalyzes the cleavage of the thioester to allow covalent binding to carbohydrates on target cells. Some mammalian and teleost species possess an additional isotype where the catalytic H is replaced by an aspartic acid (D), which binds preferentially to proteins. We found the two C4 isotypes in many other jawed vertebrates, including sharks and birds/reptiles. Phylogenetic analysis suggested that C4 gene duplication occurred in the early days of the jawed vertebrate evolution. The D-type C4 of bony fish except for mammals formed a cluster, termed D-lineage. The D-lineage genes were located in a syntenic region outside MHC, and evolved conservatively. Mammals lost the D-lineage before speciation, but D-type C4 was regenerated by recent gene duplication in some mammalian species or groups. Dual C4 molecules with different substrate specificities would have contributed to development of the antibody-dependent classical pathway.

  8. Amino acid residues 1101-1105 of the isotypic region of human C4B is important to the covalent binding activity of complement component C4.

    PubMed

    Reilly, B D; Levine, R P; Skanes, V M

    1991-11-01

    The C4A and C4B isotypes of human C4 show certain functional differences that stem from their relative preference for transacylation to amino (-NH2) vs hydroxyl (-OH) nucleophiles, respectively, on complement-activating surfaces. Comparison of amino acid sequences of the alpha-chain fragment of C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 are the only consistent structural difference between isotype, i.e., Pro, Cys, Pro, Val, Leu, Asp in C4A and Leu, Ser, Pro, Val Ile, His in C4B. These residues may be responsible either in part or entirely for properties associated with isotype. To examine the functional role of residues 1101-1106 in C4B-mediated hemolysis, whole serum or immunopurified human C4 with allotypes, A3B1, A3, B2B1, or B1 were preincubated in the presence or absence of an antipeptide mAb (BII-1) specific for amino acid residues 1101-1105 of C4B. Sensitized sheep E and C4-deficient guinea pig serum was then added and lysis measured by absorbance at 415 nm. Our results show lysis of antibody-sensitized sheep E is inhibited by antibody and C4B2B1, C4B1, or C4A3B1 but not antibody and C4A3. The interference of hemolysis by BII-1 could not be explained by inhibition of activation of C4B or inhibition of C3 or C5 convertase activity. Furthermore, results from uptake experiments show that BII-1 interferes with the covalent binding activity of C4B, indicating residues 1101-1105 play a role in the covalent binding reaction of C4B to the target E-antibody complex.

  9. Complement C4 maintains peripheral B-cell tolerance in a myeloid cell-dependent manner

    PubMed Central

    Alimzhanov, Marat B.; Degn, Soren; Tsiftsoglou, Stefanos A.; Alicot, Elisabeth; Jones, Sarah A.; Ma, Minghe; Carroll, Michael C.

    2014-01-01

    The factors that allow self-reactive B cells to escape negative selection and become activated remain poorly defined. Using a B-cell receptor-knock-in mouse strain, we identify a pathway by which B-cell selection to nucleolar self-antigens is complement-dependent. Deficiency in complement component C4 led to a breakdown in the elimination of autoreactive B-cell clones at the transitional stage, characterized by a relative increase in their response to a range of stimuli, entrance into follicles and a greater propensity to form self-reactive germinal centers. Using mixed bone marrow chimeras we found that the myeloid compartment was sufficient to restore negative selection in the auto-reactive mice. A model is proposed in which in the absence of complement C4, inappropriate clearance of apoptotic debris promotes chronic activation of myeloid cells, allowing the maturation and activation of self-reactive B-cell clones leading to increased spontaneous formation of germinal centers. PMID:23749435

  10. Substitution of a single amino acid (aspartic acid for histidine) converts the functional activity of human complement C4B to C4A.

    PubMed Central

    Carroll, M C; Fathallah, D M; Bergamaschini, L; Alicot, E M; Isenman, D E

    1990-01-01

    The C4B isotype of the fourth component of human complement (C4) displays 3- to 4-fold greater hemolytic activity than does its other isotype C4A. This correlates with differences in their covalent binding efficiencies to erythrocytes coated with antibody and complement C1. C4A binds to a greater extent when C1 is on IgG immune aggregates. The differences in covalent binding properties correlate only with amino acid changes between residues 1101 and 1106 (pro-C4 numbering)--namely, Pro-1101, Cys-1102, Leu-1105, and Asp-1106 in C4A and Leu-1101, Ser-1102, Ile-1105, and His-1106 in C4B, which are located in the C4d region of the alpha chain. To more precisely identify the residues that are important for the functional differences, C4A-C4B hybrid proteins were constructed by using recombinant DNA techniques. Comparison of these by hemolytic assay and binding to IgG aggregates showed that the single substitution of aspartic acid for histidine at position 1106 largely accounted for the change in functional activity and nature of the chemical bond formed (ester vs. amide). Surprisingly, substitution of a neutral residue, alanine, for histidine at position 1106 resulted in an increase in binding to immune aggregates without subsequent reduction in the hemolytic activity. This result strongly suggests that position 1106 is not "catalytic" as previously proposed but interacts sterically/electrostatically with potential acceptor sites and serves to "select" binding sites on potential acceptor molecules. Images PMID:2395880

  11. Complement-activated oligodendroglia: a new pathogenic entity identified by immunostaining with antibodies to human complement proteins C3d and C4d.

    PubMed

    Yamada, T; Akiyama, H; McGeer, P L

    1990-05-04

    Clusters of oligodendroglial fibers were identified immunohistochemically in human brain tissue with antibodies to the complement proteins C3d and C4d in several neurological disorders. These included Pick's, Huntington's, Parkinson's and Alzheimer's disease, amyotrophic lateral sclerosis, progressive supranuclear palsy and Shy-Drager syndrome. These complement-activated oligodendroglia occurred in selected areas of gray and white matter. They were rarely observed in control tissue. Immunogold electron microscopy established that the C4d antibody was attached to degenerating myelin sheaths. These data indicate attachment of classical complement pathway proteins to selective oligodendroglia in several neurological disorders.

  12. The interaction of soluble human complement receptor type 1 (sCR1, BRL55730) with human complement component C4.

    PubMed

    Gibb, A L; Freeman, A M; Smith, R A; Edmonds, S; Sim, E

    1993-01-22

    Human CR1 is a membrane-bound protein which plays an important role in the control of the human complement system. In addition to its involvement in the processing and clearance of immune complexes with C3b or C4b on their surface, CR1 acts as a cofactor for the proteolysis of C3b and C4b by Factor I. sCR1 is a recombinant, soluble form of CR1 which retains the cofactor activities of CR1, and is of potential therapeutic value for the suppression of complement-mediated tissue damage in vivo. An assay has been established using microtitre plates to explore the binding of sCR1 to the two isotypes of C4, C4A and C4B, and to C4 fragments. Specific binding of 125I-sCR1 to C4b and ammonia-treated C4 has been demonstrated. The binding of 125I-sCR1 to ammonia-treated C4 is dependent on pH and ionic strength, decreasing with an increase in pH and with an increase in ionic strength. At physiological ionic strength, up to twice as much 125I-sCR1 bound to ammonia-treated C4A as bound to ammonia-treated C4B. This preference of sCR1 for binding to the C4A isotype has implications for the clinical association of immune complex disease with C4A null alleles.

  13. A Novel Interaction between Complement Inhibitor C4b-binding Protein and Plasminogen That Enhances Plasminogen Activation*

    PubMed Central

    Agarwal, Vaibhav; Talens, Simone; Grandits, Alexander M.; Blom, Anna M.

    2015-01-01

    The complement, coagulation, and fibrinolytic systems are crucial for the maintenance of tissue homeostasis. To date numerous interactions and cross-talks have been identified between these cascades. In line with this, here we propose a novel, hitherto unknown interaction between the complement inhibitor C4b-binding protein (C4BP) and plasminogen of the fibrinolytic pathway. Binding of C4BP to Streptococcus pneumoniae is a known virulence mechanism of this pathogen and it was increased in the presence of plasminogen. Interestingly, the acute phase variant of C4BP lacking the β-chain and protein S binds plasminogen much stronger than the main isoform containing the β-chain and protein S. Indeed, the complement control protein (CCP) 8 domain of C4BP, which would otherwise be sterically hindered by the β-chain, primarily mediates this interaction. Moreover, the lysine-binding sites in plasminogen kringle domains facilitate the C4BP-plasminogen interaction. Furthermore, C4BP readily forms complexes with plasminogen in fluid phase and such complexes are present in human serum and plasma. Importantly, whereas the presence of plasminogen did not affect the factor I cofactor activity of C4BP, the activation of plasminogen by urokinase-type plasminogen activator to active plasmin was significantly augmented in the presence of C4BP. Taken together, our data demonstrate a novel interaction between two proteins of the complement and fibrinolytic system. Most complexes might be formed during the acute phase of inflammation and have an effect on the homeostasis at the site of injury or acute inflammation. PMID:26067271

  14. Secreted Aspergillus fumigatus Protease Alp1 Degrades Human Complement Proteins C3, C4, and C5▿

    PubMed Central

    Behnsen, Judith; Lessing, Franziska; Schindler, Susann; Wartenberg, Dirk; Jacobsen, Ilse D.; Thoen, Marcel; Zipfel, Peter F.; Brakhage, Axel A.

    2010-01-01

    The opportunistic human pathogenic fungus Aspergillus fumigatus is a major cause of fungal infections in immunocompromised patients. Innate immunity plays an important role in the defense against infections. The complement system represents an essential part of the innate immune system. This cascade system is activated on the surface of A. fumigatus conidia and hyphae and enhances phagocytosis of conidia. A. fumigatus conidia but not hyphae bind to their surface host complement regulators factor H, FHL-1, and CFHR1, which control complement activation. Here, we show that A. fumigatus hyphae possess an additional endogenous activity to control complement activation. A. fumigatus culture supernatant efficiently cleaved complement components C3, C4, C5, and C1q as well as immunoglobulin G. Secretome analysis and protease inhibitor studies identified the secreted alkaline protease Alp1, which is present in large amounts in the culture supernatant, as the central molecule responsible for this cleavage. An alp1 deletion strain was generated, and the culture supernatant possessed minimal complement-degrading activity. Moreover, protein extract derived from an Escherichia coli strain overproducing Alp1 cleaved C3b, C4b, and C5. Thus, the protease Alp1 is responsible for the observed cleavage and degrades a broad range of different substrates. In summary, we identified a novel mechanism in A. fumigatus that contributes to evasion from the host complement attack. PMID:20498262

  15. [Levels of total hemolytic complement, C3, C4 and antibodies against the myocardium in rheumatic fever].

    PubMed

    Martinez, R D

    1978-01-01

    The levels of the hemolytic complement (UH 50%), C3, C4 and the antibodies against myocardium and against the antigenic fractions of myocardium precipitated with ammonium sulphate were studied in 8 patients with active rehumatic fever (ARF), 28 with inactive rheumatic fever (IRF) and 26 people without cardiopaties (NI). The UH 50% was low in 2 out of 36 patients with rheumatic fever (RF). C3 was normal and C4 low in 12.5% of the ARF patients. C3 had subnormal values in 25% and C4 in 33% of IRF patients, this last value had a stadistic significant decrease with respect to the values of C4 in normal people. The 36 patients with RF had antibodies against the myocardium and also against the heart antigenic fractions precipitated with 10% ammonium sulphate. 11.5% of the normal group had anti-myocardial antibodies and none had antibodies against the fractions. The levels of anti-streptolysin-O and C-reactive protein were higher in the ARF group than in the patients with IRF or the normal people. The participation of the hemolytic complement, the anti-myocardium antibodies, the anti-streptococcus antibodies and the cytophilic activity in the etiopathogeny of rheumatic fever is discussed.

  16. [A case of traumatic anterior dislocation of C4 recovered from complete tetraplegia].

    PubMed

    Okada, K; Tasaki, T; Komatsu, S; Asakura, K

    1985-07-01

    A case of traumatic anterior dislocation of C4 is presented. A 65-year-old man who was beastly drunken fell down backward and severely struck occipital region against the door and immediately developed tetraplegia. Neurological examination 12 hours after the trauma revealed complete flaccid tetraplegia, abdominal respiration, bladder-bowel disturbance, anesthesia below C5 and hyperpathia in C3 and C4 dermatomes. Plain films of the cervical spine disclosed anterior dislocation of C4 upon C5 approximately 6 mm and possible disc herniation of C4/5. On Amipaque cervical myelography via C1C2 lateral puncture, there was almost complete block of the dye at C4/5 level. With diagnosis of acute cervical spinal cord injury on C4/5 caused by pincer mechanism and herniated disc material, the patient was operated on 19 hours after the trauma by anterior discectomy of C4/5 and fusion under Crutchfield skull traction. Neurological recovery began with the right leg from the day after the operation and it's recovery pattern showed the syndrome of acute central cervical spinal cord injury reported by Schneider. The patient discharged on March '84 four months after the trauma walking by himself with tetraparesis especially weakness of the hands and hypesthesia of glove and stocking type. We emphasized importance of Amipaque cervical myelography via C1C2 lateral puncture and anterior approach on the treatment of acute cervical spinal cord injury to be done as soon as possible.

  17. A soluble deletion mutant of the human complement receptor type 1, which lacks the C4b binding site, is a selective inhibitor of the alternative complement pathway.

    PubMed

    Scesney, S M; Makrides, S C; Gosselin, M L; Ford, P J; Andrews, B M; Hayman, E G; Marsh, H C

    1996-08-01

    The human complement receptor type 1 (CR1, CD35), is a single-chain glycoprotein consisting of 30 repeating homologous protein domains known as short consensus repeats (SCR) followed by transmembrane and cytoplasmic domains. The SCR themselves, considered in groups of seven, form long homologous repeats (LHR) which have been designated LHR-A, -B, -C, and -D for the most common human allotype of CR1. A soluble deletion mutant of CR1 which lacks the first seven N-terminal SCR (LHR-A) as well as the transmembrane and cytoplasmic domains was produced and characterized. The resulting protein, designated sCR1[desLHR-A], lacks the C4b binding site found in LHR-A, but retains the two C3b binding sites found in LHR-B and -C, respectively. The functional activities of sCR1[desLHR-A] were quantitatively compared in vitro to those of soluble complement receptor type 1 (sCR1) which has been shown to retain all known functions of the native cell surface receptor. sCR1[desLHR-A] and sCR1 competed equally for the binding of dimeric C3b to erythrocyte CR1. sCR1[desLHR-A] and sCR1 were similar in their capacity to serve as a cofactor in the factor I-mediated degradation of the C3b and C4b alpha chains. sCR1[desLHR-A] and sCR1 were comparable in their capacity to inhibit erythrocyte lysis and anaphylatoxin production mediated by the alternative complement pathway. sCR1[desLHR-A], however, was significantly less effective an inhibitor of erythrocyte lysis and anaphylatoxin production than sCR1 under conditions which allow classical pathway activation. These results demonstrate sCR1[desLHR-A] to be a selective inhibitor of the alternative complement pathway in vitro.

  18. Sites within the complement C3b/C4b receptor important for the specificity of ligand binding.

    PubMed Central

    Krych, M; Hourcade, D; Atkinson, J P

    1991-01-01

    Cysteine-rich repeated units of 40-70 amino acids are building blocks of many mammalian proteins, including 12 proteins of the complement system. Human complement arranged motifs, designated short consensus repeats (SCRs), which constitute the entire extracellular portion of this protein. Klickstein et al. [Klickstein, L. B., Bartow, T. J., Miletic, V., Rabson, L. D., Smith, J. A. & Fearon, D. T. (1988) J. Exp. Med. 168, 1699-1717 (abstr.)] localized a C4b binding domain to SCR-1 and/or SCR-2 and a C3b binding domain to SCR-8 and/or SCR-9. These SCRs bind different ligands, although SCR-1 and SCR-8 are 55% homologous and SCR-2 and SCR-9 are 70% homologous. To examine if one or two SCRs are required for ligand binding and to define sites within the SCRs that determine specificity of binding, mutagenesis analysis of a truncated, secreted form of CR1, called CR1-4 by Hourcade et al. [Hourcade, D., Meisner, D. R., Atkinson, J. P. & Holers, V. M. (1988) J. Exp. Med. 168, 1255-1270], was undertaken. The latter, composed of the first eight and one-half amino-terminal SCRs of CR1, efficiently bound C4b but not iC3. SCR-1 and SCR-2 were necessary for this interaction. Analysis of the mutant CR1-4 proteins, in which amino acids in SCR-1 and SCR-2 were substituted a few at a time with the homologous amino acids of SCR-8 and SCR-9, led to the identification of one amino acid in SCR-1 and three amino acids in SCR-2 important for C4b binding. Furthermore, five amino acids at the end of SCR-9, if placed in the homologous positions of SCR-2, conferred iC3 binding and are likely essential for ligand binding activity of SCR-8 and SCR-9. This iC3 binding occurred only if SCR-1 was present, indicating that two contiguous SCRs are necessary for this interaction. These results provide identification of amino acids within SCRs that are important for ligand binding. Images PMID:1827918

  19. Gene Copy-Number Variations (CNVs) and Protein Levels of Complement C4A and C4B as Novel Biomarkers for Partial Disease Remissions in New-Onset Type 1 Diabetes Patients

    PubMed Central

    Kingery, Suzanne E.; Wu, Yee Ling; Zhou, Bi; Hoffman, Robert P.; Yu, C. Yung

    2014-01-01

    Objective To determine the roles of complement C4A and C4B gene CNVs and their plasma protein concentrations in residual insulin secretion and loss of pancreatic beta-cell function in new-onset type 1 diabetes patients. Methods We studied 34 patients of European ancestry with new-onset type 1 diabetes, aged between 3 and 17 years (10.7±3.45), at Nationwide Children's Hospital in Columbus, Ohio. Gene copy-number and size variations of complement C4A and C4B were determined by genomic Southern blot analyses. C4A and C4B protein phenotypes were elucidated by immunofixation and radial immunodiffusion. Two-digit HLA-DRB1 genotypes were determined by sequence-specific PCR. At 1 month and 9-month post diagnosis, stimulated C-peptide levels were measured after a standardized mixed-meal tolerance test. Results The diploid gene copy-numbers of C4A varied from 0 to 4, and those of C4B from 0 to 3. Patients with higher copy-number of C4A or higher C4A plasma protein concentrations at diagnosis had higher C-peptide levels at 1 month post diagnosis (p=0.008; p=0.008). When controlled by the Z-score of body-mass index, C4A copy-numbers, C4A protein concentrations, the age of disease-onset, the number of HLA-DR3 but not DR4 alleles were significant parameters in determining C-peptide levels. At 9-month post diagnosis, 42.3% of patients remained in partial remission, and these patients were characterized by lower total C4B copy-numbers or lower C4B protein concentrations (p=0.02, p=0.0004). Conclusions C4A appears to associate with the protection of residual beta-cell function in new-onset type 1 diabetes; C4B is correlated with the end of disease remission at 9-month post diagnosis. PMID:22151770

  20. Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia.

    PubMed

    Malm, Sven; Jusko, Monika; Eick, Sigrun; Potempa, Jan; Riesbeck, Kristian; Blom, Anna M

    2012-01-01

    Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with (125)I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases.

  1. Polymorphism of the human complement C4 and steroid 21-hydroxylase genes. Restriction fragment length polymorphisms revealing structural deletions, homoduplications, and size variants.

    PubMed Central

    Schneider, P M; Carroll, M C; Alper, C A; Rittner, C; Whitehead, A S; Yunis, E J; Colten, H R

    1986-01-01

    Several autoimmune disorders as well as congenital adrenal hyperplasia (CAH) are either associated or closely linked with genetic variants of the fourth component of complement (C4A and C4B) and the enzyme steroid 21-hydroxylase (21-OH). These proteins are encoded by genes that are located downstream from the genes for complement proteins, C2 and factor B (BF) between HLA-B and -DR in the major histocompatibility complex (MHC). Previous studies of variants and null alleles were based on electrophoretic mobility of C4 protein and linkage with disease phenotypes. These data did not permit analysis of the basis for the observed null alleles and duplicated variants. We studied this region of the MHC in 126 haplotypes for a structural analysis of the four adjacent loci, C4A, 21-OHA, C4B, and 21-OHB. About half of the C4 genes typed as C4 null are deleted and several unrecognized homoduplicated C4 alleles were detected. Hence the frequencies of different C4 structural variants must be recalculated based on a direct analysis of the genes. Analysis of the C4/21-OH genes of patients with the classical (salt-wasting) form of CAH showed that some involve a deletion of the C4B and 21-OHB genes; whereas for two only the 21-OHB gene is deleted, i.e., the C4B gene is present. Together, these data provide a better understanding of the mechanisms generating and importance of deleted C4 and 21-OH null alleles in human disease. Images PMID:3018042

  2. Great Genotypic and Phenotypic Diversities Associated with Copy-Number Variations of Complement C4 and RP-C4-CYP21-TNX (RCCX) Modules: a Comparison of Asian Indian and European American Populations

    PubMed Central

    Saxena, Kapil; Kitzmiller, Kathryn J.; Wu, Yee Ling; Zhou, Bi; Esack, Nazreen; Hiremath, Leena; Chung, Erwin K.; Yang, Yan; Yu, C. Yung

    2009-01-01

    Inter-individual gene copy-number variations (CNVs) probably afford human populations the flexibility to respond to a variety of environmental challenges, but also lead to differential disease predispositions. We investigated gene CNVs for complement component C4 and steroid 21-hydroxylase from the RP-C4-CYP21-TNX (RCCX) modules located in the major histocompatibility complex among healthy Asian-Indian Americans (AIA) and compared them to European Americans. A combination of definitive techniques that yielded cross-confirmatory results was used. The medium gene copy-numbers for C4 and its isotypes, acidic C4A and basic C4B, were 4, 2 and 2, respectively, but their frequencies were only 53–56%. The distribution patterns for total C4 and C4A are skewed towards the high copy-number side. For example, the frequency of AIA-subjects with three copies of C4A (30.7%) was 3.92-fold of those with a single copy (7.83%). The monomodular-short haplotype with a single C4B gene and the absence of C4A, which is in linkage- disequilibrium with HLA DRB1*0301 in Europeans and a strong risk factor for autoimmune diseases, has a frequency of 0.012 in AIA but 0.106 among healthy European Americans (p=6.6×10−8). The copy-number and the size of C4 genes strongly determine the plasma C4 protein concentrations. Parallel variations in copy-numbers of CYP21A (CYP21A1P) and TNXA with total C4 were also observed. Notably, 13.1% of AIA-subjects had three copies of the functional CYP21B, which were likely generated by recombinations between monomodular and bimodular RCCX haplotypes. The high copy-numbers of C4 and the high frequency of RCCX recombinants offer important insights to the prevalence of autoimmune and genetic diseases. PMID:19135723

  3. Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations.

    PubMed

    Boteva, Lora; Wu, Yee Ling; Cortes-Hernández, Josefina; Martin, Javier; Vyse, Timothy J; Fernando, Michelle M A

    2011-01-01

    Genetic variants resulting in non-expression of complement C4A and C4B genes are common in healthy European populations and have shown association with a number of diseases, most notably the autoimmune disease, systemic lupus erythematosus. The most frequent cause of a C4 "null" allele, following that of C4 gene copy number variation (CNV), is a non-sense mutation arising from a 2 bp CT insertion into codon 1232 of exon 29. Previous attempts to accurately genotype this polymorphism have not been amenable to high-throughput typing, and have been confounded by failure to account for CNV at this locus, as well as by inability to distinguish between paralogs. We have developed a novel, high-throughput, paralog-specific assay to detect the presence and copy number of this polymorphism. We have genotyped healthy cohorts from the United Kingdom (UK) and Spain. Overall, 30/719 (4.17%) individuals from the UK cohort and 8/449 (1.78%) individuals from the Spanish cohort harboured the CT insertion in a C4A gene. A single Spanish individual possessed a C4B CT insertion. There is weak correlation between the C4 CT insertion and flanking MHC polymorphism. Therefore it is important to note that, as with C4 gene CNV, disease-association due to this variant will be missed by current SNP-based genome-wide association strategies.

  4. Complement C4-derived monocyte-directed chemotaxis-inhibitory factor. A molecular mechanism to cause polymorphonuclear leukocyte-predominant infiltration in rheumatoid arthritis synovial cavities.

    PubMed Central

    Matsubara, S.; Yamamoto, T.; Tsuruta, T.; Takagi, K.; Kambara, T.

    1991-01-01

    To reveal the mechanism of the lesser infiltration of monocytes in synovial cavities with rheumatoid arthritis despite the presence of chronic inflammation, the synovial fluid from 15 rheumatoid arthritis patients was analyzed with respect to leukocyte chemotaxis. The synovial fluid possessed strong chemotactic activity to polymorphonuclear leukocytes but rather suppressed one to monocytes. The synovial fluid contained two different inhibitory activities in monocyte chemotaxis. One, which also suppressed polymorphonuclear leukocyte chemotaxis, was identified as alpha 1 protease inhibitor. The other, with molecular weight of 8 kd, possessed the specificity to monocytes and shared the antigenicity with complement C4 but not with C3 or C5. A similar inhibitor was generated in normal human plasma when the classical pathway of the complement system was initiated with aggregated human IgG, while it was not when alternative pathway was initiated with zymosan. The small size factor in the synovial fluid, apparently derived from C4, seemed to be a cyto-directed factor that might block an early part of signal transduction system of monocytes in the chemotaxis. After removal of the small-size inhibitor, the synovial fluid exhibited chemotactic ability to monocytes. Therefore the apparent C4-derived factor might play a key role in the polymorphonuclear leukocyte-predominant infiltration in the synovial fluid of rheumatoid arthritis. PMID:2024711

  5. Complement

    MedlinePlus

    ... fungal infections and some parasitic infections such as malaria . Normal Results Total blood complement level: 41 to ... Glomerulonephritis Hepatitis Hereditary angioedema Kidney transplant Lupus nephritis Malaria Protein in diet Rheumatoid arthritis Septicemia Shock Systemic ...

  6. Re-evaluation of low-resolution crystal structures via interactive molecular-dynamics flexible fitting (iMDFF): a case study in complement C4.

    PubMed

    Croll, Tristan Ian; Andersen, Gregers Rom

    2016-09-01

    While the rapid proliferation of high-resolution structures in the Protein Data Bank provides a rich set of templates for starting models, it remains the case that a great many structures both past and present are built at least in part by hand-threading through low-resolution and/or weak electron density. With current model-building tools this task can be challenging, and the de facto standard for acceptable error rates (in the form of atomic clashes and unfavourable backbone and side-chain conformations) in structures based on data with dmax not exceeding 3.5 Å reflects this. When combined with other factors such as model bias, these residual errors can conspire to make more serious errors in the protein fold difficult or impossible to detect. The three recently published 3.6-4.2 Å resolution structures of complement C4 (PDB entries 4fxg, 4fxk and 4xam) rank in the top quartile of structures of comparable resolution both in terms of Rfree and MolProbity score, yet, as shown here, contain register errors in six β-strands. By applying a molecular-dynamics force field that explicitly models interatomic forces and hence excludes most physically impossible conformations, the recently developed interactive molecular-dynamics flexible fitting (iMDFF) approach significantly reduces the complexity of the conformational space to be searched during manual rebuilding. This substantially improves the rate of detection and correction of register errors, and allows user-guided model building in maps with a resolution lower than 3.5 Å to converge to solutions with a stereochemical quality comparable to atomic resolution structures. Here, iMDFF has been used to individually correct and re-refine these three structures to MolProbity scores of <1.7, and strategies for working with such challenging data sets are suggested. Notably, the improved model allowed the resolution for complement C4b to be extended from 4.2 to 3.5 Å as demonstrated by paired refinement.

  7. Human complement C3b/C4b receptor (CR1) mRNA polymorphism that correlates with the CR1 allelic molecular weight polymorphism

    SciTech Connect

    Holers, V.M.; Chaplin, D.D.; Leykam, J.F.; Gruner, B.A.; Kumar, V.; Atkinson, J.P.

    1987-04-01

    The human C3b/C4b receptor (CR1) is a M/sub r/ approx. = 200,000 single-chain integral membrane glycoprotein of human erythrocytes and leukocytes. It functions both as a receptor for C3b- and C4b-coated ligands and as a regulator of complement activation. Prior structural studies have defined an unusual molecular weight allelic polymorphism in which the allelic products differ in molecular weight by as much as 90,000. On peripheral blood cells there is codominant expression of CR1 gene products of M/sub r/ 190,000 (A), 220,000 (B), 160,000 (C), and 250,000 (D). Results of prior biosynthetic and tryptic peptide mapping experiments have suggested that the most likely basis for the allelic molecular weight differences if at the polypeptide level. In order to define further the molecular basis for these molecular weight differences, human CR1 was purified to homogeneity, tryptic peptide fragments were isolated by HPLC and sequenced, oligonucleotide probes were prepared, and a CR1 cDNA was identified. A subclone of this CR1 cDNA was used as a probe of RNA blots of Epstein-Barr virus-transformed cell lines expressing the allelic variants. Each allelic variant encodes two distinct transcripts. A mRNA size polymorphism was identified that correlated with the gene product molecular weight polymorphism. This finding, in addition to a prior report of several homologous repeats in CR1, is consistent with the hypothesis that the molecular weight polymorphism is determined at the genomic level and may have been generated by unequal crossing-over.

  8. Interaction between complement regulators and Streptococcus pyogenes: binding of C4b-binding protein and factor H/factor H-like protein 1 to M18 strains involves two different cell surface molecules.

    PubMed

    Pérez-Caballero, David; García-Laorden, Isabel; Cortés, Guadalupe; Wessels, Michael R; de Córdoba, Santiago Rodríguez; Albertí, Sebastián

    2004-12-01

    Streptococcus pyogenes, or group A Streptococcus, is one of the most frequent causes of pharyngitis and skin infections in humans. Many virulence mechanisms have been suggested to be involved in the infectious process. Among them is the binding to the bacterial cell surface of the complement regulatory proteins factor H, factor H-like protein 1 (FHL-1), and C4b-binding protein. Previous studies indicate that binding of these three regulators to the streptococcal cell involves the M protein encoded by the emm gene. M-type 18 strains are prevalent among clinical isolates and have been shown to interact with all three complement regulators simultaneously. Using isogenic strains lacking expression of the Emm18 or the Enn18 proteins, we demonstrate in this study that, in contradistinction to previously described S. pyogenes strains, M18 strains bind the complement regulators factor H, FHL-1, and C4b-binding protein through two distinct cell surface proteins. Factor H and FHL-1 bind to the Emm18 protein, while C4BP binds to the Enn18 protein. We propose that expression of two distinct surface structures that bind complement regulatory proteins represents a unique adaptation of M18 strains that enhances their resistance to opsonization by human plasma and increases survival of this particular S. pyogenes strain in the human host. These new findings illustrate that S. pyogenes has evolved diverse mechanisms for recruitment of complement regulatory proteins to the bacterial surface to evade immune clearance in the human host.

  9. Molecular characterization of the complement C1q, C2 and C4 genes in Brazilian patients with juvenile systemic lupus erythematosus

    PubMed Central

    Liphaus, Bernadete L; Umetsu, Natalia; Jesus, Adriana A; Bando, Silvia Y; Silva, Clovis A; Carneiro-Sampaio, Magda

    2015-01-01

    OBJECTIVE: To perform a molecular characterization of the C1q, C2 and C4 genes in patients with juvenile systemic lupus erythematosus. METHODS: Patient 1 (P1) had undetectable C1q, patient 2 (P2) and patient 3 (P3) had decreased C2 and patient 4 (P4) had decreased C4 levels. All exons and non-coding regions of the C1q and C2 genes were sequenced. Mononuclear cells were cultured and stimulated with interferon gamma to evaluate C1q, C2 and C4 mRNA expression by quantitative real-time polymerase chain reaction. RESULTS: C1q sequencing revealed heterozygous silent mutations in the A (c.276 A>G Gly) and C (c.126 C>T Pro) chains, as well as a homozygous single-base change in the 3′ non-coding region of the B chain (c*78 A>G). C1qA mRNA expression without interferon was decreased compared with that of healthy controls (p<0.05) and was decreased after stimulation compared with that of non-treated cells. C1qB mRNA expression was decreased compared with that of controls and did not change with stimulation. C1qC mRNA expression was increased compared with that of controls and was even higher after stimulation. P2 and P3 had Type I C2 deficiency (heterozygous 28 bp deletion at exon 6). The C2 mRNA expression in P3 was 23 times lower compared with that of controls and did not change after stimulation. The C4B mRNA expression of P4 was decreased compared with that of controls and increased after stimulation. CONCLUSIONS: Silent mutations and single-base changes in the 3′ non-coding regions may modify mRNA transcription and C1q production. Type I C2 deficiency should be evaluated in JSLE patients with decreased C2 serum levels. Further studies are needed to clarify the role of decreased C4B mRNA expression in JSLE pathogenesis. PMID:26017655

  10. Major-histocompatibility-complex gene markers and restriction-fragment analysis of steroid 21-hydroxylase (CYP21) and complement C4 genes in classical congenital adrenal hyperplasia patients in a single population.

    PubMed Central

    Partanen, J; Koskimies, S; Sipilä, I; Lipsanen, V

    1989-01-01

    The gene CYP21B, encoding the steroid 21-hydroxylase enzyme of adrenal steroid biosynthesis, has been mapped to the human major histocompatibility complex (MHC). Deficiency of this enzyme leads to congenital adrenal hyperplasia (CAH). We report the phenotypes of the HLA and complement C4 and Bf genes, which are closely linked to the CYP21B gene, together with a detailed analysis of the CYP21 and C4 RFLP, in 17 Finnish families with CAH. The RFLP analysis with six restriction enzymes suggested that, altogether, 35% of the affected chromosomes had a CYP21B + C4B gene deletion, 9% an obvious gene conversion of the CYP21B gene to a CYP21A-like gene, and 3% a CYP21A + C4B duplication. The remaining 53% gave the RFLP patterns also found in nonaffected chromosomes. We also found that a 14.0-kb EcoRI RFLP marker of the CYP21 genes was strongly associated with the presence of a short C4B gene, suggesting that some of the RFLP markers found with the CYP21 probe may actually derive from C4B gene polymorphism. Three particular MHC haplotypes, each with a characteristic RFLP pattern, were found in many unrelated families. These three haplotypes accounted for 59% of the affected chromosomes in our study group, the rest (41%) of the affected chromosomes being distributed among various subtypes. The results suggest that, within a single, well-defined population such as in Finland, only a few CYP21B gene defects may constitute a substantial part of the affected chromosomes. This finding will help in genetic studies of CAH in such populations. Images Figure 2 PMID:2565078

  11. Familial C4B Deficiency and Immune Complex Glomerulonephritis

    PubMed Central

    Soto, K; Wu, YL; Ortiz, A; Aparício, SR; Yu, CY

    2010-01-01

    Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient’s deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. PMID:20580617

  12. Familial C4B deficiency and immune complex glomerulonephritis.

    PubMed

    Soto, K; Wu, Y L; Ortiz, A; Aparício, S R; Yu, C Y

    2010-10-01

    Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient's deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits.

  13. The partly folded back solution structure arrangement of the 30 SCR domains in human complement receptor type 1 (CR1) permits access to its C3b and C4b ligands.

    PubMed

    Furtado, Patricia B; Huang, Chen Y; Ihyembe, Demvihin; Hammond, Russell A; Marsh, Henry C; Perkins, Stephen J

    2008-01-04

    differ from those in CR2, and the SCR arrangement in CR1 will permit C3b or C4b to access all three ligand sites.

  14. Completely ES cell-derived mice produced by tetraploid complementation using inner cell mass (ICM) deficient blastocysts.

    PubMed

    Wen, Duancheng; Saiz, Nestor; Rosenwaks, Zev; Hadjantonakis, Anna-Katerina; Rafii, Shahin

    2014-01-01

    Tetraploid complementation is often used to produce mice from embryonic stem cells (ESCs) by injection of diploid (2n) ESCs into tetraploid (4n) blastocysts (ESC-derived mice). This method has also been adapted to mouse cloning and the derivation of mice from induced pluripotent stem (iPS) cells. However, the underlying mechanism(s) of the tetraploid complementation remains largely unclear. Whether this approach can give rise to completely ES cell-derived mice is an open question, and has not yet been unambiguously proven. Here, we show that mouse tetraploid blastocysts can be classified into two groups, according to the presence or absence of an inner cell mass (ICM). We designate these as type a (presence of ICM at blastocyst stage) or type b (absence of ICM). ESC lines were readily derived from type a blastocysts, suggesting that these embryos retain a pluripotent epiblast compartment; whereas the type b blastocysts possessed very low potential to give rise to ESC lines, suggesting that they had lost the pluripotent epiblast. When the type a blastocysts were used for tetraploid complementation, some of the resulting mice were found to be 2n/4n chimeric; whereas when type b blastocysts were used as hosts, the resulting mice are all completely ES cell-derived, with the newborn pups displaying a high frequency of abdominal hernias. Our results demonstrate that completely ES cell-derived mice can be produced using ICM-deficient 4n blastocysts, and provide evidence that the exclusion of tetraploid cells from the fetus in 2n/4n chimeras can largely be attributed to the formation of ICM-deficient blastocysts.

  15. Gene Copy-Number Variation and Associated Polymorphisms of Complement Component C4 in Human Systemic Lupus Erythematosus (SLE): Low Copy Number Is a Risk Factor for and High Copy Number Is a Protective Factor against SLE Susceptibility in European Americans

    PubMed Central

    Yang, Yan ; Chung, Erwin K. ; Wu, Yee Ling ; Savelli, Stephanie L. ; Nagaraja, Haikady N. ; Zhou, Bi ; Hebert, Maddie ; Jones, Karla N. ; Shu, Yaoling ; Kitzmiller, Kathryn ; Blanchong, Carol A. ; McBride, Kim L. ; Higgins, Gloria C. ; Rennebohm, Robert M. ; Rice, Robert R. ; Hackshaw, Kevin V. ; Roubey, Robert A. S. ; Grossman, Jennifer M. ; Tsao, Betty P. ; Birmingham, Daniel J. ; Rovin, Brad H. ; Hebert, Lee A. ; Yu, C. Yung 

    2007-01-01

    Interindividual gene copy-number variation (CNV) of complement component C4 and its associated polymorphisms in gene size (long and short) and protein isotypes (C4A and C4B) probably lead to different susceptibilities to autoimmune disease. We investigated the C4 gene CNV in 1,241 European Americans, including patients with systemic lupus erythematosus (SLE), their first-degree relatives, and unrelated healthy subjects, by definitive genotyping and phenotyping techniques. The gene copy number (GCN) varied from 2 to 6 for total C4, from 0 to 5 for C4A, and from 0 to 4 for C4B. Four copies of total C4, two copies of C4A, and two copies of C4B were the most common GCN counts, but each constituted only between one-half and three-quarters of the study populations. Long C4 genes were strongly correlated with C4A (R=0.695; P<.0001). Short C4 genes were correlated with C4B (R=0.437; P<.0001). In comparison with healthy subjects, patients with SLE clearly had the GCN of total C4 and C4A shifting to the lower side. The risk of SLE disease susceptibility significantly increased among subjects with only two copies of total C4 (patients 9.3%; unrelated controls 1.5%; odds ratio [OR] = 6.514; P=.00002) but decreased in those with ⩾5 copies of C4 (patients 5.79%; controls 12%; OR=0.466; P=.016). Both zero copies (OR=5.267; P=.001) and one copy (OR=1.613; P=.022) of C4A were risk factors for SLE, whereas ⩾3 copies of C4A appeared to be protective (OR=0.574; P=.012). Family-based association tests suggested that a specific haplotype with a single short C4B in tight linkage disequilibrium with the −308A allele of TNFA was more likely to be transmitted to patients with SLE. This work demonstrates how gene CNV and its related polymorphisms are associated with the susceptibility to a human complex disease. PMID:17503323

  16. [C4 type photosynthesis].

    PubMed

    Drozak, Anna; Wasilewska, Wioleta; Buczyńska, Alicja; Romanowska, Elzbieta

    2012-01-01

    C4 photosynthesis includes several anatomical and biochemical modifications that allow plants to concentrate CO2 at the site of Rubisco. The photorespiratory pathway is repressed in C4 plants, since the rates of photosynthesis and biomass production are increased. This is an adaptation to high light intensities, high temperatures and dryness. C4 plants contain two distinct types of photosynthetic cells, mesophyll and bundle sheath. The processes of assimilation and reduction of CO2 are separated spatiality and catayzed by two different enzymes. Only the bundle sheath chloroplasts perform the reactions of the Calvin-Benson cycle with the help of the Rubisco enzyme present exclusively in this cell type. The primary CO2 fixation occurs in mesophyll cells through the action of the phosphoenolpyruvate carboxylase. The light-dependent reactions of the photosynthesis occur exclusively in the latter cell type. These differences in photochemistry lead to distinct redox profiles in both types of cells. C4 plants are divided into three biochemical subtypes on the basis of differences in the mechanisms of decarboxylation of the C4 acids. C4 plants will provide the main source of food for humans and animals in the nearest decade.

  17. Complete amino acid sequence of the A chain of human complement-classical-pathway enzyme C1r.

    PubMed Central

    Arlaud, G J; Willis, A C; Gagnon, J

    1987-01-01

    The amino acid sequence of human C1r A chain was determined, from sequence analysis performed on fragments obtained from C1r autolytic cleavage, cleavage of methionyl bonds, tryptic cleavages at arginine and lysine residues, and cleavages by staphylococcal proteinase. The polypeptide chain has an N-terminal serine residue and contains 446 amino acid residues (Mr 51,200). The sequence data allow chemical characterization of fragments alpha (positions 1-211), beta (positions 212-279) and gamma (positions 280-446) yielded from C1r autolytic cleavage, and identification of the two major cleavage sites generating these fragments. Position 150 of C1r A chain is occupied by a modified amino acid residue that, upon acid hydrolysis, yields erythro-beta-hydroxyaspartic acid, and that is located in a sequence homologous to the beta-hydroxyaspartic acid-containing regions of Factor IX, Factor X, protein C and protein Z. Sequence comparison reveals internal homology between two segments (positions 10-78 and 186-257). Two carbohydrate moieties are attached to the polypeptide chain, both via asparagine residues at positions 108 and 204. Combined with the previously determined sequence of C1r B chain [Arlaud & Gagnon (1983) Biochemistry 22, 1758-1764], these data give the complete sequence of human C1r. PMID:3036070

  18. Toward a definition of the complete proteome of plant peroxisomes: Where experimental proteomics must be complemented by bioinformatics.

    PubMed

    Reumann, Sigrun

    2011-05-01

    In the past few years, proteome analysis of Arabidopsis peroxisomes has been established by the complementary efforts of four research groups and has emerged as the major unbiased approach to identify new peroxisomal proteins on a large scale. Collectively, more than 100 new candidate proteins from plant peroxisomes have been identified, including long-awaited low-abundance proteins. More than 50 proteins have been validated as peroxisome targeted, nearly doubling the number of established plant peroxisomal proteins. Sequence homologies of the new proteins predict unexpected enzyme activities, novel metabolic pathways and unknown non-metabolic peroxisome functions. Despite this remarkable success, proteome analyses of plant peroxisomes remain highly material intensive and require major preparative efforts. Characterization of the membrane proteome or post-translational protein modifications poses major technical challenges. New strategies, including quantitative mass spectrometry methods, need to be applied to allow further identifications of plant peroxisomal proteins, such as of stress-inducible proteins. In the long process of defining the complete proteome of plant peroxisomes, the prediction of peroxisome-targeted proteins from plant genome sequences emerges as an essential complementary approach to identify additional peroxisomal proteins that are, for instance, specific to peroxisome variants from minor tissues and organs or to abiotically stressed model and crop plants.

  19. Sundanese Complementation

    ERIC Educational Resources Information Center

    Kurniawan, Eri

    2013-01-01

    The focus of this thesis is the description and analysis of clausal complementation in Sundanese, an Austronesian language spoken in Indonesia. The thesis examined a range of clausal complement types in Sundanese, which consists of (i) "yen/(wi)rehna" "that" complements, (ii) "pikeun" "for" complements,…

  20. C4a: An Anaphylatoxin in Name Only.

    PubMed

    Barnum, Scott R

    2015-01-01

    Activation of complement leads to generation of the 3 anaphylatoxins C3a, C4a, and C5a. Although all 3 peptides are structurally similar, only C3a and C5a share a similar functional profile that includes the classic inflammatory activities and, more recently, developmental homing and regenerative properties among others. In contrast, the functional profile of C4a is questionable in most cases owing to contamination of C4a preparations with physiologically relevant levels of C3a and/or C5a. Combined with the absence of an identified C4a receptor and the inability of C4a to signal through the C3a and C5a receptors, it is clear that C4a should not be included in the family of complement anaphylatoxins.

  1. Complement Evasion by Pathogenic Leptospira.

    PubMed

    Fraga, Tatiana Rodrigues; Isaac, Lourdes; Barbosa, Angela Silva

    2016-01-01

    Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira. Pathogenic microorganisms, notably those which reach the blood circulation such as Leptospira, have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. Leptospira avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the Leptospira surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor Leptospira survival and multiplication in the host.

  2. Complement Evasion by Pathogenic Leptospira

    PubMed Central

    Fraga, Tatiana Rodrigues; Isaac, Lourdes; Barbosa, Angela Silva

    2016-01-01

    Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira. Pathogenic microorganisms, notably those which reach the blood circulation such as Leptospira, have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. Leptospira avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the Leptospira surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor Leptospira survival and multiplication in the host. PMID:28066433

  3. Encapsidation of poliovirus replicons encoding the complete human immunodeficiency virus type 1 gag gene by using a complementation system which provides the P1 capsid protein in trans.

    PubMed Central

    Porter, D C; Ansardi, D C; Morrow, C D

    1995-01-01

    Poliovirus genomes which contain small regions of the human immunodeficiency virus type 1 (HIV-1) gag, pol, and env genes substituted in frame for the P1 capsid region replicate and express HIV-1 proteins as fusion proteins with the P1 capsid precursor protein upon transfection into cells (W. S. Choi, R. Pal-Ghosh, and C. D. Morrow, J. Virol. 65:2875-2883, 1991). Since these genomes, referred to as replicons, do not express capsid proteins, a complementation system was developed to encapsidate the genomes by providing P1 capsid proteins in trans from a recombinant vaccinia virus, VV-P1. Virus stocks of encapsidated replicons were generated after serial passage of the replicon genomes into cells previously infected with VV-P1 (D. C. Porter, D. C. Ansardi, W. S. Choi, and C. D. Morrow, J. Virol. 67:3712-3719, 1993). Using this system, we have further defined the role of the P1 region in viral protein expression and RNA encapsidation. In the present study, we constructed poliovirus replicons which contain the complete 1,492-bp gag gene of HIV-1 substituted for the entire P1 region of poliovirus. To investigate whether the VP4 coding region was required for the replication and encapsidation of poliovirus RNA, a second replicon in which the complete gag gene was substituted for the VP2, VP3, and VP1 capsid sequences was constructed. Transfection of replicon RNA with and without the VP4 coding region into cells resulted in similar levels of expression of the HIV-1 Gag protein and poliovirus 3CD protein, as indicated by immunoprecipitation using specific antibodies. Northern (RNA) blot analysis of RNA from transfected cells demonstrated comparable levels of RNA replication for each replicon. Transfection of the replicon genomes into cells infected with VV-P1 resulted in the encapsidation of the genomes; serial passage in the presence of VV-P1 resulted in the generation of virus stocks of encapsidated replicons. Analysis of the levels of protein expression and encapsidated

  4. An evaluation of association between common variants in C4BPB/C4BPA genes and schizophrenia.

    PubMed

    Wang, Shuihong; Lu, Houquan; Ni, Jianliang; Zhang, Jiangtao; Tang, Wenxin; Lu, Weihong; Cai, Jun; Zhang, Chen

    2015-03-17

    Epidemiological studies have indicated that both maternal bacterial and viral infections during pregnancy increase the risk of schizophrenia among offspring, but to date there is not clear explanation for this increased risk. Previously, the decreased C4b-binding protein (C4BP), a potent circulating soluble inhibitor of the classical and lectin pathways of complement, was reported to be associated with risk of schizophrenia. Here, we analyzed 4 common single nucleotide polymorphisms (SNPs) of C4BPB and 5 SNPs of C4BPA in a group of 556 schizophrenia patients and a matched group of 610 healthy controls to see if the genes C4BPB and C4BPA, which encode C4BP, may confer a susceptibility to schizophrenia. Comparing the genotype and allele frequencies of those SNPs between cases and controls, we found no association between the C4BPB/C4BPA variants and schizophrenia. Our results provided preliminary evidence that C4BPB/C4BPA may not confer susceptibility to schizophrenia among Han Chinese. Further genetic studies from large-scale population are required to obtain more conclusive results.

  5. N-ethyl-N-nitrosourea mutagenesis of a 6- to 11-cM subregion of the Fah-Hbb interval of mouse chromosome 7: Completed testing of 4557 gametes and deletion mapping and complementation analysis of 31 mutations.

    PubMed

    Rinchik, E M; Carpenter, D A

    1999-05-01

    An interval of mouse chromosome (Chr) 7 surrounding the albino (Tyr; c) locus, and corresponding to a long 6- to 11-cM Tyr deletion, has been the target of a large-scale mutagenesis screen with the chemical supermutagen N-ethyl-N-nitrosourea (ENU). A segment of Chr 7, from a mutagenized genome bred from ENU-treated males, was made hemizygous opposite the long deletion for recognition and recovery of new recessive mutations that map within the albino deletion complex. Over 6000 pedigrees were analyzed, and 4557 of these were completely tested for mutations specifying both lethal and gross visible phenotypes. Thirty-one nonclustered mutations were identified and assigned to 10 complementation groups by pairwise trans-complementation crosses. Deletion-mapping analyses, using the extensive series of radiation-induced Tyr deletions, placed the loci defined by each of these complementation groups into defined intervals of the Tyr-region deletion map, which facilitates the identification of each locus on physical and transcription maps of the region. These mutations identified seven new loci and provided new ENU-induced alleles at three previously defined loci. Interestingly, no mutations were recovered that recapitulated three phenotypes defined by analysis of homozygous or partially complementing albino deletions. On the basis of our experience with this screen, we discuss a number of issues (e.g., locus mutability, failure to saturate, number of gametes to screen, allelic series) of concern when application of chemical mutagenesis screens to megabase regions of the mouse genome is considered.

  6. Multiple C4/Slp genes distinguished by expression after transfection.

    PubMed Central

    Robins, D M; Malissen, M; Hood, L; Ferreira, A; Walthall, D; Mitchell, M

    1986-01-01

    The S region of the murine major histocompatibility complex contains two closely related genes: C4, encoding the fourth component of complement, and Slp, encoding sex-limited protein. We cloned these genes from a cosmid library of the B10.W7R strain that does not show androgen regulation of the Slp protein. Restriction site polymorphisms revealed at least four C4-like genes within the Sw7 locus, indicating evolutionary amplification of this region. Transfection of these genes into L cells resulted in expression, processing, and secretion of immunologically correct C4 and Slp proteins. At least two different Slp genes and one C4 gene were capable, after transfection, of expressing C4 and Slp indistinguishable from macrophage-derived protein. A third Slp gene exists within this locus whose recombinant cognate did not express in L cells. Thus, the B10.W7R S region includes one C4 gene and at least three Slp-like genes. Images PMID:3023818

  7. Complements do not lie.

    PubMed

    Robert, Stefanie Christina; Forbes, Suzanne Helen; Soleimanian, Surusch; Hadley, Julia S

    2011-12-13

    A 74-year-old patient presented with constitutional symptoms and was found to have acute kidney injury. He was known to have a prosthetic aortic valve. He was febrile with splenomegaly and vasculitic lesions on both hands. Nephritic screen revealed strongly positive cytoplasmic-antineutrophil cytoplasmic antibodies (c-ANCA). Differential diagnosis thus included a small vessel vasculitis or infective endocarditis. Transoesophageal echocardiography demonstrated no vegetations and serial blood cultures were negative. Immunosuppression for presumed granulomatosis with polyangiitis (Wegeners granulomatosis) was therefore instituted. The patient deteriorated, requiring multi-organ support. Renal biopsy showed a proliferative glomerulopathy and complements were low. Atypical screen for culture negative endocarditis revealed a strongly positive IgG-antibody titre against Bartonella henselae. Immunosuppression was discontinued and treatment for chronic Bartonellosis commenced. The patient made a remarkable recovery. His renal function quickly returned to normal, and ANCA titres and complements normalised. He was discharged home after completing a 6 week course of antibiotic therapy.

  8. Complements do not lie

    PubMed Central

    Robert, Stefanie Christina; Forbes, Suzanne Helen; Soleimanian, Surusch; Hadley, Julia S

    2011-01-01

    A 74-year-old patient presented with constitutional symptoms and was found to have acute kidney injury. He was known to have a prosthetic aortic valve. He was febrile with splenomegaly and vasculitic lesions on both hands. Nephritic screen revealed strongly positive cytoplasmic-antineutrophil cytoplasmic antibodies (c-ANCA). Differential diagnosis thus included a small vessel vasculitis or infective endocarditis. Transoesophageal echocardiography demonstrated no vegetations and serial blood cultures were negative. Immunosuppression for presumed granulomatosis with polyangiitis (Wegeners granulomatosis) was therefore instituted. The patient deteriorated, requiring multi-organ support. Renal biopsy showed a proliferative glomerulopathy and complements were low. Atypical screen for culture negative endocarditis revealed a strongly positive IgG-antibody titre against Bartonella henselae. Immunosuppression was discontinued and treatment for chronic Bartonellosis commenced. The patient made a remarkable recovery. His renal function quickly returned to normal, and ANCA titres and complements normalised. He was discharged home after completing a 6 week course of antibiotic therapy. PMID:22674942

  9. Complements do not lie.

    PubMed

    Robert, Stefanie Christina; Forbes, Suzanne Helen; Soleimanian, Surusch; Hadley, Julia S

    2011-12-01

    A 74-year-old patient presented with constitutional symptoms and was found to have acute kidney injury. He was known to have a prosthetic aortic valve. He was febrile with splenomegaly and vasculitic lesions on both hands. Nephritic screen revealed strongly positive cytoplasmic-antineutrophil cytoplasmic antibodies (c-ANCA). Differential diagnosis thus included a small vessel vasculitis or infective endocarditis. Transoesophageal echocardiography demonstrated no vegetations and serial blood cultures were negative. Immunosuppression for presumed granulomatosis with polyangiitis (Wegeners granulomatosis) was therefore instituted. The patient deteriorated, requiring multi-organ support. Renal biopsy showed a proliferative glomerulopathy and complements were low. Atypical screen for culture negative endocarditis revealed a strongly positive IgG-antibody titre against Bartonella henselae. Immunosuppression was discontinued and treatment for chronic Bartonellosis commenced. The patient made a remarkable recovery. His renal function quickly returned to normal, and ANCA titres and complements normalised. He was discharged home after completing a 6 week course of antibiotic therapy.

  10. Reibergram of Intrathecal Synthesis of C4 in Patients with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis

    PubMed Central

    Padilla-Docal, Bárbara; Dorta-Contreras, Alberto Juan; Bu-Coifiu-Fanego, Raisa; Rodríguez-Rey, Alexis; Gutiérrez-Hernández, Juan Carlos; de Paula-Almeida, Susana Olga

    2010-01-01

    Angiostrongylus cantonensis produces eosinophilic meningitis in humans and is endemic in Thailand, Taiwan, China, and the Caribbean region. During infection with this parasite, it is important to know if the complement system may be activated by the classical or lectin pathway. Cerebrospinal fluid and serum samples from 20 patients with meningitic angiostrongyliasis were used to quantify C4 levels and albumin. Results were plotted on a C4 CSF/serum quotient diagram or Reibergram. Twelve patients showed intrathecal synthesis of C4. Antibody-dependent complement cytotoxicity should be considered as a possible mechanism that destroys third-stage larvae of this helminth in cerebrospinal fluid of affected patients. PMID:20519605

  11. Small passenger car transmission test; Ford C4 transmission

    NASA Technical Reports Server (NTRS)

    Bujold, M. P.

    1980-01-01

    A 1979 Ford C4 automatic transmission was tested per a passenger car automatic transmission test code (SAE J651b) which required drive performance, coast performance, and no load test conditions. Under these test conditions, the transmission attained maximum efficiencies in the mid-eighty percent range for both drive performance tests and coast performance tests. The major results of this test (torque, speed, and efficiency curves) are presented. Graphs map the complete performance characteristics for the Ford C4 transmission.

  12. 42 CFR 52c.4 - Application.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Application. 52c.4 Section 52c.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.4 Application. An institution interested in applying for a grant under this...

  13. 42 CFR 52c.4 - Application.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Application. 52c.4 Section 52c.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.4 Application. An institution interested in applying for a grant under this...

  14. 42 CFR 52c.4 - Application.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Application. 52c.4 Section 52c.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.4 Application. An institution interested in applying for a grant under this...

  15. 42 CFR 52c.4 - Application.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Application. 52c.4 Section 52c.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.4 Application. An institution interested in applying for a grant under this...

  16. 42 CFR 52c.4 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Application. 52c.4 Section 52c.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.4 Application. An institution interested in applying for a grant under this...

  17. DNase I hypersensitivity mapping and promoter polymorphism analysis of human C4

    SciTech Connect

    Vaishnaw, A.K.; Hargreaves, R.; Morley, B.J.

    1995-04-01

    Human complement component C4 is encoded by two structurally distinct loci in the major histocompatibility complex (MHC) class III region. The two isotypes, C4A and C4B, differ at only four residues in the C4d fragment, but C4 constitutes the most polymorphic of the complement components. It is not known, however, whether the regions involved in the regulation of C4 expression also display polymorphic variation. By using the technique of DNase I hypersensitivity mapping, we established that the only area of transcriptional activity for C4 in the hepatocyte cell line, HepG2, occurs approximately 500 base pairs upstream of the transcriptional start site. This region was found to be remarkably constant in sequence when analyzed in the context of differing MHC haplotypes including HLA B57, C4A6, C4B1, DR7, which has been correlated with reduced expression of the C4A isotype. Similarly, polymerase chain reaction followed by single-strand conformation polymorphism analysis failed to demonstrate any promoter polymorphisms in 103 individuals comprising 52 systemic lupus erythermatosus patients and 51 healthy controls. 36 refs., 3 figs., 2 tabs.

  18. Exploiting the engine of C(4) photosynthesis.

    PubMed

    Sage, Rowan F; Zhu, Xin-Guang

    2011-05-01

    Ever since the discovery of C(4) photosynthesis in the mid-1960s, plant biologists have envisaged the introduction of the C(4) photosynthetic pathway into C(3) crops such as rice and soybeans. Recent advances in genomics capabilities, and new evolutionary and developmental studies indicate that C(4) engineering will be feasible in the next few decades. Furthermore, better understanding of the function of C(4) photosynthesis provides new ways to improve existing C(4) crops and bioenergy species, for example by creating varieties with ultra-high water and nitrogen use efficiencies. In the case of C(4) engineering, the main enzymes of the C(4) metabolic cycle have already been engineered into various C(3) plants. In contrast, knowledge of the genes controlling Kranz anatomy lags far behind. Combining traditional genetics, high-throughput sequencing technologies, systems biology, bioinformatics, and the use of the new C(4) model species Setaria viridis, the discovery of the key genes controlling the expression of C(4) photosynthesis can be dramatically accelerated. Sustained investment in the research areas directly related to C(4) engineering has the potential for substantial return in the decades to come, primarily by increasing crop production at a time when global food supplies are predicted to fall below world demand.

  19. Schizophrenia risk from complex variation of complement component 4.

    PubMed

    Sekar, Aswin; Bialas, Allison R; de Rivera, Heather; Davis, Avery; Hammond, Timothy R; Kamitaki, Nolan; Tooley, Katherine; Presumey, Jessy; Baum, Matthew; Van Doren, Vanessa; Genovese, Giulio; Rose, Samuel A; Handsaker, Robert E; Daly, Mark J; Carroll, Michael C; Stevens, Beth; McCarroll, Steven A

    2016-02-11

    Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

  20. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    PubMed Central

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  1. The evolutionary ecology of C4 plants.

    PubMed

    Christin, Pascal-Antoine; Osborne, Colin P

    2014-12-01

    C4 photosynthesis is a physiological syndrome resulting from multiple anatomical and biochemical components, which function together to increase the CO2 concentration around Rubisco and reduce photorespiration. It evolved independently multiple times and C4 plants now dominate many biomes, especially in the tropics and subtropics. The C4 syndrome comes in many flavours, with numerous phenotypic realizations of C4 physiology and diverse ecological strategies. In this work, we analyse the events that happened in a C3 context and enabled C4 physiology in the descendants, those that generated the C4 physiology, and those that happened in a C4 background and opened novel ecological niches. Throughout the manuscript, we evaluate the biochemical and physiological evidence in a phylogenetic context, which demonstrates the importance of contingency in evolutionary trajectories and shows how these constrained the realized phenotype. We then discuss the physiological innovations that allowed C4 plants to escape these constraints for two important dimensions of the ecological niche--growth rates and distribution along climatic gradients. This review shows that a comprehensive understanding of C4 plant ecology can be achieved by accounting for evolutionary processes spread over millions of years, including the ancestral condition, functional convergence via independent evolutionary trajectories, and physiological diversification.

  2. Can Cell Bound Complement Activation Products Predict Inherited Complement Deficiency in Systemic Lupus Erythematosus?

    PubMed Central

    Waters, Barry

    2016-01-01

    Activation of the classical pathway complement system has long been implicated in stimulating immune complex mediated tissue destruction in systemic lupus erythematosus (SLE). C3 and C4 complement levels are utilized as part of SLE diagnosis and monitoring criteria. Recently, cell bound complement activation products (CBCAPs) have shown increased sensitivity in diagnosing and monitoring lupus activity, compared to traditional markers. CBCAPs are increasingly utilized in rheumatology practice as additional serological markers in evaluating SLE patients. We report a case of a patient diagnosed with SLE that had chronically low C3 and C4, along with negative CBCAPs. We surmise that the patient has an inherited complement deficiency as the etiology of her SLE and that CBCAPs could be used to predict such deficiency. PMID:28074166

  3. Despite phylogenetic effects, C3-C4 lineages bridge the ecological gap to C4 photosynthesis.

    PubMed

    Lundgren, Marjorie R; Christin, Pascal-Antoine

    2017-01-01

    C4 photosynthesis is a physiological innovation involving several anatomical and biochemical components that emerged recurrently in flowering plants. This complex trait evolved via a series of physiological intermediates, broadly termed 'C3-C4', which have been widely studied to understand C4 origins. While this research program has focused on biochemistry, physiology, and anatomy, the ecology of these intermediates remains largely unexplored. Here, we use global occurrence data and local habitat descriptions to characterize the niches of multiple C3-C4 lineages, as well as their close C3 and C4 relatives. While C3-C4 taxa tend to occur in warm climates, their abiotic niches are spread along other dimensions, making it impossible to define a universal C3-C4 niche. Phylogeny-based comparisons suggest that, despite shifts associated with photosynthetic types, the precipitation component of the C3-C4 niche is particularly lineage specific, being highly correlated with that of closely related C3 and C4 taxa. Our large-scale analyses suggest that C3-C4 lineages converged toward warm habitats, which may have facilitated the transition to C4 photosynthesis, effectively bridging the ecological gap between C3 and C4 plants. The intermediates retained some precipitation aspects of their C3 ancestors' habitat, and likely transmitted them to their C4 descendants, contributing to the diversity among C4 lineages seen today.

  4. Complement activation by antibodies to Sm in systemic lupus erythematosus.

    PubMed

    Sabharwal, U K; Fong, S; Hoch, S; Cook, R D; Vaughan, J H; Curd, J G

    1983-02-01

    An enzyme linked immunosorbent assay was developed to quantitate antibodies to Sm (anti-Sm) and to measure complement activation by anti-Sm in vitro. Anti-Sm in plasma of patients with systemic lupus erythematosus (SLE) were bound to purified Sm bound to polyvinyl chloride microtitre plates and assayed for bound IgG or IgM using enzyme linked anti-gamma or anti-mu. The activation of C4 by anti-Sm was measured by adding diluted normal human serum (complement) to the wells and quantitating the amount of C4 bound to the well surface using (Fab')2 goat anti-C4 followed by enzyme linked rabbit anti-goat IgG. The plasmas of 12 of 36 patients with SLE contained anti-Sm and all 12 activated complement (complement activating anti-Sm). Twenty-eight plasmas containing anti-Sm from 12 patients with SLE were studied. Ten of the 12 patients had anti-Sm of the IgG class whereas two had anti-Sm of both IgG and IgM classes. The amount of C4 activating anti-Sm correlated significantly with the in vivo activation of C4 measured by rocket immunoelectrophoresis for C4d and C4, suggesting that complement activation by anti-Sm is important in vivo.

  5. Complement associated pathogenic mechanisms in myasthenia gravis.

    PubMed

    Tüzün, Erdem; Christadoss, Premkumar

    2013-07-01

    The complement system is profoundly involved in the pathogenesis of acetylcholine receptor (AChR) antibody (Ab) related myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG). The most characteristic finding of muscle pathology in both MG and EAMG is the abundance of IgG and complement deposits at the nerve-muscle junction (NMJ), suggesting that AChR-Ab induces muscle weakness by complement pathway activation and consequent membrane attack complex (MAC) formation. This assumption has been supported with EAMG resistance of complement factor C3 knockout (KO), C4 KO and C5 deficient mice and amelioration of EAMG symptoms following treatment with complement inhibitors such as cobra venom factor, soluble complement receptor 1, anti-C1q, anti-C5 and anti-C6 Abs. Moreover, the complement inhibitor decay accelerating factor (DAF) KO mice exhibit increased susceptibility to EAMG. These findings have brought forward improvisation of novel therapy methods based on inhibition of classical and common complement pathways in MG treatment.

  6. Schizophrenia risk from complex variation of complement component 4

    PubMed Central

    Sekar, Aswin; Bialas, Allison R.; de Rivera, Heather; Davis, Avery; Hammond, Timothy R.; Kamitaki, Nolan; Tooley, Katherine; Presumey, Jessy; Baum, Matthew; Van Doren, Vanessa; Genovese, Giulio; Rose, Samuel A.; Handsaker, Robert E.; Daly, Mark J.; Carroll, Michael C.; Stevens, Beth; McCarroll, Steven A.

    2016-01-01

    Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia’s strongest genetic association at a population level involves variation in the Major Histocompatibility Complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to recognize. We show here that schizophrenia’s association with the MHC locus arises in substantial part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles promoted widely varying levels of C4A and C4B expression and associated with schizophrenia in proportion to their tendency to promote greater expression of C4A in the brain. Human C4 protein localized at neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals affected with schizophrenia. PMID:26814963

  7. CSF/serum quotient graphs for the evaluation of intrathecal C4 synthesis

    PubMed Central

    Padilla-Docal, Barbara; Dorta-Contreras, Alberto J; Bu-Coifiu-Fanego, Raisa; Rey, Alexis Rodriguez

    2009-01-01

    Background Cerebrospinal fluid (CSF)/serum quotient graphs have been used previously to determine local synthesis in brain of immunoglobulins and C3 complement component. The aim of this study was to use the same technique to construct quotient graphs, or Reibergrams, for the beta globulin C4 and to evaluate the method for assessing intrathecal synthesis in neurological disease. Methods The constants in the previously-defined Reibergram for immunoglobulin IgA were used to calculate the CSF/serum quotient for C4. CSF and serum were analyzed for C4, IgA and albumin from a total of 12 patients with meningoencephalitis caused by encapsulated microorganisms and 10 subjects without infections or inflammatory neurological disease, some of which had dysfunction of the blood-CSF barrier, Results The formula and C4 Reibergram with the constants previously found for IgA, determined the intrathecal C4 synthesis in CSF. The intrathecal C4 fraction in CSF (C4 loc in mg/l) was compared to the C4-Index (fraction of CSF: serum for C 4/fraction of CSF: serum for albumin). There was a significant correlation between the two formulae. The CSF/Serum quotient graph was superior for detecting intrathecal synthesis of C4 under variable conditions of blood-CSF barrier permeability. Conclusion The C4 Reibergram can be used to quantify the intrathecal synthesis of this component of the complement system in different infectious diseases of the central nervous system and is especially useful for patients with blood-brain barrier dysfunction. PMID:19573230

  8. Characterization of the complement inhibitory function of rhesus rhadinovirus complement control protein (RCP).

    PubMed

    Okroj, Marcin; Mark, Linda; Stokowska, Anna; Wong, Scott W; Rose, Nicola; Blackbourn, David J; Villoutreix, Bruno O; Spiller, O Brad; Blom, Anna M

    2009-01-02

    Rhesus rhadinovirus (RRV) is currently the closest known, fully sequenced homolog of human Kaposi sarcoma-associated herpesvirus. Both these viruses encode complement inhibitors as follows: Kaposi sarcoma-associated herpesvirus-complement control protein (KCP) and RRV-complement control protein (RCP). Previously we characterized in detail the functional properties of KCP as a complement inhibitor. Here, we performed comparative analyses for two variants of RCP protein, encoded by RRV strains H26-95 and 17577. Both RCP variants and KCP inhibited human and rhesus complement when tested in hemolytic assays measuring all steps of activation via the classical and the alternative pathway. RCP variants from both RRV strains supported C3b and C4b degradation by factor I and decay acceleration of the classical C3 convertase, similar to KCP. Additionally, the 17577 RCP variant accelerated decay of the alternative C3 convertase, which was not seen for KCP. In contrast to KCP, RCP showed no affinity to heparin and is the first described complement inhibitor in which the binding site for C3b/C4b does not interact with heparin. Molecular modeling shows a structural disruption in the region of RCP that corresponds to the KCP-heparin-binding site. This makes RRV a superior model for future in vivo investigations of complement evasion, as RCP does not play a supportive role in viral attachment as KCP does.

  9. Cold urticaria associated with C4 deficiency and elevated IgM.

    PubMed

    Stafford, C T; Jamieson, D M

    1986-04-01

    Various immunologic abnormalities have been implicated in cold urticaria. This is the first report of cold urticaria associated with C4 deficiency and elevated IgM. A 12-year-old male developed urticaria upon exposure to cold. He denied fever, purpura, hemoglobinuria, Raynaud's disease, or arthralgias. Family history was negative for cold urticaria. Immunologic studies revealed elevated IgM (186 mg/dL) as well as decreased CH100 and C4 (8.0 mg/dL). C1, C2, and C3 were normal. Ice cube skin test was positive, but passive transfer tests were negative. Biopsy was not diagnostic for vasculitis, although it revealed a few immunofluorescent deposits of IgM and C4. Complement genetic studies revealed deficiency of two half-null C4 haplotypes expressed as C4A*3QO and B*2QO.

  10. Do "savanna" chimpanzees consume C4 resources?

    PubMed

    Sponheimer, M; Loudon, J E; Codron, D; Howells, M E; Pruetz, J D; Codron, J; de Ruiter, D J; Lee-Thorp, J A

    2006-08-01

    Several stable carbon isotopic studies have shown that South African australopiths consumed significant quantities of C(4) resources (tropical grasses, sedges, or animals that eat those foods), but relatively little is known about the consumption of such resources by chimpanzees. Here, we present stable carbon isotopic data for 36 chimpanzee hair samples from Fongoli, one of the driest and most open areas inhabited by chimpanzees. These data suggest that the Fongoli chimpanzees consume little in the way of C(4) vegetation or animals that eat such vegetation, even though these resources are locally abundant and preferred fruits are more widely scattered than at most chimpanzee study sites. The homogeneity of the Fongoli results is especially striking and recalls the narrow isotopic distribution of stenotopic savanna mammals. This is in stark contrast to what has been observed for australopiths, which had highly variable diets and consumed about 35% C(4) vegetation on average. Carbon isotope data for modern and fossil Papio depict a dietarily variable genus with a tendency to consume C(4) vegetation. This trophic flexibility, or willingness to consume C(4) savanna resources, may make Papio a more profitable ecological analog for australopiths than chimpanzees.

  11. Rubisco gene expression in C4 plants.

    PubMed

    Patel, Minesh; Berry, James O

    2008-01-01

    In leaves of most C(4) plants, ribulose 1,5 bisphosphate carboxylase (Rubisco) accumulates only in bundle sheath (bs) cells that surround the vascular centres, and not in mesophyll (mp) cells. It has been shown previously that in the C(4) dicots amaranth and Flaveria bidentis, post-transcriptional control of mRNA translation and stability mediate the C(4) expression patterns of genes encoding the large and small Rubisco subunits (chloroplast rbcL and nuclear RbcS, respectively). Translational control appears to regulate bs cell-specific Rubisco gene expression during early dicot leaf development, while control of mRNA stability appears to mediate bs-specific accumulation of RbcS and rbcL transcripts in mature leaves. Post-transcriptional control is also involved in the regulation of Rubisco gene expression by light, and in response to photosynthetic activity. Transgenic and transient expression studies in F. bidentis provide direct evidence for post-transcriptional control of bs cell-specific RbcS expression, which is mediated by the 5' and 3' untranslated regions (UTRs) of the mRNA. Comparisons of Rubisco gene expression in these dicots and in the monocot maize indicates possible commonalities in the regulation of RbcS and rbcL genes in these divergent C(4) species. Now that the role of post-transcriptional regulation in C(4) gene expression has been established, it is likely that future studies of mRNA-protein interactions will address long-standing questions about the establishment and maintenance of cell type-specificity in these plants. Some of these regulatory mechanisms may have ancestral origins in C(3) species, through modification of pre-existing factors, or by the acquisition of novel C(4) processes.

  12. Ectromelia virus inhibitor of complement enzymes protects intracellular mature virus and infected cells from mouse complement.

    PubMed

    Moulton, Elizabeth A; Bertram, Paula; Chen, Nanhai; Buller, R Mark L; Atkinson, John P

    2010-09-01

    Poxviruses produce complement regulatory proteins to subvert the host's immune response. Similar to the human pathogen variola virus, ectromelia virus has a limited host range and provides a mouse model where the virus and the host's immune response have coevolved. We previously demonstrated that multiple components (C3, C4, and factor B) of the classical and alternative pathways are required to survive ectromelia virus infection. Complement's role in the innate and adaptive immune responses likely drove the evolution of a virus-encoded virulence factor that regulates complement activation. In this study, we characterized the ectromelia virus inhibitor of complement enzymes (EMICE). Recombinant EMICE regulated complement activation on the surface of CHO cells, and it protected complement-sensitive intracellular mature virions (IMV) from neutralization in vitro. It accomplished this by serving as a cofactor for the inactivation of C3b and C4b and by dissociating the catalytic domain of the classical pathway C3 convertase. Infected murine cells initiated synthesis of EMICE within 4 to 6 h postinoculation. The levels were sufficient in the supernatant to protect the IMV, upon release, from complement-mediated neutralization. EMICE on the surface of infected murine cells also reduced complement activation by the alternative pathway. In contrast, classical pathway activation by high-titer antibody overwhelmed EMICE's regulatory capacity. These results suggest that EMICE's role is early during infection when it counteracts the innate immune response. In summary, ectromelia virus produced EMICE within a few hours of an infection, and EMICE in turn decreased complement activation on IMV and infected cells.

  13. Enhancing drought tolerance in C(4) crops.

    PubMed

    Lopes, Marta S; Araus, Jose Luis; van Heerden, Philippus D R; Foyer, Christine H

    2011-05-01

    Adaptation to abiotic stresses is a quantitative trait controlled by many different genes. Enhancing the tolerance of crop plants to abiotic stresses such as drought has therefore proved to be somewhat elusive in terms of plant breeding. While many C(4) species have significant agronomic importance, most of the research effort on improving drought tolerance has focused on maize. Ideally, drought tolerance has to be achieved without penalties in yield potential. Possibilities for success in this regard are highlighted by studies on maize hybrids performed over the last 70 years that have demonstrated that yield potential and enhanced stress tolerance are associated traits. However, while our understanding of the molecular mechanisms that enable plants to tolerate drought has increased considerably in recent years, there have been relatively few applications of DNA marker technologies in practical C(4) breeding programmes for improved stress tolerance. Moreover, until recently, targeted approaches to drought tolerance have concentrated largely on shoot parameters, particularly those associated with photosynthesis and stay green phenotypes, rather than on root traits such as soil moisture capture for transpiration, root architecture, and improvement of effective use of water. These root traits are now increasingly considered as important targets for yield improvement in C(4) plants under drought stress. Similarly, the molecular mechanisms underpinning heterosis have considerable potential for exploitation in enhancing drought stress tolerance. While current evidence points to the crucial importance of root traits in drought tolerance in C(4) plants, shoot traits may also be important in maintaining high yields during drought.

  14. On the smell of Composition C-4.

    PubMed

    Kranz, William; Kitts, Kelley; Strange, Nicholas; Cummins, Joshua; Lotspeich, Erica; Goodpaster, John

    2014-03-01

    In efforts to locate hidden explosives, humans have had few allies as valuable as the explosives-detecting canine. The unrivaled sensitivity and selectivity of the canine nose have combined to make these animals an attractive choice for law enforcement, military, and private security applications. Although the efficacy of trained detector dogs is well-established, the question of which chemical compounds are responsible for causing a dog to recognize a particular odor and alert to it remains a subject of debate for several explosive formulations--including, perhaps most notably, Composition C-4. Previous studies have indicated that cyclohexanone, 2,3-dimethyl-2,3-dinitrobutane, and 2-ethyl-1-hexanol are the chemicals that may cause canines to alert to C-4. This has led to the suggestion that these substances could be used as a substitute for genuine C-4 in the training, testing, and maintenance of explosives-detecting canines. In this paper, we present an alternative view. Using gas chromatography-mass spectrometry with solid phase microextraction as a pre-concentration technique, we have discovered that 2-ethyl-1-hexanol off-gasses not only from C-4, but also from benign sources, such as the common plasticizers bis(2-ethylhexyl)adipate, bis(2-ethylhexyl)sebacate, and bis(2-ethylhexyl)phthalate; as well as several plasticized items common to our everyday world, including PVC tile, PVC pipe, electrical tape, and credit cards. This observation may potentially discourage the use of 2-ethyl-1-hexanol for training purposes. We also present the results of our own canine field trials focused on the detection of C-4. Through the use of contingency tables and statistical testing, we demonstrate the failure of trained law enforcement dogs in our study to respond in any significant way to these potential odor compounds.

  15. Complement in autoimmune diseases.

    PubMed

    Vignesh, Pandiarajan; Rawat, Amit; Sharma, Madhubala; Singh, Surjit

    2017-02-01

    The complement system is an ancient and evolutionary conserved element of the innate immune mechanism. It comprises of more than 20 serum proteins most of which are synthesized in the liver. These proteins are synthesized as inactive precursor proteins which are activated by appropriate stimuli. The activated forms of these proteins act as proteases and cleave other components successively in amplification pathways leading to exponential generation of final effectors. Three major pathways of complement pathways have been described, namely the classical, alternative and lectin pathways which are activated by different stimuli. However, all the 3 pathways converge on Complement C3. Cleavage of C3 and C5 successively leads to the production of the membrane attack complex which is final common effector. Excessive and uncontrolled activation of the complement has been implicated in the host of autoimmune diseases. But the complement has also been bemusedly described as the proverbial "double edged sword". On one hand, complement is the final effector of tissue injury in autoimmune diseases and on the other, deficiencies of some components of the complement can result in autoimmune diseases. Currently available tools such as enzyme based immunoassays for functional assessment of complement pathways, flow cytometry, next generation sequencing and proteomics-based approaches provide an exciting opportunity to study this ancient yet mysterious element of innate immunity.

  16. Targeting complement in therapy.

    PubMed

    Kirschfink, M

    2001-04-01

    With increasing evidence that complement activation significantly contributes to the pathogenesis of a large number of inflammatory diseases, strategies that interfere with its deleterious action have become a major focus in pharmacological research. Endogenous soluble complement inhibitors (C1 inhibitor, recombinant soluble complement receptor 1, antibodies) blocking key proteins of the cascade reaction, neutralizing the action of the complement-derived anaphylatoxin C5a, or interfering with complement receptor 3 (CR3, CD18/11b)-mediated adhesion of inflammatory cells to the vascular endothelium have successfully been tested in various animal models over the past years. Promising results consequently led to clinical trials. Furthermore, incorporation of membrane-bound complement regulators (decay-accelerating factor (CD55), membrane co-factor protein (CD46), CD59) in transgenic animals has provided a major step forward in protecting xenografts from hyperacute rejection. At the same time, the poor contribution of complement to the antitumor response, which is caused by multiple resistance mechanisms that hamper the efficacy of antibody-based tumor therapy, is increasingly recognized and requires pharmacologic intervention. First attempts have now been made to interfere with the resistance mechanisms, thereby improving complement-mediated tumor cell destruction.

  17. Climate-driven C4 plant distributions in China: divergence in C4 taxa

    NASA Astrophysics Data System (ADS)

    Wang, Renzhong; Ma, Linna

    2016-06-01

    There have been debates on the driving factors of C4 plant expansion, such as PCO2 decline in the late Micocene and warmer climate and precipitation at large-scale modern ecosystems. These disputes are mainly due to the lack of direct evidence and extensive data analysis. Here we use mass flora data to explore the driving factors of C4 distribution and divergent patterns for different C4 taxa at continental scale in China. The results display that it is mean annual climate variables driving C4 distribution at present-day vegetation. Mean annual temperature is the critical restriction of total C4 plants and the precipitation gradients seem to have much less impact. Grass and sedge C4 plants are largely restricted to mean annual temperature and precipitation respectively, while Chenopod C4 plants are strongly restricted by aridity in China. Separate regression analysis can succeed to detect divergences of climate distribution patterns of C4 taxa at global scale.

  18. Climate-driven C4 plant distributions in China: divergence in C4 taxa

    PubMed Central

    Wang, Renzhong; Ma, Linna

    2016-01-01

    There have been debates on the driving factors of C4 plant expansion, such as PCO2 decline in the late Micocene and warmer climate and precipitation at large-scale modern ecosystems. These disputes are mainly due to the lack of direct evidence and extensive data analysis. Here we use mass flora data to explore the driving factors of C4 distribution and divergent patterns for different C4 taxa at continental scale in China. The results display that it is mean annual climate variables driving C4 distribution at present-day vegetation. Mean annual temperature is the critical restriction of total C4 plants and the precipitation gradients seem to have much less impact. Grass and sedge C4 plants are largely restricted to mean annual temperature and precipitation respectively, while Chenopod C4 plants are strongly restricted by aridity in China. Separate regression analysis can succeed to detect divergences of climate distribution patterns of C4 taxa at global scale. PMID:27302686

  19. Complement activation in chronic liver disease.

    PubMed Central

    Munoz, L E; De Villiers, D; Markham, D; Whaley, K; Thomas, H C

    1982-01-01

    Patients with HBsAg positive chronic active liver disease (CALD) and primary biliary cirrhosis (PBC) exhibit increased C3d concentrations and changes in the serum concentrations of the complement components consistent with activation of the classical and alternative pathways. In these patients the concentrations of the regulatory proteins, C3b inactivator (C3bINA) and beta IH globulin, are normal. Patients with HBsAg negative CALD and alcohol induced liver disease (ALD) exhibit no evidence of an increased level of complement system activation. In these patients diminished serum concentrations of complement components appear to be related to diminished hepatic synthetic function. C4 synthesis may be specifically reduced in autoimmune chronic active liver disease. PMID:7083631

  20. Erythrocyte C3d and C4d for Monitoring Disease Activity in Systemic Lupus Erythematosus

    PubMed Central

    Kao, Amy H.; Navratil, Jeannine S.; Ruffing, Margie J.; Liu, Chau-Ching; Hawkins, Douglas; McKinnon, Kathleen M.; Danchenko, Natalya; Ahearn, Joseph M.; Manzi, Susan

    2010-01-01

    Objective Disease activity in systemic lupus erythematosus (SLE) is typically monitored by measuring serum C3 and C4. However, these proteins have limited utility as lupus biomarkers, because they are substrates rather than products of complement activation. The aim of this study was to evaluate the utility of measuring the erythrocyte-bound complement activation products, erythrocyte-bound C3d (E-C3d) and E-C4d, compared with that of serum C3 and C4 for monitoring disease activity in patients with SLE. Methods The levels of E-C3d and E-C4d were measured by flow cytometry in 157 patients with SLE, 290 patients with other diseases, and 256 healthy individuals. The patients with SLE were followed up longitudinally. Disease activity was measured at each visit, using the validated Systemic Lupus Activity Measure (SLAM) and the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Results At baseline, patients with SLE had higher median levels of E-C3d and E-C4d (P < 0.0001) in addition to higher within-patient and between-patient variability in both E-C3d and E-C4d when compared with the 2 non-SLE groups. In a longitudinal analysis of patients with SLE, E-C3d, E-C4d, serum C3, and anti–double-stranded DNA (anti-dsDNA) antibodies were each significantly associated with the SLAM and SELENA–SLEDAI. In a multivariable analysis, E-C4d remained significantly associated with these SLE activity measures after adjusting for serum C3, C4, and anti-dsDNA antibodies; however, E-C3d was associated with the SLAM but not with the SELENA–SLEDAI. Conclusion Determining the levels of the erythrocyte-bound complement activation products, especially E-C4d, is an informative measure of SLE disease activity as compared with assessing serum C4 levels and should be considered for monitoring disease activity in patients with SLE. PMID:20187154

  1. Operational Protection of C4I.

    DTIC Science & Technology

    2007-11-02

    The American way of war has been dependent upon information dominance in the battlefield for a long time. But the old ways of waging wars where the overwhelming force of the US provided a clear advantage may not be successful in fighting the wars of the future. This paper explores some of the problems associated with the protection of operational C4I assets in the current era and how CINCs can approach this planning issue.

  2. Cometary Coma Chemical Composition (C4) Mission

    NASA Technical Reports Server (NTRS)

    Carle, Glenn C.; Clark, Benton C.; Knocke, Philip C.; OHara, Bonnie J.; Adams, Larry; Niemann, Hasso B.; Alexander, Merle; Veverka, Joseph; Goldstein, Raymond; Huebner, Walter; Morrison, David (Technical Monitor)

    1994-01-01

    Cometary exploration remains of great importance to virtually all of space science. Because comets are presumed to be remnants of the early solar nebula, they are expected to provide fundamental knowledge as to the origin and development of the solar system as well as to be key to understanding of the source of volatiles and even life itself in the inner solar system. Clearly the time for a detailed study of the composition of these apparent messages from the past has come. A comet rendezvous mission, the Cometary Coma Chemical Composition (C4) Mission, is now being studied as a candidate for the new Discovery program. This mission is a highly-focussed and usefully-limited subset of the Cometary Rendezvous Asteroid Flyby (CRAF) Mission. The C4 mission will concentrate on measurements that will produce an understanding of the composition and physical makeup of a cometary nucleus. The core science goals of the C4 mission are 1) to determine the chemical, elemental, and isotopic composition of a cometary nucleus and 2) to characterize the chemical and isotopic nature of its atmosphere. A related goal is to obtain temporal information about the development of the cometary coma as a function of time and orbital position. The four short-period comets -- Tempel 1, Tempel 2, Churyumov-Gerasimenko, and Wirtanen -which all appear to have acceptable dust production rates, were identified as candidate targets. Mission opportunities have been identified beginning as early as 1998. Tempel I with a launch in 1999, however, remains the baseline comet for studies of and planning the C4 mission. The C4 mission incorporates two science instruments and two engineering instruments in the payload to obtain the desired measurements. The science instruments include an advanced version of the Cometary Ice and Dust Experiment (CIDEX), a mini-CIDEX with a sample collection system, an X-ray Fluorescence Spectrometer and a Pyrolysis-Gas Chromatograph, and a simplified version of the Neutral

  3. Phylogeny of C4-photosynthesis enzymes based on algal transcriptomic and genomic data supports an archaeal/proteobacterial origin and multiple duplication for most C4-related genes.

    PubMed

    Chi, Shan; Wu, Shuangxiu; Yu, Jun; Wang, Xumin; Tang, Xuexi; Liu, Tao

    2014-01-01

    Both Calvin-Benson-Bassham (C3) and Hatch-Slack (C4) cycles are most important autotrophic CO2 fixation pathways on today's Earth. C3 cycle is believed to be originated from cyanobacterial endosymbiosis. However, studies on evolution of different biochemical variants of C4 photosynthesis are limited to tracheophytes and origins of C4-cycle genes are not clear till now. Our comprehensive analyses on bioinformatics and phylogenetics of novel transcriptomic sequencing data of 21 rhodophytes and 19 Phaeophyceae marine species and public genomic data of more algae, tracheophytes, cyanobacteria, proteobacteria and archaea revealed the origin and evolution of C4 cycle-related genes. Almost all of C4-related genes were annotated in extensive algal lineages with proteobacterial or archaeal origins, except for phosphoenolpyruvate carboxykinase (PCK) and aspartate aminotransferase (AST) with both cyanobacterial and archaeal/proteobacterial origin. Notably, cyanobacteria may not possess complete C4 pathway because of the flawed annotation of pyruvate orthophosphate dikinase (PPDK) genes in public data. Most C4 cycle-related genes endured duplication and gave rise to functional differentiation and adaptation in different algal lineages. C4-related genes of NAD-ME (NAD-malic enzyme) and PCK subtypes exist in most algae and may be primitive ones, while NADP-ME (NADP-malic enzyme) subtype genes might evolve from NAD-ME subtype by gene duplication in chlorophytes and tracheophytes.

  4. Complement activation by Coccidioides immitis: in vitro and clinical studies.

    PubMed Central

    Galgiani, J N; Yam, P; Petz, L D; Williams, P L; Stevens, D A

    1980-01-01

    Mycelial- or spherule-phase derivatives of Coccidioides immitis caused a decrease in vitro of total hemolytic complement in serum from a nonsensitized person. Activation involved both classic and alternative pathways as shown by deprssion of hemolytic C4 and by generation of products of activation of components C3, C4, and factor B. In addition, functional complement activity or immunoreactive levels of complement components or both were measured in 23 patients with self-limited or disseminated coccidioidomycosis. Low total hemolytic complement was found in nine, usually during the early phase of primary illness, and was transient. Hemolytic C4 was low, and the effect of inulin to decrease complement levels was blunted, suggested both classic and alternative pathways may be deficient. However, associated depression of immunoreactive levels of components assayed (C3, C4, C5, factor B, and properdin) was not consistently found. This disparity raises the possibility of enhanced in vitro inactivation analogous to activation by immune complexes. Images Fig. 2 PMID:6901703

  5. The effects of soluble recombinant complement receptor 1 on complement-mediated experimental glomerulonephritis.

    PubMed

    Couser, W G; Johnson, R J; Young, B A; Yeh, C G; Toth, C A; Rudolph, A R

    1995-05-01

    Complement is a major mediator of tissue injury in several types of glomerulonephritis. However, no therapeutic agents that inhibit complement activation are available for human use. sCR1 (TP10, BRL 55736) is a recombinant, soluble human complement receptor 1 (CR1) molecule lacking transmembrane and cytoplasmic domains that inhibits C3 and C5 convertase activity by preferentially binding C4b and C3b. To test the efficacy of sCR1 on complement-mediated glomerulonephritis, rats were pretreated with sCR1 (60 mg/kg per day) before and during the induction of three models of complement-dependent glomerulonephritis (concanavalin A and antithymocyte serum models of proliferative glomerulonephritis, passive Heyman nephritis). Daily sCR1 and complement hemolytic activity levels were measured, and renal histology and urine protein excretion were examined. Mean serum sCR1 levels of 100 to 200 micrograms/mL were maintained with a reduction in complement hemolytic activity to less than 15% in most animals. In the antithymocyte serum model, sCR1-treated animals had significant reductions in mesangiolysis, glomerular platelet and macrophage infiltrates, and proteinuria at 48 h. In the concanavalin A model, sCR1 significantly reduced glomerular C3 and fibrin deposits, platelet infiltrates, and proteinuria at 48 h. In passive Heymann nephritis, proteinuria was also significantly reduced (199 +/- 8.5 versus 125 +/- 16 mg/day, P < 0.002) at 5 days. It was concluded that sCR1 significantly reduces both morphologic and functional consequences of several different types of complement-mediated glomerulonephritis and deserves evaluation as a potential therapeutic agent in complement-mediated immune glomerular disease in humans.

  6. Monoclonal antipeptide antibodies against amino acid residues 1101-1106 of human C4 distinguish C4A from C4B.

    PubMed

    Reilly, B D; Levine, P; Rothbard, J; Skanes, V M

    1991-01-01

    Comparison of amino acid sequences of the alpha-chain fragment of human C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 in which the aspartic acid-histidine substitution at position 1106 may be related to the amide and ester bond forming properties of these molecules. Peptides containing twelve amino acid residues of the C4A- or C4B-specific sequences were synthesized and injected into female Balb/c mice. Serum from 2 mice, one immunized with the C4A-specific peptide and the other with the C4B-specific peptide, gave strong isotype-specific responses in an enzyme-linked immunosorbent assay against affinity-purified C4A3 and C4B2B1. Spleen cells from these mice were fused with the mouse myeloma SP2/0-Ag 14, and two cloned cell lines, AII-1 and BII-1, were established from hybrids. Enzyme-linked immunosorbent assay and western blotting of monoclonal antibodies AII-1 and BII-1 show that the former reacts with the C4A but not with the C4B alpha-chain and the latter with C4B but not with the C4A alpha-chain. Furthermore, immunoblotting of C4 allelic variants showed that AII-1 reacted with all C4A allotypes tested, including A6, A4, A3 and A2, whereas BII-1 reacted with all C4B allotypes tested, including B5, B3, B2, and B1.

  7. Copper Causes Regiospecific Formation of C4 F8 -Containing Six-Membered Rings and their Defluorination/Aromatization to C4 F4 -Containing Rings in Triphenylene/1,4-C4 F8 I2 Reactions.

    PubMed

    Rippy, Kerry C; Bukovsky, Eric V; Clikeman, Tyler T; Chen, Yu-Sheng; Hou, Gao-Lei; Wang, Xue-Bin; Popov, Alexey A; Boltalina, Olga V; Strauss, Steven H

    2016-01-18

    The presence of Cu in reactions of triphenylene (TRPH) and 1,4-C4 F8 I2 at 360 °C led to regiospecific substitution of TRPH ortho C(β) atoms to form C4 F8 -containing rings, completely suppressing substitution on C(α) atoms. In addition, Cu caused selective reductive-defluorination/aromatization (RD/A) to form C4 F4 -containing aromatic rings. Without Cu, the reactions of TRPH and 1,4-C4 F8 I2 were not regiospecific and no RD/A was observed. These results, supported by DFT calculations, are the first examples of Cu-promoted 1) regiospecific perfluoroannulation, 2) preparative C-F activation, and 3) RD/A. HPLC-purified products were characterized by X-ray diffraction, low-temperature PES, and (1) H/(19) F NMR.

  8. Copper Causes Regiospecific Formation of C4F8-Containing Six-Membered Rings and their Defluorination/Aromatization to C4F4-Containing Rings in Triphenylene/1,4-C4F8I2 Reactions

    SciTech Connect

    Rippy, Kerry C.; Bukovsky, Eric V.; Clikeman, Tyler T.; Chen, Yu-Sheng; Hou, Gao-Lei; Wang, Xue B.; Popov, Alexey; Boltalina, Olga V.; Strauss, Steven H.

    2016-01-18

    The presence of Cu in reactions of triphenylene (TRPH) and 1,4-C4F8I2 at 360 °C led to regiospecific substitution of TRPH ortho C(β) atoms to form C4F8-containing rings, completely suppressing substitution on C(α) atoms. In addition, Cu caused selective reductive-defluorination/aromatization (RD/A) to form C4F4- containing aromatic rings. Without Cu, the reactions of TRPH and 1,4- C4F8I2 were not regiospecific and no RD/A was observed. These results, supported by DFT calculations, are the first examples of Cupromoted (i) regiospecific perfluoroannulation, (ii) preparative C–F activation, and (iii) RD/A. HPLC-purified products were characterized by X-ray diffraction, low-temperature PES, and 1H/19F NMR.

  9. Incorporation of Host Complement Regulatory Proteins into Newcastle Disease Virus Enhances Complement Evasion

    PubMed Central

    Biswas, Moanaro; Johnson, John B.; Kumar, Sandeep R. P.; Parks, Griffith D.

    2012-01-01

    Newcastle disease virus (NDV), an avian paramyxovirus, is inherently tumor selective and is currently being considered as a clinical oncolytic virus and vaccine vector. In this study, we analyzed the effect of complement on the neutralization of NDV purified from embryonated chicken eggs, a common source for virus production. Fresh normal human serum (NHS) neutralized NDV by multiple pathways of complement activation, independent of neutralizing antibodies. Neutralization was associated with C3 deposition and the activation of C2, C3, C4, and C5 components. Interestingly, NDV grown in mammalian cell lines was resistant to complement neutralization by NHS. To confirm whether the incorporation of regulators of complement activity (RCA) into the viral envelope afforded complement resistance, we grew NDV in CHO cells stably transfected with CD46 or HeLa cells, which strongly express CD46 and CD55. NDV grown in RCA-expressing cells was resistant to complement by incorporating CD46 and CD55 on virions. Mammalian CD46 and CD55 molecules on virions exhibited homologous restriction, since chicken sera devoid of neutralizing antibodies to NDV were able to effectively neutralize these virions. The incorporation of chicken RCA into NDV produced in embryonated eggs similarly provided species specificity toward chicken sera. PMID:22973037

  10. From proto-Kranz to C4 Kranz: building the bridge to C4 photosynthesis.

    PubMed

    Sage, Rowan F; Khoshravesh, Roxana; Sage, Tammy L

    2014-07-01

    In this review, we examine how the specialized "Kranz" anatomy of C4 photosynthesis evolved from C3 ancestors. Kranz anatomy refers to the wreath-like structural traits that compartmentalize the biochemistry of C4 photosynthesis and enables the concentration of CO2 around Rubisco. A simplified version of Kranz anatomy is also present in the species that utilize C2 photosynthesis, where a photorespiratory glycine shuttle concentrates CO2 into an inner bundle-sheath-like compartment surrounding the vascular tissue. C2 Kranz is considered to be an intermediate stage in the evolutionary development of C4 Kranz, based on the intermediate branching position of C2 species in 14 evolutionary lineages of C4 photosynthesis. In the best-supported model of C4 evolution, Kranz anatomy in C2 species evolved from C3 ancestors with enlarged bundle sheath cells and high vein density. Four independent lineages have been identified where C3 sister species of C2 plants exhibit an increase in organelle numbers in the bundle sheath and enlarged bundle sheath cells. Notably, in all of these species, there is a pronounced shift of mitochondria to the inner bundle sheath wall, forming an incipient version of the C2 type of Kranz anatomy. This incipient version of C2 Kranz anatomy is termed proto-Kranz, and is proposed to scavenge photorespiratory CO2. By doing so, it may provide fitness benefits in hot environments, and thus represent a critical first stage of the evolution of both the C2 and C4 forms of Kranz anatomy.

  11. Association between C4, C4A, and C4B copy number variations and susceptibility to autoimmune diseases: a meta-analysis

    PubMed Central

    Li, Na; Zhang, Jun; Liao, Dan; Yang, Lu; Wang, Yingxiong; Hou, Shengping

    2017-01-01

    Although several studies have investigated the association between C4, C4A, and C4B gene copy number variations (CNVs) and susceptibility to autoimmune diseases, the results remain inconsistency for those diseases. Thus, in this study, a comprehensive meta-analysis was conducted to assess the role of C4, C4A, and C4B CNVs in autoimmune diseases in different ethnic groups. A total of 16 case-control studies described in 12 articles (8663 cases and 11099 controls) were included in this study. The pooled analyses showed that a low C4 gene copy number (GCN) (<4) was treated as a significant risk factor (odds ratio [OR] = 1.46, 95% confidence interval [CI] = 1.19–1.78) for autoimmune diseases compared with a higher GCN (>4). The pooled statistical results revealed that low C4 (<4) and low C4A (<2) GCNs could be risk factors for systemic lupus erythematosus (SLE) in Caucasian populations. Additionally, the correlation between C4B CNVs and all type of autoimmune diseases could not be confirmed by the current meta-analysis (OR = 1.07, 95% CI = 0.93–1.24). These data suggest that deficiency or absence of C4 and C4A CNVs may cause susceptibility to SLE. PMID:28205620

  12. Complement and Antibody-Mediated Enhancement of Erythrocyte Invasion by Plasmodium Falciparum

    DTIC Science & Technology

    2016-04-01

    take place via antibody-dependent or independent mechanisms. Complement is activated during malaria infection (4), especially in the presence of...that complement activation during malaria infection enhances the invasion of RBCs by P. falciparum. In this research we tested our hypothesis by... infection have an enhancing effect on invasion and, if so, what is the mechanism. A - C3/C4 + C3/C4 % I n h ib it io n -10 -5 0 5 10 15 - C3/C4 + C3/C4

  13. Complement activation promotes muscle inflammation during modified muscle use

    NASA Technical Reports Server (NTRS)

    Frenette, J.; Cai, B.; Tidball, J. G.

    2000-01-01

    Modified muscle use can result in muscle inflammation that is triggered by unidentified events. In the present investigation, we tested whether the activation of the complement system is a component of muscle inflammation that results from changes in muscle loading. Modified rat hindlimb muscle loading was achieved by removing weight-bearing from the hindlimbs for 10 days followed by reloading through normal ambulation. Experimental animals were injected with the recombinant, soluble complement receptor sCR1 to inhibit complement activation. Assays for complement C4 or factor B in sera showed that sCR1 produced large reductions in the capacity for activation of the complement system through both the classical and alternative pathways. Analysis of complement C4 concentration in serum in untreated animals showed that the classical pathway was activated during the first 2 hours of reloading. Analysis of factor B concentration in untreated animals showed activation of the alternative pathway at 6 hours of reloading. Administration of sCR1 significantly attenuated the invasion of neutrophils (-49%) and ED1(+) macrophages (-52%) that occurred in nontreated animals after 6 hours of reloading. The presence of sCR1 also reduced significantly the degree of edema by 22% as compared to untreated animals. Together, these data show that increased muscle loading activated the complement system which then briefly contributes to the early recruitment of inflammatory cells during modified muscle loading.

  14. Outline of Hungarian Complementation.

    ERIC Educational Resources Information Center

    Szamosi, Michael

    This study presents a preliminary analysis of Hungarian complement constructions and the syntactic operations needed to account for them. The expository framework (and the implicit framework of the research itself) is based upon that of Rosenbaum (1967). The aim of the paper is to arrive at a rough picture of the kinds of structures and syntactic…

  15. Verbal Complementizers in Arabic

    ERIC Educational Resources Information Center

    Ahmed, Hossam Eldin Ibrahim

    2015-01-01

    A class of Modern Standard Arabic complementizers known as "'?inna' and its sisters" demonstrate unique case and word order restrictions. While CPs in Arabic allow both Subject-Verb (SV) and Verb-Subject (VS) word order and their subjects show nominative morphology, CPs introduced by "?inna" ban a verb from directly following…

  16. 29 CFR 2560.502c-4 - Civil penalties under section 502(c)(4).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... determined by the Department of Labor, taking into consideration the degree or willfulness of the failure or... for each violation under section 502(c)(4) of the Act shall not exceed $1,000 a day (or such other... applicable, or on a showing by such person of mitigating circumstances regarding the degree or willfulness...

  17. 29 CFR 2560.502c-4 - Civil penalties under section 502(c)(4).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... determined by the Department of Labor, taking into consideration the degree or willfulness of the failure or... for each violation under section 502(c)(4) of the Act shall not exceed $1,000 a day (or such other... applicable, or on a showing by such person of mitigating circumstances regarding the degree or willfulness...

  18. Tracking the evolutionary rise of C4 metabolism

    PubMed Central

    2016-01-01

    Upregulation of the C4 metabolic cycle is a major step in the evolution of C4 photosynthesis. Why this happened remains unclear, in part because of difficulties measuring the C4 cycle in situ in C3-C4 intermediate species. Now, Alonso-Cantabrana and von Caemmerer (2016) have described a new approach for quantifying C4 cycle activity, thereby providing the means to analyze its upregulation in an evolutionary context. PMID:27085185

  19. Tracking the evolutionary rise of C4 metabolism.

    PubMed

    Sage, Rowan F

    2016-05-01

    Upregulation of the C4 metabolic cycle is a major step in the evolution of C4 photosynthesis. Why this happened remains unclear, in part because of difficulties measuring the C4 cycle in situ in C3-C4 intermediate species. Now, Alonso-Cantabrana and von Caemmerer (2016) have described a new approach for quantifying C4 cycle activity, thereby providing the means to analyze its upregulation in an evolutionary context.

  20. Complement components in Nigerians with bronchial asthma.

    PubMed

    Onyemelukwe, G C

    1989-10-01

    Serum complement components C1q, C3, C4, factor B, and C3d breakdown products were measured in asthmatic Nigerians and in age-matched and sex-matched controls. C3 mean level was higher than in controls while C1q and C4 mean levels were lower than in controls. High levels of C3d in asthmatic patients suggest the possible role of C3a and C5a anaphylatoxins in the etiopathogenesis of perennial asthma in Nigerian patients in a tropical environment with ubiquitous airborne allergens and infective agents. The significantly elevated levels of IgM and IgG may suggest recurrent respiratory challenge of perennial antigens in our environment.

  1. Systemic complement activation in age-related macular degeneration.

    PubMed

    Scholl, Hendrik P N; Charbel Issa, Peter; Walier, Maja; Janzer, Stefanie; Pollok-Kopp, Beatrix; Börncke, Florian; Fritsche, Lars G; Chong, Ngaihang V; Fimmers, Rolf; Wienker, Thomas; Holz, Frank G; Weber, Bernhard H F; Oppermann, Martin

    2008-07-02

    Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001), were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  2. Triatoma infestans Calreticulin: Gene Cloning and Expression of a Main Domain That Interacts with the Host Complement System.

    PubMed

    Weinberger, Katherine; Collazo, Norberto; Aguillón, Juan Carlos; Molina, María Carmen; Rosas, Carlos; Peña, Jaime; Pizarro, Javier; Maldonado, Ismael; Cattan, Pedro E; Apt, Werner; Ferreira, Arturo

    2017-02-08

    Triatoma infestans is an important hematophagous vector of Chagas disease, a neglected chronic illness affecting approximately 6 million people in Latin America. Hematophagous insects possess several molecules in their saliva that counteract host defensive responses. Calreticulin (CRT), a multifunctional protein secreted in saliva, contributes to the feeding process in some insects. Human CRT (HuCRT) and Trypanosoma cruzi CRT (TcCRT) inhibit the classical pathway of complement activation, mainly by interacting through their central S domain with complement component C1. In previous studies, we have detected CRT in salivary gland extracts from T. infestans We have called this molecule TiCRT. Given that the S domain is responsible for C1 binding, we have tested its role in the classical pathway of complement activation in vertebrate blood. We have cloned and characterized the complete nucleotide sequence of CRT from T. infestans, and expressed its S domain. As expected, this S domain binds to human C1 and, as a consequence, it inhibits the classical pathway of complement, at its earliest stage of activation, namely the generation of C4b. Possibly, the presence of TiCRT in the salivary gland represents an evolutionary adaptation in hematophagous insects to control a potential activation of complement proteins, present in the massive blood meal that they ingest, with deleterious consequences at least on the anterior digestive tract of these insects.

  3. Anti-glycoprotein g antibodies of herpes simplex virus 2 contribute to complete protection after vaccination in mice and induce antibody-dependent cellular cytotoxicity and complement-mediated cytolysis.

    PubMed

    Görander, Staffan; Ekblad, Maria; Bergström, Tomas; Liljeqvist, Jan-Åke

    2014-11-12

    We investigated the role of antibodies against the mature portion of glycoprotein G (mgG-2) of herpes simplex virus 2 (HSV-2) in protective immunity after vaccination. Mice were immunized intramuscularly with mgG-2 and oligodeoxynucleotides containing two CpG motifs plus alum as adjuvant. All C57BL/6 mice survived and presented no genital or systemic disease. High levels of immunoglobulin G subclass 1 (IgG1) and IgG2 antibodies were detected and re-stimulated splenic CD4+ T cells proliferated and produced IFN-γ. None of the sera from immunized mice exhibited neutralization, while all sera exerted antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytolysis (ACMC) activity. Passive transfer of anti-mgG-2 monoclonal antibodies, or immune serum, to naive C57BL/6 mice did not limit disease progression. Immunized B‑cell KO mice presented lower survival rate and higher vaginal viral titers, as compared with vaccinated B-cell KO mice after passive transfer of immune serum and vaccinated C57BL/6 mice. Sera from mice that were vaccinated subcutaneously and intranasally with mgG-2 presented significantly lower titers of IgG antibodies and lower ADCC and ACMC activity. We conclude that anti-mgG-2 antibodies were of importance to limit genital HSV‑2 infection. ADCC and ACMC activity are potentially important mechanisms in protective immunity, and could tentatively be evaluated in future animal vaccine studies and in clinical trials.

  4. IXO: The Instrument Complement

    NASA Astrophysics Data System (ADS)

    Nousek, John A.; IWG, IXO

    2009-01-01

    The International X-ray Observatory (IXO) has recently been created as a mission concept by a joint team of NASA, ESA and JAXA scientists, based on the previous Constellation-X and XEUS concepts. Definition of the IXO instruments is still under evolution, but the core instrument complement will include a Wide Field X-ray Imager, an X-ray Calorimeter / Narrow Field X-ray Imager, and an X-ray Grating Spectrometer. Other, modest additional instruments (such as a hard X-ray capability, a polarimeter, and a high time resolution detector) will also be considered. We present the current status of the IXO instrument complement and offer the opportunity for discussion of ideas relevant to the IXO mission concept process.

  5. Modulation of C4b-binding protein isoforms during the acute phase response caused by orthopedic surgery.

    PubMed

    Criado-García, O; González-Rubio, C; López-Trascasa, M; Pascual-Salcedo, D; Munuera, L; Rodríguez de Córdoba, S

    1997-01-01

    Orthopedic surgery is described as an event with a high risk of thromboembolic diseases. This is probably a consequence of a synergistic combination of different risk factors in the patients subjected to this type of surgery, including age, immobilization, anesthesia and different hypercoagulable states. After surgery patients develop an acute-phase response that leads to changes in several plasma proteins. One of these proteins is the complement regulator C4b-binding protein (C4BP). We have recently shown that in some acute-phase patients C4BP is incorrectly controlled (with elevation of the C4BP beta-containing isoforms), leading to a potential hypercoagulable state by decreasing the plasma levels of free (active) protein S. Here we have studied whether patients subjected to orthopedic surgery have an appropriate modulation of the C4BP isoforms during their postoperative acute-phase responses. We have analyzed the evolution of the C4BP isoforms in serial samples from 11 patients who have undergone knee (or hip) prosthesis surgery (mean age 70 years), or scoliosis surgery (mean age 18 years). Our data suggest a similar evolution of C4BP isoforms in all these patients, with an almost exclusive increase of C4BP isoforms lacking C4BP beta polypeptides and steady levels of free protein S.

  6. Complement activity and pharmacological inhibition in cardiovascular disease

    PubMed Central

    Théroux, Pierre; Martel, Catherine

    2006-01-01

    While complement is the most important component of humoral autoimmunity, and inflammation plays a key role in atherosclerosis, relatively few studies have looked at complement implications in atherosclerosis and its complications. C-reactive protein is a marker of inflammation and is also involved in atherosclerosis; it activates complement and colocalizes with activated complement proteins within the infarcting myocardium and the active atherosclerotic plaques. As new agents capable of modulating complement activity are being developed, new targets for the management of atherosclerosis are emerging that are related to autoimmunity and inflammation. The present paper reviews the putative roles of the various complement activation pathways in the development of atherosclerosis, in ST segment elevation and non-ST segment elevation acute coronary syndromes, and in coronary artery bypass graft surgery. It also provides a perspective on new therapeutic interventions being developed to modulate complement activity. These interventions include the C1 esterase inhibitor, which may be consumed in some inflammatory states resulting in the loss of one of the mechanisms inhibiting activation of the classical and lectin pathways; TP10, a recombinant protein of the soluble complement receptor type 1 (sCR1) which inhibits the C3 and C5 convertases of the common pathway by binding C3b and C4b; a truncated version of the soluble complement receptor type 1 CRI lacking the C4b binding site which selectively inhibits the alternative pathway; and pexelizumab, a monoclonal antibody selectively blocking C5 to prevent the activation of the terminal pathway that is involved in excessive inflammation and autoimmune responses. PMID:16498508

  7. Complement receptor 1 inhibitors for prevention of immune-mediated red cell destruction: potential use in transfusion therapy.

    PubMed

    Yazdanbakhsh, Karina; Kang, Stanley; Tamasauskas, Daniel; Sung, Dorothy; Scaradavou, Andromachi

    2003-06-15

    Activation of complement cascade via the antibody-mediated classical pathway can initiate red blood cell (RBC) destruction, causing transfusion reactions and hemolytic anemia. In the present study, we have assessed the ability of a human recombinant soluble form of complement receptor 1 (sCR1) to inhibit complement-mediated RBC destruction in vitro and in vivo. Using an in vitro alloimmune incompatibility model, sCR1 inhibited complement activation and prevented hemolysis. Following transfusion of human group O RBCs into mice lacking detectable pre-existing antibodies against the transfused RBCs, systemic coadministration of 10 mg/kg sCR1, a dose well tolerated in human subjects for prevention of tissue injury, completely inhibited the in vivo clearance of the transfused RBCs and surface C3 deposition in the first hour after transfusion, correlating with the half-life of sCR1 in the circulation. Treatment with sCR1 increased the survival of transfused human group A RBCs in the circulation of mice with pre-existing anti-A for 2 hours after transfusion by 50%, reduced intravascular hemolysis, and lowered the levels of complement deposition (C3 and C4), but not immunoglobulin G (IgG) or IgM, on the transfused cells by 100-fold. We further identified potential functional domains in CR1 that can act to limit complement-mediated RBC destruction in vitro and in vivo. Collectively, our data highlight a potential use of CR1-based inhibitors for prevention of complement-dependent immune hemolysis.

  8. Inactivation of complement by Loxosceles reclusa spider venom.

    PubMed

    Gebel, H M; Finke, J H; Elgert, K D; Cambell, B J; Barrett, J T

    1979-07-01

    Zymosan depletion of serum complement in guinea pigs rendered them highly resistant to lesion by Loxosceles reclusa spider venom. Guinea pigs deficient in C4 of the complement system are as sensitive to the venom as normal guinea pigs. The injection of 35 micrograms of whole recluse venom intradermally into guinea pigs lowered their complement level by 35.7%. Brown recluse spider venom in concentrations as slight as 0.02 micrograms protein/ml can totally inactivate one CH50 of guinea pig complement in vitro. Bee, scorpion, and other spider venoms had no influence on the hemolytic titer of complement. Fractionation of recluse spider venom by Sephadex G-200 filtration separated the complement-inactivating property of the venom into three major regions which could be distinguished on the basis of heat stability as well as size. None was neutralized by antivenom. Polyacrylamide gel electrophoresis of venom resolved the complement inactivators into five fractions. Complement inactivated by whole venom or the Sephadex fractions could be restored to hemolytic activity by supplements of fresh serum but not by heat-inactivated serum, pure C3, pure C5, or C3 and C5 in combination.

  9. Oxford classification of IgA nephropathy and C4d deposition; correlation and its implication.

    PubMed

    Rath, Ashutosh; Tewari, Rohit; Mendonca, Satish; Badwal, Sonia; Nijhawan, Vijay Shrawan

    2016-01-01

    Introduction: IgA nephropathy (IgAN) is well known to be the most common form of primary glomerulonephritis throughout the world. The histopathological changes are wide and varied as brought out by the various classification systems like the Haas and Oxford systems. C4d is a well-known biomarker of the complement cascade and has recently been implicated in certain native renal diseases. We attempted to characterize C4d deposition in IgAN and correlate this with histopathology by the Oxford classification system. Patients and Methods: This retrospective study included renal biopsies of 15 cases of IgAN diagnosed on histopathology and immunofluorescence over a period of 2 years. Demographic parameters of age and sex were reviewed. The Oxford classification system was applied to score the cases and immunohistochemistry for C4d was done on all cases to characterize staining pattern and intensity and was correlated with Oxford classification. Results: On histological examination, the cases showed various combinations of lesions ranging from M0E0S0T0 to M1E1S1T1. C4d deposition was found to be occurring mainly in mesangial location (12/15 cases, 80%). Forty percent cases showed C4d deposition in the glomerular capillary walls in a segmental fashion and 26.67% showed global pattern. Other patterns of deposition were arteriolar (53.33%), in peritubular capillaries (26.67%) and in tubular epithelium (20%). Conclusion: On comparing the various patterns of deposition of C4d with the four variables of the Oxford classification system, we found that segmental and global deposition of C4d correlated best with endocapillary proliferation.

  10. When do different C4 leaf anatomies indicate independent C4 origins? Parallel evolution of C4 leaf types in Camphorosmeae (Chenopodiaceae).

    PubMed

    Kadereit, Gudrun; Lauterbach, Maximilian; Pirie, Michael D; Arafeh, Rami; Freitag, Helmut

    2014-07-01

    Broad-scale phylogenetic studies give first insights in numbers, relationships, and ages of C4 lineages. They are, however, generally limited to a model that treats the evolution of the complex C4 syndrome in different lineages as a directly comparable process. Here, we use a resolved and well-sampled phylogenetic tree of Camphorosmeae, based on three chloroplast and one nuclear marker and on leaf anatomical traits to infer a more detailed picture of C4 leaf-type evolution in this lineage. Our ancestral character state reconstructions allowed two scenarios: (i) Sedobassia is a derived C3/C4 intermediate, implying two independent gains of C4 in Bassia and Camphorosma; or (ii) Sedobassia is a plesiomorphic C3/C4 intermediate, representing a syndrome ancestral to the Bassia/Camphorosma/Sedobassia lineage. In Bassia, a kochioid leaf type (Bassia muricata and/or Bassia prostrata type) is ancestral. At least three independent losses of water-storage tissue occurred, resulting in parallel shifts towards an atriplicoid leaf type. These changes in leaf anatomy are adaptations to different survival strategies in steppic or semi-desert habitats with seasonal rainfall. In contrast, Camphorosma shows a fixed C4 anatomy differing from Bassia types in its continuous Kranz layer, which indeed points to an independent origin of the full C4 syndrome in Camphorosma, either from an independent C3 or from a common C3/C4 intermediate ancestor, perhaps similar to its C3/C4 intermediate sister genus Sedobassia. The enlarged bundle sheath cells of Sedobassia might represent an important early step in C4 evolution in Camphorosmeae.

  11. Quo vadis C(4)? An ecophysiological perspective on global change and the future of C(4) plants.

    PubMed

    Sage, Rowan F; Kubien, David S

    2003-01-01

    C(4) plants are directly affected by all major global change parameters, often in a manner that is distinct from that of C(3) plants. Rising CO(2) generally stimulates C(3) photosynthesis more than C(4), but C(4) species still exhibit positive responses, particularly at elevated temperature and arid conditions where they are currently common. Acclimation of photosynthesis to high CO(2) occurs in both C(3) and C(4) plants, most notably in nutrient-limited situations. High CO(2) aggravates nitrogen limitations and in doing so may favor C(4) species, which have greater photosynthetic nitrogen use efficiency. C(4) photosynthesis is favored by high temperature, but global warming will not necessarily favor C(4) over C(3) plants because the timing of warming could be more critical than the warming itself. C(3) species will likely be favored where harsh winter climates are moderated, particularly where hot summers also become drier and less favorable to C(4) plant growth. Eutrophication of soils by nitrogen deposition generally favors C(3) species by offsetting the superior nitrogen use efficiency of C(4) species; this should allow C(3) species to expand at the expense of C(4) plants. Land-use change and biotic invasions are also important global change factors that affect the future of C(4) plants. Human exploitation of forested landscapes favors C(4) species at low latitude by removing woody competitors and opening gaps in which C(4) grasses can establish. Invasive C(4) grasses are causing widespread forest loss in Asia, the Americas and Oceania by accelerating fire cycles and reducing soil nutrient status. Once established, weedy C(4) grasses can prevent woodland establishment, and thus arrest ecological succession. In sum, in the future, certain C(4) plants will prosper at the expense of C(3) species, and should be able to adjust to the changes the future brings.

  12. Complementing Gender Analysis Methods.

    PubMed

    Kumar, Anant

    2016-01-01

    The existing gender analysis frameworks start with a premise that men and women are equal and should be treated equally. These frameworks give emphasis on equal distribution of resources between men and women and believe that this will bring equality which is not always true. Despite equal distribution of resources, women tend to suffer and experience discrimination in many areas of their lives such as the power to control resources within social relationships, and the need for emotional security and reproductive rights within interpersonal relationships. These frameworks believe that patriarchy as an institution plays an important role in women's oppression, exploitation, and it is a barrier in their empowerment and rights. Thus, some think that by ensuring equal distribution of resources and empowering women economically, institutions like patriarchy can be challenged. These frameworks are based on proposed equality principle which puts men and women in competing roles. Thus, the real equality will never be achieved. Contrary to the existing gender analysis frameworks, the Complementing Gender Analysis framework proposed by the author provides a new approach toward gender analysis which not only recognizes the role of economic empowerment and equal distribution of resources but suggests to incorporate the concept and role of social capital, equity, and doing gender in gender analysis which is based on perceived equity principle, putting men and women in complementing roles that may lead to equality. In this article the author reviews the mainstream gender theories in development from the viewpoint of the complementary roles of gender. This alternative view is argued based on existing literature and an anecdote of observations made by the author. While criticizing the equality theory, the author offers equity theory in resolving the gender conflict by using the concept of social and psychological capital.

  13. CitA (citrate) and DcuS (C4-dicarboxylate) sensor kinases in thermophilic Geobacillus kaustophilus and Geobacillus thermodenitrificans.

    PubMed

    Graf, Sabrina; Broll, Constanze; Wissig, Juliane; Strecker, Alexander; Parowatkin, Maria; Unden, Gottfried

    2016-01-01

    The thermophilic Geobacillus thermodenitrificans and Geobacillus kaustophilus are able to use citrate or C4-dicarboxylates like fumarate or succinate as the substrates for growth. The genomes of the sequenced Geobacillus strains (nine strains) each encoded a two-component system of the CitA family. The sensor kinase of G. thermodenitrificans (termed CitAGt) was able to replace CitA of Escherichia coli (CitAEc) in a heterologous complementation assay restoring expression of the CitAEc-dependent citC-lacZ reporter gene and anaerobic growth on citrate. Complementation was specific for citrate. The sensor kinase of G. kaustophilus (termed DcuSGk) was able to replace DcuSEc of E. coli. It responded in the heterologous expression system to C4-dicarboxylates and to citrate, suggesting that DcuSGk is, like DcuSEc, a C4-dicarboxylate sensor with a side-activity for citrate. DcuSGk, unlike the homologous DctS from Bacillus subtilis, required no binding protein for function in the complementation assay. Thus, the thermophilic G. thermodenitrificans and G. kaustophilus contain citrate and C4-dicarboxylate sensor kinases of the CitA and DcuS type, respectively, and retain function and substrate specificity under mesophilic growth conditions in E. coli.

  14. The Paleo-ecology of C4 Evolution

    NASA Astrophysics Data System (ADS)

    Sage, R. F.; Khoshravesh, R.

    2014-12-01

    Molecular clock analysis of extant plant lineages consistently place the earliest appearance of the C4 photosynthetic pathway in the mid-to-late Oligocene, coincident with a decline in atmospheric CO2 and a spread of dry environments. Most of the approximately 70 known lineages of C4 photosynthesis, however, evolved over the subsequent 23 million years since the Oligocene. Examination of living C3-C4 intermediate species, and close C3 relatives of modern C4 lineages, indicate that the C4 pathway evolved in regions of high heat and episodic drought and/or salinity, usually in the drier ends of the monsoon belts of the subtropics. Soils associated with transitional species are typically sandy, rocky, or salinized, and have low vegetation density, which in combination with high air temperature allows for high surface heat loads that warm leaves to near 45°C. Under such conditions in low CO2 atmospheres, the rate of photorespiration is very high and would greatly impair C3 photosynthesis and establish conditions favoring C4 evolution. However, studies with modern taxa do not address whether the extreme habitats proposed to facilitate C4 evolution were actually present at the time when the C4 pathway evolved in any given lineage. Here, we examine the paleo-record to evaluate the environmental conditions present in the C4 centres of origin when the respective transitions from C3 to C4 photosynthesis are estimated to have occurred.

  15. C4 rice - an ideal arena for systems biology research.

    PubMed

    Zhu, Xin-Guang; Shan, Lanlan; Wang, Yu; Quick, William Paul

    2010-08-01

    Engineering the C4 photosynthetic pathway into C3 crops has the potential to dramatically increase the yields of major C3 crops. The genetic control of features involved in C4 photosynthesis are still far from being understood; which partially explains why we have gained little success in C4 engineering thus far. Next generation sequencing techniques and other high throughput technologies are offering an unprecedented opportunity to elucidate the developmental and evolutionary processes of C4 photosynthesis. Two contrasting hypotheses about the evolution of C4 photosynthesis exist, i.e. the master switch hypothesis and the incremental gain hypothesis. These two hypotheses demand two different research strategies to proceed in parallel to maximize the success of C4 engineering. In either case, systems biology research will play pivotal roles in identifying key regulatory elements controlling development of C4 features, identifying essential biochemical and anatomical features required to achieve high photosynthetic efficiency, elucidating genetic mechanisms underlining C4 differentiation and ultimately identifying viable routes to engineer C4 rice. As a highly interdisciplinary project, the C4 rice project will have far-reaching impacts on both basic and applied research related to agriculture in the 21st century.

  16. Identification of hot spots in the variola virus complement inhibitor (SPICE) for human complement regulation.

    PubMed

    Yadav, Viveka Nand; Pyaram, Kalyani; Mullick, Jayati; Sahu, Arvind

    2008-04-01

    Variola virus, the causative agent of smallpox, encodes a soluble complement regulator named SPICE. Previously, SPICE has been shown to be much more potent in inactivating human complement than the vaccinia virus complement control protein (VCP), although they differ only in 11 amino acid residues. In the present study, we have expressed SPICE, VCP, and mutants of VCP by substituting each or more of the 11 non-variant VCP residues with the corresponding residue of SPICE to identify hot spots that impart functional advantage to SPICE over VCP. Our data indicate that (i) SPICE is approximately 90-fold more potent than VCP in inactivating human C3b, and the residues Y98, Y103, K108 and K120 are predominantly responsible for its enhanced activity; (ii) SPICE is 5.4-fold more potent in inactivating human C4b, and residues Y98, Y103, K108, K120 and L193 mainly dictate this increase; (iii) the classical pathway decay-accelerating activity of activity is only twofold higher than that of VCP, and the 11 mutations in SPICE do not significantly affect this activity; (iv) SPICE possesses significantly greater binding ability to human C3b compared to VCP, although its binding to human C4b is lower than that of VCP; (v) residue N144 is largely responsible for the increased binding of SPICE to human C3b; and (vi) the human specificity of SPICE is dictated primarily by residues Y98, Y103, K108, and K120 since these are enough to formulate VCP as potent as SPICE. Together, these results suggest that principally 4 of the 11 residues that differ between SPICE and VCP partake in its enhanced function against human complement.

  17. Combined C4d and CD3 immunostaining predicts immunoglobulin (Ig)A nephropathy progression

    PubMed Central

    Faria, B; Henriques, C; Matos, A C; Daha, M R; Pestana, M; Seelen, M

    2015-01-01

    A number of molecules have been shown recently to be involved in the pathogenesis and progression of immunoglobulin (Ig)A nephropathy (IgAN). Among these, we have selected C4d (complement lectin pathway involvement), CD3 (T cell marker, traducing interstitial inflammation), transglutaminase 2 (TGase-2, involved in tissue fibrosis development) and p-extracelluar-regulated kinase (ERK)1/2 (protein kinase intracellular signaling molecule) to perform a panel of immunohistological biomarkers and assess its predictive value for disease progression. Immunohistochemical staining of these biomarkers was performed in paraffin sections from 74 renal biopsy cases with the clinical diagnosis of IgAN. Association between score analysis of these parameters and disease course was assessed through univariate and multivariate analysis, including baseline clinical and histological data. Univariate analysis showed that glomerular C4d, tubulointerstitial TGase2 and CD3 scores were associated with baseline proteinuria and disease progression. Multivariate analysis showed that only baseline estimated glomerular filtration rate (eGFR), C4d and CD3 were associated independently with progressive kidney disease (decline of at least 50% in the eGFR or progression to end-stage renal disease (ESRD) during the follow-up period). Establishing an accurate prediction model for IgAN progression is still a matter of research in clinical nephrology. The complement system, particularly lectin pathway activation, and T cell activation, have been shown previously to be potential modifiers of the disease course. Here we show that the combination of two histological biomarkers (C4d and CD3) can be a powerful predictor of IgAN progression and a potential useful tool for the clinical approach of this disease. PMID:25267249

  18. Complement inhibition in cancer therapy.

    PubMed

    Pio, Ruben; Ajona, Daniel; Lambris, John D

    2013-02-01

    For decades, complement has been recognized as an effector arm of the immune system that contributes to the destruction of tumor cells. In fact, many therapeutic strategies have been proposed that are based on the intensification of complement-mediated responses against tumors. However, recent studies have challenged this paradigm by demonstrating a tumor-promoting role for complement. Cancer cells seem to be able to establish a convenient balance between complement activation and inhibition, taking advantage of complement initiation without suffering its deleterious effects. Complement activation may support chronic inflammation, promote an immunosuppressive microenvironment, induce angiogenesis, and activate cancer-related signaling pathways. In this context, inhibition of complement activation would be a therapeutic option for treating cancer. This concept is relatively new and deserves closer attention. In this article, we summarize the mechanisms of complement activation on cancer cells, the cancer-promoting effect of complement initiation, and the rationale behind the use of complement inhibition as a therapeutic strategy against cancer.

  19. Photorespiration and the evolution of C4 photosynthesis.

    PubMed

    Sage, Rowan F; Sage, Tammy L; Kocacinar, Ferit

    2012-01-01

    C(4) photosynthesis is one of the most convergent evolutionary phenomena in the biological world, with at least 66 independent origins. Evidence from these lineages consistently indicates that the C(4) pathway is the end result of a series of evolutionary modifications to recover photorespired CO(2) in environments where RuBisCO oxygenation is high. Phylogenetically informed research indicates that the repositioning of mitochondria in the bundle sheath is one of the earliest steps in C(4) evolution, as it may establish a single-celled mechanism to scavenge photorespired CO(2) produced in the bundle sheath cells. Elaboration of this mechanism leads to the two-celled photorespiratory concentration mechanism known as C(2) photosynthesis (commonly observed in C(3)-C(4) intermediate species) and then to C(4) photosynthesis following the upregulation of a C(4) metabolic cycle.

  20. Photorespiration connects C3 and C4 photosynthesis.

    PubMed

    Bräutigam, Andrea; Gowik, Udo

    2016-05-01

    C4 plants evolved independently more than 60 times from C3 ancestors. C4 photosynthesis is a complex trait and its evolution from the ancestral C3 photosynthetic pathway involved the modification of the leaf anatomy and the leaf physiology accompanied by changes in the expression of thousands of genes. Under high temperature, high light, and the current CO2 concentration in the atmosphere, the C4 pathway is more efficient than C3 photosynthesis because it increases the CO2 concentration around the major CO2 fixating enzyme Rubisco. The oxygenase reaction and, accordingly, photorespiration are largely suppressed. In the present review we describe a scenario for C4 evolution that not only includes the avoidance of photorespiration as the major driving force for C4 evolution but also highlights the relevance of changes in the expression of photorespiratory genes in inducing and establishing important phases on the path from C3 to C4.

  1. C4-Dicarboxylate Utilization in Aerobic and Anaerobic Growth.

    PubMed

    Unden, Gottfried; Strecker, Alexander; Kleefeld, Alexandra; Kim, Ok Bin

    2016-06-01

    C4-dicarboxylates and the C4-dicarboxylic amino acid l-aspartate support aerobic and anaerobic growth of Escherichia coli and related bacteria. In aerobic growth, succinate, fumarate, D- and L-malate, L-aspartate, and L-tartrate are metabolized by the citric acid cycle and associated reactions. Because of the interruption of the citric acid cycle under anaerobic conditions, anaerobic metabolism of C4-dicarboxylates depends on fumarate reduction to succinate (fumarate respiration). In some related bacteria (e.g., Klebsiella), utilization of C4-dicarboxylates, such as tartrate, is independent of fumarate respiration and uses a Na+-dependent membrane-bound oxaloacetate decarboxylase. Uptake of the C4-dicarboxylates into the bacteria (and anaerobic export of succinate) is achieved under aerobic and anaerobic conditions by different sets of secondary transporters. Expression of the genes for C4-dicarboxylate metabolism is induced in the presence of external C4-dicarboxylates by the membrane-bound DcuS-DcuR two-component system. Noncommon C4-dicarboxylates like l-tartrate or D-malate are perceived by cytoplasmic one-component sensors/transcriptional regulators. This article describes the pathways of aerobic and anaerobic C4-dicarboxylate metabolism and their regulation. The citric acid cycle, fumarate respiration, and fumarate reductase are covered in other articles and discussed here only in the context of C4-dicarboxylate metabolism. Recent aspects of C4-dicarboxylate metabolism like transport, sensing, and regulation will be treated in more detail. This article is an updated version of an article published in 2004 in EcoSal Plus. The update includes new literature, but, in particular, the sections on the metabolism of noncommon C4-dicarboxylates and their regulation, on the DcuS-DcuR regulatory system, and on succinate production by engineered E. coli are largely revised or new.

  2. Relation of platelet C4d with all-cause mortality and ischemic stroke in patients with systemic lupus erythematosus.

    PubMed

    Kao, Amy H; McBurney, Christine A; Sattar, Abdus; Lertratanakul, Apinya; Wilson, Nicole L; Rutman, Sarah; Paul, Barbara; Navratil, Jeannine S; Scioscia, Andrea; Ahearn, Joseph M; Manzi, Susan

    2014-08-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease associated with significant morbidity, including premature cardiovascular disease, and mortality. Platelets bearing complement protein C4d (P-C4d) were initially determined to be specific for diagnosis of SLE and were later found to be associated with acute ischemic stroke in non-SLE patients. P-C4d may identify a subset of SLE patients with a worse clinical prognosis. This study investigated the associations of P-C4d with all-cause mortality and vascular events in a lupus cohort. A cohort of 356 consecutive patients with SLE was followed from 2001 to 2009. Primary outcome was all-cause mortality. Secondary outcomes were vascular events (myocardial infarction, coronary artery bypass graft, percutaneous coronary transluminal angioplasty, ischemic stroke, venous thromboembolism, pulmonary embolism, or other thrombosis). P-C4d was measured at study baseline. Seventy SLE patients (19.7%) had P-C4d. Mean follow-up was 4.7 years. All-cause mortality was 4%. P-C4d was associated with all-cause mortality (hazard ratio 7.52, 95% confidence interval (CI) 2.14-26.45, p = 0.002) after adjusting for age, ethnicity, sex, cancer, and anticoagulant use. Vascular event rate was 21.6%. Patients with positive P-C4d were more likely to have had vascular events compared to those with negative P-C4d (35.7 vs. 18.2%, p = 0.001). Specifically, P-C4d was associated with ischemic stroke (odds ratio 4.54, 95% CI 1.63-12.69, p = 0.004) after adjusting for age, ethnicity, and antiphospholipid antibodies. Platelet-C4d is associated with all-cause mortality and stroke in SLE patients. P-C4d may be a prognostic biomarker as well as a pathogenic clue that links platelets, complement activation, and thrombosis.

  3. Pathogenesis and significance of glomerular C4d deposition in lupus nephritis: activation of classical and lectin pathways

    PubMed Central

    Kim, Min-Kyung; Maeng, Young-In; Lee, Sun-Jae; Lee, In Hee; Bae, Jisuk; Kang, Yu-Na; Park, Byung-Tae; Park, Kwan-Kyu

    2013-01-01

    Immune complex-mediated complement activation through the classic pathway plays a key role in the pathogenesis of lupus nephritis (LN). C4d deposition in renal tissue reflects the prognosis of systemic lupus erythematosus (SLE). The aim of the current study is to investigate the pathogenesis and clinicopathologic significance of glomerular C4d deposition in LN. We retrospectively analyzed clinical and histopathological data of 20 SLE patients with renal biopsy-proven LN and 10 non-SLE renal biopsy samples as control. LN biopsies showed varying degrees of glomerular C4d staining associated with immune complex deposits, IgG (p = 0.015), C1q (p = 0.032) and C3 (p = 0.049). 7 LN biopsies had all of C4d, C1q and C3 deposits in their glomeruli, indicative of the activation of the classical pathway, whereas 2 LN biopsies had C4d and C3 deposits without accompanying C1q deposits, indicating the activation of the lectin pathway. Glomerular C4d deposition was correlated with the LN subtype (p < 0.001). In particular, a diffusely intense and coarsely granular pattern of C4d deposition in all glomeruli was detected in class V membranous LN. However, glomerular C4d deposition was correlated with neither disease activity of SLE nor histological activity and chronicity of LN. In conclusion, the activation of the lectin pathway as well as the classical pathway seems to play a crucial role in the pathogenesis of LN. Glomerular C4d staining could be helpful for diagnosing class V membranous LN, although glomerular C4d deposition does not reflect SLE disease activity and histological activity and chronicity. PMID:24133594

  4. Complement System in Lung Disease

    PubMed Central

    Pandya, Pankita H.

    2014-01-01

    In addition to its established contribution to innate immunity, recent studies have suggested novel roles for the complement system in the development of various lung diseases. Several studies have demonstrated that complement may serve as a key link between innate and adaptive immunity in a variety of pulmonary conditions. However, the specific contributions of complement to lung diseases based on innate and adaptive immunity are just beginning to emerge. Elucidating the role of complement-mediated immune regulation in these diseases will help to identify new targets for therapeutic interventions. PMID:24901241

  5. The bacteria binding glycoprotein salivary agglutinin (SAG/gp340) activates complement via the lectin pathway.

    PubMed

    Leito, Jelani T D; Ligtenberg, Antoon J M; van Houdt, Michel; van den Berg, Timo K; Wouters, Diana

    2011-10-01

    Salivary agglutinin (SAG), also known as gp-340 and Deleted in Malignant Brain Tumours 1, is a glycoprotein that is present in tears, lung fluid and mucosal surfaces along the gastrointestinal tract. It is encoded by the Deleted in Malignant Brain Tumours 1 gene, a member of the Scavenger Receptor Cysteine Rich group B protein superfamily. SAG aggregates bacteria thus promoting their clearance from the oral cavity and activates the complement system. Complement proteins may enter the oral cavity in case of serum leakage, which occurs after mucosal damage. The purpose of this study was to investigate the mode of complement activation. We showed a dose-dependent C4 deposition on SAG-coated microplates showing that either the classical or lectin pathway of complement was activated. Antibodies against mannose binding lectin inhibited C4 deposition and SAG induced no C4 deposition in MBL deficient sera showing SAG activated complement through the MBL pathway. Periodate treatment of SAG abolished MBL pathway activation consistent with an involvement of SAG glycans in complement activation. This provides the first evidence for a role of SAG in complement activation through the MBL pathway and suggests a potential role of SAG as a complement activating factor at the mucosal epithelia.

  6. Comparative cell-specific transcriptomics reveals differentiation of C4 photosynthesis pathways in switchgrass and other C4 lineages

    PubMed Central

    Rao, Xiaolan; Lu, Nan; Li, Guifen; Nakashima, Jin; Tang, Yuhong; Dixon, Richard A.

    2016-01-01

    Almost all C4 plants require the co-ordination of the adjacent and fully differentiated cell types, mesophyll (M) and bundle sheath (BS). The C4 photosynthetic pathway operates through two distinct subtypes based on how malate is decarboxylated in BS cells; through NAD-malic enzyme (NAD-ME) or NADP-malic enzyme (NADP-ME). The diverse or unique cell-specific molecular features of M and BS cells from separate C4 subtypes of independent lineages remain to be determined. We here provide an M/BS cell type-specific transcriptome data set from the monocot NAD-ME subtype switchgrass (Panicum virgatum). A comparative transcriptomics approach was then applied to compare the M/BS mRNA profiles of switchgrass, monocot NADP-ME subtype C4 plants maize and Setaria viridis, and dicot NAD-ME subtype Cleome gynandra. We evaluated the convergence in the transcript abundance of core components in C4 photosynthesis and transcription factors to establish Kranz anatomy, as well as gene distribution of biological functions, in these four independent C4 lineages. We also estimated the divergence between NAD-ME and NADP-ME subtypes of C4 photosynthesis in the two cell types within C4 species, including differences in genes encoding decarboxylating enzymes, aminotransferases, and metabolite transporters, and differences in the cell-specific functional enrichment of RNA regulation and protein biogenesis/homeostasis. We suggest that C4 plants of independent lineages in both monocots and dicots underwent convergent evolution to establish C4 photosynthesis, while distinct C4 subtypes also underwent divergent processes for the optimization of M and BS cell co-ordination. The comprehensive data sets in our study provide a basis for further research on evolution of C4 species. PMID:26896851

  7. Comparative cell-specific transcriptomics reveals differentiation of C4 photosynthesis pathways in switchgrass and other C4 lineages.

    PubMed

    Rao, Xiaolan; Lu, Nan; Li, Guifen; Nakashima, Jin; Tang, Yuhong; Dixon, Richard A

    2016-03-01

    Almost all C4 plants require the co-ordination of the adjacent and fully differentiated cell types, mesophyll (M) and bundle sheath (BS). The C4 photosynthetic pathway operates through two distinct subtypes based on how malate is decarboxylated in BS cells; through NAD-malic enzyme (NAD-ME) or NADP-malic enzyme (NADP-ME). The diverse or unique cell-specific molecular features of M and BS cells from separate C4 subtypes of independent lineages remain to be determined. We here provide an M/BS cell type-specific transcriptome data set from the monocot NAD-ME subtype switchgrass (Panicum virgatum). A comparative transcriptomics approach was then applied to compare the M/BS mRNA profiles of switchgrass, monocot NADP-ME subtype C4 plants maize and Setaria viridis, and dicot NAD-ME subtype Cleome gynandra. We evaluated the convergence in the transcript abundance of core components in C4 photosynthesis and transcription factors to establish Kranz anatomy, as well as gene distribution of biological functions, in these four independent C4 lineages. We also estimated the divergence between NAD-ME and NADP-ME subtypes of C4 photosynthesis in the two cell types within C4 species, including differences in genes encoding decarboxylating enzymes, aminotransferases, and metabolite transporters, and differences in the cell-specific functional enrichment of RNA regulation and protein biogenesis/homeostasis. We suggest that C4 plants of independent lineages in both monocots and dicots underwent convergent evolution to establish C4 photosynthesis, while distinct C4 subtypes also underwent divergent processes for the optimization of M and BS cell co-ordination. The comprehensive data sets in our study provide a basis for further research on evolution of C4 species.

  8. A theoretical study on the reaction mechanism of O2 with C4H9• radical.

    PubMed

    Du, Hong-chen; Gong, Xue-dong

    2012-05-01

    Ab initio calculations have been performed using the complete basis set model (CBS-QB3) to study the reaction mechanism of butane radical (C(4)H(9)•) with oxygen (O(2)). On the calculated potential energy surface, the addition of O(2) to C(4)H(9)• forms three intermediates barrierlessly, which can undergo subsequent isomerization or decomposition reaction leading to various products: HOO• + C(4)H(8), C(2)H(5)• + CH(2)CHOOH, OH• + C(3)H(7)CHO, OH• + cycle-C(4)H(8)O, CH(3)• + CH(3)CHCHOOH, CH(2)OOH• + C(3)H(6). Five pathways are supposed in this study. After taking into account the reaction barrier and enthalpy, the most possible reaction pathway is C(4)H(9)• + O(2) → IM1 → TS5 → IM3 → TS6 → IM4 → TS7 → OH• + cycle-C(4)H(8)O.

  9. The Anticomplementary Activity of ’Fusobacterium polymorphum’ in Normal and C-4 Deficient Sources of Guinea Pig Complement.

    DTIC Science & Technology

    1977-01-12

    alternative activation pathway appears possible which involves the reaction of certain polymeric m i- tiators (inulin, endotoxin, or zyinosan) with non ...displayed the ability to consume C’3, and anti-C’2 did not interfere with this activity. These findings suggested that there was an alternate ( non ...included using 5 g dextrose per liter veronal buffered diluent (VBD) . VBD prepared with the stock buffer containing Mg~~ and Ca++ was designated VBD

  10. Soluble complement receptor 1 inhibits both complement and granulocyte activation during ex vivo hemodialysis.

    PubMed

    Himmelfarb, J; McMonagle, E; Holbrook, D; Toth, C

    1995-10-01

    Hemodialysis with cellulosic membranes results in both complement and granulocyte activation. We investigated the effects of soluble complement receptor 1 (sCR1), a potent complement inhibitor, on both complement and granulocyte activation in an ex vivo model of dialysis. Measurements were made of complement activation (radioimmunoassay for C3a desArg) as well as granulocyte activation (flow cytometric measurements of reactive oxygen species production, granulocyte CD11b/CD18 (MAC-1) expression and CD62L (L-selectin) expression). sCR1 completely abolished the generation of plasma C3a desArg during ex vivo hemodialysis. Without sCR1, C3a desArg levels rose from 968 +/- 373 ng/ml to 4961 +/- 40 ng/ml by the end of the ex vivo procedure (p < 0.001). sCR1 also completely inhibited MAC-1 upregulation and L-selectin shedding from granulocytes during ex vivo hemodialysis. With sCR1 there was still a statistically significant increase in granulocyte reactive oxygen species production (from 2.42 +/- 0.1 fluorescence channels to 6.47 +/- 0.7 fluorescence channels, p < 0.01) but a 50% inhibition when compared with experiments without sCR1 (3.15 +/- 0.5 to 11.2 +/- 1.9, p < 0.01). We conclude that sCR1 completely abolishes complement activation and changes in granulocyte cell adhesion molecules during ex vivo hemodialysis with cellulosic membranes. sCR1 partially inhibits granulocyte reactive oxygen species formation.

  11. C4I Community of Interest C2 Roadmap

    DTIC Science & Technology

    2015-03-24

    public release; distribution is unlimited C4I COI Overview • Purpose: The C4I CoI provides the DoD S&T EXCOM recommendations on matters related to...info guard functions • Partners left in dark • Dependence on Field Support Reps. • Communicate but can’t share ideas • Unintuitive interface

  12. Diversity and plasticity of C4 photosynthesis in Eleocharis (Cyperaceae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eleocharis contains many amphibious species, and displays diversity of photosynthetic mechanism (C3, C4 or C3-C4 intermediates). A unique feature of Eleocharis is the plasticity in the photosynthetic mechanism of some species in response to the environment. In this study, we have examined the culm a...

  13. 19 CFR 142.49 - Deletion of C-4 Code.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... with any justification and without prior notification in cases of willfulness or when public health... 19 Customs Duties 2 2011-04-01 2011-04-01 false Deletion of C-4 Code. 142.49 Section 142.49... TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.49 Deletion of C-4 Code. (a) By Customs. A...

  14. 19 CFR 142.49 - Deletion of C-4 Code.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... with any justification and without prior notification in cases of willfulness or when public health... 19 Customs Duties 2 2012-04-01 2012-04-01 false Deletion of C-4 Code. 142.49 Section 142.49... TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.49 Deletion of C-4 Code. (a) By Customs. A...

  15. 19 CFR 142.49 - Deletion of C-4 Code.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... with any justification and without prior notification in cases of willfulness or when public health... 19 Customs Duties 2 2013-04-01 2013-04-01 false Deletion of C-4 Code. 142.49 Section 142.49... TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.49 Deletion of C-4 Code. (a) By Customs. A...

  16. 17 CFR 240.16c-4 - Derivative securities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Derivative securities. 240.16c-4 Section 240.16c-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the...

  17. 17 CFR 240.16c-4 - Derivative securities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Derivative securities. 240.16c-4 Section 240.16c-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the...

  18. 17 CFR 240.16c-4 - Derivative securities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Derivative securities. 240.16c-4 Section 240.16c-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the...

  19. 17 CFR 240.16c-4 - Derivative securities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Derivative securities. 240.16c-4 Section 240.16c-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the...

  20. 42 CFR 68c.4 - Who is eligible to participate?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Who is eligible to participate? 68c.4 Section 68c.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT CONTRACEPTION AND INFERTILITY...

  1. 42 CFR 68c.4 - Who is eligible to participate?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Who is eligible to participate? 68c.4 Section 68c.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT CONTRACEPTION AND INFERTILITY...

  2. 42 CFR 68c.4 - Who is eligible to participate?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Who is eligible to participate? 68c.4 Section 68c.4 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT CONTRACEPTION AND INFERTILITY...

  3. Insect herbivory on C3 and C4 grasses.

    PubMed

    Boutton, Thomas W; Cameron, Guy N; Smith, Bruce N

    1978-01-01

    This study tested the hypothesis that grasses with the C4 photosynthetic pathway are avoided as a food source by insect herbivores in natural communities. Insects were sampled from ten pairs of C3-C4 grasses and their distributions analyzed by paired comparisons tests. Results showed no statistically significant differences in herbivore utilization of C3-C4 species. However, there was a trend towards heavier utilization of C3 species when means for both plant groups were compared. In particular, Homoptera and Diptera showed heavier usage of C3 plants. Significant correlations between insect abundances and plant protein levels suggest that herbivores respond to the higher protein content of C3 grasses. δ(13)C values for six of the most common grasshopper species in the study area indicated that three species fed on C3 plants, two species fed on C4 plants, and one species consumed a mixture of C3 and C4 tissue.

  4. Photosynthesis of C3, C3–C4, and C4 grasses at glacial CO2

    PubMed Central

    Pinto, Harshini; Sharwood, Robert E.; Tissue, David T.; Ghannoum, Oula

    2014-01-01

    Most physiology comparisons of C3 and C4 plants are made under current or elevated concentrations of atmospheric CO2 which do not reflect the low CO2 environment under which C4 photosynthesis has evolved. Accordingly, photosynthetic nitrogen (PNUE) and water (PWUE) use efficiency, and the activity of the photosynthetic carboxylases [Rubisco and phosphoenolpyruvate carboxylase (PEPC)] and decarboxylases [NADP-malic enzyme (NADP-ME) and phosphoenolpyruvate carboxykinase (PEP-CK)] were compared in eight C4 grasses with NAD-ME, PCK, and NADP-ME subtypes, one C3 grass, and one C3–C4 grass grown under ambient (400 μl l–1) and glacial (180 μl l–1) CO2. Glacial CO2 caused a smaller reduction of photosynthesis and a greater increase of stomatal conductance in C4 relative to C3 and C3–C4 species. Panicum bisulcatum (C3) acclimated to glacial [CO2] by doubling Rubisco activity, while Rubisco was unchanged in Panicum milioides (C3–C4), possibly due to its high leaf N and Rubisco contents. Glacial CO2 up-regulated Rubisco and PEPC activities in concert for several C4 grasses, while NADP-ME and PEP-CK activities were unchanged, reflecting the high control exerted by the carboxylases relative to the decarboxylases on the efficiency of C4 metabolism. Despite having larger stomatal conductance at glacial CO2, C4 species maintained greater PWUE and PNUE relative to C3–C4 and C3 species due to higher photosynthetic rates. Relative to other C4 subtypes, NAD-ME and PEP-CK grasses had the highest PWUE and PNUE, respectively; relative to C3, the C3–C4 grass had higher PWUE and similar PNUE at glacial CO2. Biomass accumulation was reduced by glacial CO2 in the C3 grass relative to the C3–C4 grass, while biomass was less reduced in NAD-ME grasses compared with NADP-ME and PCK grasses. Under glacial CO2, high resource use efficiency offers a key evolutionary advantage for the transition from C3 to C4 photosynthesis in water- and nutrient-limited environments. PMID:24723409

  5. Nouns, Verbs and NP Complements.

    ERIC Educational Resources Information Center

    Platt, J. T.

    This paper investigates restrictions on three types of noun-phrase complements (gerundive, infinitive, clause) in English and seeks to point out some parallels between the occurrence of these three types in object positions. The author first presents a list of verbs which may be followed by noun-phrase complements; he then considers the occurrence…

  6. Exploitation of complement regulatory proteins by Borrelia and Francisella.

    PubMed

    Madar, Marian; Bencurova, Elena; Mlynarcik, Patrik; Almeida, André M; Soares, Renata; Bhide, Katarina; Pulzova, Lucia; Kovac, Andrej; Coelho, Ana V; Bhide, Mangesh

    2015-06-01

    Pathogens have developed sophisticated mechanisms of complement evasion such as binding to the host complement regulatory proteins (CRPs) on their surface or expression of CRP mimicking molecules. The ability of pathogens to evade the complement system has been correlated with pathogenesis and host selectivity. Hitherto, little work has been undertaken to determine whether Borrelia and Francisella exploit various CRPs to block complement attack. Seventeen Borrelia (twelve species) and six Francisella (three subspecies) strains were used to assess their ability to bind human, sheep and cattle CRPs or mimic membrane associated complement regulators. A series of experiments including affinity ligand binding experiments, pull-down assays and mass spectrometry based protein identification, revealed an array of CRP binding proteins of Borrelia and Francisella. Unlike Francisella, Borrelia strains were able to bind multiple human CRPs. Three strains of Borrelia (SKT-4, SKT-2 and HO14) showed the presence of a human CD46-homologous motif, indicating their ability to possess putative human CD46 mimicking molecules. Similarly, five strains of Borrelia and two strains of Francisella may have surface proteins with human CD59-homologous motifs. Among ovine and bovine CRPs, the only CRP bound by Francisella (LVS, Tul4 strain) was vitronectin, while ovine C4BP, ovine factor H and bovine factor H were bound to Borrelia strains SKT-2, DN127 and Co53. This study presents an array of proteins of Borrelia and Francisella that bind CRPs or may mimic membrane-CRPs, thus enabling multiphasic complement evasion strategies of these pathogens.

  7. Activation of the complement system and accumulation of hemoglobin-haptoglobin complexes in plasma during an adverse reaction to penicillin treatment.

    PubMed

    Brandslund, I; Svehag, S E; Teisner, B; Hyltoft Petersen, P

    1983-01-01

    A patient treated with penicillin intravenously developed a serum sickness-like reaction. Classical pathway complement (C) activation was indicated by quantitation of the split products C3c and C3d as well as demonstration of C4 conversion. Circulating immune complexes could, however, not be detected by the solid-phase Clq and PEG-precipitation methods. A concomitant accumulation of circulating hemoglobin-haptoglobin complexes and a marked fall in serum-fibronectin concentrations suggested saturation of the reticuloendothelial system. The plasma became a deep-red color, and a diffuse intravascular coagulation followed. The patient recovered completely upon discontinuation of penicillin administration.

  8. The Roles of Organic Acids in C4 Photosynthesis.

    PubMed

    Ludwig, Martha

    2016-01-01

    Organic acids are involved in numerous metabolic pathways in all plants. The finding that some plants, known as C4 plants, have four-carbon dicarboxylic acids as the first product of carbon fixation showed these organic acids play essential roles as photosynthetic intermediates. Oxaloacetate (OAA), malate, and aspartate (Asp) are substrates for the C4 acid cycle that underpins the CO2 concentrating mechanism of C4 photosynthesis. In this cycle, OAA is the immediate, short-lived, product of the initial CO2 fixation step in C4 leaf mesophyll cells. The malate and Asp, resulting from the rapid conversion of OAA, are the organic acids delivered to the sites of carbon reduction in the bundle-sheath cells of the leaf, where they are decarboxylated, with the released CO2 used to make carbohydrates. The three-carbon organic acids resulting from the decarboxylation reactions are returned to the mesophyll cells where they are used to regenerate the CO2 acceptor pool. NADP-malic enzyme-type, NAD-malic enzyme-type, and phosphoenolpyruvate carboxykinase-type C4 plants were identified, based on the most abundant decarboxylating enzyme in the leaf tissue. The genes encoding these C4 pathway-associated decarboxylases were co-opted from ancestral C3 plant genes during the evolution of C4 photosynthesis. Malate was recognized as the major organic acid transferred in NADP-malic enzyme-type C4 species, while Asp fills this role in NAD-malic enzyme-type and phosphoenolpyruvate carboxykinase-type plants. However, accumulating evidence indicates that many C4 plants use a combination of organic acids and decarboxylases during CO2 fixation, and the C4-type categories are not rigid. The ability to transfer multiple organic acid species and utilize different decarboxylases has been suggested to give C4 plants advantages in changing and stressful environments, as well as during development, by facilitating the balance of energy between the two cell types involved in the C4 pathway of CO2

  9. The Roles of Organic Acids in C4 Photosynthesis

    PubMed Central

    Ludwig, Martha

    2016-01-01

    Organic acids are involved in numerous metabolic pathways in all plants. The finding that some plants, known as C4 plants, have four-carbon dicarboxylic acids as the first product of carbon fixation showed these organic acids play essential roles as photosynthetic intermediates. Oxaloacetate (OAA), malate, and aspartate (Asp) are substrates for the C4 acid cycle that underpins the CO2 concentrating mechanism of C4 photosynthesis. In this cycle, OAA is the immediate, short-lived, product of the initial CO2 fixation step in C4 leaf mesophyll cells. The malate and Asp, resulting from the rapid conversion of OAA, are the organic acids delivered to the sites of carbon reduction in the bundle-sheath cells of the leaf, where they are decarboxylated, with the released CO2 used to make carbohydrates. The three-carbon organic acids resulting from the decarboxylation reactions are returned to the mesophyll cells where they are used to regenerate the CO2 acceptor pool. NADP-malic enzyme-type, NAD-malic enzyme-type, and phosphoenolpyruvate carboxykinase-type C4 plants were identified, based on the most abundant decarboxylating enzyme in the leaf tissue. The genes encoding these C4 pathway-associated decarboxylases were co-opted from ancestral C3 plant genes during the evolution of C4 photosynthesis. Malate was recognized as the major organic acid transferred in NADP-malic enzyme-type C4 species, while Asp fills this role in NAD-malic enzyme-type and phosphoenolpyruvate carboxykinase-type plants. However, accumulating evidence indicates that many C4 plants use a combination of organic acids and decarboxylases during CO2 fixation, and the C4-type categories are not rigid. The ability to transfer multiple organic acid species and utilize different decarboxylases has been suggested to give C4 plants advantages in changing and stressful environments, as well as during development, by facilitating the balance of energy between the two cell types involved in the C4 pathway of CO2

  10. Phosphoethanolamine Residues on the Lipid A Moiety of Neisseria gonorrhoeae Lipooligosaccharide Modulate Binding of Complement Inhibitors and Resistance to Complement Killing

    PubMed Central

    Shafer, William M.; Dutta Ray, Tathagat; Ram, Sanjay; Rice, Peter A.

    2013-01-01

    Loss of phosphoethanolamine (PEA) from the lipid A of gonococcal strain FA19 results in increased sensitivity to killing by the classical pathway of complement. Here we demonstrate that loss of PEA from lipid A diminishes binding of the complement regulatory protein C4b binding protein (C4BP) to the FA19 porin B (PorB), providing a molecular basis to explain the susceptibility of an lptA null strain of FA19 to killing by normal human serum (NHS). Loss of PEA from lipid A in three additional gonococcal strains that expressed diverse PorB molecules also resulted in decreased C4BP binding, increased deposition of C4b, and increased susceptibility to killing by NHS. Complementation of lptA null strains with lptA restored C4BP binding, decreased C4b deposition, and increased resistance to killing by NHS. These effects of lipid A PEA on C4BP binding to gonococcal PorB and serum resistance were simulated when gonococcal PorB was expressed in a meningococcal background. Loss of PEA from lipid A also affected binding of the alternative pathway regulator factor H (fH) to PorB of some strains. For instance, PorB molecules of lptA null mutants of strains 252 and 1291 bound less fH than those of their parent strains when lipooligosaccharide (LOS) was sialylated, whereas PorB molecules of lptA null mutants of strains FA1090 and 273 retained the ability to bind fH when LOS was sialylated. These data indicate that replacement of lipid A with PEA alters binding of C4BP and fH to PorB and contributes to the ability of gonococci to resist complement-mediated killing. PMID:23071134

  11. Carbon isotope discrimination as a diagnostic tool for C4 photosynthesis in C3-C4 intermediate species

    PubMed Central

    Alonso-Cantabrana, Hugo; von Caemmerer, Susanne

    2016-01-01

    The presence and activity of the C4 cycle in C3-C4 intermediate species have proven difficult to analyze, especially when such activity is low. This study proposes a strategy to detect C4 activity and estimate its contribution to overall photosynthesis in intermediate plants, by using tunable diode laser absorption spectroscopy (TDLAS) coupled to gas exchange systems to simultaneously measure the CO2 responses of CO2 assimilation (A) and carbon isotope discrimination (Δ) under low O2 partial pressure. Mathematical models of C3-C4 photosynthesis and Δ are then fitted concurrently to both responses using the same set of constants. This strategy was applied to the intermediate species Flaveria floridana and F. brownii, and to F. pringlei and F. bidentis as C3 and C4 controls, respectively. Our results support the presence of a functional C4 cycle in F. floridana, that can fix 12–21% of carbon. In F. brownii, 75–100% of carbon is fixed via the C4 cycle, and the contribution of mesophyll Rubisco to overall carbon assimilation increases with CO2 partial pressure in both intermediate plants. Combined gas exchange and Δ measurement and modeling is a powerful diagnostic tool for C4 photosynthesis. PMID:26862154

  12. Molecular genetics of the fourth component of human complement

    SciTech Connect

    Carroll, M.C.

    1987-05-15

    The fourth component of complement in humans is coded for by two closely linked loci, i.e., C4A and C4B, that have been positioned within the class III region of the human major histocompatibility complex along with the genes for C2, Bf, and steroid 21-OH. Both C4 loci are highly polymorphic and certain alleles, particularly the nulls, are associated with susceptibility to autoimmune disease. About one-half of the null alleles are due to a large deletion that includes both a C4 and flanking 21-OH gene. Despite the near identity of the products of the two loci, the proteins differ dramatically in their efficiency of covalent binding to antigen. The amino acid substitutions responsible for the functional differences have been identified and they are clustered relatively near the covalent binding site within the C4d region of the ..cap alpha.. chain. These observations support the hypothesis that the susceptibility to autoimmune disease is related to the structural variation of the C4 protein.

  13. Complement activation in very early Alzheimer disease.

    PubMed

    Zanjani, H; Finch, C E; Kemper, C; Atkinson, J; McKeel, D; Morris, J C; Price, J L

    2005-01-01

    The activation of the classical complement (C)-system in early-stage Alzheimer disease (AD) and nondemented aging was examined with immunohistochemistry in subjects assessed by the Clinical Dementia Rating (CDR). Activation (staining for C3 and C4 fragments) was found in all brains with amyloid deposits, including all nondemented (CDR 0) cases, with either small numbers of diffuse plaques or with sufficient plaques and tangles to indicate preclinical AD. Staining for C3 and C4 increased in parallel with plaque density in very mild to severe clinical AD. A subset of very mild AD (CDR 0.5) cases also showed C1q (on plaques) and C5b-9 (on neuritic plaques and tangles), whereas these C-fragments were consistently found in severe AD (CDR 3). Mirror section (split-face) analysis showed that C1q, C3, and apoJ (clusterin) occurred on the same plaques. However, C-system regulators CD59, CR1, DAF, and MCP were not detected on plaques or tangles at any stage, indicating that C-activation related to AD is incompletely controlled.

  14. New evidence for grain specific C4 photosynthesis in wheat

    PubMed Central

    Rangan, Parimalan; Furtado, Agnelo; Henry, Robert J

    2016-01-01

    The C4 photosynthetic pathway evolved to allow efficient CO2 capture by plants where effective carbon supply may be limiting as in hot or dry environments, explaining the high growth rates of C4 plants such as maize. Important crops such as wheat and rice are C3 plants resulting in efforts to engineer them to use the C4 pathway. Here we show the presence of a C4 photosynthetic pathway in the developing wheat grain that is absent in the leaves. Genes specific for C4 photosynthesis were identified in the wheat genome and found to be preferentially expressed in the photosynthetic pericarp tissue (cross- and tube-cell layers) of the wheat caryopsis. The chloroplasts exhibit dimorphism that corresponds to chloroplasts of mesophyll- and bundle sheath-cells in leaves of classical C4 plants. Breeding to optimize the relative contributions of C3 and C4 photosynthesis may adapt wheat to climate change, contributing to wheat food security. PMID:27530078

  15. Photosynthetic diversity meets biodiversity: the C4 plant example.

    PubMed

    Sage, Rowan F; Stata, Matt

    2015-01-01

    Physiological diversification reflects adaptation for specific environmental challenges. As the major physiological process that provides plants with carbon and energy, photosynthesis is under strong evolutionary selection that gives rise to variability in nearly all parts of the photosynthetic apparatus. Here, we discuss how plants, notably those using C4 photosynthesis, diversified in response to environmental challenges imposed by declining atmospheric CO2 content in recent geological time. This reduction in atmospheric CO2 increases the rate of photorespiration and reduces photosynthetic efficiency. While plants have evolved numerous mechanisms to compensate for low CO2, the most effective are the carbon concentration mechanisms of C4, C2, and CAM photosynthesis; and the pumping of dissolved inorganic carbon, mainly by algae. C4 photosynthesis enables plants to dominate warm, dry and often salinized habitats, and to colonize areas that are too stressful for most plant groups. Because C4 lineages generally lack arborescence, they cannot form forests. Hence, where they predominate, C4 plants create a different landscape than would occur if C3 plants were to predominate. These landscapes (mostly grasslands and savannahs) present unique selection environments that promoted the diversification of animal guilds able to graze upon the C4 vegetation. Thus, the rise of C4 photosynthesis has made a significant contribution to the origin of numerous biomes in the modern biosphere.

  16. Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia.

    PubMed

    Penning, Marlies; Chua, Jamie S; van Kooten, Cees; Zandbergen, Malu; Buurma, Aletta; Schutte, Joke; Bruijn, Jan Anthonie; Khankin, Eliyahu V; Bloemenkamp, Kitty; Karumanchi, S Ananth; Baelde, Hans

    2015-07-01

    A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia.

  17. Does Bienertia cycloptera with the single-cell system of C(4) photosynthesis exhibit a seasonal pattern of delta (13)C values in nature similar to co-existing C (4) Chenopodiaceae having the dual-cell (Kranz) system?

    PubMed

    Akhani, Hossein; Lara, María Valeria; Ghasemkhani, Maryam; Ziegler, Hubert; Edwards, Gerald E

    2009-01-01

    Family Chenopodiaceae is an intriguing lineage, having the largest number of C(4) species among dicots, including a number of anatomical variants of Kranz anatomy and three single-cell C(4) functioning species. In some previous studies, during the culture of Bienertia cycloptera Bunge ex Boiss., carbon isotope values (delta(13)C values) of leaves deviated from C(4) to C(3)-C(4) intermediate type, raising questions as to its mode of photosynthesis during growth in natural environments. This species usually co-occurs with several Kranz type C(4) annuals. The development of B. cycloptera morphologically and delta(13)C values derived from plant samples (cotyledons, leaves, bracts, shoots) were analyzed over a complete growing season in a salt flat in north central Iran, along with eight Kranz type C(4) species and one C(3) species. For a number of species, plants were greenhouse-grown from seeds collected from the site, in order to examine leaf anatomy and C(4) biochemical subtype. Among the nine C(4) species, the cotyledons of B. cycloptera, and of the Suaeda spp. have the same respective forms of C(4) anatomy occurring in leaves, while cotyledons of members of tribe Caroxyloneae lack Kranz anatomy, which is reflected in the delta(13)C values found in plants grown in the natural habitat. The nine C(4) species had average seasonal delta(13)C values of -13.9 per thousand (with a range between species from -11.3 to -15.9 per thousand). The measurements of delta(13)C values over a complete growing season show that B. cycloptera performs C(4) photosynthesis during its life cycle in nature, similar to Kranz type species, with a seasonal average delta(13)C value of -15.2 per thousand.

  18. The rise of C4 grassland ecosystems, a climate puzzle

    NASA Astrophysics Data System (ADS)

    Henderson, A.; Fox, D.; Freeman, K. H.

    2011-12-01

    The expansion of grasslands was one of the most profound ecological changes in the Cenozoic. Understanding the history of forest to grassland transitions, and the development of C4 grasslands in particular, is critical for understanding the relationship between land surface climate feedbacks, seasonality, and temperature. Modern distributions and ecological experiments demonstrate a strong correlation between C4 biogeography and high growing season temperatures and precipitation, as well as low pCO2 concentrations. The rise of C4 grasses in North America, as documented by carbonate nodule and mammal teeth δ13C values, began during a warm period with relatively stable pCO2 in the late Miocene. Surprisingly, C4 grasses continued to expand and then rose to dominance in the Great Plains as climates progressively cooled, moisture availability increased, and ice sheets formed further north on the continent. To understand this seemingly paradoxical scenario, we need constraints on the rate and character of increasing abundances of C4 vegetation. To this end, we use molecular and isotopic tools from terrestrial plant leaf wax n-alkanes extracted from carbonate nodules in the Meade Basin, Kansas and sites in Texas for the past 12 Ma. These records offer site-specific reconstructions tied directly to vegetation source. We compare our results to published continental-scale reconstructions of n-alkanes from the Mississippi River drainage basin and to climate records. From the distribution of C27 to C33 n-alkane abundances and patterns in δ13C values, we infer that C4 grasses coexisted with patches of C3 vegetation, including both grasses and trees. C4 grasses increasingly dominated the landscape, reaching modern abundances as ice sheets were reaching their southern limit in North America. Our results confirm that C4 grasslands emerged under cool and wet conditions, something we would not predict based on modern analogues, raising questions about our understanding of the

  19. The complement system in ischemia-reperfusion injuries.

    PubMed

    Gorsuch, William B; Chrysanthou, Elvina; Schwaeble, Wilhelm J; Stahl, Gregory L

    2012-11-01

    Tissue injury and inflammation following ischemia and reperfusion of various organs have been recognized for many years. Many reviews have been written over the last several decades outlining the role of complement in ischemia/reperfusion injury. This short review provides a current state of the art knowledge on the complement pathways activated, complement components involved and a review of the clinical biologics/inhibitors used in the clinical setting of ischemia/reperfusion. This is not a complete review of the complement system in ischemia and reperfusion injury but will give the reader an updated view point of the field, potential clinical use of complement inhibitors, and the future studies needed to advance the field.

  20. The Complement System in Ischemia-Reperfusion Injuries

    PubMed Central

    Gorsuch, William B.; Chrysanthou, Elvina; Schwaeble, Wilhelm J.; Stahl, Gregory L.

    2012-01-01

    Tissue injury and inflammation following ischemia and reperfusion of various organs has been recognized for many years. Many reviews have been written over the last several decades outlining the role of complement in ischemia/reperfusion injury. This short review provides a current state of the art knowledge on the complement pathways activated, complement components involved and a review of the clinical biologics/inhibitors used in the clinical setting of ischemia/reperfusion. This is not a complete review of the complement system in ischemia and reperfusion injury but will give the reader an updated view point of the field, potential clinical use of complement inhibitors, and the future studies needed to advance the field. PMID:22964228

  1. Complement in health and disease.

    PubMed

    Carroll, Maria V; Sim, Robert B

    2011-09-16

    The complement system consists of about 35-40 proteins and glycoproteins present in blood plasma or on cell surfaces. Its main biological function is to recognise "foreign" particles and macromolecules, and to promote their elimination either by opsonisation or lysis. Although historically complement has been studied as a system for immune defence against bacteria, it has an important homeostatic role in which it recognises damaged or altered "self" components. Thus complement has major roles in both immune defence against microorganisms, and in clearance of damaged or "used" host components. Since complement proteins opsonise or lyse cells, complement can damage healthy host cells and tissues. The system is regulated by many endogenous regulatory proteins. Regulation is sometimes imperfect and both too much and too little complement activation is associated with many diseases. Excessive or inappropriate activation can cause tissue damage in diseases such as rheumatoid arthritis, age-related macular degeneration (AMD), multiple sclerosis, ischemia-reperfusion injury (e.g. ischemic stroke). Insufficient complement activity is associated with susceptibility to infection (mainly bacterial) and development of autoimmune disease, like SLE (systemic lupus erythematosus).

  2. Salt tolerance evolves more frequently in C4 grass lineages.

    PubMed

    Bromham, L; Bennett, T H

    2014-03-01

    Salt tolerance has evolved many times in the grass family, and yet few cereal crops are salt tolerant. Why has it been so difficult to develop crops tolerant of saline soils when salt tolerance has evolved so frequently in nature? One possible explanation is that some grass lineages have traits that predispose them to developing salt tolerance and that without these background traits, salt tolerance is harder to achieve. One candidate background trait is photosynthetic pathway, which has also been remarkably labile in grasses. At least 22 independent origins of the C4 photosynthetic pathway have been suggested to occur within the grass family. It is possible that the evolution of C4 photosynthesis aids exploitation of saline environments, because it reduces transpiration, increases water-use efficiency and limits the uptake of toxic ions. But the observed link between the evolution of C4 photosynthesis and salt tolerance could simply be due to biases in phylogenetic distribution of halophytes or C4 species. Here, we use a phylogenetic analysis to investigate the association between photosynthetic pathway and salt tolerance in the grass family Poaceae. We find that salt tolerance is significantly more likely to occur in lineages with C4 photosynthesis than in C3 lineages. We discuss the possible links between C4 photosynthesis and salt tolerance and consider the limitations of inferring the direction of causality of this relationship.

  3. Mitochondrial haplogroup C4c: a rare lineage entering America through the ice-free corridor?

    PubMed

    Hooshiar Kashani, Baharak; Perego, Ugo A; Olivieri, Anna; Angerhofer, Norman; Gandini, Francesca; Carossa, Valeria; Lancioni, Hovirag; Semino, Ornella; Woodward, Scott R; Achilli, Alessandro; Torroni, Antonio

    2012-01-01

    Recent analyses of mitochondrial genomes from Native Americans have brought the overall number of recognized maternal founding lineages from just four to a current count of 15. However, because of their relative low frequency, almost nothing is known for some of these lineages. This leaves a considerable void in understanding the events that led to the colonization of the Americas following the Last Glacial Maximum (LGM). In this study, we identified and completely sequenced 14 mitochondrial DNAs belonging to one extremely rare Native American lineage known as haplogroup C4c. Its age and geographical distribution raise the possibility that C4c marked the Paleo-Indian group(s) that entered North America from Beringia through the ice-free corridor between the Laurentide and Cordilleran ice sheets. The similarities in ages andgeographical distributions for C4c and the previously analyzed X2a lineage provide support to the scenario of a dual origin for Paleo-Indians. Taking into account that C4c is deeply rooted in the Asian portion of the mtDNA phylogeny and is indubitably of Asian origin, the finding that C4c and X2a are characterized by parallel genetic histories definitively dismisses the controversial hypothesis of an Atlantic glacial entry route into North America.

  4. The Si(001) c(4×4) surface reconstruction: a comprehensive experimental study

    NASA Astrophysics Data System (ADS)

    Nörenberg, H.; Briggs, G. A. D.

    1999-06-01

    We have carried out a comprehensive experimental study of the Si(001) c(4×4) surface reconstruction by scanning tunneling microscopy (STM) (at room temperature and elevated temperatures), Auger electron spectroscopy (AES), reflection high-energy electron diffraction (RHEED) and low-energy electron diffraction (LEED). Si(001) samples were kept under ultra-high vacuum (UHV) at around 550°C until the c(4×4) reconstruction appeared. STM contrast of the c(4×4) reconstruction is strongly influenced by electronic effects and changes considerably over a range of bias voltages. The c(4×4) surface reconstruction is a result of stress which is caused by incorporation of impurities or adsorbates in sub-surface locations. The resulting c(4×4) reconstruction in the top layer is a pure silicon structure. The main structural element is a one-dimer vacancy (1-DV). At this vacancy, second layer Si-atoms rebond and cause the adjacent top Si-dimers to brighten up in the STM image at low bias voltages. At higher bias voltage the contrast is similar to Si-dimers on the (2×1) reconstructed Si(001). Therefore, besides the 1-DV and the two adjacent Si-dimers, another Si-dimer under tensile stress may complete the 4× unit cell. This is a refinement of the missing dimer model.

  5. Genetics of the complement system.

    PubMed Central

    Lachmann, P

    1975-01-01

    The complement system, unlike the coagulation system, was largely characterized by in-vitro techniques which did not make use of genetically deficient plasmas. The existence of the genetically deficient plasmas. The existence of the genetically deficient subjects therefore has served largely to increase our knowledge of the in-vivo role of complement. At the present time its clearest role is in the resistance to infection; obviously in the case of C3 deficiency and bacterial infection and possibly more subtly in the case of deficiency of the early active complement components and low virulence organisms. There is so far no evidence that genetic complement deficiency interferes with antibody formation or with the generation of tolerance as has been suggested in the pas (Azar et al, 1968; Dukor and Hartmann, 1973). PMID:768477

  6. How antibodies use complement to regulate antibody responses.

    PubMed

    Sörman, Anna; Zhang, Lu; Ding, Zhoujie; Heyman, Birgitta

    2014-10-01

    Antibodies, forming immune complexes with their specific antigen, can cause complete suppression or several 100-fold enhancement of the antibody response. Immune complexes containing IgG and IgM may activate complement and in such situations also complement components will be part of the immune complex. Here, we review experimental data on how antibodies via the complement system upregulate specific antibody responses. Current data suggest that murine IgG1, IgG2a, and IgG2b upregulate antibody responses primarily via Fc-receptors and not via complement. In contrast, IgM and IgG3 act via complement and require the presence of complement receptors 1 and 2 (CR1/2) expressed on both B cells and follicular dendritic cells. Complement plays a crucial role for antibody responses not only to antigen complexed to antibodies, but also to antigen administered alone. Lack of C1q, but not of Factor B or MBL, severely impairs antibody responses suggesting involvement of the classical pathway. In spite of this, normal antibody responses are found in mice lacking several activators of the classical pathway (complement activating natural IgM, serum amyloid P component (SAP), specific intracellular adhesion molecule-grabbing non-integrin R1 (SIGN-R1) or C-reactive protein. Possible explanations to these observations will be discussed.

  7. Complement Activation Alters Platelet Function

    DTIC Science & Technology

    2013-10-01

    mice and mice transfused with Syk inhibitor-treated platelets . Platelet lodging was remarkably decreased in lungs of mice transfused with Syk...AD_________________ Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet ...30September2012–29September2013 4. TITLE AND SUBTITLE Complement Activation Alters Platelet Function 5a. CONTRACT NUMBER W81XWH-12-1-0523 5b. GRANT NUMBER

  8. Renal Transplant Patients Biopsied for Cause and Tested for C4d, DSA, and IgG Subclasses and C1q: Which Humoral Markers Improve Diagnosis and Outcomes?

    PubMed Central

    Cicciarelli, James C.; Chang, Youngil; Koss, Michael; Hacke, Katrin; Kasahara, Noriyuki; Burns, Kevin M.; Min, David I.; Naraghi, Robert; Shah, Tariq

    2017-01-01

    The association between donor specific antibodies (DSA) and renal transplant rejection has been generally established, but there are cases when a DSA is present without rejection. We examined 73 renal transplant recipients biopsied for transplant dysfunction with DSA test results available: 23 patients diffusely positive for C4d (C4d+), 25 patients focally positive for C4d, and 25 patients negative for C4d (C4d−). We performed C1q and IgG subclass testing in our DSA+ and C4d+ patient group. Graft outcomes were determined for the C4d+ group. All 23 C4d+ patients had IgG DSA with an average of 12,500 MFI (cumulative DSA MFI). The C4d− patients had average DSA less than 500 MFI. Among the patients with C4d+ biopsies, 100% had IgG DSA, 70% had C1q+ DSA, and 83% had complement fixing IgG subclass antibodies. Interestingly, IgG4 was seen in 10 of the 23 recipients' sera, but always along with complement fixing IgG1, and we have previously seen excellent function in patients when IgG4 DSA exists alone. Cumulative DSA above 10,000 MFI were associated with C4d deposition and complement fixation. There was no significant correlation between graft loss and C1q positivity, and IgG subclass analysis seemed to be a better correlate for complement fixing antibodies in the C4d+ patient group. PMID:28182088

  9. Phylogenetic analyses reveal the shady history of C4 grasses.

    PubMed

    Edwards, Erika J; Smith, Stephen A

    2010-02-09

    Grasslands cover more than 20% of the Earth's terrestrial surface, and their rise to dominance is one of the most dramatic events of biome evolution in Earth history. Grasses possess two main photosynthetic pathways: the C(3) pathway that is typical of most plants and a specialized C(4) pathway that minimizes photorespiration and thus increases photosynthetic performance in high-temperature and/or low-CO(2) environments. C(4) grasses dominate tropical and subtropical grasslands and savannas, and C(3) grasses dominate the world's cooler temperate grassland regions. This striking pattern has been attributed to C(4) physiology, with the implication that the evolution of the pathway enabled C(4) grasses to persist in warmer climates than their C(3) relatives. We combined geospatial and molecular sequence data from two public archives to produce a 1,230-taxon phylogeny of the grasses with accompanying climate data for all species, extracted from more than 1.1 million herbarium specimens. Here we show that grasses are ancestrally a warm-adapted clade and that C(4) evolution was not correlated with shifts between temperate and tropical biomes. Instead, 18 of 20 inferred C(4) origins were correlated with marked reductions in mean annual precipitation. These changes are consistent with a shift out of tropical forest environments and into tropical woodland/savanna systems. We conclude that C(4) evolution in grasses coincided largely with migration out of the understory and into open-canopy environments. Furthermore, we argue that the evolution of cold tolerance in certain C(3) lineages is an overlooked innovation that has profoundly influenced the patterning of grassland communities across the globe.

  10. Phylogenetic analyses reveal the shady history of C4 grasses

    PubMed Central

    Edwards, Erika J.; Smith, Stephen A.

    2010-01-01

    Grasslands cover more than 20% of the Earth's terrestrial surface, and their rise to dominance is one of the most dramatic events of biome evolution in Earth history. Grasses possess two main photosynthetic pathways: the C3 pathway that is typical of most plants and a specialized C4 pathway that minimizes photorespiration and thus increases photosynthetic performance in high-temperature and/or low-CO2 environments. C4 grasses dominate tropical and subtropical grasslands and savannas, and C3 grasses dominate the world's cooler temperate grassland regions. This striking pattern has been attributed to C4 physiology, with the implication that the evolution of the pathway enabled C4 grasses to persist in warmer climates than their C3 relatives. We combined geospatial and molecular sequence data from two public archives to produce a 1,230-taxon phylogeny of the grasses with accompanying climate data for all species, extracted from more than 1.1 million herbarium specimens. Here we show that grasses are ancestrally a warm-adapted clade and that C4 evolution was not correlated with shifts between temperate and tropical biomes. Instead, 18 of 20 inferred C4 origins were correlated with marked reductions in mean annual precipitation. These changes are consistent with a shift out of tropical forest environments and into tropical woodland/savanna systems. We conclude that C4 evolution in grasses coincided largely with migration out of the understory and into open-canopy environments. Furthermore, we argue that the evolution of cold tolerance in certain C3 lineages is an overlooked innovation that has profoundly influenced the patterning of grassland communities across the globe. PMID:20142480

  11. SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis.

    PubMed

    Ferreira, Viviana P; Fazito Vale, Vladimir; Pangburn, Michael K; Abdeladhim, Maha; Mendes-Sousa, Antonio Ferreira; Coutinho-Abreu, Iliano V; Rasouli, Manoochehr; Brandt, Elizabeth A; Meneses, Claudio; Lima, Kolyvan Ferreira; Nascimento Araújo, Ricardo; Pereira, Marcos Horácio; Kotsyfakis, Michalis; Oliveira, Fabiano; Kamhawi, Shaden; Ribeiro, Jose M C; Gontijo, Nelder F; Collin, Nicolas; Valenzuela, Jesus G

    2016-01-13

    Blood-feeding insects inject potent salivary components including complement inhibitors into their host's skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the same chromatographic properties as the Lu. longipalpis salivary gland homogenate (SGH)counterparts and anti-rSALO antibodies blocked the classical pathway complement activity of rSALO and SGH. Both rSALO and SGH inhibited C4b deposition and cleavage of C4. rSALO, however, did not inhibit the protease activity of C1s nor the enzymatic activity of factor Xa, uPA, thrombin, kallikrein, trypsin and plasmin. Importantly, rSALO did not inhibit the alternative or the lectin pathway of complement. In conclusion our data shows that SALO is a specific classical pathway complement inhibitor present in the saliva of Lu. longipalpis. Importantly, due to its small size and specificity, SALO may offer a therapeutic alternative for complement classical pathway-mediated pathogenic effects in human diseases.

  12. Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells

    PubMed Central

    Meulenbroek, Elisabeth M.; Wouters, Diana; Zeerleder, Sacha

    2014-01-01

    Antibodies against red blood cells (RBCs) can lead to complement activation resulting in an accelerated clearance via complement receptors in the liver (extravascular hemolysis) or leading to intravascular lysis of RBCs. Alloantibodies (e.g. ABO) or autoantibodies to RBC antigens (as seen in autoimmune hemolytic anemia, AIHA) leading to complement activation are potentially harmful and can be - especially when leading to intravascular lysis - fatal1. Currently, complement activation due to (auto)-antibodies on RBCs is assessed in vitro by using the Coombs test reflecting complement deposition on RBC or by a nonquantitative hemolytic assay reflecting RBC lysis1-4. However, to assess the efficacy of complement inhibitors, it is mandatory to have quantitative techniques. Here we describe two such techniques. First, an assay to detect C3 and C4 deposition on red blood cells that is induced by antibodies in patient serum is presented. For this, FACS analysis is used with fluorescently labeled anti-C3 or anti-C4 antibodies. Next, a quantitative hemolytic assay is described. In this assay, complement-mediated hemolysis induced by patient serum is measured making use of spectrophotometric detection of the released hemoglobin. Both of these assays are very reproducible and quantitative, facilitating studies of antibody-induced complement activation. PMID:24514151

  13. SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis

    PubMed Central

    Ferreira, Viviana P.; Fazito Vale, Vladimir; Pangburn, Michael K.; Abdeladhim, Maha; Ferreira Mendes-Sousa, Antonio; Coutinho-Abreu, Iliano V.; Rasouli, Manoochehr; Brandt, Elizabeth A.; Meneses, Claudio; Lima, Kolyvan Ferreira; Nascimento Araújo, Ricardo; Horácio Pereira, Marcos; Kotsyfakis, Michalis; Oliveira, Fabiano; Kamhawi, Shaden; Ribeiro, Jose M. C.; Gontijo, Nelder F.; Collin, Nicolas; Valenzuela, Jesus G.

    2016-01-01

    Blood-feeding insects inject potent salivary components including complement inhibitors into their host’s skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the same chromatographic properties as the Lu. longipalpis salivary gland homogenate (SGH)counterparts and anti-rSALO antibodies blocked the classical pathway complement activity of rSALO and SGH. Both rSALO and SGH inhibited C4b deposition and cleavage of C4. rSALO, however, did not inhibit the protease activity of C1s nor the enzymatic activity of factor Xa, uPA, thrombin, kallikrein, trypsin and plasmin. Importantly, rSALO did not inhibit the alternative or the lectin pathway of complement. In conclusion our data shows that SALO is a specific classical pathway complement inhibitor present in the saliva of Lu. longipalpis. Importantly, due to its small size and specificity, SALO may offer a therapeutic alternative for complement classical pathway-mediated pathogenic effects in human diseases. PMID:26758086

  14. The C4 clustering algorithm: Clusters of galaxies in the Sloan Digital Sky Survey

    SciTech Connect

    Miller, Christopher J.; Nichol, Robert; Reichart, Dan; Wechsler, Risa H.; Evrard, August; Annis, James; McKay, Timothy; Bahcall, Neta; Bernardi, Mariangela; Boehringer, Hans; Connolly, Andrew; Goto, Tomo; Kniazev, Alexie; Lamb, Donald; Postman, Marc; Schneider, Donald; Sheth, Ravi; Voges, Wolfgang; /Cerro-Tololo InterAmerican Obs. /Portsmouth U., ICG /North Carolina U. /Chicago U., Astron. Astrophys. Ctr. /Chicago U., EFI /Michigan U. /Fermilab /Princeton U. Observ. /Garching, Max Planck Inst., MPE /Pittsburgh U. /Tokyo U., ICRR /Baltimore, Space Telescope Sci. /Penn State U. /Chicago U. /Stavropol, Astrophys. Observ. /Heidelberg, Max Planck Inst. Astron. /INI, SAO

    2005-03-01

    We present the ''C4 Cluster Catalog'', a new sample of 748 clusters of galaxies identified in the spectroscopic sample of the Second Data Release (DR2) of the Sloan Digital Sky Survey (SDSS). The C4 cluster-finding algorithm identifies clusters as overdensities in a seven-dimensional position and color space, thus minimizing projection effects that have plagued previous optical cluster selection. The present C4 catalog covers {approx}2600 square degrees of sky and ranges in redshift from z = 0.02 to z = 0.17. The mean cluster membership is 36 galaxies (with redshifts) brighter than r = 17.7, but the catalog includes a range of systems, from groups containing 10 members to massive clusters with over 200 cluster members with redshifts. The catalog provides a large number of measured cluster properties including sky location, mean redshift, galaxy membership, summed r-band optical luminosity (L{sub r}), velocity dispersion, as well as quantitative measures of substructure and the surrounding large-scale environment. We use new, multi-color mock SDSS galaxy catalogs, empirically constructed from the {Lambda}CDM Hubble Volume (HV) Sky Survey output, to investigate the sensitivity of the C4 catalog to the various algorithm parameters (detection threshold, choice of passbands and search aperture), as well as to quantify the purity and completeness of the C4 cluster catalog. These mock catalogs indicate that the C4 catalog is {approx_equal}90% complete and 95% pure above M{sub 200} = 1 x 10{sup 14} h{sup -1}M{sub {circle_dot}} and within 0.03 {le} z {le} 0.12. Using the SDSS DR2 data, we show that the C4 algorithm finds 98% of X-ray identified clusters and 90% of Abell clusters within 0.03 {le} z {le} 0.12. Using the mock galaxy catalogs and the full HV dark matter simulations, we show that the L{sub r} of a cluster is a more robust estimator of the halo mass (M{sub 200}) than the galaxy line-of-sight velocity dispersion or the richness of the cluster. However, if we

  15. The Lectin Pathway of Complement and Rheumatic Heart Disease

    PubMed Central

    Beltrame, Marcia Holsbach; Catarino, Sandra Jeremias; Goeldner, Isabela; Boldt, Angelica Beate Winter; de Messias-Reason, Iara José

    2014-01-01

    The innate immune system is the first line of host defense against infection and is comprised of humoral and cellular mechanisms that recognize potential pathogens within minutes or hours of entry. The effector components of innate immunity include epithelial barriers, phagocytes, and natural killer cells, as well as cytokines and the complement system. Complement plays an important role in the immediate response against microorganisms, including Streptococcus sp. The lectin pathway is one of three pathways by which the complement system can be activated. This pathway is initiated by the binding of mannose-binding lectin (MBL), collectin 11 (CL-K1), and ficolins (Ficolin-1, Ficolin-2, and Ficolin-3) to microbial surface oligosaccharides and acetylated residues, respectively. Upon binding to target molecules, MBL, CL-K1, and ficolins form complexes with MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2), which cleave C4 and C2 forming the C3 convertase (C4b2a). Subsequent activation of complement cascade leads to opsonization, phagocytosis, and lysis of target microorganisms through the formation of the membrane-attack complex. In addition, activation of complement may induce several inflammatory effects, such as expression of adhesion molecules, chemotaxis and activation of leukocytes, release of reactive oxygen species, and secretion of cytokines and chemokines. In this chapter, we review the general aspects of the structure, function, and genetic polymorphism of lectin-pathway components and discuss most recent understanding on the role of the lectin pathway in the predisposition and clinical progression of Rheumatic Fever. PMID:25654073

  16. Snake venoms. The amino-acid sequence of protein S5C4 from Dendroaspis jamesoni kaimosae (Jameson's mamba) venom.

    PubMed

    Joubert, F J; Strydom, A J; Taljaard, N

    1978-06-01

    A major component (S5C4) was purified from Jameson's mamba by gel filtration on Sephadex G-50 and by ion-exchange chromotography on CM-cellulose. Protein S5C4 contains 60 amino acid residues and is cross-linked by four intrachain disulphide bridges. The complete primary structure of the protein has been elucidated. The toxicities, the immunochemical properties, the sequence and the invariant amino acid residues of protein S5C4 resemble subgroup II of the angusticeps-type proteins.

  17. Mycoplasma polysaccharide protects against complement

    PubMed Central

    Bolland, Jeffrey R.; Simmons, Warren L.; Daubenspeck, James M.

    2012-01-01

    Although they lack a cell wall, mycoplasmas do possess a glycocalyx. The interactions between the glycocalyx, mycoplasmal surface proteins and host complement were explored using the murine pathogen Mycoplasma pulmonis as a model. It was previously shown that the length of the tandem repeat region of the surface lipoprotein Vsa is associated with susceptibility to complement-mediated killing. Cells producing a long Vsa containing about 40 repeats are resistant to complement, whereas strains that produce a short Vsa of five or fewer repeats are susceptible. We show here that the length of the Vsa protein modulates the affinity of the M. pulmonis EPS-I polysaccharide for the mycoplasma cell surface, with more EPS-I being associated with mycoplasmas producing a short Vsa protein. An examination of mutants that lack EPS-I revealed that planktonic mycoplasmas were highly susceptible to complement killing even when the Vsa protein was long, demonstrating that both EPS-I and Vsa length contribute to resistance. In contrast, the mycoplasmas were resistant to complement even in the absence of EPS-I when the cells were encased in a biofilm. PMID:22504437

  18. Wild Manihot Species Do Not Possess C4 Photosynthesis

    PubMed Central

    CALATAYUD, P.‐A.; BARÓN, C. H.; VELÁSQUEZ, H.; ARROYAVE, J. A.; LAMAZE, T.

    2002-01-01

    Cultivated cassava (Manihot esculenta) has a higher rate of photosynthesis than is usual for C3 plants and photosynthesis is not light saturated. For these reasons it has been suggested that cultivated cassava could be derived from wild species possessing C4 photosynthesis. The natural abundance of 13C and activities of phosphoenolpyruvate carboxylase and phosphoglycolate phosphatase were measured in leaves of 20 wild cassava species to test this hypothesis. All the species studied, including M. flabellifolia the potential wild progenitor of cultivated cassava, clearly exhibited C3 not C4 characteristics. PMID:12096814

  19. Evolution of CAM and C4 carbon-concentrating mechanisms

    USGS Publications Warehouse

    Keeley, Jon E.; Rundel, Philip W.

    2003-01-01

    Mechanisms for concentrating carbon around the Rubisco enzyme, which drives the carbon-reducing steps in photosynthesis, are widespread in plants; in vascular plants they are known as crassulacean acid metabolism (CAM) and C4 photosynthesis. CAM is common in desert succulents, tropical epiphytes, and aquatic plants and is characterized by nighttime fixation of CO2. The proximal selective factor driving the evolution of this CO2-concentrating pathway is low daytime CO2, which results from the unusual reverse stomatal behavior of terrestrial CAM species or from patterns of ambient CO2 availability for aquatic CAM species. In terrestrials the ultimate selective factor is water stress that has selected for increased water use efficiency. In aquatics the ultimate selective factor is diel fluctuations in CO2 availability for palustrine species and extreme oligotrophic conditions for lacustrine species. C4 photosynthesis is based on similar biochemistry but carboxylation steps are spatially separated in the leaf rather than temporally as in CAM. This biochemical pathway is most commonly associated with a specialized leaf anatomy known as Kranz anatomy; however, there are exceptions. The ultimate selective factor driving the evolution of this pathway is excessively high photorespiration that inhibits normal C3 photosynthesis under high light and high temperature in both terrestrial and aquatic habitats. CAM is an ancient pathway that likely has been present since the Paleozoic era in aquatic species from shallow-water palustrine habitats. While atmospheric CO2 levels have undoubtedly affected the evolution of terrestrial plant carbon-concentrating mechanisms, there is reason to believe that past atmospheric changes have not played as important a selective role in the aquatic milieu since palustrine habitats today are not generally carbon sinks, and the selective factors driving aquatic CAM are autogenic. Terrestrial CAM, in contrast, is of increasing selective value under

  20. Applicability of Virtual Environments as C4ISR Displays

    DTIC Science & Technology

    2006-06-01

    simulator sickness questionnaire (ssq): A method for quantifying simulator sickness. International Journal of Aviation Psychology, 3(3):203ff. Ergonomie ...Displays Thomas Alexander FGAN - Research Institute for Communication, Information Processing, and Ergonomics Wachtberg, Germany Ergonomie und...Führungssysteme FORSCHUNGSINSTITUT FÜR KOMMUNIKATION, INFORMATIONSVERARBEITUNG UND ERGONOMIE 1 FGAN Applicability of Virtual Environments as C4ISR Displays

  1. DNA-Mediated Prophage Induction in Bacillus subtilis Lysogenic for φ105c4

    PubMed Central

    Garro, Anthony J.

    1973-01-01

    Prophage was induced when strains of Bacillus subtilis 168 lysogenic for φ105c4 were grown to competence and exposed to specific bacterial DNAs. The time course of phage production was similar to that observed for mitomycin C induction of wild-type prophage. Induction was directly dependent upon DNA concentration up to levels which were saturating for the transformation of bacterial auxotrophic markers. The extent of induction varied with the source of DNA. The burst of phage induced by DNA isolated from a W23 strain of B. subtilis was fivefold less than that induced by DNA from B. subtilis 168 strains, while B. licheniformis DNA was completely inactive. This order of inducing activity was correlated with the ability of the respective DNAs to transform auxotrophic markers carried by one of the φ105c4 lysogens. Differences in inducing activity also were observed for different forms of φ105 DNA. The DNAs isolated from φ105 phage particles and φ105c4 lysogens were inactive, whereas DNA from cells lysogenized by wild-type φ105 induced a burst of phage. When tested for transforming activity, however, both φ105c4 and φ105 lysogen DNAs were equally effective. An induction mechanism which involves recombination at the prophage insertion site is proposed to explain these differences. PMID:4199106

  2. Transition from half metal to semiconductor in Li doped g-C4N3

    NASA Astrophysics Data System (ADS)

    Hashmi, Arqum; Hu, Tao; Hong, Jisang

    2014-03-01

    We have investigated the structural and magnetic properties of Li doped graphitic carbon nitride (g-C4N3) using the van der Waals density functional theory. A free standing g-C4N3 was known to show a half metallic state with buckling geometry, but this feature completely disappears in the presence of Li doping. Besides this structural modification, very interestingly, we have obtained that the Li doped g-C4N3 shows dramatic change in its electronic structure. Both ferromagnetic and nonmagnetic states are almost degenerated in one Li atom doped system. However, the transition from half metallic state to semiconductor is observed with further increase of Li concentration and the calculated energy gap is 1.97 eV. We found that Li impurity plays as a donor element and charge transfer from the Li atom to neighboring N atoms induces a band gap. Overall, we have observed that the electronic and magnetic properties of g-C4N3 are substantially modified by Li doping.

  3. Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors

    PubMed Central

    Ermert, David; Shaughnessy, Jutamas; Joeris, Thorsten; Kaplan, Jakub; Pang, Catherine J.; Kurt-Jones, Evelyn A.; Rice, Peter A.; Ram, Sanjay; Blom, Anna M.

    2015-01-01

    Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and consequent phagocytosis. Several strains of GAS bind to human-specific complement inhibitors, C4b-binding protein (C4BP) and/or Factor H (FH), to curtail complement C3 (a critical opsonin) deposition. This results in diminished activation of phagocytes and clearance of GAS that may lead to the host being unable to limit the infection. Herein we describe the course of GAS infection in three human complement inhibitor transgenic (tg) mouse models that examined each inhibitor (human C4BP or FH) alone, or the two inhibitors together (C4BPxFH or ‘double’ tg). GAS infection with strains that bound C4BP and FH resulted in enhanced mortality in each of the three transgenic mouse models compared to infection in wild type mice. In addition, GAS manifested increased virulence in C4BPxFH mice: higher organism burdens and greater elevations of pro-inflammatory cytokines and they died earlier than single transgenic or wt controls. The effects of hu-C4BP and hu-FH were specific for GAS strains that bound these inhibitors because strains that did not bind the inhibitors showed reduced virulence in the ‘double’ tg mice compared to strains that did bind; mortality was also similar in wild-type and C4BPxFH mice infected by non-binding GAS. Our findings emphasize the importance of binding of complement inhibitors to GAS that results in impaired opsonization and phagocytic killing, which translates to enhanced virulence in a humanized whole animal model. This novel hu-C4BPxFH tg model may prove invaluable in studies of GAS pathogenesis and for developing vaccines and therapeutics that rely on human complement activation for efficacy. PMID:26200783

  4. [The role of complement factor H in the pathogenesis of Borrelia infection].

    PubMed

    Gęca, Aleksandra; Mazurek, Urszula; Muc-Wierzgoń, Małgorzata; Nowakowska-Zajdel, Ewa; Niedworok, Elżbieta; Ziółko, Ewa; Kokot, Teresa

    2012-07-20

    Complement factor H (CFH) is one of the most important negative regulators of the alternative pathway of the complement system. It is a glycoprotein belonging to the protein H family, which is synthesized mainly in the liver and is composed into a globular protein consisting of 60 amino acid domains in the serum. It shows specificity for C3b molecule of the complement system present in the serum or bound to the cell surface. It inhibits the steady formation of C3 convertase enzymes and the binding of C2 to C4b and factor B to C3b. It accelerates the decomposition of C2a into C4b and the displacement of Bb from C3b. The present paper discusses the composition, properties and functions of the complement factor and the family it belongs to. The paper focuses in particular on its role in the pathogenesis of an infection caused by the spirochetes of the Borrelia genus. Through binding CFH and other related proteins, bacteria of the Borrelia species inhibit the key effect of the alternative pathway of the complement system - the lysis of spirochete cells dependent on the complement's activation. The mechanism enables pathogens to spread in the host organism and facilitates the evolution of the disease. Discovering the immune mechanisms of the infection caused by the spirochetes of the Borrelia genus may allow for implementing a therapy blocking the binding of complement factor H early enough, apart from the standard treatment of the disease.

  5. Improvisation: A Complement to Curriculum

    ERIC Educational Resources Information Center

    Ronald, Green A.

    2006-01-01

    With the growth of standardized assessment benchmarks in both the public and private paradigms, testing performance matters to institutions more than ever. In an attempt to take as many hindering variables out of this process, such as test anxiety, socioeconomic influences, and latency in cognition, Improvisation: A Complement to Curriculum seeks…

  6. Role of complement in xenotransplantation.

    PubMed

    Mollnes, Tom Eirik; Fiane, A E

    2002-01-01

    The xenotransplantation research is driven by the increasing gap between the number of patients with end-stage organ failure on waiting lists for transplantation and the supply of allografts. The lack of success in developing suitable artificial organs for permanent treatment of organ failure has further strengthened the need for xenotransplantation research. Pigs are now generally accepted to be the source animal of choice. Transplantation of pig organs to humans faces several barriers which have to be overcome before it comes to clinical application: (1) anatomical and physiological conditions; (2) immunological rejection mechanisms; (3) molecular compatibility between signal molecules of the two species; (4) risk of transmission of microorganisms, particularly pig endogenous retroviruses; and (5) legal and ethical aspects both with respect to the animal and the recipient. Here we will focus on the role of the complement system in the rejection of immediately vascularized pig-to-primate xenografts. The hyperacute rejection occurring within minutes after transplantation is mediated by binding of natural antibodies to the Galalpha(l-3)Gal epitope on the endothelial cells with subsequent complement activation. Whereas inhibition of complement activation protects against hyperacute rejection, the role of complement in the later rejection phases is less clarified.

  7. Sentential Complementation--An Overview.

    ERIC Educational Resources Information Center

    Nuessel, Frank H., Jr.

    A review of traditional and transformational studies on the phenomenon of sentential complementation (noun clauses) reveals many areas of agreement. Although some adherents of generative grammar may have occasionally obscured this aspect because of the offensive nature of their criticism of other modes of analysis, it is seen that, in several…

  8. 670-nm light treatment reduces complement propagation following retinal degeneration

    PubMed Central

    2012-01-01

    Aim Complement activation is associated with the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate whether 670-nm light treatment reduces the propagation of complement in a light-induced model of atrophic AMD. Methods Sprague–Dawley (SD) rats were pretreated with 9 J/cm2 670-nm light for 3 minutes daily over 5 days; other animals were sham treated. Animals were exposed to white light (1,000 lux) for 24 h, after which animals were kept in dim light (5 lux) for 7 days. Expression of complement genes was assessed by quantitative polymerase chain reaction (qPCR), and immunohistochemistry. Counts were made of C3-expressing monocytes/microglia using in situ hybridization. Photoreceptor death was also assessed using outer nuclear layer (ONL) thickness measurements, and oxidative stress using immunohistochemistry for 4-hydroxynonenal (4-HNE). Results Following light damage, retinas pretreated with 670-nm light had reduced immunoreactivity for the oxidative damage maker 4-HNE in the ONL and outer segments, compared to controls. In conjunction, there was significant reduction in retinal expression of complement genes C1s, C2, C3, C4b, C3aR1, and C5r1 following 670 nm treatment. In situ hybridization, coupled with immunoreactivity for the marker ionized calcium binding adaptor molecule 1 (IBA1), revealed that C3 is expressed by infiltrating microglia/monocytes in subretinal space following light damage, which were significantly reduced in number after 670 nm treatment. Additionally, immunohistochemistry for C3 revealed a decrease in C3 deposition in the ONL following 670 nm treatment. Conclusions Our data indicate that 670-nm light pretreatment reduces lipid peroxidation and complement propagation in the degenerating retina. These findings have relevance to the cellular events of complement activation underling the pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive anti-inflammatory therapy. PMID:23181358

  9. Structural insights on complement activation.

    PubMed

    Alcorlo, Martín; López-Perrote, Andrés; Delgado, Sandra; Yébenes, Hugo; Subías, Marta; Rodríguez-Gallego, César; Rodríguez de Córdoba, Santiago; Llorca, Oscar

    2015-10-01

    The proteolytic cleavage of C3 to generate C3b is the central and most important step in the activation of complement, a major component of innate immunity. The comparison of the crystal structures of C3 and C3b illustrates large conformational changes during the transition from C3 to C3b. Exposure of a reactive thio-ester group allows C3b to bind covalently to surfaces such as pathogens or apoptotic cellular debris. The displacement of the thio-ester-containing domain (TED) exposes hidden surfaces that mediate the interaction with complement factor B to assemble the C3-convertase of the alternative pathway (AP). In addition, the displacement of the TED and its interaction with the macroglobulin 1 (MG1) domain generates an extended surface in C3b where the complement regulators factor H (FH), decay accelerating factor (DAF), membrane cofactor protein (MCP) and complement receptor 1 (CR1) can bind, mediating accelerated decay of the AP C3-convertase and proteolytic inactivation of C3b. In the last few years, evidence has accumulated revealing that the structure of C3b in solution is significantly more flexible than anticipated. We review our current knowledge on C3b structural flexibility to propose a general model where the TED can display a collection of conformations around the MG ring, as well as a few specialized positions where the TED is held in one of several fixed locations. Importantly, this conformational heterogeneity in C3b impacts complement regulation by affecting the interaction with regulators.

  10. Complement activation and effect of eculizumab in scleroderma renal crisis

    PubMed Central

    Devresse, Arnaud; Aydin, Selda; Le Quintrec, Moglie; Demoulin, Nathalie; Stordeur, Patrick; Lambert, Catherine; Gastoldi, Sara; Pirson, Yves; Jadoul, Michel; Morelle, Johann

    2016-01-01

    Abstract Background: Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis characterized by abrupt onset of hypertension, thrombotic microangiopathy, and kidney injury. The mechanisms of the disease remain ill-defined, but a growing body of evidence suggests that activation of the complement system may be involved. Methods: Here, we report the case of a patient presenting with severe SRC and strong evidence of complement activation, both in serum and in the kidney, in the absence of genetic defect of the complement system. Results: Immunofluorescence studies on kidney biopsy showed significant deposits of C1q and C4d in the endothelium of renal arterioles, pointing toward activation of the classical pathway. Because of the dramatic clinical and histological severity, and the lack of response to early treatment with angiotensin-converting enzyme inhibitors, calcium channel blockers and plasma exchange, the patient was treated with the specific C5 blocker eculizumab. Contrarily to conventional treatment, eculizumab efficiently blocked C5b-9 deposition ex vivo and maintained hematological remission. Unfortunately, the patient died from heart failure a few weeks later. Postmortem examination of the heart showed diffuse patchy interstitial fibrosis, the typical lesion of systemic sclerosis-related cardiomyopathy, but normal coronary arteries and myocardial microvasculature. Conclusion: SRC may lead to complement system activation through the classical pathway. Early administration of C5 inhibitor eculizumab may have therapeutic potential in patients with life-threatening SRC refractory to conventional treatment using angiotensin-converting enzyme inhibitors. PMID:27472742

  11. Deriving C4 photosynthetic parameters from combined gas exchange and chlorophyll fluorescence using an Excel tool: theory and practice.

    PubMed

    Bellasio, Chandra; Beerling, David J; Griffiths, Howard

    2016-06-01

    The higher photosynthetic potential of C4 plants has led to extensive research over the past 50 years, including C4 -dominated natural biomes, crops such as maize, or for evaluating the transfer of C4 traits into C3 lineages. Photosynthetic gas exchange can be measured in air or in a 2% Oxygen mixture using readily available commercial gas exchange and modulated PSII fluorescence systems. Interpretation of these data, however, requires an understanding (or the development) of various modelling approaches, which limit the use by non-specialists. In this paper we present an accessible summary of the theory behind the analysis and derivation of C4 photosynthetic parameters, and provide a freely available Excel Fitting Tool (EFT), making rigorous C4 data analysis accessible to a broader audience. Outputs include those defining C4 photochemical and biochemical efficiency, the rate of photorespiration, bundle sheath conductance to CO2 diffusion and the in vivo biochemical constants for PEP carboxylase. The EFT compares several methodological variants proposed by different investigators, allowing users to choose the level of complexity required to interpret data. We provide a complete analysis of gas exchange data on maize (as a model C4 organism and key global crop) to illustrate the approaches, their analysis and interpretation. © 2015 John Wiley & Sons Ltd.

  12. Cigarette smoke can activate the alternative pathway of complement in vitro by modifying the third component of complement.

    PubMed Central

    Kew, R R; Ghebrehiwet, B; Janoff, A

    1985-01-01

    Cigarette smoking is associated with significant increases in the number of pulmonary mononuclear phagocytes and neutrophils. A potent chemoattractant for these cells is C5a, a peptide generated during complement (C) activation. We, therefore, investigated the possibility that cigarette smoke could activate the complement system in vitro. Our results show that factor(s) (mol wt less than 1,000) present in an aqueous solution of whole, unfiltered cigarette smoke can deplete the hemolytic capacity of whole human serum in a dose-dependent manner. The particle-free, filtered gas phase of cigarette smoke is inactive. The smoke factor(s) do not activate serum C1, but do deplete serum C4 activity. Treatment of purified human C3 with whole smoke solution modifies the molecule such that its subsequent addition to serum (containing Mg/EGTA to block the classical pathway) results in consumption of hemolytic complement by activation of the alternative pathway. Smoke-modified C3 shows increased anodal migration in agarose electrophoresis, but this is not due to proteolytic cleavage of the molecule as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In contrast to methylamine-treated C3, C3 treated with smoke is only partially susceptible to the action of the complement regulatory proteins Factors H and I. In addition, smoke-modified C3 has diminished binding to Factor H as compared with methylamine-treated C3. Finally, smoke-modified C3 incorporates [14C]methylamine which suggests that the thiolester bond may be intact. These data indicate that aqueous whole cigarette smoke solution can modify C3 and activate the alternative pathway of complement, perhaps by a previously unrecognized mechanism. Should this occur in vivo, complement activation might partly account for the extensive pulmonary leukocyte recruitment observed in smokers. Images PMID:3156879

  13. Cometary coma chemical composition (C4) mission. [Abstract only

    NASA Technical Reports Server (NTRS)

    Carle, G. C.; Clark, B. C.; Niemann, H. B.; Alexander, M.; Knocke, P. C.; O'Hara, B. J.

    1994-01-01

    Cometary missions are of enormous fundamental importance for many different space science disciplines, including exobiology. Comets are presumed relics of the earliest, most primitive material in the solar nebula and are related to the planetesimals. They undoubtedly provided a general enrichment of volatiles to the inner solar system (contributing to atmospheres and oceans) and may have been key to the origin of life. A Discovery class, comet rendezvous mission, the Cometary Coma Chemical Composition (C4) Mission, was selected for further study by NASA earlier this year. The C4 Mission is a highly focused and usefully-limited subset of the Cometary Rendezvous Asteroid Flyby (CRAF) Mission, concentrating exclusively on measurements which will lead to an understanding of the chemical composition and make-up of the cometary nucleus. The scientific goals of the Cometary Coma Chemical Composition (C4) Mission are to rendezvous with a short-period comet and (1) to determine the elemental, chemical, and isotopic composition of the nucleus and (2) to characterize the chemical and isotopic nature of its atmosphere. Further, it is a goal to obtain preliminary data on the development of the coma (dust and gas composition) as a function of time and orbital position.

  14. Photorespiration in C4 grasses remains slow under drought conditions.

    PubMed

    Carmo-Silva, Ana E; Powers, Stephen J; Keys, Alfred J; Arrabaça, Maria Celeste; Parry, Martin A J

    2008-07-01

    The CO(2)-concentrating mechanism present in C(4) plants decreases the oxygenase activity of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and, consequently, photorespiratory rates in air. Under drought conditions, the intercellular CO(2) concentration may decrease and cause photorespiration to increase. The C(4) grasses Paspalum dilatatum Poiret, Cynodon dactylon (L.) Pers. and Zoysia japonica Steudel were grown in soil and drought was imposed by ceasing to provide water. Net CO(2) assimilation (A) and stomatal conductance to water vapour decreased with leaf dehydration. Decreased carbon and increased oxygen isotope composition were also observed under drought. The response of A to CO(2) suggested that the compensation point was zero in all species irrespective of the extent of drought stress. A slight decrease of A as O(2) concentration increased above 10% provided evidence for slow photorespiratory gas exchanges. Analysis of amino acids contained in the leaves, particularly the decrease of glycine after 30 s in darkness, supported the presence of slow photorespiration rates, but these were slightly faster in Cynodon dactylon than in Paspalum dilatatum and Zoysia japonica. Although the contents of glycine and serine increased with dehydration and mechanistic modelling of C(4) photosynthesis suggested slightly increased photorespiration rates in proportion to photosynthesis, the results provide evidence that photorespiration remained slow under drought conditions.

  15. C4: a real-time object detection framework.

    PubMed

    Wu, Jianxin; Liu, Nini; Geyer, Christopher; Rehg, James M

    2013-10-01

    A real-time and accurate object detection framework, C(4), is proposed in this paper. C(4) achieves 20 fps speed and the state-of-the-art detection accuracy, using only one processing thread without resorting to special hardware such as GPU. The real-time accurate object detection is made possible by two contributions. First, we conjecture (with supporting experiments) that contour is what we should capture and signs of comparisons among neighboring pixels are the key information to capture contour cues. Second, we show that the CENTRIST visual descriptor is suitable for contour based object detection, because it encodes the sign information and can implicitly represent the global contour. When CENTRIST and linear classifier are used, we propose a computational method that does not need to explicitly generate feature vectors. It involves no image preprocessing or feature vector normalization, and only requires O(1) steps to test an image patch. C(4) is also friendly to further hardware acceleration. It has been applied to detect objects such as pedestrians, faces, and cars on benchmark data sets. It has comparable detection accuracy with state-of-the-art methods, and has a clear advantage in detection speed.

  16. Inactivation of C4orf26 in toothless placental mammals.

    PubMed

    Springer, Mark S; Starrett, James; Morin, Phillip A; Lanzetti, Agnese; Hayashi, Cheryl; Gatesy, John

    2016-02-01

    Previous studies have reported inactivated copies of six enamel-related genes (AMBN, AMEL, AMTN, ENAM, KLK4, MMP20) and one dentin-related gene (DSPP) in one or more toothless vertebrates and/or vertebrates with enamelless teeth, thereby providing evidence that these genes are enamel or tooth-specific with respect to their critical functions that are maintained by natural selection. Here, we employ available genome sequences for edentulous and enamelless mammals to evaluate the enamel specificity of four genes (WDR72, SLC24A4, FAM83H, C4orf26) that have been implicated in amelogenesis imperfecta, a condition in which proper enamel formation is abrogated during tooth development. Coding sequences for WDR72, SCL24A4, and FAM83H are intact in four edentulous taxa (Chinese pangolin, three baleen whales) and three taxa (aardvark, nine-banded armadillo, Hoffmann's two-toed sloth) with enamelless teeth, suggesting that these genes have critical functions beyond their involvement in tooth development. By contrast, genomic data for C4orf26 reveal inactivating mutations in pangolin and bowhead whale as well as evidence for deletion of this gene in two minke whale species. Hybridization capture of exonic regions and PCR screens provide evidence for inactivation of C4orf26 in eight additional baleen whale species. However, C4orf26 is intact in all three species with enamelless teeth that were surveyed, as well as in 95 additional mammalian species with enamel-capped teeth. Estimates of selection intensity suggest that dN/dS ratios on branches leading to taxa with enamelless teeth are similar to the dN/dS ratio on branches leading to taxa with enamel-capped teeth. Based on these results, we conclude that C4orf26 is tooth-specific, but not enamel-specific, with respect to its essential functions that are maintained by natural selection. A caveat is that an alternative splice site variant, which translates exon 3 in a different reading frame, is putatively functional in

  17. Properdin is critical for antibody-dependent bactericidal activity against Neisseria gonorrhoeae that recruit C4b-binding protein1

    PubMed Central

    Gulati, Sunita; Agarwal, Sarika; Vasudhev, Shreekant; Rice, Peter A.; Ram, Sanjay

    2012-01-01

    Gonorrhea, a sexually transmitted disease caused by Neisseria gonorrhoeae, is an important cause of morbidity worldwide. A safe and effective vaccine against gonorrhea is needed because of emerging resistance of gonococci to almost every class of antibiotic. A gonococcal lipooligosaccharide (LOS) epitope defined by the monoclonal antibody (mAb), 2C7, is being evaluated as a candidate for development of an antibody-based vaccine. Immune antibodies against N. gonorrhoeae need to overcome several subversive mechanisms whereby gonococcus evades complement, including binding to C4b-binding protein (C4BP; classical pathway inhibitor) and factor H (alternative pathway [AP] inhibitor). The role of AP recruitment and in particular properdin in assisting killing of gonococci by specific antibodies is the subject of this study. We show that only those gonococcal strains that bind C4BP require properdin for killing by 2C7, whereas strains that do not bind C4BP are efficiently killed by 2C7 even when AP function is blocked. C3 deposition on bacteria mirrored killing. Recruitment of the AP by mAb 2C7, as measured by factor B binding, occurred in a properdin-dependent manner. These findings were confirmed using isogenic mutant strains that differed in their ability to bind to C4BP. Immune human serum that contained bactericidal antibodies directed against the 2C7 LOS epitope as well as murine anti-gonococcal antiserum, required functional properdin to kill C4BP binding strains, but not C4BP non-binding strains. Collectively, these data point to an important role for properdin in facilitating immune antibody-mediated complement-dependent killing of gonococcal strains that inhibit the classical pathway by recruiting C4BP. PMID:22368277

  18. Complement in lupus nephritis: the good, the bad, and the unknown.

    PubMed

    Bao, Lihua; Quigg, Richard J

    2007-01-01

    The complement system consists of 3 pathways and more than 30 proteins, including those with biological activity that directly or indirectly mediate the effects of this system, plus a set of regulatory proteins necessary to prevent injudicious complement activation on host tissue. The role for complement in the pathogenesis of systemic lupus erythematosus (SLE) is paradoxic. On one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classic pathway components are associated with an increased risk for SLE. On the other hand, immune complex-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathologic features that are logical consequences of complement activation. By using accurate mouse models of SLE, we have gained remarkable insights into pathogenic features likely relevant to the human disease, and the ability to test potential therapies, some of which have made it to standard clinical use. Studies in genetically altered mice and using recombinant protein inhibitors of complement have confirmed what was believed but unproven-early complement proteins C1q and C4 are protective whereas complement activation later in the pathways is proinflammatory and deleterious. Two complement inhibitors, soluble complement receptor 1 (TP10, Avant Immunotherapeutics, Needham, MA) and a monoclonal anti-C5 antibody (Eculizumab, Alexion Pharmaceuticals, Inc., Cheshire, CT) have been shown to inhibit complement safely and now are being investigated in a variety of clinical conditions. Although these and others earlier in their clinical development hold promise to be used therapeutically in lupus nephritis, this optimism must be tempered by the fact that the clinical trials to prove this remain fraught with obstacles.

  19. Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium

    PubMed Central

    Prechl, József; Papp, Krisztián; Hérincs, Zoltán; Péterfy, Hajna; Lóránd, Veronika; Szittner, Zoltán; Estonba, Andone; Rovero, Paolo; Paolini, Ilaria; del Amo, Jokin; Uribarri, Maria; Alcaro, Maria Claudia; Ruiz-Larrañaga, Otsanda; Migliorini, Paola; Czirják, László

    2016-01-01

    Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n = 211), with other systemic autoimmune diseases (n = 65) and non-autoimmune control subjects (n = 149). Standard clinical and laboratory data were collected and serum complement levels were determined. The genotype of SNP rs1143679 in the ITGAM gene was also determined. Ex vivo formation of immune complexes, with respect to IgM, IgG, complement C4 and C3 binding, was examined using a functional immunoassay on autoantigen microarray comprising nucleic acids, proteins and lipids. Complement consumption of nucleic acids increased upon binding of IgM and IgG even when serum complement levels were decreased due to consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, complement deposition on tested protein and lipid autoantigens showed positive correlation with C4 levels. Genetic analysis revealed that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) had lower levels of dsDNA specific IgM among SLE patients. Both the non-synonymous variant rs1143679 and the high ratio of nucleic acid specific IgG/IgM were associated with multiple organ involvement. In summary, secondary complement deficiency in SLE does not impair opsonization of nucleic-acid-containing autoantigens but does affect other antigens and potentially other complement dependent processes. Dysfunction of the receptor recognizing complement

  20. Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium.

    PubMed

    Prechl, József; Papp, Krisztián; Hérincs, Zoltán; Péterfy, Hajna; Lóránd, Veronika; Szittner, Zoltán; Estonba, Andone; Rovero, Paolo; Paolini, Ilaria; Del Amo, Jokin; Uribarri, Maria; Alcaro, Maria Claudia; Ruiz-Larrañaga, Otsanda; Migliorini, Paola; Czirják, László

    2016-01-01

    Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n = 211), with other systemic autoimmune diseases (n = 65) and non-autoimmune control subjects (n = 149). Standard clinical and laboratory data were collected and serum complement levels were determined. The genotype of SNP rs1143679 in the ITGAM gene was also determined. Ex vivo formation of immune complexes, with respect to IgM, IgG, complement C4 and C3 binding, was examined using a functional immunoassay on autoantigen microarray comprising nucleic acids, proteins and lipids. Complement consumption of nucleic acids increased upon binding of IgM and IgG even when serum complement levels were decreased due to consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, complement deposition on tested protein and lipid autoantigens showed positive correlation with C4 levels. Genetic analysis revealed that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) had lower levels of dsDNA specific IgM among SLE patients. Both the non-synonymous variant rs1143679 and the high ratio of nucleic acid specific IgG/IgM were associated with multiple organ involvement. In summary, secondary complement deficiency in SLE does not impair opsonization of nucleic-acid-containing autoantigens but does affect other antigens and potentially other complement dependent processes. Dysfunction of the receptor recognizing complement

  1. The potential of C4 grasses for cellulosic biofuel production

    PubMed Central

    van der Weijde, Tim; Alvim Kamei, Claire L.; Torres, Andres F.; Vermerris, Wilfred; Dolstra, Oene; Visser, Richard G. F.; Trindade, Luisa M.

    2013-01-01

    With the advent of biorefinery technologies enabling plant biomass to be processed into biofuel, many researchers set out to study and improve candidate biomass crops. Many of these candidates are C4 grasses, characterized by a high productivity and resource use efficiency. In this review the potential of five C4 grasses as lignocellulosic feedstock for biofuel production is discussed. These include three important field crops—maize, sugarcane and sorghum—and two undomesticated perennial energy grasses—miscanthus and switchgrass. Although all these grasses are high yielding, they produce different products. While miscanthus and switchgrass are exploited exclusively for lignocellulosic biomass, maize, sorghum, and sugarcane are dual-purpose crops. It is unlikely that all the prerequisites for the sustainable and economic production of biomass for a global cellulosic biofuel industry will be fulfilled by a single crop. High and stable yields of lignocellulose are required in diverse environments worldwide, to sustain a year-round production of biofuel. A high resource use efficiency is indispensable to allow cultivation with minimal inputs of nutrients and water and the exploitation of marginal soils for biomass production. Finally, the lignocellulose composition of the feedstock should be optimized to allow its efficient conversion into biofuel and other by-products. Breeding for these objectives should encompass diverse crops, to meet the demands of local biorefineries and provide adaptability to different environments. Collectively, these C4 grasses are likely to play a central role in the supply of lignocellulose for the cellulosic ethanol industry. Moreover, as these species are evolutionary closely related, advances in each of these crops will expedite improvements in the other crops. This review aims to provide an overview of their potential, prospects and research needs as lignocellulose feedstocks for the commercial production of biofuel. PMID:23653628

  2. Adaptation responses in C4 photosynthesis of maize under salinity.

    PubMed

    Omoto, Eiji; Taniguchi, Mitsutaka; Miyake, Hiroshi

    2012-03-15

    The effect of salinity on C(4) photosynthesis was examined in leaves of maize, a NADP-malic enzyme (NADP-ME) type C(4) species. Potted plants with the fourth leaf blade fully developed were treated with 3% NaCl solution for 5d. Under salt treatment, the activities of pyruvate orthophosphate dikinase (PPDK), phosphoenolpyruvate carboxylase (PEPCase), NADP-dependent malate dehydrogenase (NADP-MDH) and NAD-dependent malate dehydrogenase (NAD-MDH), which are derived mainly from mesophyll cells, increased, whereas those of NADP-ME and ribulose-1,5-bisphosphate carboxylase, which are derived mainly from bundle sheath cells (BSCs), decreased. Immunocytochemical studies by electron microscopy revealed that PPDK protein increased, while the content of ribulose-1,5-bisphosphate carboxylase/oxygenase protein decreased under salinity. In salt-treated plants, the photosynthetic metabolites malate, pyruvate and starch decreased by 40, 89 and 81%, respectively. Gas-exchange analysis revealed that the net photosynthetic rate, the transpiration rate, stomatal conductance (g(s)) and the intercellular CO(2) concentration decreased strongly in salt-treated plants. The carbon isotope ratio (δ(13)C) in these plants was significantly lower than that in control. These findings suggest that the decrease in photosynthetic metabolites under salinity was induced by a reduction in gas-exchange. Moreover, in addition to the decrease in g(s), the decrease in enzyme activities in BSCs was responsible for the decline of C(4) photosynthesis. The increase of PPDK, PEPCase, NADP-MDH, and NAD-MDH activities and the decrease of NADP-ME activity are interpreted as adaptation responses to salinity.

  3. Systemic complement profiling in multiple sclerosis as a biomarker of disease state

    PubMed Central

    Ingram, G; Hakobyan, S; Hirst, CL; Harris, CL; Loveless, S; Mitchell, JP; Pickersgill, TP; Robertson, NP

    2012-01-01

    Background: There is increasing evidence of significant and dynamic systemic activation and upregulation of complement in multiple sclerosis (MS), which may contribute to disease pathogenesis. Objective: We aimed to investigate the pathological role of complement in MS and the potential role for complement profiling as a biomarker of MS disease state. Methods: Key components of the classical, alternative and terminal pathways of complement were measured in plasma and cerebrospinal fluid (CSF) of patients with MS in different clinical phases of disease and in matched controls. Results: Increased plasma levels of C3 (p<0.003), C4 (p<0.001), C4a (p<0.001), C1 inhibitor (p<0.001), and factor H (p<0.001), and reduced levels of C9 (p<0.001) were observed in MS patients compared with controls. Combined profiling of these analytes produced a statistical model with a predictive value of 97% for MS and 73% for clinical relapse when combined with selected demographic data. CSF-plasma correlations suggested that source of synthesis of these components was both systemic and central. Conclusion: These data provide further evidence of alterations in both local and systemic expression and activation of complement in MS and suggest that complement profiling may be informative as a biomarker of MS disease, although further work is needed to determine its use in distinguishing MS from its differential. PMID:22354735

  4. Bayesian truthing as experimental verification of C4ISR sensors

    NASA Astrophysics Data System (ADS)

    Jannson, Tomasz; Forrester, Thomas; Romanov, Volodymyr; Wang, Wenjian; Nielsen, Thomas; Kostrzewski, Andrew

    2015-05-01

    In this paper, the general methodology for experimental verification/validation of C4ISR and other sensors' performance, is presented, based on Bayesian inference, in general, and binary sensors, in particular. This methodology, called Bayesian Truthing, defines Performance Metrics for binary sensors in: physics, optics, electronics, medicine, law enforcement, C3ISR, QC, ATR (Automatic Target Recognition), terrorism related events, and many others. For Bayesian Truthing, the sensing medium itself is not what is truly important; it is how the decision process is affected.

  5. The Complement System and Adverse Pregnancy Outcomes

    PubMed Central

    Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.

    2015-01-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

  6. Current Understanding of the Role of Complement in IgA Nephropathy

    PubMed Central

    Maillard, Nicolas; Wyatt, Robert J.; Julian, Bruce A.; Kiryluk, Krzysztof; Gharavi, Ali; Fremeaux-Bacchi, Veronique

    2015-01-01

    Complement activation has a role in the pathogenesis of IgA nephropathy, an autoimmune disease mediated by pathogenic immune complexes consisting of galactose-deficient IgA1 bound by antiglycan antibodies. Of three complement-activation pathways, the alternative and lectin pathways are involved in IgA nephropathy. IgA1 can activate both pathways in vitro, and pathway components are present in the mesangial immunodeposits, including properdin and factor H in the alternative pathway and mannan-binding lectin, mannan–binding lectin–associated serine proteases 1 and 2, and C4d in the lectin pathway. Genome–wide association studies identified deletion of complement factor H–related genes 1 and 3 as protective against the disease. Because the corresponding gene products compete with factor H in the regulation of the alternative pathway, it has been hypothesized that the absence of these genes could lead to more potent inhibition of complement by factor H. Complement activation can take place directly on IgA1–containing immune complexes in circulation and/or after their deposition in the mesangium. Notably, complement factors and their fragments may serve as biomarkers of IgA nephropathy in serum, urine, or renal tissue. A better understanding of the role of complement in IgA nephropathy may provide potential targets and rationale for development of complement-targeting therapy of the disease. PMID:25694468

  7. Activation of complement pathways after contusion-induced spinal cord injury.

    PubMed

    Anderson, Aileen J; Robert, Stephanie; Huang, Wencheng; Young, Wise; Cotman, Carl W

    2004-12-01

    Previous studies have shown that a cellular inflammatory response is initiated, and inflammatory cytokines are synthesized, following experimental spinal cord injury (SCI). In the present study, we tested the hypothesis that the complement cascade, a major component of both the innate and adaptive immune response, is also activated following experimental SCI. We investigated the pathways, cellular localization, timecourse, and degree of complement activation in rat spinal cord following acute contusion-induced SCI using the New York University (NYU) weight drop impactor. Mild and severe injuries (12.5 and 50 mm drop heights) at 1, 7, and 42 days post injury time points were evaluated. Classical (C1q and C4), alternative (Factor B) and terminal (C5b-9) complement pathways were strongly activated within 1 day of SCI. Complement protein immunoreactivity was predominantly found in cell types vulnerable to degeneration, neurons and oligodendrocytes, and was not generally observed in inflammatory or astroglial cells. Surprisingly, immunoreactivity for complement proteins was also evident 6 weeks after injury, and complement activation was observed as far as 20 mm rostral to the site of injury. Axonal staining by C1q and Factor B was also observed, suggesting a potential role for the complement cascade in demyelination or axonal degeneration. These data support the hypothesis that complement activation plays a role in SCI.

  8. C4 grasses prosper as carbon dioxide eliminates desiccation in warmed semi-arid grassland.

    PubMed

    Morgan, Jack A; LeCain, Daniel R; Pendall, Elise; Blumenthal, Dana M; Kimball, Bruce A; Carrillo, Yolima; Williams, David G; Heisler-White, Jana; Dijkstra, Feike A; West, Mark

    2011-08-03

    Global warming is predicted to induce desiccation in many world regions through increases in evaporative demand. Rising CO(2) may counter that trend by improving plant water-use efficiency. However, it is not clear how important this CO(2)-enhanced water use efficiency might be in offsetting warming-induced desiccation because higher CO(2) also leads to higher plant biomass, and therefore greater transpirational surface. Furthermore, although warming is predicted to favour warm-season, C(4) grasses, rising CO(2) should favour C(3), or cool-season plants. Here we show in a semi-arid grassland that elevated CO(2) can completely reverse the desiccating effects of moderate warming. Although enrichment of air to 600 p.p.m.v. CO(2) increased soil water content (SWC), 1.5/3.0 °C day/night warming resulted in desiccation, such that combined CO(2) enrichment and warming had no effect on SWC relative to control plots. As predicted, elevated CO(2) favoured C(3) grasses and enhanced stand productivity, whereas warming favoured C(4) grasses. Combined warming and CO(2) enrichment stimulated above-ground growth of C(4) grasses in 2 of 3 years when soil moisture most limited plant productivity. The results indicate that in a warmer, CO(2)-enriched world, both SWC and productivity in semi-arid grasslands may be higher than previously expected.

  9. Genetics Home Reference: complement component 8 deficiency

    MedlinePlus

    ... the membranes surrounding the brain and spinal cord (meningitis). Although meningitis can be life-threatening, individuals with complement component ... leaves affected individuals prone to recurrent episodes of meningitis. Learn more about the genes associated with complement ...

  10. Complement fixation test to C. burnetii

    MedlinePlus

    ... ency/article/003520.htm Complement fixation test to C burnetii To use the sharing features on this ... JavaScript. The complement fixation test to Coxiella burnetii ( C burnetti ) is a blood test that checks for ...

  11. Activation of the lectin complement pathway in post-streptococcal acute glomerulonephritis.

    PubMed

    Hisano, Satoshi; Matsushita, Misao; Fujita, Teizo; Takeshita, Morishige; Iwasaki, Hiroshi

    2007-06-01

    The aim of the present study was to elucidate the correlation between complement pathways and clinicopathological findings in post-streptococcal acute glomerulonephritis (PSAGN). Immunohistological staining was performed on renal specimens obtained from 18 patients with PSAGN and 20 controls, using antibodies against IgG, IgA, IgM, C1q, C3c, C4, fibrinogen, factor B, C4-binding protein (C4-bp), C5b-9, CD59, mannose-binding lectin (MBL) and MBL-associated serine protease-1 (MASP-1). Controls showed no deposition of any antibody. In seven patients, glomerular deposits of C3c, C4, factor B, C4-bp, C5b-9, CD59, MBL and MASP-1 were found. In the remaining 11 patients, glomerular deposits of neither C4 nor MBL/MASP-1 were found, and glomerular deposits of C3c, factor B, C5b-9 and CD59 were evident. C4-bp was detected in seven of these 11 patients. Glomerular deposits of fibrinogen were detected in five of seven patients with MBL/MASP-1 deposits and in only two of 11 patients without MBL/MASP-1 deposits. Hematuria was prolonged in three of seven patients with MBL/MASP-1 deposits through follow up, whereas urinalysis was normal in all patients without MBL/MASP-1 deposits. However, the histological indicators were not different between the two groups. To the authors' knowledge this is the first report to show that complement activation through both the alternative and lectin pathways is evident in some patients with PSAGN. Complement activation is promoted in situ in the glomerulus.

  12. An Integrated Theory of Complement Control.

    ERIC Educational Resources Information Center

    Sag, Ivan A.; Pollard, Carl

    1991-01-01

    Presents an integrated theory of the syntactic and semantic representation of complements where the unexpressed subjects of the embedded verb-phrase complement are subject to certain interpretation restrictions. It is argued that the grammar of English controlled complements can be derived from the interaction of semantically based principles of…

  13. [The practical assessment of complement involvement in anaphylactoid reactions].

    PubMed

    Watkins, J

    1982-01-01

    While no single test is entirely satisfactory for the investigation of anaphylactoid response to intravenous anaesthetic drugs, changes in plasma chemistry are particularly easy to measure and may be carried out at centres remote from the clinical incident. Analysis should be carried out on a sequence of blood samples taken into EDTA over the 24 hours following such reaction. Few reactions are classical Type I, IgE antibody mediated, reactions and most involved the complement proteins in some specific manner. By measuring changes in the levels and activity of the complement proteins, particularly C3, C4 and C5, between samples, it is possible to deduce the likely mechanism of a reaction and thus to advise more wisely on future treatment of the patient. Although levels of any plasma protein may be readily measured by single radial immunodiffusion (Mancini technique) using appropriate specific antisera, one assessment of complement activity (degree of conversion) has until now largely been restricted to technically exacting Laurell immunoelectrophoresis. Two simple immunoelectrophoretic techniques are described here which do not require such expertise.

  14. Leukotriene C4 elimination and metabolism in man

    SciTech Connect

    Maltby, N.H.; Taylor, G.W.; Ritter, J.M.; Moore, K.; Fuller, R.W.; Dollery, C.T. )

    1990-01-01

    Three doses of radiolabeled leukotriene C4 (0.2 to 15 muCi) were infused into three subjects to investigate its metabolism and routes of elimination during 4 days. Between 12% and 20% of the infused dose was recovered in the urine within 24 hours, of which a substantial and relatively constant proportion (4.1% to 6.3% total dose) appeared as leukotriene E4 (LTE4), mainly in the first 4 hours. Polar omega-oxidation products, N-acetyl LTE4, and tritiated water were also present. Fecal elimination accounted for a further 30% to 40% of the infused dose. In the absence of altered metabolism or biliary excretion, urinary LTE4 may be a useful measure of whole body production of the cysteinyl leukotrienes.

  15. Electron-impact detachment and dissociation of C4- ions

    NASA Astrophysics Data System (ADS)

    Le Padellec, A.; Rabilloud, F.; Pegg, D.; Neau, A.; Hellberg, F.; Thomas, R.; Schmidt, H. T.; Larsson, M.; Danared, H.; Källberg, A.; Andersson, K.; Hanstorp, D.

    2001-12-01

    CRYRING was used to study collision processes between an electron and a negative ion cluster C4-. The total detachment cross sections for the production of the neutral 4C, 3C, 2C, and C fragments were measured. The cross sections for pure detachment, and for detachment plus dissociation leading to the production of C3+C, 2C2, and C2+2C were extracted using a grid. It was found that the pure detachment process overwhelmingly dominates all other fragmentation processes. The threshold location for the detachment channel is found to be around 6.0 eV. Although the doubly charged negative ion C42- has received little previous attention, a defined near-threshold resonance observed in the detachment cross section curve, has been associated with the short-lived state C42- (0.7 fs lifetime).

  16. Simulation of the Reflected Blast Wave froma C-4 Charge

    SciTech Connect

    Howard, W M; Kuhl, A L; Tringe, J W

    2011-08-01

    The reflection of a blast wave from a C4 charge detonated above a planar surface is simulated with our ALE3D code. We used a finely-resolved, fixed Eulerian 2-D mesh (167 {micro}m per cell) to capture the detonation of the charge, the blast wave propagation in nitrogen, and its reflection from the surface. The thermodynamic properties of the detonation products and nitrogen were specified by the Cheetah code. A programmed-burn model was used to detonate the charge at a rate based on measured detonation velocities. Computed pressure histories are compared with pressures measured by Kistler 603B piezoelectric gauges at 8 ranges (GR = 0, 2, 4, 8, 10, and 12 inches) along the reflecting surface. Computed and measured waveforms and positive-phase impulses were similar, except at close-in ranges (GR < 2 inches), which were dominated by jetting effects.

  17. Pharmacological modulation of human platelet leukotriene C4-synthase.

    PubMed

    Sala, A; Folco, G; Henson, P M; Murphy, R C

    1997-03-21

    The aim of this study was to test if human platelet leukotriene C4-synthase (LTC4-S) is pharmacologically different from cloned and expressed LTC4-S and, in light of the significant homologies between 5-lipoxygenase activating protein (FLAP) and LTC4-S, if different potencies of leukotriene synthesis inhibitors acting through binding with FLAP (FLAP inhibitors) reflect in different potencies as LTC4-S inhibitors. Leukotriene C4 (LTC4) synthesis by washed human platelets supplemented with synthetic leukotriene A4 (LTA4) was studied in the absence and presence of two different, structurally unrelated FLAP inhibitors (MK-886 and BAY-X1005) as well as a direct 5-lipoxygenase inhibitor (zileuton). LTC4 production was analyzed by RP-HPLC coupled to diode array detection. We report that human platelet LTC4-S was inhibited by MK-886 and BAY-X1005 (IC50 of 4.7 microM and 91.2 microM, respectively), but not by zileuton (inactive up to 300 microM); all 3 compounds were able to inhibit 5-lipoxygenase metabolite biosynthesis in intact human polymorphonuclear leukocytes (IC50 of 0.044 microM, 0.85 microM, and 1.5 microM, respectively). Platelet LTC4-S does not appear pharmacologically different from expression cloned LTC4-S. LTC4-S inhibition by FLAP inhibitors is in agreement with the significant homology reported for expression-cloned LTC4-S with FLAP, Furthermore, functional homology of the binding sites for inhibitors on LTC4-S and FLAP is suggested by the conservation of the relative potencies of MK-886 and BAY-X1005 vs FLAP-dependent 5-lipoxygenase activity and LTC4-S inhibition: MK-886 was 19.3-fold more potent than BAY-X1005 as FLAP inhibitor and 19.6-fold more potent than BAY-X1005 as LTC4-S inhibitor.

  18. Hydrogen peroxide regulated photosynthesis in C4-pepc transgenic rice.

    PubMed

    Ren, C G; Li, X; Liu, X L; Wei, X D; Dai, C C

    2014-01-01

    In this study, we investigated the photosynthetic physiological basis in 'PC' transgenic rice (Oryza sativa L.), showing high-level expression of the gene encoding C4 phosphoenolpyruvate carboxylase (pepc), by hydrogen peroxide (H2O2). The C4-PEPC gene (pepc) from maize in the transgenic rice plants was checked by PCR. Comparison of yield components and photosynthetic indices between PC and untransformed wild-type (WT) plants indicated that increased yield in PC was associated with higher net photosynthetic rate and higher activities of phosphoenolpyruvate carboxylase (PEPC). Both PC and WT plants were treated with 1 mmol L(-1) abscisic acid (ABA), 0.04% 1-butanol (BA), 2 mmol L(-1) neomycin (NS), or 2 mmol L(-1) diphenyleneiodonium chloride (DPI) to investigate the relationship between photosynthesis and levels of H2O2 and phosphatidic acid. In both PC and WT, ABA induced H2O2 generation and simultaneous decrease in stomatal conductance (g(s)). PC plants treated with BA showed decreased H2O2 content and strongly increased g(s) within 2 h of treatment. Similar results were observed in response to DPI treatment in PC. However, WT did not observe the decrease of H2O2 during the treatments of BA and DPI. The reduced H2O2 content in PC caused by BA treatment differed to that induced by DPI because BA did not inhibit NADPH oxidase activities. While BA induced a larger PEPC activity in PC, and higher catalase activity as well. These results indicated that the regulation of endogenous H2O2 metabolism of PC could be helpful for enhancing photosynthetic capability.

  19. Senescence, dormancy and tillering in perennial C4 grasses.

    PubMed

    Sarath, Gautam; Baird, Lisa M; Mitchell, Robert B

    2014-03-01

    Perennial, temperate, C4 grasses, such as switchgrass and miscanthus have been tabbed as sources of herbaceous biomass for the production of green fuels and chemicals based on a number of positive agronomic traits. Although there is important literature on the management of these species for biomass production on marginal lands, numerous aspects of their biology are as yet unexplored at the molecular level. Perenniality, a key agronomic trait, is a function of plant dormancy and winter survival of the below-ground parts of the plants. These include the crowns, rhizomes and meristems that will produce tillers. Maintaining meristem viability is critical for the continued survival of the plants. Plant tillers emerge from the dormant crown and rhizome meristems at the start of the growing period in the spring, progress through a phase of vegetative growth, followed by flowering and eventually undergo senescence. There is nutrient mobilization from the aerial portions of the plant to the crowns and rhizomes during tiller senescence. Signals arising from the shoots and from the environment can be expected to be integrated as the plants enter into dormancy. Plant senescence and dormancy have been well studied in several dicot species and offer a potential framework to understand these processes in temperate C4 perennial grasses. The availability of latitudinally adapted populations for switchgrass presents an opportunity to dissect molecular mechanisms that can impact senescence, dormancy and winter survival. Given the large increase in genomic and other resources for switchgrass, it is anticipated that projected molecular studies with switchgrass will have a broader impact on related species.

  20. The Semantics of Complementation in English: A Cognitive Semantic Account of Two English Complement Constructions

    ERIC Educational Resources Information Center

    Smith, Michael B.

    2009-01-01

    Studies on complementation in English and other languages have traditionally focused on syntactic issues, most notably on the constituent structures of different complement types. As a result, they have neglected the role of meaning in the choice of different complements. This paper investigates the semantics of complementation within the…

  1. Meningococcal disease and the complement system

    PubMed Central

    Lewis, Lisa A; Ram, Sanjay

    2014-01-01

    Despite considerable advances in the understanding of the pathogenesis of meningococcal disease, this infection remains a major cause of morbidity and mortality globally. The role of the complement system in innate immune defenses against invasive meningococcal disease is well established. Individuals deficient in components of the alternative and terminal complement pathways are highly predisposed to invasive, often recurrent meningococcal infections. Genome-wide analysis studies also point to a central role for complement in disease pathogenesis. Here we review the pathophysiologic events pertinent to the complement system that accompany meningococcal sepsis in humans. Meningococci use several often redundant mechanisms to evade killing by human complement. Capsular polysaccharide and lipooligosaccharide glycan composition play critical roles in complement evasion. Some of the newly described protein vaccine antigens interact with complement components and have sparked considerable research interest. PMID:24104403

  2. Invasive C4 Perennial Grass Alters Net Ecosystem Exchange in Mixed C3/C4 Savanna Grassland

    NASA Astrophysics Data System (ADS)

    Basham, T. S.; Litvak, M.

    2006-12-01

    The invasion of ecosystems by non-native plants that differ from native plants in physiological characteristics and phenology has the potential to alter ecosystem function. In Texas and other regions of the southern central plains of the United States, the introduced C4 perennial grass, Bothriochloa ischaemum, invades C3/C4 mixed grasslands and savannas, resulting in decreased plant community diversity (Gabbard 2003; Harmoney et al 2004). The objective of this study was to quantify how the conversion of these mixed grass communities to C4 dominated, B. ischaemum monocultures impacts carbon cycling and sequestration. Seasonal measurements of Net Ecosystem Exchange (NEE) of CO2, leaf level gas exchange and soil respiration were compared between savanna grassland plots composed of either naturally occurring B. ischaemum monocultures or native mixed grasses (n=16). NEE was measured using a closed system chamber that attached to permanently installed stainless steel bases. Temperature, soil moisture, aerial percent species cover and leaf area index were also monitored in plots to explain variability in measured responses. Results showed that NEE differed seasonally between invaded and native plots due to 1) greater leaf surface area per unit ground area in invaded plots, 2) differences in phenological patterns of plant activity and 3) differences in responses to water limitation between invaded and native plots. Cold season and summer drought NEE were driven primarily by belowground respiration in both plot types, however spring uptake activity commenced two months later in invaded plots. This later start in invaded plots was compensated for by greater uptake throughout the growing season and in particular during the drier summer months. Differences in NEE between plot types were not due to differences in soil respiration nor were they due to greater leaf level photosynthetic capabilities of B. ischaemum relative to the dominant native grasses. NEE, soil respiration and

  3. The role of complement in antibody-mediated rejection in kidney transplantation.

    PubMed

    Stegall, Mark D; Chedid, Marcio F; Cornell, Lynn D

    2012-11-01

    Over the past decade, several studies have suggested that the complement system has an active role in both acute and chronic allograft rejection. These studies have been facilitated by improved techniques to detect antibody-mediated organ rejection, including immunohistological staining for C4d deposition in the allograft and solid-phase assays that identify donor-specific alloantibodies (DSAs) in the serum of transplant recipients. Studies with eculizumab, a humanized monoclonal antibody directed against complement component C5, have shown that activation of the terminal complement pathway is necessary for the development of acute antibody-mediated rejection in recipients of living-donor kidney allografts who have high levels of DSAs. The extent to which complement activation drives chronic antibody-mediated injury leading to organ rejection is less clear. In chronic antibody-mediated injury, early complement activation might facilitate chemotaxis of inflammatory cells into the allograft in a process that later becomes somewhat independent of DSA levels and complement factors. In this Review, we discuss the different roles that the complement system might have in antibody-mediated allograft rejection, with specific emphasis on renal transplantation.

  4. Systemic Lupus Erythematosus and Deficiencies of Early Components of the Complement Classical Pathway

    PubMed Central

    Macedo, Ana Catarina Lunz; Isaac, Lourdes

    2016-01-01

    The complement system plays an important role in the innate and acquired immune response against pathogens. It consists of more than 30 proteins found in soluble form or attached to cell membranes. Most complement proteins circulate in inactive forms and can be sequentially activated by the classical, alternative, or lectin pathways. Biological functions, such as opsonization, removal of apoptotic cells, adjuvant function, activation of B lymphocytes, degranulation of mast cells and basophils, and solubilization and clearance of immune complex and cell lysis, are dependent on complement activation. Although the activation of the complement system is important to avoid infections, it also can contribute to the inflammatory response triggered by immune complex deposition in tissues in autoimmune diseases. Paradoxically, the deficiency of early complement proteins from the classical pathway (CP) is strongly associated with development of systemic lupus erythematous (SLE) – mainly C1q deficiency (93%) and C4 deficiency (75%). The aim of this review is to focus on the deficiencies of early components of the CP (C1q, C1r, C1s, C4, and C2) proteins in SLE patients. PMID:26941740

  5. Species having C4 single-cell-type photosynthesis in the Chenopodiaceae family evolved a photosynthetic phosphoenolpyruvate carboxylase like that of Kranz-type C4 species.

    PubMed

    Lara, María Valeria; Chuong, Simon D X; Akhani, Hossein; Andreo, Carlos Santiago; Edwards, Gerald E

    2006-10-01

    Spatial and temporal regulation of phosphoenolpyruvate carboxylase (PEPC) is critical to the function of C(4) photosynthesis. The photosynthetic isoform of PEPC in the cytosol of mesophyll cells in Kranz-type C(4) photosynthesis has distinctive kinetic and regulatory properties. Some species in the Chenopodiaceae family perform C(4) photosynthesis without Kranz anatomy by spatial separation of initial fixation of atmospheric CO(2) via PEPC from C(4) acid decarboxylation and CO(2) donation to Rubisco within individual chlorenchyma cells. We studied molecular and functional features of PEPC in two single-cell functioning C(4) species (Bienertia sinuspersici, Suaeda aralocaspica) as compared to Kranz type (Haloxylon persicum, Salsola richteri, Suaeda eltonica) and C(3) (Suaeda linifolia) chenopods. It was found that PEPC from both types of C(4) chenopods displays higher specific activity than that of the C(3) species and shows kinetic and regulatory characteristics similar to those of C(4) species in other families in that they are subject to light/dark regulation by phosphorylation and display differential malate sensitivity. Also, the deduced amino acid sequence from leaf cDNA indicates that the single-cell functioning C(4) species possesses a Kranz-type C(4) isoform with a Ser in the amino terminal. A phylogeny of PEPC shows that isoforms in the two single-cell functioning C(4) species are in a clade with the C(3) and Kranz C(4) Suaeda spp. with high sequence homology. Overall, this study indicates that B. sinuspersici and S. aralocaspica have a C(4)-type PEPC similar to that in Kranz C(4) plants, which likely is required for effective function of C(4) photosynthesis.

  6. Complement Depletion Deteriorates Clinical Outcomes of Severe Abdominal Sepsis: A Conspirator of Infection and Coagulopathy in Crime?

    PubMed Central

    Zhao, Yunzhao; Han, Gang; Li, Weiqin; Huang, Qian; Tong, Zhihui; Li, Jieshou

    2012-01-01

    Background The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction. Objective This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored. Methods Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II) and sepsis related organ failure assessment (SOFA) scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups. Results Within the study period, eight (17.8%) patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845–0.998, P<0.001), with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications. Conclusions Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care

  7. Complement Activation and Inhibition in Wound Healing

    PubMed Central

    Cazander, Gwendolyn; Jukema, Gerrolt N.; Nibbering, Peter H.

    2012-01-01

    Complement activation is needed to restore tissue injury; however, inappropriate activation of complement, as seen in chronic wounds can cause cell death and enhance inflammation, thus contributing to further injury and impaired wound healing. Therefore, attenuation of complement activation by specific inhibitors is considered as an innovative wound care strategy. Currently, the effects of several complement inhibitors, for example, the C3 inhibitor compstatin and several C1 and C5 inhibitors, are under investigation in patients with complement-mediated diseases. Although (pre)clinical research into the effects of these complement inhibitors on wound healing is limited, available data indicate that reduction of complement activation can improve wound healing. Moreover, medicine may take advantage of safe and effective agents that are produced by various microorganisms, symbionts, for example, medicinal maggots, and plants to attenuate complement activation. To conclude, for the development of new wound care strategies, (pre)clinical studies into the roles of complement and the effects of application of complement inhibitors in wound healing are required. PMID:23346185

  8. The FAK scaffold inhibitor C4 disrupts FAK-VEGFR-3 signaling and inhibits pancreatic cancer growth

    PubMed Central

    Kurenova, Elena; Liao, Jianqun; He, Di-Hua; Hunt, Darrell; Yemma, Michael; Bshara, Wiam; Seshadri, Mukund; Cance, William G.

    2013-01-01

    Even with successful surgical resection and perioperative chemotherapy and radiation, pancreatic ductal adenocarcinoma (PDA) has a high incidence of recurrence. Tumor cell survival depends on activation of signaling pathways that suppress the apoptotic stimuli of invasion and metastasis. Focal adhesion kinase (FAK) is a critical signaling molecule that has been implicated in tumor cell survival, invasion and metastasis. We have previously shown that FAK and vascular endothelial growth factor receptor 3 (VEGFR-3) are overexpressed in cancer cells and physically interact to confer a significant survival advantage. We subsequently identified a novel small molecule inhibitor C4 that targeted the VEGFR-3-FAK site of interaction. In this study, we have shown that C4 disrupted the FAK-VEGFR-3 complexes in PDA cells. C4 treatment caused dose-dependent dephosphorylation and inactivation of the VEGFR-3 and FAK, reduction in cell viability and proliferation, cell cycle arrest and apoptosis in PDA cells. C4 increased the sensitivity of tumor cells to gemcitabine chemotherapy in vitro that lead to apoptosis at nanomolar concentrations of both drugs. C4 reduced tumor growth in vivoin subcutaneous and orthotopic murine models of PDA. The drug alone at low dose, decreased tumor growth; however, concomitant administration with low dose of gemcitabine had significant synergistic effect and led to 70% tumor reduction. Combination of C4 with gemcitabine had a prolonged cytostatic effect on tumor growth after treatment withdrawal. Finally, we report an anecdotal case of stage IV pancreatic cancer treated with gemcitabine in combination with C4 that showed a significant clinical response in primary tumor and complete clinical response in liver metastasis over an eight month period. Taken together, these results demonstrate that targeting the scaffolding function of FAK with a small-molecule FAK-VEGFR-3 inhibitor can be an effective therapeutic strategy against PDA. PMID:24142503

  9. Selective inhibition of the alternative complement pathway by sCR1[desLHR-A] protects the rabbit isolated heart from human complement-mediated damage.

    PubMed

    Gralinski, M R; Wiater, B C; Assenmacher, A N; Lucchesi, B R

    1996-09-01

    Evidence is presented that treatment with a selective inhibitor of the alternative complement pathway, sCR1[desLHR-A], protects the ex vivo perfused rabbit heart from human complement-mediated injury. Hearts from male New Zealand white rabbits were perfused in the Langendorff mode. After equilibration, normal human plasma was added to the perfusate as a source of complement. Concomitant with the addition of human plasma, vehicle (n = 13), soluble complement receptor type 1 (sCR1) (n = 10), or sCR1[desLHR-A], a truncated version of sCR1 that lacks the C4b binding region (n = 10) was included in the perfusate. Hemodynamic variables were obtained for all groups before (baseline) and after the addition of human plasma. Compared to vehicle-treated hearts, variables recorded during perfusion with human plasma including coronary perfusion pressure, left ventricular developed pressure, and left ventricular end diastolic pressure, along with a reduction of creatine kinase efflux, were improved in hearts perfused with either complement inhibitor. In addition, in vitro hemolysis assays were utilized to discriminate between the classical and alternative pathways. The addition of sCR1 to human serum prevented both the classical and alternative pathway-mediated hemolysis while sCR1[desLHR-A] prevented only the alternative pathway-mediated lysis. This study indicates that deletion of the C4b-binding site from sCR1 results in a new pharmacological moiety, sCR1[desLHR-A], that primarily inhibits the alternative pathway of human complement.

  10. Active C4 Electrodes for Local Field Potential Recording Applications

    PubMed Central

    Wang, Lu; Freedman, David; Sahin, Mesut; Ünlü, M. Selim; Knepper, Ronald

    2016-01-01

    Extracellular neural recording, with multi-electrode arrays (MEAs), is a powerful method used to study neural function at the network level. However, in a high density array, it can be costly and time consuming to integrate the active circuit with the expensive electrodes. In this paper, we present a 4 mm × 4 mm neural recording integrated circuit (IC) chip, utilizing IBM C4 bumps as recording electrodes, which enable a seamless active chip and electrode integration. The IC chip was designed and fabricated in a 0.13 μm BiCMOS process for both in vitro and in vivo applications. It has an input-referred noise of 4.6 μVrms for the bandwidth of 10 Hz to 10 kHz and a power dissipation of 11.25 mW at 2.5 V, or 43.9 μW per input channel. This prototype is scalable for implementing larger number and higher density electrode arrays. To validate the functionality of the chip, electrical testing results and acute in vivo recordings from a rat barrel cortex are presented. PMID:26861324

  11. Metabolite Diffusion into Bundle Sheath Cells from C4 Plants

    PubMed Central

    Weiner, Hendrik; Burnell, James N.; Woodrow, Ian E.; Heldt, Hans W.; Hatch, Marshall D.

    1988-01-01

    The present studies provide the first measurements of the resistance to diffusive flux of metabolites between mesophyll and bundle sheath cells of C4 plants. Species examined were Panicum miliaceum, Urochloa panicoides, Atriplex spongiosa, and Zea mays. Diffusive flux of metabolites into isolated bundle sheath cells was monitored by following their metabolic transformation. Evidence was obtained that the observed rapid fluxes occurred via functional plasmodesmata. Diffusion constants were determined from the rate of transformation of limiting concentrations of metabolites via cytosolic enzymes with high potential velocities and favorable equilibrium constants. Values on a leaf chlorophyll basis ranged between 1 and 5 micromoles per minute per milligram of chlorophyll per millimolar gradient depending on the molecular weight of the metabolite and the source of bundle sheath cells. Diffusion of metabolites into these cells was unaffected by a wide variety of compounds including respiratory inhibitors, monovalent and divalent cations, and plant hormones, but it was interrupted by treatments inducing cell plasmolysis. The molecular weight exclusion limit for permeation of compounds into bundle sheath cells was in the range of 850 to 900. These cells provide an ideal system for the quantitative study of plasmodesmatal function. PMID:16666390

  12. Identification of Photosynthesis-Associated C4 Candidate Genes through Comparative Leaf Gradient Transcriptome in Multiple Lineages of C3 and C4 Species

    PubMed Central

    Ding, Zehong; Weissmann, Sarit; Wang, Minghui; Du, Baijuan; Huang, Lei; Wang, Lin; Tu, Xiaoyu; Zhong, Silin; Myers, Christopher; Brutnell, Thomas P.; Sun, Qi; Li, Pinghua

    2015-01-01

    Leaves of C4 crops usually have higher radiation, water and nitrogen use efficiencies compared to the C3 species. Engineering C4 traits into C3 crops has been proposed as one of the most promising ways to repeal the biomass yield ceiling. To better understand the function of C4 photosynthesis, and to identify candidate genes that are associated with the C4 pathways, a comparative transcription network analysis was conducted on leaf developmental gradients of three C4 species including maize, green foxtail and sorghum and one C3 species, rice. By combining the methods of gene co-expression and differentially co-expression networks, we identified a total of 128 C4 specific genes. Besides the classic C4 shuttle genes, a new set of genes associated with light reaction, starch and sucrose metabolism, metabolites transportation, as well as transcription regulation, were identified as involved in C4 photosynthesis. These findings will provide important insights into the differential gene regulation between C3 and C4 species, and a good genetic resource for establishing C4 pathways in C3 crops. PMID:26465154

  13. Role of Complement in Autoimmune Hemolytic Anemia

    PubMed Central

    Berentsen, Sigbjørn

    2015-01-01

    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed. PMID:26696798

  14. Subversion of complement by hematophagous parasites

    PubMed Central

    Schroeder, Hélène; Skelly, Patrick; Zipfel, Peter F.; Losson, Bertrand; Vanderplasschen, Alain

    2008-01-01

    The complement system is a crucial part of innate and adaptive immunity which exerts a significant evolutionary pressure on pathogens. It has selected for those pathogens, mainly micro-organisms but also parasites, that have evolved countermeasures. The characterization of how pathogens evade complement attack is a rapidly developing field of current research. In recent years, multiple complement evasion strategies have been characterized. In this review, we focus on complement escape mechanisms expressed by hematophagous parasites, a heterogeneous group of metazoan parasites that share the property of ingesting the whole blood of their host. Complement inhibition is crucial for parasite survival within the host tissue or to facilitate blood feeding. Finally, complement inhibition by hematophagous parasites may also contribute to their success as pathogen vectors. PMID:18762211

  15. Role of Complement in Autoimmune Hemolytic Anemia.

    PubMed

    Berentsen, Sigbjørn

    2015-09-01

    The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed.

  16. Eosinophil granule cationic proteins regulate the classical pathway of complement.

    PubMed Central

    Weiler, J M; Edens, R E; Bell, C S; Gleich, G J

    1995-01-01

    Major basic protein, the primary constituent of eosinophil granules, regulates the alternative and classical pathways of complement. Major basic protein and other eosinophil granule cationic proteins, which are important in mediating tissue damage in allergic disease, regulate the alternative pathway by interfering with C3b interaction with factor B to assemble an alternative pathway C3 convertase. In the present study, eosinophil peroxidase, eosinophil cationic protein and eosinophil-derived neurotoxin, as well as major basic protein, were examined for capacity to regulate the classical pathway. Eosinophil peroxidase, eosinophil cationic protein and major basic protein inhibited formation of cell-bound classical pathway C3 convertase (EAC1,4b,2a), causing 50% inhibition of complement-mediated lysis at about 0.19, 0.75 and 0.5 micrograms/10(7) cellular intermediates, respectively. Eosinophil-derived neurotoxin had no activity on this pathway of complement. The eosinophil granule proteins were examined for activity on the formation of the membrane attack complex. Major basic protein and eosinophil cationic protein had no activity on terminal lysis. In contrast, eosinophil peroxidase inhibited lysis of EAC1,4b,2a,3b,5b, but had only minimal activity on later events in complement lysis. These polycations were then examined to determine the site(s) at which they regulated the early classical pathway. Eosinophil granule polycationic proteins: (1) reduced the Zmax at all time points but had only minimal effect on the Tmax during the formation of the classical pathway C3 convertase (EAC1,4b,2a); (2) inhibited formation of EAC1,4b,2a proportional to C4 but independent of C2 concentration; (3) inhibited fluid phase formation of C1,4b,2a, as reflected by a decrease in C1-induced consumption of C2 over time; and (4) inhibited C1 activity over time without a direct effect on either C4 or C2. These observations suggest that polycations regulate the early classical pathway by

  17. Serum complement and immunoconglutinin in malnutrition.

    PubMed Central

    Chandra, R K

    1975-01-01

    Serum haemolytic complement activity and C3 were significantly decreased in 35 malnourished children. The changes were more pronounced in those with infection. Electrophoretically altered forms of complement C were detected in 14. There was an inverse correlation between C3 levels and immunoconglutinin titres. Nutritional rehabilitation and eradication of infection reversed the abnormalities. It is suggested that reduced complement function in malnutrition is the combined result of impaired synthesis, complement activation in vivo, and changes in plasma volume, and that it may contribute to an increased susceptibility to infection in undernourished individuals. PMID:807166

  18. SHOCK INITIATION EXPERIMENTS AND MODELING OF COMPOSITION B AND C-4

    SciTech Connect

    Urtiew, P A; Vandersall, K S; Tarver, C M; Garcia, F; Forbes, J W

    2006-06-13

    Shock initiation experiments on the explosives Composition B and C-4 were performed to obtain in-situ pressure gauge data for the purpose of determining the Ignition and Growth reactive flow model with proper modeling parameters. A 101 mm diameter propellant driven gas gun was utilized to initiate the explosive charges containing manganin piezoresistive pressure gauge packages embedded in the explosive sample. Experimental data provided new information on the shock velocity versus particle velocity relationship for each of the investigated materials in their respective pressure range. The run-distance-to-detonation points on the Pop-plot for these experiments showed agreement with previously published data, and Ignition and Growth modeling calculations resulted in a good fit to the experimental data. These experimental data were used to determine Ignition and Growth reactive flow model parameters for these explosives. Identical ignition and growth reaction rate parameters were used for C-4 and Composition B, and the Composition B model also included a third reaction rate to simulate the completion of reaction by the TNT component. The Composition B model was then tested on existing short pulse duration, gap test, and projectile impact shock initiation with good results. This Composition B model can be applied to shock initiation scenarios that have not or cannot be tested experimentally with a high level of confidence in its predictions.

  19. SHOCK INITIATION OF COMPOSITION B AND C-4 EXPLOSIVES; EXPERIMENTS AND MODELING

    SciTech Connect

    Urtiew, P A; Vandersall, K S; Tarver, C M; Garcia, F; Forbes, J W

    2006-08-18

    Shock initiation experiments on the explosives Composition B and C-4 were performed to obtain in-situ pressure gauge data for the purpose of providing the Ignition and Growth reactive flow model with proper modeling parameters. A 100 mm diameter propellant driven gas gun was utilized to initiate the explosive charges containing manganin piezoresistive pressure gauge packages embedded in the explosive sample. Experimental data provided new information on the shock velocity--particle velocity relationship for each of the investigated material in their respective pressure range. The run-distance-to-detonation points on the Pop-plot for these experiments showed agreement with previously published data, and Ignition and Growth modeling calculations resulted in a good fit to the experimental data. Identical ignition and growth reaction rate parameters were used for C-4 and Composition B, and the Composition B model also included a third reaction rate to simulate the completion of reaction by the TNT component. This model can be applied to shock initiation scenarios that have not or cannot be tested experimentally with a high level of confidence in its predictions.

  20. Infectious diseases associated with complement deficiencies.

    PubMed Central

    Figueroa, J E; Densen, P

    1991-01-01

    The complement system consists of both plasma and membrane proteins. The former influence the inflammatory response, immune modulation, and host defense. The latter are complement receptors, which mediate the cellular effects of complement activation, and regulatory proteins, which protect host cells from complement-mediated injury. Complement activation occurs via either the classical or the alternative pathway, which converge at the level of C3 and share a sequence of terminal components. Four aspects of the complement cascade are critical to its function and regulation: (i) activation of the classical pathway, (ii) activation of the alternative pathway, (iii) C3 convertase formation and C3 deposition, and (iv) membrane attack complex assembly and insertion. In general, mechanisms evolved by pathogenic microbes to resist the effects of complement are targeted to these four steps. Because individual complement proteins subserve unique functional activities and are activated in a sequential manner, complement deficiency states are associated with predictable defects in complement-dependent functions. These deficiency states can be grouped by which of the above four mechanisms they disrupt. They are distinguished by unique epidemiologic, clinical, and microbiologic features and are most prevalent in patients with certain rheumatologic and infectious diseases. Ethnic background and the incidence of infection are important cofactors determining this prevalence. Although complement undoubtedly plays a role in host defense against many microbial pathogens, it appears most important in protection against encapsulated bacteria, especially Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. The availability of effective polysaccharide vaccines and antibiotics provides an immunologic and chemotherapeutic rationale for preventing and treating infection in patients with these deficiencies. PMID

  1. Detection of surface bound complement at increasing serum anticoagulant concentrations.

    PubMed

    Arvidsson, S; Askendal, A; Lindahl, T L; Tengvall, P

    2008-04-01

    Surface mediated immune complement activation can be detected by a variety of antibody utilizing methods such as ELISA, fluorescence- or radiolabelling techniques, QCM, and ellipsometry. In the present work we investigated how the common anticoagulants heparin, dalteparin, fondaparinux and sodium citrate affected the binding of anti-complement factor 3c (anti-C3c) on a model complement activator surface, immobilised IgG, after incubation in human blood serum. The results show, as expected, that different anticoagulants affect the antibody binding differently. Increasing amounts of heparin, dalteparin and sodium citrate in normal serum resulted in a decreasing anti-C3c binding. The antibody deposition was not sensitive for the fondaparinux concentration. Surprisingly high concentrations of anti-coagulantia were needed to completely eradicate the antibody binding. Experiments in EGTA-serum showed that anticoagulants interfered directly with both the classical and alternative pathways. Control C3a-des arg ELISA measurements show that the lowered antibody surface binding was not a result of complement depletion in serum. Kallikrein generation by hydrophilic glass surfaces was not affected by high anticoagulant concentrations.

  2. Activated Complement Factors as Disease Markers for Sepsis

    PubMed Central

    Charchaflieh, Jean; Rushbrook, Julie; Worah, Samrat; Zhang, Ming

    2015-01-01

    Sepsis is a leading cause of death in the United States and worldwide. Early recognition and effective management are essential for improved outcome. However, early recognition is impeded by lack of clinically utilized biomarkers. Complement factors play important roles in the mechanisms leading to sepsis and can potentially serve as early markers of sepsis and of sepsis severity and outcome. This review provides a synopsis of recent animal and clinical studies of the role of complement factors in sepsis development, together with their potential as disease markers. In addition, new results from our laboratory are presented regarding the involvement of the complement factor, mannose-binding lectin, in septic shock patients. Future clinical studies are needed to obtain the complete profiles of complement factors/their activated products during the course of sepsis development. We anticipate that the results of these studies will lead to a multipanel set of sepsis biomarkers which, along with currently used laboratory tests, will facilitate earlier diagnosis, timely treatment, and improved outcome. PMID:26420913

  3. Review on complement analysis method and the roles of glycosaminoglycans in the complement system.

    PubMed

    Li, Lian; Li, Yan; Ijaz, Muhammad; Shahbaz, Muhammad; Lian, Qianqian; Wang, Fengshan

    2015-12-10

    Complement system is composed of over 30 proteins and it plays important roles in self-defence and inflammation. There are three activation pathways, including classical pathway, alternative pathway and lectin pathway, in complement system, and they are associated with many diseases such as osteoarthritis and age-related macular degeneration. Modulation of the complement system may be a promising strategy in the treatment of related diseases. Glycosaminoglycans are anionic linear polysaccharides without branches. They are one kind of multi-functional macromolecules which have great potential in regulating complement system. This review is organized around two aspects between the introduction of complement system and the interaction of glycosaminoglycans with complement system. Three complement activation pathways and the biological significance were introduced first. Then functional analysis methods were compared to provide a strategy for potential glycosaminoglycans screen. Finally, the roles of glycosaminoglycans played in the complement system were summed up.

  4. The role of complement in AMD.

    PubMed

    Zipfel, Peter F; Lauer, Nadine; Skerka, Christine

    2010-01-01

    Age related macular degeneration (AMD) is a common form of blindness in the western world and genetic variations of several complement genes, including the complement regulator Factor H, the central complement component C3, Factor B, C2, and also Factor I confer a risk for the disease. However deletion of a chromosomal segment in the Factor H gene cluster on human chromosome 1, which results in the deficiency of the terminal pathway regulator CFHR1, and of the putative complement regulator CFHR3 has a protective effect for development of AMD. The Factor H gene encodes two proteins Factor H and FHL1 which are derived from alternatively processed transcripts. In particular a sequence variation at position 402 of both Factor H and FHL1 is associated with a risk for AMD. A tyrosine residue at position 402 represents the protective and a histidine residue the risk variant. AMD is considered a chronic inflammatory disease, which can be caused by defective and inappropriate regulation of the continuously activated alternative complement pathway. This activation generates complement effector products and inflammatory mediators that stimulate further inflammatory reactions. Defective regulation can lead to formation of immune deposits, drusen and ultimately translate into damage of retinal pigment epithelial cells, rupture of the interface between these epithelial cells and the Bruch's membrane and vision loss. Here we describe the role of complement in the retina and summarize the current concept how defective or inappropriate local complement control contributes to inflammation and the pathophysiology of AMD.

  5. Progress and Trends in Complement Therapeutics

    PubMed Central

    Ricklin, Daniel; Lambris, John D.

    2012-01-01

    The past few years have proven to be a highly successful and exciting period for the field of complement-directed drug discovery and development. Driven by promising experiences with the first marketed complement drugs, increased knowledge about the involvement of complement in health and disease, and improvements in structural and analytical techniques as well as animal models of disease, the field has seen a surge in creative approaches to therapeutically intervene at various stages of the cascade. An impressive panel of compounds that show promise in clinical trials is meanwhile being lined up in the pipelines of both small biotechnology and big pharmaceutical companies. Yet with this new focus on complement-targeted therapeutics, important questions concerning target selection, point and length of intervention, safety, and drug delivery emerge. In view of the diversity of the clinical disorders involving abnormal complement activity or regulation, which include both acute and chronic diseases and affect a wide range of organs, diverse yet specifically tailored therapeutic approaches may be needed to shift complement back into balance. This chapter highlights the key changes in the field that shape our current perception of complement-targeted drugs and provides a brief overview of recent strategies and emerging trends. Selected examples of complement-related diseases and inhibitor classes are highlighted to illustrate the diversity and creativity in field. PMID:22990692

  6. Kranz and single-cell forms of C4 plants in the subfamily Suaedoideae show kinetic C4 convergence for PEPC and Rubisco with divergent amino acid substitutions

    PubMed Central

    Rosnow, Josh J.; Evans, Marc A.; Kapralov, Maxim V.; Cousins, Asaph B.; Edwards, Gerald E.; Roalson, Eric H.

    2015-01-01

    The two carboxylation reactions performed by phosphoenolpyruvate carboxylase (PEPC) and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) are vital in the fixation of inorganic carbon for C4 plants. The abundance of PEPC is substantially elevated in C4 leaves, while the location of Rubisco is restricted to one of two chloroplast types. These differences compared with C3 leaves have been shown to result in convergent enzyme optimization in some C4 species. Investigation into the kinetic properties of PEPC and Rubisco from Kranz C4, single cell C4, and C3 species in Chenopodiaceae s. s. subfamily Suaedoideae showed that these major carboxylases in C4 Suaedoideae species lack the same mutations found in other C4 systems which have been examined; but still have similar convergent kinetic properties. Positive selection analysis on the N-terminus of PEPC identified residues 364 and 368 to be under positive selection with a posterior probability >0.99 using Bayes empirical Bayes. Compared with previous analyses on other C4 species, PEPC from C4 Suaedoideae species have different convergent amino acids that result in a higher K m for PEP and malate tolerance compared with C3 species. Kinetic analysis of Rubisco showed that C4 species have a higher catalytic efficiency of Rubisco (k catc in mol CO2 mol–1 Rubisco active sites s–1), despite lacking convergent substitutions in the rbcL gene. The importance of kinetic changes to the two-carboxylation reactions in C4 leaves related to amino acid selection is discussed. PMID:26417023

  7. Complement System Part II: Role in Immunity

    PubMed Central

    Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.

    2015-01-01

    The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target. PMID:26074922

  8. Complement expression in retinal pigment epithelial cells is modulated by activated macrophages.

    PubMed

    Luo, Chang; Zhao, Jiawu; Madden, Angelina; Chen, Mei; Xu, Heping

    2013-07-01

    Complement activation is involved in a variety of retinal diseases. We have shown previously that a number of complement components and regulators can be produced locally in the eye, and that retinal pigment epithelial (RPE) cells are the major source of complement expression at the retina-choroidal interface. The expression of complement components by RPE cells is regulated by inflammatory cytokines. Under aging or inflammatory conditions, microglia and macrophages accumulate in the subretinal space, where they are in close contact with RPE cells. In this study, we investigated the effect of activated macrophages on complement expression by RPE cells. Mouse RPE cells were treated with the supernatants from un-activated bone marrow-derived macrophages (BM-DMs), the classically activated BM-DMs (M1) and different types of the alternatively activated BM-DMs (M2a by IL-4, M2b by immune complex and lipopolysaccharide (LPS), M2c by IL-10). The expression of inflammatory cytokines and complement genes by RPE cells were determined by real-time RT-PCR. The protein expression of CFB, C3, C1INH, and C1r was examined by Western blot. Our results show that un-stimulated RPE cells express a variety of complement-related genes, and that the expression levels of complement regulators, including C1r, factor H (CFH), DAF1, CD59, C1INH, Crry, and C4BP genes are significantly higher than those of complement component genes (C2, C4, CFB, C3, and C5). Macrophage supernatants increased inflammatory cytokine (IL-1β, IL-6, iNOS), chemokine (CCL2) and complement expression in RPE cells. The supernatants from M0, M2a and M2c macrophages mildly up-regulated (2-3.5-fold) CFB, CFH and C3 gene expression in RPE cells, whereas the supernatants from M1 and M2b macrophages massively increased (10-30-fold) CFB and C3 gene expression in RPE cells. The expression of other genes, including C1r, C2, C4, CFH, Masp1, C1INH, and C4BP in RPE cells was also increased by the supernatants of M1 and M2b

  9. Immune evasion by pathogenic Leptospira strains: the secretion of proteases that directly cleave complement proteins.

    PubMed

    Fraga, Tatiana Rodrigues; Courrol, Daniella Dos Santos; Castiblanco-Valencia, Mónica Marcela; Hirata, Izaura Yoshico; Vasconcellos, Sílvio Arruda; Juliano, Luiz; Barbosa, Angela Silva; Isaac, Lourdes

    2014-03-01

    Leptospirosis is an infectious disease of public health importance. To successfully colonize the host, pathogens have evolved multiple strategies to escape the complement system. Here we demonstrate that the culture supernatant of pathogenic but not saprophytic Leptospira inhibit the three complement pathways. We showed that the proteolytic activity in the supernatants of pathogenic strains targets the central complement molecule C3 and specific proteins from each pathway, such as factor B, C2, and C4b. The proteases cleaved α and β chains of C3 and work in synergy with host regulators to inactivate C3b. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. A recombinant leptospiral metalloprotease from the thermolysin family cleaved C3 in serum and could be one of the proteases responsible for the supernatant activity. We conclude that pathogenic leptospiral proteases can deactivate immune effector molecules and represent potential targets to the development of new therapies in leptospirosis.

  10. High-level ab initio predictions for the ionization energies and heats of formation of five-membered-ring molecules: thiophene, furan, pyrrole, 1,3-cyclopentadiene, and borole, C4H4X/C4H4X+ (X = S, O, NH, CH2, and BH).

    PubMed

    Lo, Po-Kam; Lau, Kai-Chung

    2011-02-10

    The ionization energies (IEs) and heats of formation (ΔH°(f0)/ΔH°(f298)) for thiophene (C(4)H(4)S), furan (C(4)H(4)O), pyrrole (C(4)H(4)NH), 1,3-cyclopentadiene (C(4)H(4)CH(2)), and borole (C(4)H(4)BH) have been calculated by the wave function-based ab initio CCSD(T)/CBS approach, which involves the approximation to the complete basis set (CBS) limit at the coupled-cluster level with single and double excitations plus a quasi-perturbative triple excitation [CCSD(T)]. Where appropriate, the zero-point vibrational energy correction (ZPVE), the core-valence electronic correction (CV), and the scalar relativistic effect (SR) are included in these calculations. The respective CCSD(T)/CBS predictions for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2), being 8.888, 8.897, 8.222, and 8.582 eV, are in excellent agreement with the experimental values obtained from previous photoelectron and photoion measurements. The ΔH°(f0)/ΔH°(f298) values for the aforementioned molecules and their corresponding cations have also been predicted by the CCSD(T)/CBS method, and the results are compared with the available experimental data. The comparisons between the CCSD(T)/CBS predictions and the experimental values for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2) suggest that the CCSD(T)/CBS procedure is capable of predicting reliable IE values for five-membered-ring molecules with an uncertainty of ±13 meV. In view of the excellent agreements between the CCSD(T)/CBS predictions and the experimental values for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2), the similar CCSD(T)/CBS IE and ΔH°(f0)/ΔH°(f298) predictions for C(4)H(4)BH, whose thermochemical data are not readily available due to its reactive nature, should constitute a reliable data set. The CCSD(T)/CBS IE(C(4)H(4)BH) value is 8.868 eV, and ΔH°(f0)/ΔH°(f298) values for C(4)H(4)BH and C(4)H(4)BH(+) are 269.5/258.6 and 1125.1/1114.6 kJ/mol, respectively. The highest occupied molecular orbitals

  11. The ultraviolet photochemistry of diacetylene - Direct detection of primary products of the metastable C4H2* + C4H2 reaction

    NASA Technical Reports Server (NTRS)

    Bandy, Ralph E.; Lakshminarayan, Chitra; Frost, Rex K.; Zwier, Timothy S.

    1993-01-01

    The products of diacetylene's ultraviolet photochemistry over the 245-220 nm region were directly determined in experiments where C4H2 was excited within a small reaction tube attached to a pulsed nozzle. The products formed in the collisions of C4H2* with C4H2 were subsequently ionized by vacuum UV radiation (at 118 nm) in the ion source of a time-of-flight mass spectrometer. It was found that the reaction of C4H2* with C4H2 produces C6H2 (+C2H2), C8H2 (+2H,H2), and C8H3 (+H), confirming the results of Glicker and Okabe (1987). Under certain conditions, secondary products were observed. Mechanisms for the observed reactions are proposed.

  12. Traces of strong selective pressures in the genomes of C4 grasses.

    PubMed

    Christin, Pascal-Antoine

    2017-01-01

    C4 photosynthesis is nature's response to CO2 limitations, and evolved recurrently in several groups of plants. To identify genes related to C4 photosynthesis, Huang et al. looked for evidence of past episodes of adaptive evolution in the genomes of C4 grasses. They identified a large number of candidate genes that evolved under divergent selection, indicating that, besides alterations to expression patterns, the history of C4 involved strong selection on protein-coding sequences.

  13. 26 CFR 1.652(c)-4 - Illustration of the provisions of sections 651 and 652.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Illustration of the provisions of sections 651 and 652. 1.652(c)-4 Section 1.652(c)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE....652(c)-4 Illustration of the provisions of sections 651 and 652. The rules applicable to a...

  14. 26 CFR 1.652(c)-4 - Illustration of the provisions of sections 651 and 652.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Illustration of the provisions of sections 651 and 652. 1.652(c)-4 Section 1.652(c)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(c)-4 Illustration of the provisions of sections 651 and 652. The rules applicable to...

  15. 26 CFR 1.652(c)-4 - Illustration of the provisions of sections 651 and 652.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Illustration of the provisions of sections 651 and 652. 1.652(c)-4 Section 1.652(c)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(c)-4 Illustration of the provisions of sections 651 and 652. The rules applicable to...

  16. 26 CFR 1.652(c)-4 - Illustration of the provisions of sections 651 and 652.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Illustration of the provisions of sections 651 and 652. 1.652(c)-4 Section 1.652(c)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(c)-4 Illustration of the provisions of sections 651 and 652. The rules applicable to...

  17. 26 CFR 1.652(c)-4 - Illustration of the provisions of sections 651 and 652.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Illustration of the provisions of sections 651 and 652. 1.652(c)-4 Section 1.652(c)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(c)-4 Illustration of the provisions of sections 651 and 652. The rules applicable to...

  18. Expression analysis of kenaf cinnamate 4-hydroxylase (C4H) ortholog during developmental and stress responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was conducted to clone and analyze the expression pattern of a C4H gene encoding cinnamate 4-hydroxylase from kenaf (Hibiscus cannabinus L.). A full-length C4H ortholog was cloned using degenerate primers and the RACE (rapid amplification of cDNA ends) method. The full-length C4H ortholog...

  19. Solvation Thermodynamic Properties of Hydrogen Sulfide in [C4mim][PF6], [C4mim][BF4], and [C4mim][Cl] Ionic Liquids, Determined by Molecular Simulations.

    PubMed

    Sánchez-Badillo, Joel; Gallo, Marco; Alvarado, Sandra; Glossman-Mitnik, Daniel

    2015-08-20

    Removal of hydrogen sulfide (H2S) and acid gases from natural gas is accomplished by absorption processes using a solvent. The gas solubility in a liquid can be used to measure the degree of removal of the gas and is quantified by the Henry's constant, the free energy of solvation at infinite dilution, or the excess chemical potential. In this work, Henry's constants and thermodynamic properties of solvation of H2S were calculated in three ionic liquids: [C4mim][PF6], [C4mim][BF4], and [C4mim][Cl] ([C4mim], 1-butyl-3-methyl imidazolium). The first step in this work was the evaluation of the force fields for the gas and condensed phases in order to obtain accurate values for the excess chemical potential for H2S on each ionic liquid using free energy perturbation techniques. In the H2S-[C4mim][PF6] and H2S-[C4mim][BF4] systems, the results obtained by molecular simulation agree with the experimental values reported in the literature. However, the solvation free energy calculated for the H2S-[C4mim][Cl] system can be considered predictive because of the lack of experimental data at the simulated conditions. Based on these results, the best solvent for removing H2S is [C4mim][Cl] because it has the highest affinity for this species (lowest value of the Henry's constant). Also, solvation thermodynamic properties such as enthalpy and entropy were calculated in order to evaluate their contribution to the free energy of solvation.

  20. Structural study of hydrated/dehydrated manganese thiophene-2,5-diphosphonate metal organic frameworks, Mn2(O3P-C4H2S-PO3)·2H2O.

    PubMed

    Rueff, Jean-Michel; Perez, Olivier; Pautrat, Alain; Barrier, Nicolas; Hix, Gary B; Hernot, Sylvie; Couthon-Gourvès, Hélène; Jaffrès, Paul-Alain

    2012-10-01

    Synthesis of thiophene-2,5-diphosphonic acid 2 is reported, and its use for synthesis of the original pristine materials Mn(2)(O(3)P-C(4)H(2)S-PO(3))·2H(2)O 3 is reported. The structure of material 3 has been fully resolved from single-crystal X-ray diffraction. Mn(2)(O(3)P-C(4)H(2)S-PO(3))·2H(2)O 3 crystallizes in a monoclinic cell (space group P2) with the following parameters: a = 11.60(1) Å, b = 4.943(5) Å, c = 19.614(13) Å, β = 107.22°. A noticeable feature of the structure of compound 3 is the orientation of the thiophene heterocycles that adopt two different orientations in two successive layers (along c). Thermal analysis of compound 3 indicates that the water molecules are easily removed from 160 to 230 °C while the dehydrated structure is stable up to 500 °C. The dehydrated compound obtained from 3 can be rehydrated to give the polymorphic compound Mn(2)(O(3)P-C(4)H(2)S-PO(3))·2H(2)O 4, which crystallizes in an orthorhombic cell (space group Pnam) with the following parameters: a = 7.5359(3) Å, b = 7.5524(3) Å, c = 18.3050(9) Å. The main difference between the structures of 3 and 4 arises from both the orientation of the thiophene rings (herringbone-type organization in 4) and the structure of the inorganic layers. The thiophene-2,5-diphosphonic acid moieties engaged in materials 3 and 4 adopt a different orientation likely due to rotation around the P-C bonds and via the dehydrated state 5, which is likely more flexible than the hydrated states. Study of the magnetic properties performed on compound 3 and 4 and on the dehydrated compounds Mn(2)(O(3)P-C(4)H(2)S-PO(3)) 5 complemented by the structural study has permitted us to characterize the antiferromagnetic ground state of sample 3, a weak ferromagnetic component in sample 4, and complete paramagnetic behavior in sample 5.

  1. C4MIP - The Coupled Climate-Carbon Cycle Model Intercomparison Project: experimental protocol for CMIP6

    NASA Astrophysics Data System (ADS)

    Jones, Chris D.; Arora, Vivek; Friedlingstein, Pierre; Bopp, Laurent; Brovkin, Victor; Dunne, John; Graven, Heather; Hoffman, Forrest; Ilyina, Tatiana; John, Jasmin G.; Jung, Martin; Kawamiya, Michio; Koven, Charlie; Pongratz, Julia; Raddatz, Thomas; Randerson, James T.; Zaehle, Sönke

    2016-08-01

    Coordinated experimental design and implementation has become a cornerstone of global climate modelling. Model Intercomparison Projects (MIPs) enable systematic and robust analysis of results across many models, by reducing the influence of ad hoc differences in model set-up or experimental boundary conditions. As it enters its 6th phase, the Coupled Model Intercomparison Project (CMIP6) has grown significantly in scope with the design and documentation of individual simulations delegated to individual climate science communities. The Coupled Climate-Carbon Cycle Model Intercomparison Project (C4MIP) takes responsibility for design, documentation, and analysis of carbon cycle feedbacks and interactions in climate simulations. These feedbacks are potentially large and play a leading-order contribution in determining the atmospheric composition in response to human emissions of CO2 and in the setting of emissions targets to stabilize climate or avoid dangerous climate change. For over a decade, C4MIP has coordinated coupled climate-carbon cycle simulations, and in this paper we describe the C4MIP simulations that will be formally part of CMIP6. While the climate-carbon cycle community has created this experimental design, the simulations also fit within the wider CMIP activity, conform to some common standards including documentation and diagnostic requests, and are designed to complement the CMIP core experiments known as the Diagnostic, Evaluation and Characterization of Klima (DECK). C4MIP has three key strands of scientific motivation and the requested simulations are designed to satisfy their needs: (1) pre-industrial and historical simulations (formally part of the common set of CMIP6 experiments) to enable model evaluation, (2) idealized coupled and partially coupled simulations with 1 % per year increases in CO2 to enable diagnosis of feedback strength and its components, (3) future scenario simulations to project how the Earth system will respond to

  2. C4MIP – The Coupled Climate–Carbon Cycle Model Intercomparison Project: Experimental protocol for CMIP6

    DOE PAGES

    Jones, Chris D.; Arora, Vivek; Friedlingstein, Pierre; ...

    2016-08-25

    Coordinated experimental design and implementation has become a cornerstone of global climate modelling. Model Intercomparison Projects (MIPs) enable systematic and robust analysis of results across many models, by reducing the influence of ad hoc differences in model set-up or experimental boundary conditions. As it enters its 6th phase, the Coupled Model Intercomparison Project (CMIP6) has grown significantly in scope with the design and documentation of individual simulations delegated to individual climate science communities. The Coupled Climate–Carbon Cycle Model Intercomparison Project (C4MIP) takes responsibility for design, documentation, and analysis of carbon cycle feedbacks and interactions in climate simulations. These feedbacks aremore » potentially large and play a leading-order contribution in determining the atmospheric composition in response to human emissions of CO2 and in the setting of emissions targets to stabilize climate or avoid dangerous climate change. For over a decade, C4MIP has coordinated coupled climate–carbon cycle simulations, and in this paper we describe the C4MIP simulations that will be formally part of CMIP6. While the climate–carbon cycle community has created this experimental design, the simulations also fit within the wider CMIP activity, conform to some common standards including documentation and diagnostic requests, and are designed to complement the CMIP core experiments known as the Diagnostic, Evaluation and Characterization of Klima (DECK). C4MIP has three key strands of scientific motivation and the requested simulations are designed to satisfy their needs: (1) pre-industrial and historical simulations (formally part of the common set of CMIP6 experiments) to enable model evaluation, (2) idealized coupled and partially coupled simulations with 1 % per year increases in CO2 to enable diagnosis of feedback strength and its components, (3) future scenario simulations to project how the Earth system will

  3. C4MIP – The Coupled Climate–Carbon Cycle Model Intercomparison Project: Experimental protocol for CMIP6

    SciTech Connect

    Jones, Chris D.; Arora, Vivek; Friedlingstein, Pierre; Bopp, Laurent; Brovkin, Victor; Dunne, John; Hoffman, Forrest; Ilyina, Tatiana; John, Jasmin G.; Kawamiya, Michio; Koven, Charlie; Pongratz, Julia; Raddatz, Thomas; Randerson, James T.; Zaehle, Sonke

    2016-08-25

    Coordinated experimental design and implementation has become a cornerstone of global climate modelling. Model Intercomparison Projects (MIPs) enable systematic and robust analysis of results across many models, by reducing the influence of ad hoc differences in model set-up or experimental boundary conditions. As it enters its 6th phase, the Coupled Model Intercomparison Project (CMIP6) has grown significantly in scope with the design and documentation of individual simulations delegated to individual climate science communities.

    The Coupled Climate–Carbon Cycle Model Intercomparison Project (C4MIP) takes responsibility for design, documentation, and analysis of carbon cycle feedbacks and interactions in climate simulations. These feedbacks are potentially large and play a leading-order contribution in determining the atmospheric composition in response to human emissions of CO2 and in the setting of emissions targets to stabilize climate or avoid dangerous climate change. For over a decade, C4MIP has coordinated coupled climate–carbon cycle simulations, and in this paper we describe the C4MIP simulations that will be formally part of CMIP6. While the climate–carbon cycle community has created this experimental design, the simulations also fit within the wider CMIP activity, conform to some common standards including documentation and diagnostic requests, and are designed to complement the CMIP core experiments known as the Diagnostic, Evaluation and Characterization of Klima (DECK).

    C4MIP has three key strands of scientific motivation and the requested simulations are designed to satisfy their needs: (1) pre-industrial and historical simulations (formally part of the common set of CMIP6 experiments) to enable model evaluation, (2) idealized coupled and partially coupled simulations with 1 % per year increases in CO2 to enable diagnosis of feedback strength and its components, (3) future scenario simulations to

  4. Properdin in Complement Activation and Tissue Injury

    PubMed Central

    Lesher, AM; B, Nilsson; Song, W-C

    2013-01-01

    The plasma protein properdin is the only known positive regulator of complement activation. Although regarded as an initiator of the alternative pathway of complement activation at the time of its discovery more than a half century ago, the role and mechanism of action of properdin in the complement cascade has undergone significant conceptual evolution since then. Despite the long history of research on properdin, however, new insight and unexpected findings on the role of properdin in complement activation, pathogen infection and host tissue injury are still being revealed by ongoing investigations. In this article, we provide a brief review on recent studies that shed new light on properdin biology, focusing on the following three topics: 1) its role as a pattern recognition molecule to direct and trigger complement activation, 2) its context-dependent requirement in complement activation on foreign and host cell surfaces, and 3) its involvement in alternative pathway complement-mediated immune disorders and considerations of properdin as a potential therapeutic target in human diseases. PMID:23816404

  5. Analysis of C3b/C4b receptor (CR1) polymorphic variants by tryptic peptide mapping.

    PubMed

    Nickells, M W; Seya, T; Holers, V M; Atkinson, J P

    1986-06-01

    The human C3b/C4b receptor (CR1) binds the major activation and opsonic fragments of the third (C3) and fourth (C4) components of complement. CR1 is a single chain integral membrane glycoprotein widely distributed on peripheral blood cells. Four codominantly inherited allelic variants with Mrs of 160,000, 190,000, 220,000 and 250,000 have been described. To address the structural basis for this unusual polymorphism, CR1 from donors expressing three of the four allelic variants was purified from surface labeled (125I) erythrocytes by iC3-Sepharose affinity chromatography and the variants compared by tryptic peptide mapping (TPM). The TPMs of each variant contained the same major peaks and minor peak areas and were nearly identical to one another. Tryptic peptide mappings of the 190,000 Mr erythrocyte CR1, which was purified prior to iodination, were similar to those derived from surface iodinated CR1. The TPMs of erythrocyte and granulocyte CR1 from the same donor differed by a single peak of increased prominence in the granulocyte map. These results indicate a conservation in amino acid sequence for those peptides detected. In view of these data and those of other studies of the structure and genetics of CR1 and related proteins, it is suggested in this paper that the allelic variation relates to CR1, being composed of repeating amino acid sequences.

  6. Cloning and functional identification of C-4 methyl sterol oxidase genes from the penicillin-producing fungus Penicillium chrysogenum.

    PubMed

    Wang, Fu-Qiang; Zhao, Ying; Dai, Meng; Liu, Jing; Zheng, Gui-Zhen; Ren, Zhi-Hong; He, Jian-Gong

    2008-10-01

    Two C-4 methyl sterol oxidase genes (Pcerg25A and Pcerg25B) that are involved in ergosterol biosynthesis have been cloned from the penicillin-producing fungus Penicillium chrysogenum. cDNAs of both Pcerg25A and Pcerg25B have an ORF 885 bp in length, encoding a peptide of 295 residues. The deduced amino acid sequences of PcErg25A and PcErg25B show 86% identity, and have high identities to the characterized C-4 methyl sterol oxidases from Candida albicans and Saccharomyces cerevisiae. The function of Pcerg25A and Pcerg25B was identified by complementation of a yeast erg25-deficient strain. Pcerg25A is located in the DNA region containing the penicillin gene cluster, and thus its copy number is dependent on the patterns of the cluster region. Up to eight copies of Pcerg25A were found in the high-productivity strain NCPC 10086. By contrast, Pcerg25B was present in just a single copy in all tested P. chrysogenum genomes. Differences in the transcript level of either Pcerg25A or Pcerg25B were observed in different P. chrysogenum strains by real-time quantitative reverse transcriptase PCR analysis.

  7. Towards an integrative model of C4 photosynthetic subtypes: insights from comparative transcriptome analysis of NAD-ME, NADP-ME, and PEP-CK C4 species

    PubMed Central

    Bräutigam, Andrea; Schliesky, Simon; Külahoglu, Canan; Osborne, Colin P.; Weber, Andreas P.M.

    2014-01-01

    C4 photosynthesis affords higher photosynthetic carbon conversion efficiency than C3 photosynthesis and it therefore represents an attractive target for engineering efforts aiming to improve crop productivity. To this end, blueprints are required that reflect C4 metabolism as closely as possible. Such blueprints have been derived from comparative transcriptome analyses of C3 species with related C4 species belonging to the NAD-malic enzyme (NAD-ME) and NADP-ME subgroups of C4 photosynthesis. However, a comparison between C3 and the phosphoenolpyruvate carboxykinase (PEP-CK) subtype of C4 photosynthesis is still missing. An integrative analysis of all three C4 subtypes has also not been possible to date, since no comparison has been available for closely related C3 and PEP-CK C4 species. To generate the data, the guinea grass Megathyrsus maximus, which represents a PEP-CK species, was analysed in comparison with a closely related C3 sister species, Dichanthelium clandestinum, and with publicly available sets of RNA-Seq data from C4 species belonging to the NAD-ME and NADP-ME subgroups. The data indicate that the core C4 cycle of the PEP-CK grass M. maximus is quite similar to that of NAD-ME species with only a few exceptions, such as the subcellular location of transfer acid production and the degree and pattern of up-regulation of genes encoding C4 enzymes. One additional mitochondrial transporter protein was associated with the core cycle. The broad comparison identified sucrose and starch synthesis, as well as the prevention of leakage of C4 cycle intermediates to other metabolic pathways, as critical components of C4 metabolism. Estimation of intercellular transport fluxes indicated that flux between cells is increased by at least two orders of magnitude in C4 species compared with C3 species. In contrast to NAD-ME and NADP-ME species, the transcription of photosynthetic electron transfer proteins was unchanged in PEP-CK. In summary, the PEP-CK blueprint of M

  8. Africa's wild C4 plant foods and possible early hominid diets.

    PubMed

    Peters, Charles R; Vogel, John C

    2005-03-01

    A small minority of Africa's wild plant foods are C4. These are primarily the seeds of some of the C4 grasses, the rootstocks and stem/leaf bases of some of the C4 sedges (especially papyrus), and the leaves of some of the C4 herbaceous dicots (forbs). These wild food plants are commonly found in disturbed ground and wetlands (particularly the grasses and sedges). Multiple lines of evidence indicate that C4 grasses were present in Africa by at least the late Miocene. It is a reasonable hypothesis that the prehistory of the C4 sedges parallels that of the C4 grasses, but the C4 forbs may not have become common until the late Pleistocene. CAM plants may have a more ancient history, but offer few opportunities for an additional C4-like dietary signal. The environmental reconstructions available for the early South African hominid sites do not indicate the presence of large wetlands, and therefore probably the absence of a strong potential for a C4 plant food diet. However, carbon isotope analyses of tooth enamel from three species of early South African hominids have shown that there was a significant but not dominant contribution of C4 biomass in their diets. Since it appears unlikely that this C4 component could have come predominantly from C4 plant foods, a broad range of potential animal contributors is briefly considered, namely invertebrates, reptiles, birds, and small mammals. It is concluded that the similar average C4 dietary intake seen in the three South African hominid species could have been acquired by differing contributions from the various sources, without the need to assume scavenging or hunting of medium to large grazing ungulates. Effectively similar dominantly dryland paleo-environments may also be part of the explanation. Theoretically, elsewhere in southern and eastern Africa, large wetlands would have offered early hominids greater opportunities for a C4 plant diet.

  9. Infections Revealing Complement Deficiency in Adults

    PubMed Central

    Audemard-Verger, A.; Descloux, E.; Ponard, D.; Deroux, A.; Fantin, B.; Fieschi, C.; John, M.; Bouldouyre, A.; Karkowsi, L.; Moulis, G.; Auvinet, H.; Valla, F.; Lechiche, C.; Davido, B.; Martinot, M.; Biron, C.; Lucht, F.; Asseray, N.; Froissart, A.; Buzelé, R.; Perlat, A.; Boutboul, D.; Fremeaux-Bacchi, V.; Isnard, S.; Bienvenu, B.

    2016-01-01

    Abstract Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies. A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis. Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35

  10. CD46: the 'multitasker' of complement proteins.

    PubMed

    Yamamoto, Hidekazu; Fara, Antonella Francesca; Dasgupta, Prokar; Kemper, Claudia

    2013-12-01

    Complement is undeniably quintessential for innate immunity by detecting and eliminating infectious microorganisms. Recent work, however, highlights an equally profound impact of complement on the induction and regulation of a wide range of immune cells. In particular, the complement regulator CD46 emerges as a key sensor of immune activation and a vital modulator of adaptive immunity. In this review, we summarize the current knowledge of CD46-mediated signalling events and their functional consequences on immune-competent cells with a specific focus on those in CD4(+) T cells. We will also discuss the promises and challenges that potential therapeutic modulation of CD46 may hold and pose.

  11. An assessment of the capacity for phosphoenolpyruvate carboxykinase to contribute to C4 photosynthesis.

    PubMed

    Koteyeva, Nuria K; Voznesenskaya, Elena V; Edwards, Gerald E

    2015-06-01

    Three C4 acid decarboxylases, phosphoenolpyruvate carboxykinase (PEPCK), NADP-malic enzyme (NADP-ME), and NAD-malic enzyme (NAD-ME) were recruited from C3 plants to support C4 photosynthesis. In Poaceae, there are established lineages having PEPCK type species, and some NADP-ME lineages in which PEPCK contributes to C4. Besides family Poaceae, recently PEPCK has been reported to function in C4 photosynthesis in eudicot species including Cleome gynandra (Cleomaceae), Trianthema portulacastrum and Zaleya pentandra (Aizoaceae). We evaluated PEPCK by enzyme assay and western blots in representatives of Poaceae, Aizoaceae, Cleomaceae, and Chenopodiaceae compared to that in the PEPCK type C4 grass Spartina anglica. Eragrostis nutans was identified as the first NAD-ME type C4 grass having substantial amounts of PEPCK. In the eudicots, including C. gynandra, Cleome angustifolia, T. portulacastrum, Z. pentandra, and nine C4 members of family Chenopodiaceae (which has the most C4 species and diversity in forms among eudicot families), amounts of PEPCK were generally very low (barely detectable up to 4% of that in S. anglica). Based on these results, C4 species can be classified biochemically according to the dominant decarboxylase recruited for C4 function; and, Poaceae remains the only family in which PEPCK is known to have a significant role in C4 photosynthesis.

  12. Complete prewetting

    NASA Astrophysics Data System (ADS)

    Yatsyshin, P.; Parry, A. O.; Kalliadasis, S.

    2016-07-01

    We study continuous interfacial transitions, analagous to two-dimensional complete wetting, associated with the first-order prewetting line, which can occur on steps, patterned walls, grooves and wedges, and which are sensitive to both the range of the intermolecular forces and interfacial fluctuation effects. These transitions compete with wetting, filling and condensation producing very rich phase diagrams even for relatively simple prototypical geometries. Using microscopic classical density functional theory to model systems with realistic Lennard-Jones fluid-fluid and fluid-substrate intermolecular potentials, we compute mean-field fluid density profiles, adsorption isotherms and phase diagrams for a variety of confining geometries.

  13. Relationship of high CH50 level and interruption of cascade reaction of complement mRNA expression in acute venous thromboembolism patients

    PubMed Central

    Wen, Siwan; Yang, Fan; Wang, Lemin; Duan, Qianglin; Gong, Zhu; Lv, Wei

    2014-01-01

    In patients with pulmonary embolism (PE), forepart components of complements were activated. However there are interruption/decrease of cascade reaction and cytolytic effects in complement system. This study detected CRP, CH50, C3 and C4 levels in patients with venous thromboembolism (VTE) and compare with the imbalance of complement associated gene mRNA expression in PE patients. There was significant increase of CH50 in acute VTE patients. Even though CH50 increased significantly in acute VTE patients and had a relatively high sensitivity, cytolytic effects of complements might decrease, based on the genomics results of complement cascade reactions imbalance/interruption and increased total complements in VTE patients. PMID:25232435

  14. Autocrine Effects of Tumor-Derived Complement

    PubMed Central

    Cho, Min Soon; Vasquez, Hernan G.; Rupaimoole, Rajesha; Pradeep, Sunila; Wu, Sherry; Zand, Behrouz; Han, Hee-Dong; Rodriguez-Aguayo, Cristian; Bottsford-Miller, Justin; Huang, Jie; Miyake, Takahito; Choi, Hyun-Jin; Dalton, Heather J.; Ivan, Cristina; Baggerly, Keith; Lopez-Berestein, Gabriel; Sood, Anil K.; Afshar-Kharghan, Vahid

    2014-01-01

    SUMMARY We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic T cells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications. PMID:24613353

  15. Regulation of humoral immunity by complement.

    PubMed

    Carroll, Michael C; Isenman, David E

    2012-08-24

    The complement system of innate immunity is important in regulating humoral immunity largely through the complement receptor CR2, which forms a coreceptor on B cells during antigen-induced activation. However, CR2 also retains antigens on follicular dendritic cells (FDCs). Display of antigen on FDCs is critical for clonal selection and affinity maturation of activated B cells. This review will discuss the role of complement in adaptive immunity in general with a focus on the interplay between CR2-associated antigen on B cells with CR2 expressed on FDCs. This latter interaction provides an opportunity for memory B cells to sample antigen over prolonged periods. The cocrystal structure of CR2 with its ligand C3d provides insight into how the complement system regulates access of antigen by B cells with implications for therapeutic manipulations to modulate aberrant B cell responses in the case of autoimmunity.

  16. On complements of coradicals of finite groups

    NASA Astrophysics Data System (ADS)

    Vedernikov, V. A.; Sorokina, M. M.

    2016-06-01

    Let F be an ω-local Fitting formation, and G a finite group that can be represented in the form of a product of n subnormal subgroups whose F-coradicals are ω-soluble, and whose Sylow p-subgroups are abelian for any p\\inω. It is established that there exist ω-complements of the F-coradical of G. New theorems on the existence of complements of coradicals of a group are obtained as corollaries. For an ω-local formation F, conditions are established for the existence of complements and ω-complements of the F-coradical of a group in any of its extensions. Bibliography: 21 titles.

  17. Solvation Structure of Imidazolium Cation in Mixtures of [C4mim][TFSA] Ionic Liquid and Diglyme by NMR Measurements and MD Simulations.

    PubMed

    Shimomura, Takuya; Kodama, Daisuke; Kanakubo, Mitsuhiro; Tsuzuki, Seiji

    2017-04-06

    Interactions of 1-butyl-3-methylimidazolium cation ([C4mim](+)) with bis(trifluoromethanesulfonyl)amide anion ([TFSA](-)) and diethyleneglycol dimethyl ether (diglyme) in mixtures of [C4mim][TFSA] ionic liquid and diglyme have been investigated using (1)H and (13)C NMR spectroscopy and molecular dynamics (MD) simulations. The results of NMR chemical shift measurements and MD simulations showed that the diglyme oxygen atoms have contact with the imidazolium hydrogen atoms of [C4mim](+) in the mixtures. The contact between the hydrogen atoms of imidazolium and the oxygen atoms of [TFSA](-) remains even when the diglyme mole fraction (xdiglyme) increases up to 0.9. However, the coordination numbers of the hydrogen atoms of [C4mim](+) with oxygen atoms of diglyme increase with xdiglyme. The [TFSA](-) anions around [C4mim](+) are not completely replaced by diglyme even at xdiglyme > 0.9. The MD simulations revealed that the diglymes also have contact with the butyl group of [C4mim](+). The methyl groups of diglyme prefer to have contact with the terminal methyl group of the butyl group, whereas the diglyme oxygen atoms prefer to have contact with the methylene group connected to the imidazolium ring of [C4mim](+).

  18. Complement-Mediated Death of Ciliate Tetrahymena pyriformis Caused by Human Blood Serum.

    PubMed

    Ivanov, P A; Faktor, M I; Karpova, N S; Cheremnykh, E G; Brusov, O S

    2016-04-01

    Toxicity of human blood serum for ciliate Tetrahymena pyriformis is determined by the complement system. When ciliate are dying after being exposed to blood serum, cell membrane permeability for low-molecular-weight compounds significantly increases, probably due to pore formation. Serine protease inhibitors or exposure to physical factors inducing complement inactivation (e.g., heating up to 56°C) completely prevented ciliate death under the effect of human serum. Activation of serum complement upon interaction with Tetrahymena cells occurred by the classical or lectin pathway, while the contribution of the alternative activation pathway was negligible.

  19. Complement activation by a B cell superantigen.

    PubMed

    Kozlowski, L M; Soulika, A M; Silverman, G J; Lambris, J D; Levinson, A I

    1996-08-01

    Staphylococcal protein A (SpA), acting as a B cell superantigen, binds to the Fab region of human VH3+ Igs. Using SpA abrogated of its IgG Fc binding activity (Mod SpA) as a model B cell superantigen, we determined whether such an interaction causes complement activation. Addition of Mod SpA to human serum led to complement consumption and the generation of C3a. To determine whether this complement activation 1) was due to an interaction between VH3+ Igs and the Fab binding site of SpA and 2) proceeded via the classical complement pathway, we tested a panel of monoclonal IgM proteins for the ability to hind C1q following interaction with SpA. C1q binding was restricted to SpA-reactive, VH3+ IgM proteins. To formally determine whether the binding of SpA to the reactive VH3+ IgM proteins led to complement activation, we reconstituted the serum from a hypogammaglobulinemic patient with monoclonal IgM proteins and measured complement consumption and C3a generation following the addition of Mod SpA. We observed complement consumption and C3a production only in Mod SpA-treated serum reconstituted with a VH3+, SpA-binding, IgM protein. Taken together, these results provide compelling evidence that the interaction of the Fab binding site of SpA and VH3+ Igs can lead to complement activation via the classical pathway. This novel interaction may have significant implications for the in vivo properties of a B cell superantigen.

  20. Effects of complement inhibition with soluble complement receptor-1 on vascular injury and inflammation during renal allograft rejection in the rat.

    PubMed

    Pratt, J R; Hibbs, M J; Laver, A J; Smith, R A; Sacks, S H

    1996-12-01

    Complement is both an effector of the humoral immune response and a stimulator of leukocyte activation. To examine the influence of complement on the allograft response, we inhibited complement using recombinant human soluble complement receptor-1 (sCR1; TP10), in an unsensitized model of rat renal allograft rejection. Lewis to DA renal transplant recipients were treated daily with 25 mg/kg sCR1 or saline and sacrificed on days 1 to 5 after transplant. Transplanted organs were examined histologically and immunohistochemically for leukocyte subset markers and for the third component of complement, C3, and membrane attack complex deposition. A second set of recipients was followed from day 5 to day 9 to assess graft survival. sCR1-treated recipients displayed > 90% inhibition of plasma complement activity and a marked reduction in tissue C3 and membrane attack complex deposition. Inactivation of complement reduced the vascular injury such that there was almost complete sparing of vascular damage in day 5 sCR1-treated rats. There was a significant reduction in infiltrating leukocytes by day 5 after transplant, and complement inhibition delayed the time to reach a histologically defined end point of graft survival from 5 days in controls to 9 days in the sCR1-treated group. These results imply that the vascular and cell-mediated injury arises, in part, from complement activation. The partial inhibition of these injuries by sCR1 may have functional implications for strategies to inhibit allograft rejection.

  1. Complement and thrombosis in the antiphospholipid syndrome.

    PubMed

    Oku, Kenji; Nakamura, Hiroyuki; Kono, Michihiro; Ohmura, Kazumasa; Kato, Masaru; Bohgaki, Toshiyuki; Horita, Tetsuya; Yasuda, Shinsuke; Amengual, Olga; Atsumi, Tatsuya

    2016-10-01

    The involvement of complement activation in the pathophysiology of antiphospholipid syndrome (APS) was first reported in murine models of antiphospholipid antibody (aPL)-related pregnancy morbidities. We previously reported that complement activation is prevalent and may function as a source of procoagulant cell activation in the sera of APS patients. Recently, autoantibodies against C1q, a component of complement 1, were reported to be correlated with complement activation in systemic lupus erythematosus. These antibodies target neoepitopes of deformed C1q bound to various molecules (i.e., anionic phospholipids) and induce accelerated complement activation. We found that anti-C1q antibodies are more frequently detected in primary APS patients than in control patients and in refractory APS patients with repeated thrombotic events. The titer of anti-C1q antibodies was significantly higher in refractory APS patients than in APS patients without flare. The binding of C1q to anionic phospholipids may be associated with the surge in complement activation in patients with anti-C1q antibodies when triggered by 'second-hit' biological stressors such as infection. Such stressors will induce overexpression of anionic phospholipids, with subsequent increases in deformed C1q that is targeted by anti-C1q antibodies.

  2. The reinvestigation of the kinetics of the metathesis reactions t-C4H9• + HBr (HI) → i-C4H10 + Br• (I•) and of the t-C4H9• free radical thermochemistry.

    PubMed

    Leplat, N; Rossi, M J

    2014-07-17

    A reinvestigation of the absolute rate constant of the metathesis reactions t-C4H9• + HBr → i-C4H10 + Br• (1) and t-C4H9• + HI → i-C4H10 + I• (2) was performed thanks to a recently developed apparatus consisting of a Knudsen reactor coupled to detection based on single-photon (VUV) photoionization mass spectrometry (SPIMS). It enables the generation of thermalized hydrocarbon free radicals owing to a source upstream of and external to the Knudsen reactor. The following Arrhenius expressions were obtained: k1 = 5.6(±1.4) × 10(–12) exp(−6.76(±0.94)/(RT)) and k2 = 2.0(±0.6) × 10(–11) exp(−8.48(±0.94)/(RT)) with R = 8.314 J mol(–1) K(–1) over the range 293 to 623 K. The mass balance of the reaction system based on closed shell product detection (CSPD) was checked in order to ensure the accuracy of the used reaction mechanism and as an independent check of k1 and k2. The wall-loss rate constants of the t-butyl free radical, kw(C4H9), were measured and found to be low compared with the corresponding escape rate constant, ke(C4H9), for effusion of t-C4H9• out of the Knudsen reactor. On the basis of the present results, the free radical standard heat of formation ΔfH298°(t-C4H9•) = 44.3 ± 1.7 kJ mol(–1) was obtained when combined with the kinetics of the inverse halogenation reaction taken from the literature and using S298°(t-C4H9•) = 322.2 J K(–1) mol(–1) following a “Third Law” evaluation method. The standard enthalpy for t-butyl free radical is consistent for both the bromination and iodination reactions within the stated uncertainties.

  3. The Carbohydrate-linked Phosphorylcholine of the Parasitic Nematode Product ES-62 Modulates Complement Activation*

    PubMed Central

    Ahmed, Umul Kulthum; Maller, N. Claire; Iqbal, Asif J.; Al-Riyami, Lamyaa; Harnett, William; Raynes, John G.

    2016-01-01

    Parasitic nematodes manufacture various carbohydrate-linked phosphorylcholine (PCh)-containing molecules, including ES-62, a protein with an N-linked glycan terminally substituted with PCh. The PCh component is biologically important because it is required for immunomodulatory effects. We showed that most ES-62 was bound to a single protein, C-reactive protein (CRP), in normal human serum, displaying a calcium-dependent, high-avidity interaction and ability to form large complexes. Unexpectedly, CRP binding to ES-62 failed to efficiently activate complement as far as the C3 convertase stage in comparison with PCh-BSA and PCh-containing Streptococcus pneumoniae cell wall polysaccharide. C1q capture assays demonstrated an ES-62-CRP-C1q interaction in serum. The three ligands all activated C1 and generated C4b to similar extents. However, a C2a active site was not generated following ES-62 binding to CRP, demonstrating that C2 cleavage was far less efficient for ES-62-containing complexes. We proposed that failure of C2 cleavage was due to the flexible nature of carbohydrate-bound PCh and that reduced proximity of the C1 complex was the reason that C2 was poorly cleaved. This was confirmed using synthetic analogues that were similar to ES-62 only in respect of having a flexible PCh. Furthermore, ES-62 was shown to deplete early complement components, such as the rate-limiting C4, following CRP interaction and thereby inhibit classical pathway activation. Thus, flexible PCh-glycan represents a novel mechanism for subversion of complement activation. These data illustrate the importance of the rate-limiting C4/C2 stage of complement activation and reveal a new addition to the repertoire of ES-62 immunomodulatory mechanisms with possible therapeutic applications. PMID:27044740

  4. The Carbohydrate-linked Phosphorylcholine of the Parasitic Nematode Product ES-62 Modulates Complement Activation.

    PubMed

    Ahmed, Umul Kulthum; Maller, N Claire; Iqbal, Asif J; Al-Riyami, Lamyaa; Harnett, William; Raynes, John G

    2016-05-27

    Parasitic nematodes manufacture various carbohydrate-linked phosphorylcholine (PCh)-containing molecules, including ES-62, a protein with an N-linked glycan terminally substituted with PCh. The PCh component is biologically important because it is required for immunomodulatory effects. We showed that most ES-62 was bound to a single protein, C-reactive protein (CRP), in normal human serum, displaying a calcium-dependent, high-avidity interaction and ability to form large complexes. Unexpectedly, CRP binding to ES-62 failed to efficiently activate complement as far as the C3 convertase stage in comparison with PCh-BSA and PCh-containing Streptococcus pneumoniae cell wall polysaccharide. C1q capture assays demonstrated an ES-62-CRP-C1q interaction in serum. The three ligands all activated C1 and generated C4b to similar extents. However, a C2a active site was not generated following ES-62 binding to CRP, demonstrating that C2 cleavage was far less efficient for ES-62-containing complexes. We proposed that failure of C2 cleavage was due to the flexible nature of carbohydrate-bound PCh and that reduced proximity of the C1 complex was the reason that C2 was poorly cleaved. This was confirmed using synthetic analogues that were similar to ES-62 only in respect of having a flexible PCh. Furthermore, ES-62 was shown to deplete early complement components, such as the rate-limiting C4, following CRP interaction and thereby inhibit classical pathway activation. Thus, flexible PCh-glycan represents a novel mechanism for subversion of complement activation. These data illustrate the importance of the rate-limiting C4/C2 stage of complement activation and reveal a new addition to the repertoire of ES-62 immunomodulatory mechanisms with possible therapeutic applications.

  5. Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway

    PubMed Central

    Sethi, Sanjeev; Gamez, Jeffrey D.; Vrana, Julie A.; Theis, Jason D.; Bergen, H. Robert; Zipfel, Peter F.; Dogan, Ahmet; Smith, Richard J. H.

    2009-01-01

    Dense Deposit Disease (DDD), or membranoproliferative glomerulonephritis type II, is a rare renal disease characterized by dense deposits in the mesangium and along the glomerular basement membranes that can be seen by electron microscopy. Although these deposits contain complement factor C3, as determined by immunofluorescence microscopy, their precise composition remains unknown. To address this question, we used mass spectrometry to identify the proteins in laser microdissected glomeruli isolated from paraffin-embedded tissue of eight confirmed cases of DDD. Compared to glomeruli from five control patients, we found that all of the glomeruli from patients with DDD contain components of the alternative pathway and terminal complement complex. Factor C9 was uniformly present as well as the two fluid-phase regulators of terminal complement complex clusterin and vitronectin. In contrast, in nine patients with immune complex–mediated membranoproliferative glomerulonephritis, glomerular samples contained mainly immunoglobulins and complement factors C3 and C4. Our study shows that in addition to fluid-phase dysregulation of the alternative pathway, soluble components of the terminal complement complex contribute to glomerular lesions found in DDD. PMID:19177158

  6. Promotion of Cyclic Electron Transport Around Photosystem I with the Development of C4 Photosynthesis.

    PubMed

    Munekage, Yuri Nakajima; Taniguchi, Yukimi Y

    2016-05-01

    C4 photosynthesis is present in approximately 7,500 species classified into 19 families, including monocots and eudicots. In the majority of documented cases, a two-celled CO2-concentrating system that uses a metabolic cycle of four-carbon compounds is employed. C4 photosynthesis repeatedly evolved from C3 photosynthesis, possibly driven by the survival advantages it bestows in the hot, often dry, and nutrient-poor soils of the tropics and subtropics. The development of the C4 metabolic cycle greatly increased the ATP demand in chloroplasts during the evolution of malic enzyme-type C4 photosynthesis, and the additional ATP required for C4 metabolism may be produced by the cyclic electron transport around PSI. Recent studies have revealed the nature of cyclic electron transport and the elevation of its components during C4 evolution. In this review, we discuss the energy requirements of C3 and C4 photosynthesis, the current model of cyclic electron transport around PSI and how cyclic electron transport is promoted during C4 evolution using studies on the genus Flaveria, which contains a number of closely related C3, C4 and C3-C4 intermediate species.

  7. Phylogenomics of C(4) photosynthesis in sedges (Cyperaceae): multiple appearances and genetic convergence.

    PubMed

    Besnard, Guillaume; Muasya, A Muthama; Russier, Flavien; Roalson, Eric H; Salamin, Nicolas; Christin, Pascal-Antoine

    2009-08-01

    C(4) photosynthesis is an adaptive trait conferring an advantage in warm and open habitats. It originated multiple times and is currently reported in 18 plant families. It has been recently shown that phosphoenolpyruvate carboxylase (PEPC), a key enzyme of the C(4) pathway, evolved through numerous independent but convergent genetic changes in grasses (Poaceae). To compare the genetics of multiple C(4) origins on a broader scale, we reconstructed the evolutionary history of the C(4) pathway in sedges (Cyperaceae), the second most species-rich C(4) family. A sedge phylogeny based on two plastome genes (rbcL and ndhF) has previously identified six fully C(4) clades. Here, a relaxed molecular clock was used to calibrate this tree and showed that the first C(4) acquisition occurred in this family between 19.6 and 10.1 Ma. According to analyses of PEPC-encoding genes (ppc), at least five distinct C(4) origins are present in sedges. Two C(4) Eleocharis species, which were unrelated in the plastid phylogeny, acquired their C(4)-specific PEPC genes from a single source, probably through reticulate evolution or a horizontal transfer event. Acquisitions of C(4) PEPC in sedges have been driven by positive selection on at least 16 codons (3.5% of the studied gene segment). These sites underwent parallel genetic changes across the five sedge C(4) origins. Five of these sites underwent identical changes also in grass and eudicot C(4) lineages, indicating that genetic convergence is most important within families but that identical genetic changes occurred even among distantly related taxa. These lines of evidence give new insights into the constraints that govern molecular evolution.

  8. Language and Theory of Mind in Autism Spectrum Disorder: The Relationship between Complement Syntax and False Belief Task Performance

    ERIC Educational Resources Information Center

    Lind, Sophie E.; Bowler, Dermot M.

    2009-01-01

    This study aimed to test the hypothesis that children with autism spectrum disorder (ASD) use their knowledge of complement syntax as a means of "hacking out" solutions to false belief tasks, despite lacking a representational theory of mind (ToM). Participants completed a "memory for complements" task, a measure of receptive vocabulary, and…

  9. Etching of porous and solid SiO2 in Ar /c-C4F8, O2/c-C4F8 and Ar /O2/c-C4F8 plasmas

    NASA Astrophysics Data System (ADS)

    Sankaran, Arvind; Kushner, Mark J.

    2005-01-01

    C-C4F8-based plasmas are used for selective etching of high aspect ratio (HAR) trenches in SiO2 and other dielectrics for microelectronics fabrication. Additives such as Ar and O2 are often used to optimize the process. Understanding the fundamentals of these processes is critical to extending technologies developed for solid SiO2 to porous SiO2, as used in low-dielectric constant insulators. To investigate these issues, reaction mechanisms developed for etching of solid and porous SiO2 in fluorocarbon plasmas and for etching of organic polymers in O2 plasmas have been incorporated into a feature profile model capable of addressing two-phase porous materials. The reaction mechanism was validated by comparison to experiments for blanket etching of solid and porous SiO2 in Ar /c-C4F8 and O2/c-C4F8 plasmas using inductively coupled plasma reactors. We found that the blanket etch rates of both solid and porous SiO2 had maxima as a function of Ar and O2 addition to c-C4F8 at mole fractions corresponding to an optimum thickness of the overlying polymer layer. Larger Ar and O2 additions were required to optimize the etch rate for porous SiO2. Whereas etch stops occurred during etching of HAR features in solid and porous SiO2 using pure c-C4F8 plasmas, Ar and O2 addition facilitated etching by reducing the polymer thickness, though with some loss of critical dimensions. Mixtures of Ar /O2/c-C4F8 can be used to manage this tradeoff.

  10. Killing of Gyrodactylus salaris (Platyhelminthes, Monogenea) mediated by host complement.

    PubMed

    Harris, P D; Soleng, A; Bakke, T A

    1998-08-01

    Gyrodactylus salaris, an important pathogen of Atlantic salmon Salmo salar, has been shown to be highly sensitive to factors in host serum and mucus, being killed rapidly (50% within 1 h) by serum at a dilution of 1:200. The time needed for killing was inversely proportional to serum concentration. Similar effects were noted using host mucus, which contained approximately 1/20th of the anti-Gyrodactylus activity of serum. Serum activity was abolished completely by heating at 45 degrees C for 30 min, and by addition of EDTA, but not by EGTA + 1 mM magnesium ions. Activity was not dependent on whether the serum was from infected or naive fishes, nor was it species specific. Attempts to pre-coat parasites in salmon anti-Gyrodactylus antibodies also failed to enhance the activity of fresh serum. These observations suggest that killing is due to the complement system of the host, acting via the alternate pathway. G. salaris appears to be exceptionally sensitive to complement, being killed at concentrations which could be experienced in vivo. The role of complement in the protection of fishes against gyrodactylid infection therefore deserves further investigation.

  11. Complement in therapy and disease: Regulating the complement system with antibody-based therapeutics.

    PubMed

    Melis, Joost P M; Strumane, Kristin; Ruuls, Sigrid R; Beurskens, Frank J; Schuurman, Janine; Parren, Paul W H I

    2015-10-01

    Complement is recognized as a key player in a wide range of normal as well as disease-related immune, developmental and homeostatic processes. Knowledge of complement components, structures, interactions, and cross-talk with other biological systems continues to grow and this leads to novel treatments for cancer, infectious, autoimmune- or age-related diseases as well as for preventing transplantation rejection. Antibodies are superbly suited to be developed into therapeutics with appropriate complement stimulatory or inhibitory activity. Here we review the design, development and future of antibody-based drugs that enhance or dampen the complement system.

  12. A Metalloproteinase Mirolysin of Tannerella forsythia Inhibits All Pathways of the Complement System.

    PubMed

    Jusko, Monika; Potempa, Jan; Mizgalska, Danuta; Bielecka, Ewa; Ksiazek, Miroslaw; Riesbeck, Kristian; Garred, Peter; Eick, Sigrun; Blom, Anna M

    2015-09-01

    Recent reports focusing on virulence factors of periodontal pathogens implicated proteinases as major determinants of remarkable pathogenicity of these species, with special emphasis on their capacity to modulate complement activity. In particular, bacteria-mediated cleavage of C5 and subsequent release of C5a seems to be an important phenomenon in the manipulation of the local inflammatory response in periodontitis. In this study, we present mirolysin, a novel metalloproteinase secreted by Tannerella forsythia, a well-recognized pathogen strongly associated with periodontitis. Mirolysin exhibited a strong effect on all complement pathways. It inhibited the classical and lectin complement pathways due to efficient degradation of mannose-binding lectin, ficolin-2, ficolin-3, and C4, whereas inhibition of the alternative pathway was caused by degradation of C5. This specificity toward complement largely resembled the activity of a previously characterized metalloproteinase of T. forsythia, karilysin. Interestingly, mirolysin released the biologically active C5a peptide in human plasma and induced migration of neutrophils. Importantly, we demonstrated that combination of mirolysin with karilysin, as well as a cysteine proteinase of another periodontal pathogen, Prevotella intermedia, resulted in a strong synergistic effect on complement. Furthermore, mutant strains of T. forsythia, devoid of either mirolysin or karilysin, showed diminished survival in human serum, providing further evidence for the synergistic inactivation of complement by these metalloproteinases. Taken together, our findings on interactions of mirolysin with complement significantly add to the understanding of immune evasion strategies of T. forsythia and expand the knowledge on molecular mechanisms driving pathogenic events in the infected periodontium.

  13. Comparative studies of C3 and C4 Atriplex hybrids in the genomics era: physiological assessments.

    PubMed

    Oakley, Jason C; Sultmanis, Stefanie; Stinson, Corey R; Sage, Tammy L; Sage, Rowan F

    2014-07-01

    We crossed the C3 species Atriplex prostrata with the C4 species Atriplex rosea to produce F1 and F2 hybrids. All hybrids exhibited C3-like δ(13)C values, and had reduced rates of net CO2 assimilation compared with A. prostrata. The activities of the major C4 cycle enzymes PEP carboxylase, NAD-malic enzyme, and pyruvate-Pi dikinase in the hybrids were at most 36% of the C4 values. These results demonstrate the C4 metabolic cycle was disrupted in the hybrids. Photosynthetic CO2 compensation points (Г) of the hybrids were generally midway between the C3 and C4 values, and in most hybrids were accompanied by low, C3-like activities in one or more of the major C4 cycle enzymes. This supports the possibility that most hybrids use a photorespiratory glycine shuttle to concentrate CO2 into the bundle sheath cells. One hybrid exhibited a C4-like Г of 4 µmol mol(-1), indicating engagement of a C4 metabolic cycle. Consistently, this hybrid had elevated activities of all measured C4 cycle enzymes relative to the C3 parent; however, C3-like carbon isotope ratios indicate the low Г is mainly due to a photorespiratory glycine shuttle. The anatomy of the hybrids resembled that of C3-C4 intermediate species using a glycine shuttle to concentrate CO2 in the bundle sheath, and is further evidence that this physiology is the predominant, default condition of the F2 hybrids. Progeny of these hybrids should further segregate C3 and C4 traits and in doing so assist in the discovery of C4 genes using high-throughput methods of the genomics era.

  14. Comparative studies of C3 and C4 Atriplex hybrids in the genomics era: physiological assessments

    PubMed Central

    Oakley, Jason C.; Sultmanis, Stefanie; Stinson, Corey R.; Sage, Tammy L.; Sage, Rowan F.

    2014-01-01

    We crossed the C3 species Atriplex prostrata with the C4 species Atriplex rosea to produce F1 and F2 hybrids. All hybrids exhibited C3-like δ13C values, and had reduced rates of net CO2 assimilation compared with A. prostrata. The activities of the major C4 cycle enzymes PEP carboxylase, NAD-malic enzyme, and pyruvate-Pi dikinase in the hybrids were at most 36% of the C4 values. These results demonstrate the C4 metabolic cycle was disrupted in the hybrids. Photosynthetic CO2 compensation points (Г) of the hybrids were generally midway between the C3 and C4 values, and in most hybrids were accompanied by low, C3-like activities in one or more of the major C4 cycle enzymes. This supports the possibility that most hybrids use a photorespiratory glycine shuttle to concentrate CO2 into the bundle sheath cells. One hybrid exhibited a C4-like Г of 4 µmol mol–1, indicating engagement of a C4 metabolic cycle. Consistently, this hybrid had elevated activities of all measured C4 cycle enzymes relative to the C3 parent; however, C3-like carbon isotope ratios indicate the low Г is mainly due to a photorespiratory glycine shuttle. The anatomy of the hybrids resembled that of C3-C4 intermediate species using a glycine shuttle to concentrate CO2 in the bundle sheath, and is further evidence that this physiology is the predominant, default condition of the F2 hybrids. Progeny of these hybrids should further segregate C3 and C4 traits and in doing so assist in the discovery of C4 genes using high-throughput methods of the genomics era. PMID:24675672

  15. Hydrogen isotopic differences between C3 and C4 land plant lipids: consequences of compartmentation in C4 photosynthetic chemistry and C3 photorespiration.

    PubMed

    Zhou, Youping; Grice, Kliti; Stuart-Williams, Hilary; Hocart, Charles H; Gessler, Arthur; Farquhar, Graham D

    2016-12-01

    The (2) H/(1) H ratio of carbon-bound H in biolipids holds potential for probing plant lipid biosynthesis and metabolism. The biochemical mechanism underlying the isotopic differences between lipids from C3 and C4 plants is still poorly understood. GC-pyrolysis-IRMS (gas chromatography-pyrolysis-isotope ratio mass spectrometry) measurement of the (2) H/(1) H ratio of leaf lipids from controlled and field grown plants indicates that the biochemical isotopic fractionation (ε(2) Hlipid_biochem ) differed between C3 and C4 plants in a pathway-dependent manner: ε(2) HC4  > ε(2) HC3 for the acetogenic pathway, ε(2) HC4  < ε(2) HC3 for the mevalonic acid pathway and the 1-deoxy-D-xylulose 5-phosphate pathway across all species examined. It is proposed that compartmentation of photosynthetic CO2 fixation into C4 mesophyll (M) and bundle sheath (BS) cells and suppression of photorespiration in C4 M and BS cells both result in C4 M chloroplastic pyruvate - the precursor for acetogenic pathway - being more depleted in (2) H relative to pyruvate in C3 cells. In addition, compartmentation in C4 plants also results in (i) the transferable H of NADPH being enriched in (2) H in C4 M chloroplasts compared with that in C3 chloroplasts for the 1-deoxy-D-xylulose 5-phosphate pathway pathway and (ii) pyruvate relatively (2) H-enriched being used for the mevalonic acid pathway in the cytosol of BS cells in comparison with that in C3 cells.

  16. Inhibition of Complement Retards Ankylosing Spondylitis Progression

    PubMed Central

    Yang, Chaoqun; Ding, Peipei; Wang, Qingkai; Zhang, Long; Zhang, Xin; Zhao, Jianquan; Xu, Enjie; Wang, Na; Chen, Jianfeng; Yang, Guang; Hu, Weiguo; Zhou, Xuhui

    2016-01-01

    Ankylosing spondylitis (AS) is a chronic axial spondyloarthritis (SpA) resulting in back pain and progressive spinal ankyloses. Currently, there are no effective therapeutics targeting AS largely due to elusive pathogenesis mechanisms, even as potential candidates such as HLA-B27 autoantigen have been identified. Herein, we employed a proteoglycan (PG)-induced AS mouse model together with clinical specimens, and found that the complement system was substantially activated in the spinal bone marrow, accompanied by a remarkable proportion alteration of neutrophils and macrophage in bone marrow and spleen, and by the significant increase of TGF-β1 in serum. The combined treatment with a bacteria-derived complement inhibitor Efb-C (C-terminal of extracellular fibrinogen-binding protein of Staphylococcus aureus) remarkably retarded the progression of mouse AS by reducing osteoblast differentiation. Furthermore, we demonstrated that two important modulators involved in AS disease, TGF-β1 and RANKL, were elevated upon in vitro complement attack in osteoblast and/or osteoclast cells. These findings further unravel that complement activation is closely related with the pathogenesis of AS, and suggest that complement inhibition may hold great potential for AS therapy. PMID:27698377

  17. Shared origins of a key enzyme during the evolution of C4 and CAM metabolism

    PubMed Central

    Christin, Pascal-Antoine; Arakaki, Monica; Osborne, Colin P.; Bräutigam, Andrea; Sage, Rowan F.; Hibberd, Julian M.; Kelly, Steven; Covshoff, Sarah; Wong, Gane Ka-Shu; Hancock, Lillian; Edwards, Erika J.

    2014-01-01

    CAM and C4 photosynthesis are two key plant adaptations that have evolved independently multiple times, and are especially prevalent in particular groups of plants, including the Caryophyllales. We investigate the origin of photosynthetic PEPC, a key enzyme of both the CAM and C4 pathways. We combine phylogenetic analyses of genes encoding PEPC with analyses of RNA sequence data of Portulaca, the only plants known to perform both CAM and C4 photosynthesis. Three distinct gene lineages encoding PEPC exist in eudicots (namely ppc-1E1, ppc-1E2 and ppc-2), one of which (ppc-1E1) was recurrently recruited for use in both CAM and C4 photosynthesis within the Caryophyllales. This gene is present in multiple copies in the cacti and relatives, including Portulaca. The PEPC involved in the CAM and C4 cycles of Portulaca are encoded by closely related yet distinct genes. The CAM-specific gene is similar to genes from related CAM taxa, suggesting that CAM has evolved before C4 in these species. The similar origin of PEPC and other genes involved in the CAM and C4 cycles highlights the shared early steps of evolutionary trajectories towards CAM and C4, which probably diverged irreversibly only during the optimization of CAM and C4 phenotypes. PMID:24638902

  18. Identification of a chitinase-producing bacterium C4 and histopathologic study on locusts.

    PubMed

    Yong, Tao; Zhangfu, Long; Jing, Xie; Hong, Jin; Hongyan, Ran; Ke, Tao; Shaorong, Ge; Kun, Liu; Shigui, Liu

    2005-02-01

    In order to develop the potential of chitinase-producing micro-organisms as biocontrol agents for insect pests, five chitinase-producing bacterial strains (C1, C2, C3, C4 and C5) previously isolated from soil samples were chosen to infect grassland locusts. The data showed that the mortality rate of locusts fed with strain C4 was significantly higher than that of other groups, and its pathogenicity was confirmed by Koch's law. Midgut tissues of locusts infected with C4 were examined with a light microscope. Apparent histopathologic changes in midgut cells partly explained the pathogenesis of locusts. Therefore, strain C4 was considered to be a potential biocontrol agent. To determine the taxonomic position of C4, physiological and biochemical characteristics were determined and molecular identification was performed. The 16S rDNA gene of C4 was amplified, cloned and sequenced. Comparative sequence analysis demonstrated that C4 corresponded to the genera Sanguibacter, Oerskovia and Cellulomonas. On the basis of phenotypic characterization and sequence similarity analysis, strain C4 was more closely related to the genus Sanguibacter. This chitinase-producing strain C4, which closely corresponds to the species of the genus Sanguibacter and is pathogenic to locusts, is here reported for the first time.

  19. Are changes in sulfate assimilation pathway needed for evolution of C4 photosynthesis?

    PubMed

    Weckopp, Silke C; Kopriva, Stanislav

    2014-01-01

    C4 photosynthesis characteristically features a cell-specific localization of enzymes involved in CO2 assimilation in bundle sheath cells (BSC) or mesophyll cells. Interestingly, enzymes of sulfur assimilation are also specifically present in BSC of maize and many other C4 species. This localization, however, could not be confirmed in C4 species of the genus Flaveria. It was, therefore, concluded that the bundle sheath localization of sulfate assimilation occurs only in C4 monocots. However, recently the sulfate assimilation pathway was found coordinately enriched in BSC of Arabidopsis, opening new questions about the significance of such cell-specific localization of the pathway. In addition, next generation sequencing revealed expression gradients of many genes from C3 to C4 species and mathematical modeling proposed a sequence of adaptations during the evolutionary path from C3 to C4. Indeed, such gradient, with higher expression of genes for sulfate reduction in C4 species, has been observed within the genus Flaveria. These new tools provide the basis for reexamining the intriguing question of compartmentalization of sulfur assimilation. Therefore, this review summarizes the findings on spatial separation of sulfur assimilation in C4 plants and Arabidopsis, assesses the information on sulfur assimilation provided by the recent transcriptomics data and discusses their possible impact on understanding this interesting feature of plant sulfur metabolism to find out whether changes in sulfate assimilation are part of a general evolutionary trajectory toward C4 photosynthesis.

  20. Genetic enablers underlying the clustered evolutionary origins of C4 photosynthesis in angiosperms.

    PubMed

    Christin, Pascal-Antoine; Arakaki, Mónica; Osborne, Colin P; Edwards, Erika J

    2015-04-01

    The evolutionary accessibility of novel adaptations varies among lineages, depending in part on the genetic elements present in each group. However, the factors determining the evolutionary potential of closely related genes remain largely unknown. In plants, CO2-concentrating mechanisms such as C4 and crassulacean acid metabolism (CAM) photosynthesis have evolved numerous times in distantly related groups of species, and constitute excellent systems to study constraints and enablers of evolution. It has been previously shown for multiple proteins that grasses preferentially co-opted the same gene lineage for C4 photosynthesis, when multiple copies were present. In this work, we use comparative transcriptomics to show that this bias also exists within Caryophyllales, a distantly related group with multiple C4 origins. However, the bias is not the same as in grasses and, when all angiosperms are considered jointly, the number of distinct gene lineages co-opted is not smaller than that expected by chance. These results show that most gene lineages present in the common ancestor of monocots and eudicots produced gene descendants that were recruited into C4 photosynthesis, but that C4-suitability changed during the diversification of angiosperms. When selective pressures drove C4 evolution, some copies were preferentially co-opted, probably because they already possessed C4-like expression patterns. However, the identity of these C4-suitable genes varies among clades of angiosperms, and C4 phenotypes in distant angiosperm groups thus represent genuinely independent realizations, based on different genetic precursors.

  1. The Road to C4 Photosynthesis: Evolution of a Complex Trait via Intermediary States.

    PubMed

    Schlüter, Urte; Weber, Andreas P M

    2016-05-01

    C4 photosynthesis enables high photosynthetic energy conversion efficiency as well as high nitrogen and water use efficiencies. Given the multitude of biochemical, structural and molecular changes in comparison with C3 photosynthesis, it appears unlikely that such a complex trait would evolve in a single step. C4 photosynthesis is therefore believed to have evolved from the ancestral C3 state via intermediary stages. Consequently, the identification and detailed characterization of plant species representing transitory states between C3 and C4 is important for the reconstruction of the sequence of evolutionary events, especially since C4 evolution occurred in very different phylogenetic backgrounds. There is also significant interest in engineering of C4 or at least C4-like elements into C3 crop plants. A detailed and mechanistic understanding of C3-C4 intermediates is likely to provide guidance for the experimental design of such approaches. Here we provide an overview on the most relevant results obtained on C3-C4 intermediates to date. Recent knowledge gains in this field will be described in more detail. We thereby concentrate especially on biochemical and physiological work. Finally, we will provide a perspective and outlook on the continued importance of research on C3-C4 intermediates.

  2. Expression of complement components and regulators by different subtypes of bone marrow-derived macrophages.

    PubMed

    Luo, Chang; Chen, Mei; Madden, Angelina; Xu, Heping

    2012-08-01

    Under inflammatory conditions, macrophages can differentiate into different functional subtypes. We show that bone marrow-derived macrophages constitutively express different levels of various complement-related genes. The relative expression levels are C1qb > Crry > CFH > C3 > C1r > CFB > DAF1 > CD59a > C2 > C1INH > C1s > C4. Upon activation, the expression of C1r, C1s, C3, C2, CFB, and C1INH was up-regulated, and CFH, CD59a, and DAF1, down-regulated in M1 (induced by interferon-γ + lipopolysaccharides (LPS)) and M2b (induced by immune complex + LPS) macrophages. The expression of C4 and CFH was slightly up-regulated in interleukin (IL)-10-induced M2c macrophages. Complement gene expression in IL-4-induced M2a macrophages was weakly down-regulated as compared to resting M0 macrophages. Higher levels of C3, C1INH, and CFB but lower levels of CFH expression in M1 and M2b macrophage suggests that they may be involved in the alternative pathway of complement activation during inflammation.

  3. Complete Makeover

    NASA Technical Reports Server (NTRS)

    2004-01-01

    [figure removed for brevity, see original site]

    Released July 23, 2004 The atmosphere of Mars is a dynamic system. Water-ice clouds, fog, and hazes can make imaging the surface from space difficult. Dust storms can grow from local disturbances to global sizes, through which imaging is impossible. Seasonal temperature changes are the usual drivers in cloud and dust storm development and growth.

    Eons of atmospheric dust storm activity has left its mark on the surface of Mars. Dust carried aloft by the wind has settled out on every available surface; sand dunes have been created and moved by centuries of wind; and the effect of continual sand-blasting has modified many regions of Mars, creating yardangs and other unusual surface forms.

    We finish our look at Mars's dynamic atmosphere with an image of the surface that has been completely modified by the wind. Even the small ridges that remain have been ground down to a cliff-face with a 'tail' of eroded material. The crosshatching shows that the wind regime has remained mainly E/W to ENE/WSW.

    Image information: VIS instrument. Latitude 8.9, Longitude 221 East (139 West). 19 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip

  4. State of Büchi Complementation

    NASA Astrophysics Data System (ADS)

    Tsai, Ming-Hsien; Fogarty, Seth; Vardi, Moshe Y.; Tsay, Yih-Kuen

    Büchi complementation has been studied for five decades since the formalism was introduced in 1960. Known complementation constructions can be classified into Ramsey-based, determinization-based, rank-based, and slice-based approaches. For the performance of these approaches, there have been several complexity analyses but very few experimental results. What especially lacks is a comparative experiment on all the four approaches to see how they perform in practice. In this paper, we review the state of Büchi complementation, propose several optimization heuristics, and perform comparative experimentation on the four approaches. The experimental results show that the determinization-based Safra-Piterman construction outperforms the other three and our heuristics substantially improve the Safra-Piterman construction and the slice-based construction.

  5. Applying Complement Therapeutics to Rare Diseases

    PubMed Central

    Reis, Edimara S.; Mastellos, Dimitrios C.; Yancopoulou, Despina; Risitano, Antonio M.; Ricklin, Daniel; Lambris, John D.

    2015-01-01

    Around 350 million people worldwide suffer from rare diseases. These may have a genetic, infectious, or autoimmune basis, and several include an inflammatory component. Launching of effective treatments can be very challenging when there is a low disease prevalence and limited scientific insights into the disease mechanisms. As a key trigger of inflammatory processes, complement has been associated with a variety of diseases and has become an attractive therapeutic target for conditions involving inflammation. In view of the clinical experience acquired with drugs licensed for the treatment of rare diseases such as hereditary angioedema and paroxysmal nocturnal hemoglobinuria, growing evidence supports the safety and efficacy of complement therapeutics in restoring immune balance and preventing aggravation of clinical outcomes. This review provides an overview of the candidates currently in the pharmaceutical pipeline with potential to treat orphan diseases and discusses the molecular mechanisms triggered by complement involved with the disease pathogenesis. PMID:26341313

  6. Applying complement therapeutics to rare diseases.

    PubMed

    Reis, Edimara S; Mastellos, Dimitrios C; Yancopoulou, Despina; Risitano, Antonio M; Ricklin, Daniel; Lambris, John D

    2015-12-01

    Around 350 million people worldwide suffer from rare diseases. These may have a genetic, infectious, or autoimmune basis, and several include an inflammatory component. Launching of effective treatments can be very challenging when there is a low disease prevalence and limited scientific insights into the disease mechanisms. As a key trigger of inflammatory processes, complement has been associated with a variety of diseases and has become an attractive therapeutic target for conditions involving inflammation. In view of the clinical experience acquired with drugs licensed for the treatment of rare diseases such as hereditary angioedema and paroxysmal nocturnal hemoglobinuria, growing evidence supports the safety and efficacy of complement therapeutics in restoring immune balance and preventing aggravation of clinical outcomes. This review provides an overview of the candidates currently in the pharmaceutical pipeline with potential to treat orphan diseases and discusses the molecular mechanisms triggered by complement involved with the disease pathogenesis.

  7. The extracellular RNA complement of Escherichia coli

    PubMed Central

    Ghosal, Anubrata; Upadhyaya, Bimal Babu; Fritz, Joëlle V; Heintz-Buschart, Anna; Desai, Mahesh S; Yusuf, Dilmurat; Huang, David; Baumuratov, Aidos; Wang, Kai; Galas, David; Wilmes, Paul

    2015-01-01

    The secretion of biomolecules into the extracellular milieu is a common and well-conserved phenomenon in biology. In bacteria, secreted biomolecules are not only involved in intra-species communication but they also play roles in inter-kingdom exchanges and pathogenicity. To date, released products, such as small molecules, DNA, peptides, and proteins, have been well studied in bacteria. However, the bacterial extracellular RNA complement has so far not been comprehensively characterized. Here, we have analyzed, using a combination of physical characterization and high-throughput sequencing, the extracellular RNA complement of both outer membrane vesicle (OMV)-associated and OMV-free RNA of the enteric Gram-negative model bacterium Escherichia coli K-12 substrain MG1655 and have compared it to its intracellular RNA complement. Our results demonstrate that a large part of the extracellular RNA complement is in the size range between 15 and 40 nucleotides and is derived from specific intracellular RNAs. Furthermore, RNA is associated with OMVs and the relative abundances of RNA biotypes in the intracellular, OMV and OMV-free fractions are distinct. Apart from rRNA fragments, a significant portion of the extracellular RNA complement is composed of specific cleavage products of functionally important structural noncoding RNAs, including tRNAs, 4.5S RNA, 6S RNA, and tmRNA. In addition, the extracellular RNA pool includes RNA biotypes from cryptic prophages, intergenic, and coding regions, of which some are so far uncharacterised, for example, transcripts mapping to the fimA-fimL and ves-spy intergenic regions. Our study provides the first detailed characterization of the extracellular RNA complement of the enteric model bacterium E. coli. Analogous to findings in eukaryotes, our results suggest the selective export of specific RNA biotypes by E. coli, which in turn indicates a potential role for extracellular bacterial RNAs in intercellular communication. PMID:25611733

  8. Vaccinia virus protein C4 inhibits NF-κB activation and promotes virus virulence

    PubMed Central

    Ember, Stuart W. J.; Ren, Hongwei; Ferguson, Brian J.

    2012-01-01

    Vaccinia virus (VACV) strain Western Reserve protein C4 has been characterized and its function and contribution to virus virulence assessed. Bioinformatic analysis showed that C4 is conserved in six orthopoxvirus species and shares 43 % amino acid identity with VACV protein C16, a known virulence factor. A recombinant VACV expressing a C-terminally tagged version of C4 showed that, like C16, this 37 kDa protein is expressed early during infection and localizes to both the cytoplasm and the nucleus. Functional assays using a firefly luciferase reporter plasmid under the control of a nuclear factor kappa B (NF-κB)-dependent promoter demonstrated that C4 inhibits NF-κB activation at, or downstream of, the inhibitor of kappa kinase (IKK) complex. Consistent with this, C4 inhibited interleukin-1β-induced translocation of p65 into the nucleus. A VACV lacking the C4L gene (vΔC4) showed no significant differences from wild-type virus in growth kinetics or spread in cell culture, but had reduced virulence in a murine intranasal model of infection. vΔC4-infected mice exhibited fewer symptoms, lost less weight and recovered 7 days earlier than animals infected with control viruses expressing C4. Furthermore, bronchoalveolar lavage fluid from vΔC4-infected mice had increased cell numbers at day 5 post-infection, which correlated with reduced lung virus titres from this time onward. C4 represents the ninth VACV protein to inhibit NF-κB activation and remarkably, in every case examined, loss of each protein individually caused an alteration in virus virulence, despite the presence of other NF-κB inhibitors. PMID:22791606

  9. Presentation and Outcomes of C4d-Negative Antibody-Mediated Rejection After Kidney Transplantation.

    PubMed

    Orandi, B J; Alachkar, N; Kraus, E S; Naqvi, F; Lonze, B E; Lees, L; Van Arendonk, K J; Wickliffe, C; Bagnasco, S M; Zachary, A A; Segev, D L; Montgomery, R A

    2016-01-01

    The updated Banff classification allows for the diagnosis of antibody-mediated rejection (AMR) in the absence of peritubular capillary C4d staining. Our objective was to quantify allograft loss risk in patients with consistently C4d-negative AMR (n = 51) compared with C4d-positive AMR patients (n = 156) and matched control subjects without AMR. All first-year posttransplant biopsy results from January 2004 through June 2014 were reviewed and correlated with the presence of donor-specific antibody (DSA). C4d-negative AMR patients were not different from C4d-positive AMR patients on any baseline characteristics, including immunologic risk factors (panel reactive antibody, prior transplant, HLA mismatch, donor type, DSA class, and anti-HLA/ABO-incompatibility). C4d-positive AMR patients were significantly more likely to have a clinical presentation (85.3% vs. 54.9%, p < 0.001), and those patients presented substantially earlier posttransplantation (median 14 [interquartile range 8-32] days vs. 46 [interquartile range 20-191], p < 0.001) and were three times more common (7.8% vs 2.5%). One- and 2-year post-AMR-defining biopsy graft survival in C4d-negative AMR patients was 93.4% and 90.2% versus 86.8% and 82.6% in C4d-positive AMR patients, respectively (p = 0.4). C4d-negative AMR was associated with a 2.56-fold (95% confidence interval, 1.08-6.05, p = 0.033) increased risk of graft loss compared with AMR-free matched controls. No clinical characteristics were identified that reliably distinguished C4d-negative from C4d-positive AMR. However, both phenotypes are associated with increased graft loss and thus warrant consideration for intervention.

  10. Multiple activities of LigB potentiate virulence of Leptospira interrogans: inhibition of alternative and classical pathways of complement.

    PubMed

    Choy, Henry A

    2012-01-01

    Microbial pathogens acquire the immediate imperative to avoid or counteract the formidable defense of innate immunity as soon as they overcome the initial physical barriers of the host. Many have adopted the strategy of directly disrupting the complement system through the capture of its components, using proteins on the pathogen's surface. In leptospirosis, pathogenic Leptospira spp. are resistant to complement-mediated killing, in contrast to the highly vulnerable non-pathogenic strains. Pathogenic L. interrogans uses LenA/LfhA and LcpA to respectively sequester and commandeer the function of two regulators, factor H and C4BP, which in turn bind C3b or C4b to interrupt the alternative or classical pathways of complement activation. LigB, another surface-proximal protein originally characterized as an adhesin binding multiple host proteins, has other activities suggesting its importance early in infection, including binding extracellular matrix, plasma, and cutaneous repair proteins and inhibiting hemostasis. In this study, we used a recent model of ectopic expression of LigB in the saprophyte, L. biflexa, to test the hypothesis that LigB also interacts with complement proteins C3b and C4b to promote the virulence of L. interrogans. The surface expression of LigB partially rescued the non-pathogen from killing by 5% normal human serum, showing 1.3- to 48-fold greater survival 4 to 6 d following exposure to complement than cultures of the non-expressing parental strain. Recombinant LigB7'-12 comprising the LigB-specific immunoglobulin repeats binds directly to human complement proteins, C3b and C4b, with respective K(d)s of 43±26 nM and 69±18 nM. Repeats 9 to 11, previously shown to contain the binding domain for fibronectin and fibrinogen, are also important in LigB-complement interactions, which interfere with the alternative and classical pathways measured by complement-mediated hemolysis of erythrocytes. Thus, LigB is an adaptable interface for L. interrogans

  11. Identification of a third secondary carrier (DcuC) for anaerobic C4-dicarboxylate transport in Escherichia coli: roles of the three Dcu carriers in uptake and exchange.

    PubMed Central

    Zientz, E; Six, S; Unden, G

    1996-01-01

    In Escherichia coli, two carriers (DcuA and DcuB) for the transport of C4 dicarboxylates in anaerobic growth were known. Here a novel gene dcuC was identified encoding a secondary carrier (DcuC) for C4 dicarboxylates which is functional in anaerobic growth. The dcuC gene is located at min 14.1 of the E. coli map in the counterclockwise orientation. The dcuC gene combines two open reading frames found in other strains of E. coli K-12. The gene product (DcuC) is responsible for the transport of C4 dicarboxylates in DcuA-DcuB-deficient cells. The triple mutant (dcuA dcuB dcuC) is completely devoid of C4-dicarboxylate transport (exchange and uptake) during anaerobic growth, and the bacteria are no longer capable of growth by fumarate respiration. DcuC, however, is not required for C4-dicarboxylate uptake in aerobic growth. The dcuC gene encodes a putative protein of 461 amino acid residues with properties typical for secondary procaryotic carriers. DcuC shows sequence similarity to the two major anaerobic C4-dicarboxylate carriers DcuA and DcuB. Mutants producing only DcuA, DcuB, or DcuC were prepared. In the mutants, DcuA, DcuB, and DcuC were each able to operate in the exchange and uptake mode. PMID:8955408

  12. Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

    PubMed Central

    Ram, Sanjay; Lewis, Lisa A.; Rice, Peter A.

    2010-01-01

    Summary: The complement system comprises several fluid-phase and membrane-associated proteins. Under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as “nonself” in an attempt to minimize damage to bystander host cells. Membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes “tagged” with complement fragments. While this review focuses on the role of complement in infectious diseases, work over the past couple of decades has defined several important functions of complement distinct from that of combating infections. Activation of complement in the fluid phase can occur through the classical, lectin, or alternative pathway. Deficiencies of components of the classical pathway lead to the development of autoimmune disorders and predispose individuals to recurrent respiratory infections and infections caused by encapsulated organisms, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. While no individual with complete mannan-binding lectin (MBL) deficiency has been identified, low MBL levels have been linked to predisposition to, or severity of, several diseases. It appears that MBL may play an important role in children, who have a relatively immature adaptive immune response. C3 is the point at which all complement pathways converge, and complete deficiency of C3 invariably leads to severe infections, including those caused by meningococci and pneumococci. Deficiencies of the alternative and terminal complement pathways result in an almost exclusive predisposition to invasive meningococcal disease. The spleen plays an important role in antigen processing and the production of antibodies. Splenic macrophages are critical in clearing opsonized encapsulated bacteria (such as pneumococci, meningococci, and Escherichia coli

  13. Therapeutic complement inhibition in complement-mediated hemolytic anemias: Past, present and future.

    PubMed

    Risitano, Antonio M; Marotta, Serena

    2016-06-01

    The introduction in the clinic of anti-complement agents represented a major achievement which gave to physicians a novel etiologic treatment for different human diseases. Indeed, the first anti-complement agent eculizumab has changed the treatment paradigm of paroxysmal nocturnal hemoglobinuria (PNH), dramatically impacting its severe clinical course. In addition, eculizumab is the first agent approved for atypical Hemolytic Uremic Syndrome (aHUS), a life-threatening inherited thrombotic microangiopathy. Nevertheless, such remarkable milestone in medicine has brought to the fore additional challenges for the scientific community. Indeed, the list of complement-mediated anemias is not limited to PNH and aHUS, and other human diseases can be considered for anti-complement treatment. They include other thrombotic microangiopathies, as well as some antibody-mediated hemolytic anemias. Furthermore, more than ten years of experience with eculizumab led to a better understanding of the individual steps of the complement cascade involved in the pathophysiology of different human diseases. Based on this, new unmet clinical needs are emerging; a number of different strategies are currently under development to improve current anti-complement treatment, trying to address these specific clinical needs. They include: (i) alternative anti-C5 agents, which may improve the heaviness of eculizumab treatment; (ii) broad-spectrum anti-C3 agents, which may improve the efficacy of anti-C5 treatment by intercepting the complement cascade upstream (i.e., preventing C3-mediated extravascular hemolysis in PNH); (iii) targeted inhibitors of selective complement activating pathways, which may prevent early pathogenic events of specific human diseases (e.g., anti-classical pathway for antibody-mediated anemias, or anti-alternative pathway for PNH and aHUS). Here we briefly summarize the status of art of current and future complement inhibition for different complement-mediated anemias

  14. Inhibition of complement-mediated cytolysis by the terminal complement inhibitor of herpesvirus saimiri.

    PubMed

    Rother, R P; Rollins, S A; Fodor, W L; Albrecht, J C; Setter, E; Fleckenstein, B; Squinto, S P

    1994-02-01

    Herpesvirus saimiri (HVS) is a lymphotropic herpesvirus that induces T-cell transformation in vitro and causes lymphomas and leukemias in New World primates other than its natural host, the squirrel monkey. Nucleotide sequence analysis of the HVS genome revealed two open reading frames with significant homology to genes for human complement regulatory molecules. One of these genes encodes a predicted protein (designated HVSCD59) with 48% amino acid sequence identity to the human terminal complement regulatory protein CD59 (HuCD59). The CD59 homolog from squirrel monkey (SMCD59) was cloned, and the corresponding amino acid sequence showed 69% identity with HVSCD59. BALB/3T3 cells stably expressing HVSCD59, SMCD59, or HuCD59 were equally protected from complement-mediated lysis by human serum. However, only HVSCD59-expressing cells were effectively protected from complement-mediated lysis when challenged with rat serum, suggesting that HVSCD59 was less species restrictive. The complement regulatory activity of HVSCD59 and SMCD59 occurred after C3b deposition, indicating terminal complement inhibition. Treatment of BALB/3T3 stable transfectants with phosphatidylinositol-specific phospholipase C prior to complement attack decreased the complement regulatory function of HVSCD59, suggesting cell surface attachment via a glycosyl-phosphatidylinositol anchor. Cells expressing HVSCD59 effectively inhibited complement-mediated lysis by squirrel monkey serum in comparison with SMCD59-expressing cells. Finally HVSCD59-specific transcripts were detected in owl monkey cells permissive for lytic HVS replication but not in T cells transformed by HVS, which failed to produce virions. These data are the first to demonstrate a functional, virally encoded terminal complement inhibitor and suggest that HVSCD59 represents a humoral immune evasion mechanism supporting the lytic life cycle of HVS.

  15. Volumetric Properties of the Mixture Oxolan-2-one C4H6O2 + C4H10O Butan-1-ol (VMSD1511, LB4906_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Oxolan-2-one C4H6O2 + C4H10O Butan-1-ol (VMSD1511, LB4906_V)' providing data from direct measurement of low-pressure thermodynamic speed of sound at variable mole fraction and constant temperature, in the single-phase region(s).

  16. The role of photorespiration during the evolution of C4 photosynthesis in the genus Flaveria.

    PubMed

    Mallmann, Julia; Heckmann, David; Bräutigam, Andrea; Lercher, Martin J; Weber, Andreas P M; Westhoff, Peter; Gowik, Udo

    2014-06-16

    C4 photosynthesis represents a most remarkable case of convergent evolution of a complex trait, which includes the reprogramming of the expression patterns of thousands of genes. Anatomical, physiological, and phylogenetic and analyses as well as computational modeling indicate that the establishment of a photorespiratory carbon pump (termed C2 photosynthesis) is a prerequisite for the evolution of C4. However, a mechanistic model explaining the tight connection between the evolution of C4 and C2 photosynthesis is currently lacking. Here we address this question through comparative transcriptomic and biochemical analyses of closely related C3, C3-C4, and C4 species, combined with Flux Balance Analysis constrained through a mechanistic model of carbon fixation. We show that C2 photosynthesis creates a misbalance in nitrogen metabolism between bundle sheath and mesophyll cells. Rebalancing nitrogen metabolism requires anaplerotic reactions that resemble at least parts of a basic C4 cycle. Our findings thus show how C2 photosynthesis represents a pre-adaptation for the C4 system, where the evolution of the C2 system establishes important C4 components as a side effect.

  17. Cinnamate 4-Hydroxylase (C4H) genes from Leucaena leucocephala: a pulp yielding leguminous tree.

    PubMed

    Kumar, Santosh; Omer, Sumita; Patel, Krunal; Khan, Bashir M

    2013-02-01

    Leucaena leucocephala is a leguminous tree species accounting for one-fourth of raw material supplied to paper and pulp industry in India. Cinnamate 4-Hydroxylase (C4H, EC 1.14.13.11) is the second gene of phenylpropanoid pathway and a member of cytochrome P450 family. There is currently intense interest to alter or modify lignin content of L. leucocephala. Three highly similar C4H alleles of LlC4H1 gene were isolated and characterized. The alleles shared more than 98 % sequence identity at amino acid level to each other. Binding of partial promoter of another C4H gene LlC4H2, to varying amounts of crude nuclear proteins isolated from leaf and stem tissues of L. leucocephala formed two loose and one strong complex, respectively, suggesting that the abundance of proteins that bind with the partial C4H promoter is higher in stem tissue than in leaf tissue. Quantitative Real Time PCR study suggested that among tissues of same age, root tissues had highest level of C4H transcripts. Maximum transcript level was observed in 30 day old root tissue. Among the tissues investigated, C4H activity was highest in 60 day old root tissues. Tissue specific quantitative comparison of lignin from developing seedling stage to 1 year old tree stage indicated that Klason lignin increased in tissues with age.

  18. Variation in Quantum Yield for CO2 Uptake among C3 and C4 Plants 1

    PubMed Central

    Ehleringer, James; Pearcy, Robert W.

    1983-01-01

    The quantum yield for CO2 uptake was measured on a number of C3 and C4 monocot and dicot species. Under normal atmospheric conditions (330 microliters per liter CO2, 21% O2) and a leaf temperature of 30°C, the average quantum yields (moles CO2 per einstein) were as follows: 0.052 for C3 dicots, 0.053 for C3 grasses, 0.053 for NAD-malic enzyme type C4 dicots, 0.060 for NAD-malic enzyme type C4 grasses, 0.064 for phosphoenolpyruvate carboxykinase type C4 grasses, 0.061 for NADP-malic enzyme C4 dicots, and 0.065 for NADP-malic enzyme type C4 grasses. The quantum yield under normal atmospheric conditions was temperature dependent in C3 species, but apparently not in C4 species. Light and temperature conditions during growth appeared not to influence quantum yield. The significance of variation in the quantum yields of C4 plants was discussed in terms of CO2 leakage from the bundle sheath cells and suberization of apoplastic regions of the bundle sheath cells. PMID:16663257

  19. 26 CFR 1.381(c)(4)-1 - Method of accounting.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 4 2011-04-01 2011-04-01 false Method of accounting. 1.381(c)(4)-1 Section 1... TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.381(c)(4)-1 Method of accounting. (a... section 381(a) applies, an acquiring corporation shall use the same method of accounting used by...

  20. 26 CFR 1.381(c)(4)-1 - Method of accounting.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Method of accounting. 1.381(c)(4)-1 Section 1... TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.381(c)(4)-1 Method of accounting. (a... section 381(a) applies, an acquiring corporation shall use the same method of accounting used by...

  1. Elements required for an efficient NADP-malic enzyme type C4 photosynthesis.

    PubMed

    Wang, Yu; Long, Stephen P; Zhu, Xin-Guang

    2014-04-01

    C4 photosynthesis has higher light, nitrogen, and water use efficiencies than C3 photosynthesis. Although the basic anatomical, cellular, and biochemical features of C4 photosynthesis are well understood, the quantitative significance of each element of C4 photosynthesis to the high photosynthetic efficiency are not well defined. Here, we addressed this question by developing and using a systems model of C4 photosynthesis, which includes not only the Calvin-Benson cycle, starch synthesis, sucrose synthesis, C4 shuttle, and CO₂ leakage, but also photorespiration and metabolite transport between the bundle sheath cells and mesophyll cells. The model effectively simulated the CO₂ uptake rates, and the changes of metabolite concentrations under varied CO₂ and light levels. Analyses show that triose phosphate transport and CO₂ leakage can help maintain a high photosynthetic rate by balancing ATP and NADPH amounts in bundle sheath cells and mesophyll cells. Finally, we used the model to define the optimal enzyme properties and a blueprint for C4 engineering. As such, this model provides a theoretical framework for guiding C4 engineering and studying C4 photosynthesis in general.

  2. The role of photorespiration during the evolution of C4 photosynthesis in the genus Flaveria

    PubMed Central

    Mallmann, Julia; Heckmann, David; Bräutigam, Andrea; Lercher, Martin J; Weber, Andreas PM; Westhoff, Peter; Gowik, Udo

    2014-01-01

    C4 photosynthesis represents a most remarkable case of convergent evolution of a complex trait, which includes the reprogramming of the expression patterns of thousands of genes. Anatomical, physiological, and phylogenetic and analyses as well as computational modeling indicate that the establishment of a photorespiratory carbon pump (termed C2 photosynthesis) is a prerequisite for the evolution of C4. However, a mechanistic model explaining the tight connection between the evolution of C4 and C2 photosynthesis is currently lacking. Here we address this question through comparative transcriptomic and biochemical analyses of closely related C3, C3–C4, and C4 species, combined with Flux Balance Analysis constrained through a mechanistic model of carbon fixation. We show that C2 photosynthesis creates a misbalance in nitrogen metabolism between bundle sheath and mesophyll cells. Rebalancing nitrogen metabolism requires anaplerotic reactions that resemble at least parts of a basic C4 cycle. Our findings thus show how C2 photosynthesis represents a pre-adaptation for the C4 system, where the evolution of the C2 system establishes important C4 components as a side effect. DOI: http://dx.doi.org/10.7554/eLife.02478.001 PMID:24935935

  3. Germination Shifts of C3 and C4 Species under Simulated Global Warming Scenario

    PubMed Central

    Zhang, Hongxiang; Yu, Qiang; Huang, Yingxin; Zheng, Wei; Tian, Yu; Song, Yantao; Li, Guangdi; Zhou, Daowei

    2014-01-01

    Research efforts around the world have been increasingly devoted to investigating changes in C3 and C4 species' abundance or distribution with global warming, as they provide important insight into carbon fluxes and linked biogeochemical cycles. However, changes in the early life stage (e.g. germination) of C3 and C4 species in response to global warming, particularly with respect to asymmetric warming, have received less attention. We investigated germination percentage and rate of C3 and C4 species under asymmetric (+3/+6°C at day/night) and symmetric warming (+5/+5°C at day/night), simulated by alternating temperatures. A thermal time model was used to calculate germination base temperature and thermal time constant. Two additional alternating temperature regimes were used to test temperature metrics effect. The germination percentage and rate increased continuously for C4 species, but increased and then decreased with temperature for C3 species under both symmetric and asymmetric warming. Compared to asymmetric warming, symmetric warming significantly overestimated the speed of germination percentage change with temperature for C4 species. Among the temperature metrics (minimum, maximum, diurnal temperature range and average temperature), maximum temperature was most correlated with germination of C4 species. Our results indicate that global warming may favour germination of C4 species, at least for the C4 species studied in this work. The divergent effects of asymmetric and symmetric warming on plant germination also deserve more attention in future studies. PMID:25137138

  4. Germination shifts of C3 and C4 species under simulated global warming scenario.

    PubMed

    Zhang, Hongxiang; Yu, Qiang; Huang, Yingxin; Zheng, Wei; Tian, Yu; Song, Yantao; Li, Guangdi; Zhou, Daowei

    2014-01-01

    Research efforts around the world have been increasingly devoted to investigating changes in C3 and C4 species' abundance or distribution with global warming, as they provide important insight into carbon fluxes and linked biogeochemical cycles. However, changes in the early life stage (e.g. germination) of C3 and C4 species in response to global warming, particularly with respect to asymmetric warming, have received less attention. We investigated germination percentage and rate of C3 and C4 species under asymmetric (+3/+6°C at day/night) and symmetric warming (+5/+5°C at day/night), simulated by alternating temperatures. A thermal time model was used to calculate germination base temperature and thermal time constant. Two additional alternating temperature regimes were used to test temperature metrics effect. The germination percentage and rate increased continuously for C4 species, but increased and then decreased with temperature for C3 species under both symmetric and asymmetric warming. Compared to asymmetric warming, symmetric warming significantly overestimated the speed of germination percentage change with temperature for C4 species. Among the temperature metrics (minimum, maximum, diurnal temperature range and average temperature), maximum temperature was most correlated with germination of C4 species. Our results indicate that global warming may favour germination of C4 species, at least for the C4 species studied in this work. The divergent effects of asymmetric and symmetric warming on plant germination also deserve more attention in future studies.

  5. Fire ecology of C3 and C4 grasses depends on evolutionary history and frequency of burning but not photosynthetic type.

    PubMed

    Ripley, Brad; Visser, Vernon; Christin, Pascal-Antoine; Archibald, Sally; Martin, Tarryn; Osborne, Colin

    2015-10-01

    Grasses using the C4 photosynthetic pathway dominate frequently burned savannas, where the pathway is hypothesized to be adaptive. However, independent C4 lineages also sort among different fire environments. Adaptations to fire may thus depend on evolutionary history, which could be as important as the possession of the C4 photosynthetic pathway for life in these environments. Here, using a comparative pot experiment and controlled burn, we examined C3 and C4 grasses belonging to four lineages from the same regional flora, and asked the following questions: Do lineages differ in their responses to fire, are responses consistent between photosynthetic types, and are responses related to fire frequency in natural habitats? We found that in the C4 Andropogoneae lineage, frost killed a large proportion of aboveground biomass and produced a large dry fuel load, which meant that only a small fraction of the living tissue was lost in the fire. C3 species from the Paniceae and Danthonioideae lineages generated smaller fuel loads and lost more living biomass, while species from the C4 lineage Aristida generated the smallest fuel loads and lost the most living tissue. Regrowth after the fire was more rapid and complete in the C4 Andropogoneae and C3 Paniceae, but incomplete and slower in the C3 Danthonioideae and C4 Aristida. Rapid recovery was associated with high photosynthetic rates, high specific leaf area, delayed flowering, and frequent fires in natural habitats. Results demonstrated that phylogenetic lineage was more important than photosynthetic type in determining the fire response of these grasses and that fire responses were related to the frequency that natural habitats burned.

  6. Variations of Leaf Cuticular Waxes Among C3 and C4 Gramineae Herbs.

    PubMed

    He, Yuji; Gao, Jianhua; Guo, Na; Guo, Yanjun

    2016-11-01

    Modern C4 plants are commonly distributed in hot and dry environments whereas C3 plants predominate in cool and shade areas. At the outmost of plant surface, the deposition and chemical composition of cuticular waxes vary under different environmental conditions. However, whether such variation of cuticular wax is related to the distribution of C3 and C4 under different environmental conditions is still not clear. In this study, leaves of six C3 Gramineae herbs distributed in spring, Roegneria kamoji, Polypogon fugax, Poa annua, Avena fatua, Alopecurus aequalis, and Oplismenus undulatifolius, and four C4 and one C3 Gramineae herbs distributed in summer, Digitaria sanguinalis, Eleusine indica, Setaria viridis, S. plicata, and O. undulatifolius, were sampled and analyzed for cuticular wax. Plates were the main epicuticular wax morphology in both C3 and C4 plants except S. plicata. The plates melted in C4 plants but not in C3 plants. The total cuticular wax amounts in C4 plants were significantly lower than those in C3 plants, except for O. undulatifolius. Primary alcohols were the most abundant compounds in C3 plants, whereas n-alkanes were relatively the most abundant compounds in C4 plants. C29 was the most abundant n-alkane in C3 plants except for O. undulatifolius, whereas the most abundant n-alkane was C31 or C33 in C4 plants. The average chain length (ACL) of n-alkanes was higher in C4 than in C3 plants, whereas the ACL of n-alkanoic acids was higher in C3 than C4 plants. The cluster analysis based on the distribution of n-alkanes clearly distinguished C3 and C4 plants into two groups, except for O. undulatifolius which was grouped with C4 plants. These results suggest that the variations of cuticular waxes among C3 and C4 Gramineae herbs are related to the distribution of C3 and C4 plants under different environmental conditions.

  7. Analysis of data mining classification by comparison of C4.5 and ID algorithms

    NASA Astrophysics Data System (ADS)

    Sudrajat, R.; Irianingsih, I.; Krisnawan, D.

    2017-01-01

    The rapid development of information technology, triggered by the intensive use of information technology. For example, data mining widely used in investment. Many techniques that can be used assisting in investment, the method that used for classification is decision tree. Decision tree has a variety of algorithms, such as C4.5 and ID3. Both algorithms can generate different models for similar data sets and different accuracy. C4.5 and ID3 algorithms with discrete data provide accuracy are 87.16% and 99.83% and C4.5 algorithm with numerical data is 89.69%. C4.5 and ID3 algorithms with discrete data provides 520 and 598 customers and C4.5 algorithm with numerical data is 546 customers. From the analysis of the both algorithm it can classified quite well because error rate less than 15%.

  8. Differential positioning of chloroplasts in C4 mesophyll and bundle sheath cells.

    PubMed

    Maai, Eri; Miyake, Hiroshi; Taniguchi, Mitsutaka

    2011-08-01

    Chloroplast photorelocation movement is extensively studied in C3 but not C4 plants. C4 plants have 2 types of photosynthetic cells: mesophyll and bundle sheath cells. Mesophyll chloroplasts are randomly distributed along cell walls, whereas bundle sheath chloroplasts are located close to the vascular tissues or mesophyll cells depending on the plant species. The cell-specific C 4 chloroplast arrangement is established during cell maturation, and is maintained throughout the life of the cell. However, only mesophyll chloroplasts can change their positions in response to environmental stresses. The migration pattern is unique to C4 plants and differs from that of C3 chloroplasts. In this mini-review, we highlight the cell-specific disposition of chloroplasts in C4 plants and discuss the possible physiological significances.

  9. The Citrus transcription factor, CitERF13, regulates citric acid accumulation via a protein-protein interaction with the vacuolar proton pump, CitVHA-c4

    PubMed Central

    Li, Shao-jia; Yin, Xue-ren; Xie, Xiu-lan; Allan, Andrew C.; Ge, Hang; Shen, Shu-ling; Chen, Kun-song

    2016-01-01

    Organic acids are essential to fruit flavor. The vacuolar H+ transporting adenosine triphosphatase (V-ATPase) plays an important role in organic acid transport and accumulation. However, less is known of V-ATPase interacting proteins and their relationship with organic acid accumulation. The relationship between V-ATPase and citric acid was investigated, using the citrus tangerine varieties ‘Ordinary Ponkan (OPK)’ and an early maturing mutant ‘Zaoshu Ponkan (ZPK)’. Five V-ATPase genes (CitVHA) were predicted as important to citric acid accumulation. Among the genes, CitVHA-c4 was observed, using a yeast two-hybrid screen, to interact at the protein level with an ethylene response factor, CitERF13. This was verified using bimolecular fluorescence complementation assays. A similar interaction was also observed between Arabidopsis AtERF017 (a CitERF13 homolog) and AtVHA-c4 (a CitVHA-c4 homolog). A synergistic effect on citric acid levels was observed between V-ATPase proteins and interacting ERFs when analyzed using transient over-expression in tobacco and Arabidopsis mutants. Furthermore, the transcript abundance of CitERF13 was concomitant with CitVHA-c4. CitERF13 or AtERF017 over-expression leads to significant citric acid accumulation. This accumulation was abolished in an AtVHA-c4 mutant background. ERF-VHA interactions appear to be involved in citric acid accumulation, which was observed in both citrus and Arabidopsis. PMID:26837571

  10. Transcriptome comparisons shed light on the pre-condition and potential barrier for C4 photosynthesis evolution in eudicots.

    PubMed

    Tao, Yimin; Lyu, Ming-Ju Amy; Zhu, Xin-Guang

    2016-05-01

    C4 photosynthesis evolved independently from C3 photosynthesis in more than 60 lineages. Most of the C4 lineages are clustered together in the order Poales and the order Caryophyllales while many other angiosperm orders do not have C4 species, suggesting the existence of biological pre-conditions in the ancestral C3 species that facilitate the evolution of C4 photosynthesis in these lineages. To explore pre-adaptations for C4 photosynthesis evolution, we classified C4 lineages into the C4-poor and the C4-rich groups based on the percentage of C4 species in different genera and conducted a comprehensive comparison on the transcriptomic changes between the non-C4 species from the C4-poor and the C4-rich groups. Results show that species in the C4-rich group showed higher expression of genes related to oxidoreductase activity, light reaction components, terpene synthesis, secondary cell synthesis, C4 cycle related genes and genes related to nucleotide metabolism and senescence. In contrast, C4-poor group showed up-regulation of a PEP/Pi translocator, genes related to signaling pathway, stress response, defense response and plant hormone metabolism (ethylene and brassinosteroid). The implications of these transcriptomic differences between the C4-rich and C4-poor groups to C4 evolution are discussed.

  11. Variation in the Activity of Some Enzymes of Photorespiratory Metabolism in C4 Grasses

    PubMed Central

    UENO, OSAMU; YOSHIMURA, YASUYUKI; SENTOKU, NAOKI

    2005-01-01

    • Background and Aims Photorespiration occurs in C4 plants, although rates are small compared with C3 plants. The amount of glycine decarboxylase in the bundle sheath (BS) varies among C4 grasses and is positively correlated with the granal index (ratio of the length of appressed thylakoid membranes to the total length of all thylakoid membranes) of the BS chloroplasts: C4 grasses with high granal index contained more glycine decarboxylase per unit leaf area than those with low granal index, probably reflecting the differences in O2 production from photosystem II and the potential photorespiratory capacity. Thus, it is hypothesized that the activities of peroxisomal enzymes involved in photorespiration are also correlated with the granal development. • Methods The granal development in BS chloroplasts was investigated and activities of the photorespiratory enzymes assayed in 28 C4 grasses and seven C3 grasses. • Key Results The NADP–malic enzyme grasses were divided into two groups: one with low granal index and the other with relatively high granal index in the BS chloroplasts. Both the NAD–malic enzyme and phosphoenolpyruvate carboxykinase grasses had high granal index in the BS chloroplasts. No statistically significant differences were found in activity of hydroxypyruvate reductase between the C3 and C4 grasses, or between the C4 subtypes. The activity of glycolate oxidase and catalase were smaller in the C4 grasses than in the C3 grasses. Among the C4 subtypes, glycolate oxidase activities were significantly smaller in the NADP–malic enzyme grasses with low granal index in the BS chloroplasts, compared with in the C4 grasses with substantial grana in the BS chloroplasts. • Conclusions There is interspecies variation in glycolate oxidase activity associated with the granal development in the BS chloroplasts and the O2 production from photosystem II, which suggests different potential photorespiration capacities among C4 grasses. PMID:16100226

  12. A Specific Transcriptome Signature for Guard Cells from the C4 Plant Gynandropsis gynandra.

    PubMed

    Aubry, Sylvain; Aresheva, Olga; Reyna-Llorens, Ivan; Smith-Unna, Richard D; Hibberd, Julian M; Genty, Bernard

    2016-03-01

    C4 photosynthesis represents an excellent example of convergent evolution that results in the optimization of both carbon and water usage by plants. In C4 plants, a carbon-concentrating mechanism divided between bundle sheath and mesophyll cells increases photosynthetic efficiency. Compared with C3 leaves, the carbon-concentrating mechanism of C4 plants allows photosynthetic operation at lower stomatal conductance, and as a consequence, transpiration is reduced. Here, we characterize transcriptomes from guard cells in C3 Tareneya hassleriana and C4 Gynandropsis gynandra belonging to the Cleomaceae. While approximately 60% of Gene Ontology terms previously associated with guard cells from the C3 model Arabidopsis (Arabidopsis thaliana) are conserved, there is much less overlap between patterns of individual gene expression. Most ion and CO2 signaling modules appear unchanged at the transcript level in guard cells from C3 and C4 species, but major variations in transcripts associated with carbon-related pathways known to influence stomatal behavior were detected. Genes associated with C4 photosynthesis were more highly expressed in guard cells of C4 compared with C3 leaves. Furthermore, we detected two major patterns of cell-specific C4 gene expression within the C4 leaf. In the first, genes previously associated with preferential expression in the bundle sheath showed continually decreasing expression from bundle sheath to mesophyll to guard cells. In the second, expression was maximal in the mesophyll compared with both guard cells and bundle sheath. These data imply that at least two gene regulatory networks act to coordinate gene expression across the bundle sheath, mesophyll, and guard cells in the C4 leaf.

  13. A Specific Transcriptome Signature for Guard Cells from the C4 Plant Gynandropsis gynandra1[OPEN

    PubMed Central

    Aresheva, Olga; Reyna-Llorens, Ivan; Genty, Bernard

    2016-01-01

    C4 photosynthesis represents an excellent example of convergent evolution that results in the optimization of both carbon and water usage by plants. In C4 plants, a carbon-concentrating mechanism divided between bundle sheath and mesophyll cells increases photosynthetic efficiency. Compared with C3 leaves, the carbon-concentrating mechanism of C4 plants allows photosynthetic operation at lower stomatal conductance, and as a consequence, transpiration is reduced. Here, we characterize transcriptomes from guard cells in C3 Tareneya hassleriana and C4 Gynandropsis gynandra belonging to the Cleomaceae. While approximately 60% of Gene Ontology terms previously associated with guard cells from the C3 model Arabidopsis (Arabidopsis thaliana) are conserved, there is much less overlap between patterns of individual gene expression. Most ion and CO2 signaling modules appear unchanged at the transcript level in guard cells from C3 and C4 species, but major variations in transcripts associated with carbon-related pathways known to influence stomatal behavior were detected. Genes associated with C4 photosynthesis were more highly expressed in guard cells of C4 compared with C3 leaves. Furthermore, we detected two major patterns of cell-specific C4 gene expression within the C4 leaf. In the first, genes previously associated with preferential expression in the bundle sheath showed continually decreasing expression from bundle sheath to mesophyll to guard cells. In the second, expression was maximal in the mesophyll compared with both guard cells and bundle sheath. These data imply that at least two gene regulatory networks act to coordinate gene expression across the bundle sheath, mesophyll, and guard cells in the C4 leaf. PMID:26818731

  14. Mesophyll Chloroplast Investment in C3, C4 and C2 Species of the Genus Flaveria.

    PubMed

    Stata, Matt; Sage, Tammy L; Hoffmann, Natalie; Covshoff, Sarah; Ka-Shu Wong, Gane; Sage, Rowan F

    2016-05-01

    The mesophyll (M) cells of C4 plants contain fewer chloroplasts than observed in related C3 plants; however, it is uncertain where along the evolutionary transition from C3 to C4 that the reduction in M chloroplast number occurs. Using 18 species in the genus Flaveria, which contains C3, C4 and a range of C3-C4 intermediate species, we examined changes in chloroplast number and size per M cell, and positioning of chloroplasts relative to the M cell periphery. Chloroplast number and coverage of the M cell periphery declined in proportion to increasing strength of C4 metabolism in Flaveria, while chloroplast size increased with increasing C4 cycle strength. These changes increase cytosolic exposure to the cell periphery which could enhance diffusion of inorganic carbon to phosphenolpyruvate carboxylase (PEPC), a cytosolic enzyme. Analysis of the transcriptome from juvenile leaves of nine Flaveria species showed that the transcript abundance of four genes involved in plastid biogenesis-FtsZ1, FtsZ2, DRP5B and PARC6-was negatively correlated with variation in C4 cycle strength and positively correlated with M chloroplast number per planar cell area. Chloroplast size was negatively correlated with abundance of FtsZ1, FtsZ2 and PARC6 transcripts. These results indicate that natural selection targeted the proteins of the contractile ring assembly to effect the reduction in chloroplast numbers in the M cells of C4 Flaveria species. If so, efforts to engineer the C4 pathway into C3 plants might evaluate whether inducing transcriptome changes similar to those observed in Flaveria could reduce M chloroplast numbers, and thus introduce a trait that appears essential for efficient C4 function.

  15. 21 CFR 866.4100 - Complement reagent.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Complement reagent. 866.4100 Section 866.4100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents §...

  16. 21 CFR 866.4100 - Complement reagent.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Complement reagent. 866.4100 Section 866.4100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents §...

  17. 21 CFR 866.4100 - Complement reagent.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Complement reagent. 866.4100 Section 866.4100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents §...

  18. 21 CFR 866.4100 - Complement reagent.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Complement reagent. 866.4100 Section 866.4100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents §...

  19. 21 CFR 866.4100 - Complement reagent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement reagent. 866.4100 Section 866.4100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents §...

  20. The complement system: an evolution in progress

    PubMed Central

    Ghebrehiwet, Berhane

    2016-01-01

    The complement system, which consists of three independent but interacting pathways, constitutes a powerful arm of innate immunity. Its major function is to recognize and destroy pathogenic microorganisms as well as eliminate modified self-antigens. Although it is a fine-tuned system with innate capacity to discriminate self from non-self as well as danger from non-danger signals, an unwarranted activation can nonetheless occur and cause tissue destruction. To prevent such activation, specific regulators present both in plasma and on the cell surface tightly control it. Data accumulated over the past four decades have also shown that the complement system is capable of not only cross-talk with the activation cascades of plasma––i.e. blood coagulation, contact activation, and the kinin/kallikrein system––but also serving as a bridge between innate and adaptive immunity. It is for these reasons that the various activation steps of the complement system have been recently targeted for therapy to treat diseases in which the role of complement is beyond doubt. This trend will certainly continue for years to come, especially as novel concepts guiding the field into areas never contemplated before are continuing to be discovered. PMID:27990282

  1. Emai Sentence Complements in Typological Perspective.

    ERIC Educational Resources Information Center

    Schaefer, Ronald P.; Egbokhare, Francis O.

    This paper explores the syntactic and semantic character of previously undescribed sentence complements (SCs) in Emai, a Benue-Congo language of Nigeria's Edoid group. Data come from ongoing documentation incorporating oral narrative texts as well as dictionary and grammar descriptions. To delineate the grammatical properties of SCs, the paper…

  2. Genetics Home Reference: complement component 2 deficiency

    MedlinePlus

    ... Page Jönsson G, Sjöholm AG, Truedsson L, Bengtsson AA, Braconier JH, Sturfelt G. Rheumatological manifestations, organ damage ... 31. Review. Citation on PubMed Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. ...

  3. Complement Constructions in English: Fairly Difficult for EFL Language Learners

    ERIC Educational Resources Information Center

    Fazeli, Fatemeh; Shokrpour, Nasrin

    2012-01-01

    Complement constructions vary significantly in English and Persian. There are more complementation structures in English than in Persian and a complement structure in Persian might have more than one equivalent in English. Producing complement structures (CSs) in English is very difficult for native speakers of Persian, especially in an EFL…

  4. Variola virus immune evasion design: expression of a highly efficient inhibitor of human complement.

    PubMed

    Rosengard, Ariella M; Liu, Yu; Nie, Zhiping; Jimenez, Robert

    2002-06-25

    Variola virus, the most virulent member of the genus Orthopoxvirus, specifically infects humans and has no other animal reservoir. Variola causes the contagious disease smallpox, which has a 30-40% mortality rate. Conversely, the prototype orthopoxvirus, vaccinia, causes no disease in immunocompetent humans and was used in the global eradication of smallpox, which ended in 1977. However, the threat of smallpox persists because clandestine stockpiles of variola still exist. Although variola and vaccinia share remarkable DNA homology, the strict human tropism of variola suggests that its proteins are better suited than those of vaccinia to overcome the human immune response. Here, we demonstrate the functional advantage of a variola complement regulatory protein over that of its vaccinia homologue. Because authentic variola proteins are not available for study, we molecularly engineered and characterized the smallpox inhibitor of complement enzymes (SPICE), a homologue of a vaccinia virulence factor, vaccinia virus complement control protein (VCP). SPICE is nearly 100-fold more potent than VCP at inactivating human C3b and 6-fold more potent at inactivating C4b. SPICE is also more human complement-specific than is VCP. By inactivating complement components, SPICE serves to inhibit the formation of the C3/C5 convertases necessary for complement-mediated viral clearance. SPICE provides the first evidence that variola proteins are particularly adept at overcoming human immunity, and the decreased function of VCP suggests one reason why the vaccinia virus vaccine was associated with relatively low mortality. Disabling SPICE may be therapeutically useful if smallpox reemerges.

  5. Targeted Inhibition of Complement Using Complement Receptor 2-Conjugated Inhibitors Attenuates EAE

    PubMed Central

    Hu, Xianzhen; Tomlinson, Stephen; Barnum, Scott R.

    2012-01-01

    Multiple sclerosis (MS) is the most common autoimmune demyelinating disease, affecting millions of individuals worldwide. In the last two decades, many therapeutic options for the treatment of MS have become available, however they are limited in terms of effectiveness and some remain plagued by safety issues. The currently available treatment options target relapsing remitting forms of MS and are not effective against the more progressive forms of the disease. These limitations highlight a significant unmet treatment need for MS. In experimental autoimmune encephalomyelitis (EAE) studies from our laboratory, we have previously shown, using a number of complement mutant and transgenic mice, that inhibition of the alternative complement pathway and the C3 convertase confers significant protection from disease. We report here that targeted inhibition of complement activation using complement receptor 2 (CR2)-conjugated inhibitors significantly attenuates EAE. Administration of CR2-Crry (blocks all complement pathways at C3 activation) and CR2-fH (specifically blocks the alternative pathway) just prior to and during the onset of EAE blocks progression of both acute and chronic disease. These data indicate that inhibition of complement may offer an effective therapeutic approach to treating both acute and chronic forms of demyelinating disease through blocking the alternative pathway or complement convertases. PMID:23079547

  6. Targeted inhibition of complement using complement receptor 2-conjugated inhibitors attenuates EAE.

    PubMed

    Hu, Xianzhen; Tomlinson, Stephen; Barnum, Scott R

    2012-11-30

    Multiple sclerosis (MS) is the most common autoimmune demyelinating disease, affecting millions of individuals worldwide. In the last two decades, many therapeutic options for the treatment of MS have become available, however they are limited in terms of effectiveness and some remain plagued by safety issues. The currently available treatment options target relapsing remitting forms of MS and are not effective against the more progressive forms of the disease. These limitations highlight a significant unmet treatment need for MS. In experimental autoimmune encephalomyelitis (EAE) studies from our laboratory, we have previously shown, using a number of complement mutant and transgenic mice, that inhibition of the alternative complement pathway and the C3 convertase confers significant protection from disease. We report here that targeted inhibition of complement activation using complement receptor 2 (CR2)-conjugated inhibitors significantly attenuates EAE. Administration of CR2-Crry (blocks all complement pathways at C3 activation) and CR2-fH (specifically blocks the alternative pathway) just prior to and during the onset of EAE blocks progression of both acute and chronic disease. These data indicate that inhibition of complement may offer an effective therapeutic approach to treating both acute and chronic forms of demyelinating disease through blocking the alternative pathway or complement convertases.

  7. In vitro inactivation of complement by a serum factor present in Junin-virus infected guinea-pigs.

    PubMed Central

    Rimoldi, M T; de Bracco, M M

    1980-01-01

    A serum factor(s) of guinea-pigs infected with Junin virus, the etiological agent of Argentine haemorrhagic fever, is endowed with a potent anticomplementary activity. It is resistant to heat (56 degrees, 30 min) and elutes from a Sephadex G-200 column between albumin and haemoglobin. It is ineffective in the presence of EDTA or EGTA and does not sediment at 82,000 g. It has no direct effect on C4 unless functional Cl is present. However, it induces Cl activation that consumes C4 haemolytic activity in normal human and guinea-pig sera. The evidence presented in this report demonstrates that the complement activation observed in experimental Argentine haemorrhagic fever is at least in part due to a direct effect of this serum factor on the classical complement pathway. PMID:6247264

  8. Effects of penicillinase on bactericidal and complement activities in normal human serum.

    PubMed Central

    Biggs, W H; Wunderlich, A C; Corbeil, L C; Davis, C E; Curd, J G

    1983-01-01

    During routine addition of penicillinase (beta-lactamase) to patients sera, we found that the capacity of some of these sera to kill serum-sensitive gram-negative organisms was significantly decreased. Further controlled studies showed that penicillinase decreased both the bactericidal activity of normal human sera and the total hemolytic activity (CH50) of complement in these sera. The decreased bactericidal activity correlated significantly (r = 0.57, P less than 0.05) with the reduction of CH50 in eight normal sera. These effects of penicillinase were time and temperature dependent. Measurement of individual complement component activities showed that penicillinase decreased the activity of C2, C4, and C3-C9, suggesting that the penicillinase preparation activated the classical pathway. These results cast doubts on the validity of bactericidal determinations when sera are pretreated with penicillinase. PMID:6603195

  9. A high-resolution map of the regulator of the complement activation gene cluster on 1q32 that integrates new genes and markers.

    PubMed

    Heine-Suñer, D; Díaz-Guillén, M A; de Villena, F P; Robledo, M; Benítez, J; Rodríguez de Córdoba, S

    1997-01-01

    Sixteen microsatellite markers, including two described here, were used to construct a high-resolution map of the 1q32 region encompassing the regulator of the complement activation (RCA) gene cluster. The RCA genes are a group of related genes coding for plasma and membrane associated proteins that collectively control activation of the complement component C3. We provide here the location of two new genes within the RCA gene cluster. These genes are PFKFB2 that maps 15 kilobases (kb) upstream of the C4BPB gene, and a gene located 4 kb downstream of C4BPA, which seems to code for the 72 000 Mr component of the signal recognition particle (SRP72). Neither of these two genes is related structurally or functionally to the RCA genes. In addition, our map shows the centromere-telomere orientation of the C4BPB/MCP linkage group, which is: centromere-PFKFB2-C4BPB-C4BPA-SRP72-C4BPAL1++ +-C4BPAL2-telomere, and outlines an interval with a significant female-male recombination difference which suggests the presence of a female-specific hotspot(s) of recombination.

  10. Investigations of electron attachment to the perfluorocarbon molecules c-C4F8, 2-C4F8, 1,3 C4F6, and c-C5F8

    NASA Astrophysics Data System (ADS)

    Feil, Stefan; Märk, Tilmann D.; Mauracher, Andreas; Scheier, Paul; Mayhew, Chris A.

    2008-11-01

    Non-dissociative and dissociative electron attachment to a series of gas-phase perfluorocarbons (PFCs), namely octafluorocyclobutane, c-C4F8, octafluorobut-2-ene (perfluoro-2-butene), 2-C4F8, hexafluorobuta-1,3-diene (1,3 perfluorobutadiene), 1,3 C4F6, and octafluorocyclopentene (perfluorocyclopentene), c-C5F8, of importance to technological plasmas, have been investigated using two different, but complimentary, instruments available in Innsbruck over the electron energy range 0-20 eV. Anion yields as a function of electron energy have been recorded, with the positions and intensities of the electron attachment resonances being determined. One of these instruments is a double focusing sector field mass spectrometer (VG-ZAB-2SEQ), which has been used for measurements requiring high sensitivity and for obtaining accurate relative anion yields. It has also been used to determine the electron detachment lifetimes of the parent anions under various accelerating voltages, and these results are also presented. The second instrument (CELIA) is a trochoidal electron monochromator coupled to a quadrupole mass filter with a pulse counting system for detecting product anionic species. This provides a much higher energy resolution than the VG-ZAB, which makes it a better instrument to investigate narrow energy resonances close to 0 eV. The results of anion yields, peak positions and the relative intensities presented in this paper are compared with previous data of electron attachment to the above PFCs, including investigations by Professor Eugen Illenberger.

  11. Levels of complement components, immunoglobulins and acute phase proteins in plasma during aging in Nigeria.

    PubMed

    Oyeyinka, G O; Salimonu, L S

    1999-01-01

    Plasma samples from Nigerians aged 6-95 years were examined for their content of complement components (C3, C4, factor B-Bf), immuloglobins (IgG, IgA, IgM IgD) and acute phase proteins (transferrin, albumin, C-reactive protein--CRP, alpha-2-macroglobulin). Albumin, was estimated colorimetrically and the other components by the single radial immunodiffusion techniques. No significant age-related changes in mean values of the four immunobulins and the four acute phase proteins could be demonstrated. Also, the mean values for C3 and Bf did not change significantly with age but C4 values rose significantly with increasing age (r -0.232: P < 0.01).

  12. Differential positioning of C4 mesophyll and bundle sheath chloroplasts: aggregative movement of C4 mesophyll chloroplasts in response to environmental stresses.

    PubMed

    Yamada, Masahiro; Kawasaki, Michio; Sugiyama, Tatsuo; Miyake, Hiroshi; Taniguchi, Mitsutaka

    2009-10-01

    In C(4) plants, mesophyll (M) chloroplasts are randomly distributed along the cell walls, while bundle sheath (BS) chloroplasts are typically located in either a centripetal or centrifugal position. We investigated whether these intracellular positions are affected by environmental stresses. When mature leaves of finger millet (Eleusine coracana) were exposed to extremely high intensity light, most M chloroplasts aggregatively re-distributed to the BS side, whereas the intracellular arrangement of BS chloroplasts was unaffected. Compared with the homologous light-avoidance movement of M chloroplasts in C(3) plants, it requires extremely high light (3,000-4,000 micromol m(-2) s(-1)) and responds more slowly (distinctive movement observed in 1 h). The high light-induced movement of M chloroplasts was also observed in maize (Zea mays), another C(4) species, but with a distinct pattern of redistribution along the sides of anticlinal walls, analogous to C(3) plants. The aggregative movement of M chloroplasts occurred at normal light intensities (250-500 micromol m(-2) s(-1)) in response to environmental stresses, such as drought, salinity and hyperosmosis. Moreover, the re-arrangement of M chloroplasts was observed in field-grown C(4) plants when exposed to mid-day sunlight, but also under midsummer drought conditions. The migration of M chloroplasts was controlled by actin filaments and also induced in a light-dependent fashion upon incubation with ABA, which may be the physiological signal transducer. Together these results suggest that M and BS cells of C(4) plants have different mechanisms controlling intracellular chloroplast positioning, and that the aggregative movement of C(4) M chloroplasts is thought to be a protective response under environmental stress conditions.

  13. Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides

    NASA Astrophysics Data System (ADS)

    Nguyen, G. T. T.; Erlenkamp, G.; Jäck, O.; Küberl, A.; Bott, M.; Fiorani, F.; Gohlke, H.; Groth, G.

    2016-06-01

    Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world’s most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2‧,3‧,4‧,3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2‧,3‧,4‧-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15–45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme.

  14. Phenotypic landscape inference reveals multiple evolutionary paths to C4 photosynthesis

    PubMed Central

    Williams, Ben P; Johnston, Iain G; Covshoff, Sarah; Hibberd, Julian M

    2013-01-01

    C4 photosynthesis has independently evolved from the ancestral C3 pathway in at least 60 plant lineages, but, as with other complex traits, how it evolved is unclear. Here we show that the polyphyletic appearance of C4 photosynthesis is associated with diverse and flexible evolutionary paths that group into four major trajectories. We conducted a meta-analysis of 18 lineages containing species that use C3, C4, or intermediate C3–C4 forms of photosynthesis to parameterise a 16-dimensional phenotypic landscape. We then developed and experimentally verified a novel Bayesian approach based on a hidden Markov model that predicts how the C4 phenotype evolved. The alternative evolutionary histories underlying the appearance of C4 photosynthesis were determined by ancestral lineage and initial phenotypic alterations unrelated to photosynthesis. We conclude that the order of C4 trait acquisition is flexible and driven by non-photosynthetic drivers. This flexibility will have facilitated the convergent evolution of this complex trait. DOI: http://dx.doi.org/10.7554/eLife.00961.001 PMID:24082995

  15. Computational Study on Dissociation Properties of C4F6 Molecules

    NASA Astrophysics Data System (ADS)

    Choi, Heechol; Song, Mi-Young; Yoon, Jung-Sik; Plasma Fundamental Technology Research Team

    2016-09-01

    Saturated or unsaturated perfluorocarbons(PFCs) have been used extensively in dry etching processes due to their relatively low global warming potential and their high CF2 radical levels in commercial plasma processes. Many experimental and theoretical studies of these species have been performed for useful information about physical and chemical properties of PFCs. Recently, it was reported that the ωB97X-D/aVTZ method is strongly recommended as the best practical density functional theory (DFT) for rigorous and extensive studies of PFCs because this theoretical level shows the high performance and reliability especially for van der Waals interactions. Among various PFCs, this study focuses on C4F6 molecules including c-C4F6, 1,3-C4F6, and 2-C4F6 isomers. All the feasible isomerization and dissociation paths of C4F6 molecules were investigated mainly at the ωB97X-D/aVTZ level. Their reaction rate constants were computed by using variational transition-state theory for a deep insight into C4F6's reaction mechanism. Fates and roles of C4F6 molecules and their fragments in plasma phases could be explained based on our theoretical results and data. This work was supported by R&D Program of Plasma Convergence & Fundamental Research through NFRI of Korea funded by the Government funds.

  16. Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides

    PubMed Central

    Nguyen, G. T. T.; Erlenkamp, G.; Jäck, O.; Küberl, A.; Bott, M.; Fiorani, F.; Gohlke, H.; Groth, G.

    2016-01-01

    Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world’s most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2′,3′,4′,3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2′,3′,4′-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15–45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme. PMID:27263468

  17. C4 Photosynthesis in the Rice Paddy: Insights from the Noxious Weed Echinochloa glabrescens1[OPEN

    PubMed Central

    Covshoff, Sarah; Szecowka, Marek; Hughes, Thomas E.; Kelly, Steven; Bailey, Karen J.; Sage, Tammy L.; Pachebat, Justin A.; Leegood, Richard

    2016-01-01

    The C4 pathway is a highly complex trait that increases photosynthetic efficiency in more than 60 plant lineages. Although the majority of C4 plants occupy disturbed, arid, and nutrient-poor habitats, some grow in high-nutrient, waterlogged conditions. One such example is Echinochloa glabrescens, which is an aggressive weed of rice paddies. We generated comprehensive transcriptome datasets for C4 E. glabrescens and C3 rice to identify genes associated with adaption to waterlogged, nutrient-replete conditions, but also used the data to better understand how C4 photosynthesis operates in these conditions. Leaves of E. glabrescens exhibited classical Kranz anatomy with lightly lobed mesophyll cells having low chloroplast coverage. As with rice and other hygrophytic C3 species, leaves of E. glabrescens accumulated a chloroplastic phosphoenolpyruvate carboxylase protein, albeit at reduced amounts relative to rice. The arid-grown species Setaria italica (C4) and Brachypodium distachyon (C3) were also found to accumulate chloroplastic phosphoenolpyruvate carboxylase. We identified a molecular signature associated with C4 photosynthesis in nutrient-replete, waterlogged conditions that is highly similar to those previously reported from C4 plants that grow in more arid conditions. We also identified a cohort of genes that have been subjected to a selective sweep associated with growth in paddy conditions. Overall, this approach highlights the value of using wild species such as weeds to identify adaptions to specific conditions associated with high-yielding crops in agriculture. PMID:26527656

  18. Phenotypic landscape inference reveals multiple evolutionary paths to C4 photosynthesis.

    PubMed

    Williams, Ben P; Johnston, Iain G; Covshoff, Sarah; Hibberd, Julian M

    2013-09-28

    C4 photosynthesis has independently evolved from the ancestral C3 pathway in at least 60 plant lineages, but, as with other complex traits, how it evolved is unclear. Here we show that the polyphyletic appearance of C4 photosynthesis is associated with diverse and flexible evolutionary paths that group into four major trajectories. We conducted a meta-analysis of 18 lineages containing species that use C3, C4, or intermediate C3-C4 forms of photosynthesis to parameterise a 16-dimensional phenotypic landscape. We then developed and experimentally verified a novel Bayesian approach based on a hidden Markov model that predicts how the C4 phenotype evolved. The alternative evolutionary histories underlying the appearance of C4 photosynthesis were determined by ancestral lineage and initial phenotypic alterations unrelated to photosynthesis. We conclude that the order of C4 trait acquisition is flexible and driven by non-photosynthetic drivers. This flexibility will have facilitated the convergent evolution of this complex trait. DOI:http://dx.doi.org/10.7554/eLife.00961.001.

  19. Three distinct biochemical subtypes of C4 photosynthesis? A modelling analysis.

    PubMed

    Wang, Yu; Bräutigam, Andrea; Weber, Andreas P M; Zhu, Xin-Guang

    2014-07-01

    C4 photosynthesis has higher light-use, nitrogen-use, and water-use efficiencies than C3 photosynthesis. Historically, most of C4 plants were classified into three subtypes (NADP-malic enzyme (ME), NAD-ME, or phosphoenolpyruvate carboxykinase (PEPCK) subtypes) according to their major decarboxylation enzyme. However, a wealth of historic and recent data indicates that flexibility exists between different decarboxylation pathways in many C4 species, and this flexibility might be controlled by developmental and environmental cues. This work used systems modelling to theoretically explore the significance of flexibility in decarboxylation mechanisms and transfer acids utilization. The results indicate that employing mixed C4 pathways, either the NADP-ME type with the PEPCK type or the NAD-ME type with the PEPCK type, effectively decreases the need to maintain high concentrations and concentration gradients of transport metabolites. Further, maintaining a mixture of C4 pathways robustly affords high photosynthetic efficiency under a broad range of light regimes. A pure PEPCK-type C4 photosynthesis is not beneficial because the energy requirements in bundle sheath cells cannot be fulfilled due to them being shaded by mesophyll cells. Therefore, only two C4 subtypes should be considered as distinct subtypes, the NADP-ME type and NAD-ME types, which both inherently involve a supplementary PEPCK cycle.

  20. Abnormal leukotriene C4 released by unaffected jejunal mucosa in patients with inactive Crohn's disease.

    PubMed Central

    Casellas, F; Guarner, F; Antolín, M; Rodríguez, R; Salas, A; Malagelada, J R

    1994-01-01

    The mucosal release of inflammatory mediators is enhanced in active inflammatory bowel disease. This study examines whether leukotriene C4 production occurs in apparently unaffected segments of the gut. The intraluminal release of leukotriene C4 was determined by jejunal perfusion in seven healthy controls, in nine patients with chronic ulcerative colitis, and in 13 patients with Crohn's disease (six with ileal disease, and seven with only colonic). All patients were in clinical remission and none of them had evidence of jejunal involvement. Mild intraluminal irritation with a 2.5 mmol/l deoxycholic acid solution was induced to stimulate local inflammatory mechanisms. The release of DNA (a marker of mucosal desquamation) and prostaglandin E2 (PGE2) was simultaneously measured. Jejunal release of DNA was higher in Crohn's disease patients than in ulcerative colitis or healthy controls. Basal release of PGE2 was similar in the three groups of patients. Basal release of leukotriene C4 was considerably enhanced, however, in Crohn's disease patients compared with healthy controls. In ulcerative colitis patients, basal leukotriene C4 release was non-significantly different from controls. Bile acid perfusion stimulated PGE2, leukotriene C4, and DNA release in all groups studied, but leukotriene C4 release was significantly higher in Crohn's disease patients. It is concluded that in inactive Crohn's disease there is an enhanced intraluminal release of leukotriene C4 in apparently unaffected segments of proximal small bowel, which may reflect fundamental changes in the function of the gut mucosal barrier. PMID:8174991

  1. Complement factor I from flatfish half-smooth tongue (Cynoglossus semilaevis) exhibited anti-microbial activities.

    PubMed

    Xiang, Jinsong; Li, Xihong; Chen, Yadong; Lu, Yang; Yu, Mengjun; Chen, Xuejie; Zhang, Wenting; Zeng, Yan; Sun, Luming; Chen, Songlin; Sha, Zhenxia

    2015-11-01

    Complement factor I (Cfi) is a soluble serine protease which plays a crucial role in the modulation of complement cascades. In the presence of substrate modulating cofactors (such as complement factor H, C4bp, CR1, etc), Cfi cleaves and inactivates C3b and C4b, thereby controlling the complement-mediated processes. In this study, we sequenced and characterized Cfi gene from Cynoglossus Semilaevis (designated as CsCfi) for the first time. The full-length cDNA of CsCfi was 2230 bp in length, including a 98 bp 5'-untranslated region (UTR), a 164 bp 3'-UTR and a 1968 bp open reading frame (ORF). It encoded a polypeptide of 656 amino acids, with a molecular mass of 72.28 kDa and an isoelectric point of 7.71. A signal peptide was defined at N-terminus, resulting in a 626-residue mature protein. Multiple sequence alignment revealed that Cfi proteins were well conserved with the typical modular architecture and identical active sites throughout the vertebrates, which suggested the conserved function of Cfi. Phylogenetic analysis indicated that CsCfi and the homologous Cfi sequences from teleosts clustered into a clade, separating from another clade from the cartilaginous fish and other vertebrates. Tissue expression profile analysis by quantitative real-time PCR (qRT-PCR) showed that CsCfi mRNA constitutively expressed in all tested tissues, with the predominant expression in liver and the lowest in stomach. Temporal expression levels of CsCfi after challenging with Vibrio anguillarum showed different expression patterns in intestine, spleen, skin, blood, head kidney and liver. The recombinant CsCfi (rCsCfi) protein showed broad-spectrum antimicrobial activities against the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa and Shewanella putrefaciens. The research revealed that CsCfi plays an important role in C. Semilaevis immunity.

  2. The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation

    SciTech Connect

    Krishnan, Vengadesan; Xu, Yuanyuan; Macon, Kevin; Volanakis, John E.; Narayana, Sthanam V. L.

    2009-03-01

    The crystal structure of C2b has been determined at 1.8 Å resolution, which reveals the arrangement of its three complement control protein (CCP) modules. A model for complement component C2 is presented and its conformational changes during the C3-convertase formation are also discussed. The second component of complement (C2) is a multi-domain serine protease that provides catalytic activity for the C3 and C5 convertases of the classical and lectin pathways of human complement. The formation of these convertases requires the Mg{sup 2+}-dependent binding of C2 to C4b and the subsequent cleavage of C2 by C1s or MASP2, respectively. The crystal structure of full-length C2 is not yet available, although the structure of its C-terminal catalytic segment C2a has been determined. The crystal structure of the N-terminal segment C2b of C2 determined to 1.8 Å resolution presented here reveals the arrangement of its three CCP domains. The domains are arranged differently compared with most other CCP-domain assemblies, but their arrangement is similar to that found in the Ba part of the full-length factor B structure. The crystal structures of C2a, C2b and full-length factor B are used to generate a model for C2 and a discussion of the domain association and possible interactions with C4b during formation of the C4b–C2 complex is presented. The results of this study also suggest that upon cleavage by C1s, C2a domains undergo conformational rotation while bound to C4b and the released C2b domains may remain folded together similar to as observed in the intact protein.

  3. Pharmacokinetic analysis of the FAK scaffold inhibitor C4 in dogs

    PubMed Central

    Wilton, John; Kurenova, Elena; Pitzonka, Laura; Gaudy, Allison; Curtin, Leslie; Sexton, Sandra; Cance, William; Fetterly, Gerald

    2014-01-01

    Purpose Inhibition of focal adhesion kinase-vascular endothelial growth factor receptor 3 complex by C4 was previously shown to reduce tumor growth alone and synergistically with other chemotherapeutic agents in animal tumor models. Single and multiple dose IV and oral dosing studies were performed in dogs to determine C4 pharmacokinetics. Methods C4 was administered to 4 dogs at 1.25 or 2.50 mg/kg IV, or 7.50 mg/kg oral gavage. Single-(IV and oral) and multiple- (IV) dose pharmacokinetic samples were collected on days 1 and 3 at predose and 0.5, 1, 2, 4, 8, 24, 120, 144, and 168 hrs post-dose. C4 concentrations were determined using liquid chromatography with tandem mass spectral detection with a limit of quantitation of 2.50 pg/mL. Pharmacokinetics of C4 was characterized by a 3-compartment model with linear distributional and elimination clearances using Phoenix 64 WinNonlin 6.3. Results Mean C4 plasma concentration-time profiles revealed a triexponential decline following either IV or oral administration, independent of dose with no accumulation. For the 2.5 mg/kg dose, the median half-life was approximately 21 hrs. Median Cmax and area-under-the-curve (AUC0-24) was similar for Days 1 and 3. Oral bioavailability for formulations of PBS, TPGS, Maalox®, and Pepcid® was greatest with TPGS (45%), followed by Maalox® (42%), Pepcid® (37%), and PBS (30%) Conclusions The pharmacokinetic study revealed C4 has linear pharmacokinetics and does not accumulate following multiple dose administration. Characterization of C4 pharmacokinetics provides a better understanding of the novel targeted agent, which will help facilitate further development of C4. PMID:25377246

  4. Evidence of shift in C4 species range in central Argentina during the late Holocene

    USGS Publications Warehouse

    Silva, L.C.R.; Giorgis, M.A.; Anand, M.; Enrico, L.; Perez-Harguindeguy, N.; Falczuk, V.; Tieszen, L.L.; Cabido, M.

    2011-01-01

    Aim: Millennial-scale biogeographic changes are well understood in many parts of the world, but little is known about long-term vegetation dynamics in subtropical regions. Here we investigate shifts in C3/C4 plant abundance occurred in central Argentina during the past few millenniaMethods: We determined present day soil organic matter ??13C signatures of grasslands, shrublands and woodlands, containing different mixtures of C3 and C4 plants. We measured past changes in the relative cover of C3/C4 plants by comparing ??13C values in soil profiles with present day ??13C signatures. We analyzed 14C activity in soil depths that showed major changes in vegetation. Results: Present day relative cover of C3/C4 plants determines whole ecosystem ??13C signatures integrated as litter and superficial soil organic matter (R2 = 0. 78; p < 0. 01). Deeper soils show a consistent shift in ??13C, indicating a continuous replacement of C4 by C3 plants since 3,870 (??210) YBP. During this period, the relative abundance of C3 plants increased 32% (average across sites) with significant changes being observed in all studied ecosystems. Conclusions: Our results show that C4 species were more abundant in the past, but C3 species became dominant during the late Holocene. We identified increases in the relative C3/C4 cover in grasslands, shrublands and woodlands, suggesting a physiological basis for changes in vegetation. The replacement of C4 by C3 plants coincided with changes in climate towards colder and wetter conditions and could represent a climatically driven shift in the C4 species optimum range. ?? 2011 Springer Science+Business Media B.V.

  5. A Serine Protease Isolated from the Bristles of the Amazonic Caterpillar, Premolis semirufa, Is a Potent Complement System Activator

    PubMed Central

    Villas Boas, Isadora Maria; Pidde-Queiroz, Giselle; Magnoli, Fabio Carlos; Gonçalves-de-Andrade, Rute M.; van den Berg, Carmen W.; Tambourgi, Denise V.

    2015-01-01

    Background The caterpillar of the moth Premolis semirufa, commonly named pararama, is found in the Brazilian Amazon region. Accidental contact with the caterpillar bristles causes an intense itching sensation, followed by symptoms of an acute inflammation, which last for three to seven days after the first incident. After multiple accidents a chronic inflammatory reaction, called “Pararamose”, characterized by articular synovial membrane thickening with joint deformities common to chronic synovitis, frequently occurs. Although complement mediated inflammation may aid the host defense, inappropriate or excessive activation of the complement system and generation of anaphylatoxins can lead to inflammatory disorder and pathologies. The aim of the present study was to evaluate, in vitro, whether the Premolis semirufa’s bristles extract could interfere with the human complement system. Results The bristles extract was able to inhibit the haemolytic activity of the alternative pathway, as well as the activation of the lectin pathway, but had no effect on the classical pathway, and this inhibition seemed to be caused by activation and consumption of complement components. The extract induced the production of significant amounts of all three anaphylatoxins, C3a, C4a and C5a, promoted direct cleavage of C3, C4 and C5 and induced a significant generation of terminal complement complexes in normal human serum. By using molecular exclusion chromatography, a serine protease of 82 kDa, which activates complement, was isolated from P. semirufa bristles extract. The protease, named here as Ps82, reduced the haemolytic activity of the alternative and classical pathways and inhibited the lectin pathway. In addition, Ps82 induced the cleavage of C3, C4 and C5 and the generation of C3a and C4a in normal human serum and it was capable to cleave human purified C5 and generate C5a. The use of Phenanthroline, metalloprotease inhibitor, in the reactions did not significantly

  6. Abundant C4 plants on the Tibetan Plateau during the Lateglacial and early Holocene

    NASA Astrophysics Data System (ADS)

    Thomas, Elizabeth K.; Huang, Yongsong; Morrill, Carrie; Zhao, Jiangtao; Wegener, Pamela; Clemens, Steven C.; Colman, Steven M.; Gao, Li

    2014-03-01

    Plants using the C4 (Hatch-Slack) photosynthetic pathway are key for global food production and account for ca 25% of terrestrial primary productivity, mostly in relatively warm, dry regions. The discovery of modern naturally-occurring C4 plant species at elevations up to 4500 m in Tibet and 3000 m in Africa and South America, however, suggests that C4 plants are present in a wider range of environments than previously thought. Environmental conditions on the Tibetan Plateau, including high irradiance, rainfall focused in summer, and saline soils, can favor C4 plants by offsetting the deleterious effects of low growing season temperature. We present evidence based on leaf wax carbon isotope ratios from Lake Qinghai that C4 plants accounted for 50% of terrestrial primary productivity on the northeastern Tibetan Plateau throughout the Lateglacial and early Holocene. Despite cold conditions, C4 plants flourished due to a combination of factors, including maximum summer insolation, pCO2 ca 250 ppmv, and sufficient summer precipitation. The modern C3 plant-dominated ecosystem around Lake Qinghai was established ca 6 thousand years ago as pCO2 increased and summer temperature and precipitation decreased. C4 plants were also intermittently abundant during the Last Glacial period; we propose that C4 plants contributed a significant portion of local primary productivity by colonizing the exposed, saline Qinghai Lake bed during low stands. Our results contrast with state-of-the-art ecosystem models that simulate <0.5% C4 plant abundance on the Tibetan Plateau in modern and past environments. The past abundance of C4 plants on the Tibetan Plateau suggests a wider temperature range for C4 plants than can be inferred from modern distributions and model simulations, and provides paleoecological evidence to support recent findings that C4 plant evolution and distribution was determined by a combination of climatic and environmental factors (temperature, irradiance, precipitation

  7. A Unique Model Platform for C4 Plant Systems and Synthetic Biology

    DTIC Science & Technology

    2015-12-10

    AFRL-AFOSR-JP-TR-2016-0001 A Unique Model Platform for C4 Plant Systems and Synthetic Biology Lars Nielsen THE UNIVERSITY OF QUEENSLAND Final Report...3. DATES COVERED 03-06-2014 to 02-06-2015 4. TITLE AND SUBTITLE A Unique Model Platform for C4 Plant Systems and Synthetic Biology 5a...Platform for C4 Plant Systems and Synthetic Biology 5a. CONTRACT NUMBER FA2386-14-1-4028 5b. GRANT NUMBER Grant AOARD-14IOA042 144028 5c

  8. Sphingolipid base modifying enzymes in sunflower (Helianthus annuus): cloning and characterization of a C4-hydroxylase gene and a new paralogous Δ8-desaturase gene.

    PubMed

    Moreno-Pérez, Antonio J; Martínez-Force, Enrique; Garcés, Rafael; Salas, Joaquín J

    2011-05-15

    Sphingolipids are components of plant cell membranes that participate in the regulation of important physiological processes. Unlike their animal counterparts, plant sphingolipids are characterized by high levels of base C4-hydroxylation. Moreover, desaturation at the Δ8 position predominates over the Δ4 desaturation typically found in animal sphingolipids. These modifications are due to the action of C4-hydroxylases and Δ8-long chain base desaturases, and they are important for complex sphingolipids finally becoming functional. The long chain bases of sunflower sphingolipids have high levels of hydroxylated and unsaturated moieties. Here, a C4-long chain base hydroxylase was functionally characterized in sunflower plant, an enzyme that could complement the sur2Δ mutation when heterologously expressed in this yeast mutant deficient in hydroxylation. This hydroxylase was ubiquitously expressed in sunflower, with the highest levels found in the developing cotyledons. In addition, we identified a new Δ8-long base chain desaturase gene that displays strong homology to a previously reported desaturase gene. This desaturase was also expressed in yeast and was able to change the long chain base composition of the transformed host. We studied the expression of this desaturase and compared it with that of the other isoform described in sunflower. The desaturase form studied in this paper displayed higher expression levels in developing seeds.

  9. Tanker avionics and aircrew complement evaluation.

    PubMed

    Moss, R W; Barbato, G J

    1982-11-01

    This paper describes an effort to determine control and display criteria for operating SAC's KC-135 tanker with a reduced crew complement. The Tanker Avionics and Aircrew Complement Evaluation (TAACE) Program was a four-phase effort addressing the control and display design issues associated with operating the tanker without the navigator position. Discussed are: the mission analysis phase, during which the tanker's operational responsibilities were defined and documented; the design phase, during which alternative crew station design concepts were developed; the mockup evaluation phase, which accomplished initial SAC crew member assessment of cockpit designs; and the simulation phase, which validated the useability of the crew system redesign. The paper also describes a recommended crew station configuration and discusses some of the philosophy underlying the selection of cockpit hardware and systems.

  10. Soluble human complement receptor type 1 inhibits complement-mediated host defense.

    PubMed

    Swift, A J; Collins, T S; Bugelski, P; Winkelstein, J A

    1994-09-01

    Soluble complement receptor type 1 (sCR1) is a powerful inhibitor of complement activation. Because of this ability, sCR1 may prove to be an important therapeutic agent that can be used to block the immunopathologic effects of uncontrolled complement activation in a variety of clinically significant disorders. Although several previous studies have examined the ability of sCR1 to inhibit complemented-mediated immunopathologic damage, there is no information on its ability to interfere with the host's defense against infection. In the current experiments sCR1 exerted a concentration-dependent inhibitory effect on the phagocytosis of Streptococcus pneumoniae by human polymorphonuclear leukocytes in vitro. Not only di sCR1 inhibit complement-dependent opsonization of the pneumococcus but at higher concentrations it also inhibited the ingestion of bacteria which had been previously opsonized. Furthermore, when rats were injected with sCR1, it inhibited both their serum hemolytic activity and serum opsonic activity in a dose-dependent fashion. Finally, for rats treated with sCR1, the 50% lethal dose was S. pneumoniae and Pseudomonas aeruginosa. These data demonstrate that sCR1 significantly inhibits complement-mediated host against bacterial infection.

  11. COMPLEMENT REGULATION IN RENAL DISEASE MODELS

    PubMed Central

    Naik, Abhijit; Sharma, Shweta; Quigg, Richard J.

    2014-01-01

    Activation of the complement system is tightly regulated by plasma and cell-associated complement regulatory proteins (CRPs), such as factor H (fH), decay-accelerating factor (DAF), and membrane cofactor protein (MCP). Animal models of disease have provided considerable insights into the important roles for CRPs in the kidney. Mice deficient in fH have excessive fluid phase C3 activation and inactivation leading to deposition of iC3b in glomerular capillary walls (GCW), comparable to dense deposit disease. In contrast, when fH lacks C-terminal surface targeting regions, local activation on the GCW leads to a disease reminiscent of thrombotic microangiopathy. The uniquely rodent protein, CR1-related y (Crry), has features analogous to human MCP. Defective Crry leads to unrestricted alternative pathway activation in the tubulointerstitium (TI) resulting in pathological features ranging from TMA, acute kidney injury and TI nephritis. In the presence of initiators of the classical or lectin pathways, commonly in the form of immune complexes in human glomerular diseases, complement regulation on self is stressed, with the potential for recruitment of the spontaneously active alternative pathway. The threshold for this activation is set by CRPs; pathology is more likely when complement regulation is defective. Within the endocapillary region of the GCW, fH is key, while DAF and Crry are protective on mesangial cells and podocytes. Arguably, acquired alterations in these CRPs is a more common event, extending from pathological states of cellular injury or production of inhibitory antibodies, to physiological fine tuning of the adaptive immune response. PMID:24161042

  12. Rotationally resolved infrared spectra of the explosive bouquet compounds associated with C-4 explosives

    NASA Astrophysics Data System (ADS)

    Clasp, Trocia N.; Johnson, Tiffani; Sullivan, Michael N.; Reeve, Scott W.

    2011-05-01

    The explosive material known as Composition C4, or simply C4, is an RDX based military grade explosive. RDX itself possesses a negligible vapor pressure at room temperature suggesting it is not a good target for conventional instruments designed to detect vapor phase chemical compounds. Recent research with canines has indicated that a better approach for detecting explosive vapors such as C4 is to focus on a characteristic mixture of impurities associated with the material. These characteristic mixtures of impurity vapors are referred to by canine researchers as the explosive bouquet and are fairly unique to the specific energetic material. In this paper, we will examine and report rotationally resolved infrared spectral signatures for the known compounds comprising the explosive bouquet for C4 based explosives including isobutylene, 2-ethyl-1-hexanol and cyclohexanone.

  13. Observation of thermal electron detachment from cyclo-C4F8- in FALP experiments

    NASA Astrophysics Data System (ADS)

    Miller, Thomas M.; Morris, Robert A.; Stevens Miller, Amy E.; Viggiano, A. A.; Paulson, John F.

    1994-08-01

    The methodology for use of a flowing afterglow--Langmuir probe apparatus to measure thermal electron detachment rate coefficients is described. We determined the thermal detachment rate coefficient (1010 ± 300 s-1) for cyclo-C4F8- ions and the rate coefficient (1.6 ± × 10-8 cm3 s-1) for electron attachment of cyclo-C4F8 at 375 K. The sole ionic product of attachment is cyclo-C4F8-. The equilibrium constant for the attachment/detachment reaction yields a free energy for attachment at 375 K of -0.63 ± 0.02 eV, from which we estimate the electron affinity (0 K value) of cyclo-C4F8 to be about 0.63 eV.

  14. Tissue-specific variation in C4 and Slp gene regulation.

    PubMed Central

    Cox, B J; Robins, D M

    1988-01-01

    C4 and Slp are highly homologous mouse genes that differ in function and regulation. Allelic variants exist in quantitative regulation of C4 and in hormonal regulation of Slp. We have examined expression in several tissues, including liver and peritoneal macrophages which are the major sites of synthesis, using a probe that allows direct comparison of C4 and Slp mRNAs. Correctly-sized and initiated RNA, within an order of magnitude of liver levels, is found in mammary gland, lung, spleen, and kidney; lower levels are detectable in testis, brain, heart and submaxillary gland. By comparing expression in congenic mouse strains differing in C4 and Slp loci, regulation of these genes is seen to vary in different tissues. This provides a well-defined genetic system in which to examine cis-acting sequences and trans-acting factors that result in tissue-specific patterns of gene regulation. Images PMID:3405752

  15. Soluble complement receptor 1 protects the peripheral nerve from early axon loss after injury.

    PubMed

    Ramaglia, Valeria; Wolterman, Ruud; de Kok, Maryla; Vigar, Miriam Ann; Wagenaar-Bos, Ineke; King, Rosalind Helen Mary; Morgan, Brian Paul; Baas, Frank

    2008-04-01

    Complement activation is a crucial early event in Wallerian degeneration. In this study we show that treatment of rats with soluble complement receptor 1 (sCR1), an inhibitor of all complement pathways, blocked both systemic and local complement activation after crush injury of the sciatic nerve. Deposition of membrane attack complex (MAC) in the nerve was inhibited, the nerve was protected from axonal and myelin breakdown at 3 days after injury, and macrophage infiltration and activation was strongly reduced. We show that both classical and alternative complement pathways are activated after acute nerve trauma. Inhibition of the classical pathway by C1 inhibitor (Cetor) diminished, but did not completely block, MAC deposition in the injured nerve, blocked myelin breakdown, inhibited macrophage infiltration, and prevented macrophage activation at 3 days after injury. However, in contrast to sCR1 treatment, early signs of axonal degradation were visible in the nerve, linking MAC deposition to axonal damage. We conclude that sCR1 protects the nerve from early axon loss after injury and propose complement inhibition as a potential therapy for the treatment of diseases in which axon loss is the main cause of disabilities.

  16. Isolation of cDNA clones specifying the fourth component of mouse complement and its isotype, sex-limited protein.

    PubMed Central

    Nonaka, M; Takahashi, M; Natsuume-Sakai, S; Nonaka, M; Tanaka, S; Shimizu, A; Honjo, T

    1984-01-01

    cDNA clones specific for the fourth component of mouse complement (C4) and its hormonally regulated isotype, sex-linked protein (Slp), were isolated using as a probe a 20-mer synthetic oligonucleotide corresponding to a known sequence of human C4 cDNA. Two types of clones, one specific for C4 (pFC4/10, with a 3.7 kilobase insert) and one specific for Slp (pFSlp/1, with a 4.7 kilobase insert), were isolated from liver cDNA libraries constructed from the Slp-producing FM mouse strain. The cDNA inserts of these clones shared 70% of the restriction sites determined. Only one type of clone was isolated from the Slp-negative DBA/1 strain; this type showed restriction maps indistinguishable from that of pFC4/10. pFC4/10 and pFSlp/1 displayed extensive homology: 94% nucleotide homology and 89% derived amino acid homology in the C4a region and 92% nucleotide homology and 89% derived amino acid homology in the thiol-ester region. An Arg-Gln-Lys-Arg sequence in the beta-alpha junction and a Cys-Ala-Glu-Gln sequence in the thiol-ester site were identified for both proteins. A remarkable divergency between C4 and Slp sequences was recognized in the region immediately following the C4a sequence. PMID:6208559

  17. Nebulized C1-Esterase Inhibitor does not Reduce Pulmonary Complement Activation in Rats with Severe Streptococcus Pneumoniae Pneumonia.

    PubMed

    de Beer, Friso; Lagrand, Wim; Glas, Gerie J; Beurskens, Charlotte J P; van Mierlo, Gerard; Wouters, Diana; Zeerleder, Sacha; Roelofs, Joris J T H; Juffermans, Nicole P; Horn, Janneke; Schultz, Marcus J

    2016-12-01

    Complement activation plays an important role in the pathogenesis of pneumonia. We hypothesized that inhibition of the complement system in the lungs by repeated treatment with nebulized plasma-derived human C1-esterase inhibitor reduces pulmonary complement activation and subsequently attenuates lung injury and lung inflammation. This was investigated in a rat model of severe Streptococcus pneumoniae pneumonia. Rats were intra-tracheally challenged with S. pneumoniae to induce pneumonia. Nebulized C1-esterase inhibitor or saline (control animals) was repeatedly administered to rats, 30 min before induction of pneumonia and every 6 h thereafter. Rats were sacrificed 20 or 40 h after inoculation with bacteria. Brochoalveolar lavage fluid and lung tissue were obtained for measuring levels of complement activation (C4b/c), lung injury and inflammation. Induction of pneumonia was associated with pulmonary complement activation (C4b/c at 20 h 1.24 % [0.56-2.59] and at 40 h 2.08 % [0.98-5.12], compared to 0.50 % [0.07-0.59] and 0.03 % [0.03-0.03] in the healthy control animals). The functional fraction of C1-INH was detectable in BALF, but no effect was found on pulmonary complement activation (C4b/c at 20 h 0.73 % [0.16-1.93] and at 40 h 2.38 % [0.54-4.19]). Twenty hours after inoculation, nebulized C1-esterase inhibitor treatment reduced total histology score, but this effect was no longer seen at 40 h. Nebulized C1-esterase inhibitor did not affect other markers of lung injury or lung inflammation. In this negative experimental animal study, severe S. pneumoniae pneumonia in rats is associated with pulmonary complement activation. Repeated treatment with nebulized C1-esterase inhibitor, although successfully delivered to the lungs, does not affect pulmonary complement activation, lung inflammation or lung injury.

  18. Spatiotemporal variation in C4-grass abundance during the early to middle Miocene in Spain

    NASA Astrophysics Data System (ADS)

    Urban, M. A.; Nelson, D. M.; Jimenez-Moreno, G.; Hu, F.

    2014-12-01

    Carbon-isotope analyses on a variety of substrates (e.g., leaf waxes, teeth, carbonates) suggest a pronounced increase in C4 plant biomass during the late Miocene and early Pliocene in many regions of the world. This spread of C4-dominated grasslands is thought to have occurred at the expense of C3-dominated grasslands. However, the earlier history of C4 grasses is uncertain, primarily because of difficulty assessing the presence and abundance of C4 grasses when they are relatively rare on the landscape. We measure d13C of individual grass pollen grains using SPIRAL (Single Pollen Isotope Ratio AnaLysis) to distinguish the relative abundance of C3 and C4 grasses during the early to middle Miocene in Spain. We analyzed a total of 3251 pollen grains isolated from 7 samples from Andalucia A1 (10-13.5 Ma), 7 samples from Gor (13-15 Ma) and 24 sediment samples from (Rubielos de Mora, (16-22 Ma). Palynological data indicate that grasses were not a significant component (5-20% of total terrestrial pollen) of the regional vegetation, which was composed of herbs, shrubs, and thermophilous (e.g., Taxodiaceae, Engelhardia) and mesothermic (Quercus, Carya) trees. Based on our SPIRAL data, 21-72% of the grasses were C4, with the older northern site (Rubielos de Mora) having lower C4-grass abundance (average of 39%) than the younger and more southern sites (average of 62%). Paleoclimate reconstructions suggest that the region was mainly subtropical (warm and semi-arid/highly seasonal) at that time, and pollen spectra suggest that the regional vegetation was similar to that found today in northern Africa where C4 grasses dominate. Our pollen-isotope results imply an increase in C4-grass abundance through time, and/or a north-south climatic gradient, with wetter and less seasonal conditions that were less favorable to C4 grasses in the north. Overall, these results suggest that C4 grasses were relatively abundant in southwestern Europe during the early and middle Miocene, prior to

  19. C4 expansion in the central Inner Mongolia during the latest Miocene and early Pliocene

    NASA Astrophysics Data System (ADS)

    Zhang, Chunfu; Wang, Yang; Deng, Tao; Wang, Xiaoming; Biasatti, Dana; Xu, Yingfeng; Li, Qiang

    2009-10-01

    The emergence of C4 photosynthesis in plants as a significant component of terrestrial ecosystems is thought to be an adaptive response to changes in atmospheric CO 2 concentration and/or climate during Neogene times and has had a profound effect on the global terrestrial biosphere. Although expansion of C4 grasses in the latest Miocene and Pliocene has been widely documented around the world, the spatial and temporal variations in the C4 expansion are still not well understood and its driving mechanisms remain a contentious issue. Here we present the results of carbon and oxygen isotope analyses of fossil and modern mammalian tooth enamel samples from the central Inner Mongolia. Our samples represent a diverse group of herbivorous mammals including deer, elephants, rhinos, horses and giraffes, ranging in age from the late Oligocene to modern. The δ13C values of 91 tooth enamel samples of early late-Miocene age or older, with the exception of two 13 Ma rhino samples (- 7.8 and - 7.6‰) and one 8.5 Ma suspected rhino sample (- 7.6‰), were all less than - 8.0‰ (VPDB), indicating that there were no C4 grasses present in their diets and thus probably few or no C4 grasses in the ecosystems of the central Inner Mongolia prior to ~ 8 Ma. However, 12 out of 26 tooth enamel samples of younger ages (~ 7.5 Ma to ~ 3.9 Ma) have δ13C values higher than - 8.0‰ (up to - 2.4‰), indicating that herbivores in the area had variable diets ranging from pure C3 to mixed C3-C4 vegetation during that time interval. The presence of C4 grasses in herbivores' diets (up to ~ 76% C4) suggests that C4 grasses were a significant component of the local ecosystems in the latest Miocene and early Pliocene, consistent with the hypothesis of a global factor as the driving mechanism of the late Miocene C4 expansion. Today, C3 grasses dominate grasslands in the central Inner Mongolia area. The retreat of C4 grasses from this area after the early Pliocene may have been driven by regional

  20. Chemical bonding in electron-deficient boron oxide clusters: core boronyl groups, dual 3c-4e hypervalent bonds, and rhombic 4c-4e bonds.

    PubMed

    Chen, Qiang; Lu, Haigang; Zhai, Hua-Jin; Li, Si-Dian

    2014-04-28

    We explore the structural and bonding properties of the electron-deficient boron oxide clusters, using a series of B3On(-/0/+) (n = 2-4) clusters as examples. Global-minimum structures of these boron oxide clusters are identified via unbiased Coalescence Kick and Basin Hopping searches, which show a remarkable size and charge-state dependence. An array of new bonding elements are revealed: core boronyl groups, dual 3c-4e hypervalent bonds (ω-bonds), and rhombic 4c-4e bonds (o-bonds). In favorable cases, oxygen can exhaust all its 2s/2p electrons to facilitate the formation of B-O bonds. The current findings should help understand the bonding nature of low-dimensional boron oxide nanomaterials and bulk boron oxides.

  1. NDH-Mediated Cyclic Electron Flow Around Photosystem I is Crucial for C4 Photosynthesis.

    PubMed

    Ishikawa, Noriko; Takabayashi, Atsushi; Noguchi, Ko; Tazoe, Youshi; Yamamoto, Hiroshi; von Caemmerer, Susanne; Sato, Fumihiko; Endo, Tsuyoshi

    2016-10-01

    C4 photosynthesis exhibits efficient CO2 assimilation in ambient air by concentrating CO2 around ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) through a metabolic pathway called the C4 cycle. It has been suggested that cyclic electron flow (CEF) around PSI mediated by chloroplast NADH dehydrogenase-like complex (NDH), an alternative pathway of photosynthetic electron transport (PET), plays a crucial role in C4 photosynthesis, although the contribution of NDH-mediated CEF is small in C3 photosynthesis. Here, we generated NDH-suppressed transformants of a C4 plant, Flaveria bidentis, and showed that the NDH-suppressed plants grow poorly, especially under low-light conditions. CO2 assimilation rates were consistently decreased in the NDH-suppressed plants under low and medium light intensities. Measurements of non-photochemical quenching (NPQ) of Chl fluorescence, the oxidation state of the reaction center of PSI (P700) and the electrochromic shift (ECS) of pigment absorbance indicated that proton translocation across the thylakoid membrane is impaired in the NDH-suppressed plants. Since proton translocation across the thylakoid membrane induces ATP production, these results suggest that NDH-mediated CEF plays a role in the supply of ATP which is required for C4 photosynthesis. Such a role is more crucial when the light that is available for photosynthesis is limited and the energy production by PET becomes rate-determining for C4 photosynthesis. Our results demonstrate that the physiological contribution of NDH-mediated CEF is greater in C4 photosynthesis than in C3 photosynthesis, suggesting that the mechanism of PET in C4 photosynthesis has changed from that in C3 photosynthesis accompanying the changes in the mechanism of CO2 assimilation.

  2. Divergent evolutionary histories of C4 grasses shape global grassland ecology

    NASA Astrophysics Data System (ADS)

    Lehmann, C.; Griffith, D.; Osborne, C.

    2014-12-01

    C4 photosynthesis has evolved in more than 23 independent lineages of grasses as an adaptation to hot, sunny conditions. Geological records demonstrate that C4 grasses abruptly became ecologically dominant during the late Cenozoic across the tropical and temperate regions, transforming the Earth System and facilitating major faunal and floral radiations. However, although each C4 grass lineage originated and specialised in different environments, the importance of these divergent evolutionary histories for global ecology remains largely unknown. Here, we address this problem by compiling the first global map of grassy biomes based entirely upon ground-based vegetation surveys of dominant species. Our analysis shows that grasses dominate the ground layer across 40% of the vegetated land surface, with C4 grasses accounting for 60% of this area, and grassy biomes occurring under almost all climatic conditions. More than 98% of C3 grassy vegetation is dominated by the cold tolerant Pooideae lineage, which is replaced by C4 lineages at mean annual temperatures exceeding 15oC. The world's C4 grassy vegetation is largely dominated by only four of the 23 independent C4 grass lineages, and these segregate strongly along global environmental gradients and across continents. The Chloridoideae lineage is globally important in dominating semi-arid environments with a long fire return interval. In contrast, although the Andropogoneae lineage dominates extremely wet regions with frequent fire in the Paleotropics and North America, the same niche space is dominated by Paspaleae in South America. Sorting of lineages along precipitation and fire gradients is strongly predicted by plant height. Our results demonstrate that the divergent histories of independent C4 grass lineages have constrained the assembly and functional traits of grassy biomes, with important implications for understanding how biome boundaries may shift in past and future environments.

  3. Sydnone C-4 heteroarylation with an indolizine ring via Chichibabin indolizine synthesis

    PubMed Central

    Albota, Florin; Draghici, Constantin; Dumitrescu, Denisa E

    2016-01-01

    The synthesis of sydnones heteroarylated at C-4 with an indolizine was achieved by Chichibabin (Tschitschibabin) indolizine synthesis starting from the corresponding sydnone-N-pyridinium bromides. The latter compounds were also transformed to sydnone-indolizines connected through a keto group at the C-4 position by refluxing them in 1,2-epoxybutane with an activated alkyne. The structures of the new compounds were assigned by FTIR, NMR spectroscopy and X-ray analysis. PMID:28144319

  4. Structure-based affinity maturation of a chimeric anti-ricin antibody C4C13.

    PubMed

    Luo, Longlong; Luo, Qun; Guo, Leiming; Lv, Ming; Lin, Zhou; Geng, Jing; Li, Xinying; Li, Yan; Shen, Beifen; Qiao, Chunxia; Feng, Jiannan

    2014-01-01

    Ricin is a highly lethal toxin. Anti-ricin chimeric monoclonal antibody (mAb) C4C13 was prepared in our lab; however, its binding affinity was much weaker than that of the parent antibody 4C13. In this study, based on the computer-guided homology modeling and conformational optimization methods, the 3-D structure of C4C13 variable regions Fv was constructed and optimized. Using molecular docking and dynamics simulation methods, the 3-D complex structure of ricin and C4C13 Fv was obtained. Considering the orientation property, surface electrostatic distribution, residues chemical and physical character and intermolecular hydrogen bond, the binding mode and key residues were predicted. According to C4C13 Fv fragment and ricin complementary binding surface, electrostatic attraction periphery and van der Waals interaction interface, three mutants (i.e., M1 (N(H102)F, W(H103)Y); M2 (W(H103)Y) and M3 (R(L90)G)) were designed, in which M1 and M2 were predicted to possess higher antigen-binding activity than C4C13, while M3 was weaker. The relative affinity assays by ELISA showed that M1 and M2 mutations had higher affinity (9.6 and 18.3 nmol/L) than C4C13 (130 nmol/L) and M3 had weaker affinity (234.5 nmol/L) than C4C13. The results showed that the modeling complex structure of the antigen (ricin) and antibody (C4C13) is reasonable. Our work offered affinity maturated antibodies by site mutations, which were beneficial for valuable anti-ricin antibody design and preparation in future.

  5. The Serine Protease Pic From Enteroaggregative Escherichia coli Mediates Immune Evasion by the Direct Cleavage of Complement Proteins.

    PubMed

    Abreu, Afonso G; Fraga, Tatiana R; Granados Martínez, Adriana P; Kondo, Marcia Y; Juliano, Maria A; Juliano, Luiz; Navarro-Garcia, Fernando; Isaac, Lourdes; Barbosa, Angela S; Elias, Waldir P

    2015-07-01

    Enteroaggregative and uropathogenic Escherichia coli, Shigella flexneri 2a, and the hybrid enteroaggregative/Shiga toxin-producing E. coli strain (O104:H4) are important pathogens responsible for intestinal and urinary tract infections, as well as sepsis and hemolytic uremic syndrome. They have in common the production of a serine protease called Pic. Several biological roles for Pic have been described, including protection of E. coli DH5α from complement-mediated killing. Hereby we showed that Pic significantly reduces complement activation by all 3 pathways. Pic cleaves purified C3/C3b and other proteins from the classic and lectin pathways, such as C4 and C2. Cleavage fragments of C3, C4, and C2 were also observed with HB101(pPic1) culture supernatants, and C3 cleavage sites were mapped by fluorescence resonance energy transfer peptides. Experiments using human serum as a source of complement proteins confirmed Pic proteolytic activity on these proteins. Furthermore, Pic works synergistically with the human complement regulators factor I and factor H, promoting inactivation of C3b. In the presence of both regulators, further degradation of C3 α' chain was observed. Therefore, Pic may contribute to immune evasion of E. coli and S. flexneri, favoring invasiveness and increasing the severity of the disorders caused by these pathogens.

  6. The non-photosynthetic phosphoenolpyruvate carboxylases of the C4 dicot Flaveria trinervia -- implications for the evolution of C4 photosynthesis.

    PubMed

    Bläsing, Oliver E; Ernst, Karin; Streubel, Monika; Westhoff, Peter; Svensson, Per

    2002-07-01

    C4 phospho enolpyruvate carboxylases (PEPCase; EC 4.1.1.3) have evolved from ancestral non-photosynthetic (C3) isoforms during the evolution of angiosperms and thereby gained distinct kinetic and regulatory properties. In order to obtain insight into this evolutionary process we have studied the C3 isoforms, ppcB and ppcC, of the C4 dicot Flaveria trinervia (Spreng.) C. Mohr and compared them with the C4 enzyme of this species, ppcA, and its orthologue in the C3 species F. pringlei Gandoger. Phylogenetic analyses indicate that the ppcB PEPCase is the closest relative of the ppcA enzyme. In addition, the presence of ppcB also in the closely related C3 species F. pringlei suggests that this gene was present already in the ancestral C3 species and consequently that ppcA has evolved by gene duplication of ppcB. Investigation of the enzymatic properties of the ppcB and ppcC enzymes showed low and similar K(0.5)-PEP values and limited activation by glucose-6-phosphate, typical of non-photosynthetic PEPCases, at pH 8.0. However, at the more physiological pH of 7.6, the ppcC enzyme displayed a substantially higher K(0.5)-PEP than the ppcB counterpart, indicating their involvement in different metabolic pathways. This indication was strengthened by malate inhibition studies in which the ppcC enzyme showed 10 times higher tolerance to the inhibitor. The ppcA enzyme was, however, by far the most tolerant enzyme towards malate. Interestingly, the increased malate tolerance was correlated with a decrease in enzyme efficiency displayed by the turnover constant k(cat). We therefore suggest that the increased malate tolerance, which is imperative for an efficient C4 cycle, is connected with a decreased enzyme efficiency that in turn is compensated by increased enzyme expression.

  7. Macro-Climatic Distribution Limits Show Both Niche Expansion and Niche Specialization among C4 Panicoids

    PubMed Central

    Aagesen, Lone; Biganzoli, Fernando; Bena, Julia; Godoy-Bürki, Ana C.; Reinheimer, Renata; Zuloaga, Fernando O.

    2016-01-01

    Grasses are ancestrally tropical understory species whose current dominance in warm open habitats is linked to the evolution of C4 photosynthesis. C4 grasses maintain high rates of photosynthesis in warm and water stressed environments, and the syndrome is considered to induce niche shifts into these habitats while adaptation to cold ones may be compromised. Global biogeographic analyses of C4 grasses have, however, concentrated on diversity patterns, while paying little attention to distributional limits. Using phylogenetic contrast analyses, we compared macro-climatic distribution limits among ~1300 grasses from the subfamily Panicoideae, which includes 4/5 of the known photosynthetic transitions in grasses. We explored whether evolution of C4 photosynthesis correlates with niche expansions, niche changes, or stasis at subfamily level and within the two tribes Paniceae and Paspaleae. We compared the climatic extremes of growing season temperatures, aridity, and mean temperatures of the coldest months. We found support for all the known biogeographic distribution patterns of C4 species, these patterns were, however, formed both by niche expansion and niche changes. The only ubiquitous response to a change in the photosynthetic pathway within Panicoideae was a niche expansion of the C4 species into regions with higher growing season temperatures, but without a withdrawal from the inherited climate niche. Other patterns varied among the tribes, as macro-climatic niche evolution in the American tribe Paspaleae differed from the pattern supported in the globally distributed tribe Paniceae and at family level. PMID:26950074

  8. Functions of OsDof25 in regulation of OsC4PPDK.

    PubMed

    Zhang, Y; Verhoeff, N I; Chen, Z; Chen, S; Wang, Mei; Zhu, Zhen; Ouwerkerk, P B F

    2015-10-01

    Relative little is known about the functions of the so-called Dof zinc factors in plants. Here we report on the analysis of OsDof25 and show a function in regulation of the important C4 photosynthesis gene, OsC4PPDK in rice. Over-expression of OsDof25 enhanced the expression of OsC4PPDK in transient expression experiments by binding in a specific way to a conserved Dof binding site which was confirmed by yeast and in vitro binding studies. Expression studies using promoter GUS plants as well as qPCR experiments showed that OsDof25 expressed in different tissues including both photosynthetic and non-photosynthetic organs and that expression of OsDof25 was partially overlapping with the OsC4PPDK gene. Conclusive evidence for a role of OsDof25 in regulation of C4PPDK came from loss-of-function and gain-of-function experiments with transgenic rice, which showed that down-regulation or over-expression of OsDof25 correlated with OsC4PPDK expression and that OsDof25 has functions as transcriptional activator.

  9. C4 Photosynthesis Promoted Species Diversification during the Miocene Grassland Expansion

    PubMed Central

    Spriggs, Elizabeth L.; Christin, Pascal-Antoine; Edwards, Erika J.

    2014-01-01

    Identifying how organismal attributes and environmental change affect lineage diversification is essential to our understanding of biodiversity. With the largest phylogeny yet compiled for grasses, we present an example of a key physiological innovation that promoted high diversification rates. C4 photosynthesis, a complex suite of traits that improves photosynthetic efficiency under conditions of drought, high temperatures, and low atmospheric CO2, has evolved repeatedly in one lineage of grasses and was consistently associated with elevated diversification rates. In most cases there was a significant lag time between the origin of the pathway and subsequent radiations, suggesting that the ‘C4 effect’ is complex and derives from the interplay of the C4 syndrome with other factors. We also identified comparable radiations occurring during the same time period in C3 Pooid grasses, a diverse, cold-adapted grassland lineage that has never evolved C4 photosynthesis. The mid to late Miocene was an especially important period of both C3 and C4 grass diversification, coincident with the global development of extensive, open biomes in both warm and cool climates. As is likely true for most “key innovations”, the C4 effect is context dependent and only relevant within a particular organismal background and when particular ecological opportunities became available. PMID:24835188

  10. Determination of leaf carbon isotope discrimination in C4 plants under variable N and water supply.

    PubMed

    Yang, Hao; Yu, Qiang; Sheng, Wen-Ping; Li, Sheng-Gong; Tian, Jing

    2017-03-23

    Understanding the mechanisms underlying variations in carbon isotope discrimination (Δ) in C4 plants is critical for predicting the C3/C4 ratio in C3/C4 mixed grassland. The value of Δ is determined by bundle sheath leakiness (Ф) and the ratio of intercellular to ambient CO2 concentration (C i /C a ). Leaf nitrogen concentration (N leaf ) is considered a driver of Δ in C4 plants. However, little is known about how N leaf affects Ф and C i /C a , and subsequently Δ. Here leaf carbon isotope composition, N leaf , Ф, and leaf gas exchange were measured in Cleistogenes squarrosa, a dominant C4 species in the Inner Mongolia grassland. Δ remained relatively stable under variable N and water supply. Higher N supply and lower water supply increased N leaf , stimulated photosynthesis and further decreased C i /C a . High N supply increased Ф, which responded weakly to water supply. N leaf exerted similar effects on C i /C a and on Ф in the field and pot experiments. Pooling all the data, N leaf explained 73% of the variation in C i /C a . Overall, both Ф and C i /C a determined Δ; however, the contribution of Ф was stronger. N leaf influenced Δ primarily though C i /C a , rather than Ф. Ф should be considered in estimating Δ of C4 endmember.

  11. Genome-scale modeling of the evolutionary path to C4 photosynthesis

    NASA Astrophysics Data System (ADS)

    Myers, Christopher R.; Bogart, Eli

    In C4 photosynthesis, plants maintain a high carbon dioxide level in specialized bundle sheath cells surrounding leaf veins and restrict CO2 assimilation to those cells, favoring CO2 over O2 in competition for Rubisco active sites. In C3 plants, which do not possess such a carbon concentrating mechanism, CO2 fixation is reduced due to this competition. Despite the complexity of the C4 system, it has evolved convergently from more than 60 independent origins in diverse families of plants around the world over the last 30 million years. We study the evolution of the C4 system in a genome-scale model of plant metabolism that describes interacting mesophyll and bundle sheath cells and enforces key nonlinear kinetic relationships. Adapting the zero-temperature string method for simulating transition paths in physics and chemistry, we find the highest-fitness paths connecting C3 and C4 positions in the model's high-dimensional parameter space, and show that they reproduce known aspects of the C3-C4 transition while making additional predictions about metabolic changes along the path. We explore the relationship between evolutionary history and C4 biochemical subtype, and the effects of atmospheric carbon dioxide levels.

  12. Carbon dioxide starvation, the development of C4 ecosystems, and mammalian evolution.

    PubMed Central

    Cerling, T E; Ehleringer, J R; Harris, J M

    1998-01-01

    The decline of atmospheric CO2 over the last 65 million years (Ma) resulted in the 'CO2-starvation' of terrestrial ecosystems and led to the widespread distribution of C4 plants, which are less sensitive to CO2 levels than are C3 plants. Global expansion of C4 biomass is recorded in the diets of mammals from Asia, Africa, North America, and South America during the interval from about 8 to 5 Ma. This was accompanied by the most significant Cenozoic faunal turnover on each of these continents, indicating that ecological changes at this time were an important factor in mammalian extinction. Further expansion of tropical C4 biomass in Africa also occurred during the last glacial interval confirming the link between atmospheric CO2 levels and C4 biomass response. Changes in fauna and flora at the end of the Miocene, and between the last glacial and interglacial, have previously been attributed to changes in aridity; however, an alternative explanation for a global expansion of C4 biomass is CO2 starvation of C3 plants when atmospheric CO2 levels dropped below a threshold significant to C3 plants. Aridity may also have been a factor in the expansion of C4 ecosystems but one that was secondary to, and perhaps because of, gradually decreasing CO2 concentrations in the atmosphere. Mammalian evolution in the late Neogene, then, may be related to the CO2 starvation of C3 ecosystems. PMID:9507562

  13. Characterization and Inhibitor Screening of Plateau Zokor Lactate Dehydrogenase C4.

    PubMed

    He, Qinghua; Zhang, Qinglian; Huang, Lin; Ma, Jinhu

    2016-07-01

    Lactate dehydrogenase C4 (LDH-C4) is considered to be a target protein for the development of contraceptives. In this work, the characterization of plateau zokor LDH-C4 and the screening of a series of N-substituted oxamic acids as inhibitors against zokor LDH-C4 were reported. The cDNA of zokor LDH-C gene was cloned and expressed in Escherichia coli, from which the protein was purified and further characterized. The protein was a tetramer (LDH-C4) and thermally stable up to 62 °C with a K m of 63.9 μM for pyruvate and with optimal pH values of 7.95 and 10.1 for the forward and backward reactions respectively. Virtual and in vitro screening against zokor LDH-C4 revealed eight N-substituted oxamic acids with IC50s ranging from 198 to 2513 μM, higher than that of oxamic acid (150 μM) and (ethylamino)(oxo)acetic acid (59 μM). The inhibition potencies of N-substituted oxamic acids tested are in the micromolar range, and the increase in the length of substituting chain seems not to increase inhibition potency.

  14. Differential resource utilization by extant great apes and australopithecines: towards solving the C4 conundrum.

    PubMed

    Sponheimer, Matt; Lee-Thorp, Julia A

    2003-09-01

    Morphological and biogeochemical evidence suggest that australopithecines had diets markedly different from those of extant great apes. Stable carbon isotope analysis, for example, has shown that significant amounts of the carbon consumed by australopithecines were derived from C(4) photosynthesis in plants. This means that australopithecines were eating large quantities of C(4) plants such as tropical grasses and sedges, or were eating animals that were themselves eating C(4) plants. In contrast, there is no evidence that modern apes consume appreciable amounts of any of these foods, even in the most arid extents of their ranges where these foods are most prevalent. Environmental reconstructions of early australopithecine environments overlap with modern chimpanzee habitats. This, in conjunction with the stable isotope evidence, suggests that australopithecines and great apes, even in similar environments, would utilize available resources differently. Thus, the desire or capacity to use C(4) foods may be a basal character of our lineage. We do not know, however, which of the nutritionally disparate C(4) foods were utilized by hominids. Here we discuss which C(4) resources were most likely consumed by australopithecines, as well as the potential nutritional, physiological, and social consequences of eating these foods.

  15. Overproduction of C4 photosynthetic enzymes in transgenic rice plants: an approach to introduce the C4-like photosynthetic pathway into rice.

    PubMed

    Taniguchi, Yojiro; Ohkawa, Hiroshi; Masumoto, Chisato; Fukuda, Takuya; Tamai, Tesshu; Lee, Kwanghong; Sudoh, Sizue; Tsuchida, Hiroko; Sasaki, Haruto; Fukayama, Hiroshi; Miyao, Mitsue

    2008-01-01

    Four enzymes, namely, the maize C(4)-specific phosphoenolpyruvate carboxylase (PEPC), the maize C(4)-specific pyruvate, orthophosphate dikinase (PPDK), the sorghum NADP-malate dehydrogenase (MDH), and the rice C(3)-specific NADP-malic enzyme (ME), were overproduced in the mesophyll cells of rice plants independently or in combination. Overproduction individually of PPDK, MDH or ME did not affect the rate of photosynthetic CO(2) assimilation, while in the case of PEPC it was slightly reduced. The reduction in CO(2) assimilation in PEPC overproduction lines remained unaffected by overproduction of PPDK, ME or a combination of both, however it was significantly restored by the combined overproduction of PPDK, ME, and MDH to reach levels comparable to or slightly higher than that of non-transgenic rice. The extent of the restoration of CO(2) assimilation, however, was more marked at higher CO(2) concentrations, an indication that overproduction of the four enzymes in combination did not act to concentrate CO(2) inside the chloroplast. Transgenic rice plants overproducing the four enzymes showed slight stunting. Comparison of transformants overproducing different combinations of enzymes indicated that overproduction of PEPC together with ME was responsible for stunting, and that overproduction of MDH had some mitigating effects. Possible mechanisms underlying these phenotypic effects, as well as possibilities and limitations of introducing the C(4)-like photosynthetic pathway into C(3) plants, are discussed.

  16. Anopheles Midgut Epithelium Evades Human Complement Activity by Capturing Factor H from the Blood Meal

    PubMed Central

    Khattab, Ayman; Barroso, Marta; Miettinen, Tiera; Meri, Seppo

    2015-01-01

    Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood. PMID:25679788

  17. Isolation and characterization of a complement-activating lipid extracted from human atherosclerotic lesions

    PubMed Central

    1990-01-01

    The major characteristics of human atherosclerotic lesions are similar to those of a chronic inflammatory reaction, namely fibrosis, mesenchymal cell proliferation, the presence of resident macrophages, and cell necrosis. Atherosclerosis exhibits in addition the feature of lipid (mainly cholesterol) accumulation. The results of the present report demonstrate that a specific cholesterol-containing lipid particle present in human atherosclerotic lesions activates the complement system to completion. Thus, lipid could represent a stimulatory factor for the inflammatory reaction, whose underlying mechanistic basis may be, at least in part, complement activation. The complement-activating lipid was purified from saline extracts of aortic atherosclerotic lesions by sucrose density gradient centrifugation followed by molecular sieve chromatography on Sepharose 2B. It contained little protein other than albumin, was 100-500 nm in size, exhibited an unesterified to total cholesterol ratio of 0.58 and an unesterified cholesterol to phospholipid ratio of 1.2. The lipid, termed lesion lipid complement (LCA), activated the alternative pathway of complement in a dose-dependent manner. Lesion-extracted low density lipoprotein (LDL) obtained during the purification procedure failed to activate complement. Specific generation of C3a desArg and C5b-9 by LCA indicated C3/C5 convertase formation with activation proceeding to completion. Biochemical and electron microscopic evaluations revealed that much of the C5b-9 present in atherosclerotic lesions is membraneous, rather than fluid phase SC5b-9. The observations reported herein establish a link between lipid insudation and inflammation in atherosclerotic lesions via the mechanism of complement activation. PMID:2373993

  18. Detection of complement activation by counterimmunoelectrophoresis (CIE).

    PubMed

    Arroyave, C M; Tan, E M

    1976-01-01

    Counterimmunoelectrophoresis (CIE) was used as a method of detecting activation of the third component of the complement system (C3). Highly purified C3, normal human serum (NHS), EDTA-treated plasma and serum activated with aggregated human immunoglobulin (agg-IgG) or inulin were used as sources of C3 and/or C3 split products. Activation of the alternative pathway of complement was assayed in the presence of EGTA (10 mM) and MgCl2 (0.3 mM), conditions which block activation of the classical pathway. When purified native C3, fresh NHS and fresh EDTA-plasma were tested in CIE against either antisera to whole C3 or to C3 split products, only one precipitin line was found, which was identified as native C3. However, when serum activated with agg-IgG or inulin were tested against the same reagents, two precipitin lines were seen. The first, with more cathodal mobility was identical to that of native C3. The second line had a more anodal mobility, was distinctly separated from the first and contained C3c and C3d as shown immunochemically with specific antisera. Native C3 and split products of C3 were identified by this CIE method in patients showing evidence of activated complement by having subnormal total complement (CH50) levels. When C3 split products were identified, the C3c-C3d precipitin line could always be distinguished from native C3 by its different electrophoretic mobility, even when C3 concentrations in serum varied from 0.25 mg/ml to 1.5 mg/ml. The sensitivity of CIE was compared to that of CH50 by asssaying at different time intervals after agg-IgG was added to fresh NHS. C3c-C3d split products were detected by CIE before any fall in CH50 and at all times when a significant decrease in CH50 was present. This study shows that the CIE technique is a highly sensitive, specific and rapid method for detecting activation of the complement system via classical or alternative pathways in human disease.

  19. Contribution of Chondroitin Sulfate A to the Binding of Complement Proteins to Activated Platelets

    PubMed Central

    Lasaosa, Maria; Ricklin, Daniel; Lambris, John D.; Nilsson, Bo; Nilsson Ekdahl, Kristina

    2010-01-01

    Background Exposure of chondroitin sulfate A (CS-A) on the surface of activated platelets is well established. The aim of the present study was to investigate to what extent CS-A contributes to the binding of the complement recognition molecule C1q and the complement regulators C1 inhibitor (C1INH), C4b-binding protein (C4BP), and factor H to platelets. Principal Findings Human blood serum was passed over Sepharose conjugated with CS-A, and CS-A-specific binding proteins were identified by Western blotting and mass spectrometric analysis. C1q was shown to be the main protein that specifically bound to CS-A, but C4BP and factor H were also shown to interact. Binding of C1INH was dependent of the presence of C1q and then not bound to CS-A from C1q-depleted serum. The specific interactions observed of these proteins with CS-A were subsequently confirmed by surface plasmon resonance analysis using purified proteins. Importantly, C1q, C4BP, and factor H were also shown to bind to activated platelets and this interaction was inhibited by a CS-A-specific monoclonal antibody, thereby linking the binding of C1q, C4BP, and factor H to exposure of CS-A on activated platelets. CS-A-bound C1q was also shown to amplify the binding of model immune complexes to both microtiter plate-bound CS-A and to activated platelets. Conclusions This study supports the concept that CS-A contributes to the binding of C1q, C4BP, and factor H to platelets, thereby adding CS-A to the previously reported binding sites for these proteins on the platelet surface. CS-A-bound C1q also seems to amplify the binding of immune complexes to activated platelets, suggesting a role for this molecule in immune complex diseases. PMID:20886107

  20. Age-related macular degeneration: Complement in action.

    PubMed

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD.

  1. Improving our understanding of environmental controls on the distribution of C3 and C4 grasses.

    PubMed

    Pau, Stephanie; Edwards, Erika J; Still, Christopher J

    2013-01-01

    A number of studies have demonstrated the ecological sorting of C3 and C4 grasses along temperature and moisture gradients. However, previous studies of C3 and C4 grass biogeography have often inadvertently compared species in different and relatively unrelated lineages, which are associated with different environmental settings and distinct adaptive traits. Such confounded comparisons of C3 and C4 grasses may bias our understanding of ecological sorting imposed strictly by photosynthetic pathway. Here, we used MaxEnt species distribution modeling in combination with satellite data to understand the functional diversity of C3 and C4 grasses by comparing both large clades and closely related sister taxa. Similar to previous work, we found that C4 grasses showed a preference for regions with higher temperatures and lower precipitation compared with grasses using the C3 pathway. However, air temperature differences were smaller (2 °C vs. 4 °C) and precipitation and % tree cover differences were larger (1783 mm vs. 755 mm, 21.3% vs. 7.7%, respectively) when comparing C3 and C4 grasses within the same clade vs. comparing all C4 and all C3 grasses (i.e., ignoring phylogenetic structure). These results were due to important differences in the environmental preferences of C3 BEP and PACMAD clades (the two main grass clades). Winter precipitation was found to be more important for understanding the distribution and environmental niche of C3 PACMADs in comparison with both C3 BEPs and C4 taxa, for which temperature was much more important. Results comparing closely related C3 -C4 sister taxa supported the patterns derived from our modeling of the larger clade groupings. Our findings, which are novel in comparing the distribution and niches of clades, demonstrate that the evolutionary history of taxa is important for understanding the functional diversity of C3 and C4 grasses, and should have implications for how grasslands will respond to global change.

  2. Leaf Vascular Systems in C3 and C4 Grasses: A Two-dimensional Analysis

    PubMed Central

    UENO, OSAMU; KAWANO, YUKIKO; WAKAYAMA, MASATAKA; TAKEDA, TOMOSHIRO

    2006-01-01

    • Background and Aims It is well documented that C4 grasses have a shorter distance between longitudinal veins in the leaves than C3 grasses. In grass leaves, however, veins with different structures and functions are differentiated: large longitudinal veins, small longitudinal veins and transverse veins. Thus, the densities of the three types of vein in leaves of C3 and C4 grasses were investigated from a two-dimensional perspective. • Methods Vein densities in cleared leaves of 15 C3 and 26 C4 grasses representing different taxonomic groups and photosynthetic subtypes were analysed. • Key Results The C4 grasses had denser transverse veins and denser small longitudinal veins than the C3 grasses (1·9 and 2·1 times in interveinal distance), but there was no significant difference in large longitudinal veins. The total length of the three vein types per unit area in the C4 grasses was 2·1 times that in the C3 grasses. The ratio of transverse vein length to total vein length was 14·3 % in C3 grasses and 9·9 % in C4 grasses. The C3 grasses generally had greater species variation in the vascular distances than the C4 grasses. The bambusoid and panicoid C3 grasses tended to have a denser vascular system than the festucoid C3 grasses. There were no significant differences in the interveinal distances of the three vein types between C4 subtypes, although the NADP-malic enzyme grasses tended to have a shorter distance between small longitudinal veins than the NAD-malic enzyme and phosphoenolpyruvate carboxykinase grasses. • Conclusions It seems that C4 grasses have structurally a superior photosynthate translocation and water distribution system by developing denser networks of small longitudinal and transverse veins, while keeping a constant density of large longitudinal veins. The bambusoid and panicoid C3 grasses have a vascular system that is more similar to that in C4 grasses than to that in the festucoid C3 grasses. PMID:16464879

  3. The role of higher-order protein structure in supporting binding by heteroclitic monoclonal antibodies: the monoclonal antibody KIM185 to CD18 also binds C4-binding protein.

    PubMed

    Gjelstrup, Louise Carstensen; Andersen, Stig Henrik; Petersen, Steen Vang; Enghild, Jan J; Blom, Anna M; Vorup-Jensen, Thomas; Thiel, Steffen

    2011-10-01

    Heteroclitic monoclonal antibodies are characterized by the ability to bind multiple epitopes with little or no similarity. Such antibodies have been reported earlier, but insight into to the molecular basis of this propensity is limited. Here we report that the KIM185 antibody to human CD18 reacts with the plasma protein C4b-binding protein (C4BP). This was revealed during affinity purification procedures where human serum was incubated with surfaces coated with monoclonal antibodies to CD18. Other monoclonal antibodies to CD18 (KIM127 and TS1/18) showed no such interaction with C4BP. We constructed a sandwich-type time-resolved immunofluorometric assay using KIM185 both as capture and developing antibody. By use of proteolytic fragments of KIM185 and recombinant deletion mutants of C4BP the interaction sites were mapped to the variable region of KIM185 and the oligomerization domain of C4BP, respectively. C4BP is a large oligomeric plasma protein that binds activated complement factor C4b and other endogenous ligands as well as microorganisms. By use of the recent crystallographic data on the structure of CD11c/CD18 and prediction of the secondary structure of the C4BP oligomerization domain, we show that epitopes bound by KIM185 in these proteins are unlikely to share any major structural similarity. However, both antigens may form oligomers that would enable avid binding by the antibody. Our report points to the astonishing ability of heteroclitic antibodies to accommodate the binding of multiple proteins with no or little structural similarity within the confined space of the variable regions.

  4. Complementing ultrafast shape recognition with an optical isomerism descriptor.

    PubMed

    Zhou, Ting; Lafleur, Karine; Caflisch, Amedeo

    2010-11-01

    We introduce the mixed product of three vectors spanning four molecular locations as a descriptor of optical isomerism. This descriptor is very efficient as it does not require molecular superposition, and is very robust in discriminating between a given isomer and its mirror image. In particular, conformational isomers that are mirror images of each other, as well as optical isomers have opposite sign of the descriptor value. For efficient database searches, the optical isomerism descriptor can be used to complement an available ultrafast shape recognition (USR) method based solely on distances, which is not able to distinguish enantiomers. By an extensive comparison of the USR-based similarity score with an approach based on Gaussian molecular volume overlap, the accuracy and completeness of the former are discussed.

  5. C4: Exploring Multiple Solutions in Graphical Models by Cluster Sampling.

    PubMed

    Porway, Jake; Zhu, Song-Chun

    2011-09-01

    This paper presents a novel Markov Chain Monte Carlo (MCMC) inference algorithm called C(4)--Clustering with Cooperative and Competitive Constraints--for computing multiple solutions from posterior probabilities defined on graphical models, including Markov random fields (MRF), conditional random fields (CRF), and hierarchical models. The graphs may have both positive and negative edges for cooperative and competitive constraints. C(4) is a probabilistic clustering algorithm in the spirit of Swendsen-Wang. By turning the positive edges on/off probabilistically, C(4) partitions the graph into a number of connected components (ccps) and each ccp is a coupled subsolution with nodes connected by positive edges. Then, by turning the negative edges on/off probabilistically, C(4) obtains composite ccps (called cccps) with competing ccps connected by negative edges. At each step, C(4) flips the labels of all nodes in a cccp so that nodes in each ccp keep the same label while different ccps are assigned different labels to observe both positive and negative constraints. Thus, the algorithm can jump between multiple competing solutions (or modes of the posterior probability) in a single or a few steps. It computes multiple distinct solutions to preserve the intrinsic ambiguities and avoids premature commitments to a single solution that may not be valid given later context. C(4) achieves a mixing rate faster than existing MCMC methods, such as various Gibbs samplers and Swendsen-Wang cuts. It is also more "dynamic" than common optimization methods such as ICM, LBP, and graph cuts. We demonstrate the C(4) algorithm in line drawing interpretation, scene labeling, and object recognition.

  6. Photosynthetic, hydraulic and biomass properties in closely related C3 and C4 species.

    PubMed

    Kocacinar, Ferit

    2015-03-01

    In plants, most water is absorbed by roots and transported through vascular conduits of xylem which evaporate from leaves during photosynthesis. As photosynthesis and transport processes are interconnected, it was hypothesized that any variation in water transport demand influencing water use efficiency (WUE), such as the evolution of C4 photosynthesis, should affect xylem structure and function. Several studies have provided evidence for this hypothesis, but none has comprehensively compared photosynthetic, hydraulic and biomass allocation properties between C3 and C4 species. In this study, photosynthetic, hydraulic and biomass properties in a closely related C3 Tarenaya hassleriana and a C4 Cleome gynandra are compared. Light response curves, measured at 30°C, showed that the C4 C. gynandra had almost twice greater net assimilation rates than the C3 T. hassleriana under each increasing irradiation level. On the contrary, transpiration rates and stomatal conductance were around twice as high in the C3 , leading to approximately 3.5 times higher WUE in the C4 compared with the C3 species. The C3 showed about 3.3 times higher hydraulic conductivity, 4.3 times greater specific conductivity and 2.6 times higher leaf-specific conductivity than the C4 species. The C3 produced more vessels per xylem area and larger vessels. All of these differences resulted in different biomass properties, where the C4 produced more biomass in general and had less root to shoot ratio than the C3 species. These results are in support of our previous findings that WUE, and any changes that affect WUE, contribute to xylem evolution in plants.

  7. Responses of carbon isotope discrimination in C4 plant to variable N and water supply

    NASA Astrophysics Data System (ADS)

    Yang, Hao; Li, Shenggong

    2016-04-01

    Understanding variations and underlying mechanisms of carbon isotope discrimination (Δ) in C4 species is critical for predicting the effects of change in C3/C4 ratio of plant community on ecosystem processes and functionning. However, little is known about the effects of soil resource gradients on Δ of C4 plants. To address Δ responses to drought and nitrogen supply, the leaf carbon isotope composition, bundle sheath leakiness (BLS), and leaf gas exchange (A, gs, Ci/Ca) were measured on Cleistogenes squarrosa, a dominant C4 species in the Inner Mongolia grassland. C. squarrosa were grown in controlled-environment pots from seed under a combination of water and N supply. High N availability and drought stimulated photosynthetic rate (A) and further decreased the ratio of internal and ambient CO2 concentrations (Ci/Ca) through increasing leaf N content. BLS was higher under high N supply and was unchanged by drought. There was significant interaction between N and water supply to affect BLS and Ci/Ca. Δ was negatively related to Ci/Ca and was positively related to BLS. Tradeoff between the responses of BLS and Ci/Ca to changing environmental conditions kept leaf Δ relatively stable, which was also supported by a field N addition experiment. Our results suggested leaf Δ of C4 plant was unchanged under variable water and N environment conditions although the operating efficiency of C4 pathway and CO2 concentration in photosynthesis were changed. Our findings have implications for predicting the change of C3/C4 ratio of plant community and understanding ecosystem processes and functionning.

  8. Electron attachment and detachment and the electron affinity of cyclo-C4F8

    NASA Astrophysics Data System (ADS)

    Miller, Thomas M.; Friedman, Jeffrey F.; Viggiano, A. A.

    2004-04-01

    New measurements have been made of rate constants for electron attachment to c-C4F8 (octafluorocyclobutane) and thermal electron detachment from the parent anion, c-C4F8-, over the temperature range 298-400 K in 133 Pa of He gas in a flowing-afterglow Langmuir-probe apparatus. From these data the electron affinity for c-C4F8 was determined, EA(c-C4F8)=0.63±0.05 eV. The motivation was to resolve a discrepancy between our earlier EA estimate and a higher value (EA=1.05±0.10 eV) reported from a recent experiment of Hiraoka et al. [J. Chem. Phys. 116, 7574 (2002)]. The electron attachment rate constant is 9.3±3.0×10-9 cm3 s-1 at 298 K. The electron detachment rate constant is negligible at room temperature but climbs to 1945±680 s-1 at 400 K. G3(MP2) calculations were carried out for the neutral (D2d, 1A1) and anion (D4h, 2A2u) and yielded EA(c-C4F8-)=0.595 eV. Bond energies were also calculated for loss of F from c-C4F8 and loss of F or F- from c-C4F8-. From these, dissociative electron attachment is found to be endothermic by at least 1.55 eV.

  9. Electron attachment and detachment and the electron affinity of cyclo-C4F8.

    PubMed

    Miller, Thomas M; Friedman, Jeffrey F; Viggiano, A A

    2004-04-15

    New measurements have been made of rate constants for electron attachment to c-C(4)F(8) (octafluorocyclobutane) and thermal electron detachment from the parent anion, c-C(4)F(8) (-), over the temperature range 298-400 K in 133 Pa of He gas in a flowing-afterglow Langmuir-probe apparatus. From these data the electron affinity for c-C(4)F(8) was determined, EA(c-C(4)F(8))=0.63+/-0.05 eV. The motivation was to resolve a discrepancy between our earlier EA estimate and a higher value (EA=1.05+/-0.10 eV) reported from a recent experiment of Hiraoka et al. [J. Chem. Phys. 116, 7574 (2002)]. The electron attachment rate constant is 9.3+/-3.0x10(-9) cm(3) s(-1) at 298 K. The electron detachment rate constant is negligible at room temperature but climbs to 1945+/-680 s(-1) at 400 K. G3(MP2) calculations were carried out for the neutral (D(2d), (1)A(1)) and anion (D(4h), (2)A(2u)) and yielded EA(c-C(4)F(8) (-))=0.595 eV. Bond energies were also calculated for loss of F from c-C(4)F(8) and loss of F or F(-) from c-C(4)F(8) (-). From these, dissociative electron attachment is found to be endothermic by at least 1.55 eV.

  10. Differential freezing resistance and photoprotection in C3 and C4 eudicots and grasses.

    PubMed

    Liu, Mei-Zhen; Osborne, Colin P

    2013-05-01

    Globally, C4 plants dominate hot, open environments, but this general pattern is underpinned by important differences in the biogeography of C4 lineages. In particular, the species richness of C4 Poaceae (grasses) increases strongly with increasing temperature, whereas that of the major C4 eudicot group Chenopodiaceae correlates positively with aridity. Freezing tolerance is a crucial determinant of biogeographical relationships with temperature and is mediated by photodamage and cellular disruption by desiccation, but little is known about differences between C4 families. This study hypothesized that there is a greater risk of freezing damage via these mechanisms in C4 Poaceae than Chenopodiaceae, that freezing protection differs between the taxonomic groups, and that freezing tolerance of species is linked to arid habitat preference. Chlorophyll fluorescence, water relations, and freezing injury were compared in four C3 and six C4 species of Poaceae and Chenopodiaceae from the same Mongolian flora. Contrary to expectations, freezing-induced leaf mortality and photodamage were lower in Poaceae than Chenopodiaceae species, and unrelated to photosynthetic pathway. The freezing resistance of Poaceae species resulted from constitutive protection and cold acclimation and an ability to protect the photosynthetic apparatus from photodamage. Freezing protection was associated with low osmotic potential and low tissue elasticity, and freezing damage was accompanied by electrolyte leakage, consistent with cell-membrane disruption by ice. Both Chenopodiaceae and Poaceae had the potential to develop cold acclimation and withstand freezing during the growing season, which conflicted with the hypothesis. Instead, freezing tolerance was more closely associated with life history and ecological preference in these Mongolian species.

  11. Construction of the plasmid, expression by Chinese hamster ovary cell, purification and characterization of the first three short consensus repeat modules of human complement receptor type 1.

    PubMed

    Yamaguchi, Atsushi; Takagawa, Hiroaki; Iwakaji, Hirofumi; Miyagawa, Shuji; Wang, Pi-Chao; Ishii, Noriyuki

    2009-04-01

    Short consensus repeat (SCR1-3), the first three SCR modules from N-terminus of type 1 complement receptor (CR1), is expected to accelerate dissociation of complement components and suppress complement activity by binding the main component of complement C4b. In order to clarify the three-dimensional structure, which triggers the activity of SCR1-3 on complement, we constructed an over-expression system in CHO DG44 cells which facilitated mass production of SCR1-3. The mass production was achieved by a two-stage culture system and optimum culture conditions using ASF104N medium and MTX-, NaBu-containing alpha-MEM/10% FBS medium, respectively. The constructed gene of SCR1-3 was confirmed by restriction enzyme digestion and DNA sequence analysis, and the expressed protein by CHO DG44 cells was confirmed by western blotting. The expressed SCR1-3 was proved containing N-linked sugar chain, an important factor to the proper expression of protein, by the cleavage with glycosidase of N-linked oligosaccharide (PNGase F). The suppression effect of the yield protein on complement-mediated inflammation was investigated by haemolytic assay and necrosis assay of stromal cells. Both assays showed that SCR1-3 possessed complement control activity. However, residing sugar chain on SCR1-3 did not show significant difference in the complement control activity.

  12. Complement blockade in ANCA-associated vasculitis: an index case, current concepts and future perspectives.

    PubMed

    Manenti, Lucio; Urban, Maria Letizia; Maritati, Federica; Galetti, Maricla; Vaglio, Augusto

    2017-02-13

    Complement alternative pathway (cAP) hyperactivation seems to be involved in ANCA-associated vasculitis (AAV). We here describe a case of AAV with severe activation of cAP that developed acute renal failure. No mutation predisposing to cAP dysregulation was identified. We treated our patient with the standard immunosuppressive therapy, but disease progression was only reversed after the addition of eculizumab, a monoclonal antibody against C5; the patient eventually achieved an almost complete renal function recovery. A review of the available literature about the role of complement targeted therapies in the treatment of AAV is discussed.

  13. Complementing asteroseismology with 4MOST spectroscopy

    NASA Astrophysics Data System (ADS)

    de Jong, R. S.; 4MOST Consortium; 4MOST Spectroscopy Consortium

    2016-09-01

    4MOST is a wide-field, high-multiplex spectroscopic survey facility under development for the VISTA telescope of the European Southern Observatory (ESO). Its main science drivers are in the areas of galactic archeology, high-energy physics, galaxy evolution and cosmology. 4MOST will in particular provide the spectroscopic complements to the large area surveys coming from space missions like Gaia, eROSITA, Euclid, and PLATO. 4MOST will have an unique operations concept in which 5-years public surveys from both the consortium and the ESO community will be combined and observed in parallel during each exposure, resulting in more than 25 million spectra of targets spread over a large fraction of the southern sky. As a dedicated spectroscopic survey facility with a large field-of-view, a high multiplex that can be reconfigured quickly, and with a broad wavelength coverage, 4MOST is particularly well suited to complement the upcoming asteroseismology space missions like TESS and PLATO. Here we show that, by dedicating the observing time during twilight and poor observing conditions to bright stars, 4MOST will obtain resolution {R>18 000} spectra of nearly all stars brighter than ˜ 12th magnitude at Dec < 30o every ˜ 2 years. 4MOST is also expected to spectroscopically complement any fainter asteroseismology target to be observed with PLATO. These observations will provide a chemical characterization of nearly all stars to be observed with the TESS and PLATO missions and place any planets found in a full chemo-dynamical context of the star formation history of the Galaxy, yield very accurate ages and masses for all stars that can be characterized with asteroseismology, and allow removal of contaminants from target samples (e.g., spectroscopic binaries).

  14. Increasing water use efficiency along the C3 to C4 evolutionary pathway: a stomatal optimization perspective.

    PubMed

    Way, Danielle A; Katul, Gabriel G; Manzoni, Stefano; Vico, Giulia

    2014-07-01

    C4 photosynthesis evolved independently numerous times, probably in response to declining atmospheric CO2 concentrations, but also to high temperatures and aridity, which enhance water losses through transpiration. Here, the environmental factors controlling stomatal behaviour of leaf-level carbon and water exchange were examined across the evolutionary continuum from C3 to C4 photosynthesis at current (400 μmol mol(-1)) and low (280 μmol mol(-1)) atmospheric CO2 conditions. To this aim, a stomatal optimization model was further developed to describe the evolutionary continuum from C3 to C4 species within a unified framework. Data on C3, three categories of C3-C4 intermediates, and C4 Flaveria species were used to parameterize the stomatal model, including parameters for the marginal water use efficiency and the efficiency of the CO2-concentrating mechanism (or C4 pump); these two parameters are interpreted as traits reflecting the stomatal and photosynthetic adjustments during the C3 to C4 transformation. Neither the marginal water use efficiency nor the C4 pump strength changed significantly from C3 to early C3-C4 intermediate stages, but both traits significantly increased between early C3-C4 intermediates and the C4-like intermediates with an operational C4 cycle. At low CO2, net photosynthetic rates showed continuous increases from a C3 state, across the intermediates and towards C4 photosynthesis, but only C4-like intermediates and C4 species (with an operational C4 cycle) had higher water use efficiencies than C3 Flaveria. The results demonstrate that both the marginal water use efficiency and the C4 pump strength increase in C4 Flaveria to improve their photosynthesis and water use efficiency compared with C3 species. These findings emphasize that the advantage of the early intermediate stages is predominantly carbon based, not water related.

  15. Increasing water use efficiency along the C3 to C4 evolutionary pathway: a stomatal optimization perspective

    PubMed Central

    Way, Danielle A.; Katul, Gabriel G.; Manzoni, Stefano; Vico, Giulia

    2014-01-01

    C4 photosynthesis evolved independently numerous times, probably in response to declining atmospheric CO2 concentrations, but also to high temperatures and aridity, which enhance water losses through transpiration. Here, the environmental factors controlling stomatal behaviour of leaf-level carbon and water exchange were examined across the evolutionary continuum from C3 to C4 photosynthesis at current (400 μmol mol–1) and low (280 μmol mol–1) atmospheric CO2 conditions. To this aim, a stomatal optimization model was further developed to describe the evolutionary continuum from C3 to C4 species within a unified framework. Data on C3, three categories of C3–C4 intermediates, and C4 Flaveria species were used to parameterize the stomatal model, including parameters for the marginal water use efficiency and the efficiency of the CO2-concentrating mechanism (or C4 pump); these two parameters are interpreted as traits reflecting the stomatal and photosynthetic adjustments during the C3 to C4 transformation. Neither the marginal water use efficiency nor the C4 pump strength changed significantly from C3 to early C3–C4 intermediate stages, but both traits significantly increased between early C3–C4 intermediates and the C4-like intermediates with an operational C4 cycle. At low CO2, net photosynthetic rates showed continuous increases from a C3 state, across the intermediates and towards C4 photosynthesis, but only C4-like intermediates and C4 species (with an operational C4 cycle) had higher water use efficiencies than C3 Flaveria. The results demonstrate that both the marginal water use efficiency and the C4 pump strength increase in C4 Flaveria to improve their photosynthesis and water use efficiency compared with C3 species. These findings emphasize that the advantage of the early intermediate stages is predominantly carbon based, not water related. PMID:24860185

  16. VISUALIZATION OF MOLECULAR INTERACTIONS BY FLUORESCENCE COMPLEMENTATION

    PubMed Central

    Kerppola, Tom K.

    2008-01-01

    The visualization of protein complexes in living cells enables validation of protein interactions in their normal environment and determination of their subcellular localization. The bimolecular fluorescence complementation (BiFC) assay has been used to visualize interactions among multiple proteins in many cell types and organisms. This assay is based on the association between two fluorescent-protein fragments when they are brought together by an interaction between proteins fused to the fragments. Modified forms of this assay have been used to visualize the competition between alternative interaction partners and the covalent modification of proteins by ubiquitin family peptides. PMID:16625152

  17. Significant involvement of PEP-CK in carbon assimilation of C4 eudicots

    PubMed Central

    Muhaidat, Riyadh; McKown, Athena D.

    2013-01-01

    Background and Aims C4 eudicot species are classified into biochemical sub-types of C4 photosynthesis based on the principal decarboxylating enzyme. Two sub-types are known, NADP-malic enzyme (ME) and NAD-ME; however, evidence for the occurrence or involvement of the third sub-type (phosphoenolpyruvate carboxykinase; PEP-CK) is emerging. In this study, the presence and activity of PEP-CK in C4 eudicot species of Trianthema and Zaleya (Sesuvioideae, Aizoaceae) is clarified through analysis of key anatomical features and C4 photosynthetic enzymes. Methods Three C4 species (T. portulacastrum, T. sheilae and Z. pentandra) were examined with light and transmission electron microscopy for leaf structural properties. Activities and immunolocalizations of C4 enzymes were measured for biochemical characteristics. Key Results Leaves of each species possess atriplicoid-type Kranz anatomy, but differ in ultrastructural features. Bundle sheath organelles are centripetal in T. portulacastrum and Z. pentandra, and centrifugal in T. sheilae. Bundle sheath chloroplasts in T. portulacastrum are almost agranal, whereas mesophyll counterparts have grana. Both T. sheilae and Z. pentandra are similar, where bundle sheath chloroplasts contain well-developed grana while mesophyll chloroplasts are grana deficient. Cell wall thickness is significantly greater in T. sheilae than in the other species. Biochemically, T. portulacastrum is NADP-ME, while T. sheilae and Z. pentandra are NAD-ME. Both T. portulacastrum and Z. pentandra exhibit considerable PEP-CK activity, and immunolocalization studies show dense and specific compartmentation of PEP-CK in these species, consistent with high PEP-CK enzyme activity. Conclusions Involvement of PEP-CK in C4 NADP-ME T. portulacastrum and NAD-ME Z. petandra occurs irrespective of biochemical sub-type, or the position of bundle sheath chloroplasts. Ultrastructural traits, including numbers of bundle sheath peroxisomes and mesophyll chloroplasts, and

  18. Temporal and spatial variations of canopy temperature over a C3C4 mixture grassland

    NASA Astrophysics Data System (ADS)

    Shimoda, S.; Oikawa, T.

    2006-10-01

    This study discusses the photosynthetic pathway types involved in canopy temperature measurements on a mixed grassland consisting of C3 and C4 plants (dominant species in biomass were Solidago altissima (C3), Miscanthus sinensis (C4), and Imperata cylindrica (C4)). In the wet conditions immediately after the rainy season, the mean canopy temperature for S. altissima was the lowest among the dominant species, mainly due to its leaf conductance being twice as large as the other two species. Despite using the same C4 photosynthetic pathway, M. sinensis had a lower apparent canopy temperature than I. cylindrica due to a smaller proportion of sunlit elements in the field of view. In the dry conditions during late July, the mean canopy temperatures of the three dominant species were within 0.3 °C of one another. These results can be explained by poor water conditions for C3 species (S. altissima). The simultaneous survey of vegetation and thermal imaging can help clarify characteristics of C3 and C4 canopy temperature over complicated grassland.

  19. Phenology and productivity of C3 and C4 grasslands in Hawaii.

    PubMed

    Pau, Stephanie; Still, Christopher J

    2014-01-01

    Grasslands account for a large proportion of global terrestrial productivity and play a critical role in carbon and water cycling. Within grasslands, photosynthetic pathway is an important functional trait yielding different rates of productivity along environmental gradients. Recently, C3-C4 sorting along spatial environmental gradients has been reassessed by controlling for confounding traits in phylogenetically structured comparisons. C3 and C4 grasses should sort along temporal environmental gradients as well, resulting in differing phenologies and growing season lengths. Here we use 10 years of satellite data (NDVI) to examine the phenology and greenness (as a proxy for productivity) of C3 and C4 grass habitats, which reflect differences in both environment and plant physiology. We perform phylogenetically structured comparisons based on 3,595 digitized herbarium collections of 152 grass species across the Hawaiian Islands. Our results show that the clade identity of grasses captures differences in their habitats better than photosynthetic pathway. Growing season length (GSL) and associated productivity (GSP) were not significantly different when considering photosynthetic type alone, but were indeed different when considering photosynthetic type nested within clade. The relationship between GSL and GSP differed most strongly between C3 clade habitats, and not between C3-C4 habitats. Our results suggest that accounting for the interaction between phylogeny and photosynthetic pathway can help improve predictions of productivity, as commonly used C3-C4 classifications are very broad and appear to mask important diversity in grassland ecosystem functions.

  20. Phenology and Productivity of C3 and C4 Grasslands in Hawaii

    PubMed Central

    Pau, Stephanie; Still, Christopher J.

    2014-01-01

    Grasslands account for a large proportion of global terrestrial productivity and play a critical role in carbon and water cycling. Within grasslands, photosynthetic pathway is an important functional trait yielding different rates of productivity along environmental gradients. Recently, C3-C4 sorting along spatial environmental gradients has been reassessed by controlling for confounding traits in phylogenetically structured comparisons. C3 and C4 grasses should sort along temporal environmental gradients as well, resulting in differing phenologies and growing season lengths. Here we use 10 years of satellite data (NDVI) to examine the phenology and greenness (as a proxy for productivity) of C3 and C4 grass habitats, which reflect differences in both environment and plant physiology. We perform phylogenetically structured comparisons based on 3,595 digitized herbarium collections of 152 grass species across the Hawaiian Islands. Our results show that the clade identity of grasses captures differences in their habitats better than photosynthetic pathway. Growing season length (GSL) and associated productivity (GSP) were not significantly different when considering photosynthetic type alone, but were indeed different when considering photosynthetic type nested within clade. The relationship between GSL and GSP differed most strongly between C3 clade habitats, and not between C3-C4 habitats. Our results suggest that accounting for the interaction between phylogeny and photosynthetic pathway can help improve predictions of productivity, as commonly used C3-C4 classifications are very broad and appear to mask important diversity in grassland ecosystem functions. PMID:25290341

  1. Metabolic Network Constrains Gene Regulation of C4 Photosynthesis: The Case of Maize.

    PubMed

    Robaina-Estévez, Semidán; Nikoloski, Zoran

    2016-05-01

    Engineering C3 plants to increase their efficiency of carbon fixation as well as of nitrogen and water use simultaneously may be facilitated by understanding the mechanisms that underpin the C4 syndrome. Existing experimental studies have indicated that the emergence of the C4 syndrome requires co-ordination between several levels of cellular organization, from gene regulation to metabolism, across two co-operating cell systems-mesophyll and bundle sheath cells. Yet, determining the extent to which the structure of the C4 plant metabolic network may constrain gene expression remains unclear, although it will provide an important consideration in engineering C4 photosynthesis in C3 plants. Here, we utilize flux coupling analysis with the second-generation maize metabolic models to investigate the correspondence between metabolic network structure and transcriptomic phenotypes along the maize leaf gradient. The examined scenarios with publically available data from independent experiments indicate that the transcriptomic programs of the two cell types are co-ordinated, quantitatively and qualitatively, due to the presence of coupled metabolic reactions in specific metabolic pathways. Taken together, our study demonstrates that precise quantitative coupling will have to be achieved in order to ensure a successfully engineered transition from C3 to C4 crops.

  2. Electron affinity of trans-2-C4F8 from electron attachment-detachment kinetics.

    PubMed

    Van Doren, Jane M; Condon, Laura R; DeSouza-Goding, Antonet; Miller, Thomas M; Bopp, Joseph C; Viggiano, A A

    2010-01-28

    Electron attachment and detachment kinetics of 2-C(4)F(8) were studied over the temperature range 298-487 K with a flowing-afterglow Langmuir-probe apparatus. Only parent anions were formed in the attachment process throughout this temperature range. At the highest temperatures, thermal electron detachment of the parent anions is important. Analysis of the 2-C(4)F(8) gas showed an 82/18 mixture of trans/cis isomers. The kinetic data at the higher temperatures were used to determine the electron affinity EA(trans-2-C(4)F(8)) = 0.79 +/- 0.06 eV after making some reasonable assumptions. The same quantity was calculated using the G3(MP2) compound method, yielding 0.74 eV. The kinetic data were not sufficient to establish a reliable value for EA(cis-2-C(4)F(8)), but G3(MP2) calculations give a value 0.017 eV greater than that for trans-2-C(4)F(8). MP2 and density functional theory were used to study the structural properties of the neutral and anion isomers.

  3. Identification of C4 photosynthesis metabolism and regulatory-associated genes in Eleocharis vivipara by SSH.

    PubMed

    Chen, Taiyu; Ye, Rongjian; Fan, Xiaolei; Li, Xianghua; Lin, Yongjun

    2011-09-01

    This is the first effort to investigate the candidate genes involved in kranz developmental regulation and C(4) metabolic fluxes in Eleocharis vivipara, which is a leafless freshwater amphibious plant and possesses a distinct culms anatomy structure and photosynthetic pattern in contrasting environments. A terrestrial specific SSH library was constructed to investigate the genes involved in kranz anatomy developmental regulation and C(4) metabolic fluxes. A total of 73 ESTs and 56 unigenes in 384 clones were identified by array hybridization and sequencing. In total, 50 unigenes had homologous genes in the databases of rice and Arabidopsis. The real-time quantitative PCR results showed that most of the genes were accumulated in terrestrial culms and ABA-induced culms. The C(4) marker genes were stably accumulated during the culms development process in terrestrial culms. With respect to C(3) culms, C(4) photosynthesis metabolism consumed much more transporters and translocators related to ion metabolism, organic acids and carbohydrate metabolism, phosphate metabolism, amino acids metabolism, and lipids metabolism. Additionally, ten regulatory genes including five transcription factors, four receptor-like proteins, and one BURP protein were identified. These regulatory genes, which co-accumulated with the culms developmental stages, may play important roles in culms structure developmental regulation, bundle sheath chloroplast maturation, and environmental response. These results shed new light on the C(4) metabolic fluxes, environmental response, and anatomy structure developmental regulation in E. vivipara.

  4. On the Origin of C4H and CH3OH in Protostellar Envelopes

    NASA Astrophysics Data System (ADS)

    Lindberg, Johan E.; Charnley, Steven B.; Cordiner, Martin A.

    2016-12-01

    The formation pathways of different types of organic molecules in protostellar envelopes and other regions of star formation are subjects of intense current interest. We present here observations of C4H and CH3OH, tracing two distinct groups of interstellar organic molecules, toward 16 protostars in the Ophiuchus and Corona Australis molecular clouds. Together with observations in the literature, we present C4H and CH3OH data from single-dish observations of 40 embedded protostars. We find no correlation between the C4H and CH3OH column densities in this large sample. Based on this lack of correlation, a difference in line profiles between C4H and CH3OH, and previous interferometric observations of similar sources, we propose that the emission from these two molecules is spatially separated, with the CH3OH tracing gas that has been transiently heated to high (˜70-100 K) temperatures and the C4H tracing the cooler large-scale envelope where CH4 molecules have been liberated from ices. These results provide insight in the differentiation between hot corino and warm carbon-chain chemistry in embedded protostars. Based on observations with the Kitt Peak 12 m telescope telescope and the Atacama Pathfinder EXperiment (APEX) telescope. The Kitt Peak 12 m telescope is operated by the Arizona Radio Observatory (ARO), Steward Observatory, University of Arizona. APEX is a collaboration between the Max Planck Institute for Radio Astronomy, the European Southern Observatory, and the Onsala Space Observatory.

  5. Cross species selection scans identify components of C4 photosynthesis in the grasses.

    PubMed

    Huang, Pu; Studer, Anthony J; Schnable, James C; Kellogg, Elizabeth A; Brutnell, Thomas P

    2017-01-01

    C4 photosynthesis is perhaps one of the best examples of convergent adaptive evolution with over 25 independent origins in the grasses (Poaceae) alone. The availability of high quality grass genome sequences presents new opportunities to explore the mechanisms underlying this complex trait using evolutionary biology-based approaches. In this study, we performed genome-wide cross-species selection scans in C4 lineages to facilitate discovery of C4 genes. The study was enabled by the well conserved collinearity of grass genomes and the recently sequenced genome of a C3 panicoid grass, Dichanthelium oligosanthes This method, in contrast to previous studies, does not rely on any a priori knowledge of the genes that contribute to biochemical or anatomical innovations associated with C4 photosynthesis. We identified a list of 88 candidate genes that include both known and potentially novel components of the C4 pathway. This set includes the carbon shuttle enzymes pyruvate, phosphate dikinase, phosphoenolpyruvate carboxylase and NADP malic enzyme as well as several predicted transporter proteins that likely play an essential role in promoting the flux of metabolites between the bundle sheath and mesophyll cells. Importantly, this approach demonstrates the application of fundamental molecular evolution principles to dissect the genetic basis of a complex photosynthetic adaptation in plants. Furthermore, we demonstrate how the output of the selection scans can be combined with expression data to provide additional power to prioritize candidate gene lists and suggest novel opportunities for pathway engineering.

  6. Nature's green revolution: the remarkable evolutionary rise of C4 plants

    PubMed Central

    Osborne, Colin P; Beerling, David J

    2005-01-01

    Plants with the C4 photosynthetic pathway dominate today's tropical savannahs and grasslands, and account for some 30% of global terrestrial carbon fixation. Their success stems from a physiological CO2-concentrating pump, which leads to high photosynthetic efficiency in warm climates and low atmospheric CO2 concentrations. Remarkably, their dominance of tropical environments was achieved in only the past 10 million years (Myr), less than 3% of the time that terrestrial plants have existed on Earth. We critically review the proposal that declining atmospheric CO2 triggered this tropical revolution via its effects on the photosynthetic efficiency of leaves. Our synthesis of the latest geological evidence from South Asia and North America suggests that this emphasis is misplaced. Instead, we find important roles for regional climate change and fire in South Asia, but no obvious environmental trigger for C4 success in North America. CO2-starvation is implicated in the origins of C4 plants 25–32 Myr ago, raising the possibility that the pathway evolved under more extreme atmospheric conditions experienced 10 times earlier. However, our geochemical analyses provide no evidence of the C4 mechanism at this time, although possible ancestral components of the C4 pathway are identified in ancient plant lineages. We suggest that future research must redress the substantial imbalance between experimental investigations and analyses of the geological record. PMID:16553316

  7. Protonation of deoxycytidine residues in dC4 tetraloops: UV spectrophotometric study of dC10 and d(A14C4T14).

    PubMed

    Raukas, E; Kooli, K

    2003-06-01

    It is shown that component analysis could be applied to study the UV difference spectra of cytidine oligomers and hairpin oligonucleotides with cytidines in the loop region in order to account for the melting and titration results in terms of cytidine stacking and protonation. Upon acid titration, the dC(10) oligomer undergoes cooperative conformational transition at pH 6.3 accompanied by protonation and formation of the i-structure with half of the residues protonated. The stability of the hemiprotonated structure increases with decreasing pH, the i-structure persisting still in the region of pHC(4) loop of the hairpin oligonucleotide d(A(14)C(4)T(14)). It is shown that upon titration, the 50% level of protonation of the deoxycytidine tetraloop is attained at pH 5.0. Simultaneously, the stacking interactions of cytidine residues reach the maximum at this pH with two residues stacked, and thereafter decline again. Only marginal stabilization of the oligomer hairpin (DeltaT(m)=1.5 degrees C) is found to accompany the formation of this single hemiprotonated dC.dC(+) base pair. We propose that at pH 5 the cytidines of the dC(4) loop form a hemiprotonated dC.dC(+) pair stacked with the last dA.dT base pair of the hairpin stem.

  8. The Production of Complement Clauses in Children with Language Impairment

    ERIC Educational Resources Information Center

    Steel, Gillian; Rose, Miranda; Eadie, Patricia

    2016-01-01

    Purpose: The purpose of this research was to provide a comprehensive description of complement-clause production in children with language impairment. Complement clauses were examined with respect to types of complement structure produced, verb use, and both semantic and syntactic accuracy. Method: A group of 17 children with language impairment…

  9. Complement: a unique innate immune sensor for danger signals.

    PubMed

    Gasque, Philippe

    2004-11-01

    The complement (C) inflammatory cascade is part of the phylogenetically ancient innate immune response and is crucial to our natural ability to ward off infection. It has three critical physiologic activities: (i) defending against microbial infections by triggering the generation of a membranolytic complex (C5b9 complex) at the surface of the pathogen and C fragments (named opsonins, i.e., C1q, C3b and iC3b) which interact with C cell surface receptors (CR1, CR3 and CR4) to promote phagocytosis. Soluble C anaphylatoxins (C4a, C3a and C5a) greatly control the local pro-inflammatory response through the chemotaxis and activation of leukocytes; (ii) bridging innate and adaptive immunity (essentially through C receptor type 2, CR2, expressed by B cells) and (iii) disposing of immune complexes and the products of the inflammatory injury (i.e., other danger signals, e.g., toxic cell debris and apoptotic corpses) to ensure the protection and healing of the host. The regulatory mechanisms of C are finely balanced so that, on the one hand, the deposition of C is focused on the surface of invading microorganisms and, on the other hand, the deposition of C on normal cells is limited by several key C inhibitors (e.g., CD46, CD55 and CD59). Knowledge of the unique molecular and cellular innate immunological interactions that occur in the development and resolution of pathology should facilitate the design of effective therapeutic strategies to fight selectively against intruders.

  10. Collective magnetic excitations of C4-symmetric magnetic states in iron-based superconductors

    NASA Astrophysics Data System (ADS)

    Scherer, Daniel D.; Eremin, Ilya; Andersen, Brian M.

    2016-11-01

    We study the collective magnetic excitations of the recently discovered C4-symmetric spin-density-wave states of iron-based superconductors with particular emphasis on their orbital character based on an itinerant multiorbital approach. This is important since the C4-symmetric spin-density-wave states exist only at moderate interaction strengths where damping effects from a coupling to the continuum of particle-hole excitations strongly modify the shape of the excitation spectra compared to predictions based on a local moment picture. We uncover a distinct orbital polarization inherent to magnetic excitations in C4-symmetric states, which provide a route to identify the different commensurate magnetic states appearing in the continuously updated phase diagram of the iron-pnictide family.

  11. Plasticity of metabolic networks and the evolution of C4 photosynthesis

    NASA Astrophysics Data System (ADS)

    Bogart, Eli; Myers, Chris

    2012-02-01

    Over 50 groups of plants have independently developed a common mechanism (C4 photosynthesis) for increasing the efficiency of photosynthetic carbon dioxide assimilation. Understanding the high degree of evolvability of the C4 system could offer useful guidance for attempts to introduce it artificially to other plants. Previously, the nonlinear relationship between carbon dioxide levels and rates of carbon assimilation and photorespiration has prevented the application of genome-scale metabolic models to the problem of the evolution of the pathway. We apply a nonlinear optimization method to find feasible flux distributions in a plant metabolic model, allowing us to explore the plasticity of the metabolic network and characterize the fitness landscape of the transition from C3 to C4 photosynthesis.

  12. C4-bound imidazolylidenes: from curiosities to high-impact carbene ligands.

    PubMed

    Albrecht, Martin

    2008-08-21

    This feature article summarizes the progress achieved thus far in using C4-bound imidazolylidenes as a new class of ligands for transition metals. Since the discovery of this unusual carbene bonding mode in 2001, various rational routes towards complexes containing C4-bound carbenes have evolved. These advances allowed for studying the impact of this new type of ligand on the transition metal center, both from a fundamental point of view as well as from a more applied perspective, in particular for catalytic applications. The promising results accomplished in this relatively short period of time demonstrate the potential of C4-bound imidazolylidenes as unique carbene ligands for inducing catalytic activity and for mediating unprecedented transformations.

  13. The Complement System in Flavivirus Infections.

    PubMed

    Conde, Jonas N; Silva, Emiliana M; Barbosa, Angela S; Mohana-Borges, Ronaldo

    2017-01-01

    The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical climates worldwide, affecting hundreds of millions of people each year. The Flaviviridae family includes dengue, West Nile, Zika, Japanese encephalitis, and yellow fever viruses that are typically transmitted by mosquitoes or ticks, and cause a wide range of symptoms, such as fever, shock, meningitis, paralysis, birth defects, and death. The flavivirus genome is composed of a single positive-sense RNA molecule encoding a single viral polyprotein. This polyprotein is further processed by viral and host proteases into three structural proteins (C, prM/M, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) that are involved in viral replication and pathogenicity. The complement system has been described to play an important role in flavivirus infection either by protecting the host and/or by influencing disease pathogenesis. In this mini-review, we will explore the role of complement system inhibition and/or activation against infection by the Flavivirus genus, with an emphasis on dengue and West Nile viruses.

  14. Complement related kidney diseases: Recurrence after transplantation.

    PubMed

    Salvadori, Maurizio; Bertoni, Elisabetta

    2016-12-24

    The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials.

  15. The Complement System in Flavivirus Infections

    PubMed Central

    Conde, Jonas N.; Silva, Emiliana M.; Barbosa, Angela S.; Mohana-Borges, Ronaldo

    2017-01-01

    The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical climates worldwide, affecting hundreds of millions of people each year. The Flaviviridae family includes dengue, West Nile, Zika, Japanese encephalitis, and yellow fever viruses that are typically transmitted by mosquitoes or ticks, and cause a wide range of symptoms, such as fever, shock, meningitis, paralysis, birth defects, and death. The flavivirus genome is composed of a single positive-sense RNA molecule encoding a single viral polyprotein. This polyprotein is further processed by viral and host proteases into three structural proteins (C, prM/M, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) that are involved in viral replication and pathogenicity. The complement system has been described to play an important role in flavivirus infection either by protecting the host and/or by influencing disease pathogenesis. In this mini-review, we will explore the role of complement system inhibition and/or activation against infection by the Flavivirus genus, with an emphasis on dengue and West Nile viruses. PMID:28261172

  16. Complement related kidney diseases: Recurrence after transplantation

    PubMed Central

    Salvadori, Maurizio; Bertoni, Elisabetta

    2016-01-01

    The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials. PMID:28058212

  17. Compartmentation of photosynthesis in cells and tissues of C(4) plants.

    PubMed

    Edwards, G E; Franceschi, V R; Ku, M S; Voznesenskaya, E V; Pyankov, V I; Andreo, C S

    2001-04-01

    Critical to defining photosynthesis in C(4) plants is understanding the intercellular and intracellular compartmentation of enzymes between mesophyll and bundle sheath cells in the leaf. This includes enzymes of the C(4) cycle (including three subtypes), the C(3) pathway and photorespiration. The current state of knowledge of this compartmentation is a consequence of the development and application of different techniques over the past three decades. Initial studies led to some alternative hypotheses on the mechanism of C(4) photosynthesis, and some controversy over the compartmentation of enzymes. The development of methods for separating mesophyll and bundle sheath cells provided convincing evidence on intercellular compartmentation of the key components of the C(4) pathway. Studies on the intracellular compartmentation of enzymes between organelles and the cytosol were facilitated by the isolation of mesophyll and bundle sheath protoplasts, which can be fractionated gently while maintaining organelle integrity. Now, the ability to determine localization of photosynthetic enzymes conclusively, through in situ immunolocalization by confocal light microscopy and transmission electron microscopy, is providing further insight into the mechanism of C(4) photosynthesis and its evolution. Currently, immunological, ultrastructural and cytochemical studies are revealing relationships between anatomical arrangements and photosynthetic mechanisms which are probably related to environmental factors associated with evolution of these plants. This includes interesting variations in the C(4) syndrome in leaves and cotyledons of species in the tribe Salsoleae of the family Chenopodiaceae, in relation to evolution and ecology. Thus, analysis of structure-function relationships using modern techniques is a very powerful approach to understanding evolution and regulation of the photosynthetic carbon reduction mechanisms.

  18. Significant accumulation of C(4)-specific pyruvate, orthophosphate dikinase in a C(3) plant, rice.

    PubMed

    Fukayama, H; Tsuchida, H; Agarie, S; Nomura, M; Onodera, H; Ono, K; Lee, B H; Hirose, S; Toki, S; Ku, M S; Makino, A; Matsuoka, M; Miyao, M

    2001-11-01

    The C(4)-Pdk gene encoding the C(4) enzyme pyruvate, orthophosphate dikinase (PPDK) of maize (Zea mays cv Golden Cross Bantam) was introduced into the C(3) plant, rice (Oryza sativa cv Kitaake). When the intact maize C(4)-Pdk gene, containing its own promoter and terminator sequences and exon/intron structure, was introduced, the PPDK activity in the leaves of some transgenic lines was greatly increased, in one line reaching 40-fold over that of wild-type plants. In a homozygous line, the PPDK protein accounted for 35% of total leaf-soluble protein or 16% of total leaf nitrogen. In contrast, introduction of a chimeric gene containing the full-length cDNA of the maize PPDK fused to the maize C(4)-Pdk promoter or the rice Cab promoter only increased PPDK activity and protein level slightly. These observations suggest that the intron(s) or the terminator sequence of the maize gene, or a combination of both, is necessary for high-level expression. In maize and transgenic rice plants carrying the intact maize gene, the level of transcript in the leaves per copy of the maize C(4)-Pdk gene was comparable, and the maize gene was expressed in a similar organ-specific manner. These results suggest that the maize C(4)-Pdk gene behaves in a quantitatively and qualitatively similar way in maize and transgenic rice plants. The activity of the maize PPDK protein expressed in rice leaves was light/dark regulated as it is in maize. This is the first reported evidence for the presence of an endogenous PPDK regulatory protein in a C(3) plant.

  19. Environmental change and hominin exploitation of C4-based resources in wetland/savanna mosaics.

    PubMed

    Stewart, Kathlyn M

    2014-12-01

    Eastern and southern Africa experienced ongoing climatic and tectonic instability in the Plio-Pleistocene, alongside declining forests and expanding grasslands. Most known hominin genera (Australopithecus spp., Kenyanthropus, Paranthropus spp., Homo spp.) appear roughly between 4.2 and 1.8 Ma (millions of years ago). Explanations for these speciation events have focused on adaptations to environmental change, particularly in terrestrial biomes. However, the links between environmental change and hominin adaptations have not always been clear. Often overlooked is that Plio-Pleistocene vegetation included not just terrestrial environments, but a large component of edaphic (wet) C4 grasses and sedges. In this paper it is suggested that in response to environmental fluctuations, hominins engaged in conservative long-term ecological and dietary patterns, based on predictable C4/C3 wetland and terrestrial resources. Data are presented from six hominin locales, which demonstrate reliance on plant-based resources (sedges, grasses, and other vegetation) in C4-inclusive wetland/savanna mosaics. After roughly 2.4 Ma, severe climate variability is associated with early Homo and perhaps Paranthropus boisei broadening their diet to familiar but less preferred foods: vertebrates and invertebrates. These foods consistently provided early Homo with essential nutrients, which reduced selection pressures and allowed for increases in brain size. After 1.65 Ma, a 20% increase in the C4 dietary component of Homo occurs alongside increased relative brain size. P. boisei also increases its C4 dietary component by 15% after 1.65 Ma. These increases imply that both taxa continued to broaden their diet within the C4-based wetlands/savanna biome, with Homo putting a greater emphasis on mammals.

  20. Preference for C4 shade grasses increases hatchling performance in the butterfly, Bicyclus safitza.

    PubMed

    Nokelainen, Ossi; Ripley, Brad S; van Bergen, Erik; Osborne, Colin P; Brakefield, Paul M

    2016-08-01

    The Miocene radiation of C4 grasses under high-temperature and low ambient CO 2 levels occurred alongside the transformation of a largely forested landscape into savanna. This inevitably changed the host plant regime of herbivores, and the simultaneous diversification of many consumer lineages, including Bicyclus butterflies in Africa, suggests that the radiations of grasses and grazers may be evolutionary linked. We examined mechanisms for this plant-herbivore interaction with the grass-feeding Bicyclus safitza in South Africa. In a controlled environment, we tested oviposition preference and hatchling performance on local grasses with C3 or C4 photosynthetic pathways that grow either in open or shaded habitats. We predicted preference for C3 plants due to a hypothesized lower processing cost and higher palatability to herbivores. In contrast, we found that females preferred C4 shade grasses rather than either C4 grasses from open habitats or C3 grasses. The oviposition preference broadly followed hatchling performance, although hatchling survival was equally good on C4 or C3 shade grasses. This finding was explained by leaf toughness; shade grasses were softer than grasses from open habitats. Field monitoring revealed a preference of adults for shaded habitats, and stable isotope analysis of field-sampled individuals confirmed their preference for C4 grasses as host plants. Our findings suggest that plant-herbivore interactions can influence the direction of selection in a grass-feeding butterfly. Based on this work, we postulate future research to test whether these interactions more generally contribute to radiations in herbivorous insects via expansions into new, unexploited ecological niches.

  1. Function and Regulation of the C4-Dicarboxylate Transporters in Campylobacter jejuni

    PubMed Central

    Wösten, Marc M. S. M.; van de Lest, Chris H. A.; van Dijk, Linda; van Putten, Jos P. M.

    2017-01-01

    C4-dicarboxylates are important molecules for the human pathogen C.jejuni, as they are used as carbon and electron acceptor molecules, as sugars cannot be utilized by this microaerophilic organism. Based on the genome analysis, C. jejuni may possess five different C4–dicarboxylate transporters: DctA, DcuA, DcuB, and two homologs of DcuC. Here, we investigated the regulation and function of various C4–dicarboxylate transporters in C. jejuni. Transcription of the dctA and dcuC homologs is constitutive, while dcuA and dcuB are both directly regulated by the two-component RacR/RacS system in response to limited oxygen availability and the presence of nitrate. The DctA transporter is the only C4-dicarboxylate transporter to allow C. jejuni to grow on C4-carbon sources such as aspartate, fumarate, and succinate at high oxygen levels (10% O2) and is indispensable for the uptake of succinate from the medium under these conditions. Both DcuA and DcuB can sequester aspartate from the medium under low-oxygen conditions (0.3% O2). However, under these conditions, DcuB is the only transporter to secrete succinate to the environment. Under low-oxygen conditions, nitrate prevents the secretion of succinate to the environment and was able to overrule the phenotype of the C4-transporter mutants, indicating that the activity of the aspartate–fumarate–succinate pathway in C. jejuni is strongly reduced by the addition of nitrate in the medium. PMID:28223978