Regulation of human lung fibroblast C1q-receptors by transforming growth factor-beta and tumor necrosis factor-alpha.

Science.gov (United States)

Lurton, J; Soto, H; Narayanan, A S; Raghu, G

1999-03-01

Transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) are two polypeptide mediators which are believed to play a role in the evolution of idiopathic pulmonary fibrosis (IPF). We have evaluated the effect of these two substances on the expression of receptors for collagen (cC1q-R) and globular (gC1q-R) domains of C1q and on type I collagen in human lung fibroblasts. Two fibroblast subpopulations differing in C1q receptor expression were obtained by culturing human lung explants in medium containing fresh human serum and heated plasma-derived serum and separating them based on C1q binding [Narayanan, Lurton and Raghu: Am J Resp Cell Mol Biol. 1998; 17:84]. The cells, referred to as HH and NL cells, respectively, were exposed to TGF-beta and TNF-alpha in serum-free conditions. The levels of mRNA were assessed by in situ hybridization and Northern analysis, and protein levels compared after SDS-polyacrylamide gel electrophoresis and Western blotting. NL cells exposed to TGF-beta and TNF-alpha contained 1.4 and 1.6 times as much cC1q-R mRNA, respectively, whereas in HH cells cC1q-R mRNA increased 2.0- and 2.4-fold. The gC1q-R mRNA levels increased to a lesser extent in both cells. These increases were not reflected in protein levels of CC1q-R and gC1q-R, which were similar to or less than controls. Both TGF-beta and TNF-alpha also increased procollagen [I] mRNA levels in both cells. Overall, TNF-alpha caused a greater increase and the degree of response by HH fibroblasts to both TGF-beta and TNF-alpha was higher than NL cells. These results indicated that TGF-beta and TNF-alpha upregulate the mRNA levels for cC1q-R and collagen and that they do not affect gC1q-R mRNA levels significantly. They also indicated different subsets of human lung fibroblasts respond differently to inflammatory mediators.

Direct interaction between CD91 and C1q

DEFF Research Database (Denmark)

Duus, Karen; Hansen, Erik W; Tacnet, Pascale

2010-01-01

. C1q binding to monocytes was shown to be correlated with CD91 expression and could be inhibited by the CD91 chaperone, receptor-associated protein. We also report data showing a direct interaction between CD91 and C1q. The interaction was investigated using various protein interaction assays....... A direct interaction between purified C1q and CD91 was observed both by ELISA and a surface plasmon resonance assay, with either C1q or CD91 immobilized. The interaction showed characteristics of specificity because it was time-dependent, saturable and could be inhibited by known ligands of both CD91 and C...

Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

Science.gov (United States)

Schaefer, S M; Süsal, C; Opelz, G; Döhler, B; Becker, L E; Klein, K; Sickmüller, S; Waldherr, R; Macher-Goeppinger, S; Schemmer, P; Beimler, J; Zeier, M; Morath, C

2016-02-01

Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Analysis of healthy cohorts for single nucleotide polymorphisms in C1q gene cluster

Directory of Open Access Journals (Sweden)

MARIA A. RADANOVA

2015-12-01

Full Text Available C1q is the first component of the classical pathway of complement activation. The coding region for C1q is localized on chromosome 1p34.1–36.3. Mutations or single nucleotide polymorphisms (SNPs in C1q gene cluster can cause developing of Systemic lupus erythematosus (SLE because of C1q deficiency or other unknown reason. We selected five SNPs located in 7.121 kbp region on chromosome 1, which were previously associated with SLE and/or low C1q level, but not causing C1q deficiency and analyzed them in terms of allele frequencies and genotype distribution in comparison with Hispanic, Asian, African and other Caucasian cohorts. These SNPs were: rs587585, rs292001, rs172378, rs294179 and rs631090. One hundred eighty five healthy Bulgarian volunteers were genotyped for the selected five C1q SNPs by quantative real-time PCR methods. International HapMap Project has been used for information about genotype distribution and allele frequencies of the five SNPs in, Hispanics, Asians, Africans and others Caucasian cohorts. Bulgarian healthy volunteers and another pooled Caucasian cohort had similar frequencies of genotypes and alleles of rs587585, rs292001, rs294179 and rs631090 SNPs. Nevertheless, genotype AA of rs172378 was significantly overrepresented in Bulgarians when compared to other healthy Caucasians from USA and UK (60% vs 31%. Genotype distribution of rs172378 in Bulgarians was similar to Greek-Cyriot Caucasians. For all Caucasians the major allele of rs172378 was A. This is the first study analyzing the allele frequencies and genotype distribution of C1q gene cluster SNPs in Bulgarian healthy population.

Anti-C1q antibodies in systemic lupus erythematosus

DEFF Research Database (Denmark)

Orbai, A-M; Truedsson, L; Sturfelt, G

2015-01-01

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information...... in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis....

Autoantibodies against C1q in systemic lupus erythematosus are antigen-driven

DEFF Research Database (Denmark)

Schaller, Monica; Bigler, Cornelia; Danner, Doris

2009-01-01

response against C1q at the molecular level, we screened a bone marrow-derived IgGkappa/IgGlambda Fab phage display library from a SLE patient with high anti-C1q Ab titer against purified human C1q. Six Fabs that exhibited strong binding to C1q in ELISA were isolated. The anti-C1q Fabs recognized...... neoepitopes that were only exposed on bound C1q and not present on soluble C1q mapping to different regions of the collagen-like region of C1q. Analysis of the genes encoding the variable H and L chains of the IgG-derived anti-C1q Fab revealed that all the variable H and L chain regions were highly mutated......, with nucleotide and amino acid homologies to the closest germline in the range of 71-97% (average 85 +/- 4) and 72-92% (average 88 +/- 6), respectively. In addition, the variable region of the Fabs exhibited high replacement to silent ratios. The six anti-C1q Fabs were shown to be of high affinity, with a K...

C1q Nephropathy: The Unique Underrecognized Pathological Entity

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Joe Devasahayam

2015-01-01

Full Text Available C1q nephropathy is a rare glomerular disease with characteristic mesangial C1q deposition noted on immunofluorescence microscopy. It is histologically defined and poorly understood. Light microscopic features are heterogeneous and comprise minimal change disease (MCD, focal segmental glomerulosclerosis (FSGS, and proliferative glomerulonephritis. Clinical presentation is also diverse, and ranges from asymptomatic hematuria or proteinuria to frank nephritic or nephrotic syndrome in both children and adults. Hypertension and renal insufficiency at the time of diagnosis are common findings. Optimal treatment is not clear and is usually guided by the underlying light microscopic lesion. Corticosteroids are the mainstay of treatment, with immunosuppressive agents reserved for steroid resistant cases. The presence of nephrotic syndrome and FSGS appear to predict adverse outcomes as opposed to favorable outcomes in those with MCD. Further research is needed to establish C1q nephropathy as a universally recognized distinct clinical entity. In this paper, we discuss the current understanding of pathogenesis, histopathology, clinical features, therapeutic options, and outcomes of C1q nephropathy.

Complement protein C1q induces maturation of human dendritic cells

DEFF Research Database (Denmark)

Csomor, Eszter; Bajtay, Zsuzsa; Sándor, Noémi

2007-01-01

Maturation of dendritic cells (DCs) is known to be induced by several stimuli, including microbial products, inflammatory cytokines and immobilized IgG, as demonstrated recently. Since immune complexes formed in vivo also contain C1q, moreover apoptotic cells and several pathogens fix C1q...... activity of the cells was assessed by measuring cytokine secretion and their ability to activate allogeneic T lymphocytes. Cytokine production by T cells co-cultured with C1q-matured DCs was also investigated. C1q, but not the structurally related mannose-binding lectin was found to bind to imMDC in a dose......-dependent manner and induced NF-kappaB translocation to the nucleus. Immobilized C1q induced maturation of MDCs and enhanced secretion of IL-12 and TNF-alpha, moreover, elevated their T-cell stimulating capacity. As IFN-gamma levels were increased in supernatants of MDC-T cell co-cultures, our data suggest that C1...

Modular organization of proteins containing C1q-like globular domain.

Science.gov (United States)

Kishore, U; Reid, K B

1999-05-01

The first step in the activation of the classical pathway of complement cascade by immune complexes involves the binding of the six globular heads of C1q to the Fc regions of immunoglobulin G (IgG) or immunoglobulin M (IgM). The globular heads of C1q are located C-terminal to the six triple-helical stalks present in the molecule, each head is considered to be composed of the C-terminal halves (3 x 135 residues) of one A-, one B- and one C-chain. It is not known if the C-terminal globular regions, present in each of the three types of chains, are independently folded modules (with each chain having distinct binding properties towards immunoglobulins) or whether the different binding functions of C1q are dependent upon a globular structure which relies on contributions from all three chains. Recent reports of recombinant production and characterisation of soluble globular head regions of all the three chains indicate that the globular regions of C1q may adopt a modular organization, i.e., each globular head of C1q may be composed of three, structurally and functionally, independent domains, thus retaining multivalency in the form of a heterotrimer. Modules of the same type as the C1q C-terminal module are also found in a variety of noncomplement proteins that include the C-terminal regions of the human type VIII and type X collagens, precerebellin, the chipmunk hibernation proteins, the human endothelial cell protein, multimerin, the serum protein, Acrp-30 which is secreted from mouse adipocytes, and the sunfish inner-ear specific structural protein. The C1q molecule is the only one of these proteins for which, to date, a function has been ascribed to the module. The existence of a shared structural region between C1q and certain collagens may suggest an evolutionarily common ancestral precursor. Various structural and biochemical data suggest that these modules may be responsible for multimerisation through patches of aromatic residues within them.

Anti-C1q autoantibodies in patients with neuromyelitis optica spectrum disorders.

Science.gov (United States)

Yoshikura, Nobuaki; Kimura, Akio; Hayashi, Yuichi; Inuzuka, Takashi

2017-09-15

We examined anti-complement C1q (C1q) autoantibody levels in serum and cerebrospinal fluid (CSF) samples of patients with neuromyelitis optica spectrum disorders (NMOSD). We analyzed the correlations between anti-C1q autoantibody levels and the clinical and other CSF characteristics of NMOSD. Serum and CSF anti-C1q autoantibody levels increased during the acute phase of NMOSD, reverting to the same levels as controls during remission. CSF anti-C1q autoantibody levels during the acute phase correlated with several markers reflecting disease severity, Expanded Disability Status Scale worsening, spinal cord lesion length in cases with myelitis, CSF protein and interleukin-6 levels, and CSF/serum albumin ratios. Copyright © 2017 Elsevier B.V. All rights reserved.

C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome

Energy Technology Data Exchange (ETDEWEB)

Konen, Osnat; Armstrong, Derek; Padfield, Nancy; Blaser, Susan [Hospital for Sick Children, Diagnostic Imaging, Toronto (Canada); Clarke, Howard [Hospital for Sick Children, Plastic Surgery, Toronto (Canada); Weksberg, Rosanna [Hospital for Sick Children, Clinical and Metabolic Genetics, Toronto (Canada)

2008-07-15

Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS. (orig.)

C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome

International Nuclear Information System (INIS)

Konen, Osnat; Armstrong, Derek; Padfield, Nancy; Blaser, Susan; Clarke, Howard; Weksberg, Rosanna

2008-01-01

Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS. (orig.)

Human and pneumococcal cell surface glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins are both ligands of human C1q protein.

Science.gov (United States)

Terrasse, Rémi; Tacnet-Delorme, Pascale; Moriscot, Christine; Pérard, Julien; Schoehn, Guy; Vernet, Thierry; Thielens, Nicole M; Di Guilmi, Anne Marie; Frachet, Philippe

2012-12-14

C1q, a key component of the classical complement pathway, is a major player in the response to microbial infection and has been shown to detect noxious altered-self substances such as apoptotic cells. In this work, using complementary experimental approaches, we identified the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a C1q partner when exposed at the surface of human pathogenic bacteria Streptococcus pneumoniae and human apoptotic cells. The membrane-associated GAPDH on HeLa cells bound the globular regions of C1q as demonstrated by pulldown and cell surface co-localization experiments. Pneumococcal strains deficient in surface-exposed GAPDH harbored a decreased level of C1q recognition when compared with the wild-type strains. Both recombinant human and pneumococcal GAPDHs interacted avidly with C1q as measured by surface plasmon resonance experiments (K(D) = 0.34-2.17 nm). In addition, GAPDH-C1q complexes were observed by transmission electron microscopy after cross-linking. The purified pneumococcal GAPDH protein activated C1 in an in vitro assay unlike the human form. Deposition of C1q, C3b, and C4b from human serum at the surface of pneumococcal cells was dependent on the presence of surface-exposed GAPDH. This ability of C1q to sense both human and bacterial GAPDHs sheds new insights on the role of this important defense collagen molecule in modulating the immune response.

Human and Pneumococcal Cell Surface Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Proteins Are Both Ligands of Human C1q Protein*

Science.gov (United States)

Terrasse, Rémi; Tacnet-Delorme, Pascale; Moriscot, Christine; Pérard, Julien; Schoehn, Guy; Vernet, Thierry; Thielens, Nicole M.; Di Guilmi, Anne Marie; Frachet, Philippe

2012-01-01

C1q, a key component of the classical complement pathway, is a major player in the response to microbial infection and has been shown to detect noxious altered-self substances such as apoptotic cells. In this work, using complementary experimental approaches, we identified the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a C1q partner when exposed at the surface of human pathogenic bacteria Streptococcus pneumoniae and human apoptotic cells. The membrane-associated GAPDH on HeLa cells bound the globular regions of C1q as demonstrated by pulldown and cell surface co-localization experiments. Pneumococcal strains deficient in surface-exposed GAPDH harbored a decreased level of C1q recognition when compared with the wild-type strains. Both recombinant human and pneumococcal GAPDHs interacted avidly with C1q as measured by surface plasmon resonance experiments (KD = 0.34–2.17 nm). In addition, GAPDH-C1q complexes were observed by transmission electron microscopy after cross-linking. The purified pneumococcal GAPDH protein activated C1 in an in vitro assay unlike the human form. Deposition of C1q, C3b, and C4b from human serum at the surface of pneumococcal cells was dependent on the presence of surface-exposed GAPDH. This ability of C1q to sense both human and bacterial GAPDHs sheds new insights on the role of this important defense collagen molecule in modulating the immune response. PMID:23086952

Prevalence and clinical significance of anti-C1q antibodies in ...

African Journals Online (AJOL)

Asmaa Hegazy

2012-04-21

Apr 21, 2012 ... sists of 20 patients with musculoskeletal manifestations, mainly arthritis ... C1q have been found in many different autoimmune diseases, ... improve our diagnostic potential, from these, anti-C1q anti- ... Subjects and methods.

Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: complement component C1q and Prnp polymorphisms

Science.gov (United States)

Blanchong, Julie A.; Heisey, Dennis M.; Scribner, Kim T.; Libants, Scot V.; Johnson, Chad; Aiken, Judd M.; Langenberg, Julia A.; Samuel, Michael D.

2009-01-01

The genetic basis of susceptibility to chronic wasting disease (CWD) in free-ranging cervids is of great interest. Association studies of disease susceptibility in free-ranging populations, however, face considerable challenges including: the need for large sample sizes when disease is rare, animals of unknown pedigree create a risk of spurious results due to population admixture, and the inability to control disease exposure or dose. We used an innovative matched case–control design and conditional logistic regression to evaluate associations between polymorphisms of complement C1q and prion protein (Prnp) genes and CWD infection in white-tailed deer from the CWD endemic area in south-central Wisconsin. To reduce problems due to admixture or disease-risk confounding, we used neutral genetic (microsatellite) data to identify closely related CWD-positive (n = 68) and CWD-negative (n = 91) female deer to serve as matched cases and controls. Cases and controls were also matched on factors (sex, location, age) previously demonstrated to affect CWD infection risk. For Prnp, deer with at least one Serine (S) at amino acid 96 were significantly less likely to be CWD-positive relative to deer homozygous for Glycine (G). This is the first characterization of genes associated with the complement system in white-tailed deer. No tests for association between any C1q polymorphism and CWD infection were significant at p of CWD infection in deer with at least one Glycine (G) at amino acid 56 of the C1qC gene. While we documented numerous amino acid polymorphisms in C1q genes none appear to be strongly associated with CWD susceptibility.

The C1q family of proteins: insights into the emerging non-traditional functions

Directory of Open Access Journals (Sweden)

Berhane eGhebrehiwet

2012-04-01

Full Text Available Research conducted over the past 20 years have helped us unravel not only the hidden structural and functional subtleties of human C1q, but also has catapulted the molecule from a mere recognition unit of the classical pathway to a well-recognized molecular sensor of damage modified self or non-self antigens. Thus, C1q is involved in a rapidly expanding list of pathological disorders—including autoimmunity, trophoblast migration, preeclampsia and cancer. The results of two recent reports are provided to underscore the critical role C1q plays in health and disease. First is the observation by Singh and colleagues showing that pregnant C1q-/- mice recapitulate the key features of human preeclampsia that correlate with increased fetal death. Treatment of the C1q-/- mice with pravastatin restored trophoblast invasiveness, placental blood flow, and angiogenic balance and, thus, prevented the onset of preeclampsia. Second is the report by Hong et al., which showed that C1q can induce apoptosis of prostate cancer cells by activating the tumor suppressor molecule WW-domain containing oxydoreductase (WWOX or WOX1 and destabilizing cell adhesion. Downregulation of C1q on the other hand enhanced prostate hyperplasia and cancer formation due to failure of WOX1 activation. Recent evidence also shows that C1q belongs to a family of structurally and functionally related TNFα-like family of proteins that may have arisen from a common ancestral gene. Therefore C1q not only shares the diverse functions with the TNF family of proteins, but also explains why C1q has retained some of its ancestral cytokine-like activities. This review is intended to highlight some of the structural and functional aspects of C1q by underscoring the growing list of its non-traditional functions.

Identification of expressed genes in cDNA library of hemocytes from the RLO-challenged oyster, Crassostrea ariakensis Gould with special functional implication of three complement-related fragments (CaC1q1, CaC1q2 and CaC3).

Science.gov (United States)

Xu, Ting; Xie, Jiasong; Li, Jianming; Luo, Ming; Ye, Shigen; Wu, Xinzhong

2012-06-01

A SMARTer™ cDNA library of hemocyte from Rickettsia-like organism (RLO) challenged oyster, Crassostrea ariakensis Gould was constructed. Random clones (400) were selected and single-pass sequenced, resulted in 200 unique sequences containing 96 known genes and 104 unknown genes. The 96 known genes were categorized into 11 groups based on their biological process. Furthermore, we identified and characterized three complement-related fragments (CaC1q1, CaC1q2 and CaC3). Tissue distribution analysis revealed that all of three fragments were ubiquitously expressed in all tissues studied including hemocyte, gills, mantle, digestive glands, gonads and adductor muscle, while the highest level was seen in the hemocyte. Temporal expression profile in the hemocyte monolayers reveled that the mRNA expression levels of three fragments presented huge increase after the RLO incubation at 3 h and 6 h in post-challenge, respectively. And the maximal expression levels at 3 h in post-challenge are about 256, 104 and 64 times higher than the values detected in the control of CaC1q1, CaC1q2 and CaC3, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Enhanced Ig production by human peripheral lymphocytes induced by aggregated C1q

NARCIS (Netherlands)

Daha, M. R.; Klar, N.; Hoekzema, R.; van Es, L. A.

1990-01-01

Because B cells express receptors for C1q, we have investigated the role of C1q in the stimulation of B cells. When B cells were cultured in the presence of C1q that had been frozen, T cells, and suboptimal concentrations of PWM, there was a dose-dependent enhancement of IgM, IgG, and IgA by the B

C anti c q anti q states

Energy Technology Data Exchange (ETDEWEB)

Chao, K T [Oxford Univ. (UK). Dept. of Theoretical Physics; Science Research Council, Chilton (UK). Rutherford and Appleton Labs.)

1980-07-01

Taking account of the colour magnetic and electric forces, we discuss the spectroscopy of various types of c anti c q anti q states. Their decay, hadronic production, production in e/sup +/e/sup -/ annihilation as well as photoproduction are also studied.

Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency

DEFF Research Database (Denmark)

van Schaarenburg, Rosanne A; Schejbel, Lone; Truedsson, Lennart

2015-01-01

OBJECTIVE: Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can...

Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19

DEFF Research Database (Denmark)

Thiel, S; Petersen, Steen Vang; Vorup-Jensen, T

2000-01-01

. There is controversy as to whether MBL can utilize C1r and C1s or, inversely, whether C1q can utilize MASP-1 and 2. Serum deficient in C1r produced no complement activation in IgG-coated microwells, whereas activation was seen in mannan-coated microwells. In serum, C1r and C1s were found to be associated only with C1q...

Dark matter gravitinos and baryons via Q-ball decay in the gauge-mediated MSSM

International Nuclear Information System (INIS)

Doddato, Francesca; McDonald, John

2013-01-01

We show that late Q-ball decay in the MSSM with gauge-mediated SUSY breaking can provide a natural source of non-thermal NLSPs which subsequently decay to gravitino dark matter without violating nucleosynthesis constraints. To show this, we perform a global analysis of Q-ball formation and decay in Affleck-Dine baryogenesis for a d = 6 (u c d c d c ) 2 flat direction of the gauge-mediated MSSM. A general phenomenological potential for the flat-direction is studied and the Q-ball decay properties are obtained as a function of its parameters. The corresponding gravitino mass necessary to account for dark matter is then determined for the case of stau NLSPs. The decay temperature depends on the charge of the Q-balls, which is determined by the fragmentation of the AD condensate. Different fragmentation scenarios are considered, and the final non-thermal NLSP density from Q-ball decay and NLSP annihilation is determined. Particular care is taken to establish that NLSPs from Q-ball decay become homogeneous and non-relativistic prior to annihilation. The gravitino mass necessary for dark matter is naturally consistent with the theoretical gravitino mass in the gauge-mediation model

A microplate adaptation of the solid-phase C1q immune complex assay

International Nuclear Information System (INIS)

Hunt, J.S.; Kennedy, M.P.; Barber, K.E.; McGiven, A.R.

1980-01-01

A method has been developed for the detection of C1q binding immune complexes in serum in which microculture plates are used as the solid-phase matrix for adsorption of C1q. This micromethod used only one-tenth of the amount of both C1q and [ 125 I]antihuman immunoglobulin per test and enabled 7 times as many samples to be tested in triplicate in comparison with the number performed in duplicate by the standard tube assay. (Auth.)

Dark matter gravitinos and baryons via Q-ball decay in the gauge-mediated MSSM

Energy Technology Data Exchange (ETDEWEB)

Doddato, Francesca; McDonald, John, E-mail: f.doddato@lancaster.ac.uk, E-mail: j.mcdonald@lancaster.ac.uk [Lancaster-Manchester-Sheffield Consortium for Fundamental Physics, Cosmology and Astroparticle Physics Group, Dept. of Physics, University of Lancaster, Lancaster LA1 4YB (United Kingdom)

2013-07-01

We show that late Q-ball decay in the MSSM with gauge-mediated SUSY breaking can provide a natural source of non-thermal NLSPs which subsequently decay to gravitino dark matter without violating nucleosynthesis constraints. To show this, we perform a global analysis of Q-ball formation and decay in Affleck-Dine baryogenesis for a d = 6 (u{sup c}d{sup c}d{sup c}){sup 2} flat direction of the gauge-mediated MSSM. A general phenomenological potential for the flat-direction is studied and the Q-ball decay properties are obtained as a function of its parameters. The corresponding gravitino mass necessary to account for dark matter is then determined for the case of stau NLSPs. The decay temperature depends on the charge of the Q-balls, which is determined by the fragmentation of the AD condensate. Different fragmentation scenarios are considered, and the final non-thermal NLSP density from Q-ball decay and NLSP annihilation is determined. Particular care is taken to establish that NLSPs from Q-ball decay become homogeneous and non-relativistic prior to annihilation. The gravitino mass necessary for dark matter is naturally consistent with the theoretical gravitino mass in the gauge-mediation model.

Complement and alcoholic liver disease: role of C1q in the pathogenesis of ethanol-induced liver injury in mice.

Science.gov (United States)

Cohen, Jessica I; Roychowdhury, Sanjoy; McMullen, Megan R; Stavitsky, Abram B; Nagy, Laura E

2010-08-01

Complement is involved in the development of alcoholic liver disease in mice; however, the mechanisms for complement activation during ethanol exposure have not been identified. C1q, the recognition subunit of the first complement component, binds to apoptotic cells, thereby activating the classical complement pathway. Because ethanol exposure increases hepatocellular apoptosis, we hypothesized that ethanol-induced apoptosis would lead to activation of complement via the classical pathway. Wild-type and C1qa-/- mice were allowed free access to ethanol-containing diets or pair-fed control diets for 4 or 25 days. Ethanol feeding for 4 days increased apoptosis of Kupffer cells in both wild-type and C1qa-/- mice. Ethanol-induced deposition of C1q and C3b/iC3b/C3c was colocalized with apoptotic Kupffer cells in wild-type, but not C1qa-/-, mice. Furthermore, ethanol-induced increases in tumor necrosis factor-alpha and interleukin-6 expression at this early time point were suppressed in C1q-deficient mice. Chronic ethanol feeding (25 days) increased steatosis, hepatocyte apoptosis, and activity of serum alanine and aspartate aminotransferases in wild-type mice. These markers of hepatocyte injury were attenuated in C1qa-/- mice. In contrast, chronic ethanol (25 days)-induced increases in cytochrome P450 2E1 expression and oxidative stress did not differ between wild-type and C1qa-/- mice. For the first time, these data indicate that ethanol activates the classical complement pathway via C1q binding to apoptotic cells in the liver and that C1q contributes to the pathogenesis of ethanol-induced liver injury. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations

DEFF Research Database (Denmark)

Schejbel, L; Skattum, L; Hagelberg, S

2011-01-01

C1q is the central pattern-recognition molecule in the classical pathway of the complement system and is known to have a key role in the crossroads between adaptive and innate immunity. Hereditary C1q deficiency is a rare genetic condition strongly associated with systemic lupus erythematosus...... and increased susceptibility to bacterial infections. However, the clinical symptoms may vary. For long, the molecular basis of C1q deficiency was ascribed to only six different mutations. In the present report, we describe five new patients with C1q deficiency, present the 12 causative mutations described till...... now and review the clinical spectrum of symptoms found in patients with C1q deficiency. With the results presented here, confirmed C1q deficiency is reported in 64 patients from at least 38 families....

Mass spectra for q c q ¯ c ¯, s c s ¯ c ¯, q b q ¯ ¯, s b s ¯ ¯ tetraquark states with JP C=0++ and 2++

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Chen, Wei; Chen, Hua-Xing; Liu, Xiang; Steele, T. G.; Zhu, Shi-Lin

2017-12-01

We have studied the mass spectra of the hidden-charm/bottom q c q ¯c ¯, s c s ¯c ¯ and q b q ¯b ¯, s b s ¯b ¯ tetraquark states with JP C=0++ and 2++ in the framework of QCD sum rules. We construct ten scalar and four tensor interpolating currents in a systematic way and calculate the mass spectra for these tetraquark states. The X*(3860 ) may be either an isoscalar tetraquark state or χc 0(2 P ). If the X*(3860 ) is a tetraquark candidate, our results prefer the 0++ option over the 2++ one. The X (4160 ) may be classified as either the scalar or tensor q c q ¯c ¯ tetraquark state, while the X (3915 ) favors a 0++ q c q ¯c ¯ or s c s ¯c ¯ tetraquark assignment over the tensor one. The X (4350 ) cannot be interpreted as a s c s ¯c ¯ tetraquark with either JP C=0++ or 2++.

Neutron electric form factor up to Q2 = 1.47 GeV/c2

International Nuclear Information System (INIS)

Madey, Richard; Semenov, Andrei; Taylor, S.; Aghalaryan, Aram; Crouse, Erick; MacLachlan, Glen; Plaster, Bradley; Shigeyuki Tajima; William Tireman; Chenyu Yan; Abdellah Ahmidouch; Brian Anderson; Hartmuth Arenhovel; Razmik Asaturyan; Baker, O.; Alan Baldwin; Herbert Breuer; Roger Carlini; Christy, E.; Steve Churchwell; Leon Cole; Areg Danagoulian; Donal Day; Mostafa Elaasar; Rolf Ent; Manouchehr Farkhondeh; Howard Fenker; John Finn; Liping Gan; Kenneth Garrow; Paul Gueye; Calvin Howell; Bitao Hu; Mark Jones; James Kelly; Cynthia Keppel; Mahbubul Khandaker; Wooyoung Kim; Stanley Kowalski; Allison Lung; David Mack; Manley, D.; Pete Markowitz; Joseph Mitchell; Hamlet Mkrtchyan; Allena Opper; Charles Perdrisat; Vina Punjabi; Brian Raue; Tilmann Reichelt; Joerg Reinhold; Julie Roche; Yoshinori Sato; Irina Semenova; Wonick Seo; Neven Simicevic; Smith, G.; Samuel Stepanyan; Vardan Tadevosyan; Liguang Tang; Paul Ulmer; William Vulcan; Watson, J. W.; Steven Wells; Frank Wesselmann; Stephen Wood; Chen Yan; Seunghoon Yang; Lulin Yuan; Wei-Ming Zhang; Hong Guo Zhu; Xiaofeng Zhu

2003-01-01

The ratio of the electric to the magnetic form factor of the neutron, g /equiv G En /G Mn , was measured via recoil polarimetry (R.G. Arnold, C.E. Carlson, F. Gross, Phys. Rev. C 23, 363 (1981)) from the quasielastic 2 H (/mathop(e)/limitse' /mathop(n)/limits) 1H reaction at three values of Q 2 (viz, 0.45, 1.15, and 1.47 (GeV/c) 2 ) in Hall C of the Thomas Jefferson National Accelerator Facility. The data reveal that GEn continues to follow the Galster parameterization up to Q 2 = 1.15 (GeV/c) 2 and rises above the Galster parameterization at Q 2 = 1.47 (GeV/c) 2

Correlation of anti C1Q antibodies with disease activity in patients with systemic lupus erythematosus

International Nuclear Information System (INIS)

Riaz, M.O.; Ahmed, T.A.

2016-01-01

Objective: To study the correlation of anti C1q antibodies with disease activity in patients with systemic lupus erythematosus (SLE). Study Design: Cross sectional, observational study. Place and Duration of study: The Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi in collaboration with Military Hospital, Rawalpindi, Pakistan Institute of Medical Sciences, Islamabad and Benazir Bhutto Hospital, Rawalpindi, from Jan 2012 to Dec 2013. Material and Methods: Patients with a clinical diagnosis of SLE were included in the study on fulfilling revised American College of Rheumatology (ACR) criteria (1997). Main outcome measures were SLE disease activity index (SLEDAI) score and anti C1q antibody levels in serum. SLEDAI scores were calculated for each patient on the basis of physical examination, patient interviews and previous clinical records. Anti C1q antibody levels in the serum were determined by enzyme-linked immunosorbent assay (ELISA) and correlated with the SLEDAI scores by calculating Pearson's correlation coefficient 'r'. The cutoff value for anti C1q antibody positivity in the serum was determined by evaluating the serum levels of anti C1q antibodies in 25 healthy subjects and was 12 U/ml. Results: Six male and forty nine female SLE patients with an age range of 16-47 years (mean 34.5 years) and 8-70 years (mean 31.7 years) respectively were studied. The correlation between anti C1q levels and SLEDAI scores in all patients was demonstrated by calculating the correlation coefficient and was not significant (r=0.19, p=0.14). However, there was an inverse correlation between anti C1q levels and SLEDAI scores in patients with severe disease and this was statistically significant (r=-0.448, p=0.037). The difference in anti C1q antibody positivity between patients with and without nephritis was not significant. The anti C1q antibody levels correlated poorly with anti double stranded deoxyribonucleic acid (dsDNA) antibody positivity. A

Agonist-induced internalisation of the glucagon-like peptide-1 receptor is mediated by the Gαq pathway.

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Thompson, Aiysha; Kanamarlapudi, Venkateswarlu

2015-01-01

The glucagon-like peptide-1 receptor (GLP-1R) is a G-protein-coupled receptor (GPCR) and an important target in the treatment of type 2 diabetes mellitus (T2DM). Upon stimulation with agonist, the GLP-1R signals through both Gαs and Gαq coupled pathways to stimulate insulin secretion. The agonist-induced GLP-1R internalisation has recently been shown to be important for insulin secretion. However, the molecular mechanisms underlying GLP-1R internalisation remain unknown. The aim of this study was to determine the role of GLP-1R downstream signalling pathways in its internalisation. Agonist-induced human GLP-1R (hGLP-1R) internalisation and activity were examined using a number of techniques including immunoblotting, ELISA, immunofluorescence and luciferase assays to determine cAMP production, intracellular Ca(2+) accumulation and ERK phosphorylation. Agonist-induced hGLP-1R internalisation is dependent on caveolin-1 and dynamin. Inhibition of the Gαq pathway but not the Gαs pathway affected hGLP-1R internalisation. Consistent with this, hGLP-1R mutant T149M and small-molecule agonists (compound 2 and compound B), which activate only the Gαs pathway, failed to induce internalisation of the receptor. Chemical inhibitors of the Gαq pathway, PKC and ERK phosphorylation significantly reduced agonist-induced hGLP-1R internalisation. These inhibitors also suppressed agonist-induced ERK1/2 phosphorylation demonstrating that the phosphorylated ERK acts downstream of the Gαq pathway in the hGLP-1R internalisation. In summary, agonist-induced hGLP-1R internalisation is mediated by the Gαq pathway. The internalised hGLP-1R stimulates insulin secretion from pancreatic β-cells, indicating the importance of GLP-1 internalisation for insulin secretion. Copyright © 2014 Elsevier Inc. All rights reserved.

The C1q complement family of synaptic organizers: not just complementary.

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Yuzaki, Michisuke

2017-08-01

Molecules that regulate formation, differentiation, and maintenance of synapses are called synaptic organizers. Recently, various 'C1q family' proteins have been shown to be released from neurons, and serve as a new class of synaptic organizers. Cbln1 and C1ql1 proteins regulate the formation and maintenance of parallel fiber-Purkinje cell and climbing fiber-Purkinje cell synapses, respectively, in the cerebellum. Cbln1 also modulates the function of postsynaptic delta2 glutamate receptors to regulate synaptic plasticity. C1ql2 and C1ql3, released from mossy fibers, determine the synaptic localization of postsynaptic kainate receptors in the hippocampus. C1ql3 also regulates the formation of synapses between the basolateral amygdala and the prefrontal cortex. These findings indicate the diverse functions of C1q family proteins in various brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neisseria meningitidis differentially controls host cell motility through PilC1 and PilC2 components of type IV Pili.

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Philippe C Morand

Full Text Available Neisseria meningitidis is a strictly human pathogen that has two facets since asymptomatic carriage can unpredictably turn into fulminant forms of infection. Meningococcal pathogenesis relies on the ability of the bacteria to break host epithelial or endothelial cellular barriers. Highly restrictive, yet poorly understood, mechanisms allow meningococcal adhesion to cells of only human origin. Adhesion of encapsulated and virulent meningococci to human cells relies on the expression of bacterial type four pili (T4P that trigger intense host cell signalling. Among the components of the meningococcal T4P, the concomitantly expressed PilC1 and PilC2 proteins regulate pili exposure at the bacterial surface, and until now, PilC1 was believed to be specifically responsible for T4P-mediated meningococcal adhesion to human cells. Contrary to previous reports, we show that, like PilC1, the meningococcal PilC2 component is capable of mediating adhesion to human ME180 epithelial cells, with cortical plaque formation and F-actin condensation. However, PilC1 and PilC2 promote different effects on infected cells. Cellular tracking analysis revealed that PilC1-expressing meningococci caused a severe reduction in the motility of infected cells, which was not the case when cells were infected with PilC2-expressing strains. The amount of both total and phosphorylated forms of EGFR was dramatically reduced in cells upon PilC1-mediated infection. In contrast, PilC2-mediated infection did not notably affect the EGFR pathway, and these specificities were shared among unrelated meningococcal strains. These results suggest that meningococci have evolved a highly discriminative tool for differential adhesion in specific microenvironments where different cell types are present. Moreover, the fine-tuning of cellular control through the combined action of two concomitantly expressed, but distinctly regulated, T4P-associated variants of the same molecule (i.e. PilC1 and PilC

Characterization of the honeybee venom proteins C1q-like protein and PVF1 and their allergenic potential

DEFF Research Database (Denmark)

Russkamp, Dennis; Van Vaerenbergh, Matthias; Etzold, Stefanie

2018-01-01

-like protein (C1q) and PDGF/VEGF-like factor 1 (PVF1). C1q and PVF1 were produced as recombinant proteins in insect cells. Their allergenic properties were examined by determining the level of specific IgE antibodies in the sera of HBV-allergic patients (n = 26) as well as by their capacity to activate...... frugiperda insect cells exhibited specific IgE reactivity with approximately 38.5% of sera of HBV-allergic patients. Interestingly, both proteins were unable to activate basophils of the patients, questioning their role in the context of clinically relevant sensitization. Recombinant C1q and PVF1 can build...

Cloning and characterization of the complementary DNA for the B chain of normal human serum C1q.

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Reid, K B; Bentley, D R; Wood, K J

1984-09-06

Normal human C1q is a serum glycoprotein of 460 kDa containing 18 polypeptide chains (6A, 6B, 6C) each 226 amino acids long and each containing an N-terminal collagen-like domain and a C-terminal globular domain. Two unusual forms of C1q have been described: a genetically defective form, which has a molecular mass of approximately 160 kDa and is found in the sera of homozygotes for the defect who show a marked susceptibility to immune complex related disease; a fibroblast form, shown to be synthesized and secreted, in vitro, with a molecular mass of about 800 kDa and with chains approximately 16 kDa greater than those of normal C1q. A higher than normal molecular mass form of C1q has also been described in human colostrum and a form of C1q has been claimed to represent one of the types of Fc receptor on guinea-pig macrophages. To initiate studies, at the genomic level, on these various forms of C1q, and to investigate the possible relation between the C1q genes and the procollagen genes, the complementary DNA corresponding to the B chain of normal C1q has been cloned and characterized.

Solid-phase classical complement activation by C-reactive protein (CRP) is inhibited by fluid-phase CRP-C1q interaction

International Nuclear Information System (INIS)

Sjoewall, Christopher; Wetteroe, Jonas; Bengtsson, Torbjoern; Askendal, Agneta; Almroth, Gunnel; Skogh, Thomas; Tengvall, Pentti

2007-01-01

C-reactive protein (CRP) interacts with phosphorylcholine (PC), Fcγ receptors, complement factor C1q and cell nuclear constituents, yet its biological roles are insufficiently understood. The aim was to characterize CRP-induced complement activation by ellipsometry. PC conjugated with keyhole limpet hemocyanin (PC-KLH) was immobilized to cross-linked fibrinogen. A low-CRP serum with different amounts of added CRP was exposed to the PC-surfaces. The total serum protein deposition was quantified and deposition of IgG, C1q, C3c, C4, factor H, and CRP detected with polyclonal antibodies. The binding of serum CRP to PC-KLH dose-dependently triggered activation of the classical pathway. Unexpectedly, the activation was efficiently down-regulated at CRP levels >150 mg/L. Using radial immunodiffusion, CRP-C1q interaction was observed in serum samples with high CRP concentrations. We propose that the underlying mechanism depends on fluid-phase interaction between C1q and CRP. This might constitute another level of complement regulation, which has implications for systemic lupus erythematosus where CRP is often low despite flare-ups

Effects of Coenzyme Q10 and Vitamin C on Growth Performance and Blood Components in Broiler Chickens under Heat Stress

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Raeisi-Zeydabad S

2017-10-01

Full Text Available This experiment was carried out to study the effects of Coenzyme Q10 (CoQ10 and vitamin C (VC on growth performance and blood biochemistry in broiler chickens under heat stress conditions. One of three levels of CoQ10 (0, 20, and 40 mg/kg of diet and one of two levels of VC (0 and 250 mg/kg of diet were supplemented to diets of chicks (from 1-42 d of age in a 3 × 2 factorial arrangement. Each dietary treatment had four replicate pens (10 chicks/pen. In order to create chronic heat stress, the house temperature was set at an ambient temperature of 35±2°C for 8 hrs daily (09:00 to 17:00 between 25-42 d of age. Feed intake, body weight gain (BWG, and feed to gain ratio (F:G were recorded at d 10, 25 and 42. At the end of experiment, two chicks/pen were randomly selected to assess blood components. CoQ10 supplementation improved BWG and F:G during 11-25 days, 26-42 days, and the whole period of the experiment (P < 0.05, while VC supplementation improved BWG and F:G only during 11-25 d of age. Blood glucose, cholesterol and triglycerides concentrations were reduced (P < 0.05 by addition of CoQ10 to the diet. Both Supplementation of CoQ10 and VC together lowered heterophil (H count but increased lymphocyte (L count, thereby reducing H/L ratio (P < 0.05. Serum concentrations of corticosterone and T4 were positively affected by dietary supplementation of CoQ10 (P < 0.05, but no differences were obtained with addition of VC to the diet. In conclusion, our observations demonstrated that dietary supplementation of 40 mg/kg CoQ10 or 250 mg/kg VC improves the growth performance of broiler chickens under the heat stress.

Unconditionally convergent series in the space C(Q)

International Nuclear Information System (INIS)

Basit, B.

1981-08-01

Let B be a Banach space and B* its dual Banach space. B contains csub(0) (B does not contain csub(0)) if B contains (does not contain) a subspace isomorphic to the space csub(0) of sequences of numbers tending to zero. The series Σsub(n=1)sup(infinity) xsub(n) of elements of B is weakly unconditionally convergent (w.u.c.) iff Σsub(n=1)sup(infinity)|x*(xsub(n))| 0 . Series of elements of C(Q) are considered here. Subspaces of C(Q) isomorphic to c 0 are constructed, and criteria for a series of elements of C(Q) to be w.u.c. or u.c. are given. Finally, an improved theorem of giving characterizations of the elements of subalgebras of C(Q) not containing c 0 is presented

Structure and function of complement protein C1q and its role in the development of autoimmune diseases

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Katarzyna Smykał-Jankowiak

2009-09-01

Full Text Available Complement plays an important role in the immune system. Three different pathways of complement activation are known: the classical, alternative, and lectin dependent. They involve more than 30 serum peptides. C1q is the first subcomponent of the classical pathway of complement activation. It is composed of three types of chains, A, B, and C, which form a molecule containing 18 peptides. Each of the chains has a short amino-terminal region followed by a collagen-like region (playing a role in the activation of C1r2C1s2 and a carboxy-terminal head, which binds to immune complexes. Recent studies have shown a great number of ligands for C1q, including aggregated IgG, IgM, human T-cell lymphotropic virus-I (HTLV-I, gp21 peptide, human immunodeficiency virus-1 (HIV-1 gp21 peptide, β-amyloid, fragments of bacterial walls, apoptotic cells, and many others. However, the role of C1q is not only associated with complement activation. It also helps in the removal of immune complexes and necrotic cells, stimulates the production of some cytokines, and modulates the function of lymphocytes. Complete C1q deficiency is a rare genetic disorder. The C1q gene is located on the short arm of chromosome 1. So far, only a few mutations in C1q gene have been reported. The presence of these mutations is strongly associated with recurrent bacterial infections and the development of systemic lupus erythematosus (SLE. Recent clinical studies point to the significance of anti-C1q antibodies in the diagnosis and assessment of lupus nephritis activity.

Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers.

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Mlynarsky, Liat; Bejarano-Achache, Idit; Muszkat, Mordechai; Caraco, Yoseph

2012-05-01

Warfarin responsiveness is characterized by marked interindividual variability. A major portion of this variability is attributed to CYP2C9 and VKORC1 polymorphisms, but almost 50% is still unaccounted for. This paper reports the first prospective study on the association between factor VII R353Q polymorphism and warfarin responsiveness during induction. Genotyping for factor VII R353Q and 323D/I polymorphisms was performed in a cohort consisting of 374 patients (198 CYP2C9*1/*1) treated with warfarin who were prospectively followed from warfarin initiation. Compared with *1/*1-R/R and *1/*1-R/Q genotype carriers, *1/*1-Q/Q homozygotes achieved higher International Normalized Ratio (INR) values while consuming lower warfarin doses. The greater sensitivity was illustrated by 82.1% higher Warfarin Sensitivity Index During Induction (WSIDI) (0.14 ± 0.11 vs. 0.08 ± 0.50 mg⁻¹ Mann-Whitney, P = 0.043). Multiple regression analysis consisting of both genetic and nongenetic factors explained 26% of WSIDI variability, with R353Q genetic polymorphism having a modest yet significant effect and accounting for 1.7% of the overall variability. Moreover, the incidence of overanticoagulation (i.e., INR > 4) was 6.94-fold higher among *1/*1-Q/Q vs. *1/*1-R/R&R/Q carriers during warfarin induction (Pearson chi-square, P = 0.005). These findings were not accounted for by a chance difference in the distribution of VKORC1 genotypes. Analysis of these parameters among the entire cohort, including CYP2C9*2 and CYP2C9*3 variant allele carriers, did not reach statistical significance. Warfarin responsiveness during induction was unrelated to factor VII 323D/I genetic polymorphism. The response to warfarin during induction is influenced by factor VII R353Q polymorphism. The prospective use of this polymorphism, along with CYP2C9 and VKORC1, may enhance the accuracy of warfarin loading. However, the impact of R353Q polymorphism on overall warfarin response is subtle, and it is therefore

Regulation of Ca2+ influx by a protein kinase C activator in chromaffin cells: differential role of P/Q- and L-type Ca2+ channels.

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Sena, C M; Santos, R M; Boarder, M R; Rosário, L M

1999-02-05

Phorbol esters reduce depolarization-evoked Ca2+ influx in adrenal chromaffin cells, suggesting that voltage-sensitive Ca2+ channels (VSCCs) are inhibited by protein kinase C-mediated phosphorylation. We now address the possibility that L- and P/Q-type Ca2+ channel subtypes might be differentially involved in phorbol ester action. In bovine chromaffin cells, short-term (10 min) incubations with phorbol 12-myristate 13-acetate (PMA) inhibited early high K+-evoked rises in cytosolic free Ca2+ concentration ([Ca2+]i) and the early component of the depolarization-evoked Mn2+ quenching of fura-2 fluorescence in a dose-dependent manner (IC50: 18 and 7 nM; maximal inhibitions: 45 and 48%, respectively). The protein kinase C inhibitor staurosporine (100 nM) reverted the inhibitory action of PMA. PMA (0.1-1 microM) inhibited the early and late phases of the ionomycin (2 microM)-evoked [Ca2+]i transients by 14-23%. Omega-agatoxin IVA, a blocker of P/Q-type Ca2+ channels, inhibited high K+-evoked [Ca2+]i rises in a dose-dependent fashion (IC50 = 50 nM). In contrast, 0.1 microM omega-conotoxin GVIA, a blocker of N-type channels, was without effect. A sizeable (< 45%) component of early Ca2+ influx persisted in the combined presence of omega-agatoxin IVA (100 nM) and nitrendipine (1 microM). Simultaneous exposure to omega-agatoxin IVA and PMA inhibited both the early [Ca2+]i transients and Mn2+ quenching to a much greater extent than each drug separately. Inhibition of the [Ca2+]i transients by nitrendipine and PMA did not significantly exceed that produced by PMA alone. It is concluded that phorbol ester-mediated activation of protein kinase C inhibits preferentially L-type VSCCs over P/Q type channels in adrenal chromaffin cells. However, the possibility cannot be ruled out that dihydropyridine-resistant, non-P/Q type channels might also be negatively regulated by protein kinase C. This may represent an important pathway for the specific control of VSCCs by protein kinase C

New Q-ball solutions in gauge-mediation, Affleck-Dine baryogenesis and gravitino dark matter

International Nuclear Information System (INIS)

Doddato, Francesca; McDonald, John

2012-01-01

Affleck-Dine (AD) baryogenesis along a d = 6 flat direction in gauge-mediated supersymmetry-breaking (GMSB) models can produce unstable Q-balls which naturally have field strength similar to the messenger scale. In this case a new kind of Q-ball is formed, intermediate between the gravity-mediated and gauge-mediated types. We study in detail these new Q-ball solutions, showing how their properties interpolate between standard gravity-mediated and gauge-mediated Q-balls as the AD field becomes larger than the messenger scale. It is shown that E/Q for the Q-balls can be greater than the nucleon mass but less than the MSSM-LSP mass, leading to Q-ball decay primarily to Standard Model fermions. More significantly, if E/Q is greater than the MSSM-LSP mass, decaying Q-balls can provide a natural source of non-thermal MSSM-LSPs, which can subsequently decay to gravitino dark matter without violating nucleosynthesis constraints. The model therefore provides a minimal scenario for baryogenesis and gravitino dark matter in the gauge-mediated MSSM, requiring no new fields

Complex Interaction of Hb Q-Thailand (HBA1: c.223G>C) with β-Thalassemia/Hb E (HBB: c.79G>A) Disease.

Science.gov (United States)

Panyasai, Sitthichai; Satthakarn, Surada; Pornprasert, Sakorn

2018-01-01

Hb Q-Thailand [α74(EF3)Asp→His (α1), GAC>CAC, HBA1: c.223G>C] is an abnormal hemoglobin (Hb) frequently found in Thailand and Southeast Asian countries. The association of the α Q-Thailand allele with other globin gene disorders has important implications in diagnosis. Here, we report how to diagnose the coinheritance of Hb Q-Thailand with β-thalassemia (β-thal)/Hb E disease in four Thai samples from high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) testing results. Understanding of the HPLC chromatogram and CE electropherogram patterns of this complex mutation is important for interpretation of testing results and providing genetic counseling.

ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

Science.gov (United States)

Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

2016-05-01

ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

Effect of calcium ions on structure and stability of the C1q-like domain of otolin-1 from human and zebrafish.

Science.gov (United States)

Hołubowicz, Rafał; Wojtas, Magdalena; Taube, Michał; Kozak, Maciej; Ożyhar, Andrzej; Dobryszycki, Piotr

2017-12-01

Otolin-1 is a collagen-like protein expressed in the inner ear of vertebrates. It provides an organic scaffold for otoliths in fish and otoconia in land vertebrates. In this study, the expression and purification procedure of C1q-like domain of otolin-1 from human and zebrafish was developed. The structure and stability of the proteins were investigated. The results of sedimentation velocity analytical ultracentrifugation and small-angle X-ray scattering indicated that the C1q-like domain of otolin-1 forms stable trimers in solution in the presence of calcium ions. It was also observed that calcium ions influenced the secondary structure of the proteins. C1q-like domains were stabilized by the calcium ions. The human variant was especially affected by the calcium ions. The results indicate the importance of the C1q-like domain for the assembly of the organic matrix of otoliths and otoconia. © 2017 Federation of European Biochemical Societies.

Storage of the complement components C4, C3, and C 3-activator in the human liver as PAS-negative globular hyaline bodies.

Science.gov (United States)

Storch, W; Riedel, H; Trautmann, B; Justus, J; Hiemann, D

1982-01-01

Liver biopsies of a 58-year-old clinically healthy patient with a hepatomegaly and intracisternal PAS-negative globular hyaline bodies were immunofluorescent-optically examined for the content of the complement components C 1 q, C 4, C 9, C 1-inactivator, C 3-activator. Further examinations were performed for fibrinogen, IgG, IgA, IgM, IgD, IgE, L-chain (type chi and lambda), alpha 1-antitrypsin, alpha 1-fetoprotein, alpha 1- and alpha 2-glycoprotein, cholinesterase, ceruloplasmin, myoglobin, hemopexin, HBsAg and HBsAg. Th inclusion bodies reacted with antisera against the complement components C 4, C 3 and C 3-activator, as also identified by double immunofluorescence. Probably this is a disturbance of the protein metabolism of the liver cell with abnormal complement storage in the presence of normal total complement and normal complement components in the serum.

Measurements of the Electric Form Factor of the Neutron at Q2=0.45 and 1.13 (GeV/c)2

International Nuclear Information System (INIS)

Shigeyuki Tajima

2003-01-01

Precise measurements of the electric form factor of the neutron, Gn E, over a wide range of the square of the four-momentum transfer, Q2, are important for understanding nucleon and nuclear electromagnetic structure. In the non-relativistic limit, the electric and magnetic form factors are related to the charge and magnetization distribution inside a nucleon, respectively. The measured values of the form factors also serve as an important test for nucleon models. Among the four nucleon form factors, the electric form factor of the neutron, Gn E, is the most difficult one to measure and therefore has been very poorly known especially in the region Q2 > 1 (GeV/c)2 due to the lack of a free neutron target and the small value of Gn E. The Jefferson Laboratory E93-038 collaboration measured the ratio of the electric to magnetic form factor of the neutron, g = Gn E/Gn M, at three acceptance-averaged Q2 values of 0.45, 1.13 and 1.45 (GeV/c)2 using the quasi-elastic 2H(∼e, e0∼n)1H reaction. In our experiment, an electron was scattered quasielastically from a neutron in a liquid-deuterium target, and the electron was detected in an electron spectrometer in coincidence with the neutron which was detected in a neutron polarimeter. The polarimeter was used to analyze the polarization of the recoil neutrons by measuring the np elastic scattering asymmetry. The experiment was performed in Hall-C at Thomas Jefferson National Accelerator Facility during the period from September 2000 to April 2001. The value of g was determined from the measured ratio of the sideways and longitudinal components of the neutron polarization vector. The values for Gn E were computed from our measured values of g = Gn E/Gn M using the Gn M values obtained from a fit to the world data. The E93-038 collaboration reported the first measurements of Gn E using polarization techniques at Q2 greater than 1 (GeV/c)2. Furthermore, our measurements of Gn E at the two higher Q2 values of 1.13 and 1.45 (GeV/c

Fc RIIA Genotypes and Its Association with Anti-C1q Autoantibodies in Lupus Nephritis (LN Patients from Western India

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Vandana Pradhan

2010-01-01

Full Text Available To identify Fc RIIA genotypes in Systemic Lupus Erythematosus (SLE patients and their association with anti-C1q antibodies. Methods. Fc RIIA genotyping was done in eighty Indian SLE patients and eighty healthy controls using allele-specific PCR. Anti-C1q antibodies were measured by ELISA. Results. LN patients showed higher SLEDAI (6–32 as compared to SLE patients without renal manifestations and had SLEDAI between 6–23. Fc RIIA polymorphic frequency in SLE patients was R131/H131 (67.5%, R131/R131 (20% and H131/ H131 (12.5% as against that of normal population (62.5%, 10%, and 27.5%, respectively. Sixty two patients (77.5% showed positivity for anti-C1q antibodies. LN patients showed elevated levels of anti-C1q antibodies (258.2u/ml±38.5U/mL as compared to SLE patients without nephritis (134.6±24.6 U/mL. Among anti-C1q positive patients, 71% had R131/H131 genotype, 22.6% had R131/R131 and remaining 6.4%, patients had H131/H131 genotype. All anti-C1q positive patients with R131/R131 genotype had elevated levels of anti-C1q antibodies (>100 U/ml, whereas among anti-C1q negative patients, none had R131/R131 genotype. Conclusion. This first report on Indian SLE patients supports the hypothesis that Fc RIIA R131 variant over expression may constitute a susceptibility factor for development of severe SLE manifestations in LN patients.

Association of anti C1q and ds-DNA levels with the pathogenesis of Lupus Nephritis among SLE patients

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Zara Sohail

2018-02-01

Full Text Available Background: Lupus nephritis (LN is the most common and serious complication associated with SLE and it results in significant morbidity and mortality. It is known by several studies that patients of LN have higher levels of anti-dsDNA and anti-C1q compared with SLE patients without renal involvement. The current study was designed to determine and compare the level of anti-dsDNA and anti-C1q in patients of SLE with and without lupus nephritis in the Pakistani population. This current study was also aimed at providing proof that anti-C1q levels are more prominent in LN/non-LN SLE as compared to anti-dsDNA. This project may help in the determination of results in Pakistan and contribute to the further confirmation of the sensitivity of anti-C1q. Method: The patient samples were collected from Sheikh Zayed hospital, Lahore. These patients were clinically diagnosed by the Rheumatologists as SLE and LN positive on the basis of ACR and SLEDAI scoring criteria. This study was performed and samples were analyzed in the Department of Medical and Laboratory Sciences, Imperial College of Business Study, Lahore on the patient’s serum by ELISA technique. Result: About 38% (12 patients with LN were positive for anti-dsDNA and 31% (9 SLE patients without LN were positive whereas about 38.7% (12 were anti-dsDNA negative in LN cases and 58.6% (17 in SLE without LN. In case of anti-C1q 100% (31 of these LN patients were positive and 93.1% (27 patients SLE without LN showed positive anti C1q results. Only 6.9% (2 patients showed negative results for anti-C1q in LN negative patients Conclusion: The higher levels of anti-C1q suggest that it may be a better diagnostic marker for LN than that of anti-dsDNA and that it can be helpful in the prognosis of SLE patients.

Open-flavor charm and bottom s q q ¯ Q ¯ and q q q ¯ Q ¯ tetraquark states

Science.gov (United States)

Chen, Wei; Chen, Hua-Xing; Liu, Xiang; Steele, T. G.; Zhu, Shi-Lin

2017-06-01

We provide comprehensive investigations for the mass spectrum of exotic open-flavor charmed/bottom s q q ¯ c ¯ , q q q ¯ c ¯ , s q q ¯ b ¯ , q q q ¯ b ¯ tetraquark states with various spin-parity assignments JP=0+,1+,2+ and 0- , 1- in the framework of QCD sum rules. In the diquark configuration, we construct the diquark-antidiquark interpolating tetraquark currents using the color-antisymmetric scalar and axial-vector diquark fields. The stable mass sum rules are established in reasonable parameter working ranges, which are used to give reliable mass predictions for these tetraquark states. We obtain the mass spectra for the open-flavor charmed/bottom s q q ¯c ¯, q q q ¯c ¯, s q q ¯b ¯, q q q ¯b ¯ tetraquark states with various spin-parity quantum numbers. In addition, we suggest searching for exotic doubly-charged tetraquarks, such as [s d ][u ¯ c ¯ ]→Ds(*)-π- in future experiments at facilities such as BESIII, BelleII, PANDA, LHCb, and CMS, etc.

Complement component C1r mediated cleavage of the heavy chain of the major histocompatibility class I antigens

DEFF Research Database (Denmark)

Eriksson, H; Nissen, Mogens Holst

1992-01-01

Apart from cleaving C1s, we demonstrate for the first time that: 1) at concentrations found in serum, the activated forms of the complement components C1r in addition to C1s can cleave the heavy chain of MHC class I antigens, 2) the cleavage by C1r and C1s is seemingly dependent upon a native con......-chain of MHC class I was shown to take place between the alpha 2- and alpha 3- domains as estimated by the Con A-Sepharose precipitation pattern on SDS-PAGE. The alpha 1/alpha 2 fragment was still shown to interact with beta 2-microglobulin as shown by immunoprecipitation....

The Electric Form Factor of the Neutron via Recoil Polarimetry to Q2 1.47 (GeV/c)2

International Nuclear Information System (INIS)

Bradley Plaster; Richard Madey; Andrei Semenov; Simon Taylor; Aram Aghalaryan; Erick Crouse; Glen MacLachlan; Shigeyuki Tajima; William Tireman; Chenyu Yan; Abdellah Ahmidouch; Brian Anderson; Hartmuth Arenhovel; Razmik Asaturyan; O. Baker; Alan Baldwin; Paul Brewer; Roger Carlini; Michael Christy; Steve Churchwell; Leon Cole; Samuel Danagoulian; Donal Day; Mostafa Elaasar; Rolf Ent; Manouchehr Farkhondeh; Howard Fenker; John Finn; Liping Gan; Kenneth Garrow; Calvin Howell; Paul Gueye; Bitao Hu; Mark Jones; James Kelly; Cynthia Keppel; Mahbubul Khandaker; Wooyoung Kim; Stanley Kowalski; Allison Lung; David Mack; D. Manley; Pete Markowitz; Tilmann Reichelt; Joerg Reinhold; Julie Roche; Yoshinori Sato; Irina Semenova; Wonick Seo; Neven Simicevic; Gregory Smith; Samuel Stepanyan; Vardan Tadevosyan; Liguang Tang; Paul Ulmer; William Vulcan; John Watson; Steven Wells; Frank Wesselmann; Stephen Wood; Chen Yan; Seunghoon Yang; Lulin Yuan; Wei-Ming Zhang; Hong Guo Zhu; Xiaofeng Zhu

2003-01-01

The Jefferson Laboratory E93-038 collaboration conducted measurements of the ratio of the electric form factor to the magnetic form factor of the neutron, G n E/G n M, via recoil polarimetry from the quasielastic 2 H((rvec e),e/(rvec n)) 1 H reaction at three values of Q 2 [viz., 0.45, 1.15, and 1.47 (GeV/c) 2 ] in Hall C of the Thomas Jefferson National Accelerator Facility. The preliminary results for G n E at Q 2 = 0.45 and 1.15 (GeV/c) 2 are consistent with the Galster parameterization; however, the preliminary result for G n E at Q 2 = 1.47 (GeV/c) 2 lies slightly above the Galster parameterization

Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience.

Science.gov (United States)

Olsson, Richard F; Hagelberg, Stefan; Schiller, Bodil; Ringdén, Olle; Truedsson, Lennart; Åhlin, Anders

2016-06-01

Human C1q deficiency is associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections. These patients require extensive medical therapy and some develop treatment-resistant disease. Because C1q is produced by monocytes, it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure this disorder. We have so far treated 5 patients with C1q deficiency. In 3 cases, SLE symptoms remained relatively mild after the start of medical therapy, but 2 patients developed treatment-resistant SLE, and we decided to pursue treatment with allo-HSCT. For this purpose, we chose a conditioning regimen composed of treosulfan (14 g/m) and fludarabine (30 mg/m) started on day -6 and given for 3 and 5 consecutive days, respectively. Thymoglobulin was given at a cumulative dose of 8 mg/kg, and graft-versus-host disease prophylaxis was composed of cyclosporine and methotrexate. A 9-year-old boy and a 12-year-old girl with refractory SLE restored C1q production after allo-HSCT. This resulted in normal functional properties of the classical complement pathway followed by reduced severity of SLE symptoms. The boy developed posttransplant lymphoproliferative disease, which resolved after treatment with rituximab and donor lymphocyte infusion. Unfortunately, donor lymphocyte infusion induced severe cortisone-resistant gastrointestinal graft-versus-host disease, and the patient died from multiple organ failure 4 months after transplantation. The girl is doing well 33 months after transplantation, and clinically, all signs of SLE have resolved. Allo-HSCT can cure SLE in human C1q deficiency and should be considered early in subjects resistant to medical therapy.

Pentaatomic planar tetracoordinate carbon molecules [XCAl(3)](q) [(X,q) = (B,-2), (C,-1), (N,0)] with C-X multiple bonding.

Science.gov (United States)

Cui, Zhong-Hua; Shao, Chang-Bin; Gao, Si-Meng; Ding, Yi-Hong

2010-11-07

Among the fascinating planar tetracoordinate carbon (ptC) species, pentaatomic molecules belong to the smallest class, well-known as "pptC". It has been generally accepted that the planarity of pptC structure is realized via the "delocalization" of the p(z) lone pair at the central carbon and the ligand-ligand bonding interaction. Although "localization" is as key driving force in organic chemistry as "delocalization", the "localization" concept has not been applied to the design of pptC molecules, to the best of our knowledge. In this paper, we apply the "localization" strategy to design computationally a series of new pptC. It is shown that the central carbon atom and one "electronegative" ligand atom X (compared to the Al ligand) effectively form a highly localized C-X multiple bond, converting the lone pair at the central carbon to a two-center two-electron π-bond. At the aug-cc-pVTZ-B3LYP, MP2 and CCSD(T) levels, the designed 18-valence-electron pptC species [XCAl(3)](q); [(X,q) = (B,-2), (C,-1), (N,0)] are found to each possess a stable ptC structure bearing a C-X double bond, indicated by the structural, molecular orbital, Wiberg bonding, potential energy surface and Born-Oppenheimer molecular dynamics (BOMD) analysis. Moreover, our OVGF calculations showed that the presently disclosed (yet previously unconsidered) pptC structure of [C(2)Al(3)](-) could well account for the observed photoelectron spectrum (previously only ascribed to a close-energy fan-like structure). Therefore, [C(2)Al(3)](-) could be the first pptC that bears the highly localized C-X double bond that has been experimentally generated. Notably, the pptC structure is the respective global minimum point for [BCAl(3)](2-) and [NCAl(3)], and the counterion(s) would further stabilize [BCAl(3)](2-) and [C(2)Al(3)](-). Thus, these newly designed pptC species with interesting bonding structure should be viable for future experimental characterization. The presently applied "localization" approach

The inhibition of the potassium channel TASK-1 in rat cardiac muscle by endothelin-1 is mediated by phospholipase C.

Science.gov (United States)

Schiekel, Julia; Lindner, Moritz; Hetzel, Andrea; Wemhöner, Konstantin; Renigunta, Vijay; Schlichthörl, Günter; Decher, Niels; Oliver, Dominik; Daut, Jürgen

2013-01-01

The two-pore-domain potassium channel TASK-1 is robustly inhibited by the activation of receptors coupled to the Gα(q) subgroup of G-proteins, but the signal transduction pathway is still unclear. We have studied the mechanisms by which endothelin receptors inhibit the current carried by TASK-1 channels (I(TASK)) in cardiomyocytes. Patch-clamp measurements were carried out in isolated rat cardiomyocytes. I(TASK) was identified by extracellular acidification to pH 6.0 and by the application of the TASK-1 blockers A293 and A1899. Endothelin-1 completely inhibited I(TASK) with an EC(50) of Application of 20 nM endothelin-1 caused a significant increase in action potential duration under control conditions; this was significantly reduced after pre-incubation of the cardiomyocytes with 200 nM A1899. The inhibition of I(TASK) by endothelin-1 was not affected by inhibitors of protein kinase C or rho kinase, but was strongly reduced by U73122, an inhibitor of phospholipase C (PLC). The ability of endothelin-1 to activate PLC-mediated signalling pathways was examined in mammalian cells transfected with TASK-1 and the endothelin-A receptor using patch-clamp measurements and total internal reflection microscopy. U73122 prevented the inhibition of I(TASK) by endothelin-1 and blocked PLC-mediated signalling, as verified with a fluorescent probe for phosphatidylinositol-(4,5)-bisphosphate hydrolysis. Our results show that I(TASK) in rat cardiomyocytes is controlled by endothelin-1 and suggest that the inhibition of TASK-1 via endothelin receptors is mediated by the activation of PLC. The prolongation of the action potential observed with 20 nM endothelin-1 was mainly due to the inhibition of I(TASK).

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...... of the cellular localization, expression and structure of the C3 receptors, especially the C3b (CR1) receptor, has been considerably extended in the last few years, whereas our understanding of the physiological role of these receptors is still fragmentary. However, it is becoming increasingly evident...

DMPD: Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs andCTRPs. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17681884 Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs an...ng) (.svg) (.html) (.csml) Show Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs andC...TRPs. PubmedID 17681884 Title Adipose tissue as an immunological organ: Toll-like

The {P,Q,k+1}-Reflexive Solution to System of Matrix Equations AX=C, XB=D

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Chang-Zhou Dong

2015-01-01

Full Text Available Let P∈Cm×m and Q∈Cn×n be Hermitian and {k+1}-potent matrices; that is, Pk+1=P=P⁎ and Qk+1=Q=Q⁎, where ·⁎ stands for the conjugate transpose of a matrix. A matrix X∈Cm×n is called {P,Q,k+1}-reflexive (antireflexive if PXQ=X (PXQ=-X. In this paper, the system of matrix equations AX=C and XB=D subject to {P,Q,k+1}-reflexive and antireflexive constraints is studied by converting into two simpler cases: k=1 and k=2. We give the solvability conditions and the general solution to this system; in addition, the least squares solution is derived; finally, the associated optimal approximation problem for a given matrix is considered.

The Electric Form Factor of the Neutron at Q² = 1.17 and 1.47(GeV/c)² from the ²H (e, en)' H reaction.

Energy Technology Data Exchange (ETDEWEB)

Tireman, William [Kent State Univ., Kent, OH (United States)

2003-12-01

The Jefferson Laboratory E93-038 collaboration measured the ratio of the electric form factor to the magnetic form factor of the neutron, g = Gne/Gnm, via recoil polarimetry from the quasielastic ²H(e,en)1 H reaction at q² = 0.45, 1.17 and 1.47 (GeV/c)² in Hall C of the Thomas Jefferson National Accelerator Facility. A polarimeter designed specifically for E93-038 was used to measure the up-down scattering asymmetry from the transverse component of the recoil neutron's polarization vector, and a dipole magnet located in front of the polarimeter was used to precess the polarization vector in the scattering plane through an angle of x. Sequential measurements of the scattering asymmetry with the polarization vector precessed through angles χ = 0° and χ = ±90° for Q² = 1.47 (GeV/c)² were made during January 2001 and through angles χ = ±40° for Q² = 1.17 (GeV/c)² during April 2001 and will be reported on in this dissertation. This ratio method removes the need to know the analyzing power

Structure of the human gene encoding the associated microfibrillar protein (MFAP1) and localization to chromosome 15q15-q21

Energy Technology Data Exchange (ETDEWEB)

Yeh, H.; Chow, M.; Abrams, W.R. [Univ. of Pennsylvania, Philadelphia, PA (United States)] [and others

1994-09-15

Microfibrils with a diameter of 10-12 nm, found either in assocation with elastin or independently, are an important component of the extracellular matrix of many tissues. To extend understanding of the proteins composing these microfibrils, the cDNA and gene encoding the human associated microfibril protein (MRAP1) have been cloned and characterized. The coding portion is contained in 9 exons, and the sequence is very homologous to the previously described chick cDNA, but does not appear to share homology or domain motifs with any other known protein. Interestingly, the gene has been localized to chromosome 15q15-q21 by somatic hybrid cell and chromosome in situ analyses. This is the same chromosomal region to which the fibrillin gene, FBN1, known to be defective in the Marfan syndrome, has been mapped. MFAP1 is a candidate gene for heritable diseases affecting microfibrils. 38 refs., 6 figs.

c-Fms signaling mediates neurofibromatosis Type-1 osteoclast gain-in-functions.

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Yongzheng He

Full Text Available Skeletal abnormalities including osteoporosis and osteopenia occur frequently in both pediatric and adult neurofibromatosis type 1 (NF1 patients. NF1 (Nf1 haploinsufficient osteoclasts and osteoclast progenitors derived from both NF1 patients and Nf1(+/- mice exhibit increased differentiation, migration, and bone resorptive capacity in vitro, mediated by hyperactivation of p21(Ras in response to limiting concentrations of macrophage-colony stimulating factor (M-CSF. Here, we show that M-CSF binding to its receptor, c-Fms, results in increased c-Fms activation in Nf1(+/ (- osteoclast progenitors, mediating multiple gain-in-functions through the downstream effectors Erk1/2 and p90RSK. PLX3397, a potent and selective c-Fms inhibitor, attenuated M-CSF mediated Nf1(+/- osteoclast migration by 50%, adhesion by 70%, and pit formation by 60%. In vivo, we administered PLX3397 to Nf1(+/- osteoporotic mice induced by ovariectomy (OVX and evaluated changes in bone mass and skeletal architecture. We found that PLX3397 prevented bone loss in Nf1(+/--OVX mice by reducing osteoclast differentiation and bone resorptive activity in vivo. Collectively, these results implicate the M-CSF/c-Fms signaling axis as a critical pathway underlying the aberrant functioning of Nf1 haploinsufficient osteoclasts and may provide a potential therapeutic target for treating NF1 associated osteoporosis and osteopenia.

Prolonged Q-T(c) interval in mild portal hypertensive cirrhosis

DEFF Research Database (Denmark)

Ytting, Henriette; Henriksen, Jens Henrik; Fuglsang, Stefan

2005-01-01

BACKGROUND/AIMS: The Q-T(c) interval is prolonged in a substantial fraction of patients with cirrhosis, thus indicating delayed repolarisation. However, no information is available in mild portal hypertensive patients. We therefore determined the Q-T(c) interval in cirrhotic patients with hepatic...... venous pressure gradient (HVPG) portal hypertension (HVPG> or = 12 mmHg) and controls without liver disease. RESULTS......), values which are significantly above that of the controls (0.410 s(1/2), P portal hypertensive group, the Q-T(c) interval was inversely related to indicators of liver function, such as indocyanine green clearance (r = -0.34, P

Cefditoren and ceftriaxone enhance complement-mediated immunity in the presence of specific antibodies against antibiotic-resistant pneumococcal strains.

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Elisa Ramos-Sevillano

Full Text Available BACKGROUND: Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae. CONCLUSIONS/SIGNIFICANCE: Using cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.

Altered bacterial metabolism, not coenzyme Q content, is responsible for the lifespan extension in Caenorhabditis elegans fed an Escherichia coli diet lacking coenzyme Q.

Science.gov (United States)

Saiki, Ryoichi; Lunceford, Adam L; Bixler, Tarra; Dang, Peter; Lee, Wendy; Furukawa, Satoru; Larsen, Pamela L; Clarke, Catherine F

2008-06-01

Coenzyme Q(n) is a fully substituted benzoquinone containing a polyisoprene tail of distinct numbers (n) of isoprene groups. Caenorhabditis elegans fed Escherichia coli devoid of Q(8) have a significant lifespan extension when compared to C. elegans fed a standard 'Q-replete'E. coli diet. Here we examine possible mechanisms for the lifespan extension caused by the Q-less E. coli diet. A bioassay for Q uptake shows that a water-soluble formulation of Q(10) is effectively taken up by both clk-1 mutant and wild-type nematodes, but does not reverse lifespan extension mediated by the Q-less E. coli diet, indicating that lifespan extension is not due to the absence of dietary Q per se. The enhanced longevity mediated by the Q-less E. coli diet cannot be attributed to dietary restriction, different Qn isoforms, reduced pathogenesis or slowed growth of the Q-less E. coli, and in fact requires E. coli viability. Q-less E. coli have defects in respiratory metabolism. C. elegans fed Q-replete E. coli mutants with similarly impaired respiratory metabolism due to defects in complex V also show a pronounced lifespan extension, although not as dramatic as those fed the respiratory deficient Q-less E. coli diet. The data suggest that feeding respiratory incompetent E. coli, whether Q-less or Q-replete, produces a robust life extension in wild-type C. elegans. We believe that the fermentation-based metabolism of the E. coli diet is an important parameter of C. elegans longevity.

C1q nephropathy and isolated CD59 deficiency manifesting as necrotizing crescentic glomerulonephritis: A rare association of two diseases

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Ruchika Gupta

2015-01-01

Full Text Available C1q nephropathy is a recently described clinico-pathologic entity with a variable clinical presentation and pathology. Crescentic glomerulonephritis (GN has been reported in only two patients in the available literature. CD59 deficiency, along with lack of CD55, is responsible for paroxysmal nocturnal hemoglobinuria (PNH. Few cases of isolated CD59 deficiency have been described with PNH-like features. A middle-aged adult male presented with rapidly progressive renal failure. Serological investigations were negative. A renal biopsy revealed necrotizing crescentic GN with rupture of Bowman′s capsule. Immunofluorescence on the frozen sections showed dominant mesangial deposits of C1q along with IgM. Hematological work-up of the patient revealed isolated CD59 deficiency. Hence, a final diagnosis of C1q nephropathy and CD59 deficiency manifesting as crescentic GN and hemolytic anemia was made. The co-existence of two rare disorders, C1q nephropathy and CD59 deficiency, in a patient with necrotizing crescentic GN is described for the first time to the best of our knowledge. The pathogenetic link of these two entities with the clinical manifestation requires further study.

Structural Elements in the Gαs and Gαq C Termini That Mediate Selective G Protein-coupled Receptor (GPCR) Signaling.

Science.gov (United States)

Semack, Ansley; Sandhu, Manbir; Malik, Rabia U; Vaidehi, Nagarajan; Sivaramakrishnan, Sivaraj

2016-08-19

Although the importance of the C terminus of the α subunit of the heterotrimeric G protein in G protein-coupled receptor (GPCR)-G protein pairing is well established, the structural basis of selective interactions remains unknown. Here, we combine live cell FRET-based measurements and molecular dynamics simulations of the interaction between the GPCR and a peptide derived from the C terminus of the Gα subunit (Gα peptide) to dissect the molecular mechanisms of G protein selectivity. We observe a direct link between Gα peptide binding and stabilization of the GPCR conformational ensemble. We find that cognate and non-cognate Gα peptides show deep and shallow binding, respectively, and in distinct orientations within the GPCR. Binding of the cognate Gα peptide stabilizes the agonist-bound GPCR conformational ensemble resulting in favorable binding energy and lower flexibility of the agonist-GPCR pair. We identify three hot spot residues (Gαs/Gαq-Gln-384/Leu-349, Gln-390/Glu-355, and Glu-392/Asn-357) that contribute to selective interactions between the β2-adrenergic receptor (β2-AR)-Gαs and V1A receptor (V1AR)-Gαq The Gαs and Gαq peptides adopt different orientations in β2-AR and V1AR, respectively. The β2-AR/Gαs peptide interface is dominated by electrostatic interactions, whereas the V1AR/Gαq peptide interactions are predominantly hydrophobic. Interestingly, our study reveals a role for both favorable and unfavorable interactions in G protein selection. Residue Glu-355 in Gαq prevents this peptide from interacting strongly with β2-AR. Mutagenesis to the Gαs counterpart (E355Q) imparts a cognate-like interaction. Overall, our study highlights the synergy in molecular dynamics and FRET-based approaches to dissect the structural basis of selective G protein interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The binding of activated Gαq to phospholipase C-β exhibits anomalous affinity.

Science.gov (United States)

Navaratnarajah, Punya; Gershenson, Anne; Ross, Elliott M

2017-10-06

Upon activation by the G q family of Gα subunits, Gβγ subunits, and some Rho family GTPases, phospholipase C-β (PLC-β) isoforms hydrolyze phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. PLC-β isoforms also function as GTPase-activating proteins, potentiating G q deactivation. To elucidate the mechanism of this mutual regulation, we measured the thermodynamics and kinetics of PLC-β3 binding to Gα q FRET and fluorescence correlation spectroscopy, two physically distinct methods, both yielded K d values of about 200 nm for PLC-β3-Gα q binding. This K d is 50-100 times greater than the EC 50 for Gα q -mediated PLC-β3 activation and for the Gα q GTPase-activating protein activity of PLC-β. The measured K d was not altered either by the presence of phospholipid vesicles, phosphatidylinositol 4,5-bisphosphate and Ca 2+ , or by the identity of the fluorescent labels. FRET-based kinetic measurements were also consistent with a K d of 200 nm We determined that PLC-β3 hysteresis, whereby PLC-β3 remains active for some time following either Gα q -PLC-β3 dissociation or PLC-β3-potentiated Gα q deactivation, is not sufficient to explain the observed discrepancy between EC 50 and K d These results indicate that the mechanism by which Gα q and PLC-β3 mutually regulate each other is far more complex than a simple, two-state allosteric model and instead is probably kinetically determined. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

C/EBPβ (CCAAT/enhancer-binding protein β) mediates progesterone production through transcriptional regulation in co-operation with SF-1 (steroidogenic factor-1).

Science.gov (United States)

Mizutani, Tetsuya; Ju, Yunfeng; Imamichi, Yoshitaka; Osaki, Tsukasa; Yazawa, Takashi; Kawabe, Shinya; Ishikane, Shin; Matsumura, Takehiro; Kanno, Masafumi; Kamiki, Yasue; Kimura, Kohei; Minamino, Naoto; Miyamoto, Kaoru

2014-06-15

The transcription factor SF-1 (steroidogenic factor-1) is a master regulator of steroidogenesis. Previously, we have found that SF-1 induces the differentiation of mesenchymal stem cells into steroidogenic cells. To elucidate the molecular mechanisms of SF-1-mediated functions, we attempted to identify protein components of the SF-1 nuclear protein complex in differentiated cells. SF-1 immunoaffinity chromatography followed by MS/MS analysis was performed, and 24 proteins were identified. Among these proteins, we focused on C/EBPβ (CCAAT/enhancer-binding protein β), which is an essential transcription factor for ovulation and luteinization, as the transcriptional mechanisms of C/EBPβ working together with SF-1 are poorly understood. C/EBPβ knockdown attenuated cAMP-induced progesterone production in granulosa tumour-derived KGN cells by altering STAR (steroidogenic acute regulatory protein), CYP11A1 (cytochrome P450, family 11, subfamily A, polypeptide 1) and HSD3B2 (hydroxy-δ-5-steroid dehydrogenase, 3β- and steroid δ-isomerase 2) expression. EMSA and ChIP assays revealed novel C/EBPβ-binding sites in the upstream regions of the HSD3B2 and CYP11A1 genes. These interactions were enhanced by cAMP stimulation. Luciferase assays showed that C/EBPβ-responsive regions were found in each promoter and C/EBPβ is involved in the cAMP-induced transcriptional activity of these genes together with SF-1. These results indicate that C/EBPβ is an important mediator of progesterone production by working together with SF-1, especially under tropic hormone-stimulated conditions.

The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant

DEFF Research Database (Denmark)

Moghadasi, Setareh; Meeks, Huong D.; Vreeswijk, Maaike Pg

2018-01-01

studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1*R1699Q carriers. METHODS: Data were collected from 129 BRCA1*R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles......BACKGROUND: We previously showed that the BRCA1 variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously......) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions. RESULTS: In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively...

Preeclampsia is associated with hypermethylation of IGF-1 promoter mediated by DNMT1.

Science.gov (United States)

Ma, Min; Zhou, Qiong-Jie; Xiong, Yu; Li, Bin; Li, Xiao-Tian

2018-01-01

Previous studies have demonstrated a dynamic epigenetic regulation of genes expression in placenta trophoblasts and a dynamic imbalance of DNA methylation and hydroxymethylation. Reduced IGF-1 has been observed in preeclampsia. This study was to investigate the interactive roles between IGF-1 and the global DNA methylation/hydroxymethylation, and the status of DNA methylation/hydroxymethylation and associated enzymes such as DNMTs and TETs in peeeclamptic placentas and hypoxic trophoblasts. It was found that IGF-1 was decreased in preeclamptic placentas and hypoxic trophoblasts when compared to the control group using immunohistochemisty, western blot, qRT-PCR and ELISA. Pyrophosphate sequencing showed IGF-1 promoter was significantly hypermethylated in preeclamptic placentas, which was responsible for reduced IGF-1 expression. Preeclamptic placentas and hypoxic trophoblasts were hypermethylated and hypohydroxymethylated accompanied by remarkably higher 5mC, DNMT1 and DNMT3b, and lower DNMT3a, 5hmC, TET1, TET2 and TET3 detected by immunohistochemisty, western blot, qRT-PCR and ELISA. Pearson's correlation confirmed a statistically significant negative correlation between IGF-1 and DNMT1. Furthermore, both treatment with 5-Aza-dc and DNMT1-siRNA significantly increased the expression of IGF-1 in HTR8 cells, indicating the potential mechanism of DNMT1-mediated DNA methylation in IGF-1 regulation. However, IGF-1 didn't change DNA methylation or hydroxymethylation. These findings suggest that preeclampsia is associated with hypermethylation of IGF-1 promoter mediated by DNMT1 and provide new insights into the diagnosis and treatment of preeclampsia.

Influence of paraoxonase-1 Q192R and cytochrome P450 2C19 polymorphisms on clopidogrel response

Directory of Open Access Journals (Sweden)

Li L

2012-02-01

Full Text Available Rolf P Kreutz1,2, Perry Nystrom2, Yvonne Kreutz2, Jia Miao2, Zeruesenay Desta2, Jeffrey A Breall1, Lang Li2, ChienWei Chiang2, Richard Kovacs1, David A Flockhart2, Yan Jin21Krannert Institute of Cardiology, 2Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USABackground: The metabolic activation of clopidogrel is a two-step process. It has been suggested that paraoxonase-1 (PON1 is a rate-limiting enzyme in the conversion of 2-oxo-clopidogrel to an active thiol metabolite. Conflicting results have been reported in regard to (1 the association of a common polymorphism of PON1 (Q192R with reduced rates of coronary stent thrombosis in patients taking clopidogrel and (2 its effects on platelet inhibition in patient populations of European descent. Methods: Blood samples from 151 subjects of mixed racial background with established coronary artery disease and who received clopidogrel were analyzed. Platelet aggregation was determined with light transmittance aggregometry and VerifyNow® P2Y12 assay. Genotyping for cytochrome P450 2C19 (CYP2C19*2 and *3 and PON1 (Q192R polymorphisms was performed.Results: Carriers of CYP2C19*2 alleles exhibited lower levels of platelet inhibition and higher on-treatment platelet aggregation than noncarriers. There was no significant difference in platelet aggregation among PON1 Q192R genotypes. Homozygous carriers of the wild-type variant of PON1 (QQ192 had similar on-treatment platelet reactivity to carriers of increased-function variant alleles during maintenance clopidogrel dosing, as well as after administration of a clopidogrel 600 mg loading dose.Conclusion: CYP2C19*2 allele is associated with impaired platelet inhibition by clopidogrel and high on-treatment platelet aggregation. PON1 (Q192R polymorphism does not appear to be a significant determinant of clopidogrel response.Keywords: PON1, platelet, aggregation, cytochrome P450 enzymes

Studies on the pathogenesis of Aleutian disease of mink. X. demonstration of immune complexes by the /sup 125/I-C 1 q binding test after experimental infection

Energy Technology Data Exchange (ETDEWEB)

Mueller-Peddinghaus, R [Kali-Chemie Pharma G.m.b.H., Hannover (Germany, F.R.). Abt. fuer Experimentelle Pathologie; Meyer zu Schwabedissen, H [Medizinische Hochschule Hannover (Germany, F.R.). Abt. fuer Klinische Immunologie und Bluttransfusionswesen; Kalden, J R [Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. und Poliklinik fuer Klinische Immunologie; Trautwein, G; Ueberschaer, S [Tieraerztliche Hochschule Hannover (Germany, F.R.). Inst. fuer Pathologie

1980-01-01

Aleutian disease (AD) of mink most closely resembles systemic lupus erythematosus (SLE) in man; both are immune complex disease. In experimental AD serum immune complexes are determined by the /sup 125/J-C 1 q-binding test using human C 1 q. Mink (n = 12) infected intraperitoneally with Aleutian disease virus (ADV), grown in fetal mink kidney cells, developed during the course of infection a mean of /sup 125/I-C 1 q serum binding equivalent to 3.62 +- 1.68 mg./ml. aggr. HGG. (aggregated human immunoglobulin). Sera of mink (n = 8) which were infected with ADV grown in L-cells showed a less marked /sup 125/I-C 1 q binding with a mean equivalent to 2.52 +- 1.43 mg./ml. aggr. HGG. In contrast control animals (n = 8) treated with non-ADV-infected mink epidermal fibroblasts or Eagle's minimal essential medium substituted with fetal calf serum only bound /sup 125/I-C 1 q equivalent to 1.02 +- 0.99 mg./ml. aggr. HGG. In mink infected with ADV propagated in fetal mink kidney cells a constant increase in the /sup 125/I-C 1 q serum binding occurred from the 4th to the 7th and 13th week after ADV infection. Mink which were infected with ADV propagated in mouse L-cells exhibited a different pattern of the /sup 125/I-C 1 q serum binding capacity with a sharp increase from the 4th to the 7th week, followed by a decline towards the 13th week post infection. The serum /sup 125/I-C 1 q binding capacity of all experimental animal groups exhibited at different times of the experiment a significant correlation with the presence of hypergammaglobulinaemia and raised ADV-antibody titers. From the data obtained it appears that the /sup 125/I-C 1 q binding test, utilizing human C 1 q, is a suitable method for the detection of circulating serum immune complexes in mink during the course of ADV-infection.

Measurements of the neutron electric to magnetic form factor ratio GEn/GMn via the 2H(e→,e'n→)1H reaction to Q2=1.45 (GeV/c)2

International Nuclear Information System (INIS)

Plaster, B.; Semenov, A.Yu.; Semenova, I.A.; Aghalaryan, A.; Asaturyan, R.; Mkrtchyan, H.; Stepanyan, S.; Tadevosyan, V.; Crouse, E.; Finn, J.M.; Perdrisat, C.; Roche, J.; MacLachlan, G.; Opper, A.K.; Tajima, S.; Churchwell, S.; Howell, C.R.; Tireman, W.; Ahmidouch, A.; Anderson, B. D.

2006-01-01

We report values for the neutron electric to magnetic form factor ratio, G En /G Mn , deduced from measurements of the neutron's recoil polarization in the quasielastic 2 H(e→,e ' n→) 1 H reaction, at three Q 2 values of 0.45, 1.13, and 1.45 (GeV/c) 2 . The data at Q 2 =1.13 and 1.45 (GeV/c) 2 are the first direct experimental measurements of G En employing polarization degrees of freedom in the Q 2 >1 (GeV/c) 2 region and stand as the most precise determinations of G En for all values of Q 2

Assignment of C1q-binding HLA antibodies as unacceptable HLA antigens avoids positive CDC-crossmatches prior to transplantation of deceased donor organs.

Science.gov (United States)

Juhl, David; Marget, Matthias; Hallensleben, Michael; Görg, Siegfried; Ziemann, Malte

2017-03-01

Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed. Sera causing positive crossmatches were investigated by the C1q-assay. 31 out of 1432 crossmatches (2.2%) were positive. Sera involved in 26 positive crossmatches were available. C1q-binding donor-specific antibodies were detected in 19 sera (73.1%). The other sera were from recipients without any HLA antibodies detectable by CDC or common solid phase assays. Three patients had known Non-HLA antibodies causing positive CDC-results. Four crossmatches were only weak positive. Therefore, avoidance of donors with HLA antigens against whom C1q-binding antibodies were detected would have prevented all positive crossmatches due to HLA antibodies. Provided that all HLA specificities against which antibodies are detected by the Luminex C1q-assay are considered as unacceptable antigens, CDC-crossmatches prior to transplantation might safely be omitted in many patients. They should be maintained in highly immunized patients, however, for whom assignment of all C1q-positive antibodies as unacceptable antigens could lead to a significant delay or even prevention of transplantation. Copyright © 2017 Elsevier B.V. All rights reserved.

IceCube potential for detecting Q-ball dark matter in gauge mediation

International Nuclear Information System (INIS)

Kasuya, Shinta; Kawasaki, Masahiro; Yanagida, Tsutomu T.

2015-01-01

We study Q-ball dark matter in gauge-mediated supersymmetry breaking, and seek the possibility of detection in the IceCube experiment. We find that the Q balls would be the dark matter in the parameter region different from that for gravitino dark matter. In particular, the Q ball is a good dark matter candidate for low reheating temperature, which may be suitable for the Affleck–Dine baryogenesis and/or nonthermal leptogenesis. Dark matter Q balls are detectable by IceCube-like experiments in the future, which is a peculiar feature compared to the case of gravitino dark matter

The Exosporium of B.cereus Contains a Binding Site for gC1qR/p33: Implication in Spore Attachment and/or Entry.

Energy Technology Data Exchange (ETDEWEB)

GHEBREHIWET,B.; TANTRAL, L.; TITMUS, M.A.; PANESSA-WARREN, B.J.; TORTORA, G.T.; WONG, S.S.; WARREN, J.B.

2008-01-01

B. cereus, is a member of a genus of aerobic, gram-positive, spore-forming rod-like bacilli, which includes the deadly, B. anthracis. Preliminary experiments have shown that gC1qR binds to B.cereus spores that have been attached to microtiter plates. The present studies were therefore undertaken, to examine if cell surface gC1qR plays a role in B.cereus spore attachment and/or entry. Monolayers of human colon carcinoma (Caco-2) and lung cells were grown to confluency on 6 mm coverslips in shell vials with gentle swirling in a shaker incubator. Then, 2 {micro}l of a suspension of strain SB460 B.cereus spores (3x10{sup 8}/ml, in sterile water), were added and incubated (1-4 h; 36{sup 0} C) in the presence or absence of anti-gC1qR mAb-carbon nanoloops. Examination of these cells by EM revealed that: (1) When B. cereus endospores contacted the apical Caco-2 cell surface, or lung cells, gClqR was simultaneously detectable, indicating upregulation of the molecule. (2) In areas showing spore contact with the cell surface, gClqR expression was often adjacent to the spores in association with microvilli (Caco-2 cells) or cytoskeletal projections (lung cells). (3) Furthermore, the exosporia of the activated and germinating spores were often decorated with mAb-nanoloops. These observations were further corroborated by experiments in which B.cereus spores were readily taken up by monocytes and neutrophils, and this uptake was partially inhibited by mAb 60.11, which recognizes the C1q binding site on gC1qR. Taken together, the data suggest a role, for gC1qR at least in the initial stages of spore attachment and/or entry.

Amblyomma americanum tick calreticulin binds C1q but does not inhibit activation of the classical complement cascade.

Science.gov (United States)

Kim, Tae Kwon; Ibelli, Adriana Mércia Guaratini; Mulenga, Albert

2015-02-01

In this study we characterized Amblyomma americanum (Aam) tick calreticulin (CRT) homolog in tick feeding physiology. In nature, different tick species can be found feeding on the same animal host. This suggests that different tick species found feeding on the same host can modulate the same host anti-tick defense pathways to successfully feed. From this perspective it's plausible that different tick species can utilize universally conserved proteins such as CRT to regulate and facilitate feeding. CRT is a multi-functional protein found in most taxa that is injected into the vertebrate host during tick feeding. Apart from it's current use as a biomarker for human tick bites, role(s) of this protein in tick feeding physiology have not been elucidated. Here we show that annotated functional CRT amino acid motifs are well conserved in tick CRT. However our data show that despite high amino acid identity levels to functionally characterized CRT homologs in other organisms, AamCRT is apparently functionally different. Pichia pastoris expressed recombinant (r) AamCRT bound C1q, the first component of the classical complement system, but it did not inhibit activation of this pathway. This contrast with reports of other parasite CRT that inhibited activation of the classical complement pathway through sequestration of C1q. Furthermore rAamCRT did not bind factor Xa in contrast to reports of parasite CRT binding factor Xa, an important protease in the blood clotting system. Consistent with this observation, rAamCRT did not affect plasma clotting or platelet aggregation. We discuss our findings in the context of tick feeding physiology.

A recombinant fusion toxin based on enzymatic inactive C3bot1 selectively targets macrophages.

Directory of Open Access Journals (Sweden)

Lydia Dmochewitz

Full Text Available BACKGROUND: The C3bot1 protein (~23 kDa from Clostridium botulinum ADP-ribosylates and thereby inactivates Rho. C3bot1 is selectively taken up into the cytosol of monocytes/macrophages but not of other cell types such as epithelial cells or fibroblasts. Most likely, the internalization occurs by a specific endocytotic pathway via acidified endosomes. METHODOLOGY/PRINCIPAL FINDINGS: Here, we tested whether enzymatic inactive C3bot1E174Q serves as a macrophage-selective transport system for delivery of enzymatic active proteins into the cytosol of such cells. Having confirmed that C3bot1E174Q does not induce macrophage activation, we used the actin ADP-ribosylating C2I (∼50 kDa from Clostridium botulinum as a reporter enzyme for C3bot1E174Q-mediated delivery into macrophages. The recombinant C3bot1E174Q-C2I fusion toxin was cloned and expressed as GST-protein in Escherichia coli. Purified C3bot1E174Q-C2I was recognized by antibodies against C2I and C3bot and showed C2I-specific enzyme activity in vitro. When applied to cultured cells C3bot1E174Q-C2I ADP-ribosylated actin in the cytosol of macrophages including J774A.1 and RAW264.7 cell lines as well as primary cultured human macrophages but not of epithelial cells. Together with confocal fluorescence microscopy experiments, the biochemical data indicate the selective uptake of a recombinant C3-fusion toxin into the cytosol of macrophages. CONCLUSIONS/SIGNIFICANCE: In summary, we demonstrated that C3bot1E174Q can be used as a delivery system for fast, selective and specific transport of enzymes into the cytosol of living macrophages. Therefore, C3-based fusion toxins can represent valuable molecular tools in experimental macrophage pharmacology and cell biology as well as attractive candidates to develop new therapeutic approaches against macrophage-associated diseases.

Pin Component Technology (V1.0) and Its C Interface

National Research Council Canada - National Science Library

Hissam, Scott; Ivers, James; Plakosh, Daniel; Wallnau, Kurt C

2005-01-01

.... Pin implements the container idiom for software components. Containers provide a pre-fabricated "shell" in which custom code executes and through which all interactions between custom code and its external environment are mediated...

SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity.

Science.gov (United States)

Lee, Soonduck; Kim, Jinsun; Jung, Samil; Li, Chengping; Yang, Young; Kim, Keun Il; Lim, Jong-Seok; Kim, Yonghwan; Cheon, Choong-Il; Lee, Myeong-Sok

2015-03-01

Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner.

Q.C.D. estimates of hadronic cross sections

International Nuclear Information System (INIS)

Navelet, H.; Peschanski, R.

1983-03-01

Estimates for hadron-hadron cross-sections are made using the leading log approximation of Q.C.D. The rise of the total inelastic pp cross-sections at high energy is reproduced, thanks to the competition between the small parton-parton interaction and the large multiplicity of gluons predicted by Q.C.D

Measurement of the Deuteron Spin Structure Function g_1^d(x) for 1 (GeV/c)^2 < Q^2 < 40 (GeV/c)^2

OpenAIRE

E155 Collaboration

1999-01-01

New measurements are reported on the deuteron spin structure function g_1^d. These results were obtained from deep inelastic scattering of 48.3 GeV electrons on polarized deuterons in the kinematic range 0.01 < x < 0.9 and 1 < Q^2 < 40 (GeV/c)^2. These are the first high dose electron scattering data obtained using lithium deuteride (6Li2H) as the target material. Extrapolations of the data were performed to obtain moments of g_1^d, including Gamma_1^d, and the net quark polarization Delta Si...

Measurement of the deuteron spin structure function $g^{d}_1(x)$ for $1\\ (GeV/c)^2 < Q^2 < 40\\ (GeV/c)^2$.

OpenAIRE

Anthony , P.L.; Arnold , R.G.; Averett , T.; Band , H.R.; Berisso , M.C.; Borel , H.; Bosted , P.E.; Bultmann , S.L.; Buenerd , M.; Chupp , T.; Churchwell , S.; Court , G.R.; Crabb , D.; Day , D.; Decowski , P.

1999-01-01

New measurements are reported on the deuteron spin structure function g_1^d. These results were obtained from deep inelastic scattering of 48.3 GeV electrons on polarized deuterons in the kinematic range 0.01 < x < 0.9 and 1 < Q^2 < 40 (GeV/c)^2. These are the first high dose electron scattering data obtained using lithium deuteride (6Li2H) as the target material. Extrapolations of the data were performed to obtain moments of g_1^d, including Gamma_1^d, and the net quark polarization Delta Si...

Influence of electron-phonon interaction on soliton mediated spin-charge conversion effects in two-component polymer model

International Nuclear Information System (INIS)

Sergeenkov, S.; Moraes, F.; Furtado, C.; Araujo-Moreira, F.M.

2010-01-01

By mapping a Hubbard-like model describing a two-component polymer in the presence of strong enough electron-phonon interactions (κ) onto the system of two coupled nonlinear Schroedinger equations with U(2) symmetry group, some nontrivial correlations between topological solitons mediated charge Q and spin S degrees of freedom are obtained. Namely, in addition to a charge fractionalization and reentrant like behavior of both Q(κ) and S(κ), the model also predicts a decrease of soliton velocity with κ as well as spin-charge conversion effects which manifest themselves through an explicit S(Q,Ω) dependence (with Ω being a mixing angle between spin-up and spin-down electron amplitudes). A possibility to observe the predicted effects in low-dimensional systems with charge and spin soliton carriers is discussed.

Measurements of the neutron electric to magnetic form-factor ratio GEn/GMn via the 2H((rvec e), e(prime)(rvec n)) 1H reaction to Q2 = 1.45-(GeV/c)2

International Nuclear Information System (INIS)

Bradley Plaster; A.Yu. Semenov; A. Aghalaryan; Erick Crouse; Glen MacLachlan; Shigeyuki Tajima; William Tireman; Abdellah Ahmidouch; Brian Anderson; Hartmuth Arenhovel; Razmik Asaturyan; O. Baker; Alan Baldwin; David Barkhuff; Herbert Breuer; Roger Carlini; Michael Christy; Steve Churchwell; Leon Cole; Samuel Danagoulian; Donal Day; T. Eden; Mostafa Elaasar; Rolf Ent; Manouchehr Farkhondeh; Howard Fenker; John Finn; Liping Gan; Ashot Gasparian; Kenneth Garrow; Paul Gueye; Calvin Howell; Bitao Hu; Mark Jones; James Kelly; Cynthia Keppel; Mahbubul Khandaker; Wooyoung Kim; Stanley Kowalski; Allison Lung; David Mack; Richard Madey; D. Manley; Pete Markowitz; Joseph Mitchell; Hamlet Mkrtchyan; Allena Opper; Charles Perdrisat; Vina Punjabi; Brian Raue; Tilmann Reichelt; Joerg Reinhold; Julie Roche; Yoshinori Sato; Nikolai Savvinov; Irina Semenova; Wonick Seo; Neven Simicevic; Gregory Smith; Stepan Stepanyan; Vardan Tadevosyan; Liguang Tang; Shawn Taylor; Paul Ulmer; William Vulcan; John Watson; Steven Wells; Frank Wesselmann; Stephen Wood; Seunghoon Yang; Lulin Yuan; Wei-Ming Zhang; Hong Guo Zhu; Xiaofeng Zhu

2006-01-01

We report values for the neutron electric to magnetic form factor ratio, G En /G Mn , deduced from measurements of the neutron's recoil polarization in the quasielastic 2 H((rvec e), e(prime)(rvec n)) 1 H reaction, at three Q 2 values of 0.45, 1.13, and 1.45 (GeV/c) 2 . The data at Q 2 = 1.13 and 1.45 (GeV/c) 2 are the first direct experimental measurements of GEn employing polarization degrees of freedom in the Q 2 > 1 (GeV/c) 2 region and stand as the most precise determinations of GEn for all values of Q 2

A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements.

Science.gov (United States)

Kohmoto, Tomohiro; Okamoto, Nana; Naruto, Takuya; Murata, Chie; Ouchi, Yuya; Fujita, Naoko; Inagaki, Hidehito; Satomura, Shigeko; Okamoto, Nobuhiko; Saito, Masako; Masuda, Kiyoshi; Kurahashi, Hiroki; Imoto, Issei

2017-01-01

Complex genomic rearrangements (CGRs) consisting of interstitial triplications in conjunction with uniparental isodisomy (isoUPD) have rarely been reported in patients with multiple congenital anomalies (MCA)/intellectual disability (ID). One-ended DNA break repair coupled with microhomology-mediated break-induced replication (MMBIR) has been recently proposed as a possible mechanism giving rise to interstitial copy number gains and distal isoUPD, although only a few cases providing supportive evidence in human congenital diseases with MCA have been documented. Here, we report on the chromosomal microarray (CMA)-based identification of the first known case with concurrent interstitial duplication at 1q42.12-q42.2 and triplication at 1q42.2-q43 followed by isoUPD for the remainder of chromosome 1q (at 1q43-qter). In distal 1q duplication/triplication overlapping with 1q42.12-q43, variable clinical features have been reported, and our 25-year-old patient with MCA/ID presented with some of these frequently described features. Further analyses including the precise mapping of breakpoint junctions within the CGR in a sequence level suggested that the CGR found in association with isoUPD in our case is a triplication with flanking duplications, characterized as a triplication with a particularly long duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) structure. Because microhomology was observed in both junctions between the triplicated region and the flanking duplicated regions, our case provides supportive evidence for recently proposed replication-based mechanisms, such as MMBIR, underlying the formation of CGRs + isoUPD implicated in chromosomal disorders. To the best of our knowledge, this is the first case of CGRs + isoUPD observed in 1q and having DUP-TRP/INV-DUP structure with a long proximal duplication, which supports MMBIR-based model for genomic rearrangements. Molecular cytogenetic analyses using CMA containing single

Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

Science.gov (United States)

Hu, Peizhen; Chung, Leland W K; Berel, Dror; Frierson, Henry F; Yang, Hua; Liu, Chunyan; Wang, Ruoxiang; Li, Qinlong; Rogatko, Andre; Zhau, Haiyen E

2013-01-01

We reported (PLoS One 6 (12):e28670, 2011) that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC) tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE) tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1) expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

On the Hopf structure of Up,q(gl(1/1)) and the universal Τ-matrix of Funp,q(GL(1/1))

International Nuclear Information System (INIS)

Chakrabarti, R.; Jagannathan, R.

1994-08-01

Using the technique developed by Fronsdal and Galindo (Lett. Math. Phys, 27 (1993) 57) for studying the Hopf duality between the quantum algebras Fun p,q (GL(2)) and U p,q (gl(2)), the Hopf structure of U p,q (gl(1/1)), dual to Fun p,q (GL(1/1)), is derived and the corresponding universal Τ-matrix of Fun p,q (GL(1/1)), embodying the suitably modified exponential relationship U p,q (gl(1/1)) → Fun p,q (GL(1/1)), is obtained. (author). 10 refs

Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers.

Science.gov (United States)

Yuzaki, Michisuke

2010-07-01

Several C1q family members, especially the Cbln and C1q-like subfamilies, are highly and predominantly expressed in the central nervous system. Cbln1, a member of the Cbln subfamily, plays two unique roles at parallel fiber (PF)-Purkinje cell synapses in the cerebellum: the formation and stabilization of synaptic contact, and the control of functional synaptic plasticity by regulating the postsynaptic endocytotic pathway. The delta2 glutamate receptor (GluD2), which is predominantly expressed in Purkinje cells, plays similar critical roles in the cerebellum. In addition, viral expression of GluD2 or the application of recombinant Cbln1 induces PF-Purkinje cell synaptogenesis in vitro and in vivo. Antigen-unmasking methods were necessary to reveal the immunoreactivities for endogenous Cbln1 and GluD2 at the synaptic junction of PF synapses. We propose that Cbln1 and GluD2 are located at the synaptic cleft, where various proteins undergo intricate molecular interactions with each other, and serve as a bidirectional synaptic organizer. © The Author (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

Directory of Open Access Journals (Sweden)

Peizhen Hu

Full Text Available We reported (PLoS One 6 (12:e28670, 2011 that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1 expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

Approximate Q.C.D. lower bound for the bag constant B

International Nuclear Information System (INIS)

Nielsen, H.B.

1978-01-01

Using an article by Savvidy from 1977 in which a state in Q.C.D. with lower energy than the perturbative vacuum was found, the author calculates an approximate lower bound for the M.I.T. bag constant B relative to the Q.C.D. coupling parameter Λ. With an M.I.T. bag constant Bsup(1/4)=145 MeV the author finds Λsub(P)<=0.89 GeV when the propagator of the gluon is used to renormalize the coupling constant. (Auth.)

Requirements for class 1C, 2C, and 3C pressure-retaining components and supports in CANDU nuclear power plants

International Nuclear Information System (INIS)

1989-01-01

This Standard applies to pressure-retaining components of CANDU nuclear power plants that have a code classification of Class 1C, 2C or 3C. These are pressure-retaining components where, because of the design concept, the rules of the ASME Boiler and Pressure Vessel Code do not exist, are not applicable, or are not sufficient. The Standard provides rules for the design, fabrication, installation, examination and inspection of these components and supports. It provides rules intended to ensure the pressure-retaining integrity of components, not the operability. It also provides rules for the support of fueling machines. The Standard applies only to new construction prior to the plant being declared in service

C1 Inhibitor in Acute Antibody-Mediated Rejection Nonresponsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study.

Science.gov (United States)

Viglietti, D; Gosset, C; Loupy, A; Deville, L; Verine, J; Zeevi, A; Glotz, D; Lefaucheur, C

2016-05-01

Complement inhibitors have not been thoroughly evaluated in the treatment of acute antibody-mediated rejection (ABMR). We performed a prospective, single-arm pilot study to investigate the potential effects and safety of C1 inhibitor (C1-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute ABMR that is nonresponsive to conventional therapy. Kidney recipients with nonresponsive active ABMR and acute allograft dysfunction were enrolled between April 2013 and July 2014 and received C1-INH and IVIG for 6 months (six patients). The primary end point was the change in eGFR at 6 months after inclusion (M+6). Secondary end points included the changes in histology and DSA characteristics and adverse events as evaluated at M+6. All patients showed an improvement in eGFR between inclusion and M+6: from 38.7 ± 17.9 to 45.2 ± 21.3 mL/min/1.73 m(2) (p = 0.0277). There was no change in histological features, except a decrease in the C4d deposition rate from 5/6 to 1/6 (p = 0.0455). There was a change in DSA C1q status from 6/6 to 1/6 positive (p = 0.0253). One deep venous thrombosis was observed. In a secondary analysis, C1-INH patients were compared with a similar historical control group (21 patients). C1-INH added to IVIG is safe and may improve allograft function in kidney recipients with nonresponsive acute ABMR. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection.

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Kazuaki Yamanaka

Full Text Available The association of complement with the progression of acute T cell mediated rejection (ATCMR is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs in acute T-cell mediated rejection using rat and human renal allografts.We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP by immunohistochemical staining in human renal grafts and their clinical course.qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry, was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.

Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice.

Science.gov (United States)

Demyanenko, Ilya A; Popova, Ekaterina N; Zakharova, Vlada V; Ilyinskaya, Olga P; Vasilieva, Tamara V; Romashchenko, Valeria P; Fedorov, Artem V; Manskikh, Vasily N; Skulachev, Maxim V; Zinovkin, Roman A; Pletjushkina, Olga Yu; Skulachev, Vladimir P; Chernyak, Boris V

2015-07-01

The process of skin wound healing is delayed or impaired in aging animals. To investigate the possible role of mitochondrial reactive oxygen species (mtROS) in cutaneous wound healing of aged mice, we have applied the mitochondria-targeted antioxidant SkQ1. The SkQ1 treatment resulted in accelerated resolution of the inflammatory phase, formation of granulation tissue, vascularization and epithelization of the wounds. The wounds of SkQ1-treated mice contained increased amount of myofibroblasts which produce extracellular matrix proteins and growth factors mediating granulation tissue formation. This effect resembled SkQ1-induced differentiation of fibroblasts to myofibroblast, observed earlierin vitro. The Transforming Growth Factor beta (TGFb) produced by SkQ1-treated fibroblasts was found to stimulated motility of endothelial cells in vitro, an effect which may underlie pro-angiogenic action of SkQ1 in the wounds. In vitro experiments showed that SkQ1 prevented decomposition of VE-cadherin containing contacts and following increase in permeability of endothelial cells monolayer, induced by pro-inflammatory cytokine TNF. Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1. Our findings point to an important role of mtROS in pathogenesis of age-related chronic wounds.

Functions of Tenascin-C and Integrin alpha9beta1 in Mediating Prostate Cancer Bone Metastasis

Science.gov (United States)

2017-10-01

AWARD  NUMBER:          W81XWH-16-1-0523 TITLE:  Functions of Tenascin- C and Integrin alpha9beta1 in Mediating Prostate Cancer Bone Metastasis...Prostat Prostate Cancer  Bone Metastasis   5a.  CONTRACT  NUMBER   Functions of Tenascin- C and Integrin alpha9beta1 in Mediating Prostate Cancer...SUPPLEMENTARY  NOTES 14. ABSTRACT The purpose of this work is to dissect mechanisms responsible for interactions between integrin a9b1 and tenascin- C that are

Divergent Total Syntheses of (-)-Huperzine Q, (+)-Lycopladine B, (+)-Lycopladine C, and (-)-4-epi-Lycopladine D.

Science.gov (United States)

Hong, Benke; Hu, Dachao; Wu, Jinbao; Zhang, Jing; Li, Houhua; Pan, Yingming; Lei, Xiaoguang

2017-07-04

We report herein our synthetic efforts towards the divergent syntheses of (-)-huperzine Q (1), (+)-lycopladine B (2), (+)-lycopladine C (3), and (-)-lycopladine D (4). The 10-step total synthesis of (-)-huperzine Q (1) and the first total syntheses of (+)-lycopladines B (2) and C (3) were accomplished through a series of cascade reactions. Our approach involved a Michael addition/aldol/intramolecular C-alkylation sequence to forge the 6/9 spirocycle ring, and this was followed by an ethylene-accelerated carbonyl-olefin metathesis to construct the common 6/5/9 ring system. Finally, late-stage enamine bromofunctionalization enabled us to access (-)-huperzine Q (1), (+)-lycopladine B (2), and (+)-lycopladine C (3), and a tandem C4-epimerization/retro-Claisen condensation furnished (-)-4-epi-lycopladine D (63). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetically heterogeneous glioblastoma recurring with disappearance of 1p/19q losses: case report.

Science.gov (United States)

Ito, Motokazu; Wakabayashi, Toshihiko; Natsume, Atsushi; Hatano, Hisashi; Fujii, Masazumi; Yoshida, Jun

2007-07-01

Intratumor heterogeneity is of great importance in many clinical aspects of glioma biology, including tumor grading, therapeutic response, and recurrence. Modifications in the genetic features of a specific primary tumor recurring after chemo- and radiotherapy are poorly understood. We report a recurrent glioblastoma case exhibiting loss of heterozygosity (LOH) on chromosome 10q, while the primary tumor exhibited heterogeneity in the LOH status of 1p, 19q, and 10q. To determine the relationship between such modifications and heterogeneous chemosensitivity, primary cultured cells heterogeneously showing 1p/19q/10q losses were established from a surgical specimen of oligoastrocytoma and were treated with chemotherapeutic agents. A 46-year-old woman with a 1-month history of headache and visual disturbances presented to our institution. A right temporoparietal craniotomy and gross total resection were performed. The pathological diagnosis was glioblastoma multiforme with oligodendroglial components. Whereas LOH on 10q was identified at all tumor sites, only the oligodendroglial components exhibited LOH on 1p and 19q. The tumor recurred 6 months after postoperative chemotherapy using interferon-beta and ranimustine, as well as a course of fractionated external-beam radiotherapy (total dose, 60 Gy). Gene analysis revealed no 1p/19q allelic losses but only 10q LOH. Intratumor heterogeneity might be explained by the presence of more than one subclone in the primary tumor. Here, the tumor cells exhibiting 1p/19q LOH with high chemosensitivity might have been killed by the adjuvant therapy and those exhibiting 10q LOH with chemoresistance recurred. This study and our preliminary laboratory findings might suggest an approach to brain tumor physiology, diagnosis, and therapy.

Qq(Q-bar)(q-bar)' states in chiral SU(3) quark model

International Nuclear Information System (INIS)

Zhang Haixia; Zhang Min; Zhang Zongye

2007-01-01

We study the masses of Qq(Q-bar)(q-bar)' states with J PC =0 ++ , 1 ++ , 1 +- and 2 ++ in the chiral SU(3) quark model, where Q is the heavy quark (c or b) and q(q') is the light quark (u,d or s). According to our numerical results, it is improbable to make the interpretation of [cn(c-bar)(n-bar)] 1 ++ and [cn(c-bar)(n-bar)] 2 ++ (n=u,d) states as X(3872) and Y(3940), respectively. However, it is interesting to find the tetraquarks in the bq(b-bar)(q-bar)' system. (authors)

Cold-Induced Ascites in Broilers: Effects of Vitamin C and Coenzyme Q10

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MH Nemati

Full Text Available ABSTRACT We hypothesized that the supplementation of vitamin C (Vit. C and coenzyme Q10 (CoQ10 alone or in combination could reduce the negative effects of cold stress in broilers. Four hundred male chicks were exposed for 24 h to cold stress (15 ºC starting from 15d of age, while a positive control group (PC, 100 birds was kept under normal temperature condition. The experimental groups under cold stress (four treatments in 5 replicates of 20 birds were: negative control (NC, basal diet, Vit. C (basal diet + 300 mg/kg Vit. C, CoQ10 (basal diet + 40 mg/kg CoQ10 and Vit. C plus CoQ10 (basal diet + Vit. C+ CoQ10at above mentioned doses. Vit. C or CoQ10 supplementation were restored (p<0.01 performance and lowered (p<0.01 ascites mortality. Blood hematocrit and hemoglobin concentration were decreased (p<0.01 to the level comparable to PC by Vit. C supplementation. Lower plasma concentrations of thyroxin (T4 and higher triiodothyronine (T3 were observed in NC birds (p<0.01 and were not affected by Vit. C or CoQ10. In conclusion, supplementation of Vit. C or CoQ10 in diet of broilers under cold stress conditions resulted improved performance parameters (body weight and feed conversion ratio and ascites related traits (low red blood cell count, hematocrit, T3, and heart weights and high T4. No additional benefit was observed by combination of Vit. C and CoQ10.

Silver-mediated oxidative C-H difluoromethylation of phenanthridines and 1,10-phenanthrolines.

Science.gov (United States)

Zhu, Sheng-Qing; Xu, Xiu-Hua; Qing, Feng-Ling

2017-10-17

A silver-mediated oxidative difluoromethylation of phenanthridines and 1,10-phenanthrolines with TMSCF 2 H is disclosed. This C-H difluoromethylation of N-containing polycyclic aromatics constitutes an efficient method for the regioselective synthesis of difluoromethylated N-heterocycles.

SVZ⊕1/q{sup 2}-expansion versus some QCD holographic models

Energy Technology Data Exchange (ETDEWEB)

Jugeau, F., E-mail: frederic.jugeau@if.ufrj.br [Instituto de Física, Universidade Federal do Rio de Janeiro, Caixa Postal 68528, RJ 21941-972, Rio de Janeiro (Brazil); Narison, S., E-mail: snarison@yahoo.fr [Laboratoire Particules et Univers de Montpellier, CNRS-IN2P3, Case 070, Place Eugène Bataillon, 34095 Montpellier (France); Ratsimbarison, H., E-mail: herysedra@yahoo.fr [Institute of High-Energy Physics of Madagascar (iHEP-MAD), University of Antananarivo (Madagascar)

2013-05-13

Considering the classical two-point correlators built from (axial-) vector, scalar q{sup ¯}q and gluonium currents, we confront results obtained using the SVZ⊕1/q{sup 2}-expansion to the ones from some QCD holographic models in the Euclidean region and with negative dilaton Φ{sub i}(z)=−|c{sub i}{sup 2}|z{sup 2}. We conclude that the presence of the 1/q{sup 2}-term in the SVZ-expansion due to a tachyonic gluon mass appears naturally in the Minimum Soft-Wall (MSW) and the Gauge/String Dual (GSD) models which can also reproduce semi-quantitatively some of the higher dimension condensate contributions appearing in the OPE. The Hard-Wall model shows a large departure from the SVZ⊕1/q{sup 2}-expansion in the vector, scalar and gluonium channels due to the absence of any power corrections. The equivalence of the MSW and GSD models is manifest in the vector channel through the relation of the dilaton parameter with the tachyonic gluon mass. For approximately reproducing the phenomenological values of the dimension d=4,6 condensates, the holographic models require a tachyonic gluon mass (α{sub s}/π)λ{sup 2}≈−(0.12–0.14) GeV{sup 2}, which is about twice the fitted phenomenological value from e{sup +}e{sup −} data. The relation of the inverse length parameter c{sub i} to the tachyonic gluon mass also shows that c{sub i} is channel dependent but not universal for a given holographic model. Using the MSW model and M{sub ρ}=0.78 GeV as input, we predict a scalar q{sup ¯}q mass M{sub S}≈(0.95–1.10) GeV and a scalar gluonium mass M{sub G}≈(1.1–1.3) GeV.

Dependence of Brown Adipose Tissue Function on CD36-Mediated Coenzyme Q Uptake

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Courtney M. Anderson

2015-02-01

Full Text Available Brown adipose tissue (BAT possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ. While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency. However, which tissues depend on exogenous CoQ uptake as well as the mechanism by which CoQ is taken up by cells and the role of this process in BAT function are not well understood. Here, we report that the scavenger receptor CD36 drives the uptake of CoQ by BAT and is required for normal BAT function. BAT from mice lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered lipid metabolism, mitochondrial dysfunction, and defective nonshivering thermogenesis. Together, these data reveal an important new role for the systemic transport of CoQ to BAT and its function in thermogenesis.

A feedback regulatory model for RifQ-mediated repression of rifamycin export in Amycolatopsis mediterranei.

Science.gov (United States)

Lei, Chao; Wang, Jingzhi; Liu, Yuanyuan; Liu, Xinqiang; Zhao, Guoping; Wang, Jin

2018-01-29

Due to the important role of rifamycin in curing tuberculosis infection, the study on rifamycin has never been stopped. Although RifZ, which locates within the rifamycin biosynthetic cluster, has recently been characterized as a pathway-specific regulator for rifamycin biosynthesis, little is known about the regulation of rifamycin export. In this work, we proved that the expression of the rifamycin efflux pump (RifP) was regulated by RifQ, a TetR-family transcriptional regulator. Deletion of rifQ had little impact on bacterial growth, but resulted in improved rifamycin production, which was consistent with the reverse transcription PCR results that RifQ negatively regulated rifP's transcription. With electrophoretic mobility shift assay and DNase I Footprinting assay, RifQ was found to directly bind to the promoter region of rifP, and a typical inverted repeat was identified within the RifQ-protected sequences. The transcription initiation site of rifP was further characterized and found to be upstream of the RifQ binding sites, well explaining the RifQ-mediated repression of rifP's transcription in vivo. Moreover, rifamycin B (the end product of rifamycin biosynthesis) remarkably decreased the DNA binding affinity of RifQ, which led to derepression of rifamycin export, reducing the intracellular concentration of rifamycin B as well as its toxicity against the host. Here, we proved that the export of rifamycin B was repressed by RifQ in Amycolatopsis mediterranei, and the RifQ-mediated repression could be specifically relieved by rifamycin B, the end product of rifamycin biosynthesis, based on which a feedback model was proposed for regulation of rifamycin export. With the findings here, one could improve the antibiotic yield by simply inactivating the negative regulator of the antibiotic transporter.

A study on the crustal Q-structure of the Korea Peninsula

International Nuclear Information System (INIS)

Chung, Tae Woong; Lee, Won Sang; Yoo, Seung Hoon; Yu, Hyun Jae; Cho, Kwang Hyun; E, Sang Hion; Yun, Sook Young; Chung, Soon Won; Lee, Joon Hee; Kim, Sun Ju

2004-12-01

For reliable seismotectonic provinces needed by the design of Nuclear Power Plant, we studied amplitude attenuation of Lg and coda waves for South Korea. For the analysis of Q Lg -1 , we applied the source pair/receiver pair method to 39 Korea earthquakes and 32 far-regional earthquakes, and obtained values for the frequencies of 0.375, 0.75, 1.5, 3 and 6 Hz. We also estimated Q C from 574 NS-component seismograms with epicentral distances less than 100 km, by using single scattering method at the center frequencies of 1 Hz, 1.5 Hz, 3 Hz, 6 Hz, 9 Hz, 12 Hz, 15 Hz and 18 Hz. Then, we calculated Q O values applying on Q C = Q O f n . The obtained Q Lg -1 for all frequencies are less than 0.002, which is a reasonable value for a seismically inactive region. In particular, the results at 1.5 and 3 Hz show very reliable values. The coda values range between 80 to 300, and agree with those of the eastern China at western border. Our results of Q Lg -1 and Q C will provide information on the seismotectonic province for not only South Korea but eastern Asia. In addition, the spatial distribution of Coda Q O will be used for the analysis of seismicity including potential seismic hazard in South Korea

26 CFR 1.414(q)-1T - Highly compensated employee (temporary).

Science.gov (United States)

2010-04-01

...-10Definition of officer and rules on inclusion of officers in highly compensated group. Q&A-11Rules with... rules for permanent and total disability and employee stock ownership plans respectively). (c) Other... pursuant to section 401(c)(1). This rule with respect to the inclusion of certain self-employed individuals...

Dicty_cDB: Contig-U06794-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available opus laevis N-acetyltransferase... 179 7e-44 ( P41227 ) RecName: Full=N-terminal acetyltransferase compl...P2... 178 1e-43 (Q9QY36) RecName: Full=N-terminal acetyltransferase complex ARD1... 178 1e-43 AK009697_1( AK...3 (Q9UTI3) RecName: Full=N-terminal acetyltransferase A complex ca... 174 2e-42 D...( AL672002 |pid:none) Mouse DNA sequence from clone RP2... 152 6e-36 ( P07347 ) RecName: Full=N-terminal acetyltransferase A compl...867 |pid:none) Methanococcus maripaludis C6, c... 55 2e-06 ( Q03503 ) RecName: Full=N-terminal acetyltransferase C compl

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

Science.gov (United States)

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

2016-01-01

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

Surface-bound capsular polysaccharide of type Ia group B Streptococcus mediates C1 binding and activation of the classic complement pathway

International Nuclear Information System (INIS)

Levy, N.J.; Kasper, D.L.

1986-01-01

The role of surface-bound type Ia group B Streptococcus (GBS) capsular polysaccharide in anti-body-independent binding of C1 and activation of the classic component pathway was investigated. In a radiolabeled bacterial-polymorphonuclear leukocyte (PMN) association assay, a measure of bacterial opsonization, preincubation of 3 H-type Ia GBS with purified F(ab') 2 to the organism blocked the association of the bacteria with PMN', and the inhibitory effect was dose dependent. The specificity of F(ab') 2 blocking was shown after adsorption of F(ab') 2 with type Ia polysaccharide-sensitized erythrocytes. Polysaccharide-adsorbed F(ab') 2 had a 70% decrease in ability to block the association of bacteria with PMN. Neuraminidase digestion removed 80% of the terminal sialic acid residues from the native polysaccharide. These neuraminidase-digested organisms had a 72% decrease in binding and transfer of purified C1 compared with non-enzyme-treated organisms. Type Ia capsular polysaccharide bound to sheep erythrocytes promoted classic complement pathway-mediated hemolysis of the cells. The role of C1 inhibitor (INH) in modulation of C1 activation by the organisms was investigated. The possibility existed that the C1 INH could be bound by the bacteria, allowing C1 activation to occur in the fluid phase. The inhibitor was purified from human serum, and its activity was measured before and after incubation with type Ia GBS. The organisms had no effect on C1 INH activity. Thus surface-bound capsular polysacchardie of type Ia GBS mediates C1 binding and classic pathway activation, and this does not involve the C1 INH

Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.

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Jong Hyun Kim

2010-03-01

Full Text Available Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated.Here, we found that AMPK-induced phospholipase D1 (PLD1 activation is required for (14C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT stimulates PLD activity, while AMPK-dominant negative (DN inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA, which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator regulate (14C-glucose uptake and cell surface glucose transport (GLUT 4 through ERK stimulation by AMPK-mediated PLD1 activation.These results suggest that AMPK-mediated PLD1 activation is required for (14C

Dicty_cDB: Contig-U09615-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U09615-1 gap included 1134 3 4459395 4458259 MINUS 1 2 U09615 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Show Contig...-U09615-1 Contig ID Contig-U09615-1 Contig update 2002. 9.13 Contig sequence >Contig-U09615-1 (Contig-U09615-1Q) /CSM_Contig/Contig-U0961...TGCAAGATTAGAAAGATTAGAAAAAGATGCTATGCTAAAAATA Gap gap included Contig length 1134 Chromosome number (1..6, M) ...*wcnlyfrcre*emgkcn iefhiintrfkiwphrcidtighnvgicw**fnfecsfisleiqyrv**mgirfkyw*ww s*c*irpyfnnhafqyydyiwwskfwh*...4. 6.10 Homology vs CSM-cDNA Query= Contig-U09615-1 (Contig-U09615-1Q) /CSM_Contig/Contig-U09615-1Q.Seq.d (1

Electron removal from H and He atoms in collisions with C q+ , O q+ ions

Science.gov (United States)

Janev, R. K.; McDowell, M. R. C.

1984-06-01

Cross sections for electron capture and ionisation in collision of partially and completely stripped C q+ , N q+ and O q+ ions with hydrogen and helium atoms have been calculated at selected energies. The classical trajectory Monte Carlo method was used with a variable-charge pseudopotential to describe the interaction of the active electron with the projectile ion. A scalling relationship has been derived for the electron removal (capture and ionisation) cross section which allows a unifield representation of the data.

Numerical study of Q-ball formation in gravity mediation

International Nuclear Information System (INIS)

Hiramatsu, Takashi; Kawasaki, Masahiro; Takahashi, Fuminobu

2010-01-01

We study Q-ball formation in the expanding universe on 1D, 2D and 3D lattice simulations. We obtain detailed Q-ball charge distributions, and find that the distribution is peaked at Q 3D peak ≅ 1.9 × 10 −2 (|Φ in |/m) 2 , which is greater than the existing result by about 60%. Based on the numerical simulations, we discuss how the Q-ball formation proceeds. Also we make a comment on possible deviation of the charge distributions from what was conjectured in the past

Dicty_cDB: Contig-U08861-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U08861-1 gap included 1295 5 2877914 2879217 PLUS 1 2 U08861 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Show Contig...-U08861-1 Contig ID Contig-U08861-1 Contig update 2002. 9.13 Contig sequence >Contig-U08861-1 (Contig-U08861-1Q) /CSM_Contig/Contig-U08861...CACATTATAAAGTACCAAATAAGTTATTAATTTTAGAAAATA AATTCCAAAGAATGCAATGTCTAAAGTTAATAAAAAAGAATACTAAAATA TTTTC Gap gap included Contig...k**iwsryccnhcl*kkqkttnef*r i*nql*tkistl*stk*vinfrk*ipknamskvnkkey*nif own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig...-U08861-1 (Contig-U08861-1Q) /CSM_Contig/Contig-U08861-1Q.Seq.d (1305 letters) Database: C

Prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18(q10;q10del(18(q11.1q12.1del(18(q22.1q22.3 presenting as apparent isochromosome 18q in a fetus with holoprosencephaly

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2011-06-01

Conclusion: Concomitant monosomy 18p and trisomy 18q can be associated with holoprosencephaly and abnormal maternal serum screening results. Array-comparative genomic hybridization, fluorescence in situ hybridization, and quantitative fluorescent polymerase chain reaction are useful in genetic counseling of prenatally detected isochromosomes by providing information on the origin and genetic components of the isochromosome.

Axino dark matter and baryon number asymmetry production by the Q-ball decay in gauge mediation

Energy Technology Data Exchange (ETDEWEB)

Kasuya, Shinta [Department of Mathematics and Physics, Kanagawa University, Kanagawa 259-1293 (Japan); Kawakami, Etsuko; Kawasaki, Masahiro, E-mail: kasuya@kanagawa-u.ac.jp, E-mail: kwkm@icrr.u-tokyo.ac.jp, E-mail: kawasaki@icrr.u-tokyo.ac.jp [Institute for Cosmic Ray Research, University of Tokyo, Chiba 277-8582 (Japan)

2016-03-01

We investigate the Q-ball decay into the axino dark matter in the gauge-mediated supersymmetry breaking. In our scenario, the Q ball decays mainly into nucleons and partially into axinos to account respectively for the baryon asymmetry and the dark matter of the universe. The Q ball decays well before the big bang nucleosynthesis so that it is not affected by the decay. We show the region of the parameters which realizes this scenario.

Vibrio cholerae interactions with Mytilus galloprovincialis hemocytes mediated by serum components.

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Laura eCanesi

2013-12-01

Full Text Available Edible bivalves (e.g., mussels, oysters can accumulate large amount of bacteria in their tissues and act as passive carriers of pathogens to humans. Bacterial persistence inside bivalves depends, at least in part, on hemolymph anti-bacterial activity that is exerted by both serum soluble factors and phagocytic cells (i.e., the hemocytes. It was previously shown that Mytilus galloprovincialis hemolymph serum contains opsonins that mediate D-mannose-sensitive interactions between hemocytes and V. cholerae O1 El Tor bacteria that carry the Mannose–Sensitive Hemagglutinin (MSHA. These opsonins enhance phagocytosis and killing of vibrios by facilitating their binding to hemocytes. Since V. cholerae strains not carrying the MSHA ligand (O1 classical, non O1/O139 are present in coastal water and can be entrapped by mussels, we studied whether in mussel serum, in addition to opsonins directed towards MSHA, other components can mediate opsonization of these bacteria. By comparing interactions of O1 classical and non O1/O139 strains with hemocytes in ASW and serum, it was found that M. galloprovincialis serum contains components that increase by at approximately two fold their adhesion to, association with and killing by hemocytes. Experiments conducted with high and low molecular mass fractions obtained by serum ultrafiltration indicated that these compounds have molecular mass higher than 5000 Da. Serum exposure to high temperature (80°C abolished its opsonizing capability suggesting that the involved serum active components are of protein nature. Further studies are needed to define the chemical properties and specificity of both the involved bacterial ligands and hemolymph opsonins. This information will be central not only to better understand V. cholerae ecology, but also to improve current bivalve depuration practices and properly protect human health.

PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP.

Science.gov (United States)

Yeom, Miji; Lee, HansongI; Shin, Seoungwoo; Park, Deokhoon; Jung, Eunsun

2018-03-23

Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP

Directory of Open Access Journals (Sweden)

Miji Yeom

2018-03-01

Full Text Available Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1 and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

De novo microdeletions of chromosome 6q14.1-q14.3 and 6q12.1-q14.1 in two patients with intellectual disability - further delineation of the 6q14 microdeletion syndrome and review of the literature

DEFF Research Database (Denmark)

Becker, Kerstin; Di Donato, Nataliya; Holder-Espinasse, Muriel

2012-01-01

with broad nasal tip, anteverted nares, long philtrum, and thin upper lip. In this study we describe two patients with overlapping 6q14 deletions presenting with developmental delay and characteristic dysmorphism. Molecular karyotyping using array CGH analysis revealed a de novo 8.9 Mb deletion at 6q14.1-q14.......3 and a de novo 11.3 Mb deletion at 6q12.1-6q14.1, respectively. We provide a review of the clinical features of twelve other patients with 6q14 deletions detected by array CGH analysis. By assessing all reported data we could not identify a single common region of deletion. Possible candidate genes in 6q14...

Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence.

Science.gov (United States)

Lin, Peng; Hartz, Sarah M; Wang, Jen-Chyong; Agrawal, Arpana; Zhang, Tian-Xiao; McKenna, Nicholas; Bucholz, Kathleen; Brooks, Andrew I; Tischfield, Jay A; Edenberg, Howard J; Hesselbrock, Victor M; Kramer, John R; Kuperman, Samuel; Schuckit, Marc A; Goate, Alison M; Bierut, Laura J; Rice, John P

2012-09-01

Excessive alcohol use is the third leading cause of preventable death and is highly correlated with alcohol dependence, a heritable phenotype. Many genetic factors for alcohol dependence have been found, but many remain unknown. In search of additional genetic factors, we examined the association between Diagnostic and StatisticalManual of Mental Disorders, Fourth Edition (DSM-IV) alcohol dependence and all common copy number variations (CNVs) with good reliability in the Study of Addiction: Genetics and Environment (SAGE). All participants in SAGE were interviewed using the Semi-Structured Assessment for the Genetics of Alcoholism, as a part of 3 contributing studies. A total of 2,610 non-Hispanic European American samples were genotyped on the Illumina Human 1M array. We performed CNV calling by CNVPartition, PennCNV, and QuantiSNP, and only CNVs identified by all 3 software programs were examined. Association was conducted with the CNV (as a deletion/duplication) as well as with probes in the CNV region. Quantitative polymerase chain reaction (qPCR) was used to validate the CNVs in the laboratory. CNVs in 6q14.1 (p = 1.04 × 10(-6)) and 5q13.2 (p = 3.37 × 10(-4)) were significantly associated with alcohol dependence after adjusting multiple tests. On chromosome 5q13.2, there were multiple candidate genes previously associated with various neurological disorders. The region on chromosome 6q14.1 is a gene desert that has been associated with mental retardation and language delay. The CNV in 5q13.2 was validated, whereas only a component of the CNV on 6q14.1 was validated by qPCR. Thus, the CNV on 6q14.1 should be viewed with caution. This is the first study to show an association between DSM-IV alcohol dependence and CNVs. CNVs in regions previously associated with neurological disorders may be associated with alcohol dependence. Copyright © 2012 by the Research Society on Alcoholism.

Q-balls in flat potentials

International Nuclear Information System (INIS)

Copeland, Edmund J.; Tsumagari, Mitsuo I.

2009-01-01

We study the classical and absolute stability of Q-balls in scalar field theories with flat potentials arising in both gravity-mediated and gauge-mediated models. We show that the associated Q-matter formed in gravity-mediated potentials can be stable against decay into their own free particles as long as the coupling constant of the nonrenormalizable term is small, and that all of the possible three-dimensional Q-ball configurations are classically stable against linear fluctuations. Three-dimensional gauge-mediated Q-balls can be absolutely stable in the thin-wall limit, but are completely unstable in the thick-wall limit.

Measuring molecular abundances in comet C/2014 Q2 (Lovejoy) using the APEX telescope

Science.gov (United States)

de Val-Borro, M.; Milam, S. N.; Cordiner, M. A.; Charnley, S. B.; Coulson, I. M.; Remijan, A. J.; Villanueva, G. L.

2018-02-01

Comet composition provides critical information on the chemical and physical processes that took place during the formation of the Solar system. We report here on millimetre spectroscopic observations of the long-period bright comet C/2014 Q2 (Lovejoy) using the Atacama Pathfinder Experiment (APEX) band 1 receiver between 2015 January UT 16.948 and 18.120, when the comet was at heliocentric distance of 1.30 au and geocentric distance of 0.53 au. Bright comets allow for sensitive observations of gaseous volatiles that sublimate in their coma. These observations allowed us to detect HCN, CH3OH (multiple transitions), H2CO and CO, and to measure precise molecular production rates. Additionally, sensitive upper limits were derived on the complex molecules acetaldehyde (CH3CHO) and formamide (NH2CHO) based on the average of the strongest lines in the targeted spectral range to improve the signal-to-noise ratio. Gas production rates are derived using a non-LTE molecular excitation calculation involving collisions with H2O and radiative pumping that becomes important in the outer coma due to solar radiation. We find a depletion of CO in C/2014 Q2 (Lovejoy) with a production rate relative to water of 2.0 per cent, and relatively low abundances of Q(HCN)/Q(H2O), 0.1 per cent, and Q(H2CO)/Q(H2O), 0.2 per cent. In contrast, the CH3OH relative abundance Q(CH3OH)/Q(H2O), 2.2 per cent, is close to the mean value observed in other comets. The measured production rates are consistent with values derived for this object from other facilities at similar wavelengths taking into account the difference in the fields of view. Based on the observed mixing ratios of organic molecules in four bright comets including C/2014 Q2, we find some support for atom addition reactions on cold dust being the origin of some of the molecules.

Dicty_cDB: Contig-U13254-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U13254-1 no gap 575 5 203798 203233 MINUS 1 1 U13254 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Show Contig...-U13254-1 Contig ID Contig-U13254-1 Contig update 2002.12.18 Contig sequence >Contig-U13254-1 (Contig...-U13254-1Q) /CSM_Contig/Contig-U13254-1Q.Seq.d AAATAATTTATTTAATTTTAAAATTAATAGATAAAAAGATGGAAATGATA A...CATTTTAACATTATTGGATAAT GTCAATGATTGGCCAANNNNNNNNN Gap no gap Contig length 575 Chromosome number (1..6, M) 5 ...2004. 6.10 Homology vs CSM-cDNA Query= Contig-U13254-1 (Contig-U13254-1Q) /CSM_Contig/Contig-U13254-1Q.Seq.d

Λ2 of effective q.c.d. in the minimal subtraction scheme

International Nuclear Information System (INIS)

Miller, R.D.C.; McKellar, B.H.J.

1981-01-01

Practical Q.C.D. is an effective field theory in that unexcited heavy quarks are decoupled from the theory. To predict effects dependent on the heavy quarks one needs the R.G. invariants of the effective Q.C.D. in which they are retained. The R.G. invariants Λsub(n) 2 of the effective n flavour Q.C.D. are calculated from the observed Λ 4 2

Proteomic analysis of cAMP-mediated signaling during differentiation of 3 T3-L1 preadipocytes

DEFF Research Database (Denmark)

Borkowski, Kamil; Wrzesinski, Krzysztow; Rogowska-Wrzesinska, Adelina

2014-01-01

Initiation of adipocyte differentiation is promoted by the synergistic action of insulin/insulin-like growth factor, glucocorticoids, and agents activating cAMP-dependent signaling. The action of cAMP is mediated via PKA and Epac, where at least part of the PKA function relates to strong repression...... a comprehensive evaluation of Epac-mediated processes and their interplay with PKA during the initiation of 3 T3-L1 preadipocyte differentiation using a combination of proteomics, molecular approaches, and bioinformatics. Proteomic analyses revealed 7 proteins specifically regulated in response to Epac activation......-dependent signaling thereby adding a novel facet to our understanding of cAMP-mediated potentiation of adipocyte differentiation....

Dicty_cDB: Contig-U10823-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U10823-1 gap included 1750 1 3559501 3561234 PLUS 85 124 U10823 0 5 0 30 1 0... 0 20 0 29 0 0 0 0 Show Contig-U10823-1 Contig ID Contig-U10823-1 Contig update 2002.12.18 Contig sequence >Contig-U10823-1 (Contig...-U10823-1Q) /CSM_Contig/Contig-U10823-1Q.Seq.d ACTGTTGGCCTACTGGTATTTTTGGTAGTGTGTTAAAA...CAACAAATAAAATTAAAATTA GTTATATTTTTTTTAAATTAAAAAAAAAAATAAAAAAAATAAATTATTTA TTAAATTTTT Gap gap included Contig ...4. 6.10 Homology vs CSM-cDNA Query= Contig-U10823-1 (Contig-U10823-1Q) /CSM_Contig/Contig-U10823-1Q.Seq.d (1

Human genes for complement components C1r and C1s in a close tail-to-tail arrangement

International Nuclear Information System (INIS)

Kusumoto, H.; Hirosawa, S.; Salier, J.P.; Hagen, F.S.; Kurachi, K.

1988-01-01

Complementary DNA clones for human C1s were isolated from cDNA libraries that were prepared with poly(A) + RNAs of human liver and HepG2 cells. A clone with the largest cDNA insert of 2,664 base pairs (bp) was analyzed for its complete nucleotide sequence. It contained 202 bp of a 5' untranslated region, 45 bp of coding for a signal peptide (15 amino acid residues), 2,019 bp for complement component C1s zymogen (673 amino acid residues), 378 bp for a 3' untranslated region, a stop codon, and 17 bp of a poly(A) tail. The amino acid sequence of C1s was 40.5% identical to that of C1r, with excellent matches of tentative disulfide bond locations conserving the overall domain structure of C1r. DNA blotting and sequencing analyses of genomic DNA and of an isolated genomic DNA clone clearly showed that the human genes for C1r and C1s are closely located in a tail-to-tail arrangement at a distance of about 9.5 kilobases. Furthermore, RNA blot analyses showed that both C1r and C1s genes are primarily expressed in liver, whereas most other tissues expressed both C1r and C1s genes at much lower levels (less than 10% of that in liver). Multiple molecular sizes of specific mRNAs were observed in the RNA blot analyses for both C1r and C1s, indicating that alternative RNA processing(s), likely an alternative polyadenylylation, might take place for both genes

Promotion of growth by Coenzyme Q10 is linked to gene expression in C. elegans.

Science.gov (United States)

Fischer, Alexandra; Niklowitz, Petra; Menke, Thomas; Döring, Frank

2014-10-03

Coenzyme Q (CoQ, ubiquinone) is an essential component of the respiratory chain, a cofactor of pyrimidine biosynthesis and acts as an antioxidant in extra mitochondrial membranes. More recently CoQ has been identified as a modulator of apoptosis, inflammation and gene expression. CoQ deficient Caenorhabditis elegans clk-1 mutants show several phenotypes including a delayed postembryonic growth. Using wild type and two clk-1 mutants, here we established an experimental set-up to study the consequences of endogenous CoQ deficiency or exogenous CoQ supply on gene expression and growth. We found that a deficiency of endogenous CoQ synthesis down-regulates a cluster of genes that are important for growth (i.e., RNA polymerase II, eukaryotic initiation factor) and up-regulates oxidation reactions (i.e., cytochrome P450, superoxide dismutase) and protein interactions (i.e., F-Box proteins). Exogenous CoQ supply partially restores the expression of these genes as well as the growth retardation of CoQ deficient clk-1 mutants. On the other hand exogenous CoQ supply does not alter the expression of a further sub-set of genes. These genes are involved in metabolism (i.e., succinate dehydrogenase complex), cell signalling or synthesis of lectins. Thus, our work provides a comprehensive overview of genes which can be modulated in their expression by endogenous or exogenous CoQ. As growth retardation in CoQ deficiency is linked to the gene expression profile we suggest that CoQ promotes growth via gene expression. Copyright © 2014 Elsevier Inc. All rights reserved.

Dicty_cDB: Contig-U16093-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U16093-1 gap included 1020 2 4899973 4899063 MINUS 29 31 U16093 7 0 0 0 0 2 ...18 0 0 0 0 0 2 0 Show Contig-U16093-1 Contig ID Contig-U16093-1 Contig update 2004. 6.11 Contig sequence >Contig-U16093-1 (Contig...-U16093-1Q) /CSM_Contig/Contig-U16093-1Q.Seq.d TTTTTTTTTTTTTTTTTAATTTTTTTTTTTCATAAAACTT...AAAATTAAATT Gap gap included Contig length 1020 Chromosome number (1..6, M) 2 Chr...pdate 2004. 6.23 Homology vs CSM-cDNA Query= Contig-U16093-1 (Contig-U16093-1Q) /CSM_Contig/Contig-U16093-1Q

Analysis of autism susceptibility gene loci on chromosomes 1p, 4p, 6q, 7q, 13q, 15q, 16p, 17q, 19q and 22q in Finnish multiplex families.

Science.gov (United States)

Auranen, M; Nieminen, T; Majuri, S; Vanhala, R; Peltonen, L; Järvelä, I

2000-05-01

The role of genetic factors in the etiology of the autistic spectrum of disorders has clearly been demonstrated. Ten chromosomal regions, on chromosomes 1p, 4p, 6q, 7q, 13q, 15q, 16p, 17q, 19q and 22q have potentially been linked to autism.1-8 We have analyzed these chromosomal regions in a total of 17 multiplex families with autism originating from the isolated Finnish population by pairwise linkage analysis and sib-pair analysis. Mild evidence for putative contribution was found only with the 1p chromosomal region in the susceptibility to autism. Our data suggest that additional gene loci exist for autism which will be detectable in and even restricted to the isolated Finnish population.

Dicty_cDB: Contig-U06829-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U06829-1 no gap 449 5 4394444 4394893 PLUS 1 1 U06829 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Show Contig...-U06829-1 Contig ID Contig-U06829-1 Contig update 2001. 8.30 Contig sequence >Contig-U06829-1 (Contig...-U06829-1Q) /CSM_Contig/Contig-U06829-1Q.Seq.d GTAAAAGAATGTAATGAAAATGAAAAAATTAATTTTATAATAAAATTATT ...ATGATTTAGAATTGGTACAATTAGTTTA Gap no gap Contig length 449 Chromosome number (1..6, M) 5 Chromosome length 50...04. 6.10 Homology vs CSM-cDNA Query= Contig-U06829-1 (Contig-U06829-1Q) /CSM_Contig/Contig-U06829-1Q.Seq.d (

Dicty_cDB: Contig-U07021-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U07021-1 no gap 601 2 3862699 3862098 MINUS 1 2 U07021 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Show Contig...-U07021-1 Contig ID Contig-U07021-1 Contig update 2001. 8.30 Contig sequence >Contig-U07021-1 (Contig...-U07021-1Q) /CSM_Contig/Contig-U07021-1Q.Seq.d AAAAAAACAAAATGAATAAATTTAATATTACATCATTATTTATTATTTTA...TTTAATATATTCAGAAGGAAATTC TTATTTACAACAAAATTTCCCATTACTTTCTTANTTAAANTCCGTTAAAA T Gap no gap Contig length 601 C...QACCRTTQLFINYADNSFLDSAGFSPFGKVISGFNNTLNFYGGYGEEPDQSLIYSE GNSYLQQNFPLLSXLXSVK own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig

JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks

DEFF Research Database (Denmark)

Watanabe, Sugiko; Watanabe, Kenji; Akimov, Vyacheslav

2013-01-01

Chromatin ubiquitylation flanking DNA double-strand breaks (DSBs), mediated by RNF8 and RNF168 ubiquitin ligases, orchestrates a two-branch pathway, recruiting repair factors 53BP1 or the RAP80-BRCA1 complex. We report that human demethylase JMJD1C regulates the RAP80-BRCA1 branch of this DNA...

Treatment of CoQ(10 deficient fibroblasts with ubiquinone, CoQ analogs, and vitamin C: time- and compound-dependent effects.

Directory of Open Access Journals (Sweden)

Luis C López

2010-07-01

Full Text Available Coenzyme Q(10 (CoQ(10 and its analogs are used therapeutically by virtue of their functions as electron carriers, antioxidant compounds, or both. However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress.To test these concepts, we have evaluated the effects of CoQ(10, coenzyme Q(2 (CoQ(2, idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ(10 deficiency. A final concentration of 5 microM of each compound was chosen to approximate the plasma concentration of CoQ(10 of patients treated with oral ubiquinone. CoQ(10 supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ(10 deficient fibroblasts therein normalizing the bioenergetics status of the cells. Other compounds did not affect cellular bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production and oxidative stress-induced cell death were normalized by all supplements.THESE RESULTS INDICATE THAT: 1 pharmacokinetics of CoQ(10 in reaching the mitochondrial respiratory chain is delayed; 2 short-tail ubiquinone analogs cannot replace CoQ(10 in the mitochondrial respiratory chain under conditions of CoQ(10 deficiency; and 3 oxidative stress and cell death can be counteracted by administration of lipophilic or hydrophilic antioxidants. The results of our in vitro experiments suggest that primary CoQ(10 deficiencies should be treated with CoQ(10 supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ(2. Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present.

An S/T-Q cluster domain census unveils new putative targets under Tel1/Mec1 control

Directory of Open Access Journals (Sweden)

Cheung Hannah C

2012-11-01

Full Text Available Abstract Background The cellular response to DNA damage is immediate and highly coordinated in order to maintain genome integrity and proper cell division. During the DNA damage response (DDR, the sensor kinases Tel1 and Mec1 in Saccharomyces cerevisiae and ATM and ATR in human, phosphorylate multiple mediators which activate effector proteins to initiate cell cycle checkpoints and DNA repair. A subset of kinase substrates are recognized by the S/T-Q cluster domain (SCD, which contains motifs of serine (S or threonine (T followed by a glutamine (Q. However, the full repertoire of proteins and pathways controlled by Tel1 and Mec1 is unknown. Results To identify all putative SCD-containing proteins, we analyzed the distribution of S/T-Q motifs within verified Tel1/Mec1 targets and arrived at a unifying SCD definition of at least 3 S/T-Q within a stretch of 50 residues. This new SCD definition was used in a custom bioinformatics pipeline to generate a census of SCD-containing proteins in both yeast and human. In yeast, 436 proteins were identified, a significantly larger number of hits than were expected by chance. These SCD-containing proteins did not distribute equally across GO-ontology terms, but were significantly enriched for those involved in processes related to the DDR. We also found a significant enrichment of proteins involved in telophase and cytokinesis, protein transport and endocytosis suggesting possible novel Tel1/Mec1 targets in these pathways. In the human proteome, a wide range of similar proteins were identified, including homologs of some SCD-containing proteins found in yeast. This list also included high concentrations of proteins in the Mediator, spindle pole body/centrosome and actin cytoskeleton complexes. Conclusions Using a bioinformatic approach, we have generated a census of SCD-containing proteins that are involved not only in known DDR pathways but several other pathways under Tel1/Mec1 control suggesting new

A cII-dependent promoter is located within the Q gene of bacteriophage lambda.

OpenAIRE

Hoopes, B C; McClure, W R

1985-01-01

We have found a cII-dependent promoter, PaQ, within the Q gene of bacteriophage lambda. Transcription experiments and abortive initiation assays performed in vitro showed that the promoter strength and the cII affinity of PaQ were comparable to the other cII-dependent lambda promoters, PE and PI. The location and leftward direction of PaQ suggests a possible role in the delay of lambda late-gene expression by cII protein, a phenomenon that has been called cII-dependent inhibition. We have con...

HTLV-1 Tax protects against CD95-mediated apoptosis by induction of the cellular FLICE-inhibitory protein (c-FLIP).

Science.gov (United States)

Krueger, Andreas; Fas, Stefanie C; Giaisi, Marco; Bleumink, Marc; Merling, Anette; Stumpf, Christine; Baumann, Sven; Holtkotte, Denise; Bosch, Valerie; Krammer, Peter H; Li-Weber, Min

2006-05-15

The HTLV-1 transactivator protein Tax is essential for malignant transformation of CD4 T cells, ultimately leading to adult T-cell leukemia/lymphoma (ATL). Malignant transformation may involve development of apoptosis resistance. In this study we investigated the molecular mechanisms by which HTLV-1 Tax confers resistance toward CD95-mediated apoptosis. We show that Tax-expressing T-cell lines derived from HTLV-1-infected patients express elevated levels of c-FLIP(L) and c-FLIP(S). The levels of c-FLIP correlated with resistance toward CD95-mediated apoptosis. Using an inducible system we demonstrated that both resistance toward CD95-mediated apoptosis and induction of c-FLIP are dependent on Tax. In addition, analysis of early cleavage of the BH3-only Bcl-2 family member Bid, a direct caspase-8 substrate, revealed that apoptosis is inhibited at a CD95 death receptor proximal level in Tax-expressing cells. Finally, using siRNA we directly showed that c-FLIP confers Tax-mediated resistance toward CD95-mediated apoptosis. In conclusion, our data suggest an important mechanism by which expression of HTLV-1 Tax may lead to immune escape of infected T cells and, thus, to persistent infection and transformation.

Possible Heavy Tetraquarks qQ(-q-Q), qq(-Q-Q) and qQ(-Q-Q)%可能的qQ(-q-Q),qq(-Q-Q)和qQ(-Q-Q)重四夸克态

Institute of Scientific and Technical Information of China (English)

崔莹; 陈晓林; 邓卫真; 朱世琳

2007-01-01

Assuming X(3872) is a qc-q-c tetraquark and using its mass as input, we perform a schematic study of the masses of possible heavy tetraquarks using the color-magnetic interaction with the flavor symmetry breaking corrections.%假设X(3872)是一个qc(-q-c)四夸克态,并用它的质量作为输入,用具有味对称性破坏的色磁相互作用系统研究了可能的重四夸克态的质量谱.

RNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans.

Science.gov (United States)

Son, Heehwa G; Seo, Mihwa; Ham, Seokjin; Hwang, Wooseon; Lee, Dongyeop; An, Seon Woo A; Artan, Murat; Seo, Keunhee; Kaletsky, Rachel; Arey, Rachel N; Ryu, Youngjae; Ha, Chang Man; Kim, Yoon Ki; Murphy, Coleen T; Roh, Tae-Young; Nam, Hong Gil; Lee, Seung-Jae V

2017-03-09

Long-lived organisms often feature more stringent protein and DNA quality control. However, whether RNA quality control mechanisms, such as nonsense-mediated mRNA decay (NMD), which degrades both abnormal as well as some normal transcripts, have a role in organismal aging remains unexplored. Here we show that NMD mediates longevity in C. elegans strains with mutations in daf-2/insulin/insulin-like growth factor 1 receptor. We find that daf-2 mutants display enhanced NMD activity and reduced levels of potentially aberrant transcripts. NMD components, including smg-2/UPF1, are required to achieve the longevity of several long-lived mutants, including daf-2 mutant worms. NMD in the nervous system of the animals is particularly important for RNA quality control to promote longevity. Furthermore, we find that downregulation of yars-2/tyrosyl-tRNA synthetase, an NMD target transcript, by daf-2 mutations contributes to longevity. We propose that NMD-mediated RNA surveillance is a crucial quality control process that contributes to longevity conferred by daf-2 mutations.

Dicty_cDB: Contig-U15883-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available ndgk*kktrggygcwttniqfnq*ifne* q**fetnigvittfntiisitwfnfdangickcivistinsieyvtfigavlstnvti*k e*kqqk*q*e*iskfrgem...IA --- ---nnnnnnnnnnnkliihksiviiriqhsqivtqlnhtryhtimtigghphlvpkh*fl liiqpiliqlktitifyslmi...ab1. 38 0.33 2 ( DY330556 ) OB_MEa0005L07.f OB_MEa Ocimum basilicum cDNA clon... 38 0.36 2 ( EY305365 ) CAWX...ZGC_9 Danio rerio cDNA clo... 42 1.3 2 ( DY338804 ) OB_SEa09A12.r OB_SEa Ocimum basil...nnnnnnnflmqqhq qyqqqyqlmqqhyqqqlsqqhhqqvwvqiqlhvv*vvvvvvvvvvvvvvvi*pvelnqvv vvveekvdliimvmdmvmdhmvmvvkvqevhvvvniiythiytlnitsivi

Protective role of complement C3 against cytokine-mediated beta cell apoptosis

DEFF Research Database (Denmark)

Dos Santos, R. S.; Marroqui, L.; Grieco, F. A.

2017-01-01

Background and aims: Type 1 diabetes is a chronic autoimmune disease characterized by pancreatic islet inflammation and β-cell destruction by pro-inflammatory cytokines and other mediators. The complement system, a major component of the immune system, has been recently shown to also act in metab...... in metabolic organs, such as liver, adipose tissue, and pancreas. In the present study we identified complement C3 as an important hub of a cytokine-modified complement network in human islets and characterized the role of C3 in β-cell survival....

Dicty_cDB: Contig-U13065-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U13065-1 no gap 718 1 3561021 3561729 PLUS 1 1 U13065 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Show Contig...-U13065-1 Contig ID Contig-U13065-1 Contig update 2002.12.18 Contig sequence >Contig-U13065-1 (Contig...-U13065-1Q) /CSM_Contig/Contig-U13065-1Q.Seq.d NNNNNNNNNNCAATCAAAGCAATCAATGGTAAATTAACTTTGTTACCATT ...TGATTCAACTCTCTCTG TTTCAAATTTACAACTTGCTTTAGATGAATCCTTTGAAGTTGATTTTGTA TTATATTAAAAATTATCA Gap no gap Contig...kny own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U13065-1 (Contig-U13065-1Q) /CSM_Contig

Dicty_cDB: Contig-U15541-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U15541-1 gap included 2750 - - - - 634 1127 U15541 1 129 1 375 19 0 2 32 4 69 1 0 1 0 Show Contig...-U15541-1 Contig ID Contig-U15541-1 Contig update 2004. 6.11 Contig sequence >Contig-U15541-1 (Contig...-U15541-1Q) /CSM_Contig/Contig-U15541-1Q.Seq.d ATAATAAACGGTGAATACCTCGACTCCTAAATCGATGAAGACCGTAG...AAAAAT AAAAATAAAAATAAATAAATAATCATTTCATATTAATATTTTTTTTTATT TTTAAAAAAA Gap gap included Contig...ffyf*k own update 2004. 6.23 Homology vs CSM-cDNA Query= Contig-U15541-1 (Contig-U15541-1Q) /CSM_Contig/Contig

Dicty_cDB: Contig-U03367-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U03367-1 no gap 323 - - - - 2 1 U03367 0 0 0 0 0 0 0 0 0 0 0 0 1 1 Show Contig-U03367-1 Contig... ID Contig-U03367-1 Contig update 2001. 8.29 Contig sequence >Contig-U03367-1 (Contig-U03367-1Q) /CSM_Contig/Contig...TTGCGGGTTGGCAGGACTGTNGGNAGGCATGGNCATCGGTATNNTTGGAG ATGCTNGTGTGAGGGCGAATGCT Gap no gap Contig length 323 Chro...HLXXGLXCGLAGLXXGMXIGXXGDAXVRANA own update 2004. 6. 9 Homology vs CSM-cDNA Query= Contig-U03367-1 (Contig...-U03367-1Q) /CSM_Contig/Contig-U03367-1Q.Seq.d (323 letters) Database: CSM 6905 sequ

Dicty_cDB: Contig-U16086-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U16086-1 gap included 1018 - - - - 3 4 U16086 0 0 0 0 0 1 1 0 0 0 1 0 0 0 Show Contig-U16086-1 Contig... ID Contig-U16086-1 Contig update 2004. 6.11 Contig sequence >Contig-U16086-1 (Contig-U16086-1Q) /CSM_Contig.../Contig-U16086-1Q.Seq.d AATTTGATGAAGTAGTAGTAGAGGTAAAACATGTATCAAAACATTATAAG ATTGCAGG...ACTTGGATATAAATGAAG GTAGCTCATCAAATTTTTCAAATAATGATAATTTTAAATCGGTAGATCAA ATTACCAATGACCTTAGCCGTATTTTAT Gap gap included Contig...KSVDQI TNDLSRIL own update 2004. 6.23 Homology vs CSM-cDNA Query= Contig-U16086-1 (Contig-U16086-1Q) /CSM_Contig/Contig

Dicty_cDB: Contig-U13737-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U13737-1 no gap 672 6 1762420 1761754 MINUS 1 1 U13737 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Show Contig...-U13737-1 Contig ID Contig-U13737-1 Contig update 2002.12.18 Contig sequence >Contig-U13737-1 (Contig...-U13737-1Q) /CSM_Contig/Contig-U13737-1Q.Seq.d NNNNNNNNNNAAAATTAGAAAATGGTACAATTGTTTTTAGAGATATTTCA...AGAATAGAAGGAAAATAT AGATCAATGGGGTGGCACAACA Gap no gap Contig length 672 Chromosome...gwhn own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U13737-1 (Contig-U13737-1Q) /CSM_Contig/Contig

Dicty_cDB: Contig-U15058-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U15058-1 no gap 1987 4 4423139 4424727 PLUS 2 4 U15058 0 0 0 0 0 0 0 0 1 0 1 0 0 0 Show Contig...-U15058-1 Contig ID Contig-U15058-1 Contig update 2004. 6.11 Contig sequence >Contig-U15058-1 (Contig...-U15058-1Q) /CSM_Contig/Contig-U15058-1Q.Seq.d AAAAAAGGTTACTCACAAAGTTAAAGAAATCAATGAAAGATTTACCACCC...ACTCAAGGGGGTAGGAGAATAAAATCAACCGATTATCCAGGCNTTAAG CGACCTTTTTCCCAAAAAAAAAAGATGTTCAGAAAAT Gap no gap Contig len...srx*atffpkkkdvq k own update 2004. 6.23 Homology vs CSM-cDNA Query= Contig-U15058-1 (Contig-U15058-1Q) /CSM_Contig/Contig

Dicty_cDB: Contig-U09640-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U09640-1 gap included 1368 2 219988 218635 MINUS 4 5 U09640 0 0 2 0 0 0 0 0 0 0 0 0 1 1 Show Contig...-U09640-1 Contig ID Contig-U09640-1 Contig update 2002. 9.13 Contig sequence >Contig-U09640-1 (Contig...-U09640-1Q) /CSM_Contig/Contig-U09640-1Q.Seq.d ACTGTTGGCCTACTGGNAAAAAATAGTGTAATAATAACCAACAAT...AACAACAACAACAAAAACAAAAACAAATTTTAATT AAATAAAATAATAATATAAAATATAATA Gap gap included Contig...ate 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U09640-1 (Contig-U09640-1Q) /CSM_Contig/Contig

Dicty_cDB: Contig-U14745-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U14745-1 no gap 1780 6 3063854 3065579 PLUS 2 4 U14745 1 0 1 0 0 0 0 0 0 0 0 0 0 0 Show Contig...-U14745-1 Contig ID Contig-U14745-1 Contig update 2002.12.18 Contig sequence >Contig-U14745-1 (Contig...-U14745-1Q) /CSM_Contig/Contig-U14745-1Q.Seq.d GCGTCCGGACAATTTCAATAAAACAAATTTAAAAATAAATAATTTTTAAT...AATAAAATA ATTTAAATAAAAAAATATTTATTTTATTTTAAGATTAACAAAATAAAATA ATTTAAATAAAAAAATATTTATTTTAAAGA Gap no gap Contig...k*kniyfk own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U14745-1 (Contig-U14745-1Q) /CSM_Contig/Contig

Optical polarimetry of Comet NEAT C/2001 Q4

Science.gov (United States)

Ganesh, S.; Joshi, U. C.; Baliyan, K. S.

2009-06-01

Comet NEAT C/2001 Q4 was observed for linear polarization using the optical polarimeter mounted at the 1.2 m telescope at Mt. Abu Observatory, during the months of May and June 2004. Observations were conducted through the International Halley Watch narrow band (continuum) and BVR broad band filters. During the observing run the phase angle ranged from 85.6° in May to 55° in June. As expected, polarization increases with wavelength in this phase angle range. Polarization colour in the narrow bands changes at different epochs, perhaps related to cometary activity or molecular emission contamination. The polarization was also measured in the cometary coma at different locations along a line, in the direction of the tail. As expected, we notice minor decrease in the polarization as photocenter (nucleus) is traversed while brightness decreases sharply away from it. Based on these polarization observations we infer that the Comet NEAT C/2001 Q4 has high polarization and a typical grain composition—mixture of silicates and organics.

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

Science.gov (United States)

Pondman, Kirsten M; Pednekar, Lina; Paudyal, Basudev; Tsolaki, Anthony G; Kouser, Lubna; Khan, Haseeb A; Shamji, Mohamed H; Ten Haken, Bennie; Stenbeck, Gudrun; Sim, Robert B; Kishore, Uday

2015-11-01

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Dicty_cDB: Contig-U05302-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available F275295 |AF275295.1 Eretmocerus queenslandensis clone 262Q c... 38 0.26 2 AF27529...4 |AF275294.1 Eretmocerus queenslandensis clone 171Q c... 38 0.26 2 AF275293 |AF275293.1 Eretmocerus queensland...ensis clone 168Qb ... 38 0.26 2 AF275292 |AF275292.1 Eretmocerus queenslandensis clone 168Qa ... 38 0.26 ...2 AF275291 |AF275291.1 Eretmocerus queenslandensis clone 165Qb ... 38 0.26 2 AF275290 |AF275290.1 Eretmocerus queensland...ensis clone 165Qa ... 38 0.26 2 AF275289 |AF275289.1 Eretmocerus queensland

Dicty_cDB: Contig-U06307-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U06307-1 no gap 637 6 29174 29801 PLUS 4 5 U06307 4 0 0 0 0 0 0 0 0 0 0 0 0 0 Show Contig...-U06307-1 Contig ID Contig-U06307-1 Contig update 2002. 9.13 Contig sequence >Contig-U06307-1 (Contig...-U06307-1Q) /CSM_Contig/Contig-U06307-1Q.Seq.d CCCGCGTCCGAATGCCTCGTATTTTACACACTATGCTCCGTGTGGGTAAT TTAG...ATAGTATTTTTATTTTATT CTTTTTCTTTTAAAAATTTTTTATATTGTCAACAATATAATCAAATAAAT GTATTTAATTATCGGGTATTAAAAAAAAAAAAAAAAA Gap no gap Contig...own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U06307-1 (Contig-U06307-1Q) /CSM_Contig/Contig-U063

Variational coupling between q-number and c-number dynamics

International Nuclear Information System (INIS)

Amaral, C.M. do; Joffily, S.

1984-01-01

The time-dependent quantum variational principle is generalized for the case of hamiltonian operators having real parameters and their time derivates. The obtained variational system is formed by a Schroedinger equation coupled to a Lagrange equation system, where the lagrangian is the average value of the parametrized hamiltonian operator. The consequent dynamics of the variational principle, describes the interaction between a q-number sub-dynamics with a c-number sub-dynamics. In the ((h/2π)) 0 -order W.K.B. approximation, the variational system reduces to a Hamilton-Jacobi-like equation, coupled to a Lagrange equation family. The formal features of the obtained variational system are appropriated for the description of, adiabatics and non-adiabatics, time-dependent q-number c-number interactions. (L.C.) [pt

Maths-type q-deformed coherent states for q>1

International Nuclear Information System (INIS)

Quesne, C.; Penson, K.A.; Tkachuk, V.M.

2003-01-01

Maths-type q-deformed coherent states with q>1 allow a resolution of unity in the form of an ordinary integral. They are sub-Poissonian and squeezed. They may be associated with a harmonic oscillator with minimal uncertainties in both position and momentum and are intelligent coherent states for the corresponding deformed Heisenberg algebra

Association of HMOX1 and NQO1 Polymorphisms with Metabolic Syndrome Components.

Science.gov (United States)

Martínez-Hernández, Angélica; Córdova, Emilio J; Rosillo-Salazar, Oscar; García-Ortíz, Humberto; Contreras-Cubas, Cecilia; Islas-Andrade, Sergio; Revilla-Monsalve, Cristina; Salas-Labadía, Consuelo; Orozco, Lorena

2015-01-01

Metabolic syndrome (MetS) is among the most important public health problems worldwide, and is recognized as a major risk factor for various illnesses, including type 2 diabetes mellitus, obesity, and cardiovascular diseases. Recently, oxidative stress has been suggested as part of MetS aetiology. The heme oxygenase 1 (HMOX1) and NADH:quinone oxidoreductase 1 (NQO1) genes are crucial mediators of cellular defence against oxidative stress. In the present study, we analysed the associations of HMOX1 (GT)n and NQO1 C609T polymorphisms with MetS and its components. Our study population comprised 735 Mexican Mestizos unrelated volunteers recruited from different tertiary health institutions from Mexico City. In order to know the HMOX1 (GT)n and NQO1 C609T allele frequencies in Amerindians, we included a population of 241 Amerindian native speakers. Their clinical and demographic data were recorded. The HMOX1 (GT)n polymorphism was genotyped using PCR and fluorescence technology. NQO1 C609T polymorphism genotyping was performed using TaqMan probes. Short allele (metabolic disorders, including high systolic and diastolic blood pressure, hypertriglyceridemia, and low HDL-c levels in Mexican Mestizo individuals.

Dicty_cDB: Contig-U06822-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U06822-1 no gap 468 3 438742 439211 PLUS 1 1 U06822 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Show Contig...-U06822-1 Contig ID Contig-U06822-1 Contig update 2001. 8.30 Contig sequence >Contig-U06822-1 (Contig...-U06822-1Q) /CSM_Contig/Contig-U06822-1Q.Seq.d ATATTATTCTATTCACTCGTAATAATACATATAAATTGATATCAATCAGA AA...TGCTATTAAGACTTTGGAGCAAAAAAC TAACAAATCAATTCAAAA Gap no gap Contig length 468 Chromosome number (1..6, M) 3 Ch...*mmlklkeikllvllrlwskkltnqfk own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U06822-1 (Contig-U06822-1Q) /CSM_Contig/Contig

Dicty_cDB: Contig-U13891-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U13891-1 no gap 1355 6 799802 798446 MINUS 4 4 U13891 0 0 0 0 1 1 1 0 0 0 1 0 0 0 Show Contig...-U13891-1 Contig ID Contig-U13891-1 Contig update 2002.12.18 Contig sequence >Contig-U13891-1 (Contig...-U13891-1Q) /CSM_Contig/Contig-U13891-1Q.Seq.d TTTTAAAATATTTCAAAATTAGCGAGCACGCATTCGCATATAAATATATT ...ACAAATAAAAAAAAAAAATAAAAAAAATA ATTTA Gap no gap Contig length 1355 Chromosome numb...own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U13891-1 (Contig-U13891-1Q) /CSM_Contig/Contig-U138

Rapid, simple and sensitive detection of Q fever by loop-mediated isothermal amplification of the htpAB gene.

Directory of Open Access Journals (Sweden)

Lei Pan

Full Text Available BACKGROUND: Q fever is the most widespread zoonosis, and domestic animals are the most common sources of transmission. It is not only difficult to distinguish from other febrile diseases because of the lack of specific clinical manifestations in humans, but it is also difficult to identify the disease in C. burnetii-carrying animals because of the lack of identifiable features. Conventional serodiagnosis requires sera from the acute and convalescent stages of infection, which are unavailable at early diagnosis. Nested PCR and real-time PCR require equipment. In this study, we developed a Loop-Mediated Isothermal Amplification (LAMP assay to identify C. burnetii rapidly and sensitively. METHODS: A universal LAMP primer set was designed to detect the repeated sequence IS1111a of the htpAB gene of C. burnetii using PrimerExplorer V4 software. The sensitivity of the LAMP assay was evaluated using known quantities of recombined reference plasmids containing the targeted genes. The specificity of the developed LAMP assay was determined using 26 members of order Rickettsiae and 18 other common pathogens. The utility of the LAMP assay was further compared with real time PCR by the examination 24 blood samples including 6 confirmed and 18 probable Q fever cases, which diagnosed by IFA serological assessment and real time PCR. In addition, 126 animal samples from 4 provinces including 97 goats, 7 cattle, 18 horses, 3 marmots and 1 deer were compared by these two methods. RESULTS: The limits of detection of the LAMP assay for the htpAB gene were 1 copy per reaction. The specificity of the LAMP assay was 100%, and no cross-reaction was observed among the bacteria used in the study. The positive rate of unknown febrile patients was 33.3%(95%CI 30.2%-36.4% for the LAMP assay and 8.3%(95%CI 7.4%-9.2% for the real time PCR(P<0.05. Similarly, the total positive rate of animals was 7.9%(95%CI 7.1%-8.7% for the LAMP assay and 0.8%(95%CI 0.7%-0.9%for the real time

SREBP-1c overactivates ROS-mediated hepatic NF-κB inflammatory pathway in dairy cows with fatty liver.

Science.gov (United States)

Li, Xinwei; Huang, Weikun; Gu, Jingmin; Du, Xiliang; Lei, Lin; Yuan, Xue; Sun, Guoquan; Wang, Zhe; Li, Xiaobing; Liu, Guowen

2015-10-01

Dairy cows with fatty liver are characterized by hepatic lipid accumulation and a severe inflammatory response. Sterol receptor element binding protein-1c (SREBP-1c) and nuclear factor κB (NF-κB) are components of the main pathways for controlling triglyceride (TG) accumulation and inflammatory levels, respectively. A previous study demonstrated that hepatic inflammatory levels are positively correlated with hepatic TG content. We therefore speculated that SREBP-1c might play an important role in the overactivation of the hepatic NF-κB inflammatory pathway in cows with fatty liver. Compared with healthy cows, cows with fatty liver exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-α, IL-6 and IL-1β. Hepatic SREBP-1c-mediated lipid synthesis and the NF-κB inflammatory pathway were both overinduced in cows with fatty liver. In vitro, treatment with non-esterified fatty acids (NEFA) further increased SREBP-1c expression and NF-κB pathway activation, which then promoted TG and inflammatory cytokine synthesis. SREBP-1c overexpression overactivated the NF-κB inflammatory pathway in hepatocytes by increasing ROS content and not through TLR4. Furthermore, SREBP-1c silencing decreased ROS content and further attenuated the activation of the NEFA-induced NF-κB pathway, thereby decreasing TNF-α, IL-6 and IL-1β synthesis. SREBP-1c-overexpressing mice exhibited hepatic steatosis and an overinduced hepatic NF-κB pathway. Taken together, these results indicate that SREBP-1c enhances the NEFA-induced overactivation of the NF-κB inflammatory pathway by increasing ROS in cow hepatocytes, thereby further increasing hepatic inflammatory injury in cows with fatty liver. Copyright © 2015. Published by Elsevier Inc.

Assignment of Alzheimer's presenilin-2 (PS-2) gene to 1q42.1 by fluorescence in situ hybridization.

Science.gov (United States)

Takano, T; Sahara, N; Yamanouchi, Y; Mori, H

1997-01-17

Presenilin-2 (PS-2) was suggested to be localized on 1q31-42 based on linkage analysis and cDNA cloning. The final identification of PS-2 as the causal gene for early-onset familial Alzheimer's disease in Voga-German pedigrees was concluded based on the point mutation found in the candidate cDNA isolated from this familial AD. We present evidence of its physical genome mapping of PS-2 on chromosome 1q42.1 by fluorescence in situ hybridization method.

Q4 2017/Q1 2018 Solar Industry Update

Energy Technology Data Exchange (ETDEWEB)

Feldman, David J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Margolis, Robert M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hoskins, Jack [U.S. Department of Energy

2018-05-16

This technical presentation provides an update on the major trends that occurred in the solar industry in Q4 2017 and Q1 2018. Major topics of focus include global and U.S. supply and demand, module and system price, investment trends and business models, and updates on U.S. government programs supporting the solar industry.

Dicty_cDB: Contig-U12545-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U12545-1 gap included 1165 3 3275272 3276395 PLUS 1 2 U12545 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Show Contig...-U12545-1 Contig ID Contig-U12545-1 Contig update 2002.12.18 Contig sequence >Contig-U12545-1 (Contig-U12545-1Q) /CSM_Contig/Contig-U12545...CGTTCTAAATCACTCATTAAAAGATTAAAAATTAAANAAGGTAATATC TCACGACNGCTNNCTCATACACACN Gap gap included Contig length 11...vliknlskrkerkis*klyqlkriqlsl vknwlklvlnhslkd*klxkvishdxxliht own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig...-U12545-1 (Contig-U12545-1Q) /CSM_Contig/Contig-U12545-1Q.Seq.d (1175 letters) Database: CSM 6905 s

TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing.

Science.gov (United States)

Seo, Gil Ju; Kim, Charlotte; Shin, Woo-Jin; Sklan, Ella H; Eoh, Hyungjin; Jung, Jae U

2018-02-09

Intracellular nucleic acid sensors often undergo sophisticated modifications that are critical for the regulation of antimicrobial responses. Upon recognition of DNA, the cytosolic sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the second messenger cGAMP, which subsequently initiates downstream signaling to induce interferon-αβ (IFNαβ) production. Here we report that TRIM56 E3 ligase-induced monoubiquitination of cGAS is important for cytosolic DNA sensing and IFNαβ production to induce anti-DNA viral immunity. TRIM56 induces the Lys335 monoubiquitination of cGAS, resulting in a marked increase of its dimerization, DNA-binding activity, and cGAMP production. Consequently, TRIM56-deficient cells are defective in cGAS-mediated IFNαβ production upon herpes simplex virus-1 (HSV-1) infection. Furthermore, TRIM56-deficient mice show impaired IFNαβ production and high susceptibility to lethal HSV-1 infection but not to influenza A virus infection. This adds TRIM56 as a crucial component of the cytosolic DNA sensing pathway that induces anti-DNA viral innate immunity.

Revisiting the gravitino dark matter and baryon asymmetry from Q-ball decay in gauge mediation

Energy Technology Data Exchange (ETDEWEB)

Kasuya, Shinta, E-mail: kasuya@kanagawa-u.ac.jp [Department of Mathematics and Physics, Kanagawa University, Kanagawa 259-1293 (Japan); Max-Planck-Institut für Kernphysik, PO Box 103980, 69029 Heidelberg (Germany); Kawasaki, Masahiro [Institute for Cosmic Ray Research, the University of Tokyo, Chiba 277-8582 (Japan); Kavli Institute for the Physics and Mathematics of the Universe (WPI), Todai Institutes for Advanced Study, the University of Tokyo, Chiba 277-8582 (Japan); Yamada, Masaki [Institute for Cosmic Ray Research, the University of Tokyo, Chiba 277-8582 (Japan)

2013-10-07

We reconsider the Q-ball decay and reinvestigate the scenario that the amount of the baryons and the gravitino dark matter is naturally explained by the decay of the Q balls in the gauge-mediated SUSY breaking. We refine the decay rates into baryons, NLSPs, and gravitinos, and estimate their branching ratios based on the consideration of Pauli blocking. We obtain a smaller branching into gravitinos than the previous estimate, and the NLSPs are more produced by the Q-ball decay. However, the efficient annihilations of NLSPs occur afterward so that their abundance does not spoil the successful BBN and they only produce negligible amount of the gravitinos to the dark matter density by their decay. In this way, we find that the scenario with the direct production of the gravitino dark matter from the Q-ball decay works naturally.

Q.C.D. predictions for the forward photoproduction of heavy vector mesons

International Nuclear Information System (INIS)

Navelet, H.; Peschanski, R.

1984-03-01

From the inelastic QantiQ-Nucleon cross section, we get predictions for the forward photoproduction of heavy QantiQ mesons by using V.D.M. and the optical theorem. These cross sections are computed from perturbative Q.C.D. through gluon radiation mechanism

Antibodies Against Complement Components: Relevance for the Antiphospholipid Syndrome-Biomarkers of the Disease and Biopharmaceuticals.

Science.gov (United States)

Bećarević, Mirjana

2017-07-01

Laboratory criterion for the diagnosis of antiphospholipid syndrome (APS) is the presence of antiphospholipid antibodies (aPL Abs). Complement system has a role in mediating aPL Abs-induced thrombosis in animal models. The importance of antibodies against complement components (potential biomarkers of APS) and the importance of antibodies with beneficial anti-complement effects in APS (as biopharmaceuticals) are reviewed. Antibodies against complement components described in APS patients, so far, are anti-C1q and anti-factor H Abs, although anti-factor B Abs and anti-C5a Abs were described in animal models of APS. Clinical studies in APS patients are limited to a small number of case reports. Studies that would confirm potential role of Abs against complement components (as potential biomarkers of APS) are lacking. Lack of randomized clinical trials (that would provide complete data for confirmation of beneficial effects of biopharmaceuticals in complement inhibition) in APS is alarming.

Dicty_cDB: Contig-U01997-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U01997-1 gap included 886 2 1683026 1682230 MINUS 3 4 U01997 1 0 0 0 0 0 2 0 0 0 0 0 0 0 Show Contig...-U01997-1 Contig ID Contig-U01997-1 Contig update 2001. 8.29 Contig sequence >Contig-U01997-1 (Contig-U01997-1Q) /CSM_Contig/Contig-U01997...ATTGAAATAATATTTATTTATTTTTTTAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA Gap gap included Contig...nfkvfgieiifiyffkkkkkkkkkkkkkkkkkkk own update 2004. 6. 9 Homology vs CSM-cDNA Query= Contig-U01997-1 (Contig-U01997-1Q) /CSM_Contig.../Contig-U01997-1Q.Seq.d (896 letters) Database: CSM 6905 sequences; 5,674,871 total l

Dicty_cDB: Contig-U06384-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U06384-1 no gap 660 5 3008439 3007779 MINUS 2 2 U06384 2 0 0 0 0 0 0 0 0 0 0 0 0 0 Show Contig...-U06384-1 Contig ID Contig-U06384-1 Contig update 2001. 8.30 Contig sequence >Contig-U06384-1 (Contig...-U06384-1Q) /CSM_Contig/Contig-U06384-1Q.Seq.d TGAAAAAATTAGAGACAACAAGTGGATCAGCACGTAAAGTATGGCGTTTA...AAATAAAAATTAATTTCC AAAAATAAAA Gap no gap Contig length 660 Chromosome number (1.....own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U06384-1 (Contig-U06384-1Q) /CSM_Contig/Contig-U063

q-deformation of ''W3'', Virasoro and U(1)-Kac-Moody algebras

International Nuclear Information System (INIS)

El Hassouni, A.; Tahri, E.H.; Zakkari, M.

1995-07-01

A deformation of the algebra of infinite matrices gl(∞, C) is given. We show that this operation leads to the realization of a deformed ''W 3 '' like algebra. The central extension of the q-U(1) Kac-Moody and the q-Virasoro algebra is performed. (author). 10 refs

A Pst I polymorphism in the human laminin B2 chain gene on 1q25-q31

Energy Technology Data Exchange (ETDEWEB)

Kallunki, T; Pikkarainen, T; Tryggvason, K; Savolainen, E R [Univ. of Oulu (Finland)

1989-06-12

pHL-210 is a 2.7 kb cDNA insert in pBR322 that codes for the central position of the 7.5 kb mRNA. A Pst I polymorphism was identified with pHL-210. The allele frequency was studied in 40 chromosomes of unrelated Finnish individuals. The probe was localized to chromosome 1q25-q31 by somatic cell and in situ hybridization. Co-dominant inheritance was shown in three families.

Identification and differentiation of major components in three different “Sheng-ma” crude drug species by UPLC/Q-TOF-MS

Directory of Open Access Journals (Sweden)

Mengxue Fan

2017-03-01

Full Text Available Cimicifugae Rhizoma (Sheng ma is a Ranunculaceae herb belonging to a composite family and well known in China. has been widely used in traditional Chinese medicine. The Pharmacopoeia of the People׳s Republic of China contains three varieties (Cimicifuga dahurica (Turcz., Cimicifuga foetida L. and Cimicifuga heracleifolia Kom. which have been used clinically as “Sheng-ma”. However, the chemical constituents of three components of “Sheng-ma” have never been documented. In this study, a rapid method for the analysis of the main components of “Sheng-ma” was developed using ultra-high performance liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS. The present study reveals the major common and distinct chemical constituents of C. dahurica, C. foetida and C. heracleifolia and also reports principal component and statistical analyses of these results. The components were identified by comparing the retention time, accurate mass, mass spectrometric fragmentation characteristic ions and matching empirical molecular formula with that of the published compounds. A total of 32 common components and 8 markers for different “Sheng-ma” components were identified. These findings provide an important basis for the further study and clinical utilities of the three “Sheng-ma” varieties.

Antioxidant vitamins C, E and coenzyme Q10 vs Dexamethasone: comparisons of their effects in pulmonary contusion model

Directory of Open Access Journals (Sweden)

Gokce Mertol

2012-09-01

Full Text Available Abstract Background The goal of our study is to evaluate the effects of antioxidant vitamins (vitamin C and E, Coenzyme Q10 (CoQ10 and dexamethasone (Dxm in experimental rat models with pulmonary contusion (PC. Methods Rats were randomly divided into six groups. Except for the control, all subgroups had a moderate pulmonary contusion. Animals in the group I and group II received intraperitoneal saline, group III received 10mg.kg-1 CoQ10 group IV received 100mg.kg-1 vitamin C, group V received 150mg.kg-1 vitamin E, and group VI received 10mg.kg-1 Dxm. Blood gas analysis, serum nitric oxide (NO and malondialdehyde (MDA levels as well as superoxide dismutase (SOD activity assays, bronchoalveolar lavage (BAL fluid and histopathological examination were performed. Results Administration of CoQ10 resulted in a significant increase in PaO2 values compared with the group I (p = 0.004. Levels of plasma MDA in group II were significantly higher than those in the group I (p = 0.01. Early administration of vitamin C, CoQ10, and Dxm significantly decreased the levels of MDA (p = 0.01. Lung contusion due to blunt trauma significantly decreased SOD activities in rat lung tissue compared with group I (p = 0.01. SOD levels were significantly elevated in animals treated with CoQ10, Vitamin E, or Dxm compared with group II (p = 0.01. Conclusions In our study, CoQ10, vitamin C, vitamin E and Dxm had a protective effect on the biochemical and histopathological outcome of PC after experimental blunt thorax trauma.

Dicty_cDB: Contig-U12073-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U12073-1 gap included 912 2 2118980 2119867 PLUS 4 5 U12073 0 0 0 2 0 0 0 1 0 1 0 0 0 0 Show Contig...-U12073-1 Contig ID Contig-U12073-1 Contig update 2002.12.18 Contig sequence >Contig-U12073-1 (Contig...-U12073-1Q) /CSM_Contig/Contig-U12073-1Q.Seq.d CTGTTGGCCTACTGGNAATTGAAACAATTGTTTCAGCAAATATTA...AAGA Gap gap included Contig length 912 Chromosome number (1..6, M) 2 Chromosome length 8467578 Start point ...GPXSXDY*r own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U12073-1 (Contig-U12073-1Q) /CSM_Contig/Contig

High Q, Miniaturized LCP-Based Passive Components

KAUST Repository

Shamim, Atif; Arabi, Eyad A.

2014-01-01

Various methods and systems are provided for high Q, miniaturized LCP-based passive components. In one embodiment, among others, a spiral inductor includes a center connection and a plurality of inductors formed on a liquid crystal polymer (LCP) layer, the plurality of inductors concentrically spiraling out from the center connection. In another embodiment, a vertically intertwined inductor includes first and second inductors including a first section disposed on a side of the LCP layer forming a fraction of a turn and a second section disposed on another side of the LCP layer. At least a portion of the first section of the first inductor is substantially aligned with at least a portion of the second section of the second inductor and at least a portion of the first section of the second inductor is substantially aligned with at least a portion of the second section of the first inductor.

High Q, Miniaturized LCP-Based Passive Components

KAUST Repository

Shamim, Atif

2014-10-16

Various methods and systems are provided for high Q, miniaturized LCP-based passive components. In one embodiment, among others, a spiral inductor includes a center connection and a plurality of inductors formed on a liquid crystal polymer (LCP) layer, the plurality of inductors concentrically spiraling out from the center connection. In another embodiment, a vertically intertwined inductor includes first and second inductors including a first section disposed on a side of the LCP layer forming a fraction of a turn and a second section disposed on another side of the LCP layer. At least a portion of the first section of the first inductor is substantially aligned with at least a portion of the second section of the second inductor and at least a portion of the first section of the second inductor is substantially aligned with at least a portion of the second section of the first inductor.

The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

Energy Technology Data Exchange (ETDEWEB)

Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Hidalgo, Cecilia [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Lavandero, Sergio, E-mail: slavander@uchile.cl [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile)

2009-10-09

Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

International Nuclear Information System (INIS)

Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo; Hidalgo, Cecilia; Lavandero, Sergio

2009-01-01

Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal α-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

Precise Extraction of the Neutron Magnetic Form Factor from Quasi-elastic 3He(pol)(e(pol),e') at Q2 = 0.1-0.6 (GeV/c)2

International Nuclear Information System (INIS)

Jens-ole Hansen; Brian Anderson; Leonard Auerbach; Todd Averett; William Bertozzi; Tim Black; John Calarco; Lawrence Cardman; Gordon Cates; Zhengwei Chai; Jiang-Ping Chen; Seonho Choi; Eugene Chudakov; Steve Churchwell; G Corrado; Christopher Crawford; Daniel Dale; Alexandre Deur; Pibero Djawotho; Dipangkar Dutta; John Finn; Haiyan Gao; Ronald Gilman; Oleksandr Glamazdin; Charles Glashausser; Walter Gloeckle; Jacek Golak; Javier Gomez; Viktor Gorbenko; F. Hersman; Douglas Higinbotham; Richard Holmes; Calvin Howell; Emlyn Hughes; Thomas Humensky; Sebastien Incerti; Piotr Zolnierczuk; Cornelis De Jager; John Jensen; Xiaodong Jiang; Cathleen Jones; Mark Jones; R Kahl; H Kamada; A Kievsky; Ioannis Kominis; Wolfgang Korsch; Kevin Kramer; Gerfried Kumbartzki; Michael Kuss; Enkeleida Lakuriqi; Meihua Liang; Nilanga Liyanage; John LeRose; Sergey Malov; Demetrius Margaziotis; Jeffery Martin; Kathy McCormick; Robert McKeown; Kevin McIlhany; Zein-Eddine Meziani; Robert Michaels; Greg Miller; Joseph Mitchell; Sirish Nanda; Emanuele Pace; Tina Pavlin; Gerassimos Petratos; Roman Pomatsalyuk; David Pripstein; David Prout; Ronald Ransome; Yves Roblin; Marat Rvachev; Giovanni Salme; Michael Schnee; Charles Seely; Taeksu Shin; Karl Slifer; Paul Souder; Steffen Strauch; Riad Suleiman; Mark Sutter; Bryan Tipton; Luminita Todor; M Viviani; Branislav Vlahovic; John Watson; Claude Williamson; H Witala; Bogdan Wojtsekhowski; Feng Xiong; Wang Xu; Jen-chuan Yeh

2006-01-01

We have measured the transverse asymmetry A T' in the quasi-elastic 3 /rvec He/(/rvec e/,e') process with high precision at Q 2 -values from 0.1 to 0.6 (GeV/c) 2 . The neutron magnetic form factor G M n was extracted at Q 2 -values of 0.1 and 0.2 (GeV/c) 2 using a non-relativistic Faddeev calculation which includes both final-state interactions (FSI) and meson-exchange currents (MEC). Theoretical uncertainties due to the FSI and MEC effects were constrained with a precision measurement of the spin-dependent asymmetry in the threshold region of 3 /rvec He/(/rvec e/,e'). We also extracted the neutron magnetic form factor G M n at Q 2 -values of 0.3 to 0.6 (GeV/c) 2 based on Plane Wave Impulse Approximation calculations

Nuclear import of transcription factor BR-C is mediated by its interaction with RACK1.

Science.gov (United States)

Cheng, Daojun; Qian, Wenliang; Wang, Yonghu; Meng, Meng; Wei, Ling; Li, Zhiqing; Kang, Lixia; Peng, Jian; Xia, Qingyou

2014-01-01

The transcription factor Broad Complex (BR-C) is an early ecdysone response gene in insects and contains two types of domains: two zinc finger domains for the activation of gene transcription and a Bric-a-brac/Tramtrack/Broad complex (BTB) domain for protein-protein interaction. Although the mechanism of zinc finger-mediated gene transcription is well studied, the partners interacting with the BTB domain of BR-C has not been elucidated until now. Here, we performed a yeast two-hybrid screen using the BTB domain of silkworm BR-C as bait and identified the receptor for activated C-kinase 1 (RACK1), a scaffolding/anchoring protein, as the novel partner capable of interacting with BR-C. The interaction between BR-C and RACK1 was further confirmed by far-western blotting and pull-down assays. Importantly, the disruption of this interaction, via RNAi against the endogenous RACK1 gene or deletion of the BTB domain, abolished the nuclear import of BR-C in BmN4 cells. In addition, RNAi against the endogenous PKC gene as well as phosphorylation-deficient mutation of the predicted PKC phosphorylation sites at either Ser373 or Thr406 in BR-C phenocopied RACK1 RNAi and altered the nuclear localization of BR-C. However, when BTB domain was deleted, phosphorylation mimics of either Ser373 or Thr406 had no effect on the nuclear import of BR-C. Moreover, mutating the PKC phosphorylation sites at Ser373 and Thr406 or deleting the BTB domain significantly decreased the transcriptional activation of a BR-C target gene. Given that RACK1 is necessary for recruiting PKC to close and phosphorylate target proteins, we suggest that the PKC-mediated phosphorylation and nuclear import of BR-C is determined by its interaction with RACK1. This novel finding will be helpful for further deciphering the mechanism underlying the role of BR-C proteins during insect development.

Nuclear import of transcription factor BR-C is mediated by its interaction with RACK1.

Directory of Open Access Journals (Sweden)

Daojun Cheng

Full Text Available The transcription factor Broad Complex (BR-C is an early ecdysone response gene in insects and contains two types of domains: two zinc finger domains for the activation of gene transcription and a Bric-a-brac/Tramtrack/Broad complex (BTB domain for protein-protein interaction. Although the mechanism of zinc finger-mediated gene transcription is well studied, the partners interacting with the BTB domain of BR-C has not been elucidated until now. Here, we performed a yeast two-hybrid screen using the BTB domain of silkworm BR-C as bait and identified the receptor for activated C-kinase 1 (RACK1, a scaffolding/anchoring protein, as the novel partner capable of interacting with BR-C. The interaction between BR-C and RACK1 was further confirmed by far-western blotting and pull-down assays. Importantly, the disruption of this interaction, via RNAi against the endogenous RACK1 gene or deletion of the BTB domain, abolished the nuclear import of BR-C in BmN4 cells. In addition, RNAi against the endogenous PKC gene as well as phosphorylation-deficient mutation of the predicted PKC phosphorylation sites at either Ser373 or Thr406 in BR-C phenocopied RACK1 RNAi and altered the nuclear localization of BR-C. However, when BTB domain was deleted, phosphorylation mimics of either Ser373 or Thr406 had no effect on the nuclear import of BR-C. Moreover, mutating the PKC phosphorylation sites at Ser373 and Thr406 or deleting the BTB domain significantly decreased the transcriptional activation of a BR-C target gene. Given that RACK1 is necessary for recruiting PKC to close and phosphorylate target proteins, we suggest that the PKC-mediated phosphorylation and nuclear import of BR-C is determined by its interaction with RACK1. This novel finding will be helpful for further deciphering the mechanism underlying the role of BR-C proteins during insect development.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes.

Science.gov (United States)

Alkholy, Usama M; Abdalmonem, Nermin; Zaki, Ahmed; Elkoumi, Mohamed A; Hashim, Mustafa I Abu; Basset, Maha A A; Salah, Hossam E

2018-02-07

The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=-0.31; p=0.022) and the duration of type 1 diabetes (r=-0.35, p=0.012). Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

C-terminal of human histamine H1 receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling.

Science.gov (United States)

Hishinuma, Shigeru; Nozawa, Hiroki; Akatsu, Chizuru; Shoji, Masaru

2016-11-01

It has been suggested that the agonist-induced internalization of G-protein-coupled receptors from the cell surface into intracellular compartments regulates cellular responsiveness. We previously reported that G q/11 -protein-coupled human histamine H 1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H 1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H 1 receptors tagged with hemagglutinin (HA) at the N-terminal in histamine-induced internalization in Chinese hamster ovary cells. The histamine-induced internalization was evaluated by the receptor binding assay with [ 3 H]mepyramine and confocal immunofluorescence microscopy with an anti-HA antibody. We found that histamine-induced internalization was inhibited under hypertonic conditions or by pitstop, a clathrin terminal domain inhibitor, but not by filipin or nystatin, disruptors of the caveolar structure and function. The histamine-induced internalization was also inhibited by truncation of a single amino acid, Ser487, located at the end of the intracellular C-terminal of H 1 receptors, but not by its mutation to alanine. In contrast, the receptor-G-protein coupling, which was evaluated by histamine-induced accumulation of [ 3 H]inositol phosphates, was potentiated by truncation of Ser487, but was lost by its mutation to alanine. These results suggest that the intracellular C-terminal of human H 1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H 1 receptors and G-protein signaling, in which truncation of Ser487 and its mutation to alanine are revealed to result in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively. © 2016 International Society for Neurochemistry.

Dicty_cDB: Contig-U09694-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U09694-1 gap included 1129 1 4027135 4026071 MINUS 3 4 U09694 2 0 1 0 0 0 0 0 0 0 0 0 0 0 Show Contig...-U09694-1 Contig ID Contig-U09694-1 Contig update 2002. 9.13 Contig sequence >Contig-U09694-1 (Contig-U09694-1Q) /CSM_Contig/Contig-U0969...TTAAATTAAAACAACAACAATTTCATAATATAAATAAT Gap gap included Contig length 1129 Chromosome number (1..6, M) 1 Chr...iklkqqqfklkqqqfhninn own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U09694-1 (Contig-U09694-1Q) /CSM_Contig/Contig...E Sequences producing significant alignments: (bits) Value Contig-U09694-1 (Contig-U09694-1Q) /CSM_Contig

Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25.

Science.gov (United States)

Burkardt, Deepika D'Cunha; Rosenfeld, Jill A; Helgeson, Maria L; Angle, Brad; Banks, Valerie; Smith, Wendy E; Gripp, Karen W; Moline, Jessica; Moran, Rocio T; Niyazov, Dmitriy M; Stevens, Cathy A; Zackai, Elaine; Lebel, Robert Roger; Ashley, Douglas G; Kramer, Nancy; Lachman, Ralph S; Graham, John M

2011-06-01

Reports of individuals with deletions of 1q24→q25 share common features of prenatal onset growth deficiency, microcephaly, small hands and feet, dysmorphic face and severe cognitive deficits. We report nine individuals with 1q24q25 deletions, who show distinctive features of a clinically recognizable 1q24q25 microdeletion syndrome: prenatal-onset microcephaly and proportionate growth deficiency, severe cognitive disability, small hands and feet with distinctive brachydactyly, single transverse palmar flexion creases, fifth finger clinodactyly and distinctive facial features: upper eyelid fullness, small ears, short nose with bulbous nasal tip, tented upper lip, and micrognathia. Radiographs demonstrate disharmonic osseous maturation with markedly delayed bone age. Occasional features include cleft lip and/or palate, cryptorchidism, brain and spinal cord defects, and seizures. Using oligonucleotide-based array comparative genomic hybridization, we defined the critical deletion region as 1.9 Mb at 1q24.3q25.1 (chr1: 170,135,865-172,099,327, hg18 coordinates), containing 13 genes and including CENPL, which encodes centromeric protein L, a protein essential for proper kinetochore function and mitotic progression. The growth deficiency in this syndrome is similar to what is seen in other types of primordial short stature with microcephaly, such as Majewski osteodysplastic primordial dwarfism, type II (MOPD2) and Seckel syndrome, which result from loss-of-function mutations in genes coding for centrosomal proteins. DNM3 is also in the deleted region and expressed in the brain, where it participates in the Shank-Homer complex and increases synaptic strength. Therefore, DNM3 is a candidate for the cognitive disability, and CENPL is a candidate for growth deficiency in this 1q24q25 microdeletion syndrome. Copyright © 2011 Wiley-Liss, Inc.

ESR1 Is Co-Expressed with Closely Adjacent Uncharacterised Genes Spanning a Breast Cancer Susceptibility Locus at 6q25.1

Science.gov (United States)

Dunbier, Anita K.; Anderson, Helen; Ghazoui, Zara; Lopez-Knowles, Elena; Pancholi, Sunil; Ribas, Ricardo; Drury, Suzanne; Sidhu, Kally; Leary, Alexandra; Martin, Lesley-Ann; Dowsett, Mitch

2011-01-01

Approximately 80% of human breast carcinomas present as oestrogen receptor α-positive (ER+ve) disease, and ER status is a critical factor in treatment decision-making. Recently, single nucleotide polymorphisms (SNPs) in the region immediately upstream of the ER gene (ESR1) on 6q25.1 have been associated with breast cancer risk. Our investigation of factors associated with the level of expression of ESR1 in ER+ve tumours has revealed unexpected associations between genes in this region and ESR1 expression that are important to consider in studies of the genetic causes of breast cancer risk. RNA from tumour biopsies taken from 104 postmenopausal women before and after 2 weeks treatment with an aromatase (oestrogen synthase) inhibitor was analyzed on Illumina 48K microarrays. Multiple-testing corrected Spearman correlation revealed that three previously uncharacterized open reading frames (ORFs) located immediately upstream of ESR1, C6ORF96, C6ORF97, and C6ORF211 were highly correlated with ESR1 (Rs = 0.67, 0.64, and 0.55 respectively, FDRaccount for the correlations. The correlations were maintained in cultured cells. An ERα antagonist did not affect the ORFs' expression or their correlation with ESR1, suggesting their transcriptional co-activation is not directly mediated by ERα. siRNA inhibition of C6ORF211 suppressed proliferation in MCF7 cells, and C6ORF211 positively correlated with a proliferation metagene in tumours. In contrast, C6ORF97 expression correlated negatively with the metagene and predicted for improved disease-free survival in a tamoxifen-treated published dataset, independently of ESR1. Our observations suggest that some of the biological effects previously attributed to ER could be mediated and/or modified by these co-expressed genes. The co-expression and function of these genes may be important influences on the recently identified relationship between SNPs in this region and breast cancer risk. PMID:21552322

Dicty_cDB: Contig-U12086-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U12086-1 gap included 1101 3 5710254 5711336 PLUS 1 2 U12086 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Show Contig...-U12086-1 Contig ID Contig-U12086-1 Contig update 2002.12.18 Contig sequence >Contig-U12086-1 (Contig-U12086-1Q) /CSM_Contig/Contig-U12086...ATCGGATTA Gap gap included Contig length 1101 Chromosome number (1..6, M) 3 Chromosome length 6358359 Start ...te 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U12086-1 (Contig-U12086-1Q) /CSM_Contig/Contig...Sequences producing significant alignments: (bits) Value Contig-U12086-1 (Contig-U12086-1Q) /CSM_Contig/Conti... 404 e-113 Contig

Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection.

Science.gov (United States)

Gong, Xin; Qian, Hongwu; Zhou, Xinhui; Wu, Jianping; Wan, Tao; Cao, Pingping; Huang, Weiyun; Zhao, Xin; Wang, Xudong; Wang, Peiyi; Shi, Yi; Gao, George F; Zhou, Qiang; Yan, Nieng

2016-06-02

Niemann-Pick disease type C (NPC) is associated with mutations in NPC1 and NPC2, whose gene products are key players in the endosomal/lysosomal egress of low-density lipoprotein-derived cholesterol. NPC1 is also the intracellular receptor for Ebola virus (EBOV). Here, we present a 4.4 Å structure of full-length human NPC1 and a low-resolution reconstruction of NPC1 in complex with the cleaved glycoprotein (GPcl) of EBOV, both determined by single-particle electron cryomicroscopy. NPC1 contains 13 transmembrane segments (TMs) and three distinct lumenal domains A (also designated NTD), C, and I. TMs 2-13 exhibit a typical resistance-nodulation-cell division fold, among which TMs 3-7 constitute the sterol-sensing domain conserved in several proteins involved in cholesterol metabolism and signaling. A trimeric EBOV-GPcl binds to one NPC1 monomer through the domain C. Our structural and biochemical characterizations provide an important framework for mechanistic understanding of NPC1-mediated intracellular cholesterol trafficking and Ebola virus infection. Copyright © 2016 Elsevier Inc. All rights reserved.

C to U RNA editing mediated by APOBEC1 requires RNA-binding protein RBM47.

Science.gov (United States)

Fossat, Nicolas; Tourle, Karin; Radziewic, Tania; Barratt, Kristen; Liebhold, Doreen; Studdert, Joshua B; Power, Melinda; Jones, Vanessa; Loebel, David A F; Tam, Patrick P L

2014-08-01

Cytidine (C) to Uridine (U) RNA editing is a post-transcriptional modification that is accomplished by the deaminase APOBEC1 and its partnership with the RNA-binding protein A1CF. We identify and characterise here a novel RNA-binding protein, RBM47, that interacts with APOBEC1 and A1CF and is expressed in tissues where C to U RNA editing occurs. RBM47 can substitute for A1CF and is necessary and sufficient for APOBEC1-mediated editing in vitro. Editing is further impaired in Rbm47-deficient mutant mice. These findings suggest that RBM47 and APOBEC1 constitute the basic machinery for C to U RNA editing. © 2014 The Authors.

Solving (1,q) KdV gravity

International Nuclear Information System (INIS)

Montano, D.; Rivlis, G.

1991-01-01

In this paper we explicitly compute the correlation functions of the (1, q) series of the KdV hierarchy, i.e. models with q-1 primary fields. We also find from algebraic considerations a ghost number conservation law for the (1, q) models. All the results in this paper follow from the algebraic properties of the KdV hierarchy without using any extraneous information from a field theory interpretation. We find the interesting result that some correlation functions vanish even when they conserve ghost number. This is an indication for further selection rules. (orig.)

A common base method for analysis of qPCR data and the application of simple blocking in qPCR experiments.

Science.gov (United States)

Ganger, Michael T; Dietz, Geoffrey D; Ewing, Sarah J

2017-12-01

qPCR has established itself as the technique of choice for the quantification of gene expression. Procedures for conducting qPCR have received significant attention; however, more rigorous approaches to the statistical analysis of qPCR data are needed. Here we develop a mathematical model, termed the Common Base Method, for analysis of qPCR data based on threshold cycle values (C q ) and efficiencies of reactions (E). The Common Base Method keeps all calculations in the logscale as long as possible by working with log 10 (E) ∙ C q , which we call the efficiency-weighted C q value; subsequent statistical analyses are then applied in the logscale. We show how efficiency-weighted C q values may be analyzed using a simple paired or unpaired experimental design and develop blocking methods to help reduce unexplained variation. The Common Base Method has several advantages. It allows for the incorporation of well-specific efficiencies and multiple reference genes. The method does not necessitate the pairing of samples that must be performed using traditional analysis methods in order to calculate relative expression ratios. Our method is also simple enough to be implemented in any spreadsheet or statistical software without additional scripts or proprietary components.

The continuing saga of the /sup 1/P/sub 1/ (q-barq) mesonic states

International Nuclear Information System (INIS)

Dalitz, R.H.; Tuan, S.F.

1986-01-01

The mesonic states predicted by the quark model to have the structure (q-barq) do not allow all combinations possible for the quantum numbers (JPC). The happy situation for the /sup 3/P/sub J/ states does not hold for the /sup 1/P/sub 1/ state. The experimenter is therefore faced by a double difficulty, the difficulty of forming the /sup 1/P/sub 1/ through the channels available to him and the difficulty of detecting the /sup 1/P/sub 1/ state when it is formed. The difficulty about the detection and study of /sup 1/P/sub 1/ states is not intrinsic but circumstantial. It is not intrinsic because the B-meson is readily produced and studied, the same being true for Q/sub B/, although this has been a more confused situation because of the mixing between the Q/sub A/ and Q/sub B/ states. Porter has devoted considerable attention to the search for the /sup 1/P/sub 1/ (c-barc) state and the authors outline that discussion in this paper. They also describe the formation of the state Psi' (3685), since this has a large cross section in e/sup +/e/sup -/ annihilation, and to look for the /sup 1/P/sub 1/ state as a product among its decay modes

Specific, sensitive, precise, and rapid functional chromogenic assay of activated first complement component (C1) in plasma

DEFF Research Database (Denmark)

Munkvad, S; Jespersen, J; Sidelmann, Johannes Jakobsen

1990-01-01

We present a new functional assay for the first complement component (C1) in plasma, based on its activation by inhibition of the C1-esterase inhibitor (C1-inh) when monospecific antiserum to C1-inh is added to the plasma. After maximal activation, we can determine the concentration of activated ...

Water-soluble Coenzyme Q10 formulation (Q-ter) promotes outer hair cell survival in a guinea pig model of noise induced hearing loss (NIHL).

Science.gov (United States)

Fetoni, Anna Rita; Piacentini, Roberto; Fiorita, Antonella; Paludetti, Gaetano; Troiani, Diana

2009-02-27

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS) also in noise induced hearing loss (NIHL) and anti-oxidants and free-radicals scavengers have been shown to attenuate the damage. Coenzyme Q(10) (CoQ(10)) or ubiquinone has a bioenergetic role as a component of the mithocondrial respiratory chain, it inhibits mitochondrial lipid peroxidation, inducing ATP production and it is involved in ROS removal and prevention of oxidative stress-induced apoptosis. However the therapeutic application of CoQ(10) is limited by the lack of solubility and poor bio- availability, therefore it is a challenge to improve its water solubility in order to ameliorate the efficacy in tissues and fluids. This study was conducted in a model of acoustic trauma in the guinea pig where the effectiveness of CoQ(10) was compared with a soluble formulation of CoQ(10) (multicomposite CoQ(10) Terclatrate, Q-ter) given intraperitoneally 1 h before and once daily for 3 days after pure tone noise exposure (6 kHz for 1 h at 120 dB SPL). Functional and morphological studies were carried out by measuring auditory brainstem responses, scanning electron microscopy for hair cell loss count, active caspase 3 staining and terminal deoxynucleotidyl transferase-mediated dUTP labelling assay in order to identify initial signs of apoptosis. Treatments decreased active caspase 3 expression and the number of apoptotic cells, but animals injected with Q-ter showed a greater degree of activity in preventing apoptosis and thus in improving hearing. These data confirm that solubility of Coenzyme Q(10) improves the ability of CoQ(10) in preventing oxidative injuries that result from mitochondrial dysfunction.

Determination of the pion charge form factor for Q2 = 0.60-1.60 (GeV/c)2

International Nuclear Information System (INIS)

Vardan Tadevosyan; Henk Blok; Garth Huber; David Abbott; Heinz Anklin; Christopher Armstrong; John Arrington; Ketevi Assamagan; Steven Avery; O. Baker; C. Bochna; Edward Brash; Herbert Breuer; Nicholas Chant; James Dunne; T. Eden; Rolf Ent; David Gaskell; Ronald Gilman; Kenneth Gustafsson; Wendy Hinton; Harold Jackson; Mark Jones; Cynthia Keppel; Pyunghun Kim; Wooyoung Kim; Andreas Klein; Douglas Koltenuk; Meihua Liang; George Lolos; Allison Lung; David Mack; David McKee; David Meekins; Joseph Mitchell; Hamlet Mkrtchyan; Robert Mueller; Gabriel Niculescu; Maria-Ioana Niculescu; David Pitz; David Potterveld; Liming Qin; Joerg Reinhold; Ilkyoung Shin; Stepan Stepanyan; Liguang Tang; Rob van der Meer; Kelley Vansyoc; D. Van Westrum; Jochen Volmer; William Vulcan; Stephen Wood; Chen Yan; Wenxia Zhao; Benedikt Zihlmann

2006-01-01

The data analysis for the reaction H(e,e(prime) pi + )n, which was used to determine values for the charged pion form factor Fpi for values of Q2 = 0.6-1.6 (gEv/C) 2 , has been repeated with careful inspection of all steps and special attention to systematic uncertainties. Also the method used to extract Fpi from the measured longitudinal cross section was critically reconsidered. Final values for the separated longitudinal and transverse cross sections and the extracted values of Fpi are presented

Duplication of C7orf58, WNT16 and FAM3C in an obese female with a t(7;22)(q32.1;q11.2) chromosomal translocation and clinical features resembling Coffin-Siris Syndrome.

Science.gov (United States)

Zhu, Jun; Qiu, Jun; Magrane, Gregg; Abedalthagafi, Malak; Zanko, Andrea; Golabi, Mahin; Chehab, Farid F

2012-01-01

We characterized the t(7;22)(q32;q11.2) chromosomal translocation in an obese female with coarse features, short stature, developmental delay and a hypoplastic fifth digit. While these clinical features suggest Coffin-Siris Syndrome (CSS), we excluded a CSS diagnosis by exome sequencing based on the absence of deleterious mutations in six chromatin-remodeling genes recently shown to cause CSS. Thus, molecular characterization of her translocation could delineate genes that underlie other syndromes resembling CSS. Comparative genomic hybridization microarrays revealed on chromosome 7 the duplication of a 434,682 bp region that included the tail end of an uncharacterized gene termed C7orf58 (also called CPED1) and spanned the entire WNT16 and FAM3C genes. Because the translocation breakpoint on chromosome 22 did not disrupt any apparent gene, her disorder was deemed to result from the rearrangement on chromosome 7. Mapping of yeast and bacterial artificial chromosome clones by fluorescent in situ hybridization on chromosome spreads from this patient showed that the duplicated region and all three genes within it were located on both derivative chromosomes 7 and 22. Furthermore, DNA sequencing of exons and splice junctional regions from C7orf58, WNT16 and FAM3C revealed the presence of potential splice site and promoter mutations, thereby augmenting the detrimental effect of the duplicated genes. Hence, dysregulation and/or disruptions of C7orf58, WNT16 and FAM3C underlie the phenotype of this patient, serve as candidate genes for other individuals with similar clinical features and could provide insights into the physiological role of the novel gene C7orf58.

Duplication of C7orf58, WNT16 and FAM3C in an obese female with a t(7;22(q32.1;q11.2 chromosomal translocation and clinical features resembling Coffin-Siris Syndrome.

Directory of Open Access Journals (Sweden)

Jun Zhu

Full Text Available We characterized the t(7;22(q32;q11.2 chromosomal translocation in an obese female with coarse features, short stature, developmental delay and a hypoplastic fifth digit. While these clinical features suggest Coffin-Siris Syndrome (CSS, we excluded a CSS diagnosis by exome sequencing based on the absence of deleterious mutations in six chromatin-remodeling genes recently shown to cause CSS. Thus, molecular characterization of her translocation could delineate genes that underlie other syndromes resembling CSS. Comparative genomic hybridization microarrays revealed on chromosome 7 the duplication of a 434,682 bp region that included the tail end of an uncharacterized gene termed C7orf58 (also called CPED1 and spanned the entire WNT16 and FAM3C genes. Because the translocation breakpoint on chromosome 22 did not disrupt any apparent gene, her disorder was deemed to result from the rearrangement on chromosome 7. Mapping of yeast and bacterial artificial chromosome clones by fluorescent in situ hybridization on chromosome spreads from this patient showed that the duplicated region and all three genes within it were located on both derivative chromosomes 7 and 22. Furthermore, DNA sequencing of exons and splice junctional regions from C7orf58, WNT16 and FAM3C revealed the presence of potential splice site and promoter mutations, thereby augmenting the detrimental effect of the duplicated genes. Hence, dysregulation and/or disruptions of C7orf58, WNT16 and FAM3C underlie the phenotype of this patient, serve as candidate genes for other individuals with similar clinical features and could provide insights into the physiological role of the novel gene C7orf58.

Defective prevention of immune precipitation in autoimmune diseases is independent of C4A*Q0

Science.gov (United States)

Arason, G J; Kolka, R; Hreidarsson, A B; Gudjonsson, H; Schneider, P M; Fry, L; Arnason, A

2005-01-01

Increased prevalence of C4 null alleles is a common feature of autoimmune diseases. We have shown previously that complement-dependent prevention of immune precipitation (PIP) is defective in patients with systemic lupus erythematosus (SLE), and correlated this defect with C4A*Q0 and low levels of the C4A isotype. To further clarify the role of C4A in the aetiology of SLE, we now extend our studies to other diseases which have been associated with C4A*Q0. The frequency of C4A*Q0 was increased in Icelandic patients with coeliac disease (0·50; P Grave's disease (0·30; P = 0·002) and insulin-dependent diabetes mellitus (0·23; P = 0·04) and in British patients with dermatitis herpetiformis (0·42; P = 0·002) and this was reflected in low levels of C4A. In spite of this, PIP was normal in these patients, and in marked contrast to our previous observations on connective tissue diseases, PIP measurements in these patient groups correlated more strongly with levels of C4B (r = 0·51, P = 0·0000004) than C4A. Patients with increased levels of anti-C1q antibodies had significantly lower PIP than patients without such antibodies (P cause of the PIP defect in autoimmune connective tissue disease. PMID:15932521

Improving nuclear envelope dynamics by EBV BFRF1 facilitates intranuclear component clearance through autophagy.

Science.gov (United States)

Liu, Guan-Ting; Kung, Hsiu-Ni; Chen, Chung-Kuan; Huang, Cheng; Wang, Yung-Li; Yu, Cheng-Pu; Lee, Chung-Pei

2018-02-26

Although a vesicular nucleocytoplasmic transport system is believed to exist in eukaryotic cells, the features of this pathway are mostly unknown. Here, we report that the BFRF1 protein of the Epstein-Barr virus improves vesicular transport of nuclear envelope (NE) to facilitate the translocation and clearance of nuclear components. BFRF1 expression induces vesicles that selectively transport nuclear components to the cytoplasm. With the use of aggregation-prone proteins as tools, we found that aggregated nuclear proteins are dispersed when these BFRF1-induced vesicles are formed. BFRF1-containing vesicles engulf the NE-associated aggregates, exit through from the NE, and putatively fuse with autophagic vacuoles. Chemical treatment and genetic ablation of autophagy-related factors indicate that autophagosome formation and autophagy-linked FYVE protein-mediated autophagic proteolysis are involved in this selective clearance of nuclear proteins. Remarkably, vesicular transport, elicited by BFRF1, also attenuated nuclear aggregates accumulated in neuroblastoma cells. Accordingly, induction of NE-derived vesicles by BFRF1 facilitates nuclear protein translocation and clearance, suggesting that autophagy-coupled transport of nucleus-derived vesicles can be elicited for nuclear component catabolism in mammalian cells.-Liu, G.-T., Kung, H.-N., Chen, C.-K., Huang, C., Wang, Y.-L., Yu, C.-P., Lee, C.-P. Improving nuclear envelope dynamics by EBV BFRF1 facilitates intranuclear component clearance through autophagy.

Dicty_cDB: Contig-U13257-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 1903.... 52 2e-05 (Q3V1N1) RecName: Full=Malignant fibrous histiocytoma-amplified ... 52 2e-05 AK171731_1( A...51 3e-05 (Q9Y4C4) RecName: Full=Malignant fibrous histiocytoma-amplified ... 51 3e-05 Z83230_4( Z83230 |pid:...gnant fibrous histiocytoma-amplified ... 44 0.003 DQ526607_1( DQ526607 |pid:none) Arabidopsis thali...ne/threonine-protein kinase roco4; EC=2.7.11.1; AltName: Full=Ras of complex proteins and C-terminal of roc ...6 0.19 2 ( EY270450 ) BF01053B1A07.f1 Normalized subtracted keck librar... 46 0.21 2 ( EK334602 ) 1095467035856 Global-Ocean-Sampli

Isometric C1-immersions for pairs of Riemannian metrics

International Nuclear Information System (INIS)

D'Ambra, Giuseppina; Datta, Mahuya

2001-08-01

Let h 1 , h 2 be two Euclidean metrics on R q , and let V be a C ∞ -manifold endowed with two Riemannian metrics g 1 and g 2 . We study the existence of C 1 -immersions f:(V,g 1 ,g 2 )→(R q ,h 1 ,h 2 ) such that f*(h i )=g i for i=1,2. (author)

Dicty_cDB: Contig-U15573-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U15573-1 gap included 2005 4 5020093 5018210 MINUS 13 13 U15573 0 5 0 1 1 0 ...0 0 0 1 1 0 2 2 Show Contig-U15573-1 Contig ID Contig-U15573-1 Contig update 2004. 6.11 Contig sequence >Contig-U15573-1 (Contig...-U15573-1Q) /CSM_Contig/Contig-U15573-1Q.Seq.d AGTCTTGAGCTTTTATTGGGTCAACCATTGGGTGAATATAC... AGCNTTAACNGGNAA Gap gap included Contig length 2005 Chromosome number (1..6, M) ...xxlfrsnxslxxxxxxsxnxx Frame C: s*afigstig*iyiylkrfhlfl*skryyqskw*fkifpilkqttiiyen

Different AMPA receptor subtypes mediate the distinct kinetic components of a biphasic EPSC in hippocampal interneurons

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Todd eStincic

2015-05-01

Full Text Available CA1 hippocampal interneurons at the border between stratum radiatum and stratum lacunosum-moleculare have AMPA receptor (AMPAR-mediated excitatory postsynaptic currents (EPSCs that consist of two distinct phases: a typical fast component (FC, and a highly unusual slow component (SC that persists for hundreds of milliseconds. To determine whether these kinetically distinct components of the EPSC are mediated by distinct AMPAR subpopulations, we examined the relative contributions of GluA2-containing and –lacking AMPARs to the SC. GluA2-containing AMPARs mediated the majority of the FC whereas GluA2-lacking AMPARs preferentially generated the SC. When glutamate uptake through the glial glutamate transporter EAAT1 was inhibited, spill over-mediated AMPAR activation recruited an even slower third kinetic component that persisted for several seconds; however, this spillover-mediated current was mediated predominantly by GluA2-containing AMPARs and therefore was clearly distinct from the SC when uptake is intact. Thus, different AMPAR subpopulations that vary in GluA2 content mediate the distinct components of the AMPAR EPSC. The SC is developmentally downregulated in mice, declining after the second postnatal week. This downregulation affects both GluA2-containing and GluA2-lacking AMPARs mediating the SC, and is not accompanied by developmental changes in the GluA2 content of AMPARs underlying the FC. Thus, the downregulation of the SC appears to be independent of synaptic GluA2 expression, suggesting the involvement of another AMPAR subunit or an auxiliary protein. Our results therefore identify GluA2-dependent and GluA2-independent determinants of the SC: GluA2-lacking AMPARs preferentially contribute to the SC, while the developmental downregulation of the SC is independent of GluA2 content.

SNARE-mediated trafficking of α5β1 integrin is required for spreading in CHO cells

International Nuclear Information System (INIS)

Skalski, Michael; Coppolino, Marc G.

2005-01-01

In this study, the role of SNARE-mediated membrane traffic in regulating integrin localization was examined and the requirement for SNARE function in cellular spreading was quantitatively assessed. Membrane traffic was inhibited with the VAMP-specific catalytic light chain from tetanus toxin (TeTx-LC), a dominant-negative form (E329Q) of N-ethylmaleimide-sensitive fusion protein (NSF), and brefeldin A (BfA). Inhibition of membrane traffic with either E329Q-NSF or TeTx-LC, but not BfA, significantly inhibited spreading of CHO cells on fibronectin. Spreading was rescued in TeTx-LC-expressing cells by co-transfection with a TeTx-resistant cellubrevin/VAMP3. E329Q-NSF, a general inhibitor of SNARE function, was a more potent inhibitor of cell spreading than TeTx-LC, suggesting that tetanus toxin-insensitive SNAREs contribute to adhesion. It was found that E329Q-NSF prevented trafficking of α 5 β 1 integrins from a central Rab11-containing compartment to sites of protrusion during cell adhesion, while TeTx-LC delayed this trafficking. These results are consistent with a model of cellular adhesion that implicates SNARE function as an important component of integrin trafficking during the process of cell spreading

DMT efficiently inhibits hepatic gluconeogenesis by regulating the Gαq signaling pathway.

Science.gov (United States)

Zhou, Ting-Ting; Ma, Fei; Shi, Xiao-Fan; Xu, Xin; Du, Te; Guo, Xiao-Dan; Wang, Gai-Hong; Yu, Liang; Rukachaisirikul, Vatcharin; Hu, Li-Hong; Chen, Jing; Shen, Xu

2017-08-01

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with complicated pathogenesis and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. G protein-coupled receptors (GPCRs) are classified as distinct families by heterotrimeric G proteins, primarily including Gαs, Gαi and Gαq. Gαs-coupled GPCRs function potently in the regulation of hepatic gluconeogenesis by activating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway and Gαi-coupled GPCRs exhibit inhibitory effect on adenylyl cyclase and reduce intracellular cAMP level. However, little is known about the regulation of Gαq-coupled GPCRs in hepatic gluconeogenesis. Here, small-molecule 2-(2,4-dimethoxy-3-methylphenyl)-7-(thiophen-2-yl)-9-(trifluoromethyl)-2,3-dihydropyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4( 1H )-one (DMT) was determined to suppress hepatic glucose production and reduce mRNA levels of gluconeogenic genes. Treatment of DMT in db/db mice decreased fasting blood glucose and hemoglobin A1C (HbA1c) levels, while improved glucose tolerance and pyruvate tolerance. Mechanism study demonstrated that DMT-inhibited gluconeogenesis by regulating the Gαq/phospholipase C (PLC)/inositol-1,4,5-triphosphate receptor (IP3R)-mediated calcium (Ca 2+ )/calmodulin (CaM)/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/forkhead box protein O1 (FOXO1) signaling pathway. To our knowledge, DMT might be the first reported small molecule able to suppress hepatic gluconeogenesis by regulating Gαq signaling, and our current work has also highlighted the potential of DMT in the treatment of T2DM. © 2017 Society for Endocrinology.

Exotic tetraquark states with the qq anti Q anti Q configuration

Energy Technology Data Exchange (ETDEWEB)

Luo, Si-Qiang; Chen, Kan; Liu, Xiang [Lanzhou University, School of Physical Science and Technology, Lanzhou (China); Lanzhou University and Institute of Modern Physics, CAS, Research Center for Hadron and CSR Physics, Lanzhou (China); Liu, Yan-Rui [Shandong University, School of Physics and Key Laboratory of Particle Physics and Particle Irradiation (MOE), Jinan (China); Zhu, Shi-Lin [Peking University, School of Physics and State Key Laboratory of Nuclear Physics and Technology, Beijing (China); Collaborative Innovation Center of Quantum Matter, Beijing (China); Peking University, Center for High Energy Physics, Beijing (China)

2017-10-15

In this work, we study systematically the mass splittings of the qq anti Q anti Q (q = u, d, s and Q = c, b) tetraquark states with the color-magnetic interaction by considering color mixing effects and estimate roughly their masses. We find that the color mixing effect is relatively important for the J{sup P} = 0{sup +} states and possible stable tetraquarks exist in the nn anti Q anti Q (n = u, d) and ns anti Q anti Q systems either with J = 0 or with J = 1. Possible decay patterns of the tetraquarks are briefly discussed. (orig.)

Significance of Ubiad1 for Epidermal Keratinocytes Involves More Than CoQ10 Synthesis: Implications for Skin Aging

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Florian Labarrade

2018-01-01

Full Text Available The significance of Coenzyme Q10 (CoQ10 as an anti-oxidant barrier of the skin, as well as a key component in anti-aging strategies for skin care products, has been firmly established. Biosynthesis of CoQ10 in the mitochondria is well known, but there is only limited information on the non-mitochondrial synthesis of CoQ10 in the skin. Recent findings in zebrafish identified that a tumor suppressor, Ubiad1, is also a key enzyme in the non-mitochondrial synthesis of CoQ10. The purpose of this study was to investigate expression of Ubiad1 in human skin, and its implication in the skin’s cutaneous response to oxidative stress. We observed Ubiad1 localization in the epidermis, particularly a subcellular localization in the Golgi apparatus. Ubiad1 modulation by a pentapeptide was associated with an observed reduction in ROS/RNS stresses (−44%/−19% respectively, lipid peroxidation (−25% and preservation of membrane fluidity under stress conditions. Electron microscopy of keratinocytes revealed a significant degree of stimulation of the Golgi complex, as well as significantly improved mitochondrial morphology. Given the importance of CoQ10 in mitigating the visible signs of skin aging, our findings identify Ubiad1 as an essential component of the defensive barriers of the epidermis.

Dicty_cDB: Contig-U01750-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U01750-1 no gap 811 3 3337090 3336279 MINUS 2 2 U01750 1 0 0 0 0 0 1 0 0 0 0 0 0 0 Show Contig...-U01750-1 Contig ID Contig-U01750-1 Contig update 2001. 8.29 Contig sequence >Contig-U01750-1 (Contig...-U01750-1Q) /CSM_Contig/Contig-U01750-1Q.Seq.d GGAAGTTGTAATAATAAAAAAATAAAAATAAAAATAAAAAAATAAAAAAA...GAATACCAAGGTGAAAGAATTTTTCAAAAACTTCCTCAA ATCAACACAAATTTCGAAAAATTAACAATTTGGGAAAAGAAAATCGTTTC AAATCTTTATT Gap no gap Contig...crncnciwsktl*tywiyskiinpi**i*ipr *knfsktssnqhkfrkinnlgkenrfksl own update 2004. 6. 7 Homology vs CSM-cDNA Query= Contig

TET1-Mediated Hydroxymethylation Facilitates Hypoxic Gene Induction in Neuroblastoma

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Christopher J. Mariani

2014-06-01

Full Text Available The ten-eleven-translocation 5-methylcytosine dioxygenase (TET family of enzymes catalyzes the conversion of 5-methylcytosine (5-mC to 5-hydroxymethylcytosine (5-hmC, a modified cytosine base that facilitates gene expression. Cells respond to hypoxia by inducing a transcriptional program regulated in part by oxygen-dependent dioxygenases that require Fe(II and α-ketoglutarate. Given that the TET enzymes also require these cofactors, we hypothesized that the TETs regulate the hypoxia-induced transcriptional program. Here, we demonstrate that hypoxia increases global 5-hmC levels, with accumulation of 5-hmC density at canonical hypoxia response genes. A subset of 5-hmC gains colocalize with hypoxia response elements facilitating DNA demethylation and HIF binding. Hypoxia results in transcriptional activation of TET1, and full induction of hypoxia-responsive genes and global 5-hmC increases require TET1. Finally, we show that 5-hmC increases and TET1 upregulation in hypoxia are HIF-1 dependent. These findings establish TET1-mediated 5-hmC changes as an important epigenetic component of the hypoxic response.

A Rare, Recurrent, De Novo 14q32.2q32.31 Microdeletion of 1.1 Mb in a 20-Year-Old Female Patient with a Maternal UPD(14-Like Phenotype and Intellectual Disability

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Almira Zada

2014-01-01

Full Text Available We present a 20-year-old female patient from Indonesia with intellectual disability (ID, proportionate short stature, motor delay, feeding problems, microcephaly, facial dysmorphism, and precocious puberty who was previously screened normal for conventional karyotyping, fragile X testing, and subtelomeric MLPA analysis. Subsequent genome wide array analysis was performed on DNA from blood and revealed a 1.1 Mb deletion in 14q32.2q32.31 (chr14:100,388,343-101,506,214; hg19. Subsequent carrier testing in the parents by array showed that the deletion had occurred de novo in the patient and that her paternal 14q32 allele was deleted. The deleted region encompasses the DLK1/GTL2 imprinted gene cluster which is consistent with the maternal UPD(14-like phenotype of the patient. This rare, recurrent microdeletion was recently shown not to be mediated by low copy repeats, but by expanded TGG repeats, flanking the 14q32.2q32.21 deletion boundaries, a novel mechanism of recurrent genomic rearrangement. This is another example how the application of high resolution genome wide testing provides an accurate genetic diagnosis, thereby improving the care for patients and optimizing the counselling for family.

Dicty_cDB: Contig-U15828-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U15828-1 gap included 1593 1 4184040 4182448 MINUS 12 19 U15828 0 0 6 0 0 0 ...0 0 2 0 4 0 0 0 Show Contig-U15828-1 Contig ID Contig-U15828-1 Contig update 2004. 6.11 Contig sequence >Contig-U15828-1 (Contig...-U15828-1Q) /CSM_Contig/Contig-U15828-1Q.Seq.d ATAAAAAAAATTAAAAAATTAAAAAAGTTATCCACCCAAGT...ACA AATATTATAACTGGTACTGCTACTGTTTCAATCCCTCAAAAAAATTTAAT TTATATTTTACCAAATTCAAATACAATTAATCAATCAACAATTACAATTA CAA Gap gap included Contig...SFNPANSDFSFSYNINTTITQPTQIYLNQDIYYPNGFTTNIITGTATVSIPQ KNLIYILPNSNTINQSTITIT own update 2004. 6.23 Homology vs CSM-cDNA Query= Contig

Complement components of nerve regeneration conditioned fluid influence the microenvironment of nerve regeneration

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Guang-shuai Li

2016-01-01

Full Text Available Nerve regeneration conditioned fluid is secreted by nerve stumps inside a nerve regeneration chamber. A better understanding of the proteinogram of nerve regeneration conditioned fluid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration. In this study, we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve. Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis confirmed that there were more than 10 complement components (complement factor I, C1q-A, C1q-B, C2, C3, C4, C5, C7, C8ß and complement factor D in the nerve regeneration conditioned fluid and each varied at different time points. These findings suggest that all these complement components have a functional role in nerve regeneration.

Syntenic homology of human unique DNA sequences within chromossome regions 5q31, 10q22, 13q32-33 and 19q13.1 in the great apes

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Rhea U. Vallente-Samonte

2000-09-01

Full Text Available Homologies between chromosome banding patterns and DNA sequences in the great apes and humans suggest an apparent common origin for these two lineages. The availability of DNA probes for specific regions of human chromosomes (5q31, 10q22, 13q32-33 and 19q13.1 led us to cross-hybridize these to chimpanzee (Pan troglodytes, PTR, gorilla (Gorilla gorilla, GGO and orangutan (Pongo pygmaeus, PPY chromosomes in a search for equivalent regions in the great apes. Positive hybridization signals to the chromosome 5q31-specific DNA probe were observed at HSA 5q31, PTR 4q31, GGO 4q31 and PPY 4q31, while fluorescent signals using the chromosome 10q22-specific DNA probe were noted at HSA 10q22, PTR 8q22, GGO 8q22 and PPY 7q22. The chromosome arms showing hybridization signals to the Quint-EssentialTM 13-specific DNA probe were identified as HSA 13q32-33, PTR 14q32-33, GGO 14q32-33 and PPY 14q32-33, while those presenting hybridization signals to the chromosome 19q13.1-specific DNA probe were identified as HSA 19q13.1, PTR 20q13, GGO 20q13 and PPY 20q13. All four probes presumably hybridized to homologous chromosomal locations in the apes, which suggests a homology of certain unique DNA sequences among hominoid species.Homologias entre os padrões de bandamento de cromossomos e seqüências de DNA em grandes macacos e humanos sugerem uma aparente origem comum para estas duas linhagens. A disponibilidade de sondas de DNA para regiões específicas de cromossomos humanos (5q31, 10q22, 13q32-33 e 19q13.1 nos levou a realizar hibridação cruzada com cromossomos de chimpanzé (Pan troglodytes, PTR, gorila (Gorilla gorilla, GGO e orangotango (Pongo pygmaeus, PPY em um pesquisa de regiões equivalentes em grandes macacos. Sinais positivos de hibridação para a sonda de DNA específica para o cromossomo 5q31 foram observados em HSA 5q31, PTR 4q31, GGO 4q31 e PPY 4q31, enquanto que sinais fluorescentes usando a sonda de DNA específica para o cromossomo 10q22 foram

C1qTNF-related protein 1 improve insulin resistance by reducing phosphorylation of serine 1101 in insulin receptor substrate 1.

Science.gov (United States)

Xin, Yaping; Zhang, Dongming; Fu, Yanqin; Wang, Chongxian; Li, Qingju; Tian, Chenguang; Zhang, Suhe; Lyu, Xiaodong

2017-08-30

C1qTNF-related protein 1 (CTRP1) is independently associated with type 2 diabetes. However, the relationship between CTRP1 and insulin resistance is still not established. This study aimed to explore the role of CTRP1 under the situation of insulin resistance in adipose tissue. Plasma CTRP1 level was investigated in type 2 diabetic subjects (n = 35) and non-diabetic subjects (n = 35). The relationship between CTRP1 and phosphorylation of multi insulin receptor substrate 1 (IRS-1) serine (Ser) sites was further explored. Our data showed that Plasma CTRP1 was higher and negative correlation with insulin resistance in diabetic subjects (r = -0.283, p = 0.018). Glucose utilisation test revealed that the glucose utilisation rate of mature adipocytes was improved by CTRP1 in the presence of insulin. CTRP1 was not only related to IRS-1 protein, but also negatively correlated with IRS-1 Ser1101 phosphorylation (r = -0.398, p = 0.031). Furthermore, Phosphorylation levels of IRS-1 Ser1101 were significantly lower after incubation with 40 ng/mL CTRP1 in mature adipocytes than those with no intervention (p insulin resistance by reducing the phosphorylation of IRS-1 Ser1101, induced in the situation of insulin resistance as a feedback adipokine.

Influence of Alkali Metal Substitution on the Phase Transition Behavior of CsGaQ2 (Q = S, Se

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Daniel Friedrich

2017-12-01

Full Text Available The formation of solid solution series Cs1−xMxGaQ2-mC64 (M = K, Rb; Q = S, Se; x = 0–1 was studied by X-ray diffraction and spectroscopic methods, revealing a complete miscibility of CsGaQ2-mC64 with RbGaQ2 and KGaSe2, and a large miscibility gap with KGaS2. All solid solution members exhibit similar Raman spectra, indicating the covalent Ga-Q bonding character. The similar optical band gaps likewise further contribute to this conclusion. Up to a certain degree of substitution, these solid solutions undergo a phase transition similar to CsGaQ2-mC64. The influence of the substitution parameter x on phase transition process was investigated in situ using high-temperature X-ray powder diffraction experiments. Phase-pure solid solutions of the high-temperature polymorphs Cs1−xMxGaQ2-mC16 were obtained up to xmax(K = 0.1 and xmax(Rb = 0.3. The crystal structures of these new CsGaQ2-mC16 analogous high-temperature phases were refined from synchrotron diffraction data by Rietveld-refinement.

Genome Sequence of Klebsiella pneumoniae KpQ3, a DHA-1 β-Lactamase-Producing Nosocomial Isolate

Science.gov (United States)

Tobes, Raquel; Codoñer, Francisco M.; López-Camacho, Elena; Salanueva, Iñigo J.; Manrique, Marina; Brozynska, Marta; Gómez-Gil, Rosa; Martínez-Blanch, Juan F.; Álvarez-Tejado, Miguel; Pareja, Eduardo

2013-01-01

Klebsiella pneumoniae KpQ3 is a multidrug-resistant isolate obtained from a blood culture of a patient in a burn unit in the Hospital Universitario La Paz (Madrid, Spain) in 2008. The genome contains multiple antibiotic resistance genes, including a plasmid-mediated DHA-1 cephalosporinase gene. PMID:23469341

Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification.

Science.gov (United States)

Andreiuolo, Felipe; Le Teuff, Gwénaël; Bayar, Mohamed Amine; Kilday, John-Paul; Pietsch, Torsten; von Bueren, André O; Witt, Hendrik; Korshunov, Andrey; Modena, Piergiorgio; Pfister, Stefan M; Pagès, Mélanie; Castel, David; Giangaspero, Felice; Chimelli, Leila; Varlet, Pascale; Rutkowski, Stefan; Frappaz, Didier; Massimino, Maura; Grundy, Richard; Grill, Jacques

2017-01-01

Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths. This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC) immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS) was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort. Stratification on a predictor that did not satisfy the proportional hazards assumption was considered. Model performance was evaluated and an internal-external cross validation was performed. Among complete cases with 5-year median follow-up (n = 470; 131 deaths), TNC and 1q25 gain were significantly associated with age at diagnosis and posterior fossa tumor location. 1q25 status added independent prognostic value for death beyond the classical variables with a hazard ratio (HR) = 2.19 95%CI = [1.29; 3.76] (p = 0.004), while TNC prognostic relation was tumor location-dependent with HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004) in posterior fossa and HR = 0.64 [0.28; 1.48] (p = 0.295) in supratentorial (interaction p value = 0.015). The derived prognostic score identified 3 different robust risk groups. The omission of upfront RT was not associated with OS for good and intermediate prognostic groups while the absence of upfront RT was negatively associated with OS in the poor risk group. Integrated TNC expression and 1q25 status are useful to better stratify patients and to eventually adapt treatment regimens in pediatric intracranial ependymoma.

Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification.

Directory of Open Access Journals (Sweden)

Felipe Andreiuolo

Full Text Available Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths.This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort. Stratification on a predictor that did not satisfy the proportional hazards assumption was considered. Model performance was evaluated and an internal-external cross validation was performed.Among complete cases with 5-year median follow-up (n = 470; 131 deaths, TNC and 1q25 gain were significantly associated with age at diagnosis and posterior fossa tumor location. 1q25 status added independent prognostic value for death beyond the classical variables with a hazard ratio (HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004, while TNC prognostic relation was tumor location-dependent with HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004 in posterior fossa and HR = 0.64 [0.28; 1.48] (p = 0.295 in supratentorial (interaction p value = 0.015. The derived prognostic score identified 3 different robust risk groups. The omission of upfront RT was not associated with OS for good and intermediate prognostic groups while the absence of upfront RT was negatively associated with OS in the poor risk group.Integrated TNC expression and 1q25 status are useful to better stratify patients and to eventually adapt treatment regimens in pediatric intracranial ependymoma.

Ire1 mediated mRNA splicing in a C-terminus deletion mutant of Drosophila Xbp1.

Directory of Open Access Journals (Sweden)

Dina S Coelho

Full Text Available The Unfolded Protein Response is a homeostatic mechanism that permits eukaryotic cells to cope with Endoplasmic Reticulum (ER stress caused by excessive accumulation of misfolded proteins in the ER lumen. The more conserved branch of the UPR relies on an ER transmembrane enzyme, Ire1, which, upon ER stress, promotes the unconventional splicing of a small intron from the mRNA encoding the transcription factor Xbp1. In mammals, two specific regions (the hydrophobic region 2--HR2--and the C-terminal translational pausing site present in the Xbp1unspliced protein mediate the recruitment of the Xbp1 mRNA-ribosome-nascent chain complex to the ER membrane, so that Xbp1 mRNA can be spliced by Ire1. Here, we generated a Drosophila Xbp1 deletion mutant (Excision101 lacking both HR2 and C-terminal region, but not the Ire1 splicing site. We show that Ire1-dependent splicing of Xbp1 mRNA is reduced, but not abolished in Excision101. Our results suggest the existence of additional mechanisms for ER membrane targeting of Xbp1 mRNA that are independent of the C-terminal domain of Drosophila Xbp1unspliced.

Dicty_cDB: Contig-U04432-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U04432-1 no gap 600 1 1520578 1521098 PLUS 1 1 U04432 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Show Contig...-U04432-1 Contig ID Contig-U04432-1 Contig update 2001. 8.29 Contig sequence >Contig-U04432-1 (Contig...-U04432-1Q) /CSM_Contig/Contig-U04432-1Q.Seq.d AATTATAATCAAAACAAATTAATAAAAAAAATGATTAATAGTTTTGTCTC ...TCAACAATATGAAATTGCAAGAT TAAATGGTTATGATAATGCCCATAATTTACCAAGAGATATTAGTCAAATA Gap no gap Contig length 600 Chro...ni**fkgrnsnknyfsrymgtiessti*n ckikwl**cp*ftkry*sn own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U04432-1 (Contig

Effects of interleukin-7/interleukin-7 receptor on RANKL-mediated osteoclast differentiation and ovariectomy-induced bone loss by regulating c-Fos/c-Jun pathway.

Science.gov (United States)

Zhao, Ji-Jun; Wu, Zhao-Feng; Yu, Ying-Hao; Wang, Ling; Cheng, Li

2018-09-01

To explore the effects of IL-7/IL-7R on the RANKL-mediated osteoclast differentiation in vitro and OVX-induced bone loss in vivo. BMMs and RAW264.7 were transfected with IL-7, IL-7R siRNA, c-Fos siRNA, and c-jun siRNA and later stimulated by RANKL. TRAP and toluidine blue staining were used to observe osteoclast formation and bone resorption, respectively. HE and TRAP staining were used to detect trabecular bone microstructure and osteoclasts of mice, respectively. qRT-PCR and Western blot analysis were used to examine expression. IL-7 unregulated the expression of CTSK, NFATc1, MMP9, and the phosphorylation of p38 and Akt by activating the c-Fos/c-Jun pathway, which increased osteoclast numbers and bone resorption in RANKL-stimulated macrophages. While IL-7R siRNA and c-Fos siRNA decreased the expression, as well as and the phosphorylation of p38 and Akt.IL-7 decreased the BMD and OPG expression in OVX-induced mice and increased the TRAP positive cells, the mRNA expression of c-fos, c-jun, and RANKL, which was contradictory to IL-7R siRNA, and c-Fos siRNA. Furthermore, IL-7R siRNA and c-Fos siRNA caused thicker trabeculae, increased trabecular number, and decreased osteolysis in OVX mice. IL-7/IL-7R can promote RANKL-mediated osteoclast formation and bone resorption by activating the c-Fos/c-Jun pathway, as well as inducing bone loss in OVX mice. © 2018 Wiley Periodicals, Inc.

Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence.

Science.gov (United States)

Hicks, Kevin G; Delbecq, Scott P; Sancho-Vaello, Enea; Blanc, Marie-Pierre; Dove, Katja K; Prost, Lynne R; Daley, Margaret E; Zeth, Kornelius; Klevit, Rachel E; Miller, Samuel I

2015-05-23

Salmonella PhoQ is a histidine kinase with a periplasmic sensor domain (PD) that promotes virulence by detecting the macrophage phagosome. PhoQ activity is repressed by divalent cations and induced in environments of acidic pH, limited divalent cations, and cationic antimicrobial peptides (CAMP). Previously, it was unclear which signals are sensed by salmonellae to promote PhoQ-mediated virulence. We defined conformational changes produced in the PhoQ PD on exposure to acidic pH that indicate structural flexibility is induced in α-helices 4 and 5, suggesting this region contributes to pH sensing. Therefore, we engineered a disulfide bond between W104C and A128C in the PhoQ PD that restrains conformational flexibility in α-helices 4 and 5. PhoQ(W104C-A128C) is responsive to CAMP, but is inhibited for activation by acidic pH and divalent cation limitation. phoQ(W104C-A128C) Salmonella enterica Typhimurium is virulent in mice, indicating that acidic pH and divalent cation sensing by PhoQ are dispensable for virulence.

Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1

Science.gov (United States)

Cai, Qiuyin; Zhang, Ben; Sung, Hyuna; Low, Siew-Kee; Kweon, Sun-Seog; Lu, Wei; Shi, Jiajun; Long, Jirong; Wen, Wanqing; Choi, Ji-Yeob; Noh, Dong-Young; Shen, Chen-Yang; Matsuo, Keitaro; Teo, Soo-Hwang; Kim, Mi Kyung; Khoo, Ui Soon; Iwasaki, Motoki; Hartman, Mikael; Takahashi, Atsushi; Ashikawa, Kyota; Matsuda, Koichi; Shin, Min-Ho; Park, Min Ho; Zheng, Ying; Xiang, Yong-Bing; Ji, Bu-Tian; Park, Sue K.; Wu, Pei-Ei; Hsiung, Chia-Ni; Ito, Hidemi; Kasuga, Yoshio; Kang, Peter; Mariapun, Shivaani; Ahn, Sei Hyun; Kang, Han Sung; Chan, Kelvin Y. K.; Man, Ellen P. S.; Iwata, Hiroji; Tsugane, Shoichiro; Miao, Hui; Liao, Jiemin; Nakamura, Yusuke; Kubo, Michiaki; Delahanty, Ryan J.; Zhang, Yanfeng; Li, Bingshan; Li, Chun; Gao, Yu-Tang; Shu, Xiao-Ou; Kang, Daehee; Zheng, Wei

2014-01-01

In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified three novel genetic loci associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene, P = 8.82 × 10−9), rs10474352 at 5q14.3 (near the ARRDC3 gene, P = 1.67 × 10−9), and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene, P = 4.25 × 10−8). These associations were replicated in European-ancestry populations including 16,003 cases and 41,335 controls (P = 0.030, 0.004, and 0.010, respectively). Data from the ENCODE project suggest that variants rs4951011 and rs10474352 may be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer. PMID:25038754

q-Deformed KP Hierarchy and q-Deformed Constrained KP Hierarchy

OpenAIRE

He, Jingsong; Li, Yinghua; Cheng, Yi

2006-01-01

Using the determinant representation of gauge transformation operator, we have shown that the general form of $au$ function of the $q$-KP hierarchy is a $q$-deformed generalized Wronskian, which includes the $q$-deformed Wronskian as a special case. On the basis of these, we study the $q$-deformed constrained KP ($q$-cKP) hierarchy, i.e. $l$-constraints of $q$-KP hierarchy. Similar to the ordinary constrained KP (cKP) hierarchy, a large class of solutions of $q$-cKP hierarchy can be represent...

The group A streptococcal collagen-like protein 1, Scl1, mediates biofilm formation by targeting the EDA-containing variant of cellular fibronectin expressed in wounded tissue

Science.gov (United States)

Oliver-Kozup, Heaven; Martin, Karen H.; Schwegler-Berry, Diane; Green, Brett J.; Betts, Courtney; Shinde, Arti V.; Van De Water, Livingston; Lukomski, Slawomir

2012-01-01

Summary Wounds are known to serve as portals of entry for group A Streptococcus (GAS). Subsequent tissue colonization is mediated by interactions between GAS surface proteins and host extracellular matrix components. We recently reported that the streptococcal collagen-like protein-1, Scl1, selectively binds the cellular form of fibronectin (cFn) and also contributes to GAS biofilm formation on abiotic surfaces. One structural feature of cFn, which is predominantly expressed in response to tissue injury, is the presence of a spliced variant containing extra domain A (EDA/EIIIA). We now report that GAS biofilm formation is mediated by the Scl1 interaction with EDA-containing cFn. Recombinant Scl1 proteins that bound cFn also bound recombinant EDA within the C-C′ loop region recognized by the α9β1 integrin. The extracellular 2-D matrix derived from human dermal fibroblasts supports GAS adherence and biofilm formation. Altogether, this work identifies and characterizes a novel molecular mechanism by which GAS utilizes Scl1 to specifically target an extracellular matrix component that is predominantly expressed at the site of injury in order to secure host tissue colonization. PMID:23217101

AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer.

Science.gov (United States)

Tian, Ying; Wang, Genjie; Hu, Qingzhu; Xiao, Xichun; Chen, Shuxia

2018-04-01

The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. © 2017 Wiley Periodicals, Inc.

A Quantitative Electrophysiological Biomarker of Duplication 15q11.2-q13.1 Syndrome.

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Joel Frohlich

Full Text Available Duplications of 15q11.2-q13.1 (Dup15q syndrome are highly penetrant for autism spectrum disorder (ASD. A distinct electrophysiological (EEG pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome.In the first study, we recorded spontaneous EEG from children with Dup15q syndrome (n = 11, age-and-IQ-matched children with ASD (n = 10 and age-matched typically developing (TD children (n = 9 and computed relative power in 6 frequency bands for 9 regions of interest (ROIs. Group comparisons were made using a repeated measures analysis of variance. In the second study, we recorded spontaneous EEG from a larger cohort of individuals with Dup15q syndrome (n = 27 across two sites and examined age, epilepsy, and duplication type as predictors of beta power using simple linear regressions.In the first study, spontaneous beta1 (12-20 Hz and beta2 (20-30 Hz power were significantly higher in Dup15q syndrome compared with both comparison groups, while delta (1-4 Hz was significantly lower than both comparison groups. Effect sizes in all three frequency bands were large (|d| > 1. In the second study, we found that beta2 power was significantly related to epilepsy diagnosis in Dup15q syndrome.Here, we have identified an electrophysiological biomarker of Dup15q syndrome that may facilitate clinical stratification, treatment monitoring, and measurement of target engagement for future clinical trials. Future work will investigate the genetic and neural underpinnings of this electrophysiological signature as well as the functional consequences of excessive beta oscillations in Dup15q syndrome.

Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Science.gov (United States)

Zhang, Mingfeng; Wang, Zhaoming; Obazee, Ofure; Jia, Jinping; Childs, Erica J.; Hoskins, Jason; Figlioli, Gisella; Mocci, Evelina; Collins, Irene; Chung, Charles C.; Hautman, Christopher; Arslan, Alan A.; Beane-Freeman, Laura; Bracci, Paige M.; Buring, Julie; Duell, Eric J.; Gallinger, Steven; Giles, Graham G.; Goodman, Gary E.; Goodman, Phyllis J.; Kamineni, Aruna; Kolonel, Laurence N.; Kulke, Matthew H.; Malats, Núria; Olson, Sara H.; Sesso, Howard D.; Visvanathan, Kala; White, Emily; Zheng, Wei; Abnet, Christian C.; Albanes, Demetrius; Andreotti, Gabriella; Brais, Lauren; Bueno-de-Mesquita, H. Bas; Basso, Daniela; Berndt, Sonja I.; Boutron-Ruault, Marie-Christine; Bijlsma, Maarten F.; Brenner, Hermann; Burdette, Laurie; Campa, Daniele; Caporaso, Neil E.; Capurso, Gabriele; Cavestro, Giulia Martina; Cotterchio, Michelle; Costello, Eithne; Elena, Joanne; Boggi, Ugo; Gaziano, J. Michael; Gazouli, Maria; Giovannucci, Edward L.; Goggins, Michael; Gross, Myron; Haiman, Christopher A.; Hassan, Manal; Helzlsouer, Kathy J.; Hu, Nan; Hunter, David J.; Iskierka-Jazdzewska, Elzbieta; Jenab, Mazda; Kaaks, Rudolf; Key, Timothy J.; Khaw, Kay-Tee; Klein, Eric A.; Kogevinas, Manolis; Krogh, Vittorio; Kupcinskas, Juozas; Kurtz, Robert C.; Landi, Maria T.; Landi, Stefano; Marchand, Le Loic; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L.; Neale, Rachel E.; Oberg, Ann L.; Panico, Salvatore; Patel, Alpa V.; Peeters, Petra H. M.; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Purdue, Mark; Quiros, J. Ramón; Riboli, Elio; Rothman, Nathaniel; Scarpa, Aldo; Scelo, Ghislaine; Shu, Xiao-Ou; Silverman, Debra T.; Soucek, Pavel; Strobel, Oliver; Sund, Malin; Małecka-Panas, Ewa; Taylor, Philip R.; Tavano, Francesca; Travis, Ruth C.; Thornquist, Mark; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Vashist, Yogesh; Vodicka, Pavel; Wactawski-Wende, Jean; Wentzensen, Nicolas; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Kooperberg, Charles; Risch, Harvey A.; Jacobs, Eric J.; Li, Donghui; Fuchs, Charles; Hoover, Robert; Hartge, Patricia; Chanock, Stephen J.; Petersen, Gloria M.; Stolzenberg-Solomon, Rachael S.; Wolpin, Brian M.; Kraft, Peter; Klein, Alison P.; Canzian, Federico; Amundadottir, Laufey T.

2016-01-01

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88×10−15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22×10−9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70×10−8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7×10−8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5×10−4-2.0×10−3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology. PMID:27579533

Conserved residues of the human mitochondrial holocytochrome c synthase mediate interactions with heme.

Science.gov (United States)

Babbitt, Shalon E; San Francisco, Brian; Bretsnyder, Eric C; Kranz, Robert G

2014-08-19

C-type cytochromes are distinguished by the covalent attachment of a heme cofactor, a modification that is typically required for its subsequent folding, stability, and function. Heme attachment takes place in the mitochondrial intermembrane space and, in most eukaryotes, is mediated by holocytochrome c synthase (HCCS). HCCS is the primary component of the eukaryotic cytochrome c biogenesis pathway, known as System III. The catalytic function of HCCS depends on its ability to coordinate interactions between its substrates: heme and cytochrome c. Recent advancements in the recombinant expression and purification of HCCS have facilitated comprehensive analyses of the roles of conserved residues in HCCS, as demonstrated in this study. Previously, we proposed a four-step model describing HCCS-mediated cytochrome c assembly, identifying a conserved histidine residue (His154) as an axial ligand to the heme iron. In this study, we performed a systematic mutational analysis of 17 conserved residues in HCCS, and we provide evidence that the enzyme contains two heme-binding domains. Our data indicate that heme contacts mediated by residues within these domains modulate the dynamics of heme binding and contribute to the stability of the HCCS-heme-cytochrome c steady state ternary complex. While some residues are essential for initial heme binding (step 1), others impact the subsequent release of the holocytochrome c product (step 4). Certain HCCS mutants that were defective in heme binding were corrected for function by exogenous aminolevulinic acid (ALA, the precursor to heme). This chemical "correction" supports the proposed role of heme binding for the corresponding residues.

Dicty_cDB: Contig-U11443-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available cal protei... 141 8e-32 BC051184_1( BC051184 |pid:none) Mus musculus USP6 N-terminal like,... 140 1e-31 (Q80...XC3) RecName: Full=USP6 N-terminal-like protein; &AL845275_... 140 1e-31 AL845275...ns clone peg2130 HHL (HH... 140 1e-31 ( Q92738 ) RecName: Full=USP6 N-terminal-like protein; AltName: ...ns cDNA FLJ57209 complet... 110 2e-22 G88391( G88391 )protein R06B10.5 [imported...hnaafngyktvmqllldagadvnshdidfntalhktsftgyhkcaelli ergsqveardnhgitpliksassknfkclsvliergwckcklkr***

On sums of q-independent SU[sub q](2) quantum variables

Energy Technology Data Exchange (ETDEWEB)

Lenczewski, R. (Politechnika Wroclawska, Wroclaw (Poland). Hugo Steinhaus Center for Stochastic Methods)

1993-05-01

A representation-free approach to the q-analog of the quantum central limit theorem for C=SU[sub 1](2) is presented. It is shown that for certain functions [phi][epsilon]-C* one can derive a version of a quantum central limit theorem (qclt) with [radical][N] as a scaling parameter, which may be viewed as a q-analog of qclt. (orig.).

FORMATION CONDITIONS OF ICY MATERIALS IN COMET C/2004 Q2 (MACHHOLZ). I. MIXING RATIOS OF ORGANIC VOLATILES

International Nuclear Information System (INIS)

Kobayashi, Hitomi; Kawakita, Hideyo

2009-01-01

We observed comet C/2004 Q2 (Machholz) with the Keck II telescope in late 2005 January and we obtained the spectra of C/2004 Q2 including many emission lines of volatile species such as H 2 O, HCN, C 2 H 2 , NH 3 , CH 4 , C 2 H 6 , CH 3 OH, and H 2 CO with high-signal-to-noise ratios. Based on our observations, we determined the mixing ratios of the molecules relative to H 2 O in C/2004 Q2. Since C/2004 Q2 is one of Oort Cloud comets, it is interesting to compare our results with other Oort Cloud comets. The mixing ratios of C 2 H 2 /H 2 O and C 2 H 6 /H 2 O in C/2004 Q2 are lower than typical Oort Cloud comets. Especially, C 2 H 2 /H 2 O ratio in C/2004 Q2 is as lower as Jupiter Family comets. However, mixing ratios of other molecules in C/2004 Q2 are similar to typical Oort Cloud comets. C/2004 Q2 might be the intermediate type between Oort Cloud and Jupiter Family comets. To investigate the formation conditions of such intermediate type comet, we focused on the (C 2 H 2 +C 2 H 6 )/H 2 O ratios and C 2 H 6 /(C 2 H 6 +C 2 H 2 ) ratios in comets from the viewpoint of conversion from C 2 H 2 to C 2 H 6 in the precometary ices. We found that (C 2 H 2 +C 2 H 6 )/H 2 O ratio in C/2004 Q2 is lower than the ratio in typical Oort Cloud comets while C 2 H 6 /(C 2 H 6 +C 2 H 2 ) ratio in C/2004 Q2 is consistent with the ratio of the typical Oort Cloud comets and Jupiter family comets. If we assume that the cometary volatiles such as H 2 O, CH 4 , and C 2 H 2 formed similar environment, the C 2 H 6 /(C 2 H 6 +C 2 H 2 ) ratio might not be sensitive in the temperature range where hydrogen-addition reactions occurred and cometesimals formed (∼30 K). We employed the dynamical-evolutional model and the chemical-evolutional model to determine the formation region of C/2004 Q2 more precisely. We found that comet C/2004 Q2 might have formed in relatively inner region of the solar nebula than the typical Oort Cloud comet (but slightly further than 5 AU from the proto-Sun).

ESR1 is co-expressed with closely adjacent uncharacterised genes spanning a breast cancer susceptibility locus at 6q25.1.

Directory of Open Access Journals (Sweden)

Anita K Dunbier

2011-04-01

Full Text Available Approximately 80% of human breast carcinomas present as oestrogen receptor α-positive (ER+ve disease, and ER status is a critical factor in treatment decision-making. Recently, single nucleotide polymorphisms (SNPs in the region immediately upstream of the ER gene (ESR1 on 6q25.1 have been associated with breast cancer risk. Our investigation of factors associated with the level of expression of ESR1 in ER+ve tumours has revealed unexpected associations between genes in this region and ESR1 expression that are important to consider in studies of the genetic causes of breast cancer risk. RNA from tumour biopsies taken from 104 postmenopausal women before and after 2 weeks treatment with an aromatase (oestrogen synthase inhibitor was analyzed on Illumina 48K microarrays. Multiple-testing corrected Spearman correlation revealed that three previously uncharacterized open reading frames (ORFs located immediately upstream of ESR1, C6ORF96, C6ORF97, and C6ORF211 were highly correlated with ESR1 (Rs =  0.67, 0.64, and 0.55 respectively, FDR<1 × 10(-7. Publicly available datasets confirmed this relationship in other groups of ER+ve tumours. DNA copy number changes did not account for the correlations. The correlations were maintained in cultured cells. An ERα antagonist did not affect the ORFs' expression or their correlation with ESR1, suggesting their transcriptional co-activation is not directly mediated by ERα. siRNA inhibition of C6ORF211 suppressed proliferation in MCF7 cells, and C6ORF211 positively correlated with a proliferation metagene in tumours. In contrast, C6ORF97 expression correlated negatively with the metagene and predicted for improved disease-free survival in a tamoxifen-treated published dataset, independently of ESR1. Our observations suggest that some of the biological effects previously attributed to ER could be mediated and/or modified by these co-expressed genes. The co-expression and function of these genes may be

A q-deformed Lorentz algebra

International Nuclear Information System (INIS)

Schmidke, W.B.; Wess, J.; Muenchen Univ.; Zumino, B.; Lawrence Berkeley Lab., CA

1991-01-01

We derive a q-deformed version of the Lorentz algebra by deformating the algebra SL(2, C). The method is based on linear representations of the algebra on the complex quantum spinor space. We find that the generators usually identified with SL q (2, C) generate SU q (2) only. Four additional generators are added which generate Lorentz boosts. The full algebra of all seven generators and their coproduct is presented. We show that in the limit q→1 the generators are those of the classical Lorentz algebra plus an additional U(1). Thus we have a deformation of SL(2, C)xU(1). (orig.)

q-analogue of summability of formal solutions of some linear q-difference-differential equations

Directory of Open Access Journals (Sweden)

Hidetoshi Tahara

2015-01-01

Full Text Available Let \\(q\\gt 1\\. The paper considers a linear \\(q\\-difference-differential equation: it is a \\(q\\-difference equation in the time variable \\(t\\, and a partial differential equation in the space variable \\(z\\. Under suitable conditions and by using \\(q\\-Borel and \\(q\\-Laplace transforms (introduced by J.-P. Ramis and C. Zhang, the authors show that if it has a formal power series solution \\(\\hat{X}(t,z\\ one can construct an actual holomorphic solution which admits \\(\\hat{X}(t,z\\ as a \\(q\\-Gevrey asymptotic expansion of order \\(1\\.

Imbalance of Circulating Monocyte Subsets and PD-1 Dysregulation in Q Fever Endocarditis: The Role of IL-10 in PD-1 Modulation

Science.gov (United States)

Ka, Mignane B.; Gondois-Rey, Françoise; Capo, Christian; Textoris, Julien; Million, Mathieu; Raoult, Didier; Olive, Daniel; Mege, Jean-Louis

2014-01-01

Q fever endocarditis, a severe complication of Q fever, is associated with a defective immune response, the mechanisms of which are poorly understood. We hypothesized that Q fever immune deficiency is related to altered distribution and activation of circulating monocyte subsets. Monocyte subsets were analyzed by flow cytometry in peripheral blood mononuclear cells from patients with Q fever endocarditis and controls. The proportion of classical monocytes (CD14+CD16− monocytes) was similar in patients and controls. In contrast, the patients with Q fever endocarditis exhibited a decrease in the non-classical and intermediate subsets of monocytes (CD16+ monocytes). The altered distribution of monocyte subsets in Q fever endocarditis was associated with changes in their activation profile. Indeed, the expression of HLA-DR, a canonical activation molecule, and PD-1, a co-inhibitory molecule, was increased in intermediate monocytes. This profile was not restricted to CD16+ monocytes because CD4+ T cells also overexpressed PD-1. The mechanism leading to the overexpression of PD-1 did not require the LPS from C. burnetii but involved interleukin-10, an immunosuppressive cytokine. Indeed, the incubation of control monocytes with interleukin-10 led to a higher expression of PD-1 and neutralizing interleukin-10 prevented C. burnetii-stimulated PD-1 expression. Taken together, these results show that the immune suppression of Q fever endocarditis involves a cross-talk between monocytes and CD4+ T cells expressing PD-1. The expression of PD-1 may be useful to assess chronic immune alterations in Q fever endocarditis. PMID:25211350

Dicty_cDB: Contig-U13894-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U13894-1 no gap 1550 2 2081463 2079913 MINUS 30 31 U13894 1 0 15 0 9 1 1 0 1 1 1 0 0 0 Show Contig...-U13894-1 Contig ID Contig-U13894-1 Contig update 2002.12.18 Contig sequence >Contig-U13894-1 (Contig...-U13894-1Q) /CSM_Contig/Contig-U13894-1Q.Seq.d CTTTTTGATTGTATAATTGAAAAAAAAAAAAAAAAAAAAAAAAAAA...TAAATTAAATAATTAAAAAAAACAAAAAAATTAAGTGAAAATCAAAAAA Gap no gap Contig length 1550 Chromosome number (1..6, M) ...V*kkkkikk*k*sk*fklnn*kkqkn*vkikk own update 2004. 6.10 Homology vs CSM-cDNA Query= Contig-U13894-1 (Contig

Potential of Murine IgG1 and Human IgG4 to Inhibit the Classical Complement and Fcγ Receptor Activation Pathways

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Gina-Maria Lilienthal

2018-05-01

Full Text Available IgG antibodies (Abs mediate their effector functions through the interaction with Fcγ receptors (FcγRs and the complement factors. The main IgG-mediated complement activation pathway is induced through the binding of complement C1q to IgG Abs. This interaction is dependent on antigen-dependent hexamer formation of human IgG1 and IgG3 to increase the affinity for the six-headed C1q molecule. By contrast, human IgG4 fails to bind to C1q. Instead, it has been suggested that human IgG4 can block IgG1 and IgG3 hexamerization required for their binding to C1q and activating the complement. Here, we show that murine IgG1, which functionally resembles human IgG4 by not interacting with C1q, inhibits the binding of IgG2a, IgG2b, and IgG3 to C1q in vitro, and suppresses IgG2a-mediated complement activation in a hemolytic assay in an antigen-dependent and IgG subclass-specific manner. From this perspective, we discuss the potential of murine IgG1 and human IgG4 to block the complement activation as well as suppressive effects of sialylated IgG subclass Abs on FcγR-mediated immune cell activation. Accumulating evidence suggests that both mechanisms seem to be responsible for preventing uncontrolled IgG (autoAb-induced inflammation in mice and humans. Distinct IgG subclass distributions and functionally opposite IgG Fc glycosylation patterns might explain different outcomes of IgG-mediated immune responses and provide new therapeutic options through the induction, enrichment, or application of antigen-specific sialylated human IgG4 to prevent complement and FcγR activation as well.

Minimum Data Set Q1a Report

Data.gov (United States)

U.S. Department of Health & Human Services — The MDS Q1a report summarizes, by state and county, percentages of residents that answered Yes to Q1a - Residents expresses or indicates preference to return to the...

Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response

International Nuclear Information System (INIS)

Zhao, Lei; Zhuang, Jianguo; Zang, Na; Lin, Yong; Lee, Lu-Yuan; Xu, Fadi

2016-01-01

Prenatal nicotinic exposure (PNE) prolongs bronchopulmonary C-fiber (PCF)-mediated apneic response to intra-atrial bolus injection of capsaicin in rat pups. The relevant mechanisms remain unclear. Pulmonary substance P and adenosine and their receptors (neurokinin-A receptor, NK1R and ADA 1 receptor, ADA 1 R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) expressed on PCFs are critical for PCF sensitization and/or activation. Here, we compared substance P and adenosine in BALF and NK1R, ADA 1 R, and TRPV1 expression in the nodose/jugular (N/J) ganglia (vagal pulmonary C-neurons retrogradely labeled) between Ctrl and PNE pups. We found that PNE failed to change BALF substance P and adenosine content, but significantly upregulated both mRNA and protein TRPV1 and NK1R in the N/J ganglia and only NK1R mRNA in pulmonary C-neurons. To define the role of NK1R in the PNE-induced PCF sensitization, the apneic response to capsaicin (i.v.) without or with pretreatment of SR140333 (a peripheral and selective NK1R antagonist) was compared and the prolonged apnea by PNE significantly shortened by SR140333. To clarify if the PNE-evoked responses depended on action of nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR, mecamylamine or methyllycaconitine (a general nAChR or a selective α7nAChR antagonist) was administrated via another mini-pump over the PNE period. Mecamylamine or methyllycaconitine eliminated the PNE-evoked mRNA and protein responses. Our data suggest that PNE is able to elevate PCF NK1R expression via activation of nAChRs, especially α7nAChR, which likely contributes to sensitize PCFs and prolong the PCF-mediated apneic response to capsaicin. - Highlights: • PNE upregulated NK1R and TRPV1 gene and protein expression in the N/J ganglia. • PNE only elevated NK1R mRNA in vagal pulmonary C-neurons. • Blockage of peripheral NK1R reduced the PNE-induced PCF sensitization. • PNE induced gene and protein changes in

The Tlo Proteins Are Stoichiometric Components of Candida albicans Mediator Anchored via the Med3 Subunit

Science.gov (United States)

Zhang, Anda; Petrov, Kostadin O.; Hyun, Emily R.; Liu, Zhongle; Gerber, Scott A.

2012-01-01

The amplification of the TLO (for telomere-associated) genes in Candida albicans, compared to its less pathogenic, close relative Candida dubliniensis, suggests a role in virulence. Little, however, is known about the function of the Tlo proteins. We have purified the Mediator coactivator complex from C. albicans (caMediator) and found that Tlo proteins are a stoichiometric component of caMediator. Many members of the Tlo family are expressed, and each is a unique member of caMediator. Protein expression analysis of individual Tlo proteins, as well as the purification of tagged Tlo proteins, demonstrate that there is a large free population of Tlo proteins in addition to the Mediator-associated population. Coexpression and copurification of Tloα12 and caMed3 in Escherichia coli established a direct physical interaction between the two proteins. We have also made a C. albicans med3Δ/Δ strain and purified an intact Mediator from this strain. The analysis of the composition of the med3Δ Mediator shows that it lacks a Tlo subunit. Regarding Mediator function, the med3Δ/Δ strain serves as a substitute for the difficult-to-make tloΔ/Δ C. albicans strain. A potential role of the TLO and MED3 genes in virulence is supported by the inability of the med3Δ/Δ strain to form normal germ tubes. This study of caMediator structure provides initial clues to the mechanism of action of the Tlo genes and a platform for further mechanistic studies of caMediator's involvement in gene regulatory patterns that underlie pathogenesis. PMID:22562472

Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.

Science.gov (United States)

Demaerel, Wolfram; Hestand, Matthew S; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luis A; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Morrow, Bernice E; Breckpot, Jeroen; Devriendt, Koenraad; Vermeesch, Joris R

2017-10-05

Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A-D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A-B 22q11.2 deletion carry inversions of LCR22B-D or LCR22C-D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders. Copyright © 2017. Published by Elsevier Inc.

Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway

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Gil Ju Seo

2015-10-01

Full Text Available Upon DNA stimulation, cyclic GMP-AMP synthase (cGAS synthesizes the second messenger cyclic GMP-AMP (cGAMP that binds to the STING, triggering antiviral interferon-β (IFN-β production. However, it has remained undetermined how hosts regulate cGAS enzymatic activity after the resolution of DNA immunogen. Here, we show that Akt kinase plays a negative role in cGAS-mediated anti-viral immune response. Akt phosphorylated the S291 or S305 residue of the enzymatic domain of mouse or human cGAS, respectively, and this phosphorylation robustly suppressed its enzymatic activity. Consequently, expression of activated Akt led to the reduction of cGAMP and IFN-β production and the increase of herpes simplex virus 1 replication, whereas treatment with Akt inhibitor augmented cGAS-mediated IFN-β production. Furthermore, expression of the phosphorylation-resistant cGAS S291A mutant enhanced IFN-β production upon DNA stimulation, HSV-1 infection, and vaccinia virus infection. Our study identifies an Akt kinase-mediated checkpoint to fine-tune hosts’ immune responses to DNA stimulation.

Reduction in erythrocyte-bound complement activation products and titres of anti-C1q antibodies associate with clinical improvement in systemic lupus erythematosus.

Science.gov (United States)

Buyon, Jill; Furie, Richard; Putterman, Chaim; Ramsey-Goldman, Rosalind; Kalunian, Kenneth; Barken, Derren; Conklin, John; Dervieux, Thierry

2016-01-01

The relationship between cell-bound complement activation products (CB-CAPs: EC4d, EC3d), anti-C1q, soluble complement C3/C4 and disease activity in systemic lupus erythematosus (SLE) was evaluated. Per protocol, at baseline all SLE subjects enrolled in this longitudinal study presented with active disease and elevated CB-CAPs. At each monthly visit, the non-serological (ns) Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG)-2004 index scores were determined as was a random urinary protein to creatinine ratio (uPCR). Short-form 36 (SF-36) questionnaires were also collected. All soluble markers were determined using immunoassays, while EC4d and EC3d were determined using flow cytometry. Statistical analysis consisted of linear mixed models with random intercept and fixed slopes. A total of 36 SLE subjects (mean age 34 years; 94% female) were enrolled and evaluated monthly for an average 11 visits per subject. Clinical improvements were observed during the study, with significant decreases in ns-SELENA-SLEDAI scores, BILAG-2004 index scores and uPCR, and increases in all domains of SF-36 (pimprovements in at least six out of the eight domains of SF-36 and outperformed C3/C4. Anti-dsDNA titres did not correlate with changes in disease activity. These data indicate that CB-CAPs and anti-C1q are helpful in monitoring patients with SLE.

Direct Comparison of 19F qNMR and 1H qNMR by Characterizing Atorvastatin Calcium Content

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Yang Liu

2016-01-01

Full Text Available Quantitative nuclear magnetic resonance (qNMR is a powerful tool in measuring drug content because of its high speed, sensitivity, and precision. Most of the reports were based on proton qNMR (1H qNMR and only a few fluorine qNMR (19F qNMR were reported. No research has been conducted to directly compare the advantage and disadvantage between these two methods. In the present study, both 19F and 1H qNMR were performed to characterize the content of atorvastatin calcium with the same internal standard. Linearity, precision, and results from two methods were compared. Results showed that 19F qNMR has similar precision and sensitivity to 1H qNMR. Both methods generate similar results compared to mass balance method. Major advantage from 19F qNMR is that the analyte signal is with less or no interference from impurities. 19F qNMR is an excellent approach to quantify fluorine-containing analytes.

Curcumin enhances the mitomycin C-induced cytotoxicity via downregulation of MKK1/2-ERK1/2-mediated Rad51 expression in non-small cell lung cancer cells

International Nuclear Information System (INIS)

Ko, Jen-Chung; Tsai, Min-Shao; Weng, Shao-Hsing; Kuo, Ya-Hsun; Chiu, Yu-Fan; Lin, Yun-Wei

2011-01-01

Curcumin (diferuloylmethane), a major active component of turmeric (Curcuma longa), has been reported to suppress the proliferation of a wide variety of tumor cells. Rad51 is a key protein in the homologous recombination (HR) pathway of DNA double-strand break repair, and HR represents a novel target for cancer therapy. A high expression of Rad51 has been reported in chemo- or radio-resistant carcinomas. Therefore, in the current study, we will examine whether curcumin could enhance the effects of mitomycin C (MMC), a DNA interstrand cross-linking agent, to induce cytotoxicity by decreasing Rad51 expression. Exposure of two human non-small lung cancer (NSCLC) cell lines (A549 and H1975) to curcumin could suppress MMC-induced MKK1/2-ERK1/2 signal activation and Rad51 protein expression. Enhancement of ERK1/2 activation by constitutively active MKK1/2 (MKK1/2-CA) increased Rad51 protein levels in curcumin and MMC co-treated human lung cells. Moreover, the synergistic cytotoxic effect induced by curcumin combined with MMC was decreased by MKK1-CA-mediated enhancement of ERK1/2 activation by a significant degree. In contrast, MKK1/2 inhibitor, U0126 was shown to augment the cytotoxicity of curcumin and MMC through downregulation of ERK1/2 activation and Rad51 expression. Depletion of endogenous Rad51 expression by siRad51 RNA transfection significantly enhanced MMC and/or curcumin induced cell death and cell growth inhibition. In contrast, an overexpression of Rad51 protected lung cancer cells from synergistic cytotoxic effects induced by curcumin and MMC. We concluded that Rad51 inhibition may be an additional action mechanism for enhancing the chemosensitization of MMC by curcumin in NSCLC. - Highlights: → Curcumin downregulates MKK-ERK-mediated Rad51 expression. → Curcumin enhances mitomycin C-induced cytotoxicity. → Rad51 protects cells from cytotoxic effects induced by curcumin and mitomycin C. → Rad51 inhibition enhances the chemosensitization of

Understanding the impact of 1q21.1 copy number variant

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Harvard Chansonette

2011-08-01

Full Text Available Abstract Background 1q21.1 Copy Number Variant (CNV is associated with a highly variable phenotype ranging from congenital anomalies, learning deficits/intellectual disability (ID, to a normal phenotype. Hence, the clinical significance of this CNV can be difficult to evaluate. Here we described the consequences of the 1q21.1 CNV on genome-wide gene expression and function of selected candidate genes within 1q21.1 using cell lines from clinically well described subjects. Methods and Results Eight subjects from 3 families were included in the study: six with a 1q21.1 deletion and two with a 1q21.1 duplication. High resolution Affymetrix 2.7M array was used to refine the 1q21.1 CNV breakpoints and exclude the presence of secondary CNVs of pathogenic relevance. Whole genome expression profiling, studied in lymphoblast cell lines (LBCs from 5 subjects, showed enrichment of genes from 1q21.1 in the top 100 genes ranked based on correlation of expression with 1q21.1 copy number. The function of two top genes from 1q21.1, CHD1L/ALC1 and PRKAB2, was studied in detail in LBCs from a deletion and a duplication carrier. CHD1L/ALC1 is an enzyme with a role in chromatin modification and DNA damage response while PRKAB2 is a member of the AMP kinase complex, which senses and maintains systemic and cellular energy balance. The protein levels for CHD1L/ALC1 and PRKAB2 were changed in concordance with their copy number in both LBCs. A defect in chromatin remodeling was documented based on impaired decatenation (chromatid untangling checkpoint (DCC in both LBCs. This defect, reproduced by CHD1L/ALC1 siRNA, identifies a new role of CHD1L/ALC1 in DCC. Both LBCs also showed elevated levels of micronuclei following treatment with a Topoisomerase II inhibitor suggesting increased DNA breaks. AMP kinase function, specifically in the deletion containing LBCs, was attenuated. Conclusion Our studies are unique as they show for the first time that the 1q21.1 CNV not only

Dicty_cDB: Contig-U15462-1 [Dicty_cDB