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Sample records for fa complementation group

  1. Cellular characterization of cells from the Fanconi anemia complementation group, FA-D1/BRCA2

    Energy Technology Data Exchange (ETDEWEB)

    Godthelp, Barbara C. [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Buul, Paul P.W. van [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Jaspers, Nicolaas G.J. [Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam (Netherlands); Elghalbzouri-Maghrani, Elhaam [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Duijn-Goedhart, Annemarie van [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Arwert, Fre [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Amsterdam (Netherlands); Joenje, Hans [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Amsterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands) and Department of Molecular Cell Genetics, Collegium Medicum, N.Copernicus University, Bydgoszcz (Poland)]. E-mail: M.Z.Zdzienicka@LUMC.nl

    2006-10-10

    Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, characterized by genomic instability and hypersensitivity to DNA cross-linking agents. The discovery of biallelic BRCA2 mutations in the FA-D1 complementation group allows for the first time to study the characteristics of primary BRCA2-deficient human cells. FANCD1/BRCA2-deficient fibroblasts appeared hypersensitive to mitomycin C (MMC), slightly sensitive to methyl methane sulfonate (MMS), and like cells derived from other FA complementation groups, not sensitive to X-ray irradiation. However, unlike other FA cells, FA-D1 cells were slightly sensitive to UV irradiation. Despite the observed lack of X-ray sensitivity in cell survival, significant radioresistant DNA synthesis (RDS) was observed in the BRCA2-deficient fibroblasts but also in the FANCA-deficient fibroblasts, suggesting an impaired S-phase checkpoint. FA-D1/BRCA2 cells displayed greatly enhanced levels of spontaneous as well as MMC-induced chromosomal aberrations (Canada), similar to cells deficient in homologous recombination (HR) and non-D1 FA cells. In contrast to Brca2-deficient rodent cells, FA-D1/BRCA2 cells showed normal sister chromatid exchange (SCE) levels, both spontaneous as well as after MMC treatment. Hence, these data indicate that human cells with biallelic BRCA2 mutations display typical features of both FA- and HR-deficient cells, which suggests that FANCD1/BRCA2 is part of the integrated FA/BRCA DNA damage response pathway but also controls other functions outside the FA pathway.

  2. Identification of the Fanconi Anemia Complementation Group I Gene, FANCI

    Directory of Open Access Journals (Sweden)

    Josephine C. Dorsman

    2007-01-01

    Full Text Available To identify the gene underlying Fanconi anemia (FA complementation group I we studied informative FA-I families by a genome-wide linkage analysis, which resulted in 4 candidate regions together encompassing 351 genes. Candidates were selected via bioinformatics and data mining on the basis of their resemblance to other FA genes/proteins acting in the FA pathway, such as: degree of evolutionary conservation, presence of nuclear localization signals and pattern of tissue-dependent expression. We found a candidate, KIAA1794 on chromosome 15q25-26, to be mutated in 8 affected individuals previously assigned to complementation group I. Western blots of endogenous FANCI indicated that functionally active KIAA1794 protein is lacking in FA-I individuals. Knock-down of KIAA1794 expression by siRNA in HeLa cells caused excessive chromosomal breakage induced by mitomycin C, a hallmark of FA cells. Furthermore, phenotypic reversion of a patient-derived cell line was associated with a secondary genetic alteration at the KIAA1794 locus. These data add up to two conclusions. First, KIAA1794 is a FA gene. Second, this gene is identical to FANCI, since the patient cell lines found mutated in this study included the reference cell line for group I, EUFA592.

  3. FA

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — An Area Forecast (FA) is a forecast of Visual Flight Rules (VFR) clouds and weather conditions over an area as large as the size of several states.

  4. ON COMPLEMENTED SUBGROUPS OF FINITE GROUPS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A subgroup H of a finite group G is said to be complemented in G if there exists a subgroup K of G such that G = HK and H ∩ K = 1. In this case, K is called a complement of H in G.In this note some results on complemented subgroups of finite groups are obtained.

  5. Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

    Energy Technology Data Exchange (ETDEWEB)

    Godthelp, Barbara C. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Wiegant, Wouter W. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Waisfisz, Quinten [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Medhurst, Annette L. [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Arwert, Fre [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Joenje, Hans [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands) and Department of Molecular Cell Genetics, Collegium Medicum, N. Copernicus University, Bydgoszcz (Poland)]. E-mail: m.z.zdzienicka@lumc.nl

    2006-02-22

    Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination.

  6. All finitely presentable groups from link complements and Kleinian groups

    CERN Document Server

    Aitchison, Iain R

    2010-01-01

    We prove that every finitely presentable group G arises as the fundamental group of an orientable 3-complex obtained from a hyperbolic link complement, by coning each boundary torus of the link exterior to a distinct point. We define the closed-link-genus, clg(G), of any finitely presentable group G, which completely characterizes fundamental groups of closed orientable 3-manifolds: clg(G)=0 if and only if G is the fundamental group of a closed orientable 3-manifold. Moreover clg(G) gives an upper bound for the concept `genus(G)' of genus defined earlier by Aitchison and Reeves, and in turn is bounded by the minimal number of relations among all finite presentations of G.

  7. Complementation in the Group of Units of Matrix Rings

    CERN Document Server

    Wilcox, Stewart

    2010-01-01

    Let $R$ be a ring with $1$ and $\\J(R)$ its Jacobson radical. Then $1+\\J(R)$ is a normal subgroup of the group of units, $G(R)$. The existence of a complement to this subgroup was explored in a paper by Coleman and Easdown; in particular the ring $R=\\Mat_n(\\Z_{p^k})$ was considered. We prove the remaining cases to determine for which $n$, $p$ and $k$ a complement exists in this ring.

  8. Gene for ataxia-telangiectasia complementation group D (ATDC)

    Energy Technology Data Exchange (ETDEWEB)

    Murnane, John P. (San Francisco, CA); Painter, Robert B. (Burlingame, CA); Kapp, Leon N. (San Rafael, CA); Yu, Loh-Chung (Redwood City, CA)

    1995-03-07

    Disclosed herein is a new gene, an AT gene for complementation group D, the ATDC gene and fragments thereof. Nucleic acid probes for said gene are provided as well as proteins encoded by said gene, cDNA therefrom, preferably a 3 kilobase (kb) cDNA, and recombinant nucleic acid molecules for expression of said proteins. Further disclosed are methods to detect mutations in said gene, preferably methods employing the polymerase chain reaction (PCR). Also disclosed are methods to detect AT genes from other AT complementation groups.

  9. Gene for ataxia-telangiectasia complementation group D (ATDC)

    Energy Technology Data Exchange (ETDEWEB)

    Murnane, J.P.; Painter, R.B.; Kapp, L.N.; Yu, L.C.

    1995-03-07

    Disclosed herein is a new gene, an AT gene for complementation group D, the ATDC gene and fragments thereof. Nucleic acid probes for the gene are provided as well as proteins encoded by the gene, cDNA therefrom, preferably a 3 kilobase (kb) cDNA, and recombinant nucleic acid molecules for expression of the proteins. Further disclosed are methods to detect mutations in the gene, preferably methods employing the polymerase chain reaction (PCR). Also disclosed are methods to detect AT genes from other AT complementation groups. 30 figs.

  10. Cohomology of hyperplane complements with group ring coefficients

    CERN Document Server

    Davis, Michael W; Leary, Ian J; Okun, Boris

    2010-01-01

    We compute the cohomology with group ring coefficients of the complement of a finite collection of affine hyperplanes in a finite dimensional complex vector space. It is nonzero in exactly one degree, namely the degree equal to the rank of the hyperplane arrangement.

  11. Xeroderma pigmentosum complementation group G associated with Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Vermeulen, W.; Jaspers, N.G.J.; Bootsma, D.; Hoeijmakers, J.H.J. (Erasmus Univ., Rotterdam (Belgium)); Jaeken, J. (Univ. Hospital Gasthuisberg, Leuven (Belgium))

    1993-07-01

    Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are two rare inherited disorders with a clinical and cellular hypersensitivity to the UV component of the sunlight spectrum. Although the two traits are generally considered as clinically and genetically distinct entities, on the biochemical level a defect in the nucleotide excision-repair (NER) pathway is involved in both. Classical CS patients are primarily deficient in the preferential repair of DNA damage in actively transcribed genes, whereas in most XP patients the genetic defect affects both [open quotes]preferential[close quotes] and [open quotes]overall[close quotes] NER modalities. Here the authors report a genetic study of two unrelated, severely affected patients with the clinical characteristics of CS but with a biochemical defect typical of XP. By complementation analysis, using somatic cell fusion and nuclear microinjection of cloned repair genes, they assign these two patients to XP complementation group G, which previously was not associated with CS. This observation extends the earlier identification of two patients with a rare combined XP/CS phenotype within XP complementation groups B and D, respectively. It indicates that some mutations in at least three of the seven genes known to be involved in XP also can result in a picture of partial or even full-blown CS. It is concluded that the syndromes XP and CS are biochemically closely related and may be part of a broader clinical disease spectrum. The authors suggest, as a possible molecular mechanism underlying this relation, that the XPGC repair gene has an additional vital function, as shown for some other NER genes. 33 refs., 5 tabs.

  12. A Small Group Activity About Bacterial Regulation And Complementation

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    Susan M. Merkel

    2010-11-01

    Full Text Available As teachers, we well understand the need for activities that help develop critical-thinking skills in microbiology. In our experience, one concept that students have difficulty understanding is transcriptional regulation of bacterial genes. To help with this, we developed and evaluated a paper-based activity to help students understand and apply the concepts of bacterial transcriptional regulation. While we don't identify it as such, we use a complementation experiment to assess student understanding of how regulation changes when new DNA is introduced. In Part 1 of this activity, students complete an open book, take-home assignment that asks them to define common terminology related to regulation, and draw the regulatory components of different scenarios involving positive and negative regulation. In Part 2, students work in small groups of 3-4 to depict the regulatory components for a different scenario. They are asked to explain the results of a complementation experiment based on this scenario. They then predict the results of a slightly different experiment. Students who completed the Regulation Activity did significantly better on post-test questions related to regulation, compared to pre-test questions.

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

    DEFF Research Database (Denmark)

    Ermert, David; Shaughnessy, Jutamas; Joeris, Thorsten;

    2015-01-01

    Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and c...... in studies of GAS pathogenesis and for developing vaccines and therapeutics that rely on human complement activation for efficacy.......Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement...

  14. Cloning and characterization of the Drosophila homolog of the xeroderma pigmentosum complementation group B correcting gene, ERCC3.

    NARCIS (Netherlands)

    M.H.M. Koken (Marcel); C. Vreeken; S.A.M. Bol (Sandra); N.C. Cheng (Ngan Ching); I. Jaspers-Dekker (Iris); J.H.J. Hoeijmakers (Jan); J.C.J. Eeken; G. Weeda (Geert); A. Pastink (Albert)

    1992-01-01

    textabstractPreviously the human nucleotide excision repair gene ERCC3 was shown to be responsible for a rare combination of the autosomal recessive DNA repair disorders xeroderma pigmentosum (complementation group B) and Cockayne's syndrome (complementation group C). The human and mouse ERCC3 prote

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

    Directory of Open Access Journals (Sweden)

    David Ermert

    2015-07-01

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

  16. The Fundamental Group of the Complement of the Branch Curve of CP1×T

    Institute of Scientific and Technical Information of China (English)

    Meirav AMRAM; Michael FRIEDMAN; Mina TEICHER

    2009-01-01

    Denoting by T the complex projective torus, we can embed the surface CP1×T in CP5. In this paper we compute the fundamental group of the complement of the branch curve of this surface. Since the embedding is not "ample enough", the embedded surface does not belong to the classes of surfaces where the fundamental group is virtually solvable: a property which holds for these groups for "ample enough" embeddings. On the other hand, as it is the first example of this computation for non simply-connected surfaces, the structure of this group (as shown in this paper) give rise to the extension of the conjecture regarding the structure of those fundamental groups of any surface.

  17. Excision repair cross complementation group 1 polymorphisms and lung cancer risk: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    CAO Chao; DENG Zai-chun; ZHANG Yan-mei; WANG Ran; SUN Shi-fang; CHEN Zhong-bo; MA Hong-ying; YU Yi-ming; DING Qun-li; SHU Li-hua

    2011-01-01

    Background Several studies have evaluated the association between polymorphisms of encoding excision repair cross complementation group 1 (ERCC1) enzyme and lung cancer risk in diverse populations but with conflicting results.By pooling the relatively small samples in each study, it is possible to perform a meta-analysis of the evidence by rigorous methods.Methods Embase, Ovid, Medline and Chinese National Knowledge Infrastructure were searched. Additional studies were identified from references in original studies or review articles. Articles meeting the inclusion criteria were reviewed systematically, and the reported data were aggregated using the statistical techniques of meta-analysis.Results We found 3810 cases with lung cancer and 4332 controls from seven eligible studies. T19007C polymorphism showed no significant effect on lung cancer risk (C allele vs. T allele: odds ratio (OR)=0.91, 95% confidence interval (CI)=0.80-1.04; CC vs. TT: OR=0.76, 95% CI=0.56-1.02; CC vs. (CT+TT): OR=0.96, 95% CI=-0.84-1.10). Similarly,there was no significant main effects for T19007C polymorphism on lung cancer risk when stratified analyses by ethnicity (Chinese or Caucasian). No significant association was found between C8092A polymorphism (3060 patients and 2729 controls) and the risk of lung cancer (A allele vs. C allele: OR=1.03, 95% CI=0.95-1.11; AA vs. CC: OR=1.08, 95% CI=-0.88-1.33; AA vs. (AC+CC): OR=1.08, 95% CI=-0.88-1.31).Conclusion We found little evidence of an association between the T1900C or C8092A polymorphisms of ERCC 1 and the risk of lung cancer in Caucasian or Han Chinese people.

  18. Expression of xeroderma pigmentosum complementation group C protein predicts cisplatin resistance in lung adenocarcinoma patients.

    Science.gov (United States)

    Lai, Tan-Chen; Chow, Kuan-Chih; Fang, Hsin-Yuan; Cho, Hsin-Ching; Chen, Chih-Yi; Lin, Tze-Yi; Chiang, I-Ping; Ho, Shu-Peng

    2011-05-01

    DNA repair has been suggested to be a major cause of spontaneous drug resistance in patients with lung adenocarcinomas (LADC). Among the DNA repair-related proteins, excision repair cross-complementation group 1 (ERCC1) has been shown to be essential for repairing cisplatin-induced interstrand cross-linkage. However, the role of other DNA repair-related proteins in drug resistance has not been clearly elucidated. In this study, we used suppression subtractive hybridization and microarray analysis to identify the DNA repair-related genes associated with cisplatin resistance. We focused on the association of XPC protein expression, which plays a pivotal role in the earliest response to global genomic repair, with the survival of LADC patients. Using suppression subtractive hybridization and a microarray analysis to identify drug resistance-associated DNA repair-related genes, we found that the mRNA levels of ERCC1, MSH-3, MSH-6 and XPC were significantly increased in LADC patients. Since the results of ERCC1 mRNA expression corresponded well with those in previous reports, in this study we focused on the clinical correlation between XPC expression and patient survival. The level of XPC protein was determined by immunohistochemical and immunoblotting analyses. We detected the XPC protein in 46 (43%) of 107 pathological LADC samples. XPC protein expression correlated with tumor stage, cigarette smoking and poor survival. In the in vitro experiments with LADC cell lines, increased XPC expression was associated with elevated drug resistance, and silencing of XPC expression reduced cisplatin resistance. Our results suggest that XPC expression predicts drug resistance in LADC.

  19. Microinjection of Micrococcus luteus UV-endonuclease restores UV-induced unscheduled DNA synthesis in cells of 9 xeroderma pigmentosum complementation groups.

    NARCIS (Netherlands)

    A.J.R. de Jonge; W. Vermeulen (Wim); W. Keijzer; J.H.J. Hoeijmakers (Jan); D. Bootsma (Dirk)

    1985-01-01

    textabstractThe UV-induced unscheduled DNA synthesis (UDS) in cultured cells of excision-deficient xeroderma pigmentosum (XP) complementation groups A through I was assayed after injection of Micrococcus luteus UV-endonuclease using glass microneedles. In all complementation groups a restoration of

  20. Cloning and analysis of the mouse Fanconi anemia group a cDNA and an overlapping penta zinc finger cDNA

    NARCIS (Netherlands)

    Wong, JCY; Alon, N; Norga, K; Kruyt, FAE; Youssoufian, H; Buchwald, M

    2000-01-01

    Despite the cloning of four disease-associated genes for Fanconi anemia (FA), the molecular pathogenesis of FA remains largely unknown. To study FA complementation group A using the mouse as a mode I system, we cloned and characterized the mouse homolog of the human FANCA cDNA, The mouse cDNA

  1. Changes in protein expression due to deleterious mutations in the FA/BRCA pathway.

    Science.gov (United States)

    Salles, Daniela; Cabral, Rosa Estela Caseira; Pizzatti, Luciana; Bisch, Paulo M; Paixão, Julio Cesar; de Almeida, Carlos Eduardo Bonacossa; Seuánez, Héctor N; Cabral-Neto, Januario Bispo

    2007-12-28

    Inherited deleterious mutations in one of the Fanconi anemia genes lead to a disease, characterized by bone marrow failure, myeloid leukemia, and hypersensitivity to DNA damage. We identified proteins likely associated to the molecular signaling pathways involved in DNA repair of interstrand cross-link lesions and in mechanisms of genomic stability mediated by FA/BRCA pathways. We compared protein maps resolved by bidimensional electrophoresis and analyzed differentially expressed proteins, by mass spectrometry, between FA complementation group C (FANCC)-deficient cells, and their ectopically corrected counterpart in physiological conditions or after treatment with MMC. We found six differentially expressed proteins; among them, the checkpoint mediator protein MDC1 whose expression was disrupted in FANCC-/- cells. The potential role of differentially expressed proteins in FA phenotype is discussed.

  2. Sundanese Complementation

    Science.gov (United States)

    Kurniawan, Eri

    2013-01-01

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

  3. Excision Repair Cross-complementation Group 1 is a Prognostic Biomarker in Patients with Colorectal Cancer Receiving Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Mu-Xing Li; Xin-Yu Bi; Hong Zhao; Zhen Huang; Yue Han; Dong-Bin Zhao; Jian-Jun Zhao

    2016-01-01

    Background:Conflicting results about the association between expression level of excision repair cross-complementation group 1 (ERCC1) and clinical outcome in patients with colorectal cancer (CRC) receiving chemotherapy have been reported.Thus,we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC.Methods:A thorough literature search using PubMed (Medline),Embase,Cochrane Library,Web of Science databases,and Chinese Science Citation Database was conducted to obtain the relevant studies.Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the results.Results:A total of 11 studies were finally enrolled in this meta-analysis.Compared with patients with lower ERCC1 expression,patients with higher ERCC1 expression tended to have unfavorable overall survival (OS) (HR =2.325,95% CI:1.720-3.143,P < 0.001),progression-free survival (PFS) (HR =1.917,95% CI:1.366-2.691,P < 0.001) and poor response to chemotherapy (OR =0.491,95% CI:0.243-0.990,P =0.047).Subgroup analyses by treatment setting,ethnicity,HR extraction,detection methods,survival analysis,and study design demonstrated that our results were robust.Conclusions:ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy,OS,and PFS.Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC 1's prognostic value.

  4. Transfection of the cloned human excision repair gene ERCC-1 to UV-sensitive CHO mutants only corrects the repair defect in complementation group 2 mutants.

    NARCIS (Netherlands)

    M. van Duin (Mark); J.H. Janssen; J. de Wit (Jan); J.H.J. Hoeijmakers (Jan); L.H. Thompson; D. Bootsma (Dirk); A. Westerveld (Andries)

    1988-01-01

    textabstractThe human DNA-excision repair gene ERCC-1 is cloned by its ability to correct the excision-repair defect of the ultraviolet light- and mitomycin-C-sensitive CHO mutant cell line 43-3B. This mutant is assigned to complementation group 2 of the excision-repair-deficient CHO mutants. In ord

  5. Transient correction of excision repair defects in fibroblasts of 9 xeroderma pigmentosum complementation groups by microinjection of crude human cell extract.

    NARCIS (Netherlands)

    W. Vermeulen (Wim); P. Osseweijer; A.J.R. de Jonge; J.H.J. Hoeijmakers (Jan)

    1986-01-01

    textabstractCrude extracts from human cells were microinjected into the cytoplasm of cultured fibroblasts from 9 excision-deficient xeroderma pigmentosum (XP) complementation groups. The level of UV-induced unscheduled DNA synthesis (UDS) was measured to determine the effect of the extract on the re

  6. Cytoplasmic localization of a functionally active Fanconi anemia group A green fluorescent protein chimera in human 293 cells

    NARCIS (Netherlands)

    Kruyt, FAE; Waisfisz, Q; Dijkmans, LM; Hermsen, M.A.; Youssoufian, H; Arwert, F; Joenje, H

    1997-01-01

    Hypersensitivity to cross-linking agents and predisposition to malignancy are characteristic of the genetically heterogeneous inherited bone marrow failure syndrome, Fanconi anemia (FA). The protein encoded by the recently cloned FA complementation group A gene, FAA, has been expected to localize in

  7. Ataxia-telangiectasia group D complementing gene (ATDC promotes lung cancer cell proliferation by activating NF-κB pathway.

    Directory of Open Access Journals (Sweden)

    Zhong-Ping Tang

    Full Text Available Previous studies suggested Ataxia-telangiectasia group D complementing gene (ATDC as an oncogene in many types of cancer. However, its expression and biological functions in non-small cell lung cancer (NSCLC remain unclear. Herein, we investigated its expression pattern in 109 cases of human NSCLC samples by immunohistochemistry and found that ATDC was overexpressed in 62 of 109 NSCLC samples (56.88%. ATDC overexpression correlated with histological type (p<0.0001, tumor status (p = 0.0227 and histological differentiation (p = 0.0002. Next, we overexpressed ATDC in normal human bronchial epithelial cell line HBE and depleted its expression in NSCLC cell lines A549 and H1299. MTT and colony formation assay showed that ATDC overexpression promoted cell proliferation while its depletion inhibited cell growth. Furthermore, cell cycle analysis showed that ATDC overexpression decreased the percentage of cells in G1 phase and increased the percentage of cells in S phase, while ATDC siRNA treatment increased the G1 phase percentage and decreased the S phase percentage. Further study revealed that ATDC overexpression could up-regulate cyclin D1 and c-Myc expression in HBE cells while its depletion down-regulated cyclin D1 and c-Myc expression in A549 and H1299 cells. In addition, ATDC overexpression was also associated with an increased proliferation index, cyclin D1 and c-Myc expression in human NSCLC samples. Further experiments demonstrated that ATDC up-regulated cyclin D1 and c-Myc expression independent of wnt/β-catenin or p53 signaling pathway. Interestingly, ATDC overexpression increased NF-κB reporter luciferase activity and p-IκB protein level. Correspondingly, NF-κB inhibitor blocked the effect of ATDC on up-regulation of cyclin D1 and c-Myc. In conclusion, we demonstrated that ATDC could promote lung cancer proliferation through NF-κB induced up-regulation of cyclin D1 and c-Myc.

  8. Substituting complements

    OpenAIRE

    Dari-Mattiacci, G.; Parisi, F.; Heller, M.

    2009-01-01

    The presence of multiple sellers in the provision of (nonsubstitutable) complementary goods leads to outcomes that are worse than those generated by a monopoly (with a vertically integrated production of complements), a problem known in the economic literature as complementary oligopoly and recently popularized in the legal literature as the tragedy of the anticommons. We ask the following question: how many substitutes for each complement are necessary to render the presence of multiple sell...

  9. On Complements of Normal Subgroups in Finite Groups Ⅱ%关于有限群的正规子群的补子群Ⅱ

    Institute of Scientific and Technical Information of China (English)

    王坤仁

    2004-01-01

    研讨了关于有限群G的一个正规子群K的补子群之存在性与共轭性的更多一些的结果.主要结果如下:(1)假设K是Abel群并且K的每个Sylow子群S在G之含S的Sylow子群中有补子群.则有:(i)K在G中有补子群;(ii)若G有Hallπ-子群H,其中π=π(K),并且K在H中的所有补子群在H中是共轭的,则K在G中的所有补子群在G中是共轭的.(2)假设K是可解的并且对所有的S/K∈Syl(G/K),K是S的一个直因子.则有:(i)K在G中有补子群;(ii)若G有Hallπ-子群H,其中π=π(K),则K在G中的所有补子群在G中共轭的充要条件是K在H中的所有补子群在H中共轭.%In this paper, some more properties of the existence and conjugacy of complements of a normal subgroup K of a finite group G are studied. The main results are as follows. (1) Suppose that K is abelian and every Sylow subgrop S of K has a complement in a Sylow subgroup of G which contains S. Then: (i) K has a complement in G; (ii) If G has a Hall π- subgroup H with π = π(K), and all complements of K in H are conjugate in H, then all complements of K in G are conjugate in G. (2) Suppose that K is solvable and K is a direct factor of S for each S/K∈ Syl(G/K).Then: (i) K has a complement in G;(ii) If G has a Hall π-subgroup H with π = π(K), then all complements of K inG are conjugate in G ff and only if all complements of K in H are conjugate in H.

  10. Substituting complements

    NARCIS (Netherlands)

    G. Dari-Mattiacci; F. Parisi

    2006-01-01

    The presence of multiple sellers in the provision of (nonsubstitutable) complementary goods leads to outcomes that are worse than those generated by a monopoly (with a vertically integrated production of complements), a problem known in the economic literature as complementary oligopoly and recently

  11. Substituting complements

    NARCIS (Netherlands)

    G. Dari-Mattiacci; F. Parisi

    2009-01-01

    The presence of multiple sellers in the provision of (nonsubstitutable) complementary goods leads to outcomes that are worse than those generated by a monopoly (with a vertically integrated production of complements), a problem known in the economic literature as complementary oligopoly and recently

  12. Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

    Science.gov (United States)

    Zhang, Xiaoling; Shang, Xun; Guo, Fukun; Murphy, Kim; Kirby, Michelle; Kelly, Patrick; Reeves, Lilith; Smith, Franklin O.; Williams, David A.

    2008-01-01

    Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway. PMID:18565850

  13. Liver oxidation and inflammation in Fa/Fa rats fed glucomannan/spirulina-surimi.

    Science.gov (United States)

    Vázquez-Velasco, Miguel; González-Torres, Laura; López-Gasco, Patricia; Bastida, Sara; Benedí, Juana; Sánchez-Reus, María Isabel; González-Muñoz, María José; Sánchez-Muniz, Francisco J

    2014-09-15

    The effect of high-fat squid-surimi diets enriched in glucomannan or glucomannan-spirulina on lipemia, liver glutathione status, antioxidant enzymes and inflammation biomarkers was determined in Zucker Fa/Fa rats. Groups of eight rats each received for 7weeks the squid-surimi control (C), glucomannan-enriched squid-surimi (G) and glucomannan-spirulina enriched squid-surimi (GS). Liver weight, cytochrome P450 7A1 expression and cholesterolemia were decreased in G and GS vs. C, improving glutathione red-ox index (pspirulina kept those hypocholesterolemic and antioxidant effects but reduced the inflammation observed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. FaRXf1

    NARCIS (Netherlands)

    Roach, Jack A.; Verma, Sujeet; Peres, Natalia A.; Jamieson, Andrew R.; Weg, van de Eric W.; Bink, Marco C.A.M.; Bassil, Nahla V.; Lee, Seonghee; Whitaker, Vance M.

    2016-01-01

    Key message: Angular leaf spot is a devastating bacterial disease of strawberry. Resistance from two wild accessions is highly heritable and controlled by a major locus on linkage group 6D.Abstract: Angular leaf spot caused by Xanthomonas fragariae is the only major bacterial disease of cultivate

  15. Deficiency of UBE2T, the E2 Ubiquitin Ligase Necessary for FANCD2 and FANCI Ubiquitination, Causes FA-T Subtype of Fanconi Anemia

    Directory of Open Access Journals (Sweden)

    Kimberly A. Rickman

    2015-07-01

    Full Text Available Fanconi anemia (FA is a rare bone marrow failure and cancer predisposition syndrome resulting from pathogenic mutations in genes encoding proteins participating in the repair of DNA interstrand crosslinks (ICLs. Mutations in 17 genes (FANCA-FANCS have been identified in FA patients, defining 17 complementation groups. Here, we describe an individual presenting with typical FA features who is deficient for the ubiquitin-conjugating enzyme (E2, UBE2T. UBE2T is known to interact with FANCL, the E3 ubiquitin-ligase component of the multiprotein FA core complex, and is necessary for the monoubiquitination of FANCD2 and FANCI. Proband fibroblasts do not display FANCD2 and FANCI monoubiquitination, do not form FANCD2 foci following treatment with mitomycin C, and are hypersensitive to crosslinking agents. These cellular defects are complemented by expression of wild-type UBE2T, demonstrating that deficiency of the protein UBE2T can lead to Fanconi anemia. UBE2T gene gains an alias of FANCT.

  16. X-ray repair cross-complementing group 1 polymorphisms and hepatocellular carcinoma: A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Tian Xie; Zhen-Guang Wang; Jing-Lei Zhang; Hui Liu

    2012-01-01

    AIM:To perform a systematic meta-analysis to investigate the association between X-ray repair crosscomplementing group 1 (XRCC1) polymorphisms and hepatocellular carcinoma (HCC) risk.METHODS:Relevant studies extracted from PubMed,Embase,Wanfang,VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study.Stata software,version 11.0,was used for the statistical analysis.The odds ratios (ORs) and 95% confidence interval (CI) of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls.The meta-analysis was performed using fixed-effect or random-effect methods,depending on the absence or presence of significant heterogeneity.RESULTS:Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria (four studies,888 cases and 938 controls for Arg194Trp,four studies,858 cases and 880 controls for Arg280His,and nine studies,1845 cases and 2401 controls for Arg399Gln).The meta-analysis revealed no associations between the Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene and HCC risk under all contrast models (codominant,dominant and recessive models) in the overall analysis and sensitivity analysis (the studies with controls not in the Hardy-Weinberg equilibrium were excluded).For XRCC1 Arg280His polymorphism,the overall analysis revealed the significant association between the His/His genotype and the increased risk of HCC (His/His vs Arg/Arg model,OR:1.96,95% CI:1.03-3.75,P =0.04).However,sensitivity analysis showed an altered pattern of result and non-significant association (OR:2.06,95% CI:0.67-6.25,P =0.20).The heterogeneity hypothesis test did not reveal any heterogeneity,and Begg's and Egger's tests did not find any obvious publication bias.CONCLUSION:The XRCC1 Arg194Trp and Arg399Gln polymorphisms are not associated with HCC risk.More rigorous association studies are needed to verify the involvement of XRCC1 Arg280His polymorphism in HCC susceptibility.

  17. Metformin ameliorates diabetes but does not normalize the decreased GLUT 4 content in skeletal muscle of obese (fa/fa) Zucker rats

    DEFF Research Database (Denmark)

    Handberg, A; Kayser, L; Høyer, P E

    1993-01-01

    We studied the expression of the glucose transporter GLUT 4 in the soleus and red gastrocnemius muscles from obese, diabetic (fa/fa) Zucker rats compared to their lean littermates (Fa/-), with and without treatment with the antidiabetic drug metformin. In the untreated groups of rats, the GLUT 4...... content in a crude membrane fraction of both the soleus and the red gastrocnemius muscles were significantly lower in the obese (fa/fa) rats (3.46 +/- 0.28 vs. 6.04 +/- 0.41, p GLUT 4 expression in soleus muscle from...... the same rats were confirmed by quantitative immunofluorescence microscopy, and the results were significantly correlated with the results obtained from quantitative immunoblotting (rho = 0.70, p GLUT 4 in fa/fa rats could contribute to the well-established insulin...

  18. FA

    African Journals Online (AJOL)

    spamer

    Portugal, Senegal and Ivory Coast-. Ghana have ..... sometimes much higher than that during the last century in California or in ... assessments of past and present experiences can be ... Some scenarios for fish productivity under climatic changes ...

  19. Correlation between X-ray cross-complementing group 1 polymorphisms and the onset risk of glioma A meta-analysis******

    Institute of Scientific and Technical Information of China (English)

    Xinquan Gu; Hongyan Sun; Liping Chang; Ran Sun; Hongfeng Yang; Xuewen Zhang; Xianling Cong

    2013-01-01

    OBJECTIVE: To evaluate the association of X-ray cross-complementing group 1 (XRCC1) Arg399Gln, Arg194Trp and Arg280His polymorphisms with the risk of glioma. DATA SOURCES:A systematic literature search of papers published from January 2000 to August 2012 in PubMed, Embase, China National Knowledge Infrastructure database, and Wanfang da-tabase was performed. The key words used were“glioma”,“polymorphism”, and“XRCC1 or X-ray repair cross-complementing group 1”. References cited in the retrieved articles were screened manual y to identify additional eligible studies. STUDY SELECTION: Studies were identified according to the fol owing inclusion criteria:case-control design was based on unrelated individuals;and genotype frequency was available to estimate an odds ratio (OR) and 95%confidence interval (CI). Meta-analysis was performed for the selected studies after strict screening. Dominant and recessive genetic models were used and the relationship between homozygous mutant genotype frequencies and mutant gene frequency and glioma incidence was investigated. We chose the fixed or random effect model according to the heterogeneity to calculate OR and 95%CI, and sensitivity analyses were conducted. Publication bias was examined using the inverted funnel plot and the Egger’s test using Stata 12.0 software. MAIN OUTCOME MEASURES: Association of XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms with the risk of glioma, and subgroup analyses were performed according to differ-ent ethnicities of the subjects. RESULTS:Twelve articles were included in the meta-analysis. Eleven of the articles were concerned with the Arg399Gln polymorphism and glioma onset risk. Significantly increased glioma risks were found only in the dominant model (Gln/Gln+Gln/Arg versus Arg/Arg:OR=1.26, 95%CI=1.03-1.54, P=0.02). In the subgroup analysis by ethnicity, significantly increased risk was found in Asian subjects in the recessive (OR = 1.46, 95%CI = 1.04-2.45, P = 0.03) and

  20. Accumulation of (5′S)-8,5′-cyclo-2′-deoxyadenosine in organs of Cockayne syndrome complementation group B gene knockout mice

    Science.gov (United States)

    Kirkali, Güldal; de Souza-Pinto, Nadja C.; Jaruga, Pawel; Bohr, Vilhelm A.; Dizdaroglu, Miral

    2009-01-01

    Cockayne syndrome (CS) is a human genetic disorder characterized by sensitivity to UV radiation, neurodegeneration, premature aging among other phenotypes. CS complementation group B (CS-B) gene (csb) encodes the CSB protein (CSB) that is involved in base excision repair of a number of oxidatively induced lesions in genomic DNA in vivo. We hypothesized that CSB may also play a role in cellular repair of the DNA helix-distorting tandem lesion (5′S)-8,5′-cyclo-2′-deoxyadenosine (S-cdA). Among many DNA lesions, S-cdA is unique in that it represents a concomitant damage to both the sugar and base moieties of the same nucleoside. Because of the presence of the C8-C5′ covalent bond, S-cdA is repaired by nucleotide excision repair unlike most of other oxidatively induced lesions in DNA, which are subject to base excision repair. To test our hypothesis, we isolated genomic DNA from brain, kidney and liver of wild type and csb knockout (csb-/-) mice. Animals were not exposed to any exogenous oxidative stress before the experiment. DNA samples were analysed by liquid chromatography/mass spectrometry with isotope-dilution. Statistically greater background levels of S-cdA were observed in all three organs of csb-/- mice than in those of wild type mice. These results suggest the in vivo accumulation of S-cdA in genomic DNA due to lack of its repair in csb-/- mice. Thus, this study provides, for the first time, the evidence that CSB plays a role in the repair of the DNA helix-distorting tandem lesion S-cdA. Accumulation of unrepaired S-cdA in vivo may contribute to the pathology associated with CS. PMID:18992371

  1. X-Ray Cross-Complementing Group 1 and Thymidylate Synthase Polymorphisms Might Predict Response to Chemoradiotherapy in Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Lamas, Maria J., E-mail: mlamasd@yahoo.es [Oncology Pharmacy Unit, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Duran, Goretti [Oncology Pharmacy Unit, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Gomez, Antonio [Department of Oncology Radiotherapy, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Balboa, Emilia [Molecular Medicine Unit, Fundacion Publica Galega de Medicina Xenomica, Choupana S/N, Santiago de Compostela (Spain); Anido, Urbano [Department of Medical Oncology, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Bernardez, Beatriz [Oncology Pharmacy Unit, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Rana-Diez, Pablo [Molecular Medicine Unit, Fundacion Publica Galega de Medicina Xenomica, Choupana S/N, Santiago de Compostela (Spain); Lopez, Rafael [Department of Medical Oncology, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Carracedo, Angel; Barros, Francisco [Fundacion Publica Galega de Medicina Xenomica and Genomic Medicine Group-CIBERER, University of Santiago de Compostela, Calle San Fransisco S/N, Santiago de Compostela (Spain)

    2012-01-01

    Purpose: 5-Fluorouracil-based chemoradiotherapy before total mesorectal excision is currently the standard treatment of Stage II and III rectal cancer patients. We used known predictive pharmacogenetic biomarkers to identify the responders to preoperative chemoradiotherapy in our series. Methods and Materials: A total of 93 Stage II-III rectal cancer patients were genotyped using peripheral blood samples. The genes analyzed were X-ray cross-complementing group 1 (XRCC1), ERCC1, MTHFR, EGFR, DPYD, and TYMS. The patients were treated with 225 mg/m{sup 2}/d continuous infusion of 5-fluorouracil concomitantly with radiotherapy (50.4 Gy) followed by total mesorectal excision. The outcomes were measured by tumor regression grade (TRG) as a major response (TRG 1 and TRG 2) or as a poor response (TRG3, TRG4, and TRG5). Results: The major histopathologic response rate was 47.3%. XRCC1 G/G carriers had a greater probability of response than G/A carriers (odds ratio, 4.18; 95% confidence interval, 1.62-10.74, p = .003) Patients with polymorphisms associated with high expression of thymidylate synthase (2R/3G, 3C/3G, and 3G/3G) showed a greater pathologic response rate compared with carriers of low expression (odds ratio, 2.65; 95% confidence interval, 1.10-6.39, p = .02) No significant differences were seen in the response according to EGFR, ERCC1, MTHFR{sub C}677 and MTHFR{sub A}1298 expression. Conclusions: XRCC1 G/G and thymidylate synthase (2R/3G, 3C/3G, and 3G/3G) are independent factors of a major response. Germline thymidylate synthase and XRCC1 polymorphisms might be useful as predictive markers of rectal tumor response to neoadjuvant chemoradiotherapy with 5-fluorouracil.

  2. Different impact of excision repair cross-complementation group 1 on survival in male and female patients with inoperable non-small-cell lung cancer treated with carboplatin and gemcitabine

    DEFF Research Database (Denmark)

    Holm, Bente; Mellemgaard, Anders; Skov, Torsten;

    2009-01-01

    PURPOSE: The excision repair cross-complementation group 1 (ERCC1) status was assessed in patients receiving carboplatin and gemcitabine for inoperable non-small-cell lung cancer (NSCLC). We analyzed the association between the ERCC1 status and the overall survival after the chemotherapy. PATIENTS...

  3. Microinjection of Escherichia coli UvrA, B, C and D proteins into fibroblasts of xeroderma pigmentosum complementation groups A and C does not result in restoration of UV-induced DNA synthesis.

    NARCIS (Netherlands)

    J.C.M. Zwetsloot; A.P. Barbeiro; W. Vermeulen (Wim); J.H.J. Hoeijmakers (Jan); C.M.P. Backendorf (Claude)

    1986-01-01

    textabstractThe UV-induced unscheduled DNA synthesis (UDS) in cultured human fibroblasts of repair-deficient xeroderma pigmentosum complementation groups A and C was assayed after injection of identical activities of either Uvr excinuclease (UvrA, B, C and D) from Escherichia coli or endonuclease V

  4. X-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms and cervical cancer risk: a huge systematic review and meta-analysis.

    Science.gov (United States)

    Li, Ya; Liu, Fei; Tan, Shi-Qiao; Wang, Yan; Li, Shang-Wei

    2012-01-01

    Previous studies investigating the association between X-ray repair cross-complementation group 1(XRCC1) polymorphisms and cervical cancer (CC) risk has provided inconsistent results. The aim of our study was to assess the association between the XRCC1 gene Arg399Gln, Arg194Trp, Arg280His polymorphisms and risk of CC. Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before March 2011.Summary odds ratios (ORs) and 95% confidence intervals (CIs) for XRCC1 polymorphisms and CC were calculated in a fixed-effects model or a random-effects model when appropriate. Ultimately, 9, 5 and 2 studies were found to be eligible for meta-analyses of Arg399Gln, Arg194Trp and Arg280His, respectively. Our analysis suggested that the variant genotypes of Arg194Trp were associated with a significantly increased CC risk (Trp/Trp vs Arg/Arg, OR = 2.21, 95% CI = 1.60-3.06; Arg/Trp vs Arg/Arg, OR = 1.23, 95% CI = 1.02-1.49; dominant model, OR = 1.36, 95% CI = 1.14-1.63; recessive model, OR = 2.06, 95% CI = 1.51-2.82). For Arg280His polymorphism, no obvious associations were found for all genetic models. For Arg399Gln polymorphism, also no obvious associations were found for all genetic models. In the subgroup analyses by ethnicity/country, a significantly increased risk was observed among Asian, especially among Chinese. To get more precise evidences, adjusted ORs (95%CI) by potential confounders (such as age, ethnicity or smoking, etc) were also calculated for XRCC1 Arg399Gln and Arg194Trp, however, the estimated pooled adjusted OR still did not change at all. This meta-analysis suggests that Arg194Trp polymorphism may be associated with CC risk, Arg399Gln polymorphism might be a low-penetrent risk factor for CC only in Asians, and there may be no association between Arg280His polymorphism and CC risk.

  5. X-ray repair cross-complementing group 1 (XRCC1 genetic polymorphisms and cervical cancer risk: a huge systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Ya Li

    Full Text Available BACKGROUND: Previous studies investigating the association between X-ray repair cross-complementation group 1(XRCC1 polymorphisms and cervical cancer (CC risk has provided inconsistent results. The aim of our study was to assess the association between the XRCC1 gene Arg399Gln, Arg194Trp, Arg280His polymorphisms and risk of CC. METHODS: Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before March 2011.Summary odds ratios (ORs and 95% confidence intervals (CIs for XRCC1 polymorphisms and CC were calculated in a fixed-effects model or a random-effects model when appropriate. RESULTS: Ultimately, 9, 5 and 2 studies were found to be eligible for meta-analyses of Arg399Gln, Arg194Trp and Arg280His, respectively. Our analysis suggested that the variant genotypes of Arg194Trp were associated with a significantly increased CC risk (Trp/Trp vs Arg/Arg, OR = 2.21, 95% CI = 1.60-3.06; Arg/Trp vs Arg/Arg, OR = 1.23, 95% CI = 1.02-1.49; dominant model, OR = 1.36, 95% CI = 1.14-1.63; recessive model, OR = 2.06, 95% CI = 1.51-2.82. For Arg280His polymorphism, no obvious associations were found for all genetic models. For Arg399Gln polymorphism, also no obvious associations were found for all genetic models. In the subgroup analyses by ethnicity/country, a significantly increased risk was observed among Asian, especially among Chinese. To get more precise evidences, adjusted ORs (95%CI by potential confounders (such as age, ethnicity or smoking, etc were also calculated for XRCC1 Arg399Gln and Arg194Trp, however, the estimated pooled adjusted OR still did not change at all. CONCLUSION: This meta-analysis suggests that Arg194Trp polymorphism may be associated with CC risk, Arg399Gln polymorphism might be a low-penetrent risk factor for CC only in Asians, and there may be no association between Arg280His polymorphism and CC risk.

  6. Deoxyribonucleic acid repair gene X-ray repair cross-complementing group 1 polymorphisms and non-carcinogenic disease risk in different populations: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Bagher Larijani

    2013-01-01

    Full Text Available Purpose: This study aims to assess a meta-analysis of the association of X-ray repair cross-complementing group 1 (XRCC1 polymorphisms with the risk of various non-carcinogenic diseases in different population. Materials and Methods: This meta-analysis was performed by critically reviewing reveals 38 studies involving 10043 cases and 11037 controls. Among all the eligible studies, 14 focused on Arg194Trp polymorphism, 33 described the Arg399Gln and three articles investigated on Arg280His. Populations were divided into three different ethnic subgroups include Caucasians, Asians and other (Turkish and Iranian. Results: Pooled results showed no correlation between Arg194Trp and non-carcinogenic disease. There was only weak relation in the recessive (odds ratio [OR] =1.11, 95% confidence interval [CI]: 0.86-1.44 model in Asian population and dominant (OR = 1.04, 95% CI: 0.66-1.63 model of other populations. In Arg399Gln polymorphism, there was no relation with diseases of interest generally. In the pooled analysis, there were weak relation in the dominant (OR = 1.08, 95% CI: 0.86-1.35 model of Asian population and quite well-correlation with recessive (OR = 1.49, 95% CI: 1.19-1.88, dominant (OR = 1.23, 95% CI: 0.94-1.62, and additive (OR = 1.23, 95% CI: 0.94-1.62 models of other subgroup. For Arg280His, there was a weak relation only in the dominant model (OR = 1.06, 95% CI: 0.74-1.51. Conclusion: The present meta-analysis correspondingly shows that Arg399Gln variant to be associated with increased non-carcinogenic diseases risk through dominant and recessive modes among Iranian and Turkish population. It also suggests a trend of dominant and recessive effect of Arg280His variant in all population and its possible protective effect on non-carcinogenic diseases.

  7. Complement system in zebrafish.

    Science.gov (United States)

    Zhang, Shicui; Cui, Pengfei

    2014-09-01

    Zebrafish is recently emerging as a model species for the study of immunology and human diseases. Complement system is the humoral backbone of the innate immune defense, and our knowledge as such in zebrafish has dramatically increased in the recent years. This review summarizes the current research progress of zebrafish complement system. The global searching for complement components in genome database, together with published data, has unveiled the existence of all the orthologues of mammalian complement components identified thus far, including the complement regulatory proteins and complement receptors, in zebrafish. Interestingly, zebrafish complement components also display some distinctive features, such as prominent levels of extrahepatic expression and isotypic diversity of the complement components. Future studies should focus on the following issues that would be of special importance for understanding the physiological role of complement components in zebrafish: conclusive identification of complement genes, especially those with isotypic diversity; analysis and elucidation of function and mechanism of complement components; modulation of innate and adaptive immune response by complement system; and unconventional roles of complement-triggered pathways.

  8. Oceanographic profile data collected from CTD and sound velocimeter - moving vessel profiler casts aboard FA2805, FA2806, FA2807, FA2808 and NOAA Ship FAIRWEATHER as part of project OPR-O190-FA-15 in the Coastal Waters of SE Alaska and North Pacific Ocean from 2015-09-23 to 2015-11-11 (NCEI Accession 0138176)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0138176 includes physical and profile data collected aboard the FA2805, FA2806, FA2807, FA2808 and NOAA Ship FAIRWEATHER during project OPR-O190-FA-15...

  9. Oceanographic profile data collected from CTD casts aboard FA2805, FA2806, FA2807, FA2808 and FAIRWEATHER as part of project OPR-P335-FA-16 in the Gulf of Alaska from 2016-06-24 to 2016-08-01 (NCEI Accession 0156699)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0156699 includes physical and profile data collected aboard the FA2805, FA2806, FA2807, FA2808 and FAIRWEATHER during project OPR-P335-FA-16 in the...

  10. Oceanographic profile data collected from CTD casts aboard FA2805, FA2806, FA2807, FA2808 and NOAA Ship FAIRWEATHER as part of project OPR-O190-FA-16 in the Coastal Waters of SE Alaska from 2016-05-08 to 2016-06-15 (NCEI Accession 0155203)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0155203 includes physical and profile data collected aboard the FA2805, FA2806, FA2807, FA2808 and NOAA Ship FAIRWEATHER during project OPR-O190-FA-16...

  11. Oceanographic profile data collected from CTD casts aboard FA2805, FA2806, FA2807, FA2808 and NOAA Ship FAIRWEATHER as part of project OPR-S327-FA-15 in the Beaufort Sea and Bering Sea from 2015-06-25 to 2015-08-14 (NCEI Accession 0131204)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0131204 includes physical and profile data collected aboard the FA2805, FA2806, FA2807, FA2808 and NOAA Ship FAIRWEATHER during project OPR-S327-FA-15...

  12. Complement and autoimmunity.

    Science.gov (United States)

    Ballanti, Eleonora; Perricone, Carlo; Greco, Elisabetta; Ballanti, Marta; Di Muzio, Gioia; Chimenti, Maria Sole; Perricone, Roberto

    2013-07-01

    The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.

  13. Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance.

    Science.gov (United States)

    Hess, Julia; Unger, Kristian; Orth, Michael; Schötz, Ulrike; Schüttrumpf, Lars; Zangen, Verena; Gimenez-Aznar, Igor; Michna, Agata; Schneider, Ludmila; Stamp, Ramona; Selmansberger, Martin; Braselmann, Herbert; Hieber, Ludwig; Drexler, Guido A; Kuger, Sebastian; Klein, Diana; Jendrossek, Verena; Friedl, Anna A; Belka, Claus; Zitzelsberger, Horst; Lauber, Kirsten

    2017-02-01

    Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance. Silencing of FancA expression in HNSCC cell lines with genomic gains on 16q23-24 resulted in significantly impaired clonogenic survival upon irradiation. Conversely, overexpression of FancA in immortalized keratinocytes conferred increased survival accompanied by improved DNA repair, reduced accumulation of chromosomal translocations, but no hyperactivation of the FA/BRCA-pathway. Downregulation of interferon signaling as identified by microarray analyses, enforced irradiation-induced senescence, and elevated production of the senescence-associated secretory phenotype (SASP) appeared to be candidate mechanisms contributing to FancA-mediated radioresistance. Data of the TCGA HNSCC cohort confirmed the association of gains on 16q24.3 with FancA overexpression and impaired overall survival. Importantly, transcriptomic alterations similar to those observed upon FancA overexpression in vitro strengthened the clinical relevance. Overall, FancA amplification and overexpression appear to be crucial for radiotherapeutic failure in HNSCC.

  14. The cathepsin B inhibitor, z-FA-CMK is toxic and readily induced cell death in human T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Liow, K.Y.; Chow, S.C., E-mail: chow.sek.chuen@monash.edu

    2013-11-01

    The cathepsin B inhibitor, benzyloxycarbonyl-phenylalanine-alanine-chloromethylketone (z-FA-CMK) was found to be toxic and readily induced cell death in the human T cell line, Jurkat, whereas two other analogs benzyloxycarbonyl-phenylalanine-alanine-fluoromethylketone (z-FA-FMK) and benzyloxycarbonyl-phenylalanine-alanine-diazomethylketone (z-FA-DMK) were not toxic. The toxicity of z-FA-CMK requires not only the CMK group, but also the presence of alanine in the P1 position and the benzyloxycarbonyl group at the N-terminal. Dose–response studies showed that lower concentrations of z-FA-CMK induced apoptosis in Jurkat T cells whereas higher concentrations induced necrosis. In z-FA-CMK-induced apoptosis, both initiator caspases (-8 and -9) and effector caspases (-3, -6 and -7) were processed to their respective subunits in Jurkat T cells. However, only the pro-form of the initiator caspases were reduced in z-FA-CMK-induced necrosis and no respective subunits were apparent. The caspase inihibitor benzyloxycarbonyl-valine-alanine-aspartic acid-(O-methyl)-fluoromehylketone (z-VAD-FMK) inhibits apoptosis and caspase processing in Jurkat T cells treated with low concentration of z-FA-CMK but has no effect on z-FA-CMK-induced necrosis and the loss of initiator caspases. This suggests that the loss of initiator caspases in Jurkat T cells during z-FA-CMK-induced necrosis is not a caspase-dependent process. Taken together, we have demonstrated that z-FA-CMK is toxic to Jurkat T cells and induces apoptosis at low concentrations, while at higher concentrations the cells die of necrosis. - Highlights: • z-FA-CMK is toxic and induce cell death in the human T cells. • z-FA-CMK toxicity requires the CMK group, alanine and the benzyloxycarbonyl group. • z-FA-CMK induced apoptosis at low concentration and necrosis at high concentration.

  15. Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats.

    Science.gov (United States)

    Legette, Leecole L; Luna, Arlyn Y Moreno; Reed, Ralph L; Miranda, Cristobal L; Bobe, Gerd; Proteau, Rosita R; Stevens, Jan F

    2013-07-01

    Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9 mg/kg BW for 6 weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3 weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet for the last 3 weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay kits. Plasma and liver tissue levels of XN and its metabolites were determined by liquid-chromatography tandem mass spectrometry. Plasma and liver tissue levels of xanthohumol were similar between low and medium dose groups and significantly (pxanthohumol, which was also not seen for female rats. Plasma cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not affected by treatment. The findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome.

  16. Antibody-mediated complement C3b/iC3b binding to group B Streptococcus in paired mother and baby serum samples in a refugee population on the Thailand-Myanmar border.

    Science.gov (United States)

    Herbert, Jenny; Thomas, Stephen; Brookes, Charlotte; Turner, Claudia; Turner, Paul; Nosten, Francois; Le Doare, Kirsty; Hudson, Michael; Heath, Paul T; Gorringe, Andrew; Taylor, Stephen

    2015-03-01

    Streptococcus agalactiae (group B streptococcus [GBS]) is the leading cause of neonatal sepsis and meningitis. In this study, we determined antibody-mediated deposition of complement C3b/iC3b onto the bacterial cell surface of GBS serotypes Ia, Ib, II, III, and V. This was determined for 520 mother and umbilical cord serum sample pairs obtained at the time of birth from a population on the Thailand-Myanmar border. Antibody-mediated deposition of complement C3b/iC3b was detected to at least one serotype in 91% of mothers, despite a known carriage rate in this population of only 12%. Antibody-mediated C3b/iC3b deposition corresponded to known carriage rates, with the highest levels of complement deposition observed onto the most prevalent serotype (serotype II) followed by serotypes Ia, III, V, and Ib. Finally, neonates born to mothers carrying serotype II GBS at the time of birth showed higher antibody-mediated C3b/iC3b deposition against serotype II GBS than neonates born to mothers with no serotype II carriage. Assessment of antibody-mediated C3b/iC3b deposition against GBS may provide insights into the seroepidemiology of anti-GBS antibodies in mothers and infants in different populations.

  17. Complement in autoimmune diseases.

    Science.gov (United States)

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

    2017-02-01

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

  18. Complement in hemolytic anemia.

    Science.gov (United States)

    Brodsky, Robert A

    2015-01-01

    Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. For optimal therapy, it is critical, but often difficult, to distinguish aHUS from other TMAs, such as thrombotic thrombocytopenic purpura; however, novel bioassays are being developed. In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. Drugs that inhibit complement activation are increasingly being used to treat these diseases. This article discusses the pathophysiology, diagnosis, and therapy for PNH, aHUS, and CAD.

  19. Complement defects in patients with chronic rhinosinusitis

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Quisgaard; Lange, Bibi; Kjeldsen, Anette D;

    2012-01-01

    The complement system is an important part of our immune system, and complement defects lead generally to increased susceptibility to infections and autoimmune diseases. We have studied the role of complement activity in relation with chronic rhinosinusitis (CRS), and more specifically studied...... whether complement defects collectively predispose individuals for CRS or affect CRS severity. The participants comprised 87 CRS patients randomly selected from the general population, and a control group of 150 healthy blood donors. The CRS patients were diagnosed according to the European Position Paper...... on Rhinosinusitis and nasal Polyps criteria, and severity was evaluated by the Sino-nasal Outcome Test-22. Serum samples were analysed by ELISA for activity of the respective pathways of complement, and subsequently for serum levels of relevant components. We found that the frequency of complement defects...

  20. Complement diagnostics: concepts, indications, and practical guidelines.

    Science.gov (United States)

    Nilsson, Bo; Ekdahl, Kristina Nilsson

    2012-01-01

    Aberrations in the complement system have been shown to be direct or indirect pathophysiological mechanisms in a number of diseases and pathological conditions such as autoimmune disease, infections, cancer, allogeneic and xenogeneic transplantation, and inflammation. Complement analyses have been performed on these conditions in both prospective and retrospective studies and significant differences have been found between groups of patients, but in many diseases, it has not been possible to make predictions for individual patients because of the lack of sensitivity and specificity of many of the assays used. The basic indications for serological diagnostic complement analysis today may be divided into three major categories: (a) acquired and inherited complement deficiencies; (b) disorders with complement activation; (c) inherited and acquired C1INH deficiencies. Here, we summarize indications, techniques, and interpretations for basic complement analyses and present an algorithm, which we follow in our routine laboratory.

  1. Complement Diagnostics: Concepts, Indications, and Practical Guidelines

    Directory of Open Access Journals (Sweden)

    Bo Nilsson

    2012-01-01

    Full Text Available Aberrations in the complement system have been shown to be direct or indirect pathophysiological mechanisms in a number of diseases and pathological conditions such as autoimmune disease, infections, cancer, allogeneic and xenogeneic transplantation, and inflammation. Complement analyses have been performed on these conditions in both prospective and retrospective studies and significant differences have been found between groups of patients, but in many diseases, it has not been possible to make predictions for individual patients because of the lack of sensitivity and specificity of many of the assays used. The basic indications for serological diagnostic complement analysis today may be divided into three major categories: (a acquired and inherited complement deficiencies; (b disorders with complement activation; (c inherited and acquired C1INH deficiencies. Here, we summarize indications, techniques, and interpretations for basic complement analyses and present an algorithm, which we follow in our routine laboratory.

  2. Generation of an induced pluripotent stem cell line that mimics the disease phenotypes from a patient with Fanconi anemia by conditional complementation

    Directory of Open Access Journals (Sweden)

    Sumitha Prameela Bharathan

    2017-04-01

    Full Text Available Generation of Fanconi anemia (FA patient-specific induced pluripotent stem cells (iPSCs has been reported to be technically challenging due to the defects in the FA-pathway in the patients' somatic cells. By inducible complementation of FA-pathway, we successfully reprogrammed the fibroblasts of an FA patient to iPSCs. CSCR19i-indCFANCA, one of the iPSC lines generated by the inducible complementation of FA-pathway, was extensively characterized for its pluripotency and karyotype. In the absence of doxycycline (DOX and FANCA expression, this line showed the cellular phenotypes of FA, suggesting it is an excellent tool for FA disease modeling and drug screening.

  3. Phosphoethanolamine substitution of lipid A and resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides and complement-mediated killing by normal human serum.

    Science.gov (United States)

    Lewis, Lisa A; Choudhury, Biswa; Balthazar, Jacqueline T; Martin, Larry E; Ram, Sanjay; Rice, Peter A; Stephens, David S; Carlson, Russell; Shafer, William M

    2009-03-01

    The capacity of Neisseria gonorrhoeae to cause disseminated gonococcal infection requires that such strains resist the bactericidal action of normal human serum. The bactericidal action of normal human serum against N. gonorrhoeae is mediated by the classical complement pathway through an antibody-dependent mechanism. The mechanism(s) by which certain strains of gonococci resist normal human serum is not fully understood, but alterations in lipooligosaccharide structure can affect such resistance. During an investigation of the biological significance of phosphoethanolamine extensions from lipooligosaccharide, we found that phosphoethanolamine substitutions from the heptose II group of the lipooligosaccharide beta-chain did not impact levels of gonococcal (strain FA19) resistance to normal human serum or polymyxin B. However, loss of phosphoethanolamine substitution from the lipid A component of lipooligosaccharide, due to insertional inactivation of lptA, resulted in increased gonococcal susceptibility to polymyxin B, as reported previously for Neisseria meningitidis. In contrast to previous reports with N. meningitidis, loss of phosphoethanolamine attached to lipid A rendered strain FA19 susceptible to complement killing. Serum killing of the lptA mutant occurred through the classical complement pathway. Both serum and polymyxin B resistance as well as phosphoethanolamine decoration of lipid A were restored in the lptA-null mutant by complementation with wild-type lptA. Our results support a role for lipid A phosphoethanolamine substitutions in resistance of this strict human pathogen to innate host defenses.

  4. International Façades - CROFT: Climate Related Optimized Façade Technologies

    NARCIS (Netherlands)

    Bilow, M.

    2012-01-01

    "International Façades - CROFT" links the fields of architecture, building services and building physics. It aims at an international diversity in façade design to reduce energy consumption in building design. Current architectural planning practices, such as the International Style, perceive the c

  5. Complement defects in patients with chronic rhinosinusitis.

    Directory of Open Access Journals (Sweden)

    Maria Q Gaunsbaek

    Full Text Available The complement system is an important part of our immune system, and complement defects lead generally to increased susceptibility to infections and autoimmune diseases. We have studied the role of complement activity in relation with chronic rhinosinusitis (CRS, and more specifically studied whether complement defects collectively predispose individuals for CRS or affect CRS severity. The participants comprised 87 CRS patients randomly selected from the general population, and a control group of 150 healthy blood donors. The CRS patients were diagnosed according to the European Position Paper on Rhinosinusitis and nasal Polyps criteria, and severity was evaluated by the Sino-nasal Outcome Test-22. Serum samples were analysed by ELISA for activity of the respective pathways of complement, and subsequently for serum levels of relevant components. We found that the frequency of complement defects was significantly higher among CRS patients than among healthy control subjects. A majority of Mannan-binding lectin deficient CRS patients was observed. The presence of complement defects had no influence on the severity of subjective symptoms. Our studies show that defects in the complement system collectively may play an immunological role related to the development of CRS. However, an association between severity of symptoms and presence of complement defects could not be demonstrated.

  6. TMA: beware of complements.

    Science.gov (United States)

    Ricklin, Daniel; Cines, Douglas B

    2013-09-19

    In this issue of Blood, Jodele and colleagues report that defective complement regulation contributes to the development of thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) with important implications for diagnosis and management of this severe clinical complication.

  7. Rescue at nonpermissive temperature of complementation group II temperature-sensitive mutants of vesicular stomatitis virus by uv-irradiated VSV

    Energy Technology Data Exchange (ETDEWEB)

    Deutsch, V.; Brun, G.

    1978-06-01

    Rescue is group-characteristic. The helper virus can be either the wt strain or a mutant belonging to any group of ts mutants except group II. With regard to genotype, the rescue progeny virus is temperature-sensitive and belongs to group II, and its ts II parent (ts O52(II)) can be characterized. As for phenotype, the in vitro thermal stability of rescue virions is intermediate between that of parental ts O52(II) and uv-irradiated wt virus, suggesting incorporation of some wt protein II molecules in the rescue virions. Different slopes (zero or different from zero) were seen in dose-effect curves representing rescue obtained by structural protein molecules, suggesting that protein II structural role could be distinguished from its functional role(s) by uv sensitivity. Differences in efficiency of the rescue of ts O52(II) by ts I mutants irradiated with low uv fluence may reflect their different transcribing capabilities at 39.6/sup 0/. The results are discussed taking into account the fact that the phenotype of group II mutants is characterized by an unstable nucleocapsid.

  8. Designing Urban Media Façades

    DEFF Research Database (Denmark)

    Dalsgaard, Peter; Halskov, Kim

    2010-01-01

    Media façades comprise a category of urban computing concerned with the integration of displays into the built environment, including buildings and street furniture. This paper identifies and discusses eight challenges faced when designing urban media façades. The challenges concern a broad range...... of issues: interfaces, physical integration, robustness, content, stakeholders, situation, social relations, and emerging use. The challenges reflect the fact that the urban setting as a domain for interaction design is characterized by a number of circumstances and socio-cultural practices that differ from...

  9. FaRe: A Mathematica package for tensor reduction of Feynman integrals

    Science.gov (United States)

    Re Fiorentin, Michele

    2016-08-01

    In this paper, we present FaRe, a package for Mathematica that implements the decomposition of a generic tensor Feynman integral, with arbitrary loop number, into scalar integrals in higher dimension. In order for FaRe to work, the package FeynCalc is needed, so that the tensor structure of the different contributions is preserved and the obtained scalar integrals are grouped accordingly. FaRe can prove particularly useful when it is preferable to handle Feynman integrals with free Lorentz indices and tensor reduction of high-order integrals is needed. This can then be achieved with several powerful existing tools.

  10. FaRe: a Mathematica package for tensor reduction of Feynman integrals

    CERN Document Server

    Fiorentin, Michele Re

    2015-01-01

    We present FaRe, a package for Mathematica that implements the decomposition of a generic tensor Feynman integral, with arbitrary loop number, into scalar integrals in higher dimension. In order for FaRe to work, the package FeynCalc is needed, so that the tensor structure of the different contributions is preserved and the obtained scalar integrals are grouped accordingly. FaRe can prove particularly useful when it is preferable to handle Feynman integrals with free Lorentz indices and tensor reduction of high-order integrals is needed. This can then be achieved with several powerful existing tools.

  11. The chromosome complement of Acomys spp. (Rodentia, Muridae) from Oursi, Burkina Faso--the ancestral karyotype of the cahirinus-dimidiatus group?

    Science.gov (United States)

    Volobouev, V; Gautun, J C; Sicard, B; Tranier, M

    1996-11-01

    We present here data on chromosome banding analysis (R- and C-bands) of Acomys sp. (Rodentia, Muridae) from Oursi, Burkina Faso, characterized by 2n = FN = 68 and comparison of its banding patterns with those of Acomys dimidiatus from Saudi Arabia (2n = 38, FN = 70), studied previously. The study revealed complete homology between acrocentric chromosomes of Acomys sp. and chromosome arms of 16 pairs of metacentric and two pairs of acrocentric chromosomes of A. dimidiatus. In addition to monobrachial homology, one tandem translocation accompanied by a centromeric shift was identified in the karyotype of the latter species. The data obtained show that karyotypes of all the species of the Acomys cahirinus-dimidiatus group studied previously may be derived from that of Acomys sp. from Oursl by means of numerous non-homologous Rb translocations and 1-2 tandem transiocations, and thus its karyotype may be considered as ancestral for the cahirinus-dimidiatus group.

  12. [BPO-Specific, complement-dependant cell-lysis of differently sensitized sheep red cells: evaluation of haptenic groups and their influence on IgM and IgG-induced lysis (author's transl)].

    Science.gov (United States)

    Wiedermann, G; Stemberger, H; Förster, O; Müller, M

    1976-04-01

    Sheep erythrocytes were coated with bencylpenicilloyl-(BPO)groups. Different incubation periods resulted in erythrocyte preparations with different hapten density. Complement dependent lysis induced by IgM or IgG antibodies was studied with the cell preparations. The calculation of hapten density on the erythrocyte surface was not possible by direct measurement of coupled radioactive BPO since more than 90% of radioactive material was found in the soluble supernatant after osmotic cell lysis and less than 10% was fixed to the cellular membrane. Measurement of membrane bound immunologically relevant BPO-groups was achieved, therefore, by comparison of the inhibitory capacity of the test cells with that of a standard cell preparation. The latter consisted of tannic acid treated erythrocytes coated with protein complexed radioactive BPO. Surface hapten density of the different target cell preparations varied between 1.9 x 10(5) and 4.8 10(5) BPO-groups per cell depending on the time of incubation. Complement dependent antibody mediated cell lysis was significantly reduced by reduction of haptenic sites per target cell, IgG induced lysis being much more affected than hemolysis induced by IgM antibodies. Statistical calculations led to the conclusion that 18,000 protein islets per cell bearing 4 or more BPO-groups are not sufficient for hemolysis induced by IgG antibodies. 48,000 protein islets with this hapten density are necessary for "optimal" sensitization. IgG antibodies must be apparently bound to the cell surface in bivalent form.

  13. Finite Complements in English

    Institute of Scientific and Technical Information of China (English)

    Ronald W. Langacker

    2008-01-01

    This paper explores the conceptual basis of finite complimentation in English.It first considem the distinguishing property of a finite clause,namely grounding,effeeted by tense and the modals.Notions crucial for clausal grounding--including a reality conception and the striving for control at the effective and epistemic levelsalso figure in the semantic import of eomplementation.An essential feature of complement constructions is the involvement of multiple conceptualizers,each with their own conception of reality.The different types of complement and their grammatical markings can be characterized on this basis.Finite complements differ from other types by virtue of expressing an autonomous proposition capable of being apprehended by multiple conceptualizers,each from their own vantage point.Acognitive model representing phases in the striving for epistemic control provides a partial basis for the semantic description of predicates taking finite complements.The same model supports the description of both personal and impersonal complement constructions.

  14. Purification and characterization of a proteinase from pineapple fruit, fruit bromelain FA2.

    Science.gov (United States)

    Yamada, F; Takahashi, N; Murachi, T

    1976-06-01

    Fruit bromelain FA2, the main proteinase component of the juice of pineapple fruit, has been purified and characterized. 1. Efficient extraction of this enzyme from the crude material was possible using "Cellulosin AP," a microbial polysaccharidase preparation containing cellulase, hemicellulase, and pectinase. The enzyme was purified mainly by successive applications of anion-exchange chromatography, yielding an apparently homogeneous protein as judged by several physical, chemical, and immunochemical criteria. Properties of FA2 include: molecular weight, 31,000; isoelectric point, pH 4.6; absorbance at 280 nm of a 1% solution at pH 7.0 per cm, 19.2. 2. FA2 gave only alanine phenylthiohydantoin upon amino-terminal group analysis by the Edman procedure. Stepwise degradation yielded the amino-terminal sequence Ala-Val-Pro-Gln-Ser-Ile-Asp-Trp-Arg-Asp-Tyr-Gly-Ala. The amino acid composition of FA2 was not markedly different from that of stem bromelain, except for a much smaller lysine content and a smaller alanine content relative to glycine in FA2. FA2 contained neither amino sugars nor neutral carbohydrates as determined by several methods, so FA2 is not a glycoprotein. 3. By labeling the reactive cysteine residue (CYS) with [14C]iodoacetate, the following partial amino acid sequence has been determined. Asn-Glx-Asn-Pro-Cys-Gly-Ala-CYS.

  15. Approach for dynamic group automatic aggregation path planning based on improved FA%基于改进萤火虫算法的动态自动聚集路径规划方法

    Institute of Scientific and Technical Information of China (English)

    刘鹏; 刘弘; 郑向伟; 丁艳辉

    2011-01-01

    针对群体动画中自动聚集场景的特点及现有方法中存在的计算代价高、行为单一、逼真程度不够、缺乏涌现特征的不足,提出了基于改进萤火虫算法的群体动态自动聚集路径规划方法.在群体自动聚集过程中,不但无须提前指定聚集目标点,而且根据外界环境的动态变化,自动寻找最优的聚集目标点.通过该方法可以为每个粒子生成运动路径,并能保证每次生成的聚集路径不完全一致,使制作的群体动画体现出群体运动的涌现特征,有效地提高群体动画的逼真效果.通过所开发的动态自动聚集路径规划系统有效地模拟群体聚集行为,验证了本方法的可行性和有效性.%Aiming at the features of automatic aggregation scene in group animation and the existing methods in the presence of high computational cost, the lack of diversity in a single act, realistic level, lack of emergence of features, this paper proposed an approach for path-planning of crowd dynamic automatic aggregation based on improved firefly algorithms. In the process of achieving the automatic aggregation of crowd, it was not only unnecessary to designate the target point of aggregation , but also could according to the dynamic changes in the external environment, the optimal target point of aggregation could be found automatically . The motion path of each particle could be generated in this approach, which could guarantee that each generated path was not exactly the same so that the produced group animation could fully reflect the features of crowd movement in reality and improve the lifelike effects of group animation effectively. Developed a system for path planning of dynamic automatic aggregation, and the experiments in the system show that the proposed approach can achieve the effects of dynamic automatic aggregation and simulate the group behavior effectively, demonstrating the feasibility and effectiveness of this method.

  16. Opuntia ficus indica (nopal) attenuates hepatic steatosis and oxidative stress in obese Zucker (fa/fa) rats.

    Science.gov (United States)

    Morán-Ramos, Sofía; Avila-Nava, Azalia; Tovar, Armando R; Pedraza-Chaverri, José; López-Romero, Patricia; Torres, Nimbe

    2012-11-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as obesity, insulin resistance, and oxidative stress. Nopal, a cactus plant widely consumed in the Mexican diet, is considered a functional food because of its antioxidant activity and ability to improve biomarkers of metabolic syndrome. The aim of this study was to assess the effect of nopal consumption on the development of hepatic steatosis and hepatic oxidative stress and on the regulation of genes involved in hepatic lipid metabolism. Obese Zucker (fa/fa) rats were fed a control diet or a diet containing 4% nopal for 7 wk. Rats fed the nopal-containing diet had ∼50% lower hepatic TG than the control group as well as a reduction in hepatomegaly and biomarkers of hepatocyte injury such as alanine and aspartate aminotransferases. Attenuation of hepatic steatosis by nopal consumption was accompanied by a higher serum concentration of adiponectin and a greater abundance of mRNA for genes involved in lipid oxidation and lipid export and production of carnitine palmitoyltransferase-1 and microsomal TG transfer proteins in liver. Hepatic reactive oxygen species and lipid peroxidation biomarkers were significantly lower in rats fed nopal compared with the control rats. Furthermore, rats fed the nopal diet had a lower postprandial serum insulin concentration and a greater liver phosphorylated protein kinase B (pAKT):AKT ratio in the postprandial state. This study suggests that nopal consumption attenuates hepatic steatosis by increasing fatty acid oxidation and VLDL synthesis, decreasing oxidative stress, and improving liver insulin signaling in obese Zucker (fa/fa) rats.

  17. Laboratory tests for disorders of complement and complement regulatory proteins.

    Science.gov (United States)

    Shih, Angela R; Murali, Mandakolathur R

    2015-12-01

    The complement pathway is a cascade of proteases that is involved in immune surveillance and innate immunity, as well as adaptive immunity. Dysfunction of the complement cascade may be mediated by aberrations in the pathways of activation, complement regulatory proteins, or complement deficiencies, and has been linked to a number of hematologic disorders, including paroxysmal noctural hemoglobinuria (PNH), hereditary angioedema (HAE), and atypical hemolytic-uremic syndrome (aHUS). Here, current laboratory tests for disorders of the complement pathway are reviewed, and their utility and limitations in hematologic disorders and systemic diseases are discussed. Current therapeutic advances targeting the complement pathway in treatment of complement-mediated hematologic disorders are also reviewed.

  18. The Production of Complement Clauses in Children with Language Impairment

    Science.gov (United States)

    Steel, Gillian; Rose, Miranda; Eadie, Patricia

    2016-01-01

    Purpose: The purpose of this research was to provide a comprehensive description of complement-clause production in children with language impairment. Complement clauses were examined with respect to types of complement structure produced, verb use, and both semantic and syntactic accuracy. Method: A group of 17 children with language impairment…

  19. The Production of Complement Clauses in Children with Language Impairment

    Science.gov (United States)

    Steel, Gillian; Rose, Miranda; Eadie, Patricia

    2016-01-01

    Purpose: The purpose of this research was to provide a comprehensive description of complement-clause production in children with language impairment. Complement clauses were examined with respect to types of complement structure produced, verb use, and both semantic and syntactic accuracy. Method: A group of 17 children with language impairment…

  20. 21 CFR 866.5260 - Complement C3b inactivator immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement C3b inactivator immunological test... Systems § 866.5260 Complement C3b inactivator immunological test system. (a) Identification. A complement... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group...

  1. A BPMN-based process map for the design and construction of façades

    Directory of Open Access Journals (Sweden)

    Eleanor Voss

    2013-12-01

    Full Text Available Corresponding author: Eleanor Voss, Glass and Façade Technology Research Group, Department of Engineering, University of Cambridge, Trumpington Street, Cambridge, UK. E-mail: ev236@cam.ac.uk Process mapping can lead to significant efficiency and quality improvements in construction engineering and is an ideal basis for developing IT support tools. The increasing complexity and multidisciplinary nature of façade design and construction suggest that a process map would be beneficial in this sector of the construction industry, but it has received limited attention to date. This paper presents a verified process map of the façade design and construction process. The map is the first of its kind to represent, in detail, the whole process relevant to all façade types, from commencement of the façade consultant's and contactor's participation, to the end of their involvement. The paper describes the process by which the mapping notation was selected, followed by the development and verification of the process map, including testing in two independent research projects. The BuildingSMART's BPMN notation is found to have superior system features and comprehensibility for this application and the resulting process map is easy to interpret and verify by industry experts. The trialling of the map in the two research projects indicate that the map is a useful tool for assessing process improvements in the façades sector.

  2. Role of excess glycogenolysis in fasting hyperglycemia among pre-diabetic and diabetic Zucker (fa/fa) rats.

    Science.gov (United States)

    Jin, Eunsook S; Park, Byung-Hyun; Sherry, A Dean; Malloy, Craig R

    2007-03-01

    Sources of plasma glucose and glucose turnover were investigated in 8-week-old (pre-diabetic) and 13-week-old (diabetic) Zucker (fa/fa) rats after a 24-h fast. Intraperitoneal (2)H(2)O was administered and [3,4-(13)C(2)]glucose and [U-(13)C(3)]propionate were infused into conscious active rats. (13)C nuclear magnetic resonance analysis of monoacetone glucose derived from blood glucose indicated that glucose production was increased significantly in 8- and 13-week-old fa/fa rats compared with age-matched Zucker (+/+) rats, and hepatic glycogen was dramatically higher among fa/fa animals regardless of age. Glycogenolysis, essentially 0 in +/+ rats after a 24-h fast, was significant in fa/fa rats (11 +/- 6 and 17 +/- 7% of glucose production in 8- and 13-week-old rats, respectively), even after a 24-h fast. Tricarboxylic acid (TCA) cycle flux and efflux of carbon skeletons from the cycle (cataplerosis) were both significantly higher in fa/fa rats compared with controls, but net gluconeogenesis from the TCA cycle was not higher because products leaving the cycle were returned to the cycle via a pyruvate cycling pathway. Thus, pyruvate cycling flux increased in proportion to TCA cycle flux, leaving net gluconeogenesis unchanged in fa/fa animals compared with control animals. The distribution of (2)H in skeletal muscle glycogen suggested that at least a fraction of glucose molecules entering glycogen pass through phosphomannose isomerase.

  3. Excessive food intake, obesity and inflammation process in Zucker fa/fa rat pancreatic islets.

    Directory of Open Access Journals (Sweden)

    Myriam Chentouf

    Full Text Available Inappropriate food intake-related obesity and more importantly, visceral adiposity, are major risk factors for the onset of type 2 diabetes. Evidence is emerging that nutriment-induced β-cell dysfunction could be related to indirect induction of a state of low grade inflammation. Our aim was to study whether hyperphagia associated obesity could promote an inflammatory response in pancreatic islets leading to ß-cell dysfunction. In the hyperphagic obese insulin resistant male Zucker rat, we measured the level of circulating pro-inflammatory cytokines and estimated their production as well as the expression of their receptors in pancreatic tissue and β-cells. Our main findings concern intra-islet pro-inflammatory cytokines from fa/fa rats: IL-1β, IL-6 and TNFα expressions were increased; IL-1R1 was also over-expressed with a cellular redistribution also observed for IL-6R. To get insight into the mechanisms involved in phenotypic alterations, abArrays were used to determine the expression profile of proteins implicated in different membrane receptors signaling, apoptosis and cell cycle pathways. Despite JNK overexpression, cell viability was unaffected probably because of decreases in cleaved caspase3 as well as in SMAC/DIABLO and APP, involved in the induction and amplification of apoptosis. Concerning β-cell proliferation, decreases in important cell cycle regulators (Cyclin D1, p35 and increased expression of SMAD4 probably contribute to counteract and restrain hyperplasia in fa/fa rat islets. Finally and probably as a result of IL-1β and IL-1R1 increased expressions with sub-cellular redistribution of the receptor, islets from fa/fa rats were found more sensitive to both stimulating and inhibitory concentrations of the cytokine; this confers some physiopathological relevance to a possible autocrine regulation of β-cell function by IL-1β. These results support the hypothesis that pancreatic islets from prediabetic fa/fa rats undergo an

  4. Excessive food intake, obesity and inflammation process in Zucker fa/fa rat pancreatic islets.

    Science.gov (United States)

    Chentouf, Myriam; Dubois, Gregor; Jahannaut, Céline; Castex, Françoise; Lajoix, Anne Dominique; Gross, René; Peraldi-Roux, Sylvie

    2011-01-01

    Inappropriate food intake-related obesity and more importantly, visceral adiposity, are major risk factors for the onset of type 2 diabetes. Evidence is emerging that nutriment-induced β-cell dysfunction could be related to indirect induction of a state of low grade inflammation. Our aim was to study whether hyperphagia associated obesity could promote an inflammatory response in pancreatic islets leading to ß-cell dysfunction. In the hyperphagic obese insulin resistant male Zucker rat, we measured the level of circulating pro-inflammatory cytokines and estimated their production as well as the expression of their receptors in pancreatic tissue and β-cells. Our main findings concern intra-islet pro-inflammatory cytokines from fa/fa rats: IL-1β, IL-6 and TNFα expressions were increased; IL-1R1 was also over-expressed with a cellular redistribution also observed for IL-6R. To get insight into the mechanisms involved in phenotypic alterations, abArrays were used to determine the expression profile of proteins implicated in different membrane receptors signaling, apoptosis and cell cycle pathways. Despite JNK overexpression, cell viability was unaffected probably because of decreases in cleaved caspase3 as well as in SMAC/DIABLO and APP, involved in the induction and amplification of apoptosis. Concerning β-cell proliferation, decreases in important cell cycle regulators (Cyclin D1, p35) and increased expression of SMAD4 probably contribute to counteract and restrain hyperplasia in fa/fa rat islets. Finally and probably as a result of IL-1β and IL-1R1 increased expressions with sub-cellular redistribution of the receptor, islets from fa/fa rats were found more sensitive to both stimulating and inhibitory concentrations of the cytokine; this confers some physiopathological relevance to a possible autocrine regulation of β-cell function by IL-1β. These results support the hypothesis that pancreatic islets from prediabetic fa/fa rats undergo an inflammatory

  5. Corynebacterium renale as a cause of reactions to the complement fixation test for Johne's disease

    NARCIS (Netherlands)

    Gilmour, N.J.L.; Goudswaard, J.

    Complement fixation (C.F.) tests and fluorescent antibody (F.A.) tests were carried out on sera from rabbits inoculated with Corynebacterium renale and Mycobacterium johnei, and on sera from cattle with C. renale pyelonephritis and with Johne's disease. Cross-reactions were a feature of the C.F.

  6. Material properties in complement activation

    DEFF Research Database (Denmark)

    Moghimi, S. Moein; Andersen, Alina Joukainen; Ahmadvand, Davoud

    2011-01-01

    -immune performance’ relationship studies in nanomedicine research at many fronts. The interaction between nanomaterials and the complement system is complex and regulated by inter-related factors that include nanoscale size, morphology and surface characteristics. Each of these parameters may affect complement...... activation differently and through different sensing molecules and initiation pathways. The importance of material properties in triggering complement is considered and mechanistic aspects discussed. Mechanistic understanding of complement events could provide rational approaches for improved material design...

  7. Microglia, Alzheimer's Disease, and Complement

    Directory of Open Access Journals (Sweden)

    Helen Crehan

    2012-01-01

    Full Text Available Microglia, the immune cell of the brain, are implicated in cascades leading to neuronal loss and cognitive decline in Alzheimer’s disease (AD. Recent genome-wide association studies have indicated a number of risk factors for the development of late-onset AD. Two of these risk factors are an altered immune response and polymorphisms in complement receptor 1. In view of these findings, we discuss how complement signalling in the AD brain and microglial responses in AD intersect. Dysregulation of the complement cascade, either by changes in receptor expression, enhanced activation of different complement pathways or imbalances between complement factor production and complement cascade inhibitors may all contribute to the involvement of complement in AD. Altered complement signalling may reduce the ability of microglia to phagocytose apoptotic cells and clear amyloid beta peptides, modulate the expression by microglia of complement components and receptors, promote complement factor production by plaque-associated cytokines derived from activated microglia and astrocytes, and disrupt complement inhibitor production. The evidence presented here indicates that microglia in AD are influenced by complement factors to adopt protective or harmful phenotypes and the challenge ahead lies in understanding how this can be manipulated to therapeutic advantage to treat late onset AD.

  8. Molecular and cellular analysis of the DNA repair defect in a patient in Xeroderma pigmentosum complementation group D who has the clinical features of Xeroderma pigmentosum and Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Broughton, B.C.; Thompson, A.F.; Harcourt, S.A.; Cole, J.; Arlett, C.F.; Lehmann, A.R. [Univ. of Sussex, Brighton (United Kingdom); Vermeulen, W.; Hoeijmakers, J.H.J. [Erasmus Univ., Rotterdam (United Kingdom); Botta, E.; Stefanini, M. [Istituto di Genetica, Pavia (Italy)] [and others

    1995-01-01

    Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are quite distinct genetic disorders that are associated with defects in excision repair of UV-induced DNA damage. A few patients have been described previously with the clinical features of both disorders. In this paper we describe an individual in this category who has unusual cellular responses to UV light. We show that his cultured fibroblasts and lymphocytes are extremely sensitive to irradiation with UV-C, despite a level of nucleotide excision repair that is 30%-40% that of normal cells. The deficiency is assigned to the XP-D complementation group, and we have identified two causative mutations in the XPD gene: a gly{yields}arg change at amino acid 675 in the allele inherited from the patient`s mother and a -1 frameshift at amino acid 669 in the allele inherited from his father. These mutations are in the C-terminal 20% of the 760-amino-acid XPD protein, in a region where we have recently identified several mutations in patients with trichothiodystrophy. 44 refs., 5 figs., 2 tabs.

  9. Zaznamek k fašistoidnim praksam in vzpostavljanju novega fašizma

    Directory of Open Access Journals (Sweden)

    Jernej Prodnik

    2013-03-01

    Full Text Available Avtor podaja teoretsko-analitičen premislek h konceptualizaciji fašizma, ki ga v zadnjem delu besedila aplicira na aktualne politično-ekonomske in politične razmere. Za razumevanje fašizma je treba tega izločiti iz zgodovinskega konteksta, čemur mora pri praktični analizi slediti vsakokratna in sočasna ponovna umestitev v aktualne zgodovinske procese v družbi. Avtor predlaga ločevanje med izgrajenim fašističnim redom in fašistoidnimi institucijami, procesi, praksami in diskurzi, ki nakazujejo diferenciacijo med makroravnjo in mikropraksami ter politikami na ravni vsakdanjega življenja. Primeren družbeni kontekst je namreč predpogoj za gradnjo celovitejšega reda, saj daje podlago za premestitev oziroma prenos teh praks na širšo družbeno raven (na primer v razširjen skupek fašistoidnih aparatov in institucij na nacionalni ali nadnacionalni ravni, ki potencialno omogočajo fašistični red. S tem je redefinirana trdna in ostra binarna opozicija med fašističnimi in nefašističnimi družbami, saj v različnih zgodovinskih trenutkih obstaja možnost gibanja od navidezno benignih fašistoidnih praks do protofašističnega konteksta in končno do celovito zgrajenega fašizma. Na ta način pa je mogoče fašizem opazovati in analizirati tudi kot gibanje in proces, ne le kot (zgrajeno strukturo. /// English title: A Note on Fascist Practices (and the Emergence of Neo-Fascism // Abstract in English: The author provides a theoretical analysis of the concept of fascism, which he then applies to the present political-economic and political circumstances. He proposes that to understand fascism it is important to separate it from the historical context, while it is at the same time of crucial importance to embed it into the current historical processes in the society. Only this kind of abstraction will enable us to consider fascism in a patently changed, but in many ways similar social context. Furthermore a differentiation is

  10. Oceanographic profile data collected from CTD and sound velocimeter - moving vessel profiler casts aboard FA2805, FA2806, FA2808 and NOAA Ship FAIRWEATHER as part of project OPR-P183-FA-15 in the Gulf of Alaska and North Pacific Ocean from 2015-05-16 to 2015-06-14 (NCEI Accession 0130665)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0130665 includes physical and profile data collected aboard the FA2805, FA2806, FA2808 and NOAA Ship FAIRWEATHER during project OPR-P183-FA-15 in the...

  11. Complement factor H related proteins (CFHRs).

    Science.gov (United States)

    Skerka, Christine; Chen, Qian; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T

    2013-12-15

    Factor H related proteins comprise a group of five plasma proteins: CFHR1, CFHR2, CFHR3, CFHR4 and CFHR5, and each member of this group binds to the central complement component C3b. Mutations, genetic deletions, duplications or rearrangements in the individual CFHR genes are associated with a number of diseases including atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathies (C3 glomerulonephritis (C3GN), dense deposit disease (DDD) and CFHR5 nephropathy), IgA nephropathy, age related macular degeneration (AMD) and systemic lupus erythematosus (SLE). Although complement regulatory functions were attributed to most of the members of the CFHR protein family, the precise role of each CFHR protein in complement activation and the exact contribution to disease pathology is still unclear. Recent publications show that CFHR proteins form homo- as well as heterodimers. Genetic abnormalities within the CFHR gene locus can result in hybrid proteins with affected dimerization or recognition domains which cause defective functions. Here we summarize the recent data about CFHR genes and proteins in order to better understand the role of CFHR proteins in complement activation and in complement associated diseases.

  12. Correlation analysis and prognostic impact of {sup 18}F-FDG PET and excision repair cross-complementation group 1 (ERCC-1) expression in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yong Hyu; Lee, Choong Kun; Jo, Kwan Hyeong; Hwang, Sang Hyun; Cha, Jong Tae; Lee, Jeong Won; Yun, Mi Jin; Cho, Arthur [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    The aim of this study was to determine the relationship between [{sup 18}]-2-fluoro-2-deoxy-D-glucose (FDG) uptake and excision repair cross-complementation group 1 (ERCC-1) expression and to evaluate the prognostic effect of these two factors in resectable non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed 212 patients with resectable NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) scan for cancer staging and ERCC-1 expression analysis between January 2008 to December 2011. All patients were then followed-up for survival analysis. Semiquantitative evaluation of ERCC-1 was performed with the H-scoring system and was correlated with maximum standardized uptake value (SUV{sub max}) of NSCLC. Univariate and multivariate analyses were performed to evaluate for FDG uptake and ERCC-1 expression predicting overall survival. In 212 patients (139 male, median age 68 ± 9.11), 112 patients had ERCC-positive tumors and 100 patients had ERCC-negative tumors. There was no significant difference in SUV{sub max} between ERCC-1-positive tumors (8.02 ±5.40) and ERCC-1-negative tumors (7.57 ± 6.56, p = 0.584). All patients were followed-up for a median of 40.5 months (95 % confidence interval [CI], 38.5–42.2 months). Univariate analysis and multivariate analysis for all patients showed that both ERCC-1 expression (hazard ratio [HR], 2.78; 95 % CI, 1.20–6.47) and FDG uptake (HR, 4.50; 95 % CI, 2.07–9.77) independently predicted overall survival. We have found no statistical correlation between FDG uptake and ERCC-1 expression in NSCLC. However, both higher FDG uptake and positive ERCC-1 expression are independent predictive markers of prognosis, suggesting that both should be obtained during patient workup.

  13. Predictive and Prognostic Value of Ribonucleotide Reductase Regulatory Subunit M1 and Excision Repair Cross-Complementation Group 1 in Advanced Urothelial Carcinoma (UC Treated with First-Line Gemcitabine Plus Platinum Combination Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Miso Kim

    Full Text Available Preclinical and clinical studies have suggested that expression of ribonucleotide reductase regulatory subunit M1 (RRM1 and excision repair cross-complementation group 1 (ERCC1 is associated with resistance to gemcitabine and cisplatin, respectively. We evaluated the significance of RRM1 and ERCC1 expression to predict tumor response to gemcitabine plus platinum chemotherapy (GP and survival in advanced UC. We retrospectively collected tumor samples and reviewed clinical data of 53 patients with unresectable or metastatic UC, who were treated with first-line GP. RRM1 and ERCC1 expression were measured by immunohistochemistry. Among 53 patients, 12 (22.6% and 26 (49.1% patients had tumors that demonstrated a high expression for RRM1 and ERCC1, respectively. Twenty-nine (70.7% of 41 patients with low RRM1 expression achieved a clinical response (complete + partial responses, but only 3 (25.0% of 12 patients with high RRM1 expression achieved a clinical response after GP (P=0.007. Nineteen (70.4% of 27 patients with low ERCC1 expression achieved a clinical response, while 13 (50.0% of 26 patients with high ERCC1 expression achieved a clinical response (P=0.130. High RRM1 expression was associated with shorter progression free survival and overall survival (PFS P=0.006, OS P=0.006. Multivariate analysis confirmed that patients with high RRM1 expression had a significantly greater risk of progression and death than those with low RRM1 expression. ERCC1 status was not a significant predictor for PFS and OS. RRM1 expression was predictive and prognostic of clinical outcome in advanced UC treated with gemcitabine plus platinum combination chemotherapy.

  14. Excision repair cross-complementation group 1 codon 118 polymorphism, micro ribonucleic acid and protein expression, clinical outcome of the advanced gastric cancer response to first-line FOLFOX-4 in Qinghai-Tibetan plateau population

    Directory of Open Access Journals (Sweden)

    Yu-Juan Qi

    2013-01-01

    Full Text Available Context: The excision repair cross-complementation group 1 (ERCC1 codon 118 C/T polymorphism has been associated with clinical outcome in cancer patients treated with platinum chemotherapy. Ethnic differences in the frequency of this polymorphism have been observed in Caucasian and African populations. Aim: The aim of this study was to evaluate the frequency and survival benefit of the ERCC1 codon 118 C/T polymorphism in a high-altitude population with advanced gastric cancer. Materials and Methods: Polymerase chain reaction-restriction fragment length polymorphism was used to determine the frequency of ERCC1 118 codon C/T polymorphism in 206 advanced gastric cancer patients residing in the high-altitude Qinghai-Tibetan plateau. The influence of the ERCC1 codon 118 C/T polymorphism on its micro ribonucleic acid (mRNA and protein expression, clinicopathological features; response to the platinum-based combination chemotherapy, and the outcome was evaluated. Statistical Analysis: The Kaplan-Meier method was used for survival analysis. The correlation of ERCC1 codon 118 polymorphism with ERCC1 mRNA and protein expression, clinicopathological characteristics, and first-line oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX-4 response was determined by χ2 -test. Results and Conclusions: ERCC1 codon 118 C/T polymorphism was not associated with ERCC1 mRNA and protein expression, FOLFOX-4 response, and progression-free survival (PFS or overall survival (OS. High ERCC1 mRNA and protein expression levels were associated with significantly lower FOLFOX-4 responses, PFS, and OS. ERCC1 codon 118 C/T polymorphism is not an important prognostic marker for advanced gastric cancer. Determination of ERCC1 mRNA and protein levels may be beneficial in predicting the response and outcome of FOLFOX-4 therapy in gastric cancer.

  15. Complement-mediated opsonization of invasive group A Streptococcus pyogenes strain AP53 is regulated by the bacterial two-component cluster of virulence responder/sensor (CovRS) system.

    Science.gov (United States)

    Agrahari, Garima; Liang, Zhong; Mayfield, Jeffrey A; Balsara, Rashna D; Ploplis, Victoria A; Castellino, Francis J

    2013-09-20

    Group A Streptococcus pyogenes (GAS) strain AP53 is a primary isolate from a patient with necrotizing fasciitis. These AP53 cells contain an inactivating mutation in the sensor component of the cluster of virulence (cov) responder (R)/sensor (S) two-component gene regulatory system (covRS), which enhances the virulence of the primary strain, AP53/covR(+)S(-). However, specific mechanisms by which the covRS system regulates the survival of GAS in humans are incomplete. Here, we show a key role for covRS in the regulation of opsonophagocytosis of AP53 by human neutrophils. AP53/covR(+)S(-) cells displayed potent binding of host complement inhibitors of C3 convertase, viz. Factor H (FH) and C4-binding protein (C4BP), which concomitantly led to minimal C3b deposition on AP53 cells, further showing that these plasma protein inhibitors are active on GAS cells. This resulted in weak killing of the bacteria by human neutrophils and a corresponding high death rate of mice after injection of these cells. After targeted allelic alteration of covS(-) to wild-type covS (covS(+)), a dramatic loss of FH and C4BP binding to the AP53/covR(+)S(+) cells was observed. This resulted in elevated C3b deposition on AP53/covR(+)S(+) cells, a high level of opsonophagocytosis by human neutrophils, and a very low death rate of mice infected with AP53/covR(+)S(+). We show that covRS is a critical transcriptional regulator of genes directing AP53 killing by neutrophils and regulates the levels of the receptors for FH and C4BP, which we identify as the products of the fba and enn genes, respectively.

  16. Missionaries and Tonic Sol-fa Music Pedagogy in 19th-Century China

    Science.gov (United States)

    Southcott, Jane E.; Lee, Angela Hao-Chun

    2008-01-01

    In the 19th century, Christian missionaries in China, as elsewhere, used the Tonic Sol-fa method of music instruction to aid their evangelizing. This system was designed to improve congregational singing in churches, Sunday schools and missions. The London Missionary Society and other evangelical groups employed the method. These missionaries took…

  17. Complement system in lung disease.

    Science.gov (United States)

    Pandya, Pankita H; Wilkes, David S

    2014-10-01

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

  18. International Façades - CROFT. Climate Related Optimized Façade Technologies

    Directory of Open Access Journals (Sweden)

    Marcel Bilow

    2012-04-01

    Full Text Available Looking at Central European building projects illustrates an awareness of sustainability and the need to save energy. This trend is based on the finiteness of natural resources, and is thus wise to follow. Developments in this region including passive house technologies, and energy plus solutions that create more energy than they use have become realisable. But it is not increasing technological knowledge alone that supported these developments; the Central European climate makes it possible to invent technological solutions that allow for maximum comfort while maintaining low energy consumption.Other regions have experienced a building boom over the past decades that has dramatically increased city sizes. A detailed examination of such building projects illustrates that most of them strive for the international standard with a high glazing ratio in the style of the Central European examples. But how can architecture be transferred to regions with entirely different climate conditions? The answer lies in the technological possibilities we have at our disposal today. The main research question of this thesis refers to utilising the local climate. Which methods are necessary to plan a building - and a façade as the interface between the inside and the outside, in particular - while working with, not against the climate? Sailing has been used as an analogy: only with the knowledge of winds and tides can we use them to efficiently move across bodies of water. Those who have not learned or understood this will have to use a motorboat and pay the price for petrol.Chapter 2 ‘Climate zones’ describes the different climate zones and their particularities, analysed with the help of eight different boomtowns. The mild Central European climate becomes particularly apparent when compared to tropic locations such as Singapore. Here, very high average temperatures and humidity levels require that we rethink and find new solutions.In chapter 3

  19. Complement receptor 2-mediated targeting of complement inhibitors to sites of complement activation.

    Science.gov (United States)

    Song, Hongbin; He, Chun; Knaak, Christian; Guthridge, Joel M; Holers, V Michael; Tomlinson, Stephen

    2003-06-01

    In a strategy to specifically target complement inhibitors to sites of complement activation and disease, recombinant fusion proteins consisting of a complement inhibitor linked to a C3 binding region of complement receptor (CR) 2 were prepared and characterized. Natural ligands for CR2 are C3 breakdown products deposited at sites of complement activation. Fusion proteins were prepared consisting of a human CR2 fragment linked to either the N terminus or C terminus of soluble forms of the membrane complement inhibitors decay accelerating factor (DAF) or CD59. The targeted complement inhibitors bound to C3-opsonized cells, and all were significantly more effective (up to 20-fold) than corresponding untargeted inhibitors at protecting target cells from complement. CR2 fusion proteins also inhibited CR3-dependent adhesion of U937 cells to C3 opsonized erythrocytes, indicating a second potential anti-inflammatory mechanism of CR2 fusion proteins, since CR3 is involved in endothelial adhesion and diapedesis of leukocytes at inflammatory sites. Finally, the in vivo validity of the targeting strategy was confirmed by the demonstration that CR2-DAF, but not soluble DAF, targets to the kidney in mouse models of lupus nephritis that are associated with renal complement deposition.

  20. Phosphoethanolamine residues on the lipid A moiety of Neisseria gonorrhoeae lipooligosaccharide modulate binding of complement inhibitors and resistance to complement killing.

    Science.gov (United States)

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

    2013-01-01

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

  1. Complement evasion by Staphylococcus aureus

    NARCIS (Netherlands)

    Jongerius, I.

    2010-01-01

    The complement system is the first line of defense against invading microorganisms. Activation of the complement system results in the coverage of bacteria with C3b, resulting in phagocytosis, and formation of C5a which is important for chemotaxis of neutrophils towards the site of infection. Staphy

  2. Evolution of the complement system.

    Science.gov (United States)

    Nonaka, Masaru

    2014-01-01

    The mammalian complement system constitutes a highly sophisticated body defense machinery comprising more than 30 components. Research into the evolutionary origin of the complement system has identified a primitive version composed of the central component C3 and two activation proteases Bf and MASP in cnidaria. This suggests that the complement system was established in the common ancestor of eumetazoa more than 500 million years ago. The original activation mechanism of the original complement system is believed to be close to the mammalian lectin and alternative activation pathways, and its main role seems to be opsonization and induction of inflammation. This primitive complement system has been retained by most deuterostomes without major change until the appearance of jawed vertebrates. At this stage, duplication of the C3, Bf and MASP genes as well as recruitment of membrane attack components added the classical and lytic pathways to the primitive complement system, converting it to the modern complement system. In contrast, the complement system was lost multiple times independently in the protostome lineage.

  3. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses....

  4. The prognostic and predictive value of excision repair cross-complementation group 1 (ERCC1) protein in 1288 patients with head and neck squamous cell carcinoma treated with platinum-based therapy: a meta-analysis.

    Science.gov (United States)

    Bišof, Vesna; Zajc Petranović, Matea; Rakušić, Zoran; Samardžić, Kristina Ruža; Juretić, Antonio

    2016-09-01

    Excision repair cross-complementation group 1 (ERCC1) protein has been extensively investigated as a prognostic and predictive factor for platinum-based treatment in head and neck squamous cell carcinoma (HNSCC) but with inconsistent results. We performed the present meta-analysis to better elucidate this issue in advanced HNSCC. A literature search was conducted using the PubMed and Web of Science databases. The inclusion criteria were head and neck cancer patients with platinum-based treatment and evaluation of the correlation between ERCC1 expression and clinical outcomes [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), both unadjusted and adjusted estimates]. In high vs. low pooled analyses, high ERCC1 expression was associated with unfavorable OS [hazard ratio (HR) = 1.95, 95 % confidence interval (CI) 1.18-3.21, p = 0.009], PFS (HR = 2.39, 95 % CI 1.74-3.28, p = 0.000) and ORR (odds ratio = 0.48, 95 % CI 0.23-0.98, p = 0.044). In the subgroup analysis of adjusted OS estimates, ERCC1 was a predictor of shorter survival in Asians (HR = 3.13, 95 % CI 2.09-4.70, p = 0.000) and Caucasians (HR = 2.02, 95 % CI 1.32-3.07, p = 0.001) but of longer survival in South Americans (HR = 0.17, 95 % CI 0.07-0.40, p = 0.000). Immunohistochemistry proved to be of predictive value irrespective of used antibody (p = 0.009). In the stratified analysis according to the tumor site, ERCC1 expression was associated with OS in nasopharyngeal cancer (HR = 2.72, 95 % CI 1.79-4.13, p = 0.000). ERCC1 has a potential to become predictive and prognostic factor enabling treatment tailoring in HNSCC patients.

  5. Mass spectrometry of the lithium adducts of diacylglycerols containing hydroxy FA in castor oil and two normal FA

    Science.gov (United States)

    Castor oil can be used in industry. The molecular species of triacylglycerols containing hydroxy fatty acids (FA) in castor oil have been identified. We report here the identification of twelve diacylglycerols (DAG) containing hydroxy FA in castor oil using positive ion electrospray ionization mass ...

  6. Complement in health and disease.

    Science.gov (United States)

    Carroll, Maria V; Sim, Robert B

    2011-09-16

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

  7. Complement Evasion by Pathogenic Leptospira.

    Science.gov (United States)

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

    2016-01-01

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

  8. Epigenetics and development of food allergy (FA) in early childhood.

    Science.gov (United States)

    Hong, Xiumei; Wang, Xiaobin

    2014-09-01

    This review aims to highlight the latest advance on epigenetics in the development of food allergy (FA) and to offer future perspectives. FA, a condition caused by an immunoglobulin (Ig) E-mediated hypersensitivity reaction to food, has emerged as a major clinical and public health problem worldwide in light of its increasing prevalence, potential fatality, and significant medical and economic impact. Current evidence supports that epigenetic mechanisms are involved in immune regulation and that the epigenome may represent a key "missing piece" of the etiological puzzle for FA. There are a growing number of population-based epigenetic studies on allergy-related phenotypes, mostly focused on DNA methylation. Previous studies mostly applied candidate-gene approaches and have demonstrated that epigenetic marks are associated with multiple allergic diseases and/or with early-life exposures relevant to allergy development (such as early-life smoking exposure, air pollution, farming environment, and dietary fat). Rapid technological advancements have made unbiased genome-wide DNA methylation studies highly feasible, although there are substantial challenge in study design, data analyses, and interpretation of findings. In conclusion, epigenetics represents both an important knowledge gap and a promising research area for FA. Due to the early onset of FA, epigenetic studies of FA in prospective birth cohorts have the potential to better understand gene-environment interactions and underlying biological mechanisms in FA during critical developmental windows (preconception, in utero, and early childhood) and may lead to new paradigms in the diagnosis, prevention, and management of FA and provide novel targets for future drug discovery and therapies for FA.

  9. Complement system in dermatological diseases – fire under the skin

    Directory of Open Access Journals (Sweden)

    Jaana Helena Panelius

    2015-01-01

    Full Text Available The complement system plays a key role in several dermatological diseases. Overactivation, deficiency or abnormality of the control proteins are often related to a skin disease. Autoimmune mechanisms with autoantibodies and a cytotoxic effect of the complement membrane attack complex (MAC on epidermal or vascular cells can cause direct tissue damage and inflammation e.g. in SLE, phospholipid antibody syndrome and bullous skin diseases like pemphigoid. By evading complement attack, some microbes like borrelia spirochetes and staphylococci can persist in the skin and cause prolonged symptoms. In this review we present the most important skin diseases connected to abnormalities in the function of the complement system. Drugs having an effect on the complement system are also briefly described. On one hand, drugs with free hydroxyl on amino groups (e.g. hydralazine, procainamide could interact with C4A, C4B or C3 and cause an SLE-like disease. On the other hand, progress in studies on complement has led to novel anti-complement drugs (recombinant C1 inhibitor and anti-C5 antibody, eculizumab that could alleviate symptoms in diseases associated with excessive complement activation.The main theme of the manuscript is to show how relevant the complement system is as an immune effector system in contributing to tissue injury and inflammation in a broad range of skin disorders.

  10. Heat differentiated complement factor profiling.

    Science.gov (United States)

    Hamsten, Carl; Skattum, Lillemor; Truedsson, Lennart; von Döbeln, Ulrika; Uhlén, Mathias; Schwenk, Jochen M; Hammarström, Lennart; Nilsson, Peter; Neiman, Maja

    2015-08-03

    Complement components and their cascade of reactions are important defense mechanisms within both innate and adaptive immunity. Many complement deficient patients still remain undiagnosed because of a lack of high throughput screening tools. Aiming towards neonatal proteome screening for immunodeficiencies, we used a multiplex profiling approach with antibody bead arrays to measure 9 complement proteins in serum and dried blood spots. Several complement components have been described as heat sensitive, thus their heat-dependent detectability was investigated. Using sera from 16 patients with complement deficiencies and 23 controls, we confirmed that the proteins C1q, C2, C3, C6, C9 and factor H were positively affected by heating, thus the identification of deficient patients was improved when preheating samples. Measurements of C7, C8 and factor I were negatively affected by heating and non-heated samples should be used in analysis of these components. In addition, a proof of concept study demonstrated the feasibility of labeling eluates from dried blood spots to perform a subsequent correct classification of C2-deficiencies. Our study demonstrates the potential of using multiplexed single binder assays for screening of complement components that open possibilities to expand such analysis to other forms of deficiencies.

  11. Framework for benchmarking FA-based string recognizers

    CSIR Research Space (South Africa)

    Ngassam, EK

    2010-10-01

    Full Text Available Previous work on implementations of FA-based string recognizers suggested a range of implementation strategies (and therefore, algorithms) aiming at improving their performance for fast string recognition. However, an efficient exploitation...

  12. Complement sentences - complementizers of causative-manipulative verbs

    Directory of Open Access Journals (Sweden)

    Alanović Milivoj B.

    2015-01-01

    Full Text Available This paper presents the key structural and semantic features of the complement sentences that have the primary function of direct or indirect objects of one type of causative verbs - causative-manipulative verbs. Since the syntactic literature frequently discusses the structural characteristics of the complement sentences, the main objective of this article is focused on the semantic diversity of this type of sentences. The goal of the article is to determine the dependence of the realized meaning of a sentence on the semantic type of the main verb. Although the conjunction da is a typical subordinator of these sentences, a series of communicative verbs allows the use of complement sentences with interrogative adverbs and pronouns in the function of conjunctions. [Projekat Ministarstva nauke Republike Srbije, br.178004: Standardni srpski jezik - sintaksička, semantička i pragmatička istraživanja

  13. Physiological Effect of New FA Antitranspirant Application on Maize

    Institute of Scientific and Technical Information of China (English)

    LI Mao-song; LI Sen; ZHANG Shu-yi; CHI Bao-liang

    2003-01-01

    The field trial was conducted to study physiological effect of new FA antitranspirant on maize.The new FA antitranspirant was sprayed at 10 d pre-tasseling, ear filling stage and 10 d pre-tasseling + earfilling stage, with the concentrations of 0, 0.5, 1.0, 1.5 and 2.0 ml L-1. The results indicated that the appli-cation of new FA antitranspirant increased nitrate reductase activity (NRA), free proline content, chlorophyllcontent and water content of leaf, thus drought stress can be mitigated. The new FA antitranspirant increasedphotosynthesis rate and reduced transpiration rate, stimulated growth and reduced water loss. 10 d pre-tassel-ing + ear filling stage application had a cumulative effect on the indices compared with 10 d pre-tasseling andear filling stage, except for NRA. The new FA antitranspirant caused an increase of grain yield by 5.37 to29.58 % with different treatments. The optimal concentration is 1.5 ml L-1 , i.e. 75 g new FA antitranspirantdissolved in 50 kg water, and the optimal apply period is 10 d pre-tasseling ± ear filling stage.

  14. The Role of Complement in Antibody Therapy for Infectious Diseases.

    Science.gov (United States)

    Wibroe, Peter P; Helvig, Shen Y; Moein Moghimi, S

    2014-04-01

    The complement system is part of the innate immune system, eliciting central immunoregulatory functions. Detection of foreign surfaces is either achieved through complement-specific patternrecognition molecules or mediated by antigen recognition of antibodies. Immunoglobulin A (IgA), IgG, and IgM all have the potential to initiate a complement response, with the efficiency and response development closely related to the antibody isotype, multimeric state, and degree of glycosylation. A group of serum proteins constitutes the central effector functions of complement, thus allowing direct cell lysis, opsonization, and inflammation. These effector functions can be used in antibody therapies, especially against infectious diseases, as the target membranes lack complement regulatory proteins. The relative contribution of each function and the interplay with direct antibody-mediated clearance is not fully exploited, thus suggesting an option for further rational optimization of antibody therapies.

  15. Design of MiSolFA Hard X-Ray Imager

    Science.gov (United States)

    Lastufka, Erica; Casadei, Diego

    2017-08-01

    Advances in the study of coronal electron-accelerating regions have so far been limited by the dynamic range of X-ray instruments. A quick and economical alternative to desirable focusing optics technology is stereo observation. The micro-satellite MiSolFA (Micro Solar-Flare Apparatus) is designed both as a stand-alone X-ray imaging spectrometer and a complement to the Spectrometer/Telescope for Imaging X-rays (STIX) mission. These instruments will be the first pair of cross-calibrated X-ray imaging spectrometers to look at solar flares from very different points of view. MiSolFA will achieve indirect imaging between 10 and 60 keV and provide spectroscopy up to 100 keV, equipped with grids producing moiré patterns in a similar way to STIX. New manufacturing techniques produce gold gratings on a graphite or silicon substrate, with periods ranging from 15 to 225 micrometers, separated by a distance of 15.47 cm, to achieve a spatial resolutions from 10" to 60" (as compared to RHESSI's separation of 150 cm and 1" resolution). We present the progress of the imager design, the performance of the first prototypes, and reach out to the community for further scientific objectives to consider in optimizing the final design.

  16. Complementation analysis of ataxia-telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Jaspers, N.G.; Painter, R.B.; Paterson, M.C.; Kidson, C.; Inoue, T.

    1985-01-01

    In a number of laboratories genetic analysis of ataxia-telangiectasia (AT) has been performed by studying the expression of the AT phenotype in fused somatic cells or mixtures of cell-free extracts from different patients. Complementation of the defective response to ionizing radiation was observed frequently, considering four different parameters for radiosensitivity in AT. The combined results from studies on cultured fibroblasts or lymphoblastoid cells from 17 unrelated families revealed the presence of at least four and possibly nine complementation groups. These findings suggest that there is an extensive genetic heterogeneity in AT. More extensive studies are needed for an integration of these data and to provide a set of genetically characterized cell strains for future research of the AT genetic defect.

  17. Force Dynamics of Verb Complementation

    Directory of Open Access Journals (Sweden)

    Jacek Woźny

    2015-12-01

    Full Text Available Force Dynamics of Verb Complementation The concepts of motion and force are both extensively discussed in cognitive linguistics literature. But they are discussed separately. The first usually in the context of ‘motion situations’ (Talmy, Slobin, Zlatev, the other as part of the Force Dynamics framework, which was developed by Talmy. The aim of this paper is twofold: first, to argue that the concepts of force and motion should not be isolated but considered as two inseparable parts of force-motion events. The second goal is to prove that the modified Force Dynamics (force-motion framework can be used for precise characterization of the verb complementation patterns. To this end, a random sample of 50 sentences containing the verb ‘went’ is analyzed, demonstrating the differences between the categories of intensive and intransitive complementation with respect to the linguistically coded parameters of force and motion.

  18. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    of the B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context...... in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses....

  19. FaPYR1 is involved in strawberry fruit ripening.

    Science.gov (United States)

    Chai, Ye-Mao; Jia, Hai-Feng; Li, Chun-Li; Dong, Qing-Hua; Shen, Yuan-Yue

    2011-10-01

    Although the plant hormone abscisic acid (ABA) has been suggested to play a role in the ripening of non-climatic fruit, direct genetic/molecular evidence is lacking. In the present study, a strawberry gene homologous to the Arabidopsis ABA receptor gene PYR1, named FaPYR1, was isolated and characterized. The 627 bp cDNA includes an intact open reading frame that encodes a deduced protein of 208 amino acids, in which putative conserved domains were detected by homology analysis. Using tobacco rattle virus-induced gene silencing (VIGS), the FaPYR1 gene was silenced in strawberry fruit. Down-regulation of the FaPYR1 gene not only significantly delayed fruit ripening, but also markedly altered ABA content, ABA sensitivity, and a set of ABA-responsive gene transcripts, including ABI1 and SnRK2. Furthermore, the loss of red colouring in FaPYR1 RNAi (RNA interference) fruits could not be rescued by exogenously applied ABA, which could promote the ripening of wild-type fruits. Collectively, these results demonstrate that the putative ABA receptor FaPYR1 acts as a positive regulator in strawberry fruit ripening. It was also revealed that the application of the VIGS technique in strawberry fruit could be used as a novel tool for studying strawberry fruit development.

  20. Complement: Alive and Kicking Nanomedicines

    DEFF Research Database (Denmark)

    Andersen, Alina Joukainen; Hashemi, S.H.; Andresen, Thomas Lars;

    2009-01-01

    Administration of liposome- and polymer-based clinical nanomedicines, as well as many other proposed multifunctional nanoparticles, often triggers hypersensitivity reactions without the involvement of IgE. These anaphylactic reactions are believed to be secondary to activation of the complement s...

  1. Milk immunoglobulins and complement factors.

    Science.gov (United States)

    Korhonen, H; Marnila, P; Gill, H S

    2000-11-01

    The importance of colostrum for the growth and health of newborn offspring is well known. In bovine colostrum, the antibody (immunoglobulin) complement system provides a major antimicrobial effect against a wide range of microbes and confers passive immunity until the calf's own immune system has matured. Bovine serum and lacteal secretions contain three major classes of immunoglobulins: IgG, IgM and IgA. The immunoglobulins are selectively transported from the serum into the mammary gland, as a result of which the first colostrum contains very high concentrations of immunoglobulins (40-200 mg/ml). IgG1 accounts for over 75 % of the immunoglobulins in colostral whey, followed by IgM, IgA and IgG2. All these immunoglobulins decrease within a few days to a total immunoglobulin concentration of 0.7-1.0 mg/ml, with IgG1 representing the major Ig class in milk throughout the lactation period. Together with the antibodies absorbed from colostrum after birth, the complement system plays a crucial role in the passive immunisation of the newborn calf. The occurrence of haemolytic or bactericidal complement activity in bovine colostrum and milk has been demonstrated in several studies. This review deals with the characteristics of bovine Igs and the complement system to be exploited as potential ingredients for health-promoting functional foods.

  2. Role of complement in xenotransplantation.

    Science.gov (United States)

    Mollnes, Tom Eirik; Fiane, A E

    2002-01-01

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

  3. The lectin pathway of complement

    DEFF Research Database (Denmark)

    Ballegaard, Vibe Cecilie Diederich; Haugaard, Anna Karen; Garred, P

    2014-01-01

    The pattern recognition molecules of the lectin complement pathway are important components of the innate immune system with known functions in host-virus interactions. This paper summarizes current knowledge of how these intriguing molecules, including mannose-binding lectin (MBL), Ficolin-1, -2...

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

    Science.gov (United States)

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

    2008-07-02

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

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

    Directory of Open Access Journals (Sweden)

    Hendrik P N Scholl

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

  6. 捣法针刺治疗枕神经痛的临床疗效观察%CLINICAL OBSERVATION OF THERAPEUTIC EFFECT ON OCCIPITAL NEURALGIA TREATED WITH DAO FA IN ACUPUNCTURE MANIPULATION

    Institute of Scientific and Technical Information of China (English)

    冯军

    2008-01-01

    Objective To observe the clinical therapeutic effect of Dao Fa in acupuncture treatment of occipital neuralgia and make the comparison with routine acupuncture. Methods Dao Fa was applied to Tiānzhù (天柱BL10), Fēngchí (风池GB20) to treat occipital neuralgia and compare its results with routine acupuncture. Results The total effective rate was 95.6% in Dao Fa group, 77.8% in routine group, indicating significant difference (P<0.05). Conclusion Comparing with routine acupuncture, Dao Fa is advantageous at selection of fewer acupoints, better therapeutic effect and quicker achievement of efficacy in treatment of occipital neuralgia.

  7. 21 CFR 866.4100 - Complement reagent.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement reagent. 866.4100 Section 866.4100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... Complement reagent. (a) Identification. A complement reagent is a device that consists of complement,...

  8. Suppression of Human T Cell Proliferation Mediated by the Cathepsin B Inhibitor, z-FA-FMK Is Due to Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Tanuja Rajah

    Full Text Available The cathepsin B inhibitor, benzyloxycarbonyl-phenylalanine-alanine-fluoromethyl ketone (z-FA-FMK readily inhibits anti-CD3-induced human T cell proliferation, whereas the analogue benzyloxycarbonyl-phenylalanine-alanine-diazomethyl ketone (z-FA-DMK had no effect. In contrast, benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK was toxic. The inhibition of T cell proliferation mediated by z-FA-FMK requires not only the FMK moiety, but also the benzyloxycarbonyl group at the N-terminal, suggesting some degree of specificity in z-FA-FMK-induced inhibition of primary T cell proliferation. We showed that z-FA-FMK treatment leads to a decrease in intracellular glutathione (GSH with a concomitant increase in reactive oxygen species (ROS levels in activated T cells. The inhibition of anti-CD3-induced T cell proliferation mediated by z-FA-FMK was abolished by the presence of low molecular weight thiols such as GSH, N-acetylcysteine (NAC and L-cysteine, whereas D-cysteine which cannot be metabolised to GSH has no effect. The inhibition of anti-CD3-induced up-regulation of CD25 and CD69 expression mediated by z-FA-FMK was also attenuated in the presence of exogenous GSH. Similar to cell proliferation, GSH, NAC and L-cysteine but not D-cysteine, completely restored the processing of caspase-8 and caspase-3 to their respective subunits in z-FA-FMK-treated activated T cells. Our collective results demonstrated that the inhibition of T cell activation and proliferation mediated by z-FA-FMK is due to oxidative stress via the depletion of GSH.

  9. La faïence de Nevers (1585-1900

    Directory of Open Access Journals (Sweden)

    Jean Rosen

    2010-10-01

    Full Text Available Depuis 1585, et sans solution de continuité jusqu’à nos jours, Nevers, aussi bien par son importance historique que par le nombre de ses manufactures – douze en 1755, plus de trente ateliers en tout –, a joué un rôle de tout premier plan dans la propagation et l’évolution de la faïence française, du xvie au xxe siècle, et peut être considéré comme le centre idéal pour une recherche sur le long terme. Si la faïence de Nevers a déjà été abordée de multiples façons dans divers colloques et exp...

  10. 基于STATA的FA-DEA与PCA-DEA%Implementing FA-DEA and PCA-DEA in STATA

    Institute of Scientific and Technical Information of China (English)

    彭江平

    2015-01-01

    针对应用FA-DEA与PCA-DEA模型时,一般都需要同时使用统计分析软件与数据包络分析软件,提出了在STATA中的实现过程与方法,并进行了案例分析。方便了在实际应用过程中使用FA-DEA与PCA-DEA的过程,并为在统一STATA的环境下设计与应用新的数据包络法提供解决思路。%In general, the dimension reduction methods, such as FA and PCA, are implemented in statistical analysis software, but the data envelopment analysis is doing by DEA software. Simultaneously implementing FA-DEA and PCA-DEA all in STATA is puts forward, and an example is also listed. This approach will facilitate the process using FA-DEA and PCA-DEA in the practical application, and will provided a new solution in the STATA to design and application of data envelopment analysis.

  11. FaSa: A Fast and Stable Quadratic Placement Algorithm

    Institute of Scientific and Technical Information of China (English)

    HOU WenTing(侯文婷); HONG XianLong(洪先龙); WU WeiMin(吴为民); CAI YiCi(蔡懿慈)

    2003-01-01

    Placement is a critical step in VLSI design because it dominates overall speed andquality of design flow. In this paper, a new fast and stable placement algorithm called FaSa is pro-posed. It uses quadratic programming model and Lagrange multiplier method to solve placementproblems. And an incremental LU factorization method is used to solve equations for speeding up.The experimental results show that FaSa is very stable, much faster than previous algorithms andits total wire length is comparable with other algorithms.

  12. Complement evasion by Plasmodium falciparum

    OpenAIRE

    Holopainen, Saila

    2008-01-01

    Patologian oppiaine Malaria remains one of the major health problems in many tropical countries, especially in sub-Saharan Africa. Among the most characteristic features of the malaria pathogens, protozoan parasites of the genus Plasmodium, is their ability to evade the immune defences of the host for extended periods of time. The complement system (C) is an essential part of the innate system in the first line of defense. It consists of over 30 soluble or membrane-bound components. C...

  13. Complement Activation Alters Platelet Function

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet Function PRINCIPAL INVESTIGATOR: George Tsokos, M.D. CONTRACTING...Activation Alters Platelet Function 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0523 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) George Tsokos, M.D...a decreased level of disease. Further studies will expand upon these observations better outlining the function of platelets in the injury associated

  14. Formal characterizations of FA-based string processors

    CSIR Research Space (South Africa)

    Ngassam, EK

    2010-08-01

    Full Text Available With this poster, the authors on the denotational semantics of algorithms to suggest an abstraction of a string recognizer. The abstraction provides a unified formalism for representing FA-based string recognizers as an instance of a parameterized...

  15. "What D'ya Mean, Project SOL-FA?"

    Science.gov (United States)

    Hardman, Olga S.

    1981-01-01

    Since 1977, Project Sol-fa, funded with an ESEA Title IV-C grant has provided Harrison County primary teachers with inservice training in the Kodaly method of music education. This article provides information on program funding, costs, and accomplishments. Evaluation forms and the inservice syllabus are appended. (SJL)

  16. Role of complement in glomerular diseases.

    Science.gov (United States)

    Mao, Song; Zhang, Jianhua

    2016-01-01

    The complement system, composed of nearly 30 proteins, is a key regulator of immunity. The complement system is critical for protecting hosts from invading pathogens. Dysregulation of this system is associated with susceptibility to infection and various autoimmune diseases. Furthermore, complement activation due to the defective regulation of the alternative pathway will induce glomerular diseases. Anti-complement therapy has been applied in various glomerular diseases. Signaling pathways might be very important in the pathogenesis of glomerular diseases. This review will give a relatively complete signaling pathway flowchart for complement and a comprehensive understanding of the underlying role of complement in glomerular diseases.

  17. The complement system and adverse pregnancy outcomes.

    Science.gov (United States)

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

    2015-09-01

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

  18. Complement activation in experimental human malaria infection.

    NARCIS (Netherlands)

    Roestenberg, M.; McCall, M.B.B.; Mollnes, T.E.; Deuren, M. van; Sprong, T.; Klasen, I.S.; Hermsen, C.C.; Sauerwein, R.W.; Ven, A.J.A.M. van der

    2007-01-01

    The objective of this study was to investigate complement activation in uncomplicated, early phases of human malaria. Fifteen healthy volunteers were experimentally infected with Plasmodium falciparum malaria. Parasitemia and complement activation products were assessed. During blood stage parasitem

  19. Targeted delivery of Bcl-2 conversion gene by MPEG-PCL-PEI-FA cationic copolymer to combat therapeutic resistant cancer.

    Science.gov (United States)

    Li, Zibiao; Liu, Xuan; Chen, Xiaohong; Chua, Ming Xuan; Wu, Yun-Long

    2017-07-01

    Deregulation of anti-apoptosis Bcl-2 protein expression was a key feature in human cancers with therapeutic resistance. Nuclear receptor Nur77 could induce the conformation change of Bcl-2 protein and converted it into an apoptosis inducer by "enemy to friend" strategy. However, the safe and effective delivery of this gene to combat therapeutic resistant cancer remained largely unexplored. In this report, we designed an amphiphilic cationic MPEG-PCL-PEI-FA copolymer, comprising biocompatible and hydrophilic methoxy-poly(ethylene glycol) (MPEG), biodegradable and hydrophobic poly(ε-caprolactone) (PCL), cationic poly(ethylene imine) (PEI) segments, and folic acid (FA) as targeting group, as a high efficient Nur77 gene carrier to folate receptor (FR) highly expressed and therapeutic resistant HeLa/Bcl-2 cancer cells. Interestingly, due to the incorporation of PCL and PEG segments, this MPEG-PCL-PEI-FA copolymer showed less toxicity but better gene transfection efficiency than non-viral gene carrier gold standard PEI (25kDa). This might be due to the formation of micelles to stabilize polyplex for enhanced gene transfection ability. More importantly, MPEG-PCL-PEI-FA copolymer exhibited excellent growth inhibition ability on therapeutic resistant HeLa/Bcl-2 cancer cells, which was FR overexpressed HeLa cervical cancer cells with high expression of Bcl-2 protein, thanks to its FA induced targeting ability, high gene transfection efficiency, and low cytotoxicity. This work signifies the first time that cationic amphiphilic MPEG-PCL-PEI-FA copolymers could be utilized for the gene delivery to therapeutic resistant cancer cells with high expression of anti-apoptosis Bcl-2 protein and the positive results are encouraging for the further design of polymeric platforms for combating drug resistant tumors. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Complement in the Homeostatic and Ischemic Brain

    Science.gov (United States)

    Alawieh, Ali; Elvington, Andrew; Tomlinson, Stephen

    2015-01-01

    The complement system is a component of the immune system involved in both recognition and response to pathogens, and it is implicated in an increasing number of homeostatic and disease processes. It is well documented that reperfusion of ischemic tissue results in complement activation and an inflammatory response that causes post-reperfusion injury. This occurs following cerebral ischemia and reperfusion and triggers secondary damage that extends beyond the initial infarcted area, an outcome that has rationalized the use of complement inhibitors as candidate therapeutics after stroke. In the central nervous system, however, recent studies have revealed that complement also has essential roles in synaptic pruning, neurogenesis, and neuronal migration. In the context of recovery after stroke, these apparent divergent functions of complement may account for findings that the protective effect of complement inhibition in the acute phase after stroke is not always maintained in the subacute and chronic phases. The development of effective stroke therapies based on modulation of the complement system will require a detailed understanding of complement-dependent processes in both early neurodegenerative events and delayed neuro-reparatory processes. Here, we review the role of complement in normal brain physiology, the events initiating complement activation after cerebral ischemia-reperfusion injury, and the contribution of complement to both injury and recovery. We also discuss how the design of future experiments may better characterize the dual role of complement in recovery after ischemic stroke. PMID:26322048

  1. Mixed compared with single-source proteins in high-protein diets affect kidney structure and function differentially in obese fa/fa Zucker rats.

    Science.gov (United States)

    Devassy, Jessay G; Wojcik, Jennifer L; Ibrahim, Naser H M; Zahradka, Peter; Taylor, Carla G; Aukema, Harold M

    2017-02-01

    Questions remain regarding the potential negative effects of dietary high protein (HP) on kidney health, particularly in the context of obesity in which the risk for renal disease is already increased. To examine whether some of the variability in HP effects on kidney health may be due to source of protein, obese fa/fa Zucker rats were given HP (35% of energy from protein) diets containing either casein, soy protein, or a mixed source of animal and plant proteins for 12 weeks. Control lean and obese rats were given diets containing casein at normal protein (15% of energy from protein) levels. Body weight and blood pressure were measured, and markers of renal structural changes, damage, and function were assessed. Obesity alone resulted in mild renal changes, as evidenced by higher kidney weights, proteinuria, and glomerular volumes. In obese rats, increasing the protein level using the single, but not mixed, protein sources resulted in higher renal fibrosis compared with the lean rats. The mixed-protein HP group also had lower levels of serum monocyte chemoattractant protein-1, even though this diet further increased kidney and glomerular size. Soy and mixed-protein HP diets also resulted in a small number of damaged glomeruli, while soy compared with mixed-protein HP diet delayed the increase in blood pressure over time. Since obesity itself confers added risk of renal disease, an HP diet from mixed-protein sources that enables weight loss but has fewer risks to renal health may be advantageous.

  2. Plaque complement activation and cognitive loss in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Camp Dianne M

    2008-03-01

    Full Text Available Abstract Background Complement activation is increased in Alzheimer's disease (AD, but its significance is unclear. The objective of this study was to determine the relationship between complement activation and cognition during the development of AD. Methods iC3b, C9, Bielschowsky, and Gallyas staining was performed on aged normal (n = 17, mild cognitively impaired (n = 12, and AD (n = 17–18 inferior temporal gyrus specimens. Plaques were counted in 10× fields with high numbers of Bielschowsky-stained plaques. One-way ANOVA was used to determine between-group differences for plaque counts and measures of cognitive function, and linear regression was used to evaluate global cognition as a function of Bielschowsky-stained plaques. Terms for iC3b- and C9-stained plaques were then added sequentially as additional predictors in a "mediation analysis" model. Results Complement was detected on plaques in all groups, and on neurofibrillary tangles only in AD specimens. iC3b, C9, and Bielschowsky-stained plaque counts increased 2.5- to 3-fold in AD vs. other groups (all p ≤ 0.01. C9 staining was present on some diffuse plaques, as well as on neuritic plaques. Bielschowsky-stained and complement-stained plaque counts were highly correlated, and were negatively correlated with cognitive measures. When the Bielschowsky plaque count was used as a predictor, its correlations with cognitive measures were statistically significant, but when iC3b and C9 plaque counts were added as additional predictors, these correlations were no longer significant. This loss of significance was attributed to multicollinearity, i.e., high correlations between Bielschowsky-stained and complement-stained plaque counts. Conclusion Both early-stage (iC3b and late-stage (C9 complement activation occurs on neocortical plaques in subjects across the cognitive spectrum; contrary to previous reports, C9 is present on some diffuse plaques. Because of high correlations between

  3. Complement in Lupus Nephritis: New Perspectives

    Science.gov (United States)

    Bao, Lihua; Cunningham, Patrick N.; Quigg, Richard J.

    2015-01-01

    Background Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to self-antigens, the production of autoantibodies and deposition of complement-fixing immune complexes (ICs) in injured tissues. SLE is characterized by a wide range of clinical manifestations and targeted organs, with lupus nephritis being one of the most serious complications. The complement system consists of three pathways and is tightly controlled by a set of regulatory proteins to prevent injudicious complement activation on host tissue. The involvement of the complement system in the pathogenesis of SLE is well accepted; yet, its exact role is still not clear. Summary Complement plays dual roles in the pathogenesis of SLE. On the one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE. On the other hand, IC-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathological features that are logical consequences of complement activation. Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis, while treatment with recombinant protein inhibitors, such as Crry-Ig, CR2-Crry, CR2-DAF and CR2-CFH, ameliorates the disease development. Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor and a monoclonal anti-C5 antibody (eculizumab), have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. Key Messages SLE is an autoimmune disorder which targets multiple systems. Complement is centrally involved and plays dual roles in the pathogenesis of SLE. Studies from experimental lupus models and clinical

  4. Penerapan Perencanaan Pajak Penghasilan pada Fa Trico Paint Factory

    Directory of Open Access Journals (Sweden)

    Stefanus Ariyanto

    2011-05-01

    Full Text Available The most important parts of government income comes from taxes, especially income taxes. The different point of view arises between government and tax payer. While the government try to increase the tax income, the taxpayers always intend to minimize their tax burden by implementing tax management/plannning. This paper is a case study in FA Trico Paint Factory (FA TPF that try to reperforming company’s income tax return preparation with the main purpose to minimize company tax burden, while it is still comply with tax regulations in Indonesia. This approach could be an alternative for the company to restate it’s annual income tax return, to avoic fines and charges for not comply with the regulations, and minimize it’s income tax expense by approximately 10% per year. 

  5. Complement the hemostatic system: an intimate relationship.

    Science.gov (United States)

    Weitz, Ilene Ceil

    2014-05-01

    The complement system is important part of our innate immune system and interacts directly with the hemostatic system. Disorders of complement activation or dysregulation resulting in excess complement generation, such as Paroxysmal Nocturnal Hemoglobinuria (PNH), atypical Hemolytic uremic Syndrome (aHUS) and antiphospholipid syndrome (APLS) have been associated with significant thrombophilia. Terminal Complement (C5b-9) deposition on endothelial and tumor cell membranes has also been reported in a variety of cancer. Recent developments in complement inhibition have given us new insights into the mechanism of thrombosis in these disorders.

  6. The Complement System in Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Xuebin Qin; Bin Gao

    2006-01-01

    The complement system plays an important role in mediating both acquired and innate responses to defend against microbial infection, and in disposing immunoglobins and apoptotic cells. The liver (mainly hepatocytes) is responsible for biosynthesis of about 80-90% of plasma complement components and expresses a variety of complement receptors.Recent evidence from several studies suggests that the complement system is also involved in the pathogenesis of a variety of liver disorders including liver injury and repair, fibrosis, viral hepatitis, alcoholic liver disease, and liver ischemia/reperfusion injury. In this review, we will discuss the potential role of the complement system in the pathogenesis of liver diseases.

  7. Odenplan: a media façade design process

    DEFF Research Database (Denmark)

    Korsgaard, Henrik; Hansen, Nicolai Brodersen; Basballe, Ditte Amund;

    2012-01-01

    of how to design for media façades by discussing how we have structured our design process to address specific sets of challenges outlined in previous literature in the field of media architecture. In our view, such research is valuable in that it helps establish common ground for researchers...... and practitioners in a developing field by building a repertoire of approaches, as well as highlight important issues that need to be addressed in this emergent field....

  8. Optimizing Maintenance Manpower for USMC F/A-18 Squadrons

    Science.gov (United States)

    2016-06-01

    for Logistics Analysis and Technical Evaluation EMT Elapsed Maintenance Time F/A Fighter/Attack FAP Fleet Assistance Program FCF Functional Check... Occupational Specialty MVP Manpower Validation Planner NAVAIR Naval Air Systems Command NMC Non-Mission Capable NMCS Non-Mission Capable Supply O...the required rank and Military Occupational Specialty (MOS) for a squadron consisting of 23 officers and 167 enlisted Marines and a VMFA(AW) squadron

  9. Using Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) Complemented with Selected 16S rRNA and gyrB Genes Sequencing to Practically Identify Clinical Important Viridans Group Streptococci (VGS).

    Science.gov (United States)

    Zhou, Menglan; Yang, Qiwen; Kudinha, Timothy; Zhang, Li; Xiao, Meng; Kong, Fanrong; Zhao, Yupei; Xu, Ying-Chun

    2016-01-01

    There are challenges in viridans group streptococci (VGS) identification especially for the mitis group. Few studies have investigated the performance of MALDI-TOF MS system in VGS identification. Using 16S rRNA gene and gyrB gene sequencing as a gold standard, the performance of two MALDI-TOF MS instruments in the identification of 181 VGS clinical isolates was studied. The Bruker Biotyper and Vitek MS IVD systems correctly identified 88.4% and 98.9% of the 181 isolates, respectively. The Vitek MS RUO system was the least reliable, only correctly identifying 38.7% of the isolates to species level with several misidentifications and invalid results. The Bruker Biotyper system was very unreliable in the identification of species within the mitis group. Among 22 non-pneumococci isolates (S. mitis/S. oralis/S. pseudopneumoniae), Biotyper misidentified 21 of them as S. pneumoniae leading to a low sensitivity and low positive predictive value in these species. In contrast, the Vitek MS IVD demonstrated a better resolution for pneumococci and non-pneumococci despite the inability to distinguish between S. mitis/S. oralis. For more accurate species-level identification, further improvements in the VGS spectra databases are needed. Based on MALDI-TOF analysis and selected 16S rRNA gene plus gyrB genes sequencing, we designed a practical VGS identification algorithm.

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

    Science.gov (United States)

    Smith, Michael B.

    2009-01-01

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

  11. Targeted Treatment of Nasopharyngeal Carcinoma with FA-CM-β-CD-CDDP Nanomedicine%FA-CM-β-CD-CDDP 纳米药物对鼻咽癌的体内靶向治疗研究

    Institute of Scientific and Technical Information of China (English)

    刘涛; 候雄军; 伍锡栋; 柯波; 王蓉; 刘素珍

    2015-01-01

    ABSTRACT:Objective To investigate the effect of folic acid(FA)-targeted cisplatin(CDDP)con-jugated carboxymethyl-β-cyclodextrin(CM-β-CD)nanomedicine(FA-CM-β-CD-CDDP)on naso-pharyngeal carcinoma(NPC)in vivo.Methods Nude mice bearing folate receptor(FR)-positive HNE-1 tumor and FR-negative CNE-2 tumor were given FA-CM-β-CD-CDDP nanomedicine(CD-DP 10 mg·kg-1 )via tail vein injection.The concentrations of CDDP in tumor tissues were deter-mined 1.5 hours after injection by using atomic absorption spectroscopy to analyze the targeting ability of FA-CM-β-CD-CDDP.Twenty nude mice bearing HNE-1 tumor were randomly given normal saline(control group,n=5),FA-CM-β-CD solution(vector group,n=5),3 mg·kg-1 CD-DP solution(CDDP group,n=5)or 3 mg/kg FA-CM-β-CD-CDDP solution(nanomedicine group, n=5)at a volume of 2 ml via tail vein injection.HNE-1 tumor volume and weight were measured 21 days after administration.Furthermore,the expression of proliferating cell nuclear antigen(PC-NA)was detected by immunohistochemistry to analyze the efficacy of FA-CM-β-CD-CDDP for tumor suppression.Results The concentration of CDDP in HNE-1 tumor was significantly higher than that in CNE-2 tumor(P <0.05).The inhibition rates of HNE-1 tumor volume and weight in nanomedicine group(43.36% and 41.67%,respectively)were significantly higher than those in vector group(7.91% and 5.56%,respectively)and CDDP group(24.51% and 22.22%,respec-tively).Moreover,positive PCNA index in HNE-1 tumor in nanomedicine group(47.75%)was significantly lower than that in control group(90.83%),vector group(89.62%)and CDDP group (68.43%).Conclusion The constructed A-CM-β-CD-CDDP nanomedicine can inhibit the growth of FR-positive NPC tumor.%目的:探讨叶酸(folic acid,FA)分子靶向载顺铂(cisplatin,CDDP)羧甲基-β-环糊精(carboxymethyl-β-cyclo-dextrin,CM-β-CD)纳米药物(FA-CM-β-CD-CDDP)对鼻咽癌(nasopharyngeal carcinoma,NPC)的体内靶向治疗效应

  12. Ligand binding to the FA3-FA4 cleft inhibits the esterase-like activity of human serum albumin.

    Directory of Open Access Journals (Sweden)

    Paolo Ascenzi

    Full Text Available The hydrolysis of 4-nitrophenyl esters of hexanoate (NphOHe and decanoate (NphODe by human serum albumin (HSA at Tyr411, located at the FA3-FA4 site, has been investigated between pH 5.8 and 9.5, at 22.0°C. Values of Ks, k+2, and k+2/Ks obtained at [HSA] ≥ 5×[NphOXx] and [NphOXx] ≥ 5×[HSA] (Xx is NphOHe or NphODe match very well each other; moreover, the deacylation step turns out to be the rate limiting step in catalysis (i.e., k+3 a-shift appears to be correlated to the length of the fatty acid tail of the substrate. The inhibition of the HSA-Tyr411-catalyzed hydrolysis of NphOHe, NphODe, and 4-nitrophenyl myristate (NphOMy by five inhibitors (i.e., diazepam, diflunisal, ibuprofen, 3-indoxyl-sulfate, and propofol has been investigated at pH 7.5 and 22.0°C, resulting competitive. The affinity of diazepam, diflunisal, ibuprofen, 3-indoxyl-sulfate, and propofol for HSA reflects the selectivity of the FA3-FA4 cleft. Under conditions where Tyr411 is not acylated, the molar fraction of diazepam, diflunisal, ibuprofen, and 3-indoxyl-sulfate bound to HSA is higher than 0.9 whereas the molar fraction of propofol bound to HSA is ca. 0.5.

  13. The complement system in human cardiometabolic disease.

    Science.gov (United States)

    Hertle, E; Stehouwer, C D A; van Greevenbroek, M M J

    2014-10-01

    The complement system has been implicated in obesity, fatty liver, diabetes and cardiovascular disease (CVD). Complement factors are produced in adipose tissue and appear to be involved in adipose tissue metabolism and local inflammation. Thereby complement links adipose tissue inflammation to systemic metabolic derangements, such as low-grade inflammation, insulin resistance and dyslipidaemia. Furthermore, complement has been implicated in pathophysiological mechanisms of diet- and alcohol induced liver damage, hyperglycaemia, endothelial dysfunction, atherosclerosis and fibrinolysis. In this review, we summarize current evidence on the role of the complement system in several processes of human cardiometabolic disease. C3 is the central component in complement activation, and has most widely been studied in humans. C3 concentrations are associated with insulin resistance, liver dysfunction, risk of the metabolic syndrome, type 2 diabetes and CVD. C3 can be activated by the classical, the lectin and the alternative pathway of complement activation; and downstream activation of C3 activates the terminal pathway. Complement may also be activated via extrinsic proteases of the coagulation, fibrinolysis and the kinin systems. Studies on the different complement activation pathways in human cardiometabolic disease are limited, but available evidence suggests that they may have distinct roles in processes underlying cardiometabolic disease. The lectin pathway appeared beneficial in some studies on type 2 diabetes and CVD, while factors of the classical and the alternative pathway were related to unfavourable cardiometabolic traits. The terminal complement pathway was also implicated in insulin resistance and liver disease, and appears to have a prominent role in acute and advanced CVD. The available human data suggest a complex and potentially causal role for the complement system in human cardiometabolic disease. Further, preferably longitudinal studies are needed to

  14. The strawberry (Fragariaxananassa) fruit-specific rhamnogalacturonate lyase 1 (FaRGLyase1) gene encodes an enzyme involved in the degradation of cell-wall middle lamellae.

    Science.gov (United States)

    Molina-Hidalgo, Francisco J; Franco, Antonio R; Villatoro, Carmen; Medina-Puche, Laura; Mercado, José A; Hidalgo, Miguel A; Monfort, Amparo; Caballero, José Luis; Muñoz-Blanco, Juan; Blanco-Portales, Rosario

    2013-04-01

    Pectins are essential components of primary plant cell walls and middle lamellae, and are related to the consistency of the fruit and its textural changes during ripening. In fact, strawberries become soft as the middle lamellae of cortical parenchyma cells are extensively degraded during ripening, leading to the observed short post-harvest shelf life. Using a custom-made oligonucleotide-based strawberry microarray platform, a putative rhamnogalacturonate lyase gene (FaRGlyase1) was identified. Bioinformatic analysis of the FaRGlyase1 sequence allowed the identification of a conserved rhamnogalacturonate lyase domain, which was also present in other putative RGlyase sequences deposited in the databases. Expression of FaRGlyase1 occurred mainly in the receptacle, concurrently with ripening, and it was positively regulated by abscisic acid and negatively by auxins. FaRGLyase1 gene expression was transiently silenced by injecting live Agrobacterium cells harbouring RNA interference constructs into fruit receptacles. Light and electron microscopy analyses of these transiently silenced fruits revealed that this gene is involved in the degradation of pectins present in the middle lamella region between parenchymatic cells. In addition, genetic linkage association analyses in a strawberry-segregating population showed that FaRGLyase1 is linked to a quantitative trait loci linkage group related to fruit hardness and firmness. The results showed that FaRGlyase1 could play an important role in the fruit ripening-related softening process that reduces strawberry firmness and post-harvest life.

  15. Defining the complement biomarker profile of c3 glomerulopathy

    DEFF Research Database (Denmark)

    Zhang, Yuzhou; Nester, Carla M; Martin, Bertha;

    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...

  16. Invariants of tangles with flat connections in their complements

    CERN Document Server

    Kashaev, R

    2010-01-01

    Let G be a simple complex algebraic group. By using a notion of a G-category we define invariants of tangles with flat G-connections in their complements. We also show that quantized universal enveloping algebras at roots of unity provide examples of G-categories.

  17. Role of Complement in Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Berentsen, Sigbjørn

    2015-09-01

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

  18. FaPOD27 functions in the metabolism of polyphenols in strawberry fruit (Fragaria sp.).

    Science.gov (United States)

    Yeh, Su-Ying; Huang, Fong-Chin; Hoffmann, Thomas; Mayershofer, Mechthild; Schwab, Wilfried

    2014-01-01

    The strawberry (Fragaria × ananassa) is one of the most preferred fresh fruit worldwide, accumulates numerous flavonoids but has limited shelf life due to excessive tissue softening caused by cell wall degradation. Since lignin is one of the polymers that strengthen plant cell walls and might contribute to some extent to fruit firmness monolignol biosynthesis was studied in strawberry fruit. Cinnamoyl-CoA reductase (CCR), cinnamyl alcohol dehydrogenase (CAD), and a peroxidase (POD27) gene were strongly expressed in red, ripe fruit whereas a second POD gene was primarily expressed in green, immature fruit. Moreover, FaPOD27 transcripts were strongly and constitutively induced in fruits exposed to Agrobacterium infection. Gene expression levels and enzymatic activities of FaCCR and FaCAD were efficiently suppressed through RNAi in FaCCR- and FaCAD-silenced strawberries. Besides, significantly elevated FaPOD transcript levels were detected after agroinfiltration of pBI-FaPOD constructs in fruits. At the same time, levels of G-monomers were considerably reduced in FaCCR-silenced fruits whereas the proportion of both G- and S-monomers decisively decreased in FaCAD-silenced and pBI-FaPOD fruits. Development, firmness, and lignin level of the treated fruits were similar to pBI-intron control fruits, presumably attributed to increased expression levels of FaPOD27 upon agroinfiltration. Additionally, enhanced firmness, accompanied with elevated lignin levels, was revealed in chalcone synthase-deficient fruits (CHS(-)), independent of down- or up-regulation of individual and combined FaCCR. FaCAD, and FaPOD genes by agroinfiltration, when compared to CHS(-)/pBI-intron control fruits. These approaches provide further insight into the genetic control of flavonoid and lignin synthesis in strawberries. The results suggest that FaPOD27 is a key gene for lignin biosynthesis in strawberry fruit and thus to improving the firmness of strawberries.

  19. FaPOD27 functions in the metabolism of polyphenols in strawberry fruit (Fragaria sp.

    Directory of Open Access Journals (Sweden)

    Su-Ying eYeh

    2014-10-01

    Full Text Available The strawberry (Fragaria × ananassa is one of the most preferred fresh fruit worldwide, accumulates numerous flavonoids but has limited shelf life due to excessive tissue softening caused by cell wall degradation. Since lignin is one of the polymers that strengthen plant cell walls and might contribute to some extent to fruit firmness monolignol biosynthesis was studied in strawberry fruit. Cinnamoyl-CoA reductase (CCR, cinnamyl alcohol dehydrogenase (CAD, and a peroxidase (POD27 gene were strongly expressed in red, ripe fruit whereas a second POD gene was primarily expressed in green, immature fruit. Moreover, FaPOD27 transcripts were strongly and constitutively induced in fruits exposed to Agrobacterium infection. Gene expression levels and enzymatic activities of FaCCR and FaCAD were efficiently suppressed through RNAi in FaCCR- and FaCAD-silenced strawberries. Besides, significantly elevated FaPOD transcript levels were detected after agroinfiltration of pBI-FaPOD constructs in fruits. At the same time, levels of G-monomers were considerably reduced in FaCCR-silenced fruits whereas the proportion of both G- and S-monomers decisively decreased in FaCAD-silenced and pBI-FaPOD fruits. Development, firmness, and lignin level of the treated fruits were similar to pBI-intron control fruits, presumably attributed to increased expression levels of FaPOD27 upon agroinfiltration. Additionally, enhanced firmness, accompanied with elevated lignin levels, was revealed in chalcone synthase-deficient fruits (CHS-, independent of down- or up-regulation of individual and combined FaCCR, FaCAD, and FaPOD genes by agroinfiltration, when compared to CHS-/pBI-intron control fruits. These approaches provide further insight into the genetic control of flavonoid and lignin synthesis in strawberries. The results suggest that FaPOD27 is a key gene for lignin biosynthesis in strawberry fruit and thus to improving the firmness of strawberries.

  20. Role of Complement in Autoimmune Hemolytic Anemia

    OpenAIRE

    Berentsen, Sigbjørn

    2015-01-01

    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorder...

  1. Deterministic Assessment of Future Costs for Dismantling (FA)

    Energy Technology Data Exchange (ETDEWEB)

    Vasko, Marek [DECOM, Trnava (Slovakia)

    2012-11-01

    The main objective of the report is to provide an re-evaluation of cost calculations by OMEGA code for the Intermediate Storage for Spent Fuel in Studsvik (FA facility) using up-to-date Swedish labour cost unit factors and available up-to-date Swedish (or international) cost unit factors for consumables, materials and substances. Furthermore, evolution of other OMEGA database parameters concerning cost calculations e.g. manpower unit factors and workgroups parameters are taken into account. This report follows up former project which introduced tentative calculations of main decommissioning parameters such as costs, manpower and exposure of personnel for activities of older nuclear facility decommissioning in Sweden represented by FA Facility in Studsvik by means of calculation code OMEGA. The project demonstrated an implementation of advanced costing methodology based on PSL structure format to achieve transparent, traceable and comparable estimates even for older nuclear facilities like FA Facility in Studsvik. This former project used Slovak origin labour costs unit factors and other cost unit factors. After successful completion of this project, there was an intent of SSM to reevaluate calculations using an up-to-date Swedish labour cost data and also available Swedish consumables and materials cost data if available. Within this report re-calculations of main decommissioning parameters using available Swedish data are presented in structure according to Proposed Standardized List of Items for Costing Purposes. Calculations are made for decommissioning scenario with post-dismantling decontamination and steel radwaste melting technologies available at the site. All parameters are documented and summed up in both table and graphic forms in text and Annexes. Further, comparison of calculated results with previous calculations together with discussion is provided.

  2. The effect of single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1 cells in a nude mouse model.

    Science.gov (United States)

    Ruda, James M; Beus, Kirt S; Hollenbeak, Christopher S; Wilson, Ronald P; Stack, Brendan C

    2006-09-01

    To determine whether oral administration of fusaric acid (FA) inhibits tumor growth in an animal model of head and neck cancer (HNSCC). In vivo murine model, two arm controlled study. Thirty-eight (38) 5-week-old athymic nude mice were randomly assigned to a fusaric acid treatment group (1 mg/mL) (n = 19) or a sterile saline group (n = 19). A left, lateral flank subcutaneous injection of 2.0 x 10(6) UM-SCC-1 cells were administered to all mice on day 1. Both groups were gavaged daily with either 0.25 mLs of oral FA or sterile saline throughout the experiment (32 days). Latency to a measurable tumor (> or =65 mm3), and tumor volumes were recorded after tumor xenografting. Tumor weights were recorded at the conclusion of the experiment. Tumor volume growth curves were modeled as polynomial functions of time with treatment interaction effects. Survivorship functions for time to measurable tumor were estimated using the Kaplan-Meier product limit estimator. Survival analysis showed mice treated with FA developed measurable tumors after a significantly longer interval post-xenografting than control mice (p = 0.00451). By Day 9, all mice in the control group had developed measurable tumors in comparison to only 78% of mice in the FA group. Likewise, estimated growth curves for both groups suggested that mice receiving FA demonstrated significantly slower tumor growth rates throughout the entire study period (p < 0.0001). At the conclusion of the experiment, tumor weights from both the control and FA groups were also significantly different (p = 0.0142). Single agent oral fusaric acid (1 mg/mL) is an inhibitor of UM-SCC-1 in a murine model. As an orally active agent, it may have a potential role in the treatment of human squamous cell carcinoma of the head and neck.

  3. Differences in complement activation between complement-resistant and complement-sensitive Moraxella (Branhamella) catarrhalis strains occur at the level of membrane attack complex formation.

    OpenAIRE

    Verduin, C.M.; Jansze, M.; Hol, C; Mollnes, T E; Verhoef, J; Van Dijk, H.

    1994-01-01

    The mechanism of resistance to human complement-mediated killing in Moraxella catarrhalis was studied by comparing different complement-sensitive and complement-resistant M. catarrhalis strains in a functional bystander hemolysis assay and an enzyme-linked immunosorbent assay (ELISA) for soluble terminal complement complexes. Complement-resistant stains appeared to activate complement to the same extent as, or even slightly better than, complement-sensitive strains. This indicates that comple...

  4. Complement: an overview for the clinician.

    Science.gov (United States)

    Varela, Juan Carlos; Tomlinson, Stephen

    2015-06-01

    The complement system is an essential component of the immune system. It is a highly integrative system and has a number of functions, including host defense, removal of injured cells and debris, modulation of metabolic and regenerative processes, and regulation of adaptive immunity. Complement is activated via different pathways and it is regulated tightly by several mechanisms to prevent host injury. Imbalance between complement activation and regulation can manifest in disease and injury to self. This article provides an outline of complement activation pathways, regulatory mechanisms, and normal physiologic functions of the system.

  5. On distribution of complementizers in contemporary Serbian

    Directory of Open Access Journals (Sweden)

    Moskovljević Jasmina

    2004-01-01

    Full Text Available The paper investigates the principles governing the distribution of complementizers in contemporary Serbian. Evidence is presented that the distribution of da, što, kako, gde, da li, and numerous interrogative pronouns and adverbials which may function as complementizers is determined not only by matrix-verb subcategorization properties and semantic co-occurrence restrictions which hold between the predicate and its complement, but by the lexical an syntactic properties of the particular verb class (or subclass to which matrix predicate belongs as well. According to their ability to govern a particular complementizer, ten major verb subclasses are identified in contemporary Serbian, and their specific properties are signaled.

  6. Role of Complement in Multiorgan Failure

    Directory of Open Access Journals (Sweden)

    Daniel Rittirsch

    2012-01-01

    Full Text Available Multiorgan failure (MOF represents the leading cause of death in patients with sepsis and systemic inflammatory response syndrome (SIRS following severe trauma. The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed.

  7. FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA

    OpenAIRE

    Ali, Abdullah Mahmood; Singh, Thiyam Ramsing; Meetei, Amom Ruhikanta

    2009-01-01

    Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA crosslinking agents. Eight FA proteins (FANCA, -B, -C, -E, -F, -G, -L and –M) and three non-FA proteins (FAAP100, FAAP24 and HES1) form the FA nuclear core complex that is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. The other three FA proteins, FANCD1/BRCA2, FANCJ/BACH1/BRIP1 and FANCN/PALB2, act in parall...

  8. Diffusion tensor MRI tractography reveals increased fractional anisotropy (FA) in arcuate fasciculus following music-cued motor training.

    Science.gov (United States)

    Moore, Emma; Schaefer, Rebecca S; Bastin, Mark E; Roberts, Neil; Overy, Katie

    2017-08-01

    Auditory cues are frequently used to support movement learning and rehabilitation, but the neural basis of this behavioural effect is not yet clear. We investigated the microstructural neuroplasticity effects of adding musical cues to a motor learning task. We hypothesised that music-cued, left-handed motor training would increase fractional anisotropy (FA) in the contralateral arcuate fasciculus, a fibre tract connecting auditory, pre-motor and motor regions. Thirty right-handed participants were assigned to a motor learning condition either with (Music Group) or without (Control Group) musical cues. Participants completed 20minutes of training three times per week over four weeks. Diffusion tensor MRI and probabilistic neighbourhood tractography identified FA, axial (AD) and radial (RD) diffusivity before and after training. Results revealed that FA increased significantly in the right arcuate fasciculus of the Music group only, as hypothesised, with trends for AD to increase and RD to decrease, a pattern of results consistent with activity-dependent increases in myelination. No significant changes were found in the left ipsilateral arcuate fasciculus of either group. This is the first evidence that adding musical cues to movement learning can induce rapid microstructural change in white matter pathways in adults, with potential implications for therapeutic clinical practice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Psychometric Properties of the Fatigue Questionnaire EORTC QLQ-FA12 in a sample of female cancer patients.

    Science.gov (United States)

    Kecke, Sophie; Ernst, Jochen; Einenkel, Jens; Singer, Susanne; Hinz, Andreas

    2017-08-11

    . Cancer patients frequently suffer from fatigue. Recently, the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life group developed a new 12-item fatigue assessment instrument. The aim of this study was to psychometrically test this questionnaire in comparison with the 3-item fatigue scale of the EORTC QLQ-C30. A sample of 354 patients who were being treated for breast cancer or gynaecological cancer were examined using the new fatigue questionnaire EORTC QLQ-FA12 and the EORTC QLQ-C30 during their hospital stay (t1) and three months after hospital discharge (t2). Confirmatory factorial analyses (CFA), item analyses, test-retest reliability analyses, and correlation analyses were performed. The analyses roughly supported the three-factorial structure of the FA12, which is comprised of the subscales Physical, Emotional, and Cognitive fatigue. The fit indices of the CFA were worse than those of the original paper but nevertheless acceptable. Cronbach's alpha of the total scale was 0.92; the coefficients of the subscales were between 0.79 and 0.93. The correlation between the EORTC QLQ-FA12 total scale and the fatigue scale of the EORTC QLQ-C30 was 0.69, the correlation between the t1 and t2 scores was 0.45 for the EORTC QLQ-FA12 total scale and between 0.37 and 0.47 for the subscales. The psychometric coefficients justify the calculation of a sum score, which can be used by clinicians to assess the general degree of fatigue. While the 3-item fatigue scale of the EORTC QLQ-C30 stresses the physical aspect of fatigue, the new EORTC QLQ-FA12 covers its emotional and cognitive aspects as well. Copyright © 2017. Published by Elsevier Inc.

  10. Development of a Holistic Evaluation System for BIPV Façades

    Directory of Open Access Journals (Sweden)

    Thorsten Schuetze

    2015-06-01

    Full Text Available Façades with building-integrated photovoltaics (BIPV have the advantage that they can produce renewable electric energy. Compared with conventional façades, BIPV façades have therefore a valuable additional property that can generally contribute to increasing the degree of sustainability of buildings. A holistic assessment system for BIPV façade systems for office and administration buildings was developed in the framework of the project “MULTIELEMENT II” at the Fraunhofer Institute for Wind Energy and Energy System Technology (IWES in Kassel, Germany. The aim of this research was a comparison of conventional façade systems with BIPV façade systems regarding different technical, economical, sustainability, and design criteria. This paper discusses the basic conditions for a holistic evaluation of BIPV façades in comparison with conventional façades. A method for the execution of a holistic evaluation and characteristic values for a comparison interpretation of results is presented. Façade systems are evaluated regarding both quantifiable and non-quantifiable properties by means of a Microsoft Excel-based evaluation tool. The tool facilitates the comparison and evaluation of planned or built façades with and without BIPV. The detailed evaluation results aim to facilitate the certification of BIPV façade systems in the framework of sustainable building certification systems such as the German DGNB.

  11. Façade fire tests – measurements and modeling

    Directory of Open Access Journals (Sweden)

    Anderson Johan

    2013-11-01

    Full Text Available In two recent papers [1, 2] the fire dynamics in a test rig for façade constructions according to the test method SP Brand 105 [3, 4] was investigated both experimentally and numerically. The experimental setup simulates a three-story apartment building (height 6.7 m, width 4 m and depth 1.6 m, with external wall-cladding and a “room fire” at the base. The numerical model was developed in the CFD program Fire Dynamics Simulator (FDS [5] with analogous geometry and instrumentation. The general features of the fire test were well reproduced in the numerical model however temperatures close to the fire source could not be properly accounted for in the model. In this paper the bi-directional probe measurements are elaborated on and the test used in Ref. [1] is revisited using different heat release rates in the numerical model. The velocity of the hot gases along the façade was well reproduced by the simulations although some deviations were found.

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

    Science.gov (United States)

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

    2015-12-10

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

  13. Noun complement clauses as referential modifiers

    Directory of Open Access Journals (Sweden)

    Carlos de Cuba

    2017-01-01

    Full Text Available A number of recent analyses propose that so-called noun complement clauses should be analyzed as a type of relative clause. In this paper, I present a number of complications for any analysis that equates noun complement clauses to relative clauses, and conclude that this type of analysis is on the wrong track. I present cross-linguistic evidence showing that the syntactic behavior of noun complement clauses does not pattern with relative clauses. Patterns of complementizer choice and complementizer drop as well as patterns involving main clause phenomena and extraction differ in the two constructions, which I argue is unexpected under a relative clause analysis that involves operator movement. Instead I present an alternative analysis in which I propose that the referentiality of a noun complement clause is linked to its syntactic behavior. Following recent work, I claim that referential clauses have a syntactically truncated left-periphery, and this truncation can account for the lack of main clause phenomena in noun complement clauses. I argue that the truncation analysis is also able to accommodate complementizer data patterns more easily than relative clause analyses that appeal to operator movement.

  14. Complement pathways and meningococcal disease : diagnostic aspects

    DEFF Research Database (Denmark)

    Sjöholm, A G; Truedsson, L; Jensenius, Jens Christian

    2001-01-01

    Complement is an immunological effector system that bridges innate and acquired immunity in several ways. There is a striking association between susceptibility to meningococcal disease and various forms of complement deficiency (1,2). In defense against bacterial infection, the most important...

  15. Hyperbolic structures on a toric arrangement complement

    NARCIS (Netherlands)

    Shen, Dali

    2015-01-01

    This thesis studies the geometric structures on toric arrangement complements. Inspired by the special hypergeometric functions associated with a root system, we consider a family of connections on a total space which is the product of the complement of a toric arrangement (=finite union of hypertor

  16. The complement system in systemic autoimmune disease

    NARCIS (Netherlands)

    Chen, Min; Daha, Mohamed R.; Kallenberg, Cees G. M.

    2010-01-01

    Complement is part of the innate immune system. Its major function is recognition and elimination of pathogens via direct killing and/or stimulation of phagocytosis. Activation of the complement system is, however, also involved in the pathogenesis of the systemic autoimmune diseases. Activation via

  17. Complement associated pathogenic mechanisms in myasthenia gravis.

    Science.gov (United States)

    Tüzün, Erdem; Christadoss, Premkumar

    2013-07-01

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

  18. The role of complement in AMD.

    Science.gov (United States)

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

    2010-01-01

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

  19. FA387型并条机性能分析与应用%Performance Analyses and Application of FA387 Drawing Frame

    Institute of Scientific and Technical Information of China (English)

    姜正俊; 袁显政

    2013-01-01

    探讨FA387型并条机的技术性能和应用效果.阐述了FA387型并条机技术规格、性能特点及操作使用方法,并与FA316B型并条机进行了纺纱对比试验.结果表明:FA387型并条机在纺纱质量和牵伸同步性能方面优于FA316B型并条机.认为:运用伺服电机及数字化闭环控制技术,实现主牵伸无级调节和动态监控的高速并条机,具有工艺调整便捷、机构简化、维护方便、改善纺纱质量、提高生产效率、减少用工的特点,代表了高速并条机技术的新趋势.%Technical performance and application effect of FA387 drawing frame were discussed. Technical specifications , performance characteristics and operating use of FA387 drawing frame were introduced, the spinning test was contrasted with FA316B drawing frame. The result shows that FA387 drawing frame is better than that of FA316B drawing frame in aspects of spinning quality and drafting synchronization performance. It is considered that servo motor and digital closed-loop control technology are applied by high-speed drawing frame, the main drafting stepless adjustment and dynamic monitoring can be realized. Performance of this kinds of drawing frame are better, such as convenient process adjustment, simplified structure, easy maintenance, better yarn quality, higher efficiency and less labor. New trend of high-speed drawing machine technology can be represented.

  20. Complement activation by Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Jensen, E T; Kharazmi, A; Garred, P

    1993-01-01

    In chronic infections, such as the bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients, bacteria persist despite an intact host immune defense and frequent antibiotic treatment. An important reason for the persistence of the bacteria is their capacity for the biofilm...... mode of growth. In this study we investigated the role of biofilms in activation of complement, a major contributor to the inflammatory process. Complement activation by P. aeruginosa was examined in a complement consumption assay, production of C3 and factor B conversion products assessed by crossed...... immuno-electrophoresis, C5a generation tested by a PMN chemotactic assay, and terminal complement complex formation measured by ELISA. Two of the four assays showed that P. aeruginosa grown in biofilm activated complement less than planktonic bacteria, and all assays showed that activation by intact...

  1. Molecules Great and Small: The Complement System.

    Science.gov (United States)

    Mathern, Douglas R; Heeger, Peter S

    2015-09-04

    The complement cascade, traditionally considered an effector arm of innate immunity required for host defense against pathogens, is now recognized as a crucial pathogenic mediator of various kidney diseases. Complement components produced by the liver and circulating in the plasma undergo activation through the classical and/or mannose-binding lectin pathways to mediate anti-HLA antibody-initiated kidney transplant rejection and autoantibody-initiated GN, the latter including membranous glomerulopathy, antiglomerular basement membrane disease, and lupus nephritis. Inherited and/or acquired abnormalities of complement regulators, which requisitely limit restraint on alternative pathway complement activation, contribute to the pathogenesis of the C3 nephropathies and atypical hemolytic uremic syndrome. Increasing evidence links complement produced by endothelial cells and/or tubular cells to the pathogenesis of kidney ischemia-reperfusion injury and progressive kidney fibrosis. Data emerging since the mid-2000s additionally show that immune cells, including T cells and antigen-presenting cells, produce alternative pathway complement components during cognate interactions. The subsequent local complement activation yields production of the anaphylatoxins C3a and C5a, which bind to their respective receptors (C3aR and C5aR) on both partners to augment effector T-cell proliferation and survival, while simultaneously inhibiting regulatory T-cell induction and function. This immune cell-derived complement enhances pathogenic alloreactive T-cell immunity that results in transplant rejection and likely contributes to the pathogenesis of other T cell-mediated kidney diseases. C5a/C5aR ligations on neutrophils have additionally been shown to contribute to vascular inflammation in models of ANCA-mediated renal vasculitis. New translational immunology efforts along with the development of pharmacologic agents that block human complement components and receptors now permit

  2. Complement system part II: role in immunity

    Directory of Open Access Journals (Sweden)

    Nicolas S. Merle

    2015-05-01

    Full Text Available The complement system has been considered for a long time as a simple lytic system, aimed to kill bacteria infecting the host organism. Nowadays this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing a direct killing by C5b-9 membrane attack complex by triggering inflammatory responses with the anaphylatoxins C3a and C5a and helps the mounting of an adaptive immune response, involving antigen presenting cells, T- and B- lymphocytes. But it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Also examples will be discussed, where inadequate complement activation becomes a disease cause, including atypical hemolytic uremic syndrome (aHUS, C3 glomerulopathies (C3G and systemic lupus erythematosus (SLE. Age related macular degeneration (AMD and cancer will be described as examples showing that complement contributes to a large variety of diseases, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target.

  3. Complement System Part II: Role in Immunity

    Science.gov (United States)

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

    2015-01-01

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

  4. Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

    Directory of Open Access Journals (Sweden)

    Ofori Michael F

    2007-12-01

    Full Text Available Abstract Background Severe anaemia (SA, intravascular haemolysis (IVH and respiratory distress (RD are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. Methods The direct Coombs test (DCT and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3bαβ and the regulatory proteins [complement receptor 1 (CD35 and decay accelerating factor (CD55] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb levels and RD were investigated. Results Of the 484 samples tested, 131(27% were positive in DCT, out of which 115/131 (87.8% were positive for C3d alone while 16/131 (12.2% were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2–6.7, p Conclusion These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding.

  5. Viral mimicry of the complement system

    Indian Academy of Sciences (India)

    John Bernet; Jayati Mullick; Akhilesh K Singh; Arvind Sahu

    2003-04-01

    The complement system is a potent innate immune mechanism consisting of cascades of proteins which are designed to fight against and annul intrusion of all the foreign pathogens. Although viruses are smaller in size and have relatively simple structure, they are not immune to complement attack. Thus, activation of the complement system can lead to neutralization of cell-free viruses, phagocytosis of C3b-coated viral particles, lysis of virus-infected cells, and generation of inflammatory and specific immune responses. However, to combat host responses and succeed as pathogens, viruses not only have developed/adopted mechanisms to control complement, but also have turned these interactions to their own advantage. Important examples include poxviruses, herpesviruses, retroviruses, paramyxoviruses and picornaviruses. In this review, we provide information on the various complement evasion strategies that viruses have developed to thwart the complement attack of the host. A special emphasis is given on the interactions between the viral proteins that are involved in molecular mimicry and the complement system.

  6. Properdin in complement activation and tissue injury.

    Science.gov (United States)

    Lesher, Allison M; Nilsson, Bo; Song, Wen-Chao

    2013-12-15

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

  7. FaDA: Fast Document Aligner using Word Embedding

    Directory of Open Access Journals (Sweden)

    Lohar Pintu

    2016-10-01

    Full Text Available FaDA is a free/open-source tool for aligning multilingual documents. It employs a novel crosslingual information retrieval (CLIR-based document-alignment algorithm involving the distances between embedded word vectors in combination with the word overlap between the source-language and the target-language documents. In this approach, we initially construct a pseudo-query from a source-language document. We then represent the target-language documents and the pseudo-query as word vectors to find the average similarity measure between them. This word vector-based similarity measure is then combined with the term overlap-based similarity. Our initial experiments show that s standard Statistical Machine Translation (SMT- based approach is outperformed by our CLIR-based approach in finding the correct alignment pairs. In addition to this, subsequent experiments with the word vector-based method show further improvements in the performance of the system.

  8. MANOVA, LDA, and FA criteria in clusters parameter estimation

    Directory of Open Access Journals (Sweden)

    Stan Lipovetsky

    2015-12-01

    Full Text Available Multivariate analysis of variance (MANOVA and linear discriminant analysis (LDA apply such well-known criteria as the Wilks’ lambda, Lawley–Hotelling trace, and Pillai’s trace test for checking quality of the solutions. The current paper suggests using these criteria for building objectives for finding clusters parameters because optimizing such objectives corresponds to the best distinguishing between the clusters. Relation to Joreskog’s classification for factor analysis (FA techniques is also considered. The problem can be reduced to the multinomial parameterization, and solution can be found in a nonlinear optimization procedure which yields the estimates for the cluster centers and sizes. This approach for clustering works with data compressed into covariance matrix so can be especially useful for big data.

  9. α1-Tubulin FaTuA1 plays crucial roles in vegetative growth and conidiation in Fusarium asiaticum.

    Science.gov (United States)

    Hu, Weiqun; Zhang, Xiaoping; Chen, Xiang; Zheng, Jingwu; Yin, Yanni; Ma, Zhonghua

    2015-04-01

    The filamentous ascomycete Fusarium asiaticum contains two homologous genes FaTUA1 and FaTUA2 encoding α-tubulins. In this study, we found that FaTUA2 was dispensable for vegetative growth and sporulation in F. asiaticum. The deletion of FaTUA1 however led to dramatically reduced mycelial growth, twisted hyphae and abnormal nuclei in apical cells of hyphae. The FaTUA1 deletion mutant (ΔFaTuA1-5) also showed a significant decrease in conidiation, and produced abnormal conidia. Pathogenicity assays showed that ΔFaTuA1-5 exhibited decreased virulence on wheat head. Unexpectedly, the deletion of FaTUA1 led to resistance to high temperatures. In addition, ΔFaTuA2 showed increased sensitivity to carbendazim. Furthermore, increased FaTUA2 expression in ΔFaTuA1-5 partially restored the defects of the mutant in mycelial growth, conidial production and virulence, vice versa, increased FaTUA1 expression in the FaTUA2 deletion mutant also partially relieved the defect of the mutant in the delay of conidial germination. Taken together, these results indicate that FaTuA1 plays crucial roles in vegetative growth and development, and the functions of FaTuA1 and FaTuA2 are partially interchangeable in F. asiaticum.

  10. Infections Revealing Complement Deficiency in Adults

    Science.gov (United States)

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

    2016-01-01

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

  11. Liiga väike, et lubada endale fašismi / Tõnis Saarts

    Index Scriptorium Estoniae

    Saarts, Tõnis

    2008-01-01

    Ilmunud ka: Molodjozh Estonii, Vesti Dnja 11. dets. lk. 11,7. Autor nimetab fašismi põhitunnused ning järeldab, et Eesti ei anna ühelgi alusel fašistliku riigi mõõtu välja; fašistlik või poolautoritaarne Eesti saab olla ainult Vene mõju all olev Eesti, ütleb ta

  12. High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Naghi Momeni

    2012-01-01

    Full Text Available Autism spectrum disorders (ASDs are neurodevelopmental and behavioural syndromes affecting social orientation, behaviour, and communication that can be classified as developmental disorders. ASD is also associated with immune system abnormality. Immune system abnormalities may be caused partly by complement system factor I deficiency. Complement factor I is a serine protease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system. Deficiency in factor I activity is associated with an increased incidence of infections in humans. In this paper, we show that the mean level of factor I activity in the ASD group is significantly higher than in the control group of typically developed and healthy children, suggesting that high activity of complement factor I might have an impact on the development of ASD.

  13. Dynamic control of the complement system by modulated expression of regulatory proteins.

    Science.gov (United States)

    Thurman, Joshua M; Renner, Brandon

    2011-01-01

    The complement system serves many biological functions, including the eradication of invasive pathogens and the removal of damaged cells and immune-complexes. Uncontrolled complement activation causes injury to host cells, however, so adequate regulation of the system is essential. Control of the complement system is maintained by a group of cell surface and circulating proteins referred to as complement regulatory proteins. The expression of the cell surface complement regulatory proteins varies from tissue to tissue. Furthermore, specific cell types can upregulate or downregulate the expression of these proteins in response to a variety of signals or insults. Altered regulation of the complement regulatory proteins can have important effects on local complement activation. In some circumstances this can be beneficial, such as in the setting of certain infections. In other circumstances, however, this can be a cause of complement-mediated injury of the tissue. A full understanding of the mechanisms by which the complement system is modulated at the local level can have important implications for how we diagnose and treat a wide range of inflammatory diseases.

  14. Autocrine Effects of Tumor-Derived Complement

    Directory of Open Access Journals (Sweden)

    Min Soon Cho

    2014-03-01

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

  15. Heredity in fundamental left complemented algebras

    Directory of Open Access Journals (Sweden)

    Marina Haralampidou

    2016-06-01

    Full Text Available In the present paper, we introduce the notion of a fundamental complemented linear space, through continuous projections. This notion is hereditary. Relative to this, we prove that if a certain topological algebra is fundamental, then a concrete subspace is fundamental too. For a fundamental complemented linear space, we define the notion of continuity of the complementor. In some cases, we employ a generalized notion of complementation, that of (left precomplementation. In our main result, the continuity of the complementor for a certain fundamental complemented (topological algebra is inherited to the induced vector complementor of the underlying linear space of a certain right ideal. Weakly fundamental algebras are also considered in the context of locally convex ones.

  16. Effect of façade systems on the performance of cooling ceilings: In situ measurements

    Directory of Open Access Journals (Sweden)

    Katharina Eder

    2015-03-01

    Full Text Available This article presents an innovative façade system designed to increase the thermal comfort inside an office room and to enhance the cooling capacity of the suspended cooling ceiling. A series of measurements is conducted in an existing office building with different façade systems (i.e., a combination of glazing and shading. An innovative façade system is developed based on this intensive set of measurements. The new system enhances the thermal comfort and cooling capacity of the suspended cooling ceiling. The main usage of the new system is the refurbishment and improvement of existing façade systems.

  17. Glucomannan and glucomannan plus spirulina added to pork significantly block dietary cholesterol effects on lipoproteinemia, arylesterase activity, and CYP7A1 expression in Zucker fa/fa rats.

    Science.gov (United States)

    González-Torres, Laura; Vázquez-Velasco, Miguel; Olivero-David, Raúl; Bastida, Sara; Benedí, Juana; González, Rafaela Raposo; González-Muñoz, Ma José; Sánchez-Muniz, Francisco J

    2015-12-01

    Zucker fa/fa rats easily develop dyslipidemia and obesity. Restructured pork (RP) is a suitable matrix for including functional ingredients. The effects of glucomannan- RP or glucomannan plus spirulina-enriched RP on plasma lipid/lipoprotein levels, cytochrome P450 7A1 (CYP7A1) expression, and arylesterase activity in growing fa/fa rats fed high-energy, high-fat cholesterol-enriched diets were tested. Groups of six rats each received diet containing 15% control-RP (C), 15% glucomannan-RP diet (G), 15% glucomannan + spirulina-RP diet (GS), and same diets enriched with 2.4% cholesterol and 0.49% cholic acid (cholesterol-enriched control (HC), cholesterol-enriched glucomannan (HG), and cholesterol-enriched glucomannan + spirulina (HGS) diets) over a 7-week period. C diet induced obesity, severe hyperglycemia, moderate hypercholesterolemia, and hypertriglyceridemia. Those facts were not significantly modified by G or GS diets. G diet increased CYP7A1 expression but decreased the total cholesterol/high density lipoproteins (HDL)-cholesterol ratio (p CYP7A1 expression. HC vs. C diet reduced food intake, body weight gain, and plasma glucose (p CYP7A1 expression (at least p CYP7A1 expression (p < 0.01) but did not modify the cholesterol/HDL-cholesterol ratio. HGS vs. HG decreased triglyceridemia, the triglyceride-glucose (TyG) index and increased arylesterase/HDL-cholesterol activity (p < 0.05). In conclusion, G- and GS-RP act as functional foods and notably blocked the dietary cholesterol effects. In addition, HGS-RP improved the glucomannan hypolipidemic effects, increased arylesterase/HDL-cholesterol activity, and decreased insulin resistance.

  18. Complement activation and inhibition: a delicate balance

    DEFF Research Database (Denmark)

    Sjöberg, A P; Trouw, L A; Blom, A M

    2009-01-01

    Complement is part of the innate immune defence and not only recognizes microbes but also unwanted host molecules to enhance phagocytosis and clearance. This process of opsonisation must be tightly regulated to prevent immunopathology. Endogenous ligands such as dying cells, extracellular matrix...... activation. Disturbances to the complement regulation on endogenous ligands can lead to diseases such as age-related macular degeneration, neurological and rheumatic disorders. A thorough understanding of these processes might be crucial to developing new therapeutic strategies....

  19. The complement system in systemic autoimmune disease.

    Science.gov (United States)

    Chen, Min; Daha, Mohamed R; Kallenberg, Cees G M

    2010-05-01

    Complement is part of the innate immune system. Its major function is recognition and elimination of pathogens via direct killing and/or stimulation of phagocytosis. Activation of the complement system is, however, also involved in the pathogenesis of the systemic autoimmune diseases. Activation via the classical pathway has long been recognized in immune complex-mediated diseases such as cryoglobulinemic vasculitis and systemic lupus erythematosus (SLE). In SLE, the role of complement is somewhat paradoxical. It is involved in autoantibody-initiated tissue damage on the one hand, but, on the other hand, it appears to have protective features as hereditary deficiencies of classical pathway components are associated with an increased risk for SLE. There is increasing evidence that the alternative pathway of complement, even more than the classical pathway, is involved in many systemic autoimmune diseases. This is true for IgA-dominant Henoch Schönlein Purpura, in which additional activation of the lectin pathway contributes to more severe disease. In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis the complement system was considered not to be involved since immunoglobulin deposition is generally absent in the lesions. However, recent studies, both in human and animal models, demonstrated complement activation via the alternative pathway as a major pathogenic mechanism. Insight into the role of the various pathways of complement in the systemic autoimmune diseases including the vasculitides opens up new ways of treatment by blocking effector pathways of complement. This has been demonstrated for monoclonal antibodies to C5 or C5a in experimental anti-phospholipid antibody syndrome and ANCA-associated vasculitis.

  20. Role of complement in neurodegeneration and neuroinflammation.

    Science.gov (United States)

    Bonifati, Domenico Marco; Kishore, Uday

    2007-02-01

    The complement system provides an innate defence mechanism against pathogenic microorganisms. Although viewed for many years as an immune-privileged organ, the central nervous system contains many components of the immune system, including components of the complement system that are synthesized by astrocytes, microglia, and neurons. During the past two decades, a wide range of inflammatory markers, typically absent in the normal elderly population, have been reported in Alzheimer's disease brains. It is becoming evident that sustained brain inflammation might be an essential cofactor in Alzheimer disease and other neurodegenerative disorders such as Parkinson disease, dementia with Lewy bodies, Huntington's and prion diseases. The complement system may be useful in eliminating aggregated and toxic proteins associated with these neurological disorders and thus have a protective effect. However, an exaggerated or insufficient activation of the complement system can have deleterious effect through the activation of microglia, secretion of many proinflammatory cytokines, and generation of oxidative products. The role of complement-mediated inflammation in Alzheimer disease has drawn greater attention recently in view of new therapeutic advances made in the management of the disease. This review is meant to update the role of complement in Alzheimer's disease and other neurodegenerative disorders in view of recent vaccination and immunotherapeutic approaches.

  1. Surviving mousepox infection requires the complement system.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Moulton

    2008-12-01

    Full Text Available Poxviruses subvert the host immune response by producing immunomodulatory proteins, including a complement regulatory protein. Ectromelia virus provides a mouse model for smallpox where the virus and the host's immune response have co-evolved. Using this model, our study investigated the role of the complement system during a poxvirus infection. By multiple inoculation routes, ectromelia virus caused increased mortality by 7 to 10 days post-infection in C57BL/6 mice that lack C3, the central component of the complement cascade. In C3(-/- mice, ectromelia virus disseminated earlier to target organs and generated higher peak titers compared to the congenic controls. Also, increased hepatic inflammation and necrosis correlated with these higher tissue titers and likely contributed to the morbidity in the C3(-/- mice. In vitro, the complement system in naïve C57BL/6 mouse sera neutralized ectromelia virus, primarily through the recognition of the virion by natural antibody and activation of the classical and alternative pathways. Sera deficient in classical or alternative pathway components or antibody had reduced ability to neutralize viral particles, which likely contributed to increased viral dissemination and disease severity in vivo. The increased mortality of C4(-/- or Factor B(-/- mice also indicates that these two pathways of complement activation are required for survival. In summary, the complement system acts in the first few minutes, hours, and days to control this poxviral infection until the adaptive immune response can react, and loss of this system results in lethal infection.

  2. Complement and thrombosis in the antiphospholipid syndrome.

    Science.gov (United States)

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

    2016-10-01

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

  3. Humoral pattern recognition and the complement system.

    Science.gov (United States)

    Degn, S E; Thiel, S

    2013-08-01

    In the context of immunity, pattern recognition is the art of discriminating friend from foe and innocuous from noxious. The basis of discrimination is the existence of evolutionarily conserved patterns on microorganisms, which are intrinsic to these microorganisms and necessary for their function and existence. Such immutable or slowly evolving patterns are ideal handles for recognition and have been targeted by early cellular immune defence mechanisms such as Toll-like receptors, NOD-like receptors, RIG-I-like receptors, C-type lectin receptors and by humoral defence mechanisms such as the complement system. Complement is a proteolytic cascade system comprising around 35 different soluble and membrane-bound proteins. It constitutes a central part of the innate immune system, mediating several major innate effector functions and modulating adaptive immune responses. The complement cascade proceeds via controlled, limited proteolysis and conformational changes of constituent proteins through three activation pathways: the classical pathway, the alternative pathway and the lectin pathway, which converge in common effector functions. Here, we review the nature of the pattern recognition molecules involved in complement activation, as well as their close relatives with no or unknown capacity for activating complement. We proceed to examine the composition of the pattern recognition complexes involved in complement activation, focusing on those of the lectin pathway, and arrive at a new model for their mechanism of operation, supported by recently emerging evidence.

  4. Colour schemes and façade work at Drottningholm and Stockholm palaces Les couleurs des façades des palais royaux de Drottningholm et de Stockholm

    OpenAIRE

    2008-01-01

    Jan Lisinski présente les couleurs des façades des palais royaux de Drottningholm et de Stockholm. Les deux palais furent construits au xviie siècle mais firent l’objet de modifications par la suite. La présentation commence par un bref rappel historique centré sur les différentes couleurs utilisées pour les façades puis aborde la façon dont doivent être traitées les façades aujourd’hui. Il sera question en particulier du traitement des pierres, des plâtres, des maçonneries, des aciers et des...

  5. Colour schemes and façade work at Drottningholm and Stockholm palaces Les couleurs des façades des palais royaux de Drottningholm et de Stockholm

    Directory of Open Access Journals (Sweden)

    Jan Lisinski

    2008-06-01

    Full Text Available Jan Lisinski présente les couleurs des façades des palais royaux de Drottningholm et de Stockholm. Les deux palais furent construits au xviie siècle mais firent l’objet de modifications par la suite. La présentation commence par un bref rappel historique centré sur les différentes couleurs utilisées pour les façades puis aborde la façon dont doivent être traitées les façades aujourd’hui. Il sera question en particulier du traitement des pierres, des plâtres, des maçonneries, des aciers et des cuivres... Les façades des deux palais sont actuellement en restauration mais les solutions mises en œuvre sont différentes. Au palais Royal de Stockholm, le plâtre est simplement nettoyé alors qu’au palais Drottningholm on refait les plâtres puis les peintures à la chaux.Jan Lisinski presents the colours of the façades of the royal palaces of Drottningholm and of Stockholm. The two palaces were constructed in the seventeenth century, but have undergone successive modifications. The presentation begins with a brief historical overview of the different colours used for the façades, then discusses the way the treatments are to be carried out. In particular, the treatment of stone, plaster, masonry, steel and copper will be examined. The façades of the two palaces are currently being restored, but the solutions for each are quite different. For the Royal Palace of Stockholm, the plaster is simply being cleaned, while at Drottningholm Palace, the plaster will be redone, then painted with lime paint.

  6. International Psychometric Validation of an EORTC Quality of Life Module Measuring Cancer Related Fatigue (EORTC QLQ-FA12).

    Science.gov (United States)

    Weis, Joachim; Tomaszewski, Krzysztof A; Hammerlid, Eva; Ignacio Arraras, Juan; Conroy, Thierry; Lanceley, Anne; Schmidt, Heike; Wirtz, Markus; Singer, Susanne; Pinto, Monica; Alm El-Din, Mohamed; Compter, Inge; Holzner, Bernhard; Hofmeister, Dirk; Chie, Wei-Chu; Czeladzki, Marek; Harle, Amelie; Jones, Louise; Ritter, Sabrina; Flechtner, Hans-Henning; Bottomley, Andrew

    2017-05-01

    The European Organisation for Research and Treatment of Cancer (EORTC) Group has developed a new multidimensional instrument measuring cancer-related fatigue to be used in conjunction with the quality of life core questionnaire (EORTC QLQ-C30). The module EORTC QLQ-FA13 assesses physical, cognitive, and emotional aspects of cancer-related fatigue. The methodology follows the EORTC guidelines for phase IV validation of modules. This paper focuses on the results of the psychometric validation of the factorial structure of the module. For validation and cross-validation confirmatory factor analysis (maximum likelihood estimation), intraclass correlation and Cronbach alpha for internal consistency were employed. The study involved an international multicenter collaboration of 11 European and non-European countries. A total of 946 patients with various tumor diagnoses were enrolled. Based on the confirmatory factor analysis, we could approve the three-dimensional structure of the module. Removing one item and reassigning the factorial mapping of another item resulted in the EORTC QLQ-FA12. For the revised scale, we found evidence supporting good local (indicator reliability ≥ 0.60, factor reliability ≥ 0.82) and global model fit (GFI t1|t2 = 0.965/0.957, CFI t1|t2 = 0.976/0.972, RMSEA t1|t2 = 0.060/0.069) for both measurement points. For each scale, test-retest reliability proved to be very good (intraclass correlation: R t1-t2 = 0.905-0.921) and internal consistency proved to be good to high (Cronbach alpha = .79-.90). Based on the former phase III module, the multidimensional structure was revised as a phase IV module (EORTC FA12) with an improved scale structure. For a comprehensive validation of the EORTC FA12, further aspects of convergent and divergent validity as well as sensitivity to change should be determined.

  7. Dimerization of complement factor H-related proteins modulates complement activation in vivo.

    Science.gov (United States)

    Goicoechea de Jorge, Elena; Caesar, Joseph J E; Malik, Talat H; Patel, Mitali; Colledge, Matthew; Johnson, Steven; Hakobyan, Svetlana; Morgan, B Paul; Harris, Claire L; Pickering, Matthew C; Lea, Susan M

    2013-03-19

    The complement system is a key component regulation influences susceptibility to age-related macular degeneration, meningitis, and kidney disease. Variation includes genomic rearrangements within the complement factor H-related (CFHR) locus. Elucidating the mechanism underlying these associations has been hindered by the lack of understanding of the biological role of CFHR proteins. Here we present unique structural data demonstrating that three of the CFHR proteins contain a shared dimerization motif and that this hitherto unrecognized structural property enables formation of both homodimers and heterodimers. Dimerization confers avidity for tissue-bound complement fragments and enables these proteins to efficiently compete with the physiological complement inhibitor, complement factor H (CFH), for ligand binding. Our data demonstrate that these CFHR proteins function as competitive antagonists of CFH to modulate complement activation in vivo and explain why variation in the CFHRs predisposes to disease.

  8. The epidermal growth factor receptor is a regulator of epidermal complement component expression and complement activation

    DEFF Research Database (Denmark)

    Abu-Humaidan, Anas H A; Ananthoju, Nageshwar; Mohanty, Tirthankar;

    2014-01-01

    The complement system is activated in response to tissue injury. During wound healing, complement activation seems beneficial in acute wounds but may be detrimental in chronic wounds. We found that the epidermal expression of many complement components was only increased to a minor extent in skin...... wounds in vivo and in cultured keratinocytes after exposure to supernatant from stimulated mononuclear cells. In contrast, the epidermal expression of complement components was downregulated in ex vivo injured skin lacking the stimulation from infiltrating inflammatory cells but with intact injury......-induced epidermal growth factor receptor (EGFR)-mediated growth factor response. In cultured primary keratinocytes, stimulation with the potent EGFR ligand, TGF-α, yielded a significant downregulation of complement component expression. Indeed, EGFR inhibition significantly enhanced the induction of complement...

  9. The dam replacing gene product enhances Neisseria gonorrhoeae FA1090 viability and biofilm formation.

    Science.gov (United States)

    Kwiatek, Agnieszka; Bacal, Pawel; Wasiluk, Adrian; Trybunko, Anastasiya; Adamczyk-Poplawska, Monika

    2014-01-01

    Many Neisseriaceae do not exhibit Dam methyltransferase activity and, instead of the dam gene, possess drg (dam replacing gene) inserted in the leuS/dam locus. The drg locus in Neisseria gonorrhoeae FA1090 has a lower GC-pairs content (40.5%) compared to the whole genome of N. gonorrhoeae FA1090 (52%). The gonococcal drg gene encodes a DNA endonuclease Drg, with GmeATC specificity. Disruption of drg or insertion of the dam gene in gonococcal genome changes the level of expression of genes as shown by transcriptome analysis. For the drg-deficient N. gonorrhoeae mutant, a total of 195 (8.94% of the total gene pool) genes exhibited an altered expression compared to the wt strain by at least 1.5 fold. In dam-expressing N. gonorrhoeae mutant, the expression of 240 genes (11% of total genes) was deregulated. Most of these deregulated genes were involved in translation, DNA repair, membrane biogenesis and energy production as shown by cluster of orthologous group analysis. In vivo, the inactivation of drg gene causes the decrease of the number of live neisserial cells and long lag phase of growth. The insertion of dam gene instead of drg locus restores cell viability. We have also shown that presence of the drg gene product is important for N. gonorrhoeae FA1090 in adhesion, including human epithelial cells, and biofilm formation. Biofilm produced by drg-deficient strain is formed by more dispersed cells, compared to this one formed by parental strain as shown by scanning electron and confocal microscopy. Also adherence assays show a significantly smaller biomass of formed biofilm (OD570 = 0.242 ± 0.038) for drg-deficient strain, compared to wild-type strain (OD570 = 0.378 ± 0.057). Dam-expressing gonococcal cells produce slightly weaker biofilm with cells embedded in an extracellular matrix. This strain has also a five times reduced ability for adhesion to human epithelial cells. In this context, the presence of Drg is more advantageous for N. gonorrhoeae biology than

  10. Neuroprotection from complement-mediated inflammatory damage.

    Science.gov (United States)

    Kulkarni, Amod P; Kellaway, Laurie A; Lahiri, Debomoy K; Kotwal, Girish J

    2004-12-01

    Several neurodegenerative disorders, such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease, are associated with inflammatory damage. The complex process of neuroinflammation involves various components of the immune system and the central nervous system. Particularly, brain astrocytes and microglial cells generate several inflammatory mediators like cytokines, leukotrienes, superoxide radicals, eicasonoids, and the components of the complement cascade. Complement plays an important role in the etiology of most of the neuroinflammatory disorders. To prevent long-term dysfunction inflammation in the central nervous system must be modulated with neuroprotective agents such as nonsteroidal anti-inflammatory drugs, steroids, phenolic thiazoles, nitrones, catechins, nitric oxide synthetase inhibitors, flavonoids, and phosphodiesterase inhibitors. Few drugs are found to be effective and their therapeutic benefit is hampered by side effects. Most of the neuroprotective agents are free radical scavengers and many inhibit only one or two aspects of inflammation. The complement inhibitory activity of most of these agents is either unknown or not established. Thus, there is doubt regarding their therapeutic value in most of the inflammatory disorders in which complement plays a major role. In this context the role of a multifunctional protein, vaccinia virus complement control protein (VCP), is quite significant as it may play a pivotal role in the treatment of several neuroinflammatory disorders. VCP is known to inhibit both complement pathways involved in inflammation. It is also known to inhibit cytokines and chemokines in inflammation. Our recent studies on rats demonstrate that VCP administration inhibits macrophage infiltration, reduces spinal cord destruction, and improves motor skills associated with spinal cord injury, establishing VCP as a strong candidate for neuroprotection. Thus, complement inhibitors such as VCP can serve as neuroprotective

  11. Complement genetics, deficiencies, and disease associations.

    Science.gov (United States)

    Mayilyan, Karine R

    2012-07-01

    The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.

  12. Protein engineering to target complement evasion in cancer.

    Science.gov (United States)

    Carter, Darrick; Lieber, André

    2014-01-21

    The complement system is composed of soluble factors in plasma that enhance or "complement" immune-mediated killing through innate and adaptive mechanisms. Activation of complement causes recruitment of immune cells; opsonization of coated cells; and direct killing of affected cells through a membrane attack complex (MAC). Tumor cells up-regulate complement inhibitory factors - one of several strategies to evade the immune system. In many cases as the tumor progresses, dramatic increases in complement inhibitory factors are found on these cells. This review focuses on the classic complement pathway and the role of major complement inhibitory factors in cancer immune evasion as well as on how current protein engineering efforts are being employed to increase complement fixing or to reverse complement resistance leading to better therapeutic outcomes in oncology. Strategies discussed include engineering of antibodies to enhance complement fixation, antibodies that neutralize complement inhibitory proteins as well as engineered constructs that specifically target inhibition of the complement system.

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

    Science.gov (United States)

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

    2015-10-01

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

  14. Solar Flare Measurements with STIX and MiSolFA

    CERN Document Server

    Casadei, Diego

    2014-01-01

    Solar flares are the most powerful events in the solar system and the brightest sources of X-rays, often associated with emission of particles reaching the Earth and causing geomagnetic storms, giving problems to communication, airplanes and even black-outs. X-rays emitted by accelerated electrons are the most direct probe of solar flare phenomena. The Micro Solar-Flare Apparatus (MiSolFA) is a proposed compact X-ray detector which will address the two biggest issues in solar flare modeling. Dynamic range limitations prevent simultaneous spectroscopy with a single instrument of all X-ray emitting regions of a flare. In addition, most X-ray observations so far are inconsistent with the high anisotropy predicted by the models usually adopted for solar flares. Operated at the same time as the STIX instrument of the ESA Solar Orbiter mission, at the next solar maximum (2020), they will have the unique opportunity to look at the same flare from two different directions: Solar Orbiter gets very close to the Sun wit...

  15. Façade fires in Swedish school buildings

    Directory of Open Access Journals (Sweden)

    Johansson Nils

    2013-11-01

    Full Text Available Fires outside school buildings caused by arson are a major problem in Sweden. The initial fire source can involve rubbish or other types of combustibles that can be found at or sometimes brought to the school. As the external fire develops the flames will extend along the façade. If the building is a one-story building, which is a common construction in Swedish school buildings, the fire can spread to the attic and further on to the rest of the building. A large research project was initiated in 2008 by the Swedish Fire Research Board in order to reduce the number and consequences of arson fires in school buildings. In this paper an evaluation of some technical systems that can be used to mitigate consequences of exterior fires is presented. The evaluation includes a literature review, experimental studies and a cost-benefit analysis. The study showed that some systems have clear cost-benefit advantages for the protection of school buildings in places where a high fire frequency can be expected.

  16. Blood compatibility of a ferulic acid (FA)-eluting PHBHHx system for biodegradable magnesium stent application.

    Science.gov (United States)

    Zhang, Erlin; Shen, Feng

    2015-01-01

    Magnesium stent has shown potential application as a new biodegradable stent. However, the fast degradation of magnesium stent limited its clinic application. Recently, a biodegradable and drug-eluting coating system was designed to prevent magnesium from fast degradation by adding ferulic acid (FA) in poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) by a physical method. In vitro study has demonstrated that the FA-eluting system exhibited strong promotion to the endothelialization, which might be a choice for the stent application. In this paper, the hemolysis rate, the plasma recalcification time (PRT), the plasma prothrombin time (PT) and the kinetic clotting time of the FA-eluting films were investigated and the platelet adhesion was observed in order to assess the blood compatibility of the FA-eluting PHBHHx films in comparison with PHBHHx film. The results have shown that the addition of FA had no influence on the hemolysis, but prolonged PRT, PT and the clotting time and reduced the platelet adhesion and activation, displaying that the FA-eluting PHBHHx exhibited better blood compatibility than PHBHHx. In addition, the effect of alkali treatment on the blood compatibility of FA-eluting PHBHHx was also studied. It was indicated that alkali treatment had no effect on the hemolysis and the coagulation time, but enhanced slightly the platelet adhesion. All these demonstrated that FA-eluting PHBHHx film had good blood compatibility and might be a candidate surface coating for the biodegradable magnesium stent.

  17. Identification and Characterization of FaFT1: A Homolog of FLOWERING LOCUS T from Strawberry

    Directory of Open Access Journals (Sweden)

    Hengjiu Lei

    2015-05-01

    Full Text Available FLOWERING LOCUS T(FT -like genes play crucial roles in flowering transition in several plant species. In this study, a homolog of FT, designated as FaFT1, was isolated and characterized from strawberry. The open reading frame of FaFT1 was 531 bp, encoding a protein of 176 amino acids. Phylogenetic and sequence analysis showed that the FaFT1 protein contained the conservation of Tyr84 and Gln139, as well as the highly conserved amino acid sequences LGRQTVYAPGWRQN and LYN and that it was a member of the FT-like genes of dicots. Subcellular localization analysis revealed that the FaFT1 protein mainly localized in the nuclei of the Arabidopsis protoplasts. FaFT1 was highly expressed in strawberry mature leaves and its expression level decreased under floral induction conditions. Additionally, FaFT1 expression exhibited diurnal circadian rhythm both under SD and LD conditions. Over expression of FaFT1 in wild-type Arabidopsis caused early flowering. Taken together, these results indicate that FaFT1 is a putative FT homolog in strawberry, acting as a floral promoter in Arabidopsis.

  18. FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Abdullah Mahmood; Singh, Thiyam Ramsing [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH 45229 (United States); Meetei, Amom Ruhikanta, E-mail: Ruhikanta.Meetei@cchmc.org [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH 45229 (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States)

    2009-07-31

    Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA-crosslinking agents. Eight FA proteins (FANCA, -B, -C, -E, -F, -G, -L and -M) and three non-FA proteins (FAAP100, FAAP24 and HES1) form the FA nuclear core complex that is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. The other three FA proteins, FANCD1/BRCA2, FANCJ/BACH1/BRIP1 and FANCN/PALB2, act in parallel or downstream of the FANCD2-FANCI dimer. Despite the isolation and characterization of several FA proteins, the mechanism by which these proteins protect cells from DNA interstrand crosslinking agents has been unclear. This is because a majority of the FA proteins lack any recognizable functional domains that can provide insight into their function. The recently discovered FANCM (Hef) and FANCJ (BRIP1/BACH1) proteins contain helicase domains, providing potential insight into the role of FA proteins in DNA repair. FANCM with its partner, FAAP24, and FANCJ bind and metabolize a variety of DNA substrates. In this review, we focus on the discovery, structure, and function of the FANCM-FAAP24 and FANCJ proteins.

  19. Arsenic exposure disrupts the normal function of the FA/BRCA repair pathway.

    Science.gov (United States)

    Peremartí, Jana; Ramos, Facundo; Marcos, Ricard; Hernández, Alba

    2014-11-01

    Chronic arsenic exposure is known to enhance the genotoxicity/carcinogenicity of other DNA-damaging agents by inhibiting DNA repair activities. Interference with nucleotide excision repair and base excision repair are well documented, but interactions with other DNA repair pathways are poorly explored so far. The Fanconi anemia FA/BRCA pathway is a DNA repair mechanism required for maintaining genomic stability and preventing cancer. Here, interactions between arsenic compounds and the FA/BRCA pathway were explored by using isogenic FANCD2(-/-) (FA/BRCA-deficient) and FANCD2(+/+) (FA/BRCA-corrected) human fibroblasts. To study whether arsenic disrupts the normal FA/BRCA function, FANCD2(+/+) cells were preexposed to subtoxic concentrations of the trivalent arsenic compounds methylarsonous acid (MMA(III)) and arsenic trioxide (ATO) for 2 weeks. The cellular response to mitomicin-C, hydroxyurea, or diepoxybutane, typical inducers of the studied pathway, was then evaluated and compared to that of FANCD2(-/-) cells. Our results show that preexposure to the trivalent arsenicals MMA(III) and ATO induces in corrected cells, a cellular FA/BRCA-deficient phenotype characterized by hypersensitivity, enhanced accumulation in the G2/M compartment and increased genomic instability--measured as micronuclei. Overall, our data demonstrate that environmentally relevant arsenic exposures disrupt the normal function of the FA/BRCA activity, supporting a novel source of arsenic co- and carcinogenic effects. This is the first study linking arsenic exposure with the FA/BRCA DNA repair pathway.

  20. Complement C3 in Bernese Mountain dogs.

    Science.gov (United States)

    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.

  1. Inhibition of Complement Retards Ankylosing Spondylitis Progression

    Science.gov (United States)

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

    2016-01-01

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

  2. Does Fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials?

    DEFF Research Database (Denmark)

    Jensen, Charlotte Floridon; Jensen, Charlotte Harken; Thorsen, Poul

    2000-01-01

    in the subcellular localisation indicating differential post-translational/post-transcriptional modifications during fetal development. FA1 may be a new marker of cellular subtypes with a regenerative potential and of specific cells with endocrine or neuroendocrine functions. Udgivelsesdato: 2000-Aug......, the localisation of FA1/dlk was analysed in embryonic and fetal tissues between week 5 to 25 of gestation and related to germinal origin and development. FA1 was observed in endodermally derived hepatocytes, glandular cells of the pancreas anlage, and in respiratory epithelial cells. FA1 was also present...... in mesodermally derived cells of the renal proximal tubules, adrenal cortex, Leydig and Hilus cells of the testes and ovaries, fetal chondroblasts, and skeletal myotubes. Ectodermally derived neuro- and adenohypophysial cells, cells in the floor of the 3rd ventricle and plexus choroideus were also FA1 positive...

  3. Physiological Effect of New FA Antitranspirant Application on Winter Wheat at Ear Filling Stage

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The physiological effect of new FA antitranspirant on winter wheat was studied by field trial. The new FA antitranspirant was sprayed at ear filling stage, using the following concentrations: 0.5, 1.0, 1.5 and 2.0 mL L-1.The results indicated that new FA antitranspirant increased nitrate reductase activity (NRA), free proline content, chlorophyll content and water content of leaf, thus drought stress can be mitigated. The new FA antitranspirant increased photosynthesis, enlarged stomatal conductance and reduced transpiration rate, thus led to growth stimulation and water loss reduction. New FA antitranspirant caused an increase of grain yield by 7.2%, under the optimal concentration 1.5 mL L-1.

  4. FaQR, required for the biosynthesis of the strawberry flavor compound 4-hydroxy-2,5-dimethyl-3(2H)-furanone, encodes an enone oxidoreductase.

    Science.gov (United States)

    Raab, Thomas; López-Ráez, Juan Antonio; Klein, Dorothée; Caballero, Jose Luis; Moyano, Enriqueta; Schwab, Wilfried; Muñoz-Blanco, Juan

    2006-04-01

    The flavor of strawberry (Fragaria x ananassa) fruit is dominated by an uncommon group of aroma compounds with a 2,5-dimethyl-3(H)-furanone structure. We report the characterization of an enzyme involved in the biosynthesis of 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF; Furaneol), the key flavor compound in strawberries. Protein extracts were partially purified, and the observed distribution of enzymatic activity correlated with the presence of a single polypeptide of approximately 37 kD. Sequence analysis of two peptide fragments showed total identity with the protein sequence of a strongly ripening-induced, auxin-dependent putative quinone oxidoreductase, Fragaria x ananassa quinone oxidoreductase (FaQR). The open reading frame of the FaQR cDNA consists of 969 bp encoding a 322-amino acid protein with a calculated molecular mass of 34.3 kD. Laser capture microdissection followed by RNA extraction and amplification demonstrated the presence of FaQR mRNA in parenchyma tissue of the strawberry fruit. The FaQR protein was functionally expressed in Escherichia coli, and the monomer catalyzed the formation of HDMF. After chemical synthesis and liquid chromatography-tandem mass spectrometry analysis, 4-hydroxy-5-methyl-2-methylene-3(2H)-furanone was confirmed as a substrate of FaQR and the natural precursor of HDMF. This study demonstrates the function of the FaQR enzyme in the biosynthesis of HDMF as enone oxidoreductase and provides a foundation for the improvement of strawberry flavor and the biotechnological production of HDMF.

  5. The Lectin Pathway of Complement and Biocompatibility

    DEFF Research Database (Denmark)

    Hein, Estrid; Garred, Peter

    2015-01-01

    In modern health technologies the use of biomaterials in the form of stents, haemodialysis tubes, artificial implants, bypass circuits etc. is rapidly expanding. The exposure of synthetic, foreign surfaces to the blood and tissue of the host, calls for strict biocompatibility in respect to contac...... been broadly documented. However, the specific role of lectin pathway and the pattern recognition molecules initiating the pathway has only been transiently investigated. Here we review the current data on the field....... activation, the coagulation system and the complement system. The complement system is an important part of the initial immune response and consists of fluid phase molecules in the blood stream. Three different activation pathways can initiate the complement system, the lectin, the classical...

  6. The Complement System in Lupus Nephritis.

    Science.gov (United States)

    Birmingham, Daniel J; Hebert, Lee A

    2015-09-01

    The complement system is composed of a family of soluble and membrane-bound proteins that historically has been viewed as a key component of the innate immune system, with a primary role of providing a first-line defense against microorganisms. Although this role indeed is important, complement has many other physiological roles, including the following: (1) influencing appropriate immune responses, (2) disposing of waste in the circulation (immune complexes, cellular debris), and (3) contributing to damage of self-tissue through inflammatory pathways. These three roles are believed to be significant factors in the pathogenesis of systemic lupus erythematosus, particularly its renal manifestation (lupus nephritis), contributing both protective and damaging effects. In this review, we provide an overview of the human complement system and its functions, and discuss its intricate and seemingly contradictory roles in the pathogenesis of lupus nephritis.

  7. Extremal Matching Energy of Complements of Trees

    Directory of Open Access Journals (Sweden)

    Wu Tingzeng

    2016-08-01

    Full Text Available Gutman and Wagner proposed the concept of the matching energy which is defined as the sum of the absolute values of the zeros of the matching polynomial of a graph. And they pointed out that the chemical applications of matching energy go back to the 1970s. Let T be a tree with n vertices. In this paper, we characterize the trees whose complements have the maximal, second-maximal and minimal matching energy. Furthermore, we determine the trees with edge-independence number p whose complements have the minimum matching energy for p = 1, 2, . . . , [n/2]. When we restrict our consideration to all trees with a perfect matching, we determine the trees whose complements have the second-maximal matching energy.

  8. Supramolecular Control over Split-Luciferase Complementation.

    Science.gov (United States)

    Bosmans, Ralph P G; Briels, Jeroen M; Milroy, Lech-Gustav; de Greef, Tom F A; Merkx, Maarten; Brunsveld, Luc

    2016-07-25

    Supramolecular split-enzyme complementation restores enzymatic activity and allows for on-off switching. Split-luciferase fragment pairs were provided with an N-terminal FGG sequence and screened for complementation through host-guest binding to cucurbit[8]uril (Q8). Split-luciferase heterocomplex formation was induced in a Q8 concentration dependent manner, resulting in a 20-fold upregulation of luciferase activity. Supramolecular split-luciferase complementation was fully reversible, as revealed by using two types of Q8 inhibitors. Competition studies with the weak-binding FGG peptide revealed a 300-fold enhanced stability for the formation of the ternary heterocomplex compared to binding of two of the same fragments to Q8. Stochiometric binding by the potent inhibitor memantine could be used for repeated cycling of luciferase activation and deactivation in conjunction with Q8, providing a versatile module for in vitro supramolecular signaling networks.

  9. Applying complement therapeutics to rare diseases.

    Science.gov (United States)

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

    2015-12-01

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

  10. The extracellular RNA complement of Escherichia coli.

    Science.gov (United States)

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

    2015-01-21

    The secretion of biomolecules into the extracellular milieu is a common and well-conserved phenomenon in biology. In bacteria, secreted biomolecules are not only involved in intra-species communication but they also play roles in inter-kingdom exchanges and pathogenicity. To date, released products, such as small molecules, DNA, peptides, and proteins, have been well studied in bacteria. However, the bacterial extracellular RNA complement has so far not been comprehensively characterized. Here, we have analyzed, using a combination of physical characterization and high-throughput sequencing, the extracellular RNA complement of both outer membrane vesicle (OMV)-associated and OMV-free RNA of the enteric Gram-negative model bacterium Escherichia coli K-12 substrain MG1655 and have compared it to its intracellular RNA complement. Our results demonstrate that a large part of the extracellular RNA complement is in the size range between 15 and 40 nucleotides and is derived from specific intracellular RNAs. Furthermore, RNA is associated with OMVs and the relative abundances of RNA biotypes in the intracellular, OMV and OMV-free fractions are distinct. Apart from rRNA fragments, a significant portion of the extracellular RNA complement is composed of specific cleavage products of functionally important structural noncoding RNAs, including tRNAs, 4.5S RNA, 6S RNA, and tmRNA. In addition, the extracellular RNA pool includes RNA biotypes from cryptic prophages, intergenic, and coding regions, of which some are so far uncharacterised, for example, transcripts mapping to the fimA-fimL and ves-spy intergenic regions. Our study provides the first detailed characterization of the extracellular RNA complement of the enteric model bacterium E. coli. Analogous to findings in eukaryotes, our results suggest the selective export of specific RNA biotypes by E. coli, which in turn indicates a potential role for extracellular bacterial RNAs in intercellular communication. © 2015 The

  11. Activation of Complement Following Total Hip Replacement.

    Science.gov (United States)

    Thordardottir, S; Vikingsdottir, T; Bjarnadottir, H; Jonsson, H; Gudbjornsson, B

    2016-03-01

    The aim of this study was to investigate whether complement activation, via the classical and alternative pathways, occurs following a cemented total hip replacement (THR) surgery due to osteoarthritis. Blood samples were collected systematically from 12 patients - six male and six women, with a median age of 75 (range: 59-90 years) - preoperatively, 6 h post-operatively and on the first, second and third post-operative day. Total function of classical (CH50) and alternative pathways (AH50) was evaluated, along with the determination of serum concentrations of the complement proteins C3, C4, C3d, the soluble terminal complement complex (sTCC) sC5b-9, as well as C-reactive protein (CRP) and albumin. Measurements of CRP and albumin levels elucidated a marked inflammatory response following the operation. The CH50, AH50 and C3 and C4 levels were significantly lower 6 h after the surgery compared with the preoperative levels, but elevated above the preoperative levels during the following 3 days. The complement activation product C3d levels increased continually during the whole observation period, from 13.5 AU/ml (range: 8-19 AU/ml) preoperative to 20 AU/ml (range: 12-34 AU/ml) on the third post-operative day. Furthermore, we observed an increase in the sC5b-9 levels between the preoperative and the third post-operative day. These results demonstrate a significant activation of the complement system following cemented THR. Further studies are needed to elucidate the time frame and the pathogenic role of this observed complement activation.

  12. Complement-mediated solubilization of immune complexes. Solubilization inhibition and complement factor levels in SLE patients

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, Ivan; Kappelgaard, E;

    1984-01-01

    Thirty-two of 36 serum samples from 19 SLE patients showed reduced capacity to mediate complement-dependent solubilization of immune complexes (IC). SLE patients with nephritis exerted the lowest complement-mediated solubilization capacity (CMSC) whereas sera from patients with inactive disease g...

  13. L^2-Betti numbers of hypersurface complements

    CERN Document Server

    Maxim, Laurentiu

    2012-01-01

    In \\cite{DJL07} it was shown that if $\\scra$ is an affine hyperplane arrangement in $\\C^n$, then at most one of the $L^2$--Betti numbers $b_i^{(2)}(\\C^n\\sm \\scra,\\id)$ is non--zero. In this note we prove an analogous statement for complements of complex affine hyperurfaces in general position at infinity. Furthermore, we recast and extend to this higher-dimensional setting results of \\cite{FLM,LM06} about $L^2$--Betti numbers of plane curve complements.

  14. HUS and the case for complement.

    Science.gov (United States)

    Conway, Edward M

    2015-10-29

    Hemolytic-uremic syndrome (HUS) is a thrombotic microangiopathy that is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Excess complement activation underlies atypical HUS and is evident in Shiga toxin-induced HUS (STEC-HUS). This Spotlight focuses on new knowledge of the role of Escherichia coli-derived toxins and polyphosphate in modulating complement and coagulation, and how they affect disease progression and response to treatment. Such new insights may impact on current and future choices of therapies for STEC-HUS.

  15. Complement inhibitory proteins expression in placentas of thrombophilic women Complement inhibitory proteins expression in placentas of thrombophilic women

    Directory of Open Access Journals (Sweden)

    Przemysław Krzysztof Wirstlein

    2012-10-01

    Full Text Available Factors controlling complement activation appear to exert a protective effect on pregnancy. This is
    particularly important in women with thrombophilia. The aim of this study was to determine the transcript and
    protein levels of complement decay-accelerating factor (DAF and membrane cofactor protein (MCP in the
    placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry staining
    of inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women.
    Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia.
    The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Western
    blot. We observed a higher transcript (p < 0.05 and protein (p < 0.001 levels of DAF and MCP in the placentas
    of thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblast
    membranes, but the assessment of staining in all groups did not differ. The observed higher expression level of
    proteins that control activation of complement control proteins is only seemingly contradictory to the changes
    observed for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changes
    associated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas is
    an effect of proinflammatory cytokines, which accompanies thrombophilia, is probable.Factors controlling complement activation appear to exert a protective effect on pregnancy. This is
    particularly important in women with thrombophilia. The aim of this study was to determine the transcript and
    protein levels of complement decay-accelerating factor (DAF and membrane cofactor protein (MCP in the
    placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry

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

    Science.gov (United States)

    Risitano, Antonio M; Marotta, Serena

    2016-06-01

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

  17. Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses.

    Directory of Open Access Journals (Sweden)

    Guido Moll

    Full Text Available Infusion of human third-party mesenchymal stromal cells (MSCs appears to be a promising therapy for acute graft-versus-host disease (aGvHD. To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46 and DAF (CD55, but were protected from complement lysis via expression of protectin (CD59. Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells.

  18. Ex vivo complement protein adsorption on positively and negatively charged cellulose dialyser membranes.

    Science.gov (United States)

    Mahiout, A; Matata, B M; Vienken, J; Courtney, J M

    1997-05-01

    An ex vivo test system was used to measure complement protein C3 and factor B adsorption onto small dialyser modules made from regenerated and modified cellulosic hollow fibre membranes in which positive diethylaminoethyl (DEAE) or negative carboxymethyl (CM) groups were introduced into the cellulose matrix. The extracorporeal system, which included test-dialysers and the dialysis environment, allowed the use of labelled proteins without contaminating the blood donors which were connected in an open-loop fashion to the extracorporeal test system. The modules were removed at selected time points from the extracorporeal system for radioactivity counting. The results were used to evaluate the mechanisms involved in complement reactions to foreign surfaces. The system therefore allowed the analysis of complement protein adsorption occurring in the dialyser modules and its relationship to the complement generation rate in the extracorporeal system to be evaluated. It was possible to demonstrate that significant complement C3 and factor B adsorption occurred in the test modules made of cellulosic membranes. Complement adsorption as a function of the pH and the release reaction of the adsorbed C3 and factor B after membrane blood perfusion were therefore found to be variable according to the cellulosic membrane type and the presence of positive or negative charged groups within the cellulose matrix. The data obtained from the ex vivo model therefore provided additional evidence on the discussion of the mechanisms involved in the increased complement activation by regenerated cellulose and in its attenuation by DEAE- or CM-modified cellulose.

  19. Oceanographic profile data collected from CTD casts aboard FA2806 and NOAA Ship FAIRWEATHER as part of project OPR-Q328-FA-15 in the Bering Sea on 2015-07-08 (NCEI Accession 0130934)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0130934 includes physical and profile data collected aboard the FA2806 and NOAA Ship FAIRWEATHER during project OPR-Q328-FA-15 in the Bering Sea on...

  20. Graphs whose complement and square are isomorphic

    DEFF Research Database (Denmark)

    Milanic, M.; Pedersen, Anders Sune; Pellicer, D.;

    2014-01-01

    We study square-complementary graphs, that is, graphs whose complement and square are isomorphic. We prove several necessary conditions for a graph to be square-complementary, describe ways of building new square-complementary graphs from existing ones, construct infinite families of square...

  1. Cross-Cultural Analysis on Complements

    Institute of Scientific and Technical Information of China (English)

    刘恒

    2014-01-01

    Nativized varieties of English must reflect native pragmatic norms and cultural conventions. Complements, as a polite social behavior, is analyzed from the perspective of Chinese English speaker and American English speaker to emphasize the im-portance of the cross-cultural differences in pragmatic uses.

  2. Spacelab carrier complement thermal design and performance

    Science.gov (United States)

    Bancroft, S.; Key, R.; Kittredge, S.

    1992-01-01

    The present discussion of the Spacelab carrier complement, which encompasses a Module Carrier, a Module-Pallet Carrier, and a Multiplexer/Demultiplexer Pallet, gives attention to both active and passive thermal performance capabilities, and presents ground testing and analytical results obtained to date. An account is given of the prospective use of a Spacelab Multipurpose Experiment Support Structure.

  3. 21 CFR 866.5240 - Complement components immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement components immunological test system....5240 Complement components immunological test system. (a) Identification. A complement components... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids,...

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

    Science.gov (United States)

    Fazeli, Fatemeh; Shokrpour, Nasrin

    2012-01-01

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

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

    Science.gov (United States)

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

    2009-01-02

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

  6. Non-specific adsorption of complement proteins affects complement activation pathways of gold nanomaterials.

    Science.gov (United States)

    Quach, Quang Huy; Kah, James Chen Yong

    2017-04-01

    The complement system is a key humoral component of innate immunity, serving as the first line of defense against intruders, including foreign synthetic nanomaterials. Although gold nanomaterials (AuNMs) are widely used in nanomedicine, their immunological response is not well understood. Using AuNMs of three shapes commonly used in biomedical applications: spherical gold nanoparticles, gold nanostars and gold nanorods, we demonstrated that AuNMs activated whole complement system, leading to the formation of SC5b-9 complex. All three complement pathways were simultaneously activated by all the AuNMs. Recognition molecules of the complement system interacted with all AuNMs in vitro, except for l-ficolin, but the correlation between these interactions and corresponding complement pathway activation was only observed in the classical and alternative pathways. We also observed the mediating role of complement activation in cellular uptake of all AuNMs by human U937 promonocytic cells, which expresses complement receptors. Taken together, our results highlighted the potential immunological challenges for clinical applications of AuNMs that were often overlooked.

  7. Role of complement and complement regulatory proteins in the complications of diabetes.

    Science.gov (United States)

    Ghosh, Pamela; Sahoo, Rupam; Vaidya, Anand; Chorev, Michael; Halperin, Jose A

    2015-06-01

    It is well established that the organ damage that complicates human diabetes is caused by prolonged hyperglycemia, but the cellular and molecular mechanisms by which high levels of glucose cause tissue damage in humans are still not fully understood. The prevalent hypothesis explaining the mechanisms that may underlie the pathogenesis of diabetes complications includes overproduction of reactive oxygen species, increased flux through the polyol pathway, overactivity of the hexosamine pathway causing intracellular formation of advanced glycation end products, and activation of protein kinase C isoforms. In addition, experimental and clinical evidence reported in past decades supports a strong link between the complement system, complement regulatory proteins, and the pathogenesis of diabetes complications. In this article, we summarize the body of evidence that supports a role for the complement system and complement regulatory proteins in the pathogenesis of diabetic vascular complications, with specific emphasis on the role of the membrane attack complex (MAC) and of CD59, an extracellular cell membrane-anchored inhibitor of MAC formation that is inactivated by nonenzymatic glycation. We discuss a pathogenic model of human diabetic complications in which a combination of CD59 inactivation by glycation and hyperglycemia-induced complement activation increases MAC deposition, activates pathways of intracellular signaling, and induces the release of proinflammatory, prothrombotic cytokines and growth factors. Combined, complement-dependent and complement-independent mechanisms induced by high glucose promote inflammation, proliferation, and thrombosis as characteristically seen in the target organs of diabetes complications.

  8. Desalination of Walls and Façades

    Science.gov (United States)

    Wedekind, W.; Jáuregui Arreola, K.; Siegesmund, S.

    2012-04-01

    For large monumental objects like walls and façades, the common technique of applying poultices for desalination often are not effective. This practice is neither cost effective nor does it lead to the desired result of desalination. To manage the conservation and desalination of these kinds of objects, several sprinkling techniques are known and have been applied on historical objects. For example, in the wooden warship Vasa, which was excavated from the sea bottom in Stockholm/Sweden, a sprinkling method was applied in 1961 for conservation and desalination. A sprinkling method to desalinate porous mineral materials will be presented using three different case studies: the rock cut monument no. 825 in Petra/Jordan, the medieval monastary church of the former Franziscan convent in Zeitz/Germany and the baroque monastary church Santa Monica in Guadalajara/Mexico. Before to start with practical conservation, the material- and petropysical properties, focoussed on water transport properties, like porosity, pore size distribution, water uptake and drying rate were investigadet. Diagnostic investigations on the objects included the mapping of deterioration, moister content measurements and salt accumulation determined by borehole cuts samples at depth. In the sprinkling method water is sprayed onto the wall surface through nozzels arranged in a modular grid. Depending on the sprinkling duration, a small or a large amount of water seeps into the porous materials, whereby the depth penetration can be adjusted accordingly. The water not absorbed by the stone runs off the facade and can be collected in liter amounts and tested by electrical conductivity with respect to the dissolved substances. After the drying of the wall's surface and the accumulation of salt at the material's surface, the procedure is repeated. For each subsequent washing a lower content of salt should be brought to the surface. Step by step the salt concentration will eventually decrease to almost

  9. Disrupting Façades of Clarity in the Teaching and Learning of Qualitative Research

    Directory of Open Access Journals (Sweden)

    Melissa Contreras-McGavin

    2013-02-01

    Full Text Available In this article we examine two methodological façades of clarity that commonly shroud critical qualitative educational inquiry. More specifically, we interrogate discussions of reflexivity and positionality and explore the ways in which methodology curricula and instructional practices perpetuate façades of clarity, or a false sense of coherence, ultimately undermining the transformative potential of critical educational research. We identify specific pedagogical opportunities, spaces, and strategies for dismantling these façades and offer ways to reconstruct methodological practices congruent with the emancipatory and empowering aims of critical scholarship.

  10. Estrogen inhibits Dlk1/FA1 production: A potential mechanism for estrogen effects on bone turnover

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Bay-Jensen, Anne-Christine; Srinivasan, Bhuma;

    2011-01-01

    We have recently identified delta-like 1/fetal antigen 1 (Dlk1/FA1) as a novel regulator of bone mass that functions to mediate bone loss under estrogen deficiency in mice. In this report, we investigated the effects of estrogen (E) deficiency and E replacement on serum (s) levels of Dlk1/FA1 (s...... estrogen-replacement therapy (ERT, n = 166). s-Dlk1/FA1 and s-CTX were elevated in postmenopausal E-deficient women compared with premenopausal E-replete women (both p ...

  11. Cloning and molecular characterization of complement component 1 inhibitor (C1INH) and complement component 8β (C8β) in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    He, Anyuan; Yang, Jie; Tang, Shoujie; Wang, Chenghui

    2013-09-01

    Nile tilapia (Oreochromis niloticus), one of the most important groups of food fishes in the world, has frequently suffered from serious challenge from pathogens in recent years. Immune responses of Nile tilapia should be understood to protect the aquaculture industry of this fish. The complement system has an important function in recognizing bacteria, opsonizing these pathogens by phagocytes, or killing them by direct lysis. In this study, two Nile tilapia complement component genes, complement component 1 inhibitor (C1INH) and complement component 8β subunit (C8β), were cloned and their expression characteristics were analyzed. C1INH cDNA was found containing a 1791 bp open reading frame (ORF) encoding a putative protein with 597 amino acids, a 101 bp 5'-untranslated region (UTR) and a 236 bp 3'-UTR. The predicted protein structure for this gene consisted of two Ig-like domains and glycosyl hydrolase family-9 active site signature 2. The C8β cDNA consisted of a 1761 bp ORF encoding 587 amino acids, a 15 bp 5'-UTR and a 170 bp 3'-UTR. The predicted protein of C8β contained three motifs, thrombospondin type-1 repeat, membrane attack complex/perforin domain, and LDL-receptor class A. Expression analysis revealed that these two complement genes were highly expressed in the liver, however, were weakly expressed in the gill, heart, brain, kidney, intestine, spleen and dorsal muscle tissues. The present study provided insights into the complement system and immune functions of Nile tilapia.

  12. Certification of Charpy V-notch Reference Test Pieces of 80 J Nominal Absorbed Energy (ERM®-FA015x and ERM®-FA015y)

    OpenAIRE

    LAMBERTY MARIE ANDREE; Dean, Alan; Roebben, Gert

    2011-01-01

    This certification report describes the processing and characterisation of ERM®-FA015x and ERM®-FA015y, two batches of Charpy V-notch certified reference test pieces. Sets of five of these test pieces are used for the verification of pendulum impact test machines according to EN 10045-2 (Charpy impact test on metallic materials, Part 2. Method for the verification of impact testing machines) or according to ISO 148-2 (Metallic materials - Charpy pendulum impact test – Part 2: Verification of ...

  13. Discrimination between Host and Pathogens by the Complement System

    OpenAIRE

    Pangburn, Michael K.; Ferreira, Viviana P.; Cortes, Claudio

    2008-01-01

    Pathogen-specific complement activation requires direct recognition of pathogens and/or the absence of complement control mechanisms on their surfaces. Antibodies direct complement activation to potential pathogens recognized by the cellular innate and adaptive immune systems. Similarly, the plasma proteins MBL and ficolins direct activation to microorganisms expressing common carbohydrate structures. The absence of complement control proteins permits amplification of complement by the altern...

  14. Complement Component C3 Binds to Activated Normal Platelets without Preceding Proteolytic Activation and Promotes Binding to Complement Receptor 1

    NARCIS (Netherlands)

    O.A. Hamad; P.H. Nilsson; D. Wouters; J.D. Lambris; K.N. Ekdahl; B. Nilsson

    2010-01-01

    It has been reported that complement is activated on the surface of activated platelets, despite the presence of multiple regulators of complement activation. To reinvestigate the mechanisms by which activated platelets bind to complement components, the presence of complement proteins on the surfac

  15. Early complement components in Alzheimer's disease brains.

    Science.gov (United States)

    Veerhuis, R; Janssen, I; Hack, C E; Eikelenboom, P

    1996-01-01

    Activation products of the early complement components C1, C4 and C3 can be found colocalized with diffuse and fibrillar beta-amyloid (beta/A4) deposits in Alzheimer's disease (AD) brains. Immunohistochemically, C1-esterase inhibitor (C1-Inh) and the C1 subcomponents C1s and C1r can not, or only occasionally, be detected in plaques or in astrocytes. The present finding that C1q, C1s and C1-Inh mRNA are present in both AD and control brains suggests that the variable immunohistochemical staining results for C1r, C1s and C1-Inh are due to a rapid consumption, and that the inability to detect C1s, C1r or C1-Inh is probably due to the dissociation of C1s-C1-Inh and C1r-C1-Inh complexes from the activator-bound C1q into the fluid phase. Employing monoclonal antibodies specific for different forms of C1-Inh, no complexed C1-Inh could be found, whereas inactivated C1-Inh seems to be present in astrocytes surrounding beta/A4 plaques in AD brains. These findings, together with our finding (using reverse transcriptase-polymerase chain reaction) that C1-Inh is locally produced in the brain, suggest that in the brain complement activation at the C1 level is regulated by C1-Inh. Immunohistochemically, no evidence for the presence of the late complement components C5, C7 and C9, or of the membrane attack complex (MAC), was found in beta/A4 plaques. In contrast to the mRNA encoding the early components, that of the late complement components appears to be hardly detectable (C7) or absent (C9). Thus, without blood-brain-barrier impairment, the late complement components are probably present at too low a concentration to allow the formation of the MAC, which is generally believed to be responsible for at least some of the neurodegenerative effects observed in AD. Therefore, the present findings support the idea that in AD, complement does not function as an inflammatory mediator through MAC formation, but through the action of early component activation products.

  16. Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

    Directory of Open Access Journals (Sweden)

    Anne Rosbjerg

    2017-05-01

    Full Text Available The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex. In addition, various regulatory proteins are important for controlling the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system. Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination.

  17. Data of evolutionary structure change: 1J3FA-1RSEA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1J3FA-1RSEA 1J3F 1RSE A A MVLSEGEWQLVLHVWAKVEADVAGHGQDILIRLFKSHPE...TLEKFDRFKHLKTEAEMKASEDLKKHGVTVLTGLGAILKKKGHHEAELKPLAQSHAT--KIPIKYLEFISEAIIHVLHSRHPGDFGADAQGAMNKALELFRKDIAAKY...pdbChain>A 1RSEA QDHATKHKIPIK

  18. Colour schemes and façade work at Drottningholm and Stockholm palaces

    OpenAIRE

    2008-01-01

    Jan Lisinski présente les couleurs des façades des palais royaux de Drottningholm et de Stockholm. Les deux palais furent construits au xviie siècle mais firent l’objet de modifications par la suite. La présentation commence par un bref rappel historique centré sur les différentes couleurs utilisées pour les façades puis aborde la façon dont doivent être traitées les façades aujourd’hui. Il sera question en particulier du traitement des pierres, des plâtres, des maçonneries, des aciers et des...

  19. Data of evolutionary structure change: 1B0FA-1O37A [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available -GYDPV >EEE - > ATOM 556 CA ARG ...ntryIDChain>1O37A KSIVHPSYNSN >EEEEE ...> 1B0FA LGRNR-GIASV > - ...KSSGTSYPDV > > ATOM 1849 CA THR ...tryIDChain> AHCYK----SGIQV >GGG ---- EEE>

  20. Data of evolutionary structure change: 1ANFA-3F5FA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ANFA-3F5FA 1ANF 3F5F A A KIEEGKLVIWINGDKGYNGLAEVGKKFEKDTGIKVTVEH...TGKKSHLRKTTEKKLPTAATIAKLQQSEIWKMENEFYEFALEQFQFVRAHAVREKDGELYILAQNFFYEKIYPK...HHHHHHHHHHHHH EEEEE EEE EVID> 0 1ANF A 1ANFA 3.7251410484313965 EVID>EVID> 1 <

  1. Adenovirus Activates Complement by Distinctly Different Mechanisms In Vitro and In Vivo: Indirect Complement Activation by Virions In Vivo▿

    OpenAIRE

    Tian, Jie; Xu, Zhili; Jeffrey S Smith; Hofherr, Sean E.; Barry, Michael A.; Byrnes, Andrew P.

    2009-01-01

    Understanding innate immunity is key to improving the safety of adenovirus (Ad) vectors for systemic gene therapy. Ad has been shown to activate complement in vitro, but activation of complement after Ad injection in vivo has not been directly measured. Using complement protein C3a as a marker of complement activation, we show that types 2 and 5 human Ads cause rapid complement activation after intravenous injection in mice. Unexpectedly, the mechanisms in vivo were different than those in vi...

  2. Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men

    DEFF Research Database (Denmark)

    Foghmar, Caroline; Brøns, Charlotte; Pilely Hansen, Katrine

    2017-01-01

    -days HFO by a hyperinsulinemic-euglycemic-clamp. Circulating C4, C3, ficolins, mannose-binding-lectin, complement activation products C3bc, terminal complement complex (TCC) and complement activation capacity were determined using turbidimetry and ELISA. HFO induced peripheral insulin resistance in LBW...... individuals only, while both groups had the same degree of hepatic insulin resistance after HFO. Viewing all individuals circulating levels of C4, C3, C3bc, TCC and complement activation capacity decreased paradoxically along the development of insulin resistance after HFO (P = 0.0015, P 

  3. Tanker avionics and aircrew complement evaluation.

    Science.gov (United States)

    Moss, R W; Barbato, G J

    1982-11-01

    This paper describes an effort to determine control and display criteria for operating SAC's KC-135 tanker with a reduced crew complement. The Tanker Avionics and Aircrew Complement Evaluation (TAACE) Program was a four-phase effort addressing the control and display design issues associated with operating the tanker without the navigator position. Discussed are: the mission analysis phase, during which the tanker's operational responsibilities were defined and documented; the design phase, during which alternative crew station design concepts were developed; the mockup evaluation phase, which accomplished initial SAC crew member assessment of cockpit designs; and the simulation phase, which validated the useability of the crew system redesign. The paper also describes a recommended crew station configuration and discusses some of the philosophy underlying the selection of cockpit hardware and systems.

  4. The influence of ventilated façade on sound insulation properties of envelope walls

    OpenAIRE

    2017-01-01

    Presented article deals with sound insulation properties of timber structures’ envelope walls. Particularly, the influence of heavy board ventilated façade on laboratory airborne sound insulation R and Rw in dB was studied. The installation method and gaps between façade boards can cause building defects originating in overrating the influence of ventilated cladding on envelope wall acoustic parameters. Real constructions were built for the experimental purposes and measurements, one with gap...

  5. Trichinella spiralis Paramyosin Binds Human Complement C1q and Inhibits Classical Complement Activation.

    Directory of Open Access Journals (Sweden)

    Ran Sun

    2015-12-01

    Full Text Available Trichinella spiralis expresses paramyosin (Ts-Pmy as a defense mechanism. Ts-Pmy is a functional protein with binding activity to human complement C8 and C9 and thus plays a role in evading the attack of the host's immune system. In the present study, the binding activity of Ts-Pmy to human complement C1q and its ability to inhibit classical complement activation were investigated.The binding of recombinant and natural Ts-Pmy to human C1q were determined by ELISA, Far Western blotting and immunoprecipitation, respectively. Binding of recombinant Ts-Pmy (rTs-Pmy to C1q inhibited C1q binding to IgM and consequently inhibited C3 deposition. The lysis of antibody-sensitized erythrocytes (EAs elicited by the classical complement pathway was also inhibited in the presence of rTs-Pmy. In addition to inhibiting classical complement activation, rTs-Pmy also suppressed C1q binding to THP-1-derived macrophages, thereby reducing C1q-induced macrophages migration.Our results suggest that T. spiralis paramyosin plays an important role in immune evasion by interfering with complement activation through binding to C1q in addition to C8 and C9.

  6. Complementing the sugar code: role of GAGs and sialic acid in complement regulation

    Directory of Open Access Journals (Sweden)

    Alex eLangford-Smith

    2015-02-01

    Full Text Available Sugar molecules play a vital role on both microbial and mammalian cells, where they are involved in cellular communication, govern microbial virulence and modulate host immunity and inflammatory responses. The complement cascade, as part of a host’s innate immune system, is a potent weapon against invading bacteria but has to be tightly regulated to prevent inappropriate attack and damage to host tissues. A number of complement regulators, such as factor H and properdin, interact with sugar molecules, such as glycosaminoglycans and sialic acid, on host and pathogen membranes and direct the appropriate complement response by either promoting the binding of complement activators or inhibitors. The binding of these complement regulators to sugar molecules can vary from location to location, due to their different specificities and because distinct structural and functional subpopulations of sugars are found in different human organs, such as the brain, kidney and eye. This review will cover recent studies that have provided important new insights into the role of glycosaminoglycans and sialic acid in complement regulation and how sugar recognition may be compromised in disease

  7. Text and Voice: Complements, Substitutes or Both?

    OpenAIRE

    Andersson, Kjetil; Foros, Øystein; Steen, Frode

    2006-01-01

    Text messaging has become an important revenue component for European and Asian mobile operators. We develop a simple model of demand for mobile services incorporating the existence of call externalities and network effects. We show that when incoming messages and calls stimulate outgoing communications, services that are perceived as substitutes, such as mobile text and voice, may evolve into complements in terms of the price effect when the network size becomes large. We esti...

  8. Complement and phagocytes - A complicated interaction.

    Science.gov (United States)

    Roos, Dirk

    2015-11-01

    Mohamed Daha and I share a common interest in innate immunity. Working in institutes only 25 miles away from each other, that meant ample opportunity and relevance for collaboration. And so we did. Moreover, we have both been members of boards and councils of Dutch national organizations, and we have also become good friends. In this short recollection, I look back on 40 years of common activities in complement research and friendship.

  9. Complement and Immunoregulation in Tissue Injury

    Science.gov (United States)

    2015-12-01

    transplantation, sepsis , and cardiovascular interventions. Ischemia induces local cellular changes such as membrane perturbation, cytoskeletal...intestinal epithelial cells Several reports have provided evidence that acute inflammatory conditions including sepsis and endotoxemia can stimulate...that detects complement precursor C3 and fragments of C3 including c3a, c3b and c3c. Intestinal tissue sections from sham-operated mice displayed

  10. A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior

    Directory of Open Access Journals (Sweden)

    Tomlinson Stephen

    2010-02-01

    Full Text Available Abstract Background Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but "cytokine storm" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment. Presentation of the hypothesis Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited. Testing the hypothesis CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in vivo and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated. Implications of the hypothesis CR2 targeting complement inhibitors

  11. Detection of the synthetic drug 4-fluoroamphetamine (4-FA) in serum and urine.

    Science.gov (United States)

    Röhrich, J; Becker, J; Kaufmann, T; Zörntlein, S; Urban, R

    2012-02-10

    4-Fluoroamphetamine (4-FA) was detected in the blood and urine of two individuals suspected for driving under the influence (DUI). The test for amphetamines in urine subjected to immunoassay screening using the CEDIA DAU assay proved positive. Further investigations revealed a 4-FA cross-reactivity of about 6% in the CEDIA amphetamine assay. 4-FA was qualitatively detected in a general unknown screening for drugs using GC/MS in full scan mode. No other drugs or fluorinated phenethylamines were detected. A validated GC/MS method was established in SIM mode for serum analysis of 4-FA with a limit of detection (LOD) of 1 ng/mL and a lower limit of quantification (LLOQ) of 5 ng/mL. Intra-assay precision was approx. 4% and inter-assay precision approx. 8%. Applying this method, the 4-FA serum concentrations of the two subjects were determined to be 350 ng/mL and 475 ng/mL, respectively. Given the pharmacological data of amphetamine, 4-FA psychoactive effects are to be expected at these serum levels. Both subjects exhibited sympathomimetic effects and psychostimulant-like impairment accordingly.

  12. Architectural Kansei of ‘Wall’ in The Façade Design by Le Corbusier

    Science.gov (United States)

    Sendai, Shoichiro

    The purpose of this paper is to discuss the modern architect Le Corbusier's architectural Kansei (sensibility) on wall in site environment through the analysis of his façade design, using Œuvres complètes (1910-1965, 8 vols., Les éditions d'architecture, Artemis, Zurich) and Le Corbusier Archives (1982-1984, 32 vols., Garland Publishing, Inc. and Fondation Le Corbusier, New York, London, Paris). At first, I arrange five façade types, according to the explanation by Le Corbusier ; ‘fenêtre en longueur (strip window)’, ‘pan de verre (glass wall)’, ‘brise-soleil (sun-breaker)’, ‘loggia’ and ‘claustra’. Through the analysis of the relationship between these types and the design process of each building, we find that Le Corbusier's façade design includes the affirmation and the negation of the ‘wall’ at the same time. In fact, the nature of façade modification during design process is divers: increase in transparency, decrease in transparency and spatialization of façade. That means, Le Corbusier studied the environmental condition by these façade types, and tried to realize the phenomenal openness. This trial bases on the function of architectural Kansei as correspondence between body and environment beyond the physical design.

  13. Ectopic Expression of FaDREB2 Enhances Osmotic Tolerance in Paper Mulberry

    Institute of Scientific and Technical Information of China (English)

    Mei-Ru Li; Yan Li; Hong-Qing Li; Guo-Jiang Wu

    2011-01-01

    Dehydration-responsive element binding (DREB) proteins are a subfamily of AP2/ERF transcription factors that have been shown to improve tolerance to osmotic stresses in plants.To improve the osmotic stress tolerance of paper mulberry (Broussonetia papyrifera L.Vent),an economically important tree,we transformed it with a plasmid carrying tall fescue (Festuca arundinacea Schreb) FaDREB2 under the control of CaMV 35S.The ectopic expression of FaDREB2 did not cause growth retardation,and the paper mulberry seedlings expressing FaDREB2 showed higher salt and drought tolerance than wild-type plants (WT).After 13 d of withholding water,or 15 d in the presence of 250 mM NaCI,all the WT plants died,while the plants expressing FaDREB2 survived.The FaDREB2 transgenic plants had higher leaf water and chlorophyll contents,accumulated more proline and soluble sugars,and had less membrane damage than the WT plants under high salt and water-deficient conditions.Taken together,the results indicate the feasibility of improving tolerance to multiple environmental stresses in paper mulberry seedlings via genetic engineering,by introducing FaDREB2,which promotes the increased accumulation of osmolytes (soluble sugars and proline),to counter osmotic stresses caused by abiotic factors.

  14. Susceptibility to advanced age-related macular degeneration and alleles of complement factor H, complement factor B, complement component 2, complement component 3, and age-related maculopathy susceptibility 2 genes in a Mexican population

    Science.gov (United States)

    Buentello-Volante, Beatriz; Rodriguez-Ruiz, Gabriela; Miranda-Duarte, Antonio; Pompa-Mera, Ericka N.; Graue-Wiechers, Federico; Bekker-Méndez, Carolina; Ayala-Ramirez, Raul; Quezada, Carlos; Rodríguez-Loaiza, Jose L.

    2012-01-01

    Purpose To investigate the association of age-related macular degeneration (AMD)–high risk alleles of the complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), complement component 3 (C3), and age-related maculopathy susceptibility 2 (ARMS2) genes in a Mexican population for the first time. Methods Genotyping was performed for the Y402H variant of CFH, for the L9H, R32Q, and K565E variants of CFB, the E318D variant of C2, the A69S variant of ARMS2, and the R102G variant of C3 in 159 Mexican mestizo patients at advanced stages of AMD, i.e., CARMS (Clinical Age-Related Maculopathy Staging System) grade 4 or 5. The frequency of these variants was also investigated in a group of 152 control subjects without AMD. Genomic DNA was extracted from blood leukocytes, and genotyping was performed using PCR followed by direct sequencing. Allele-specific restriction enzyme digestion was used to detect the R102G polymorphism in C3. Results There were significant differences in the allelic distribution between the two groups for CFH Y402H (p=1×10−5), ARMS A69S (p=4×10−7), and CFB R32Q (p=0.01). The odds ratios (95% confidence interval) obtained for the risk alleles of these three variants were 3.8 (2.4–5.9), 3.04 (2.2–4.3), and 2.5 (1.1–5.7), respectively. Haplotype analysis including the two most significantly associated alleles (CFH Y402H and ARMS A69S) indicated that the C-T combination conferred an odds ratio (95% confidence interval) of 6.9 (3.2–14.8). The exposed attributable risk for this particular haplotype was 85.5%. Conclusions This is the first case-control investigation of AMD–high risk alleles in a Latino population. Our results support that CFH, ARMS2, and CFB AMD-risk alleles are consistently associated with the disease, even in ethnic groups with a complex admixture of ancestral populations such as Mexican mestizos. PMID:23112567

  15. Vasculitides and the Complement System: a Comprehensive Review.

    Science.gov (United States)

    Chimenti, Maria Sole; Ballanti, Eleonora; Triggianese, Paola; Perricone, Roberto

    2015-12-01

    Systemic vasculitides are a group of rare diseases characterized by inflammation of the arterial or venous vessel wall, causing stenosis or thrombosis. Clinical symptoms may be limited to skin or to other organs or may include multiple manifestations as systemic conditions. The pathogenesis is related to the presence of leukocytes in the vessels and to the IC deposition, which implies the activation of the complement system (CS) and then the swelling and damage of vessel mural structures. The complement system (CS) is involved in the pathogenesis of several autoimmune diseases, including systemic vasculitides. This enzymatic system is a part of the innate immune system, and its function is linked to the modulation of the adaptive immunity and in bridging innate and adaptive responses. Its activation is also critical for the development of natural antibodies and T cell response and for the regulation of autoreactive B cells. Complement triggering contributes to inflammation-driven tissue injury, which occurs during the ischemia/reperfusion processes, vasculitides, nephritis, arthritis, and many others diseases. In systemic vasculitides, a group of uncommon diseases characterized by blood vessel inflammation, the contribution of CS in the development of inflammatory damage has been demonstrated. Treatment is mainly based on clinical manifestations and severity of organ involvement. Evidences on the efficacy of traditional immunosuppressive therapies have been collected as well as data from clinical trials that involve the modulation of the CS. In particular in small-medium-vessel vasculitides, the CS represents an attractive target. Herein, we reviewed the pathogenetic role of CS in these systemic vasculitides as urticarial vasculitis, ANCA-associated vasculitides, anti-glomerular basement membrane disease, cryoglobulinaemic vasculitides, Henoch-Schönlein purpura/IgA nephropathy, and Kawasaki disease and therefore its potential therapeutic use in this context.

  16. A study of immunoglobulins and complements (C3 &C4 in alopecia areata

    Directory of Open Access Journals (Sweden)

    Sharma R

    1995-01-01

    Full Text Available Estimation of serum Immunoglobulins (IgG, IgM and IgA and complements (C3 and C4 was carried out in 100 cases of alopecia areata as per method described by Mancini (1965.[1] Clinically patients were divided in two groups, alopecia areata circumscribed (group I and severe alopecia areata (group II. Significant decrease in levels of one or more Immunoglobulins were observed in most of the patients. However, Serum complements (C3 and C4 were within range of normal control values

  17. Complement factor B activation in patients with preeclampsia.

    Science.gov (United States)

    Velickovic, Ivan; Dalloul, Mudar; Wong, Karen A; Bakare, Olufunke; Schweis, Franz; Garala, Maya; Alam, Amit; Medranda, Giorgio; Lekovic, Jovana; Shuaib, Waqas; Tedjasukmana, Andreas; Little, Perry; Hanono, Daniel; Wijetilaka, Ruvini; Weedon, Jeremy; Lin, Jun; Toledano, Roulhac d'Arby; Zhang, Ming

    2015-06-01

    Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Bb, the active fragment of complement factor B (fB), has been reported to be a predictor of preeclampsia. However, conflicting results have been found by some investigators. We hypothesized that the disagreement in findings may be due to the racial/ethnic differences among various study groups, and that fB activation is significant in women of an ethnic minority with preeclampsia. We investigated the maternal and fetal levels of Bb (the activated fB fragment) in pregnant women of an ethnic minority with or without preeclampsia. We enrolled 291 pregnant women (96% of an ethnic minority, including 78% African-American). Thirteen percent of these were diagnosed with preeclampsia. Maternal venous blood was collected from all participants together with fetal umbilical cord blood samples from 154 deliveries in the 291 women. The results were analyzed using the Mann-Whitney U test and multivariate analyses. Maternal Bb levels were significantly higher in the preeclamptic group than in the nonpreeclamptic group. Levels of Bb in fetal cord blood were similar in both groups. Subgroup analyses of African-American patients' results confirmed the study hypothesis that there would be a significant increase in Bb in the maternal blood of the preeclamptic group and no increase in Bb in the fetal cord blood of this group. These results suggest that a maternal immune response through complement fB might play a role in the development of preeclampsia, particularly in African-American patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Small-Medium Vessel Vasculitides: is the Complement System a Potential Forgotten Target?

    Science.gov (United States)

    Ballanti, Eleonora; Chimenti, Maria S; Perricone, Roberto

    2015-02-01

    Systemic vasculitides are a group of uncommon diseases characterized by blood vessel inflammation. The complement system is involved in the pathogenesis and clinical manifestations of several autoimmune diseases, including systemic vasculitides. This enzymatic system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens, but research in recent years has demonstrated the important role that complement proteins play in modulating adaptive immunity and in bridging innate and adaptive responses. Its activation is also critical for the development of T cell immunity and natural antibodies as well as for the regulation of autoreactive B cells. In systemic vasculitides, particularly small-medium vesselvasculitides, the complement system has been shown to contribute to the development of inflammatory damage. In view of these crucial functions, the complement system represents an attractive therapeutic target for a wide range of diseases. including vasculitic disorders.

  19. Age-related macular degeneration: Complement in action.

    Science.gov (United States)

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD.

  20. FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2.

    Directory of Open Access Journals (Sweden)

    Maria Castella

    2015-10-01

    Full Text Available The Fanconi anemia (FA-BRCA pathway mediates repair of DNA interstrand crosslinks. The FA core complex, a multi-subunit ubiquitin ligase, participates in the detection of DNA lesions and monoubiquitinates two downstream FA proteins, FANCD2 and FANCI (or the ID complex. However, the regulation of the FA core complex itself is poorly understood. Here we show that the FA core complex proteins are recruited to sites of DNA damage and form nuclear foci in S and G2 phases of the cell cycle. ATR kinase activity, an intact FA core complex and FANCM-FAAP24 were crucial for this recruitment. Surprisingly, FANCI, but not its partner FANCD2, was needed for efficient FA core complex foci formation. Monoubiquitination or ATR-dependent phosphorylation of FANCI were not required for the FA core complex recruitment, but FANCI deubiquitination by USP1 was. Additionally, BRCA1 was required for efficient FA core complex foci formation. These findings indicate that FANCI functions upstream of FA core complex recruitment independently of FANCD2, and alter the current view of the FA-BRCA pathway.

  1. Glucomannan or Glucomannan Plus Spirulina-Enriched Squid-Surimi Diets Reduce Histological Damage to Liver and Heart in Zucker fa/fa Rats Fed a Cholesterol-Enriched and Non-Cholesterol-Enriched Atherogenic Diet.

    Science.gov (United States)

    Vázquez-Velasco, Miguel; González-Torres, Laura; García-Fernández, Rosa A; Méndez, María Teresa; Bastida, Sara; Benedí, Juana; González-Muñoz, María José; Sánchez-Muniz, Francisco J

    2017-06-01

    Glucomannan-enriched squid surimi improves cholesterolemia and liver antioxidant status. The effect of squid surimi enriched with glucomannan or glucomannan plus spirulina on liver and heart structures and cell damage markers was tested in fa/fa rats fed highly saturated-hyper-energetic diets. Animals were fed 70% AIN-93M rodent diet plus six versions of 30% squid surimi for 7 weeks: control (C), glucomannan (G), and glucomannan plus spirulina (GS). The cholesterol-control (HC), cholesterol-glucomannan (HG), and cholesterol-glucomannan plus spirulina (HGS) groups were given similar diets that were enriched with 2% cholesterol and 0.4% cholic acid. G and GS diets versus C diet significantly inhibited weight gain and lowered plasma alanine aminotransferase and aspartate aminotransferase, liver steatosis, lipogranulomas, and total inflammation and alteration scores. The hypercholesterolemic agent significantly increased the harmful effects of the C diet. Liver weight, the hepatosomatic index, all damage markers, and total histological scoring rose for HC versus C (at least P spirulina were observed except for the total liver alteration score. In conclusion, glucomannan and glucomannan plus spirulina blocked the highly saturated-hyper-energetic diet negative effects both with and without added cholesterol. Results suggest the usefulness of including these functional ingredients in fish products.

  2. GLUCOMANNAN AND GLUCOMANNAN PLUS SPIRULINA-ENRICHED SQUID-SURIMI ADDED TO HIGH SATURATED DIET AFFECT GLYCEMIA, PLASMA AND ADIPOSE LEPTIN AND ADIPONECTIN LEVELS IN GROWING FA/FA RATS.

    Science.gov (United States)

    Vázquez-Velasco, Miguel; González-Torres, Laura; Méndez, María Teresa; Bastida, Sara; Benedí, Juana; González-Muñoz, M José; Sánchez-Muniz, Francisco J

    2015-12-01

    Type 2 diabetes is a very prevalent chronic disease. Among dietary factors for its prevention and treatment, interest has grown in satiating fibre (konjac glucomannan) and spirulina. Our previous studies suggest that glucomannan itself and/or in conjunction to spirulina displayed hypolipemic and antioxidant effects when incorporated to squid surimi as functional ingredients. The present study aims to determine whether glucomannan- enriched or glucomannan plus spirulina-enriched squid-surimi improve plasma glucose and insulin levels in Zucker fa/fa rats fed a high saturated fat diet. Twenty four growing rats, divided into three groups, were given modified AIN-93M diets for seven weeks: 30% squid-surimi control diet (C), 30% glucomannan-enriched squid-surimi diet (G) and 30% glucomannan plus spirulina-enriched squid-surimi diet (GS). All rats became hyperglycemics and hyperinsulinemics, but G and GS diets induced significantly lower glucose levels (20%; p Spirulina inclusion increased insulin availability. Although results are promising, the utility of consuming glucomannan surimis as part of usual diets demands future studies. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  3. Berberine-induced anticancer activities in FaDu head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Seo, Yo-Seob; Yim, Min-Ji; Kim, Bok-Hee; Kang, Kyung-Rok; Lee, Sook-Young; Oh, Ji-Su; You, Jae-Seek; Kim, Su-Gwan; Yu, Sang-Joun; Lee, Gyeong-Je; Kim, Do Kyung; Kim, Chun Sung; Kim, Jin-Soo; Kim, Jae-Sung

    2015-12-01

    In the present study, we investigated berberine‑induced apoptosis and the signaling pathways underlying its activity in FaDu head and neck squamous cell carcinoma cells. Berberine did not affect the viability of primary human normal oral keratinocytes. In contrast, the cytotoxicity of berberine was significantly increased in FaDu cells stimulated with berberine for 24 h. Furthermore, berberine increased nuclear condensation and apoptosis rates in FaDu cells than those in untreated control cells. Berberine also induced the upregulation of apoptotic ligands, such as FasL and TNF-related apoptosis-inducing ligand, and triggered the activation of caspase-8, -7 and -3, and poly(ADP ribose) polymerase, characteristic of death receptor-dependent extrinsic apoptosis. Moreover, berberine activated the mitochondria‑dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bax, Bad, Apaf-1, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. In addition, berberine increased the expression of the tumor suppressor p53 in FaDu cells. The pan-caspase inhibitor Z-VAD-fmk suppressed the activation of caspase-3 and prevented cytotoxicity in FaDu cells treated with berberine. Interestingly, berberine suppressed cell migration through downregulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38, components of the mitogen-activated protein kinase pathway that are associated with the expression of MMP and VEGF, was suppressed in FaDu cells treated with berberine for 24 h. Therefore, these data suggested that berberine exerted anticancer effects in FaDu cells through induction of apoptosis and suppression of migration. Berberine may have potential applications as a chemotherapeutic agent for the management of head and neck squamous carcinoma.

  4. Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells.

    Science.gov (United States)

    Lu, Sumei; Yu, Liang; Mu, Yakui; Ma, Juke; Tian, Jiajun; Xu, Wei; Wang, Haibo

    2014-07-01

    Multidrug resistance (MDR) is one of the most important obstacles affecting the efficacy of chemotherapy treatments for numerous types of cancer. In the present study, we have demonstrated the possible function of Twist1 in the chemosensitivity of head and neck squamous cell carcinoma (HNSCC) and have identified that its mechanism maybe associated with MDR1/P-gp regulation. To investigate this, the hypopharyngeal cancer cell line, FaDu, and its MDR cell line induced by taxol, FaDu/T, were employed. Stable transfectants targeted to Twist1 overexpression and Twist1 silencing based on FaDu were also conducted. Morphological observation, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), western blotting and laser scanning confocal microscope detection were utilized to detect the associations between Twist1 and the chemosensitivity of FaDu cells. Our results demonstrated that Twist1 and MDR1/P-gp were upregulated in FaDu/T cells in a MDR dose-dependent manner. The anti-apoptotic capabilities of FaDu/T cells were enhanced during MDR progression, with apoptosis-related proteins (Bcl-2, Bax, activated caspase-3 and caspase-9) changing to resist apoptosis. Twist1 overexpression decreased the sensitivity of cells to taxol as revealed by a significant increase in MDR1/P-gp and IC50 (Pcell death, and inhibited Ca2+ release induced by taxol (Pcells also confirmed this result. This study provided evidence that alterations of Twist1 expression modulates the chemosensitivity of FaDu cells to taxol. Therefore, Twist1 knockdown may be a promising treatment regimen for advanced hypopharyngeal carcinoma patients with MDR.

  5. Novel bioactive Co-based alloy/FA nanocomposite for dental applications

    Directory of Open Access Journals (Sweden)

    Mohammadhossein Fathi

    2012-01-01

    Full Text Available Background: Dental cobalt base alloys are biocompatible dental materials and have been widely used in dentistry. However, metals are bioinert and may not present bioactivity in human body. Bioactivity is the especial ability to interact with human body and make a bonding to soft and hard tissues. The aim of the present research was fabrication and bioactivity evaluation of novel cobalt alloy/Fluorapatite nanocomposite (CoA/FaNC with different amounts of Fluorapatite (FA nanopowder. Materials and Methods: Co-Cr-Mo alloy (ASTM F75 powder was prepared and mixed in a planetary ball mill with different amounts of FA nanopowders (10, 15, 20% wt. Prepared composite powders were cold pressed and sintered at 1100°C for 4 h. X-ray diffraction (XRD, scanning electron microscopy and transition electron microscopy techniques were used for phase analysis, crystallite size determination of FA and also for phase analysis and evaluation of particle distribution of composites. Bioactivity behavior of prepared nanocomposites was evaluated in simulated body fluid (SBF for 1 up to 28 days. Results: Results showed that nucleus of apatite were formed on the surface of the prepared CoA/FaNC during 1 up to 28 days immersion in the SBF solution. On the other hand, CoA/FaNC unlike Co-base alloy possessed bone-like apatite-formation ability. Conclusion: It was concluded that bioinert Co-Cr-Mo alloy could be successfully converted into bioactive nanocomposite by adding 10, 15, 20 wt% of FA nano particles.

  6. New methods for testing fire resistance of wood façade systems

    Directory of Open Access Journals (Sweden)

    Mårtensson August

    2016-01-01

    Full Text Available Arson in schools has been a huge problem in Sweden over the last fifteen years. The average amount of school arsons between 2000 and 2014 was 285 cases each year which corresponds to 50% of the total amount of reported fires in school buildings. This is a well-known problem and a lot of research has been done in this area. Investigations has been done about fire and heat detection systems, different technical factors significance in fire scenarios and how to prevent adolescents from starting fires. Another part of the problem that partly been investigated is how the schools are constructed. Roughly 50% of the arsons are outside of the school building. In Sweden one and two storey buildings are allowed to be built with wooden façades in accordance with the building code, which is one of the reasons many schools are built with wooden façade systems. The most critical part in a wood façade system from a fire safety perspective is concluded to be the eaves because of how they usually are built to let air pass through. Even though a wood façade isn't as well resistant to fire compared to a concrete façade, three versions of new test methods for combustible façades have been developed to make it possible to make sure in advance that a construction is resistant enough. The new test methods are focused on specific details and parts of a façade system to provide a more informative and useful result compared to SP Fire 105. Observations and measurements of flame spread and temperature changes in the eave, over the window joints and in the air gap are made. With these parameters in consideration criteria's has been chosen for a critical temperature of 280 ∘C at a critical time of 20 minutes.

  7. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.;

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three...

  8. Factor H-related proteins determine complement-activating surfaces.

    Science.gov (United States)

    Józsi, Mihály; Tortajada, Agustin; Uzonyi, Barbara; Goicoechea de Jorge, Elena; Rodríguez de Córdoba, Santiago

    2015-06-01

    Complement factor H-related proteins (FHRs) are strongly associated with different diseases involving complement dysregulation, which suggests a major role for these proteins regulating complement activation. Because FHRs are evolutionarily and structurally related to complement inhibitor factor H (FH), the initial assumption was that the FHRs are also negative complement regulators. Whereas weak complement inhibiting activities were originally reported for these molecules, recent developments indicate that FHRs may enhance complement activation, with important implications for the role of these proteins in health and disease. We review these findings here, and propose that FHRs represent a complex set of surface recognition molecules that, by competing with FH, provide improved discrimination of self and non-self surfaces and play a central role in determining appropriate activation of the complement pathway.

  9. Begin and start: aspect and complement choice

    Directory of Open Access Journals (Sweden)

    Tünde Nagy

    2008-01-01

    Full Text Available The paper offers a semantic analysis of begin and start and their non-finite complementation: the to-infinitive and –ing constructions. The core idea of the paper is that the aspectual constructions ‘begin+ to infinitive’, ‘begin + ing’, ‘start+ to infinitive’, and ‘start+ ing’ have both a schematic and a prototypical meaning, and that the subtle differences between them are motivated by several factors, like viewing (perfectivity vs. imperfectivity, temporality (future orientation vs. ongoing reading dynamicity (graduality vs. abruptness, agentivity, etc.

  10. On Wiener index of graph complements

    Directory of Open Access Journals (Sweden)

    Jaisankar Senbagamalar

    2014-06-01

    Full Text Available Let $G$ be an $(n,m$-graph. We say that $G$ has property $(ast$ if for every pair of its adjacent vertices $x$ and $y$, there exists a vertex $z$, such that $z$ is not adjacent to either $x$ or $y$. If the graph $G$ has property $(ast$, then its complement $overline G$ is connected, has diameter 2, and its Wiener index is equal to $binom{n}{2}+m$, i.e., the Wiener index is insensitive of any other structural details of the graph $G$. We characterize numerous classes of graphs possessing property $(ast$, among which are trees, regular, and unicyclic graphs.

  11. Hyperbolicity of the complement of plane algebraic curves

    CERN Document Server

    Dethloff, G E; Dethloff, Gerd; Schumacher, Georeg

    1993-01-01

    The paper is a contribution of the conjecture of Kobayashi that the complement o f a generic plain curve of degree at least five is hyperbolic. The main result is that the complement of a generic configuration of three quadr ics is hyperbolic and hyperbolically embedded as well as the complement of two q uadrics and a line.

  12. Complement activation by tubular cells is mediated by properdin binding

    NARCIS (Netherlands)

    Gaarkeuken, E.M.; Siezenga, M.A.; Zuidwijk, K.; Kooten, C. van; Rabelink, T.J.; Daha, M.R.; Berger, S.P.

    2008-01-01

    Activation of filtered complement products on the brush border of the tubular epithelium is thought to be a key factor underlying proteinuria-induced tubulointerstitial injury. However, the mechanism of tubular complement activation is still unclear. Recent studies on mechanisms of complement activa

  13. Complement-mediated solubilization of immune complexes and their interaction with complement C3 receptors

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Jepsen, H H;

    1985-01-01

    Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components of the me......Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components...

  14. A BPMN-Based Process Map for the Design and Construction of Façades

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    Eleanor Voss

    2013-12-01

    Full Text Available Process mapping can lead to significant efficiency and quality improvements in construction engineering and is an ideal basis for developing IT support tools. The increasing complexity and multidisciplinary nature of façade design and construction suggest that a process map would be beneficial in this sector of the construction industry, but it has received limited attention to date. This paper presents a verified process map of the façade design and construction process.  The map is the first of its kind to represent, in detail, the whole process relevant to all façade types, from commencement of the façade consultant’s and contactor’s participation, to the end of their involvement. The paper describes the process by which the mapping notation was selected, followed by the development and verification of the process map, including testing in two independent research projects. The BuildingSMART’s BPMN notation is found to have superior system features and comprehensibility for this application and the resulting process map is easy to interpret and verify by industry experts. The trialling of the map in the two research projects indicate that the map is a useful tool for assessing process improvements in the façades sector.

  15. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent.

    Science.gov (United States)

    Jeppesen, J; Albers, P H; Rose, A J; Birk, J B; Schjerling, P; Dzamko, N; Steinberg, G R; Kiens, B

    2011-04-01

    The aim of this study was to investigate the molecular mechanisms regulating FA translocase CD36 (FAT/CD36) translocation and FA uptake in skeletal muscle during contractions. In one model, wild-type (WT) and AMP-dependent protein kinase kinase dead (AMPK KD) mice were exercised or extensor digitorum longus (EDL) and soleus (SOL) muscles were contracted, ex vivo. In separate studies, FAT/CD36 translocation and FA uptake in response to muscle contractions were investigated in the perfused rat hindlimb. Exercise induced a similar increase in skeletal muscle cell surface membrane FAT/CD36 content in WT (+34%) and AMPK KD (+37%) mice. In contrast, 5-aminoimidazole-4-carboxamide ribonucleoside only induced an increase in cell surface FAT/CD36 content in WT (+29%) mice. Furthermore, in the perfused rat hindlimb, muscle contraction induced a rapid (1 min, +15%) and sustained (10 min, +24%) FAT/CD36 relocation to cell surface membranes. The increase in cell surface FAT/CD36 protein content with muscle contractions was associated with increased FA uptake, both in EDL and SOL muscle from WT and AMPK KD mice and in the perfused rat hindlimb. This suggests that AMPK is not essential in regulation of FAT/CD36 translocation and FA uptake in skeletal muscle during contractions. However, AMPK could be important in regulation of FAT/CD36 distribution in other physiological situations.

  16. Reduced PAK1 activity sensitizes FA/BRCA-proficient breast cancer cells to PARP inhibition.

    Science.gov (United States)

    Villamar Cruz, Olga; Prudnikova, Tatiana Y; Araiza-Olivera, Daniela; Perez-Plasencia, Carlos; Johnson, Neil; Bernhardy, Andrea J; Slifker, Michael; Renner, Catherine; Chernoff, Jonathan; Arias-Romero, Luis E

    2016-11-22

    Cells that are deficient in homologous recombination, such as those that have mutations in any of the Fanconi Anemia (FA)/BRCA genes, are hypersensitive to inhibition of poly(ADP-ribose) polymerase (PARP). However, FA/BRCA-deficient tumors represent a small fraction of breast cancers, which might restrict the therapeutic utility of PARP inhibitor monotherapy. The gene encoding the serine-threonine protein kinase p21-activated kinase 1 (PAK1) is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors. This enzyme controls many cellular processes by phosphorylating both cytoplasmic and nuclear substrates. Here, we show that depletion or pharmacological inhibition of PAK1 down-regulated the expression of genes involved in the FA/BRCA pathway and compromised the ability of cells to repair DNA by Homologous Recombination (HR), promoting apoptosis and reducing colony formation. Combined inhibition of PAK1 and PARP in PAK1 overexpressing breast cancer cells had a synergistic effect, enhancing apoptosis, suppressing colony formation, and delaying tumor growth in a xenograft setting. Because reduced PAK1 activity impaired FA/BRCA function, inhibition of this kinase in PAK1 amplified and/or overexpressing breast cancer cells represents a plausible strategy for expanding the utility of PARP inhibitors to FA/BRCA-proficient cancers.

  17. The effect of architectural façade design on energy savings in the student dormitory

    Directory of Open Access Journals (Sweden)

    Pejić Petar Č.

    2014-01-01

    Full Text Available There are many reasons for adequate use of natural light inside students' dormitories. Intensity of light required for student activities and temperature inside the rooms are the major factors for an occupant's comfortable work and life. Design of building façades has a significant impact both on the use of natural light and energy consumption. In this paper, a comparative analysis of student rooms with different orientations and different façade designs was performed in order to investigate what type of refurbishment in the façade is necessary. The goal of the refurbishment was generation of optimal thermal and lighting comfort for students' work with maximal energy saving for a new student dormitory in Nis, Serbia. An analysis of annual energy consumption of the newly designed student dormitory and proposed replacements on the exterior façade was performed by using the software EnergyPlus. Based on the energy consumption analysis it could be concluded that significant energy savings would be possible by upgrading the shading devices across the width of the window. In other words, changing the façade of the dorm could generally improve students' comfort, while the energy costs would be reduced. [Projekat Ministarstva nauke Republike Srbije, br. TR 36037: Development of student dorms in Serbia at the beginning of the 21st century i br. TR 33051: The concept of sustainable energy supply of settlements with energy efficient buildings

  18. Complement Interception Across Humoral Incompatibility in Solid Organ Transplantation: A Clinical Perspective.

    Science.gov (United States)

    Biglarnia, Ali-Reza; Ekdahl, Kristina N; Nilsson, Bo

    2015-01-01

    The humoral barrier in transplant biology is the result of preformed donor-specific antibodies (DSAs), directed either against human leukocyte antigens (HLA) or non-HLA antigens such as blood group (ABO) molecules. The term "sensitization" applies to patients carrying these antibodies. Transplantation is widely accepted as a life-saving opportunity for patients with terminal end-organ disease. However, in sensitized patients, transplant outcome is hampered by antibody-mediated rejection (AMR) as a consequence of DSA exposure. Furthermore, sensitized patients have limited access to "matched" organs from the both living and deceased donor pool.Considering the crucial role of the complement system in the pathophysiology of AMR and the availability of complement intervention therapeutics, there is a growing interest in complement-targeting strategies. This review highlights the emerging importance of monitoring and modulation of the complement system in the context of enabling transplantation across humoral incompatibility in sensitized recipients with preformed anti-HLA or natural anti-ABO antibodies. It also discusses the significance of the complement system in the induction of accommodation and further emphasizes current and future perspectives of novel complement therapeutics.

  19. The Complement System in Flavivirus Infections

    Science.gov (United States)

    Conde, Jonas N.; Silva, Emiliana M.; Barbosa, Angela S.; Mohana-Borges, Ronaldo

    2017-01-01

    The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical climates worldwide, affecting hundreds of millions of people each year. The Flaviviridae family includes dengue, West Nile, Zika, Japanese encephalitis, and yellow fever viruses that are typically transmitted by mosquitoes or ticks, and cause a wide range of symptoms, such as fever, shock, meningitis, paralysis, birth defects, and death. The flavivirus genome is composed of a single positive-sense RNA molecule encoding a single viral polyprotein. This polyprotein is further processed by viral and host proteases into three structural proteins (C, prM/M, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) that are involved in viral replication and pathogenicity. The complement system has been described to play an important role in flavivirus infection either by protecting the host and/or by influencing disease pathogenesis. In this mini-review, we will explore the role of complement system inhibition and/or activation against infection by the Flavivirus genus, with an emphasis on dengue and West Nile viruses. PMID:28261172

  20. Complementing asteroseismology with 4MOST spectroscopy

    Science.gov (United States)

    de Jong, R. S.; 4MOST Consortium; 4MOST Spectroscopy Consortium

    2016-09-01

    4MOST is a wide-field, high-multiplex spectroscopic survey facility under development for the VISTA telescope of the European Southern Observatory (ESO). Its main science drivers are in the areas of galactic archeology, high-energy physics, galaxy evolution and cosmology. 4MOST will in particular provide the spectroscopic complements to the large area surveys coming from space missions like Gaia, eROSITA, Euclid, and PLATO. 4MOST will have an unique operations concept in which 5-years public surveys from both the consortium and the ESO community will be combined and observed in parallel during each exposure, resulting in more than 25 million spectra of targets spread over a large fraction of the southern sky. As a dedicated spectroscopic survey facility with a large field-of-view, a high multiplex that can be reconfigured quickly, and with a broad wavelength coverage, 4MOST is particularly well suited to complement the upcoming asteroseismology space missions like TESS and PLATO. Here we show that, by dedicating the observing time during twilight and poor observing conditions to bright stars, 4MOST will obtain resolution {R>18 000} spectra of nearly all stars brighter than ˜ 12th magnitude at Dec TESS and PLATO missions and place any planets found in a full chemo-dynamical context of the star formation history of the Galaxy, yield very accurate ages and masses for all stars that can be characterized with asteroseismology, and allow removal of contaminants from target samples (e.g., spectroscopic binaries).

  1. Dialyzer membranes: effect of surface area and chemical modification of cellulose on complement and platelet activation.

    Science.gov (United States)

    Mahiout, A; Meinhold, H; Kessel, M; Schulze, H; Baurmeister, U

    1987-04-01

    Using an ex vivo model, the effects of membrane composition and surface area on both the complement system (as reflected by plasma C3a levels) and platelets [as indicated by plasma concentrations of thromboxane B2 (TXB2) and platelet factor 4 (PF4)] were studied. In this model, polyacrylonitrile (PAN) was associated with less complement activation than cuprammonium cellulose (CC). A new "modified cellulose" (MC) membrane, in which a small number of the free hydroxyl groups on cellulose are substituted with a tertiary amino compound, was also associated with a low degree of complement activation, similar to that with PAN. However, the extent of hydroxyl group substitution in four MC membrane subtypes did not correlate with the reduction in complement activation. In studies using CC, the amount of generated C3a correlated with the membrane surface area, although the relationship was curvilinear. Plasma concentrations at the "dialyzer" outlet of TXB2 and PF4 were similar with CC, PAN, and MC. In studies with the MC subtypes, increasing the extent of hydroxyl group substitution paradoxically increased, albeit slightly, the amount of TXB2 generation. In studies with CC, a linear relationship between membrane surface area and TXB2 generation was found. The results suggest a dissociation between platelet and complement effects among different dialyzer membranes, and underline the importance of membrane surface area.

  2. Evaluación del efecto de niacina en un modelo de obesidad con sindrome metábolico en ratas Zucker-Zucker (fa/fa) longevas

    OpenAIRE

    Ana Laura Esquivel Campos; María Cristina Fresán Orozco; Miguel Mosqueda Cabrera; Julia Pérez Ramos

    2012-01-01

    Se evaluó el efecto farmacológico de la niacina sobre los niveles plasmáticos de adiponectina, leptina, IL-6 y TNF-α, así como el intercambio gaseoso, en un modelo de obesidad-vejez con hiperglicemia y dislipidemia en ratas macho de la cepa Zucker-Zucker (fa/fa) La niacina disminuyó significativamente los niveles de colesterol y triglicéridos. Mejoró el intercambio gaseoso, incrementó la presión parcial arterial de oxígeno, y disminuyó la presión parcial de dióxido de carbono y redujo los niv...

  3. Production planning support system using. Phi. NET in FA. FA bun prime ya ni okeru. Phi. NET oyo seisan keikau shien system

    Energy Technology Data Exchange (ETDEWEB)

    Igawa, Y.; Hibino, K. (Fuji Electric Co. Ltd., Tokyo (Japan))

    1991-08-10

    In response to a wide use of the production simulation for production scheduling in the domain of factory automation (FA), a system of a machining flexible manufacturing system (FMS) production line using a general-purpose distribution control system building tool {Phi}NET was developed by Fuji Electric. In this report, an outline of this system was introduced as to its constitution and performance. This FMS production line has functions of the production scheduling, the production simulation, and the production instruction. Among them, the {Phi}NET model, in which the network model called petri-net and the production rule were combined, was applied to the production simulation. Consequently, was provided a prospect that the {Phi}NET would be developed to an FA simulator with which a production engineer can build a model with his own field language and conduct a simulation. 4 figs.

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

    Science.gov (United States)

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

    2015-07-01

    A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia. © 2015 American Heart Association, Inc.

  5. A Preliminary Genetic Analysis of Complement 3 Gene and Schizophrenia.

    Directory of Open Access Journals (Sweden)

    Jianliang Ni

    Full Text Available Complement pathway activation was found to occur frequently in schizophrenia, and complement 3 (C3 plays a major role in this process. Previous studies have provided evidence for the possible role of C3 in the development of schizophrenia. In this study, we hypothesized that the gene encoding C3 (C3 may confer susceptibility to schizophrenia in Han Chinese. We analyzed 7 common single nucleotide polymorphisms (SNPs of C3 in 647 schizophrenia patients and 687 healthy controls. Peripheral C3 mRNA expression level was measured in 23 drug-naïve patients with schizophrenia and 24 controls. Two SNPs (rs1047286 and rs2250656 that deviated from Hardy-Weinberg equilibrium were excluded for further analysis. Among the remaining 5 SNPs, there was no significant difference in allele and genotype frequencies between the patient and control groups. Logistic regression analysis showed no significant SNP-gender interaction in either dominant model or recessive model. There was no significant difference in the level of peripheral C3 expression between the drug-naïve schizophrenia patients and healthy controls. In conclusion, the results of this study do not support C3 as a major genetic susceptibility factor in schizophrenia. Other factors in AP may have critical roles in schizophrenia and be worthy of further investigation.

  6. Complement analysis 2016: Clinical indications, laboratory diagnostics and quality control.

    Science.gov (United States)

    Prohászka, Zoltán; Nilsson, Bo; Frazer-Abel, Ashley; Kirschfink, Michael

    2016-11-01

    In recent years, complement analysis of body fluids and biopsies, going far beyond C3 and C4, has significantly enhanced our understanding of the disease process. Such expanded complement analysis allows for a more precise differential diagnosis and for critical monitoring of complement-targeted therapy. These changes are a result of the growing understanding of the involvement of complement in a diverse set of disorders. To appreciate the importance of proper complement analysis, it is important to understand the role it plays in disease. Historically, it was the absence of complement as manifested in severe infection that was noted. Since then complement has been connected to a variety of inflammatory disorders, such as autoimmune diseases and hereditary angioedema. While the role of complement in the rejection of renal grafts has been known longer, the significant impact of complement. In certain nephropathies has now led to the reclassification of some rare kidney diseases and an increased role for complement analysis in diagnosis. Even more unexpected is that complement has also been implicated in neural, ophtalmological and dermatological disorders. With this level of involvement in some varied and impactful health issues proper complement testing is clearly important; however, analysis of the complement system varies widely among laboratories. Except for a few proteins, such as C3 and C4, there are neither well-characterized standard preparations nor calibrated assays available. This is especially true for the inter-laboratory variation of tests which assess classical, alternative, or lectin pathway function. In addition, there is a need for the standardization of the measurement of complement activation products that are so critical in determining whether clinically relevant complement activation has occurred in vivo. Finally, autoantibodies to complement proteins (e.g. anti-C1q), C3 and C4 convertases (C3 and C4 nephritic factor) or to regulatory proteins

  7. The new self-supporting face brick façades

    Directory of Open Access Journals (Sweden)

    C. del Río

    2016-12-01

    Full Text Available The ‘Self-Supporting’ face brick façade is the result of a profound reflection on the different façade solutions that have been used throughout the last century for the pillar-structured buildings, and is based on the utilization of the potential that ceramic materials have when they work in compression. The construction solution consists in placing the entire outer sheet of the enclosure ahead of the building’s structure, so as to use the brick wall itself as its own supporting structure. This construction type eliminates the thermal bridges at façade-slab joints, and is more effective regarding mechanical behaviour than conventional solutions, since the own-weight effect contributes beneficially to stability against horizontal actions.

  8. [Data mining analysis of professor Li Fa-zhi AIDS itchy skin medical record].

    Science.gov (United States)

    Wang, Dan-Ni; Li, Zhen; Xu, Li-Ran; Guo, Hui-Jun

    2013-08-01

    Analysis of professor Li Fa-zhi in the treatment of AIDS drug laws of itchy skin, provide the corresponding drug reference basis for Chinese medicine treatment of AIDS, skin itching. By using the method of analyzing the complex network of Weishi county, Henan in 2007 October to 2011 July during an interview with professor Li Fa-zhi treatment of AIDS patients with skin pruritus, etiology and pathogenesis analysis, skin itching AIDS syndrome differentiation of old Chinese medicine treatment and medication rule. The use of multi-dimensional query analysis, core drug skin itching AIDS treatment in this study as a windbreak, cicada slough, bupleurum, Qufeng solution table drug, licorice detoxification efficacy of drugs, Radix Scutellariae, Kochia scoparia, clearing away heat and promoting diuresis medicine; core prescription for Jingfang San streak virus. Professor Li Fa-zhi treatment of AIDS in the skin itching Qufeng solution table dehumidification antipruritic treatment.

  9. Numerical simulations of the ISO 13785-2 façade fire tests

    Directory of Open Access Journals (Sweden)

    Hostikka Simo

    2016-01-01

    Full Text Available In this work we created a numerical model of the ISO 13785-2 test setup for testing the fire behaviour of building façade systems, and used the model to simulate the thermal environment on the façade. The model, created using Fire Dynamics Simulator –software, was first validated using the experimental data by Yoshioka et al.(2012. Next, the sensitivity of the façade heat fluxes on the geometrical and model parameters was studied, revealing for instance that the size of the combustion chamber window will influence the thermal exposure high above the window. Finally, the model was used to estimate the thickness of non-combustible insulation layer that is needed to protect combustible materials from melting or decomposition.

  10. The influence of ventilated façade on sound insulation properties of envelope walls

    Directory of Open Access Journals (Sweden)

    Fišarová Zuzana

    2017-01-01

    Full Text Available Presented article deals with sound insulation properties of timber structures’ envelope walls. Particularly, the influence of heavy board ventilated façade on laboratory airborne sound insulation R and Rw in dB was studied. The installation method and gaps between façade boards can cause building defects originating in overrating the influence of ventilated cladding on envelope wall acoustic parameters. Real constructions were built for the experimental purposes and measurements, one with gaps between boards and one with simply eliminated gaps for mutual comparison. The results obtained were processed to make tables and graphs and to derive recommendations for the design of this type of constructions involving the general installation method of façade boards. Detailed results are depicted in conclusions.

  11. Interactive Coherence-Based Façade Modeling

    KAUST Repository

    Musialski, Przemyslaw

    2012-05-01

    We propose a novel interactive framework for modeling building facades from images. Our method is based on the notion of coherence-based editing which allows exploiting partial symmetries across the facade at any level of detail. The proposed workflow mixes manual interaction with automatic splitting and grouping operations based on unsupervised cluster analysis. In contrast to previous work, our approach leads to detailed 3d geometric models with up to several thousand regions per facade. We compare our modeling scheme to others and evaluate our approach in a user study with an experienced user and several novice users.

  12. complement C3, Complement C4 and C-reactive protein

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... Serum levels of complement C3, C4 and C-reactive protein were determined in 24 male smokers ... ability to alter the function of immune cells (Sopori, 2002). ... history of ≥1 cigarette per day and smoking period of at least 6.

  13. A new treatment for neurogenic inflammation caused by EV71 with CR2-targeted complement inhibitor

    Directory of Open Access Journals (Sweden)

    Qiu Shaofu

    2012-11-01

    Full Text Available Abstract Background Enterovirus 71 (EV71, one of the most important neurotropic EVs, has caused death and long-term neurological sequelae in hundreds of thousands of young children in the Asia-Pacific region in the past decade. The neurological diseases are attributed to infection by EV71 inducing an extensive peripheral and central nervous system (CNS inflammatory response with abnormal cytokine production and lymphocyte depletion induced by EV71 infection. In the absence of specific antiviral agents or vaccines, an effective immunosuppressive strategy would be valuable to alleviate the severity of the local inflammation induced by EV71 infection. Presentation of the hypothesis The complement system plays a pivotal role in the inflammatory response. Inappropriate or excessive activation of the complement system results in a severe inflammatory reaction or numerous pathological injuries. Previous studies have revealed that EV71 infection can induce complement activation and an inflammatory response of the CNS. CR2-targeted complement inhibition has been proved to be a potential therapeutic strategy for many diseases, such as influenza virus-induced lung tissue injury, postischemic cerebral injury and spinal cord injury. In this paper, a mouse model is proposed to test whether a recombinant fusion protein consisting of CR2 and a region of Crry (CR2-Crry is able to specifically inhibit the local complement activation induced by EV71 infection, and to observe whether this treatment strategy can alleviate or even cure the neurogenic inflammation. Testing the hypothesis CR2-Crry is expressed in CHO cells, and its biological activity is determined by complement inhibition assays. 7-day-old ICR mice are inoculated intracranially with EV71 to duplicate the neurological symptoms. The mice are then divided into two groups, in one of which the mice are treated with CR2-Crry targeted complement inhibitor, and in the other with phosphate-buffered saline. A

  14. Explication of Definitional Description and Empirical Use of Fraction of Orally Administered Drugs Absorbed From the Intestine (Fa) and Intestinal Availability (Fg): Effect of P-glycoprotein and CYP3A on Fa and Fg.

    Science.gov (United States)

    Tanaka, Yuta; Kitamura, Yoshiaki; Maeda, Kazuya; Sugiyama, Yuichi

    2016-02-01

    Conventionally, it is believed that the fraction of orally administered drugs absorbed from the intestine (Fa) and intestinal availability (Fg) are independently determined by the apical membrane permeation and intestinal metabolism, respectively. However, the validity of this belief has not been well discussed, and Fa and Fg are often used without careful definition. In this review, Fa and Fg are mathematically described based on their definitions under the linear kinetics of metabolism and transport. Even considering with different models, intestinal metabolic enzymes such as cytochrome P450 3A affected both Fa and Fg, whereas apical efflux transporters including P-glycoprotein had no influence on Fg at least under the linear condition. To determine whether Fa and Fg calculated using different clinical methods are identical, empirical Fa and Fg were mathematically described based on "feces method" and "grapefruit juice method" and compared with their definitions. Fa and Fg obtained by the feces method corresponded with their definitions whereas the grapefruit juice method provided smaller Fa and larger Fg particularly for dual substrates of P-glycoprotein and cytochrome P450 3A with low membrane permeability. Our analyses suggest that the definitions and calculation methods of Fa and Fg should be considered when we intend to separately determine these values.

  15. The application of Westcott Formalism k0 NAA method to estimate short and medium lived elements in some Ghanaian herbal medicines complemented by AAS

    Science.gov (United States)

    Ayivor, J. E.; Okine, L. K. N.; Dampare, S. B.; Nyarko, B. J. B.; Debrah, S. K.

    2012-04-01

    The epithermal neutron shape factor, α of the inner and outer irradiation sites of the Ghana Research Reactor-1 (GHARR-1) was determined obtaining results of 0.105 for the inner (Channel 1) Irradiation site and 0.020 for the outer (channel 6) irradiation site. The neutron temperatures for the inner and outer irradiation sites were 27 °C and 20 °C, respectively. The α values used in Westcott Formalism k0 INAA was applied to determine multi elements in 13 Ghanaian herbal medicines used by the Centre for Scientific Research into Plant Medicine (CSRPM) for the management of various diseases complemented by Atomic Absorption Spectrometry. They are namely Mist. Antiaris, Mist. Enterica, Mist. Morazia, Mist. Nibima, Mist. Modium, Mist. Ninger, Mist Sodenia, Mist. Tonica, Chardicca Powder, Fefe Powder, Olax Powder, Sirrapac powder and Lippia Tea. Concentrations of Al, As, Br, K, Cl, Cu, Mg, Mn, Na and V were determined by short and medium irradiations at a thermal neutron flux of 5×1011 ncm-2 s-1. Fe, Cr, Pb, Co, Ni, Sn, Ca, Ba, Li and Sb were determined using Atomic Absorption Spectrometry (AAS). Ba, Cu, Li and V were present at trace levels whereas Al, Cl, Na, Ca were present at major levels. K, Br, Mg, Mn, Co, Ni, Fe and Sb were also present at minor levels. Arsenic was not detected in all samples. Standard Reference material, IAEA-V-10 Hay Powder was simultaneously analysed with samples. The precision and accuracy of the method using real samples and standard reference materials were evaluated and within ±10% of the reported value. Multivariate analytical techniques, such as cluster analysis (Q-mode and R-mode CA) and principal component analysis (PCA)/factor analysis (FA), have been applied to evaluate the chemical variations in the herbal medicine dataset. All the 13 samples may be grouped into 2 statistically significant clusters (liquid based and powdered herbal medicines), reflecting the different chemical compositions. R-mode CA and PCA suggest common

  16. [Biological roles of complement and recent topics in clinical medicine].

    Science.gov (United States)

    Wakamiya, Nobutaka

    2012-08-01

    The complement has been identified as a complementation factor to compensate for the function of an antibody. The complement consists of C1-C9, a complement-related molecule, and its regulating molecules. Three major biological roles of the complement have been classified: First: opsonization following phagocytosis and the elimination of microbes; second: direct destruction of bacteria due to membrane attack complex (MAC); third: complement activation following the induction of anaphylactoid factors and local recruitment and activation of neutrophilic leukocytes. In this review, the basic findings and recent treatments of paroxysmal nocturnal hemoglobinuria (PNH) and hereditary angioedema (HAE) are summarized. Finally, there is a short review of a rare autosomal recessive disorder of 3MC syndrome and new biological functions of complement factors except for that of innate immunity are proposed.

  17. The Complement System and Antibody-Mediated Transplant Rejection.

    Science.gov (United States)

    Stites, Erik; Le Quintrec, Moglie; Thurman, Joshua M

    2015-12-15

    Complement activation is an important cause of tissue injury in patients with Ab-mediated rejection (AMR) of transplanted organs. Complement activation triggers a strong inflammatory response, and it also generates tissue-bound and soluble fragments that are clinically useful markers of inflammation. The detection of complement proteins deposited within transplanted tissues has become an indispensible biomarker of AMR, and several assays have recently been developed to measure complement activation by Abs reactive to specific donor HLA expressed within the transplant. Complement inhibitors have entered clinical use and have shown efficacy for the treatment of AMR. New methods of detecting complement activation within transplanted organs will improve our ability to diagnose and monitor AMR, and they will also help guide the use of complement inhibitory drugs.

  18. Targeted complement inhibition and microvasculature in transplants: a therapeutic perspective.

    Science.gov (United States)

    Khan, M A; Hsu, J L; Assiri, A M; Broering, D C

    2016-02-01

    Active complement mediators play a key role in graft-versus-host diseases, but little attention has been given to the angiogenic balance and complement modulation during allograft acceptance. The complement cascade releases the powerful proinflammatory mediators C3a and C5a anaphylatoxins, C3b, C5b opsonins and terminal membrane attack complex into tissues, which are deleterious if unchecked. Blocking complement mediators has been considered to be a promising approach in the modern drug discovery plan, and a significant number of therapeutic alternatives have been developed to dampen complement activation and protect host cells. Numerous immune cells, especially macrophages, develop both anaphylatoxin and opsonin receptors on their cell surface and their binding affects the macrophage phenotype and their angiogenic properties. This review discusses the mechanism that complement contributes to angiogenic injury, and the development of future therapeutic targets by antagonizing activated complement mediators to preserve microvasculature in rejecting the transplanted organ.

  19. Theoretical implications of complement structure acquisition in Korean.

    Science.gov (United States)

    Kim, Y J

    1989-10-01

    The acquisition of complement phrasal constructions in Korean is examined in spontaneous speech data from two children, who were observed from one and a half to three years of age. In spite of typological differences between English and Korean, both syntactic and semantic characteristics are found to be shared by children acquiring complement constructions in the two languages. However, certain language-specific features of Korean complement structures make it possible to address theoretical points concerning the structure of infinitival complements which cannot be resolved with the acquisition data on English. The error pattern in the acquisition of certain 'subject-equi' verbs in Korean poses problems both for LFG and GB accounts of the constituent structure of infinitival complements and the acquisition of those constructions. On the basis of the Korean data, I propose that base-generated VP complements are acquired first, with semantically motivated reanalysis of previously acquired infinitival complement structures occurring at a later stage.

  20. The role of complement in experimental autoimmune myasthenia gravis

    Science.gov (United States)

    Kusner, Linda L.; Kaminski, Henry J.

    2012-01-01

    Complement plays an important role in the pathophysiology of experimental autoimmune myasthenia gravis (EAMG). The deposition of IgG at the neuromuscular junction, followed by the activation and observance of C3 at the site, and finally the insertion of the membrane attack complex, which results in the destruction of the plasma membrane at the neuromuscular junction. Animal models’ of complement-deficient components show the importance of the mediated lysisin EAMG. These events have regulators that allow for the limitation in the cascade and the ability of the cell to inhibit complement at many places along the pathway. The complement regulatory proteins have many roles in reducing the activation of the complement cascade and the inflammatory pathways. Mice deficient in complement regulatory proteins, decay accelerating factor and CD59, demonstrate a significant increase in the destruction at the neuromuscular junction. Inhibition of complement-mediated lysis is an attractive therapeutic in MG. PMID:23252907

  1. Calculation Method and Analysis for the Annual Power Generation of PV Façades in China

    Institute of Scientific and Technical Information of China (English)

    Shen Xu; ZhongMing Hu; Jian Kang; Wei Liao; Jing Huang

    2014-01-01

    The application of PV façades emerges greatly in recent years and however its calculation methods and analysis remains insufficient under the weather conditions of China. In such demand, this paper investigates PV façade in terms of PV electricity generation in different arrangements and weather conditions of four major cities in China. The calculation models for PV façade are developed and validated by comparing the results with the measured data from the field experiments. A parametric study is carried out to provide a reference for the optimal design of the PV façades. The results show that with various cities, building orientations, building forms, materials and arrangements of PV modules, there is a distinct difference in the electrical output energy of PV façades. Weather conditions play a very important role in terms of PV generation performance of PV façades.

  2. FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression

    DEFF Research Database (Denmark)

    Tornehave, D; Jensen, Charlotte Harken; Teisner, B;

    1996-01-01

    proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine...... tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing...... development, gradually disappeared from these cells and became restricted to insulin-producing beta cells. Throughout development FA1 was not detected in endocrine glucagon, somatostatin or pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed glucagon were negative for FA1. Thus...

  3. Interpain A, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3.

    Directory of Open Access Journals (Sweden)

    Michal Potempa

    2009-02-01

    Full Text Available Periodontitis is an inflammatory disease of the supporting structures of the teeth caused by, among other pathogens, Prevotella intermedia. Many strains of P. intermedia are resistant to killing by the human complement system, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with recombinant cysteine protease of P. intermedia (interpain A resulted in a drastic decrease in bactericidal activity of the serum. Furthermore, a clinical strain 59 expressing interpain A was more serum-resistant than another clinical strain 57, which did not express interpain A, as determined by Western blotting. Moreover, in the presence of the cysteine protease inhibitor E64, the killing of strain 59 by human serum was enhanced. Importantly, we found that the majority of P. intermedia strains isolated from chronic and aggressive periodontitis carry and express the interpain A gene. The protective effect of interpain A against serum bactericidal activity was found to be attributable to its ability to inhibit all three complement pathways through the efficient degradation of the alpha-chain of C3 -- the major complement factor common to all three pathways. P. intermedia has been known to co-aggregate with P. gingivalis, which produce gingipains to efficiently degrade complement factors. Here, interpain A was found to have a synergistic effect with gingipains on complement degradation. In addition, interpain A was able to activate the C1 complex in serum, causing deposition of C1q on inert and bacterial surfaces, which may be important at initial stages of infection when local inflammatory reaction may be beneficial for a pathogen. Taken together, the newly characterized interpain A proteinase appears to be an important virulence factor of P. intermedia.

  4. A Security-façade Library for Virtual-observatory Software

    Science.gov (United States)

    Rixon, G.

    2009-09-01

    The security-façade library implements, for Java, IVOA's security standards. It supports the authentication mechanisms for SOAP and REST web-services, the sign-on mechanisms (with MyProxy, AstroGrid Accounts protocol or local credential-caches), the delegation protocol, and RFC3820-enabled HTTPS for Apache Tomcat. Using the façade, a developer who is not a security specialist can easily add access control to a virtual-observatory service and call secured services from an application. The library has been an internal part of AstroGrid software for some time and it is now offered for use by other developers.

  5. El rol de los nuevos anticoagulantes en pacientes con fibrilación auricular (FA)

    OpenAIRE

    Ferrari, Eliseo; Pérez Duhalde, Carolina; Bertaini, Omar; Farina, Juan P

    2016-01-01

    Alrededor de un 15 % de los accidentes cardiovasculares (ACV) son de tipo embolico, consecuencia principalmente de la Fibrilación Auricular (FA)1,2. Los anticoagulantes cumarínicos han demostrado reducir en forma significativa el riesgo de embolia en pacientes con FA 2,3. Las desventajas de estos fármacos son el riesgo de sangrado y que requieren un monitoreo estricto; lo que conlleva una adherencia poco confiable, alrededor de un 30 a 60%, y una extrema variabilidad en sus efectos 4. En a...

  6. Acidosis activates complement system in vitro

    Directory of Open Access Journals (Sweden)

    Michael Emeis

    1998-01-01

    Full Text Available We investigated the in vitro effect of different form s of acidosis (pH 7.0 on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 μ mol/ml blood or lactic acid (5.5 μ mol/ml to heparin blood (N=12 caused significant activation of C3a and C5a compared to control (both p=0.002. Respiratory acidosis activated C3a (p=0.007 and C5a (p=0.003 compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5.

  7. Acidosis activates complement system in vitro.

    Science.gov (United States)

    Emeis, M; Sonntag, J; Willam, C; Strauss, E; Walka, M M; Obladen, M

    1998-01-01

    We investigated the in vitro effect of different forms of acidosis (pH 7.0) on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 micromol/ml blood) or lactic acid (5.5 micromol/ml) to heparin blood (N=12) caused significant activation of C3a and C5a compared to control (both p=0.002). Respiratory acidosis activated C3a (p=0.007) and C5a (p=0.003) compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5. PMID:9927235

  8. Lectin Complement Pathway Proteins in Healthy Individuals

    DEFF Research Database (Denmark)

    Troldborg, Anne; Hansen, Annette; Hansen, Søren W K

    2017-01-01

    Since the discovery of the lectin pathway of complement activation, numerous clinical cohorts have been examined for one or more of the proteins, with the intention of uncovering the functions of the proteins or with the aim of discovering new biomarkers or diagnostic tools. To unveil the abnormal......, it is pivotal to know the normal. Our aim was to describe the concentrations of the eleven known proteins of the lectin pathway in serum and plasma and to uncover possible gender differences, age and diurnal variations, which must be taken into account for investigations in different cohorts. We examined...... the concentrations of all lectin pathway proteins (mannan-binding lectin (MBL), H-ficolin, L-ficolin, M-ficolin, collectin-K1, collectin-L1, MBL-associated serine protease 2 (MASP-2), MASP-3, MBL associated protein of 44 kDa (MAp44) and MAp19 in 300 Danish blood donors in serum and EDTA plasma in established assays...

  9. Complement depletion deteriorates clinical outcomes of severe abdominal sepsis: a conspirator of infection and coagulopathy in crime?

    Directory of Open Access Journals (Sweden)

    Jianan Ren

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

  10. Role of complement receptor 1 (CR1; CD35) on epithelial cells: A model for understanding complement-mediated damage in the kidney.

    Science.gov (United States)

    Java, Anuja; Liszewski, M Kathryn; Hourcade, Dennis E; Zhang, Fan; Atkinson, John P

    2015-10-01

    The regulators of complement activation gene cluster encodes a group of proteins that have evolved to control the amplification of complement at the critical step of C3 activation. Complement receptor 1 (CR1) is the most versatile of these inhibitors with both receptor and regulatory functions. While expressed on most peripheral blood cells, the only epithelial site of expression in the kidney is by the podocyte. Its expression by this cell population has aroused considerable speculation as to its biologic function in view of many complement-mediated renal diseases. The goal of this investigation was to assess the role of CR1 on epithelial cells. To this end, we utilized a Chinese hamster ovary cell model system. Among our findings, CR1 reduced C3b deposition by ∼ 80% during classical pathway activation; however, it was an even more potent regulator (>95% reduction in C3b deposition) of the alternative pathway. This inhibition was primarily mediated by decay accelerating activity. The deposited C4b and C3b were progressively cleaved with a t½ of ∼ 30 min to C4d and C3d, respectively, by CR1-dependent cofactor activity. CR1 functioned intrinsically (i.e, worked only on the cell on which it was expressed). Moreover, CR1 efficiently and stably bound but didn't internalize C4b/C3b opsonized immune complexes. Our studies underscore the potential importance of CR1 on an epithelial cell population as both an intrinsic complement regulator and an immune adherence receptor. These results provide a framework for understanding how loss of CR1 expression on podocytes may contribute to complement-mediated damage in the kidney.

  11. The complement system in systemic lupus erythematosus: an update.

    Science.gov (United States)

    Leffler, Jonatan; Bengtsson, Anders A; Blom, Anna M

    2014-09-01

    The complement system plays a major role in the autoimmune disease, systemic lupus erythematosus (SLE). However, the role of complement in SLE is complex since it may both prevent and exacerbate the disease. In this review, we explore the latest findings in complement-focused research in SLE. C1q deficiency is the strongest genetic risk factor for SLE, although such deficiency is very rare. Various recently discovered genetic associations include mutations in the complement receptors 2 and 3 as well as complement inhibitors, the latter related to earlier onset of nephritis. Further, autoantibodies are a distinct feature of SLE that are produced as the result of an adaptive immune response and how complement can affect that response is also being reviewed. SLE generates numerous disease manifestations involving contributions from complement such as glomerulonephritis and the increased risk of thrombosis. Furthermore, since most of the complement system is present in plasma, complement is very accessible and may be suitable as biomarker for diagnosis or monitoring of disease activity. This review highlights the many roles of complement for SLE pathogenesis and how research has progressed during recent years.

  12. The Expression Profile of Complement Components in Podocytes.

    Science.gov (United States)

    Li, Xuejuan; Ding, Fangrui; Zhang, Xiaoyan; Li, Baihong; Ding, Jie

    2016-03-30

    Podocytes are critical for maintaining the glomerular filtration barrier and are injured in many renal diseases, especially proteinuric kidney diseases. Recently, reports suggested that podocytes are among the renal cells that synthesize complement components that mediate glomerular diseases. Nevertheless, the profile and extent of complement component expression in podocytes remain unclear. This study examined the expression profile of complement in podocytes under physiological conditions and in abnormal podocytes induced by multiple stimuli. In total, 23/32 complement component components were detected in podocyte by conventional RT-PCR. Both primary cultured podocytes and immortalized podocytes expressed the complement factors C1q, C1r, C2, C3, C7, MASP, CFI, DAF, CD59, C4bp, CD46, Protein S, CR2, C1qR, C3aR, C5aR, and Crry (17/32), whereas C4, CFB, CFD, C5, C6, C8, C9, MBL1, and MBL2 (9/32) complement factors were not expressed. C3, Crry, and C1q-binding protein were detected by tandem mass spectrometry. Podocyte complement gene expression was affected by several factors (puromycin aminonucleoside (PAN), angiotensin II (Ang II), interleukin-6 (IL-6), and transforming growth factor-β (TGF-β)). Representative complement components were detected using fluorescence confocal microscopy. In conclusion, primary podocytes express various complement components at the mRNA and protein levels. The complement gene expressions were affected by several podocyte injury factors.

  13. A vital role for complement in heart disease.

    Science.gov (United States)

    Lappegård, Knut T; Garred, Peter; Jonasson, Lena; Espevik, Terje; Aukrust, Pål; Yndestad, Arne; Mollnes, Tom E; Hovland, Anders

    2014-10-01

    Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors, emerging evidence points to an association between the complement system and heart diseases. Thus, complement seems to be important in coronary heart disease as well as in heart failure, where several studies underscore the prognostic importance of complement activation. Furthermore, patients with atrial fibrillation often share risk factors both with coronary heart disease and heart failure, and there is some evidence implicating complement activation in atrial fibrillation. Moreover, Chagas heart disease, a protozoal infection, is an important cause of heart failure in Latin America, and the complement system is crucial for the protozoa-host interaction. Thus, complement activation appears to be involved in the pathophysiology of a diverse range of cardiac conditions. Determination of the exact role of complement in the various heart diseases will hopefully help to identify patients that might benefit from therapeutic complement intervention.

  14. HFC245fa热物性数学模型及其lgp-h图%Modeling of Thermodynamic Properties and Transport Properties of HFC245fa and its lgp-h Diagram

    Institute of Scientific and Technical Information of China (English)

    张淑彦; 李岩; 张吉礼

    2011-01-01

    高温热泵适宜采用高温工质.HFC245fa被普遍认为是替代CFC11和HCFC123的HFCs类新型高温工质.本文以试验数据为基础,采用Soave-Redlich-Kwong方程,辩识了HFC245fa的状态方程;采用Wagner模型拟合了HFC245fa的饱和蒸汽压力模型;基于基团原理,建立了HFC245fa的气体定压比热容模型;由Clausius-Clapegron方程得到了HFC245fa的汽化潜热模型;利用多项式模型,拟合了HFC245fa的粘度﹑导热系数等迁移性质模型;最后,根据上述模型,绘制其lgp-h图.结果表明,上述模型和图表的精度能够满足HFC245fa在设备研发和制造中的实际应用.%High temperature work fluids are greatly suitable for the high temperature heat pump,and HFC245fa has been widely considered as a new high temperature work fluid to substitute CFC11 and HCFC123.Based on the experimental results of HFC245fa ,thermodynamic properties models and transport properties models of HFC245fa have been regressed.Namely ,the state equation and saturation vapor pressure equation of HFC245fa have been regressed respectively on the basis of Soave-RedlichKwong model and Wagner model.The vapor isotonic ratio specific heat model of HFC245fa has been created by the group theory.The evaporation latent heat model of HFC245fa has been finished by Clausius-Clapegron equation.Coefficient of viscosity,coefficient of heat transfer and other transport properties equations of HFC245fa have been built by various polynomial models.Finally,the lgp-h diagram of HFC245fa has been drawn out according to the built thermedynamic properties models.The error analyzed results of the thermodynamic properties models and transport properties models of HFC245fa show that all the models can meet the calculation precision demands of its applications in the development of the heat pump.

  15. Effects of inbreeding on survival, body weight and fluctuating asymmetry (FA) in Nile tilapia, Oreochromis niloticus

    NARCIS (Netherlands)

    Fessehaye, Y.; Komen, J.; Rezk, M.A.; Arendonk, van J.A.M.; Bovenhuis, H.

    2007-01-01

    The present study investigated the effects of different levels of inbreeding on survival, growth, body weight and fluctuating asymmetry (FA) in O. niloticus. We mated 20 sires and 35 dams in a full-sib/half-sib mating design to produce 35 full-sib families with expected level of inbreeding (F%.) of

  16. Obesity is accompanied by disturbances in peripheral glucocorticoid metabolism and changes in FA recycling

    DEFF Research Database (Denmark)

    Simonyte, Kotryna; Rask, Eva; Näslund, Ingmar;

    2009-01-01

    The glucocorticoid activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is of major interest in obesity-related morbidity. Alterations in tissue-specific cortisol levels may influence lipogenetic and gluco/glyceroneogenetic pathways in fat and liver. We analyzed the expressio...... acid (FA) recycling in adipose tissue (AT)....

  17. HEAT TRANSFER EVALUATION OF HFC-236FA IN CONDENSATION AND EVAPORATION

    Science.gov (United States)

    The report gives results of an evaluation of the shell-side heat transfer performance of hydrofluorocarbon (HFC)-236fa, which is considered to be a potential substitute for chlorofluorocarbon (CFC)-114 in Navy shipboard chillers, for both conventional finned [1024- and 1575-fpm (...

  18. First International Workshop on Human Factors in Modeling (HuFaMo 2015)

    DEFF Research Database (Denmark)

    Störrle, Harald; Chaudron, Michel R. V.; Amaral, Vasco

    2015-01-01

    and systematic approaches to assert usability in modeling and confirm the claims of productivity. This workshop creates a space for discussion being a get together of both MDE, Usability, Human Interfaces and the Experimental Software engineering community. HuFaMo expressly focuses on human factors, in order...

  19. MISCIBILITY, SOLUBILITY, VISCOSITY, AND DENSITY MEASUREMENTS FOR R-236FA WITH POTENTIAL LUBRICANTS

    Science.gov (United States)

    The report gives results of miscibility, solubility, viscosity, and density measurements for refrigerant R-236fa and two potential lubricants . (The data are needed to determine the suitability of refrigerant/lubricant combinations for use in refrigeration systems.) The tested oi...

  20. Foetal antigen 2 (FA2) in the stromal reaction induced by breast carcinoma

    DEFF Research Database (Denmark)

    Rasmussen, H B; Teisner, B; Andersen, J A

    1992-01-01

    An indirect immunoperoxidase technique was used to examine the distribution of foetal antigen 2 (FA2), a recently described basement membrane (BM)-associated antigen, in invasive breast carcinoma (n = 34), fibroadenoma (n = 5) and normal breast tissue (n = 5), and to compare its distribution...

  1. Objective and subjective evaluation of façade sound insulation

    DEFF Research Database (Denmark)

    Ordoñez, Rodrigo Pizarro; Visentin, Chiara; Markovic, Milos;

    2013-01-01

    Façade insulation of several different construction types were subjectively evaluated using two psychoacoustic methods: paired comparisons using a two alternative forced choice (2-AFC) paradigm and direct scaling using a visual analogue scale (VAS). The stimuli used in the evaluations were obtained...

  2. Data of evolutionary structure change: 1B0FA-1O3AA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available YDPV >EEE - > ATOM 556 CA ARG A ...ryIDChain>1O3AA KSIVHPSYNSN cture>EEEEE ucture...bChain> 1B0FA LGRNR-GIASV > - ...ence>TKSSGTSYPDV > > ATOM 1849 C...A AHCYK----SGIQV >GGG ---- EEEe>

  3. F.A. FON HAYEK''S AUSTRIAN THEORY OF COMPETITION

    OpenAIRE

    Nesterenko, O.

    2008-01-01

    F.A. fon Hayek's approach to competition's understanding has been clarified, critical analysis directions of neo-classical model of perfect competition have been analyzed. Specific points of Austrian competitive theory have been determined and scientist ideas evolution to competitive process has been worked out.

  4. Data of evolutionary structure change: 1A3FA-2NOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1A3FA-2NOTA 1A3F 2NOT A A NLYQFKNMIKCTV-PSRSWWDFADYGCYCGRGGSGTPVD...ignment> 0 2NOT A 2NOTA...in> -65.49500274658203 5.223999977111816 14.175999641418457 ...99998712539673 0.8920000195503235 tion> 1.2738020420074463 2.701137065887451 ...

  5. Consumption of fa cai Nostoc soup: a potential for BMAA exposure from Nostoc cyanobacteria in China?

    Science.gov (United States)

    Roney, Britton R; Renhui, Li; Banack, Sandra Anne; Murch, Susan; Honegger, Rosmarie; Cox, Paul Alan

    2009-01-01

    Grown in arid regions of western China the cyanobacterium Nostoc flagelliforme--called fa cai in Mandarin and fat choy in Cantonese--is wild-harvested and used to make soup consumed during New Year's celebrations. High prices, up to $125 USD/kg, led to overharvesting in Inner Mongolia, Ningxia, Gansu, Qinghai, and Xinjiang. Degradation of arid ecosystems, desertification, and conflicts between Nostoc harvesters and Mongol herdsmen concerned the Chinese environmental authorities, leading to a government ban of Nostoc commerce. This ban stimulated increased marketing of a substitute made from starch. We analysed samples purchased throughout China as well as in Chinese markets in the United States and the United Kingdom. Some were counterfeits consisting of dyed starch noodles. A few samples from California contained Nostoc flagelliforme but were adulterated with starch noodles. Other samples, including those from the United Kingdom, consisted of pure Nostoc flagelliforme. A recent survey of markets in Cheng Du showed no real Nostoc flagelliforme to be marketed. Real and artificial fa cai differ in the presence of beta-N-methylamino-L-alanine (BMAA). Given its status as a high-priced luxury food, the government ban on collection and marketing, and the replacement of real fa cai with starch substitutes consumed only on special occasions, it is anticipated that dietary exposure to BMAA from fa cai will be reduced in the future in China.

  6. Toward a structure-based comprehension of the lectin pathway of complement

    DEFF Research Database (Denmark)

    Kjaer, Troels R; Thiel, Steffen; Andersen, Gregers R

    2013-01-01

    To initiate the lectin pathway of complement pattern recognition molecules bind to surface-linked carbohydrates or acetyl groups on pathogens or damaged self-tissue. This leads to activation of the serine proteases MASP-1 and MASP-2 resulting in deposition of C4 on the activator and assembly...

  7. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

  8. Complement-Mediated Regulation of Metabolism and Basic Cellular Processes.

    Science.gov (United States)

    Hess, Christoph; Kemper, Claudia

    2016-08-16

    Complement is well appreciated as a critical arm of innate immunity. It is required for the removal of invading pathogens and works by directly destroying them through the activation of innate and adaptive immune cells. However, complement activation and function is not confined to the extracellular space but also occurs within cells. Recent work indicates that complement activation regulates key metabolic pathways and thus can impact fundamental cellular processes, such as survival, proliferation, and autophagy. Newly identified functions of complement include a key role in shaping metabolic reprogramming, which underlies T cell effector differentiation, and a role as a nexus for interactions with other effector systems, in particular the inflammasome and Notch transcription-factor networks. This review focuses on the contributions of complement to basic processes of the cell, in particular the integration of complement with cellular metabolism and the potential implications in infection and other disease settings.

  9. Complement, a target for therapy in inflammatory and degenerative diseases.

    Science.gov (United States)

    Morgan, B Paul; Harris, Claire L

    2015-12-01

    The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.

  10. Protein ultrastructure and the nanoscience of complement activation.

    Science.gov (United States)

    Vorup-Jensen, Thomas; Boesen, Thomas

    2011-09-16

    The complement system constitutes an important barrier to infection of the human body. Over more than four decades structural properties of the proteins of the complement system have been investigated with X-ray crystallography, electron microscopy, small-angle scattering, and atomic force microscopy. Here, we review the accumulated evidence that the nm-scaled dimensions and conformational changes of these proteins support functions of the complement system with regard to tissue distribution, molecular crowding effects, avidity binding, and conformational regulation of complement activation. In the targeting of complement activation to the surfaces of nanoparticulate material, such as engineered nanoparticles or fragments of the microbial cell wall, these processes play intimately together. This way the complement system is an excellent example where nanoscience may serve to unravel the molecular biology of the immune response.

  11. Slicing Method for curved façade and window extraction from point clouds

    Science.gov (United States)

    Iman Zolanvari, S. M.; Laefer, Debra F.

    2016-09-01

    Laser scanning technology is a fast and reliable method to survey structures. However, the automatic conversion of such data into solid models for computation remains a major challenge, especially where non-rectilinear features are present. Since, openings and the overall dimensions of the buildings are the most critical elements in computational models for structural analysis, this article introduces the Slicing Method as a new, computationally-efficient method for extracting overall façade and window boundary points for reconstructing a façade into a geometry compatible for computational modelling. After finding a principal plane, the technique slices a façade into limited portions, with each slice representing a unique, imaginary section passing through a building. This is done along a façade's principal axes to segregate window and door openings from structural portions of the load-bearing masonry walls. The method detects each opening area's boundaries, as well as the overall boundary of the façade, in part, by using a one-dimensional projection to accelerate processing. Slices were optimised as 14.3 slices per vertical metre of building and 25 slices per horizontal metre of building, irrespective of building configuration or complexity. The proposed procedure was validated by its application to three highly decorative, historic brick buildings. Accuracy in excess of 93% was achieved with no manual intervention on highly complex buildings and nearly 100% on simple ones. Furthermore, computational times were less than 3 sec for data sets up to 2.6 million points, while similar existing approaches required more than 16 hr for such datasets.

  12. Valve inlet fluid conditions for pressurizer safety and relief valves for B and W 177-FA and 205-FA plants. Final report. [PWR

    Energy Technology Data Exchange (ETDEWEB)

    Cartin, L.R.; Winks, R.W.; Merchent, J.W.; Brandt, R.T.

    1982-12-01

    The overpressurization transients for the Babcock and Wilcox Company's 177- and 205-FA units are reviewed to determine the range of fluid conditions expected at the inlet of pressurizer safety and relief valves. The final Safety Analysis Report, extended high-pressure injection, and cold overpressurization events are considered. The results of this review, presented in the form of tables and graphs, provide input to the PWR utilities in their justification that the fluid conditions under which their valve designs were tested as part of the EPRI PWR Safety and Relief Valve Test Program are representative of those expected in their unit(s).

  13. PROTEIN ENGINEERING TO TARGET COMPLEMENT EVASION IN CANCER

    OpenAIRE

    Carter, Darrick; Lieber, André

    2013-01-01

    The complement system is composed of soluble factors in plasma that enhance or “complement” immune-mediated killing through innate and adaptive mechanisms. Activation of complement causes recruitment of immune cells; opsonization of coated cells; and direct killing of affected cells through a membrane attack complex (MAC). Tumor cells up-regulate complement inhibitory factors -one of several strategies to evade the immune system. In many cases as the tumor progresses, dramatic increases in co...

  14. The Complement of Normal Fuzzy Numbers: An Exposition

    Directory of Open Access Journals (Sweden)

    Mamoni Dhar

    2013-07-01

    Full Text Available In this article, our main intention is to revisit the existing definition of complementation of fuzzy sets and thereafter various theories associated with it are also commented on. The main contribution of this paper is to suggest a new definition of complementation of fuzzy sets on the basis of reference function. Some other results have also been introduced whenever possible by using this new definition of complementation.

  15. The Complement of Normal Fuzzy Numbers: An Exposition

    OpenAIRE

    Mamoni Dhar; Baruah, Hemanta K

    2013-01-01

    In this article, our main intention is to revisit the existing definition of complementation of fuzzy sets and thereafter various theories associated with it are also commented on. The main contribution of this paper is to suggest a new definition of complementation of fuzzy sets on the basis of reference function. Some other results have also been introduced whenever possible by using this new definition of complementation.

  16. Initiation and Regulation of Complement during Hemolytic Transfusion Reactions

    Directory of Open Access Journals (Sweden)

    Sean R. Stowell

    2012-01-01

    Full Text Available Hemolytic transfusion reactions represent one of the most common causes of transfusion-related mortality. Although many factors influence hemolytic transfusion reactions, complement activation represents one of the most common features associated with fatality. In this paper we will focus on the role of complement in initiating and regulating hemolytic transfusion reactions and will discuss potential strategies aimed at mitigating or favorably modulating complement during incompatible red blood cell transfusions.

  17. Complement component 5 promotes lethal thrombosis

    Science.gov (United States)

    Mizuno, Tomohiro; Yoshioka, Kengo; Mizuno, Masashi; Shimizu, Mie; Nagano, Fumihiko; Okuda, Tomoyuki; Tsuboi, Naotake; Maruyama, Shoichi; Nagamatsu, Tadashi; Imai, Masaki

    2017-01-01

    Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis. PMID:28205538

  18. Altmetrics - a complement to conventional metrics.

    Science.gov (United States)

    Melero, Remedios

    2015-01-01

    Emerging metrics based on article-level does not exclude traditional metrics based on citations to the journal, but complements them. Both can be employed in conjunction to offer a richer picture of an article use from immediate to long terms. Article-level metrics (ALM) is the result of the aggregation of different data sources and the collection of content from multiple social network services. Sources used for the aggregation can be broken down into five categories: usage, captures, mentions, social media and citations. Data sources depend on the tool, but they include classic metrics indicators based on citations, academic social networks (Mendeley, CiteULike, Delicious) and social media (Facebook, Twitter, blogs, or Youtube, among others). Altmetrics is not synonymous with alternative metrics. Altmetrics are normally early available and allow to assess the social impact of scholarly outputs, almost at the real time. This paper overviews briefly the meaning of altmetrics and describes some of the existing tools used to apply this new metrics: Public Library of Science--Article-Level Metrics, Altmetric, Impactstory and Plum.

  19. Altmetrics – a complement to conventional metrics

    Science.gov (United States)

    Melero, Remedios

    2015-01-01

    Emerging metrics based on article-level does not exclude traditional metrics based on citations to the journal, but complements them. Both can be employed in conjunction to offer a richer picture of an article use from immediate to long terms. Article-level metrics (ALM) is the result of the aggregation of different data sources and the collection of content from multiple social network services. Sources used for the aggregation can be broken down into five categories: usage, captures, mentions, social media and citations. Data sources depend on the tool, but they include classic metrics indicators based on citations, academic social networks (Mendeley, CiteULike, Delicious) and social media (Facebook, Twitter, blogs, or Youtube, among others). Altmetrics is not synonymous with alternative metrics. Altmetrics are normally early available and allow to assess the social impact of scholarly outputs, almost at the real time. This paper overviews briefly the meaning of altmetrics and describes some of the existing tools used to apply this new metrics: Public Library of Science - Article-Level Metrics, Altmetric, Impactstory and Plum. PMID:26110028

  20. Lack of a Y-Chromosomal Complement in the Majority of Gestational Trophoblastic Neoplasms

    Directory of Open Access Journals (Sweden)

    Kai Lee Yap

    2010-01-01

    Full Text Available Gestational trophoblastic neoplasms (GTNs are a rare group of neoplastic diseases composed of choriocarcinomas, placental site trophoblastic tumors (PSTTs and epithelioid trophoblastic tumors (ETTs. Since these tumors are derivatives of fetal trophoblastic tissue, approximately 50% of GTN cases are expected to originate from a male conceptus and carry a Y-chromosomal complement according to a balanced sex ratio. To investigate this hypothesis, we carried out a comprehensive analysis by genotyping a relatively large sample size of 51 GTN cases using three independent sex chromosome genetic markers; Amelogenin, Protein Kinase and Zinc Finger have X and Y homologues that are distinguishable by their PCR product size. We found that all cases contained the X-chromosomal complement while only five (10% of 51 tumors harbored the Y-chromosomal complement. Specifically, Y-chromosomal signals were detected in one (5% of 19 choriocarcinomas, one (7% of 15 PSTTs and three (18% of 17 ETTs. The histopathological features of those with a Y-chromosome were similar to those without. Our results demonstrate the presence of a Y-chromosomal complement in GTNs, albeit a low 10% of cases. This shortfall of Y-chromosomal complements in GTNs may reinforce the notion that the majority of GTNs are derived from previous molar gestations.

  1. Mechanisms of evasion of Schistosoma mansoni schistosomula to the lethal activity of complement

    Directory of Open Access Journals (Sweden)

    F. Juarez Ramalho-Pinto

    1992-01-01

    Full Text Available Schistosomula of Schistosoma mansoni became resistant to antibody-dependent complement damage in vitro after pre-incubation with normal human erythrocytes (NHuE whatever the ABO or Rh blood group. Resistant parasites were shown to acquire host decay accelerating factor (DAF , a 70 kDa glycoprotein attached to the membrane of NHue by a GPI anchor. IgG2a mAb anti-human DAF (IA10 immunoprecipitated a 70 kDa molecule from 125I-labeled schistosomula pre-incubated with NHuE and inhibited their resistance to complement-dependent killing in vtro. Incubationof schistosomula with erytrocytes from patients with paroxsimal nocturnal hemoglobinuria (PNHE or SRBC, wich are DAF-deficient, did not protect the parasites from complement lesion. Supernatant of 100,000 x g collected from NHuE incubated for 24 h in defined medium was shown to contain a soluble form of DAF and to protect schistosomula from complement killing. Schistosomula treated with trypsin before incubation with NHuE ghosts did not become resistant to complement damage. On the other hand, pre-treatment with chymotrypsin did not interfere with the acquisition of resistance by the schistosomula. These results indicate that, in vitro, NHuE DAF can be transferred to schistosomula in a soluble form and that the binding of this molecule to the parasite surface is dependent upon trypsin-sensitive chymotrypsin-insensitive polipeptide(s present on the surface of the worm.

  2. The structure of bovine complement component 3 reveals the basis for thioester function

    DEFF Research Database (Denmark)

    Fredslund, Folmer; Jenner, Lasse Bohl; Husted, Lise Bjerre;

    2006-01-01

    The third component of complement (C3) is a 190 kDa glycoprotein essential for eliciting the complement response. The protein consists of two polypeptide chains (α and β) held together with a single disulfide bridge. The β-chain is made up of six MG domains of which one of which is shared...... but not in C5) is cleaved during complement activation. This mediates covalent attachment of the activated C3b to immune complexes and invading microorganisms hereby opsonising the target. We present the structure of bovine C3 determined at 3 Å resolution. The structure shows that the ester is deeply buried...... activation. This rearrangement is proposed to be the basis for the high reactivity of the thioester group. A strictly conserved glutamate is suggested to function catalytically in thioester proteins. Structure based design of inhibitors of C3 activation may target a conserved pocket between the α- and the β...

  3. Activated complement classical pathway in a murine model of oxygen-induced retinopathy

    Institute of Scientific and Technical Information of China (English)

    Xue-Ying; Tao; Shi-Jie; Zheng; Bo; Lei

    2015-01-01

    AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.

  4. CFD model of air movement in ventilated façade: comparison between natural and forced air flow

    Directory of Open Access Journals (Sweden)

    Miguel Mora Pérez, Gonzalo López Patiño, P. Amparo López Jiménez

    2013-01-01

    Full Text Available This study describes computational fluid dynamics (CFD modeling of ventilated façade. Ventilated façades are normal façade but it has an extra channel between the concrete wall and the (double skin façade. Several studies found in the literature are carried out with CFD simulations about the behavior of the thermodynamic phenomena of the double skin façades systems. These studies conclude that the presence of the air gap in the ventilated façade affects the temperature in the building skin, causing a cooling effect, at least in low-rise buildings. One of the most important factors affecting the thermal effects of ventilated façades is the wind velocity. In this contribution, a CFD analysis applied on two different velocity assumptions for air movement in the air gap of a ventilated façade is presented. A comparison is proposed considering natural wind induced velocity with forced fan induced velocity in the gap. Finally, comparing temperatures in the building skin, the differences between both solutions are described determining that, related to the considered boundary conditions, there is a maximum height in which the thermal effect of the induced flow is significantly observed.

  5. CD55 is a key complement regulatory protein that counteracts complement-mediated inactivation of Newcastle Disease Virus.

    Science.gov (United States)

    Rangaswamy, Udaya S; Cotter, Christopher R; Cheng, Xing; Jin, Hong; Chen, Zhongying

    2016-08-01

    Newcastle disease virus (NDV) is being developed as an oncolytic virus for virotherapy. In this study we analysed the regulation of complement-mediated inactivation of a recombinant NDV in different host cells. NDV grown in human cells was less sensitive to complement-mediated virus inactivation than NDV grown in embryonated chicken eggs. Additionally, NDV produced from HeLa-S3 cells is more resistant to complement than NDV from 293F cells, which correlated with higher expression and incorporation of complement regulatory proteins (CD46, CD55 and CD59) into virions from HeLa-S3 cells. Further analysis of the recombinant NDVs individually expressing the three CD molecules showed that CD55 is the most potent in counteracting complement-mediated virus inactivation. The results provide important information on selecting NDV manufacture substrate to mitigate complement-mediated virus inactivation.

  6. Application of FA-SVM optimization algorithm in emotion recognition%FA-SVM优化算法在情感识别中的应用

    Institute of Scientific and Technical Information of China (English)

    张兢; 曾建梅; 李冠迪; 史文进

    2016-01-01

    SVM有着良好的分类性能,在各种分类实践中得到了广泛应用.针对SVM的关键参数,如惩罚因子C和核函数参数γ选取不当会影响SVM性能的问题,提出采用收敛速度快、寻优精度高的萤火虫算法(FA)对SVM关键参数进行自动寻优,建立FA-SVM分类模型,并将该模型应用于脉搏信号的情感识别中.情感分类结果表明,SVM经FA算法优化后,对样本分类的识别率比未经任何处理的SVM高出7.9%,验证了该方法的有效性.

  7. Kodamaea neixiangensis f.a., sp. nov. and Kodamaea jinghongensis f.a., sp. nov., two yeast species isolated from rotting wood.

    Science.gov (United States)

    Gao, Wan-Li; Liu, Tian-Tian; Zheng, Jun; Hui, Feng-Li

    2017-08-25

    Seven strains representing two novel yeast species were isolated from rotting wood in Henan and Yunnan Provinces, PR China. The results of phylogenetic analysis based on the D1/D2 domains of the large subunit (LSU) rRNA gene revealed that these two species are members of the genus Kodamaea, although the formation of ascospores was not observed. Kodamaea neixiangensis f.a., sp. nov. (type strain NYNU 167139T=CICC 33170T=CBS 14699T) formed a clade with Candida kaohsiungensis and Candida hsintzibuensis, from which it differed by 10-16 substitutions in the D1/D2 domain. The ITS sequences of K. neixiangensis sp. nov. differed by 27 substitutions from those of the type strain of C. kaohsiungensis. The most closely related species with a validly published name to Kodamaea jinghongensis f.a., sp. nov. (type strain NYNU 167162T=CICC 33171T=CBS 14700T) was Candida fukazawae, but this differed by 14 substitutions in the D1/D2 domain and by 15 substitutions in the ITS region.

  8. Genetics and complementation of Haemophilus influenzae mutants deficient in adenosine 5'-triphosphate-dependent nuclease

    Energy Technology Data Exchange (ETDEWEB)

    Kooistra, J.; Small, G.D.; Setlow, J.K.; Shapanka, R.

    1976-04-01

    Eight different mutations in Haemophilus influenzae leading to deficiency in adenosine 5'-triphosphate (ATP)-dependent nuclease have been investigated in strains in which the mutations of the originally mutagenized strains have been transferred into the wild type. Sensitivity to mitomycin C and deoxycholate and complementation between extracts and deoxyribonucleic acid (DNA)-dependent ATPase activity have been measured. Genetic crosses have provided information on the relative position of the mutations on the genome. There are three complementation groups, corresponding to three genetic groups. The strains most sensitive to mitomycin and deoxycholate, derived from mutants originally selected on the basis of sensitivity to mitomycin C or methyl methanesulfonate, are in one group. Apparently all these sensitive strains lack DNA-dependent ATPase activity, as does a strain intermediate in sensitivity to deoxycholate, which is the sole representative of another group. There are four strains that are relatively resistant to deoxycholate and mitomycin C, and all of these contain the ATPase activity.

  9. Keeping It All Going-Complement Meets Metabolism.

    Science.gov (United States)

    Kolev, Martin; Kemper, Claudia

    2017-01-01

    The complement system is an evolutionary old and crucial component of innate immunity, which is key to the detection and removal of invading pathogens. It was initially discovered as a liver-derived sentinel system circulating in serum, the lymph, and interstitial fluids that mediate the opsonization and lytic killing of bacteria, fungi, and viruses and the initiation of the general inflammatory responses. Although work performed specifically in the last five decades identified complement also as a critical instructor of adaptive immunity-indicating that complement's function is likely broader than initially anticipated-the dominant opinion among researchers and clinicians was that the key complement functions were in principle defined. However, there is now a growing realization that complement activity goes well beyond "classic" immune functions and that this system is also required for normal (neuronal) development and activity and general cell and tissue integrity and homeostasis. Furthermore, the recent discovery that complement activation is not confined to the extracellular space but occurs within cells led to the surprising understanding that complement is involved in the regulation of basic processes of the cell, particularly those of metabolic nature-mostly via novel crosstalks between complement and intracellular sensor, and effector, pathways that had been overlooked because of their spatial separation. These paradigm shifts in the field led to a renaissance in complement research and provide new platforms to now better understand the molecular pathways underlying the wide-reaching effects of complement functions in immunity and beyond. In this review, we will cover the current knowledge about complement's emerging relationship with the cellular metabolism machinery with a focus on the functional differences between serum-circulating versus intracellularly active complement during normal cell survival and induction of effector functions. We will also

  10. Complement-coagulation cross-talk: a potential mediator of the physiological activation of complement by low pH

    Directory of Open Access Journals (Sweden)

    Hany Ibrahim Kenawy

    2015-05-01

    Full Text Available The complement system is a major constituent of the innate immune system. It not only bridges innate and adaptive arms of the immune system but also links the immune system with the coagulation system. Current understanding of the role of complement has extended far beyond fighting of infections, and now encompasses maintenance of homeostasis, tissue regeneration and pathophysiology of multiple diseases. It has been known for many years that complement activation is strongly pH sensitive, but only relatively recently has the physiological significance of this been appreciated. Most complement assays are carried out at the physiological pH 7.4. However, pH in some extracellular compartments, for example renal tubular fluid in parts of the tubule, and extracellular fluid at inflammation loci, is sufficiently acidic to activate complement. The exact molecular mechanism of this activation is still unclear, but possible cross talk between the contact system and complement may exist at low pH with subsequent complement activation. The current article reviews the published data on the effect of pH on the contact system and complement activity, the nature of the pH sensor molecules, and the clinical implications of these effects. Of particular interest is chronic kidney disease (CKD accompanied by metabolic acidosis, in which therapeutic alkalinisation of urine has been shown significantly to reduce tubular complement activation products, an effect which may have important implications for slowing progression of CKD.

  11. Complement-Coagulation Cross-Talk: A Potential Mediator of the Physiological Activation of Complement by Low pH.

    Science.gov (United States)

    Kenawy, Hany Ibrahim; Boral, Ismet; Bevington, Alan

    2015-01-01

    The complement system is a major constituent of the innate immune system. It not only bridges innate and adaptive arms of the immune system but also links the immune system with the coagulation system. Current understanding of the role of complement has extended far beyond fighting of infections, and now encompasses maintenance of homeostasis, tissue regeneration, and pathophysiology of multiple diseases. It has been known for many years that complement activation is strongly pH sensitive, but only relatively recently has the physiological significance of this been appreciated. Most complement assays are carried out at the physiological pH 7.4. However, pH in some extracellular compartments, for example, renal tubular fluid in parts of the tubule, and extracellular fluid at inflammation loci, is sufficiently acidic to activate complement. The exact molecular mechanism of this activation is still unclear, but possible cross-talk between the contact system (intrinsic pathway) and complement may exist at low pH with subsequent complement activation. The current article reviews the published data on the effect of pH on the contact system and complement activity, the nature of the pH sensor molecules, and the clinical implications of these effects. Of particular interest is chronic kidney disease (CKD) accompanied by metabolic acidosis, in which therapeutic alkalinization of urine has been shown significantly to reduce tubular complement activation products, an effect, which may have important implications for slowing progression of CKD.

  12. Complement and membrane-bound complement regulatory proteins as biomarkers and therapeutic targets for autoimmune inflammatory disorders, RA and SLE.

    Science.gov (United States)

    Das, Nibhriti

    2015-11-01

    Complement system is a major effecter system of the innate immunity that bridges with adaptive immunity. The system consists of about 40 humoral and cell surface proteins that include zymogens, receptors and regulators. The zymogens get activated in a cascade fashion by antigen-antibody complex, antigen alone or by polymannans, respectively, by the classical, alternative and mannose binding lectin (MBL) pathways. The ongoing research on complement regulators and complement receptors suggest key role of these proteins in the initiation, regulation and effecter mechanisms of the innate and adaptive immunity. Although, the complement system provides the first line of defence against the invading pathogens, its aberrant uncontrolled activation causes extensive self tissue injury. A large number of humoral and cell surface complement regulatory protein keep the system well-regulated in healthy individuals. Complement profiling had brought important information on the pathophysiology of several infectious and chronic inflammatory disorders. In view of the diversity of the clinical disorders involving abnormal complement activity or regulation, which include both acute and chronic diseases that affect a wide range of organs, diverse yet specifically tailored therapeutic approaches may be needed to shift complement back into balance. This brief review discusses on the complement system, its functions and its importance as biomarkers and therapeutic targets for autoimmune diseases with focus on SLE and RA.

  13. Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement

    DEFF Research Database (Denmark)

    Mortensen, Sofia; Kidmose, Rune Thomas; Petersen, Steen Vang;

    2015-01-01

    Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface...... for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. In this article, we present the crystal and solution structures of the 195-kDa C4b. Our results provide the molecular details...

  14. The role of FaBG3 in fruit ripening and B. cinerea fungal infection of strawberry.

    Science.gov (United States)

    Li, Qian; Ji, Kai; Sun, Yufei; Luo, Hao; Wang, Hongqing; Leng, Ping

    2013-10-01

    In plants, β-glucosidases (BG) have been implicated in developmental and pathogen defense, and are thought to take part in abscisic acid (ABA) synthesis via hydrolysis of ABA glucose ester to release active ABA; however, there is no genetic evidence for the role of BG genes in ripening and biotic/abiotic stress in fruits. To clarify the role of BG genes in fruit, eight Fa/FvBG genes encoding β-glucosidase were isolated using information from the GenBank strawberry nucleotide database. Of the Fa/FvBG genes examined, expression of FaBG3 was the highest, showing peaks at the mature stage, coincident with the changes observed in ABA content. To verify the role of this gene, we suppressed the expression of FaBG3 via inoculation with Agrobacterium tumefaciens containing tobacco rattle virus carrying a FaBG3 fragment (RNAi). The expression of FaBG3 in FaBG3-RNAi-treated fruit was markedly reduced, and the ABA content was lower than that of the control. FaBG3-RNAi-treated fruit did not exhibit full ripening, and were firmer, had lower sugar content, and were pale compared with the control due to down-regulation of ripening-related genes. FaBG3-RNAi-treated fruit with reduced ABA levels were much more resistant to Botrytis cinerea fungus but were more sensitive to dehydration stress than control fruit. These results indicate that FaBG3 may play key roles in fruit ripening, dehydration stress and B. cinerea fungal infection in strawberries via modulation of ABA homeostasis and transcriptional regulation of ripening-related genes.

  15. [The changes of complement activities in sera of mice after subcutaneous administration of beryllium chloride].

    Science.gov (United States)

    Sakaguchi, T; Sakaguchi, S; Nakamura, I; Kudo, Y

    1996-02-01

    We studied changes of the complement pathway activities and the content of C3 in sera of mice, administered BeCl2 (containing 5 micrograms of Be per mouse) or CuCl2 (containing 5 micrograms of Cu per mouse) by a single subcutaneous injection. The value of the classical complement pathway activity (CH50) of the Be group 3 days after administration was significantly higher than that of the control group (P < 0.001). It was significantly lower than in the control group after 7 days (P < 0.001). On the other hand, the CH50 value of the Cu group 3 hr after administration tended to increase, however, it was significantly lower than in the control group after 7 days (P < 0.01). The change of the alternative complement pathway activity (ACH50) value of the Be group was similar to the change of the CH50 value of the group. The ACH50 value of the Cu group 3 days after administration tended to increase but it was the same as the ACH50 value of the control group after 7 days. The C3 contents of both the Be and Cu groups 3 days after administration were significantly higher than in the control group (P < 0.001). The aspartate aminotransferase (AST) activity of the Be group 7 days after administration was significantly higher than that of the control group (P < 0.01). By contrast, AST activity of the Cu group 3 hr after administration was significantly higher than in the control group (P < 0.05). The value of the alanine aminotransferase (ALT) activity of the Be group was low (P < 0.01), but that of the Cu group was high (P < 0.05), 3 hr after administration. These values of both groups after 7 days, however, were significantly higher than in the control group (P < 0.05). The AST/ALT ratio in mice was very high at 3 hr, and it remained high by 7 days after Be injection. On the other hand, the ratio of the Cu group was almost constant for 7 days after Cu injection. Thus, these values changed with relative expedition after Be injection. Therefore, we confirmed that measurements of

  16. An Experimental Study on Mitigating Alkali Silica Reaction by Using Fly Ash (FA in Combination with Silica Fume and Expanded Perlite Powder (EPP

    Directory of Open Access Journals (Sweden)

    Isneini Mohd

    2016-01-01

    Full Text Available ASR suppression by FA, SF, EPP, FA in combination with SF and EPP were evaluated by both mortar bar and concrete prism test. Mortar bars were made based on JIS A 1146, meanwhile concrete prism bars were casted in accordance with Rilem AAR-3. Both specimens were stored in 40°C 100% R.H. controlled room. Mortar and concrete mixtures used reactive aggregate in pessimum proportion. The results indicated that FA in combination with SF and EPP showed smaller expansion compared to FA. The best of concrete mixtures in reducing expansion is combination of FA with SF (FA15SF10.

  17. Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome

    DEFF Research Database (Denmark)

    Suhasini, Avvaru N; Rawtani, Nina A; Wu, Yuliang

    2011-01-01

    Bloom's syndrome (BS) and Fanconi anemia (FA) are autosomal recessive disorders characterized by cancer and chromosomal instability. BS and FA group J arise from mutations in the BLM and FANCJ genes, respectively, which encode DNA helicases. In this work, FANCJ and BLM were found to interact...

  18. Complement activation in leprosy: a retrospective study shows elevated circulating terminal complement complex in reactional leprosy.

    Science.gov (United States)

    Bahia El Idrissi, N; Hakobyan, S; Ramaglia, V; Geluk, A; Morgan, B Paul; Das, P Kumar; Baas, F

    2016-06-01

    Mycobacterium leprae infection gives rise to the immunologically and histopathologically classified spectrum of leprosy. At present, several tools for the stratification of patients are based on acquired immunity markers. However, the role of innate immunity, particularly the complement system, is largely unexplored. The present retrospective study was undertaken to explore whether the systemic levels of complement activation components and regulators can stratify leprosy patients, particularly in reference to the reactional state of the disease. Serum samples from two cohorts were analysed. The cohort from Bangladesh included multi-bacillary (MB) patients with (n = 12) or without (n = 46) reaction (R) at intake and endemic controls (n = 20). The cohort from Ethiopia included pauci-bacillary (PB) (n = 7) and MB (n = 23) patients without reaction and MB (n = 15) patients with reaction. The results showed that the activation products terminal complement complex (TCC) (P ≤ 0·01), C4d (P ≤ 0·05) and iC3b (P ≤ 0·05) were specifically elevated in Bangladeshi patients with reaction at intake compared to endemic controls. In addition, levels of the regulator clusterin (P ≤ 0·001 without R; P < 0·05 with R) were also elevated in MB patients, irrespective of a reaction. Similar analysis of the Ethiopian cohort confirmed that, irrespective of a reaction, serum TCC levels were increased significantly in patients with reactions compared to patients without reactions (P ≤ 0·05). Our findings suggests that serum TCC levels may prove to be a valuable tool in diagnosing patients at risk of developing reactions. © 2016 British Society for Immunology.

  19. Assessing reprogramming by chimera formation and tetraploid complementation.

    Science.gov (United States)

    Li, Xin; Xia, Bao-long; Li, Wei; Zhou, Qi

    2015-01-01

    Pluripotent stem cells can be evaluated by pluripotent markers expression, embryoid body aggregation, teratoma formation, chimera contribution and even more, tetraploid complementation. Whether iPS cells in general are functionally equivalent to normal ESCs is difficult to establish. Here, we present the detailed procedure for chimera formation and tetraploid complementation, the most stringent criterion, to assessing pluripotency.

  20. Complement in neuroinflammation : Studies in leprosy and Amyotrophic Lateral Sclerosis

    NARCIS (Netherlands)

    Bahia El Idrissi, N.

    2017-01-01

    The complement system is a part of the innate immunity, and plays an important role in host immunity and inflammation. We previously identified the terminal membrane attack complex (MAC) of the complement system as a key determinant of neurodegeneration and demonstrated that its inhibition is neurop

  1. How antibodies use complement to regulate antibody responses.

    Science.gov (United States)

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

    2014-10-01

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

  2. Complementation of mutant phenotypes and genotypes of cultured mammalian cells

    NARCIS (Netherlands)

    A.J.R. de Jonge

    1985-01-01

    textabstractThis dissertation describes experiments aimed at the complementation of a genetic mutation in cultured mammalian cells in order to investigate several aspects of the structure and functioning of the human genome. Complementation is indicated by the correction of a biochemical function in

  3. Demand Heterogeneity and the Adoption of Platform Complements

    NARCIS (Netherlands)

    J. Rietveld (Joost); J.P. Eggers

    2016-01-01

    textabstractThis paper offers a demand-based theory of how platform maturity affects the adoption of platform complements. We argue that differences between early and late adopters of the platform include willingness to pay for the platform-and-complement bundle, risk preferences, preference for

  4. Demand Heterogeneity and the Adoption of Platform Complements

    NARCIS (Netherlands)

    J. Rietveld (Joost); J.P. Eggers

    2016-01-01

    textabstractThis paper offers a demand-based theory of how platform maturity affects the adoption of platform complements. We argue that differences between early and late adopters of the platform include willingness to pay for the platform-and-complement bundle, risk preferences, preference for nov

  5. Molecular interplay between bacteria and the terminal complement pathway

    NARCIS (Netherlands)

    Berends, E.T.M.

    2015-01-01

    The plasma proteins of the complement system fulfill important immune defense functions, including opsonization of bacteria for phagocytosis, generation of chemo-attractants and direct bacterial killing via assembly of the Membrane Attack Complex (MAC or C5b-9 complex). The terminal complement pathw

  6. Complement inhibitors to treat IgM-mediated autoimmune hemolysis.

    Science.gov (United States)

    Wouters, Diana; Zeerleder, Sacha

    2015-11-01

    Complement activation in autoimmune hemolytic anemia may exacerbate extravascular hemolysis and may occasionally result in intravascular hemolysis. IgM autoantibodies as characteristically found in cold autoantibody autoimmune hemolytic anemia, in cold agglutinin disease but also in a considerable percentage of patients with warm autoantibodies are very likely to activate complement in vivo. Therapy of IgM-mediated autoimmune hemolytic anemia mainly aims to decrease autoantibody production. However, most of these treatments require time to become effective and will not stop immediate ongoing complement-mediated hemolysis nor prevent hemolysis of transfused red blood cells. Therefore pharmacological inhibition of the complement system might be a suitable approach to halt or at least attenuate ongoing hemolysis and improve the recovery of red blood cell transfusion in autoimmune hemolytic anemia. In recent years, several complement inhibitors have become available in the clinic, some of them with proven efficacy in autoimmune hemolytic anemia. In the present review, we give a short introduction on the pathogenesis of autoimmune hemolytic anemia, followed by an overview on the complement system with a special focus on its regulation. Finally, we will discuss complement inhibitors with regard to their potential efficacy to halt or attenuate hemolysis in complement-mediated autoimmune hemolytic anemia.

  7. Production of Infinitival Complements by Children with Specific Language Impairment

    Science.gov (United States)

    Arndt, Karen Barako; Schuele, C. Melanie

    2012-01-01

    The purpose of this study was to explore the production of infinitival complements by children with specific language impairment (SLI) as compared with mean length of utterance (MLU)-matched children in an effort to clarify inconsistencies in the literature. Spontaneous language samples were analysed for infinitival complements (reduced…

  8. The emerging role of complement inhibitors in transplantation.

    Science.gov (United States)

    Frémeaux-Bacchi, Véronique; Legendre, Christophe M

    2015-11-01

    The role of complement in the biology of kidney transplantation is becoming more and more significant, especially but not only because we now have access to drugs inhibiting complement. After describing the main characteristics of complement biology, both activation of the complement cascade and the many regulatory factors, we will review the precise role of complement in kidney transplant biology. Complement activation has been involved in ischemia-reperfusion injury, in the recurrence of several diseases such as atypical hemolytic uremic syndrome, C3 glomerulopathies, and antiphospholipid syndrome, as well as the process of antibody-mediated rejection, either acute or chronic. There are many potentially interesting drugs interfering with complement inhibition that have been or may be studied in kidney transplantation. Currently, the bulk of data concerns eculizumab, a monoclonal antibody blocking the complement cascade at the C5. Its efficacy has been demonstrated in the treatment and prevention of recurrence of atypical hemolytic uremic syndrome with an overall good safety profile. Although it has been reported to be efficacious to prevent antibody-mediated rejection, properly designed trials are currently being performed to state this efficacy. In addition, randomized trials are, in the process, regarding the prevention of ischemia-reperfusion injury after kidney transplantation.

  9. Molecular interplay between bacteria and the terminal complement pathway

    NARCIS (Netherlands)

    Berends, E.T.M.

    2015-01-01

    The plasma proteins of the complement system fulfill important immune defense functions, including opsonization of bacteria for phagocytosis, generation of chemo-attractants and direct bacterial killing via assembly of the Membrane Attack Complex (MAC or C5b-9 complex). The terminal complement

  10. Schur complements of matrices with acyclic bipartite graphs

    DEFF Research Database (Denmark)

    Britz, Thomas Johann; Olesky, D.D.; van den Driessche, P.

    2005-01-01

    Bipartite graphs are used to describe the generalized Schur complements of real matrices having nos quare submatrix with two or more nonzero diagonals. For any matrix A with this property, including any nearly reducible matrix, the sign pattern of each generalized Schur complement is shown to be ...

  11. Identification of a central role for complement in osteoarthritis.

    Science.gov (United States)

    Wang, Qian; Rozelle, Andrew L; Lepus, Christin M; Scanzello, Carla R; Song, Jason J; Larsen, D Meegan; Crish, James F; Bebek, Gurkan; Ritter, Susan Y; Lindstrom, Tamsin M; Hwang, Inyong; Wong, Heidi H; Punzi, Leonardo; Encarnacion, Angelo; Shamloo, Mehrdad; Goodman, Stuart B; Wyss-Coray, Tony; Goldring, Steven R; Banda, Nirmal K; Thurman, Joshua M; Gobezie, Reuben; Crow, Mary K; Holers, V Michael; Lee, David M; Robinson, William H

    2011-11-06

    Osteoarthritis, characterized by the breakdown of articular cartilage in synovial joints, has long been viewed as the result of 'wear and tear'. Although low-grade inflammation is detected in osteoarthritis, its role is unclear. Here we identify a central role for the inflammatory complement system in the pathogenesis of osteoarthritis. Through proteomic and transcriptomic analyses of synovial fluids and membranes from individuals with osteoarthritis, we find that expression and activation of complement is abnormally high in human osteoarthritic joints. Using mice genetically deficient in complement component 5 (C5), C6 or the complement regulatory protein CD59a, we show that complement, specifically, the membrane attack complex (MAC)-mediated arm of complement, is crucial to the development of arthritis in three different mouse models of osteoarthritis. Pharmacological modulation of complement in wild-type mice confirmed the results obtained with genetically deficient mice. Expression of inflammatory and degradative molecules was lower in chondrocytes from destabilized joints from C5-deficient mice than C5-sufficient mice, and MAC induced production of these molecules in cultured chondrocytes. Further, MAC colocalized with matrix metalloprotease 13 (MMP13) and with activated extracellular signal-regulated kinase (ERK) around chondrocytes in human osteoarthritic cartilage. Our findings indicate that dysregulation of complement in synovial joints has a key role in the pathogenesis of osteoarthritis.

  12. Complement Attack against Aspergillus and Corresponding Evasion Mechanisms

    Directory of Open Access Journals (Sweden)

    Cornelia Speth

    2012-01-01

    Full Text Available Invasive aspergillosis shows a high mortality rate particularly in immunocompromised patients. Perpetually increasing numbers of affected patients highlight the importance of a clearer understanding of interactions between innate immunity and fungi. Innate immunity is considered to be the most significant host defence against invasive fungal infections. Complement represents a crucial part of this first line defence and comprises direct effects against invading pathogens as well as bridging functions to other parts of the immune network. However, despite the potency of complement to attack foreign pathogens, the prevalence of invasive fungal infections is increasing. Two possible reasons may explain that phenomenon: First, complement activation might be insufficient for an effective antifungal defence in risk patients (due to, e.g., low complement levels, poor recognition of fungal surface, or missing interplay with other immune elements in immunocompromised patients. On the other hand, fungi may have developed evasion strategies to avoid recognition and/or eradication by complement. In this review, we summarize the most important interactions between Aspergillus and the complement system. We describe the various ways of complement activation by Aspergillus and the antifungal effects of the system, and also show proven and probable mechanisms of Aspergillus for complement evasion.

  13. Polysomnographic correlates of inflammatory complement components in young healthy males.

    Science.gov (United States)

    Hussain, M Ejaz; Golam Sarwar, Abu Hasnath M; Alam, Mohd Shoeb; Noohu, Majumi M; Zannat, Wassilatul; Pandi-Perumal, Seithikurippu R; Bahammam, Ahmed S; Manzar, Md Dilshad

    2016-01-01

    A growing body of evidence has delineated the predominant role of humoral mediators of inflammation in linking sleep with immunity. Nonetheless, characterization of the relationship between complement components with inflammatory functions and objective sleep measures has not been performed. In this study we investigated the relationships between objective measures of sleep and complement components with inflammatory functions. Thirty-six healthy male university students (age, 23.94±4.23 years; BMI, 23.44±2.67 kg/m(2)) completed the study. An RMS Quest 32 polysomnograph (PSG) was used for sleep recording. Non-fasting blood was collected before subjects went to bed on the second night in the sleep laboratory to estimate complement component 3 (C-3), complement component 4 (C-4), complement factor-H (Factor-H), C1-inhibitor (C1INH), complement factor I (CFI) and other inflammatory mediators, such as IL-6 and sICAM-1. Multiple linear regression analysis was used to assess the association between PSG sleep measures and inflammatory mediators. Higher values of C-3 and lower values of sICAM-1, C1INH, and CFI (adjusted model, R2=0.211, ppro-inflammatory complement components and decreased anti-inflammatory complement components.

  14. A vital role for complement in heart disease

    DEFF Research Database (Denmark)

    Lappegård, Knut T; Garred, Peter; Jonasson, Lena;

    2014-01-01

    Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors...

  15. Physicochemical signatures of nanoparticle-dependent complement activation

    Science.gov (United States)

    Thomas, Dennis G.; Chikkagoudar, Satish; Heredia-Langner, Alejandro; Tardiff, Mark F.; Xu, Zhixiang; Hourcade, Dennis E.; Pham, Christine T. N.; Lanza, Gregory M.; Weinberger, Kilian Q.; Baker, Nathan A.

    2014-01-01

    Nanoparticles are potentially powerful therapeutic tools that have the capacity to target drug payloads and imaging agents. However, some nanoparticles can activate complement, a branch of the innate immune system, and cause adverse side-effects. Recently, we employed an in vitro hemolysis assay to measure the serum complement activity of perfluorocarbon nanoparticles that differed by size, surface charge, and surface chemistry, quantifying the nanoparticle-dependent complement activity using a metric called Residual Hemolytic Activity (RHA). In the present work, we have used a decision tree learning algorithm to derive the rules for estimating nanoparticle-dependent complement response based on the data generated from the hemolytic assay studies. Our results indicate that physicochemical properties of nanoparticles, namely, size, polydispersity index, zeta potential, and mole percentage of the active surface ligand of a nanoparticle, can serve as good descriptors for prediction of nanoparticle-dependent complement activation in the decision tree modeling framework.

  16. Complement C3 and High Risk of Venous Thromboembolism

    DEFF Research Database (Denmark)

    Nørgaard, Ina; Nielsen, Sune Fallgaard; Nordestgaard, Børge Grønne

    2016-01-01

    BACKGROUND: Complement activation may contribute to venous thromboembolism, including deep venous thrombosis and pulmonary embolism. We tested the hypothesis that high complement C3 concentrations are associated with high risk of venous thromboembolism in the general population. METHODS: We...... similar for deep venous thrombosis and pulmonary embolism separately. The multivariable-adjusted hazard ratio for venous thromboembolism for a 1-g/L increase in complement C3 was 2.43 (1.74-3.40). CONCLUSIONS: High concentrations of complement C3 were associated with high risk of venous thromboembolism...... included 80 517 individuals without venous thromboembolism from the Copenhagen General Population Study recruited in 2003-2012. Plasma complement C3 concentrations were measured at baseline, and venous thromboembolism (n = 1176) was ascertained through April 2013 in nationwide registries. No individuals...

  17. Complement system part I - molecular mechanisms of activation and regulation

    Directory of Open Access Journals (Sweden)

    Nicolas eMerle

    2015-06-01

    Full Text Available Complement is a complex innate immune surveillance system, playing a key role in defense against pathogens and in host homeostasis. The complement system is initiated by conformational changes in recognition molecular complexes upon sensing danger signals. The subsequent cascade of enzymatic reactions is tightly regulated to assure that complement is activated only at specific locations requiring defense against pathogens, thus avoiding host tissue damage. Here we discuss the recent advances describing the molecular and structural basis of activation and regulation of the complement pathways and their implication on physiology and pathology. This article will review the mechanisms of activation of alternative, classical and lectin pathways, the formation of C3 and C5 convertases, the action of anaphylatoxins and the membrane attack complex. We will also discuss the importance of structure-function relationships using the example of atypical hemolytic uremic syndrome. Lastly we will discuss the development and benefits of therapies using complement inhibitors.

  18. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

    Nielsen, C H; Fischer, E M; Leslie, R G

    2000-01-01

    Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed...... on B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation...... participate in intercellular bridging. Finally, current studies suggest that CR2 may also play a role in the determination of B-cell tolerance towards self-antigens and thereby hold the key to the previously observed correlation between deficiencies of the early complement components and autoimmune disease....

  19. Complement regulators in human disease: lessons from modern genetics.

    Science.gov (United States)

    K Liszewski, M; Atkinson, J P

    2015-03-01

    First identified in human serum in the late 19th century as a 'complement' to antibodies in mediating bacterial lysis, the complement system emerged more than a billion years ago probably as the first humoral immune system. The contemporary complement system consists of nearly 60 proteins in three activation pathways (classical, alternative and lectin) and a terminal cytolytic pathway common to all. Modern molecular biology and genetics have not only led to further elucidation of the structure of complement system components, but have also revealed function-altering rare variants and common polymorphisms, particularly in regulators of the alternative pathway, that predispose to human disease by creating 'hyperinflammatory complement phenotypes'. To treat these 'complementopathies', a monoclonal antibody against the initiator of the membrane attack complex, C5, has received approval for use. Additional therapeutic reagents are on the horizon.

  20. Protease-dependent mechanisms of complement evasion by bacterial pathogens.

    Science.gov (United States)

    Potempa, Michal; Potempa, Jan

    2012-09-01

    The human immune system has evolved a variety of mechanisms for the primary task of neutralizing and eliminating microbial intruders. As the first line of defense, the complement system is responsible for rapid recognition and opsonization of bacteria, presentation to phagocytes and bacterial cell killing by direct lysis. All successful human pathogens have mechanisms of circumventing the antibacterial activity of the complement system and escaping this stage of the immune response. One of the ways in which pathogens achieve this is the deployment of proteases. Based on the increasing number of recent publications in this area, it appears that proteolytic inactivation of the antibacterial activities of the complement system is a common strategy of avoiding targeting by this arm of host innate immune defense. In this review, we focus on those bacteria that deploy proteases capable of degrading complement system components into non-functional fragments, thus impairing complement-dependent antibacterial activity and facilitating pathogen survival inside the host.

  1. Novel Evasion Mechanisms of the Classical Complement Pathway.

    Science.gov (United States)

    Garcia, Brandon L; Zwarthoff, Seline A; Rooijakkers, Suzan H M; Geisbrecht, Brian V

    2016-09-15

    Complement is a network of soluble and cell surface-associated proteins that gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of nonself cells by one of three initiating mechanisms known as the classical, lectin, and alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. Although many complement-inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review, we focus on several recent investigations that revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules.

  2. [Renal risks of dietary complements: a forgotten cause].

    Science.gov (United States)

    Dori, Olympia; Humbert, Antoine; Burnier, Michel; Teta, Daniel

    2014-02-26

    The use of dietary complements like vitamins, minerals, trace elements, proteins, aminoacids and plant-derived agents is prevalent in the general population, in order to promote health and treat diseases. Dietary complements are considered as safe natural products and are easily available without prescription. However, these can lead to severe renal toxicity, especially in cases of unknown pre-existing chronic kidney disease (CKD). In particular, Chinese herbs including aristolochic acid, high doses of vitamine C, creatine and protein complements may lead to acute and chronic renal failure, sometimes irreversible. Dietary complement toxicity should be suspected in any case of unexplained renal impairement. In the case of pre-existing CKD, the use of potentially nephrotoxic dietary complements should be screened for.

  3. The complement system in ischemia-reperfusion injuries.

    Science.gov (United States)

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

    2012-11-01

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

  4. Efficient Thermal Insulation of Passive House with Curved Façades in Cold Climate

    Directory of Open Access Journals (Sweden)

    Aznabaev Askar

    2016-01-01

    Full Text Available In this paper there is exploration of the possibility of creating effective sealed building envelope in zero energy building (ZEB with unique façades. This article describes passive and active measures of decrease of thermal loss through enclosure structures, usage of modern insulation materials; positive effect of rationalization of the façade orientation and form of a building in a plan; on the base of existing architecture concept structural solutions of building envelope are suggested. Using thermal FEA the enclosure structure was optimized. The results of modeling of units and elements of building envelope are: heat transfer coefficient U-value for heterogeneous multilayer structure, picture of temperature distribution and magnitude of the thermal conductivity and temperature of internal wall surface.

  5. Fetal antigen 1 (FA1), a circulating member of the epidermal growth factor (EGF) superfamily

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, T N; Støving, René Klinkby;

    1997-01-01

    We describe an ELISA technique for quantification of fetal antigen 1 (FA1), a glycoprotein belonging to the EGF-superfamily. The ELISA is based on immunospecifically purified polyclonal antibodies and has a dynamic range of 0.7-5.3 ng/ml, intra- and inter-assay C.V.s of less than 3.2% and an aver......We describe an ELISA technique for quantification of fetal antigen 1 (FA1), a glycoprotein belonging to the EGF-superfamily. The ELISA is based on immunospecifically purified polyclonal antibodies and has a dynamic range of 0.7-5.3 ng/ml, intra- and inter-assay C.V.s of less than 3...

  6. High-intensity running in English FA Premier League soccer matches

    DEFF Research Database (Denmark)

    Bradley, Paul S.; Sheldon, William; Wooster, Blake

    2009-01-01

    The aims of this study were to (1) determine the activity profiles of a large sample of English FA Premier League soccer players and (2) examine high-intensity running during elite-standard soccer matches for players in various playing positions. Twenty-eight English FA Premier League games were.......01), attackers (2341 m, s=575, P game, high-intensity running distance was approximately 20% less than in the first 15-min period for wide midfielders (467 m, s=104 vs. 589 m, s=134, P ....01) and without ball possession (229 m, s=85 vs. 278 m, s=97, P game. Mean recovery time between very high-intensity running bouts was 72 s (s=28), with a 28% longer recovery time during the last 15 min than the first 15 min of the game (83 s, s=26 vs...

  7. Development, structure and strength properties of PP/PMMA/FA blends

    Indian Academy of Sciences (India)

    Navin Chand; S R Vashishtha

    2000-04-01

    A new type of flyash filled PP/PMMA blend has been developed. Structural and thermal properties of flyash (FA) filled polypropylene (PP)/polymethyl methacrylate (PMMA) blend system have been determined and analysed. Filled polymer blends were developed on a single screw extruder. Strength and thermal properties of FA filled and unfilled PP/PMMA blends were determined. Addition of flyash imparted dimensional and thermal stability, which has been observed in scanning electron micrographs and in TGA plot. Increase of flyash concentration increased the initial degradation temperature of PP/PMMA blend. The increase of thermal stability has been explained based on increased mechanical interlocking of PP/PMMA chains inside the hollow structure of flyash.

  8. Complement-fixing properties of antinuclear antibodies distinguish drug-induced lupus from systemic lupus erythematosus.

    Science.gov (United States)

    Rubin, R L; Teodorescu, M; Beutner, E H; Plunkett, R W

    2004-01-01

    The immunofluorescence antinuclear antibody (ANA) test has been widely used to monitor autoimmune disease, but its value for diagnostic purposes is compromised by low specificity and high prevalence in disease-free individuals. The capacity of autoantibodies to fix serum complement proteins when bound to antigen is an important effector function because this property is associated with acute and chronic inflammatory processes. The current study evaluates the complement-fixing properties of antinuclear antibodies (CANA) in three well-defined and clinically-related patient groups: systemic lupus erythematosus (SLE), drug-induced lupus (DIL) and drug-induced autoimmunity (DIA). Of 20 patients diagnosed with SLE, 90% displayed complement-fixing ANA while this feature was present in only two of 18 patients with DIL and no patients with DIA without associated disease even though the mean ANA titres were similar among these patient groups. CANA was significantly correlated with anti-Sm activity. Because SLE but not DIL or DIA can be a life-threatening disease associated with complement consumption in vivo, these results demonstrate that measurement of CANA is a diagnostically useful tool and may have immunopathologic implications.

  9. Aggressive Recurrence of Oral Squamous Cell Carcinoma in a patient with Fanconi’s Anaemia (FA)

    LENUS (Irish Health Repository)

    Nolan, M.

    2017-03-01

    Fanconi’s Anaemia is a rare autosomal recessive disease for which the incidence of head and neck cancer can be increased 700-fold1. We report a case of a 31-year old Caucasian male with FA who initially presented in July 2007 with oral squamous cell carcinoma for which he received radical surgery and radiotherapy. He was disease-free until August 2015 when he presented with an extremely aggressive recurrence.

  10. FaCSI: A block parallel preconditioner for fluid-structure interaction in hemodynamics

    Science.gov (United States)

    Deparis, Simone; Forti, Davide; Grandperrin, Gwenol; Quarteroni, Alfio

    2016-12-01

    Modeling Fluid-Structure Interaction (FSI) in the vascular system is mandatory to reliably compute mechanical indicators in vessels undergoing large deformations. In order to cope with the computational complexity of the coupled 3D FSI problem after discretizations in space and time, a parallel solution is often mandatory. In this paper we propose a new block parallel preconditioner for the coupled linearized FSI system obtained after space and time discretization. We name it FaCSI to indicate that it exploits the Factorized form of the linearized FSI matrix, the use of static Condensation to formally eliminate the interface degrees of freedom of the fluid equations, and the use of a SIMPLE preconditioner for saddle-point problems. FaCSI is built upon a block Gauss-Seidel factorization of the FSI Jacobian matrix and it uses ad-hoc preconditioners for each physical component of the coupled problem, namely the fluid, the structure and the geometry. In the fluid subproblem, after operating static condensation of the interface fluid variables, we use a SIMPLE preconditioner on the reduced fluid matrix. Moreover, to efficiently deal with a large number of processes, FaCSI exploits efficient single field preconditioners, e.g., based on domain decomposition or the multigrid method. We measure the parallel performances of FaCSI on a benchmark cylindrical geometry and on a problem of physiological interest, namely the blood flow through a patient-specific femoropopliteal bypass. We analyze the dependence of the number of linear solver iterations on the cores count (scalability of the preconditioner) and on the mesh size (optimality).

  11. L2 Acquisition of Complement Clauses by Persian Learners of English

    Directory of Open Access Journals (Sweden)

    Masoud Khalili Sabet

    2015-01-01

    Full Text Available This research concentrates on the acquisition of complement clauses within Universal Grammar framework which theoretically plays the strongest linguistic role in second language acquisition research in recent years. This study aims to investigate how Persian learners of English at three levels of proficiency acquire complement clauses.  In fact, this study reports the results of the learners’ responses to GJT and specifically investigates the six linguistic variables associated with complement Clauses: using complement in finite/ non-finite clauses, small-clauses, exceptional-clauses, that-trace effect in clauses and subcategorization of two verbs (i. e. want and let.  The responses were given by 50 Persian learners of English divided into three proficiency levels: Elementary, Intermediate and Advanced. The statistical analyses of the data revealed that, by increasing the participants’ level of proficiency their judgment of grammatical and ungrammatical items was improved whereas the differences between groups were also significant. The results can indicate that the development of their complement acquisition is generally systematic.  In addition, by carrying out syntactic analyses of the sentences that the participants produced, we conclude that, as UG predicted, Persian learners do not use any wild grammar at any level of their L2 acquisition.  The above findings are generally in harmony with the view that L2 learners somehow attain the unconscious knowledge that goes beyond what they receive as L2 input.  Finally, our findings may have implications for language teaching by deepening our understanding of the nature of L2 acquisition. Keywords: Second Language Acquisition, Complements, Clauses, Developmental stages, Systematicity, Universal Grammar, Fundamental Different Hypothesis (FDH

  12. Evolutionary analysis of heterochromatin protein compatibility by interspecies complementation in Saccharomyces.

    Science.gov (United States)

    Zill, Oliver A; Scannell, Devin R; Kuei, Jeffrey; Sadhu, Meru; Rine, Jasper

    2012-11-01

    The genetic bases for species-specific traits are widely sought, but reliable experimental methods with which to identify functionally divergent genes are lacking. In the Saccharomyces genus, interspecies complementation tests can be used to evaluate functional conservation and divergence of biological pathways or networks. Silent information regulator (SIR) proteins in S. bayanus provide an ideal test case for this approach because they show remarkable divergence in sequence and paralog number from those found in the closely related S. cerevisiae. We identified genes required for silencing in S. bayanus using a genetic screen for silencing-defective mutants. Complementation tests in interspecies hybrids identified an evolutionarily conserved Sir-protein-based silencing machinery, as defined by two interspecies complementation groups (SIR2 and SIR3). However, recessive mutations in S. bayanus SIR4 isolated from this screen could not be complemented by S. cerevisiae SIR4, revealing species-specific functional divergence in the Sir4 protein despite conservation of the overall function of the Sir2/3/4 complex. A cladistic complementation series localized the occurrence of functional changes in SIR4 to the S. cerevisiae and S. paradoxus branches of the Saccharomyces phylogeny. Most of this functional divergence mapped to sequence changes in the Sir4 PAD. Finally, a hemizygosity modifier screen in the interspecies hybrids identified additional genes involved in S. bayanus silencing. Thus, interspecies complementation tests can be used to identify (1) mutations in genetically underexplored organisms, (2) loci that have functionally diverged between species, and (3) evolutionary events of functional consequence within a genus.

  13. Development and characterization of a high sensitivity segmented Fast Neutron Spectrometer (FaNS-2)

    Science.gov (United States)

    Langford, T. J.; Beise, E. J.; Breuer, H.; Heimbach, C. R.; Ji, G.; Nico, J. S.

    2016-01-01

    We present the development of a segmented fast neutron spectrometer (FaNS-2) based upon plastic scintillator and 3He proportional counters. It was designed to measure both the flux and spectrum of fast neutrons in the energy range of few MeV to 1 GeV. FaNS-2 utilizes capture-gated spectroscopy to identify neutron events and reject backgrounds. Neutrons deposit energy in the plastic scintillator before capturing on a 3He nucleus in the proportional counters. Segmentation improves neutron energy reconstruction while the large volume of scintillator increases sensitivity to low neutron fluxes. A main goal of its design is to study comparatively low neutron fluxes, such as cosmogenic neutrons at the Earth's surface, in an underground environment, or from low-activity neutron sources. In this paper, we present details of its design and construction as well as its characterization with a calibrated 252Cf source and monoenergetic neutron fields of 2.5 MeV and 14 MeV. Detected monoenergetic neutron spectra are unfolded using a Singular Value Decomposition method, demonstrating a 5% energy resolution at 14 MeV. Finally, we discuss plans for measuring the surface and underground cosmogenic neutron spectra with FaNS-2.

  14. Multiple Dissipative Devices for Blast-Resisting Cable-Supported Glazing Façades

    Directory of Open Access Journals (Sweden)

    Claudio Amadio

    2013-01-01

    Full Text Available The paper analyzes the structural response of a high-level air blast loaded cable-supported façade. Since the glass panels and the cables present a typical brittle behavior and are subjected to elevated tensile stresses when a high-level explosion occurs, multiple dissipative devices are simultaneously introduced in the conventional glazing system to mitigate the maximum effects of the design blast wave. Dynamic analyses are performed using a sophisticated FE-model to describe accurately the response of the façade equipped by dissipative devices. Based on numerical results of previous contributions, viscoelastic spider connectors (VESCs are introduced in the points of connection between glass panels and pretensioned cables, to replace “rigid” spider connectors commonly used in practice. At the same time, rigid-plastic frictional devices (RPDs are installed at the top of the bearing cables to mitigate furthermore the bracing system. As a result, due to the combined use of VESCs and RPDs opportunely calibrated, the maximum tensile stresses in the glass panels and in the cables appear strongly reduced. In addition, the proposed devices do not trouble the aesthetics of such transparent structural systems. At last, simple design rules are presented to predict the response of cable-supported façades subjected to high-level dynamic loads and to preliminary estimate the mechanical parameters of combined VESCs and RPDs.

  15. [Data mining analysis of professor Li Fa-zhi AIDS herpes zoster medical record].

    Science.gov (United States)

    Wang, Dan-Ni; Li, Zhen; Xu, Li-Ran; Guo, Hui-Jun

    2013-08-01

    Analysis of professor Li Fa-zhi in the treatment of AIDS drug laws of herpes zoster and postherpetic neuralgia, provide reference for the use of Chinese medicine treatment of AIDS, herpes zoster and postherpetic neuralgia. By using the method of analyzing the complex network of Weishi county, Henan in 2007 October to 2011 July during an interview with professor Li Fa-zhi treatment of AIDS of herpes zoster and postherpetic neuralgia patients, patients are input structured clinical information collection system, into the analysis of the data, carries on the research analysis theory of traditional Chinese medicine compatibility system algorithm and complex network analysis the use of complex networks. The use of multi-dimensional query analysis of AIDS drugs, the core of herpes zoster and postherpetic neuralgia treated in this study are Scutellariae Radix, Glucyrrhizae Radix, Carthame Flos, Plantaginis Semen, Trichosamthis Fructus, Angelicae Sinensis Radix, Gentianae Radix; core prescription for Longdan Xiegan decoction and Trichosanthes red liquorice decoction. Professor Li Fa-zhi treatment of AIDS, herpes zoster and postherpetic neuralgia by clearing heat and removing dampness and activating blood circulation to.

  16. EPS insulated façade fires from a fire and rescue perspective

    Directory of Open Access Journals (Sweden)

    Kumm M.

    2013-11-01

    Full Text Available This paper highlights the challenges the fire and rescue services can meet at façade fires involving EPS insulation during construction and use of a building. The EPS characteristics are discussed in respect to the fire and rescue operation and results from orientating fire tests performed at a fire and rescue services training and test field are presented. Types of evacuation solutions, involving the fire and rescue services, where façade fires can delay or completely rule out the possibilities for safe evacuation, are presented. The restrictions in the Swedish building codes regarding use of combustible insulation are analysed and reflections over the practical problems with following the instructions to keep an EPS insulated façade safe through the building's whole lifespan are made. A number of occurred fires involving EPS are discussed and analysed from a fire and rescue perspective. Finally, recommendations are given for the fire and rescue services and future research fields are proposed.

  17. Fire protection concepts for Timber-Glass Composite façades

    Directory of Open Access Journals (Sweden)

    Schleicher Andreas

    2016-01-01

    The main objectives can be summarized as follows: Growth and densification in urban areas require the development of intelligent and resource-efficient building systems for “Smart Cities” of the future. By using timber-glass composites (TGC the primary energy demand of buildings can be reduced substantially. This research project examines the feasibility of applications of this new technology in multi-story and high-rise buildings. Critical aspects concerning fire protection such as flammability of timber elements, fire spread and failure of façade elements with bracing capacity will be analyzed. Different strategies will be developed in case studies and validated by structural analysis. Large scale mock ups of TGC façade elements will be checked on their suitability in fire tests. The findings of this research will lead to innovative fire safety concepts for building systems with TGC façades. Compliance with the high safety standards for multi-story buildings in urban areas like Vienna is one of the main objectives of this work. The adaptation of these fire safety concepts to the national standards of the neighboring countries will be continued subsequently. The gained knowledge should lead to further cooperation with companies for serial productions with TGC technology.

  18. Hemolytic plate assay for quantification of active human complement component C3 using methylamine-treated plasma as complement source

    DEFF Research Database (Denmark)

    Ploug, M; Jessen, T E; Welinder, K. G.

    1985-01-01

    A hemolytic plate assay specific for active human complement component C3 is described. The method is well suited for tracing active C3 during preparative purification or for screening of plasma samples. The assay is based on activation of the alternative pathway of complement by unmodified rabbi...

  19. New insights into the operative network of FaEO, an enone oxidoreductase from Fragaria x ananassa Duch.

    Science.gov (United States)

    Collu, Gabriella; Farci, Domenica; Esposito, Francesca; Pintus, Francesca; Kirkpatrick, Joanna; Piano, Dario

    2017-05-01

    The 2-methylene-furan-3-one reductase or Fragaria x ananassa Enone Oxidoreductase (FaEO) catalyses the last reductive step in the biosynthesis of 4-hydroxy-2,5-dimethyl-3(2H)-furanone, a major component in the characteristic flavour of strawberries. In the present work, we describe the association between FaEO and the vacuolar membrane of strawberry fruits. Even if FaEO lacks epitopes for stable or transient membrane-interactions, it contains a calmodulin-binding region, suggesting that in vivo FaEO may be associated with the membrane via a peripheral protein complex with calmodulin. Moreover, we also found that FaEO occurs in dimeric form in vivo and, as frequently observed for calmodulin-regulated proteins, it may be expressed in different isoforms by alternative gene splicing. Further mass spectrometry analysis confirmed that the isolated FaEO consists in the already known isoform and that it is the most characteristic during ripening. Finally, a characterization by absorption spectroscopy showed that FaEO has specific flavoprotein features. The relevance of these findings and their possible physiological implications are discussed.

  20. Differential protection of Cry1Fa toxin against Spodoptera frugiperda larval gut proteases by cadherin orthologs correlates with increased synergism.

    Science.gov (United States)

    Rahman, Khalidur; Abdullah, Mohd Amir F; Ambati, Suresh; Taylor, Milton D; Adang, Michael J

    2012-01-01

    The Cry proteins produced by Bacillus thuringiensis (Bt) are the most widely used biopesticides effective against a range of crop pests and disease vectors. Like chemical pesticides, development of resistance is the primary threat to the long-term efficacy of Bt toxins. Recently discovered cadherin-based Bt Cry synergists showed the potential to augment resistance management by improving efficacy of Cry toxins. However, the mode of action of Bt Cry synergists is thus far unclear. Here we elucidate the mechanism of cadherin-based Cry toxin synergism utilizing two cadherin peptides, Spodoptera frugiperda Cad (SfCad) and Manduca sexta Cad (MsCad), which differentially enhance Cry1Fa toxicity to Spodoptera frugiperda neonates. We show that differential SfCad- and MsCad-mediated protection of Cry1Fa toxin in the Spodoptera frugiperda midgut correlates with differential Cry1Fa toxicity enhancement. Both peptides exhibited high affinity for Cry1Fa toxin and an increased rate of Cry1Fa-induced pore formation in S. frugiperda. However, only SfCad bound the S. frugiperda brush border membrane vesicle and more effectively prolonged the stability of Cry1Fa toxin in the gut, explaining higher Cry1Fa enhancement by this peptide. This study shows that cadherin fragments may enhance B. thuringiensis toxicity by at least two different mechanisms or a combination thereof: (i) protection of Cry toxin from protease degradation in the insect midgut and (ii) enhancement of pore-forming ability of Cry toxin.

  1. Spread of smoke and heat along narrow air cavity in double-skin façade fires

    Directory of Open Access Journals (Sweden)

    Chow Lun Cheuk

    2014-01-01

    Full Text Available A scenario on double-skin façade fire was identified earlier for hazard assessment. A flashover room fire occurred next to the façade, broke the interior glass pane and spread to the façade cavity. As observed in experiments, hot gas moved up as a vertical channel flow for narrow façade cavity. Heat and smoke spread along the narrow air cavity of a double-skin façade will be studied in this paper. A simple mathematical model is developed from basic heat transfer theory for studying the vertical air temperature profiles of the hot gas flowing along the cavity. Assuming one-dimensional flow for hot gas moving up the façade cavity, conservation equations on mass and enthalpy were solved. Experimental results on two double-skin façade rigs of height 6 m and 15 m with narrow cavity depth were used to justify the results. A total of 11 tests were carried out. Correlation expressions between cavity air temperature and the height above ceiling of the fire room were derived.

  2. Nutritional Stress Causes Heterogeneous Relationships with Multi-Trait FA in Lesser Black-Backed Gull Chicks: An Aviary Experiment

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    Trisha Gupta

    2016-11-01

    Full Text Available Environmental stressors have the potential to induce perturbations in the development of young individuals, leading to aberrant and unstable development. This may manifest as fluctuating asymmetry (FA; small, non-directional changes in the bilateral symmetry of morphological traits. Although widely regarded as a proxy for stress effects, the use of FA as a biomarker is still a topic of much debate. We investigated the applicability of FA as an indicator of nutritional stress (brought about by energetic constraints by experimental manipulation of the diet composition and quantity during the growth of Lesser Black-backed Gull (Larus fuscus chicks. FA as an endpoint was measured across the tarsus, wing and 10th primary feather when chicks reached 30 days of age. Although levels of asymmetry were found to increase with stress in the feather, relationships with tarsus and wing FA were mixed and mostly non-significant. Furthermore, we did not find any correlations in unsigned FA between traits, indicating the absence of organism-wide asymmetry. Our study was therefore unable to find unequivocal evidence in support of the application of FA as a reliable estimator of nutritional stress.

  3. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.

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    Michael Huber

    2006-11-01

    Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

  4. Keeping It All Going—Complement Meets Metabolism

    Science.gov (United States)

    Kolev, Martin; Kemper, Claudia

    2017-01-01

    The complement system is an evolutionary old and crucial component of innate immunity, which is key to the detection and removal of invading pathogens. It was initially discovered as a liver-derived sentinel system circulating in serum, the lymph, and interstitial fluids that mediate the opsonization and lytic killing of bacteria, fungi, and viruses and the initiation of the general inflammatory responses. Although work performed specifically in the last five decades identified complement also as a critical instructor of adaptive immunity—indicating that complement’s function is likely broader than initially anticipated—the dominant opinion among researchers and clinicians was that the key complement functions were in principle defined. However, there is now a growing realization that complement activity goes well beyond “classic” immune functions and that this system is also required for normal (neuronal) development and activity and general cell and tissue integrity and homeostasis. Furthermore, the recent discovery that complement activation is not confined to the extracellular space but occurs within cells led to the surprising understanding that complement is involved in the regulation of basic processes of the cell, particularly those of metabolic nature—mostly via novel crosstalks between complement and intracellular sensor, and effector, pathways that had been overlooked because of their spatial separation. These paradigm shifts in the field led to a renaissance in complement research and provide new platforms to now better understand the molecular pathways underlying the wide-reaching effects of complement functions in immunity and beyond. In this review, we will cover the current knowledge about complement’s emerging relationship with the cellular metabolism machinery with a focus on the functional differences between serum-circulating versus intracellularly active complement during normal cell survival and induction of effector functions

  5. Differential modulation of the functionality of white adipose tissue of obese Zucker (fa/fa) rats by the type of protein and the amount and type of fat.

    Science.gov (United States)

    Díaz-Villaseñor, Andrea; Granados, Omar; González-Palacios, Berenice; Tovar-Palacio, Claudia; Torre-Villalvazo, Ivan; Olivares-García, Verónica; Torres, Nimbe; Tovar, Armando R

    2013-11-01

    Recent evidence indicates that several metabolic abnormalities developed during obesity are associated with the presence of dysfunctional adipose tissue. Diet is a key factor that modulates several functions of adipose tissue; however, each nutrient in the diet produces specific changes. Thus, the aim of this work was to study the effect of the interaction of the type (coconut or soybean oil) and amount (5% or 10%) of fat with the type of dietary protein (casein or soy protein) on the functionality of white adipose tissue of Zucker (fa/fa) rats. The results showed that soybean oil reduced adipocyte size and decreased esterified saturated fatty acids in white adipose tissue. Excess dietary fat also modified the composition of esterified fatty acids in white adipose tissue, increased the secretion of saturated fatty acids to serum from white adipose tissue and reduced the process of fatty acids re-esterification. On the other hand, soy protein sensitized the activation of the hormone-sensitive lipase by increasing the phosphorylation of this enzyme (Ser 563) despite rats fed soy protein were normoglucagonemic, in contrast with rats fed casein that showed hyperglucagonemia but reduced hormone-sensitive lipase phosphorylation. Finally, in white adipose tissue, the interaction between the tested dietary components modulated the transcription/translation process of lipid and carbohydrate metabolism genes via the activity of the PERK-endoplasmic reticulum stress response. Therefore, our results showed that the type of protein and the type and amount of dietary fat selectively modify the activity of white adipose tissue, even in a genetic model of obesity. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Complement in Pancreatic Disease—Perpetrator or Savior?

    Science.gov (United States)

    Bettac, Lucas; Denk, Stephanie; Seufferlein, Thomas; Huber-Lang, Markus

    2017-01-01

    The complement system is a major pillar of the humoral innate immune system. As a first line of defense against pathogens, it mediates early inflammatory response and links different branches of humoral and cellular immunity. Disorders affecting the exocrine pancreas, such as acute pancreatitis, potentially lead to a life-threatening systemic inflammatory response with aberrant activation of complement and coagulation cascades. Pancreatic proteases can activate key effectors of the complement system, which in turn drive local and systemic inflammation. Beyond that, the extent of pancreas–complement interaction covers complex pro- and anti-inflammatory mechanisms, which to this day remain to be fully elucidated. This review provides a comprehensive overview of the pathophysiological role of complement in diseases of the exocrine pancreas, based on existing experimental and clinical data. Participation of complement in acute and chronic pancreatitis is addressed, as well as its role in tumor immunology. Therapeutic strategies targeting complement in these diseases have long been proposed but have not yet arrived in the clinical setting. PMID:28144242

  7. Complement factor B expression profile in a spontaneous uveitis model.

    Science.gov (United States)

    Zipplies, Johanna K; Kirschfink, Michael; Amann, Barbara; Hauck, Stefanie M; Stangassinger, Manfred; Deeg, Cornelia A

    2010-12-01

    Equine recurrent uveitis serves as a spontaneous model for human autoimmune uveitis. Unpredictable relapses and ongoing inflammation in the eyes of diseased horses as well as in humans lead to destruction of the retina and finally result in blindness. However, the molecular mechanisms leading to inflammation and retinal degeneration are not well understood. An initial screening for differentially regulated proteins in sera of uveitic cases compared to healthy controls revealed an increase of the alternative pathway complement component factor B in ERU cases. To determine the activation status of the complement system, sera were subsequently examined for complement split products. We could demonstrate a significant higher concentration of the activation products B/Ba, B/Bb, Bb neoantigen, iC3b and C3d in uveitic condition compared to healthy controls, whereas for C5b-9 no differences were detected. Additionally, we investigated complement activation directly in the retina by immunohistochemistry, since it is the main target organ of this autoimmune disease. Interestingly, infiltrating cells co-expressed activated factor Bb neoantigen, complement split product C3d as well as CD68, a macrophage marker. In this study, we could demonstrate activation of the complement system both systemically as well as in the eye, the target organ of spontaneous recurrent uveitis. Based on these novel findings, we postulate a novel role for macrophages in connection with complement synthesis at the site of inflammation.

  8. Complement activation promotes muscle inflammation during modified muscle use

    Science.gov (United States)

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

    2000-01-01

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

  9. Complement in different stages of HIV infection and pathogenesis.

    Science.gov (United States)

    Speth, Cornelia; Stoiber, Heribert; Dierich, Manfred P

    2003-04-01

    The complement system is one of the most important weapons of innate immunity and is involved in all infectious processes. It is not only a mechanism for direct protection against an invading pathogen but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defence cascade in the body. One of the greatest challenges for the complement system is infection by HIV with its chronic course and sequential destruction of immune cells and immune organs. Due to its dual role as direct effector and as fine tuner of adaptive immunity, we focussed on complement in this review and analysed in detail the contribution of complement to the antiviral defence and to HIV pathogenesis on the one hand and the complement evasion strategies of the virus on the other hand. In the present review, this interplay between complement and the virus is illuminated for the three different stages of HIV pathogenesis and for events during therapy: (1) the acute infection process with the early events in mucosa and serum; (2) the asymptomatic stage with the complex interplay between complement-induced lysis and viral evasion strategies; (3) the symptomatic infection and AIDS stage with progressive destruction of the lymph nodes, opportunistic infections and development of neuropathogenesis, and (4) finally, during highly active antiretroviral therapy and in vaccination approaches. Copyright 2003 S. Karger AG, Basel

  10. Complement activation in the Parkinson's disease substantia nigra: an immunocytochemical study

    Directory of Open Access Journals (Sweden)

    Conant Stephanie B

    2006-10-01

    Full Text Available Abstract Background Inflammatory processes are increased in the Parkinson's disease (PD brain. The long-term use of nonsteroidal anti-inflammatory drugs has been associated, in retrospective studies, with decreased risk for PD, suggesting that inflammation may contribute to development of this disorder. The objective of this study was to determine the extent of complement activation, a major inflammatory mechanism, in PD. Methods Substantia nigra specimens from young normal subjects (n = 11–13, aged normal subjects (n = 24–28, and subjects with PD (n = 19–20, Alzheimer's disease (AD; n = 12–13, and dementia with Lewy bodies (DLB; n = 9 were stained for iC3b and C9, representing early- and late-stage complement activation, respectively. Numbers of iC3b+, C9+, and total melanized neurons in each section were counted in a blinded fashion. Nonparametric analyses were used to evaluate differences between groups and to evaluate correlations between complement staining, numbers of melanized neurons, and the duration of PD. Results Lewy bodies in both PD and DLB specimens stained for iC3b and C9. Staining was also prominent on melanized neurons. The percentage of iC3b+ neurons was significantly increased in PD vs. aged normal and AD specimens, and in young normal vs. aged normal specimens. C9 immunoreactivity was significantly increased in PD vs. AD specimens, but unlike iC3b, the increased C9 staining in PD and young normal specimens did not achieve statistical significance vs. aged normal specimens. iC3b and C9 staining in PD specimens was not correlated with the numbers of remaining melanized neurons, nor with the duration of PD. Conclusion Complement activation occurs on Lewy bodies and melanized neurons in the PD substantia nigra. Early complement activation (iC3b is increased on melanized neurons in PD vs. aged normal specimens, and late-stage complement activation (C9 also tends to increase. This latter finding suggests that complement

  11. Complement-Mediated Glomerular Diseases: A Tale of 3 Pathways

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    Andrew S. Bomback

    2016-09-01

    Full Text Available A renewed interest in the role of complement in the pathogenesis of glomerular diseases has improved our understanding of their basic, underlying physiology. All 3 complement pathways—classical, lectin, and alternative—have been implicated in glomerular lesions both rare (e.g., dense deposit disease and common (e.g., IgA nephropathy. Here we review the basic function of these pathways and highlight, with a disease-specific focus, how activation can lead to glomerular injury. We end by exploring the promise of complement-targeted therapies as disease-specific interventions for glomerular diseases.

  12. Early intra-articular complement activation in ankle fractures

    DEFF Research Database (Denmark)

    Schmal, Hagen; Salzmann, Gian M; Niemeyer, Philipp;

    2014-01-01

    osteochondritis dissecans (OCD) of the ankle. All fractures needed external fixation during which joint effusions were collected. Fluid analysis was done by ELISA measuring aggrecan, bFGF, IL-1 β, IGF-1, and the complement components C3a, C5a, and C5b-9. The time periods between occurrence of fracture...... and OCD patients, bFGF, IGF-1, and all complement components were significantly higher concentrated in ankle joints with fractures (P Complement activation and inflammatory cell infiltration characterize the joint biology following acute ankle fractures....

  13. Staphylococcal Proteases Aid in Evasion of the Human Complement System

    DEFF Research Database (Denmark)

    Jusko, Monika; Potempa, Jan; Kantyka, Tomasz

    2014-01-01

    Staphylococcus aureus is an opportunistic pathogen that presents severe health care concerns due to the prevalence of multiple antibiotic-resistant strains. New treatment strategies are urgently needed, which requires an understanding of disease causation mechanisms. Complement is one of the first...... lines of defense against bacterial pathogens, and S. aureus expresses several specific complement inhibitors. The effect of extracellular proteases from this bacterium on complement, however, has been the subject of limited investigation, except for a recent report regarding cleavage of the C3 component...

  14. Restrained and insolent features complement each other

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    How will you imagine such a person who designed the Shanghai Oriental Pearl TV Tower and the world? It is reported that recently a surprising decision was made by him that he has become the first engineering academician who established his own designing company.He is Jiang Huanchend,senior general engineer of Shanghai Modern Construction Designing Group.

  15. Complement activation and liver impairment in trichloroethylene-sensitized BALB/c mice.

    Science.gov (United States)

    Zhang, Jiaxiang; Zha, Wansheng; Wang, Feng; Jiang, Tao; Xu, Shuhai; Yu, Junfeng; Zhou, Chengfan; Shen, Tong; Wu, Changhao; Zhu, Qixing

    2013-01-01

    Our recent studies have shown that trichloroethylene (TCE) was able to induce multisystem injuries in the form of occupational medicamentosa-like dermatitis, including skin, kidney, and liver damages. However, the role of complement activation in the immune-mediated liver injury is not known. This study examined the role of complement activation in the liver injury in a mouse model of TCE-induced sensitization. Treatment of female BALB/c mice with TCE under specific dosing protocols resulted in skin inflammation and sensitization. Skin edema and erythema occurred in TCE-sensitized groups. Trichloroethylene sensitization produced liver histopathological lesions, increased serum alanine aminotransferase, aspartate transaminase activities, and the relative liver weight. The concentrations of serum complement components C3a-desArg, C5a-desArg, and C5b-9 were significantly increased in 24-hour, 48-hour, and 72-hour sensitization-positive groups treated with TCE and peaked in the 72-hour sensitization-positive group. Depositions of C3a, C5a, and C5b-9 into the liver tissue were also revealed by immunohistochemistry. Immunofluorescence further verified high C5b-9 expression in 24-hour, 48-hour, and 72-hour sensitization-positive groups in response to TCE treatment. Reverse transcription-polymerase chain reaction detected C3 messenger RNA expression in the liver, and this was significantly increased in 24-hour and 48-hour sensitization-positive groups with a transient reduction at 72 hours. These results provide the first experimental evidence that complement activation may play a key role in the generation and progression of immune-mediated hepatic injury by exposure to TCE.

  16. Visualization of molecular interactions using bimolecular fluorescence complementation analysis: characteristics of protein fragment complementation.

    Science.gov (United States)

    Kerppola, Tom K

    2009-10-01

    Investigations of the molecular processes that sustain life must include studies of these processes in their normal cellular environment. The bimolecular fluorescence complementation (BiFC) assay provides an approach for the visualization of protein interactions and modifications in living cells. This assay is based on the facilitated association of complementary fragments of a fluorescent protein that are fused to interaction partners. Complex formation by the interaction partners tethers the fluorescent protein fragments in proximity to each other, which can facilitate their association. The BiFC assay enables sensitive visualization of protein complexes with high spatial resolution. The temporal resolution of BiFC analysis is limited by the time required for fluorophore formation, as well as the stabilization of complexes by association of the fluorescent protein fragments. Many modifications and enhancements to the BiFC assay have been developed. The multicolor BiFC assay enables simultaneous visualization of multiple protein complexes in the same cell, and can be used to investigate competition among mutually exclusive interaction partners for complex formation in cells. The ubiquitin-mediated fluorescence complementation (UbFC) assay enables visualization of covalent ubiquitin family peptide conjugation to substrate proteins in cells. The BiFC assay can also be used to visualize protein binding to specific chromatin domains, as well as other molecular scaffolds in cells. BiFC analysis therefore provides a powerful approach for the visualization of a variety of processes that affect molecular proximity in living cells. The visualization of macromolecular interactions and modifications is of great importance owing to the central roles of proteins, nucleic acids and other macromolecular complexes in the regulation of cellular functions. This tutorial review describes the BiFC assay, and discusses the advantages and disadvantages of this experimental approach

  17. Mouse fetal antigen 1 (mFA1), the circulating gene product of mdlk, pref-1 and SCP-1: isolation, characterization and biology

    DEFF Research Database (Denmark)

    Bachmann, E; Krogh, T N; Højrup, P

    1996-01-01

    The mouse homologue to human fetal antigen 1 (hFA1) was purified from mouse amniotic fluid by cation exchange chromatography and immunospecific affinity chromatography. Mouse FA1 (mFA1) is a single chain glycoprotein with an M(r) of 42-50 kDa (SDS-PAGE). The N-terminal amino acid sequence (39 res...

  18. Genetic and phenotypic heterogeneity in disorders of peroxisome biogenesis--a complementation study involving cell lines from 19 patients.

    Science.gov (United States)

    Roscher, A A; Hoefler, S; Hoefler, G; Paschke, E; Paltauf, F; Moser, A; Moser, H

    1989-07-01

    Disorders of peroxisomal biogenesis include the Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum syndrome, and hyperpipecolic acidemia. These names were assigned before the recognition of the peroxisomal defect and the distinction between phenotypes is uncertain. Recent studies have identified at least four complementation groups, and indicate the presence of at least that number of distinct genotypes. The purpose of the present study was to examine the relationship between genotype and phenotype. We studied cultured skin fibroblasts from 19 patients in whom deficiency of peroxisomes had been established. Complementation analysis was performed with the criterion of complementation being the restoration of the capacity to synthesize plasmalogens when fibroblasts from two patients were fused. Six complementation groups were identified, and consisted of one 13 member group, one two member group, and four groups comprising single cases. The phenotype of each group was examined with respect to age of survival, clinical manifestations, and biochemical alterations. The 13 member group included patients with all of the four currently designated phenotypic entities, while the most common phenotype (Zellweger syndrome) was distributed among five of the six groups. We conclude that the currently used clinical categories do not represent distinct genotypes. Apparently different genes code for a similar phenotype and one defective gene may lead to variant phenotypes. Definitive classification and understanding of these disorders await definition of the specific biochemical defect in each of the genotypes.

  19. A novel trifunctional IgG-like bispecific antibody to inhibit HIV-1 infection and enhance lysis of HIV by targeting activation of complement

    Directory of Open Access Journals (Sweden)

    Tomlinson Stephen

    2010-06-01

    Full Text Available Abstract Background The complement system is not only a key component of innate immunity but also provides a first line of defense against invading pathogens, especially for viral pathogens. Human immunodeficiency virus (HIV, however, possesses several mechanisms to evade complement-mediated lysis (CoML and exploit the complement system to enhance viral infectivity. Responsible for this intrinsic resistance against complement-mediated virolysis are complement regulatory membrane proteins derived from the host cell that inherently downregulates complement activation at several stages of the cascade. In addition, HIV is protected from complement-mediated lysis by binding soluble factor H (fH through the viral envelope proteins, gp120 and gp41. Whereas inhibition of complement activity is the desired outcome in the vast majority of therapeutic approaches, there is a broader potential for complement-mediated inhibition of HIV by complement local stimulation. Presentation of the hypothesis Our previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that another new activator of complement, consisting of two dsFv (against gp120 and against C3d respectively linked to a complement-activating human IgG1 Fc domain ((anti-gp120 × anti-C3d-Fc, can not only target and amplify complement activation on HIV virions for enhancing the efficiency of HIV lysis, but also reduce the infectivity of HIV through blocking the gp120 and C3d on the surface of HIV. Testing the hypothesis Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified (anti-gp120 × anti-C3d-Fc proteins. As a control group, viruses

  20. Peptide Inhibitor of Complement C1 (PIC1 Rapidly Inhibits Complement Activation after Intravascular Injection in Rats.

    Directory of Open Access Journals (Sweden)

    Julia A Sharp

    Full Text Available The complement system has been increasingly recognized to play a pivotal role in a variety of inflammatory and autoimmune diseases. Consequently, therapeutic modulators of the classical, lectin and alternative pathways of the complement system are currently in pre-clinical and clinical development. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement and is referred to as Peptide Inhibitor of Complement C1 (PIC1. In this study, we determined that the lead PIC1 variant demonstrates a salt-dependent binding to C1q, the initiator molecule of the classical pathway. Additionally, this peptide bound to the lectin pathway initiator molecule MBL as well as the ficolins H, M and L, suggesting a common mechanism of PIC1 inhibitory activity occurs via binding to the collagen-like tails of these collectin molecules. We further analyzed the effect of arginine and glutamic acid residue substitution on the complement inhibitory activity of our lead derivative in a hemolytic assay and found that the original sequence demonstrated superior inhibitory activity. To improve upon the solubility of the lead derivative, a pegylated, water soluble variant was developed, structurally characterized and demonstrated to inhibit complement activation in mouse plasma, as well as rat, non-human primate and human serum in vitro. After intravenous injection in rats, the pegylated derivative inhibited complement activation in the blood by 90% after 30 seconds, demonstrating extremely rapid function. Additionally, no adverse toxicological effects were observed in limited testing. Together these results show that PIC1 rapidly inhibits classical complement activation in vitro and in vivo and is functional for a variety of animal species, suggesting its utility in animal models of classical complement-mediated diseases.

  1. AFSC/ABL: Origins of sockeye and chum salmon seized from the F/V Ying Fa

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Samples of chum (Oncorhynchus keta) and sockeye (O. nerka) salmon seized from the stateless fishing vessel Ying Fa were analyzed to determine their region of origin...

  2. Complement involvement in periodontitis: molecular mechanisms and rational therapeutic approaches

    Science.gov (United States)

    Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D.

    2015-01-01

    The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis. PMID:26306443

  3. Complement Inhibition as a Proposed Neuroprotective Strategy following Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Brad E. Zacharia

    2009-01-01

    Full Text Available Out-of-hospital cardiac arrest (OHCA is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA.

  4. The Complement-Fixation Test in Hepatic Coccidiosis of Rabbits

    Science.gov (United States)

    Rose, M. Elaine

    1961-01-01

    Antibodies to Eimeria stiedae were measured in rabbit serum by complement fixation. The titre rose to a maximum at about the 22nd day after infection, remained at this level for about 20 days and then declined. Antibodies were still detectable up to 160 days after infection. Evidence of past or present slight E. stiedae infection was found in clinically normal rabbits whose sera fixed complement with E. stiedae antigens. Challenge of rabbits which had recovered from a near-fatal infection had no effect upon the complement fixation titres of their sera. The serum of a rabbit which had been injected with alum-precipitated antigen fixed complement with E. stiedae antigens. However, the animal was still susceptible to a superimposed oral infection which had the effect of further increasing the serum titre. PMID:14493840

  5. Lessons learned from mice deficient in lectin complement pathway molecules

    DEFF Research Database (Denmark)

    Genster, Ninette; Takahashi, Minoru; Sekine, Hideharu

    2014-01-01

    in complement activation, pathogen infection, coagulation, host tissue injury and developmental biology have been revealed by in vivo investigations. This review provides an overview of the mice deficient in lectin pathway molecules and highlights some of the most important findings that have resulted from......The lectin pathway of the complement system is initiated when the pattern-recognition molecules, mannose-binding lectin (MBL), ficolins or collectin-11, bind to invading pathogens or damaged host cells. This leads to activation of MBL/ficolin/collectin-11 associated serine proteases (MASPs), which...... in turn activate downstream complement components, ultimately leading to elimination of the pathogen. Mice deficient in the key molecules of lectin pathway of complement have been generated in order to build knowledge of the molecular mechanisms of the lectin pathway in health and disease. Despite...

  6. The 'Complementality' Realities Between History and the Social ...

    African Journals Online (AJOL)

    The 'Complementality' Realities Between History and the Social Science. ... of society and process of change, which are the subject matter of history. ... nature of the relationship between History as a distinct discipline and the Social Sciences, ...

  7. Complement in neuroinflammation: Studies in leprosy and Amyotrophic Lateral Sclerosis

    OpenAIRE

    Bahia El Idrissi, N.

    2017-01-01

    The complement system is a part of the innate immunity, and plays an important role in host immunity and inflammation. We previously identified the terminal membrane attack complex (MAC) of the complement system as a key determinant of neurodegeneration and demonstrated that its inhibition is neuroprotective. Besides being part of a mechanism of defence to invading pathogens, MAC has the capacity to cause damage to self-cells and is consequently implicated in many diseases. I describe studies...

  8. Evolutionary relationships of a "primitive" shark (Heterodontus) assessed by micro-complement fixation of serum transferrin.

    Science.gov (United States)

    Davies, D H; Lawson, R; Burch, S J; Hanson, J E

    1987-01-01

    The evolutionary relationships of six sharks were investigated by comparing their transferrins using the micro-complement fixation method. The immunological distances observed were used to build a tree that confirms that the squaloid and galeoid species examined belong to two separate groups and that Heterodontus, a genus of hitherto uncertain position, belongs with the galeoids. The divergence time estimated from the transferrin comparisons is roughly 240 +/- 65 million years between Heterodontus and galeoids.

  9. Genetic analysis of strawberry fruit aroma and identification of O-methyltransferase FaOMT as the locus controlling natural variation in mesifurane content.

    Science.gov (United States)

    Zorrilla-Fontanesi, Yasmín; Rambla, José-Luis; Cabeza, Amalia; Medina, Juan J; Sánchez-Sevilla, José F; Valpuesta, Victoriano; Botella, Miguel A; Granell, Antonio; Amaya, Iraida

    2012-06-01

    Improvement of strawberry (Fragaria × ananassa) fruit flavor is an important goal in breeding programs. To investigate genetic factors controlling this complex trait, a strawberry mapping population derived from genotype '1392', selected for its superior flavor, and '232' was profiled for volatile compounds over 4 years by headspace solid phase microextraction coupled to gas chromatography and mass spectrometry. More than 300 volatile compounds were detected, of which 87 were identified by comparison of mass spectrum and retention time to those of pure standards. Parental line '1392' displayed higher volatile levels than '232', and these and many other compounds with similar levels in both parents segregated in the progeny. Cluster analysis grouped the volatiles into distinct chemically related families and revealed a complex metabolic network underlying volatile production in strawberry fruit. Quantitative trait loci (QTL) detection was carried out over 3 years based on a double pseudo-testcross strategy. Seventy QTLs covering 48 different volatiles were detected, with several of them being stable over time and mapped as major QTLs. Loci controlling γ-decalactone and mesifurane content were mapped as qualitative traits. Using a candidate gene approach we have assigned genes that are likely responsible for several of the QTLs. As a proof of concept we show that one homoeolog of the O-methyltransferase gene (FaOMT) is the locus responsible for the natural variation of mesifurane content. Sequence analysis identified 30 bp in the promoter of this FaOMT homoeolog containing putative binding sites for basic/helix-loop-helix, MYB, and BZIP transcription factors. This polymorphism fully cosegregates with both the presence of mesifurane and the high expression of FaOMT during ripening.

  10. Activation of human complement by immunoglobulin G antigranulocyte antibody.

    Science.gov (United States)

    Rustagi, P K; Currie, M S; Logue, G L

    1982-01-01

    The ability of antigranulocyte antibody to fix the third component of complement (C3) to the granulocyte surface was investigated by an assay that quantitates the binding of monoclonal anti-C3 antibody to paraformaldehyde-fixed cells preincubated with Felty's syndrome serum in the presence of human complement. The sera from 7 of 13 patients with Felty's syndrome bound two to three times as much C3 to granulocytes as sera from patients with uncomplicated rheumatoid arthritis. The complement-activating ability of Felty's syndrome serum seemed to reside in the monomeric IgG-containing serum fraction. For those sera capable of activating complement, the amount of C3 fixed to granulocytes was proportional to the amount of granulocyte-binding IgG present in the serum. Thus, complement fixation appeared to be a consequence of the binding of antigranulocyte antibody to the cell surface. These studies suggest a role for complement-mediated injury in the pathophysiology of immune granulocytopenia, as has been demonstrated for immune hemolytic anemia and immune thrombocytopenia. PMID:7174786

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

    Science.gov (United States)

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

    2015-06-01

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

  12. The Role of Complement System in Septic Shock

    Directory of Open Access Journals (Sweden)

    Jean Charchaflieh

    2012-01-01

    Full Text Available Septic shock is a critical clinical condition with a high mortality rate. A better understanding of the underlying mechanisms is important to develop effective therapies. Basic and clinical studies suggest that activation of complements in the common cascade, for example, complement component 3 (C3 and C5, is involved in the development of septic shock. The involvement of three upstream complement pathways in septic shock is more complicated. Both the classical and alternative pathways appear to be activated in septic shock, but the alternative pathway may be activated earlier than the classical pathway. Activation of these two pathways is essential to clear endotoxin. Recent investigations have shed light on the role of lectin complement pathway in septic shock. Published reports suggest a protective role of mannose-binding lectin (MBL against sepsis. Our preliminary study of MBL-associated serine protease-2 (MASP-2 in septic shock patients indicated that acute decrease of MASP-2 in the early phase of septic shock might correlate with in-hospital mortality. It is unknown whether excessive activation of these three upstream complement pathways may contribute to the detrimental effects in septic shock. This paper also discusses additional complement-related pathogenic mechanisms and intervention strategies for septic shock.

  13. Complementing SRCNN by Transformed Self-Exemplars

    DEFF Research Database (Denmark)

    Aakerberg, Andreas; Rasmussen, Christoffer Bøgelund; Nasrollahi, Kamal

    2017-01-01

    Super-resolution algorithms are used to improve the qualityand resolution of low-resolution images. These algorithms can be dividedinto two classes of hallucination- and reconstruction-based ones. Theimprovement factors of these algorithms are limited, however, previousresearch [10], [9] has shown...... that combining super-resolution algorithmsfrom these two different groups can push the improvement factor further.We have shown in this paper that combining super-resolution algorithmsof the same class can also push the improvement factor up. For thispurpose, we have combined two hallucination based algorithms...

  14. Cercetări experimentale privind comportarea sistemelor pentru faţade, expuse la acţiunea focului

    Directory of Open Access Journals (Sweden)

    Ştefania Rădulescu

    2010-12-01

    Full Text Available Visually, it is often the goal of any architecture to define a personality or individual character through the design of the façade. This face or skin, wrapped to the structural frame beneath, is often key to an architect's desire to evoke our emotions, instilling a sense of grandeur as if each new building were an artist's sculpture. In recent decades the desire for taller structures and, particularly, those that are competing for recognition to be among the tallest, if not the world's tallest, is reason to review the fire safety issues related to façade or curtain wall design. Additionally, due to the creativity of architects, new and unique façade designs are continually appearing. The risk of fire spread through articulated elements of the façade or vertically around the façade via the mechanism of flame leap, poses new concerns for the newest class of super highrise structures. Our understanding of fire and its mechanisms of spread in buildings no longer eludes us, however, the risks of fire spread related to super high-rise buildings and the façades that define their character has not been well examined. Current code practices recognize the successful record of fully sprinkler protected high-rise buildings and only require that the void space between the curtain wall and the floor slab be resistive to fire spread using a perimeter fire barrier system.

  15. The therapeutic potential of Rho kinase inhibitor fasudil derivative FaD-1 in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Zhao, Yong-Fei; Zhang, Xiang; Ding, Zhi-Bin; Yang, Xing-Wang; Zhang, Hui; Yu, Jie-Zhong; Li, Yan-Hua; Liu, Chun-Yun; Zhang, Qing; Zhang, Hong-Zhen; Ma, Cun-Gen; Xiao, Bao-Guo

    2015-03-01

    Although therapeutic potential of fasudil in EAE is promising, action mechanism and clinical limitations are still not fully understood and resolved. In this study, we observed the therapeutic potential of a novel Rho kinase (ROCK) inhibitor FaD-1, a fasudil derivative, and explored possible mechanism in MOG35-55-induced EAE. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG35-55) immunization. The pathology of spinal cord was measured by immunohistochemistry and neurological impairment was evaluated using clinical scores. FaD-1, as a novel ROCK inhibitor, inhibited the expression of ROCK II that is mainly expressed in the CNS. We show here that FaD-1 ameliorates the neurological defects and the severity of MOG-induced EAE in mice, accompanied by the protection of demyelination and the inhibition of neuroinflammation in spinal cord of EAE. In addition, FaD-1 dampened TLR2 and TLR4 signaling as well as Th1 (IFN-γ) and Th17 (IL-17) responses in spinal cord of EAE. FaD-1 also prevented the expression of iNOS and production of inflammatory cytokine IL-1β, IL-6, and TNF-α which are specific markers for M1 inflammatory microglia/macrophages. This study highlights the therapeutic potential of FaD-1 as a ROCK inhibitor for the treatment of human autoimmune diseases with both inflammatory and autoimmune components.

  16. Birth order and recalled childhood gender nonconformity in Samoan men and fa'afafine.

    Science.gov (United States)

    Semenyna, Scott W; VanderLaan, Doug P; Vasey, Paul L

    2017-04-01

    Having a greater than average number of older biological brothers is a robust correlate of male androphilia (i.e., sexual attraction and arousal to adult males). Previous investigations have sought to understand whether this fraternal birth order (FBO) effect is also systematically related to recalled indicators of childhood gender nonconformity (CGN). However, these investigations have relied on data from low-fertility Western populations in which expressions of femininity in male children are routinely stigmatized and consequently, suppressed. The present study examined the FBO effect (among other sibship characteristics) and recalled indicators of CGN in Samoa, a high-fertility population, whose members are relatively tolerant of male femininity. Indeed, Samoans identify feminine androphilic males as belonging to an alternative gender category, known locally as fa'afafine. The present study compared the sibship characteristics of 231 fa'afafine and 231 opposite-sex attracted men from Samoa, as well as how these characteristics related to recalled CGN. Results replicated the well-established FBO effect for predicting male sexual orientation, with each older brother increasing the odds of being androphilic by 21%. However, no relationship was found between the number of older brothers (or other siblings) a participant had and their recalled CGN. Although fa'afafine reported significantly more CGN than Samoan men, CGN did not mediate the FBO effect, nor did the FBO effect and CGN interact to predict male sexual orientation. These findings are consistent with previous studies suggesting that the FBO effect is associated with male sexual orientation, but not childhood female-typical gender expression among androphilic males.

  17. "Near-bottom sonar mapping along the Eastern Lau Spreading Center and Valu Fa Ridge"

    Science.gov (United States)

    Sleeper, J. D.; Martinez, F.; Edwards, M.; Dunn, R.; Baker, E. T.

    2009-12-01

    We present results from high resolution sidescan sonar mapping at the Ridge 2000 Lau Integrated Studies Site, a back-arc spreading center in the Southwest Pacific. The survey covered segments of the Eastern Lau Spreading Center (ELSC) and Valu Fa Ridge (VFR), which exhibit strong contrasts in geologic and geophysical characteristics, including variations in ridge morphology, volcanic and tectonic structures, lava composition and texture, magma production, and spreading rate. The bulk of the data were collected in 2008 aboard R/V Kilo Moana (KM0804), using the deep-towed IMI120 (DSL120A) sonar, with an array of miniature autonomous plume recorder's (MAPR's) tethered to the tow cable to detect hydrothermal plume signatures in the water column. The ELSC survey covered an area ~10 km wide by 100 km long centered on the spreading axis, with tracks spaced ~1 km apart, but as close as ~500 m in the vicinity of the ABE hydrothermal vent field, and also included the Tow Cam and Kilo Moana vent fields. The VFR survey covered a ~5 km wide by 100 km long area with ~700 m-spaced tracks, including the Vai Lili, Mariner, and Tui Malila vent sites. The IMI120 has a resolution of ~1-2 meters, giving the first detailed view of the on- and off-axis structures in the two focus regions. Navigational corrections to the sidescan data were made through feature-matching between the deep-towed data and a lower resolution background ship bathymetry grid, using software developed by the Hawaiian Mapping and Research Group. Background bathymetry and lower resolution (~100 m) sidescan data were compiled from previous cruises on R/V Kilo Moana, and an early-2009 seismic survey on R/V Marcus G. Langseth (L-SCAN). Hydrothermal plume data collected with the MAPR's are coregistered with the deep-towed sidescan data to illuminate correlations between seafloor structures and plume signatures. The axis of the VFR in the south forms a peaked ridge, inflated by abundant melt supply, and draped with

  18. Up-regulation of the complement system in subcutaneous adipocytes from nonobese, hypertriglyceridemic subjects is associated with adipocyte insulin resistance.

    Science.gov (United States)

    van Greevenbroek, M M J; Ghosh, S; van der Kallen, C J H; Brouwers, M C G J; Schalkwijk, C G; Stehouwer, C D A

    2012-12-01

    Dysfunctional adipose tissue plays an important role in the etiology of the metabolic syndrome, type 2 diabetes, and dyslipidemia. However, the molecular mechanisms underlying adipocyte dysfunction are incompletely understood. The aim of the study was to identify differentially regulated pathways in sc adipocytes of dyslipidemic subjects. Whole-genome expression profiling was conducted on sc adipocytes from a discovery group of nine marginally overweight subjects with familial combined hyperlipidemia (FCHL) and nine controls of comparable body sizes as well as two independent confirmation groups. In this study, FCHL served as a model of familial insulin resistance and dyslipidemia, in the absence of frank obesity. Functional analyses and gene set enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes or a custom pathway database identified the complement system and complement regulators as one of the top up-regulated pathways in FCHL [false discovery rate (FDR) set and with triglycerides and/or waist circumference in the confirmation groups. Complement pathway up-regulation did not appear to be driven by hypertriglyceridemia because a 40% pharmacological reduction in triglycerides did not affect complement expression. These findings point to an up-regulation of a complement-related transcriptome in sc adipocytes under metabolically stressed conditions, even in the absence of overt obesity. Such up-regulation may subsequently influence downstream processes, including macrophage infiltration into adipose tissue and adipocyte insulin resistance.

  19. Development of a Façade Assessment and Design Tool for Solar Energy (FASSADES)

    OpenAIRE

    Jouri Kanters; Maria Wall; Marie-Claude Dubois

    2014-01-01

    Planning energy-efficient buildings which produce on-site renewable energy in an urban context is a challenge for all involved actors in the planning process. The primary objective of this study was to develop a façade assessment and design tool for solar energy (FASSADES) providing the necessary information for all stakeholders in the design process. The secondary objective was to demonstrate the tool by performing an assessment analysis of a building block. The FASSADES tool is a DIVA4Rhino...

  20. Transparent Façade Panel Typologies Based on Recyclable Polymer Materials

    Directory of Open Access Journals (Sweden)

    Harry Giles

    2012-11-01

    Full Text Available Buildings are large consumers of energy. In the United States of America; they constitute over 33% of the total annual energy consumption, produce 35% of the total carbon dioxide emissions and attribute 40% of landfill wastes. The building industry is also a large consumer of non-renewable materials and this trend has escalated dramatically over the past century. It is essential that we find ways to save on energy consumption through the use of solar energy, improved thermal insulation, and alternative efficient glazed façade systems. In this paper, we demonstrate how alternative typologies of transparent and translucent load-bearing façade systems based on biocomposite and recyclable materials, are structurally and thermally efficient at the same time they contribute towards reduced pollutant emissions and non-renewable material uses.Composite insulated panel systems are used extensively in the engineering and building industry, owing to their structural and thermal efficiency. However, these systems are generally opaque and offer little flexibility in building applications. As an alternative, we demonstrate how building products comprised of hybrid material typologie scan be made to perform efficiently as load-bearing façade systems that substitute for current glazing systems with adequate thermal and structural performance, which also possess good light transmission characteristics and integral shading capability. The materials are configured to work as composite panel systems made from a combination of biocomposite and recyclable polymer materials. These materials are environmentally sustainable, because they either originate from naturally grown renewable resources or are recyclable. Our research program includes the design and development of prototype panel systems; the evaluation of structural and thermal performance, together with their role in reducing energy consumption and pollution emission through life cycle analysis. The paper

  1. Increasing Ranks of Linear Finite Automata and Complexity of FA Public Key Cryptosystem

    Institute of Scientific and Technical Information of China (English)

    鲍丰

    1994-01-01

    The encryption algorithm of finite automata (FA) public key cryptosystem is implemented by a weakly invertible finite automata (WIFA) which is composed of a nonlinear WIFA with delay 0 and a linear WIFA with delay τ. In this paper, we proved that such an automaton bears the same properties as the linear WIFA and the increasing ranks of the latter are key factors to affecting the former. A probabilistic algorithm is given to realize a ciphertext attack, and its complexity is analysed through the increasing ranks of the linear WIFA. The size of the parameters for safe linear WIFA is estimated.

  2. Objective and subjective evaluation of façade sound insulation

    DEFF Research Database (Denmark)

    Ordoñez, Rodrigo Pizarro; Visentin, Chiara; Markovic, Milos

    2013-01-01

    Façade insulation of several different construction types were subjectively evaluated using two psychoacoustic methods: paired comparisons using a two alternative forced choice (2-AFC) paradigm and direct scaling using a visual analogue scale (VAS). The stimuli used in the evaluations were obtained...... by filtering recordings of traffic noise with the frequency response of sound insulation measurements. The measurements were performed in typical Italian buildings in accordance with the ISO 140-5 standard. The objectives of the present paper are to compare the subjective evaluations obtained with the two...... psychoacoustic methods, and to investigate the correlation between subjective assessments and objective ratings in different construction types....

  3. Una experiencia en GPU Computing entre FaMAF e INVAP.

    OpenAIRE

    Bustos, Fabio; Wolovick, Nicolás

    2014-01-01

    Mostramos la experiencia realizada entre INVAP SE y FaMAF-UNC, para el desarrollo del software de imágenes sobre placas de procesamiento gráfico de propósitos generales (GPGPU por sus siglas en inglés). En el contexto de un sistema de adquisición de imágenes desarrollado por INVAP para uno de sus clientes, resulta necesario incluir un módulo de software capaz de realizar un seguimiento automático de puntos de interés identificados en un video....

  4. Isolation and Characterization of Frankia sp. Strain FaC1 Genes Involved in Nitrogen Fixation

    OpenAIRE

    Ligon, James M.; James P. Nakas

    1987-01-01

    Genomic DNA was isolated from Frankia sp. strain FaC1, an Alnus root nodule endophyte, and used to construct a genomic library in the cosmid vector pHC79. The genomic library was screened by in situ colony hybridization to identify clones of Frankia nitrogenase (nif) genes based on DNA sequence homology to structural nitrogenase genes from Klebsiella pneumoniae. Several Frankia nif clones were isolated, and hybridization with individual structural nitrogenase gene fragments (nifH, nifD, and n...

  5. Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement

    DEFF Research Database (Denmark)

    Mortensen, Sofia; Kidmose, Rune Thomas; Petersen, Steen Vang;

    2015-01-01

    Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface...... for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. In this article, we present the crystal and solution structures of the 195-kDa C4b. Our results provide the molecular details...... of substrate recognition. We propose an overall molecular model for the classical pathway C5 convertase in complex with C5, suggesting that C3b increases the affinity for the substrate by inducing conformational changes in C4b rather than a direct interaction with C5. C4b-specific features revealed by our...

  6. Derivatives of human complement component C3 for therapeutic complement depletion: a novel class of therapeutic agents.

    Science.gov (United States)

    Fritzinger, David C; Hew, Brian E; Lee, June Q; Newhouse, James; Alam, Maqsudul; Ciallella, John R; Bowers, Mallory; Gorsuch, William B; Guikema, Benjamin J; Stahl, Gregory L; Vogel, Carl-Wilhelm

    2008-01-01

    To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, we have prepared human C3/CVF hybrid proteins, in which the C-terminus of the alpha-chain of human C3 is exchanged with homologous regions of the C-terminus of the beta-chain of CVF. We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. Human C3/CVF hybrid proteins represent a novel class ofbiologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis.

  7. The Development of Thung Fa Bot Weekend Market into Cultural Tourism Attraction in San Pa Tong District, Chiang Mai Province

    Directory of Open Access Journals (Sweden)

    Phuwanatwichit Thongchai

    2014-01-01

    Full Text Available This study aimed to investigate for the socio-cultural and economic context, along with the issues of tourism potentiality of Thung Fa Bot weekend market into the cultural tourism attraction in San Pa Tong District, Chiang Mai Province. A study was created containing Mixed Methodology Research. The data collection was focus group and in-depth interviews from the target population and questionnaires of stakeholders. The study was determined that context of socio-cultural and economic structure,which was relying on farming in the past. The potentiality level to be the cultural tourist attraction in overall was moderate.the aspect of tourist Attraction and Spirit of a community were in high level. On the other hand Accessibility, Activities and Participation civil organizations were in moderate level. There were only the Amenities and Ancillary Services had shown on low level. The results suggested the need to develop its potentiality of cultural tourist attraction in [1] Amenities and Ancillary Services management at the tourist spots and tourism promoting and [2] Linking network with government agencies, private sectors, and communities to join in tourism management in order to enlarge Thung Fha Bod Weekend Market becoming the greater cultural tourism attraction for the tourists.

  8. Delta-like 1/fetal antigen-1 (Dlk1/FA1) is a novel regulator of chondrogenic cell differentiation via inhibition of the Akt kinase-dependent pathway

    DEFF Research Database (Denmark)

    Chen, Li; Qanie, Diyako; Jafari, Abbas

    2011-01-01

    Delta-like 1 (Dlk1, also known as fetal antigen-1, FA1) is a member of Notch/Delta family that inhibits adipocyte and osteoblast differentiation; however, its role in chondrogenesis is still not clear. Thus, we overexpressed Dlk1/FA1 in mouse embryonic ATDC5 cells and tested its effects...... on chondrogenic differentiation. Dlk1/FA1 inhibited insulin-induced chondrogenic differentiation as evidenced by reduction of cartilage nodule formation and gene expression of aggrecan, collagen Type II and X. Similar effects were obtained either by using Dlk1/FA1-conditioned medium or by addition of a purified......, secreted, form of Dlk1 (FA1) directly to the induction medium. The inhibitory effects of Dlk1/FA1 were dose-dependent and occurred irrespective of the chondrogenic differentiation stage: proliferation, differentiation, maturation, or hypertrophic conversion. Overexpression or addition of the Dlk1/FA1...

  9. Bullous pemphigoid autoantibodies directly induce blister formation without complement activation.

    Science.gov (United States)

    Ujiie, Hideyuki; Sasaoka, Tetsumasa; Izumi, Kentaro; Nishie, Wataru; Shinkuma, Satoru; Natsuga, Ken; Nakamura, Hideki; Shibaki, Akihiko; Shimizu, Hiroshi

    2014-11-01

    Complement activation and subsequent recruitment of inflammatory cells at the dermal/epidermal junction are thought to be essential for blister formation in bullous pemphigoid (BP), an autoimmune blistering disease induced by autoantibodies against type XVII collagen (COL17); however, this theory does not fully explain the pathological features of BP. Recently, the involvement of complement-independent pathways has been proposed. To directly address the question of the necessity of the complement activation in blister formation, we generated C3-deficient COL17-humanized mice. First, we show that passive transfer of autoantibodies from BP patients induced blister formation in neonatal C3-deficient COL17-humanized mice without complement activation. By using newly generated human and murine mAbs against the pathogenic noncollagenous 16A domain of COL17 with high (human IgG1, murine IgG2), low (murine IgG1), or no (human IgG4) complement activation abilities, we demonstrate that the deposition of Abs, and not complements, is relevant to the induction of blister formation in neonatal and adult mice. Notably, passive transfer of BP autoantibodies reduced the amount of COL17 in lesional mice skin, as observed in cultured normal human keratinocytes treated with the same Abs. Moreover, the COL17 depletion was associated with a ubiquitin/proteasome pathway. In conclusion, the COL17 depletion induced by BP autoantibodies, and not complement activation, is essential for the blister formation under our experimental system. Copyright © 2014 by The American Association of Immunologists, Inc.

  10. Functional analysis of Ficolin-3 mediated complement activation.

    Directory of Open Access Journals (Sweden)

    Estrid Hein

    Full Text Available The recognition molecules of the lectin complement pathway are mannose-binding lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to be associated with life threatening infections. Thus, we aimed to develop a functional method based on the ELISA platform for evaluating Ficolin-3 mediated complement activation that could be applicable for research and clinical use. Bovine serum albumin (BSA was acetylated (acBSA and chosen as a solid phase ligand for Ficolins in microtiter wells. Binding of Ficolins on acBSA was evaluated, as was functional complement activation assessed by C4, C3 and terminal complement complex (TCC deposition. Serum Ficolin-3 bound to acBSA in a calcium dependent manner, while only minimal binding of Ficolin-2 and no binding of Ficolin-1 were observed. No binding to normal BSA was seen for any of the Ficolins. Serum C4, C3 and TCC deposition on acBSA were dependent only on Ficolin-3 in appropriate serum dilutions. Deposition of down stream complement components correlated highly significantly with the serum concentration of Ficolin-3 but not with Ficolin-2 in healthy donors. To make the assay robust for clinical use a chemical compound was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides the possibility to diagnose functional and genetic defects of Ficolin-3 and down stream components in the lectin complement pathway.

  11. Complement activation and interleukin response in major abdominal surgery.

    Science.gov (United States)

    Kvarnström, A L; Sarbinowski, R T; Bengtson, J-P; Jacobsson, L M; Bengtsson, A L

    2012-05-01

    The objective of this study was to evaluate whether major abdominal surgery leads to complement activation and interleukin response and whether the kind of anaesthesia influence complement activation and the release of inflammatory interleukins. The study design was prospective and randomised. Fifty patients undergoing open major colorectal surgery due to cancer disease or inflammatory bowel disease were studied. Twenty-five patients were given total intravenous anaesthesia (TIVA) with propofol and remifentanil, and 25 patients were given inhalational anaesthesia with sevoflurane and fentanyl. To determine complement activation (C3a and SC5b-9) and the release of pro- and anti-inflammatory interleukins (tumour necrosis factor-a (TNF-a)), interleukin-1b (IL-1b), IL-6, IL-8, IL-4 and IL-10), blood samples were drawn preoperatively, 60 minutes after start of surgery, 30 minutes after end of surgery and 24 hours postoperatively. Complement was activated and pro-inflammatory interleukins (IL-6 and IL-8) and anti-inflammatory interleukins (IL-10) were released during major colorectal surgery. There was no significant difference between TIVA and inhalational anaesthesia regarding complement activation and cytokine release. Major colorectal surgery leads to activation of the complement cascade and the release of both pro-inflammatory and anti-inflammatory cytokines. There are no significant differences between total intravenous anaesthesia (TIVA) with propofol and remifentanil and inhalational anaesthesia with sevoflurane and fentanyl regarding complement activation and the release of pro- and anti-inflammatory interleukins. © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd. Scandinavian Journal of Immunology.

  12. A novel method for direct measurement of complement convertases activity in human serum

    NARCIS (Netherlands)

    Blom, A.M.; Volokhina, E.B.; Fransson, V.; Stromberg, P.; Berghard, L.; Viktorelius, M.; Mollnes, T.E.; Lopez-Trascasa, M.; Heuvel, B. van den; Goodship, T.H.; Marchbank, K.J.; Okroj, M.

    2014-01-01

    Complement convertases are enzymatic complexes that play a central role in sustaining and amplification of the complement cascade. Impairment of complement function leads directly or indirectly to pathological conditions, including higher infection rate, kidney diseases, autoimmune- or neurodegenera

  13. Levels of complement components C3a and C5a in renal injury among trichloroethylene-sensitized BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    查晚生

    2014-01-01

    Objective To determine the levels of complement components C3a and C5a in the kidneys of trichloroethylene(TCE)-sensitized BALB/c mice,and to investigate the role of complement components in TCE-induced renal injury among BALB/c mice.Methods Sixty-two female BALB/c mice were randomly divided into blank control group,vehicle control group,and TCE sensitization

  14. Development and Characterization of a High Sensitivity Segmented Fast Neutron Spectrometer (FaNS-2)

    CERN Document Server

    Langford, T J; Breuer, H; Heimbach, C R; Ji, G; Nico, J S

    2015-01-01

    We present the development of a segmented fast neutron spectrometer (FaNS-2) based upon plastic scintillator and $^3$He proportional counters. It was designed to measure both the flux and spectrum of fast neutrons in the energy range of few MeV to 1 GeV. FaNS-2 utilizes capture-gated spectroscopy to identify neutron events and reject backgrounds. Neutrons deposit energy in the plastic scintillator before capturing on a $^3$He nucleus in the proportional counters. Segmentation improves neutron energy reconstruction while the large volume of scintillator increases sensitivity to low neutron fluxes. A main goal of its design is to study comparatively low neutron fluxes, such as cosmogenic neutrons at the Earth's surface, in an underground environment, or from low-activity neutron sources. In this paper, we present details of its design and construction as well as its characterization with a calibrated $^{252}$Cf source and monoenergetic neutron fields of 2.5 MeV and 14 MeV. Detected monoenergetic neutron spectra...

  15. Thermal Performance of Ventilated Double Skin Façades with Venetian Blinds

    Directory of Open Access Journals (Sweden)

    Jordi Parra

    2015-05-01

    Full Text Available Venetian blinds (VB are shading devices of widespread use in residential and corporate buildings. They can reflect or transmit light into buildings and at the same time allow daylighting and exterior views. They can also efficiently block radiative heat from entering the building, and if combined with a heat dissipation system such as forced ventilation, they can improve the thermal performance of double skin façades (DSF. Computational Fluid Dynamics (CFD has proven to be a useful tool for modeling flow and heat transfer in DSF, including conduction, convection and radiation heat transfer phenomena. The aim of this work is to evaluate, by means of CFD, the influence of several optical, construction and operation parameters of a DSF (such as optical properties of the materials, geometrical relations of the VB or flow stream conditions in terms of energy savings, measured as a reduction of the solar load entering the building. Results obtained show that parameters such as the proximity of the VB to the exterior skin of the façade or a differentiated surface treatment for the exterior and interior faces of the VB louvers can notably affect the thermal performance of the DSF and hence the heat gains experienced by the building.

  16. Ultrathin Fluidic Laminates for Large-Area Façade Integration and Smart Windows.

    Science.gov (United States)

    Heiz, Benjamin P V; Pan, Zhiwen; Lautenschläger, Gerhard; Sirtl, Christin; Kraus, Matthias; Wondraczek, Lothar

    2017-03-01

    Buildings represent more than 40% of Europe's energy demands and about one third of its CO2 emissions. Energy efficient buildings and, in particular, building skins have therefore been among the key priorities of international research agendas. Here, glass-glass fluidic devices are presented for large-area integration with adaptive façades and smart windows. These devices enable harnessing and dedicated control of various liquids for added functionality in the building envelope. Combining a microstructured glass pane, a thin cover sheet with tailored mechanical performance, and a liquid for heat storage and transport, a flat-panel laminate is generated with thickness adapted to a single glass sheet in conventional windows. Such multimaterial devices can be integrated with state-of-the-art window glazings or façades to harvest and distribute thermal as well as solar energy by wrapping buildings into a fluidic layer. High visual transparency is achieved through adjusting the optical properties of the employed liquid. Also secondary functionality, such as chromatic windows, polychromatism, or adaptive energy uptake can be generated on part of the liquid.

  17. The Arabic Hyperbolic Pattern 'Fa??al' in Two Recent Translations of the Qur'an

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    Amr M. El-Zawawy

    2014-06-01

    Full Text Available The present study addresses the problem of rendering the فعال'fa??al' hyperbolic pattern into English in two recent translations of the Qur'an. Due to the variety of Qur'an translations and the large amount of hyperbolic forms of Arabic verbs recorded in the Qur'an, only two translations of the Qur'an are consulted and analyzed: these two translations, namely Saheeh International Translation (1997 and Prof. Abdel-Haleem's (2004, are distinguished by the fact that they are recent and well-received. Moreover, the investigation of hyperbolic forms is confined to the Arabic formفعال    'fa??al'. The study reveals that the Saheeh translator has applied morphological shifting in many examples while Abdel-Haleem's translation exhibits a considerable amount of syntactic transposition, coupled with paraphrasing. The test of accuracy as administered here is to give a clear picture of the need to pay particular attention to hyperboles of the form examined and other ones not analyzed here for limitations of space.

  18. Color Image Evaluation for Small Space Based on FA and GEP

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    Li Deng

    2014-01-01

    Full Text Available Aiming at the problem that color image is difficult to quantify, this paper proposes an evaluation method of color image for small space based on factor analysis (FA and gene expression programming (GEP and constructs a correlation model between color image factors and comprehensive color image. The basic color samples of small space and color images are evaluated by semantic differential method (SD method, color image factors are selected via dimension reduction in FA, factor score function is established, and by combining the entropy weight method to determine each factor weights then the comprehensive color image score is calculated finally. The best fitting function between color image factors and comprehensive color image is obtained by GEP algorithm, which can predict the users’ color image values. A color image evaluation system for small space is developed based on this model. The color evaluation of a control room on AC frequency conversion rig is taken as an example, verifying the effectiveness of the proposed method. It also can assist the designers in other color designs and provide a fast evaluation tool for testing users’ color image.

  19. Comparison and development of sustainable office façade renovation solutions in the Netherlands

    Directory of Open Access Journals (Sweden)

    Michiel Ritzen

    2013-12-01

    Full Text Available Environmental, commercial and societal developments in the Netherlands stimulate the environmental improvement of the existing office building stock. In the Netherlands, about 15% of all office area was vacant in 2012, and the majority of offices have a relative poor energy performance. To measure the improvement, different assessment tools are applied. These tools either focus on one aspect, such as operation energy, and result in a specific outcome such as MJ/m2, or these tools combine different aspects, such as energy and materials, through a weighted system and result in a generic outcome, such as ‘excellent’.In this research, the relation between assessment outcome and actual environmental impact is investigated of both types of tools, by reflecting the outcome of the tool to the carrying capacity of a system. The relation is investigated through a comparison of the energy and material aspect of three office façade renovation solutions using four different assessment tools. Using a tool in which energy and material impact is related to the carrying capacity, current energy focused optimization might lead to a sub optimization of actual environmental impact. To illustrate this, a calculated façade solution is presented with minimal environmental impact based on carrying capacity.

  20. Function and principle innovative design of mechanical products based on TRIZ/FA

    Institute of Scientific and Technical Information of China (English)

    YUAN Feng; WANG Tai-yong; NIE Hui-juan

    2006-01-01

    Function and principle innovation is the ultimate innovation of a product.To achieve Function and principle innovation design of mechanical products,a new process model of function and principle solving is proposed,based on TRIZ and FA.In this model,abstraction of general function,confirmation of principle solution to general function,and functional decomposition were included in FA.Confirmation of principle solution to general function was the premise of functional decomposition.To provide a dependable pattern for functional decomposition,a new functional analysis method was put forward based on the generalized process function along with the introduction of the input constraint function;and its five-decomposition-steps were also presented.To provide powerful support for innovation design tools in principle solution,some TRIZ tools in the model were imbedded,such as SU-field Analysis,Scientific Effects,and Contradiction Solving Principles so as to boost up the innovation of principle solution.As a case study,an innovative design of paint-bottling machine has been achieved with application of the proposed model.

  1. Composting of food waste subjected to hydrothermal pretreatment and inoculated with Paecilomyces sp. FA13.

    Science.gov (United States)

    Nakasaki, Kiyohiko; Mimoto, Hiroshi; Tran, Quyen Ngoc Minh; Oinuma, Akiko

    2015-03-01

    Food waste collected from restaurants, convenience stores, and food-processing factories was mixed with sawdust and subjected to hydrothermal pretreatment at 180°C for 30min to prepare compost raw material. Furan compounds such as 5-HMF (5-hydroxymethyl furfural) and furfural were produced at concentration levels of approximately 8 and 0.5mg/g-ds, respectively, through hydrothermal pretreatment. The furan compounds inhibited the activity of composting microorganisms, thus delaying the start of organic matter degradation during composting. A newly identified fungus, Paecilomyces sp. FA13, which possesses the ability to degrade furan compounds, was isolated and used as an inoculum for the composting of the raw material prepared by hydrothermal pretreatment. By inoculating the FA13 into the compost raw material at 10(5)CFU/g-ds, the degradation of furan compounds was accelerated. As a result, bacterial activity, which contributed to composting, was enhanced, significantly promoting the start of vigorous degradation of organic materials.

  2. Climate Based Façade Design for Business Buildings with Examples from Central London

    Directory of Open Access Journals (Sweden)

    John Napier

    2015-01-01

    Full Text Available There is a disconnection between commercial architecture and environmental thinking, where green features can be included as part of a strategy for gaining approvals and marketing projects, but those features are not reviewed after completion and occupation of the building and knowledge is not shared. High levels of air conditioning are still considered unavoidable. Elaborate double skin façades and complex motorized shading systems are adopted; often masking an underlying lack of basic environmental thinking. This article returns (in principle to the physics of comfort in buildings and the passive strategies which can help achieve this with a low energy and carbon footprint. Passive and active façade design strategies are outlined as the basis of a critical tool and a design methodology for new projects. A new architectural sensibility can arise based on modeling the inputs of sunlight, daylight and air temperature in time and space at the early stages of design. Early but sound strategies can be tested and refined using advanced environmental modeling techniques. Architecture and environmental thinking can proceed hand in hand through the design process.

  3. Cloning and Expression Analysis of Cysteine Protease Gene (FaCP) in Strawberry (Fragaria × ananassa)%草莓半胱氨酸蛋白酶基因(FaCP)的克隆及表达分析

    Institute of Scientific and Technical Information of China (English)

    朱海生; 陈敏氡; 温庆放; 林珲

    2013-01-01

    Cysteine protease (CP) is one of the important hydrolysis protease, which widely participates in a variety of physiological processes of plants. The FaCP gene cDNA was cloned from strawberry (Fragaria x ananassa) using RT-PCR and RACE techniques. The cDNA sequence was 1 338 bp (GenBank accession number: JN979371), including 1 065 bp of open reading frame (ORF), which encoded a protein of 354 amino acids with a predicted molecular weight of 39 130 D and a hypothetical pI (isoelectric point) of 4.93. Homology analysis showed that the deduced CP protein was highly homologous to other CP proteins from different plant species. Phylogenetic analysis indicated that FaCP was more related to castor, trichocarpa, kiwi and grape. Real-time PCR analysis revealed FaCP could be expressed in different strawberry tissues including root, stem, leaf, calyx and fruit, of which the highest expression level in fruit. The FaCP expressed continuously during the whole period of strawberry fruit development and reached the maximum at the pink ripening stage and decreased slightly at the red ripening stage. The expression level of FaCP gene in leaves was gradually increased with leaf senescence, which the expression in the young leaves stage (leaf unfolding within 15 days) was low, but in the old leaves (leaf unfolding for more than 45 days), the FaCP had a higher expression. This result showed that FaCP may play a role in the fruit ripening and leaf senescence.%半胱氨酸蛋白酶作为一种重要的水解蛋白酶,参与植物的许多生理过程.采用RT-PCR和RACE技术从草莓(Fragaria×ananassa)中克隆到半胱氨酸蛋白酶基因FaCP (GenBank登录号:JN979371),该基因cDNA全长1 338 bp,包含一个1 062 bp完整的开放阅读框(ORF),编码354氨基酸.生物信息学序列分析表明,FaCP开放阅读框编码的氨基酸序列与其他植物的CP蛋白同源性较高.Real-time PCR分析发现,FaCP基因在草莓果实、叶、根、茎和花萼中都有表达;在果

  4. Color Vision and the Railways: Part 3. Comparison of FaLant, OPTEC 900, and Railway LED Lantern Tests.

    Science.gov (United States)

    Dain, Stephen J; Casolin, Armand; Long, Jennifer

    2015-02-01

    The Farnsworth Lantern (FaLant) and the OPTEC 900 are nominated in the Commission Internationale de l'Éclairage (CIE) Color Vision Standard 2. Neither test uses the railway signal color code of red, yellow, and green, and only the OPTEC 900 is commercially available. The Railway LED Lantern Test (RLLT) is based on railway signaling practices in New South Wales, Australia, and is nominated in the Australian railway medical standard. The objective of this study is to compare the performance of the three lantern tests. The RLLT, FaLant, and OPTEC 900 were administered to 46 color vision-normal and 37 color vision-deficient (CVD) subjects. The pattern of errors on the RLLT was different from that of the FaLant and OPTEC 900. This may be accounted for, at least in part, by the different colors and the use of blank presentations in the RLLT. The three lanterns showed agreement in failing 21 and passing 6 of the CVD subjects (72.9%). The lanterns gave different results for 10 CVD subjects (27.9%): n = 5 passed only the RLLT and n = 3 passed only the FaLant; n = 1 failed only the FaLant and n = 1 failed only the RLLT. The overall failure rate by CVD for each lantern was 67.6% (RLLT), 73.0% (FaLant), and 78.4% (OPTEC 900). Despite the different construction principles, the pass/fail levels of the RLLT, FaLant, and OPTEC 900 are comparable and consistent with the performance of other lanterns listed by the CIE for Color Vision Standard 2. The RLLT may be a little easier to pass and is based on the signal color code used and actual signaling practice. We propose that the RLLT is also an appropriate lantern for CIE Color Vision Standard 2.

  5. Computer-simulation study on fire behaviour in the ventilated cavity of ventilated façade systems

    Directory of Open Access Journals (Sweden)

    Giraldo María P.

    2013-11-01

    Full Text Available Fire spread through the façades is widely recognized as one of the fastest pathways of fire spreading in the buildings. Fire may spread through the façade in different ways depending on the type of façade system and on the elements and materials from which it is constructed. Ventilated façades are multilayer systems whose main feature is the creation of an air chamber of circulating air between the original building wall and the external cladding. The “chimney effect” in the air cavity is a mechanism that improves the façade's thermal behaviour and avoids the appearance of moisture from rain or condensation. However, in a event of fire, it may contribute to the quickest spreading of fire, representing a significant risk to the upper floors of a building. This study deals with some aspects of fire propagation through the ventilated cavity in ventilated façade systems. Also we review the provisions stipulated by the Spanish building code (Código Técnico de la Edificación, CTE [1] to avoid fire spread outside the building. The results highlight the importance of the use of proper fire barriers to ensure the compartmentalization of the ventilated cavity, as well as the use of non-combustible thermal insulation materials, among others. In addition, based on the results, it might be considered that the measures stipulated by the CTE are insufficient to limit the risks associated with this kind of façades systems. The study has been performed using field models of computational fluid-dynamics. In particular, the Fire Dynamics Simulator (FDS software has been used to numerically solve the mathematical integration models.

  6. Complement C3c as a Biomarker in Heart Failure

    Directory of Open Access Journals (Sweden)

    A. Frey

    2013-01-01

    Full Text Available Introduction. Experimental data indicates an important role of the innate immune system in cardiac remodeling and heart failure (HF. Complement is a central effector pathway of the innate immune system. Animals lacking parts of the complement system are protected from adverse remodeling. Based on these data, we hypothesized that peripheral complement levels could be a good marker for adverse remodeling and prognosis in patients with HF. Methods and Results. Since complement activation converges on the complement factor C3, we measured serum C3c, a stable C3-conversion product, in 197 patients with stable systolic HF. Subgroups with normal and elevated C3c levels were compared. C3c levels were elevated in 17% of the cohort. Patients with elevated C3c levels exhibited a trend to better survival, slightly higher LVEF, and lower NTpro-BNP values in comparison to patients with normal C3c values. No differences were found regarding NYHA functional class. Significantly more patients with elevated C3c had preexisting diabetes. The prevalence of CAD, arterial hypertension, and atrial fibrillation was not increased in patients with elevated C3c. Conclusion. Elevated C3c levels are associated with less adverse remodeling and improved survival in patients with stable systolic heart failure.

  7. Coagulation and complement system in critically ill patients.

    Science.gov (United States)

    Helling, H; Stephan, B; Pindur, G

    2015-01-01

    Activation of coagulation and inflammatory response including the complement system play a major role in the pathogenesis of critical illness. However, only limited data are available addressing the relationship of both pathways and its assessment of a predictive value for the clinical outcome in intense care medicine. Therefore, parameters of the coagulation and complement system were studied in patients with septicaemia and multiple trauma regarded as being exemplary for critical illness. 34 patients (mean age: 51.38 years (±16.57), 15 females, 19 males) were investigated at day 1 of admittance to the intensive care unit (ICU). Leukocytes, complement factors C3a and C5a were significantly (p complement system as part of the inflammatory response is a significant mechanism in septicaemia, whereas loss and consumption of blood components including parts of the coagulation and complement system is more characteristic for multiple trauma. Protein C in case of severe reduction might be of special concern for surviving in sepsis. Activation of haemostasis was occurring in both diseases, however, overt DIC was not confirmed in this study to be a leading mechanism in critically ill patients. MOF score, lactate, C1-inhibitor and prothrombin time have been the only statistically significant predictors for lethal outcome suggesting that organ function, microcirculation, haemostasis and inflammatory response are essential elements of the pathomechanism and clinical course of diseases among critically ill patients.

  8. Complement factor H in host defense and immune evasion.

    Science.gov (United States)

    Parente, Raffaella; Clark, Simon J; Inforzato, Antonio; Day, Anthony J

    2017-05-01

    Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.

  9. Function of Serum Complement in Drinking Water Arsenic Toxicity

    Directory of Open Access Journals (Sweden)

    Laila N. Islam

    2012-01-01

    Full Text Available Serum complement function was evaluated in 125 affected subjects suffering from drinking water arsenic toxicity. Their mean duration of exposure was 7.4±5.3 yrs, and the levels of arsenic in drinking water and urine samples were 216±211 and 223±302 μg/L, respectively. The mean bactericidal activity of complement from the arsenic patients was 92% and that in the unexposed controls was 99% (P<0.01, but heat-inactivated serum showed slightly elevated activity than in controls. In patients, the mean complement C3 was 1.56 g/L, and C4 was 0.29 g/L compared to 1.68 g/L and 0.25 g/L, respectively, in the controls. The mean IgG in the arsenic patients was 24.3 g/L that was highly significantly elevated (P<0.001. Arsenic patients showed a significant direct correlation between C3 and bactericidal activity (P=0.014. Elevated levels of C4 indicated underutilization and possibly impaired activity of the classical complement pathway. We conclude reduced function of serum complement in drinking water arsenic toxicity.

  10. Complement Biomarkers as Predictors of Disease Progression in Alzheimer's Disease.

    Science.gov (United States)

    Hakobyan, Svetlana; Harding, Katharine; Aiyaz, Mohammed; Hye, Abdul; Dobson, Richard; Baird, Alison; Liu, Benjamine; Harris, Claire Louise; Lovestone, Simon; Morgan, Bryan Paul

    2016-09-06

    There is a critical unmet need for reliable markers of disease and disease course in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The growing appreciation of the importance of inflammation in early AD has focused attention on inflammatory biomarkers in cerebrospinal fluid or plasma; however, non-specific inflammation markers have disappointed to date. We have adopted a targeted approach, centered on an inflammatory pathway already implicated in the disease. Complement, a core system in innate immune defense and potent driver of inflammation, has been implicated in pathogenesis of AD based on a confluence of genetic, histochemical, and model data. Numerous studies have suggested that measurement of individual complement proteins or activation products in cerebrospinal fluid or plasma is useful in diagnosis, prediction, or stratification, but few have been replicated. Here we apply a novel multiplex assay to measure five complement proteins and four activation products in plasma from donors with MCI, AD, and controls. Only one complement analyte, clusterin, differed significantly between control and AD plasma (controls, 295 mg/l; AD, 388 mg/l: p converted to dementia one year later compared to non-converters; a model combining these three analytes with informative co-variables was highly predictive of conversion. The data confirm the relevance of complement biomarkers in MCI and AD and build the case for using multi-parameter models for disease prediction and stratification.

  11. Micrurus snake venoms activate human complement system and generate anaphylatoxins

    Directory of Open Access Journals (Sweden)

    Tanaka Gabriela D

    2012-01-01

    Full Text Available Abstract Background The genus Micrurus, coral snakes (Serpentes, Elapidae, comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process.

  12. Functional analysis of Ficolin-3 mediated complement activation

    DEFF Research Database (Denmark)

    Hein, Estrid; Honoré, Christian; Skjoedt, Mikkel-Ole

    2010-01-01

    The recognition molecules of the lectin complement pathway are mannose-binding lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to be associated with life threatening infections. Thus, we aimed to develop a functional method based on the ELISA platform for evaluating...... on acBSA were dependent only on Ficolin-3 in appropriate serum dilutions. Deposition of down stream complement components correlated highly significantly with the serum concentration of Ficolin-3 but not with Ficolin-2 in healthy donors. To make the assay robust for clinical use a chemical compound...... the possibility to diagnose functional and genetic defects of Ficolin-3 and down stream components in the lectin complement pathway....

  13. Complement monitoring of Pluronic 127 gel and micelles

    DEFF Research Database (Denmark)

    Hamad, Islam; Hunter, A Christy; Moghimi, Seyed Moien

    2013-01-01

    Poloxamer 407 is a non-ionic polyethylene oxide (PEO)/polypropylene oxide (PPO) block copolymer, which exhibits reversible thermogelation properties. Poloxamer gel has attracted many applications for controlled release of therapeutic agents as well as in surgical interventions such as controlled...... vascular occlusion. We show that poloxamer gel can trigger the complement system, which is an integral part of innate immunity and its inadvertent activation can induce clinically significant anaphylaxis. Complement activation by the poloxamer gel is through the alternative pathway, but material...... transformations from gel to the solution state further incite complement through calcium-sensitive pathways, where a role for C1q and antibodies has been eliminated. Poloxamer addition to plasma/serum (at levels above its critical micelle concentration, cmc) induced formation of large and diffused structures...

  14. Structural basis for simvastatin competitive antagonism of complement receptor 3

    DEFF Research Database (Denmark)

    Jensen, Maria Risager; Bajic, Goran; Zhang, Xianwei;

    2016-01-01

    The complement system is an important part of the innate immune response to infection, but may also cause severe complications during inflammation. Small molecule antagonists to complement receptor (CR)3 have been widely sought, but a structural basis for their mode of action is not available. We...... report here on the structure of the human CR3 ligand-binding I domain in complex with simvastatin. Simvastatin targets the metal ion-dependent adhesion site of the open, ligand-binding conformation of the CR3 I domain by direct contact with the chelated Mg2+ ion. Simvastatin antagonizes I domain binding...... to the complement fragments iC3b and C3d, but not to intercellular adhesion molecule-1. By virtue of the I domain's wide distribution in binding kinetics to ligands, it was possible to identify ligand binding kinetics as discriminator for simvastatin antagonism. In static cellular experiments, 15-25 μM simvastatin...

  15. Dual-Color Click Beetle Luciferase Heteroprotein Fragment Complementation Assays

    Science.gov (United States)

    Villalobos, Victor; Naik, Snehal; Bruinsma, Monique; Dothager, Robin S.; Pan, Mei-Hsiu; Samrakandi, Mustapha; Moss, Britney; Elhammali, Adnan; Piwnica-Worms, David

    2010-01-01

    Summary Understanding the functional complexity of protein interactions requires mapping biomolecular complexes within the cellular environment over biologically-relevant time scales. Herein we describe a novel set of reversible, multicolored heteroprotein complementation fragments based on various firefly and click beetle luciferases that utilize the same substrate, D-luciferin. Luciferase heteroprotein fragment complementation systems enabled dual-color quantification of two discreet pairs of interacting proteins simultaneously or two distinct proteins interacting with a third shared protein in live cells. Using real-time analysis of click beetle green and click beetle red luciferase heteroprotein fragment complementation applied to β-TrCP, an E3-ligase common to the regulation of both β-catenin and IκBα, GSK3β was identified as a novel candidate kinase regulating IκBα processing. These dual-color protein interaction switches may enable directed dynamic analysis of a variety of protein interactions in living cells. PMID:20851351

  16. Progress in Parallel Schur Complement Preconditioning for Computational Fluid Dynamics

    Science.gov (United States)

    Barth, Timothy J.; Chan, Tony F.; Tang, Wei-Pai; Chancellor, Marisa K. (Technical Monitor)

    1997-01-01

    We consider preconditioning methods for nonself-adjoint advective-diffusive systems based on a non-overlapping Schur complement procedure for arbitrary triangulated domains. The ultimate goal of this research is to develop scalable preconditioning algorithms for fluid flow discretizations on parallel computing architectures. In our implementation of the Schur complement preconditioning technique, the triangulation is first partitioned into a number of subdomains using the METIS multi-level k-way partitioning code. This partitioning induces a natural 2X2 partitioning of the p.d.e. discretization matrix. By considering various inverse approximations of the 2X2 system, we have developed a family of robust preconditioning techniques. A computer code based on these ideas has been developed and tested on the IBM SP2 and the SGI Power Challenge array using MPI message passing protocol. A number of example CFD calculations will be presented to illustrate and assess various Schur complement approximations.

  17. Role of complement in IgA nephropathy.

    Science.gov (United States)

    Daha, Mohamed R; van Kooten, Cees

    2016-02-01

    Immunoglobulin A nephropathy (IgAN) is characterized by the deposition of IgA in the mesangium of glomeruli. This mesangial IgA has been found to consist mainly of polymeric IgA1 which drives the activation of the mesangial cells and results in excessive production of several inflammatory mediators. The activation of mesangial cells is amplified by the ability of IgA to activate the complement system, originally thought to occur mainly via the alternative pathway of complement. However more recent studies indicate that lectin pathway involvement has a strong association with progression of renal disease. In this review we summarize the contribution of complement to the IgA- mediated inflammatory process.

  18. Adaptive Augmenting Control Flight Characterization Experiment on an F/A-18

    Science.gov (United States)

    VanZwieten, Tannen S.; Orr, Jeb S.; Wall, John H.; Gilligan, Eric T.

    2014-01-01

    This paper summarizes the Adaptive Augmenting Control (AAC) flight characterization experiments performed using an F/A-18 (TN 853). AAC was designed and developed specifically for launch vehicles, and is currently part of the baseline autopilot design for NASA's Space Launch System (SLS). The scope covered here includes a brief overview of the algorithm (covered in more detail elsewhere), motivation and benefits of flight testing, top-level SLS flight test objectives, applicability of the F/A-18 as a platform for testing a launch vehicle control design, test cases designed to fully vet the AAC algorithm, flight test results, and conclusions regarding the functionality of AAC. The AAC algorithm developed at Marshall Space Flight Center is a forward loop gain multiplicative adaptive algorithm that modifies the total attitude control system gain in response to sensed model errors or undesirable parasitic mode resonances. The AAC algorithm provides the capability to improve or decrease performance by balancing attitude tracking with the mitigation of parasitic dynamics, such as control-structure interaction or servo-actuator limit cycles. In the case of the latter, if unmodeled or mismodeled parasitic dynamics are present that would otherwise result in a closed-loop instability or near instability, the adaptive controller decreases the total loop gain to reduce the interaction between these dynamics and the controller. This is in contrast to traditional adaptive control logic, which focuses on improving performance by increasing gain. The computationally simple AAC attitude control algorithm has stability properties that are reconcilable in the context of classical frequency-domain criteria (i.e., gain and phase margin). The algorithm assumes that the baseline attitude control design is well-tuned for a nominal trajectory and is designed to adapt only when necessary. Furthermore, the adaptation is attracted to the nominal design and adapts only on an as-needed basis

  19. An Experimental Study on a Microclimatic Layer of a Bionic Fa(c)ade Inspired by Vertical Greenery

    Institute of Scientific and Technical Information of China (English)

    Toma(z) (S)uklje; Sa(s)o Medved; Ciril Arkar

    2013-01-01

    A microclimatic layer of the green fa(c)ade is proven to have specific temperature and flow conditions on the building envelope.Lower temperatures and wind velocities,and higher relative humidity in the microclimatic layer are the characteristics of vertical greenery systems,which cause lower energy consumption for the cooling and heating of buildings.Despite innovative architectural solutions,there are some drawbacks to applying vertical greenery on building envelopes.In this study,a bionic fa(c)ade that mimics the positive effects and eliminates the disadvantages of green fa(c)ades is presented.The bionic fa(c)ade consists of bionic leaves,which are made of photovoltaic cells and evaporative matrices.A real scale experiment was carried out in the summer to evaluate the potential of the cooling efficiency of the microclimatic layer and a new photovoltaic cooling technique.The results show a good agreement of the thermal performance between the bionic and the green fa(c)ade and up to 20.8 K lower surface temperatures of photovoltaic cells,which increase the daily electricity yield by 6.6%.

  20. Interspecific hybridization does not affect the level of fluctuating asymmetry (FA) in the Drosophila bipectinata species complex.

    Science.gov (United States)

    Banerjee, Parul; Singh, B N

    2015-08-01

    The Drosophila bipectinata species complex comprises of four very closely related species namely D. bipectinata, D. parabipectinata, D. malerkotliana and D. pseudoananassae. It was found that irrespective of the evolutionary divergence among the species, FA which is reflective of the developmental precision remains nearly same in four species. During the present study, the level of FA in different morphological traits was studied in interspecific hybrids and compared with that of parental species with the view that it would throw light on the degree of divergence between the parental species. If they have not diverged much, the interspecific hybrids may have a similar FA level, incompatibilities between their genomes being negligible. On the other hand, if there is substantial divergence, the level of FA may be higher due to incompatibility between the genomes of the parental species. The morphological traits taken were sternopleural bristle number and wing length in both males and females and ovariole number and sex-comb tooth number in females and males respectively. However, except in a few cases, we could not detect any significant differences in the level of FA in hybrids as compared to pure species. On the other hand, a number of abnormalities like poor viability, dystrophied ovaries, asymmetrical eyes etc., could be detected in hybrids from crosses involving D. pseudoananassae as one of the parents. Therefore, we conclude that specific developmental pathways are more susceptible to developmental disturbances due to genomic incompatibilities than the large complex system bringing about developmental stability.