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Sample records for c3 ssti polymorphism

  1. Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians

    PubMed Central

    Chhabra, S; Narang, R; Krishnan, LR; Vasisht, S; Agarwal, DP; Srivastava, LM; Manchanda, SC; Das, N

    2002-01-01

    Background A close association between Sst I polymorphism in the 3' untranslated region of the apolipoproteinC3 (APOC3) gene and levels of plasma triglycerides (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a known risk factor for coronary artery disease (CAD) in the context of Asian Indians. We conducted a study on the relationship between APOC3 SstI polymorphism (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male healthy volunteers from Northern India. Methods DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Digested PCR products were run on 3% agarose gel and visualized by ethidium bromide staining. Results Rare S2 allele was highly prevalent in our study population (0.313) as compared to the Caucasians (0.00–0.11). The genotypic distribution was in agreement with Hardy-Weinberg equilibrium. S2 allele was almost two times more prevalent in the HTG group (N = 34) as compared to NTG group (N = 105) (p = 0.001). Multiple logistic regression revealed S1S2 individuals had age-adjusted odds ratio of 2.43 (95%CI = 0.99–6.01, p = 0.054) and S2S2 had 9.9 (95%CI = 2.66–37.29, p = 0.0006) for developing HTG in comparison to S1S1 genotype. Conclusions Our study shows a significant association between rare S2 allele and HTG in Asian Indians. PMID:12052247

  2. C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients.

    PubMed

    Nsaiba, Mohamed Jalloul; Lapointe, Marc; Mabrouk, Hajer; Douki, Wahiba; Gaha, Lotfi; Pérusse, Louis; Bouchard, Claude; Jrad, Besma Bel Hadj; Cianflone, Katherine

    2015-05-01

    Excessive activation of complement is associated with many diseases including schizophrenia. Investigation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross-sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p < 0.05-0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p < 0.05-0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences.

  3. Polymorphism of the complement receptor for C3bi.

    PubMed Central

    Russ, G R; Haddad, A P; Tait, B D; d'Apice, A J

    1985-01-01

    RM2.184, a mouse IgG2a monoclonal antibody, recognizes a polymorphic determinant on the complement receptor for C3bi which is present on granulocytes and monocytes. The RM2.184 epitope is distinct from the monomorphic determinant recognized by the monoclonal antibody OKM1. The RM2.184 epitope is probably on the alpha subunit and dependent on the association of the alpha and beta subunits for its configuration, as it can not be detected after the subunits have been dissociated. The phenotypic frequency of the RM2.184 antigen is approximately 14%, and its segregation in families is independent of HLA and consistent with an autosomal co-dominant mode of inheritance. Images PMID:2414326

  4. Polymorphism of C3 complement in association with myocardial infarction in a sample of central Tunisia

    PubMed Central

    2013-01-01

    Background Myocardial infarction (MI) is a major clinical problem because of its large contribution to mortality. The genetic bases of this disease have been widely studied in recent years to find a clear association with some genetic markers that increase the risk of its occurrence. In the present investigation, the correlation between MI and the C3 complement polymorphism was analyzed using a case–control study. Methods Our study ported on one hundred seventy survived myocardial infarction patients and ninety five healthy controls. The C3 allele identification was investigated using the amplification refractory mutation system PCR to determine the C3*S and the C3*F alleles of the C3 polymorphism. Results Frequencies of C3*S and C3*F in patients are 0.59 and 0.41 respectively. Fisher test results showed a significant increase of C3*F allele in the sample of patients (0.41; odds ratio: 2.616; C.I [1.738-3.938]) compared to controls (0.21; odds ratio: 0.382; 95% CI [0.254-0.575]), p = 2.742 × 10-6. Conclusion A strong positive correlation was found between C3 polymorphism and MI estimating that the risk of myocardial infarction is significantly increased among patients with C3*F allele of this polymorphism. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1190484203893646 PMID:23764154

  5. Spacecraft System Integration and Test: SSTI Lewis critical design audit

    NASA Technical Reports Server (NTRS)

    Brooks, R. P.; Cha, K. K.

    1995-01-01

    The Critical Design Audit package is the final detailed design package which provides a comprehensive description of the SSTI mission. This package includes the program overview, the system requirements, the science and applications activities, the ground segment development, the assembly, integration and test description, the payload and technology demonstrations, and the spacecraft bus subsystems. Publication and presentation of this document marks the final requirements and design freeze for SSTI.

  6. Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk

    PubMed Central

    Heurich, Meike; Martínez-Barricarte, Ruben; Francis, Nigel J.; Roberts, Dawn L.; Rodríguez de Córdoba, Santiago; Morgan, B. Paul; Harris, Claire L.

    2011-01-01

    Common polymorphisms in complement alternative pathway (AP) proteins C3 (C3R102G), factor B (fBR32Q), and factor H (fHV62I) are associated with age-related macular degeneration (AMD) and other pathologies. Our published work showed that fBR32Q influences C3 convertase formation, whereas fHV62I affects factor I cofactor activity. Here we show how C3R102G (C3S/F) influences AP activity. In hemolysis assays, C3102G activated AP more efficiently (EC50 C3102G: 157 nM; C3102R: 191 nM; P < 0.0001). fB binding kinetics and convertase stability were identical, but native and recombinant fH bound more strongly to C3b102R (KD C3b102R: 1.0 μM; C3b102G: 1.4 μM; P < 0.0001). Accelerated decay was unaltered, but fH cofactor activity was reduced for C3b102G, favoring AP amplification. Combining disease “risk” variants (C3102G, fB32R, and fH62V) in add-back assays yielded sixfold higher hemolytic activity compared with “protective” variants (C3102R, fB32Q, and fH62I; P < 0.0001). These data introduce the concept of a functional complotype (combination of polymorphisms) defining complement activity in an individual, thereby influencing susceptibility to AP-driven disease. PMID:21555552

  7. A revised mechanism for the activation of complement C3 to C3b: a molecular explanation of a disease-associated polymorphism.

    PubMed

    Rodriguez, Elizabeth; Nan, Ruodan; Li, Keying; Gor, Jayesh; Perkins, Stephen J

    2015-01-23

    The solution structure of complement C3b is crucial for the understanding of complement activation and regulation. C3b is generated by the removal of C3a from C3. Hydrolysis of the C3 thioester produces C3u, an analog of C3b. C3b cleavage results in C3c and C3d (thioester-containing domain; TED). To resolve functional questions in relation to C3b and C3u, analytical ultracentrifugation and x-ray and neutron scattering studies were used with C3, C3b, C3u, C3c, and C3d, using the wild-type allotype with Arg(102). In 50 mm NaCl buffer, atomistic scattering modeling showed that both C3b and C3u adopted a compact structure, similar to the C3b crystal structure in which its TED and macroglobulin 1 (MG1) domains were connected through the Arg(102)-Glu(1032) salt bridge. In physiological 137 mm NaCl, scattering modeling showed that C3b and C3u were both extended in structure, with the TED and MG1 domains now separated by up to 6 nm. The importance of the Arg(102)-Glu(1032) salt bridge was determined using surface plasmon resonance to monitor the binding of wild-type C3d(E1032) and mutant C3d(A1032) to immobilized C3c. The mutant did not bind, whereas the wild-type form did. The high conformational variability of TED in C3b in physiological buffer showed that C3b is more reactive than previously thought. Because the Arg(102)-Glu(1032) salt bridge is essential for the C3b-Factor H complex during the regulatory control of C3b, the known clinical associations of the major C3S (Arg(102)) and disease-linked C3F (Gly(102)) allotypes of C3b were experimentally explained for the first time.

  8. Apolipoprotein C3 polymorphism is associated with cognitive function in Caribbean Hispanics

    USDA-ARS?s Scientific Manuscript database

    Background: Apolipoprotein C3(APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired ...

  9. Association of Apolipoprotein C3 Genetic Polymorphisms with the Risk of Ischemic Stroke in the Northern Chinese Han Population

    PubMed Central

    Wang, Yanzhe; Yin, Xiaoyu; Li, Lei; Deng, Shumin; He, Zhiyi

    2016-01-01

    The apolipoprotein C3 (APOC3) gene, which is a member of the APOA1/C3/A4/A5 gene cluster, plays a crucial role in lipid metabolism. Dyslipidemia is an important risk factor for ischemic stroke. In the present study, we performed a hospital-based case—control study of 895 ischemic stroke patients and 883 control subjects to examine the effects of four APOC3 single nucleotide polymorphisms (SNPs) (rs2854116, rs2854117, rs4520 and rs5128) on the risk of ischemic stroke in a northern Chinese Han population. The SNaPshot Multiplex sequencing assay was used for SNP genotyping, and the potential association of genotype distributions and allele frequencies with ischemic stroke was analyzed statistically. Compared with the GG genotype, the CC+GC genotype of rs5128 was significantly associated with an increased risk in females (adjusted OR = 3.38, 95% CI = 1.82–6.28, P <0.01) after all of the risk factors were adjusted for with logistic regression analyses. A similar relationship was found between the rs4520 polymorphism and ischemic stroke risk in Han Chinese women. Under a recessive genetic model, the TT+TC genotypes of this variant increased ischemic stroke risk (adjusted OR = 2.05; 95% CI = 1.28–3.29; P <0.01). Haplotype analysis revealed that in males, the T-C-T-C haplotype of rs2854116-rs2854117-rs4520-rs5128 was significantly more frequent in the ischemic stroke group than in the control group (OR = 1.49, 95% CI = 1.18–1.87, P<0.01). The results of our study indicate that the APOC3 polymorphisms contribute to ischemic stroke susceptibility in females in the northern Chinese Han population. PMID:27690381

  10. 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.

  11. 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.

  12. Association between apolipoprotein C3 Sst I, T-455C, C-482T and C1100T polymorphisms and risk of coronary heart disease.

    PubMed

    Lin, Bin; Huang, Yiwei; Zhang, Mingying; Wang, Jun; Wu, Yihua

    2014-01-14

    Apolipoprotein C3 (ApoC3) polymorphisms have been suggested to be associated with risk of coronary heart disease (CHD). However, the results of relevant studies were inconsistent. We aimed to systematically evaluate this issue. PubMed, EMBASE and Cochrane library databases (up to March 2013) were systematically searched to identify studies evaluating the association between ApoC3 polymorphisms and CHD risk. Two reviewers independently identified studies, extracted and analysed the data. Either a fixed-effects or a random-effects model was adopted to estimate overall ORs. Finally, 20 studies comprising 15 591 participants were included in this systematic review. Fifteen studies with 11 539 individuals were included in the meta-analysis of Sst I polymorphism, four studies comprising 3378 individuals assessed T-455C polymorphism, four studies with 3070 participants evaluated C-482T polymorphism and C1100T polymorphism was assessed by three studies comprising 4662 participants. Under dominant model, Sst I polymorphism was borderline significantly associated with CHD risk (S1S2+S2S2 vs S1S1, pooled OR=1.19, 95% CI 1.00 to 1.42). Subgroup analyses suggested that Sst I polymorphism was significantly associated with myocardial infarction (MI) risk (pooled OR=1.42, 95% CI 1.06 to 1.91), and Sst I polymorphism was statistically associated with CHD risk among Asian population (pooled OR=1.35, 95% CI 1.08 to 1.69) and in retrospective studies (pooled OR=1.30, 95% CI 1.04 to 1.61). A significant association was observed between T-455C polymorphism and CHD risk (TC+CC vs TT, pooled OR=1.22, 95% CI 1.06 to 1.42). A borderline significant association was suggested between T-455C polymorphism and MI risk (pooled OR=1.21, 95% CI 1.00 to 1.46). C-482T and C1100T polymorphisms were not indicated to be associated with CHD risk or MI risk. ApoC3 Sst I and T-455C polymorphisms might be associated with CHD risk.

  13. 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.

  14. The C3b/C4b receptor (CR1, CD35) on erythrocytes: methods for study of the polymorphisms.

    PubMed

    Cohen, J H; Atkinson, J P; Klickstein, L B; Oudin, S; Subramanian, V B; Moulds, J M

    1999-01-01

    This report is devoted to methodologies used in analyzing the C3b/C4b receptor (CR1, CD35) on erythrocytes (E), its soluble form, the CRI structural or allotype polymorphism, and CR1 density polymorphism. In primates E CR1 serves as the main system for processing and clearance of complement opsonized immune complexes (IC). CR1 copy numbers decrease with aging of E in normal individuals. Erythrocyte CR1 is also decreased in pathological conditions such as systemic lupus erythematosus (SLE), HIV infection, certain hemolytic anemias, and many other conditions featuring immune complexes. Consequently, CRI on E has an important physiological role in immune complex handling and has interesting alterations in disease.

  15. System Critical Design Audit (CDA). Books 1, 2 and 3; [Small Satellite Technology Initiative (SSTI Lewis Spacecraft Program)

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Small Satellite Technology Initiative (SSTI) Lewis Spacecraft Program is evaluated. Spacecraft integration, test, launch, and spacecraft bus are discussed. Payloads and technology demonstrations are presented. Mission data management system and ground segment are also addressed.

  16. The Astro Edge solar array for the NASA SSTI Clark Spacecraft

    NASA Technical Reports Server (NTRS)

    Spence, B. R.

    1995-01-01

    The Astro Edge solar array is a new and innovative reflective low concentrator power generating system which has been selected for the CTA Incorporate/Lockheed Martin Clark spacecraft under the NASA Small Spacecraft Technology Initiative (SSTI) program. In support of this program, Astro Aerospace Corporation has produced one qualification and two flight solar array wings to support a July 1996 launch. The Astro Edge solar array was selected as a new technology to benefit future NASA, military and commercial missions by providing high specific power, high deployed stiffness, low stowed volume, low risk, and cost reduction features which meet the agency's 'better, faster, cheaper' goals. This novel array accounts for five of the thirty-six advanced technologies which the Clark spacecraft will demonstrate. A brief SSTI Astro Edge solar array program overview is presented. Completed qualification and acceptance testing is discussed. Finally, the major discriminators which make the Astro Edge solar array 'better, faster, cheaper' technology are provided.

  17. Earth imaging and scientific observations by SSTI ``Clark'' a NASA technology demonstration spacecraft

    NASA Astrophysics Data System (ADS)

    Hayduk, Robert J.; Scott, Walter S.; Walberg, Gerald D.; Butts, James J.; Starr, Richard D.

    1997-01-01

    The Small Satellite Technology Initiative (SSTI) is a National Aeronautics and Space Administration (NASA) program to demonstrate smaller, high technology satellites constructed rapidly and less expensively. Under SSTI, NASA funded the development of ``Clark,'' a high technology demonstration satellite to provide 3-m resolution panchromatic and 15-m resolution multispectral images, as well as collect atmospheric constituent and cosmic x-ray data. The 690-lb. satellite, to be launched in early 1997, will be in a 476 km, circular, sun-synchronous polar orbit. This paper describes the program objectives, the technical characteristics of the sensors and satellite, image processing, archiving and distribution. Data archiving and distribution will be performed by NASA Stennis Space Center and by the EROS Data Center, Sioux Falls, South Dakota, USA.

  18. Autonomous Navigation of the SSTI/Lewis Spacecraft Using the Global Positioning System (GPS)

    NASA Technical Reports Server (NTRS)

    Hart, R. C.; Long, A. C.; Lee, T.

    1997-01-01

    The National Aeronautics and Space Administration (NASA) Goddard Space Flight Center (GSFC) Flight Dynamics Division (FDD) is pursuing the application of Global Positioning System (GPS) technology to improve the accuracy and economy of spacecraft navigation. High-accuracy autonomous navigation algorithms are being flight qualified in conjunction with GSFC's GPS Attitude Determination Flyer (GADFLY) experiment on the Small Satellite Technology Initiative (SSTI) Lewis spacecraft, which is scheduled for launch in 1997. Preflight performance assessments indicate that these algorithms can provide a real-time total position accuracy of better than 10 meters (1 sigma) and velocity accuracy of better than 0.01 meter per second (1 sigma), with selective availability at typical levels. This accuracy is projected to improve to the 2-meter level if corrections to be provided by the GPS Wide Area Augmentation System (WAAS) are included.

  19. Quality of life effects of androgen deprivation therapy in a prostate cancer cohort in New Zealand: can we minimize effects using a stratification based on the aldo-keto reductase family 1, member C3 rs12529 gene polymorphism?

    PubMed

    Karunasinghe, Nishi; Zhu, Yifei; Han, Dug Yeo; Lange, Katja; Zhu, Shuotun; Wang, Alice; Ellett, Stephanie; Masters, Jonathan; Goudie, Megan; Keogh, Justin; Benjamin, Benji; Holmes, Michael; Ferguson, Lynnette R

    2016-08-02

    Androgen deprivation therapy (ADT) is an effective palliation treatment in men with advanced prostate cancer (PC). However, ADT has well documented side effects that could alter the patient's health-related quality of life (HRQoL). The current study aims to test whether a genetic stratification could provide better knowledge for optimising ADT options to minimize HRQoL effects. A cohort of 206 PC survivors (75 treated with and 131 without ADT) was recruited with written consent to collect patient characteristics, clinical data and HRQoL data related to PC management. The primary outcomes were the percentage scores under each HRQoL subscale assessed using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaires (QLQ-C30 and PR25) and the Depression Anxiety Stress Scales developed by the University of Melbourne, Australia. Genotyping of these men was carried out for the aldo-keto reductase family 1, member C3 (AKR1C3) rs12529 single nucleotide polymorphism (SNP). Analysis of HRQoL scores were carried out against ADT duration and in association with the AKR1C3 rs12529 SNP using the generalised linear model. P-values <0 · 05 were considered significant, and were further tested for restriction with Bonferroni correction. Increase in hormone treatment-related effects were recorded with long-term ADT compared to no ADT. The C and G allele frequencies of the AKR1C3rs12529 SNP were 53·4 % and 46·6 % respectively. Hormone treatment-related symptoms showed an increase with ADT when associated with the AKR1C3 rs12529 G allele. Meanwhile, decreasing trends on cancer-specific symptoms and increased sexual interest were recorded with no ADT when associated with the AKR1C3 rs12529 G allele and reverse trends with the C allele. As higher incidence of cancer-specific symptoms relate to cancer retention it is possible that associated with the C allele there could be higher incidence of unresolved cancers under no ADT options. If these

  20. Direct Detection of Staphylococcus Osteoarticular Infections by Use of Xpert MRSA/SA SSTI Real-Time PCR ▿

    PubMed Central

    Dubouix-Bourandy, Anne; de Ladoucette, Aymard; Pietri, Valerie; Mehdi, Nazim; Benzaquen, David; Guinand, Régis; Gandois, Jean-Marc

    2011-01-01

    We evaluated the Xpert MRSA/SA SSTI real-time PCR assay (Cepheid, Sunnyvale, CA) directly on perioperative bone and joint samples. The sensitivity and specificity for detection of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and methicillin-resistant coagulase-negative Staphylococcus were, respectively, 100% and 98.3%, 100% and 100%, and 100% and 95.3%. The median total test turnaround time was 72 min for PCR versus 79 h for culture. Using these rapid results, appropriate antibiotic treatment could be rapidly initiated. PMID:21998420

  1. C3 glomerulopathy

    PubMed Central

    Cook, H. Terence

    2017-01-01

    C3 glomerulopathy is a recently defined entity that encompasses a group of kidney diseases caused by abnormal control of complement activation with deposition of complement component C3 in glomeruli leading to variable glomerular inflammation. Before the recognition of the unique pathogenesis of these cases, they were variably classified according to their morphological features. C3 glomerulopathy accounts for roughly 1% of all renal biopsies. Clear definition of this entity has allowed a better understanding of its pathogenesis and clinical course and is likely to lead to the design of rational therapies over the next few years. PMID:28357053

  2. Intraoperative diagnosis of Staphylococcus aureus and coagulase-negative Staphylococcus using Xpert MRSA/SA SSTI assay in prosthetic joint infection.

    PubMed

    Sambri, Andrea; Pignatti, Giovanni; Romagnoli, Matteo; Donati, Davide; Marcacci, Maurilio; Cadossi, Matteo

    2017-04-01

    The aim of this prospective study was to evaluate the performance of the Polymerase Chain Reaction (PCR) tool Xpert MRSA/SA SSTI test (Cepheid, Sunnyvale, CA, USA) on periprosthetic samples from a cohort of patients with suspected prosthetic joint infection (PJI). Seventy adult patients were included in this prospective study. On the basis of the preoperative evaluation, 39 patients were clinically considered to have a PJI, whereas 31 were presumed to suffer from an aseptic mobilization of the implant. Xpert MRSA/SA SSTI identified 4 out of 4 MRSA, 7 out of 7 MSSA, and 14 out of 16 methicillin resistant CoNS. Among the 31 patients not having a PJI, the rapid PCR did not find any bacteria among those identifiable, thus demonstrating an excellent performance in terms of specificity. Statistical analysis of the analytical performance showed a high correlation (p<0.001) between the result of Xpert MRSA/SA SSTI and culture. Xpert MRSA/SA SSTI assay is a novel, yet well known, rapid and accurate method for the identification of different species of staphylococci. The test can be used with peri-operative samples thus dramatically improving the diagnostic sensitivity. In addition, thanks to the very short turnaround time the use of Xpert assay can modify the clinical management of patients suffering from PJI during the ongoing operative procedure.

  3. Apolipoprotein A5 and apolipoprotein C3 single nucleotide polymorphisms are correlated with an increased risk of coronary heart disease: a case-control and meta-analysis study.

    PubMed

    Yang, Guang; Lei, Ming-Ming; Yu, Chun-Lei; Liu, Xiao-Xiao; An, Zhe; Song, Chun-Li

    2015-09-19

    Triglycerides (TGs) are proatherogenic lipoproteins involving the risk of coronary heart disease (CHD), while apolipoprotein A5 (APOA5) and apolipoprotein C3 (APOC3) are main lipoproteins composing TG-rich lipoproteins. In this study, we aim to explore the correlation of CHD with APOA5 -1131 T > C and APOC3 -455 T > C single nucleotide polymorphisms (SNPs). A sum of 210 CHD patients, hospitalized between Jan. 2013 and Mar. 2015 at China-Japan Union Hospital, Jilin University, were selected as our case group and 223 healthy individuals who had physical examination at same hospital at the same period were selected as control group. The frequency distribution of genotypes of APOA5 -1131 T > C and APOC3 -455 T > C SNPs were measured by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Stata 12.0 software was utilized for statistical analyses. There was no significant difference on age and sex between case and control group (P > 0.05). History of smoking, drinking, hypertension and diabetes mellitus, body mass index and levels of TG and fasting blood sugar in case group were shown to be higher than control group (P < 0.05), while levels of total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in case group were lower than control group (P < 0.05). Both CC and TC' + CC frequencies of APOA5 -1131 T > C and APOC3 -455 T > C in case group were higher compared to control group (both P < 0.05). Additionally, T allele frequencies of the two SNPs in case group were lower than control group, while C allele in case group has higher frequencies compared to control group (both P < 0.05). The results of meta-analysis under allele and dominant models showed that APOA5 -1131 T > C and APOC3 -455 T > C SNPs are likely to increase the risk of CHD (both P < 0.05). APOA5 -1131 T > C and APOC3 -455 T > C SNPs may play potent roles in the development

  4. Genomic Characterization of USA300 Methicillin-Resistant Staphylococcus aureus (MRSA) to Evaluate Intraclass Transmission and Recurrence of Skin and Soft Tissue Infection (SSTI) Among High-Risk Military Trainees.

    PubMed

    Millar, Eugene V; Rice, Gregory K; Elassal, Emad M; Schlett, Carey D; Bennett, Jason W; Redden, Cassie L; Mor, Deepika; Law, Natasha N; Tribble, David R; Hamilton, Theron; Ellis, Michael W; Bishop-Lilly, Kimberly A

    2017-08-01

    Military trainees are at increased risk for methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI). Whole genome sequencing (WGS) can refine our understanding of MRSA transmission and microevolution in congregate settings. We conducted a prospective case-control study of SSTI among US Army infantry trainees at Fort Benning, Georgia, from July 2012 to December 2014. We identified clusters of USA300 MRSA SSTI within select training classes and performed WGS on clinical isolates. We then linked genomic, phylogenetic, epidemiologic, and clinical data in order to evaluate intra- and interclass disease transmission. Furthermore, among cases of recurrent MRSA SSTI, we evaluated the intrahost relatedness of infecting strains. Nine training classes with ≥5 cases of USA300 MRSA SSTI were selected. Eighty USA300 MRSA clinical isolates from 74 trainees, 6 (8.1%) of whom had recurrent infection, were subjected to WGS. We identified 2719 single nucleotide variants (SNVs). The overall median (range) SNV difference between isolates was 173 (1-339). Intraclass median SNV differences ranged from 23 to 245. Two phylogenetic clusters were suggestive of interclass MRSA transmission. One of these clusters stemmed from 2 classes that were separated by a 13-month period but housed in the same barracks. Among trainees with recurrent MRSA SSTI, the intrahost median SNV difference was 7.5 (1-48). Application of WGS revealed intra- and interclass transmission of MRSA among military trainees. An interclass cluster between 2 noncontemporaneous classes suggests a long-term reservoir for MRSA in this setting.

  5. C3 glomerulopathy: consensus report.

    PubMed

    Pickering, Matthew C; D'Agati, Vivette D; Nester, Carla M; Smith, Richard J; Haas, Mark; Appel, Gerald B; Alpers, Charles E; Bajema, Ingeborg M; Bedrosian, Camille; Braun, Michael; Doyle, Mittie; Fakhouri, Fadi; Fervenza, Fernando C; Fogo, Agnes B; Frémeaux-Bacchi, Véronique; Gale, Daniel P; Goicoechea de Jorge, Elena; Griffin, Gene; Harris, Claire L; Holers, V Michael; Johnson, Sally; Lavin, Peter J; Medjeral-Thomas, Nicholas; Paul Morgan, B; Nast, Cynthia C; Noel, Laure-Hélène; Peters, D Keith; Rodríguez de Córdoba, Santiago; Servais, Aude; Sethi, Sanjeev; Song, Wen-Chao; Tamburini, Paul; Thurman, Joshua M; Zavros, Michael; Cook, H Terence

    2013-12-01

    C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition. This meeting report represents the current consensus view of the group.

  6. Rapid detection of Staphylococcus aureus and methicillin resistance in bone and joint infection samples: evaluation of the GeneXpert MRSA/SA SSTI assay.

    PubMed

    Valour, Florent; Blanc-Pattin, Viviane; Freydière, Anne-Marie; Bouaziz, Anissa; Chanard, Emmanuel; Lustig, Sébastien; Ferry, Tristan; Laurent, Frédéric

    2014-03-01

    The GeneXpert MRSA/SA SSTI assay was compared to conventional cultures to detect Staphylococcus aureus and methicillin-resistance from 91 bone and joint infection samples. Sensitivity and specificity were 94.4% and 100%. Three false-positive results were observed, in fact providing from patients known to be infected by S. aureus on the basis of other concomitant osteoarticular samples, which suggests that PCR was more sensitive than culture. This diagnosis accuracy may help shorten toxic and non-optimal empirical therapies such as glycopeptides in case of methicillin-susceptible strains. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Apolipoprotein A1/C3/A5 haplotypes and serum lipid levels

    USDA-ARS?s Scientific Manuscript database

    The association of single nucleotide polymorphisms (SNPs) in the apolipoprotein (Apo) A1/C3/A4/A5 gene cluster and serum lipid profiles is inconsistent. The present study was undertaken to detect the association between the ApoA1/C3/A5 gene polymorphisms and their haplotypes with serum lipid levels ...

  8. Complement component 3 (C3)

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003539.htm Complement component 3 (C3) To use the sharing features on ... and C4 are the most commonly measured complement components. A complement test may be used to monitor ...

  9. Update on C3 glomerulopathy

    PubMed Central

    Barbour, Thomas D.; Ruseva, Marieta M.; Pickering, Matthew C.

    2016-01-01

    C3 glomerulopathy refers to a disease process in which abnormal control of complement activation, degradation or deposition results in predominant C3 fragment deposition within the glomerulus and glomerular damage. Recent studies have improved our understanding of its pathogenesis. The key abnormality is uncontrolled C3b amplification in the circulation and/or along the glomerular basement membrane. Family studies in which disease segregates with structurally abnormal complement factor H-related (CFHR) proteins demonstrate that abnormal CFHR proteins are important in some types of C3 glomerulopathy. This is currently thought to be due to the ability of these proteins to antagonize the major negative regulator of C3 activation, complement factor H (CFH), a process termed ‘CFH de-regulation’. Recent clinicopathological cohort studies have led to further refinements in case definition, culminating in a 2013 consensus report, which provides recommendations regarding investigation and treatment. Early clinical experience with complement-targeted therapeutics, notably C5 inhibitors, has also now been published. Here, we summarize the latest developments in C3 glomerulopathy. PMID:25326473

  10. The Speaking Section of the TOEFL iBT[TM] (SSTiBT): Test-Takers' Reported Strategic Behaviors. TOEFL iBT[TM] Research Report. RR-09-30

    ERIC Educational Resources Information Center

    Swain, Merrill; Huang, Li-Shih; Barkaoui, Khaled; Brooks, Lindsay; Lapkin, Sharon

    2009-01-01

    This study responds to the Test of English as a Foreign Language[TM] (TOEFL[R]) research agenda concerning the need to understand the processes and knowledge that test-takers utilize. Specifically, it investigates the strategic behaviors test-takers reported using when taking the Speaking section of the TOEFL iBT[TM] (SSTiBT). It also investigates…

  11. The {\\triangledown}^{\\!\\!\\!\\!\\!\\!\\smash{\\raise2pt\\\\ssty\\rightharpoonup}} \\cdot \\skew2\\vec{E} term does not change the Aharonov-Casher scattering cross section

    NASA Astrophysics Data System (ADS)

    Shikakhwa, M. S.; Al-Qaq, E.

    2010-09-01

    The Aharonov-Casher (AC) Hamiltonian with the inclusion of the {\\triangledown}^{\\!\\!\\!\\!\\!\\!\\smash{\\raise2pt\\\\ssty\\rightharpoonup}} \\cdot \\skew2\\vec{E} term, which introduces a new singular interaction at the origin, is considered. Proceeding within the framework of the model of a finite-radius filament that is shrunk to zero at the end, the effect of the inclusion of this term on the original AC cross section is investigated. While the inclusion of this term gives rise to components of the radial wavefunctions that are irregular at the origin, it is found that the original AC cross section is the same whether one includes it or not, and regardless of whether the resulting singular interaction is attractive or repulsive. The underlying physics is discussed, and the physical equivalence with the spin one-half AB case is established.

  12. C3I graphical applications

    NASA Astrophysics Data System (ADS)

    Labatt, Earl C., Jr.

    1991-09-01

    Past research efforts in the field of command, control, communications, and intelligence (C3I), have concentrated on the application and refinement of advanced artificial intelligence (AI) concepts. However, the man-machine interface to these advanced applications has experienced little improvement and does not adequately reflect some of the AI concepts embedded within these systems. The development of more advanced computing techniques requires a more sophisticated interface to the system. These enhancements cannot be adequately conceived by a user using traditional display techniques. The underlying AI concepts that help facilitate the transfer of information between acquired C3I data and an operator are revealed. Many of these concepts are discussed in regard to their application in current Tactical Air Force Research Projects. In addition, the limitations of previous program interfaces and the current advances in graphical interface techniques are discussed. The focus is on two decision aid systems that incorporate several AI concepts: the Tactical Expert Mission Planner (TEMPLAR) and the Identification of Command and Control Operations Nodes (ICON).

  13. C3 photosynthesis in silico.

    PubMed

    Laisk, Agu; Eichelmann, Hillar; Oja, Vello

    2006-10-01

    A computer model comprising light reactions, electron-proton transport, enzymatic reactions, and regulatory functions of C3 photosynthesis has been developed as a system of differential budget equations for intermediate compounds. The emphasis is on electron transport through PSII and PSI and on the modeling of Chl fluorescence and 810 nm absorptance signals. Non-photochemical quenching of PSII excitation is controlled by lumenal pH. Alternative electron transport is modeled as the Mehler type O2 reduction plus the malate-oxaloacetate shuttle based on the chloroplast malate dehydrogenase. Carbon reduction enzymes are redox-controlled by the ferredoxin-thioredoxin system, sucrose synthesis is controlled by the fructose 2,6-bisphosphate inhibition of cytosolic FBPase, and starch synthesis is controlled by ADP-glucose pyrophosphorylase. Photorespiratory glycolate pathway is included in an integrated way, sufficient to reproduce steady-state rates of photorespiration. Rate-equations are designed on principles of multisubstrate-multiproduct enzyme kinetics. The parameters of the model were adopted from literature or were estimated from fitting the photosynthetic rate and pool sizes to experimental data. The model provided good simulations for steady-state photosynthesis, Chl fluorescence, and 810 nm transmittance signals under varying light, CO2 and O2 concentrations, as well as for the transients of post-illumination CO2 uptake, Chl fluorescence induction and the 810 nm signal. The modeling shows that the present understanding of photosynthesis incorporated in the model is basically correct, but still insufficient to reproduce the dark-light induction of photosynthesis, the time kinetics of non-photochemical quenching, 'photosynthetic control' of plastoquinone oxidation, cyclic electron flow around PSI, oscillations in photosynthesis. The model may find application for predicting the results of gene transformations, the analysis of kinetic experimental data, the

  14. The Importance of the C3 Framework

    ERIC Educational Resources Information Center

    Social Education, 2013

    2013-01-01

    "The C3 Framework for Social Studies State Standards will soon be released under the title "The College, Career, and Civic Life (C3) Framework for Social Studies State Standards: State Guidance for Enhancing the Rigor of K-12 Civics, Economics, Geography, and History." The C3 Project Director and Lead Writer was NCSS member Kathy…

  15. 42 CFR 52c.3 - Eligibility.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Eligibility. 52c.3 Section 52c.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.3 Eligibility. To be eligible for a grant under this Program, an applicant must...

  16. 42 CFR 52c.3 - Eligibility.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Eligibility. 52c.3 Section 52c.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.3 Eligibility. To be eligible for a grant under this Program, an applicant must...

  17. 42 CFR 52c.3 - Eligibility.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Eligibility. 52c.3 Section 52c.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.3 Eligibility. To be eligible for a grant under this Program, an applicant must...

  18. 42 CFR 52c.3 - Eligibility.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Eligibility. 52c.3 Section 52c.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.3 Eligibility. To be eligible for a grant under this Program, an applicant must...

  19. 42 CFR 52c.3 - Eligibility.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Eligibility. 52c.3 Section 52c.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM § 52c.3 Eligibility. To be eligible for a grant under this Program, an applicant must...

  20. The Importance of the C3 Framework

    ERIC Educational Resources Information Center

    Social Education, 2013

    2013-01-01

    "The C3 Framework for Social Studies State Standards will soon be released under the title "The College, Career, and Civic Life (C3) Framework for Social Studies State Standards: State Guidance for Enhancing the Rigor of K-12 Civics, Economics, Geography, and History." The C3 Project Director and Lead Writer was NCSS member Kathy…

  1. A Revised Mechanism for the Activation of Complement C3 to C3b

    PubMed Central

    Rodriguez, Elizabeth; Nan, Ruodan; Li, Keying; Gor, Jayesh; Perkins, Stephen J.

    2015-01-01

    The solution structure of complement C3b is crucial for the understanding of complement activation and regulation. C3b is generated by the removal of C3a from C3. Hydrolysis of the C3 thioester produces C3u, an analog of C3b. C3b cleavage results in C3c and C3d (thioester-containing domain; TED). To resolve functional questions in relation to C3b and C3u, analytical ultracentrifugation and x-ray and neutron scattering studies were used with C3, C3b, C3u, C3c, and C3d, using the wild-type allotype with Arg102. In 50 mm NaCl buffer, atomistic scattering modeling showed that both C3b and C3u adopted a compact structure, similar to the C3b crystal structure in which its TED and macroglobulin 1 (MG1) domains were connected through the Arg102–Glu1032 salt bridge. In physiological 137 mm NaCl, scattering modeling showed that C3b and C3u were both extended in structure, with the TED and MG1 domains now separated by up to 6 nm. The importance of the Arg102–Glu1032 salt bridge was determined using surface plasmon resonance to monitor the binding of wild-type C3d(E1032) and mutant C3d(A1032) to immobilized C3c. The mutant did not bind, whereas the wild-type form did. The high conformational variability of TED in C3b in physiological buffer showed that C3b is more reactive than previously thought. Because the Arg102-Glu1032 salt bridge is essential for the C3b-Factor H complex during the regulatory control of C3b, the known clinical associations of the major C3S (Arg102) and disease-linked C3F (Gly102) allotypes of C3b were experimentally explained for the first time. PMID:25488663

  2. Dense Deposit Disease and C3 Glomerulopathy

    PubMed Central

    Barbour, Thomas D.; Pickering, Matthew C.; Terence Cook, H.

    2013-01-01

    Summary C3 glomerulopathy refers to those renal lesions characterized histologically by predominant C3 accumulation within the glomerulus, and pathogenetically by aberrant regulation of the alternative pathway of complement. Dense deposit disease is distinguished from other forms of C3 glomerulopathy by its characteristic appearance on electron microscopy. The extent to which dense deposit disease also differs from other forms of C3 glomerulopathy in terms of clinical features, natural history, and outcomes of treatment including renal transplantation is less clear. We discuss the pathophysiology of C3 glomerulopathy, with evidence for alternative pathway dysregulation obtained from affected individuals and complement factor H (Cfh)-deficient animal models. Recent linkage studies in familial C3 glomerulopathy have shown genomic rearrangements in the Cfh-related genes, for which the novel pathophysiologic concept of Cfh deregulation has been proposed. PMID:24161036

  3. Current concepts in C3 glomerulopathy.

    PubMed

    Thomas, S; Ranganathan, D; Francis, L; Madhan, K; John, G T

    2014-11-01

    Complement component 3 glomerulopathy (C3G) is a recently defined entity comprising of dense deposit disease and C3 glomerulonephritis. The key histological feature is the presence of isolated C3 deposits without immunoglobulins. Often masqueradng as some of the common glomerulonephritides this is a prototype disorder occurring from dysregulated alternate complement pathway with recently identified genetic defects and autoantibodies. We review the pathophysiology, clinical features, and diagnostic and treatment strategies.

  4. Electron Interactions With C3F8

    NASA Astrophysics Data System (ADS)

    Christophorou, L. G.; Olthoff, J. K.

    1998-09-01

    To aid the many and diverse applications for which perfluoropropane (C3F8) is suited, we critically evaluate and synthesize existing knowledge on electron scattering and electron energy-loss processes for the C3F8 molecule, and provide recommendations for the most reliable data. We also draw attention to electron-interaction data that are not presently available, but are needed for modeling the behavior of C3F8 in practical uses, especially plasma processing.

  5. Association of serum lipids and coronary artery disease with polymorphisms in the apolipoprotein AI-CIII-AIV gene cluster.

    PubMed

    Rai, Himanshu; Sinha, Nakul; Finn, James; Agrawal, Suraksha; Mastana, Sarabjit

    2016-12-31

    Genetic variants are considered as one of the main determinants of the concentration of serum lipids and coronary artery disease (CAD). Polymorphisms in the Apolipoprotein (Apo) AI-CIII-AIV gene cluster has been known to affect the concentrations of various lipid sub-fractions and the risk of CAD. The present study assessed associations between polymorphisms of the Apo AI-CIII-AIV gene cluster, [ApoA-I,-75G > A, (rs1799837); ApoC-III 3238C > G, (SstI), (rs5128) and ApoA-IV, Thr347Ser(347A > T), (rs675)] with serum lipids and their contributions to CAD in North Indian population. We recruited age, sex matched, 200 CAD patients and 200 healthy controls and tested them for fasting levels of serum lipids. We genotyped selected polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. There were no statistically significant association of selected polymorphisms (or their combinations) with CAD even after employing additive, dominant and recessive models. However there was significant association of selected polymorphisms with various lipid traits amongst the control cohort (p < 0.05). Mean levels of high density lipoprotein cholesterol and triglycerides were found to be significantly higher among controls carrying at least one mutant allele at ApoA1-75G > A (p = 0.019) and ApoCIII SstI (p < 0.001) polymorphism respectively. Our study observed that the selected polymorphisms in the ApoAI-CIII-AIV gene cluster although significantly affect various lipid traits but this affect does not seem to translate into association with CAD, at least among North Indian population.

  6. Association of serum lipids and coronary artery disease with polymorphisms in the apolipoprotein AI-CIII-AIV gene cluster

    PubMed Central

    Rai, Himanshu; Sinha, Nakul; Finn, James; Agrawal, Suraksha; Mastana, Sarabjit

    2016-01-01

    Abstract Genetic variants are considered as one of the main determinants of the concentration of serum lipids and coronary artery disease (CAD). Polymorphisms in the Apolipoprotein (Apo) AI-CIII-AIV gene cluster has been known to affect the concentrations of various lipid sub-fractions and the risk of CAD. The present study assessed associations between polymorphisms of the Apo AI-CIII-AIV gene cluster, [ApoA-I,-75G > A, (rs1799837); ApoC-III 3238C > G, (SstI), (rs5128) and ApoA-IV, Thr347Ser(347A > T), (rs675)] with serum lipids and their contributions to CAD in North Indian population. We recruited age, sex matched, 200 CAD patients and 200 healthy controls and tested them for fasting levels of serum lipids. We genotyped selected polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. There were no statistically significant association of selected polymorphisms (or their combinations) with CAD even after employing additive, dominant and recessive models. However there was significant association of selected polymorphisms with various lipid traits amongst the control cohort (p < 0.05). Mean levels of high density lipoprotein cholesterol and triglycerides were found to be significantly higher among controls carrying at least one mutant allele at ApoA1-75G > A (p = 0.019) and ApoCIII SstI (p < 0.001) polymorphism respectively. Our study observed that the selected polymorphisms in the ApoAI-CIII-AIV gene cluster although significantly affect various lipid traits but this affect does not seem to translate into association with CAD, at least among North Indian population. PMID:28261635

  7. Small Spacecraft Technology Initiative (SSTI)

    NASA Technical Reports Server (NTRS)

    Reppucci, George

    1995-01-01

    This is the second in a series of semi-annual reports that describe the technology areas being advanced under this contract and the progress achieved to date. The last technology report concentrated on the spacecraft. This report places greater emphasis on the payloads. White papers by several of the payload providers are attached. These are HSI, UCB, PRKE, and CAFE. This report covers the period from January 1995 through June 1995.

  8. Ionic tethering contributes to the conformational stability and function of complement C3b.

    PubMed

    López-Perrote, Andrés; Harrison, Reed E S; Subías, Marta; Alcorlo, Martín; Rodríguez de Córdoba, Santiago; Morikis, Dimitrios; Llorca, Oscar

    2017-02-27

    C3b, the central component of the alternative pathway (AP) of the complement system, coexists as a mixture of conformations in solution. These conformational changes can affect interactions with other proteins and complement regulators. Here we combine a computational model for electrostatic interactions within C3b with molecular imaging to study the conformation of C3b. The computational analysis shows that the TED domain in C3b is tethered ionically to the macroglobulin (MG) ring. Monovalent counterion concentration affects the magnitude of electrostatic forces anchoring the TED domain to the rest of the C3b molecule in a thermodynamic model. This is confirmed by observing NaCl concentration dependent conformational changes using single molecule electron microscopy (EM). We show that the displacement of the TED domain is compatible with C3b binding to Factor B (FB), suggesting that the regulation of the C3bBb convertase could be affected by conditions that promote movement in the TED domain. Our molecular model also predicts mutations that could alter the positioning of the TED domain, including the common R102G polymorphism, a risk variant for developing age-related macular degeneration. The common C3b isoform, C3bS, and the risk isoform, C3bF, show distinct energetic barriers to displacement in the TED that are related to a network of electrostatic interactions at the interface of the TED and MG-ring domains of C3b. These computational predictions agree with experimental evidence that shows differences in conformation observed in C3b isoforms purified from homozygous donors. Altogether, we reveal an ionic, reversible attachment of the TED domain to the MG ring that may influence complement regulation in some mutations and polymorphisms of C3b.

  9. The interstellar chemistry of C3H and C3H2 isomers

    NASA Astrophysics Data System (ADS)

    Loison, Jean-Christophe; Agúndez, Marcelino; Wakelam, Valentine; Roueff, Evelyne; Gratier, Pierre; Marcelino, Núria; Reyes, Dianailys Nuñez; Cernicharo, José; Gerin, Maryvonne

    2017-10-01

    We report the detection of linear and cyclic isomers of C3H and C3H2 towards various starless cores and review the corresponding chemical pathways involving neutral (C3Hx with x = 1,2) and ionic (C3Hx+ with x = 1,2,3) isomers. We highlight the role of the branching ratio of electronic dissociative recombination (DR) reactions of C3H2+ and C3H3+ isomers, showing that the statistical treatment of the relaxation of C3H* and C3H2* produced in these DR reactions may explain the relative c,l-C3H and c,l-C3H2 abundances. We have also introduced in the model the third isomer of C3H2 (HCCCH). The observed cyclic-to-linear C3H2 ratio varies from 110 ± 30 for molecular clouds with a total density of about 1 × 104 molecules cm-3 to 30 ± 10 for molecular clouds with a total density of about 4 × 105 molecules cm-3, a trend well reproduced with our updated model. The higher ratio for molecular clouds with low densities is determined mainly by the importance of the H + l-C3H2 → H + c-C3H2 and H + t-C3H2 → H + c-C3H2 isomerization reactions.

  10. RECEPTOR FOR SOLUBLE C3 AND C3b ON HUMAN LYMPHOBLASTOID (RAJI) CELLS

    PubMed Central

    Theofilopoulos, Argyrios N.; Bokisch, Viktor A.; Dixon, Frank J.

    1974-01-01

    This study describes the presence of a receptor for fluid phase human C3 and C3b on Raji cell membranes. The binding of C3 and C3b was demonstrated indirectly by a fluoresceinated anti-C3 serum and directly by using radioiodinated proteins. No other complement proteins or serum factors were needed to mediate binding of C3 and C3b to the receptor. The possibility of enzymatic cleavage of C3 before or after its attachment on the cell membrane was ruled out by the demonstration of antigenically intact C3 on Raji cells. Inhibition and dissociation of Raji cell-EAC1423 rosettes by C3 and C3b indicated that both of these proteins bind to the same receptor site or closely associated receptor sites on Raji cells. C3b-bearing Raji cells were immune adherence negative, indicating that C3b binding to the receptor is brought about through the immune adherence region of the molecule and not the C3d portion. The C3 receptor on Raji cell membranes is uniformly distributed and can move on the membrane plane. Approximately 4 x 105 molecules of C3 or C3b bind per Raji cell. The receptor had a higher affinity for C3 than C3b, as was shown by uptake experiments and inhibition of Raji cell-EAC1423 rosette formation. Apart from the described receptor for C3 and C3b another specific receptor for C3b inactivator-cleaved C3b (C3d) bound to red cells was shown to be present on Raji cells. Raji cells cultured in medium containing fresh normal human serum and cobra venom factor were lysed. Similar results were obtained when C3b-bearing Raji cells were cultured in medium with fresh normal human serum. The lytic effect could be abolished by inactivating serum C3 proactivator (C3PA) and required C6. It was concluded that C3b bound to the Raji cell membrane activates the complement system through the alternate pathway and results in membrane damage and cytolysis. It is postulated that cell destruction by this mechanism may play an important role in vivo in controlling cell growth. PMID:4591176

  11. C3 — EDRN Public Portal

    Cancer.gov

    Complement component C3, a secreted protein found in plasma, plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are susceptible to bacterial infection.

  12. Complement C3 in Bernese Mountain dogs.

    PubMed

    Gerber, Bernhard; Eichenberger, Simone; Joller-Jemelka, Helen I; Wittenbrink, Max M; Reusch, Claudia E

    2010-06-01

    Previous research suggests that low serum concentrations of the third component of complement (C3) are associated with both the susceptibility to infectious agents such as Borrelia burgdorferi and the development of glomerular disease. We hypothesized that low levels of C3 are associated with the coincident occurrence of B. burgdorferi infection and glomerulonephritis in Bernese Mountain dogs. The aims of this study were to evaluate the serum concentration of C3 in Bernese Mountain dogs with and without antibodies against B. burgdorferi and to compare this concentration with that of healthy control dogs. Eighty-three clinically healthy Bernese Mountain dogs and 46 control dogs were included. Antibodies against B. burgdorferi were determined using an ELISA with a whole cell sonicate as antigen. Results were confirmed using Western blot. C3 was measured using a single radial immunodiffusion test. Results were reported as the percentage concentration of C3 compared with that in pooled preserved canine serum (100% C3 concentration). Median C3 concentration was 128.5% in Bernese Mountain dogs with antibodies against B. burgdorferi, 133.5% in B. burgdorferi-negative Bernese Mountain dogs, 87.8% in positive control dogs, and 102.2% in negative control dogs. Within Bernese Mountain and control groups, C3 was lower in dogs with antibodies against B. burgdorferi compared with those without. Percentage concentration of C3 was higher in healthy Bernese Mountain dogs compared with control dogs. Low C3 concentration is not an explanation for the high prevalence of B. burgdorferi infections and glomerular disease in Bernese Mountain dogs.

  13. C3-class Solar Flare Eruption

    NASA Image and Video Library

    Just as sunspot 1105 was turning away from Earth on Sept. 8, the active region erupted, producing a C3-class solar flare (peak @ 2330 UT) and a fantastic prominence. This is a three color closeup o...

  14. 29 CFR 2575.502c-3 - Adjusted civil penalty under section 502(c)(3).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... ACT OF 1974 ADJUSTMENT OF CIVIL PENALTIES UNDER ERISA TITLE I Adjustment of Civil Penalties Under ERISA Title I § 2575.502c-3 Adjusted civil penalty under section 502(c)(3). In accordance with the... section 502(c)(3) of the Employee Retirement Income Security Act of 1974, as amended (ERISA), is...

  15. 29 CFR 2575.502c-3 - Adjusted civil penalty under section 502(c)(3).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... ACT OF 1974 ADJUSTMENT OF CIVIL PENALTIES UNDER ERISA TITLE I Adjustment of Civil Penalties Under ERISA Title I § 2575.502c-3 Adjusted civil penalty under section 502(c)(3). In accordance with the... section 502(c)(3) of the Employee Retirement Income Security Act of 1974, as amended (ERISA), is...

  16. 29 CFR 2575.502c-3 - Adjusted civil penalty under section 502(c)(3).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... ACT OF 1974 ADJUSTMENT OF CIVIL PENALTIES UNDER ERISA TITLE I Adjustment of Civil Penalties Under ERISA Title I § 2575.502c-3 Adjusted civil penalty under section 502(c)(3). In accordance with the... section 502(c)(3) of the Employee Retirement Income Security Act of 1974, as amended (ERISA), is...

  17. 29 CFR 2575.502c-3 - Adjusted civil penalty under section 502(c)(3).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ACT OF 1974 ADJUSTMENT OF CIVIL PENALTIES UNDER ERISA TITLE I Adjustment of Civil Penalties Under ERISA Title I § 2575.502c-3 Adjusted civil penalty under section 502(c)(3). In accordance with the... section 502(c)(3) of the Employee Retirement Income Security Act of 1974, as amended (ERISA), is...

  18. 29 CFR 2575.502c-3 - Adjusted civil penalty under section 502(c)(3).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ACT OF 1974 ADJUSTMENT OF CIVIL PENALTIES UNDER ERISA TITLE I Adjustment of Civil Penalties Under ERISA Title I § 2575.502c-3 Adjusted civil penalty under section 502(c)(3). In accordance with the... section 502(c)(3) of the Employee Retirement Income Security Act of 1974, as amended (ERISA), is...

  19. C3H8 and C3H4 in Titan's atmosphere

    NASA Technical Reports Server (NTRS)

    Maguire, W. C.; Hanel, R. A.; Jennings, D. E.; Kunde, V. G.; Samuelson, R. E.

    1981-01-01

    Four bands of propane C3H8 and two of methyl acetylene C3H4 have been identified in the Voyager IR spectrum of Titan. Stratospheric abundances of 2 x 10 to the -5 for C3H8 and 3 x 10 to the -8 for C3H4 have been determined for the mid-latitude region. A feature at 1,154/cm, previously assigned solely to CH3D, is now identified at least in part due to C3H8.

  20. Genotyping of skin and soft tissue infection (SSTI)-associated methicillin-resistant Staphylococcus aureus (MRSA) strains among outpatients in a teaching hospital in Japan: application of a phage-open reading frame typing (POT) kit.

    PubMed

    Maeda, Tadashi; Saga, Tomoo; Miyazaki, Taito; Kouyama, Yuichi; Harada, Sohei; Iwata, Morihiro; Yoshizawa, Sadako; Kimura, Soichiro; Ishii, Yoshikazu; Urita, Yoshihisa; Sugimoto, Motonobu; Yamaguchi, Keizo; Tateda, Kazuhiro

    2012-12-01

    We aimed to elucidate the current epidemiological features of outpatient skin and soft tissue infection (SSTI)-associated methicillin-resistant Staphylococcus aureus (MRSA) in Japan. Altogether, we evaluated the performance of a phage-open reading frame typing (POT) kit for genotyping these MRSA strains. We collected 57 MRSA strains from all outpatients with SSTIs attending a teaching hospital in Japan. Drug susceptibility measurement and genotyping including SCCmec typing, spa typing, multilocus sequence typing, pulsed-field gel electrophoresis, and commercial POT-kit were performed. The majority of strains (39 strains, 68 %) had the SCCmec-II element. Seventeen strains (30 %) with SCCmec-IV accounted for the second largest population. Strains with SCCmec-IV and SCCmec-V appeared multiclonal, and a predominance of Panton-Valentine leukocidin (PVL) gene-negative CC8/spa-CC008 strains, as well as the first isolate of an ST93 strain in Japan, was observed among them. Only one USA300 strain was identified. Strains with SCCmec-IV and SCCmec-V were significantly susceptible to antimicrobials. The PVL gene was found in 5 SCCmec-IV strains and 1 SCCmec-V strain. The POT-kit successfully predicted the SCCmec type in 54 strains (95 %), and typing by POT1 scores was highly concordant with SCCmec typing and spa typing. Moreover, three PVL-positive strains fell into a particular POT type (POT scores, 106-77-113). Simpson's index of the POT-kit was 0.977. In conclusion, the present study clarified the multiclonal nature of outpatient SSTI-associated MRSA in a teaching hospital in Japan. These data also underscore the utility of the POT-kit for non-outbreak surveillance through its simple platform consisting of two multiplex PCRs without sequencing.

  1. C3 glomerulonephritis and autoimmune disease: more than a fortuitous association?

    PubMed

    Alexander, Mariam P; Fervenza, Fernando C; De Vriese, An S; Smith, Richard J H; Nasr, Samih H; Cornell, Lynn D; Herrera Hernandez, Loren P; Zhang, Yuzhou; Sethi, Sanjeev

    2016-04-01

    C3 glomerulonephritis (C3GN) results from genetic or acquired dysregulation of the alternative complement pathway. A subset of patients may have clinical and biochemical characteristics compatible with an autoimmune disorder. We studied a cohort of 85 patients with confirmed C3GN (2007-2014), of which ten patients (3 male, 7 female; mean age 38.5 years) had an associated autoimmune disorder. All patients had abnormal ANA titers, 6 also had positive ds-DNA titers. At the time of presentation with C3GN, all 7 female patients had autoimmune-related presentations. Of the 3 male patients, only 1 patient had autoimmune-related presentations. Kidney biopsy showed predominantly mesangial proliferative or membranoproliferative glomerulonephritis. In 5 patients, the alternative pathway was evaluated. All had allele variants/polymorphisms associated with C3GN. One patient was also positive for C3Nefs. Treatment varied form conservative management to the use of prednisone alone or with cytotoxic therapy. Mean serum creatinine decreased from 2.0 to 1.4 mg/dL while proteinuria decreased from 2300 to 994 mg/24 h in 8 patients with follow-up. The study highlights the association between C3GN and autoimmune disorders, particularly in female patients. The study suggests that an autoimmune milieu may act as a trigger for the development of C3GN in genetically susceptible patients. Short-term prognosis of C3GN associated with autoimmune disorders appears excellent.

  2. The Development of the C3 Framework

    ERIC Educational Resources Information Center

    Social Education, 2013

    2013-01-01

    Susan Griffin, executive director of NCSS, was chair of the Task Force of Professional Organizations that initiated and guided the development of "The College, Career, and Civic Life (C3) Framework for Social Studies State Standards", which will soon be released. In this interview with "Social Education", Susan explains how the…

  3. The Development of the C3 Framework

    ERIC Educational Resources Information Center

    Social Education, 2013

    2013-01-01

    Susan Griffin, executive director of NCSS, was chair of the Task Force of Professional Organizations that initiated and guided the development of "The College, Career, and Civic Life (C3) Framework for Social Studies State Standards", which will soon be released. In this interview with "Social Education", Susan explains how the…

  4. Anomalous absorption in c-C_3H and c-C_3D radicals

    NASA Astrophysics Data System (ADS)

    Chandra, S.; Shinde, S. V.; Kegel, W. H.; Sedlmayr, E.

    Yamamoto et al. (1987) reported the first detection of the c-C_3H radical in TMC-1 through its transition 2_1 2 rightarrow 1_1 1 at 91.5 GHz. The column density of c-C_3H in TMC-1 was estimated to be 6 times 10^12 cm^-2, which is about one order of magnitude lower than that of the c-C_3H_2 which is ubiquitous in galactic objects. Mangum & Wootten (1990) detected c-C_3H through the transition 1_1 0 rightarrow 1_1 1 at 14.8 GHz in 12 additional galactic objects. The most probable production mechanism of both the c-C_3H and c-C_3H_2 in dark clouds is a common dissociation reaction of the C_3H_3^+ ion (Adams & Smith 1987). Although the c-C_3H is 0.8 eV less stable than its isomer l-C_3H, finding of comparable column densities of both the isomers in TMC-1 suggests that the formation rate for both, c-C_3H and l-C_3H, are of about the same order in the cosmic objects. The existence of a metastable isomer under interstellar conditions is a well known phenomenon in astronomy. The aim of this investigation is a quantitative estimate of relative line intensities under NLTE conditions. For wide ranges of physical parameters, where these molecules may be found, we have solved a set of statistical equilibrium equations coupled with the equations of radiative transfer in an on-the-spot approximation. For c-C_3H, we accounted for 51 energy levels connected by 207 radiative transitions and for c-C_3D, we accounted for 51 energy levels connected by 205 radiative transitions. Our results show that the 3_3 1 rightarrow 3_3 0 transition of c-C_3H and c-C_3D may be found in absorption against the cosmic microwave background (CMB). Furthermore, we found population inversion for the 1_1 0 rightarrow 1_1 1 transition. These findings may be useful in identifying these molecules in other cosmic objects, as well as for the determination of physical parameters in these objects.

  5. Photosynthesis of C3, C3-C4, and C4 grasses at glacial CO2.

    PubMed

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

    2014-07-01

    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. © The Author 2014

  6. Extinct I-129 in C3 chondrites

    NASA Astrophysics Data System (ADS)

    Crabb, J.; Lewis, R. S.; Anders, E.

    1982-12-01

    Eight C3 chondrites were examined by the I-129 to Xe-129 dating method to determine whether their initial I-129/I-127 ratios, or R(0), correlate with any other properties. The R(0)'s range from 1.60 x 10 to the -4th to 1.09 x 10 to the -4th, corresponding to I to Xe ages from 2.0 Myr before to 6.7 Myr after the Murchison magnetite. Three C30's have essentially indistinguishable R(0)'s, while a fourth is undatable. Four C3V's show a distinct spread, ranging from 1.60 + or 0.07 x 10 to the -4th to 1.09 + or - 0.10 x 10 to the -4th. These R(0)'s correlate inversely with four other properties: I, Br, and Cd content, olivine composition, both percent mean deviation, and proportion of iron-poor olivine grains. The simplest model that accounts for the correlations with R(0) involves mixing of two iodine components in the solar nebula, associated with gas and grains, respectively. The second, of lower I-129/I-127 ratio, predominated at later times and thus became enriched in late-formed meteorites.

  7. [Plasma concentrations of complement components C3, C4, and C3PA in juvenile nephropathies].

    PubMed

    Brai, M; Amato, G; Ziino, M; Tolone, G

    1975-01-01

    Complement profiles in children suffering for nephropathy have been investigated. The approach has proved useful in differentiating distinct nosologic entities. Plasma C3 and, to a lesser extent, C4 levels were found to be markedly reduced in glomerulonephritis and significantly increased in nephrotic syndrome. Although in both conditions plasma C3PA concentration ranges normally, additional data are request before assuming that alternate pathway is not involved. The extensive serial study of complement profiles should be widely adopted by clinicians managing nephropatic patients.

  8. A Familial C3GN Secondary to Defective C3 Regulation by Complement Receptor 1 and Complement Factor H

    PubMed Central

    Roumenina, Lubka T.; Bruneau, Sarah; Marinozzi, Maria Chiara; Rybkine, Tania; Schramm, Elizabeth C.; Java, Anuja; Atkinson, John P.; Aldigier, Jean Claude; Bridoux, Frank; Touchard, Guy; Fremeaux-Bacchi, Veronique

    2016-01-01

    C3 glomerulopathy is a recently described form of CKD. C3GN is a subtype of C3 glomerulopathy characterized by predominant C3 deposits in the glomeruli and is commonly the result of acquired or genetic abnormalities in the alternative pathway (AP) of the complement system. We identified and characterized the first mutation of the C3 gene (p. I734T) in two related individuals diagnosed with C3GN. Immunofluorescence and electron microscopy studies showed C3 deposits in the subendothelial space, associated with unusual deposits located near the complement receptor 1 (CR1)-expressing podocytes. In vitro, this C3 mutation exhibited decreased binding to CR1, resulting in less CR1-dependent cleavage of C3b by factor 1. Both patients had normal plasma C3 levels, and the mutant C3 interacted with factor B comparably to wild-type (WT) C3 to form a C3 convertase. Binding of mutant C3 to factor H was normal, but mutant C3 was less efficiently cleaved by factor I in the presence of factor H, leading to enhanced C3 fragment deposition on glomerular cells. In conclusion, our results reveal that a CR1 functional deficiency is a mechanism of intraglomerular AP dysregulation and could influence the localization of the glomerular C3 deposits. PMID:26471127

  9. Cytolytic effects of the complement cleavage product, C3a.

    PubMed Central

    Ferluga, J.; Schorlemmer, H. U.; Baptista, L. C.; Allison, A. C.

    1976-01-01

    Purified C3a, a cleavage product of the third component of complement,was incubated with various cell types of human and mouse origin. All the tumour cell types tested were lysed by low concentrations of C3a, whereas normal human lymphocytes were relatively resistant. No lysis was produced by C3 or C3b. The possible role of C3a in immunity against tumours is discussed. PMID:827304

  10. Anomalous absorption in c-C3H and c-C3D radicals

    NASA Astrophysics Data System (ADS)

    Chandra, S.; Shinde, S. V.; Kegel, W. H.; Sedlmayr, E.

    2007-05-01

    Context: The c-C3H radical was first detected in TMC-1 by Yamamoto et al. (1987, ApJ, 322, L55), who observed the 2{12} → 1{11} transition at 91.5 GHz in emission. Mangum & Wootten (1990, A&A, 239, 319) observed the 1{10} → 1{11} transition at 14.8 GHz in emission in 12 additional galactic objects. Aims: The aim of this investigation is a quantitative estimate of relative line intensities under NLTE conditions. Methods: For wide ranges of physical parameters, where these molecules may be found, we have solved a set of statistical equilibrium equations coupled with the equations of radiative transfer in an on-the-spot approximation. For c-C3H, we accounted for 51 energy levels connected by 207 radiative transitions, and for c-C3D, we accounted for 51 energy levels connected by 205 radiative transitions. Results: Our results show that the 3{31} → 3{30} transition of c-C3H and c-C3D may be found in absorption against the cosmic microwave background (CMB). Furthermore, we found population inversion for the 1{10} → 1{11} transition. These findings may be useful in identifying these molecules in other cosmic objects, as well as for the determination of physical parameters in these objects. Tables 1-3 and Figs. 4, 5 are only available in electronic form at http://www.aanda.org

  11. Influence of C3 level on the determination of C3d in plasma and synovial fluid by radial immunodiffusion.

    PubMed

    Hack, C E; Paardekooper, J; Hannema, A J

    1986-02-12

    The influence of C3 levels on the determination of C3d in plasma and synovial fluid by radial immunodiffusion was investigated. In the method used, C3 is precipitated by 11% polyethylene glycol (PEG), and C3d is measured in the supernatant. In 51 healthy donors, a weak though significant correlation between C3 and C3d levels was found. The mean concentration of C3d was 1.6% of that in aged serum from healthy donors. So, small amounts of C3 (i.e., 1-2% of the normal plasma level) in the 11% PEG supernatants may contribute significantly to the C3d levels measured. A radioimmunoassay that detects C3, C3b, iC3b and C3c was used to measure C3 levels in the PEG supernatants. In PEG supernatants of 4 plasma samples, 0.3-0.6% of the C3 level in normal plasma was found, whereas in those of 2 synovial fluids much higher levels were found (4-10% of the normal plasma level). When purified 125I-labeled antibodies against C3c were added to the gel of the radial immunodiffusion, C3c antigen was detected in the precipitation rings obtained with all PEG supernatants of plasma samples from patients. Therefore, the quantitative contribution of C3 to the precipitation rings in the C3d radial immunodiffusion was analyzed after the addition of an excess of anti-C3c antibodies to the gel. No effect on the size of the C3d-precipitation rings obtained with plasma samples from patients was observed. However, the C3d precipitation rings obtained with synovial fluids were significantly smaller when the gel used in the radial immunodiffusion contained an excess of anti-C3c antibodies together with the anti-C3d serum. We conclude that it is necessary to add an excess of anti-C3c antibodies to the gel used for the radial immunodiffusion, for the determination of C3d levels in synovial fluid. An antiserum against human C3b, which contains both anti-C3c and anti-C3d antibodies, can be used for this purpose.

  12. Geminivirus C3 Protein: Replication Enhancement and Protein Interactions

    PubMed Central

    Settlage, Sharon B.; See, Renee G.; Hanley-Bowdoin, Linda

    2005-01-01

    Most dicot-infecting geminiviruses encode a replication enhancer protein (C3, AL3, or REn) that is required for optimal replication of their small, single-stranded DNA genomes. C3 interacts with C1, the essential viral replication protein that initiates rolling circle replication. C3 also homo-oligomerizes and interacts with at least two host-encoded proteins, proliferating cell nuclear antigen (PCNA) and the retinoblastoma-related protein (pRBR). It has been proposed that protein interactions contribute to C3 function. Using the C3 protein of Tomato yellow leaf curl virus, we examined the impact of mutations to amino acids that are conserved across the C3 protein family on replication enhancement and protein interactions. Surprisingly, many of the mutations did not affect replication enhancement activity of C3 in tobacco protoplasts. Other mutations either enhanced or were detrimental to C3 replication activity. Analysis of mutated proteins in yeast two-hybrid assays indicated that mutations that inactivate C3 replication enhancement activity also reduce or inactivate C3 oligomerization and interaction with C1 and PCNA. In contrast, mutated C3 proteins impaired for pRBR binding are fully functional in replication assays. Hydrophobic residues in the middle of the C3 protein were implicated in C3 interaction with itself, C1, and PCNA, while polar resides at both the N and C termini of the protein are important for C3-pRBR interaction. These experiments established the importance of C3-C3, C3-C1, and C3-PCNA interactions in geminivirus replication. While C3-pRBR interaction is not required for viral replication in cycling cells, it may play a role during infection of differentiated cells in intact plants. PMID:16014949

  13. DNA restriction-site polymorphisms associated with the alpha 1-antitrypsin gene.

    PubMed Central

    Cox, D W; Billingsley, G D; Mansfield, T

    1987-01-01

    Restriction-site variation in and around the alpha 1-antitrypsin gene has been studied using two genomic probes. With use of restriction enzymes SstI, MspI, and AvaII, three polymorphic sites have been described with a 4.6-kb probe in the 5' portion of the gene. With use of a 6.5-kb probe, polymorphisms in the coding and 3' regions of the gene have been detected with AvaII, MaeIII, and TaqI. All of these polymorphisms are of sufficiently high frequency to be useful in genetic mapping studies. The polymorphisms with AvaII and MaeIII (6.5-kb probe) are particularly useful for prenatal diagnosis. PI types and M subtypes tend to be associated with specific DNA haplotypes; there are two different types of DNA haplotypes associated with PI M1. The extent of linkage disequilibrium differs throughout the region of the alpha 1-antitrypsin gene. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:2890296

  14. Step 1: C3 Flight Demo Data Analysis Plan

    NASA Technical Reports Server (NTRS)

    2005-01-01

    The Data Analysis Plan (DAP) describes the data analysis that the C3 Work Package (WP) will perform in support of the Access 5 Step 1 C3 flight demonstration objectives as well as the processes that will be used by the Flight IPT to gather and distribute the data collected to satisfy those objectives. In addition to C3 requirements, this document will encompass some Human Systems Interface (HSI) requirements in performing the C3 flight demonstrations. The C3 DAP will be used as the primary interface requirements document between the C3 Work Package and Flight Test organizations (Flight IPT and Non-Access 5 Flight Programs). In addition to providing data requirements for Access 5 flight test (piggyback technology demonstration flights, dedicated C3 technology demonstration flights, and Airspace Operations Demonstration flights), the C3 DAP will be used to request flight data from Non- Access 5 flight programs for C3 related data products

  15. Defining the Complement Biomarker Profile of C3 Glomerulopathy

    PubMed Central

    Zhang, Yuzhou; Nester, Carla M.; Martin, Bertha; Skjoedt, Mikkel-Ole; Meyer, Nicole C.; Shao, Dingwu; Borsa, Nicolò; Palarasah, Yaseelan

    2014-01-01

    Background and objectives C3 glomerulopathy (C3G) applies to a group of renal diseases defined by a specific renal biopsy finding: a dominant pattern of C3 fragment deposition on immunofluorescence. The primary pathogenic mechanism involves abnormal control of the alternative complement pathway, although a full description of the disease spectrum remains to be determined. This study sought to validate and define the association of complement dysregulation with C3G and to determine whether specific complement pathway abnormalities could inform disease definition. Design, setting, participants, & measurements This study included 34 patients with C3G (17 with C3 glomerulonephritis [C3GN] and 17 with dense deposit disease [DDD]) diagnosed between 2008 and 2013 selected from the C3G Registry. Control samples (n=100) were recruited from regional blood drives. Nineteen complement biomarkers were assayed on all samples. Results were compared between C3G disease categories and with normal controls. Results Assessment of the alternative complement pathway showed that compared with controls, patients with C3G had lower levels of serum C3 (P<0.001 for both DDD and C3GN) and factor B (P<0.001 for both DDD and C3GN) as well as higher levels of complement breakdown products including C3d (P<0.001 for both DDD and C3GN) and Bb (P<0.001 for both DDD and C3GN). A comparison of terminal complement pathway proteins showed that although C5 levels were significantly suppressed (P<0.001 for both DDD and C3GN) its breakdown product C5a was significantly higher only in patients with C3GN (P<0.05). Of the other terminal pathway components (C6–C9), the only significant difference was in C7 levels between patients with C3GN and controls (P<0.01). Soluble C5b-9 was elevated in both diseases but only the difference between patients with C3GN and controls reached statistical significance (P<0.001). Levels of C3 nephritic factor activity were qualitatively higher in patients with DDD compared

  16. Interplay between invertebrate C3a with vertebrate macrophages: functional characterization of immune activities of amphioxus C3a.

    PubMed

    Gao, Zhan; Li, Mengyang; Wu, Jie; Zhang, Shicui

    2013-10-01

    Our current knowledge of the structure and function of C3a comes from the study of vertebrate C3a anaphylatoxins, virtually nothing is known about the structure and function of C3a molecules in invertebrates. Here we demonstrated that C3a from the invertebrate chordate Branchiostoma japonicum, BjC3a, was similar to vertebrate C3a possessing potential antibacterial activity, as revealed by sequence analysis and computational modeling. The antibacterial activity of BjC3a was definitely confirmed by both antibacterial assay and TEM observation showing that recombinant BjC3a was directly bactericidal. Additionally, recombinant BjC3a, like vertebrate C3a, was capable of inducing sea bass macrophage migration and enhancing macrophage phagocytosis and respiratory burst response. Moreover, recombinant BjC3a-desArg (generated by removal of the C-terminal arginine), like mammalian C3a-desArg, retained the immunological activities of BjC3a such as antibacterial and respiratory burst-stimulating activities, indicating that the immunological functions of C3a-desArg were conserved throughout chordate evolution. Altogether, our findings show that invertebrate (amphioxus) BjC3a is able to interact with vertebrate (sea bass) macrophages and mediate immune activities, suggesting the emergence of the inflammatory pathway of the complement system similar to that of vertebrates in the basal chordate amphioxus.

  17. Functional analysis and quantification of the complement C3 derived anaphylatoxin C3a with a monoclonal antibody.

    PubMed Central

    Burger, R; Bader, A; Kirschfink, M; Rother, U; Schrod, L; Wörner, I; Zilow, G

    1987-01-01

    The C3 fragment C3a belongs to the anaphylatoxins. It has immune regulatory activity and contributes to the pathogenesis of the adult respiratory distress syndrome (ARDS). The low molecular weight (9 kD) of C3a complicates the production of antibodies to C3a. We obtained a monoclonal antibody (designated H13) to human C3a. It reacts with C3a or C3a-desArg and with native C3 but not with C5 or C5a. In immunoblot analysis it reacts with the alpha- but not with beta-chain of C3 and binds to a protein with a mol. wt of about 10 kD present in zymosan-activated sera which is only marginally detectable in nonactivated serum and absent in plasma. H13 crossreacts with the analogous proteins of rabbit, guinea pig and sheep. H13 has the capacity to bind 125I-radiolabelled C3a efficiently but fails totally to react with 125I-C5a or with other C3 alpha-chain fragments. H13 blocks C3a functional activity. It markedly inhibits C3a-induced 3H-serotonin release from platelets in vitro and similarly inhibits the C3a-induced extravasation of Evans blue into the skin in vivo. H13 does not interfere with the haemolytic activity of C3. An ELISA system was established using H13 which permits quantification of C3a in sera of polytrauma patients. The antibody H13 should facilitate further functional analysis of C3a in experimental systems. It should be useful for quantification of C3a in diagnostic assays and also for application in immunopathology. Images Fig. 3 PMID:3498585

  18. Toward Genomics-Based Breeding in C3 Cool-Season Perennial Grasses

    PubMed Central

    Talukder, Shyamal K.; Saha, Malay C.

    2017-01-01

    Most important food and feed crops in the world belong to the C3 grass family. The future of food security is highly reliant on achieving genetic gains of those grasses. Conventional breeding methods have already reached a plateau for improving major crops. Genomics tools and resources have opened an avenue to explore genome-wide variability and make use of the variation for enhancing genetic gains in breeding programs. Major C3 annual cereal breeding programs are well equipped with genomic tools; however, genomic research of C3 cool-season perennial grasses is lagging behind. In this review, we discuss the currently available genomics tools and approaches useful for C3 cool-season perennial grass breeding. Along with a general review, we emphasize the discussion focusing on forage grasses that were considered orphan and have little or no genetic information available. Transcriptome sequencing and genotype-by-sequencing technology for genome-wide marker detection using next-generation sequencing (NGS) are very promising as genomics tools. Most C3 cool-season perennial grass members have no prior genetic information; thus NGS technology will enhance collinear study with other C3 model grasses like Brachypodium and rice. Transcriptomics data can be used for identification of functional genes and molecular markers, i.e., polymorphism markers and simple sequence repeats (SSRs). Genome-wide association study with NGS-based markers will facilitate marker identification for marker-assisted selection. With limited genetic information, genomic selection holds great promise to breeders for attaining maximum genetic gain of the cool-season C3 perennial grasses. Application of all these tools can ensure better genetic gains, reduce length of selection cycles, and facilitate cultivar development to meet the future demand for food and fodder. PMID:28798766

  19. Toward Genomics-Based Breeding in C3 Cool-Season Perennial Grasses.

    PubMed

    Talukder, Shyamal K; Saha, Malay C

    2017-01-01

    Most important food and feed crops in the world belong to the C3 grass family. The future of food security is highly reliant on achieving genetic gains of those grasses. Conventional breeding methods have already reached a plateau for improving major crops. Genomics tools and resources have opened an avenue to explore genome-wide variability and make use of the variation for enhancing genetic gains in breeding programs. Major C3 annual cereal breeding programs are well equipped with genomic tools; however, genomic research of C3 cool-season perennial grasses is lagging behind. In this review, we discuss the currently available genomics tools and approaches useful for C3 cool-season perennial grass breeding. Along with a general review, we emphasize the discussion focusing on forage grasses that were considered orphan and have little or no genetic information available. Transcriptome sequencing and genotype-by-sequencing technology for genome-wide marker detection using next-generation sequencing (NGS) are very promising as genomics tools. Most C3 cool-season perennial grass members have no prior genetic information; thus NGS technology will enhance collinear study with other C3 model grasses like Brachypodium and rice. Transcriptomics data can be used for identification of functional genes and molecular markers, i.e., polymorphism markers and simple sequence repeats (SSRs). Genome-wide association study with NGS-based markers will facilitate marker identification for marker-assisted selection. With limited genetic information, genomic selection holds great promise to breeders for attaining maximum genetic gain of the cool-season C3 perennial grasses. Application of all these tools can ensure better genetic gains, reduce length of selection cycles, and facilitate cultivar development to meet the future demand for food and fodder.

  20. Binding of Clostridium botulinum C3 exoenzyme to intact cells.

    PubMed

    Rohrbeck, Astrid; von Elsner, Leonie; Hagemann, Sandra; Just, Ingo

    2014-06-01

    C3 from Clostridium botulinum (C3) specifically modifies Rho GTPases RhoA, RhoB, and RhoC by mono-ADP-ribosylation. The confined substrate profile of C3 is the basis for its use as pharmacological tool in cell biology to study cellular functions of Rho GTPases. Although C3 exoenzyme does not possess a cell-binding/-translocation domain, C3 is taken up by intact cells via an unknown mechanism. In the present work, binding of C3 to the hippocampus-derived HT22 cells and J774A.1 macrophages was characterized. C3 bound concentration-dependent to HT22 and J774A.1 cells. Pronase treatment of intact cells significantly reduced both C3 binding and C3 cell entry. Removal of sugar residues by glycosidase F treatment resulted in an increased binding of C3, but a reduced cell entry. To explore the involvement of phosphorylation in the binding process of C3, intact HT22 and J774A.1 cells were pre-treated with vanadate prior to incubation with C3. Inhibition of de-phosphorylation by vanadate resulted in an increased binding of C3. To differentiate between intracellular and extracellular phosphorylation, intact cells were treated with CIP (calf intestine phosphatase) to remove extracellular phosphate residues. The removal of phosphate residues resulted in a strong reduction in binding of C3 to cells. In sum, the C3 membranous binding partner is proteinaceous, and the glycosylation as well as the phosphorylation state is critical for efficient binding of C3.

  1. 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.

  2. C3 Glomerulopathy: Clinicopathologic Features and Predictors of Outcome

    PubMed Central

    Medjeral-Thomas, Nicholas R.; O’Shaughnessy, Michelle M.; O’Regan, John A.; Traynor, Carol; Flanagan, Michael; Wong, Limy; Teoh, Chia Wei; Awan, Atif; Waldron, Mary; Cairns, Tom; O’Kelly, Patrick; Dorman, Anthony M.; Pickering, Matthew C.; Conlon, Peter J.

    2014-01-01

    Summary Background and objectives The term C3 glomerulopathy describes renal disorders characterized by the presence of glomerular deposits composed of C3 in the absence of significant amounts of Ig. On the basis of electron microscopy appearance, subsets of C3 glomerulopathy include dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The full spectrum of histologic change observed in C3 glomerulopathy has yet to be defined and pathologic predictors of renal outcome within this patient population remain largely unknown. This study thus characterized a large C3 glomerulopathy cohort and identified clinicopathologic predictors of renal outcome. Design, setting, participants, & measurements All patients with kidney biopsies fulfilling criteria for C3 glomerulopathy from two quaternary renal centers within the United Kingdom and Ireland between 1992 and 2012 were retrospectively reviewed. We recorded histologic, demographic, and clinical data and determined predictors of ESRD using the Cox proportional hazards model. Results Eighty patients with C3 glomerulopathy were identified: 21 with DDD and 59 with C3GN. Patients with DDD were younger, more likely to have low serum C3 levels, and more likely to have crescentic GN than patients with C3GN. Patients with C3GN were older and had more severe arteriolar sclerosis, glomerular sclerosis, and interstitial scarring than patients with DDD. Of 70 patients with available follow-up data, 20 (29%) progressed to ESRD after a median of 28 months. Age >16 years, DDD subtype, and crescentic GN were independent predictors of ESRD within the entire cohort. Renal impairment at presentation predicted ESRD only among patients with DDD. Conclusions Although detailed serologic and genetic data are lacking, this study nevertheless identifies important clinicopathologic distinctions between patients with DDD and C3GN. These include independent predictors of renal outcome. If replicated in other cohorts, these predictors could be

  3. Toward a working definition of C3 glomerulopathy by immunofluorescence.

    PubMed

    Hou, Jean; Markowitz, Glen S; Bomback, Andrew S; Appel, Gerald B; Herlitz, Leal C; Barry Stokes, M; D'Agati, Vivette D

    2014-02-01

    Precise immunofluorescence criteria for C3 glomerulopathy remain to be defined. Here we tested hierarchical immunofluorescence criteria with varying stringency for C3 glomerulopathy in a cohort with dense deposit disease as the gold standard and then applied these criteria to analyze the incidence of C3 glomerulopathy in membranoproliferative glomerulonephritis (MPGN) types 1 and 3. Among 319 archived cases of primary MPGN types 1-3, immunofluorescence reports were retrospectively coded as glomerular deposits of the following: C3 only; C3 dominant with trace or 1+ immunoglobulin (Ig)M only; and C3 dominant and at least two orders of intensity stronger than any combination of IgG, IgM, IgA, and C1q. The most restrictive criteria of 'C3 only' captured only half of the cases with dense deposit disease (compared with 8% of type 1 and 10% of type 3). Adding the most liberal definition identified 88% of those with dense deposit disease (compared with 31% of type 1 and 39% of type 3). The unaccounted 12% had stronger intensity of Ig staining, but it never exceeded the intensity of C3. Among MPGN type 3, 90% of C3 glomerulopathy cases were the Strife and Anders variant. Repeat biopsies in C3 glomerulopathy revealed a change in immunofluorescence pattern in 10 of 23 biopsies. The prevalence of low serum C3 and/or low C4 did not significantly differ among the three immunofluorescence criteria. Thus, 'C3 only' is an impractical definition of C3 glomerulopathy, and we propose a definition of C3 dominant and at least two orders of magnitude more intense than any other immune reactant, which requires validation by alternative pathway evaluation. These criteria provide a framework for identifying patients most likely to benefit from investigations of alternative complement pathway dysregulation.

  4. Anaphylatoxin C3a induced mediator release from mast cells

    SciTech Connect

    Herrscher, R.; Hugli, T.E.; Sullivan, T.J.

    1986-03-01

    The authors investigated the biochemical and functional consequences of the binding of highly purified human C3a to isolated rat serosal mast cells. C3a caused a dose-dependent (1-30 ..mu..M), noncytotoxic release of up to 64% (+/- 7 SEM) of the mast cell histamine content. C3a (10..mu..M) increased /sup 45/Ca/sup + +/ uptake 8.2- fold (+/- 2.2 SEM) above unstimulated control values within 10 minutes. Arachidonyl-diacylglycerol and arachidonyl-monoacylglycerol levels increased significantly within 2 minutes after C3a (10 ..mu..M) stimulation. Turnover of phosphatidylinositol, phosphatidic acid, and phosphatidylcholine were increased within 15 minutes. In contrast to antigen, C3a stimulation (10 ..mu..M) was not enhanced by exogenous phosphatidylserine, and was not inhibited by ethanol (100 ..mu..mM). C3a suppressed arachidonic acid (AA) release to 38% (+/- 9 SEM) below baseline, and did not cause PGD/sub 2/ formation. C3a and the desarginine form of C3a caused identical responses in all experiments. These studies indicate that C3a stimulation activates mast cell preformed mediator release in a manner very similar to antigen-IgE stimulation, but C3a suppresses free AA levels and does not stimulate PGD/sub 2/ synthesis.

  5. Why Are C3-C4 Intermediate Species Rare?

    NASA Astrophysics Data System (ADS)

    Johnson, J. E.; Field, C. B.; Berry, J. A.

    2014-12-01

    While C3-C4 intermediate photosynthesis is thought to represent the evolutionary bridge between C3 and C4 photosynthesis, C3-C4 intermediate species are ecologically rare in comparison to both C3 and C4 species. Here, we report results from a laboratory experiment, field observations, and model simulations that suggest a new explanation for the ecological rarity of C3-C4 intermediate species. In the laboratory experiment, we combined gas exchange and fluorescence to characterize the temperature response of photosynthesis in three closely-related species in the genus Flaveria that are representatives of the C3, C3-C4 intermediate, and C4 photosynthetic pathways. The leaf temperature that maximized the quantum yield for CO2 assimilation (Topt(ΦCO2)) was 24.9 ± 0.7°C in Flaveria robusta (C3), 29.8 ± 1.0°C in F. chloraefolia (C3-C4), and 35.7 ± 0.8°C in F. bidentis (C4), and was linearly related to the temperature sensitivity of the coupling between CO2 assimilation and electron transport (d(ΦCO2/ ΦPSII)/dT)). While F. chloraefolia does not simultaneously occur with F. robusta and F. bidentis in naturally-assembled communities, this C3-C4 intermediate species does occur with other C3 and C4 species. During the growing season in two of these mixed-photosynthetic-type communities, leaf temperatures for F. chloraefolia were similar to the Topt(ΦCO2) determined in the laboratory. A model of maximum potential carbon gain suggests that competitive coexistence of C3, C3-C4 intermediate, and C4 species could be dependent on a temperature regime that highlights the distinct relative advantages of the C3-C4 intermediate pathway. In combination, these results suggest that the relative temperature sensitivity of the C3, C3-C4 intermediate, and C4 photosynthetic pathways combined with environmental variation in temperature may help to explain why C3-C4 intermediate species are generally rare.

  6. Platelet-associated complement C3 in immune thrombocytopenic purpura

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Baldini, M.G.

    1982-05-01

    Platelet-associated C3 (PA-C3) was measured with a quantitative immunofluorescence assay. With this assay, PA-C3 levels were determined for 78 normal volunteers, 30 patients with immune thrombocytopenic purpura (ITP), and 20 patients with nonimmune thrombocytopenias. Platelet-associatd IgG (PA-lgG) levels were also measured with our standard quantitative immunofluorescence assay. All patients with nonimmune thrombocytopenias and ITP in remission had normal PA-C3 levels. Twenty-four patients with active ITP wre classified into 3 groups: 9 (38%) with increased PA-IgG and normal PA-C3 levels, 10 (42%) with elevated PA-C3 and PA-IgG levels, and 5 (20%) with increased PA-C3 values only. A direct correlation was found between PA-C3 and PA-IgG levels. PA-IgG levels were higher in the group of patients with elevated PA-C3 levels than in those with normal values. Platelet survival studies showed reduced survival times of 1.5-2.5 days for the 5 patients with elevated PA-C3 levels only. Elevated PA-C3 levels returned to normal in 7 ITP patients whose platelet counts increased in response to corticosteriod therapy or to splenectomy. Therefore, PA-C3 and PA-IgG assays can be used to identify patients with ITP, to follow their response to therapy, and to classify them into immunologic subgroups similar to red cell classifiation by Coombs' testing in immune hemolytic anemia.

  7. Identification of a C3bi-specific membrane complement receptor that is expressed on lymphocytes, monocytes, neutrophils, and erythrocytes

    PubMed Central

    Ross, GD; Lambris, JD

    1982-01-01

    Cells expressing a membrane C receptor (CR(3)) specific for C3b-inactivator- cleaved C3b (C3bi) were identified by rosette assay with C3bi-coated sheep erythrocytes (EC3bi) or C3bi-coated fluorescent microspheres (C3bi-ms). C3bi- ms, probably because of their smaller size, bound to a higher proportion of cells than did EC3bi. C3bi-ms bound to greater than 90 percent of mature neutrophils, 85 percent of monocytes, 92 percent of erythrocytes, and 12 percent of peripheral blood lymphocytes. Binding of C3bi-ms to neutrophils, monocytes, and erythrocytes was inhibited by fluid-phase C3bi, Fab anti-C3c, or Fab anti-C3d but was not inhibited by F(ab’)(2) anti-CR(1) (C3b receptor) or F(ab’)(2) anti-CR(2) (C3d receptor) nor by fluid-phase C3b, C3c, or C3d. This indicated that monocytes, neutrophils, and erythrocytes expressed C3bi receptors (CR(3)) that were separate and distinct from CR(1) and CR(2) and specific for a site in the C3 molecule that was only exposed subsequently to cleavage of C3b by C3b inactivator and that was either destroyed, covered, or liberated by cleavage of C3bi into C3c and C3d fragments. Lymphocytes differed from these other cell types in that they expressed CR2 in addition to CRa. Lymphocyte C3bi-ms rosettes were inhibited from 50 to 84 percent by F(ab’)(2)-anti-CR(2) or fluid-phase C3d, whereas C3d-ms rosettes were inhibited completely by F(ab’)(2) anti-CR(2), fluid-phase C3bi, or fluid- phase C3d. Thus, with lymphocytes, C3bi was bound to CR(3), and in addition was bound to CR(2) by way of the intact d region of the C3bi molecule. In studies of the acquisition of C receptors occurring during myeloid cell maturation, the ability to rosette with C3bi-coated particles was detected readily with immature low-density cells, whereas this ability was nearly undetectable with high density mature polymorphonuclear cells. This absence of C3bi binding to polymorphs was not due to a loss of the CR(3) but instead was due to the maturation

  8. Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes

    PubMed Central

    Figueroa, Jonine D.; Malats, Núria; García-Closas, Montserrat; Real, Francisco X.; Silverman, Debra; Kogevinas, Manolis; Chanock, Stephen; Welch, Robert; Dosemeci, Mustafa; Lan, Qing; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Castaño-Vinyals, Gemma; Rothman, Nathaniel

    2008-01-01

    Aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) are carcinogens present in tobacco smoke and functional polymorphisms in NAT2 and GSTM1 metabolizing genes are associated with increased bladder cancer risk. We evaluated whether genetic variation in other candidate metabolizing genes are also associated with risk. Candidates included genes that control the transcription of metabolizing genes [aryl hydrocarbon receptor (AHR), AHRR and aryl hydrocarbon nuclear translocator (ARNT)] and genes that activate/detoxify AA or PAH (AKR1C3, CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, EPHX2, NQO1, MPO, UGT1A4, SULT1A1 and SULT1A2). Using genotype data from 1150 cases of urothelial carcinomas and 1149 controls from the Spanish Bladder Cancer Study, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. Based on a test for trend, we observed 10 non-redundant single-nucleotide polymorphisms (SNPs) in five genes (AKR1C3, ARNT, CYP1A1, CYP1B1 and SULT1A2) significantly associated with bladder cancer risk. We observed an inverse association with risk for the AKR1C3 promoter SNP rs1937845 [OR (95% CI) for heterozygote and homozygote variant compared with common homozygote genotype were 0.86 (0.70–1.06) and 0.74 (0.57–0.96), respectively; P for trend = 0.02]. Interestingly, genetic variation in this region has been associated with lung, non-Hodgkin lymphoma and prostate cancer risk. Analysis of additional SNPs to capture most (∼90%) of common genetic variation in AKR1C3 and haplotype walking analyses based on all AKR1C3 SNPs (n = 25) suggest two separate regions associated with bladder cancer risk. These results indicate that genetic variation in carcinogen-metabolizing genes, particularly AKR1C3, could be associated with bladder cancer risk. PMID:18632753

  9. Stabilization/solidification on chromium (III) wastes by C(3)A and C(3)A hydrated matrix.

    PubMed

    Li, Xiangguo; He, Chao; Bai, Yun; Ma, Baoguo; Wang, Guandong; Tan, Hongbo

    2014-03-15

    Hazardous wastes are usually used in the Portland cement production in order to save energy, costs and/or stabilize toxic substances and heavy metals inside the clinker. This work focus on the stabilization/solidification on chromium (III) wastes by C(3)A and C(3)A hydrated matrix. The immobilization rate of chromium in C(3)A and the leaching characteristics of the C(3)A hydrated matrixes containing chromium were investigated by ICP-AES. The results indicated that C(3)A had a good solidifying effect on chromium using the clinkering process, however, the Cr leaching content of Cr-doped C(3)A was higher than that of hydrated C(3)A matrix in Cr(NO(3))3 solution and was lower than that of the hydrated C(3)A matrix in K(2)CrO(4) solution, no matter the leachant was sulphuric acid & nitric acid or water. To explain this, C(3)A formation, chemical valence states of chromium in C(3)A, hydration products and Cr distribution in the C(3)A-gypsum hydrated matrixes were studied by XRD, XPS and FESEM-EDS. The investigation showed that part of Cr(3+) was oxidized to Cr(6+) in the clinkering process and identified as the chromium compounds Ca(4)Al(6)O(12)CrO(4) (3CaO·Al(20O(3)·CaCrO(4)), which resulted in the higher leaching of hydrated matrix of Cr-doped C(3)A.

  10. 12 CFR 563c.3 - Qualification of public accountant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Qualification of public accountant. 563c.3... REQUIREMENTS Form and Content of Financial Statements § 563c.3 Qualification of public accountant. (See also 17 CFR 210.2-01.) The term “qualified public accountant” means a certified public accountant or...

  11. 12 CFR 563c.3 - Qualification of public accountant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 5 2011-01-01 2011-01-01 false Qualification of public accountant. 563c.3... REQUIREMENTS Form and Content of Financial Statements § 563c.3 Qualification of public accountant. (See also 17 CFR 210.2-01.) The term “qualified public accountant” means a certified public accountant or...

  12. 42 CFR 68c.3 - Who is eligible to apply?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Who is eligible to apply? 68c.3 Section 68c.3 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...

  13. 42 CFR 68c.3 - Who is eligible to apply?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Who is eligible to apply? 68c.3 Section 68c.3 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...

  14. 42 CFR 68c.3 - Who is eligible to apply?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Who is eligible to apply? 68c.3 Section 68c.3 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...

  15. Treatment of C3 glomerulopathy with complement blockers.

    PubMed

    Vivarelli, Marina; Emma, Francesco

    2014-06-01

    C3 glomerulopathy (C3G) is a newly defined clinical entity comprising glomerular lesions with predominant C3 staining. Under this definition are now included membranoproliferative glomerulonephritis type II (dense deposit disease) and C3 glomerulonephritis. This group of glomerular diseases with a heterogeneous histological aspect shares a common pathogenesis, that is, a dysregulation of the alternative pathway of complement in the fluid phase leading to C3 deposition in the kidney. Recent advances have expanded our understanding of the underlying mechanisms, leading to the hypothesis that blocking the alternative complement pathway may be an effective treatment for C3Gs, as has been shown in other renal diseases driven by alternative pathway dysregulation, such as atypical hemolytic uremic syndrome. Results of 11 published cases of patients with different forms of C3G treated with eculizumab, an anti-C5 humanized monoclonal antibody, are encouraging. Given the complexity of disease pathogenesis in C3G, a patient-tailored approach including a comprehensive workup of complement abnormalities is necessary to evaluate the best treatment options. Clinical trials assessing effectiveness of different complement blockers on the background of the individual complement profile are needed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. 12 CFR 563c.3 - Qualification of public accountant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 6 2012-01-01 2012-01-01 false Qualification of public accountant. 563c.3... REQUIREMENTS Form and Content of Financial Statements § 563c.3 Qualification of public accountant. (See also 17 CFR 210.2-01.) The term “qualified public accountant” means a certified public accountant or licensed...

  17. 12 CFR 563c.3 - Qualification of public accountant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 6 2013-01-01 2012-01-01 true Qualification of public accountant. 563c.3... REQUIREMENTS Form and Content of Financial Statements § 563c.3 Qualification of public accountant. (See also 17 CFR 210.2-01.) The term “qualified public accountant” means a certified public accountant or licensed...

  18. 12 CFR 563c.3 - Qualification of public accountant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 6 2014-01-01 2012-01-01 true Qualification of public accountant. 563c.3... REQUIREMENTS Form and Content of Financial Statements § 563c.3 Qualification of public accountant. (See also 17 CFR 210.2-01.) The term “qualified public accountant” means a certified public accountant or licensed...

  19. Mapping the Complement Factor H-Related Protein 1 (CFHR1):C3b/C3d Interactions

    PubMed Central

    Laskowski, Jennifer; Thurman, Joshua M.; Hageman, Gregory S.; Holers, V. Michael

    2016-01-01

    Complement factor H-related protein 1 (CFHR1) is a complement regulator which has been reported to regulate complement by blocking C5 convertase activity and interfering with C5b surface association. CFHR1 also competes with complement factor H (CFH) for binding to C3b, and may act as an antagonist of CFH-directed regulation on cell surfaces. We have employed site-directed mutagenesis in conjunction with ELISA-based and functional assays to isolate the binding interaction that CFHR1 undertakes with complement components C3b and C3d to a single shared interface. The C3b/C3d:CFHR1 interface is identical to that which occurs between the two C-terminal domains (SCR19-20) of CFH and C3b. Moreover, we have been able to corroborate that dimerization of CFHR1 is necessary for this molecule to bind effectively to C3b and C3d, or compete with CFH. Finally, we have established that CFHR1 competes with complement factor H-like protein 1 (CFHL-1) for binding to C3b. CFHL-1 is a CFH gene splice variant, which is almost identical to the N-terminal 7 domains of CFH (SCR1-7). CFHR1, therefore, not only competes with the C-terminus of CFH for binding to C3b, but also sterically blocks the interaction that the N-terminus of CFH undertakes with C3b, and which is required for CFH-regulation. PMID:27814381

  20. Skipping of exon 27 in C3 gene compromises TED domain and results in complete human C3 deficiency.

    PubMed

    da Silva, Karina Ribeiro; Fraga, Tatiana Rodrigues; Lucatelli, Juliana Faggion; Grumach, Anete Sevciovic; Isaac, Lourdes

    2016-05-01

    Primary deficiency of complement C3 is rare and usually associated with increased susceptibility to bacterial infections. In this work, we investigated the molecular basis of complete C3 deficiency in a Brazilian 9-year old female patient with a family history of consanguinity. Hemolytic assays revealed complete lack of complement-mediated hemolytic activity in the patient's serum. While levels of the complement regulatory proteins Factor I, Factor H and Factor B were normal in the patient's and family members' sera, complement C3 levels were undetectable in the patient's serum and were reduced by at least 50% in the sera of the patient's parents and brother. Additionally, no C3 could be observed in the patient's plasma and cell culture supernatants by Western blot. We also observed that patient's skin fibroblasts stimulated with Escherichia coli LPS were unable to secrete C3, which might be accumulated within the cells before being intracellularly degraded. Sequencing analysis of the patient's C3 cDNA revealed a genetic mutation responsible for the complete skipping of exon 27, resulting in the loss of 99 nucleotides (3450-3549) located in the TED domain. Sequencing of the intronic region between the exons 26 and 27 of the C3 gene (nucleotides 6690313-6690961) showed a nucleotide exchange (T→C) at position 6690626 located in a splicing donor site, resulting in the complete skipping of exon 27 in the C3 mRNA. Copyright © 2016. Published by Elsevier GmbH.

  1. Stereochemistry analysis and comparison of two C(3)-alkyl substituted cyclohexonedicarboxylates with their C(3)-aryl substituted analogues

    NASA Astrophysics Data System (ADS)

    Chen, Chao-Yue; Wang, Qi; Zhu, Bing-Long; Zhao, Wen-Jie; Hu, Jin-Song

    2016-03-01

    Two representative C(3)-alkyl substituted cyclohexonedicarboxylates (4a and 4b) were synthesized and their conformational features were investigated by single crystal X-ray crystallography for the first time. These stereochemistry results of 4a and 4b were compared with those obtained from the earlier research of C(3)-aryl substituted analogues (1-3).

  2. 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

  3. Reduction of uranium by cytochrome c3 of Desulfovibrio vulgaris.

    PubMed Central

    Lovley, D R; Widman, P K; Woodward, J C; Phillips, E J

    1993-01-01

    The mechanism for U(VI) reduction by Desulfovibrio vulgaris (Hildenborough) was investigated. The H2-dependent U(VI) reductase activity in the soluble fraction of the cells was lost when the soluble fraction was passed over a cationic exchange column which extracted cytochrome c3. Addition of cytochrome c3 back to the soluble fraction that had been passed over the cationic exchange column restored the U(VI)-reducing capacity. Reduced cytochrome c3 was oxidized by U(VI), as was a c-type cytochrome(s) in whole-cell suspensions. When cytochrome c3 was combined with hydrogenase, its physiological electron donor, U(VI) was reduced in the presence of H2. Hydrogenase alone could not reduce U(VI). Rapid U(VI) reduction was followed by a subsequent slow precipitation of the U(IV) mineral uraninite. Cytochrome c3 reduced U(VI) in a uranium-contaminated surface water and groundwater. Cytochrome c3 provides the first enzyme model for the reduction and biomineralization of uranium in sedimentary environments. Furthermore, the finding that cytochrome c3 can catalyze the reductive precipitation of uranium may aid in the development of fixed-enzyme reactors and/or organisms with enhanced U(VI)-reducing capacity for the bioremediation of uranium-contaminated waters and waste streams. PMID:8285665

  4. Reduction of uranium by cytochrome c3 of Desulfovibrio vulgaris

    USGS Publications Warehouse

    Lovley, D.R.; Widman, P.K.; Woodward, J.C.; Phillips, E.J.P.

    1993-01-01

    The mechanism for U(VI) reduction by Desulfovibrio vulgaris (Hildenborough) was investigated. The H2-dependent U(VI) reductase activity in the soluble fraction of the cells was lost when the soluble fraction was passed over a cationic exchange column which extracted cytochrome c3. Addition of cytochrome c3 back to the soluble fraction that had been passed over the cationic exchange column restored the U(VI)-reducing capacity. Reduced cytochrome c3 was oxidized by U(VI), as was a c-type cytochrome(s) in whole-cell suspensions. When cytochrome c3 was combined with hydrogenase, its physiological electron donor, U(VI) was reduced in the presence of H2. Hydrogenase alone could not reduce U(VI). Rapid U(VI) reduction was followed by a subsequent slow precipitation of the U(IV) mineral uraninite. Cytochrome c3 reduced U(VI) in a uranium-contaminated surface water and groundwater. Cytochrome c3 provides the first enzyme model for the reduction and biomineralization of uranium in sedimentary environments. Furthermore, the finding that cytochrome c3 can catalyze the reductive precipitation of uranium may aid in the development of fixed-enzyme reactors and/or organisms with enhanced U(VI)-reducing capacity for the bioremediation of uranium- contaminated waters and waste streams.

  5. Photosynthesis in C3-C4 intermediate Moricandia species.

    PubMed

    Schlüter, Urte; Bräutigam, Andrea; Gowik, Udo; Melzer, Michael; Christin, Pascal-Antoine; Kurz, Samantha; Mettler-Altmann, Tabea; Weber, Andreas Pm

    2017-01-01

    Evolution of C4 photosynthesis is not distributed evenly in the plant kingdom. Particularly interesting is the situation in the Brassicaceae, because the family contains no C4 species, but several C3-C4 intermediates, mainly in the genus Moricandia Investigation of leaf anatomy, gas exchange parameters, the metabolome, and the transcriptome of two C3-C4 intermediate Moricandia species, M. arvensis and M. suffruticosa, and their close C3 relative M. moricandioides enabled us to unravel the specific C3-C4 characteristics in these Moricandia lines. Reduced CO2 compensation points in these lines were accompanied by anatomical adjustments, such as centripetal concentration of organelles in the bundle sheath, and metabolic adjustments, such as the balancing of C and N metabolism between mesophyll and bundle sheath cells by multiple pathways. Evolution from C3 to C3-C4 intermediacy was probably facilitated first by loss of one copy of the glycine decarboxylase P-protein, followed by dominant activity of a bundle sheath-specific element in its promoter. In contrast to recent models, installation of the C3-C4 pathway was not accompanied by enhanced activity of the C4 cycle. Our results indicate that metabolic limitations connected to N metabolism or anatomical limitations connected to vein density could have constrained evolution of C4 in Moricandia. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  6. Influence of Lysobacter enzymogenes Strain C3 on Nematodes

    PubMed Central

    Chen, J.; Moore, W. H.; Yuen, G. Y.; Kobayashi, D.; Caswell-Chen, E. P.

    2006-01-01

    Chitinolytic microflora may contribute to biological control of plant-parasitic nematodes by causing decreased egg viability through degradation of egg shells. Here, the influence of Lysobacter enzymogenes strain C3 on Caenorhabditis elegans, Heterodera schachtii, Meloidogyne javanica, Pratylenchus penetrans, and Aphelenchoides fragariae is described. Exposure of C. elegans to L. enzymogenes strain C3 on agar resulted in almost complete elimination of egg production and death of 94% of hatched juveniles after 2 d. Hatch of H. schachtii eggs was about 50% on a lawn of L. enzymogenes strain C3 on agar as compared to 80% on a lawn of E. coli. Juveniles that hatched on a lawn of L. enzymogenes strain C3 on agar died due to disintegration of the cuticle and body contents. Meloidogyne javanica juveniles died after 4 d exposure to a 7-d-old chitin broth culture of L. enzymogenes strain C3. Immersion of A. fragariae, M. javanica, and P. penetrans juveniles and adults in a nutrient broth culture of L. enzymogenes strain C3 led to rapid death and disintegration of the nematodes. Upon exposure to L. enzymogenes strain C3 cultures in nutrient broth, H. schachtii juveniles were rapidly immobilized and then lysed after three days. The death and disintegration of the tested nematodes suggests that toxins and enzymes produced by this strain are active against a range of nematode species. PMID:19259452

  7. Degradation of C3a anaphylatoxins by rat mast cells

    SciTech Connect

    Fukuoka, Y.; Hugli, T.E.

    1986-05-01

    Incubation of /sup 125/I-human C3a with rat peritoneal mast cells (RMC) causes extensive degradation of the ligand. Both cell-bound and free /sup 125/I-C3a (hu) was degraded by RMC, even at 0/sup 0/C, based on SDS-PAGE analysis. The authors examined several protease inhibitors for their ability to prevent degradation of /sup 125/I-C3a (hu). Degradation of /sup 125/I-C3a (hu) by RMC was not inhibited by leupeptin, antipain, elastatinal, pepstatin, ..cap alpha../sub 1/-antitrypsin or EDTA. TPCK and TLCK were only partially effective. PMSF, chymostatin and SBTI were most effective in preventing /sup 125/I-C3a (hu) degradation. These latter compounds are effective inhibitors of the chymotrypsin-like enzyme chymase extracted from RMC, as is TPCK, based on hydrolysis of the substrate BTEE. Degradation of cell-bound ligand is totally prevented only by PMSF (or DFP). Therefore, /sup 125/I-C3a (hu) bound to the RMC appears to be degraded predominantly by chymase; however the cell-bound ligand is attacked by other surface proteases. Degradation of rat C3a by RMC was examined. After incubation with RMC, cell-bound and free /sup 125/I-C3a (rat) showed no evidence of degradation with or without inhibitors present. From these results, the authors conclude that chymase may not play a significant role in regulating anaphylatoxin activity. Furthermore, the authors propose that rat C3a is a preferred ligand for identifying receptors on mast cells because of its resistance to proteolysis.

  8. Development of a C3 generic workstation: System overview

    NASA Technical Reports Server (NTRS)

    Strome, David R.

    1988-01-01

    A command, control, and communications (C3) environment is described which will be applied to the evaluation of performance of aircrews, particularly in situations in which they are subjected to chemical defense protection drugs and antihistamines.

  9. Lifetimes of the ˜{A} States of the C_3-NE and C_3-AR Complexes

    NASA Astrophysics Data System (ADS)

    Wang, Yi-Jen; Chen, Chiao-Wei; Merer, Anthony J.; Hsu, Yen-Chu

    2013-06-01

    Under similar experimental conditions to our previous paper, the fluorescence lifetimes of the ˜{A} states of C_3-Ne and C_3-Ar have been determined. The uncertainties in the measured lifetimes are estimated to be better than 10%. About 50 perpendicular bands and 11 parallel bands of the ˜{A}-˜{X} system of C_3 were used to probe the fluorescence lifetimes of the Ne and Ar complexes. It is not possible to reduce the backing pressure while measuring lifetimes of the complexes; we therefore reduced the average pressure of the chamber to 1-2 × 10^{-5} torr by lowering the repetition rate. No sign of predissociation was found in either complex. Transitions to high vibrational levels of the ˜{A} state of C_3, above 4500 cm^{-1}, give weak laser-induced fluorescence signals, so that lifetime measurements are not possible for some of these bands. The lifetimes of the levels of the Ne complex lying below 4300 cm^{-1} are generally shorter than 300 ns, except for some levels with C-C stretch excitation. The lifetimes of the Ne complex behave quite similarly to those of C_3. In contrast, the lifetimes of the Ar complex do not follow the vibrational dependence of the lifetimes of C_3 and C_3-Ne. We speculate that the complicated lifetime pattern observed in the Ar complex can be attributed to interactions with nearby triplet levels.

  10. Preliminary characterization of complement in a colonial tunicate: C3, Bf and inhibition of C3 opsonic activity by compstatin.

    PubMed

    Franchi, Nicola; Ballarin, Loriano

    2014-10-01

    The complement system is a fundamental effector mechanism of the innate immunity in both vertebrates and invertebrates. The comprehension of its roots in the evolution is a useful step to understand how the main complement-related proteins had changed in order to adapt to new environmental conditions and life-cycles or, in the case of vertebrates, to interact with the adaptive immunity. Data on organisms evolutionary close to vertebrates, such as tunicates, are of primary importance for a better understanding of the changes in immune responses associated with the invertebrate-vertebrate transition. Here we report on the characterization of C3 and Bf transcripts from the colonial ascidian Botryllus schlosseri (BsC3 and BsBf, respectively), a reliable model organism for immunobiological research, and present a comparative analysis of amino acid sequences of C3s and Bfs suggesting that, in deuterostomes, the structure of these proteins remained largely unchanged. We also present new data on the cells responsible of the expression of BsC3 and BsBf showing that cytotoxic immunocytes are the sole cells where the relative transcripts can be found. Finally, using the C3 specific inhibitor compstatin, we demonstrate the opsonic role of BsC3 in accordance with the idea that promotion of phagocytosis is one of the main function of C3 in metazoans.

  11. The interstellar chemistry of H2C3O isomers.

    PubMed

    Loison, Jean-Christophe; Agúndez, Marcelino; Marcelino, Núria; Wakelam, Valentine; Hickson, Kevin M; Cernicharo, José; Gerin, Maryvonne; Roueff, Evelyne; Guélin, Michel

    2016-03-11

    We present the detection of two H2C3O isomers, propynal and cyclopropenone, toward various starless cores and molecular clouds, together with upper limits for the third isomer propadienone. We review the processes controlling the abundances of H2C3O isomers in interstellar media showing that the reactions involved are gas-phase ones. We show that the abundances of these species are controlled by kinetic rather than thermodynamic effects.

  12. Optimization of Chemical Syntheses of Vitamin D C3-Epimers.

    PubMed

    Kattner, Lars; Rauch, Erik

    2016-03-01

    Due to the widespread impact of vitamin D on human health, the development of appropriate assays to detect deficiency of all vitamin D metabolites of pharmacological interest is being continuously improved. Although over 50 naturally-occurring metabolites of vitamin D are known to date, only very few are routinely detected in commercially available assays. This is particularly true regarding C3-epimers of vitamin D3 and D2, which not only may interfere in analytical measurements with other metabolites of interest, but also have controversial and not yet fully understood physiological functions. In this study we optimized a synthetic method to obtain various vitamin D3 and D2 C3-epimers in order to make them available in gram quantities for further evaluation and for their use in assay development or drug discovery. Particularly, the inversion of the C3-OH group at the A-ring of vitamin D2, which, in turn, serves as a suitable starting material for most of chemical syntheses of vitamin D metabolites, can be converted to the corresponding C3-epimer under so-called "Mitsunobu conditions". Thus, the C3-OH group is converted into the corresponding ester by treatment with an aromatic acid, subsequent addition of an azodicarboxlate and triphenylphoshine, leading to the corresponding ester, concomitant to the inversion of the stereogenic center at C3. Reduction or saponification of the resulting ester finally leads to the corresponding C3-epimer, that may serve as starting material for a wide variety of vitamin D3 and D2 C3-epimers. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. The interstellar chemistry of H2C3O isomers

    PubMed Central

    Loison, Jean-Christophe; Agúndez, Marcelino; Marcelino, Núria; Wakelam, Valentine; Hickson, Kevin M.; Cernicharo, José; Gerin, Maryvonne; Roueff, Evelyne; Guélin, Michel

    2016-01-01

    We present the detection of two H2C3O isomers, propynal and cyclopropenone, toward various starless cores and molecular clouds, together with upper limits for the third isomer propadienone. We review the processes controlling the abundances of H2C3O isomers in interstellar media showing that the reactions involved are gas-phase ones. We show that the abundances of these species are controlled by kinetic rather than thermodynamic effects. PMID:27013768

  14. Clarifying complex inheritance: apolipoprotein C3 and atherosclerosis.

    PubMed

    Galton, David J

    2017-08-01

    To describe some steps in the progress in the molecular biology of a peptide, apolipoprotein C3; its gene mutations that render individuals susceptible or resistant to developing hyperlipidaemia and atherosclerosis. Data that lead to the development of a new therapeutic agent volanesorsen. The agent blocks the function of the mRNA of apolipoprotein C3 and successfully treats severe hypertriglyceridaemia in phase 3 trials (Ionis Pharmaceuticals).

  15. Systems Engineering for Air Force C3I Systems

    DTIC Science & Technology

    1993-01-01

    filll11111111 ff I!’ 14. SUBJECT TERMS 15. NUMBER OF PAGES systems engineering, command, control, communications , and 204 intelligence (C3 1), 16. PRICE...activities includes national security matters in the area of command, control, communications , and intelligence (C3 I), as well as civil sys- tem areas for...component discussions such as computers, radars, or communications devices. However, some quotations from the earlier books help to establish what

  16. Density functional study of Pu2C3

    NASA Astrophysics Data System (ADS)

    Yang, Rong; Tang, Bin; Gao, Tao; Ao, Bing Yun

    2017-08-01

    The structural, magnetic, electronic, vibrational, thermodynamic and elastic properties of plutonium sesquicarbide (Pu2C3) are investigated based on density functional theory. The use of the Hubbard term to describe the 5 f electrons of plutonium is discussed according the lattice parameters and magnetism. The calculated lattice constants, magnetism and density of states agree well with the experimental data or other theoretical calculations. The Pu-C bonds of Pu2C3 have a mixture of covalent character and ionic character, while covalent character is stronger than ionic character. The phonon frequencies and the assignment of infrared-active, Raman-active and silent modes at Γ point are obtained. Furthermore, the enthalpy difference H-H298, entropy S, heat capacity and linear thermal expansion coefficient α of Pu2C3 have been calculated and compared with the available data. Lastly, the calculated elastic properties predict that Pu2C3 is ductile metal. In addition, the effect of spin-orbit coupling on the structural, magnetic, and electronic properties of Pu2C3 has been discussed. We hope that our results can provide a useful reference for further theoretical and experimental research on Pu2C3.

  17. Complotype affects the extent of down-regulation by Factor I of the C3b feedback cycle in vitro

    PubMed Central

    Lay, E; Nutland, S; Smith, J E; Hiles, I; Smith, R A G; Seilly, D J; Buchberger, A; Schwaeble, W; Lachmann, P J

    2015-01-01

    Sera from a large panel of normal subjects were typed for three common polymorphisms, one in C3 (R102G) and two in Factor H (V62I and Y402H), that influence predisposition to age-related macular degeneration and to some forms of kidney disease. Three groups of sera were tested; those that were homozygous for the three risk alleles; those that were heterozygous for all three; and those homozygous for the low-risk alleles. These groups vary in their response to the addition of exogenous Factor I when the alternative complement pathway is activated by zymosan. Both the reduction in the maximum amount of iC3b formed and the rate at which the iC3b is converted to C3dg are affected. For both reactions the at-risk complotype requires higher doses of Factor I to produce similar down-regulation. Because iC3b reacting with the complement receptor CR3 is a major mechanism by which complement activation gives rise to inflammation, the breakdown of iC3b to C3dg can be seen to have major significance for reducing complement-induced inflammation. These findings demonstrate for the first time that sera from subjects with different complement alleles behave as predicted in an in-vitro assay of the down-regulation of the alternative complement pathway by increasing the concentration of Factor I. These results support the hypothesis that exogenous Factor I may be a valuable therapeutic aid for down-regulating hyperactivity of the C3b feedback cycle, thereby providing a treatment for age-related macular degeneration and other inflammatory diseases of later life. PMID:25124117

  18. The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study

    USDA-ARS?s Scientific Manuscript database

    The APOA1/C3/A4/A5 cluster encodes key regulators of plasma lipids. Interactions between dietary factors and single nucleotide polymorphisms (SNPs) in the cluster have been reported. Allostatic load, or physiological dysregulation in response to stress, has been implicated in shaping health disparit...

  19. High Tibetan Plateau: a Nature Reserve of C3 Flora

    NASA Astrophysics Data System (ADS)

    Zhuang, G.; Pagani, M.; Brandon, M. T.

    2015-12-01

    Uplift of the Tibetan Plateau and associated climate changes leading to enhanced seasonality in precipitation and drying, are argued to have induced a global ecological shift from C3-frorest to C4-grassland between 8 and 5 million years ago. However, both tectonic and climatic changes predate the timing of the C3-C4 transition, with paleoaltimetry studies pointing to a high Tibetan Plateau no later than 10 Ma and the existence of an intense monsoon since ca. 11 Ma. To better understand the role of the Tibetan Plateau, we present results of a paleoecology study based on the carbon isotope compositions of leaf-wax n-alkanes (δ13Calk) from Qaidam basin, an intermontane basin on the youngest and the northernmost portion of Tibetan Plateau. Samples were collected from a 5-km thick, fluvial-lacustrine sequence dated 15 Ma to 1.8 Ma. Organic geochemical indices and detrital thermochronological studies preclude post-depositional thermal alteration of the studied materials. Our results, which show persistently low δ13Calk values, are consistent with the dominance of C3 flora on the Tibetan Plateau, in contrast to the prominent C4 rise surrounding the Tibetan Plateau and around the globe. We argue that a high Tibetan Plateau, established prior to the global ecological C3-C4 shift, served as a shelter of C3 flora since the Miocene. High-elevation and cold environments provided a competitive advantage for C3 by damping/counteracting the physiological advantage of C4 which outperforms C3 plants under warm, high-irradiance, water-stress and low pCO2 conditions.

  20. Highly Accurate Quantum-Chemical Calculations for the Interstellar Molecules C_3 and l-C_3H^+

    NASA Astrophysics Data System (ADS)

    Botschwina, Peter; Schröder, Benjamin; Stein, Christopher; Sebald, Peter; Oswald, Rainer

    2014-06-01

    Composite potential energy surfaces with coupled-cluster contributions up to CCSDTQP were constructed for C_3 and l-C_3H^+ and used in the calculation of spectroscopic properties. The use of very large AO basis sets and the consideration of higher-order correlation beyond CCSD(T) is of utmost importance for C_3 in order to arrive at quantitative spectroscopic data. The first detection of l-C_3H^+ in the interstellar medium was reported by Pety et al., who attributed 9 radio lines observed in the horsehead photodissociation region to that species. That assignment was questioned by the recent theoretical work of Huang et al. However, our more accurate calculations are well in support of the original assignment. The calculated ground-state rotational constant is B_0 = 11248 MHz, only 0.03% off from the radio astronomical value of 11244.9512±0.0015 MHz. The ratio of centrifugal distortion constants D_0(exp.)/D_e(theor.) of 1.8 is quite large, but reasonable in comparison with C_3O and C_3. J. Pety, P. Gratier, V. Guzmán, E. Roueff, M. Gerin et al., Astron. Astrophys. 2012, A68, 1-8. X. Huang, R. C. Fortenberry, T. J. Lee, Astrophys. J. Lett. 2013, 768:L25, 1-5. P. Botschwina, R. Oswald, J. Chem. Phys. 2008, 129, 044305

  1. Complement C3 participation in monocyte adhesion to different surfaces.

    PubMed Central

    McNally, A K; Anderson, J M

    1994-01-01

    As part of an ongoing investigation into the role of the monocyte/macrophage in biocompatibility, a major goal is to identify the adhesion mechanisms that initiate and promote the observed in vivo morphologic progression of monocyte-to-macrophage-to-foreign body giant cell on biomaterials. We have exploited differently modified polystyrenes, specific component-depleted sera, and monoclonal antibodies (mAbs) to leukocyte integrins to ask what adhesion mechanisms mediate human blood monocyte adhesion to different surfaces in vitro. Preliminary findings are that monocyte interactions with fluorinated, siliconized, nitrogenated, and oxygenated surfaces are reduced by 50-100% when complement component C3-depleted serum is used for adsorption; reductions vary with material surface properties. Adhesion is restored on all surfaces when C3-depleted serum is replenished with purified C3. Monocyte adhesion to serum-adsorbed surfaces is inhibited by mAbs to the leukocyte integrin beta subunit, CD18 (mAbs 60.3 and MHM23), and partially inhibited by a mAb to the alpha subunit, CD11b (mAb 60.1), suggesting adhesive interactions between adsorbed C3bi (the hemolytically inactive form of the C3b fragment) and the leukocyte integrin CD11b/CD18. However, adsorbed fibrinogen reduces the effectiveness of these mAbs, indicating that alternative adhesion mechanisms may operate depending on the propensities of critical adhesion-mediating components to be adsorbed onto different surfaces. Images PMID:7937848

  2. Deletion of both ICAM-1 and C3 Enhances Severity of Experimental Autoimmune Encephalomyelitis Compared to C3-Deficient Mice

    PubMed Central

    Smith, Sherry S.; Ludwig, Michael; Wohler, Jillian E.; Bullard, Daniel C.; Szalai, Alex J.; Barnum, Scott R.

    2008-01-01

    Multiple sclerosis (MS) is an autoimmune disease characterized by central nervous system (CNS) inflammation and leukocyte infiltration, demyelination of neurons, and blood-brain barrier breakdown. The development of experimental autoimmune encephalomyelitis (EAE), the animal model for MS is dependent on a number of components of the immune system including complement and adhesion molecules. Previous studies in our lab have examined the role of C3, the central complement component, and intercellular adhesion molecule-1 (ICAM-1) a key cell adhesion molecule involved in leukocyte trafficking to sites of inflammation including the CNS. In these studies we demonstrated that myelin oligodendrocyte glycoprotein (MOG)-induced EAE is markedly attenuated in both ICAM-1−/− and C3−/− mice. Given the pivotal role that these proteins play in EAE, we hypothesized that EAE in ICAM-1−/− and C3−/− double mutant mice would likely fail to develop. Unexpectedly, EAE in ICAM-1−/− × C3−/− mice was only modestly attenuated compared to wild type mice and significantly worse than C3−/− mice. Leukocyte infiltration was commensurate with disease severity between the three groups of mice. Spinal cord T cells from ICAM-1−/− × C3−/− mice produced the highest levels of IFN-γ and TNF-α, despite reduced disease severity compared to wild type mice. The mechanisms behind the elevated EAE severity in ICAM-1−/− × C3−/− mice may relate to altered homing of leukocytes or processing of self-antigens in the double mutant background. PMID:18634851

  3. C3 glomerulopathy: A new complement-based entity.

    PubMed

    de Lorenzo, A; Tallón, S; Hernández-Sevillano, B; de Arriba, G

    2014-01-01

    C3 glomerulopathy is a new, recently described entity that has changed the perspective, treatment and classification of a number of glomerular diseases. It encompasses 2 similar but clearly differentiated pathologies -the dense-deposit disease and C3 glomerulonephritis itself. The alternative complement pathway plays a fundamental role in its pathogenesis and, specifically, the mutations and defects in its regulatory factors (mainly factor H and factor I), as well as the presence of acquired autoantibodies (C3 nephritic factor), which generates an unbridled activation of the system, and ultimately, a deposit of its products at the glomerular level. Its poor prognosis and onset in young populations makes the detailed study of new therapeutic alternatives for this disease essential. Recently eculizumab, an anti-C5 antibody, has demonstrated effectiveness in the treatment of these patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  4. [Incidence of factor VII and C3 in vascular anastomosis].

    PubMed

    Skóra, Jan; Janczak, Dariusz; Korta, Krzysztof; Pupka, Artur; Ruciński, Artur; Szyber, Piotr; Pawłowski, Stanisław; Milnerowicz, Artur; Stepiński, Piotr

    2004-06-01

    In order to study pathogenesis of vascular prosthesis healing process the following experiment was designed. 16 dogs underwent implantation of unilateral straight aorto-femoral teflon (PTFE, polytetrafluoroethylene) by-pass. After 6 months all dogs were killed, dissected and vascular prostheses with margin of adjacent aorta and femoral artery were collected for further study. Areas of proximal and distal anastomosis were examined immunohistochemically. Presence of coagulation factor VII, and C3 complement factor were studied. The obtained results were analyzed statistically by means of t-Student test. Factor VII as well C3 were found in areas of both proximal and distal anastomosis. Concentration of all two substances in proximal and distal anastomosis was compared. No statistically valid differences in factor VII concentration in proximal and distal anastomosis were found, whereas amounts of C3 factor as well as degree of extracellular matrix infiltration were markedly higher in distal anastomosis.

  5. Atypical Plasmacytic Proliferation in a Case of C3 Glomerulopathy

    PubMed Central

    Elfituri, Osama; Aardsma, Nathan; Setty, Suman; Behm, Frederick; Czech, Kimberly

    2017-01-01

    An 11-year-old Hispanic female underwent evaluation of asymptomatic proteinuria and hematuria. The patient denied fever, edema, and gross hematuria. Urinalysis showed mild proteinuria, and a urine microscopic examination revealed red blood cells. Screening tests for glomerulonephritis revealed a low C3 and negative ANA, ASO, DNAse-B, and ANCA. Histological examination of a renal biopsy specimen showed glomeruli with endocapillary proliferation, a predominant C3 deposition in the capillary loops by immunofluorescence, and electron dense deposits in the mesangium, paramesangium, and capillary walls by electron microscopy consistent with a diagnosis of C3 glomerulopathy. An interstitial plasmacytosis was also present with focal clustering of plasma cells, which were found to be kappa light chain restricted by in situ hybridization suggestive of a clonal proliferation. One can speculate that these plasma cells may be directly responsible for the renal pathology that was seen. PMID:28210641

  6. Communications processor for C3 analysis and wargaming

    NASA Astrophysics Data System (ADS)

    Clark, L. N.; Pless, L. D.; Rapp, R. L.

    1982-03-01

    This thesis developed the software capability to allow the investigation of c3 problems, procedures and methodologies. The resultant communications model, that while independent of a specific wargame, is currently implemented in conjunction with the McClintic Theater Model. It provides a computerized message handling system (C3 Model) which allows simulation of communication links (circuits) with user-definable delays; garble and loss rates; and multiple circuit types, addresses, and levels of command. It is designed to be used for test and evaluation of command and control problems in the areas of organizational relationships, communication networks and procedures, and combat doctrine or tactics.

  7. Viability of Stored Rabbit Erythrocytes Carrying Number C3c.

    DTIC Science & Technology

    1984-05-31

    A-A165 440 VIABILITY OF STORED RABBIT ERYTHROCYTES CARRYING NUBR V no C3C(U) MASSACHUSETTS UNIV MEDICAL SCHOOL MORCESTER UNCLRSSIFI 0 SZYMANSKI 31...Carrying No C3c 0 Annual and Final Report Irma 0. Szymanski, M.D. Ln CD May 31, 1984 I Supported by U.S. ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMAND...Fort Detrick, Frederick, Maryland 21701-5012 Contract No. DAMD17-82-C-2150 .TICD ET University of Massachusetts Medical Center .EC, Worcester

  8. The Quest for a C3 Theory: Dreams and Realities,

    DTIC Science & Technology

    1987-08-01

    o • • O • i ....o- - -o -o .- ’ AUGUST 1987 LIDS-P-1691 00 In3 WTHE QUEST FOR A C3 THEORY: DREAMS AND REALITIES 00 ___ by Alexander H. Levis I...Distribution Unlimited 87 8 28 007 THE QUEST FOR A C3 THEORY: DREAMS AND REALITIES * by Alexander H. Levis Michael Athans Laboratory for Information and Decision...of realities have affected these dreams , progress towards a ’Theory of C"’ can be achieved changed them and adapted them. ... " (1] that articulates

  9. 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. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Regioselective synthesis of C3 alkylated and arylated benzothiophenes

    PubMed Central

    Shrives, Harry J.; Fernández-Salas, José A.; Hedtke, Christin; Pulis, Alexander P.; Procter, David J.

    2017-01-01

    Benzothiophenes are heterocyclic constituents of important molecules relevant to society, including those with the potential to meet modern medical challenges. The construction of molecules would be vastly more efficient if carbon–hydrogen bonds, found in all organic molecules, can be directly converted into carbon–carbon bonds. In the case of elaborating benzothiophenes, functionalization of carbon–hydrogen bonds at carbon-number 3 (C3) is markedly more demanding than at C2 due to issues of regioselectivity (C3 versus C2), and the requirement of high temperatures, precious metals and the installation of superfluous directing groups. Herein, we demonstrate that synthetically unexplored but readily accessible benzothiophene S-oxides serve as novel precursors for C3-functionalized benzothiophenes. Employing an interrupted Pummerer reaction to capture and then deliver phenol and silane coupling partners, we have discovered a directing group-free method that delivers C3-arylated and -alkylated benzothiophenes with complete regioselectivity, under metal-free and mild conditions. PMID:28317882

  11. Regioselective synthesis of C3 alkylated and arylated benzothiophenes

    NASA Astrophysics Data System (ADS)

    Shrives, Harry J.; Fernández-Salas, José A.; Hedtke, Christin; Pulis, Alexander P.; Procter, David J.

    2017-03-01

    Benzothiophenes are heterocyclic constituents of important molecules relevant to society, including those with the potential to meet modern medical challenges. The construction of molecules would be vastly more efficient if carbon-hydrogen bonds, found in all organic molecules, can be directly converted into carbon-carbon bonds. In the case of elaborating benzothiophenes, functionalization of carbon-hydrogen bonds at carbon-number 3 (C3) is markedly more demanding than at C2 due to issues of regioselectivity (C3 versus C2), and the requirement of high temperatures, precious metals and the installation of superfluous directing groups. Herein, we demonstrate that synthetically unexplored but readily accessible benzothiophene S-oxides serve as novel precursors for C3-functionalized benzothiophenes. Employing an interrupted Pummerer reaction to capture and then deliver phenol and silane coupling partners, we have discovered a directing group-free method that delivers C3-arylated and -alkylated benzothiophenes with complete regioselectivity, under metal-free and mild conditions.

  12. Rituximab for Treatment of Membranoproliferative Glomerulonephritis and C3 Glomerulopathies

    PubMed Central

    2017-01-01

    Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function. Rituximab, a chimeric B-cell depleting anti-CD20 antibody, has emerged in the last decade as a treatment option for patients with primary glomerular diseases such as minimal change disease, focal-segmental glomerulosclerosis, or idiopathic membranous nephropathy. However, data on the use of rituximab in MPGN, C3GN, and DDD are limited to case reports and retrospective case series. Patients with immunoglobulin-associated and idiopathic MPGN who were treated with rituximab showed partial and complete responses in the majorities of cases. However, rituximab was not effective in few cases of C3GN and DDD. Despite promising results in immunoglobulin-associated and idiopathic MPGN, current evidence on this treatment remains weak, and controlled and prospective data are urgently needed. PMID:28573137

  13. Hydrology of C-3 watershed, Seney National Wildlife Refuge, Michigan

    USGS Publications Warehouse

    Sweat, Michael J.

    2001-01-01

    Proposed changes to watershed management practices near C-3 Pool at Seney National Wildlife Refuge will affect surface-water flow patterns, ground-water levels, and possibly local plant communities. Data were collected between fall 1998 and spring 2000 to document existing conditions and to assess potential changes in hydrology that might occur as a consequence of modifications to water management practices in C-3 watershed.Minimum and maximum measured inflows and outflows for the study period are presented in light of proposed management changes to C-3 watershed. Streamflows ranged from 0 to 8.61 cubic meters per second. Low or zero flow was generally measured in late summer and early fall, and highest flows were measured during spring runoff and winter rain events. Ground-water levels varied by about a half meter, with levels closest to or above the land surface during spring runoff into the early summer, and with levels generally below land surface during late fall into early winter.A series of optional management practices that could conserve and restore habitat of the C-3 watershed is described. Modifications to the existing system of a drainage ditch and control structures are examined, as are the possibilities of reconnecting streams to their historical channels and the construction of additional or larger control structures to further manage the distribution of water in the watershed. The options considered could reduce erosion, restore presettlement streamflow conditions, and modify the ground-water gradient.

  14. Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.

    PubMed

    Rabasco, Cristina; Cavero, Teresa; Román, Elena; Rojas-Rivera, Jorge; Olea, Teresa; Espinosa, Mario; Cabello, Virginia; Fernández-Juarez, Gema; González, Fayna; Ávila, Ana; Baltar, José María; Díaz, Montserrat; Alegre, Raquel; Elías, Sandra; Antón, Monserrat; Frutos, Miguel Angel; Pobes, Alfonso; Blasco, Miguel; Martín, Francisco; Bernis, Carmen; Macías, Manuel; Barroso, Sergio; de Lorenzo, Alberto; Ariceta, Gema; López-Mendoza, Manuel; Rivas, Begoña; López-Revuelta, Katia; Campistol, José María; Mendizábal, Santiago; de Córdoba, Santiago Rodríguez; Praga, Manuel

    2015-11-01

    C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

  15. Implementing the C3 Framework: Monitoring the Instructional Shifts

    ERIC Educational Resources Information Center

    Herczog, Michelle M.

    2014-01-01

    The College, Career, and Civic Life (C3) Framework for Social Studies State Standards calls upon social studies teachers to enhance the rigor of civics, economics, geography, history and the other social studies disciplines while building the critical thinking, problem solving, and participatory skills of students to help them become actively…

  16. Amperometric cytochrome c3-based biosensor for chromate determination.

    PubMed

    Michel, Caroline; Battaglia-Brunet, Fabienne; Minh, Canh Tran; Bruschi, Mireille; Ignatiadis, Ioannis

    2003-12-15

    The chromate reductase activity of cytochrome c(3) (Cyt c(3), M(r) 13000), isolated from the sulfate-reducing bacterium Desulfomicrobium norvegicum, was used to develop an amperometric biosensor to measure chromate (CrO(4)(2-)) bioavailability. The performance of various biosensor configurations for qualitative and quantitative determination of Cr(VI) was studied. Biosensor properties depend on the technique used to immobilize the enzyme on the electrode (glassy carbon electrode). Immobilization of Cyt c(3) by entrapment in poly 3,4-ethylenedioxythiophene films denatured the enzyme, while application of an adsorption technique did not affect enzyme activity but the detection range was limited. The best results were obtained with dialysis membranes, which allowed the determination of Cr(VI) from 0.20 to 6.84 mg l(-1) (3.85-132 microM) with a sensitivity of 35 nA mg(-1) l (1.82 nA microM(-1)). No interference was observed with As(V), As(III) and Fe(III). Only a small amount of Cyt c(3) (372 ng of protein) was needed for this biosensor.

  17. Field nanoemitter: One-dimension Al4C3 ceramics

    NASA Astrophysics Data System (ADS)

    Sun, Y.; Cui, H.; Gong, L.; Chen, Jian; Shen, P. K.; Wang, C. X.

    2011-07-01

    As a kind of ionic (or salt-like) carbide, Al4C3 hardly any active functions have been found except for structure material purposes. However, considering the unique characteristic features of its crystal structure, we think Al4C3 in fact might have huge potential for exhibiting active functionality on field-emission application. Herein, we report for the first time the catalyst-free synthesis and excellent field emission properties of Al4C3 one-dimension (1-D) nanostructures. The 1-D nanostructures acting as cold electron emitters display excellent field emission performance with the turn-on field as low as 1.4-2.0 V μm-1 and the threshold field down to 4.2-4.4 V μm-1. Such emitters are technologically useful, because they can be easily fabricated on large substrates, and the synthesis process is simple and broadly applicable. The findings conceptually provide new opportunities for the application of Al4C3 ceramic material in vacuum microelectronic devices.

  18. Field nanoemitter: one-dimension Al4C3 ceramics.

    PubMed

    Sun, Y; Cui, H; Gong, L; Chen, Jian; Shen, P K; Wang, C X

    2011-07-01

    As a kind of ionic (or salt-like) carbide, Al(4)C(3) hardly any active functions have been found except for structure material purposes. However, considering the unique characteristic features of its crystal structure, we think Al(4)C(3) in fact might have huge potential for exhibiting active functionality on field-emission application. Herein, we report for the first time the catalyst-free synthesis and excellent field emission properties of Al(4)C(3) one-dimension (1-D) nanostructures. The 1-D nanostructures acting as cold electron emitters display excellent field emission performance with the turn-on field as low as 1.4-2.0 V μm(-1) and the threshold field down to 4.2-4.4 V μm(-1). Such emitters are technologically useful, because they can be easily fabricated on large substrates, and the synthesis process is simple and broadly applicable. The findings conceptually provide new opportunities for the application of Al(4)C(3) ceramic material in vacuum microelectronic devices.

  19. A fluorescence model of the C3 radical in comets

    NASA Astrophysics Data System (ADS)

    Rousselot, P.; Arpigny, C.; Rauer, H.; Cochran, A. L.; Gredel, R.; Cochran, W. D.; Manfroid, J.; Fitzsimmons, A.

    2001-03-01

    Theoretical resonance fluorescence calculations are presented of the triatomic C3 radical and are compared with observations of the C3 emission in comets Hale-Bopp and de Vico. A theoretical model of the C3 vibration-rotational structure in the A1Piu - X1Sigmag + electronic system is introduced. The model takes into account the detailed structure of the bending mode nu2 which is responsible for the emission of the 4050 Å group. A total of 1959 levels are considered, with 515 levels in the ground state. The main effort is to model high-resolution spectra of the 4050 Å emission in comets C/1995 O1 Hale-Bopp and 122P/1995 S1 de Vico. The agreement between observed and theoretical spectra is good for a value of the dipole moment derivative of dmu/dr ~ 2.5 Debye Å-1. The modeled C3 emission exhibits a pronounced Swings effect. Based on observations made with William Herschel Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias, and on observations made at the McDonald Observatory, which is operated by the University of Texas at Austin, USA.

  20. Implementing the C3 Framework: Monitoring the Instructional Shifts

    ERIC Educational Resources Information Center

    Herczog, Michelle M.

    2014-01-01

    The College, Career, and Civic Life (C3) Framework for Social Studies State Standards calls upon social studies teachers to enhance the rigor of civics, economics, geography, history and the other social studies disciplines while building the critical thinking, problem solving, and participatory skills of students to help them become actively…

  1. Negative C3 Launch Options for Solar System Exploration

    NASA Technical Reports Server (NTRS)

    Leifer, S.; Noca, M.

    1998-01-01

    Low thrust trajectory analyses were used to examine the feasibility of using solar electronic propulsion for Earth escape from a negative C3 launch for deep space missions in order to significantly increase the net delivered mass capability of inexpensive launch vehicles.

  2. Modelling C3 photosynthesis from the chloroplast to the ecosystem

    USDA-ARS?s Scientific Manuscript database

    Globally, photosynthesis accounts for the largest flux of CO2 from the atmosphere into ecosystems and is the driving process for terrestrial ecosystem function. The importance of accurate predictions of photosynthesis over a range of plant growth conditions led to the development of a C3 photosynthe...

  3. Pressure Effects on Product Channels of the Allyl Radical Reactions; C3H5+C3H5 and C3H5+CH3

    NASA Astrophysics Data System (ADS)

    Halpern, J. B.; N'Doumi, M.; Fahr, A.

    2011-12-01

    Relatively large hydrocarbon molecules (C4, C6 and larger) have been detected in several planetary environments. The mechanism for the formation of such large molecular species and detailed mechanism for their potential destruction are not well understood and are of considerable current interest. Previously we have studied the kinetics and product channels of small unsaturated hydrocarbon radical (C2 and C3s) reactions relevant to planetary atmospheric modeling. Reactions of C2 radicals (such as vinyl, H2CCH and ethynyl C2H) and C3 radicals (such as propargyl, HCCCH2) can affect the abundances of a large number of stable observable C3, C4, C5, C6 and larger molecules, including linear, aromatic and even poly aromatic molecules. Pressure-dependent product yields have been determined experimentally for the self- and cross-radical reactions performed at 298 K and at pressures between ~4 Torr (0.5 kPa) and 760 Torr (101 kPa). Final reaction products were quantitatively determined using a gas chromatograph with mass spectrometry/flame ionization detection (GC/MS/FID). In some cases complementary computational studies extended the pressure and temperature range of the experiments and provided valuable information on the complex reaction mechanisms. Theses studies provide a systematic framework so that important energetic and structural parameters for radical-radical reactions can be assessed. Here we report recent results for the allyl radical reactions H2CCCH3+ H2CCCH3 and H2CCCH3+CH3. For the allyl radical self-reaction, at high pressures the "head -to-head", combination channel forming 1,5-hexadiene is dominant with a combination/disproportionation = 1,5-hexadiene/propyne ratio of about 24 at 500 Torr (67 kPa, T=298K). At low pressures the ratio is substantially reduced to about 1.2 (at 0.3 kPa) and other major products are observed including allene, propene, 1-butene and propyne.

  4. Contribution of polymorphisms in the apolipoprotein AI-CIII-AIV cluster to hyperlipidaemia in patients with gout.

    PubMed

    Cardona, F; Tinahones, F J; Collantes, E; Escudero, A; García-Fuentes, E; Soriguer, F J

    2005-01-01

    Studies have shown that hyperuricaemia is independently related to the insulin resistance syndrome and that polymorphisms of the apolipoprotein AI-CIII-AIV cluster are also related to insulin resistance. To study the prevalence of polymorphisms of the apolipoprotein AI-CIII-AIV cluster in persons with gout and to determine whether these polymorphisms contribute to the pathophysiology of gout or to altered lipid concentrations. Plasma cholesterol, triglycerides, uric acid, VLDL, LDL, IDL, and HDL triglycerides, cholesterol, and the renal excretion of uric acid were measured in 68 patients with gout with gout and 165 healthy subjects. Polymorphisms were studied by amplification and RFLP in all subjects, using XmnI and MspI in the apolipoprotein AI gene and SstI in the apolipoprotein CIII gene. The A allele at position -75 bp in the apolipoprotein AI gene was more common in patients with gout than in controls (p = 0.01). Levels of cholesterol, triglycerides, uric acid, basal glycaemia, and HDL cholesterol were higher in the patients (p<0.001). In the patients there was also an interaction between mutations at the two polymorphic loci studied in the apolipoprotein AI gene (p = 0.04). An absence of the mutation at position -75 bp of the apolipoprotein AI gene resulted in increased plasma triglyceride levels. Gouty patients have an altered allelic distribution in the apolipoprotein AI-CIII-AIV cluster, which could lead to changes in levels of lipoproteins. This is not caused by a single mutation but rather by a combination of different mutations.

  5. Contribution of polymorphisms in the apolipoprotein AI-CIII-AIV cluster to hyperlipidaemia in patients with gout

    PubMed Central

    Cardona, F; Tinahones, F; Collantes, E; Escudero, A; Garcia-Fuentes, E; Soriguer, F

    2005-01-01

    Background: Studies have shown that hyperuricaemia is independently related to the insulin resistance syndrome and that polymorphisms of the apolipoprotein AI-CIII-AIV cluster are also related to insulin resistance. Objective: To study the prevalence of polymorphisms of the apolipoprotein AI-CIII-AIV cluster in persons with gout and to determine whether these polymorphisms contribute to the pathophysiology of gout or to altered lipid concentrations. Methods: Plasma cholesterol, triglycerides, uric acid, VLDL, LDL, IDL, and HDL triglycerides, cholesterol, and the renal excretion of uric acid were measured in 68 patients with gout with gout and 165 healthy subjects. Polymorphisms were studied by amplification and RFLP in all subjects, using XmnI and MspI in the apolipoprotein AI gene and SstI in the apolipoprotein CIII gene. Results: The A allele at position –75 bp in the apolipoprotein AI gene was more common in patients with gout than in controls (p = 0.01). Levels of cholesterol, triglycerides, uric acid, basal glycaemia, and HDL cholesterol were higher in the patients (p<0.001). In the patients there was also an interaction between mutations at the two polymorphic loci studied in the apolipoprotein AI gene (p = 0.04). An absence of the mutation at position –75 bp of the apolipoprotein AI gene resulted in increased plasma triglyceride levels. Conclusions: Gouty patients have an altered allelic distribution in the apolipoprotein AI-CIII-AIV cluster, which could lead to changes in levels of lipoproteins. This is not caused by a single mutation but rather by a combination of different mutations. PMID:15115711

  6. Insights into the Effects of Complement Factor H on the Assembly and Decay of the Alternative Pathway C3 Proconvertase and C3 Convertase.

    PubMed

    Bettoni, Serena; Bresin, Elena; Remuzzi, Giuseppe; Noris, Marina; Donadelli, Roberta

    2016-04-08

    The activated fragment of C3 (C3b) and factor B form the C3 proconvertase (C3bB), which is cleaved by factor D to C3 convertase (C3bBb). Older studies (Conrad, D. H., Carlo, J. R., and Ruddy, S. (1978)J. Exp. Med.147, 1792-1805; Pangburn, M. K., and Müller-Eberhard, H. J. (1978)Proc. Natl. Acad. Sci. U.S.A.75, 2416-2420; Kazatchkine, M. D., Fearon, D. T., and Austen, K. F. (1979)J. Immunol.122, 75-81) indicated that the complement alternative pathway regulator factor H (FH) competes with factor B for C3b binding; however, the capability of FH to prevent C3bB assembly has not been formally investigated. Moreover, in the few published studies FH did not favor C3bB dissociation. Whether FH may affect C3bBb formation from C3bB is unknown. We set up user-friendly assays based on combined microplate/Western blotting techniques that specifically detect either C3bB or C3bBb, with the aim of investigating the effect of FH on C3bB assembly and decay and C3bBb formation and decay. We document that FH does not affect C3bB assembly, indicating that FH does not efficiently compete with factor B for C3b binding. We also found that FH does not dissociate C3bB. FH showed a strong C3bBb decay-accelerating activity, as reported previously, and also exerted an apparent inhibitory effect on C3bBb formation. The latter effect was not fully attributable to a rapid FH-mediated dissociation of C3bBb complexes, because blocking decay with properdin and C3 nephritic factor did not restore C3bBb formation. FH almost completely prevented release of the smaller cleavage subunit of FB (Ba), without modifying the amount of C3bB complexes, suggesting that FH inhibits the conversion of C3bB to C3bBb. Thus, the inhibitory effect of FH on C3bBb formation is likely the sum of inhibition of C3bB conversion to C3bBb and of C3bBb decay acceleration. Further studies are required to confirm these findings in physiological cell-based settings.

  7. Insights into the Effects of Complement Factor H on the Assembly and Decay of the Alternative Pathway C3 Proconvertase and C3 Convertase*

    PubMed Central

    Bettoni, Serena; Bresin, Elena; Remuzzi, Giuseppe; Noris, Marina; Donadelli, Roberta

    2016-01-01

    The activated fragment of C3 (C3b) and factor B form the C3 proconvertase (C3bB), which is cleaved by factor D to C3 convertase (C3bBb). Older studies (Conrad, D. H., Carlo, J. R., and Ruddy, S. (1978) J. Exp. Med. 147, 1792–1805; Pangburn, M. K., and Müller-Eberhard, H. J. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 2416–2420; Kazatchkine, M. D., Fearon, D. T., and Austen, K. F. (1979) J. Immunol. 122, 75–81) indicated that the complement alternative pathway regulator factor H (FH) competes with factor B for C3b binding; however, the capability of FH to prevent C3bB assembly has not been formally investigated. Moreover, in the few published studies FH did not favor C3bB dissociation. Whether FH may affect C3bBb formation from C3bB is unknown. We set up user-friendly assays based on combined microplate/Western blotting techniques that specifically detect either C3bB or C3bBb, with the aim of investigating the effect of FH on C3bB assembly and decay and C3bBb formation and decay. We document that FH does not affect C3bB assembly, indicating that FH does not efficiently compete with factor B for C3b binding. We also found that FH does not dissociate C3bB. FH showed a strong C3bBb decay-accelerating activity, as reported previously, and also exerted an apparent inhibitory effect on C3bBb formation. The latter effect was not fully attributable to a rapid FH-mediated dissociation of C3bBb complexes, because blocking decay with properdin and C3 nephritic factor did not restore C3bBb formation. FH almost completely prevented release of the smaller cleavage subunit of FB (Ba), without modifying the amount of C3bB complexes, suggesting that FH inhibits the conversion of C3bB to C3bBb. Thus, the inhibitory effect of FH on C3bBb formation is likely the sum of inhibition of C3bB conversion to C3bBb and of C3bBb decay acceleration. Further studies are required to confirm these findings in physiological cell-based settings. PMID:26903516

  8. C3 and infrared spectrophotometry of Y Canum Venaticorum

    NASA Technical Reports Server (NTRS)

    Goebel, J. H.; Bregman, J. D.; Strecker, D. W.; Witteborn, F. C.; Erickson, E. F.

    1978-01-01

    The 1.2- to 5.6-micron spectrum of the carbon star Y CVn is presented and discussed. The observations were made from the Kuiper Airborne Observatory at an altitude of 12.5 km, thereby avoiding most of the absorption due to terrestrial water vapor. Comparison of Y CVn near 5 microns with laboratory spectra provides possible evidence for the presence of the linear triatomic molecule C3. For the first time in a carbon star the clearly formed band heads of the CN red system between 1.2 and 2.3 microns are observed. Corroborative evidence for the presence of the molecules HCN and C2H2 is presented, and the relative contributions of C3, HCN, and C2H2 to the 3.1-micron absorption band are discussed. Spectra of two other carbon stars, TX Psc and S Cep, are presented for comparison.

  9. Serum immunoglobulins and complement (C'3) in oral lichen planus.

    PubMed

    Sklavounou, A D; Laskaris, G; Angelopoulos, A P

    1983-01-01

    Serum immunoglobulins and complement (C'3) were determined by single radial immunodiffusion according to the method of Mancini and co-workers in fifty patients with oral lichen planus and twenty persons with clinically normal oral mucosa. Significantly increased levels of serum IgG (p less than 0.05) and a significant reduction of serum IgA concentration (p less than 0.05) in the experimental group as compared with normal controls were observed. Mean serum IgM and complement (C'3) levels were similar in patients and controls. No correlation between disease variety or extensiveness and immunoglobulin or complement levels was noticed. These results suggest that patients with oral lichen planus may have a generalized immunologic disorder in which humoral immunity is disturbed. Whether humoral immunity is of etiologic significance, contributes to the disease process, or, finally, represents an event secondary to the pathologic changes seen in the disease remains to be determined.

  10. Super-Whittaker vector at c = 3/2

    NASA Astrophysics Data System (ADS)

    Desrosiers, Patrick; Lapointe, Luc; Mathieu, Pierre

    2014-02-01

    The degenerate Whittaker vector of the superconformal algebra can be represented in terms of Jack superpolynomials. However, in this representation the norm of the Whittaker vector involves a scalar product with respect to which the Jack superpolynomials are not orthogonal. In this note, we point out that this defect can be cured at c = 3/2 by means of a trick specific to the supersymmetric case. At c = 3/2, we thus end up with a closed-form expression for the norm of the degenerate super-Whittaker vector. Granting the super-version of the AGT conjecture, this closed-form expression should be equal to the { {Z}}_2-symmetric SU(2) pure-gauge instanton partition function—the corresponding equality taking the form of a rather nontrivial combinatorial identity.

  11. Partial discharges and breakdown in C3F8

    NASA Astrophysics Data System (ADS)

    Koch, M.; Franck, C. M.

    2014-10-01

    Traditional search processes of gases or gas mixtures for replacing SF6 involve time consuming measurements of partial discharges and breakdown behaviour for several voltage waveforms and different field configurations. Recently a model for prediction of this behaviour for SF6 was described in literature. The model only requires basic properties of the gas such as the critical field strength and the effective ionization coefficient, which can be obtained by swarm parameter measurements, and thermodynamic properties, which can be calculated. In this paper, we show for the well-known and electronegative gas octafluoropropane (C3F8) that it is possible to transfer the model developed for SF6 to this gas to describe the breakdown behaviour of C3F8. Thus the model can be beneficial in the screening process of new insulation gases.

  12. C2-C3 Anterior Cervical Fusion: Technical Report.

    PubMed

    Finn, Michael A; MacDonald, Joel D

    2016-12-01

    Retrospective review of patients at a university hospital. To describe the anterior approach for cervical discectomy and fusion (ACDF) at C2-C3 level and evaluate its suitability for treatment of instability and degenerative disease in this region. The anterior approach is commonly used for ACDF in the lower cervical spine but is used less often in the high cervical spine. We retrospectively reviewed a database of consecutive cervical spine surgeries performed at our institution to identify patients who underwent ACDF at the C2-C3 level during a 10-year period. Demographic data, clinical indications, surgical technique, complications, and immediate results were evaluated. Of the 11 patients (7 female, 4 male; mean age 46 y) identified, 7 were treated for traumatic fractures and 4 for degenerative disk disease. Three patients treated for myelopathy showed improvement in mean Nurick grade from 3.6 to 1.3. Pain was significantly improved in all patients who had preoperative pain. Solid bony fusion was achieved in 5 of 7 patients at 3-month follow-up. Complications included dysphagia in 4 patients (which resolved in 3), aspiration pneumonia, mild persistent dysphonia, and construct failure at C2 requiring posterior fusion. One patient died of a pulmonary embolism 2 weeks postoperatively. ACDF at the C2-C3 level is an option for the treatment of high cervical disease or trauma but is associated with a higher rate of approach-related morbidity. Familiarity with local anatomy may help to reduce complications. ACDF at C2-C3 appears to have a fusion rate similar to ACDF performed at other levels.

  13. Functional C3 Interoperability Architecture for Air Operations

    DTIC Science & Technology

    1991-08-20

    prevent effective joint operations. JTC3A developed this architecture after a review and analysis of joint and service documentation and discussions with...unified, component command, and service staff personnel. An interim report, referred to as the supporting analysis , was previously distributed for...service comment and provides extensive supplemental information on C3 for joint air operations. The supporting analysis will be available as soon as it is

  14. Rate of metastasis from C3H mouse mammary tumours.

    PubMed

    Nias, A H

    1992-01-01

    Transplants from the same C3H mouse mammary tumour have been used for radiobiological experiments with curative intent for more than 8 years. During that time, the rate of metastasis to the lungs has varied between 0 and 63% and an explanation has been sought for this change. The results of immunological assays showed no obvious pattern. An inverse relationship was found between tumour latency and metastasis.

  15. Deuterium hyperfine structure in interstellar C3HD

    NASA Technical Reports Server (NTRS)

    Bell, M. B.; Watson, J. K.; Feldman, P. A.; Matthews, H. E.; Madden, S. C.; Irvine, W. M.

    1987-01-01

    The deuterium nuclear quadrupole hyperfine structure of the transition 1(10)-1(01) of the ring molecule cyclopropenylidene-d1 (C3HD) has been observed in emission from interstellar molecular clouds. The narrowest linewidths (approximately 7 kHz) so far observed are in the cloud L1498. The derived D coupling constants Xzz = 186.9(1.4) kHz, eta=0.063(18) agree well with correlations based on other molecules.

  16. Polymorphous light eruption

    MedlinePlus

    Polymorphous light eruption (PMLE) is a common skin reaction in people who are sensitive to sunlight (ultraviolet light). ... Polymorphic light eruption; Photodermatosis; PMLE; Benign summer light eruption

  17. Characterization of a functional C3A liver spheroid model.

    PubMed

    Gaskell, Harriet; Sharma, Parveen; Colley, Helen E; Murdoch, Craig; Williams, Dominic P; Webb, Steven D

    2016-06-01

    More predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells. Spheroids were viable and maintained a compact in vivo-like structure with zonation features for up to 32 days. MRP2 and Pgp transporters had polarised expression on the canalicular membrane of cells in the spheroids and were able to functionally transport CMFDA substrate into these canalicular structures. Spheroids expressed CYP2E1 and were able to synthesise and secrete albumin and urea to a higher degree than monolayer C3A cultures. Penetration of doxorubicin throughout the spheroid core was demonstrated. Spheroids showed increased susceptibility to hepatotoxins when compared to 2D cultures, with acetaminophen having an IC50 of 7.2 mM in spheroids compared to 33.8 mM in monolayer culture. To conclude, we developed an alternative method for creating C3A liver spheroids and demonstrated cellular polarisation and zonation, as well as superior liver-specific functionality and more sensitive toxicological response compared to standard 2D liver models, confirming a more in vivo-like liver model.

  18. High-Resolution Infrared Spectroscopy of Ge_2C_3

    NASA Astrophysics Data System (ADS)

    Thorwirth, S.; Lutter, V.; Schlemmer, S.; Giesen, T. F.; Gauss, J.

    2013-06-01

    Carbon-rich systems are of great importance in diverse areas of research like material science as well as astro- and structural chemistry. Despite this relevance, our knowledge of smaller cluster units is still fragmentary, particularly with respect to investigations at high-spectral resolution in the gas phase. Unequivocal assignment of spectral features to their molecular carriers is critically dependent on predictions from high-level quantum-chemical calculations. In turn, high-resolution studies provide useful information to assess the predictive power of quantum-chemical methods. This is particularly interesting for cluster systems harboring heavy elements for which so far relatively little is known from experiment. With this contribution, we would like to present a recent gas-phase study of a polyatomic germanium-carbon cluster, linear Ge_2C_3 (Ge=C=C=C=Ge), which was previously studied in an Ar matrix. The cluster was produced through laser ablation of germanium-graphite sample rods and observed in a free jet at wavelengths around 5μm. Additionally, quantum-chemical calculations of Ge_2C_3 were performed at the CCSD(T) level of theory. The production and observation of Ge_2C_3 suggests that many more binary clusters should be amenable to high-resolution spectroscopic techniques not only in the infrared but also in the microwave region. D. L. Robbins, C. M. L. Rittby, and W. R. M. Graham, J. Chem. Phys. 114, 3570 (2001).

  19. The Climate Change Consortium of Wales (C3W)

    NASA Astrophysics Data System (ADS)

    Hendry, K. R.; Reis, J.; Hall, I. R.

    2011-12-01

    In response to the complexity and multidisciplinary nature of climate change research, the Climate Change Consortium of Wales (C3W) was formed in 2009 by the Welsh universities of Aberystwyth, Bangor, Cardiff and Swansea. Initially funded by Welsh Government, through the Higher Education Funding Council for Wales, the Countryside Council for Wales and the universities, C3W aims to bring together climate change researchers from a wide range of disciplines to explore scientific and sociological drivers, impacts and implications at local, national and international scale. The specific aims are to i) improve our fundamental understanding of the causes, nature, timing and consequences of climate change on Planet Earth's environment and on humanity, and ii) to reconfigure climate research in Wales as a recognisable centre of excellence on the world stage. In addition to improving the infrastructure for climate change research, we aim to improve communication, networking, collaborative research, and multidisciplinary data assimilation within and between the Welsh universities, and other UK and international institutions. Furthermore, C3W aims to apply its research by actively contributing towards national policy development, business development and formal and informal education activities within and beyond Wales.

  20. The role of complement in C3 glomerulopathy.

    PubMed

    Zipfel, Peter F; Skerka, Christine; Chen, Qian; Wiech, Thorsten; Goodship, Tim; Johnson, Sally; Fremeaux-Bacchi, Veronique; Nester, Clara; de Córdoba, Santiago Rodríguez; Noris, Marina; Pickering, Matthew; Smith, Richard

    2015-09-01

    C3 glomerulopathy describes a spectrum of disorders with glomerular pathology associated with C3 cleavage product deposition and with defective complement action and regulation (Fakhouri et al., 2010; Sethi et al., 2012b). Kidney biopsies from these patients show glomerular accumulation or deposition of C3 cleavage fragments, but no or minor deposition of immunoglobulins (Appel et al., 2005; D'Agati and Bomback, 2012; Servais et al., 2007; Sethi and Fervenza, 2011). At present the current situation asks for a better definition of the underlining disease mechanisms, for precise biomarkers, and for a treatment for this disease. The complement system is a self activating and propelling enzymatic cascade type system in which inactive, soluble plasma components are activated spontaneously and lead into an amplification loop (Zipfel and Skerka, 2009). Activation of the alternative pathway is spontaneous, occurs by default, and cascade progression leads to amplification by complement activators. The system however is self-controlled by multiple regulators and inhibitors, like Factor H that control cascade progression in fluid phase and on surfaces. The activated complement system generates a series of potent effector components and activation products, which damage foreign-, as well as modified self cells, recruit innate immune cells to the site of action, coordinate inflammation and the response of the adaptive immune system in form of B cells and T lymphocytes (Kohl, 2006; Medzhitov and Janeway, 2002; Ogden and Elkon, 2006; Carroll, 2004; Kemper and Atkinson, 2007; Morgan, 1999; Muller-Eberhard, 1986; Ricklin et al., 2010). Complement controls homeostasis and multiple reactions in the vertebrate organism including defense against microbial infections (Diaz-Guillen et al., 1999; Mastellos and Lambris, 2002; Nordahl et al., 2004; Ricklin et al., 2010). In consequence defective control of the spontaneous self amplifying cascade or regulation is associated with numerous

  1. Zinc-induced Self-association of Complement C3b and Factor H

    PubMed Central

    Nan, Ruodan; Tetchner, Stuart; Rodriguez, Elizabeth; Pao, Po-Jung; Gor, Jayesh; Lengyel, Imre; Perkins, Stephen J.

    2013-01-01

    The sub-retinal pigment epithelial deposits that are a hallmark of age-related macular degeneration contain both C3b and millimolar levels of zinc. C3 is the central protein of complement, whereas C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3. During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical ultracentrifugation and x-ray scattering. C3, C3u, and C3b associated strongly in >100 μm zinc, whereas C3c and C3d showed weak association. With zinc, C3 forms soluble oligomers, whereas C3u and C3b precipitate. We conclude that the C3, C3u, and C3b association with zinc depended on the relative positions of C3d and C3c in each protein. Computational predictions showed that putative weak zinc binding sites with different capacities exist in all five proteins, in agreement with experiments. Factor H forms large oligomers in >10 μm zinc. In contrast to C3b or Factor H alone, the solubility of the central C3b-Factor H complex was much reduced at 60 μm zinc and even more so at >100 μm zinc. The removal of the C3b-Factor H complex by zinc explains the reduced C3u/C3b inactivation rates by zinc. Zinc-induced precipitation may contribute to the initial development of sub-retinal pigment epithelial deposits in the retina as well as reducing the progression to advanced age-related macular degeneration in higher risk patients. PMID:23661701

  2. Phylogeny of Y-chromosome haplogroup C3b-F1756, an important paternal lineage in Altaic-speaking populations.

    PubMed

    Wei, Lan-Hai; Huang, Yun-Zhi; Yan, Shi; Wen, Shao-Qing; Wang, Ling-Xiang; Du, Pan-Xin; Yao, Da-Li; Li, Shi-Lin; Yang, Ya-Jun; Jin, Li; Li, Hui

    2017-06-01

    In previous studies, a specific paternal lineage with a null value for the Y-chromosome short tandem repeat (Y-STR) marker DYS448 was identified as common among Mongolic- and Turkic-speaking populations. This paternal lineage (temporarily named C3*-DYS448del) was determined to be M217+, M93-, P39-, M48-, M407-, and P53.1-, and its origin and phylogeny remain ambiguous. Here, we analyzed Y-chromosome sequences of 10 male that are related this paternal lineage and redefined it as C3b1a1a1a-F1756 (C3b-F1756). We generated a highly revised phylogenetic tree of haplogroup C3b-F1756, including 21 sub-clades and 360 non-private Y-chromosome polymorphisms. Additionally, we performed a comprehensive analysis of the C3*-DYS448del lineage in eastern Eurasia, including 18 270 samples from 297 populations. Whole Y-chromosome sequences, Y-STR haplotypes, and frequency data were used to generate a distribution map, a network, and age estimations for lineage C3*-DYS448del and its sub-lineages. Considering the historical records of the studied populations, we propose that two major sub-branches of C3b-F1756 may correspond to early expansions of ancestors of modern Mongolic- and Turkic-speaking populations. The large number of newly defined Y-chromosome polymorphisms and the revised phylogenetic tree for C3b-F1756 will assist in investigation of the early history of Altaic-speaking populations in the future.Journal of Human Genetics advance online publication, 1 June 2017; doi:10.1038/jhg.2017.60.

  3. Quasiclassical calculation of the chemical reaction Ba+C3H7Br→BaBr+C3H7

    NASA Astrophysics Data System (ADS)

    Jiang, Yong-Chao; Li, Gui-Xia; Shi, Xiao-Feng; Huang, Shu-Lai

    2012-12-01

    The quasi-classical trajectory (QCT) method based on the extended London—Eyring—Polanyi—Sato potential energy surface is used to investigate the product vibrational distribution, angular distribution and angle-resolved kinetic distribution of the reaction Ba+C3H7Br→BaBr+C3H7 at 2.58 kcal/mol. The calculated results show that the product BaBr vibrational distribution is quite hot, the vibrational population peaks are located at v = 12, and the angular product distribution tends to backward scattering. The calculated angle-resolved kinetic distribution shows that the kinetic distribution is obviously related to angle. The QCT results are always qualitatively acceptable and sometimes even quantitatively.

  4. Total and differential cross sections of C3H8 and C3F8 by electron and positron impacts

    NASA Astrophysics Data System (ADS)

    Sueoka, Osamu; Kitajima, Masashi; Sakamoto, Y.; Suzuki, T.; Samukawa, S.; Sueoka, Osamu; Hamada, Akira; Kimura, Mineo

    1998-10-01

    Total and differential elastic cross sections in e-/e+ + C3H8 and C3F8 scattering have been investigated experimentally and theoretically. The differential cross section measurement by electron impact has been carried out from 2 eV to 100 eV, while the total cross section measurement by electron and positron has been for 0.7 eV to 600 eV. The theoretical study has been performed by using the continuum multiple-scattering method. The present total cross sections are found to agree reasonably well with those by Wayne State Univ. group, and theoretical rationale for origins of shape resonances are provided.

  5. Formation of C3 and C2 in Cometary Comae

    NASA Astrophysics Data System (ADS)

    Hölscher, Alexander

    2015-03-01

    Comets are remnants from the Solar System formation. They reside at large distances from the Sun and are believed to store deep freeze imprints of the chemical and physical conditions at the time the Solar System formed. The main ice component of a comet is H2O followed by CO and CO2 with additional small amounts of molecules with varying complexity. Comets also contain large amounts of dust. If a comet approaches the Sun the ices begin to sublimate giving rise to the cometary coma. The molecules producing the coma can be observed in the infrared, the radio wavelength range and at optical wavelengths. To constrain the formation of the Solar System, models require knowledge of the composition for a statistically significant number of comets. This favors optical observations of e.g. C3 (tricarbon) and C2 (dicarbon) since these species allow observations even of relatively faint comets and do not require space missions (infrared observations). However, one has to link these observed photodissociation product species (daughter species) to the molecules that originally sublimated from the comet nucleus surface, i.e. the so-called parent molecules, as e.g. C2H2 (acetylene) for C2. However, for C3 no parent molecules have been identified so far. This thesis investigates the formation of C3 and C2 radicals in cometary comae due to photodissociation of observed and in the literature proposed hydrocarbon parent molecules. For this purpose a one-dimensional multi-fluid coma chemistry model has been improved and applied. This work added new photo reactions to the model, updated the hydrocarbon photo rate coefficients and quantified their uncertainty. A sensitivity analysis has been carried out to determine the reactions whose uncertainty most affect the model output uncertainty. Special attention should be paid to these so-called key reactions in future laboratory experiments and quantum chemical computations to reduce the model output uncertainty more effectively. This will

  6. Identification, mapping and linkage analysis of randomly amplified DNA polymorphisms in Tetrahymena thermophila

    SciTech Connect

    Brickner, J.H.; Lynch, T.J.; Zeilinger, D.; Orias, E.

    1996-06-01

    Using the random amplified polymorphic DNA (RAPD) technique and exploiting the unique genetics of Tetrahymena thermophila, we have identified and characterized 40 DNA polymorphisms occurring between two inbred strains (B and C3) of this ciliated protozoan. These RAPD markers permit the PCR amplification of a DNA species using template DNA from SB1969 (B strain) but fail to do so using DNA from C3-368-5 (C3 strain). Polymorphisms were mapped to chromosomes using a panel of monosomic strains constructed by crossing B strain-derived nullisomic strains to inbred strain C3. They map to all five chromosomes and appear to be evenly distributed throughout the genome. Chromosomal groups were then analyzed for linkage using meiotic segregants; four linkage groups were identified in chromosomes 1R, 2L, 3 and 5. The RAPD method appears useful for the construction of a genetic map of the Tetrahymena genome based on DNA polymorphisms. 37 refs., 4 figs., 6 tabs.

  7. Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans

    PubMed Central

    Chandak, Giriraj R; Ward, Kirsten J; Yajnik, Chittaranjan S; Pandit, Anand N; Bavdekar, Ashish; Joglekar, Charu V; Fall, Caroline HD; Mohankrishna, P; Wilkin, Terence J; Metcalf, Bradley S; Weedon, Michael N; Frayling, Timothy M; Hattersley, Andrew T

    2006-01-01

    Background The APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects. Methods We genotyped 557 Indian adults from Pune, India, and 237 UK white adults for -1131T>C and S19W variants in the APOA5 gene, compared their allelic and genotype frequency and determined their association with fasting serum triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune Indian subjects for analysis of linkage disequilibrium with the APOA5 variants. Results The APOA5 -1131C allele was more prevalent in Indians from Pune (Pune Indians) compared to UK white subjects (allele frequency 20% vs. 4%, p = 0.00001), whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015). Patterns of linkage disequilibrium between the two variants were similar between the two populations and confirmed that they occur on two different haplotypes. In Pune Indians, the presence of -1131C allele and the 19W allele was associated with a 19% and 15% increase respectively in triglyceride concentrations although only -1131C was significant (p = 0.0003). This effect size was similar to that seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175 Pune Indian subjects showed that this variant is not in appreciable linkage disequilibrium with the APOA5 -1131T>C variant (r2 = 0.07). Conclusion This is the first study to look at the role of APOA5 in Asian Indian subjects that reside in India. The -1131C allele is more prevalent and the 19W allele is less prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5 variants are associated with triglyceride levels

  8. Carbon nitride frameworks and dense crystalline polymorphs

    NASA Astrophysics Data System (ADS)

    Pickard, Chris J.; Salamat, Ashkan; Bojdys, Michael J.; Needs, Richard J.; McMillan, Paul F.

    2016-09-01

    We used ab initio random structure searching (AIRSS) to investigate polymorphism in C3N4 carbon nitride as a function of pressure. Our calculations reveal new framework structures, including a particularly stable chiral polymorph of space group P 43212 containing mixed s p2 and s p3 bonding, that we have produced experimentally and recovered to ambient conditions. As pressure is increased a sequence of structures with fully s p3 -bonded C atoms and three-fold-coordinated N atoms is predicted, culminating in a dense P n m a phase above 250 GPa. Beyond 650 GPa we find that C3N4 becomes unstable to decomposition into diamond and pyrite-structured CN2.

  9. Toward a General Theory of C3 Processes. Part 2

    DTIC Science & Technology

    1989-01-01

    CE) con- ALDP ’ PAL DP P’ ditional event algebra extending both ordinary prob- ability logic and fu y logic (in Zadeh’s sense), and where equivalently...further assumptions of a full alge- thus determined through steps 1-8. braic logic description pair ALDP , i.e., compatible 10. Obtain for C3 Design...functional descriptions for AX and ALDP , etc., for each side. PALDP ) 1+ ALOP (AX);pALDPOO)J .1 .1 (Again, see [I] for further details.) In order to

  10. MCCx C3I Control Center Interface Emulator

    NASA Technical Reports Server (NTRS)

    Mireles, James R.

    2010-01-01

    This slide presentation reviews the project to develop and demonstrate alternate Information Technologies and systems for new Mission Control Centers that will reduce the cost of facility development, maintenance and operational costs and will enable more efficient cost and effective operations concepts for ground support operations. The development of a emulator for the Control Center capability will enable the facilities to conduct the simulation requiring interactivity with the Control Center when it is off line or unavailable, and it will support testing of C3I interfaces for both command and telemetry data exchange messages (DEMs).

  11. The C3E Women in Clean Energy Symposium

    SciTech Connect

    Saylors-Laster, Kim; Kirsch, Emily; Brown, Sandra; Jordan, Rhonda; Mukherjee, Anuradha; Martin, Cheryl; Madden, Alice; Araujo, Kathy

    2013-09-30

    The Clean Energy Education & Empowerment initiative (C3E), provides a forum for thought leaders across the clean energy sector to devise innovative solutions to the nation's most pressing energy challenges. This year, the symposium was held at MIT's Media Lab in Cambridge, MA, on September 19-20, 2013. What sets the annual conference apart is its focus on building a strong community of professionals dedicated to advancing more women leaders in clean energy fields. By working to leverage the skills, talents and perspectives of women, the symposium helps to better position the U.S. to lead the global clean energy revolution.

  12. The C3E Women in Clean Energy Symposium

    ScienceCinema

    Saylors-Laster, Kim; Kirsch, Emily; Brown, Sandra; Jordan, Rhonda; Mukherjee, Anuradha; Martin, Cheryl; Madden, Alice; Araujo, Kathy

    2016-07-12

    The Clean Energy Education & Empowerment initiative (C3E), provides a forum for thought leaders across the clean energy sector to devise innovative solutions to the nation's most pressing energy challenges. This year, the symposium was held at MIT's Media Lab in Cambridge, MA, on September 19-20, 2013. What sets the annual conference apart is its focus on building a strong community of professionals dedicated to advancing more women leaders in clean energy fields. By working to leverage the skills, talents and perspectives of women, the symposium helps to better position the U.S. to lead the global clean energy revolution.

  13. Beryllium-induced immune response in C3H mice

    SciTech Connect

    Benson, J.M.; Bice, D.E.; Nikula, K.J.

    1995-12-01

    Studies conducted at ITRI over the past several years have investigated whether Beagle dogs, monkeys, and mice are suitable models for human chronic beryllium-induced lung disease (CBD). Recent studies have focused on the histopathological and immunopathological changes occurring in A/J and C3H/HeJ mice acutely exposed by inhalation to Be metal. Lung lesions in both strains of mice included focal lymphocyte aggregates comprised primarily of B lymphocytes and lesser amounts of T-helper lymphocytes and microgranulomas consisting chiefly of macrophages and T-helper lymphocytes. The distribution of proliferating cells within the microgranulomas was similar to the distribution of T-helper cells. These results strongly suggested that A/J and C3H/HeJ mice responded to inhaled Be metal in a fashion similar to humans in terms of pulmonary lesions and the apparent in situ proliferation of T-helper cells. Results of these studies confirm lymphocyte involvement in the pulmonary response to inhaled Be metal.

  14. A Search for Interstellar Oxiranecarbonitrile (C3H3NO)

    NASA Technical Reports Server (NTRS)

    Dicken, J. E.; Irvine, W. M.; Ohishi, M.; Arrhenius, G.; Bauder, A.; Mueller, F.; Eschenmoser, A.

    1996-01-01

    We report a search in cold, quiescent and in 'hot core' type interstellar molecular clouds for the small cyclic molecule oxiranecarbonitrile (C3H3NO), which has been suggested as a precursor of important prebiotic molecules. We have determined upper limits to the column density and fractional abundance for the observed sources and find that, typically, the fractional abundance by number relative to molecular hydrogen Of C3H3NO is less than a few times 10(exp -10). This limit is one to two orders of magnitude less than the measured abundance of such similarly complex species as CH3CH2CN and HCOOCH3 in well-studied hot cores. A number of astrochemical discoveries were made, including the first detection of the species CH3CH2CN in the massive star-forming clouds G34.3+0.2 and W51M and the first astronomical detections of some eight rotational transitions of CH3CH2CN, CH3CCH, and HCOOCH3. In addition, we found 8 emission lines in the 89 GHz region and 18 in the 102 GHz region which we were unable to assign.

  15. Experiment of vitreous liquefaction induced by C3F8.

    PubMed

    Wang, Jing; Li, Qiuming

    2017-01-01

    To investigate the effect and safety of vitreous liquefaction induced by C3F8 (an inert gas) injected into vitreous cavit of rabbit eyes. 24 rabbits (48 eyes) were randomly divided into four groups, named group A, group B, group C and group D, with 6 rabbits in each group. The right eye in each rabbit was taken as the experimental eye while the left as the control eye. The experimental eyes in group A were injected with 0.1mL disinfectant air; the experimental eyes in group B, group C and group D were all injected with C3F8 0.1mL, 0.2mL and 0.3mL respectively after receiving anterior chamber penetration; and the controlled eyes in all group were injected with 0.1mL balanced salt solution (BSS). During the first 7 d after injection, all the rabitts' eyes were examined by slit lamp, ophthalmoscope, intraocular pressure (IOP) and dark-adapted retina Electroretinography (ERG) each day. After that, the examination of IOG and ERP were reviewed weekly. Besides, B ultrasound should be examined to observe the situation of posterior vitreous detachment (PVD) in the 4th and 8th weeks. The rabbits were killed in the end of the 8th week, with their specimens examined by the light microscope, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Except group A, all the experimental eyes were produced with vitreous liquefaction. In group C and group D, in addition to the produced vitreous liquefaction, posterior vitreous detachment (PVD), even complete PVD, were induced in different extent. But in group B, the vitreous body was returned to the gel state at 2 weeks after gas absorption. In group C and group D, the vitreous body was not found to recover its original state at 8 weeks. In group D, there was a little increase of intraocular pressure, a mild delay of wave a and wave b after ERG in the 4th day after the gas injection. While there was no such situation in other groups. After the examination of B ultrasound in the 8th week, the complete PVD

  16. Manipulating the mediator: modulation of the alternative complement pathway C3 convertase in health, disease and therapy.

    PubMed

    Ricklin, Daniel

    2012-11-01

    The complement network is increasingly recognized as an important triage system that is able to differentiate between healthy host cells, microbial intruders, cellular debris and immune complexes, and tailor its actions accordingly. At the center of this triage mechanism is the alternative pathway C3 convertase (C3bBb), a potent enzymatic protein complex capable of rapidly converting the inert yet abundant component C3 into powerful effector fragments (C3a and C3b), thereby amplifying the initial response on unprotected surfaces and inducing a variety of effector functions. A fascinating molecular mechanism of convertase assembly and intrinsic regulation, as well as the interplay with a panel of cell surface-bound and soluble inhibitors are essential for directing complement attack to intruders and protecting healthy host cells. While efficiently keeping immune surveillance and homeostasis on track, the reliance on an intricate cascade of interaction and conversion steps also renders the C3 convertase vulnerable to derail. On the one hand, tissue damage, accumulation of debris, or polymorphisms in complement genes may unfavorably shift the balance between activation and regulation, thereby contributing to a variety of clinical conditions. On the other hand, pathogens developed powerful evasion strategies to avoid complement attack by targeting the convertase. Finally, we increasingly challenge our bodies with foreign materials such as biomaterial implants or drug delivery vehicles that may induce adverse effects that are at least partially caused by complement activation and amplification via the alternative pathway. The involvement of the C3 convertase in a range of pathological conditions put this complex into the spotlight of complement-targeted drug discovery efforts. Fortunately, the physiological regulation and microbial evasion approaches provide a rich source of inspiration for the development of powerful treatment options. This review provides insight into

  17. Infrared Predissociation Spectroscopy of the Hydrocarbon Cations C_3H^+, C_2H^+, and C_3H_2^+

    NASA Astrophysics Data System (ADS)

    Brünken, Sandra; Lipparini, Filippo; Gauss, Jürgen; Stoffels, Alexander; Redlich, Britta; van der Meer, Lex; Berden, Giel; Oomens, Jos; Schlemmer, Stephan

    2016-06-01

    Reactive hydrocarbon cations play an important role in the astrochemistry of the interstellar medium, but spectroscopic data, needed for their identification in astronomical observations, is sparse. Here we report the first gas-phase vibrational spectra of the linear C_3H^+ (^1 Σ), the radical cation C_2H^+ (^3 Π), and the linear-/cyclic-C_3H_2^+ (^2 Π /^2A_1, resp.). Broadband spectra were recorded by Ne- and He-messenger infrared-predissociation (IR-PD) action spectroscopy in a cryogenic (4-11 K) ion trap instrument (FELion) in the 250-3500 {wn} range using a free electron laser and a MIR-OPO at the FELIX (Free-Electron Laser for Infrared eXperiments) laboratory. The band positions (determined with a precision of 1-2 wn) covering the C-H and C-C stretching as well as several bending modes are compared to high-level (CCSD(T) with large basis sets) quantum-chemical calculations with an emphasis on anharmonic effects and on the influence of the rare-gas messenger atom. The experimental and theoretical data provide a solid basis for subsequent IR high-resolution studies, with the ultimate goal to predict and measure accurate rotational spectra for a radio-astronomical search of these molecular ions in space.

  18. Supramolecular assembly of C3 peptidic molecules into helical polymers.

    PubMed

    Dai, Yutang; Zhao, Xin; Su, Xinyan; Li, Guangyu; Zhang, Afang

    2014-08-01

    Self-assembly of C3 discotic molecules bearing dipeptide pendants into helical supramolecular polymers is investigated. The dipeptides are constituted from glycine and alanine with altered sequence, aiming at modulating the steric hindrance and examining the steric effects on the assembly. This steric hindrance effect is further illustrated with a dipeptide formed from glycine and valine, which carries a much larger isopropyl side unit. Their supramolecular polymerization is examined in various organic solvents and at different temperatures. The assembly morphology is directly visualized with atomic force microscopy. It is found that small changes in the dipeptide motifs in combination with solvent structure and the solution concentrations lead to different expression of the supramolecular assembly.

  19. C3 generic workstation: Performance metrics and applications

    NASA Technical Reports Server (NTRS)

    Eddy, Douglas R.

    1988-01-01

    The large number of integrated dependent measures available on a command, control, and communications (C3) generic workstation under development are described. In this system, embedded communications tasks will manipulate workload to assess the effects of performance-enhancing drugs (sleep aids and decongestants), work/rest cycles, biocybernetics, and decision support systems on performance. Task performance accuracy and latency will be event coded for correlation with other measures of voice stress and physiological functioning. Sessions will be videotaped to score non-verbal communications. Physiological recordings include spectral analysis of EEG, ECG, vagal tone, and EOG. Subjective measurements include SWAT, fatigue, POMS and specialized self-report scales. The system will be used primarily to evaluate the effects on performance of drugs, work/rest cycles, and biocybernetic concepts. Performance assessment algorithms will also be developed, including those used with small teams. This system provides a tool for integrating and synchronizing behavioral and psychophysiological measures in a complex decision-making environment.

  20. Lipopolysaccharide-specific bacteriophage for Klebsiella pneumoniae C3.

    PubMed Central

    Tomás, J M; Jofre, J T

    1985-01-01

    Bacteriophage FC3-1 is one of several specific bacteriophages of Klebsiella pneumoniae C3 isolated in our laboratory. Unlike receptors for other Klebsiella phages, the bacteriophage FC3-1 receptor was shown to be lipopolysaccharide, specifically the polysaccharide fraction (O-antigen and core region). We concluded that capsular polysaccharide, outer membrane proteins, and lipid A were not involved in phage binding. Mutants resistant to this phage were isolated and were found to be devoid of lipopolysaccharide O-antigen by several criteria but to contain capsular material serologically identical to that of the wild type. The polysaccharide fraction was concluded to be the primary phage receptor, indicating that it is available to the phage. Images PMID:3888963

  1. Complement C3a enhances CXCL12 (SDF-1)-mediated chemotaxis of bone marrow hematopoietic cells independently of C3a receptor.

    PubMed

    Honczarenko, Marek; Ratajczak, Mariusz Z; Nicholson-Weller, Anne; Silberstein, Leslie E

    2005-09-15

    Complement C3a promotes CXCL12-induced migration and engraftment of human and murine hemopoietic progenitor cells, suggesting a cross-influence between anaphylatoxin and chemokine axes. Here we have explored the underlying mechanism(s) of complement anaphylatoxin and chemokine cooperation. In addition to C3a, C3a-desArg and C4a but not C5a, are potent enhancers of CXCL12-induced chemotaxis of human and murine bone marrow (BM) stem/progenitor cells and B lineage cells. C3a enhancement of chemotaxis is chemokine specific because it is also observed for chemotaxis to CCL19 but not to CXCL13. The potentiating effect of C3a on CXCL12 is independent of the classical C3a receptor (C3aR). First, human BM CD34(+) and B lineage cells do not express C3aR by flow cytometry. Second, the competitive C3aR inhibitor SB290157 does not affect C3a-mediated enhancement of CXCL12-induced chemotaxis. Third, enhancement of chemotaxis of hemopoietic cells is also mediated by C3a-desArg, which does not bind to C3aR. Finally, C3a enhances CXCL12-induced chemotaxis of BM cells from C3aR knockout mice similar to BM cells from wild-type mice. Subsequent studies revealed that C3a increased the binding affinity of CXCL12 to human CXCR4(+)/C3aR(-), REH pro-B cells, which is compatible with a direct interaction between C3a and CXCL12. BM stromal cells were able to generate C3a, C3a-desArg, C4a, as well as CXCL12, suggesting that this pathway could function in vivo. Taken together, we demonstrate a C3a-CXCL12 interaction independent of the C3aR, which may provide a mechanism to modulate the function of CXCL12 in the BM microenvironment.

  2. Carbon Isotope Discrimination in Leaves of C3 Plants

    NASA Astrophysics Data System (ADS)

    Cuntz, M.; Gleixner, G.

    2009-04-01

    Carbon isotope composition is regarded as a powerful tool in understanding carbon cycling, both as a tracer and as a process recorder. However, accurate predictions of, for example, partitioning the net carbon flux into its components or obtaining climate information from tree rings, requires a good understanding of plant metabolism and related isotopic fractionations. Mechanistic models have concentrated largely on photosynthetic pathways and their isotopic composition. This cannot be said for respiratory processes. The mechanistic models of leaf isotope discrimination hence do not describe dawn, dusk and night very realistically or not at all. A new steady-state approach of the carbon isotope distribution in glucose potentially addresses the time of twilight and night (Tcherkez et al. 2004). Here, a new model of 13C discrimination in leaves of C3 plants is presented. The model is based on the steady-state approach of Tcherkez et al. (2004) but with much reduced complexity while retaining its general characteristics. In addition, the model introduces some new concepts such as a day-length dependent starch synthesis, night-length dependent starch degradation, energy-driven biosynthesis rates, and continuous leaf discrimination calculation for the whole diel cycle. It is therefore well adapted for biosphere-atmosphere exchange studies. The model predicts enriched sucrose and starch pools in the leaf compared to assimilated CO2. Biosynthesis on the other hand acts as the sink of the remaining, depleted carbon. The model calculates slightly different absolute starch compositions from the Tcherkez et al. (2004) model but this depends on chosen fractionation factors. The greatest difference between the two models is during dawn, dusk and night. For example, while Tcherkez et al. has changing phloem sucrose isotope composition during night, the model here predicts constant sucrose export composition. Observations seem to support rather constant phloem isotope composition

  3. Crystallography of in-situ transformations of the M 7C3 carbide in the cast Fe-Cr-Ni alloy

    NASA Astrophysics Data System (ADS)

    Kraposhin, V. S.; Kondrat'ev, S. Yu.; Talis, A. L.; Anastasiadi, G. P.

    2017-03-01

    In the process of holding of the cast heat-resistant Fe-Cr-Ni (0.45C-25Cr-35Ni) alloy at 1150°C, the eutectic chromium carbide present in its structure undergoes a gradual transition M 7C3 → M 23C6. The gradual formation of domains of the M 23C6 carbide inside the particles of the M 7C3 carbide makes it possible to assume that the observed phase transition is the well-known carbide transformation of the in situ type. The mechanism of the in situ transformation of the crystal structure of the carbide from M 7C3 into M 23C6 with a change in the number of nearest metal neighbors of carbon atoms is explained within the previously developed combinatory model of polymorphic transitions in the metals.

  4. Glomerular C3c localization indicates ongoing immune deposit formation and complement activation in experimental glomerulonephritis.

    PubMed Central

    Schulze, M.; Pruchno, C. J.; Burns, M.; Baker, P. J.; Johnson, R. J.; Couser, W. G.

    1993-01-01

    In antibody-mediated glomerular disease, deposits of C3 (C3b) are common and are degraded by factor I to C3c and C3d. However, the kinetics of C3b degradation in glomerulonephritis have not been defined. To do this, we studied three models of complement-dependent glomerulonephritis with established C3 deposits (passive Heymann nephritis, cationized immunoglobulin G membranous nephropathy, and concanavalin A-anticoncanavalin A glomerulonephritis). C3b deposition was halted by administration of cobra venom factor, and the disappearance of C3c and C3d from glomeruli was measured with specific antibodies and quantitative fluorescence densitometry. Results showed that C3c deposits were reduced by over 85% within 24 hours in all three models. C3c clearance was unaffected by site or mechanism of deposit formation. C3d deposits persisted despite lack of ongoing complement activation. In passive Heymann nephritis when disease activity was monitored by urinary C5b-9 excretion, C3c was cleared in parallel with return of urine C5b-9 excretion to normal values. We conclude that glomerular deposits of C3c are cleared within 24 hours of cessation of complement activation. Positive staining for C3 utilizing antibody specific for the C3c portion documents recent complement activation usually reflecting new immune deposit formation. Images Figure 1 Figure 2 Figure 3 PMID:7678717

  5. Mapping of the C3d receptor (CR2)-binding site and a neoantigenic site in the C3d domain of the third component of complement.

    PubMed Central

    Lambris, J D; Ganu, V S; Hirani, S; Müller-Eberhard, H J

    1985-01-01

    The C3d domain of C3 contains the site that binds to the C3d receptor (CR2) which is expressed on B lymphocytes. It also contains a neoantigenic determinant that is recognized by monoclonal antibody (mAb) 130 and is expressed when C3b is cleaved to iC3b and subsequently to C3dg or C3d. mAb 130 inhibits the binding of C3d to CR2. In this study, the locations of the CR2-binding site and of the neoantigen recognized by mAb 130 within the C3d domain were investigated. Treatment of human C3d with CNBr generated two major fragments with Mrs of 12,500 and 8600. Binding studies showed that only the Mr 8600 fragment was capable of binding to both CR2 and mAb 130. Amino-terminal sequence analysis of the Mr 8600 fragment and comparison with the amino acid sequence derived from human C3 cDNA [de Bruijn, M. H. L. & Fey, G. H. (1985) Proc. Natl. Acad. Sci. USA 82, 708-712] placed it between residues 1199 and 1274 of the C3 sequence. Several peptides were synthesized according to the derived C3 sequence of amino acid residues 1209-1236. Based on their differential binding to CR2 and mAb 130, we localized the CR2-binding site and mAb 130 neoantigenic site, respectively, to residues 1227-1232 and 1217-1232 of the C3 sequence. PMID:2408276

  6. Investigation of dielectric properties of cold C3F8 mixtures and hot C3F8 gas as Substitutes for SF6

    NASA Astrophysics Data System (ADS)

    Wang, Xiaohua; Zhong, Linlin; Yan, Jing; Yang, Aijun; Han, Guohui; Han, Guiquan; Wu, Yi; Rong, Mingzhe

    2015-10-01

    In order to reduce the global warming potential resulting from SF6 widely used as an insulating and arc quenching medium, the substitutes need to be found. This paper focuses on different cold C3F8 mixtures (at room temperature) as an insulating gas and hot C3F8 gas (at temperatures of 300-3500 K) as an arc quenching medium, which seem to be a good replacement of SF6. Firstly, the dielectric properties, including the reduced ionization coefficient α / N, reduced electron attachment coefficient η / N and reduced critical electric field strength ( E / N)cr, of the cold C3F8-CF4, C3F8-CO2, C3F8-N2, C3F8-O2 and C3F8-Ar mixtures are calculated numerically using the two-term approximation of the Boltzmann equation. The dependence of such dielectric properties on the buffer gas proportion is investigated. Among the various C3F8 mixtures, the C3F8-N2 mixture has the lowest α / N and the C3F8-CF4 mixture has the largest η / N, and moreover, the C3F8-N2 mixture is the best insulator in terms of breakdown strength because it has the largest ( E / N)cr. Secondly, the ( E / N)cr of hot C3F8 at temperatures up to 3500 K and various pressures is determined and compared with that of hot SF6 gas. It is found that the hot C3F8 gas has much poorer dielectric performance than hot SF6 because the ( E / N)cr of C3F8 decreases significantly above room temperature.

  7. Glycerate kinase from leaves of C3 plants.

    PubMed

    Schmitt, M R; Edwards, G E

    1983-07-01

    D-Glycerate-3-kinase (EC 2.7.1.31) in six C3 species, including dicots (Pisum sativum, Spinacea oleracea, Antirrhinum majus) and monocots (Secale cereale, Hordeum vulgare, Avena sativa), ranged in activity from 44 to 353 mumol X mg chl-1 X h-1. Studies with protoplast extracts of these species indicate that the enzyme is localized in the chloroplasts. Glycerate kinase was partially purified from Secale (rye, 288-fold) and Pisum (pea, 252-fold) chloroplasts by DEAE-cellulose chromatography, sucrose gradient centrifugation, and chromatofocusing. The enzymes from both species showed similar physical (Mr = 41,000, pI = 4.6-4.7) and kinetic (Km ATP = 655 to 692 microM, Km D-glycerate = 180-188 microM) properties. Activity of the enzyme was essentially insensitive to variations in assay pH from 6.4 to 9.0 and to energy charge variations from 0.4 to 1.0. Rye glycerate kinase was able to utilize UTP and GTP but less effectively than ATP. Neither ADP nor pyrophosphate served as an energy source. Mn2+, Co2+, Ca2+, and Sr2+ could function as metal cofactors, although to a lesser extent than Mg2+. Millimolar levels of sulfate were found to significantly inhibit the enzyme while similar concentrations of other anions (Cl-, NO-3, NO-2, and acetate) had little or no effect.

  8. Lifetimes of the ˜{A} States of C_3

    NASA Astrophysics Data System (ADS)

    Wang, Yi-Jen; Chen, Chiao-Wei; Zhou, Liuzhu; Merer, Anthony J.; Hsu, Yen-Chu

    2013-06-01

    Fluorescence lifetimes have been measured for 66 Π_u and 16 Σ^+_u vibronic levels of the ˜{A}^1Π_u state of C_3 under nearly collision-free conditions. The vibrational levels studied were v_1=0-5, v_2=0-22, and v_3=0-4, covering the energy range up to 6000 cm^{-1}, and for most of them only the R(0) line was investigated. The measurements are estimated to be accurate to better than ±3 ns. General features of the lifetimes are as follows: Pure bending levels with Π_u-symmetry have shorter lifetimes (as short as 190 ns). With increasing excitation of the stretching vibrations, the lifetimes increase. Bending excitation generally reduces the lifetimes, though exceptions occur for v_1=1. Levels with v_1+v_3 ≥ 3 or with vibrational energy greater than 4000 cm^{-1} have lifetimes longer than 300 ns; some of these levels even have a long-lived component with a lifetime of up to several microseconds. This implies that the predicted dark states, (˜{B}^1Σ_u^- and ˜{B}' ^1Δ_u), lie at least 4000 cm^{-1} above the 0 0 0 level of the ˜{A} state. It is interesting to note that most of the Σ_u^+-symmetry levels lying above 4000 cm^{-1} also have lifetimes longer than 300 ns.

  9. C3: A Collaborative Web Framework for NASA Earth Exchange

    NASA Astrophysics Data System (ADS)

    Foughty, E.; Fattarsi, C.; Hardoyo, C.; Kluck, D.; Wang, L.; Matthews, B.; Das, K.; Srivastava, A.; Votava, P.; Nemani, R. R.

    2010-12-01

    The NASA Earth Exchange (NEX) is a new collaboration platform for the Earth science community that provides a mechanism for scientific collaboration and knowledge sharing. NEX combines NASA advanced supercomputing resources, Earth system modeling, workflow management, NASA remote sensing data archives, and a collaborative communication platform to deliver a complete work environment in which users can explore and analyze large datasets, run modeling codes, collaborate on new or existing projects, and quickly share results among the Earth science communities. NEX is designed primarily for use by the NASA Earth science community to address scientific grand challenges. The NEX web portal component provides an on-line collaborative environment for sharing of Eearth science models, data, analysis tools and scientific results by researchers. In addition, the NEX portal also serves as a knowledge network that allows researchers to connect and collaborate based on the research they are involved in, specific geographic area of interest, field of study, etc. Features of the NEX web portal include: Member profiles, resource sharing (data sets, algorithms, models, publications), communication tools (commenting, messaging, social tagging), project tools (wikis, blogs) and more. The NEX web portal is built on the proven technologies and policies of DASHlink.arc.nasa.gov, (one of NASA's first science social media websites). The core component of the web portal is a C3 framework, which was built using Django and which is being deployed as a common framework for a number of collaborative sites throughout NASA.

  10. Toll-Like Receptor 4-Defective C3H/HeJ Mice Are Not More Susceptible than Other C3H Substrains to Infection with Mycobacterium tuberculosis

    PubMed Central

    Kamath, Arati B.; Alt, Jennifer; Debbabi, Hajer; Behar, Samuel M.

    2003-01-01

    Mycobacterium tuberculosis produces a variety of molecules capable of activating Toll-like receptors, a family of pattern recognition receptors expressed by macrophages and a variety of other cells. To determine whether Toll-like receptor 4 (TLR4) was critical in resistance to M. tuberculosis infection, we compared the morbidity and mortality of TLR4-defective C3H/HeJ mice to those of TLR4-sufficient C3H mouse substrains. TLR4-defective C3H/HeJ mice and TLR4-sufficient C3H/HeSnJ, C3HeB/FeJ, and C3H/HeOuJ mice were infected by the aerosol route with M. tuberculosis. TLR4-defective C3H/HeJ mice had levels of cytokines in their bronchoalveolar lavage fluids and in vitro mycobacterial antigen-specific recall responses similar to those of other C3H mouse substrains. In addition, bacterial replication and long-term survival of mice following infection appeared to be independent of TLR4. Interestingly, C3HeB/FeJ mice were significantly more susceptible to M. tuberculosis infection, indicating that genetic heterogeneity among inbred C3H mouse substrains modifies resistance to infection. Therefore, cautious interpretation is required when the C3H/HeJ strain is used as a model of a TLR4-defective mouse strain, as there are significant allelic differences between C3H/HeJ and other C3H mouse substrains in response to M. tuberculosis infection. With this caveat, our data indicate that TLR4 may not be required for optimal immunity of mice to M. tuberculosis. PMID:12819102

  11. Molecular Basis for Complement Recognition and Inhibition Determined by Crystallographic Studies of the Staphylococcal Complement Inhibitor (SCIN) Bound to C3c and C3b

    SciTech Connect

    Garcia, Brandon L.; Ramyar, Kasra X.; Tzekou, Apostolia; Ricklin, Daniel; McWhorter, William J.; Lambris, John D.; Geisbrecht, Brian V.

    2010-10-22

    The human complement system plays an essential role in innate and adaptive immunity by marking and eliminating microbial intruders. Activation of complement on foreign surfaces results in proteolytic cleavage of complement component 3 (C3) into the potent opsonin C3b, which triggers a variety of immune responses and participates in a self-amplification loop mediated by a multi-protein assembly known as the C3 convertase. The human pathogen Staphylococcus aureus has evolved a sophisticated and potent complement evasion strategy, which is predicated upon an arsenal of potent inhibitory proteins. One of these, the staphylococcal complement inhibitor (SCIN), acts at the level of the C3 convertase (C3bBb) and impairs downstream complement function by trapping the convertase in a stable but inactive state. Previously, we have shown that SCIN binds C3b directly and competitively inhibits binding of human factor H and, to a lesser degree, that of factor B to C3b. Here, we report the co-crystal structures of SCIN bound to C3b and C3c at 7.5 and 3.5 {angstrom} limiting resolution, respectively, and show that SCIN binds a critical functional area on C3b. Most significantly, the SCIN binding site sterically occludes the binding sites of both factor H and factor B. Our results give insight into SCIN binding to activated derivatives of C3, explain how SCIN can recognize C3b in the absence of other complement components, and provide a structural basis for the competitive C3b-binding properties of SCIN. In the future, this may suggest templates for the design of novel complement inhibitors based upon the SCIN structure.

  12. Climate Change Communicators: The C3E3 Project

    NASA Astrophysics Data System (ADS)

    Sharif, H. O.; Joseph, J.

    2013-12-01

    The University of Texas at San Antonio (UTSA), San Antonio College (SAC), and the University of North Dakota (UND) have partnered with NASA to provide underrepresented undergraduates from UTSA, SAC, and other community colleges climate-related research and education experiences through the Climate Change Communication: Engineer, Environmental science, and Education (C3E3) project. The program aims to develop a robust response to climate change by providing K-16 climate change education; enhance the effectiveness of K-16 education particularly in engineering and other STEM disciplines by use of new instructional technologies; increase the enrollment in engineering programs and the number of engineering degrees awarded by showing engineering's usefulness in relation to the much-discussed contemporary issue of climate change; increase persistence in STEM degrees by providing student research opportunities; and increase the ethnic diversity of those receiving engineering degrees and help ensure an ethnically diverse response to climate change. Students participated in the second summer internship funded by the project. More than 60 students participated in guided research experiences aligned with NASA Science Plan objectives for climate and Earth system science and the educational objectives of the three institutions. The students went through training in modern media technology (webcasts), and in using this technology to communicate the information on climate change to others, especially high school students, culminating in production of webcasts on investigating the aspects of climate change using NASA data. Content developed is leveraged by NASA Earth observation data and NASA Earth system models and tools. Several departments are involved in the educational program.

  13. Disaster Prevention Coastal Map Production by MMS & C3D

    NASA Astrophysics Data System (ADS)

    Hatake, Shuhei; Kohori, Yuki; Watanabe, Yasushi

    2016-06-01

    In March 2011, Eastern Japan suffered serious damage of Tsunami caused by a massive earthquake. In 2012, Ministry of Land, Infrastructure and Transport published "Guideline of setting assumed areas of inundation by Tsunami" to establish the conditions of topography data used for simulation of Tsunami. In this guideline, the elevation data prepared by Geographical Survey Institute of Japan and 2m/5m/10m mesh data of NSDI are adopted for land area, while 500m mesh data of Hydrographic and Oceanographic Department of Japan Coast Guard and sea charts are adopted for water area. These data, however, do not have continuity between land area and water area. Therefore, in order to study the possibility of providing information for coastal disaster prevention, we have developed an efficient method to acquire continuous topography over land and water including tidal zone. Land area data are collected by Mobile Mapping System (MMS) and water area depth data are collected by interferometry echo sounder (C3D), and both data are simultaneously acquired on a same boat. Elaborate point cloud data of 1m or smaller are expected to be used for realistic simulation of Tsunami waves going upstream around shoreline. Tests were made in Tokyo Bay (in 2014) and Osaka Bay (in 2015). The purpose the test in Osaka Bay is to make coastal map for disaster prevention as a countermeasure for predicted Nankai massive earthquake. In addition to Tsunami simulation, the continuous data covering land and marine areas are expected to be used effectively for maintenance and repair of aged port and river facilities, maintenance and investigation of dykes, and ecosystem preservation.

  14. Comparative study of global warming effects during silicon nitride etching using C3F6O/O2 and C3F6/O2 gas mixtures

    NASA Astrophysics Data System (ADS)

    Kim, Ka Youn; Moon, Hock Key; Lee, Nae-Eung; Hong, Bo Han; Oh, Soo Ho

    2015-01-01

    C3F6 and C3F6 gases were investigated as replacement gases for SF6 used in display industry due to their low global warming potential and short lifetime. In the C3F6/O2 and C3F6/O2 capacitively coupled plasmas, Si3N4 etch conditions were varied by controlling process parameters. The global warming effects were quantified as million metric ton carbon equivalents (MMTCEs) obtained from the volumetric emission of by-product and etch gases. A lower MMTCE value and higher etch rate process with combination of high and low source frequencies, f HF (27.12 MHz)/ f LF (2 MHz), were observed for the C3F6/O2 chemistry than for the C3F6/O2 chemistry.

  15. Highly Unsaturated Platinum and Palladium Carbenes PtC_3 and PdC_3 Isolated and Characterized in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Bittner, Dror M.; Zaleski, Daniel P.; Tew, David Peter; Walker, Nick; Legon, Anthony

    2016-06-01

    Carbenes of platinum and palladium, PtC_3 and PdC_3, were generated in the gas phase through laser vaporization of a metal target in the presence of a low concentration of a hydrocarbon precursor undergoing supersonic expansion. Rotational spectroscopy and ab initio calculations confirm that both molecules are linear. The geometry of PtC_3 was accurately determined by fitting to the experimental moments of inertia of twenty-six isotopologues.

  16. Homozygous human C3 deficiency. The role of C3 in antibody production, C-1s-induced vasopermeability, and cobra venom-induced passive hemolysis.

    PubMed Central

    Alper, C A; Colten, H R; Gear, J S; Rabson, A R; Rosen, F S

    1976-01-01

    Studies of the family of a patient with marked deficiency of the third component of complement (C3) demonstrated that the patient was homozygous for a blank allele at the C3 locus, C3-. Metabolic studies with purified radiolabeled C3 in the patient revealed a mildly elevated fractional catabolic rate and a markedly reduced synthesis rate, consistent with a lack of C3 synthesis as the patient's primary defect. There was also a mild increase in the rate of conversion of purified C3 added to her serum and incubated at 37 degrees C in vitro. Major blood group-compatible erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria had the same shortened survival in the C3-deficient patient as in a normal control. Although no leukocytosis developed in the patient in spontaneous infection by pyogenic organisms, there was a normal leukocytosis in response to the injection of thyphoid vaccine. The intradermal injection of C-1s, which produces a marked increase in vasopermeability in the skin of normal subjects, produced no definite change in the patient, possibly implicating C3 or a protein in the alternative pathway as the normal mediator of this response. The patient's serum exhibited near-normal immune adherence activity, confirming the lack of requirement of C3 for this function. C5 inactivation and passive hemolysis of unsensitized guinea pig erythrocytes occurred normally in C3-deficient serum on incubation with cobra venom factor, indicating that C3 is not required for these reactions. The patient's humoral antibody response to both protein and carbohydrate antigens was entirely normal, making it unlikely that C3 is required for antigen processing. Images PMID:1107355

  17. Technology For Command, Control, Communications And Intelligence (C3I)

    NASA Astrophysics Data System (ADS)

    Burgess, John S.

    1980-02-01

    I am happy to be here this morning with this distinguished technical audience of the Society of Photo-Optical Instrumentation Engineers. You have recognized a very important problem area and I think that through this conference or seminar, you will address many technical aspects of the problems associated with Command, Control, Communications and Intelligence (C³I). C³I is a term that is gaining more and more visibility and acceptance in all areas of military operations. In the past, the transfer of technology into military operations has been concentrated on force effectiveness. Our leaders now recognize more fully that force effectiveness depends to a very high degree on the command and control functions which in turn need to know the status of enemy as well as friendly forces. Perhaps the best way to start this discussion of C³I is to arrive at a definition. Unfortunately, I'm sure that if I ask each of you to give me a definition of C³I, I would have just as many definitions as there are people in the audience. The situation is similar to the old story about the three blind men trying to describe an elephant. I would like to paraphrase a few remarks of Julian Lake in a recent editorial in Military Electronics/Countermeasures Magazine. As he points out, C3 is many things to many people. To the intelligence specialist who is so wrapped up in his intelligence community activity, C³I is simply an extension of the modern applications of intelligence. In fact, the intelligence officer feels that he is the actual center of the C³I structure. On the other hand, the communications specialist thinks that communications is the actual heartbeat of C³I activity, and this is right to a point because communications is a fundamental building block of the C3 function. The computer specialist will point out that C³I is merely a product of the computer age. One reason there was very little done about C³I in the past was the nonavailability of computer techniques and

  18. A Scanning Transmission X-ray Microscopy Study of Cubic and Orthorhombic C3A and Their Hydration Products in the Presence of Gypsum

    PubMed Central

    Rheinheimer, Vanessa; Chae, Sejung Rosie; Rodríguez, Erich D.; Geng, Guoqing; Kirchheim, Ana Paula; Monteiro, Paulo J. M.

    2016-01-01

    This paper shows the microstructural differences and phase characterization of pure phases and hydrated products of the cubic and orthorhombic (Na-doped) polymorphs of tricalcium aluminate (C3A), which are commonly found in traditional Portland cements. Pure, anhydrous samples were characterized using scanning transmission X-ray microscopy (STXM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) and demonstrated differences in the chemical and mineralogical composition as well as the morphology on a micro/nano-scale. C3A/gypsum blends with mass ratios of 0.2 and 1.9 were hydrated using a water/C3A ratio of 1.2, and the products obtained after three days were assessed using STXM. The hydration process and subsequent formation of calcium sulfate in the C3A/gypsum systems were identified through the changes in the LIII edge fine structure for Calcium. The results also show greater Ca LII binding energies between hydrated samples with different gypsum contents. Conversely, the hydrated samples from the cubic and orthorhombic C3A at the same amount of gypsum exhibited strong morphological differences but similar chemical environments. PMID:28773865

  19. Activation of C3a receptor is required in cigarette smoke-mediated emphysema.

    PubMed

    Yuan, X; Shan, M; You, R; Frazier, M V; Hong, M J; Wetsel, R A; Drouin, S; Seryshev, A; Song, L-Z; Cornwell, L; Rossen, R D; Corry, D B; Kheradmand, F

    2015-07-01

    Exposure to cigarette smoke can initiate sterile inflammatory responses in the lung and activate myeloid dendritic cells (mDCs) that induce differentiation of T helper type 1 (Th1) and Th17 cells in the emphysematous lungs. Consumption of complement proteins increases in acute inflammation, but the contribution of complement protein 3 (C3) to chronic cigarette smoke-induced immune responses in the lung is not clear. Here, we show that following chronic exposure to cigarette smoke, C3-deficient (C3(-/-)) mice develop less emphysema and have fewer CD11b(+)CD11c(+) mDCs infiltrating the lungs as compared with wild-type mice. Proteolytic cleavage of C3 by neutrophil elastase releases C3a, which in turn increases the expression of its receptor (C3aR) on lung mDCs. Mice deficient in the C3aR (C3ar(-/-)) partially phenocopy the attenuated responses to chronic smoke observed in C3(-/-) mice. Consistent with a role for C3 in emphysema, C3 and its active fragments are deposited on the lung tissue of smokers with emphysema, and smoke-exposed mice. Together, these findings suggest a critical role for C3a through autocrine/paracrine induction of C3aR in the pathogenesis of cigarette smoke-induced sterile inflammation and provide new therapeutic targets for the treatment of emphysema.

  20. Activation of C3a receptor is required in cigarette smoke-mediated emphysema

    PubMed Central

    Yuan, Xiaoyi; Shan, Ming; You, Ran; Frazier, Michael V.; Hong, Monica Jeongsoo; Wetsel, Rick A.; Drouin, Scott; Seryshev, Alexander; MD, Li-zhen Song; Cornwell, Lorraine; Rossen, Roger D; Corry, David B.; Kheradmand, Farrah

    2014-01-01

    Exposure to cigarette smoke can initiate sterile inflammatory responses in the lung and activate myeloid dendritic cells (mDCs) that induce differentiation of T helper type 1 (Th1) and Th17 cells in the emphysematous lungs. Consumption of complement proteins increases in acute inflammation, but the contribution of complement protein 3 (C3) to chronic cigarette smoke-induced immune responses in the lung is not clear. Here we show that following chronic exposure to cigarette smoke, C3 deficient (C3−/−) mice develop less emphysema and have fewer CD11b+CD11c+ mDCs infiltrating the lungs as compared to wild type mice. Proteolytic cleavage of C3 by neutrophil elastase releases C3a, which in turn increases expression of its receptor (C3aR) on lung mDCs. Mice deficient in the C3aR (C3ar−/−) partially phenocopy the attenuated responses to chronic smoke observed in C3−/− mice. Consistent with a role for C3 in emphysema C3 and its active fragments are deposited on the lung tissue of smokers with emphysema, and smoke exposed mice. Together, these findings suggest a critical role for C3a through autocrine/paracrine induction of C3aR in the pathogenesis of cigarette smoke induced sterile inflammation and provide new therapeutic targets for the treatment of emphysema. PMID:25465103

  1. Complement in Experimental Autoimmune Encephalomyelitis Revisited: C3 is Required for Development of Maximal Disease

    PubMed Central

    Szalai, Alexander J.; Hu, Xianzhen; Adams, Jillian E.; Barnum, Scott R.

    2007-01-01

    Complement per se has been shown to play an important role in demyelinating disease but controversy remains regarding the role of C3 in the development and progression of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. In this study we used C3-/- mice to confirm previous findings that C3 is required for full development of EAE. Furthermore, C3+/- mice (with serum C3 levels 50% that of wild type mice) developed EAE with a severity intermediate between wild type and C3-/- mice. Importantly transfer of wild type encephalitogenic T cells to C3-/- mice resulted in attenuated EAE. C3-/- mice with EAE had fewer CD4+ and CD8+ T cells in the CNS and 50% fewer of these cells produced IFN-γ compared to wild type mice. When treated with anti-CD3 antibody, CD4+ T cell from wild type and C3-/- mice had similar activation profiles as judged by IFN-γ production and CD25 and CD69 expression, indicating there is no gross or intrinsic defect in T cells from C3-/- mice. T cells from primed C3-/- mice proliferated comparably to that of control T cells on re-stimulation with MOG peptide. Our results confirm a requirement for C3 for maximal development of EAE and suggest that receptors for C3-derived activation fragments might be a viable therapeutic target for prevention and treatment demyelinating disease. PMID:17353050

  2. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in...

  3. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in...

  4. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in...

  5. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in...

  6. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in...

  7. Matrix isolation IR spectroscopic and ab initio studies of C3N- and related species

    NASA Astrophysics Data System (ADS)

    Kołos, Robert; Gronowski, Marcin; Botschwina, Peter

    2008-04-01

    Coupled cluster calculations were carried out for C3N-, CCNC -, C3N, CCNC, C3N+, and C3O. They support the experimental identification of the C3N- ion by means of matrix isolation infrared (IR) spectroscopy. The anion was generated in electric discharges through the cyanoacetylene isotopomers HC3N14, HC3N15, and H2C3N, trapped in cryogenic rare gas matrices (Ne, Ar, Kr), and detected via its two most intense IR absorption bands, assigned to the ν1 and ν2 stretching vibrations. C3N - appears to be quite a stable anion, with a vertical detachment energy predicted to be as high as 4.42eV. A large equilibrium electric dipole moment of 3.10D facilitates the investigation of C3N- by microwave spectroscopy and radio astronomy. Various structural parameters and spectroscopic properties have been calculated for all tetra-atomic species considered.

  8. One-stage posterior C2 and C3 pedicle screw fixation or combined anterior C2-C3 fusion for the treatment of unstable hangman's fracture.

    PubMed

    Liu, Jingchen; Li, Ye; Wu, Yuntao

    2013-03-01

    The present study aimed to evaluate the effect of using one-stage posterior C2 and C3 pedicle screw fixation or combined anterior C2-C3 fusion in the treatment of unstable hangman's fracture. A total of 13 patients with unstable hangman's fractures underwent C2 and C3 pedicle screw fixation, lamina interbody fusion or combined anterior C2-C3 fusion and imaging examinations to evaluate the fracture fixation and healing condition at three days and three months following surgery. Postoperative X-ray and computed tomography (CT) results showed high fracture reduction, good internal fixation position and reliable fracture fixation. The three-month postoperative CT showed good vertebral fracture healing. C2 and C3 pedicle screw fixation has a good curative effect in the treatment of unstable hangman's fracture. The direct fixation of the fracture enables early ambulation by the patients.

  9. On the origin of C3 nephritic factor (antibody to the alternative pathway C3 convertase): evidence for the Adam and Eve concept of autoantibody production.

    PubMed

    Spitzer, R E; Stitzel, A E; Tsokos, G

    1992-09-01

    The antibody to the alternative pathway C3 convertase, designated C3 nephritic factor or C3NeF, is an autoantibody that is produced in everyone from the time of birth. The elaboration of C3NeF utilizes germline V-region genes which undergo antigen-driven affinity maturation, resulting in an autoantibody that is produced in large amounts with high affinity and narrow specificity. Our data also suggest that under normal conditions, the idiotypic network may play an important part in the control of this autoantibody. Further, a defect in the network with loss of control or inappropriate stimulation may be an underlying mechanism in the unrestricted production of C3NeF in patients with membranoproliferative glomerulonephritis.

  10. Neuronal ClC-3 Splice Variants Differ in Subcellular Localizations, but Mediate Identical Transport Functions*

    PubMed Central

    Guzman, Raul E.; Miranda-Laferte, Erick; Franzen, Arne; Fahlke, Christoph

    2015-01-01

    ClC-3 is a member of the CLC family of anion channels and transporters, for which multiple functional properties and subcellular localizations have been reported. Since alternative splicing often results in proteins with diverse properties, we investigated to what extent alternative splicing might influence subcellular targeting and function of ClC-3. We identified three alternatively spliced ClC-3 isoforms, ClC-3a, ClC-3b, and ClC-3c, in mouse brain, with ClC-3c being the predominant splice variant. Whereas ClC-3a and ClC-3b are present in late endosomes/lysosomes, ClC-3c is targeted to recycling endosomes via a novel N-terminal isoleucine-proline (IP) motif. Surface membrane insertion of a fraction of ClC-3c transporters permitted electrophysiological characterization of this splice variant through whole-cell patch clamping on transfected mammalian cells. In contrast, neutralization of the N-terminal dileucine-like motifs was required for functional analysis of ClC-3a and ClC-3b. Heterologous expression of ClC-3a or ClC-3b carrying mutations in N-terminal dileucine motifs as well as WTClC-3c in HEK293T cells resulted in outwardly rectifying Cl− currents with significant capacitive current components. We conclude that alternative splicing of Clcn3 results in proteins with different subcellular localizations, but leaves the transport function of the proteins unaffected. PMID:26342074

  11. Neuronal ClC-3 Splice Variants Differ in Subcellular Localizations, but Mediate Identical Transport Functions.

    PubMed

    Guzman, Raul E; Miranda-Laferte, Erick; Franzen, Arne; Fahlke, Christoph

    2015-10-23

    ClC-3 is a member of the CLC family of anion channels and transporters, for which multiple functional properties and subcellular localizations have been reported. Since alternative splicing often results in proteins with diverse properties, we investigated to what extent alternative splicing might influence subcellular targeting and function of ClC-3. We identified three alternatively spliced ClC-3 isoforms, ClC-3a, ClC-3b, and ClC-3c, in mouse brain, with ClC-3c being the predominant splice variant. Whereas ClC-3a and ClC-3b are present in late endosomes/lysosomes, ClC-3c is targeted to recycling endosomes via a novel N-terminal isoleucine-proline (IP) motif. Surface membrane insertion of a fraction of ClC-3c transporters permitted electrophysiological characterization of this splice variant through whole-cell patch clamping on transfected mammalian cells. In contrast, neutralization of the N-terminal dileucine-like motifs was required for functional analysis of ClC-3a and ClC-3b. Heterologous expression of ClC-3a or ClC-3b carrying mutations in N-terminal dileucine motifs as well as WTClC-3c in HEK293T cells resulted in outwardly rectifying Cl(-) currents with significant capacitive current components. We conclude that alternative splicing of Clcn3 results in proteins with different subcellular localizations, but leaves the transport function of the proteins unaffected.

  12. The C3-bending vibrational levels of the C3-Kr and C3-Xe van der Waals complexes studied by their Ã-X̃ electronic transitions and by ab initio calculations.

    PubMed

    Chao, Jun-Mei; Tham, Keng Seng; Zhang, Guiqiu; Merer, Anthony J; Hsu, Yen-Chu; Hu, Wei-Ping

    2011-02-21

    Fluorescence excitation spectra and wavelength-resolved emission spectra of the C(3)-Kr and C(3)-Xe van der Waals (vdW) complexes have been recorded near the 2(2-)(0), 2(2+)(0), 2(4-)(0), and 1(1)(0) bands of the Ã(1)Π(u)-X̃(1)Σ(g)(+) system of the C(3) molecule. In the excitation spectra, the spectral features of the two complexes are red-shifted relative to those of free C(3) by 21.9-38.2 and 34.3-36.1 cm(-1), respectively. The emission spectra from the à state of the Kr complex consist of progressions in the two C(3)-bending vibrations (ν(2), ν(4)), the vdW stretching (ν(3)), and bending vibrations (ν(6)), suggesting that the equilibrium geometry in the X̃ state is nonlinear. As in the Ar complex [Zhang et al., J. Chem. Phys. 120, 3189 (2004)], the C(3)-bending vibrational levels of the Kr complex shift progressively to lower energy with respect to those of free C(3) as the bending quantum number increases. Their vibrational structures could be modeled as perturbed harmonic oscillators, with the dipole-induced dipole terms of the Ar and Kr complexes scaled roughly by the polarizabilities of the Ar and Kr atoms. Emission spectra of the Xe complex, excited near the Ã, 2(2-) level of free C(3), consist only of progressions in even quanta of the C(3)-bending and vdW modes, implying that the geometry in the higher vibrational levels (υ(bend) ≥ 4, E(vib) ≥ 328 cm(-1)) of the X̃ state is (vibrationally averaged) linear. In this structure the Xe atom bonds to one of the terminal carbons nearly along the inertial a-axis of bent C(3). Our ab initio calculations of the Xe complex at the level of CCSD(T)∕aug-cc-pVTZ (C) and aug-cc-pVTZ-PP (Xe) predict that its equilibrium geometry is T-shaped (as in the Ar and Kr complexes), and also support the assignment of a stable linear isomer when the amplitude of the C(3) bending vibration is large (υ(4) ≥ 4).

  13. 18 CFR 3c.3 - Reporting fraud, waste, abuse, and corruption and cooperation with official inquiries.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., abuse, and corruption and cooperation with official inquiries. 3c.3 Section 3c.3 Conservation of Power... OF CONDUCT § 3c.3 Reporting fraud, waste, abuse, and corruption and cooperation with official..., abuse, and corruption in Commission programs, including on the part of Commission employees, contractors...

  14. 18 CFR 3c.3 - Reporting fraud, waste, abuse, and corruption and cooperation with official inquiries.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., abuse, and corruption and cooperation with official inquiries. 3c.3 Section 3c.3 Conservation of Power... OF CONDUCT § 3c.3 Reporting fraud, waste, abuse, and corruption and cooperation with official..., abuse, and corruption in Commission programs, including on the part of Commission employees, contractors...

  15. 18 CFR 3c.3 - Reporting fraud, waste, abuse, and corruption and cooperation with official inquiries.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., abuse, and corruption and cooperation with official inquiries. 3c.3 Section 3c.3 Conservation of Power... OF CONDUCT § 3c.3 Reporting fraud, waste, abuse, and corruption and cooperation with official..., abuse, and corruption in Commission programs, including on the part of Commission employees, contractors...

  16. 18 CFR 3c.3 - Reporting fraud, waste, abuse, and corruption and cooperation with official inquiries.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., abuse, and corruption and cooperation with official inquiries. 3c.3 Section 3c.3 Conservation of Power... OF CONDUCT § 3c.3 Reporting fraud, waste, abuse, and corruption and cooperation with official..., abuse, and corruption in Commission programs, including on the part of Commission employees,...

  17. The C3 Framework: One Year Later - an Interview with Kathy Swan

    ERIC Educational Resources Information Center

    Social Education, 2014

    2014-01-01

    On September 17, 2013 (Constitution Day), the C3 Framework was released under the title "The College, Career and Civic Life (C3) Framework for Social Studies State Standards: Guidance for Enhancing the Rigor of K-12 Civics, Economics, Geography, and History." The C3 Project Director and lead writer was NCSS member Kathy Swan, who is…

  18. Characterization of the third component of complement (C3) after activation by cigarette smoke

    SciTech Connect

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

    1987-08-01

    Activation of lung complement by tobacco smoke may be an important pathogenetic factor in the development of pulmonary emphysema in smokers. We previously showed that cigarette smoke can modify C3 and activate the alternative pathway of complement in vitro. However, the mechanism of C3 activation was not fully delineated in these earlier studies. In the present report, we show that smoke-treated C3 induces cleavage of the alternative pathway protein, Factor B, when added to serum containing Mg-EGTA. This effect of cigarette smoke is specific for C3 since smoke-treated C4, when added to Mg-EGTA-treated serum, fails to activate the alternative pathway and fails to induce Factor B cleavage. Smoke-modified C3 no longer binds significant amounts of (/sup 14/C)methylamine (as does native C3), and relatively little (/sup 14/C)methylamine is incorporated into its alpha-chain. Thus, prior internal thiolester bond cleavage appears to have occurred in C3 activated by cigarette smoke. Cigarette smoke components also induce formation of noncovalently associated, soluble C3 multimers, with a Mr ranging from 1 to 10 million. However, prior cleavage of the thiolester bond in C3 with methylamine prevents the subsequent formation of these smoke-induced aggregates. These data indicate that cigarette smoke activates the alternative pathway of complement by specifically modifying C3 and that these modifications include cleavage of the thiolester bond in C3 and formation of noncovalently linked C3 multimers.

  19. Detection of complement activation using monoclonal antibodies against C3d.

    PubMed

    Thurman, Joshua M; Kulik, Liudmila; Orth, Heather; Wong, Maria; Renner, Brandon; Sargsyan, Siranush A; Mitchell, Lynne M; Hourcade, Dennis E; Hannan, Jonathan P; Kovacs, James M; Coughlin, Beth; Woodell, Alex S; Pickering, Matthew C; Rohrer, Bärbel; Holers, V Michael

    2013-05-01

    During complement activation the C3 protein is cleaved, and C3 activation fragments are covalently fixed to tissues. Tissue-bound C3 fragments are a durable biomarker of tissue inflammation, and these fragments have been exploited as addressable binding ligands for targeted therapeutics and diagnostic agents. We have generated cross-reactive murine monoclonal antibodies against human and mouse C3d, the final C3 degradation fragment generated during complement activation. We developed 3 monoclonal antibodies (3d8b, 3d9a, and 3d29) that preferentially bind to the iC3b, C3dg, and C3d fragments in solution, but do not bind to intact C3 or C3b. The same 3 clones also bind to tissue-bound C3 activation fragments when injected systemically. Using mouse models of renal and ocular disease, we confirmed that, following systemic injection, the antibodies accumulated at sites of C3 fragment deposition within the glomerulus, the renal tubulointerstitium, and the posterior pole of the eye. To detect antibodies bound within the eye, we used optical imaging and observed accumulation of the antibodies within retinal lesions in a model of choroidal neovascularization (CNV). Our results demonstrate that imaging methods that use these antibodies may provide a sensitive means of detecting and monitoring complement activation-associated tissue inflammation.

  20. Detection of complement activation using monoclonal antibodies against C3d

    PubMed Central

    Thurman, Joshua M.; Kulik, Liudmila; Orth, Heather; Wong, Maria; Renner, Brandon; Sargsyan, Siranush A.; Mitchell, Lynne M.; Hourcade, Dennis E.; Hannan, Jonathan P.; Kovacs, James M.; Coughlin, Beth; Woodell, Alex S.; Pickering, Matthew C.; Rohrer, Bärbel; Holers, V. Michael

    2013-01-01

    During complement activation the C3 protein is cleaved, and C3 activation fragments are covalently fixed to tissues. Tissue-bound C3 fragments are a durable biomarker of tissue inflammation, and these fragments have been exploited as addressable binding ligands for targeted therapeutics and diagnostic agents. We have generated cross-reactive murine monoclonal antibodies against human and mouse C3d, the final C3 degradation fragment generated during complement activation. We developed 3 monoclonal antibodies (3d8b, 3d9a, and 3d29) that preferentially bind to the iC3b, C3dg, and C3d fragments in solution, but do not bind to intact C3 or C3b. The same 3 clones also bind to tissue-bound C3 activation fragments when injected systemically. Using mouse models of renal and ocular disease, we confirmed that, following systemic injection, the antibodies accumulated at sites of C3 fragment deposition within the glomerulus, the renal tubulointerstitium, and the posterior pole of the eye. To detect antibodies bound within the eye, we used optical imaging and observed accumulation of the antibodies within retinal lesions in a model of choroidal neovascularization (CNV). Our results demonstrate that imaging methods that use these antibodies may provide a sensitive means of detecting and monitoring complement activation–associated tissue inflammation. PMID:23619360

  1. 26 CFR 1.662(c)-3 - Termination of existence of other beneficiaries.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Termination of existence of other beneficiaries. 1.662(c)-3 Section 1.662(c)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Distribute Corpus § 1.662(c)-3 Termination of existence of other beneficiaries. If the existence of a...

  2. 26 CFR 1.662(c)-3 - Termination of existence of other beneficiaries.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Termination of existence of other beneficiaries. 1.662(c)-3 Section 1.662(c)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Which Distribute Corpus § 1.662(c)-3 Termination of existence of other beneficiaries. If the existence...

  3. 26 CFR 1.652(c)-3 - Termination of existence of other beneficiaries.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Termination of existence of other beneficiaries. 1.652(c)-3 Section 1.652(c)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....652(c)-3 Termination of existence of other beneficiaries. If the existence of a beneficiary which is...

  4. 26 CFR 1.662(c)-3 - Termination of existence of other beneficiaries.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Termination of existence of other beneficiaries. 1.662(c)-3 Section 1.662(c)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Which Distribute Corpus § 1.662(c)-3 Termination of existence of other beneficiaries. If the existence...

  5. 26 CFR 1.652(c)-3 - Termination of existence of other beneficiaries.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Termination of existence of other beneficiaries. 1.652(c)-3 Section 1.652(c)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....652(c)-3 Termination of existence of other beneficiaries. If the existence of a beneficiary which is...

  6. 26 CFR 1.652(c)-3 - Termination of existence of other beneficiaries.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Termination of existence of other beneficiaries. 1.652(c)-3 Section 1.652(c)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....652(c)-3 Termination of existence of other beneficiaries. If the existence of a beneficiary which is...

  7. 26 CFR 1.662(c)-3 - Termination of existence of other beneficiaries.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Termination of existence of other beneficiaries. 1.662(c)-3 Section 1.662(c)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Which Distribute Corpus § 1.662(c)-3 Termination of existence of other beneficiaries. If the existence...

  8. 26 CFR 1.662(c)-3 - Termination of existence of other beneficiaries.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Termination of existence of other beneficiaries. 1.662(c)-3 Section 1.662(c)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Which Distribute Corpus § 1.662(c)-3 Termination of existence of other beneficiaries. If the existence...

  9. 26 CFR 1.652(c)-3 - Termination of existence of other beneficiaries.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Termination of existence of other beneficiaries. 1.652(c)-3 Section 1.652(c)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY....652(c)-3 Termination of existence of other beneficiaries. If the existence of a beneficiary which is...

  10. The C3 Framework: One Year Later - an Interview with Kathy Swan

    ERIC Educational Resources Information Center

    Social Education, 2014

    2014-01-01

    On September 17, 2013 (Constitution Day), the C3 Framework was released under the title "The College, Career and Civic Life (C3) Framework for Social Studies State Standards: Guidance for Enhancing the Rigor of K-12 Civics, Economics, Geography, and History." The C3 Project Director and lead writer was NCSS member Kathy Swan, who is…

  11. 17 CFR 270.6c-3 - Exemptions for certain registered variable life insurance separate accounts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemptions for certain registered variable life insurance separate accounts. 270.6c-3 Section 270.6c-3 Commodity and Securities... 1940 § 270.6c-3 Exemptions for certain registered variable life insurance separate accounts. A separate...

  12. 17 CFR 270.6c-3 - Exemptions for certain registered variable life insurance separate accounts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Exemptions for certain registered variable life insurance separate accounts. 270.6c-3 Section 270.6c-3 Commodity and Securities... 1940 § 270.6c-3 Exemptions for certain registered variable life insurance separate accounts. A separate...

  13. 17 CFR 270.6c-3 - Exemptions for certain registered variable life insurance separate accounts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Exemptions for certain registered variable life insurance separate accounts. 270.6c-3 Section 270.6c-3 Commodity and Securities... 1940 § 270.6c-3 Exemptions for certain registered variable life insurance separate accounts. A separate...

  14. 17 CFR 270.6c-3 - Exemptions for certain registered variable life insurance separate accounts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Exemptions for certain registered variable life insurance separate accounts. 270.6c-3 Section 270.6c-3 Commodity and Securities... 1940 § 270.6c-3 Exemptions for certain registered variable life insurance separate accounts. A separate...

  15. 17 CFR 270.6c-3 - Exemptions for certain registered variable life insurance separate accounts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Exemptions for certain registered variable life insurance separate accounts. 270.6c-3 Section 270.6c-3 Commodity and Securities... 1940 § 270.6c-3 Exemptions for certain registered variable life insurance separate accounts. A separate...

  16. Polymorphous computing fabric

    DOEpatents

    Wolinski, Christophe Czeslaw [Los Alamos, NM; Gokhale, Maya B [Los Alamos, NM; McCabe, Kevin Peter [Los Alamos, NM

    2011-01-18

    Fabric-based computing systems and methods are disclosed. A fabric-based computing system can include a polymorphous computing fabric that can be customized on a per application basis and a host processor in communication with said polymorphous computing fabric. The polymorphous computing fabric includes a cellular architecture that can be highly parameterized to enable a customized synthesis of fabric instances for a variety of enhanced application performances thereof. A global memory concept can also be included that provides the host processor random access to all variables and instructions associated with the polymorphous computing fabric.

  17. a Study of the c-C_{3HD}/c-C_{3H_{2}} Ratio in Low-Mass Star Forming Regions.

    NASA Astrophysics Data System (ADS)

    Chantzos, Johanna; Spezzano, Silvia; Caselli, Paola; Chacon-Tanarro, Ana

    2017-06-01

    Deuterium fractionation increases significantly in cold (T<25 K), dense (n_{H}>10^4 cm^{-3}) molecular clouds, in which molecules like CO freeze out onto dust grains leading to an enhanced abundance of {H_{2D^{+}}}, {D_{2H^{+}}} and {D_{3^{+}}}. c-C_{3H_{2}} is formed and deuterated exclusively by gas-phase chemistry. This makes it to a very good indicator of gas-phase deuteration and therefore to an excellent tool to study the early phases of star formation. We observed the c-C_{3HD}/c-C_{3H_{2}} ratio toward 13 prestellar and 4 protostellar cores in the Taurus and Perseus Complex, respectively. In particular, the 3_{0,3}-2_{1,2} and 2_{1,2}-1_{0,1} transitions of the isotopologues c-C_{3HD} and c-{^{13CC_{2}H_{2}}} were observed in all prestellar and protostellar cores with a very high S/N. In both samples a high deuteration factor was found. In the prestellar cores the c-C_{3HD}/c-C_{3H_{2}} ratio varies between 5% and 13% while in protostellar cores is found to be 9%-23%. I will present our results on the correlation between the deuterium fractionation of c-C_{3H_{2}} and evolutionary indicators such as central density and dust temperature and compare them with the deuteration of N_{2H^{+}} observed in the same sources.

  18. Origins of enigmatic C-3 methyl and C-3 H porphyrins in ancient sediments revealed from formation of pyrophaeophorbide d in simulation experiments

    NASA Astrophysics Data System (ADS)

    Pickering, Matthew D.; Keely, Brendan J.

    2013-03-01

    The reaction of methyl pyrophaeophorbide a with hydrogen sulfide and oxygen under mild conditions (low temperature, moderate pH), which resemble those in certain natural environments, leads to its near quantitative conversion into methyl pyrophaeophorbide d (82-89%). The transformation, via oxidative cleavage of the C-3 vinyl substituent of pyrophaeophorbide a to afford an aldehyde at C-3, results from co-oxidation of the vinyl group and hydrogen sulfide by molecular oxygen. The co-oxidation transformation pathway operating on vinyl substituted chlorophyll derivatives can explain the origins of C-3 methyl and C-3 H porphyrins in ancient sediments and oils, structures for which the origins were previously unresolved. Evaluation of previous reports of C-3 methyl and C-3 H porphyrins in ancient sediments and oils reveals that their distributions are consistent with insights provided from analysis of the reaction mechanisms revealed by the laboratory studies. Thus, the sedimentary distributions reveal key features of the depositional settings, in particular the presence of a deep or a shallow chemocline. The oxidative cleavage of the C-3 vinyl group also provides insight into the biosynthesis of chlorophyll d by the cyanobacterium Acaryochloris marina, and offers a mild alternative to classical methods for the synthetic manipulation of the vinyl substituents of tetrapyrroles.

  19. Dehydrogenation and C-H Bond Insertion of Propene: La(η^2-C_3H_4) and HLa(η^3-C_3H_5)

    NASA Astrophysics Data System (ADS)

    Kumari, Sudesh; Yang, Dong-Sheng

    2011-06-01

    Dehydrogenation and C-H bond insertion are observed in the reaction of laser-ablated La atoms with propene (C_3H_6) in a pulsed molecular beam source. Several dehydrogenated and inserted products are identified by the time-of-flight mass spectrometry. La(C_3H_4) formed from H_2 elimination and HLa(C_3H_5) formed by C-H bond insertion are characterized by pulsed-field-ionization electron and ion spectroscopy, in combination with density functional theory. Two isomers of La(C_3H_4) are identified from 1,2- and 1,3-dehydrogenation. The adiabatic ionization energies of 1,2- and 1,3-dehydrogenated isomers are measured to be 40506(5) and 40941(5) Cm-1, respectively. For the inserted product HLa(C_3H_5), La atom is bound to the allyl radical in a three-fold binding mode (η^3). It is observed that the ionization energy of the HLa(η^3-C_3H_5) insertion complex (41130(5) Cm-1) is close to that of the 1,3-dehydrogented La(η^2-C_3H_4) species.

  20. DiO-C3-(5) and DiS-C3-(5): Interactions with RBC, ghosts and phospholipid vesicles.

    PubMed

    Guillet, E G; Kimmich, G A

    1981-03-15

    The experiments presented below compare the interaction of diO-C3-(5) and diS-C3-(5) with erythrocytes, erythrocyte ghosts and phospholipid vesicles derived from erythrocyte membranes. The results confirm earlier reports of diS-C3-(5) dimerization in the presence of hemoglobin and of dye aggregate formation in erythrocyte suspensions. DiO-C3-(5), on the other hand, binds to vesicles and ghosts freed of hemoglobin in a potential-dependent manner but without forming dye aggregates. The two dyes bind to the different preparations in similar proportions, but diS-C3-(5) is bound in amounts 3-40 times greater depending on the degree of polarization. The results show that mechanism other than binding to hemoglobin must occur in order to explain the potential-dependent binding of both dyes to ghosts and vesicles. A primary interaction must exist between the dye molecule and the lipid bilayer in a biological membrane, and this would be expected to occur in the presence of hemoglobin or other cytosolic components. DiO-C3-(5) is a better dye to use than diS-C3-(5) for mechanistic studies, in order to avoid problems associated with formation of complex aggregates of the latter dye, especially in hyperpolarized membrane suspensions.

  1. Complement C3 is expressed by mast cells in cutaneous vasculitis and is degraded by chymase.

    PubMed

    Lipitsä, Tiina; Naukkarinen, Anita; Laitala, Joel; Harvima, Ilkka T

    2016-10-01

    The complement factor C3 and chymase released from tryptase(+), chymase(+) mast cells may be involved in the pathogenesis of cutaneous leukocytoclastic vasculitis. To study whether mast cells contain C3 in vasculitis and whether chymase interacts with C3, cryosections from vasculitis biopsies were double-stained histochemically for C3c in tryptase(+) mast cells, as well as for chymase and vessel wall C3c, or they were treated with 5 µg/ml rh-chymase for 24 h followed by immunofluorescence (IF) analysis of C3c, IgG, IgM and IgA. The effect of rh-chymase on purified human C3, C3a and IgG was studied using SDS-PAGE electrophoresis and LAD2 mast cell cultures. The results show that 34.2 ± 17.9, 37.4 ± 15.5 and 43.4 ± 18.6 % (mean ± SD) of the mast cells express C3c immunoreactivity in the healthy skin, initial petechial (IP) and palpable purpura (PP) lesions, respectively. About 9.4-12.1 % of the chymase(+) mast cells were in apparent contact with C3c(+) vessels in IP and PP. The treatment of cryosections with rh-chymase decreased the IF staining of C3c, but not that of immunoglobulins. In SDS-PAGE, 1-10 µg/ml rh-chymase degraded the alpha- and beta-chains of C3, but did not degrade IgG. Unexpectedly, the rh-chymase treatment of C3 produced fragments that resulted in the release of tryptase and histamine from LAD2 cells. However, rh-chymase degraded C3a and consequently inhibited C3a activity on LAD2. In conclusion, mast cells can be one source for C3 in the early and late phases of vasculitis pathogenesis. However, rh-chymase degraded native C3, vessel wall C3c, and biologically active C3a. Therefore, chymase may control C3-related pathology.

  2. Characterization of a C3a receptor in rainbow trout and Xenopus: the first identification of C3a receptors in nonmammalian species

    USGS Publications Warehouse

    Boshra, Hani; Wang, Tiehui; Hove-Madsen, Leif; Hansen, John D.; Li, Jun; Matlapudi, Anjun; Secombes, Christopher J.; Tort, Lluis; Sunyer, J. Oriol

    2005-01-01

    Virtually nothing is known about the structure, function, and evolutionary origins of the C3aR in nonmammalian species. Because C3aR and C5aR are thought to have arisen from the same common ancestor, the recent characterization of a C5aR in teleost fish implied the presence of a C3aR in this animal group. In this study we report the cloning of a trout cDNA encoding a 364-aa molecule (TC3aR) that shows a high degree of sequence homology and a strong phylogenetic relationship with mammalian C3aRs. Northern blotting demonstrated that TC3aR was expressed primarily in blood leukocytes. Flow cytometric analysis and immunofluorescence microscopy showed that Abs raised against TC3aR stained to a high degree all blood B lymphocytes and, to a lesser extent, all granulocytes. More importantly, these Abs inhibited trout C3a-mediated intracellular calcium mobilization in trout leukocytes. A fascinating structural feature of TC3aR is the lack of a significant portion of the second extracellular loop (ECL2). In all C3aR molecules characterized to date, the ECL2 is exceptionally large when compared with the same region of C5aR. However, the exact function of the extra portion of ECL2 is unknown. The lack of this segment in TC3aR suggests that the extra piece of ECL2 was not necessary for the interaction of the ancestral C3aR with its ligand. Our findings represent the first C3aR characterized in nonmammalian species and support the hypothesis that if C3aR and C5aR diverged from a common ancestor, this event occurred before the emergence of teleost fish.

  3. Highly Unsaturated Platinum and Palladium Carbenes PtC3 and PdC3 Isolated and Characterized in the Gas Phase

    DOE PAGES

    Bittner, Dror M.; Zaleski, Daniel P.; Tew, David P.; ...

    2016-02-16

    Carbenes of platinum and palladium, PtC3 and PdC3 , were generated in the gas phase through laser vaporization of a metal target in the presence of a low concentration of a hydrocarbon precursor undergoing supersonic expansion. Rotational spectroscopy and abinitio calculations confirm that both molecules are linear. The geometry of PtC3 was accurately determined by fitting to the experimental moments of inertia of twenty-six isotopologues. In conclusion, the results are consistent with the proposal of an autogenic isolobal relationship between O, Au+ , and Ptatoms.

  4. C3I for Crisis, Emergency and Consequence Management (C3I pour la gestion des crises, des urgences et de leurs consequences)

    DTIC Science & Technology

    2009-05-01

    May 2009 C3I for Crisis, Emergency and Consequence Management (C3I pour la gestion des crises , des urgences et de leurs conséquences) Research and...consequence management. ES - 2 RTO-MP-IST-086 C3I pour la gestion des crises , des urgences et de leurs conséquences (RTO-MP-IST-086...contre-terrorisme, de sécurité nationale/publique et de réponse collective face aux situations d’urgence (à la fois gestion des crises et gestion de leurs

  5. Eculizumab treatment: stochastic occurrence of C3 binding to individual PNH erythrocytes.

    PubMed

    Sica, Michela; Rondelli, Tommaso; Ricci, Patrizia; De Angioletti, Maria; Risitano, Antonio M; Notaro, Rosario

    2017-06-19

    C5 blockade by eculizumab prevents complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH). However, C3-bound PNH red blood cells (RBCs), arising in almost all treated patients, may undergo extravascular hemolysis reducing clinical benefits. Despite the uniform deficiency of CD55 and of CD59, there are always two distinct populations of PNH RBCs, with (C3+) and without (C3-) C3 binding. To investigate this paradox, the phenomenon has been modeled in vitro by incubating RBCs from eculizumab untreated PNH patients with compatible sera containing eculizumab, and by assessing the C3 binding after activation of complement alternative pathway. When RBCs from untreated patients were exposed in vitro to activated complement in the context of C5-blockade, there was the prompt appearance of a distinct C3+ PNH RBC population whose size increased with time and also with the rate of complement activation. Eventually, all PNH RBCs become C3+ to the same extent, without differences between old and young (reticulocytes) PNH RBCs. This study indicates that the distinct (C3+ and C3-) PNH RBC populations are not intrinsically different; rather, they result from a stochastic all-or-nothing phenomenon linked to the time-dependent cumulative probability of each individual PNH red cell to be exposed to levels of complement activation able to trigger C3 binding. These findings may envision novel approaches to reduce C3 opsonization and the subsequent extravascular hemolysis in PNH patients on eculizumab.

  6. Complement C3 gene: Expression characterization and innate immune response in razor clam Sinonovacula constricta.

    PubMed

    Peng, Maoxiao; Niu, Donghong; Wang, Fei; Chen, Zhiyi; Li, Jiale

    2016-08-01

    Complement component 3 (C3) is central to the complement system, playing an important role in immune defense, immune regulation and immune pathology. Several C3 genes have been characterized in invertebrates but very few in shellfish. The C3 gene was identified from the razor clam Sinonovacula constricta, referred to here as Sc-C3. It was found to be highly homologous with the C3 gene of Ruditapes decussatus. All eight model motifs of the C3 gene were found to be included in the thiolester bond and the C345C region. Sc-C3 was widely expressed in all healthy tissues with expression being highest in hemolymph. A significant difference in expression was revealed at the umbo larvae development stage. The expression of Sc-C3 was highly regulated in the hemolymph and liver, with a distinct response pattern being noted after a challenge with Micrococcus lysodeikticus and Vibrio parahemolyticus. It is therefore suggested that a complicated and unique response pathway may be present in S. constricta. Further, serum of S. constricta containing Sc-C3 was extracted. This was activated by LPS or bacterium for verification for function. The more obvious immune function of Sc-C3 was described as an effective membrane rupture in hemocyte cells of rabbit, V. parahemolyticus and Vibrio anguillarum. Thus, Sc-C3 plays an essential role in the immune defense of S. constricta.

  7. Improvement of g-C3N4 photocatalytic properties using the Hummers method.

    PubMed

    Feng, Jing; Chen, Tingting; Liu, Shenna; Zhou, Qihang; Ren, Yueming; Lv, Yanzhuo; Fan, Zhuangjun

    2016-10-01

    In this study, graphitic C3N4 (g-C3N4) with high photocatalytic properties to methylene blue (MB) was synthesized by treating the bulk g-C3N4 using the Hummers method. The bulk g-C3N4 was obtained by calcining dicyandiamide. The g-C3N4 treated by the Hummers method (E-g-C3N4) was characterized and utilized for the photocatalytic removal of MB. The results showed that the Hummers treatment exfoliated the nanosheets bulk g-C3N4 into nanorods and improved the dispersion of E-g-C3N4 in an aqueous solution. It also distinctly enhanced the photocatalytic activity of g-C3N4 to MB, i.e., the removal efficiency increased from 38.45% for the bulk g-C3N4 to 96.61% for the E-g-C3N4.

  8. Metal-free melem/g-C3N4 hybrid photocatalysts for water treatment.

    PubMed

    Liu, Shizhen; Sun, Hongqi; O'Donnell, Kane; Ang, H M; Tade, Moses O; Wang, Shaobin

    2016-02-15

    In this study, graphitic carbon nitride was engineered to produce metal-free melem/g-C3N4 hybrid photocatalysts through a hydrothermal technique. It was revealed that the hydrothermal treatment of g-C3N4 could produce a hybrid structure of "thorn ball" liked melem on g-C3N4 layer at a high temperature, and was able to modify the photoelectronic properties of g-C3N4. The spectroscopic measurements implied that a melem/g-C3N4 hybrid has better light absorption and lower electron/hole recombination than pristine g-C3N4. Therefore, the melem/g-C3N4 photocatalysts can decompose methylene blue solution under artificial sunlight with a higher rate and also present good stability.

  9. Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia.

    PubMed

    Stokowska, Anna; Atkins, Alison L; Morán, Javier; Pekny, Tulen; Bulmer, Linda; Pascoe, Michaela C; Barnum, Scott R; Wetsel, Rick A; Nilsson, Jonas A; Dragunow, Mike; Pekna, Marcela

    2017-02-01

    Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. To determine the role of C3a-C3a receptor signalling in ischaemia-induced neural plasticity, we subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. We found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43 (P < 0.01), a marker of axonal sprouting and plasticity, in the peri-infarct cortex. To verify the translational potential of these findings, we used a pharmacological approach. Daily intranasal treatment of wild-type mice with C3a beginning 7 days after stroke induction robustly increased synaptic density (P < 0.01) and expression of GAP43 in peri-infarct cortex (P < 0.05). Importantly, the C3a treatment led to faster and more complete recovery of forepaw motor function (P < 0.05). We conclude that C3a-C3a receptor signalling stimulates post-ischaemic neural plasticity and intranasal treatment with C3a receptor agonists is an attractive approach to improve functional recovery after ischaemic brain injury.

  10. Viral Vector Effects on Exoenzyme C3 Transferase–Mediated Actin Disruption and on Outflow Facility

    PubMed Central

    Slauson, Sarah R.; Peters, Donna M.; Schwinn, Marie K.; Kaufman, Paul L.; Gabelt, B'Ann T.; Brandt, Curtis R.

    2015-01-01

    Purpose. Purified Clostridium botulinum exoenzyme C3 transferase (C3) effects on the actin cytoskeleton in human trabecular meshwork cells (HTM) and on the outflow facility response in monkey organ-cultured anterior segments (MOCAS) were determined in the presence or absence of viral vectors. Methods. Human adenovirus type 5 (AdV) and feline immunodeficiency virus (FIV) vectors were produced using kits. Cell soluble purified C3 (C3cs) was purchased commercially. Recombinant C3 (C3rec) cDNA was overexpressed in Escherichia coli and purified. The HTM cells were incubated with up to 10 μg/mL C3cs or with 5 μg of C3rec and/or viral vector (multiplicity of infection [MOI] = 25). Cells then were fixed and stained for actin. Outflow facility in MOCAS was measured at baseline, 4 hours, 24 hours, and 3 to 4 days following bolus injection of AdV (1.6 × 107 transducing units) and/or 2.5 μg C3rec. Results. The HTM cells treated for 4 hours with C3cs (all doses) or for 24 hours with C3rec developed a rounded morphology and lost stress fibers. Cells transduced with vectors alone showed no changes at any time point. Cells exposed to C3rec and cotransduced with either viral vector showed significant disruption of the actin cytoskeleton within 4 hours after exposure, which persisted at 24 hours. In MOCAS, the AdV vector alone had no effect on outflow facility, but enhanced the response to C3rec at 4 hours. Conclusions. Coadministration of viral vectors enhances the ability of C3 transferase to disrupt actin stress fiber formation in HTM cells and increase outflow facility in MOCAS. Viral vectors potentially could be used to increase the bioavailability of proteins for cells that are difficult to transfect. PMID:25783606

  11. Inhibitors of HIV-1 maturation: Development of structure-activity relationship for C-28 amides based on C-3 benzoic acid-modified triterpenoids.

    PubMed

    Swidorski, Jacob J; Liu, Zheng; Sit, Sing-Yuen; Chen, Jie; Chen, Yan; Sin, Ny; Venables, Brian L; Parker, Dawn D; Nowicka-Sans, Beata; Terry, Brian J; Protack, Tricia; Rahematpura, Sandhya; Hanumegowda, Umesh; Jenkins, Susan; Krystal, Mark; Dicker, Ira B; Meanwell, Nicholas A; Regueiro-Ren, Alicia

    2016-04-15

    We have recently reported on the discovery of a C-3 benzoic acid (1) as a suitable replacement for the dimethyl succinate side chain of bevirimat (2), an HIV-1 maturation inhibitor that reached Phase II clinical trials before being discontinued. Recent SAR studies aimed at improving the antiviral properties of 2 have shown that the benzoic acid moiety conferred topographical constraint to the pharmacophore and was associated with a lower shift in potency in the presence of human serum albumin. In this manuscript, we describe efforts to improve the polymorphic coverage of the C-3 benzoic acid chemotype through modifications at the C-28 position of the triterpenoid core. The dimethylaminoethyl amides 17 and 23 delivered improved potency toward bevirimat-resistant viruses while increasing C24 in rat oral PK studies.

  12. Mutational analysis of the complement receptor type 2 (CR2/CD21)-C3d interaction reveals a putative charged SCR1 binding site for C3d.

    PubMed

    Hannan, Jonathan P; Young, Kendra A; Guthridge, Joel M; Asokan, Rengasamy; Szakonyi, Gerda; Chen, Xiaojiang S; Holers, V Michael

    2005-02-25

    We have characterized the interaction between the first two short consensus repeats (SCR1-2) of complement receptor type 2 (CR2, CD21) and C3d in solution, by utilising the available crystal structures of free and C3d-bound forms of CR2 to create a series of informative mutations targeting specific areas of the CR2-C3d complex. Wild-type and mutant forms of CR2 were expressed on the surface of K562 erythroleukemia cells and their binding ability assessed using C3dg-biotin tetramers complexed to fluorochrome conjugated streptavidin and measured by flow cytometry. Mutations directed at the SCR2-C3d interface (R83A, R83E, G84Y) were found to strongly disrupt C3dg binding, supporting the conclusion that the SCR2 interface reflected in the crystal structure is correct. Previous epitope and peptide mapping studies have also indicated that the PILN11GR13IS sequence of the first inter-cysteine region of SCR1 is essential for the binding of iC3b. Mutations targeting residues within or in close spatial proximity to this area (N11A, N11E, R13A, R13E, Y16A, S32A, S32E), and a number of other positively charged residues located primarily on a contiguous face of SCR1 (R28A, R28E, R36A, R36E, K41A, K41E, K50A, K50E, K57A, K57E, K67A, K67E), have allowed us to reassess those regions on SCR1 that are essential for CR2-C3d binding. The nature of this interaction and the possibility of a direct SCR1-C3d association are discussed extensively. Finally, a D52N mutant was constructed introducing an N-glycosylation sequence at an area central to the CR2 dimer interface. This mutation was designed to disrupt the CR2-C3d interaction, either directly through steric inhibition, or indirectly through disruption of a physiological dimer. However, no difference in C3dg binding relative to wild-type CR2 could be observed for this mutant, suggesting that the dimer may only be found in the crystal form of CR2.

  13. Polymorphism and solvatomorphism 2008.

    PubMed

    Brittain, Harry G

    2010-09-01

    Papers and patents that deal with polymorphism and solvatomorphism have been summarized in an annual review. The review is divided into sections that cover articles of general interest, computational and theoretical studies, preparative and isolation methods, structural characterization and properties of polymorphic and solvatomorphic systems, studies of phase transformations, effects associated with secondary processing, and United States patents issued during 2008.

  14. Nqrs Data for C3H12INO7 [C3H7NO2·HIO3·2(H2O)] (Subst. No. 0646)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C3H12INO7 [C3H7NO2·HIO3·2(H2O)] (Subst. No. 0646)

  15. CO2 enrichment inhibits shoot nitrate assimilation in C3 but not C4 plants and slows growth under nitrate in C3 plants.

    PubMed

    Bloom, Arnold J; Asensio, Jose Salvador Rubaio; Randall, Lesley; Rachmilevitch, Shimon; Cousins, Asaph B; Carlisle, Eli A

    2012-02-01

    The CO2 concentration in Earth's atmosphere may double during this century. Plant responses to such an increase depend strongly on their nitrogen status, but the reasons have been uncertain. Here, we assessed shoot nitrate assimilation into amino acids via the shift in shoot CO2 and O2 fluxes when plants received nitrate instead of ammonium as a nitrogen source (deltaAQ). Shoot nitrate assimilation became negligible with increasing CO2 in a taxonomically diverse group of eight C3 plant species, was relatively insensitive to CO2 in three C4 species, and showed an intermediate sensitivity in two C3-C4 intermediate species. We then examined the influence of CO2 level and ammonium vs. nitrate nutrition on growth, assessed in terms of changes in fresh mass, of several C3 species and a Crassulacean acid metabolism (CAM) species. Elevated CO2 (720 micromol CO2/mol of all gases present) stimulated growth or had no effect in the five C3 species tested when they received ammonium as a nitrogen source but inhibited growth or had no effect if they received nitrate. Under nitrate, two C3 species grew faster at sub-ambient (approximately 310 micromol/mol) than elevated CO2. A CAM species grew faster at ambient than elevated or sub-ambient CO2 under either ammonium or nitrate nutrition. This study establishes that CO2 enrichment inhibits shoot nitrate assimilation in a wide variety of C3 plants and that this phenomenon can have a profound effect on their growth. This indicates that shoot nitrate assimilation provides an important contribution to the nitrate assimilation of an entire C3 plant. Thus, rising CO2 and its effects on shoot nitrate assimilation may influence the distribution of C3 plant species.

  16. Characterization of botulinum C3-catalyzed ADP-ribosylation of rho proteins and identification of mammalian C3-like ADP-ribosyltransferase.

    PubMed

    Maehama, T; Sekine, N; Nishina, H; Takahashi, K; Katada, T

    1994-09-01

    The exoenzyme C3 produced by Clostridium botulinum catalyzes ADP-ribosylation of rho gene products which belong to a family of small molecular-weight GTP-binding proteins. The C3 enzyme-catalyzed ADP-ribosylation of rho proteins partially purified from bovine brain was markedly activated by certain types of detergents or phospholipids and by endogenous factors present in the brain cytosol. Rho A protein that had been expressed in E. coli and subsequential purified was readily ADP-ribosylated by the C3 enzyme even in the absence of the activating factors. These results suggest that partially purified rho proteins contain an inhibitor, probably rho GDI (GDP-dissociation inhibitor for rho p21), of C3-catalyzed ADP-ribosylation. The activity of an endogenous enzyme, having the same substrate as botulinum C3 enzyme, was also found in brain cytosol. The enzyme activity was partially purified and characterized. The enzyme appeared to have a molecular mass of approximately 20,000 on a gel filtration and displayed unique properties similar to those observed with the botulinum C3 enzyme. The alpha-subunits of alpha beta gamma-trimeric G proteins which served as the substrates of cholera or pertussis toxin were not ADP-ribosylated by the brain enzyme.

  17. Polymorphism in Carbamazepine Cocrystals

    PubMed Central

    Porter, William W.; Elie, Sophia C.; Matzger, Adam J.

    2009-01-01

    Cocrystals of carbamazepine with nicotinamide and saccharin are shown to be polymorphic. Two polymorphs of carbamazepine-nicotinamide (CBZ-NCT) cocrystals and two polymorphs of carbamazepine-saccharin (CBZ-SAC) cocrystals were grown from solution in the presence of polymer heteronuclei. The two CBZ-NCT polymorphs, CBZ-NCT I and a polymer nucleated (PN) form of CBZ-NCT, were characterized by Raman spectroscopy and powder X-ray diffraction. CBZ-SAC II, a new polymorph, was found to be in the monoclinic space group C2/c with a = 35.72 Å, b = 6.84 Å, c = 16.11 Å, and β = 98.03°. The unique feature of CBZ-SAC II is the formation of a heterosynthon between the carbamazepine and saccharin. These results are notable because CBZ-NCT and CBZ-SAC are among the most widely studied pharmaceutical cocrystals. PMID:19367342

  18. Two-Dimensional Nb-Based M 4 C 3 Solid Solutions (MXenes)

    DOE PAGES

    Yang, Jian; Naguib, Michael; Ghidiu, Michael; ...

    2015-10-15

    Two new two-dimensional Nb4C3-based solid solutions (MXenes), (Nb0.8,Ti0.2)4C3Tx and (Nb0.8,Zr0.2)4C3Tx (where T is a surface termination) were synthesizedas confirmed by X-ray diffractionfrom their corresponding MAX phase precursors (Nb0.8,Ti0.2)4AlC3 and (Nb0.8,Zr0.2)4AlC3. In our report we discuss Zr-containing MXene. We also studied intercalation of Li ions into these two compositions, and Nb4C3Tx in order to determine the potential of those materials for energy storage applications. Lithiation and delithiation peaks at 2.26 and 2.35 V, respectively, appeared in the case of Nb4C3Tx, but were not present in Nb2CTx. After 20 cycles at a rate of C/4, the specific capacities of (Nb0.8,Ti0.2)4C3Txand (Nb0.8,Ti0.2)4C3Tx weremore » 158 and 132 mAh/g, respectively, both slightly lower than the capacity of Nb4C3Tx.« less

  19. 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.

  20. Loss of Properdin Exacerbates C3 Glomerulopathy Resulting from Factor H Deficiency

    PubMed Central

    Ruseva, Marieta M.; Vernon, Katherine A.; Lesher, Allison M.; Schwaeble, Wilhelm J.; Ali, Youssif M.; Botto, Marina; Cook, Terence; Song, Wenchao; Stover, Cordula M.

    2012-01-01

    Complement factor H (CFH) is a negative regulator of the alternative pathway of complement, and properdin is the sole positive regulator. CFH-deficient mice (CFH−/−) develop uncontrolled C3 activation and spontaneous renal disease characterized by accumulation of C3 along the glomerular basement membrane, but the role of properdin in the pathophysiology is unknown. Here, we studied mice deficient in both CFH and properdin (CFH−/−.P−/−). Although CFH−/− mice had plasma depleted of both C3 and C5, CFH−/−.P−/− animals exhibited depletion of C3 predominantly, recapitulating the plasma complement profile observed in humans with properdin-independent C3 nephritic factors. Glomerular inflammation, thickening of the capillary wall, and glomerular C3 staining were significantly increased in CFH−/−.P−/− compared with CFH−/− mice. We previously reported that exogenous CFH ameliorates C3 staining of the glomerular basement membrane and triggers the appearance of mesangial C3 deposits in CFH−/− mice; here, we show that these effects require properdin. In summary, during uncontrolled activation of C3 driven by complete CFH deficiency, properdin influences the intraglomerular localization of C3, suggesting that therapeutic inhibition of properdin would be detrimental in this setting. PMID:23184055

  1. Re-Analysis of the Dispersed Fluorescence Spectra of the C_3-RARE Gas Atom Complexes

    NASA Astrophysics Data System (ADS)

    Wang, Yi-Jen; Merer, Anthony; Hsu, Yen-Chu

    2015-06-01

    The dispersed fluorescence (DF) spectra of the C_3Ne, C_3Ar, C_3Kr, and C_3Xe complexes near the 0 2^- 0- 000, 0 4^- 0- 000, 0 2^+ 0- 000 and 100-000 bands of the {A}- {X} system of C_3 have been revisited. Some of the DF spectra of the Ne and Ar complexes have been recently obtained with a slightly improved resolution of 6-10 wn. All the DF spectra have been reassigned as emission from van der Waals (vdW) complexes and C_3 fragments. The optically excited C_3-Rg (Rg = rare-gas atom) complexes fluorescence and/or decay down to slightly lower (about 2-30 wn) vibrational levels without changing the internal energy of C_3 and then predissociate via the continua of the nearby vibronic states of C_3. The available dissociation channels depend on the binding energy of the ground electronic state complex. Exceptions have been found at the vdW bands near the 0 4^- 0- 000 band of C_3. The binding energies of the ground electronic states of these four complexes will be discussed. G. Zhang, B.-G. Lin, S.-M. Wen, and Y.-C. Hsu, J. Chem. Phys. 20, 3189(2004) J.-M. Chao, K. S. Tham, G. Zhang, A. J. Merer, Y.-C. Hsu, and W.-P. Hu, J. Chem. Phys. 34, 074313(2011)

  2. Factor C acts as a lipopolysaccharide-responsive C3 convertase in horseshoe crab complement activation.

    PubMed

    Ariki, Shigeru; Takahara, Shusaku; Shibata, Toshio; Fukuoka, Takaaki; Ozaki, Aya; Endo, Yuichi; Fujita, Teizo; Koshiba, Takumi; Kawabata, Shun-ichiro

    2008-12-01

    The complement system in vertebrates plays an important role in host defense against and clearance of invading microbes, in which complement component C3 plays an essential role in the opsonization of pathogens, whereas the molecular mechanism underlying C3 activation in invertebrates remains unknown. In an effort to understand the molecular activation mechanism of invertebrate C3, we isolated and characterized an ortholog of C3 (designated TtC3) from the horseshoe crab Tachypleus tridentatus. Flow cytometric analysis using an Ab against TtC3 revealed that the horseshoe crab complement system opsonizes both Gram-negative and Gram-positive bacteria. Evaluation of the ability of various pathogen-associated molecular patterns to promote the proteolytic conversion of TtC3 to TtC3b in hemocyanin-depleted plasma indicated that LPS, but not zymosan, peptidoglycan, or laminarin, strongly induces this conversion, highlighting the selective response of the complement system to LPS stimulation. Although originally characterized as an LPS-sensitive initiator of hemolymph coagulation stored within hemocytes, we identified factor C in hemolymph plasma. An anti-factor C Ab inhibited various LPS-induced phenomena, including plasma amidase activity, the proteolytic activation of TtC3, and the deposition of TtC3b on the surface of Gram-negative bacteria. Moreover, activated factor C present on the surface of Gram-negative bacteria directly catalyzed the proteolytic conversion of the purified TtC3, thereby promoting TtC3b deposition. We conclude that factor C acts as an LPS-responsive C3 convertase on the surface of invading Gram-negative bacteria in the initial phase of horseshoe crab complement activation.

  3. Dynamic Structural Changes During Complement C3 Activation Analyzed by Hydrogen/Deuterium Exchange Mass Spectrometry

    PubMed Central

    Schuster, Michael C.; Ricklin, Daniel; Papp, Krisztián; Molnar, Kathleen S.; Coales, Stephen J.; Hamuro, Yoshitomo; Sfyroera, Georgia; Chen, Hui; Winters, Michael S.; Lambris, John D.

    2008-01-01

    Proteolytic cleavage of component C3 to C3b is a central step in the activation of complement. Whereas C3 is largely biologically inactive, C3b is directly involved in various complement activities. While the recently described crystal structures of C3 and C3b provide a molecular basis of complement activation, they do not reflect the dynamic changes that occur in solution. In addition, the available C3b structures diverge in some important aspects. Here we have utilized hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) to investigate relative changes in the solution-phase structures of C3 and C3b. By combining two forms of mass spectrometry we could maximize the primary sequence coverage of C3b and demonstrate the feasibility of this method for large plasma proteins. While the majority of the 82 peptides that could be followed over time showed only minor alterations in HDX, we observed clear changes in solvent accessibility for 16 peptides, primarily in the α-chain (α’NT, MG6-8, CUB, TED, C345C domains). Most of these peptides could be directly linked to the structural transitions visible in the crystal structures and revealed additional information about the probability of the structural variants of C3b. In addition, a discontinuous cluster of seven peptides in the MG3, MG6, LNK and α’NT domains showed a decreased accessibility after activation to C3b. Although no gross conformational changes are detected in the crystal structure, this area may reflect a structurally flexible region in solution that contributes to C3 activation and function. PMID:18456336

  4. Surface complement C3 fragments and cellular binding of microparticles in patients with SLE

    PubMed Central

    Winberg, Line Kjær; Nielsen, Claus Henrik; Jacobsen, Søren

    2017-01-01

    Objectives To examine microparticles (MPs) from patients with SLE and healthy controls (HCs) by determining the cellular origin of the MPs, quantifying attached fragments of complement component 3 (C3) and assessing the ability of MPs to bind to circulating phagocytes and erythrocytes. These features may be relevant for clearance of MPs in SLE pathogenesis. Methods Attached C3 fragments (C3b, iC3b, C3d), membrane integrity and cell surface markers of MPs from 18 patients with SLE and 11 HCs were measured by adding specific antibodies, 7-aminoactinomycin D (7AAD) and annexin V. MPs from all subjects were labelled with carboxyfluorescein diacetate succinimidyl ester and allowed to bind to autologous phagocytes and erythrocytes in the presence of autologous serum, and the binding to individual cell populations was assessed by flow cytometry. Results The proportion of MPs bearing C3 fragments was higher in patients with SLE than in HCs (p=0.026), but the amount of opsonising C3b/iC3b molecules was lower (p=0.004). The C3b/iC3b level correlated with the concentration of circulating C3 (rs=0.53, p=0.036). Phagocytes and erythrocytes from patients and HCs bound autologous MPs, and granulocytes from patients bound 13% more MPs than those from HCs (p=0.043). The presence of erythrocytes inhibited the MP binding to granulocytes by approximately 50%. Conclusions Our demonstration of altered composition of C3 fragments on MPs from patients with SLE, including decreased numbers of opsonising C3 fragments, and competitive binding of MPs to circulating phagocytes and erythrocytes corroborates the hypothesis of defective clearance of apoptotic material in SLE, and indicates that differences in both MP opsonisation and binding of MPs to cells are important in the pathogenesis of SLE. PMID:28409016

  5. Increased expression of the C3b receptor by neutrophils and complement activation during haemodialysis.

    PubMed Central

    Lee, J; Hakim, R M; Fearon, D T

    1984-01-01

    Activation of complement and the relative number of C3b receptors expressed by neutrophils was assessed in patients undergoing haemodialysis with new and reused cellulosic membranes, and with polymethylmethacrylate (PMMA) membranes. Activation of complement was assessed by radioimmunoassay of plasma C3adesArg, and neutrophil C3b receptors were measured by fluorescent flow cytometry of cells indirectly stained with F(ab')2 anti-C3b receptor. During first use of cellulosic dialysis membranes by four patients, the mean expression of C3b receptors by neutrophils in blood taken from the afferent line of the extra-corporeal system after 10, 20, 60 and 120 min of dialysis increased to 127, 189, 255 and 296%, respectively. The mean plasma C3adesArg concentrations in the corresponding samples of blood were 225, 320, 236 and 160% of the pre-dialysis levels. During third and fifth use of the same membranes by these patients, the mean C3b receptor expression by neutrophils did not exceed 150% of the predialysis determination, and correspondingly minimal increases in plasma C3adesArg were observed. Analysis of blood taken simultaneously from the afferent and efferent lines of the first use cellulosic dialysis system indicated that the increase in C3b receptor expression by neutrophils and generation of C3adesArg occurred when blood came in contact with the dialysis membrane. Haemodialysis of four additional patients with the non-complement activating PMMA membrane caused only modest or no increases in neutrophil C3b receptors. Thus, complement activation in vivo is associated with up-regulation of neutrophilic C3b receptors, indicating that this cellular response previously described only in model, in vitro systems, is a physiological mechanism by which this cell can augment its capacity for responding to C3b opsonized material. PMID:6232024

  6. Demonstration of a specific C3a receptor on guinea pig platelets

    SciTech Connect

    Fukuoka, Y.; Hugli, T.E.

    1988-05-15

    Guinea pig platelets reportedly contain receptors specific for the anaphylatoxin C3a based on both ligand-binding studies and functional responses. A portion of the human 125I-C3a that binds to guinea pig platelets is competitively displaced by excess unlabeled C3a; however, the majority of ligand uptake was nonspecific. Uptake of 125I-C3a by guinea pig platelets is maximal in 1 min, and stimulation of guinea pig platelets by thrombin, ADP, or the Ca2+ ionophore A23187 showed little influence on binding of the ligand. Scatchard analysis indicated that approximately 1200 binding sites for C3a exist per cell with an estimated Kd of 8 x 10(-10) M. Human C3a des Arg also binds to guinea pig platelets, but Scatchard analysis indicated that no specific binding occurred. Because the ligand-binding studies were complicated by high levels of nonspecific uptake, we attempted to chemically cross-link the C3a molecule to a specific component on the platelet surface. Cross-linkage of 125I-C3a to guinea pig platelets with bis(sulfosuccinimidyl)suberate revealed radioactive complexes at 105,000 and 115,000 m.w. on SDS-PAGE gels by autoradiographic analysis. In the presence of excess unlabeled C3a, complex formation was inhibited. No cross-linkage could be demonstrated between the inactive 125I-C3a des Arg and the putative C3a-R on guinea pig platelets. Human C3a, but not C3a des Arg induces serotonin release and aggregation of the guinea pig platelets. Human C3a was unable to induce either serotonin release or promote aggregation of human platelets. Uptake of human 125I-C3a by human platelets was not saturable, and Scatchard analysis was inconclusive. Attempts to cross-link 125I-C3a to components on the surface of human platelets also failed to reveal a ligand-receptor complex. Therefore, we conclude that guinea pig platelets have specific surface receptors to C3a and that human platelets appear devoid of receptors to the anaphylatoxin.

  7. Enhanced Photocatalytic Performance of Luminescent g-C3N4 Photocatalyst in Darkroom

    NASA Astrophysics Data System (ADS)

    Li, Huihui; Yin, Shu; Sato, Tsugio; Wang, Yuhua

    2016-02-01

    Graphitic-C3N4(g-C3N4), a low-cost visible-light-driven photocatalyst, was used for the photocatalytic oxidation of aqueous methylene blue (MB) in the dark with Sr4Al14O25:(Eu,Dy) assistance. The Sr4Al14O25:(Eu,Dy)/g-C3N4 photocatalysts were fabricated through the ultrasonic dispersion method. The commercial Sr4Al14O25:(Eu,Dy) phosphor was used as a long afterglow supplier for exciting g-C3N4 in the dark. The results demonstrated that the metal-free g-C3N4 photocatalyst could use the eye-visible long afterglow to photocatalytically decompose MB dyes in the dark. This work may expand the appealing application of g-C3N4 for the environmental cleanup.

  8. Strong Theoretical Support for the Assignment of B11244 to l-C3H+

    NASA Astrophysics Data System (ADS)

    Botschwina, P.; Stein, C.; Sebald, P.; Schröder, B.; Oswald, R.

    2014-05-01

    Highly accurate quantum chemical calculations beyond CCSD(T) have been used to study the molecular cation l-C3H+ which is the carrier of harmonically related radio lines observed in the Horsehead photodissociation region and toward Sgr B2(N). Excellent agreement with spectroscopic and radioastronomical measurements is obtained for the rotational constant, with the calculated value of B 0 = 11246.4 MHz only 1.5 MHz or 0.01% above the experimental value. The unusually large ratio of centrifugal distortion constants D 0(exp.)/De(theor.) = 1.80 is attributed to the shallow CCC bending potential of l-C3H+ and is quantitatively reproduced by variational calculations within a pseudo-triatomic model. A comparative study of centrifugal distortion constants in a series of four linear interstellar molecules (C3N-, C3O, l-C3H+, and C3) is made and some general conclusions are drawn.

  9. Enhanced Photocatalytic Performance of Luminescent g-C3N4 Photocatalyst in Darkroom.

    PubMed

    Li, Huihui; Yin, Shu; Sato, Tsugio; Wang, Yuhua

    2016-12-01

    Graphitic-C3N4(g-C3N4), a low-cost visible-light-driven photocatalyst, was used for the photocatalytic oxidation of aqueous methylene blue (MB) in the dark with Sr4Al14O25:(Eu,Dy) assistance. The Sr4Al14O25:(Eu,Dy)/g-C3N4 photocatalysts were fabricated through the ultrasonic dispersion method. The commercial Sr4Al14O25:(Eu,Dy) phosphor was used as a long afterglow supplier for exciting g-C3N4 in the dark. The results demonstrated that the metal-free g-C3N4 photocatalyst could use the eye-visible long afterglow to photocatalytically decompose MB dyes in the dark. This work may expand the appealing application of g-C3N4 for the environmental cleanup.

  10. Deuterated C3H2 as a clue to deuterium chemistry

    NASA Technical Reports Server (NTRS)

    Gerin, M.; Combes, F.; Wootten, H. A.; Boulanger, F.; Peters, W. L., III; Kuiper, T. B. H.

    1987-01-01

    The deuterated cyclopropenylidene ring molecule, C3HD, has been detected toward several sources in four rotational lines, at 19, 79, 104, and 107 GHz. The relative integrated intensities of the 2-sub-12 - 1-sub-01 lines of C3HD and C3H2 are found in the ratio 1:5, indicating a high deuterium fractionation ratio for cyclopropenylidene. The detection of the C-13 isotope of C3H2 at the same position allows a determination of the optical thickness (about 3) of the line. The detection of such a large enhancement in the deuterated form of C3H2 very strongly suggests that a molecular ion is the chemical precursor of the molecules. Consideration of the amount of the enhancement relative to that in other molecules suggests that the precursor ion is C3H3+.

  11. Altered cognitive performance and synaptic function in the hippocampus of mice lacking C3.

    PubMed

    Perez-Alcazar, Marta; Daborg, Jonny; Stokowska, Anna; Wasling, Pontus; Björefeldt, Andreas; Kalm, Marie; Zetterberg, Henrik; Carlström, Karl E; Blomgren, Klas; Ekdahl, Christine T; Hanse, Eric; Pekna, Marcela

    2014-03-01

    Previous work implicated the complement system in adult neurogenesis as well as elimination of synapses in the developing and injured CNS. In the present study, we used mice lacking the third complement component (C3) to elucidate the role the complement system plays in hippocampus-dependent learning and synaptic function. We found that the constitutive absence of C3 is associated with enhanced place and reversal learning in adult mice. Our findings of lower release probability at CA3-CA1 glutamatergic synapses in combination with unaltered overall efficacy of these synapses in C3 deficient mice implicate C3 as a negative regulator of the number of functional glutamatergic synapses in the hippocampus. The C3 deficient mice showed no signs of spontaneous epileptiform activity in the hippocampus. We conclude that C3 plays a role in the regulation of the number and function of glutamatergic synapses in the hippocampus and exerts negative effects on hippocampus-dependent cognitive performance.

  12. g-C3N4 decorated ZnO nanorod arrays for enhanced photoelectrocatalytic performance

    NASA Astrophysics Data System (ADS)

    Kuang, Pan-Yong; Su, Yu-Zhi; Chen, Gao-Feng; Luo, Zhuo; Xing, Shu-Yang; Li, Nan; Liu, Zhao-Qing

    2015-12-01

    Heterojunction can not only offer a wide range of solar light absorption but also facilitate the separation of photoinduced charge carriers, and thereby lead to enhanced photoelectrochemical efficiency. Herein, we report the heterostructured g-C3N4/ZnO nanorod arrays (NRAs) for enhanced photoelectrocatalytic performance. The g-C3N4 shell layer of about 20-30 nm was coated on the surface of ZnO nanorod uniformly through thermal annealing the melamine precursor. Compared to the pristine ZnO and g-C3N4, the as-prepared g-C3N4/ZnO NRAs exhibit enhanced photoelectrocatalytic activity for methylene blue (MB) decolorization under visible light illumination. This enhancement of photoelectrocatalytic performance may be mainly attributed to improved separation efficiency of charge carriers from photoexcited g-C3N4 to ZnO across the g-C3N4/ZnO interfaces.

  13. The LspC3-41I restriction-modification system is the major determinant for genetic manipulations of Lysinibacillus sphaericus C3-41.

    PubMed

    Fu, Pan; Ge, Yong; Wu, Yiming; Zhao, Ni; Yuan, Zhiming; Hu, Xiaomin

    2017-05-19

    Lysinibacillus sphaericus has been widely used in integrated mosquito control program and it is one of the minority bacterial species unable to metabolize carbohydrates. In consideration of the high genetic conservation at genomic level and difficulty of genetic horizontal transfer, it is hypothesized that effective restriction-modification (R-M) systems existed in mosquitocidal L. sphaericus. In this study, six type II R-M systems including LspC3-41I were predicted in L. sphaericus C3-41 genome. It was found that the cell free extracts (CFE) from this strain shown similar restriction and methylation activity on exogenous Bacillus/Escherichia coli shuttle vector pBU4 as the HaeIII, which is an isoschizomer of BspRI. The Bsph_0498 (encoding the predicted LspC3-41IR) knockout mutant Δ0498 and the complement strain RC0498 were constructed. It was found that the unmethylated pBU4 can be digested by the CFE of C3-41 and RC0498, but not by that of Δ0498. Furthermore, the exogenous plasmid pBU4 can be transformed at very high efficacy into Δ0498, low efficacy into RC0498, but no transformation into C3-41, indicating that LspC3-41I might be a major determinant for the genetic restriction barrier of strain C3-41. Besides, lspC3-41IR and lspC3-41IM genes are detected in other two strains besides C3-41 of the tested 16 L. sphaericus strains, which all belonging to serotype H5 and MLST sequence type (ST) 1. Furthermore, the three strains are not horizontal transferred, and this restriction could be overcome by in vitro methylation either by the host CFE or by commercial methytransferase M. HaeIII. The results provide an insight to further study the genetic restriction, modification and evolution of mosquitocidal L. sphaericus, also a theoretical basis and a method for the genetic manipulations of L. sphaericus. LspC3-41I is identified as the major determinant for the restriction barrier of L. sphaericus C3-41. Only three strains of the tested 16 L. sphaericus strains

  14. The receptor for the complement C3a anaphylatoxin (C3aR) provides host protection against Listeria monocytogenes-induced apoptosis.

    PubMed

    Mueller-Ortiz, Stacey L; Morales, John E; Wetsel, Rick A

    2014-08-01

    Listeria monocytogenes is a Gram-positive intracellular bacterium that is acquired through tainted food and may lead to systemic infection and possible death. Despite the importance of the innate immune system in fighting L. monocytogenes infection, little is known about the role of complement and its activation products, including the potent C3a anaphylatoxin. In a model of systemic L. monocytogenes infection, we show that mice lacking the receptor for C3a (C3aR(-/-)) are significantly more sensitive to infection compared with wild-type mice, as demonstrated by decreased survival, increased bacterial burden, and increased damage to their livers and spleens. The inability of the C3aR(-/-) mice to clear the bacterial infection was not caused by defective macrophages or by a reduction in cytokines/chemokines known to be critical in the host response to L. monocytogenes, including IFN-γ and TNF-α. Instead, TUNEL staining, together with Fas, active caspase-3, and Bcl-2 expression data, indicates that the increased susceptibility of C3aR(-/-) mice to L. monocytogenes infection was largely caused by increased L. monocytogenes-induced apoptosis of myeloid and lymphoid cells in the spleen that are required for ultimate clearance of L. monocytogenes, including neutrophils, macrophages, dendritic cells, and T cells. These findings reveal an unexpected function of C3a/C3aR signaling during the host immune response that suppresses Fas expression and caspase-3 activity while increasing Bcl-2 expression, thereby providing protection to both myeloid and lymphoid cells against L. monocytogenes-induced apoptosis. Copyright © 2014 by The American Association of Immunologists, Inc.

  15. The Receptor for the Complement C3a Anaphylatoxin (C3aR) Provides Host Protection against Listeria monocytogenes Induced Apoptosis

    PubMed Central

    Mueller-Ortiz, Stacey L.; Morales, John E.; Wetsel, Rick A.

    2014-01-01

    Listeria monocytogenes (LM) is a Gram-positive intracellular bacterium that is acquired through tainted food and may lead to systemic infection and possible death. Despite the importance of the innate immune system in fighting LM infection, little is known about the role of complement and its activation products, including the potent C3a anaphylatoxin. In a model of systemic LM infection, we show here that mice lacking the receptor for C3a (C3aR-/-) are significantly more sensitive to infection compared to WT mice as demonstrated by decreased survival, increased bacterial burden, and increased damage to their livers and spleens. The inability of the C3aR-/- mice to clear the bacterial infection was not caused by defective macrophages or by reduction of cytokines/chemokines known to be critical in the host response to LM, including IFN-γ and TNF-α. Instead, TUNEL staining together with Fas, active caspase-3, and Bcl-2 expression data indicate that the increased susceptibility of C3aR-/- mice to LM infection was largely caused by increased LM-induced apoptosis of myeloid and lymphoid cells in the spleen that are required for ultimate clearance of LM, including neutrophils, macrophages, dendritic cells, and T cells. These findings reveal an unexpected function of C3a/C3aR signaling during the host immune response that suppresses Fas expression and caspase-3 activity while increasing Bcl-2 expression, thereby providing protection to both myeloid and lymphoid cells against LM-induced apoptosis. PMID:24981453

  16. Knockdown of AKR1C3 exposes a potential epigenetic susceptibility in prostate cancer cells

    PubMed Central

    Doig, Craig L.; Battaglia, Sebastiano; Khanim, Farhat L.; Bunce, Christopher M.; Campbell, Moray J.

    2017-01-01

    Background The aldo-keto reductase 1C3 (AKR1C3) has been heavily implicated in the propagation of prostate malignancy. AKR1C3 protein is elevated within prostate cancer tissue, it contributes to the formation of androgens and downstream stimulation of the androgen receptor (AR). Elevated expression of AKR1C3 is also reported in acute myeloid leukemia but the target nuclear receptors have been identified as members of the peroxisome-proliferator activated receptor (PPARs) subfamily. Thus, AKR1C3 cancer biology is likely to be tissue dependent and hormonally linked to the availability of ligands for both the steroidogenic and non-steroidogenic nuclear receptors. Methods In the current study we investigated the potential for AKR1C3 to regulate the availability of prostaglandin-derived ligands for PPARg mainly, prostaglandin J2 (PGJ2). Using prostate cancer cell lines with stably reduced AKR1C3 levels we examined the impact of AKR1C3 upon proliferation mediated by PPAR ligands. Results These studies revealed knockdown of AKR1C3 had no effect upon the sensitivity of androgen receptor independent prostate cancer cells towards PPAR ligands. However, the reduction of levels of AKR1C3 was accompanied by a significantly reduced mRNA expression of a range of HDACs, transcriptional co-regulators, and increased sensitivity towards SAHA, a clinically approved histone deacetylase inhibitor. Conclusions These results suggest a hitherto unidentified link between AKR1C3 levels and the epigenetic status in prostate cancer cells. This raises an interesting possibility of a novel rational to target AKR1C3, the utilization of AKRIC3 selective inhibitors in combination with HDAC inhibition as part of novel epigenetic therapies in androgen deprivation therapy recurrent prostate cancer. PMID:26429394

  17. Renal cortical complement C3 gene expression in IgA nephropathy.

    PubMed

    Montinaro, V; Gesualdo, L; Ranieri, E; Monno, R; Grandaliano, G; Schena, F P

    1997-03-01

    Glomerular C3 deposits are commonly found in immunoglobulin A (IgA) nephropathy. Renal gene expression and protein synthesis of complement components have been shown in settings of tissue inflammation. In this study, the pathogenetic involvement of locally produced C3 in IgA nephropathy was analyzed. C3 gene expression was analyzed by reverse transcription, polymerase chain reaction, and in situ hybridization techniques. C3 mRNA was detected in 56% of cases, with a significantly higher percentage in patients with moderate-to-severe lesions than in those with mild lesions (P < 0.01). By in situ hybridization, C3 transcript was predominantly expressed by tubular cells and some interstitial cells. C3 mRNA was also observed on glomerular parietal epithelial cells. Immunoreactive native C3 was detected on cortical tubuli by an anti-C3c immunoalkaline-phosphatase technique. A significant correlation was found between renal C3 transcription and glomerulosclerosis, intracapillary proliferation (both P < 0.005) and markers of interstitial damage, including tubular atrophy (P < 0.05), interstitial infiltration (P < 0.05), and fibrosis (P < 0.005). Proteinuria (P < 0.05), but not serum creatinine, at the time of renal biopsy correlated with C3 mRNA. In conclusion, it was demonstrated that the C3 gene was expressed primarily in proximal tubular cells and occasionally in glomerular crescents, and that its expression correlated with clinical and histologic markers of severity and poor outcome of IgA nephropathy. Thus, a pathogenetic involvement of the local transcription and translation of the C3 gene in IgA nephropathy was suggested.

  18. Functional Characterization of Autoantibodies against Complement Component C3 in Patients with Lupus Nephritis*

    PubMed Central

    Vasilev, Vasil V.; Noe, Remi; Dragon-Durey, Marie-Agnes; Chauvet, Sophie; Lazarov, Valentin J.; Deliyska, Boriana P.; Fremeaux-Bacchi, Veronique; Dimitrov, Jordan D.; Roumenina, Lubka T.

    2015-01-01

    Lupus nephritis (LN) is a complication of the autoimmune disease systemic lupus erythematosus. Because the complement system plays a critical role in orchestrating inflammatory and immune responses as well as in the clearance of immune complexes, autoreactivity to complement components may have considerable pathological consequences. Autoantibodies against the central complement component C3 have been reported in systemic lupus erythematosus, but their molecular mechanism and functional relevance are not well understood. The objective of this study was to evaluate the frequency and the functional properties of the anti-C3 autoantibodies. Anti-C3 autoantibodies were measured in plasma of 39 LN patients, and identification of their epitopes on the C3 molecule was performed. By using surface plasmon resonance, we analyzed the influence of patient-derived IgG antibodies on the interaction of C3b with Factor B, Factor H, and complement receptor 1. The capacity of these antibodies to dysregulate the C3 convertase on the surface of endothelial cell was measured by flow cytometry. Here we report that the frequency of anti-C3 autoantibodies in LN is ∼30%. They inhibited interactions of the negative complement regulators Factor H and complement receptor 1 with C3b. An enhanced C3 deposition was also observed on human endothelial cells in the presence of C3 autoantibodies. In addition, anti-C3 autoantibody levels correlated with disease activity. In conclusion, the anti-C3 autoantibodies in LN may contribute to the autoimmune pathology by their capacity to overactivate the complement system. PMID:26245903

  19. Microstructure and Mechanical Properties of Al-AL4C3 Materials

    DTIC Science & Technology

    2004-03-18

    MICROSTRUCTURE AND MECHANICAL PROPERTIES OF AL- AL4C3 MATERIALS Michal BESTERCI, Ľudovít PARILÁK Institute of Materials Research, Slovak Academy of...Carbon transformation to carbide Al4C3 is characterised for different heat treatment schedules and nine commercial carbon powders tested. The...transformed dispersed phase Al4C3 is than produced by a chemical reaction, which starts during milling, and it is completed at the next heat treatment

  20. Knockdown of AKR1C3 exposes a potential epigenetic susceptibility in prostate cancer cells.

    PubMed

    Doig, Craig L; Battaglia, Sebastiano; Khanim, Farhat L; Bunce, Christopher M; Campbell, Moray J

    2016-01-01

    The aldo-keto reductase 1C3 (AKR1C3) has been heavily implicated in the propagation of prostate malignancy. AKR1C3 protein is elevated within prostate cancer tissue, it contributes to the formation of androgens and downstream stimulation of the androgen receptor (AR). Elevated expression of AKR1C3 is also reported in acute myeloid leukemia but the target nuclear receptors have been identified as members of the peroxisome-proliferator activated receptor (PPARs) subfamily. Thus, AKR1C3 cancer biology is likely to be tissue dependent and hormonally linked to the availability of ligands for both the steroidogenic and non-steroidogenic nuclear receptors. In the current study we investigated the potential for AKR1C3 to regulate the availability of prostaglandin-derived ligands for PPARg mainly, prostaglandin J2 (PGJ2). Using prostate cancer cell lines with stably reduced AKR1C3 levels we examined the impact of AKR1C3 upon proliferation mediated by PPAR ligands. These studies revealed knockdown of AKR1C3 had no effect upon the sensitivity of androgen receptor independent prostate cancer cells towards PPAR ligands. However, the reduction of levels of AKR1C3 was accompanied by a significantly reduced mRNA expression of a range of HDACs, transcriptional co-regulators, and increased sensitivity towards SAHA, a clinically approved histone deacetylase inhibitor. These results suggest a hitherto unidentified link between AKR1C3 levels and the epigenetic status in prostate cancer cells. This raises an interesting possibility of a novel rational to target AKR1C3, the utilization of AKRIC3 selective inhibitors in combination with HDAC inhibition as part of novel epigenetic therapies in androgen deprivation therapy recurrent prostate cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Enhanced Attitude Control Experiment for SSTI Lewis Spacecraft

    NASA Technical Reports Server (NTRS)

    Maghami, Peoman G.

    1997-01-01

    The enhanced attitude control system experiment is a technology demonstration experiment on the NASA's small spacecraft technology initiative program's Lewis spacecraft to evaluate advanced attitude control strategies. The purpose of the enhanced attitude control system experiment is to evaluate the feasibility of designing and implementing robust multi-input/multi-output attitude control strategies for enhanced pointing performance of spacecraft to improve the quality of the measurements of the science instruments. Different control design strategies based on modern and robust control theories are being considered for the enhanced attitude control system experiment. This paper describes the experiment as well as the design and synthesis of a mixed H(sub 2)/H(sub infinity) controller for attitude control. The control synthesis uses a nonlinear programming technique to tune the controller parameters and impose robustness and performance constraints. Simulations are carried out to demonstrate the feasibility of the proposed attitude control design strategy. Introduction

  2. Functional analysis of Cobra Venom Factor/human C3 chimeras transiently expressed in mammalian cells.

    PubMed

    Kölln, Johanna; Matzas, Mark; Jänner, Nathalie; Mix, Thorsten; Klensang, Katrin; Bredehorst, Reinhard; Spillner, Edzard

    2004-05-01

    The complement activating venom component Cobra Venom Factor (CVF), a functional and structural homologue of the human complement component C3, forms a stable CVF-dependent C3 convertase complex, which, in contrast to C3-dependent convertase effects continuous activation of the complement and, thereby, decomplementation. In order to elucidate the mechanism underlying the enhanced activity of CVF compared to human C3, we generated two CVF/C3 chimeras and established different affinity-based assay systems for functional analysis of these constructs. To allow for convenient expression and subsequent functional characterisation, the CVF/C3 chimeras as well as CVF and C3 were transiently expressed in mammalian cells. Problems due to the low concentration of the recombinant proteins in the supernatants of transient expressions were circumvented by fusion to peptide tags enabling their efficient immobilisation onto suitable surfaces and subsequent characterisation. In an alternative approach monoclonal antibody fragments generated from a semisynthetic phage display scFv library were employed for concentrating the recombinant proteins by immunoprecipitation. Utilising both approaches all transiently expressed proteins could be characterised for their complement consumption activity. The data obtained with the CVF/C3 chimeras demonstrate that the increased stability of the CVFBb complex is independent of the domains in CVF corresponding to binding sites of factor B and H and the cleavage sites of factor I in the human C3 molecule.

  3. Growth characteristics of primary M7C3 carbide in hypereutectic Fe-Cr-C alloy

    NASA Astrophysics Data System (ADS)

    Liu, Sha; Zhou, Yefei; Xing, Xiaolei; Wang, Jibo; Ren, Xuejun; Yang, Qingxiang

    2016-09-01

    The microstructure of the hypereutectic Fe-Cr-C alloy is observed by optical microscopy (OM). The initial growth morphology, the crystallographic structure, the semi-molten morphology and the stacking faults of the primary M7C3 carbide are observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The in-suit growth process of the primary M7C3 carbide was observed by confocal laser microscope (CLM). It is found that the primary M7C3 carbide in hypereutectic Fe-Cr-C alloy is irregular polygonal shape with several hollows in the center and gaps on the edge. Some primary M7C3 carbides are formed by layers of shell or/and consist of multiple parts. In the initial growth period, the primary M7C3 carbide forms protrusion parallel to {} crystal planes. The extending and revolving protrusion forms the carbide shell. The electron backscattered diffraction (EBSD) maps show that the primary M7C3 carbide consists of multiple parts. The semi-molten M7C3 carbide contains unmelted shell and several small-scale carbides inside, which further proves that the primary M7C3 carbide is not an overall block. It is believed that the coalescence of the primary M7C3 carbides is ascribed to the growing condition of the protrusion and the gap filling process.

  4. Two Novel C3N4 Phases: Structural, Mechanical and Electronic Properties

    PubMed Central

    Fan, Qingyang; Chai, Changchun; Wei, Qun; Yang, Yintang

    2016-01-01

    We systematically studied the physical properties of a novel superhard (t-C3N4) and a novel hard (m-C3N4) C3N4 allotrope. Detailed theoretical studies of the structural properties, elastic properties, density of states, and mechanical properties of these two C3N4 phases were carried out using first-principles calculations. The calculated elastic constants and the hardness revealed that t-C3N4 is ultra-incompressible and superhard, with a high bulk modulus of 375 GPa and a high hardness of 80 GPa. m-C3N4 and t-C3N4 both exhibit large anisotropy with respect to Poisson’s ratio, shear modulus, and Young’s modulus. Moreover, m-C3N4 is a quasi-direct-bandgap semiconductor, with a band gap of 4.522 eV, and t-C3N4 is also a quasi-direct-band-gap semiconductor, with a band gap of 4.210 eV, with the HSE06 functional. PMID:28773550

  5. Potent complement C3a receptor agonists derived from oxazole amino acids: Structure-activity relationships.

    PubMed

    Singh, Ranee; Reed, Anthony N; Chu, Peifei; Scully, Conor C G; Yau, Mei-Kwan; Suen, Jacky Y; Durek, Thomas; Reid, Robert C; Fairlie, David P

    2015-12-01

    Potent ligands for the human complement C3a receptor (C3aR) were developed from the almost inactive tripeptide Leu-Ala-Arg corresponding to the three C-terminal residues of the endogenous peptide agonist C3a. The analogous Leu-Ser-Arg was modified by condensing the serine side chain with the leucine carbonyl with elimination of water to form leucine-oxazole-arginine. Subsequent elaboration with a variety of N-terminal amide capping groups produced agonists as potent as human C3a itself in stimulating Ca(2+) release from human macrophages. Structure-activity relationships are discussed.

  6. Structural basis for single-stranded RNA recognition and cleavage by C3PO

    PubMed Central

    Zhang, Jing; Liu, Hehua; Yao, Qingqing; Yu, Xiang; Chen, Yiqing; Cui, Ruixue; Wu, Baixing; Zheng, Lina; Zuo, Junjun; Huang, Zhen; Ma, Jinbiao; Gan, Jianhua

    2016-01-01

    Translin and translin-associated factor-x are highly conserved in eukaroytes; they can form heteromeric complexes (known as C3POs) and participate in various nucleic acid metabolism pathways. In humans and Drosophila, C3POs cleave the fragmented siRNA passenger strands and facilitate the activation of RNA-induced silencing complex, the effector complex of RNA interference (RNAi). Here, we report three crystal structures of Nanoarchaeum equitans (Ne) C3PO. The apo-NeC3PO structure adopts an open form and unravels a potential substrates entryway for the first time. The NeC3PO:ssRNA and NeC3PO:ssDNA complexes fold like closed football with the substrates captured at the inner cavities. The NeC3PO:ssRNA structure represents the only catalytic form C3PO complex available to date; with mutagenesis and in vitro cleavage assays, the structure provides critical insights into the substrate binding and the two-cation-assisted catalytic mechanisms that are shared by eukaryotic C3POs. The work presented here further advances our understanding on the RNAi pathway. PMID:27596600

  7. Growth characteristics of primary M7C3 carbide in hypereutectic Fe-Cr-C alloy

    PubMed Central

    Liu, Sha; Zhou, Yefei; Xing, Xiaolei; Wang, Jibo; Ren, Xuejun; Yang, Qingxiang

    2016-01-01

    The microstructure of the hypereutectic Fe-Cr-C alloy is observed by optical microscopy (OM). The initial growth morphology, the crystallographic structure, the semi-molten morphology and the stacking faults of the primary M7C3 carbide are observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The in-suit growth process of the primary M7C3 carbide was observed by confocal laser microscope (CLM). It is found that the primary M7C3 carbide in hypereutectic Fe-Cr-C alloy is irregular polygonal shape with several hollows in the center and gaps on the edge. Some primary M7C3 carbides are formed by layers of shell or/and consist of multiple parts. In the initial growth period, the primary M7C3 carbide forms protrusion parallel to {} crystal planes. The extending and revolving protrusion forms the carbide shell. The electron backscattered diffraction (EBSD) maps show that the primary M7C3 carbide consists of multiple parts. The semi-molten M7C3 carbide contains unmelted shell and several small-scale carbides inside, which further proves that the primary M7C3 carbide is not an overall block. It is believed that the coalescence of the primary M7C3 carbides is ascribed to the growing condition of the protrusion and the gap filling process. PMID:27596718

  8. Halogenation and proteolysis of complement component C3 on Salmonella typhimurium during phagocytosis by human neutrophils

    SciTech Connect

    Joiner, K.A.; Schweinle, J.E.

    1989-05-01

    We examined the fate of C component C3 on the surface of Salmonella typhimurium during ingestion by human neutrophils. Initial experiments showed that C3 fragments and C3-acceptor complexes were the major serum ligands which were surface iodinated by canine myeloperoxidase on serum-incubated rough and smooth isolates of S. typhimurium. In contrast, labeled C3 was not identified when the same organisms were ingested by neutrophils in the presence of 125I-Na, a situation previously shown to iodinate particulate targets via the neutrophil myeloperoxidase-halide-H2O2 system. Pretreatment of neutrophils before phagocytosis with the lipid-soluble protease inhibitor diisopropylfluorophosphate (DFP), but not with other protease inhibitors (p-nitrophenylguanidinobenzoate, leupeptin, pepstatin), substantially blocked proteolysis of 125I-C3 on S. typhimurium strain RG108 during ingestion by neutrophils. Purification of neutrophil phagosomes containing S. typhimurium-bearing 125I-C3 showed that DFP but no other protease inhibitors blocked proteolysis of 125I-C3 within phagosomes. Iodinated C3-acceptor complexes were identified by immunoprecipitation from the detergent-insoluble fraction of phagosomes prepared from DFP-treated cells ingesting S. typhimurium in the presence of 125I-Na. These results show that C3 fragments on the surface of S. typhimurium are the major serum ligands which are halogenated and degraded by proteolysis during phagocytosis by human neutrophils, and suggest that the majority of proteolysis on the ingested target occurs within the neutrophil phagosome.

  9. C3 Glomerulopathy and post-infectious glomerulonephritis define a disease spectrum.

    PubMed

    Al-Ghaithi, Badria; Chanchlani, Rahul; Riedl, Magdalena; Thorner, Paul; Licht, Christoph

    2016-11-01

    Post-infectious glomerulonephritis (PIGN) usually follows a benign course, but few children have an atypical, severe presentation, and these exceptional cases have been linked to the dysregulation of the complement alternative pathway (CAP). There is a considerable overlap in the histopathological features of PIGN and C3 glomerulopathy (C3G), which is also associated with CAP dysregulation but has a poorer outcome. We hypothesized that PIGN and C3G define a disease spectrum, and that in the past there may be some children with C3G who were misclassified with PIGN before C3G was described as a separate disease entity. Children with PIGN (n = 33) diagnosed between 1985 and 2010 who underwent a renal biopsy due to their unusual course were reviewed and of them, 8 were reclassified into C3G based on the current classification criteria. Outcome was based on the degree of proteinuria, C3 level, and renal function at follow-up. Sixteen (72.7%) children with typical PIGN recovered completely as compared to only 2 (25%) with C3G. Of note, children with "typical" PIGN had a more severe disease course at onset; however, the outcome at last follow up was favorable. Our results support the hypothesis that PIGN and C3G form a disease spectrum and have different long-term clinical implications and management strategies.

  10. Ag/g-C3N4 layered composites with enhanced visible light photocatalytic performance

    NASA Astrophysics Data System (ADS)

    Chen, Lu; Man, Yuhong; Chen, Zhiqian; Zhang, Yongping

    2016-11-01

    The synthesized Ag/g-C3N4 composite is composed of Ag nanoparticles with size of about 4 nm and mesoporous g-C3N4 nanosheet with uniform thickness of about 1.06 nm. The photoinduced charge carrier separation of the Ag/g-C3N4 composites is closely related to the doping mass contents of the Ag nanoparticles. The as-prepared composite exhibits optimal photocatalytic performance at 5% Ag doping content. The enhanced photocatalytic performance can be ascribed to the good synergetic effect between the Ag nanoparticle and the mesoporous g-C3N4 nanosheet.

  11. Clostridial C3 Toxins Target Monocytes/Macrophages and Modulate Their Functions

    PubMed Central

    Barth, Holger; Fischer, Stephan; Möglich, Amelie; Förtsch, Christina

    2015-01-01

    The C3 enzymes from Clostridium (C.) botulinum (C3bot) and Clostridium limosum (C3lim) are single chain protein toxins of about 25 kDa that mono-ADP-ribosylate Rho-A, -B, and -C in the cytosol of mammalian cells. We discovered that both C3 proteins are selectively internalized into the cytosol of monocytes and macrophages by an endocytotic mechanism, comparable to bacterial AB-type toxins, while they are not efficiently taken up into the cytosol of other cell types including epithelial cells and fibroblasts. C3-treatment results in disturbed macrophage functions, such as migration and phagocytosis, suggesting a novel function of clostridial C3 toxins as virulence factors, which selectively interfere with these immune cells. Moreover, enzymatic inactive C3 protein serves as a transport system to selectively deliver pharmacologically active molecules into the cytosol of monocytes/macrophages without damaging these cells. This review addresses also the generation of C3-based molecular tools for experimental macrophage pharmacology and cell biology as well as the exploitation of C3 for development of novel therapeutic strategies against monocyte/macrophage-associated diseases. PMID:26175735

  12. Proteome Alterations of Hippocampal Cells Caused by Clostridium botulinum C3 Exoenzyme.

    PubMed

    Schröder, Anke; Rohrbeck, Astrid; Just, Ingo; Pich, Andreas

    2015-11-06

    C3bot from Clostridium botulinum is a bacterial mono-ADP-ribosylating enzyme, which transfers an ADP-ribose moiety onto the small GTPases Rho A/B/C. C3bot and the catalytic inactive mutant (C3E174Q) cause axonal and dendritic growth as well as branching in primary hippocampal neurons. In cultured murine hippocampal HT22 cells, protein abundances were analyzed in response to C3bot or C3E174Q treatment using a shotgun proteomics approach. Proteome analyses were performed at four time points over 6 days. More than 4000 protein groups were identified at each time point and quantified in triplicate analyses. On day one, 46 proteins showed an altered abundance, and after 6 days, more than 700 proteins responded to C3bot with an up- or down-regulation. In contrast, C3E174Q had no provable impact on protein abundance. Protein quantification was verified for several proteins by multiple reaction monitoring. Data analysis of altered proteins revealed different cellular processes that were affected by C3bot. They are particularly involved in mitochondrial and lysosomal processes, adhesion, carbohydrate and glucose metabolism, signal transduction, and nuclear proteins of translation and ribosome biogenesis. The results of this study gain novel insights into the function of C3bot in hippocampal cells.

  13. Soluble CR1 Therapy Improves Complement Regulation in C3 Glomerulopathy

    PubMed Central

    Zhang, Yuzhou; Nester, Carla M.; Holanda, Danniele G.; Marsh, Henry C.; Hammond, Russell A.; Thomas, Lawrence J.; Meyer, Nicole C.; Hunsicker, Lawrence G.; Sethi, Sanjeev

    2013-01-01

    Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are widely recognized subtypes of C3 glomerulopathy. These ultra-rare renal diseases are characterized by fluid-phase dysregulation of the alternative complement pathway that leads to deposition of complement proteins in the renal glomerulus. Disease triggers are unknown and because targeted treatments are lacking, progress to end stage renal failure is a common final outcome. We studied soluble CR1, a potent regulator of complement activity, to test whether it restores complement regulation in C3 glomerulopathy. In vitro studies using sera from patients with DDD showed that soluble CR1 prevents dysregulation of the alternative pathway C3 convertase, even in the presence of C3 nephritic factors. In mice deficient in complement factor H and transgenic for human CR1, soluble CR1 therapy stopped alternative pathway activation, resulting in normalization of serum C3 levels and clearance of iC3b from glomerular basement membranes. Short-term use of soluble CR1 in a pediatric patient with end stage renal failure demonstrated its safety and ability to normalize activity of the terminal complement pathway. Overall, these data indicate that soluble CR1 re-establishes regulation of the alternative complement pathway and provide support for a limited trial to evaluate soluble CR1 as a treatment for DDD and C3GN. PMID:23907509

  14. Structural and friction characteristics of g-C3N4/PVDF composites

    NASA Astrophysics Data System (ADS)

    Zhu, Lin; Wang, Ya; Hu, Fang; Song, Haojie

    2015-08-01

    This paper introduced the preparation, structural, and friction characteristics of graphite-like carbon nitride (g-C3N4)/poly(vinylidene difluoride) (PVDF) composites. The g-C3N4/PVDF composites with different g-C3N4 contents were prepared via wet mixing and hot press molding technique. The structure, morphology, thermal properties, and friction characteristics were studied by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), thermo-gravimetric analysis (TGA), and universal micro-tribotester under dry sliding conditions. The XRD and FT-IR studies confirmed the incorporation of g-C3N4 into the PVDF matrix. The SEM results showed good dispersion of g-C3N4 in PVDF matrix. The "onset" temperature To of the composites increased with increasing the content of g-C3N4 filler, which confirmed the enhancement of thermal stability of the composites. The friction characteristics results indicated that small amount of g-C3N4 filler was not beneficial to reduce friction coefficient of the composite while large amount of filler had little effect on it. In addition, the g-C3N4 filler was beneficial to reduce wear loss of the composite, and the wear loss decreased with increasing the content of g-C3N4 filler.

  15. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome

    PubMed Central

    Miller, Elizabeth C.; Liszewski, M. Kathryn; Strain, Lisa; Blouin, Jacques; Brown, Alison L.; Moghal, Nadeem; Kaplan, Bernard S.; Weiss, Robert A.; Lhotta, Karl; Kapur, Gaurav; Mattoo, Tej; Nivet, Hubert; Wong, William; Gie, Sophie; de Ligny, Bruno Hurault; Fischbach, Michel; Gupta, Ritu; Hauhart, Richard; Meunier, Vincent; Loirat, Chantal; Dragon-Durey, Marie-Agnès; Fridman, Wolf H.; Janssen, Bert J. C.

    2008-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS. PMID:18796626

  16. A triclinic polymorph of 1,3-thiazolidine-2-thione (2-mercaptothiazoline).

    PubMed

    Corrêa, Rodrigo S; Santana, Sarita A; Salloum, Rogério; Silva, Rosalice M; Doriguetto, Antônio C

    2006-03-01

    A planar conformation of 1,3-thiazolidine-2-thione (TZDTH), C3H5NS2, was crystallized for the first time. The new triclinic polymorph (P\\overline 1) obtained was compared in terms of its intra- and intermolecular geometry with three previous reports of a monoclinic polymorph (P2(1)/n). The packing is based on centrosymmetric dimers of TZDTH, linked by N-H...S hydrogen bonds.

  17. Replication of association of the apolipoprotein A1-C3-A4 gene cluster with the risk of gout.

    PubMed

    Rasheed, Humaira; Phipps-Green, Amanda J; Topless, Ruth; Smith, Malcolm D; Hill, Catherine; Lester, Susan; Rischmueller, Maureen; Janssen, Matthijs; Jansen, Timothy L; Joosten, Leo A; Radstake, Timothy R; Riches, Philip L; Tausche, Anne-Kathrin; Lioté, Frederic; So, Alexander; van Rij, Andre; Jones, Gregory T; McCormick, Sally P; Harrison, Andrew A; Stamp, Lisa K; Dalbeth, Nicola; Merriman, Tony R

    2016-08-01

    Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout. We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Māori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C). In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10). Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. C3 Rho-Inhibitor for Targeted Pharmacological Manipulation of Osteoclast-Like Cells

    PubMed Central

    Tautzenberger, Andrea; Förtsch, Christina; Zwerger, Christian; Dmochewitz, Lydia; Kreja, Ludwika; Ignatius, Anita; Barth, Holger

    2013-01-01

    The C3 toxins from Clostridium botulinum (C3bot) and Clostridium limosum (C3lim) as well as C3-derived fusion proteins are selectively taken up into the cytosol of monocytes/macrophages where the C3-catalyzed ADP-ribosylation of Rho results in inhibition of Rho-signalling and characteristic morphological changes. Since the fusion toxin C2IN-C3lim was efficiently taken up into and inhibited proliferation of murine macrophage-like RAW 264.7 cells, its effects on RAW 264.7-derived osteoclasts were investigated. C2IN-C3lim was taken up into differentiated osteoclasts and decreased their resorption activity. In undifferentiated RAW 264.7 cells, C2IN-C3lim-treatment significantly decreased their differentiation into osteoclasts as determined by counting the multi-nucleated, TRAP-positive cells. This inhibitory effect was concentration- and time-dependent and most efficient when C2IN-C3lim was applied in the early stage of osteoclast-formation. A single-dose application of C2IN-C3lim at day 0 and its subsequent removal at day 1 reduced the number of osteoclasts in a comparable manner while C2IN-C3lim-application at later time points did not reduce the number of osteoclasts to a comparable degree. Control experiments with an enzymatically inactive C3 protein revealed that the ADP-ribosylation of Rho was essential for the observed effects. In conclusion, the results indicate that Rho-activity is crucial during the early phase of osteoclast-differentiation. Other bone cell types such as pre-osteoblastic cells were not affected by C2IN-C3lim. Due to their cell-type selective and specific mode of action, C3 proteins and C3-fusions might be valuable tools for targeted pharmacological manipulation of osteoclast formation and activity, which could lead to development of novel therapeutic strategies against osteoclast-associated diseases. PMID:24386487

  19. Defective binding of the third component of complement (C3) to Streptococcus pneumoniae in multiple myeloma.

    PubMed

    Cheson, B D; Walker, H S; Heath, M E; Gobel, R J; Janatova, J

    1984-04-01

    Patients with multiple myeloma (MM) are at an increased risk for infections with bacteria that require opsonization with complement. Because Streptococcus pneumoniae is the most frequently encountered pathogen in these patients, we investigated the ability of serum from patients with MM to mediate the binding of C3b, the major opsonin of the complement system, to S. pneumoniae. S. pneumoniae types 3, 14, and 25 were chosen for study, since S. pneumoniae type 3 activates primarily the classical complement pathway (CCP), type 25 primarily the alternative complement pathway (ACP), and type 14 both pathways. S. pneumoniae were treated with normal serum or serum from 17 patients with MM, and the bound C3b was quantified with fluorescein-conjugated anti-C3 in a spectrophotofluorometric assay. Despite normal or elevated serum concentrations of C3, total hemolytic complement, and C-reactive protein in all of the MM sera, factor B in 16/17 such sera, and C4 in 14/17 MM sera studied, all 17 sera demonstrated a defect in C3b binding to type 3 (32.7% +/- 6% of normal). In addition, serum from 15/17 patients bound decreased amounts of C3b to types 14 (39.6% +/- 8%) and 25 (52.2% +/- 8%). Mixing normal serum with MM serum restored MM C3b binding activity to all three S. pneumoniae types, suggesting that the defect was related to a deficiency rather than an inhibitor of C3 activation. Although MM patients are unable to produce specific antibodies to bacterial antigens, the addition of anti-S. pneumoniae antibodies to MM serum did not enhance C3b binding to any of the S. pneumoniae types. However, when S. pneumoniae were opsonized in a mixture of MM serum and C3-depleted normal serum, C3b binding was restored to all three S. pneumoniae types, demonstrating that MM C3 functions normally in the presence of other normal serum factors. In the present studies, the MM C3b binding defect appeared to correlate with the incidence of S. pneumoniae infections. Serum from patients with a

  20. Hyperglycemic conditions inhibit C3-mediated immunologic control of Staphylococcus aureus.

    PubMed

    Hair, Pamela S; Echague, Charlene G; Rohn, Reuben D; Krishna, Neel K; Nyalwidhe, Julius O; Cunnion, Kenji M

    2012-03-05

    Diabetic patients are at increased risk for bacterial infections; these studies provide new insight into the role of the host defense complement system in controlling bacterial pathogens in hyperglycemic environments. The interactions of complement C3 with bacteria in elevated glucose were assayed for complement activation to opsonic forms, phagocytosis and bacterial killing. C3 was analyzed in euglycemic and hyperglycemic conditions by mass spectrometry to measure glycation and structural differences. Elevated glucose inhibited S. aureus activation of C3 and deposition of C3b and iC3b on the bacterial surface. S. aureus-generated C5a and serum-mediated phagocytosis by neutrophils were both decreased in elevated glucose conditions. Interestingly, elevated glucose increased the binding of unactivated C3 to S. aureus, which was reversible on return to normal glucose concentrations. In a model of polymicrobial infection, S. aureus in elevated glucose conditions depleted C3 from serum resulting in decreased complement-mediated killing of E. coli. To investigate the effect of differing glucose concentration on C3 structure and glycation, purified C3 incubated with varying glucose concentrations was analyzed by mass spectrometry. Glycation was limited to the same three lysine residues in both euglycemic and hyperglycemic conditions over one hour, thus glycation could not account for observed changes between glucose conditions. However, surface labeling of C3 with sulfo-NHS-biotin showed significant changes in the surface availability of seven lysine residues in response to increasing glucose concentrations. These results suggest that the tertiary structure of C3 changes in response to hyperglycemic conditions leading to an altered interaction of C3 with bacterial pathogens. These results demonstrate that hyperglycemic conditions inhibit C3-mediated complement effectors important in the immunological control of S. aureus. Mass spectrometric analysis reveals that the

  1. Overexpression of AKR1C3 significantly enhances human prostate cancer cells resistance to radiation

    PubMed Central

    Gao, Xian-Shu; Li, Yi; Yu, Hongliang; Xiong, Wei; Yu, Hao; Wang, Wen; Li, Yingbo; Teng, Yingqi; Zhou, Demin

    2016-01-01

    Aldo-keto reductase 1C3(AKR1C3) is an enzyme involved in prostaglandins metabolism. Studies suggest that AKR1C3 has a pivotal role in the radioresistance of esophageal cancer and non-small-cell lung cancer, yet the role of AKR1C3 in prostate cancer cells radiation resistance has not yet been clarified. In our study, we established a stable overexpressing AKR1C3 cell line (AKR1C3-over) derived from the prostate cell line DU145 and its control cell line (Control). We conducted colony formation assay to determine the role of AKR1C3 in radioresistance and we used its chemical inhibitor to detect whether it can restored the sensitivity of the acquired tumor cells. Flow cytometry assay was carried out to detect IR-induced ROS accumulation. Elisa was adopted to dedect the concentration of PGF2α in the suspension of the cells after 6GY radiation. Western blotting was used to dedect the MAPK and PPAR γ. The results demonstrated that overexpression of AKR1C3 in prostate cancer can result in radioresistance and suppression of AKR1C3 via its chemical inhibitor indocin restored the sensitivity of the acquired tumor cells. According to the flow cytometry assay, ROS was decreased by 80% in DU145-over cells. Also overexpression of AKR1C3 could result in the accumulation of prostaglandin F2α (PGF2α), which can not only promote prostate cancer cell 's proliferation but also could enhance prostate cancer cells resistance to radiation and activated the MAPK pathway and inhibited the expression of PPARγ. In conclusion, we found that overexpression of AKR1C3 significantly enhanced human prostate cancer cells resistance to radiation through activation of MAPK pathway. PMID:27385003

  2. Circulating C3 levels predict renal and global outcome in patients with renal vasculitis.

    PubMed

    Villacorta, Javier; Diaz-Crespo, Francisco; Acevedo, Mercedes; Cavero, Teresa; Guerrero, Carmen; Praga, Manuel; Fernandez-Juarez, Gema

    2016-11-01

    Several studies have demonstrated the crucial role of complement activation in the pathogenesis of ANCA-associated vasculitis. We aimed to assess the association between baseline serum C3 (sC3) levels and long-term outcomes in patients with renal vasculitis. This retrospective study included 111 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Serum levels of C3 were measured at the onset and the study population was divided into three tertiles according to sC3 concentrations (tertile 1 <106 mg/dl; tertile 2 106-128 mg/dl; tertile 3 >128 mg/dl). Patients with lower sC3 (tertile 1) were compared with those having higher levels of sC3 (tertile 2 and tertile 3). Histological, clinical, and laboratory data were recorded for analysis. The primary end point was the composite of end-stage renal disease (ESRD) and death from any cause. Lower sC3 levels were associated with a higher need for dialysis and lower response rate to treatment (p = 0.04 and p = 0.007, respectively). Renal and global survival at 1 and 5 years was 53 and 46 % in patients with lower sC3 (tertile 1) compared with 72 and 65 % in patients with higher sC3 (upper two tertiles) (p = 0.04). In a multivariate Cox-regression model, when adjusted by renal function and histopatholologic categories, lower sC3 remained as an independent predictor of ESRD and death (HR, 1.9; 95 % CI, 1.1 to 3.4; p = 0.02). Baseline serum C3 levels have an independent prognostic value in predicting long-term renal and global survival in patients with renal vasculitis.

  3. Properdin binding to complement activating surfaces depends on initial C3b deposition

    PubMed Central

    Harboe, Morten; Johnson, Christina; Nymo, Stig; Ekholt, Karin; Schjalm, Camilla; Lindstad, Julie K.; Pharo, Anne; Hellerud, Bernt Christian; Nilsson Ekdahl, Kristina; Mollnes, Tom Eirik

    2017-01-01

    Two functions have been assigned to properdin; stabilization of the alternative convertase, C3bBb, is well accepted, whereas the role of properdin as pattern recognition molecule is controversial. The presence of nonphysiological aggregates in purified properdin preparations and experimental models that do not allow discrimination between the initial binding of properdin and binding secondary to C3b deposition is a critical factor contributing to this controversy. In previous work, by inhibiting C3, we showed that properdin binding to zymosan and Escherichia coli is not a primary event, but rather is solely dependent on initial C3 deposition. In the present study, we found that properdin in human serum bound dose-dependently to solid-phase myeloperoxidase. This binding was dependent on C3 activation, as demonstrated by the lack of binding in human serum with the C3-inhibitor compstatin Cp40, in C3-depleted human serum, or when purified properdin is applied in buffer. Similarly, binding of properdin to the surface of human umbilical vein endothelial cells or Neisseria meningitidis after incubation with human serum was completely C3-dependent, as detected by flow cytometry. Properdin, which lacks the structural homology shared by other complement pattern recognition molecules and has its major function in stabilizing the C3bBb convertase, was found to bind both exogenous and endogenous molecular patterns in a completely C3-dependent manner. We therefore challenge the view of properdin as a pattern recognition molecule, and argue that the experimental conditions used to test this hypothesis should be carefully considered, with emphasis on controlling initial C3 activation under physiological conditions. PMID:28069958

  4. The complement anaphylatoxin C3a receptor (C3aR) contributes to the inflammatory response in dextran sulfate sodium (DSS)-induced colitis in mice.

    PubMed

    Wende, Elisabeth; Laudeley, Robert; Bleich, André; Bleich, Eva; Wetsel, Rick A; Glage, Silke; Klos, Andreas

    2013-01-01

    Inflammatory bowel diseases are a critical public health issue, and as treatment options remain limited, there is a need to unravel the underlying pathomechanisms in order to identify new therapeutic targets. Complement activation was found in patients suffering from inflammatory bowel disease, and the complement anaphylatoxin C5a and its receptor C5aR have been implicated in disease pathogenesis in animal models of bowel inflammation. To further characterize complement-related pathomechanisms in inflammatory bowel disease, we have investigated the role of the anaphylatoxin C3a receptor in acute dextran sulfate sodium-induced colitis in mice. For this, colitis was induced in C3a receptor-deficient BALB/c and C57BL/6 mice, and disease severity was evaluated by clinical and histological examination, and by measuring the mRNA expression or protein levels of inflammatory mediators in the tissue. C3a receptor deficiency was partially protective in BALB/c mice, which had significantly reduced weight loss, clinical and histological scores, colon shortening, and CXCL-1/KC mRNA, myeloperoxidase and interleukin-6 tissue levels compared to the corresponding wild type mice. In C57BL/6 mice the differences between wild type and C3a receptor-deficient animals were much smaller and reached no significance. Our data demonstrate that the contribution of C3a receptor to disease pathogenesis and severity of dextran sulfate sodium-induced colitis in mice depends on the genetic background. Further studies will be required to clarify whether targeting of C3a receptor, possibly in combination with C5a receptor, might be considered as a therapeutic strategy for inflammatory bowel disease.

  5. Activation of the endothelium by IL-1 alpha and glucocorticoids results in major increase of complement C3 and factor B production and generation of C3a.

    PubMed Central

    Coulpier, M; Andreev, S; Lemercier, C; Dauchel, H; Lees, O; Fontaine, M; Ripoche, J

    1995-01-01

    Constitutive secretion of complement C3 and factor B by the endothelial cell (EC) is lowered by therapeutic concentrations of glucocorticoids such as hydrocortisone or dexamethasone, whereas regulatory protein factor H production is increased by these hormones. In contrast, the proinflammatory cytokine IL-1 alpha has a stimulatory effect on C3 and factor B secretion by the endothelium and an inhibitory effect on factor H secretion. In this study, we examined the combined effect of IL-1 alpha and glucocorticoids on C3 and factor B expression by the endothelial cell. When dexamethasone or hydrocortisone were added to IL-1 alpha, significant potentialization of IL-1 alpha-induced stimulation of C3 and factor B production was observed, occurring at various concentrations of either stimuli. Dose-response experiments indicate that, in vitro, optimal concentrations are in the range of 10(-7) to 10(-5) M for dexamethasone and 50-200 U for IL-1 alpha. In contrast, dexamethasone counteracts, in an additive way, the inhibitory effect of IL-1 alpha on regulatory complement protein factor H production by EC. Such a potentialization between glucocorticoids and IL-1 alpha was not observed for another marker of endothelial activation, IL-1 alpha-induced stimulation of coagulation tissue factor expression. The association of glucocorticoids and IL-1 alpha therefore appears to be a specific and major stimulus for the secretion of complement C3 and factor B, two acute-phase proteins, by the endothelium. As a result of the in vitro endothelium stimulation by glucocorticoids and IL-1 alpha, C3a is generated in the vicinity of the endothelial cell. This study further suggests that complement activation, with its deleterious consequences, may result from the stimulation of endothelium in situations where high levels of IL-1 alpha and endogenous glucocorticoids coexist, such as in septic shock. Images Fig. 4 Fig. 6 PMID:7621583

  6. A combined crossed beam and theoretical investigation of O(3P)+C3H3→C3H2+OH

    NASA Astrophysics Data System (ADS)

    Lee, Hohjai; Joo, Sun-Kyu; Kwon, Lee-Kyoung; Choi, Jong-Ho

    2004-02-01

    The radical-radical reaction dynamics of ground-state atomic oxygen [O(3P)] with propargyl radicals (C3H3) has first been investigated in a crossed beam configuration. The radical reactants O(3P) and C3H3 were produced by the photodissociation of NO2 and the supersonic flash pyrolysis of precursor propargyl bromide, respectively. A new exothermic channel of O(3P)+C3H3→C3H2+OH was identified and the nascent distributions of the product OH in the ground vibrational state (X 2Π:ν″=0) showed bimodal rotational excitations composed of the low- and high-N″ components without spin-orbit propensities. The averaged ratios of Π(A')/Π(A″) were determined to be 0.60±0.28. With the aid of ab initio theory it is predicted that on the lowest doublet potential energy surface, the reaction proceeds via the addition complexes formed through the barrierless addition of O(3P) to C3H3. The common direct abstraction pathway through a collinear geometry does not occur due to the high entrance barrier in our low collision energy regime. In addition, the major reaction channel is calculated to be the formation of propynal (CHCCHO)+H, and the counterpart C3H2 of the probed OH product in the title reaction is cyclopropenylidene (1c-C3H2) after considering the factors of barrier height, reaction enthalpy and structural features of the intermediates formed along the reaction coordinate. On the basis of the statistical prior and rotational surprisal analyses, the ratio of population partitioning for the low- and high-N″ is found to be about 1:2, and the reaction is described in terms of two competing addition-complex mechanisms: a major short-lived dynamic complex and a minor long-lived statistical complex. The observed unusual reaction mechanism stands in sharp contrast with the reaction of O(3P) with allyl radical (C3H5), a second significant conjugated hydrocarbon radical, which shows totally dynamic processes [J. Chem. Phys. 117, 2017 (2002)], and should be understood based

  7. Final Hazard Categorization for the Remediation of the 116-C-3 Chemical Waste Tanks

    SciTech Connect

    T. M. Blakley; W. D. Schofield

    2007-09-10

    This final hazard categorization (FHC) document examines the hazards, identifies appropriate controls to manage the hazards, and documents the commitments for the 116-C-3 Chemical Waste Tanks Remediation Project. The remediation activities analyzed in this FHC are based on recommended treatment and disposal alternatives described in the Engineering Evaluation for the Remediation to the 116-C-3 Chemical Waste Tanks (BHI 2005e).

  8. Analysis of C3 Counterinsurgency-Inspired Policing and the Flip Side of the Coin

    DTIC Science & Technology

    2014-12-01

    33 A. MEASURING THE IMPACT, A CASE STUDY OF C3 ..........................35 1. Medical Calls Related to Criminal Acts...ACRONYMS AND ABBREVIATIONS AMR American Medical Response C3 Counter Criminal Continuum CIA Central Intelligence Agency COIN counterinsurgency COMPSTAT...crime-related medical calls, should afford a broader understanding of the actual effects on the community than crime statistics alone could provide

  9. Electronic and rovibrational quantum chemical analysis of C3P-: the next interstellar anion?

    NASA Astrophysics Data System (ADS)

    Fortenberry, Ryan C.; Lukemire, Joseph A.

    2015-11-01

    C3P- is analogous to the known interstellar anion C3N- with phosphorus replacing nitrogen in a simple step down the periodic table. In this work, it is shown that C3P- is likely to possess a dipole-bound excited state. It has been hypothesized and observationally supported that dipole-bound excited states are an avenue through which anions could be formed in the interstellar medium. Additionally, C3P- has a valence excited state that may lead to further stabilization of this molecule, and C3P- has a larger dipole moment than neutral C3P (˜6 D versus ˜4 D). As such, C3P- is probably a more detectable astromolecule than even its corresponding neutral radical. Highly accurate quantum chemical quartic force fields are also applied to C3P- and its singly 13C substituted isotopologues in order to provide structures, vibrational frequencies, and spectroscopic constants that may aid in its detection.

  10. Modeling the Impact of Value of Information on Situational Awareness using C3TRACE

    DTIC Science & Technology

    2016-05-01

    researchers use C3TRACE software to simulate a basic human intelligence reports analysis process and observe if the results support the hypothesis that the VoI...model used in this experiment is created and exercised using the C3TRACE software (Fig. 4). As stated previously, the model is the product of several

  11. Guiding Inquiry with Biography Breaks and the C3 Framework: Can One Person Make a Difference?

    ERIC Educational Resources Information Center

    Young, Terrell A.; Miner, Amy Baird

    2015-01-01

    The purpose of this article is to explore how teachers can use biography breaks to address the National Council of the Social Studies C3 inquiry framework and in the process meet requirements of the Common Core State Standards. We begin by illustrating and explaining biography breaks. Then we introduce the C3 framework and explain as well as…

  12. 18 CFR 3c.3 - Reporting fraud, waste, abuse, and corruption and cooperation with official inquiries.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Reporting fraud, waste, abuse, and corruption and cooperation with official inquiries. 3c.3 Section 3c.3 Conservation of Power..., whether orally or in writing, and must provide documents and other materials concerning matters of...

  13. Enhancement of photocatalytic and photoelectrocatalytic activity of Ag modified Mpg-C3N4 composites

    NASA Astrophysics Data System (ADS)

    He, Qiuchen; Zhou, Feng; Zhan, Su; Yang, Yifan; Liu, Yujun; Tian, Yu; Huang, Naibao

    2017-01-01

    In this study, mpg-C3N4/Ag composites of surface plasmon resonance structures were fabricated to improve the photocatalytic and photoelectrocatalytic activities of g-C3N4 via photo-assisted reduction method, which were characterized by XRD, EDS, XPS, FT-IR, FE-SEM, TEM, DRS and BET. The photocatalytic and photoelectrocatalytic activities were evaluated by the degradation of methylene blue (MB) and the oxygen reduction experiment under visible light. The results showed the photocatalytic and photoelectrocatalytic activities were dependent on the weight ratio of Ag and the optimum photocatalytic activity of mpg-C3N4/Ag at a weight ratio of 3% is almost 3 times as high as that of mpg-C3N4. Additionally, mpg-C3N4/Ag exhibited a significantly enhanced oxygen reduction performance under visible light. The limit current density was increased about 2 times by the modification of Ag nanoparticles, compared with that of pristine mpg-C3N4. Finally, based on the first principle, the enhancement mechanism of the photocatalytic and photoelectrocatalytic activities was discussed by the calculation on the band structure and density of states in the mpg-C3N4/Ag composites. The appropriate amount of Ag modification would cause the surface plasmon resonance effect, which improved the photocatalytic, photoelectrocatalytic, and oxygen reduction activities of mpg-C3N4.

  14. High-yield synthesis and optical properties of g-C3N4.

    PubMed

    Yuan, Yanwen; Zhang, Lulu; Xing, Jun; Utama, M Iqbal Bakti; Lu, Xin; Du, Kezhao; Li, Yongmei; Hu, Xiao; Wang, Shijie; Genç, Aziz; Dunin-Borkowski, Rafal; Arbiol, Jordi; Xiong, Qihua

    2015-08-07

    Graphitic carbon nitride (g-C3N4), a metal-free semiconductor with a band gap of 2.7 eV, has received considerable attention owing to its fascinating photocatalytic performances under visible-light. g-C3N4 exhibits high thermal and chemical stability and non-toxicity such that it has been considered as the most promising photocatalyst for environmental improvement and energy conservation. Hence, it is of great importance to obtain high-quality g-C3N4 and gain a clear understanding of its optical properties. Herein, we report a high-yield synthesis of g-C3N4 products via heating of high vacuum-sealed melamine powder in an ampoule at temperatures between 450 and 650 °C. Using transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), electron energy loss spectroscopy (EELS), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS), the chemical composition and crystallization of the as-produced g-C3N4 are demonstrated. A systematic optical study of g-C3N4 is carried out with several approaches. The optical phonon behavior of g-C3N4 is revealed by infrared and Raman spectroscopy, and the emission properties of g-C3N4 are investigated using photoluminescence (PL) spectroscopy, while the photocatalytic properties are explored by the photodegradation experiment.

  15. 26 CFR 301.6501(n)-2 - Certain contributions to section 501(c)(3) organizations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 18 2013-04-01 2013-04-01 false Certain contributions to section 501(c)(3) organizations. 301.6501(n)-2 Section 301.6501(n)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Assessment and Collection § 301.6501(n)-2 Certain contributions to section 501(c)(3) organizations. If a...

  16. 26 CFR 301.6501(n)-2 - Certain contributions to section 501(c)(3) organizations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Certain contributions to section 501(c)(3) organizations. 301.6501(n)-2 Section 301.6501(n)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Assessment and Collection § 301.6501(n)-2 Certain contributions to section 501(c)(3) organizations. If a...

  17. 26 CFR 301.6501(n)-2 - Certain contributions to section 501(c)(3) organizations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 18 2012-04-01 2012-04-01 false Certain contributions to section 501(c)(3) organizations. 301.6501(n)-2 Section 301.6501(n)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Assessment and Collection § 301.6501(n)-2 Certain contributions to section 501(c)(3) organizations. If a...

  18. First-principles calculations on Mg/Al4C3 interfaces

    NASA Astrophysics Data System (ADS)

    Li, K.; Sun, Z. G.; Wang, F.; Zhou, N. G.; Hu, X. W.

    2013-04-01

    In order to explore the interfacial structure of Mg/Al4C3 interface and clarify the heterogeneous nucleation potential of Al4C3 particles in Mg melt. The atomic structure, bonding, and interfacial energy of Mg/Al4C3 interfaces were studied by first-principles calculations to analyze the sequence of Mg atoms onto the surface of Al4C3 (0 0 0 1) slab. Surface energy calculations show that the outmost layer of Al4C3 free surface having a preference of C atom termination. And polar covalent/ionic mixed bonds are formed across interface during the combination of Mg atoms with C-terminated Al4C3 surface. The calculated interfacial energy of Mg/Al4C3 interface is much smaller than that between α-Mg and magnesium melts, proving the excellent nucleation potency of Al4C3 particles for α-Mg grains from interfacial atomic structure and atomic bonding energy considerations.

  19. Establishing a Research Center: The Minority Male Community College Collaborative (M2C3)

    ERIC Educational Resources Information Center

    Wood, J. Luke; Urias, Marissa Vasquez; Harris, Frank, III

    2016-01-01

    This chapter describes the establishment of the Minority Male Community College Collaborative (M2C3), a research and practice center at San Diego State University. M2C3 partners with community colleges across the United States to enhance access, achievement, and success among men of color. This chapter begins with a description of the national…

  20. 26 CFR 1.652(c)-3 - Termination of existence of other beneficiaries.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Termination of existence of other beneficiaries. 1.652(c)-3 Section 1.652(c)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Termination of existence of other beneficiaries. If the existence of a beneficiary which is not an individual...

  1. Guiding Inquiry with Biography Breaks and the C3 Framework: Can One Person Make a Difference?

    ERIC Educational Resources Information Center

    Young, Terrell A.; Miner, Amy Baird

    2015-01-01

    The purpose of this article is to explore how teachers can use biography breaks to address the National Council of the Social Studies C3 inquiry framework and in the process meet requirements of the Common Core State Standards. We begin by illustrating and explaining biography breaks. Then we introduce the C3 framework and explain as well as…

  2. C3 glomerulopathy associated to multiple myeloma successfully treated by autologous stem cell transplant

    PubMed Central

    Hamzi, M. A.; Zniber, A.; Badaoui, G. E.; Mahtat, E.; Alhamany, Z.; Bayahia, R.; Ouzeddoun, N.

    2017-01-01

    A 32-year-old male presented with advanced renal failure and nephrotic proteinuria due to lambda light chain multiple myeloma. Renal biopsy showed a proliferative glomerulonephritis with isolated C3 deposits. Renal recovery was obtained after chemotherapy and autologous stem cell transplant. We review previously described cases of C3 glomerulopathy associated with monoclonal gammopathy. PMID:28356669

  3. Isoelectric point and adsorption activity of porous g-C3N4

    NASA Astrophysics Data System (ADS)

    Zhu, Bicheng; Xia, Pengfei; Ho, Wingkei; Yu, Jiaguo

    2015-07-01

    The isoelectric point (IEP) is an important physicochemical parameter of many compounds, such as oxides, hydroxides, and nitrides, and can contribute to estimation of the surface charges of compound particles at various pH conditions. In this work, three types of graphitic carbon nitrides (g-C3N4) were synthesized by directly heating melamine, thiourea, and urea. The prepared samples showed different microstructures and IEPs that influenced their adsorption activity. Differences in microstructure resulted from the various precursors used during synthesis. The IEPs of the obtained g-C3N4 were measured to be approximately 4-5, which is due to the equilibrium of chemical reactions between hydrogen ions, hydroxyl ions, and amine groups on the g-C3N4 surface. The IEP of g-C3N4 prepared from thiourea was lower than those of the corresponding samples prepared from melamine and urea. The adsorption activity of methylene blue on g-C3N4 prepared from urea and thiourea was excellent, which indicates that g-C3N4 is a promising adsorbent. This work provides a useful reference for choosing precursors with which to prepare g-C3N4 and combining g-C3N4 with other compounds in solution.

  4. C3 glomerulopathy–associated CFHR1 mutation alters FHR oligomerization and complement regulation

    PubMed Central

    Tortajada, Agustín; Yébenes, Hugo; Abarrategui-Garrido, Cynthia; Anter, Jaouad; García-Fernández, Jesús M.; Martínez-Barricarte, Rubén; Alba-Domínguez, María; Malik, Talat H.; Bedoya, Rafael; Pérez, Rocío Cabrera; Trascasa, Margarita López; Pickering, Matthew C.; Harris, Claire L.; Sánchez-Corral, Pilar; Llorca, Oscar; Rodríguez de Córdoba, Santiago

    2013-01-01

    C3 glomerulopathies (C3G) are a group of severe renal diseases with distinct patterns of glomerular inflammation and C3 deposition caused by complement dysregulation. Here we report the identification of a familial C3G-associated genomic mutation in the gene complement factor H–related 1 (CFHR1), which encodes FHR1. The mutation resulted in the duplication of the N-terminal short consensus repeats (SCRs) that are conserved in FHR2 and FHR5. We determined that native FHR1, FHR2, and FHR5 circulate in plasma as homo- and hetero-oligomeric complexes, the formation of which is likely mediated by the conserved N-terminal domain. In mutant FHR1, duplication of the N-terminal domain resulted in the formation of unusually large multimeric FHR complexes that exhibited increased avidity for the FHR1 ligands C3b, iC3b, and C3dg and enhanced competition with complement factor H (FH) in surface plasmon resonance (SPR) studies and hemolytic assays. These data revealed that FHR1, FHR2, and FHR5 organize a combinatorial repertoire of oligomeric complexes and demonstrated that changes in FHR oligomerization influence the regulation of complement activation. In summary, our identification and characterization of a unique CFHR1 mutation provides insights into the biology of the FHRs and contributes to our understanding of the pathogenic mechanisms underlying C3G. PMID:23728178

  5. ClC-3 chloride channel functions as a mechanically sensitive channel in osteoblasts.

    PubMed

    Wang, Huan; Wang, Rong; Wang, Zhe; Liu, Qian; Mao, Yong; Duan, Xiaohong

    2015-12-01

    Mechanical stimulation usually causes the volume changes of osteoblasts. Whether these volume changes could be sensed by the ClC-3 chloride channel, a volume-sensitive ion channel, and further promote the osteodifferentiation in osteoblasts has not been determined. In this study, we applied persistent static compression on MC3T3-E1 cells to detect the expression changes of ClC-3, osteogenic markers, as well as some molecules related with signaling transduction pathway. We tested the key role of ClC-3 in transferring the mechanical signal to osteoinduction by ClC-3 overexpressing and siRNA technique. We found that ClC-3 level was up-regulated by mechanical stimulation in MC3T3-E1 cells. Mechanical force also up-regulated the mRNA level of osteogenic markers such as alkaline phosphatase (Alp), bone sialoprotein (Bsp), and osteocalcin (Oc), which could be blocked or strengthened by Clcn3 siRNA or overexpressing, and Alp expression was more sensitive to the changes of ClC-3 level. We also found that runt-related transcription factor 2 (Runx2), transforming growth factor beta 1 (TGF-β1), and Wnt pathway might be involved in ClC-3 mediated mechanical transduction in osteoblasts. The data from the current study suggest that the ClC-3 chloride channel acts as a mechanically sensitive channel to regulate osteodifferentiation in osteoblasts.

  6. 26 CFR 301.6501(n)-2 - Certain contributions to section 501(c)(3) organizations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Certain contributions to section 501(c)(3) organizations. 301.6501(n)-2 Section 301.6501(n)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Assessment and Collection § 301.6501(n)-2 Certain contributions to section 501(c)(3) organizations. If...

  7. Inhibition of AKR1C3 Activation Overcomes Resistance to Abiraterone in Advanced Prostate Cancer.

    PubMed

    Liu, Chengfei; Armstrong, Cameron M; Lou, Wei; Lombard, Alan; Evans, Christopher P; Gao, Allen C

    2017-01-01

    Abiraterone suppresses intracrine androgen synthesis via inhibition of CYP17A1. However, clinical evidence suggests that androgen synthesis is not fully inhibited by abiraterone and the sustained androgen production may lead to disease relapse. In the present study, we identified AKR1C3, an important enzyme in the steroidogenesis pathway, as a critical mechanism driving resistance to abiraterone through increasing intracrine androgen synthesis and enhancing androgen signaling. We found that overexpression of AKR1C3 confers resistance to abiraterone while downregulation of AKR1C3 resensitizes resistant cells to abiraterone treatment. In abiraterone-resistant prostate cancer cells, AKR1C3 is overexpressed and the levels of intracrine androgens are elevated. In addition, AKR1C3 activation increases intracrine androgen synthesis and enhances androgen receptor (AR) signaling via activating AR transcriptional activity. Treatment of abiraterone-resistant cells with indomethacin, an AKR1C3 inhibitor, overcomes resistance and enhances abiraterone therapy both in vitro and in vivo by reducing the levels of intracrine androgens and diminishing AR transcriptional activity. These results demonstrate that AKR1C3 activation is a critical mechanism of resistance to abiraterone through increasing intracrine androgen synthesis and enhancing androgen signaling. Furthermore, this study provides a preclinical proof-of-principle for clinical trials investigating the combination of targeting AKR1C3 using indomethacin with abiraterone for advanced prostate cancer. Mol Cancer Ther; 16(1); 35-44. ©2016 AACR.

  8. 26 CFR 301.6501(n)-2 - Certain contributions to section 501(c)(3) organizations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Certain contributions to section 501(c)(3) organizations. 301.6501(n)-2 Section 301.6501(n)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Assessment and Collection § 301.6501(n)-2 Certain contributions to section 501(c)(3) organizations. If a...

  9. 17 CFR 240.15c3-2 - Customers' free credit balances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... balances. 240.15c3-2 Section 240.15c3-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Customers' free credit balances. No broker or dealer shall use any funds arising out of any free credit balance carried for the account of any customer in connection with the operation of the business of such...

  10. 17 CFR 240.15c3-2 - Customers' free credit balances.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... balances. 240.15c3-2 Section 240.15c3-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Customers' free credit balances. No broker or dealer shall use any funds arising out of any free credit balance carried for the account of any customer in connection with the operation of the business of such...

  11. 17 CFR 240.15c3-2 - Customers' free credit balances.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... balances. 240.15c3-2 Section 240.15c3-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Customers' free credit balances. No broker or dealer shall use any funds arising out of any free credit balance carried for the account of any customer in connection with the operation of the business of such...

  12. 17 CFR 240.15c3-2 - Customers' free credit balances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... balances. 240.15c3-2 Section 240.15c3-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Customers' free credit balances. No broker or dealer shall use any funds arising out of any free credit balance carried for the account of any customer in connection with the operation of the business of such...

  13. Establishing a Research Center: The Minority Male Community College Collaborative (M2C3)

    ERIC Educational Resources Information Center

    Wood, J. Luke; Urias, Marissa Vasquez; Harris, Frank, III

    2016-01-01

    This chapter describes the establishment of the Minority Male Community College Collaborative (M2C3), a research and practice center at San Diego State University. M2C3 partners with community colleges across the United States to enhance access, achievement, and success among men of color. This chapter begins with a description of the national…

  14. 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. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

  15. A Quantum Chemical Study of the Dissociative Recombination of C3H3+ - The Formation of Interstellar C3H2

    NASA Astrophysics Data System (ADS)

    Talbi, D.

    Quantum chemical calculations: Talbi & all (1993), Talbi & Ellinger (1998), Hickman & all (2005) have proven to be extremely useful for the understanding of electronic dissociative recombination processes (hereafter DR). Such processes may occur by direct and/or indirect mechanism; while the former involves a direct transition from the ionic state to the final neutral dissociative state, the second one is a two step process involving the formation of a vibrationally (rotationally) excited state of the neutral molecule. For this last case, either autoionization takes place or the state obtained after binding of the electron relaxes to lower energy states, leading if they have a dissociative charactere, to fragmentation of the molecule. Understanding such processes requires the knowledge of the potential energy surfaces governing the corresponding mechanism i.e. the potential energy surfaces of the ionic, excited and dissociative states of the parent neutral molecule. The difficulty in treating such problems resides in, first of all, the description of excited and dissociative states along the dissociative coordinate. This is not a trivial task because, very often, the nature of the states changes along such channels; carefully designed wavefunctions are thus necessary to follow those transformations. But the difficulty is also in the even handed treatment required for all the states involved in the mechanism. State of the art ab-initio quantum chemical methods are needed for a quantitative study of this kind of processes. To illustrate this matter, a quantum chemical investigation undertaken on the DR of the ion thought to be the source of the ubiquitous linear and cyclic C3H2 in diffuse and dense clouds : the C3H3+ ion, will be presented Our quantum chemical study of the c-C3H3+ + e- → c-C3H2 + H and l-C3H3+ + e- → l-C3H2 + H processes shows that while, for the first process, there is an efficient curve crossing (i.e for v = 0) between the ionic state of c-C3H3

  16. C3G regulates the size of the cerebral cortex neural precursor population

    PubMed Central

    Voss, Anne K; Krebs, Danielle L; Thomas, Tim

    2006-01-01

    The mechanisms regulating the size of the cerebral cortex are poorly understood. Here, we demonstrate that the Rap1 guanine nucleotide exchange factor, C3G (Grf2, Rapgef1), controls the size of the cerebral precursor population. Mice lacking C3G show overproliferation of the cortical neuroepithelium. C3G-deficient neuroepithelial cells accumulate nuclear β-catenin and fail to exit the cell cycle in vivo. C3G mutant neural precursor cells fail to activate Rap1, exhibit activation of Akt/PKB, inhibition of the β-catenin-degrading enzyme, Gsk3β and accumulation of cytosolic and nuclear β-catenin when exposed to growth factors, in vitro. Our results show that the size of the cortical neural precursor population is controlled by C3G-mediated inhibition of the Ras signalling pathway. PMID:16858399

  17. Convergence of potential net ecosystem production among contrasting C3 grasslands

    NASA Astrophysics Data System (ADS)

    Peichl, Matthias; Sonnentag, Oliver; Wohlfahrt, Georg; Flanagan, Lawrence B.; Baldocchi, Dennis D.; Kiely, Gerard; Galvagno, Marta; Gianelle, Damiano; Marcolla, Barbara; Pio, Casimiro; Migliavacca, Mirco; Jones, Michael B.; Saunders, Matthew

    2013-04-01

    Metabolic theory and body size constraints on biomass production and decomposition suggest that differences in the intrinsic potential net ecosystem production (NEPpot) should be small among contrasting C3 grasslands and therefore unable to explain the wide range in the annual apparent net ecosystem production (NEPapp) reported by previous studies. We estimated NEPpot for nine C3 grasslands under contrasting climate and management regimes using multi-year eddy covariance data. NEPpot converged within a narrow range suggesting little difference in the net carbon dioxide uptake capacity among C3 grasslands. Our results indicate a unique feature of C3 grasslands compared to other terrestrial ecosystems and suggest a state of stability in NEPpot due to tightly coupled production and respiration processes. Consequently, the annual NEPapp of C3 grasslands is primarily a function of seasonal and short-term environmental and management constraints, and therefore especially susceptible to changes in future climate patterns and associated adaptation of management practices.

  18. Contribution to Kinetics of Superplastic Deformation of Dispersion Strengthened Al-Al4C3 System

    NASA Astrophysics Data System (ADS)

    Besterci, Michal; Varchola, Marián; Kováč, Ladislav; Velgosová, Oksana

    2012-02-01

    The influence of temperature at constant strain rate has been evaluated with respect to superplastic behavior of dispersion strengthened Al-Al4C3 composite with 4 vol.% of Al4C3 phase. The dispersion strengthened Al-Al4C3 was prepared by powder metallurgy. Material can be characterized by grain size around 1 μm and dispersed particle Al4C3 size around 50 nm. This material showed superplastic behavior for strain rate 10-3 s-1 by test temperature 573 K. The mechanism of superplastic deformation was also investigated. For the presented material with low content of disperse particle slip on grain boundaries is typical. The final fracture is transcrystalline with dimples with their mean size 1.25 μm. The dimples are initialized by Al4C3 particles in size from 40 to 50 nm.

  19. Influence of Si ion implantation on structure and morphology of g-C3N4

    NASA Astrophysics Data System (ADS)

    Varalakshmi, B.; Sreenivasulu, K. V.; Asokan, K.; Srikanth, V. V. S. S.

    2016-07-01

    Effect of Si ion implantation on structural and morphological features of graphite-like carbon nitride (g-C3N4) was investigated. g-C3N4 was prepared by using a simple atmospheric thermal decomposition process. The g-C3N4 pellets were irradiated with a Si ion beam of energy 200 keV with different fluencies. Structural, morphological and elemental, and phase analysis of the implanted samples in comparison with the pristine samples was carried out by using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) with energy dispersive spectroscopy (EDS) and Fourier transform infrared spectroscopy (FTIR) techniques, respectively. The observations revealed that Si ion implantation results in a negligible change in the crystallite size and alteration of the network-like to the sheet-like morphology of g-C3N4 and Si ions in the g-C3N4 network.

  20. Convergence of potential net ecosystem production among contrasting C3 grasslands

    PubMed Central

    Peichl, Matthias; Sonnentag, Oliver; Wohlfahrt, Georg; Flanagan, Lawrence B.; Baldocchi, Dennis D.; Kiely, Gerard; Galvagno, Marta; Gianelle, Damiano; Marcolla, Barbara; Pio, Casimiro; Migliavacca, Mirco; Jones, Michael B.; Saunders, Matthew

    2013-01-01

    Metabolic theory and body size dependent constraints on biomass production and decomposition suggest that differences in the intrinsic potential net ecosystem production (NEPPOT) should be small among contrasting C3 grasslands and therefore unable to explain the wide range in the annual apparent net ecosystem production (NEPAPP) reported by previous studies. We estimated NEPPOT for nine C3 grasslands under contrasting climate and management regimes using multi-year eddy covariance data. NEPPOT converged within a narrow range suggesting little difference in the net carbon dioxide uptake capacity across C3 grasslands. Our results indicate a unique feature of C3 grasslands compared to other terrestrial ecosystems and suggest a state of stability in NEPPOT due to tightly coupled production and respiration processes. Consequently, the annual NEPAPP of C3 grasslands is primarily a function of seasonal and short-term environmental and management constraints, and therefore especially susceptible to changes in future climate patterns and associated adaptation of management practices. PMID:23346985

  1. Structural basis for duplex RNA recognition and cleavage by Archaeoglobus fulgidus C3PO

    PubMed Central

    Parizotto, Eneida A; Lowe, Edward D; Parker, James S

    2013-01-01

    Oligomeric complexes of Trax and Translin proteins, known as C3POs, participate in a variety of eukaryotic nucleic acid metabolism pathways including RNAi and tRNA processing. In RNAi in humans and Drosophila, C3PO activates pre-RISC by removing the passenger strand of the siRNA precursor duplex using nuclease activity present in Trax. It is not known how C3POs engage with nucleic acid substrates. Here we identify a single protein from Archaeoglobus fulgidus that assembles into an octamer with striking similarity to human C3PO. The structure in complex with duplex RNA reveals that the octamer entirely encapsulates a single thirteen base-pair RNA duplex inside a large inner cavity. Trax-like subunit catalytic sites target opposite strands of the duplex for cleavage, separated by seven base pairs. The structure provides insight into the mechanism of RNA recognition and cleavage by an archaeal C3PO-like complex. PMID:23353787

  2. Identification of C3 acceptors responsible for complement activation in Crithidia fasciculata

    SciTech Connect

    Guether, M.L.T.; Travassos, L.R.; Schenkman, S.

    1988-11-01

    Crithidia fasciculata, an insect trypanosomatid is readily lysed by normal human serum at concentrations as low as 3%. Lysis occurs in the presence of Mg+2-EGTA and is antibody independent, indicating that the alternative pathway of complement activation is involved. Analysis of (131I)C3 deposition on C. fasciculata cells using C8-deficient serum, revealed that about 4 x 10(5) C3 molecules bound to each cell. Most of the C3 was bound to cells as C3b, part of it forming high molecular weight complexes, which could be dissociated by methylamine treatment at alkaline pH. To characterize the C3 acceptors on C. fasciculata, surface-iodinated cells were incubated with C8D or heat-inactivated serum, extracted and immunoprecipitated with anti-C3 or anti-arabinogalactan antisera. Analysis of the immunoprecipitated material on SDS gels showed high-molecular weight components, which disappeared after methylamine treatment, giving rise to a component of 200 kDa molecular size. This 200-kDa component corresponded to a purified arabinogalactan complex, which was immunoprecipitated from labeled cell extracts, without incubation with C8D, using anti-arabinogalactan antibodies. These results suggest that the arabinogalactan glycoconjugate is a C3 acceptor in C. fasciculata during complement activation. Purified arabinogalactan complexes were able to inactivate C3 in vitro. Solubilization in KOH to cleave the peptide moiety rendered it unable to inactivate C3. Apparently, the aggregated state of the purified arabinogalactan component at the cell surface is important for C3 deposition and activation.

  3. Effect of xid on autoimmune C3H-gld/gld mice.

    PubMed

    Seldin, M F; Reeves, J P; Scribner, C L; Roths, J B; Davidson, W F; Morse, H C; Steinberg, A D

    1987-06-01

    The xid gene was introduced into C3H-gld/gld mice to determine its effects on the development of autoimmune disease. C3H-gld/gld.xid mice were compared with C3H-gld/gld mice for the development of lymphadenopathy, surface phenotype of lymph node (LN) cells, c-myb oncogene RNA production, serum immunoglobulin (Ig) levels, and autoantibody production. In addition, C3H-gld/gld and C3H-lpr/lpr mice were examined for serum Ig and autoantibody levels. The results showed that the xid gene had no effect on either the development of the severe lymphadenopathy characteristic of C3H-gld/gld mice or the phenotype of the Ly-2-, L3T4-, Ly-5(B220)+ T-cell subset that is expanded in the LN and spleens of these mice. Similarly, xid did not affect the high levels of c-myb oncogene RNA expression by C3H-gld/gld LN and spleen cells. By contrast, the xid gene caused a significant reduction in serum IgM but not IgA levels and almost completely ablated the generation of both IgM and IgG anti-ssDNA antibodies and anti-dsDNA antibodies. These data suggest that the xid gene can dramatically decrease the B-cell manifestations of autoimmunity in gld homozygotes without affecting their abnormal T-cell expansion. Comparisons of age-matched C3H-gld/gld and C3H-lpr/lpr mice showed that they had similarly elevated serum IgM and IgA levels and anti-ssDNA and anti-dsDNA antibody levels providing further evidence that gld and lpr produce parallel defects in C3H mice.

  4. Functional regulation of ClC-3 in the migration of vascular smooth muscle cells.

    PubMed

    Ganapathi, Sindura B; Wei, Shun-Guang; Zaremba, Angelika; Lamb, Fred S; Shears, Stephen B

    2013-01-01

    Migration of vascular smooth muscle cells (VSMCs) into neointima contributes to atherosclerosis and restenosis. This migration requires coordinated plasmalemmal fluxes of water and ions. Here, we show that aortic VSMC migration depends on the regulation of transmembrane Cl(-) flux by ClC-3, a Cl(-) channel/transporter. The contribution of ClC-3 to plasmalemmal Cl(-) current was studied in VSMCs by electrophysiological recordings. Cl(-) current was negligible in cells perfused with 0 [Ca(2+)]. Raising intracellular [Ca(2+)] to 0.5 μM activated a Cl(-) current (I(Cl.Ca)), approximately half of which was eliminated on inhibition by KN-93 of calmodulin-dependent protein kinase II. I(Cl.Ca) was also halved by inositol-3,4,5,6-tetrakisphosphate, a cellular signal with the biological function of specifically preventing calmodulin-dependent protein kinase II from activating I(Cl.Ca). Gene disruption of ClC-3 reduced I(Cl.Ca) by 50%. Moreover, I(Cl.Ca) in the ClC-3 null VSMCs was not affected by either KN-93 or inositol-3,4,5,6-tetrakisphosphate. We conclude that I(Cl.Ca) is composed of 2 components, one is ClC-3 independent whereas the other is ClC-3 dependent, activated by calmodulin-dependent protein kinase II and inhibited by inositol-3,4,5,6-tetrakisphosphate. We also assayed VSMC migration in transwell assays. Migration was halved in ClC-3 null cells versus wild-type cells. In addition, inhibition of ClC-3 by niflumic acid, KN-93, or inositol-3,4,5,6-tetrakisphosphate each reduced cell migration in wild-type cells but not in ClC-3 null cells. These cell-signaling roles of ClC-3 in VSMC migration suggest new therapeutic approaches to vascular remodeling diseases.

  5. The ClC-3 chloride channel and osmoregulation in the European sea bass, Dicentrarchus labrax.

    PubMed

    Bossus, Maryline; Charmantier, Guy; Blondeau-Bidet, Eva; Valletta, Bianca; Boulo, Viviane; Lorin-Nebel, Catherine

    2013-07-01

    Dicentrarchus labrax migrates between sea (SW), brackish and fresh water (FW) where chloride concentrations and requirements for chloride handling change: in FW, fish absorb chloride and restrict renal losses; in SW, they excrete chloride. In this study, the expression and localization of ClC-3 and Na(+)/K(+)-ATPase (NKA) were studied in fish adapted to SW, or exposed to FW from 10 min to 30 days. In gills, NKA-α1 subunit expression transiently increased from 10 min and reached a stabilized intermediate expression level after 24 h in FW. ClC-3 co-localized with NKA in the basolateral membrane of mitochondria-rich cells (MRCs) at all conditions. The intensity of MRC ClC-3 immunostaining was significantly higher (by 50 %) 1 h after the transfer to FW, whereas the branchial ClC-3 protein expression was 30 % higher 7 days after the transfer as compared to SW. This is consistent with the increased number of immunopositive MRCs (immunostained for NKA and ClC-3). However, the ClC-3 mRNA expression was significantly lower in FW gills. In the kidney, after FW transfer, a transient decrease in NKA-α1 subunit expression was followed by significantly higher stable levels from 24 h. The low ClC-3 protein expression detected at both salinities was not observed by immunocytochemistry in the SW kidney; ClC-3 was localized in the basal membrane of the collecting ducts and tubules 7 and 30 days after transfer to FW. Renal ClC-3 mRNA expression, however, seemed higher in SW than in FW. The potential role of this chloride channel ClC-3 in osmoregulatory and osmosensing mechanisms is discussed.

  6. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

    SciTech Connect

    Wang, Qian-fei; Liu, Xin; O'Connell, Jeff; Peng, Ze; Krauss, Ronald M.; Rainwater, David L.; VandeBerg, John L.; Rubin, Edward M.; Cheng, Jan-Fang; Pennacchio, Len A.

    2003-09-15

    Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human QTL genes in a highly controlled non-human primate model.

  7. 17 CFR 240.15c3-1d - Satisfactory Subordination Agreements (Appendix D to 17 CFR 240.15c3-1).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (D). (2) Certain Definitions. For purposes of 17 CFR 240.15c3-1 and this Appendix (D): (i) A... market value of commodity options purchased by option customers subject to the rules of a contract market, each such deduction not to exceed the amount of funds in the option customer's account), if greater....

  8. Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications.

    PubMed

    Subías Hidalgo, Marta; Yébenes, Hugo; Rodríguez-Gallego, César; Martín-Ambrosio, Adrián; Domínguez, Mercedes; Tortajada, Agustin; Rodríguez de Córdoba, Santiago; Llorca, Oscar

    2017-03-01

    C3 is the central component of the complement system. Upon activation, C3 sequentially generates various proteolytic fragments, C3a, C3b, iC3b, C3dg, each of them exposing novel surfaces, which are sites of interaction with other proteins. C3 and its fragments are therapeutic targets and markers of complement activation. We report the structural and functional characterization of four monoclonal antibodies (mAbs) generated by immunizing C3-deficient mice with a mixture of human C3b, iC3b and C3dg fragments, and discuss their potential applications. This collection includes three mAbs interacting with native C3 and inhibiting AP complement activation; two of them by blocking the cleavage of C3 by the AP C3-converase and one by impeding formation of the AP C3-convertase. The interaction sites of these mAbs in the target molecules were determined by resolving the structures of Fab fragments bound to C3b and/or iC3b using electron microscopy. A fourth mAb specifically recognizes the iC3b, C3dg, and C3d fragments. It binds to an evolutionary-conserved neoepitope generated after C3b cleavage by FI, detecting iC3b/C3dg deposition over opsonized surfaces by flow cytometry and immunohistochemistry in human and other species. Because well-characterized anti-complement mAbs are uncommon, the mAbs reported here may offer interesting therapeutic and diagnostic opportunities.

  9. 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.

  10. Structural influence of gene networks on their inference: analysis of C3NET

    PubMed Central

    2011-01-01

    Background The availability of large-scale high-throughput data possesses considerable challenges toward their functional analysis. For this reason gene network inference methods gained considerable interest. However, our current knowledge, especially about the influence of the structure of a gene network on its inference, is limited. Results In this paper we present a comprehensive investigation of the structural influence of gene networks on the inferential characteristics of C3NET - a recently introduced gene network inference algorithm. We employ local as well as global performance metrics in combination with an ensemble approach. The results from our numerical study for various biological and synthetic network structures and simulation conditions, also comparing C3NET with other inference algorithms, lead a multitude of theoretical and practical insights into the working behavior of C3NET. In addition, in order to facilitate the practical usage of C3NET we provide an user-friendly R package, called c3net, and describe its functionality. It is available from https://r-forge.r-project.org/projects/c3net and from the CRAN package repository. Conclusions The availability of gene network inference algorithms with known inferential properties opens a new era of large-scale screening experiments that could be equally beneficial for basic biological and biomedical research with auspicious prospects. The availability of our easy to use software package c3net may contribute to the popularization of such methods. Reviewers This article was reviewed by Lev Klebanov, Joel Bader and Yuriy Gusev. PMID:21696592

  11. MnO2/g-C3N4 nanocomposite with highly enhanced supercapacitor performance

    NASA Astrophysics Data System (ADS)

    Chang, Xueting; Zhai, Xinxin; Sun, Shibin; Gu, Danxia; Dong, Lihua; Yin, Yansheng; Zhu, Yanqiu

    2017-03-01

    A novel sandwich-like MnO2/g-C3N4 nanocomposite (NC) based on the integration of high-density MnO2 nanorods (NRs) onto the surfaces of two-dimensional (2D) g-C3N4 sheets has been successfully fabricated through a facile soft chemical route at low temperature. The MnO2/g-C3N4 NC electrode enhanced the supercapacitor (SC) performance, benchmarked against both the bare MnO2 NRs electrode and the MnO2/graphene oxide (GO) NC electrode, exhibiting high specific capacitance of 211 F/g at a current density of 1 A/g, with good rate capacity and cycling stability. The sandwich-like hybrid structure, the unique 2D structure of the g-C3N4 sheets and the presence of nitrogen in the g-C3N4 all contributed to the promising SC performance of the MnO2/g-C3N4 NC. This work demonstrated the advantages of the g-C3N4 sheets over the commonly-used GO sheets in the design of novel hybrid composite for enhanced capacitance performance of MnO2-based electrochemical SCs, and the results could be extended to other electrode materials for SCs.

  12. Improving g-C3N4 photocatalysis for NOx removal by Ag nanoparticles decoration

    NASA Astrophysics Data System (ADS)

    Sun, Yanjuan; Xiong, Ting; Ni, Zilin; Liu, Jie; Dong, Fan; Zhang, Wei; Ho, Wing-Kei

    2015-12-01

    In order to overcome the intrinsic drawback of pristine g-C3N4, we prepared g-C3N4 nanosheets with enhanced photocatalytic performance by Ag nanoparticles decoration using urea as the precursor. It was revealed that the monodispersed Ag nanoparticles were deposited on the surface of g-C3N4 nanosheets. The Ag/g-C3N4 nanocomposites were applied in removal of NOx in air under visible light irradiation. The results showed that the decoration of Ag nanoparticles not only enhanced the photocatalytic activity of g-C3N4 nanosheets, but also benefited the oxidation of NO to final products. The increased visible light absorption arising from the surface plasmon resonance of Ag and improved separation and transfer of photoinduced carriers over Ag/g-C3N4 composites were demonstrated by the UV-vis diffuse reflectance spectra and photoluminescence spectra, respectively. It was therefore proposed that the enhanced photocatalytic activity of Ag/g-C3N4 composites could be attributed to the extended light response range and enhanced charge separation due to the introduction of Ag nanoparticles.

  13. MnO2/g-C3N4 nanocomposite with highly enhanced supercapacitor performance.

    PubMed

    Chang, Xueting; Zhai, Xinxin; Sun, Shibin; Gu, Danxia; Dong, Lihua; Yin, Yansheng; Zhu, Yanqiu

    2017-03-01

    A novel sandwich-like MnO2/g-C3N4 nanocomposite (NC) based on the integration of high-density MnO2 nanorods (NRs) onto the surfaces of two-dimensional (2D) g-C3N4 sheets has been successfully fabricated through a facile soft chemical route at low temperature. The MnO2/g-C3N4 NC electrode enhanced the supercapacitor (SC) performance, benchmarked against both the bare MnO2 NRs electrode and the MnO2/graphene oxide (GO) NC electrode, exhibiting high specific capacitance of 211 F/g at a current density of 1 A/g, with good rate capacity and cycling stability. The sandwich-like hybrid structure, the unique 2D structure of the g-C3N4 sheets and the presence of nitrogen in the g-C3N4 all contributed to the promising SC performance of the MnO2/g-C3N4 NC. This work demonstrated the advantages of the g-C3N4 sheets over the commonly-used GO sheets in the design of novel hybrid composite for enhanced capacitance performance of MnO2-based electrochemical SCs, and the results could be extended to other electrode materials for SCs.

  14. C3d enhanced DNA vaccination induced humoral immune response to glycoprotein C of pseudorabies virus

    SciTech Connect

    Tong Tiezhu; Fan Huiying; Tan Yadi; Xiao Shaobo; Ling Jieyu; Chen Huanchun; Guo Aizhen . E-mail: aizhen@mail.hzau.edu.cn

    2006-09-08

    Murine C3d were utilized to enhance immunogenicity of pseudorabies virus (PrV) gC DNA vaccination. Three copies of C3d and four copies of CR2-binding domain M28{sub 4} were fused, respectively, to truncated gC gene encoding soluble glycoprotein C (sgC) in pcDNA3.1. BALB/c mice were, respectively, immunized with recombinant plasmids, blank vector, and inactivated vaccine. The antibody ELISA titer for sgC-C3d{sub 3} DNA was 49-fold more than that for sgC DNA, and the neutralizing antibody obtained 8-fold rise. Protection of mice from death after lethal PrV (316 LD{sub 5}) challenge was augmented from 25% to 100%. Furthermore, C3d fusion increased Th2-biased immune response by inducing IL-4 production. The IL-4 level for sgC-C3d{sub 3} DNA immunization approached that for the inactivated vaccine. Compared to C3d, M28 enhanced sgC DNA immunogenicity to a lesser extent. In conclusion, we demonstrated that murine C3d fusion significantly enhanced gC DNA immunity by directing Th1-biased to a balanced and more effective Th1/Th2 response.

  15. Fabrication and Characterization of AL-AL4C3 Nanocomposite by Mechanical Alloying

    NASA Astrophysics Data System (ADS)

    Mohammad Sharifi, E.; Enayati, M. H.; Karimzadeh, F.

    Aluminum carbide (Al4C3) seems to be an ideal reinforcement for producing aluminum matrix composites. Al4C3 has high hardness and shear strength as well as a high melting point. The dispersion of Al4C3 particles in the matrix produces a pinning effect that reduces aluminum grain growth, which improves the mechanical properties. In this study, aluminum powders were mixed with 4.5 wt.% graphite and mechanically alloyed using a high-energy ball mill in order to produce Al-Al4C3 nanocomposite. The structural evaluation of powder particles after different milling times was studied by X-ray diffractometry, scanning electron microscopy and microhardness measurements. The aluminum crystallite size estimated with broadening of XRD peaks by Williamson-Hall formula. XRD results suggested that the grain size of aluminum decreased to nanometer range (30 nm) during ball milling. No Al4C3 formed during the mechanical alloying process. Milled powders were then annealed at 300-600 °C for 1 h under argon atmosphere. Annealing at temperatures higher than 300 °C led to formation of Al4C3 phase which increased as annealing temperature increased. Aluminum grain size remained in nanometer range after annealing process. The microhardness of powder particles increased after annealing. Both effects are due to the formation of nanosized Al4C3 particles.

  16. Carbon-in-Al4C3 nanowire superstructures for field emitters.

    PubMed

    Sun, Yong; Cui, Hao; Gong, Li; Chen, Jian; She, Juncong; Ma, Yanming; Shen, Peikang; Wang, Chengxin

    2011-02-22

    As a kind of ionic (or salt-like) carbide, for Al(4)C(3), hardly any active functions have been found except for structure material purposes. However, considering the unique characteristic features of its crystal structure, we think Al(4)C(3) in fact might have huge potential for exhibiting active functionality on field-emission applications. Herein, we report the feasibility to approach such emitters by creating Al(4)C(3)-based nanowire superstructures. The conductive amorphous carbon (a-C) nanolayers are embedded quasi-periodically in Al(4)C(3) nanowire and generate essential electrical contact to the insulating Al(4)C(3). The superstructures acting as cold electron emitters display excellent field emission performance with the turn-on field as low as 0.65-1.3 V/μm and the threshold field down to 2.1-2.6 V/μm. We speculate that the emission characteristics, which are ever better than carbon nanotubes, are attributed to the unique crystal structure of Al(4)C(3) and the enhanced electrons transport in the nanowires due to the existence of a-C nanolayers. Such emitters are technologically useful, because they can be easily fabricated on large substrates, and the synthesis process is simple and broadly applicable. The findings conceptually provide new opportunities for the application of Al(4)C(3) ceramic material in vacuum microelectronic devices.

  17. Superoxide radical sensing using a cytochrome c3 immobilized conducting polymer electrode.

    PubMed

    Darain, Farzana; Park, Jang-Su; Akutsu, Hideo; Shim, Yoon-Bo

    2007-09-30

    A biosensor based on cytochrome c3 (cyt c3) has been introduced to detect and quantify superoxide radical (O2*-). Cyt c3, isolated from the sulfate-reducing bacterium (Desulfovibrio vulgaris Miyazaki F. strain), and its mutant were immobilized onto a conducting polymer coated electrodes by the covalent bonding with carbodiimide chemistry. The immobilization of cyt c3 was investigated with quartz crystal microbalance, electrochemical impedance spectroscopy, and cyclic voltammetric studies. The CVs recorded for cyt c3 and a mutant modified-electrodes showed a quasi-reversible behavior having the formal potential of about -471 and -476 mV (versus Ag/AgCl), respectively, in a 0.1M phosphate buffer solution (pH 7.0). The modified electrodes showed the surface controlled process and the electron transfer rate constants (ks) were evaluated to be 0.47 and 0.51 s(-1) for cyt c3 and mutant modified electrodes, respectively. A potential application of the cyt c3 modified electrode was evaluated by monitoring the bioelectrocatalytic response towards the O2*-. The hydrodynamic range of 0.2-2.7 micromole L(-1) and the detection limit of 0.05 micromole L(-1) were obtained.

  18. Hydrothermal synthesis of C3N4/BiOIO3 heterostructures with enhanced photocatalytic properties.

    PubMed

    Wang, Wenjun; Cheng, Hefeng; Huang, Baibiao; Liu, Xiaolei; Qin, Xiaoyan; Zhang, Xiaoyang; Dai, Ying

    2015-03-15

    The C3N4/BiOIO3 composites with heterostructures have been fabricated by simply depositing BiOIO3 on the surface of C3N4 at hydrothermal conditions, using bismuth nitrate and potassium iodate as precursors. C3N4 is an excellent organic semiconductor, which can be excited by visible light. BiOIO3 is a layered bismuth-based compound that has an internal polar field. Coupling C3N4 with BiOIO3 can combine the advantages of the two compounds and obtain better photocatalytic properties. X-ray diffraction, scanning electron microscopy, transmission electron microscopy and Fourier transformation infrared spectra have been carried out to confirm the structures and morphologies of as-prepared products. The absorption properties have been characterized by diffuse reflectance spectra and the photocatalytic activities have been evaluated by photodegradation of methyl orange, Rhodamine B and 2,4-dichlorophenol. Compared with C3N4, all C3N4/BiOIO3 composites exhibit better visible-light-driven photocatalytic properties. It is a synergetic effect that enables the composites to harvest light and promote charge separation, which eventually leads to the enhancement of the photocatalytic efficiencies. Under UV-vis light irradiation, C3N4/BiOIO3 composites also exhibit better activities, and the charge transfer process is similar to a redox mediator-free Z-scheme system. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Interleukin 2 mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells.

    PubMed Central

    Brooimans, R A; Stegmann, A P; van Dorp, W T; van der Ark, A A; van der Woude, F J; van Es, L A; Daha, M R

    1991-01-01

    Previous reports have suggested the production of complement components C4, C2, and factor B by renal tissue. However, the cells involved in production of complement have not been identified. In this study metabolic labeling experiments demonstrated that human proximal tubular epithelial cells (PTEC) synthesize a 180-kD precursor of C3 that is secreted after proteolytic cleavage into a disulphide linked two-chain molecule as found in plasma. C3 present in culture supernatants of PTEC was functionally active, however, during the culture period there was a partial inactivation of the C3 molecule as assessed by hemolytic titration. Recombinant IL-2 enhances the rate of C3 synthesis in a dose-dependent manner reaching maximal stimulation at doses of 200-400 U/ml IL-2. Northern blot analysis demonstrated a 5.2-kb C3 mRNA species present in PTEC that was increased within 24 h of IL-2 treatment. IL-2-induced enhancement of C3 production by PTEC could be neutralized with specific antibodies to IL-2. This study demonstrates that C3 synthesis in PTEC is upregulated by IL-2, the major cytokine produced by activated T cells. Images PMID:1864952

  20. The Y-chromosome C3* star-cluster attributed to Genghis Khan's descendants is present at high frequency in the Kerey clan from Kazakhstan.

    PubMed

    Abilev, Serikbai; Malyarchuk, Boris; Derenko, Miroslava; Wozniak, Marcin; Grzybowski, Tomasz; Zakharov, Ilya

    2012-02-01

    To verify the possibility that the Y-chromosome C3* star-cluster attributed to Genghis Khan and his patrilineal descendants is relatively frequent in the Kereys, who are the dominant clan in Kazakhstan and in Central Asia as a whole, polymorphism of the Y-chromosome was studied in Kazakhs, represented mostly by members of the Kerey clan. The Kereys showed the highest frequency (76.5%) of individuals carrying the Y-chromosome variant known as C3* star-cluster ascribed to the descendants of Genghis Khan. C3* star-cluster haplotypes were found in two subclans, Abakh-Kereys and Ashmaily-Kereys, diverged about 20-22 generations ago according to the historical data. Median network of the Kerey star-cluster haplotypes at 17 STR loci displays a bipartite structure, with two subclusters defined by the only difference at the DYS448 locus. Noteworthy is a strong correspondence of these subclusters with the Kerey subclans affiliation. The data obtained suggest that the Kerey clan appears to be the largest known clan in the world descending from a common Y-chromosome ancestor. Possible ways of Genghis Khan's relationship to the Kereys are discussed.

  1. Rituximab fails where eculizumab restores renal function in C3nef-related DDD.

    PubMed

    Rousset-Rouvière, Caroline; Cailliez, Mathilde; Garaix, Florentine; Bruno, Daniele; Laurent, Daniel; Tsimaratos, Michel

    2014-06-01

    Dense deposit disease (DDD), a C3 glomerulopathy (C3G), is a rare disease with unfavorable progression towards end-stage kidney disease. The pathogenesis of DDD is due to cytotoxic effects related to acquired or genetic dysregulation of the complement alternative pathway, which is at times accompanied by the production of C3 nephritic factor (C3NeF), an auto-antibody directed against the alternative C3 convertase. Available treatments include plasma exchange, CD20-targeted antibodies, and a terminal complement blockade via the anti-C5 monoclonal antibody eculizumab. We report here the case of an 8-year-old child with C3NeF and refractory DDD who presented with a nephritic syndrome. She tested positive for C3NeF activity; C3 was undetectable. Genetic analyses of the alternative complement pathway were normal. Methylprednisolone pulses and mycophenolate mofetil treatment resulted in complete recovery of renal function and a reduction in proteinuria. Corticosteroids were tapered and then withdrawn. Four months after corticosteroid discontinuation, hematuria and proteinuria recurred, and a renal biopsy confirmed an active DDD with a majority of extracapillary crescents. Despite an increase in immunosuppressive drugs, including methylprednisolone pulses and rituximab therapy, the patient suffered acute renal failure within 3 weeks, requiring dialysis. Eculizumab treatment resulted in a quick and impressive response. Hematuria very quickly resolved, kidney function improved, and no further dialysis was required. The patient received bimonthly eculizumab injections of 600 mg, allowing for normalization of renal function and reduction of proteinuria to <0.5 g per day. Since then, she continues to receive eculizumab. Complement regulation pathway-targeted therapy may be a specific and useful treatment for rapidly progressing DDD prior to the development of glomerulosclerosis. Our data provide evidence supporting the pivotal role of complement alternative pathway

  2. Abundances of C3Hx Hydrocarbons in Titan's Stratosphere from Cassini CIRS

    NASA Astrophysics Data System (ADS)

    Nixon, C. A.; Jennings, D. E.; Bezard, B.; Vinatier, S.; Teanby, N. A.; Sung, K.; Ansty, T. M.; Irwin, P. G.; Gorius, N.; Cottini, V.; Coustenis, A.; Flasar, F. M.

    2014-12-01

    During the ten years since entry into Saturn orbit in 2004, the Cassini spacecraft has made more than 100 close flybys of Titan, measuring the properties of the atmosphere by both in situ and remote sensing techniques. Cassini's Composite Infrared Spectrometer (CIRS) senses the infrared spectrum from 7-1000 μm (1400-10 cm-1), a region which exhibits the vibrational emissions of many different molecular species. CIRS has therefore been able to map the spatial distributions and temporal variations of hydrocarbons, nitriles and other gas species in Titan's atmosphere, yielding information about the chemistry and dynamics. Recently, Nixon et al. (2013) made the first detection of a new stratospheric gas species from Cassini using CIRS - the C3H6 molecule (propene). This filled in a long-time missing link in the chemical picture of Titan's lower atmosphere, since the C3H4 (propyne) and C3H8 (propane) molecules had been detected in 1981 by Voyager 1 IRIS. The inferred abundance of C3H6 is less than both C3H8 and C3H4, and this pattern is repeated also in the C2Hx molecules where C2H4 is less abundant than C2H2 and C2H6. Therefore a pattern emerges whereby: alkanes > alkynes > alkenes within the C2Hx and C3Hx chemical families in the lower stratosphere. We comment on how this trend compares to published photochemical model predictions, and also give updates on the search for C3Hx isomers (allene: CH2CCH2, and cyclopropane: c-C3H6) and C4Hx species using CIRS.

  3. Spin-forbidden c 3Sigma1+<--X 1Sigma+ band system of YF.

    PubMed

    Nagarajan, Ramya; Morse, Michael D

    2007-04-14

    Optical spectra of jet-cooled diatomic YF have been recorded using resonant two-photon ionization spectroscopy. A vibrational progression corresponding to the c 3Sigma1+<--X 1Sigma+ system has been identified. The vibrational frequency omegae' and anharmonicity omegae'xe' of the c 3Sigma+ state are 546.70 and 2.45 cm-1, respectively. The 0-0, 1-0, and 2-0 bands of the c 3Sigma1+<--X 1Sigma+ system were rotationally resolved and analyzed, allowing the v'=0, 1, and 2 levels of the c 3Sigma1+ substate to be characterized. From these studies, Be'=0.269 81(3) cm-1, alphae'=0.001 72(3) cm-1, and re'=1.9979(1) A were obtained (1sigma error limits). For these levels the spin-spin coupling constant lambdav is identical within experimental error, as lambda=-22.5 cm-1. The spin-forbidden c 3Sigma1+<--X 1Sigma+ transition is made allowed by spin-orbit interaction between the c 3Sigma1+ and the B 1Pi states. Excited state lifetimes of the c 3Sigma1+ and the B 1Pi states have been measured as 7.11(41) and 0.133(15) micros, respectively. A spin-orbit analysis shows that the c 3Sigma1+ state is contaminated with 2% B 1Pi character, which is approximately sufficient to explain the 7 micros lifetime of the c 3Sigma1+ state.

  4. A theoretical view of the C3d:CR2 binding controversy.

    PubMed

    Mohan, Rohith R; Gorham, Ronald D; Morikis, Dimitrios

    2015-03-01

    The C3d:CR2(SCR1-2) interaction plays an important role in bridging innate and adaptive immunity, leading to enhanced antibody production at sites of complement activation. Over the past decade, there has been much debate over the binding mode of this interaction. An initial cocrystal structure (PDB: 1GHQ) was published in 2001, in which the only interactions observed were between the SCR2 domain of CR2 and a side-face of C3d whereas a cocrystal structure (PDB: 3OED) published in 2011 showed both the SCR1 and SCR2 domains of CR2 interacting with an acidic patch on the concave surface of C3d. The initial 1GHQ structure is at odds with the majority of existing biochemical data and the publication of the 3OED structure renewed uncertainty regarding the physiological relevance of 1GHQ, suggesting that crystallization may have been influenced by the presence of zinc acetate in the crystallization process. In our study, we used a variety of computational approaches to gain insight into the binding mode between C3d and CR2 and demonstrate that the binding site at the acidic patch (3OED) is electrostatically more favorable, exhibits better structural and dissociative stability, specifically at the SCR1 domain, and has higher binding affinity than the 1GHQ binding mode. We also observe that nonphysiological zinc ions enhance the formation of the C3d:CR2 complex at the side face of C3d (1GHQ) through increases in electrostatic favorability, intermolecular interactions, dissociative character and overall energetic favorability. These results provide a theoretical basis for the association of C3d:CR2 at the acidic cavity of C3d and provide an explanation for binding of CR2 at the side face of C3d in the presence of nonphysiological zinc ions.

  5. Complement component C3aR constitutes a novel regulator for chick eye morphogenesis.

    PubMed

    Grajales-Esquivel, Erika; Luz-Madrigal, Agustin; Bierly, Jeffrey; Haynes, Tracy; Reis, Edimara S; Han, Zeyu; Gutierrez, Christian; McKinney, Zachary; Tzekou, Apostolia; Lambris, John D; Tsonis, Panagiotis A; Del Rio-Tsonis, Katia

    2017-08-01

    Complement components have been implicated in a wide variety of functions including neurogenesis, proliferation, cell migration, differentiation, cancer, and more recently early development and regeneration. Following our initial observations indicating that C3a/C3aR signaling induces chick retina regeneration, we analyzed its role in chick eye morphogenesis. During eye development, the optic vesicle (OV) invaginates to generate a bilayer optic cup (OC) that gives rise to the retinal pigmented epithelium (RPE) and neural retina. We show by immunofluorescence staining that C3 and the receptor for C3a (the cleaved and active form of C3), C3aR, are present in chick embryos during eye morphogenesis in the OV and OC. Interestingly, C3aR is mainly localized in the nuclear compartment at the OC stage. Loss of function studies at the OV stage using morpholinos or a blocking antibody targeting the C3aR (anti-C3aR Ab), causes eye defects such as microphthalmia and defects in the ventral portion of the eye that result in coloboma. Such defects were not observed when C3aR was disrupted at the OC stage. Histological analysis demonstrated that microphthalmic eyes were unable to generate a normal optic stalk or a closed OC. The dorsal/ventral patterning defects were accompanied by an expansion of the ventral markers Pax2, cVax and retinoic acid synthesizing enzyme raldh-3 (aldh1a3) domains, an absence of the dorsal expression of Tbx5 and raldh-1 (aldh1a1) and a re-specification of the ventral RPE to neuroepithelium. In addition, the eyes showed overall decreased expression of Gli1 and a change in distribution of nuclear β-catenin, suggesting that Shh and Wnt pathways have been affected. Finally, we observed prominent cell death along with a decrease in proliferating cells, indicating that both processes contribute to the microphthalmic phenotype. Together our results show that C3aR is necessary for the proper morphogenesis of the OC. This is the first report implicating C3aR in

  6. Reduction of U(VI) and Toxic Metals by Desulfovibrio Cytochrome c3

    SciTech Connect

    Wall, Judy D.

    2003-06-01

    The project, ''Reduction of U(VI) and toxic metals by Desulfovibrio cytochrome c3'', is designed to obtain spectroscopic information for or against a functional interaction of cytochrome c3 and uranium in the whole cells. That is, is the cytochrome c3 the uranium reductase? Our approach has been to start with purified cytochrome and determine any unique spectral disturbances during electron flow to U(VI). Then we will attempt to identify these signals emanating from cells actively reducing uranium. This project is being carried out in collaboration with Dr. William Woodruff at the Los Alamos National Laboratory where the spectral experiments are being carried out.

  7. 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.

  8. Systematic comparison of C3 and C4 plants based on metabolic network analysis.

    PubMed

    Wang, Chuanli; Guo, Longyun; Li, Yixue; Wang, Zhuo

    2012-01-01

    The C4 photosynthetic cycle supercharges photosynthesis by concentrating CO2 around ribulose-1,5-bisphosphate carboxylase and significantly reduces the oxygenation reaction. Therefore engineering C4 feature into C3 plants has been suggested as a feasible way to increase photosynthesis and yield of C3 plants, such as rice, wheat, and potato. To identify the possible transition from C3 to C4 plants, the systematic comparison of C3 and C4 metabolism is necessary. We compared C3 and C4 metabolic networks using the improved constraint-based models for Arabidopsis and maize. By graph theory, we found the C3 network exhibit more dense topology structure than C4. The simulation of enzyme knockouts demonstrated that both C3 and C4 networks are very robust, especially when optimizing CO2 fixation. Moreover, C4 plant has better robustness no matter the objective function is biomass synthesis or CO2 fixation. In addition, all the essential reactions in C3 network are also essential for C4, while there are some other reactions specifically essential for C4, which validated that the basic metabolism of C4 plant is similar to C3, but C4 is more complex. We also identified more correlated reaction sets in C4, and demonstrated C4 plants have better modularity with complex mechanism coordinates the reactions and pathways than that of C3 plants. We also found the increase of both biomass production and CO2 fixation with light intensity and CO2 concentration in C4 is faster than that in C3, which reflected more efficient use of light and CO2 in C4 plant. Finally, we explored the contribution of different C4 subtypes to biomass production by setting specific constraints. All results are consistent with the actual situation, which indicate that Flux Balance Analysis is a powerful method to study plant metabolism at systems level. We demonstrated that in contrast to C3, C4 plants have less dense topology, higher robustness, better modularity, and higher CO2 and radiation use efficiency

  9. Calculation of the C3A Percentage in High Sulfur Clinker

    PubMed Central

    Horkoss, Sayed; Lteif, Roger; Rizk, Toufic

    2010-01-01

    The aim of this paper is to clarify the influence of the clinker SO3 on the amount of C3A. The calculation of the cement phases percentages is based on the research work, Calculation of the Compounds in Portland Cement, published by Bogue in 1929 .The usage of high sulphur fuels, industrial wastes, and tires changes completely the working condition of Bogue because the assumed phase compositions may change. The results prove that increasing the amount of SO3 in the low alkali clinker decreases the percentages of C3A due to the high incorporation of alumina in the clinker phases mainly C2S and C3S. The correlation is linear till the clinker SO3 reaches the 2%. Over that the influence of the clinker SO3 became undetectable. A new calculation method for the determination of the C3A in the high sulphur and low alkali clinker was proposed. PMID:20689732

  10. Percolative Conduction in Biological Conductor: Cytochrome c3 Anhydrous Film of Desulfovibrio vulgaris, Miyazaki Strain

    NASA Astrophysics Data System (ADS)

    Kimura, Keisaku; Inokuchi, Hiroo

    1982-07-01

    Electrical conductivity of the thin film of cytochrome c3, electron carrier protein of anaerobic bacteria, was measured as a function of ferri- to ferro-ratio. At the initial reduction stage of ferric cytochrome c3, the conductivity was gradually increased and was explained by doping effect. This was the first observation of doping effect for biological molecules. At 0.95 ferro-ratio, the conductivity was abruptly increased. The observation was analysed by the percolation theory which predicts that there is very strong heme-heme interaction between fully reduced cytochrome c3 molecules in a condensed phase. The anomalous physico-chemical behaviors of ferrocytochrome c3 film such as very low ionization potential and intermolecular heme-heme interaction observed by Mössbauer spectroscopy were also discussed in relation to the present results.

  11. Functional properties of type I and type II cytochromes c3 from Desulfovibrio africanus.

    PubMed

    Paquete, Catarina M; Pereira, Patrícia M; Catarino, Teresa; Turner, David L; Louro, Ricardo O; Xavier, António V

    2007-02-01

    Type I cytochrome c(3) is a key protein in the bioenergetic metabolism of Desulfovibrio spp., mediating electron transfer between periplasmic hydrogenase and multihaem cytochromes associated with membrane bound complexes, such as type II cytochrome c(3). This work presents the NMR assignment of the haem substituents in type I cytochrome c(3) isolated from Desulfovibrio africanus and the thermodynamic and kinetic characterisation of type I and type II cytochromes c(3) belonging to the same organism. It is shown that the redox properties of the two proteins allow electrons to be transferred between them in the physiologically relevant direction with the release of energised protons close to the membrane where they can be used by the ATP synthase.

  12. Electron-impact dissociation cross sections for CHF3 and C3F8

    NASA Astrophysics Data System (ADS)

    Baio, J. E.; Yu, H.; Flaherty, D. W.; Winters, H. F.; Graves, D. B.

    2007-11-01

    Absolute total dissociation cross sections, σt,diss, by electron-impact are reported for CHF3 and C3F8 from 10 to 300 eV using the chemical gettering technique described by Winters and Inokuti (1982 Phys. Rev. A 25 1420). Data are concentrated in the near-threshold region (10-30 eV). The thresholds for dissociation of CHF3 and C3F8 are determined to be 10.4 eV and 11.9 eV, respectively. Ionization thresholds occur at 16 eV for CHF3 and 16.2 eV for C3F8. Neutral dissociation cross sections of both CHF3 and C3F8 are obtained by subtracting the ionization cross sections, σt,ion, from the total dissociation cross sections, σt,diss.

  13. 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

  14. 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

  15. Effect of Hypertriglyceridemia on Beta Cell Mass and Function in ApoC3 Transgenic Mice.

    PubMed

    Liu, Yun-Zi; Cheng, Xiaoyun; Zhang, Ting; Lee, Sojin; Yamauchi, Jun; Xiao, Xiangwei; Gittes, George; Qu, Shen; Jiang, Chun-Lei; Dong, H Henry

    2016-07-08

    Hypertriglyceridemia results from increased production and decreased clearance of triglyceride-rich very low-density lipoproteins, a pathological condition that accounts for heightened risk of ischemic vascular diseases in obesity and type 2 diabetes. Despite its intimate association with insulin resistance, whether hypertriglyceridemia constitutes an independent risk for beta cell dysfunction in diabetes is unknown. Answering this fundamental question is stymied by the fact that hypertriglyceridemia is intertwined with hyperglycemia and insulin resistance in obese and diabetic subjects. To circumvent this limitation, we took advantage of apolipoprotein C3 (ApoC3)-transgenic mice, a model with genetic predisposition to hypertriglyceridemia. We showed that ApoC3-transgenic mice, as opposed to age/sex-matched wild-type littermates, develop hypertriglyceridemia with concomitant elevations in plasma cholesterol and non-esterified fatty acid levels. Anti-insulin and anti-glucagon dual immunohistochemistry in combination with morphometric analysis revealed that ApoC3-transgenic and wild-type littermates had similar beta cell and alpha cell masses as well as islet size and architecture. These effects correlated with similar amplitudes of glucose-stimulated insulin secretion and similar degrees of postprandial glucose excursion in ApoC3-transgenic versus wild-type littermates. Oil Red O histology did not visualize lipid infiltration into islets, correlating with the lack of ectopic triglyceride and cholesterol depositions in the pancreata of ApoC3-transgenic versus wild-type littermates. ApoC3-transgenic mice, despite persistent hypertriglyceridemia, maintained euglycemia under both fed and fasting conditions without manifestation of insulin resistance and fasting hyperinsulinemia. Thus, hypertriglyceridemia per se is not an independent risk factor for beta cell dysfunction in ApoC3 transgenic mice. © 2016 by The American Society for Biochemistry and Molecular Biology

  16. Lentil (Lens culinaris) lipid transfer protein Len c 3: a novel legume allergen.

    PubMed

    Akkerdaas, J; Finkina, E I; Balandin, S V; Santos Magadán, S; Knulst, A; Fernandez-Rivas, M; Asero, R; van Ree, R; Ovchinnikova, T V

    2012-01-01

    Lentils are increasingly consumed in many parts of the world.Two allergens, Len c 1 and 2, have been reported previously. Recently, peanut and green bean lipid transfer proteins (LTPs) have been identified as the first two members of an important group of allergens that might be associated with severe food allergies. To investigate lentil LTP as a potential new allergen. Efficacy of LTP extraction was monitored at different acidic pH values, using immunoblotting with cross-reactive anti-peach LTP antiserum. Natural LTP was purified from lentil extract and expressed as recombinant allergen in Escherichia coli. Sera from 10 lentil-allergic and/or -sensitized patients (Spain: 6, Italy: 1 and the Netherlands: 3) were used to further characterize lentil LTP. Natural lentil LTP, purified from the homogenized germinated seeds and optimally extracted at pH 3, was identified and designated as allergen Len c 3. By CAP, 9/10 sera showed specific IgE to Len c 3. Recombinant (r) Len c 3 was successfully purified. The natural (n) Len c 3 CAP was completely inhibited by rLen c 3/rPru p 3. IgE binding to lentil pH 3 extract blot was completely inhibited by rLen c 3. The availability of immunochemically active nLen/rLen c 3 as a novel legume allergen facilitates further development and implementation of a third (next to peanut and green bean) legume LTP in component-resolved diagnosis strategies and contributes to evaluate the clinical importance of legume LTPs. Preferential extraction of Len c 3 (pH 3) will affect the production of sensitive extract-based diagnostic tests. Copyright © 2011 S. Karger AG, Basel.

  17. A study of the C3H2 isomers and isotopologues: first interstellar detection of HDCCC

    NASA Astrophysics Data System (ADS)

    Spezzano, S.; Gupta, H.; Brünken, S.; Gottlieb, C. A.; Caselli, P.; Menten, K. M.; Müller, H. S. P.; Bizzocchi, L.; Schilke, P.; McCarthy, M. C.; Schlemmer, S.

    2016-02-01

    The partially deuterated linear isomer HDCCC of the ubiquitous cyclic carbene (c-C3H2) was observed in the starless cores TMC-1C and L1544 at 96.9 GHz, and a confirming line was observed in TMC-1 at 19.38 GHz. To aid the identification in these narrow line sources, four centimetre-wave rotational transitions (two in the previously reported Ka = 0 ladder and two new ones in the Ka = 1 ladder) and 23 transitions in the millimetre band between 96 and 272 GHz were measured in high-resolution laboratory spectra. Ten spectroscopic constants in a standard asymmetric top Hamiltonian allow the main transitions of astronomical interest in the Ka ≤ 3 rotational ladders to be calculated to within 0.1 km s-1 in radial velocity up to 400 GHz. Conclusive identification of the two astronomical lines of HDCCC was provided by the VLSR, which is the same as for the normal isotopic species (H2CCC) in the three narrow line sources. In these sources, deuterium fractionation in singly substituted H2CCC (HDCCC/H2CCC ~4-19%) is comparable to that in c-C3H2 (c-C3H2/c-C3HD ~5-17%) and similarly in doubly deuterated c-C3H2 (c-C3D2/c-C3HD ~3-17%), implying that the efficiency of the deuteration processes in the H2CCC and c-C3H2 isomers are comparable in dark clouds. Based on observations carried out with the IRAM 30 m Telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain).

  18. C3 deposits worsens the prognosis in type iii extracapillary glomerulonephritis.

    PubMed

    Sánchez-Agesta Martínez, Marina; Rabasco Ruiz, Cristina; Sánchez Sánchez, Rafael; Ortega Salas, Rosa; López Andreu, María; Aljama García, Pedro; Espinosa Hernández, Mario

    2017-10-05

    Type iii extracapillary glomerulonephritis (PEGN) is a common cause of rapidly progressive glomerulonephritis and it is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). Recent evidence points to complement activation as an important factor in the pathogenesis of PEGN. The aim of the present study was to assess the value of C3 deposits in the prognosis of PEGN. All patients diagnosed of PEGN from 1995 to 2015 (n=72) were included in this study. Progression of renal disease in patients with positive staining for C3 by immunofluorescence was compared with those with negative staining. Mean follow up was 73 months. Progression to end-stage renal disease in relation to clinical and histological variables was analyzed. Positive staining for C3 was observed in 22 out of the 72 patients (30.5%). At the time of diagnosis, patients with C3 deposits had higher serum creatinine concentration than those without C3 staining (5.00 vs. 3.85mg/dl, P=0.050). Renal survival at 10 years was 36.9% in patients with positive C3 staining vs. 64.4% in patients with negative staining (P=0.005). Mortality at 10 years was higher in patients with C3 deposits than in patients without deposits (77 vs. 49.3%). Thus, our study shows that PEGN with deposits of C3 is associated with worse renal prognosis and greater mortality. These results would support the hypothesis that activation of the alternative pathway complement may play an important role in the generation of renal injury associated with PEGN. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  19. 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

  20. 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. © 2014 Scandinavian Plant Physiology Society.

  1. Bisulfite induced chemiluminescence of g-C3N4 nanosheets and enhanced by metal ions.

    PubMed

    Zheng, Yongzan; Dou, Xiangnan; Li, Haifang; Lin, Jin-Ming

    2016-03-07

    In this work, a novel chemiluminescence (CL) phenomenon was found: a g-C3N4 nanosheets suspension was mixed with NaHSO3 solution directly to produce luminescence, and the intensity of luminescence could be obviously enhanced by some metal ions, which was distinctly different from the phenomenon that Cu(2+) ions can quench the fluorescence of g-C3N4 nanosheets as reported before.

  2. Effect of Hypertriglyceridemia on Beta Cell Mass and Function in ApoC3 Transgenic Mice*

    PubMed Central

    Liu, Yun-Zi; Cheng, Xiaoyun; Zhang, Ting; Lee, Sojin; Yamauchi, Jun; Xiao, Xiangwei; Gittes, George; Qu, Shen; Jiang, Chun-Lei; Dong, H. Henry

    2016-01-01

    Hypertriglyceridemia results from increased production and decreased clearance of triglyceride-rich very low-density lipoproteins, a pathological condition that accounts for heightened risk of ischemic vascular diseases in obesity and type 2 diabetes. Despite its intimate association with insulin resistance, whether hypertriglyceridemia constitutes an independent risk for beta cell dysfunction in diabetes is unknown. Answering this fundamental question is stymied by the fact that hypertriglyceridemia is intertwined with hyperglycemia and insulin resistance in obese and diabetic subjects. To circumvent this limitation, we took advantage of apolipoprotein C3 (ApoC3)-transgenic mice, a model with genetic predisposition to hypertriglyceridemia. We showed that ApoC3-transgenic mice, as opposed to age/sex-matched wild-type littermates, develop hypertriglyceridemia with concomitant elevations in plasma cholesterol and non-esterified fatty acid levels. Anti-insulin and anti-glucagon dual immunohistochemistry in combination with morphometric analysis revealed that ApoC3-transgenic and wild-type littermates had similar beta cell and alpha cell masses as well as islet size and architecture. These effects correlated with similar amplitudes of glucose-stimulated insulin secretion and similar degrees of postprandial glucose excursion in ApoC3-transgenic versus wild-type littermates. Oil Red O histology did not visualize lipid infiltration into islets, correlating with the lack of ectopic triglyceride and cholesterol depositions in the pancreata of ApoC3-transgenic versus wild-type littermates. ApoC3-transgenic mice, despite persistent hypertriglyceridemia, maintained euglycemia under both fed and fasting conditions without manifestation of insulin resistance and fasting hyperinsulinemia. Thus, hypertriglyceridemia per se is not an independent risk factor for beta cell dysfunction in ApoC3 transgenic mice. PMID:27226540

  3. Analysis of complement C3 deposition and degradation on Klebsiella pneumoniae.

    PubMed Central

    Albertí, S; Alvarez, D; Merino, S; Casado, M T; Vivanco, F; Tomás, J M; Benedí, V J

    1996-01-01

    The majority of Klebsiella pneumoniae serum-resistant strains activate complement and bind C3b, the opsonic fragment of C3, without C5b-9 formation and bacterial killing. The mechanisms leading to C3b deposition without cell death were studied, and the results indicate that serum-resistant strains activate principally the alternative pathway and that serum-sensitive strains activate both the alternative and classical pathways. Bacterial molecules implicated in C3b deposition are the outer membrane porin proteins and smooth and rough lipopolysaccharides. Porins activate both complement pathways, and the rough lipopolysaccharide activates the classical pathway, causing deposition of C3b in serum-sensitive strains. The smooth lipopolysaccharide of serum-resistant strains activates only the alternative pathway, impeding the binding of C1q to porins (S. Albertí, G. Marqués, S. Camprubí, S. Merino, J. M. Tomás, F. Vivanco, and V. J. Benedí, Infect. Immun. 61:852-860, 1993; S. Albertí, F. Rodríguez-Quinónes, T. Schirmer, G. Rummel, J. M. Tomás, J. P. Rosenbusch, and V. J. Benedí, Infect. Immun. 63:903-910, 1995) and rough lipopolysaccharide molecules and thereby preventing activation of the classical pathway. After its deposition, C3b is quickly degraded to iC3b on both types of strains, but the higher-level deposition of C3b on serum-sensitive strains, resulting from activation of both the alternative and classical complement pathways, supports further complement activation and killing of serum-sensitive strains. PMID:8890232

  4. Bisulfite induced chemiluminescence of g-C3N4 nanosheets and enhanced by metal ions

    NASA Astrophysics Data System (ADS)

    Zheng, Yongzan; Dou, Xiangnan; Li, Haifang; Lin, Jin-Ming

    2016-02-01

    In this work, a novel chemiluminescence (CL) phenomenon was found: a g-C3N4 nanosheets suspension was mixed with NaHSO3 solution directly to produce luminescence, and the intensity of luminescence could be obviously enhanced by some metal ions, which was distinctly different from the phenomenon that Cu2+ ions can quench the fluorescence of g-C3N4 nanosheets as reported before.In this work, a novel chemiluminescence (CL) phenomenon was found: a g-C3N4 nanosheets suspension was mixed with NaHSO3 solution directly to produce luminescence, and the intensity of luminescence could be obviously enhanced by some metal ions, which was distinctly different from the phenomenon that Cu2+ ions can quench the fluorescence of g-C3N4 nanosheets as reported before. Electronic supplementary information (ESI) available: Kinetic curves of CL of g-C3N4 nanosheets-M-NaHSO3 (M = Fe2+, Zn2+, Ni2+, Pb2+, Cr3+ and Co2+) systems, kinetic curves of CL of g-C3N4 nanosheets-M-NaHSO3 systems after the solution was bubbled with O2 or N2, kinetic curves of CL of g-C3N4 nanosheets-M-NaHSO3 systems with different radical scavengers, ESR spectra of &z.rad;SO3- radicals in the CL systems, CL spectra of the g-C3N4 nanosheets-Cu2+-NaHSO3 system. See DOI: 10.1039/c5nr08943c

  5. 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.

  6. Synthesis and biological evaluation of C-3 aliphatic coumarins as vitamin K antagonists.

    PubMed

    Montagut-Romans, Adrien; Boulven, Manon; Jacolot, Maïwenn; Moebs-Sanchez, Sylvie; Hascoët, Claire; Hammed, Abdessalem; Besse, Stéphane; Lemaire, Marc; Benoit, Etienne; Lattard, Virginie; Popowycz, Florence

    2017-04-01

    Since the discovery of Warfarin in the 1940s, the design of new warfarin-derived anticoagulants for rodent management has been challenging, with mainly structural modifications performed on the C3 position of the coumarin skeleton. In order to better understand the pharmacomodulation of such derivatives, we have synthesized a family of C3 (linear and branched) alkyl-4-hydroxycoumarins, which led to the identification of compounds 5e and 5f as potential short-term active anticoagulants.

  7. Cytochrome c3 from the sulfate-reducing anaerobe Desulfovibrio africanus Benghazi: antigenic properties.

    PubMed Central

    Singleton, R; Denis, J; Campbell, L L

    1982-01-01

    Antisera were prepared against cytochromes c3 from Desulfovibrio africanus, D. vulgaris, and D. salexigens. Cross-reactions were observed between antisera to D. vulgaris and D. africanus cytochromes and heterologous cytochromes c3. A weak cross-reaction with antisera against both D. vulgaris and D. africanus cytochromes and the acid form of the D. salexigens cytochrome was seen; the basic form did not react. Images PMID:6181052

  8. The g-C3 N4 /C2 N Nanocomposite: A g-C3 N4 -Based Water-Splitting Photocatalyst with Enhanced Energy Efficiency.

    PubMed

    Wang, Huimin; Li, Xingxing; Yang, Jinlong

    2016-07-04

    Water-splitting photocatalysts with good energy efficiency are highly desirable, among which metal-free graphitic carbon nitride (g-C3 N4 ) is considered to be very promising and has been intensively studied in recent years. However, its practical application is hindered by the relatively low efficiencies of visible-light absorption and electron-hole separation. Herein, based on first-principles calculations, it is predicted that, by forming nanocomposites with another carbon nitride (C2 N), the energy efficiency of g-C3 N4 can be significantly improved. On one hand, C2 N has a wide, strong optical absorption in the visible-light region, which acts as a photosensitizer and enhances the photoabsorption efficiency of the composite photocatalyst. On the other hand, C2 N forms a type II heterojunction with g-C3 N4 , which leads to efficient separation of photogenerated electron-hole pairs through the chemical potential difference between the two components. These results provide a potential route to achieve highly efficient metal-free photocatalysts for water splitting. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Enhanced electrogenerated chemiluminescence behavior of C3N4 QDs@ C3N4 nanosheet and its signal-on aptasensing for platelet derived growth factor.

    PubMed

    Xu, Huifeng; Liang, Shijing; Zhu, Xi; Wu, Xiuqin; Dong, Yongqiang; Wu, Haishan; Zhang, Wenxia; Chi, Yuwu

    2017-06-15

    A novel g-C3N4 nanosheets embedded with C3N4 QDs nanocomposites (QD@CNNS) was prepared by simple oxidation using hydrogen peroxide and UV light irradiation. This nanocomposite exhibits more stable and stronger electrochemiluminescent (ECL) behavior compared with CNNS. Coupling this nanocomposite with Fc-labeled aptamer, a signal-on aptasensor for platelet derived growth factor BB (PDGF-BB) is fabricated. Initially, the Fc-labeled aptamer binds onto QD@CNNS via π-π conjugation and electrostatic interaction, quenching ECL emission from QD@CNNS. The introduction of target efficiently recovers the ECL signal by the formation of PDGF-BB/aptamer complex. The ECL intensity is proportion to the concentration of PDGF-BB in the range of 0.02-80nM with a detection limit of 0.013nM. This work demonstrates a simple synthesis method to obtain QD@CNNS with excellent ECL behavior, and opens up the application of g-C3N4 nanocomposite in signal-on aptasensing.

  10. 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

  11. Thermomagnetic analysis of meteorites, 3. C3 and C4 chondrites

    USGS Publications Warehouse

    Herndon, J.M.; Rowe, M.W.; Larson, E.E.; Watson, D.E.

    1976-01-01

    Thermomagnetic analysis was made on samples of all known C3 and C4 chondrites in a controlled oxygen atmosphere. Considerable variation was noted in the occurrence of magnetic minerals, comparable to the variation observed earlier in the C2 chondrites. Magnetite was found as the only major magnetic phase in samples of only three C3 chondrites (2-4 wt.%) and the Karoonda C4 chondrite (7.7 wt.%). The magnetite content of these three C3 chondrites is only about one-third that observed in the C1 and C2 chondrites which were found to contain magnetite as the only magnetic phase. Five C3 chondrites were observed to undergo chemical change during heating, producing magnetite: this behavior is characteristic of troilite oxidation. Upper limits on initial magnetite content of about 1-9% were established for these meteorites. Samples of the remaining five C3 chondrites and the Coolidge C4 chondrite were found to contain both magnetite and metallic iron. In two samples, iron containing ???2% Ni was observed, while in the other four, the iron contained 6-8 wt.% Ni. In addition to containing both magnetite and iron metal, three of these samples reacted during heating to form additional magnetite. Variations in the magnetic mineralogy and, hence by inference bulk mineralogy, of C3 and C4 chondrites indicate a more complex genesis than is evident from whole-rock elemental abundance patterns. ?? 1976.

  12. 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.

  13. AKR1C3 as a target in castrate resistant prostate cancer.

    PubMed

    Adeniji, Adegoke O; Chen, Mo; Penning, Trevor M

    2013-09-01

    Aberrant androgen receptor (AR) activation is the major driver of castrate resistant prostate cancer (CRPC). CRPC is ultimately fatal and more therapeutic agents are needed to treat this disease. Compounds that target the androgen axis by inhibiting androgen biosynthesis and or AR signaling are potential candidates for use in CRPC treatment and are currently being pursued aggressively. Aldo-keto reductase 1C3 (AKR1C3) plays a pivotal role in androgen biosynthesis within the prostate. It catalyzes the 17-ketoreduction of weak androgen precursors to give testosterone and 5α-dihydrotestosterone. AKR1C3 expression and activity has been implicated in the development of CRPC, making it a rational target. Selective inhibition of AKR1C3 will be important, however, due to the presence of closely related isoforms, AKR1C1 and AKR1C2 that are also involved in androgen inactivation. We examine the evidence that supports the vital role of AKR1C3 in CRPC and recent developments in the discovery of potent and selective AKR1C3 inhibitors. This article is part of a Special Issue entitled 'CSR 2013'.

  14. Complement component C3 - The "Swiss Army Knife" of innate immunity and host defense.

    PubMed

    Ricklin, Daniel; Reis, Edimara S; Mastellos, Dimitrios C; Gros, Piet; Lambris, John D

    2016-11-01

    As a preformed defense system, complement faces a delicate challenge in providing an immediate, forceful response to pathogens even at first encounter, while sparing host cells in the process. For this purpose, it engages a tightly regulated network of plasma proteins, cell surface receptors, and regulators. Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses. In recent years, it has become evident that nature engages the power of C3 not only to clear pathogens but also for a variety of homeostatic processes ranging from tissue regeneration and synapse pruning to clearing debris and controlling tumor cell progression. At the same time, its central position in immune surveillance makes C3 a target for microbial immune evasion and, if improperly engaged, a trigger point for various clinical conditions. In our review, we look at the versatile roles and evolutionary journey of C3, discuss new insights into the molecular basis for C3 function, provide examples of disease involvement, and summarize the emerging potential of C3 as a therapeutic target. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Synthesis and photocatalytic performance of g-C3N4 nanosheets via liquid phase stripping

    NASA Astrophysics Data System (ADS)

    Miao, Jilin; Xu, Guangqing; Liu, Jiaqin; Lv, Jun; Wu, Yucheng

    2017-02-01

    Well dispersed g-C3N4 nanosheets were prepared by exfoliating the bulk g-C3N4 in concentrated sulfuric acid. Phase structures, morphologies and elemental compositions were characterized by X-ray diffractometer, scanning electron microscope, transmission electron microscope and X-ray photoelectron spectrometer, respectively. Optical absorption and photoluminescence were also used to explain the optical performances of samples. NaI, BQ and IPA were used as the sacrificial agents for studying the surface reactions in the photocatalytic process. By the precipitation of g-C3N4 nanosheets in ethanol with different ratios between concentrated sulfuric acid and ethyl alcohol, well dispersed g-C3N4 nanosheets with high specific surface area can be obtained. The optimized g-C3N4 (1:10) nanosheets achieve the highest photocatalytic activities under UV light illumination, which can degrade 10 mg/L RhB about 98% in 60 min, which is 6 times that of bulk g-C3N4 under UV light.

  16. Aldo-Keto Reductase (AKR) 1C3 inhibitors: a patent review.

    PubMed

    Penning, Trevor M

    2017-09-19

    AKR1C3 is a drug target in hormonal and hormonal independent malignancies and acts as a major peripheral 17β-hydroxysteroid dehydrogenase to yield the potent androgens testosterone and dihydrotestosterone, and as a prostaglandin (PG) F synthase to produce proliferative ligands for the PG FP receptor. AKR1C3 inhibitors may have distinct advantages over existing therapeutics for the treatment of castration resistant prostate cancer, breast cancer and acute myeloid leukemia. Area covered: This article reviews the patent literature on AKR1C3 inhibitors using SciFinder which identified inhibitors in the following chemical classes: N-phenylsulfonyl-indoles, N-(benzimidazoylylcarbonyl)- N-(indoylylcarbonyl)- and N-(pyridinepyrrolyl)- piperidines, N-benzimidazoles and N-benzindoles, repurposed nonsteroidal antiinflammatory drugs (indole acetic acids, N-phenylanthranilates and aryl propionic acids), isoquinolines, and nitrogen and sulfur substituted estrenes. The article evaluates inhibitor AKR potency, specificity, efficacy in cell-based and xenograft models and clinical utility. The advantage of bifunctional compounds that either competitively inhibit AKR1C3 and block its androgen receptor (AR) coactivator function or act as AKR1C3 inhibitors and direct acting AR antagonists are discussed. Expert opinion: A large number of potent and selective inhibitors of AKR1C3 have been described however, preclinical optimization, is required before their benefit in human disease can be assessed.

  17. Modeling electron transfer thermodynamics in protein complexes: interaction between two cytochromes c(3).

    PubMed

    Teixeira, Vitor H; Baptista, António M; Soares, Cláudio M

    2004-05-01

    Redox protein complexes between type I and type II tetraheme cytochromes c(3) from Desulfovibrio vulgaris Hildenborough are here analyzed using theoretical methodologies. Various complexes were generated using rigid-body docking techniques, and the two lowest energy complexes (1 and 2) were relaxed using molecular dynamics simulations with explicit solvent and subjected to further characterization. Complex 1 corresponds to an interaction between hemes I from both cytochromes c(3). Complex 2 corresponds to an interaction between the heme IV from type I and the heme I from type II cytochrome c(3). Binding free energy calculations using molecular mechanics, Poisson-Boltzmann, and surface accessibility methods show that complex 2 is more stable than complex 1. Thermodynamic calculations on complex 2 show that complex formation induces changes in the reduction potential of both cytochromes c(3), but the changes are larger in the type I cytochrome c(3) (the largest one occurring on heme IV, of approximately 80 mV). These changes are sufficient to invert the global titration curves of both cytochromes, generating directionally in electron transfer from type I to type II cytochrome c(3), a phenomenon of obvious thermodynamic origin and consequences, but also with kinetic implications. The existence of processes like this occurring at complex formation may constitute a natural design of efficient redox chains.

  18. Membranoproliferative glomerulonephritis with isolated C3 deposits: case report and literature review.

    PubMed

    Darouich, Sihem; Goucha, Rym; Jaafoura, Mohamed Habib; Zekri, Semy; Kheder, Adel; Ben Maiz, Hédi

    2011-02-01

    Membranoproliferative glomerulonephritis with isolated C3 deposits (MPGNC3) is an uncommon condition characterized by overt glomerular C3 deposits in the absence of immunoglobulins and intramembranous dense deposits. Here the authors describe the clinical and morphological features of primary MPGNC3 in a 13-year-old boy and critically review the previously published cases. The patient presented with nephrotic syndrome and microscopic hematuria. Blood tests revealed very low circulating C3 levels. The renal biopsy exhibited subendothelial, subepithelial, and mesangial deposits, with C3 but not immunoglobulins seen on immunofluorescence. This case and the review of the literature indicate that the serum complement profile with decreased levels of C3 and normal levels of classical pathway components together with glomerular deposits containing exclusively complement C3 is highly suggestive of alternative pathway activation. The diagnosis of acquired and/or genetic complement abnormalities in some cases supports that complement dysregulation is implicated in the pathogenesis of MPGNC3. Such data show great promise to provide new therapy strategies based on modulation of the complement system activity.

  19. Boron doped g-C3N4 with enhanced photocatalytic UO22+ reduction performance

    NASA Astrophysics Data System (ADS)

    Lu, Changhai; Chen, Rongyue; Wu, Xi; Fan, Meifeng; Liu, Yunhai; Le, Zhanggao; Jiang, Shujuan; Song, Shaoqing

    2016-01-01

    Tuning the band gap and absorption intensity of visible-light by element doping is an attractive strategy to enhance the photocatalytic activity of semiconductor materials. Here we doped boron into g-C3N4 to construct highly efficient photocatalysts (B-g-C3N4) for the photocatalytic reduction of UO22+. Characterization and photocatalysis tests showed the band gap of B-g-C3N4 was narrowed, and the absorption intensity of visible-light was enhanced with increasing the formed N-B-C (BCN) of B-g-C3N4, which is consistent with the trend of the photocatalytic performance of B-g-C3N4. The optimized B-g-C3N4 photocatalyst with BCN content of 1.01 at.% exhibited excellent removal efficiency of UO22+ and good photocatalytic stability. Therefore, these results may lead to a new strategy for exploring the advanced photocatalysts based on the carbon nanomaterials with abundant BCN for the photocatalytic reduction of U(VI) pollutant.

  20. First Detection of c-C3H2 in a Circumstellar Disk

    NASA Astrophysics Data System (ADS)

    Qi, Chunhua; Öberg, Karin I.; Wilner, David J.; Rosenfeld, Katherine A.

    2013-03-01

    We report the first detection of c-C3H2 in a circumstellar disk. The c-C3H2 J = 6-5 line (217.882 GHz) is detected and imaged through Atacama Large Millimeter Array (ALMA) Science Verification observations toward the disk around the Herbig Ae star HD 163296 at 0.''8 resolution. The emission is consistent with that arising from a Keplerian rotating disk. Two additional c-C3H2 transitions are also tentatively detected, bolstering the identification of this species, but with insufficient signal-to-noise ratio to constrain the spatial distribution. Using a previously developed model for the physical structure of this disk, we fit a radial power-law distribution model to the c-C3H2 6-5 emission and find that c-C3H2 is present in a ring structure from an inner radius of about 30 AU to an outer radius of about 165 AU. The column density is estimated to be 1012-1013 cm-2. The clear detection and intriguing ring structure suggest that c-C3H2 has the potential to become a useful probe of radiation penetration in disks.

  1. Recent advances in functional mesoporous graphitic carbon nitride (mpg-C3N4) polymers.

    PubMed

    Sun, Shaodong; Liang, Shuhua

    2017-08-03

    Mesoporous micro-/nanostructures acting as supports for catalysts or used directly in catalysis reactions generally show fascinating performances that could lead to great potential for application. In the past few decades, extensive efforts have been devoted to the exploration and enrichment of graphitic carbon nitride (g-C3N4) based research. Especially, mesoporous g-C3N4 (mpg-C3N4) with controllable porosity and electronic/atomic structure can bring to bear unique physicochemical properties and has been widely applied in the fields of photocatalysis, adsorbents, sensors and chemical templates. However, a comprehensive summary on mpg-C3N4 micro/nanostructures is less reported and there is an urgent need to further promote the development of function-oriented mpg-C3N4-based materials. Herein, we will overview the significant advances in functional mpg-C3N4 polymers, including general synthesis strategies and growth mechanisms, modifications of electronic/atomic structures and interfacial properties (such as exfoliation, doping and hybridizing), as well as their current applications. Finally, several emerging issues and perspectives are also proposed.

  2. Disappearing Polymorphs Revisited

    PubMed Central

    Bučar, Dejan-Krešimir; Lancaster, Robert W; Bernstein, Joel

    2015-01-01

    Nearly twenty years ago, Dunitz and Bernstein described a selection of intriguing cases of polymorphs that disappear. The inability to obtain a crystal form that has previously been prepared is indeed a frustrating and potentially serious problem for solid-state scientists. This Review discusses recent occurrences and examples of disappearing polymorphs (as well as the emergence of elusive crystal forms) to demonstrate the enduring relevance of this troublesome, but always captivating, phenomenon in solid-state research. A number of these instances have been central issues in patent litigations. This Review, therefore, also highlights the complex relationship between crystal chemistry and the law. PMID:26031248

  3. Structure of Complement C3(H2O) Revealed By Quantitative Cross-Linking/Mass Spectrometry And Modeling*

    PubMed Central

    Pellarin, Riccardo; Sali, Andrej; Barlow, Paul N.

    2016-01-01

    The slow but spontaneous and ubiquitous formation of C3(H2O), the hydrolytic and conformationally rearranged product of C3, initiates antibody-independent activation of the complement system that is a key first line of antimicrobial defense. The structure of C3(H2O) has not been determined. Here we subjected C3(H2O) to quantitative cross-linking/mass spectrometry (QCLMS). This revealed details of the structural differences and similarities between C3(H2O) and C3, as well as between C3(H2O) and its pivotal proteolytic cleavage product, C3b, which shares functionally similarity with C3(H2O). Considered in combination with the crystal structures of C3 and C3b, the QCMLS data suggest that C3(H2O) generation is accompanied by the migration of the thioester-containing domain of C3 from one end of the molecule to the other. This creates a stable C3b-like platform able to bind the zymogen, factor B, or the regulator, factor H. Integration of available crystallographic and QCLMS data allowed the determination of a 3D model of the C3(H2O) domain architecture. The unique arrangement of domains thus observed in C3(H2O), which retains the anaphylatoxin domain (that is excised when C3 is enzymatically activated to C3b), can be used to rationalize observed differences between C3(H2O) and C3b in terms of complement activation and regulation. PMID:27250206

  4. Diosgenone: a second P21 polymorph

    PubMed Central

    Hernández Linares, María-Guadalupe; Guerrero-Luna, Gabriel; Bernès, Sylvain; Flores-Alamo, Marcos; Fernández-Herrera, María A.

    2012-01-01

    Diosgenone [(20S,22R,25R)-spirost-4-en-3-one, C27H40O3] has been proposed as a new therapeutic alternative for the treatment of malaria. The first X-ray structure report for diosgenone was by Piro et al. [(2002). Z. Naturforsch. Teil C, 57, 947–950] in the space group P21 (Z′ = 2). We now report a new polymorph in the same space group, with two mol­ecules in the asymmetric unit. Both mol­ecules have similar conformations, characterized by a skewed envelope A ring, which contains the C=C bond conjugated with the ketone functionality at C3. The dimorphism results from a modification of the relative orientation of the mol­ecules in the asymmetric unit: two independent mol­ecules were arranged anti­parallel in the Piro report, while they are parallel in the present determination. PMID:22904824

  5. Polymorphism of sorbitol

    NASA Astrophysics Data System (ADS)

    Nezzal, Amale; Aerts, Luc; Verspaille, Marleen; Henderickx, Geert; Redl, Andreas

    2009-07-01

    The polymorphism of sorbitol was investigated, confirming the existence of four anhydrous crystalline phases plus the hydrate. The crystallised melt (CM), the alpha form, and the gamma form were obtained via a dry route. The CM was confirmed to be a crystalline state with a spherulite morphology. The alpha form was obtained via direct conversion from the CM, in contrast to more complicated routes previously reported, and was found to have a very high crystallinity. Gamma crystals were obtained by seeding the melt at high temperature; however, crystallinity was clearly less than for alpha crystals. Despite its lower crystallinity, the gamma polymorph was found to be the most stable of the anhydrous crystalline forms; this was confirmed by its high melting point and low hygroscopicity. In contrast, the alpha polymorph has a relatively high melting point but lacks moisture stability at high relative humidity. The hydrate form has the same resistance to moisture as the gamma form, but melts at a lower temperature. The combination of both a high melting point and high stability in the presence of water makes the gamma polymorph best suited for confectionary applications.

  6. Polymorphous Perversity in Texts

    ERIC Educational Resources Information Center

    Johnson-Eilola, Johndan

    2012-01-01

    Here's the tricky part: If we teach ourselves and our students that texts are made to be broken apart, remixed, remade, do we lose the polymorphous perversity that brought us pleasure in the first place? Does the pleasure of transgression evaporate when the borders are opened?

  7. Enzyme polymorphisms in Canarium

    USDA-ARS?s Scientific Manuscript database

    Fifty-two accessions of Canarium involving seven species, C. ovatum, C. album, C. megalanthum, C. harveyi, C. indicum, C. mehenbethene, and C. odontophyllum were studied for isozyme polymorphisms. Starch gel electrophoresis with a histidine-citrate buffer system (pH 6.5) was employed to assay six en...

  8. Investigation of Uranium Polymorphs

    SciTech Connect

    Sweet, Lucas E.; Henager, Charles H.; Hu, Shenyang Y.; Johnson, Timothy J.; Meier, David E.; Peper, Shane M.; Schwantes, Jon M.

    2011-08-01

    The UO3-water system is complex and has not been fully characterized, even though these species are common throughout the nuclear fuel cycle. As an example, most production schemes for UO3 result in a mixture of up to six or more different polymorphic phases, and small differences in these conditions will affect phase genesis that ultimately result in measureable changes to the end product. As a result, this feature of the UO3-water system may be useful as a means for determining process history. This research effort attempts to better characterize the UO3-water system with a variety of optical techniques for the purpose of developing some predictive capability for estimating process history in polymorphic phases of unknown origin. Three commercially relevant preparation methods for the production of UO3 were explored. Previously unreported low temperature routes to β- and γ-UO3 were discovered. Raman and fluorescence spectroscopic libraries were established for pure and mixed polymorphic forms of UO3 in addition to the common hydrolysis products of UO3. An advantage of the sensitivity of optical fluorescence microscopy over XRD has been demonstrated. Preliminary aging studies of the α and γ forms of UO3 have been conducted. In addition, development of a 3-D phase field model used to predict phase genesis of the system was initiated. Thermodynamic and structural constants that will feed the model have been gathered from the literature for most of the UO3 polymorphic phases.

  9. Polymorphism in Energetic Materials

    DTIC Science & Technology

    2008-01-01

    salicylic acid ) was first prepared by Charles Frederic Gerhardt in 1853, a second polymorph of this drug was not discovered until 2005. Studies have...the crystallization conditions post- synthesis were not recorded, reproducing the condi- tions resulting in the analyzed sample was not possible. All

  10. The draft genome of the C3 panicoid grass species Dichanthelium oligosanthes.

    PubMed

    Studer, Anthony J; Schnable, James C; Weissmann, Sarit; Kolbe, Allison R; McKain, Michael R; Shao, Ying; Cousins, Asaph B; Kellogg, Elizabeth A; Brutnell, Thomas P

    2016-10-28

    Comparisons between C3 and C4 grasses often utilize C3 species from the subfamilies Ehrhartoideae or Pooideae and C4 species from the subfamily Panicoideae, two clades that diverged over 50 million years ago. The divergence of the C3 panicoid grass Dichanthelium oligosanthes from the independent C4 lineages represented by Setaria viridis and Sorghum bicolor occurred approximately 15 million years ago, which is significantly more recent than members of the Bambusoideae, Ehrhartoideae, and Pooideae subfamilies. D. oligosanthes is ideally placed within the panicoid clade for comparative studies of C3 and C4 grasses. We report the assembly of the nuclear and chloroplast genomes of D. oligosanthes, from high-throughput short read sequencing data and a comparative transcriptomics analysis of the developing leaf of D. oligosanthes, S. viridis, and S. bicolor. Physiological and anatomical characterizations verified that D. oligosanthes utilizes the C3 pathway for carbon fixation and lacks Kranz anatomy. Expression profiles of transcription factors along developing leaves of D. oligosanthes and S. viridis were compared with previously published data from S. bicolor, Zea mays, and Oryza sativa to identify a small suite of transcription factors that likely acquired functions specifically related to C4 photosynthesis. The phylogenetic location of D. oligosanthes makes it an ideal C3 plant for comparative analysis of C4 evolution in the panicoid grasses. This genome will not only provide a better C3 species for comparisons with C4 panicoid grasses, but also highlights the power of using high-throughput sequencing to address questions in evolutionary biology.

  11. The draft genome of the C3 panicoid grass species Dichanthelium oligosanthes

    DOE PAGES

    Studer, Anthony J.; Schnable, James C.; Weissmann, Sarit; ...

    2016-10-28

    Comparisons between C3 and C4 grasses often utilize C3 species from the subfamilies Ehrhartoideae or Pooideae and C4 species from the subfamily Panicoideae, two clades that diverged over 50 million years ago. The divergence of the C3 panicoid grass Dichanthelium oligosanthes from the independent C4 lineages represented by Setaria viridis and Sorghum bicolor occurred approximately 15 million years ago, which is significantly more recent than members of the Bambusoideae, Ehrhartoideae, and Pooideae subfamilies. D. oligosanthes is ideally placed within the panicoid clade for comparative studies of C3 and C4 grasses. Here, we report the assembly of the nuclear and chloroplastmore » genomes of D. oligosanthes, from high-throughput short read sequencing data and a comparative transcriptomics analysis of the developing leaf of D. oligosanthes, S. viridis, and S. bicolor. Physiological and anatomical characterizations verified that D. oligosanthes utilizes the C3 pathway for carbon fixation and lacks Kranz anatomy. Expression profiles of transcription factors along developing leaves of D. oligosanthes and S. viridis were compared with previously published data from S. bicolor, Zea mays, and Oryza sativa to identify a small suite of transcription factors that likely acquired functions specifically related to C4 photosynthesis. In conclusion, the phylogenetic location of D. oligosanthes makes it an ideal C3 plant for comparative analysis of C4 evolution in the panicoid grasses. This genome will not only provide a better C3 species for comparisons with C4 panicoid grasses, but also highlights the power of using high-throughput sequencing to address questions in evolutionary biology.« less

  12. Intracrine androgens and AKR1C3 activation confer resistance to enzalutamide in prostate cancer

    PubMed Central

    Liu, Chengfei; Lou, Wei; Zhu, Yezi; Yang, Joy C.; Nadiminty, Nagalakshmi; Gaikwad, Nilesh W.; Evans, Christopher P.; Gao, Allen C.

    2015-01-01

    The introduction of enzalutamide and abiraterone has led to improvement in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, acquired resistance to enzalutamide and abiraterone therapies frequently develops within a short period in many patients. In the present study, we developed enzalutamide resistant prostate cancer cells in an effort to understand the mechanisms of resistance. Global gene expression analysis showed that steroid biosynthesis pathway is activated in enzalutamide resistant prostate cancer cells. One of the crucial steroidogenic enzymes, AKR1C3, was significantly elevated in enzalutamide resistant cells. In addition, AKR1C3 is highly expressed in metastatic and recurrent prostate cancer and in enzalutamide resistant prostate xenograft tumors. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis of the steroid metabolites revealed that androgen precursors such as cholesterol, DHEA and progesterone, as well as androgens are highly up regulated in enzalutamide resistant prostate cancer cells compared to the parental cells. Knock down of AKR1C3 expression by shRNA or inhibition of AKR1C3 enzymatic activity by indomethacin resensitized enzalutamide resistant prostate cancer cells to enzalutamide treatment both in vitro and in vivo. In contrast, overexpression of AKR1C3 confers resistance to enzalutamide. Furthermore, the combination of indomethacin and enzalutamide resulted in significant inhibition of enzalutamide-resistant tumor growth. These results suggest that AKR1C3 activation is a critical resistance mechanism associated with enzalutamide resistance, targeting intracrine androgens and AKR1C3 will overcome enzalutamide resistance and improve survival of advanced prostate cancer patients. PMID:25649766

  13. Functions of the complement components C3 and C5 during sepsis

    PubMed Central

    Flierl, Michael A.; Rittirsch, Daniel; Nadeau, Brian A.; Day, Danielle E.; Zetoune, Firas S.; Sarma, J. Vidya; Huber-Lang, Markus S.; Ward, Peter A.

    2008-01-01

    Activation of the complement system is a key event in the pathogenesis of sepsis. Nevertheless, the exact mechanisms remain inadequately understood. In the current study, we examined the role of complement C3 and C5 in sepsis in wild-type and C3- or C5-deficient mice induced by cecal ligation and puncture. When compared to wild-type mice, C5−/− showed identical survival, and C3−/− presented significantly reduced survival. Interestingly, this was associated with significant decreases in plasma levels of proinflammatory mediators. Moreover, although septic C3−/− animals displayed a 10-fold increase of blood-borne bacteria, C5−/− animals exhibited a 400-fold increase in bacteremia when compared to wild-type mice. These effects were linked to the inability of C5−/− mice to assemble the terminal membrane attack complex (MAC), as determined by complement hemolytic activity (CH-50). Surprisingly, although negative control C3−/− mice failed to generate the MAC, significant increases of MAC formation was found in septic C3−/− mice. In conclusion, our data corroborate that hemolytic complement activity is essential for control of bacteremia in septic mice. Thus, during sepsis, blockade of C5a or its receptors (rather than C5) seems a more promising strategy, because C5a-blockade still allows for MAC formation while the adverse effects of C5a are prevented.—Flierl, M. A., Rittirsch, D., Nadeau, B. A., Day, D. E., Zetoune, F. S., Sarma, J. V., Huber-Lang, M. S., Ward, P. A. Functions of the complement components C3 and C5 during sepsis. PMID:18587006

  14. Molecular recognition of an ADP-ribosylating Clostridium botulinum C3 exoenzyme by RalA GTPase

    PubMed Central

    Holbourn, Kenneth P.; Sutton, J. Mark; Evans, Hazel R.; Shone, Clifford C.; Acharya, K. Ravi

    2005-01-01

    C3 exoenzymes (members of the ADP-ribosyltranferase family) are produced by Clostridium botulinum (C3bot1 and -2), Clostridium limosum (C3lim), Bacillus cereus (C3cer), and Staphylococcus aureus (C3stau1–3). These exoenzymes lack a translocation domain but are known to specifically inactivate Rho GTPases in host target cells. Here, we report the crystal structure of C3bot1 in complex with RalA (a GTPase of the Ras subfamily) and GDP at a resolution of 2.66 Å. RalA is not ADP-ribosylated by C3 exoenzymes but inhibits ADP-ribosylation of RhoA by C3bot1, C3lim, and C3cer to different extents. The structure provides an insight into the molecular interactions between C3bot1 and RalA involving the catalytic ADP-ribosylating turn–turn (ARTT) loop from C3bot1 and helix α4 and strand β6 (which are not part of the GDP-binding pocket) from RalA. The structure also suggests a molecular explanation for the different levels of C3-exoenzyme inhibition by RalA and why RhoA does not bind C3bot1 in this manner. PMID:15809419

  15. Molecular recognition of an ADP-ribosylating Clostridium botulinum C3 exoenzyme by RalA GTPase.

    PubMed

    Holbourn, Kenneth P; Sutton, J Mark; Evans, Hazel R; Shone, Clifford C; Acharya, K Ravi

    2005-04-12

    C3 exoenzymes (members of the ADP-ribosyltranferase family) are produced by Clostridium botulinum (C3bot1 and -2), Clostridium limosum (C3lim), Bacillus cereus (C3cer), and Staphylococcus aureus (C3stau1-3). These exoenzymes lack a translocation domain but are known to specifically inactivate Rho GTPases in host target cells. Here, we report the crystal structure of C3bot1 in complex with RalA (a GTPase of the Ras subfamily) and GDP at a resolution of 2.66 A. RalA is not ADP-ribosylated by C3 exoenzymes but inhibits ADP-ribosylation of RhoA by C3bot1, C3lim, and C3cer to different extents. The structure provides an insight into the molecular interactions between C3bot1 and RalA involving the catalytic ADP-ribosylating turn-turn (ARTT) loop from C3bot1 and helix alpha4 and strand beta6 (which are not part of the GDP-binding pocket) from RalA. The structure also suggests a molecular explanation for the different levels of C3-exoenzyme inhibition by RalA and why RhoA does not bind C3bot1 in this manner.

  16. "Invar"-like behavior in compressed Fe7C3 with implication for deep carbon cycle

    NASA Astrophysics Data System (ADS)

    Liu, J.; Li, J.; Ikuta, D.

    2014-12-01

    Iron carbide Fe7C3 has recently emerged as a leading candidate component of the inner core because it is likely the first phase to solidify from a liquid containing iron and a small amount of carbon, and previous studies suggest that it provides a good match for the density of the inner core under relevant conditions. Pressure-induced magnetic transitions have been observed in Fe7C3 (Chen et al., 2012). The pressure of the ferromagnetic to paramagnetic transition remains controversial and its effect on equation of state (EoS) is unclear, thus introducing uncertainties in estimating the density of Fe7C3 under inner core pressures. Here we report the lattice parameters and unit cell volume of hexagonal Fe7C3 at 300 K and up to 70 GPa, obtained through synchrotron x-ray diffraction measurements using a diamond anvil cell. The experiments used fine powder of Fe7C3 that was synthesized in the multi-anvil apparatus at the University of Michigan. The sample was embedded in neon pressure medium together with Au powder and ruby spheres as additional pressure markers. We observed significant softening at 5~8 GPa, similar to the reported "invar"-like behavior in Fe-Ni alloy (Dubrovinsky et al., 2001). For comparison, the compression curve of iron in the same loading turned out to be smooth as expected, which confirms that the abnormal behavior in Fe7C3 compression curve is due to its own property change and not an artifact. The new data allow us to establish the equation-of-state (EoS) of Fe7C3 and then estimate the density of Fe7C3 at inner core conditions. References: Chen, B., Gao, L.L., Lavina, B., Dera, P., Alp, E.E., Zhao, J.Y., Li, J., 2012. Magneto-elastic coupling in compressed Fe7C3 supports carbon in Earth's inner core. Geophys Res Lett 39. Dubrovinsky, L., Dubrovinskaia, N., Abrikosov, I.A., Vennstrom, M., Westman, F., Carlson, S., van Schilfgaarde, M., Johansson, B., 2001. Pressure-induced invar effect in Fe-Ni alloys. Phys Rev Lett 86, 4851-4854.

  17. P7C3 Neuroprotective Chemicals Block Axonal Degeneration and Preserve Function after Traumatic Brain Injury

    PubMed Central

    Yin, Terry C.; Britt, Jeremiah K.; De Jesús-Cortés, Héctor; Lu, Yuan; Genova, Rachel M.; Khan, Michael Z.; Voorhees, Jaymie R.; Shao, Jianqiang; Katzman, Aaron C.; Huntington, Paula J.; Wassink, Cassie; McDaniel, Latisha; Newell, Elizabeth A.; Dutca, Laura M.; Naidoo, Jacinth; Cui, Huxing; Bassuk, Alexander G.; Harper, Matthew M.; McKnight, Steven L.; Ready, Joseph M.; Pieper, Andrew A.

    2014-01-01

    SUMMARY The P7C3 class of neuroprotective aminopropyl carbazoles has been shown to block neuronal cell death in models of neurodegeneration. We now show that P7C3 molecules additionally preserve axonal integrity after injury, before neuronal cell death occurs, in a rodent model of blast-mediated traumatic brain injury (TBI). This protective quality may be linked to the ability of P7C3 molecules to activate nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in nicotinamide adenine dinucleotide salvage. Initiation of daily treatment with our recently reported lead agent, P7C3-S243, one day after blast-mediated TBI blocks axonal degeneration and preserves normal synaptic activity, learning and memory, and motor coordination in mice. We additionally report persistent neurologic deficits and acquisition of an anxiety-like phenotype in untreated animals eight months after blast exposure. Optimized variants of P7C3 thus offer hope for identifying neuroprotective agents for conditions involving axonal damage, neuronal cell death, or both, such as occurs in TBI. PMID:25220467

  18. Enhancing C3 photosynthesis: an outlook on feasible interventions for crop improvement.

    PubMed

    Singh, Jitender; Pandey, Prachi; James, Donald; Chandrasekhar, Kottakota; Achary, V Mohan Murali; Kaul, Tanushri; Tripathy, Baishnab C; Reddy, Malireddy K

    2014-12-01

    Despite the declarations and collective measures taken to eradicate hunger at World Food Summits, food security remains one of the biggest issues that we are faced with. The current scenario could worsen due to the alarming increase in world population, further compounded by adverse climatic conditions, such as increase in atmospheric temperature, unforeseen droughts and decreasing soil moisture, which will decrease crop yield even further. Furthermore, the projected increase in yields of C3 crops as a result of increasing atmospheric CO2 concentrations is much less than anticipated. Thus, there is an urgent need to increase crop productivity beyond existing yield potentials to address the challenge of food security. One of the domains of plant biology that promises hope in overcoming this problem is study of C3 photosynthesis. In this review, we have examined the potential bottlenecks of C3 photosynthesis and the strategies undertaken to overcome them. The targets considered for possible intervention include RuBisCO, RuBisCO activase, Calvin-Benson-Bassham cycle enzymes, CO2 and carbohydrate transport, and light reactions among many others. In addition, other areas which promise scope for improvement of C3 photosynthesis, such as mining natural genetic variations, mathematical modelling for identifying new targets, installing efficient carbon fixation and carbon concentrating mechanisms have been touched upon. Briefly, this review intends to shed light on the recent advances in enhancing C3 photosynthesis for crop improvement.

  19. Suggestion for search of cyclopropenone (c-C3H2O) in a cosmic object

    NASA Astrophysics Data System (ADS)

    Sharma, M. K.; Sharma, M.; Chandra, S.

    2017-03-01

    Following Minimum Energy Principle, out of the three isomers of chemical formula C3H2O, the cyclopropenone (c-C3H2O) is the most stable and therefore may be the most abundant and easily detectable in a cosmic object. The cyclopropenone is detected in Sgr B2(N). Owing to half-spin of each of two hydrogen atoms, the c-C3H2O has two distinct ortho and para species. Using the rotational and centrifugal distortion constants along with the electric dipole moment, we have calculated energies of 100 rotational levels of each of the ortho and para species of c-C3H2O and the Einstein A-coefficients for radiative transitions between the levels. The values of Einstein A-coefficients along with the scaled values for collisional rate coefficients are used for solving a set of statistical equilibrium equations coupled with the equations of radiative transfer. Brightness temperatures of seven rotational transitions of each of the ortho and para species of c-C3H2O are investigated. Out of fourteen transitions, seven are found to show anomalous absorption and rest seven are found to show emission feature. We find that the transitions 110 -111 (1.544 GHz) may play important role in identification of cyclopropenone in a cosmic object.

  20. Physiological and growth responses of C3 and C4 plants at the Pleistocene glacial maximum

    SciTech Connect

    Strain, B.R.

    1995-06-01

    A C3 plant (Abutilon theophrasti) and a C4 plant (Amaranthus retroflexus) were grown from seed in the Duke University Phytotron under four CO2 concentrations (15 Pa, below the Pleistocene minimum), 27 Pa (pre-industrial), 35 Pa (current), and 70 Pa (future) to examine photosynthetic, growth and reproduction responses of annual plants to historic and future levels of CO2. Net photosynthesis and growth were greatly inhibited at 15 Pa and greatly stimulated at 70 Pa. in the C3 Abutilon but only slightly affected in the C4 Amaranthus. Flower bud initiation was not affected by CO2 treatment in either species but all flower buds in 15 Pa CO2 aborted in the C3 within two days of appearance while no inhibition of reproduction was observed at low CO2 in the C4. Differences in physiology, growth and reproduction to the low levels of atmospheric CO2 of the Pleistocene suggest that competitive interactions of C3 and C4 annuals have changed through geologic time. A major question concerning the survival and evolution of obligate C3 annuals during the CO2 minima of the Pleistocene is raised by the results of this study.

  1. Preliminary Mission Results and Project Evaluation of the Delfi-C3 Nano-satellite

    NASA Astrophysics Data System (ADS)

    Bouwmeester, J.; Aalbers, G. T.; Ubbels, W. J.

    2008-08-01

    This paper discusses preliminary mission results of Delfi-C3 up till the early operations phase. The first section will discuss the design philosophy of Delfi-C3. To reduce operational risks, Delfi-C3 followed the KISS principle and is designed to be Single-Point-of-Failure- free. A balance is made between adoption of professional space engineering customs and standards on one hand and the limitations of small satellites, financial budgets and limited human resources on the other hand. The second section of the paper discusses the project planning and management of Delfi-C3. Addressed are reasonable timelines for the development of a nano-satellite, how to deal with a launch slip and the occasional conflicts between the interest of the students and the interest of the project. The third section of the paper will present the results of the early operations of Delfi-C3. Discussed are the performance of the payloads, the bus and the ground network of the satellite. Finally, an early statement of the mission success will be given.

  2. Vertical Distribution of C3-hydrocarbons in the Stratosphere of Titan

    NASA Astrophysics Data System (ADS)

    Li, Cheng; Zhang, Xi; Gao, Peter; Yung, Yuk

    2015-04-01

    Motivated by the recent detection of propene (C3H6) in the atmosphere of Titan, we use a one-dimensional Titan photochemical model with an updated eddy diffusion profile to systematically study the vertical profiles of the stable species in the C3-hydrocarbon family. We find that the stratospheric volume mixing ratio of propene (C3H6) peaks at 150 km with a value of 5 × 10-9, which is in good agreement with recent observations by the Composite Infrared Spectrometer on the Cassini spacecraft. Another important species that is currently missing from the hydrocarbon family in Titan's stratosphere is allene (CH2CCH2), an isomer of methylacetylene (CH3C2H). We predict that its mixing ratio in the stratosphere is about 10-9, which is on the margin of the detection limit. CH2CCH2 and CH3C2H equilibrate at a constant ratio in the stratosphere by hydrogen-exchanging reactions. Thus, by precisely measuring the ratio of CH2CCH2 to CH3C2H, the abundance of atomic hydrogen in the atmosphere can be inferred. No direct yield for the production of cyclopropane (c-C3H6) is available. From the discharge experiments of Navarro-González & Ramírez, the abundance of cyclopropane is estimated to be 100 times less than that of C3H6.

  3. P7C3 neuroprotective chemicals block axonal degeneration and preserve function after traumatic brain injury.

    PubMed

    Yin, Terry C; Britt, Jeremiah K; De Jesús-Cortés, Héctor; Lu, Yuan; Genova, Rachel M; Khan, Michael Z; Voorhees, Jaymie R; Shao, Jianqiang; Katzman, Aaron C; Huntington, Paula J; Wassink, Cassie; McDaniel, Latisha; Newell, Elizabeth A; Dutca, Laura M; Naidoo, Jacinth; Cui, Huxing; Bassuk, Alexander G; Harper, Matthew M; McKnight, Steven L; Ready, Joseph M; Pieper, Andrew A

    2014-09-25

    The P7C3 class of neuroprotective aminopropyl carbazoles has been shown to block neuronal cell death in models of neurodegeneration. We now show that P7C3 molecules additionally preserve axonal integrity after injury, before neuronal cell death occurs, in a rodent model of blast-mediated traumatic brain injury (TBI). This protective quality may be linked to the ability of P7C3 molecules to activate nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in nicotinamide adenine dinucleotide salvage. Initiation of daily treatment with our recently reported lead agent, P7C3-S243, 1 day after blast-mediated TBI blocks axonal degeneration and preserves normal synaptic activity, learning and memory, and motor coordination in mice. We additionally report persistent neurologic deficits and acquisition of an anxiety-like phenotype in untreated animals 8 months after blast exposure. Optimized variants of P7C3 thus offer hope for identifying neuroprotective agents for conditions involving axonal damage, neuronal cell death, or both, such as occurs in TBI.

  4. C3 plants enhance rates of photosynthesis by reassimilating photorespired and respired CO2.

    PubMed

    Busch, Florian A; Sage, Tammy L; Cousins, Asaph B; Sage, Rowan F

    2013-01-01

    Photosynthetic carbon gain in plants using the C(3) photosynthetic pathway is substantially inhibited by photorespiration in warm environments, particularly in atmospheres with low CO(2) concentrations. Unlike C(4) plants, C(3) plants are thought to lack any mechanism to compensate for the loss of photosynthetic productivity caused by photorespiration. Here, for the first time, we demonstrate that the C(3) plants rice and wheat employ a specific mechanism to trap and reassimilate photorespired CO(2) . A continuous layer of chloroplasts covering the portion of the mesophyll cell periphery that is exposed to the intercellular air space creates a diffusion barrier for CO(2) exiting the cell. This facilitates the capture and reassimilation of photorespired CO(2) in the chloroplast stroma. In both species, 24-38% of photorespired and respired CO(2) were reassimilated within the cell, thereby boosting photosynthesis by 8-11% at ambient atmospheric CO(2) concentration and 17-33% at a CO(2) concentration of 200 µmol mol(-1) . Widespread use of this mechanism in tropical and subtropical C(3) plants could explain why the diversity of the world's C(3) flora, and dominance of terrestrial net primary productivity, was maintained during the Pleistocene, when atmospheric CO(2) concentrations fell below 200 µmol mol(-1) . © 2012 Blackwell Publishing Ltd.

  5. Ti-decorated graphitic-C3N4 monolayer: A promising material for hydrogen storage

    NASA Astrophysics Data System (ADS)

    Zhang, Weibin; Zhang, Zhijun; Zhang, Fuchun; Yang, Woochul

    2016-11-01

    Ti-decorated graphitic carbon nitride (g-C3N4) monolayer as a promising material system for high-capacity hydrogen storage is proposed through density functional theory calculations. The stability and hydrogen adsorption of Ti-decorated g-C3N4 is analyzed by computing the adsorption energy, the charge population, and electronic density of states. The most stable decoration site of Ti atom is the triangular N hole in g-C3N4 with an adsorption energy of -7.58 eV. The large diffusion energy barrier of the adsorbed Ti atom of ∼6.00 eV prohibits the cluster formation of Ti atoms. The electric field induced by electron redistribution of Ti-adsorbed porous g-C3N4 significantly enhanced hydrogen adsorption up to five H2 molecules at each Ti atom with an average adsorption energy of -0.30 eV/H2. The corresponding hydrogen capacity reaches up to 9.70 wt% at 0 K. In addition, the hydrogen capacity is predicted to be 6.30 wt% at 233 K and all adsorbed H2 are released at 393 K according to molecular dynamics simulation. Thus, the Ti-decorated g-C3N4 monolayer is suggested to be a promising material for hydrogen storage suggested by the DOE for commercial applications.

  6. Expression of the Pseudomonas aeruginosa Gentamicin Resistance Gene aacC3 in Escherichia coli

    PubMed Central

    van Boxtel, Renée A. J.; van de Klundert, Jos A. M.

    1998-01-01

    The Pseudomonas aeruginosa aacC3 gene was expressed in Escherichia coli after cloning of the single gene behind the strong tac promoter. In the original Pseudomonas strain, aacC3 is preceded by cysC; together they form a single transcription unit. The ribosome-binding site and start codon of aacC3 are involved in a putative intercistronic hairpin, the stability of which interfered with the aminoglycoside resistance level. In Northern blots, full-length transcripts comprising both cysC and aacC3 could not be detected either in the original Pseudomonas strain or in E. coli harboring a plasmid with the cloned operon. In contrast, cysC transcripts were abundant. Cloning of the operon between the tac promoter and a transcription termination signal resulted in higher mRNA levels and phenotypic expression in E. coli. The absence of a transcription termination signal in the wild-type cysC-aacC3 sequence is associated with transcripts of heterogeneous size that were undetected in Northern blots. Our results shed more light on the expression of this gentamicin resistance determinant, although the discrepancies between its expression in E. coli and Pseudomonas are not fully solved. PMID:9835511

  7. Hostility, Anger and Depression Predict Increases in C3 over a 10-Year Period

    PubMed Central

    Boyle, Stephen H.; Jackson, William G.; Suarez, Edward C.

    2007-01-01

    We examined the relation of hostility, anger and depression to 10-year changes in the third (C3) and fourth (C4) complement in 313, apparently healthy male participants enrolled in the Air Force Health Study (AFHS), a 20-year study designed to evaluate the health consequences of dioxin exposure. Hostility, depression and anger were assessed using subscales from the Minnesota Multiphasic Personality Inventory (MMPI), which was administered in 1985. Given the high intercorrelations among these psychological scales, we used a principal component analysis to generate a composite score representing the linear combination of the hostility, anger and depression scales. The dependent variables, C3 and C4 levels, were determined from samples collected in 1992, 1997 and 2002. Regression analyses controlling for age, race, alcohol use, body mass index and cigarette use as well as onset of disease and use of lipid lowering and blood pressure medications during follow-up revealed a significant time X composite score interaction for C3 complement (p < .0003), but not C4. Post-hoc analyses revealed that high composite scores were associated with larger 10-year increases in C3. These observations suggest that men who are hostile and are prone to experience frequent and intense feelings of anger and depression show activation of the complement system, and specifically increases in C3, that may contribute to the development of coronary heart disease. PMID:17321106

  8. Hostility, anger, and depression predict increases in C3 over a 10-year period.

    PubMed

    Boyle, Stephen H; Jackson, William G; Suarez, Edward C

    2007-08-01

    We examined the relation of hostility, anger, and depression to 10-year changes in the third (C3), and fourth (C4) complement in 313, apparently healthy male participants enrolled in the Air Force Health Study (AFHS), a 20-year study designed to evaluate the health consequences of dioxin exposure. Hostility, depression, and anger were assessed using subscales from the Minnesota Multiphasic Personality Inventory (MMPI), which was administered in 1985. Given the high intercorrelations among these psychological scales, we used a principal component analysis to generate a composite score representing the linear combination of the hostility, anger, and depression scales. The dependent variables, C3 and C4 levels, were determined from samples collected in 1992, 1997, and 2002. Regression analyses controlling for age, race, alcohol use, body mass index, and cigarette use as well as onset of disease, and use of lipid lowering and blood pressure medications during follow-up revealed a significant timexcomposite score interaction for C3 complement (p<.0003), but not C4. Post-hoc analyses revealed that high composite scores were associated with larger 10-year increases in C3. These observations suggest that men who are hostile and are prone to experience frequent and intense feelings of anger, and depression show activation of the complement system, and specifically increases in C3, that may contribute to the development of coronary heart disease.

  9. Preparation and characterization of photoactive antimicrobial graphitic carbon nitride (g-C3N4) films.

    PubMed

    Thurston, John H; Hunter, Necia M; Cornell, Kenneth A

    Photoactive films derived from nanostructured samples of metal-free, intermediate band gap semiconductor graphitic carbon nitride (ns-g-C3N4) have been synthesized and characterized for their particle properties and antimicrobial activity. Physical characterization reveals that these materials are composed of discrete nanoparticles whose dimensions range from 200 nm to 700 nm. Investigation of the photochemical reactivity of ns-g-C3N4 using coumarin-3-carboxylic acid (3-CCA) indicates that this material produces reactive oxygen species (ROS) under visible radiation. When irradiated with 0.31J visible light, ns-g-C3N4-based materials reduced the viability of both gram-negative Escherichia coli O157:H7 and gram-positive Staphylococcus aureus by approximately 50%. Nearly complete inactivation of both strains of microorganisms was achieved upon administration of a 0.62J dose of visible radiation. Importantly, no biocidal activity was observed for non-irradiated samples, indicating that the g-C3N4-derived films are not inherently toxic in the absence of visible light. The results of this study suggest that materials and, by extention, films and coatings derived from g-C3N4 may present a novel route for controlling pathogenic microorganisms on surfaces in the environment, and could be useful in reducing incidents of hospital-acquired infections.

  10. A review on g-C3N4-based photocatalysts

    NASA Astrophysics Data System (ADS)

    Wen, Jiuqing; Xie, Jun; Chen, Xiaobo; Li, Xin

    2017-01-01

    As one of the most appealing and attractive technologies, heterogeneous photocatalysis has been utilized to directly harvest, convert and store renewable solar energy for producing sustainable and green solar fuels and a broad range of environmental applications. Due to their unique physicochemical, optical and electrical properties, a wide variety of g-C3N4-based photocatalysts have been designed to drive various reduction and oxidation reactions under light irradiation with suitable wavelengths. In this review, we have systematically summarized the photocatalytic fundamentals of g-C3N4-based photocatalysts, including fundamental mechanism of heterogeneous photocatalysis, advantages, challenges and the design considerations of g-C3N4-based photocatalysts. The versatile properties of g-C3N4-based photocatalysts are highlighted, including their crystal structural, surface phisicochemical, stability, optical, adsorption, electrochemical, photoelectrochemical and electronic properties. Various design strategies are also thoroughly reviewed, including band-gap engineering, defect control, dimensionality tuning, pore texture tailoring, surface sensitization, heterojunction construction, co-catalyst and nanocarbon loading. Many important applications are also addressed, such as photocatalytic water splitting (H2 evolution and overall water splitting), degradation of pollutants, carbon dioxide reduction, selective organic transformations and disinfection. Through reviewing the important state-of-the-art advances on this topic, it may provide new opportunities for designing and constructing highly effective g-C3N4-based photocatalysts for various applications in photocatalysis and other related fields, such as solar cell, photoelectrocatalysis, electrocatalysis, lithium battery, supercapacitor, fuel cell and separation and purification.

  11. High cervical C3-4 'disc' compression associated with basilar invagination.

    PubMed

    Goel, Atul

    2008-01-01

    A 20-year-old male had torticollis and short neck since birth. He presented with symptom of progressive quadriparesis over a two-year period. Investigations revealed basilar invagination with marked rotation in the craniovertebral region and relatively large C3-4 region osteophytes. Serial MRI over two years showed persistent signal opposite C3-4 disc space suggestive of cord compression. Although the cord was humped over the odontoid process, there was no clear radiological evidence that the cord was compromised at this level. During surgery, instability was identified only at the craniovertebral region and not at the level of C3-4. Distraction of the lateral masses of atlas and axis and fixation using interarticular spacers and bone graft and direct screw implantation in the lateral mass of the atlas and pars of the axis resulted in reduction of the basilar invagination and of atlantoaxial dislocation. The patient had marked clinical recovery, despite the fact that no direct procedure was done for C3-4 disc decompression. The case suggests that C3-4 disc changes could be secondary to primary instability at the craniovertebral junction.

  12. Membrane ruffles capture C3bi-opsonized particles in activated macrophages.

    PubMed

    Patel, Prerna C; Harrison, Rene E

    2008-11-01

    A widespread belief in phagocyte biology is that FcgammaR-mediated phagocytosis utilizes membrane pseudopods, whereas Mac-1-mediated phagocytosis does not involve elaborate plasma membrane extensions. Here we report that dynamic membrane ruffles in activated macrophages promote binding of C3bi-opsonized particles. We identify these ruffles as components of the macropinocytosis machinery in both PMA- and LPS-stimulated macrophages. C3bi-particle capture is facilitated by enrichment of high-affinity Mac-1 and the integrin-regulating protein talin in membrane ruffles. Membrane ruffle formation and C3bi-particle binding are cytoskeleton dependent events, having a strong requirement for F-actin and microtubules (MTs). MT disruption blunts ruffle formation and PMA- and LPS-induced up-regulation of surface Mac-1 expression. Furthermore, the MT motor, kinesin participates in ruffle formation implicating a requirement for intracellular membrane delivery to active membrane regions during Mac-1-mediated phagocytosis. We observed colocalization of Rab11-positive vesicles with CLIP-170, a MT plus-end binding protein, at sites of particle adherence using TIRF imaging. Rab11 has been implicated in recycling endosome dynamics and mutant Rab11 expression inhibits both membrane ruffle formation and C3bi-sRBC adherence to macrophages. Collectively these findings represent a novel membrane ruffle "capture" mechanism for C3bi-particle binding during Mac-1-mediated phagocytosis. Importantly, this work also demonstrates a strong functional link between integrin activation, macropinocytosis and phagocytosis in macrophages.

  13. Bypass-activation of the complement system starting with C3

    PubMed Central

    Bitter-Suermann, D.; Dierich, M.; König, W.; Hadding, U.

    1972-01-01

    Antibody independent activation of the complement system starting with C3 can be achieved by means of a purified factor from cobra venom (VF), which interacts with a purified serum factor (SF). The latter is a normal constituent of guinea-pig and human serum (C3-proactivator). The interaction between VF and SF is Mg+ + dependent and leads to the formation of a complex. Immunological analysis reveals that both VF- and SF-antigens are contained in the complex. The VF—SF complex activates enzymatically isolated C3, which in the presence of the subsequent components yields all effects of the normal complement sequence. Purified C5 is not affected by the complex. Its activation is mediated by activated C3. The VF—SF system represents a model for direct activation of C3 to C9 independent of antibody, C1, C4 and C2. An analogous pathway of alternate complement activation might be used by other substances, e.g. endotoxin, guinea-pig γ1-immune aggregates and zymosan. The corresponding serum factors are under investigation. ImagesFIG. 5FIG. 6 PMID:4214761

  14. Transcorporeal approach for disc herniation at the C2-C3 level: a technical case report.

    PubMed

    Shim, Chan Shik; Jung, Tag-Geun; Lee, Sang-Ho

    2009-08-01

    The authors describe a less invasive approach for a disc herniation at the high cervical region. A 68-year-old female patient presented with posterior neck and shoulder pain, and tingling sensation and numbness in the left hand after she fell down stairs 2 months before presentation. On neurologic examination, the power of flexion and extension of the left elbow and grasping of the left hand was decreased. Hoffmann sign was positive in both hands. Magnetic resonance imaging showed a huge herniation of the C2-C3 disc compressing the left paramedian area of the spinal cord. After a routine surgical exposure for discectomy of the C3-C4 disc, a drill hole of about 5 mm diameter was made at the middle of the C3 vertebral body. The hole was extended cranioposteriorly to the superoposterior border of the C3 endplate. The posterior disc at the midline of the C2-C3 was removed first then the herniated disc completely removed. Postoperatively, the patient showed improvement of the neck and shoulder pain and numbness of the hand. At 7-month follow-up, she completely recovered from her neurologic symptoms. Compared with the other approaches to high cervical lesion, the current approach was straightforward and less invasive. If there is no need to stabilize the spinal motion segment, this transcorporeal approach can be a useful surgical option as it decreases the extent of tissue dissection of the submandibular retropharyngeal area that might increase the risk of neurovascular injury.

  15. Regulation of the activity of the promoter of RNA-induced silencing, C3PO.

    PubMed

    Sahu, Shriya; Williams, Leo; Perez, Alberto; Philip, Finly; Caso, Giuseppe; Zurawsky, Walter; Scarlata, Suzanne

    2017-09-01

    RNA-induced silencing is a process which allows cells to regulate the synthesis of specific proteins. RNA silencing is promoted by the protein C3PO (component 3 of RISC). We have previously found that phospholipase Cβ, which increases intracellular calcium levels in response to specific G protein signals, inhibits C3PO activity towards certain genes. Understanding the parameters that control C3PO activity and which genes are impacted by G protein activation would help predict which genes are more vulnerable to downregulation. Here, using a library of 10(18) oligonucleotides, we show that C3PO binds oligonucleotides with structural specificity but little sequence specificity. Alternately, C3PO hydrolyzes oligonucleotides with a rate that is sensitive to substrate stability. Importantly, we find that oligonucleotides with higher Tm values are inhibited by bound PLCβ. This finding is supported by microarray analysis in cells over-expressing PLCβ1. Taken together, this study allows predictions of the genes whose post-transcriptional regulation is responsive to the G protein/phospholipase Cβ/calcium signaling pathway. © 2017 The Protein Society.

  16. Rotational (de-)excitation of C3N- by collision with He atoms

    NASA Astrophysics Data System (ADS)

    Lara-Moreno, Miguel; Stoecklin, Thierry; Halvick, Philippe

    2017-06-01

    Since their recent detection in the interstellar medium, anions have raised the question of their possible mechanisms of formation, destruction and excitation. Among the observed anions, C3N- is an interesting species owing to its large dipole moment and its remarkable stability, since the electron affinity of C3N is particularly large. In this work, a quantum mechanical treatment of the rotational (de-)excitation of C3N- in collisions with He is reported. Full close-coupling calculations are performed within the rigid rotor approximation for the j = 0 up to 15 rotational levels of C3N- and for collision energies in the range 0.1-2000 cm-1. These results are complemented for the j = 16 up to 30 rotational levels of C3N- by using two different approximations whose accuracies are tested against close-coupling results. The uniform J-shifting is found to give the most accurate results. At high collision energy, a strong propensity to favour |Δj| = 2 transitions is observed and discussed. The rate coefficients for the rotational transitions between 1 and 300 K are reported.

  17. Liver ubiquitome uncovers nutrient-stress-mediated trafficking and secretion of complement C3

    PubMed Central

    Magliarelli, Helena de Fatima; Matondo, Mariette; Mészáros, Gergő; Goginashvili, Alexander; Erbs, Eric; Zhang, Zhirong; Mihlan, Michael; Wolfrum, Christian; Aebersold, Ruedi; Sumara, Izabela; Ricci, Romeo

    2016-01-01

    Adaptation to changes in nutrient availability is crucial for cells and organisms. Posttranslational modifications of signaling proteins are very dynamic and are therefore key to promptly respond to nutrient deprivation or overload. Herein we screened for ubiquitylation of proteins in the livers of fasted and refed mice using a comprehensive systemic proteomic approach. Among 1641 identified proteins, 117 were differentially ubiquitylated upon fasting or refeeding. Endoplasmic reticulum (ER) and secretory proteins were enriched in the livers of refed mice in part owing to an ER-stress-mediated response engaging retro-translocation and ubiquitylation of proteins from the ER. Complement C3, an innate immune factor, emerged as the most prominent ER-related hit of our screen. Accordingly, we found that secretion of C3 from the liver and primary hepatocytes as well as its dynamic trafficking are nutrient dependent. Finally, obese mice with a chronic nutrient overload show constitutive trafficking of C3 in the livers despite acute changes in nutrition, which goes in line with increased C3 levels and low-grade inflammation reported for obese patients. Our study thus suggests that nutrient sensing in the liver is coupled to release of C3 and potentially its metabolic and inflammatory functions. PMID:27735945

  18. A previously unrecognized role of C3a in proteinuric progressive nephropathy

    PubMed Central

    Morigi, Marina; Locatelli, Monica; Rota, Cinzia; Buelli, Simona; Corna, Daniela; Rizzo, Paola; Abbate, Mauro; Conti, Debora; Perico, Luca; Longaretti, Lorena; Benigni, Ariela; Zoja, Carlamaria; Remuzzi, Giuseppe

    2016-01-01

    Podocyte loss is the initial event in the development of glomerulosclerosis, the structural hallmark of progressive proteinuric nephropathies. Understanding mechanisms underlying glomerular injury is the key challenge for identifying novel therapeutic targets. In mice with protein-overload induced by bovine serum albumin (BSA), we evaluated whether the alternative pathway (AP) of complement mediated podocyte depletion and podocyte-dependent parietal epithelial cell (PEC) activation causing glomerulosclerosis. Factor H (Cfh−/−) or factor B-deficient mice were studied in comparison with wild-type (WT) littermates. WT+BSA mice showed podocyte depletion accompanied by glomerular complement C3 and C3a deposits, PEC migration to capillary tuft, proliferation, and glomerulosclerosis. These changes were more prominent in Cfh−/− +BSA mice. The pathogenic role of AP was documented by data that factor B deficiency preserved glomerular integrity. In protein-overload mice, PEC dysregulation was associated with upregulation of CXCR4 and GDNF/c-Ret axis. In vitro studies provided additional evidence of a direct action of C3a on proliferation and CXCR4-related migration of PECs. These effects were enhanced by podocyte-derived GDNF. In patients with proteinuric nephropathy, glomerular C3/C3a paralleled PEC activation, CXCR4 and GDNF upregulation. These results indicate that mechanistically uncontrolled AP complement activation is not dispensable for podocyte-dependent PEC activation resulting in glomerulosclerosis. PMID:27345360

  19. 5-aminolevulinic acid-mediated photodynamic therapy on Hep-2 and MCF-7c3 cells.

    PubMed

    Alvarez, María Gabriela; Lacelli, M S; Rivarola, Viviana; Batlle, Alcira; Fukuda, Haydée

    2007-01-01

    The cytotoxic effect of 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PPIX) on two human carcinoma cell lines, MCF-7c3 cells and Hep 2 cells, was studied. In both cell lines, PPIX content depends on the ALA concentration and incubation time. The maximal PPIX content was higher in the MCF-7c3 cells, reaching a value of 8 microg/10(6) cells, compared to the Hep-2 cells, which accumulated 3.2 microg/10(6) cells. Treatment of cells with the iron chelator desferrioxamine prior to ALA exposure enhances the amount of PPIX, consequently diminishing enzymatic activity of ferroquelatase. Photo sensitization of the cells was in correlation with the PPIX content; therefore, conditions leading to 80% cell death in the MCF-7c3 cells provoke a 50% cell death in the Hep 2 cells. Using fluorescence microscopy, cell morphology was analyzed after incubation with 1 mM ALA during 5 hr and irradiation with 54 Jcm(-2); 24 hr post-PDT, MCF-7c3 cells revealed the typical morphological changes of necrosis. Under the same conditions, Hep-2 cells produced chromatine fragmentation characteristic of apoptosis. PPIX accumulation was observed to occur in a perinuclear region in the MCF-7c3 cells; while in Hep-2 cells, it was localized in lysosomes. Different mechanisms of cell death were observed in both cell lines, depending on the different intracellular localization of PPIX.

  20. Differential allelic expression in leukoblast from patients with acute myeloid leukemia suggests genetic regulation of CDA, DCK, NT5C2, NT5C3, and TP53.

    PubMed

    Jordheim, L P; Nguyen-Dumont, T; Thomas, X; Dumontet, C; Tavtigian, S V

    2008-12-01

    mRNA expression levels of certain genes have shown predictive value for the outcome of cytarabine-treated AML-patients. We hypothesized that genetic variants play a role in the regulation of the transcription of these genes. We studied leukoblasts from 82 patients with acute myeloid leukemia and observed various extent and frequency of differential allelic expression in the CDA, DCK, NT5C2, NT5C3, and TP53 genes. Our attempts to identify the causative regulatory single nucleotide polymorphisms by a bioinformatics approach did not succeed. However, our results indicate that genetic variations are at least in part responsible for the differences in overall expression levels of these genes.

  1. Spacecraft Maximum Allowable Concentrations (SMACs) for C3 to C8 Aliphatic Saturated Aldehydes

    NASA Technical Reports Server (NTRS)

    Langford, Shannon D.

    2007-01-01

    Spacecraft maximum allowable concentrations (SMACs) for C3 to C8, straight-chain, aliphatic aldehydes have been previously assessed and have been documented in volume 4 of Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants (James, 2000). These aldehydes as well as associated physical properties are shown in Table 1. The C3 to C8 aliphatic aldehydes can enter the habitable compartments and contaminate breathing air of spacecraft by several routes including incomplete oxidation of alcohols in the Environmental Control and Life Support System (ECLSS) air revitalization subsystem, as a byproduct of human metabolism, through materials off-gassing, or during food preparation. These aldehydes have been detected in the atmosphere of manned space vehicles in the past. Analysis performed by NASA of crew cabin air samples from the Russian Mir Space Station revealed the presence of C3 to C8 aldehydes at concentrations peaking at approximately 0.1 mg/cu m.

  2. Far-infrared Detection of C3 in Sagittarius B2 and IRC +10216.

    PubMed

    Cernicharo; Goicoechea; Caux

    2000-05-10

    We report on the detection of nine lines of the nu2 bending mode of triatomic carbon, C3, in the direction of Sagittarius B2. The R(4) and R(2) lines of C3 have been also detected in the carbon-rich star IRC +10216. The abundances of C3 in the direction of Sgr B2 and IRC +10216 are approximately 3x10-8 and approximately 10-6, respectively. In Sgr B2 we have also detected the 23-12 line of NH with an abundance of a few times 10-9. Polyatomic molecules will have a weak contribution from their pure rotational spectrum to the emission/absorption in the far-infrared. We suggest, however, that they could be, through their low-lying vibrational bending modes, the dominant carriers of emission/absorption in the spectrum of bright far-infrared sources.

  3. Superconductivity at 28 K in CaB3C3 predicted from first-principles

    NASA Astrophysics Data System (ADS)

    Chen, Wanjin

    2013-11-01

    The structural parameters, electronic properties, and superconducting state in the graphite-like BxC1-x intercalation compound, CaB3C3, have been studied using pseudopotential density functional theory within the generalized gradient approximation. Electronic and electron-phonon coupling calculations reveal that CaB3C3 is hole conducting and superconducting with critical temperature 28.2 K, which is much higher than that of CaC6 (11.5 K). The excellent superconducting state in CaB3C3 stems from the simultaneous presence of highly mobile and extremely confined conduction electrons, which enhances electron pairing and superconductivity. The current calculations might stimulate further theoretical and experimental investigation in search of new superconducting states in graphite-like BxC1-x intercalated compounds.

  4. Multigap Superconductivity in Y2C3: A 13C-NMR Study

    NASA Astrophysics Data System (ADS)

    Harada, A.; Akutagawa, S.; Miyamichi, Y.; Mukuda, H.; Kitaoka, Y.; Akimitsu, J.

    2007-02-01

    We report on the superconducting properties of Y2C3 with a relatively high transition temperature Tc = 15.7 K investigated by 13C nuclear-magnetic-resonance (NMR) measurements under a magnetic field. The 13C Knight shift has revealed a significant decrease below Tc, suggesting a spin-singlet superconductivity. From an analysis of the temperature dependence of the nuclear spin-lattice relaxation rate 1/T1 in the superconducting state, Y2C3 is demonstrated to be a multigap superconductor that exhibits a large gap 2Δ/kBTc=5 at the main band and a small gap 2Δ/kBTc=2 at other bands. These results have revealed that Y2C3 is a unique multigap s-wave superconductor similar to MgB2.

  5. Reduction of U(VI) and Toxic Metals by Desulfovibrio Cytochrome C3

    SciTech Connect

    Wall, Judy D

    2013-04-11

    The central objective of our proposed research was twofold: 1) to investigate the structure-function relationship of Desulfovibrio desulfuricans (now Desulfovibrio alaskensis G20) cytochrome c3 with uranium and 2) to elucidate the mechanism for uranium reduction in vitro and in vivo. Physiological analysis of a mutant of D. desulfuricans with a mutation of the gene encoding the type 1 tetraheme cytochrome c3 had demonstrated that uranium reduction was negatively impacted while sulfate reduction was not if lactate were the electron donor. This was thought to be due to the presence of a branched pathway of electron flow from lactate leading to sulfate reduction. Our experimental plan was to elucidate the structural and mechanistic details of uranium reduction involving cytochrome c3.

  6. C3 as the dominant carbon cluster in high pressure discharges in graphite hollow cathodes

    NASA Astrophysics Data System (ADS)

    Janjua, Sohail Ahmad; Ahmad, Mashkoor; Khan, Sabih-ud-Din; Khalid, Rahila; Aleem, Abid; Ahmad, Shoaib

    2007-03-01

    Results are presented that have been obtained while operating the graphite hollow cathode duoplasmatron ion source in dual mode under constant discharge current. This dual mode operation enabled us to obtain the mass and emission spectra simultaneously. In mass spectra C3 is the main feature but C4 and C5 are also prominent, whereas in emission spectra C2 is also there and its presence shows that it is in an excited state rather than in an ionic state. These facts provide evidence that C3 is produced due to the regeneration of a soot forming sequence and leave it in ionic state. C3 is a stable molecule and the only dominant species among the carbon clusters that survives in a regenerative sooting environment at high-pressure discharges.

  7. Production of chiral C3- and C4-units by microbial enzymes.

    PubMed

    Shimizu, S; Kataoka, M

    1999-01-01

    Enzyme (biocatalysis) reactions display far greater specificities, such as substrate specificity, stereospecificity, regiospecificity and so on, than more conventional forms of organic reactions. Using these specificities of the enzymes, many useful compounds have been enzymatically produced. Compounds possessing C3- and C4-units with additional functional groups are promising materials for the synthesis of various useful compounds. In particular, optically active C3- and C4-synthetic units are quite important intermediates for the preparation of pharmaceuticals and fine chemicals. Microbial transformation with enzymes showing stereo-specificities have been applied to the asymmetric synthesis of optically active substances. In this article the recent works on the practical production of chiral C3- and C4-synthetic units with microbial enzymes are described.

  8. Trypanosoma musculi Infections in Normocomplementemic, C5-Deficient, and C3-Depleted Mice

    PubMed Central

    Jarvinen, Julie A.; Dalmasso, Agustin P.

    1977-01-01

    The role of complement in host resistance to infection with Trypanosoma musculi was studied in normal, C5-deficient, and C3-depleted mice. Infections in normocomplementemic strains (CBA and B10.D2/n) were generally similar to those in strains genetically deficient in C5 (A and B10.D2/o). There were no differences in inhibition of reproduction, duration of infection, persistence of parasites in the kidneys, or resistance to reinfection. However, peak parasitemias in B10.D2/o mice were slightly greater than in B10.D2/n mice. In addition, B10.D2/o mice had slightly decreased serum levels of C1 early in the course of infection and of C3 early during the elimination of adult forms. These components were unchanged or increased in infections of B10.D2/n. Depletion of C3 and late-acting components in B10.D2/n mice by treatment with cobra venom factor during the reproductive stage of infection resulted in an increase of reproductive forms before the apparent development of ablastic immunity as well as slightly greater peak parasitemias when compared with those of untreated controls. Cobra venom factor treatment of B10.D2/o mice during the reproductive stage did not alter the course of infection. Cobra venom factor treatment of C3H mice during the adult stage prolonged infections by interfering with parasite elimination. It is concluded that complement-mediated lysis is not involved in control of T. musculi. It is not clear whether a C3-dependent function such as phagocytosis may facilitate elimination of the parasites. The major difference in degree of parasitemias among the various strains of mice studied is due to genetic factors rather than the levels of C3, C5, or late-acting complement components. PMID:863515

  9. ClC-3 expression enhances etoposide resistance by increasing acidification of the late endocytic compartment.

    PubMed

    Weylandt, Karsten H; Nebrig, Maxim; Jansen-Rosseck, Nils; Amey, Joanna S; Carmena, David; Wiedenmann, Bertram; Higgins, Christopher F; Sardini, Alessandro

    2007-03-01

    Resistance to anticancer drugs and consequent failure of chemotherapy is a complex problem severely limiting therapeutic options in metastatic cancer. Many studies have shown a role for drug efflux pumps of the ATP-binding cassette transporters family in the development of drug resistance. ClC-3, a member of the CLC family of chloride channels and transporters, is expressed in intracellular compartments of neuronal cells and involved in vesicular acidification. It has previously been suggested that acidification of intracellular organelles can promote drug resistance by increasing drug sequestration. Therefore, we hypothesized a role for ClC-3 in drug resistance. Here, we show that ClC-3 is expressed in neuroendocrine tumor cell lines, such as BON, LCC-18, and QGP-1, and localized in intracellular vesicles co-labeled with the late endosomal/lysosomal marker LAMP-1. ClC-3 overexpression increased the acidity of intracellular vesicles, as assessed by acridine orange staining, and enhanced resistance to the chemotherapeutic drug etoposide by almost doubling the IC(50) in either BON or HEK293 cell lines. Prevention of organellar acidification, by inhibition of the vacuolar H(+)-ATPase, reduced etoposide resistance. No expression of common multidrug resistance transporters, such as P-glycoprotein or multidrug-related protein-1, was detected in either the BON parental cell line or the derivative clone overexpressing ClC-3. The probable mechanism of enhanced etoposide resistance can be attributed to the increase of vesicular acidification as consequence of ClC-3 overexpression. This study therefore provides first evidence for a role of intracellular CLC proteins in the modulation of cancer drug resistance.

  10. Drusen complement components C3a and C5a promote choroidal neovascularization

    PubMed Central

    Nozaki, Miho; Raisler, Brian J.; Sakurai, Eiji; Sarma, J. Vidya; Barnum, Scott R.; Lambris, John D.; Chen, Yali; Zhang, Kang; Ambati, Balamurali K.; Baffi, Judit Z.; Ambati, Jayakrishna

    2006-01-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrialized nations, affecting 30–50 million people worldwide. The earliest clinical hallmark of AMD is the presence of drusen, extracellular deposits that accumulate beneath the retinal pigmented epithelium. Although drusen nearly always precede and increase the risk of choroidal neovascularization (CNV), the late vision-threatening stage of AMD, it is unknown whether drusen contribute to the development of CNV. Both in patients with AMD and in a recently described mouse model of AMD, early subretinal pigmented epithelium deposition of complement components C3 and C5 occurs, suggesting a contributing role for these inflammatory proteins in the development of AMD. Here we provide evidence that bioactive fragments of these complement components (C3a and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce VEGF expression in vitro and in vivo. Further, we demonstrate that C3a and C5a are generated early in the course of laser-induced CNV, an accelerated model of neovascular AMD driven by VEGF and recruitment of leukocytes into the choroid. We also show that genetic ablation of receptors for C3a or C5a reduces VEGF expression, leukocyte recruitment, and CNV formation after laser injury, and that antibody-mediated neutralization of C3a or C5a or pharmacological blockade of their receptors also reduces CNV. Collectively, these findings establish a mechanistic basis for the clinical observation that drusen predispose to CNV, revealing a role for immunological phenomena in angiogenesis and providing therapeutic targets for AMD. PMID:16452172

  11. Characterization of cytochrome c3 from the thermophilic sulfate reducer Thermodesulfobacterium commune.

    PubMed Central

    Hatchikian, E C; Papavassiliou, P; Bianco, P; Haladjian, J

    1984-01-01

    A c3 type cytochrome has been purified from the thermophilic, non-spore-forming, sulfate-reducing bacterium Thermodesulfobacterium commune. The purified protein was homogeneous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gel filtration, and isoelectric focusing. A pI of 6.83 was observed. The molecular weight of the cytochrome was estimated to be ca. 13,000 from both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The hemoprotein exhibited absorption maxima at 530, 408.5, and 351 nm in the oxidized form and 551.5 (alpha band), 522.5 (beta band), and 418.5 nm (gamma band) in the reduced form. The extinction coefficients of T. commune cytochrome c3 were 130,000, 74,120, and 975,000 M-1 cm-1 at 551.5, 522.5, and 418.5 nm, respectively. It contains four hemes per molecule, on the basis of both the iron estimation and the extinction coefficient value of its pyridine hemochrome. The amino acid composition showed the presence of eight cysteine residues involved in heme binding. T. commune cytochrome c3 had low threonine, serine, and glycine contents and high glutamic acid and hydrophobic residue contents. The electrochemical study of T. commune cytochrome c3 by cyclic voltammetry and differential pulse polarography has shown that the cytochrome system behaves like a reversible system. Four redox potential values at Eh1 = -0.140 +/- 0.010 V, Eh2 = Eh3 = Eh4 = -0.280 +/- 0.010 V have been determined. T. commune cytochrome c3, which acts as the physiological electron carrier of hydrogenase, is similar in most respects to the multiheme low-potential cytochrome c3 which is characteristic of the genus Desulfovibrio. PMID:6090384

  12. Identification of C3b-Binding Small-Molecule Complement Inhibitors Using Cheminformatics.

    PubMed

    Garcia, Brandon L; Skaff, D Andrew; Chatterjee, Arindam; Hanning, Anders; Walker, John K; Wyckoff, Gerald J; Geisbrecht, Brian V

    2017-05-01

    The complement system is an elegantly regulated biochemical cascade formed by the collective molecular recognition properties and proteolytic activities of more than two dozen membrane-bound or serum proteins. Complement plays diverse roles in human physiology, such as acting as a sentry against invading microorganisms, priming of the adaptive immune response, and removal of immune complexes. However, dysregulation of complement can serve as a trigger for a wide range of human diseases, which include autoimmune, inflammatory, and degenerative conditions. Despite several potential advantages of modulating complement with small-molecule inhibitors, small-molecule drugs are highly underrepresented in the current complement-directed therapeutics pipeline. In this study, we have employed a cheminformatics drug discovery approach based on the extensive structural and functional knowledge available for the central proteolytic fragment of the cascade, C3b. Using parallel in silico screening methodologies, we identified 45 small molecules that putatively bind C3b near ligand-guided functional hot spots. Surface plasmon resonance experiments resulted in the validation of seven dose-dependent C3b-binding compounds. Competition-based biochemical assays demonstrated the ability of several C3b-binding compounds to interfere with binding of the original C3b ligand that guided their discovery. In vitro assays of complement function identified a single complement inhibitory compound, termed cmp-5, and mechanistic studies of the cmp-5 inhibitory mode revealed it acts at the level of C5 activation. This study has led to the identification of a promising new class of C3b-binding small-molecule complement inhibitors and, to our knowledge, provides the first demonstration of cheminformatics-based, complement-directed drug discovery. Copyright © 2017 by The American Association of Immunologists, Inc.

  13. Elevated serum complement C3 levels are associated with prehypertension in an adult population.

    PubMed

    Bao, Xue; Meng, Ge; Zhang, Qing; Liu, Li; Wu, Hongmei; Du, Huanmin; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Han, Peipei; Dong, Renwei; Wang, Xiuyang; Li, Chunlei; Su, Qian; Gu, Yeqing; Fang, Liyun; Yu, Fei; Yang, Huijun; Kang, Li; Ma, Yixuan; Yu, Bin; Ma, Xinyu; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Guo, Qi; Song, Kun; Wang, GuoLin; Huang, Guowei; Niu, Kaijun

    2017-01-01

    Prehypertension is a public health epidemic associated with various adverse outcomes, but can be reversed by timely intervention. However, little attention has been paid to prehypertension. Complement C3 is a central hub of complement-related immune system. We examined the association between C3 and prehypertension in an adult population for the first time, aiming to investigate whether pro-inflammatory immune response is involved in the prehypertensive state. About 7820 Tianjin residents without hypertension were categorized into sex-specific quintiles based on their serum concentration of complement C3. Adjusted logistic regression models were used separately by gender to assess the association between C3 quintiles and the prevalence of prehypertension. After multiple adjustment, the odds ratios (95% confidence interval) for prehypertension across increasing quintiles of C3 were 1.00 (reference), 1.02 (0.84, 1.25), 1.15 (0.94, 1.42), 1.25 (1.01, 1.54), and 1.71 (1.35, 2.17) (p for trend < 0.0001) among men and were 1.00 (reference), 1.17 (0.92, 1.49), 1.13 (0.88, 1.44), 1.15 (0.89, 1.48), and 1.40 (1.07, 1.84) (p for trend = 0.03) among women. The findings suggested that elevated serum C3 levels are associated with prehypertension. Reducing inflammation may be a potential therapeutic strategy for prehypertension and hypertension that is worthy of further studies and discussion.

  14. Root functional diversity in C3 and C4 grasslands in Hawaii

    NASA Astrophysics Data System (ADS)

    Angelo, C. L.; Pau, S.

    2014-12-01

    Root systems play an integral role in grassland ecosystem functioning due to their resource acquisition and conservation strategies. A considerable gap in our knowledge of C3 and C4 grasslands is our understanding of belowground root functional diversity. Our aim was to determine whether root system traits allowed for the identification of functional strategies of grass species and to see if these traits differed along resource gradients (precipitation and nitrogen). The functional root traits (specific root length, diameter, root tissue density, root length density, and % of fine roots) of nine grass species, four C3 and five C4, were evaluated from root samples collected from field plots at 100 -150 m intervals along an elevation gradient in Hawaii Volcanoes National Park. An analysis of variance found that there were significant differences in individual root trait values between species (P < 0.000) and photosynthetic pathway (P < 0.025). There was also evidence that the relationships between individual root traits and gradient resources were influenced by photosynthetic pathway (P and r2-values for all interactions were < 0.001 and > 0.625, respectively). A principal component analysis (PCA) found that two components accounted for 86 % of the explainable variation in our data. PCA found that C4 species had larger root diameters, whereas, C3 species had higher % of fine roots and specific root lengths. C3 and C4 species diverged less in root tissue density. C3 species had more resource acquisition root traits, while C4 grasses had a more conservative resource strategy. These results have important implications for how grassland ecosystem dynamics may be altered by shifting patterns of C3-C4 grasses with global change.

  15. [C3F8 in the treatment of retinal detachment associated with vitreoretinal proliferation].

    PubMed

    Fleury, J; Bonnet, M

    1989-01-01

    The perfluoropropane gas was used as an adjunct to vitreoretinal microsurgery in 60 eyes of 60 patients with rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy. 0.3 ml to 1.8 ml (average 0.9 ml) of pure perfluoropropane gas was used. The surgical procedure included vitrectomy and scleral buckling in all patients. The follow-up after complete gas absorption ranged from 6 months to 3 years in the successful eyes. Total retinal reattachment was achieved in 41 eyes (68.3%). The anatomical success rate was 88% (22/25 eyes) in grade C1-C2 PVR cases, 68.7% (11/15 eyes) in grade C3-D1 PVR cases, and 42% (8/19 eyes) in grade D2-D3 PVR cases. Visual acuity of 0.1 or better was achieved in 80% of eyes with grade C PVR and 61% of eyes with grade D PVR. Visual acuity of 0.4 or better was achieved in 26.9% of eyes with grade C PVR. Macular changes were revealed by fluorescein angiography in 53% of successful eyes. We recommend the use of C3F8 rather than SF6 in the management of rhegmatogenous retinal detachment complicated by PVR. In our experience the anatomical success rate achieved with C3F8 is approximately the same as that achieved with SF6. However permanent retinal reattachment was achieved with a single operation in 87.8% of successful eyes of the present series of patients managed with C3F8 as compared to only 12% of successful eyes of a previous series of patients managed with SF6. The anatomical results achieved with a single operation in the C3F8 series are probably related to the greater longevity of C3F8 as compared to that of SF6.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Chimpanzee isotopic ecology: a closed canopy C3 template for hominin dietary reconstruction.

    PubMed

    Carlson, Bryce A; Kingston, John D

    2014-11-01

    The most significant hominin adaptations, including features used to distinguish and/or classify taxa, are critically tied to the dietary environment. Stable isotopic analyses of tooth enamel from hominin fossils have provided intriguing evidence for significant C4/CAM (crassulacean acid metabolism) resource consumption in a number of Plio-Pleistocene hominin taxa. Relating isotopic tooth signatures to specific dietary items or proportions of C3 versus C4/CAM plants, however, remains difficult as there is an ongoing need to document and quantify isotopic variability in modern ecosystems. This study investigates the ecological variables responsible for carbon isotopic discrimination and variability within the C3-dominated dietary niche of a closed canopy East African hominoid, Pan troglodytes, from Ngogo, Kibale National Park, Uganda. δ(13)C values among C3 resources utilized by Ngogo chimpanzees were highly variable, ranging over 13‰. Infrequent foraging on papyrus (the only C4 plant consumed by chimpanzees at the site) further extended this isotopic range. Variation was ultimately most attributable to mode of photosynthesis (C3 versus C4), food type, and elevation, which together accounted for approximately 78% of the total sample variation. Among C3 food types, bulk carbon values ranged from -24.2‰ to -31.1‰ with intra-plant variability up to 12.1‰. Pith and sapling leaves were statistically more (13)C depleted than pulp, seeds, flowers, cambium, roots, leaf buds, and leaves from mature trees. The effect of elevation on carbon variation was highly significant and equivalent to an approximately 1‰ increase in δ(13)C for every 150 m of elevation gain, likely reflecting habitat variability associated with topography. These results indicate significant δ(13)C variation attributable to food type and elevation among C3 resources and provide important data for hominin dietary interpretations based on carbon isotopic analyses. Copyright © 2014 Elsevier Ltd

  17. Selective Oxidation of Alcohols Using Photoactive VO@g??C3N4

    EPA Pesticide Factsheets

    A photoactive VO@g-C3N4 catalyst has been developed for the selective oxidation of alcohols to the corresponding aldehydes and ketones. The visible light mediated activity of the catalyst could be attributed to photoactive graphitic carbon nitrides surface.This dataset is associated with the following publication:Verma, S., R.B. Nasir Baig, M. Nadagouda , and R. Varma. Selective oxidation of alcohols using photoactive VO@g-C3N4.. ACS Sustainable Chemistry & Engineering. American Chemical Society, Washington, DC, USA, 4(3): 1094-1098, (2015).

  18. Photocatalytic C??H Activation of Hydrocarbons over VO@g??C3N4

    EPA Pesticide Factsheets

    A highly selective and sustainable method has been developed for the oxidation of methyl arenes and their analogues. The VO@g-C3N4 catalyst is very efficient in the C??H activation and oxygen insertion reaction resulting in formation of the corresponding carbonyl compounds and phenols.This dataset is associated with the following publication:Verma, S., R.B. Nasir Baig, M. Nadagouda , and R. Varma. Photocatalytic C−H Activation of Hydrocarbons over VO@g‑C3N4. ACS Sustainable Chemistry & Engineering. American Chemical Society, Washington, DC, USA, 4(4): 2333-2336, (2016).

  19. [Immunoturbidimetric determination of C-3 components of complement systems using nonlinear calibration].

    PubMed

    Rohácek, J; Semrád, V; Klierová, E; Zápotocná, M

    1991-01-01

    A method for the immunoturbidimetric analysis of the C-3-component in the complement system was elaborated by means of the antiserum Q-SwAHu/C3 USOL (SEVAG) Praha. A diluted human control serum USOL (SEVAG) Praha with declared values of plasma proteins was applied as a standard solution. The relation between concentration and absorption in an eight step calibration series is well described by a parabola of the 2nd degree. The precision in series and the accuracy of the method are mentioned. The proposed technique is in a relatively good correlation with the radial immunodiffusion according to MANCINI.

  20. Shock tube measurements of the optical absorption of triatomic carbon, C3

    NASA Technical Reports Server (NTRS)

    Jones, J. J.

    1977-01-01

    The spectral absorption of C3 has been measured in a shock tube using a test gas mixture of acetylene diluted with argon. The absorption of a pulsed xenon light source was measured by means of eight photomultiplier channels to a spectrograph and an accompanying drum camera. The postshock test gas temperature and pressure were varied over the range 3300-4300 K and 0.36 to 2.13 atmospheres, respectively. The results showed appreciable absorption from C3 for the wavelength range 300 to 540 nanometers. The computed electronic oscillator strength varied from 0.12 to 0.06 as a function of temperature.

  1. Advanced Concurrent Interfaces for High-Performance Multi-Media Distributed C3 Systems

    DTIC Science & Technology

    1993-03-01

    RL-TR-93-17 Final Technical Report AD-A267 051 "March 1993i II l IIII I H ’PeIle ADVANCED CONCURRENT INTERFACES FOR HIGH-PERFORMANCE MULTI- MEDIA ...DISTRIBUTED C3 SYSTEMS MIT Media Lab Sponsored by Defense Advanced Research Projects Agency JJo DARPA Order No. 8474 APPR9OVED FOR PUBLIC RELEASE...that it be returned. ADVANCED CONCURRENT INTERFACES FOR HIGH-PERFORMANCE MULTI- MEDIA DISTRIBUTED C3 SYSTEMS Nicholas P. Negroponte Dr. Richard A

  2. Calculations on the competition between association and reaction for C3H(+) + H2

    NASA Technical Reports Server (NTRS)

    Maluendes, Sergio A.; Mclean, A. D.; Yamashita, Koichi; Herbst, Eric

    1993-01-01

    The ab initio results presently obtained for the potential energy surface of competing associative and reactive ion-molecule processes of the reactants H2 and C3H(+) show that the linear ion is able to directly access the deep potential well of the propargyl ion H2CCCH(+). Using the minimum energy potential pathway and properties of the stationary point structures determined via the ab initio methods, calculation results are obtained for both the association-rate coefficient for C3H3(+) production as a function of density, and the branching ratio between the propargyl and cyclic structures of the ion.

  3. Photochemical CO2 reduction using structurally controlled g-C3N4.

    PubMed

    Walsh, James J; Jiang, Chaoran; Tang, Junwang; Cowan, Alexander J

    2016-09-14

    Graphitic carbon nitride (g-C3N4) synthesised from a urea precursor is an excellent CO2 reduction photocatalyst using [Co(bpy)n](2+) as a co-catalyst. A five-fold increase in activity for the highly polymerised urea derived g-C3N4 is achieved compared to alternative precursors. Transient absorption, time-resolved and steady-state emission studies indicate that the enhanced activity is related to both an increased driving force for photoelectron transfer and a greater availability of photogenerated charges.

  4. Vanadate stimulates ornithine decarboxylase activity in C3H/10T1/2 cells.

    PubMed

    Davison, A J; Stern, A; Fatur, D J; Tsang, S S

    1991-06-01

    Ornithine decarboxylase (ODC) activity of C3H/10T1/2 cells reflects their response to conflicting actions of many tumor promoters and tumor suppressors. In cultured C3H/10T1/2 cells, addition of vanadate (50 nM) increased ODC activity. Over the range 0.05-5 microM, vanadate increased ODC levels in a dose dependent manner to 11 times control levels. The presence of retinoic acid (5 microM) or the absence of fetal calf serum blocked the stimulation by vanadate.

  5. 3C3R Modified PBL Pediatric Teaching of Chinese Medical Students

    PubMed Central

    Xue, Haihong; Qian, Jihong; Wang, Lianwen; Yuan, Xiaojun; Chen, Yi; Wu, Weilan; Chen, Yan; Sun, Kun

    2013-01-01

    A Content, Context, Connection and Researching, Reasoning, Reflecting (3C3R) model is a conceptual framework for problem-based learning (PBL) problem design. We introduced the 3C3R-PBL method into a pediatric teaching plan, and evaluated its effectiveness and feasibility. The 3C3R model was applied in a pediatric problem design teaching plan “why the lips turn purple when a baby is crying”. All students were assigned either into a traditional PBL course or into a 9-step 3C3R model PBL course (3C3R-PBL). The performance outcomes of both groups were compared. For the PBL group, the proportion of students scoring ≥4 for content, context, and problem design connection, was 90.8%, 80.3%, and 64.5% respectively, while for tutors, it was 71.4%, 71.4%, and 28.6%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 81.6%, 55.3%, and 40.8%, while for tutors, it was 71.4%, 100%, and 57.1%. The learning difficulty was not considered high with only 31.6% of students and 42.9% of tutors rating the task as difficult. For the 3C3R-PBL group, the proportion of students scoring content, context, and connection, ≥4 was 100%, 98.4%, and 90.5%, while for tutors it was 100%, 100%, 83.3%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 95.2%, 88.9%, and 76.2%, while for tutors it was 100% for all 3 R components. Students and tutors were convinced by the content, case context, research process and reasoning process of both teaching plans, while scores for connection and reflecting were significantly improved when the PBL plan was amended by a 3C3R model (p<0.05) and the case learning difficulty was statistically increased (p<0.05). The 3C3R model, evaluated for the first time in China, was helpful for effective and reliable problem design in a pediatric PBL teaching plan for Chinese students. PMID:23667610

  6. 3C3R modified PBL pediatric teaching of Chinese medical students.

    PubMed

    Xue, Haihong; Qian, Jihong; Wang, Lianwen; Yuan, Xiaojun; Chen, Yi; Wu, Weilan; Chen, Yan; Sun, Kun

    2013-01-01

    A Content, Context, Connection and Researching, Reasoning, Reflecting (3C3R) model is a conceptual framework for problem-based learning (PBL) problem design. We introduced the 3C3R-PBL method into a pediatric teaching plan, and evaluated its effectiveness and feasibility. The 3C3R model was applied in a pediatric problem design teaching plan "why the lips turn purple when a baby is crying". All students were assigned either into a traditional PBL course or into a 9-step 3C3R model PBL course (3C3R-PBL). The performance outcomes of both groups were compared. For the PBL group, the proportion of students scoring ≥4 for content, context, and problem design connection, was 90.8%, 80.3%, and 64.5% respectively, while for tutors, it was 71.4%, 71.4%, and 28.6%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 81.6%, 55.3%, and 40.8%, while for tutors, it was 71.4%, 100%, and 57.1%. The learning difficulty was not considered high with only 31.6% of students and 42.9% of tutors rating the task as difficult. For the 3C3R-PBL group, the proportion of students scoring content, context, and connection, ≥4 was 100%, 98.4%, and 90.5%, while for tutors it was 100%, 100%, 83.3%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 95.2%, 88.9%, and 76.2%, while for tutors it was 100% for all 3 R components. Students and tutors were convinced by the content, case context, research process and reasoning process of both teaching plans, while scores for connection and reflecting were significantly improved when the PBL plan was amended by a 3C3R model (p<0.05) and the case learning difficulty was statistically increased (p<0.05). The 3C3R model, evaluated for the first time in China, was helpful for effective and reliable problem design in a pediatric PBL teaching plan for Chinese students.

  7. C3: Command-line Catalogue Crossmatch for modern astronomical surveys

    NASA Astrophysics Data System (ADS)

    Riccio, Giuseppe; Brescia, Massimo; Cavuoti, Stefano

    2016-10-01

    The Command-line Catalogue Cross-matching (C3) software efficiently performs the positional cross-match between massive catalogues from modern astronomical surveys, whose size have rapidly increased in the current data-driven science era. Based on a multi-core parallel processing paradigm, it is executed as a stand-alone command-line process or integrated within any generic data reduction/analysis pipeline. C3 provides its users with flexibility in portability, parameter configuration, catalogue formats, angular resolution, region shapes, coordinate units and cross-matching types.

  8. A quantum model for bending vibrations and thermodynamic properties of C3.

    NASA Technical Reports Server (NTRS)

    Hansen, C. F.; Pearson, W. E.

    1973-01-01

    The investigation reported was conducted to clarify the thermodynamic properties of C3 by further developing the limit to the partition function suggested by Strauss and Thiele (1967). A quantum solution for the energy levels of a quadratically perturbed square well potential is presented and the consistency of this limit with observe