Crystal Chemistry and Magnetism of Ternary Actinoid Boron Carbides UB 1- xC 1+ x and U 1- xMxB 2C with M = Sc, Lu, and Th

NASA Astrophysics Data System (ADS)

Rogl, P.; Rupp, B.; Felner, I.; Fischer, P.

1993-06-01

Within the homogeneous range of uranium monocarbide UB 1- xC 1+ x, the crystal structures of stoichiometric UBC and of the carbon-rich solid solution UB 0.78C 1.22, have been refined from single-crystal X-ray counter data. From X-ray analysis crystal symmetry in both cases is consistent with the centro-symmetric space group Cmcm and there are no indications of superstructure formation. In contrast to the fully ordered atom arrangement revealed for stoichiometric UBC ( a = 0.35899(4), b = 1.19781(12), c = 0.33474(3) nm), random occupation by boron and carbon atoms is observed for the boron site in UB 0.78C 1.22 ( a = 0.35752(4), b = 1.18584(3), c = 0.33881(4) nm). For 279(278) reflections (|F 0| > 3σ) the obtained reliability factors R x = ∑|ΔF|/∑| F0| were R x = 0.069 for UBC and R x = 0.050 for UB 0.78C 1.22. Neutron powder diffraction experiments at 9 and 295 K unambiguously revealed full occupancy by the nonmetal atoms in UB 0.78C 1.22 and prove the statistical occupation of B and C atoms in the B-sites. For the orthorhombic symmetry Cmcm, refinement was not better than R1 = 0.044. A model calculation in monoclinic symmetry C12/ m1, however, resulted in a significant reduction of the residual value to R1 = 0.030, releasing spatial constraints on the boron atoms. Thus the boron-boron chain in Cmcm (B-B = 0.1874 nm) is dissolved into boron pairs (B-B = 0.1706 nm) which are loosely bound at a distance of 0.2043 nm. The formation of C-B-B-C groups corresponds to the structure types of ThBC and Th 3B 2C 3. The magnetic behavior has been investigated in the temperature range from 4.2 K to 1000 K for UB 1- xC 1+ x (UBC-type) and U 1- xMxB 2C (ThB 2C-type for the high temperature modification and 1-UB 2C-type for the low temperature modification) with U partially substituted by Th or Sc, Lu. From magnetic susceptibilities, the alloys UB 1- xC 1+ x reveal temperature independent paramagnetism with typical intermediate valence fluctuation behavior ( TSF ˜ 350 K

Structure investigation of maltacine B1a, B1b, B2a and B2b: cyclic peptide lactones of the maltacine complex from Bacillus subtilis.

PubMed

Hagelin, Gunnar

2005-04-01

A new complex of cyclic peptide lactone antibiotics from Bacillus subtilis, which we named maltacines, has recently been described. The structure elucidation of four of them is reported in this paper. The amino acid sequences and structures of the peptides were found by MSn of the ring-opened linear peptides that gave uninterrupted sequences of Bn and Y''n ions. The identities of three unknown residues in the sequences were solved by a combination of derivatization with phenyl isothiocyanate (PITC), high-resolution mass spectrometry and H/D exchange. The nature and position of the cyclic structure were revealed by a chemoselective ring opening with Na18OH and was found to be a lactone formed between a hydroxyl of residue number 4 and the C-terminal amino acid number 12. For verification of the structure of the B2+ ion, peptides with different combinations of P/Q and P/K at the N-terminus were synthesized. The structures of the four peptides were found to be as follows: B1a/B2a, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-Orn-103-Y-I-OH); and B1b/B2b, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-K-103-Y-I-OH). Copyright 2005 John Wiley & Sons, Ltd.

Alcohol binding in the C1 (C1A + C1B) domain of protein kinase C epsilon

PubMed Central

Pany, Satyabrata; Das, Joydip

2015-01-01

Background Alcohol regulates the expression and function of protein kinase C epsilon (PKCε). In a previous study we identified an alcohol binding site in the C1B, one of the twin C1 subdomains of PKCε. Methods In this study, we investigated alcohol binding in the entire C1 domain (combined C1A and C1B) of PKCε. Fluorescent phorbol ester, SAPD and fluorescent diacylglycerol (DAG) analog, dansyl-DAG were used to study the effect of ethanol, butanol, and octanol on the ligand binding using fluorescence resonance energy transfer (FRET). To identify alcohol binding site(s), PKCεC1 was photolabeled with 3-azibutanol and 3-azioctanol, and analyzed by mass spectrometry. The effects of alcohols and the azialcohols on PKCε were studied in NG108-15 cells. Results In the presence of alcohol, SAPD and dansyl-DAG showed different extent of FRET, indicating differential effects of alcohol on the C1A and C1B subdomains. Effects of alcohols and azialcohols on PKCε in NG108-15 cells were comparable. Azialcohols labeled Tyr-176 of C1A and Tyr-250 of C1B. Inspection of the model structure of PKCεC1 reveals that these residues are 40 Å apart from each other indicating that these residues form two different alcohol binding sites. Conclusions The present results provide evidence for the presence of multiple alcohol-binding sites on PKCε and underscore the importance of targeting this PKC isoform in developing alcohol antagonists. PMID:26210390

A Novel Role for C5a in B-1 Cell Homeostasis

PubMed Central

Bröker, Katharina; Figge, Julia; Magnusen, Albert F.; Manz, Rudolf A.; Köhl, Jörg; Karsten, Christian M.

2018-01-01

B-1 cells constitute a unique subpopulation of lymphocytes residing mainly in body cavities like the peritoneal cavity (PerC) but are also found in spleen and bone marrow (BM). As innate-like B cells, they mediate first line immune defense through low-affinity natural IgM (nIgM) antibodies. PerC B-1 cells can egress to the spleen and differentiate into nIgM antibody-secreting plasma cells that recognize conserved exogenous and endogenous cellular structures. Homing to and homeostasis within the PerC are regulated by the chemokine CXCL13 released by PerC macrophages and stroma cells. However, the exact mechanisms underlying the regulation of CXCL13 and B-1 homeostasis are not fully explored. B-1 cells play important roles in the inflammatory response to infection, autoimmunity, ischemia/reperfusion injury, obesity, and atherosclerosis. Remarkably, this list of inflammatory entities has a strong overlap with diseases that are regulated by complement suggesting a link between B-1 cells and the complement system. Interestingly, up to now, no data exist regarding the role of complement in B-1 cell biology. Here, we demonstrate for the first time that C5a regulates B-1 cell steady-state dynamics within the peritoneum, the spleen, and the BM. We found decreased B-1a cell numbers in the peritoneum and the spleen of C5aR1−/− mice associated with increased B1-a and B1-b numbers in the spleen and high serum titers of nIgM antibodies directed against phosphorylcholine and several pneumococcal polysaccharides. Similarly, peritoneal B-1a cells were decreased in the peritoneum and splenic B-1a and B-1b cells were increased in C5aR2−/− mice. The decrease in peritoneal B-1 cell numbers was associated with decreased peritoneal CXCL13 levels in C5aR1−/− and C5aR2−/− mice. In search for mechanisms, we found that combined TLR2 and IL-10 receptor activation in PerC macrophages induced strong CXCL13 production, which was significantly reduced in cells from C5aR1- and C5a

Observation of b 2 symmetry vibrational levels of the SO 2C 1B 2 state: Vibrational level staggering, Coriolis interactions, and rotation-vibration constants

DOE PAGES

Park, G. Barratt; Jiang, Jun; Saladrigas, Catherine A.; ...

2016-04-14

Here, the C 1B 2 state of SO 2 has a double-minimum potential in the antisymmetric stretch coordinate, such that the minimum energy geometry has nonequivalent SO bond lengths. However, low-lying levels with odd quanta of antisymmetric stretch (b 2 vibrational symmetry) have not previously been observed because transitions into these levels from the zero-point level of the X ~ state are vibronically forbidden. We use IR-UV double resonance to observe the b 2 vibrational levels of the C state below 1600 cm –1 of vibrational excitation. This enables a direct characterization of the vibrational level staggering that results frommore » the double-minimum potential. In addition, it allows us to deperturb the strong c-axis Coriolis interactions between levels of a 1 and b 2 vibrational symmetry, and to determine accurately the vibrational dependence of the rotational constants in the distorted C electronic state.« less

Observation of b 2 symmetry vibrational levels of the SO 2C 1B 2 state: Vibrational level staggering, Coriolis interactions, and rotation-vibration constants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, G. Barratt; Jiang, Jun; Saladrigas, Catherine A.

Here, the C 1B 2 state of SO 2 has a double-minimum potential in the antisymmetric stretch coordinate, such that the minimum energy geometry has nonequivalent SO bond lengths. However, low-lying levels with odd quanta of antisymmetric stretch (b 2 vibrational symmetry) have not previously been observed because transitions into these levels from the zero-point level of the X ~ state are vibronically forbidden. We use IR-UV double resonance to observe the b 2 vibrational levels of the C state below 1600 cm –1 of vibrational excitation. This enables a direct characterization of the vibrational level staggering that results frommore » the double-minimum potential. In addition, it allows us to deperturb the strong c-axis Coriolis interactions between levels of a 1 and b 2 vibrational symmetry, and to determine accurately the vibrational dependence of the rotational constants in the distorted C electronic state.« less

Enhanced susceptibility to acute pneumococcal otitis media in mice deficient in complement C1qa, factor B, and factor B/C2.

PubMed

Tong, Hua Hua; Li, Yong Xing; Stahl, Gregory L; Thurman, Joshua M

2010-03-01

To define the roles of specific complement activation pathways in host defense against Streptococcus pneumoniae in acute otitis media (AOM), we investigated the susceptibility to AOM in mice deficient in complement factor B and C2 (Bf/C2(-/)(-)), C1qa (C1qa(-/)(-)), and factor B (Bf(-)(/)(-)). Bacterial titers of both S. pneumoniae serotype 6A and 14 in the middle ear lavage fluid samples from Bf/C2(-/)(-), Bf(-)(/)(-), and C1qa(-/)(-) mice were significantly higher than in samples from wild-type mice 24 h after transtympanical infection (P < 0.05) and remained persistently higher in samples from Bf/C2(-/)(-) mice than in samples from wild-type mice. Bacteremia occurred in Bf/C2(-/)(-), Bf(-)(/)(-), and C1qa(-/)(-) mice infected with both strains, but not in wild-type mice. Recruitment of inflammatory cells was paralleled by enhanced production of inflammatory mediators in the middle ear lavage samples from Bf/C2(-/)(-) mice. C3b deposition on both strains was greatest for sera obtained from wild-type mice, followed by C1qa(-)(/)(-) and Bf(-)(/)(-) mice, and least for Bf/C2(-)(/)(-) mice. Opsonophagocytosis and whole-blood killing capacity of both strains were significantly decreased in the presence of sera or whole blood from complement-deficient mice compared to wild-type mice. These findings indicate that both the classical and alternative complement pathways are critical for middle ear immune defense against S. pneumoniae. The reduced capacity of complement-mediated opsonization and phagocytosis in the complement-deficient mice appears to be responsible for the impaired clearance of S. pneumoniae from the middle ear and dissemination to the bloodstream during AOM.

Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer.

PubMed

O'Hara, F Patrick; Beck, Ernestine; Barr, Lauren K; Wong, Lily L; Kessler, Daniel S; Riddle, Robert D

2005-07-01

The mesencephalic and metencephalic region (MMR) of the vertebrate central nervous system develops in response to signals produced by the isthmic organizer (IsO). We have previously reported that the LIM homeobox transcription factor Lmx1b is expressed within the chick IsO, where it is sufficient to maintain expression of the secreted factor wnt1. In this paper, we show that zebrafish express two Lmx1b orthologs, lmx1b.1 and lmx1b.2, in the rostral IsO, and demonstrate that these genes are necessary for key aspects of MMR development. Simultaneous knockdown of Lmx1b.1 and Lmx1b.2 using morpholino antisense oligos results in a loss of wnt1, wnt3a, wnt10b, pax8 and fgf8 expression at the IsO, leading ultimately to programmed cell death and the loss of the isthmic constriction and cerebellum. Single morpholino knockdown of either Lmx1b.1 or Lmx1b.2 has no discernible effect on MMR development. Maintenance of lmx1b.1 and lmx1b.2 expression at the isthmus requires the function of no isthmus/pax2.1, as well as Fgf signaling. Transient misexpression of Lmx1b.1 or Lmx1b.2 during early MMR development induces ectopic wnt1 and fgf8 expression in the MMR, as well as throughout much of the embryo. We propose that Lmx1b.1- and Lmx1b.2-mediated regulation of wnt1, wnt3a, wnt10b, pax8 and fgf8 maintains cell survival in the isthmocerebellar region.

Measurement of sigma(Lambda(b)0) / sigma(anti-B 0) x B(Lambda0(b) ---> Lambda+(c) pi-) / B(anti-B0 ---> D+ pi-) in p anti-p collisions at S**(1/2) = 1.96-TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abulencia, A.; Acosta, D.; Adelman, Jahred A.

2006-01-01

The authors present the first observation of the baryon decay {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +} {pi}{sup -} followed by {Lambda}{sub c}{sup +} {yields} pK{sup -} {pi}{sup +} in 106 pb{sup -1} p{bar p} collisions at {radical}s = 1.96 TeV in the CDF experiment. IN order to reduce systematic error, the measured rate for {Lambda}{sub b}{sup 0} decay is normalized to the kinematically similar meson decay {bar B}{sup 0} {yields} D{sup +}{pi}{sup -} followed by D{sup +} {yields} {pi}{sup +}K{sup -}{pi}{sup +}. They report the ratio of production cross sections ({sigma}) times the ratio of branching fractions ({Beta}) formore » the momentum region integrated above p{sub T} > 6 GeV/c and pseudorapidity range |{eta}| < 1.3: {sigma}(p{bar p} {yields} {Lambda}{sub b}{sup 0}X)/{sigma}(p{bar p} {yields} {bar B}{sup 0} X) x {Beta}({Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +}{pi}{sup -})/{Beta}({bar B}{sup 0} {yields} D{sup +}{pi}{sup -}) = 0.82 {+-} 0.08(stat) {+-} 0.11(syst) {+-} 0.22 ({Beta}({Lambda}{sub c}{sup +} {yields} pK{sup -} {pi}{sup +})).« less

7 CFR 1b.2 - Policy.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 1 2013-01-01 2013-01-01 false Policy. 1b.2 Section 1b.2 Agriculture Office of the Secretary of Agriculture NATIONAL ENVIRONMENTAL POLICY ACT § 1b.2 Policy. (a) All policies and programs of... environment for present and future generations. (b) Each USDA agency is responsible for compliance with this...

7 CFR 1b.2 - Policy.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Policy. 1b.2 Section 1b.2 Agriculture Office of the Secretary of Agriculture NATIONAL ENVIRONMENTAL POLICY ACT § 1b.2 Policy. (a) All policies and programs of... environment for present and future generations. (b) Each USDA agency is responsible for compliance with this...

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

PubMed Central

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

2016-01-01

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

Cyclin-dependent kinase inhibitor Cdkn2c regulates B cell homeostasis and function in the NZM2410-derived murine lupus susceptibility locus Sle2c1

PubMed Central

Xu, Zhiwei; Potula, Hari-Hara SK; Vallurupalli, Anusha; Perry, Daniel; Baker, Henry; Croker, Byron P.; Dozmorov, Igor; Morel, Laurence

2013-01-01

Sle2c1 is an NZM2410 and NZB-derived lupus susceptibility locus that induces an expansion of the B1a cell compartment. B1a cells have a repertoire enriched for autoreactivity, and an expansion of this B cell subset occurs in several mouse models of lupus. A combination of genetic mapping and candidate gene analysis presents Cdkn2c, a gene encoding for cyclin-dependent kinase inhibitor p18INK4c (p18), as the top candidate gene for inducing the Slec2c1 associated expansion of B1a cells. A novel SNP in the NZB allele of the Cdkn2c promoter is associated with a significantly reduced Cdkn2c expression in the splenic B cells and Pc B1a cells from Sle2c1-carrying mice, which leads to a defective G1 cell cycle arrest in splenic B cells and increased proliferation of Pc B1a cells. As cell cycle is differentially regulated in B1a and B2 cells, these results suggest that Cdkn2c plays a critical role in B1a cell self-renewal, and that its impaired expression leads to an accumulation of these cells with high autoreactive potential. PMID:21543644

Association of Neuropeptide Y (NPY), Interleukin-1B (IL1B) Genetic Variants and Correlation of IL1B Transcript Levels with Vitiligo Susceptibility

PubMed Central

Laddha, Naresh C.; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Mala; Patel, Hetanshi H.; Agarwal, Nishtha; Shah, Anish M.; Begum, Rasheedunnisa

2014-01-01

Background Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels. Objectives Aim of the present study was to explore NPY promoter −399T/C (rs16147) and exon2 +1128T/C (rs16139) polymorphisms as well as IL1B promoter −511C/T (rs16944) polymorphism and to correlate IL1B transcript levels with vitiligo. Methods PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B −511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR. Results Genotype and allele frequencies for NPY −399T/C, +1128T/C and IL1B −511C/T SNPs differed significantly (p<0.0001, p<0.0001; p = 0.0161, p = 0.0035 and p<0.0001, p<0.0001) between patients and controls. ‘TC’ haplotype containing minor alleles of NPY polymorphisms was significantly higher in patients and increased the risk of vitiligo by 2.3 fold (p<0.0001). Transcript levels of IL1B were significantly higher, in patients compared to controls (p = 0.0029), in patients with active than stable vitiligo (p = 0.015), also in female patients than male patients (p = 0.026). Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes. Conclusion Our results suggest that NPY −399T/C, +1128T/C and IL1B −511C/T polymorphisms are associated with vitiligo and IL1B −511C/T SNP influences its transcript levels leading to increased risk for vitiligo in

Impact of hepatitis C virus recombinant form RF1_2k/1b on treatment outcomes within the Georgian national hepatitis C elimination program.

PubMed

Karchava, Marine; Chkhartishvili, Nikoloz; Sharvadze, Lali; Abutidze, Akaki; Dvali, Natia; Gatserelia, Lana; Dzigua, Lela; Bolokadze, Natalia; Dolmazashvili, Ekaterine; Kotorashvili, Adam; Imnadze, Paata; Gamkrelidze, Amiran; Tsertsvadze, Tengiz

2018-01-01

Hepatitis C virus (HCV) recombinant form RF1_2k/1b is common in ethnic Georgians. This chimera virus contains genomic fragments of genotype 2 and genotype 1 and is misclassified as genotype 2 by standard genotyping. We aimed to identify RF1_2k/1b strains among genotype 2 patients and assess its impact on treatment outcomes. The study included 148 patients with HCV genotype 2 as determined by 5-untranslated region/core genotyping assay. RF1_2k/1b was identified by sequencing the non-structural protein 5B region. Patients were treated within the national hepatitis C elimination program with sofosbuvir/ribavirin (SOF/RBV), interferon (IFN)/SOF/RBV, or ledipasvir (LDV)/SOF/RBV. Of 148 patients, 103 (69.5%) had RF1_ 2k/1b. Sustained virologic response (SVR) data was available for 136 patients (RF1_ 2k/1b, n = 103; genotype 2, n = 33). Sustained virologic response was achieved in more genotype 2 patient than in RF1_2k/1b patients (97.0% vs. 76.7%, P = 0.009). Twelve weeks of LDV/SOF/RBV treatment was highly effective (100% SVR) in both genotypes. Among RF1_2k/1b patients, LDV/SOF/RBV for 12 weeks was superior (100% SVR) to SOF/RBV for 12 weeks (56.4%, P < 0.0001) or 20 weeks (79.2%, P = 0.05). Twelve weeks of IFN/SOF/RBV also showed better response than SOF/RBV for 12 weeks (88.9% vs. 56.4%, P = 0.02) in these patients. High prevalence of the RF1_2k/1b strain can significantly affect treatment outcomes. Treatment with IFN/SOF/RBV and especially LDV/SOF/RBV ensured significantly higher SVR in patients infected with RF1_2k/1b strain compared to standard HCV genotype 2 treatment with SOF/RBV. There is a need to reassess existing methods for the management of HCV genotype 2 infections, especially in areas with high prevalence of the RF1_2k/1b strain. © 2017 The Japan Society of Hepatology.

The B(E2;4^+1->2^+1) / B(E2;2^+1->0^+1) Ratio in Even-Even Nuclei

NASA Astrophysics Data System (ADS)

Loelius, C.; Sharon, Y. Y.; Zamick, L.; G"Urdal, G.

2009-10-01

We considered 207 even-even nuclei throughout the chart of nuclides for which the NNDC Tables had data on the energies and lifetimes of the 2^+1 and 4^+1 states. Using these data we calculated for each nucleus the electric quadrupole transition strengths B(E2;4^+1->2^+1) and B(E2;2^+1->0^+1), as well as their ratio. The internal conversion coefficients were obtained by using the NNDC HSICC calculator. For each nucleus we plotted the B(E2) ratio against A, N, and Z. We found that for close to 90% of the nuclei considered the ratio had values between 0.5 and 2.5. Most of the outliers had magic numbers of protons or neutrons. Our ratio results were compared with the theoretical predictions for this ratio by different models--10/7 in the rotational model and 2 in the simplest vibrational model. In the rotational regions (for 150 < A < 180 and A > 220) the ratios were indeed close to 10/7. For the few nuclei thought to be vibrational the ratios were usually less than 2. Otherwise, we got a wide scatter of ratio values. Hence other models, including the NpNn scheme, must be considered in interpreting these results.

Evaluation of synergistic antimicrobial effect of vitamins (A, B1, B2, B6, B12, C, D, E and K) with antibiotics against resistant bacterial strains.

PubMed

Shahzad, Shakeel; Ashraf, M Adnan; Sajid, M; Shahzad, Aqeel; Rafique, Azhar; Mahmood, M Shahid

2018-02-02

Multiple drug resistant super bugs of Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) are becoming challenge for healthcare professionals. In this study, vitamins were evaluated for synergistic activity with the antibiotics. Synergistic effect between antibiotic and stock solutions of vitamins is evaluated by using Kirby-Bauer disc diffusion assay. Distilled water and propylene glycol were used as solvent for water soluble vitamins and fat-soluble vitamins respectively. The final concentration of 10mg/ml of each water-soluble vitamin B1 (Thiamine), B2 (Riboflavin), B6 (Pyridoxine) B12 (Methylcobalamin), C (Ascorbic acid) and 0.1mg/ml of each fat soluble vitamin A (retinol), D (cholecalciferol) E (αTocopherol) K (Menadione) were used with the antibiotics. The results depicted that vitamin K and E have better synergistic activity with piperacillin-tazobactam, imipenem and doripenem antibiotics against A. baumannii. While vitamin B1, B2 and B12 showed remarkable synergistic activity with linezolid against MRSA. Vitamin B1 was further tested to have better synergism with antibiotics oxacillin, tetracycline, rifampicin and linezolid against MRSA. The fat-soluble vitamins E and K were good in synergism against Gram negative A. baumannii while water soluble vitamins as B1, B2 and B12 were effective against MRSA but not against A. baumannii. This synergistic action of vitamins with the antibiotics can be used as a tool to treat multiple drug resistant super bugs with further evaluation at molecular level. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

18 CFR 1b.2 - Scope.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to investigations...

18 CFR 1b.2 - Scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to investigations...

18 CFR 1b.2 - Scope.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to investigations...

18 CFR 1b.2 - Scope.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to investigations...

Preparation of dimeric procyanidins B1, B2, B5, and B7 from a polymeric procyanidin fraction of black chokeberry ( Aronia melanocarpa ).

PubMed

Esatbeyoglu, Tuba; Winterhalter, Peter

2010-04-28

A semisynthetic approach has been used for the preparative formation of dimeric procyanidins B1, B2, B5, and B7. As starting material for the semisynthesis, polymeric procyanidins from black chokeberry were applied. These polymers were found to consist almost exclusively of (-)-epicatechin units. Under acidic conditions the interflavanoid linkages of the polymeric procyanidins are cleaved and the liberated (-)-epicatechin can react with nucleophiles, such as (+)-catechin or (-)-epicatechin. In this way, the polymeric procyanidins are degraded while dimeric procyanidins are formed. During this reaction only dimeric procyanidins are formed that contain (-)-epicatechin in the upper unit, that is, B1 [(-)-EC-4beta-->8-(+)-C)], B2 [(-)-EC-4beta-->8-(-)-EC], B5 [(-)-EC-4beta-->6-(-)-EC], and B7 [(-)-EC-4beta-->6-(+)-C]. The reaction mixtures of the semisynthesis can be successfully fractionated with high-speed countercurrent chromatography (HSCCC), and it is possible to isolate pure procyanidins B1, B2, B5, and B7 on a preparative scale.

BPN, a marine-derived PTP1B inhibitor, activates insulin signaling and improves insulin resistance in C2C12 myotubes.

PubMed

Xu, Qi; Luo, Jiao; Wu, Ning; Zhang, Renshuai; Shi, Dayong

2018-01-01

Insulin resistance is a key feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of insulin signaling cascade and has attracted intensive investigation in recent T2DM therapy study. BPN, a marine-derived bromophenol compound, was isolated from the red alga Rhodomela confervoides. This study investigated the effects of BPN on the insulin signaling pathway in insulin-resistant C2C12 myotubes by inhibiting PTP1B. Molecular docking study and analysis of small- molecule interaction with PTP1B all showed BPN inhibited PTP1B activity via binding to the catalytic site through hydrogen bonds. We then found that BPN permeated into C2C12 myotubes, on the one hand, activated insulin signaling in an insulin-independent manner in C2C12 cells; on the other hand, ameliorated palmitate-induced insulin resistance through augmenting insulin sensitivity. Moreover, our studies also showed that PTP1B inhibition by BPN increased glucose uptake in normal and insulin-resistant C2C12 myotubes through glucose transporter 4 (GLUT4) translocation. Taken together, BPN activates insulin signaling and alleviates insulin resistance and represents a potential candidate for further development as an antidiabetic agent. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of organic anion-transporting polypeptides 1B1, 1B3 and 2B1 on the antitumor activity of flavopiridol in breast cancer cells.

PubMed

Brenner, Stefan; Riha, Juliane; Giessrigl, Benedikt; Thalhammer, Theresia; Grusch, Michael; Krupitza, Georg; Stieger, Bruno; Jäger, Walter

2015-01-01

The contribution of organic anion transporting polypeptides (OATPs) to the cellular uptake of flavopiridol was investigated in OATP1B1-, OATP1B3- and OATP2B1-expressing Chinese hamster ovary (CHO) cells. Uptake of flavopiridol into these cells showed typical Michaelis-Menten kinetics with much higher transport capacity for OATP1B3 compared to OATP1B1 and OATP2B1 (Vmax/Km, 33.9 vs. 8.84 and 2.41 µl/mg/min, respectively). The predominant role of OATPs was further supported by a dramatic inhibition of flavopiridol uptake in the presence of the OATP substrate rifampicin. Uptake of flavopiridol by OATPs also seems to be an important determinant in breast cancer cells. The much higher mRNA level for OATP1B1 found in wild-type compared to ZR-75-1 OATP1B1 knockdown cells correlated with higher flavopiridol initial uptake leading to 4.6-fold decreased IC50 values in the cytotoxicity assay (IC50, 1.45 vs. 6.64 µM). Cell cycle profile also showed a clear incidence for a stronger cell cycle arrest in the G2/M phase for ZR-75-1 wild-type cells compared to OATP1B1 knockdown cells, further indicating an active uptake via OATP1B1. In conclusion, our results revealed OATP1B1, OATP1B3 and OATP2B1 as uptake transporters for flavopiridol in cancer cells, which may also apply in patients during cancer therapy.

Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population.

PubMed

Lee, K W; Oh, D H; Lee, C; Yang, S Y

2005-05-01

High-resolution human leukocyte antigen (HLA) typing exposes the unique patterns of HLA allele and haplotype frequencies in each population. In this study, HLA-A, -B, -C, -DRB1, and -DQB1 genotypes were analyzed in 485 apparently unrelated healthy Korean individuals. A total of 20 HLA-A, 43 HLA-B, 21 HLA-C, 31 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. Eleven alleles (A*0201, A*1101, A*2402, A*3303, B*1501, Cw*0102, Cw*0302, Cw*0303, DQB1*0301, DQB1*0302, and DQB1*0303) were found in more than 10% of the population. In each serologic group, a maximum of three alleles were found with several exceptions (A2, B62, DR4, DR14, and DQ6). In each serologic group exhibiting multiple alleles, two major alleles were present at 62-96% (i.e. A*0201 and A*0206 comprise 85% of A2-positive alleles). Multiple-locus haplotypes estimated by the maximum likelihood method revealed 51 A-C, 43 C-B, 52 B-DRB1, 34 DRB1-DQB1, 48 A-C-B, 42 C-B-DRB1, 46 B-DRB1-DQB1, and 30 A-C-B-DRB1-DQB1 haplotypes with frequencies of more than 0.5%. In spite of their high polymorphism in B and DRB1, identification of relatively small numbers of two-locus (B-C and DRB1-DQB1) haplotypes suggested strong associations of those two loci, respectively. Five-locus haplotypes defined by high-resolution DNA typing correlated well with previously identified serology-based haplotypes in the population. The five most frequent haplotypes were: A*3303-Cw*1403-B*4403-DRB1*1302-DQB1*0604 (4.2%), A*3303-Cw*0701/6-B*4403-DRB1*0701-DQB1*0201/2 (3.0%), A*3303-Cw*0302-B*5801-DRB1*1302-DQB1*0609 (3.0%), A*2402-Cw*0702-B*0702-DRB1*0101-DQB1*0501 (2.9%), and A*3001-Cw*0602-B*1302-DRB1*0701-DQB1*0201/2 (2.7%). Several sets of allele level haplotypes that could not be discriminated by routine HLA-A, -B, and -DRB1 low-resolution typing originated from allelic diversity of A2, B61, DR4, and DR8 serologic groups. Information obtained in this study will be useful for medical and forensic applications as well as in anthropology.

A SEARCH FOR l-C{sub 3}H{sup +} AND l-C{sub 3}H IN Sgr B2(N), Sgr B2(OH), AND THE DARK CLOUD TMC-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, Brett A.; Carroll, P. Brandon; Loomis, Ryan A.

2013-09-01

Pety et al. recently reported the detection of several transitions of an unknown carrier in the Horsehead PDR and attribute them to l-C{sub 3}H{sup +}. Here, we have tested the predictive power of their fit by searching for, and identifying, the previously unobserved J = 1-0 and J = 2-1 transitions of the unknown carrier (B11244) toward Sgr B2(N) in data from the publicly available PRIMOS project. Also presented here are observations of the J = 6-5 and J = 7-6 transitions toward Sgr B2(N) and Sgr B2(OH) using the Barry E. Turner Legacy Survey and results from the Kaifumore » et al. survey of TMC-1. We calculate an excitation temperature and column density of B11244 of {approx}10 K and {approx}10{sup 13} cm{sup -2} in Sgr B2(N) and {approx}79 K with an upper limit of {<=}1.5 Multiplication-Sign 10{sup 13} cm{sup -2} in Sgr B2(OH) and find trace evidence for the cation's presence in TMC-1. Finally, we present spectra of the neutral species in both Sgr B2(N) and TMC-1, and comment on the robustness of the assignment of the detected signals to l-C{sub 3}H{sup +}.« less

76 FR 39254 - Airworthiness Directives; Schweizer Aircraft Corporation (Schweizer) Model 269A, A-1, B, C, C-1...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-06

... Airworthiness Directives; Schweizer Aircraft Corporation (Schweizer) Model 269A, A-1, B, C, C-1, and TH-55... reviewed Schweizer Service Bulletins No. B-295 for Model 269A, A-1, B, and C helicopters, and No. C1B-032... citation for Part 39 continues to read as follows: Authority: 49 U.S.C. 106(g), 40113, 44701. Sec. 39.13...

Intrinsic fluorescence spectra characteristics of vitamin B1, B2, and B6

NASA Astrophysics Data System (ADS)

Yang, Hui; Xiao, Xue; Zhao, Xuesong; Hu, Lan; Lv, Caofang; Yin, Zhangkun

2015-11-01

This paper presents the intrinsic fluorescence characteristics of vitamin B1, B2 and B6 measured with 3D fluorescence Spectrophotometer. Three strong fluorescence areas of vitamin B2 locate at λex/λem=270/525nm, 370/525nm and 450/525nm, one fluorescence areas of vitamin B1 locates at λex/λem=370/460nm, two fluorescence areas of vitamin B6 locates at λex/λem=250/370nm and 325/370nm were found. The influence of pH of solution to the fluorescence profile was also discussed. Using the PARAFAC algorithm, 10 vitamin B1, B2 and B6 mixed solutions were successfully decomposed, and the emission profiles, excitation profiles, central wavelengths and the concentration of the three components were retrieved precisely through about 5 iteration times.

HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in the Serbian population.

PubMed

Andric, Zorana; Popadic, Dusan; Jovanovic, Barbara; Jaglicic, Ivana; Bojic, Svetlana; Simonovic, Ruzica

2014-03-01

This study provides the first published detailed analysis of five loci polymorphisms as well as reports of two, three and five loci haplotype frequencies in the Serbian population in a sample of 1992 volunteer bone marrow donors recruited from different part of the country. Typing was performed by PCR SSO method combined with PCR SSP techniques to resolve ambiguities. In total, 16 HLA-A, 28 HLA-B, 14 HLA-C, 13 HLA-DRB1 and 5 HLA-DQB1 allelic groups were identified. The most frequent in allele groups are HLA-A(∗)02 (29.5%), HLA-A(∗)01 (14.2%), HLA-B(∗)35 (13.1%), HLA-B(∗)51 (12.8%), HLA-C(∗)07 (24.8%), HLA-DRB1(∗)11 (16.9%), HLA-DRB1(∗)13 (13.2%), HLA-DQB1(∗)03 (33.3%) and DQB1(∗)05 (33.0%). The most frequent three- and five-loci haplotypes were A(∗)01-B(∗)08-DRB1(∗)03 (5.9%) and A(∗)02-B(∗)18-DRB1(∗)11 (1.9%), A(∗)01-B(∗)08-C(∗)07-DRB1(∗)03-DQB1(∗)02 (6.6%) followed by A(∗)02-B(∗)18-C(∗)07-DRB1(∗)11-DQB1(∗)03 (2.5%), then A(∗)33-B(∗)14-C(∗)08-DRB1(∗)01-DQB1(∗)05 and A(∗)02-B(∗)35-C(∗)04-DRB1(∗)16-DQB1(∗)05 (2.2% both), respectively. The results of cluster analysis showed that the Serbian population is closely related to the populations living in central Balkan and neighboring European regions. The level of allelic diversity found in this study are relevant to facilitate searching for unrelated matched donor and provide a healthy control population from our region that should be useful in the future disease association study. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

"Send & hold" clinical decision support rules improvement to reduce unnecessary testing of vitamins A, E, K, B1, B2, B3, B6 and C.

PubMed

Rodriguez-Borja, Enrique; Corchon-Peyrallo, Africa; Barba-Serrano, Esther; Villalba Martínez, Celia; Carratala Calvo, Arturo

2018-06-27

We assessed the impact of several "send & hold" clinical decision support rules (CDSRs) within the electronical request system for vitamins A, E, K, B1, B2, B3, B6 and C for all outpatients at a large health department. When ordered through electronical request, providers (except for all our primary care physicians who worked as a non-intervention control group) were always asked to answer several compulsory questions regarding main indication, symptomatology, suspected diagnosis, vitamin active treatments, etc., for each vitamin test using a drop-down list format. After samples arrival, tests were later put on hold internally by our laboratory information system (LIS) until review for their appropriateness was made by two staff pathologists according to the provided answers and LIS records (i.e. "send & hold"). The number of tests for each analyte was compared between the 10-month period before and after CDSRs implementation in both groups. After implementation, vitamins test volumes decreased by 40% for vitamin A, 29% for vitamin E, 42% for vitamin K, 37% for vitamin B1, 85% for vitamin B2, 68% for vitamin B3, 65% for vitamin B6 and 59% for vitamin C (all p values 0.03 or lower except for vitamin B3), whereas in control group, the majority increased or remained stable. In patients with rejected vitamins, no new requests and/or adverse clinical outcome comments due to this fact were identified. "Send & hold" CDSRs are a promising informatics tool that can support in utilization management and enhance the pathologist's leadership role as tests specialist.

HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR expression in infertile women with endometriosis.

PubMed

Osiński, Maciej; Wirstlein, Przemysław; Wender-Ożegowska, Ewa; Mikołajczyk, Mateusz; Jagodziński, Paweł Piotr; Szczepańska, Małgorzata

2018-01-01

The development of endometriosis is associated with changes in the expression of genes encoding the 3β-hydroxysteroid dehydrogenase type II (HSD3B2) and 17β-hydroxysteroid dehydrogenase type II (HSD17B2), estrogen receptors 1 (ESR1) and 2 (ESR2) and the androgen receptor (AR). However, little is known about the expression of HSD3B2, HSD17B1, HSD17B2, ESR1 ESR2 and AR during the endometrial phases in eutopic endometrium from infertile women with endometriosis. Using RT-qPCR analysis, we assessed the expression of the studied genes in the follicular and luteal phases in eutopic endometrium from fertile women (n = 17) and infertile women (n = 35) with endometriosis. In the mid-follicular eutopic endometrium, we observed a significant increase in HSD3B2 transcript levels in all infertile women with endometriosis (p = 0.003), in infertile women with stage I/II endometriosis (p = 0.008) and in infertile women with stage III/IV endometriosis (p = 0.009) compared to all fertile women. There was a significant increase in ESR1 tran-scripts in all infertile women with endometriosis (p = 0.008) and in infertile women with stage I/II endometriosis (p = 0.019) and in infertile women with stage III/IV endometriosis (p = 0.023) compared to all fertile women. In the mid-luteal eutopic endometrium, we did not observe significant differences in HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR transcripts between infertile women with endometriosis and fertile women. Observed significant increase in HSD3B2 and ESR1 transcripts in follicular eutopic endometrium from infer-tile women with endometriosis may be related to abnormal biological effect of E2 in endometrium, further affecting the development of human embryos.

Tissue kallikrein protects neurons from hypoxia/reoxygenation-induced cell injury through Homer1b/c.

PubMed

Su, Jingjing; Tang, Yuping; Zhou, Houguang; Liu, Ling; Dong, Qiang

2012-11-01

Previous studies have demonstrated that human tissue kallikrein (TK) gene delivery protects against mouse cerebral ischemia/reperfusion (I/R) injury through bradykinin B2 receptor (B2R) activation. We have also reported that exogenous TK administration can suppress glutamate- or acidosis-induced neurotoxicity through the extracellular signal-regulated kinase1/2 (ERK1/2) pathway. To further explore the neuroprotection mechanisms of TK, in the present study we performed immunoprecipitation analysis and identified a scaffolding protein Homer1b/c using MALDI-TOF MS analysis. Here, we tested the hypothesis that TK reduces cell injury induced by oxygen and glucose deprivation/reoxygenation (OGD/R) through activating Homer1b/c. We found that TK increased the expression of Homer1b/c in a concentration- and time-dependent manner. Moreover, TK facilitated the translocation of Homer1b/c to the plasma membrane under OGD/R condition by confocal microscope assays. We also observed that overexpression of Homer1b/c showed the neuroprotection against OGD/R-induced cell injury by enhancing cell survival, reducing LDH release, caspase-3 activity and cell apoptosis. However, the knockdown of Homer1b/c by small interfering RNA showed the opposite effects, indicating that Homer1b/c had protective effects against OGD/R-induced neuronal injury. More interestingly, TK exerted its much more significantly neuroprotective effects after Homer1b/c overexpression, whereas it exerted its reduced effects after Homer1b/c knockdown. In addition, TK pretreatment increased the phosphorylation of the ERK1/2 and Akt-GSK3β through Homer1b/c activation. The beneficial effects of Homer1b/c were abolished by the ERK1/2 or PI3K antagonist. Therefore, we propose novel signaling mechanisms involved in the anti-hypoxic function of TK through activation of Homer1b/c-ERK1/2 and Homer1b/c-PI3K-Akt signaling pathways. Copyright © 2012 Elsevier Inc. All rights reserved.

Optimization of chromatographic conditions for determination of aflatoxin B1, B2, G1 and G2 by using liquid chromatography-mass Spectrometry

NASA Astrophysics Data System (ADS)

Ramadhaningtyas, Dillani Putri; Aryana, Nurhani; Aristiawan, Yosi; Styarini, Dyah

2017-11-01

The optimization of instrument condition and chromatographic separation for analysis of aflatoxin B1, B2, G1 and G2 using liquid chromatography tandem with mass spectrometer detector was conducted in the aim to provide more accurate and reliable analysis results. The aflatoxin known to be serious threat for human health as it is classified as the carcinogenic compounds. The aflatoxin B1, B2, G1 and G2 were selected due to its extensive contamination in various agricultural commodities. The best chromatographic separation was obtained using C-18 column with gradient elution of solvent 5 mM ammonium acetate and 0.1% formic acid in methanol at 7 minutes runtime analysis. The linearity of the detector showed satisfied results as the coefficient determination found to be 0.9994, 0.9996, 0.9998 and 0.9987 for aflatoxin B1, G1, B2, and G2 respectively in the range concentration from 1 to 20 ng/g. The quantifier ion selected for the aflatoxin B1, B2, G1 and G2 was m/z 285.1, 259, 243 and 313 respectively. The instrument precision at these quantifier ions also showed satisfied result with %RSD was around 3.4 to 6.8%. The optimized method present in this study can be used for further sample analysis.

NF-κB1, NF-κB2 and c-Rel differentially regulate susceptibility to colitis-associated adenoma development in C57BL/6 mice.

PubMed

Burkitt, Michael D; Hanedi, Abdalla F; Duckworth, Carrie A; Williams, Jonathan M; Tang, Joseph M; O'Reilly, Lorraine A; Putoczki, Tracy L; Gerondakis, Steve; Dimaline, Rod; Caamano, Jorge H; Pritchard, D Mark

2015-07-01

NF-κB signalling is an important factor in the development of inflammation-associated cancers. Mouse models of Helicobacter-induced gastric cancer and colitis-associated colorectal cancer have demonstrated that classical NF-κB signalling is an important regulator of these processes. In the stomach, it has also been demonstrated that signalling involving specific NF-κB proteins, including NF-κB1/p50, NF-κB2/p52, and c-Rel, differentially regulate the development of gastric pre-neoplasia. To investigate the effect of NF-κB subunit loss on colitis-associated carcinogenesis, we administered azoxymethane followed by pulsed dextran sodium sulphate to C57BL/6, Nfkb1(-/-), Nfkb2(-/-), and c-Rel(-/-) mice. Animals lacking the c-Rel subunit were more susceptible to colitis-associated cancer than wild-type mice, developing 3.5 times more colonic polyps per animal than wild-type mice. Nfkb2(-/-) mice were resistant to colitis-associated cancer, developing fewer polyps per colon than wild-type mice (median 1 compared to 4). To investigate the mechanisms underlying these trends, azoxymethane and dextran sodium sulphate were administered separately to mice of each genotype. Nfkb2(-/-) mice developed fewer clinical signs of colitis and exhibited less severe colitis and an attenuated cytokine response compared with all other groups following DSS administration. Azoxymethane administration did not fully suppress colonic epithelial mitosis in c-Rel(-/-) mice and less colonic epithelial apoptosis was also observed in this genotype compared to wild-type counterparts. These observations demonstrate different functions of specific NF-κB subunits in this model of colitis-associated carcinogenesis. NF-κB2/p52 is necessary for the development of colitis, whilst c-Rel-mediated signalling regulates colonic epithelial cell turnover following DNA damage. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain

HTR1B and HTR2C in autism spectrum disorders in Brazilian families.

PubMed

Orabona, G M; Griesi-Oliveira, K; Vadasz, E; Bulcão, V L S; Takahashi, V N V O; Moreira, E S; Furia-Silva, M; Ros-Melo, A M S; Dourado, F; Matioli, S R; Matioli, R; Otto, P; Passos-Bueno, M R

2009-01-23

Autism spectrum disorders (ASD) is a group of behaviorally defined neurodevelopmental disabilities characterized by multiple genetic etiologies and a complex presentation. Several studies suggest the involvement of the serotonin system in the development of ASD, but only few have investigated serotonin receptors. We have performed a case-control and a family-based study with 9 polymorphisms mapped to two serotonin receptor genes (HTR1B and HTR2C) in 252 Brazilian male ASD patients of European ancestry. These analyses showed evidence of undertransmission of the HTR1B haplotypes containing alleles -161G and -261A at HTR1B gene to ASD (P=0.003), but no involvement of HTR2C to the predisposition to this disease. Considering the relatively low level of statistical significance and the power of our sample, further studies are required to confirm the association of these serotonin-related genes and ASD.

Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function

PubMed Central

1994-01-01

Antigen-specific T cell activation requires the engagement of the T cell receptor (TCR) with antigen as well as the engagement of appropriate costimulatory molecules. The most extensively characterized pathway of costimulation has been that involving the interaction of CD28 and CTLA4 on the T cell with B7 (now termed B7-1) on antigen presenting cells. Recently, B7-2 a second costimulatory ligand for CTLA4, was described, demonstrating the potential complexity of costimulatory interactions. This report examines and compares the expression and function of B7-1 and B7-2. Overall these results indicate that (a) B7-1 and B7-2 can be expressed by multiple cell types, including B cells, T cells, macrophages, and dendritic cells, all of which are therefore candidate populations for delivering costimulatory signals mediated by these molecules; (b) stimulating B cells with either LPS or anti-IgD-dextran induced expression of both B7- 1 and B7-2, and peak expression of both costimulatory molecules occurred after 18-42 h of culture. Expression of B7-2 on these B cell populations was significantly higher than expression of B7-1 at all times assayed after stimulation; (c) blocking of B7-2 costimulatory activity inhibited TCR-dependent T cell proliferation and cytokine production, without affecting early consequences of TCR signaling such as induction of CD69 or interleukin 2 receptor alpha (IL-2R alpha); and (d) expression of B7-1 and of B7-2 can be regulated by a variety of stimuli. Moreover, expression of B7-1 and B7-2 can be independently regulated by the same stimulus, providing an additional complexity in the mechanisms available for regulating costimulation and hence immune response. PMID:7519245

MISR Level 1A CCD, 1B1, 1B2, and Browse Products

Atmospheric Science Data Center

2013-04-01

... ESDT Product File Name Prefix Current Quality Designations MI1B2E MISR_AM1_GRP_ELLIPSOID_GM, ... should be used. All calibration files for the life of the mission have been reprocessed using the best available calibration. ...

Crystal structures of fission yeast histone chaperone Asf1 complexed with the Hip1 B-domain or the Cac2 C terminus.

PubMed

Malay, Ali D; Umehara, Takashi; Matsubara-Malay, Kazuko; Padmanabhan, Balasundaram; Yokoyama, Shigeyuki

2008-05-16

The assembly of core histones onto eukaryotic DNA is modulated by several histone chaperone complexes, including Asf1, CAF-1, and HIRA. Asf1 is a unique histone chaperone that participates in both the replication-dependent and replication-independent pathways. Here we report the crystal structures of the apo-form of fission yeast Asf1/Cia1 (SpAsf1N; residues 1-161) as well as its complexes with the B-domain of the fission yeast HIRA orthologue Hip1 (Hip1B) and the C-terminal region of the Cac2 subunit of CAF-1 (Cac2C). The mode of the fission yeast Asf1N-Hip1B recognition is similar to that of the human Asf1-HIRA recognition, suggesting that Asf1N recognition of Hip1B/HIRA is conserved from yeast to mammals. Interestingly, Hip1B and Cac2C show remarkably similar interaction modes with Asf1. The binding between Asf1N and Hip1B was almost completely abolished by the D37A and L60A/V62A mutations in Asf1N, indicating the critical role of salt bridge and van der Waals contacts in the complex formation. Consistently, both of the aforementioned Asf1 mutations also drastically reduced the binding to Cac2C. These results provide a structural basis for a mutually exclusive Asf1-binding model of CAF-1 and HIRA/Hip1, in which Asf1 and CAF-1 assemble histones H3/H4 (H3.1/H4 in vertebrates) in a replication-dependent pathway, whereas Asf1 and HIRA/Hip1 assemble histones H3/H4 (H3.3/H4 in vertebrates) in a replication-independent pathway.

Fractographic Analysis of HfB2-SiC and ZrB2-SiC Composites

NASA Technical Reports Server (NTRS)

Mecholsky, J.J., Jr.; Ellerby, D. T.; Johnson, S. M.; Stackpoole, M. M.; Loehman, R. E.; Arnold, Jim (Technical Monitor)

2001-01-01

Hafnium diboride-silicon carbide and zirconium diboride-silicon carbide composites are potential materials for high temperature leading edge applications on reusable launch vehicles. In order to establish material constants necessary for evaluation of in-situ fracture, bars fractured in four point flexure were examined using fractographic principles. The fracture toughness was determined from measurements of the critical crack sizes and the strength values, and the crack branching constants were established to use in forensic fractography of materials for future flight applications. The fracture toughnesses range from about 13 MPam (sup 1/2) at room temperature to about 6 MPam (sup 1/2) at 1400 C for ZrB2-SiC composites and from about 11 MPam (sup 1/2) at room temperature to about 4 MPam (sup 1/2) at 1400 C for HfB2-SiC composites.

Genetic polymorphisms of ADH1B, ADH1C and ALDH2 in Turkish alcoholics: lack of association with alcoholism and alcoholic cirrhosis.

PubMed

Vatansever, Sezgin; Tekin, Fatih; Salman, Esin; Altintoprak, Ender; Coskunol, Hakan; Akarca, Ulus Salih

2015-05-17

No data exists regarding the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) gene polymorphisms in Turkish alcoholic cirrhotics. We studied the polymorphisms of ADH1B, ADH1C and ALDH2 genes in alcoholic cirrhotics and compared the results with non-cirrhotic alcoholics and healthy volunteers. Overall, 237 subjects were included for the study: 156 alcoholic patients (78 cirrhotics, 78 non-cirrhotic alcoholics) and 81 healthy volunteers. Three different single-nucleotide-polymorphism genotyping methods were used. ADH1C genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism method. The identified ADH1C genotypes were named according to the presence or absence of the enzyme restriction sites. ADH1B (Arg47Hys) genotyping was performed using the allele specific primer extension method, and ALDH2 (Glu487Lys) genotyping was performed by a multiplex polymerase chain reaction using two allele-specific primer pairs. For ADH1B, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 97.4%, 94.9% and 99.4%, respectively. For ADH1C, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 47%, 36.3% and 45%, respectively. There was no statistical difference between the groups for ADH1B and ADH1C (p>0.05). All alcoholic and non-alcoholic subjects (100%) had the allele *1 for ALDH2. The obtained results for ADH1B, ADH1C, and ALDH gene polymorphisms in the present study are similar to the results of Caucasian studies. ADH1B and ADH1C genetic variations are not related to the development of alcoholism or susceptibility to alcoholic cirrhosis. ALDH2 gene has no genetic variation in the Turkish population.

ANKRD1 modulates inflammatory responses in C2C12 myoblasts through feedback inhibition of NF-κB signaling activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xin-Hua; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029; Bauman, William A.

2015-08-14

Transcription factors of the nuclear factor-kappa B (NF-κB) family play a pivotal role in inflammation, immunity and cell survival responses. Recent studies revealed that NF-κB also regulates the processes of muscle atrophy. NF-κB activity is regulated by various factors, including ankyrin repeat domain 2 (AnkrD2), which belongs to the muscle ankyrin repeat protein family. Another member of this family, AnkrD1 is also a transcriptional effector. The expression levels of AnkrD1 are highly upregulated in denervated skeletal muscle, suggesting an involvement of AnkrD1 in NF-κB mediated cellular responses to paralysis. However, the molecular mechanism underlying the interactive role of AnkrD1 inmore » NF-κB mediated cellular responses is not well understood. In the current study, we examined the effect of AnkrD1 on NF-κB activity and determined the interactions between AnkrD1 expression and NF-κB signaling induced by TNFα in differentiating C2C12 myoblasts. TNFα upregulated AnkrD1 mRNA and protein levels. AnkrD1-siRNA significantly increased TNFα-induced transcriptional activation of NF-κB, whereas overexpression of AnkrD1 inhibited TNFα-induced NF-κB activity. Co-immunoprecipitation studies demonstrated that AnkrD1 was able to bind p50 subunit of NF-κB and vice versa. Finally, CHIP assays revealed that AnkrD1 bound chromatin at a NF-κB binding site in the AnrkD2 promoter and required NF-κB to do so. These results provide evidence of signaling integration between AnkrD1 and NF-κB pathways, and suggest a novel anti-inflammatory role of AnkrD1 through feedback inhibition of NF-κB transcriptional activity by which AnkrD1 modulates the balance between physiological and pathological inflammatory responses in skeletal muscle. - Highlights: • AnkrD1 is upregulated by TNFα and represses NF-κB-induced transcriptional activity. • AnkrD1 binds to p50 subunit of NF-κB and is recruited to NF-κB bound to chromatin. • AnkrD1 mediates a feed

Heat shock factors HsfB1 and HsfB2b are involved in the regulation of Pdf1.2 expression and pathogen resistance in Arabidopsis.

PubMed

Kumar, Mukesh; Busch, Wolfgang; Birke, Hannah; Kemmerling, Birgit; Nürnberger, Thorsten; Schöffl, Friedrich

2009-01-01

In order to assess the functional roles of heat stress-induced class B-heat shock factors in Arabidopsis, we investigated T-DNA knockout mutants of AtHsfB1 and AtHsfB2b. Micorarray analysis of double knockout hsfB1/hsfB2b plants revealed as strong an up-regulation of the basal mRNA-levels of the defensin genes Pdf1.2a/b in mutant plants. The Pdf expression was further enhanced by jasmonic acid treatment or infection with the necrotrophic fungus Alternaria brassicicola. The single mutant hsfB2b and the double mutant hsfB1/B2b were significantly improved in disease resistance after A. brassicicola infection. There was no indication for a direct interaction of Hsf with the promoter of Pdf1.2, which is devoid of perfect HSE consensus Hsf-binding sequences. However, changes in the formation of late HsfA2-dependent HSE binding were detected in hsfB1/B2b plants. This suggests that HsfB1/B2b may interact with class A-Hsf in regulating the shut-off of the heat shock response. The identification of Pdf genes as targets of Hsf-dependent negative regulation is the first evidence for an interconnection of Hsf in the regulation of biotic and abiotic responses.

Heat Shock Factors HsfB1 and HsfB2b Are Involved in the Regulation of Pdf1.2 Expression and Pathogen Resistance in Arabidopsis

PubMed Central

Kumar, Mukesh; Busch, Wolfgang; Birke, Hannah; Kemmerling, Birgit; Nürnberger, Thorsten; Schöffl, Friedrich

2009-01-01

In order to assess the functional roles of heat stress-induced class B-heat shock factors in Arabidopsis, we investigated T-DNA knockout mutants of AtHsfB1 and AtHsfB2b. Micorarray analysis of double knockout hsfB1/hsfB2b plants revealed as strong an up-regulation of the basal mRNA-levels of the defensin genes Pdf1.2a/b in mutant plants. The Pdf expression was further enhanced by jasmonic acid treatment or infection with the necrotrophic fungus Alternaria brassicicola. The single mutant hsfB2b and the double mutant hsfB1/B2b were significantly improved in disease resistance after A. brassicicola infection. There was no indication for a direct interaction of Hsf with the promoter of Pdf1.2, which is devoid of perfect HSE consensus Hsf-binding sequences. However, changes in the formation of late HsfA2-dependent HSE binding were detected in hsfB1/B2b plants. This suggests that HsfB1/B2b may interact with class A-Hsf in regulating the shut-off of the heat shock response. The identification of Pdf genes as targets of Hsf-dependent negative regulation is the first evidence for an interconnection of Hsf in the regulation of biotic and abiotic responses. PMID:19529832

Transcriptional Regulation of JARID1B/KDM5B Histone Demethylase by Ikaros, Histone Deacetylase 1 (HDAC1), and Casein Kinase 2 (CK2) in B-cell Acute Lymphoblastic Leukemia*

PubMed Central

Wang, Haijun; Song, Chunhua; Ding, Yali; Pan, Xiaokang; Ge, Zheng; Tan, Bi-Hua; Gowda, Chandrika; Sachdev, Mansi; Muthusami, Sunil; Ouyang, Hongsheng; Lai, Liangxue; Francis, Olivia L.; Morris, Christopher L.; Abdel-Azim, Hisham; Dorsam, Glenn; Xiang, Meixian; Payne, Kimberly J.; Dovat, Sinisa

2016-01-01

Impaired function of the Ikaros (IKZF1) protein is associated with the development of high-risk B-cell precursor acute lymphoblastic leukemia (B-ALL). The mechanisms of Ikaros tumor suppressor activity in leukemia are unknown. Ikaros binds to the upstream regulatory elements of its target genes and regulates their transcription via chromatin remodeling. Here, we report that Ikaros represses transcription of the histone H3K4 demethylase, JARID1B (KDM5B). Transcriptional repression of JARID1B is associated with increased global levels of H3K4 trimethylation. Ikaros-mediated repression of JARID1B is dependent on the activity of the histone deacetylase, HDAC1, which binds to the upstream regulatory element of JARID1B in complex with Ikaros. In leukemia, JARID1B is overexpressed, and its inhibition results in cellular growth arrest. Ikaros-mediated repression of JARID1B in leukemia is impaired by pro-oncogenic casein kinase 2 (CK2). Inhibition of CK2 results in increased binding of the Ikaros-HDAC1 complex to the promoter of JARID1B, with increased formation of trimethylated histone H3 lysine 27 and decreased histone H3 Lys-9 acetylation. In cases of high-risk B-ALL that carry deletion of one Ikaros (IKZF1) allele, targeted inhibition of CK2 restores Ikaros binding to the JARID1B promoter and repression of JARID1B. In summary, the presented data suggest a mechanism through which Ikaros and HDAC1 regulate the epigenetic signature in leukemia: via regulation of JARID1B transcription. The presented data identify JARID1B as a novel therapeutic target in B-ALL and provide a rationale for the use of CK2 inhibitors in the treatment of high-risk B-ALL. PMID:26655717

Erythrocyte concentrations of B1, B2, B6 but not plasma C and E are reliable indicators of nutrition status in the presence of systemic inflammation.

PubMed

Ghashut, Rawia A; McMillan, Donald C; Kinsella, John; Talwar, Dinesh

2017-02-01

There is increasing evidence that the plasma concentration of vitamin D, carotenoids, zinc and selenium are associated with the magnitude of the systemic inflammatory response. In order to examine whether other vitamins may be affected and whether red cell concentrations are less affected by systemic inflammation the aim of the present study was to examine the effect of the systemic inflammatory response on red cell measurements of vitamins B1, B2 and B6, and plasma concentration of vitamin C and E in a large cohort of patients referred for a nutritional screen. Patients referred for nutritional assessment of B1 (n = 551), B2 (n = 251), B6 (n = 313), ascorbic acid (n = 494) and α-tocopherol (n = 395) concentrations. These vitamins were measured using routine laboratory methods. The median concentrations of vitamin B1 grouped according to C-reactive protein concentrations ≤10, 11-80 and >80 mg/L were 543, 664 and 766 ng/g Hb respectively (p < 0.001, 41% higher). The median concentration of vitamin B1 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 547, 664 and 701 ng/g Hb respectively (p < 0.001, 28% higher). The median concentrations of red cell vitamin B2 grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 2.2, 2.3 and 2.4 nmol/g Hb respectively (p < 0.001, 9% higher). The median red cell concentrations of vitamin B2 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 2.1, 2.4 and 2.3 nmol/g Hb respectively (p < 0.001, 14% higher). The median concentrations of red cell vitamin B6 grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 534, 548 and 767 pmol/g Hb respectively (p < 0.001, 44% higher). The median red cell concentrations of vitamin B6 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 462, 644 and 840 pmol/g Hb respectively (p < 0.001, 82% higher). In contrast, the median plasma concentrations of ascorbic acid

Modulation of intracellular Ca(2+) via alpha(1B)-adrenoreceptor signaling molecules, G alpha(h) (transglutaminase II) and phospholipase C-delta 1.

PubMed

Kang, Sung Koo; Kim, Dae Kyong; Damron, Derek S; Baek, Kwang Jin; Im, Mie-Jae

2002-04-26

We characterized the alpha(1B)-adrenoreceptor (alpha(1B)-AR)-mediated intracellular Ca(2+) signaling involving G alpha(h) (transglutaminase II, TGII) and phospholipase C (PLC)-delta 1 using DDT1-MF2 cell. Expression of wild-type TGII and a TGII mutant lacking transglutaminase activity resulted in significant increases in a rapid peak and a sustained level of intracellular Ca(2+) concentration ([Ca(2+)](i)) in response to activation of the alpha(1B)-AR. Expression of a TGII mutant lacking the interaction with the receptor or PLC-delta 1 substantially reduced both the peak and sustained levels of [Ca(2+)](i). Expression of TGII mutants lacking the interaction with PLC-delta 1 resulted in a reduced capacitative Ca(2+) entry. Reduced expression of PLC-delta 1 displayed a transient elevation of [Ca(2+)](i) and a reduction in capacitative Ca(2+) entry. Expression of the C2-domain of PLC-delta 1, which contains the TGII interaction site, resulted in reduction of the alpha(1B)-AR-evoked peak increase in [Ca(2+)](i), while the sustained elevation in [Ca(2+)](i) and capacitative Ca(2+) entry remained unchanged. These findings demonstrate that stimulation of PLC-delta 1 via coupling of the alpha(1B)-AR with TGII evokes both Ca(2+) release and capacitative Ca(2+) entry and that capacitative Ca(2+) entry is mediated by the interaction of TGII with PLC-delta 1.

Unusual behaviour of (Np,Pu)B2C

NASA Astrophysics Data System (ADS)

Klimczuk, Tomasz; Boulet, Pascal; Griveau, Jean-Christophe; Colineau, Eric; Bauer, Ernst; Falmbigl, Matthias; Rogl, Peter; Wastin, Franck

2015-02-01

Two transuranium metal boron carbides, NpB2C and PuB2C have been synthesized by argon arc melting. The crystal structures of the {Np,Pu}B2C compounds were determined from single-crystal X-ray data to be isotypic with the ThB2C-type (space group ?, a = 0.6532(2) nm; c = 1.0769(3) nm for NpB2C and a = 0.6509(2) nm; c = 1.0818(3) nm for PuB2C; Z = 9). Physical properties have been derived from polycrystalline bulk material in the temperature range from 2 to 300 K and in magnetic fields up to 9 T. Magnetic susceptibility and heat capacity data indicate the occurrence of antiferromagnetic ordering for NpB2C with a Neel temperature TN = 68 K. PuB2C is a Pauli paramagnet most likely due to a strong hybridization of s(p,d) electrons with the Pu-5f states. A pseudo-gap, as concluded from the Sommerfeld value and the electronic transport, is thought to be a consequence of the hybridization. The magnetic behaviour of {Np,Pu}B2C is consistent with the criterion of Hill.

Differential binding of RhoA, RhoB, and RhoC to protein kinase C-related kinase (PRK) isoforms PRK1, PRK2, and PRK3: PRKs have the highest affinity for RhoB.

PubMed

Hutchinson, Catherine L; Lowe, Peter N; McLaughlin, Stephen H; Mott, Helen R; Owen, Darerca

2013-11-12

Protein kinase C-related kinases (PRKs) are members of the protein kinase C superfamily of serine-threonine kinases and can be activated by binding to members of the Rho family of GTPases via a Rho-binding motif known as an HR1 domain. Three tandem HR1 domains reside at the N-terminus of the PRKs. We have assessed the ability of the HR1a and HR1b domains from the three PRK isoforms (PRK1, PRK2, and PRK3) to interact with the three Rho isoforms (RhoA, RhoB, and RhoC). The affinities of RhoA and RhoC for a construct encompassing both PRK1 HR1 domains were similar to those for the HR1a domain alone, suggesting that these interactions are mediated solely by the HR1a domain. The affinities of RhoB for both the PRK1 HR1a domain and the HR1ab didomain were higher than those of RhoA or RhoC. RhoB also bound more tightly to the didomain than to the HR1a domain alone, implicating the HR1b domain in the interaction. As compared with PRK1 HR1 domains, PRK2 and PRK3 domains bind less well to all Rho isoforms. Uniquely, however, the PRK3 domains display a specificity for RhoB that requires both the C-terminus of RhoB and the PRK3 HR1b domain. The thermal stability of the HR1a and HR1b domains was also investigated. The PRK2 HR1a domain was found to be the most thermally stable, while PRK2 HR1b, PRK3 HR1a, and PRK3 HR1b domains all exhibited lower melting temperatures, similar to that of the PRK1 HR1a domain. The lower thermal stability of the PRK2 and PRK3 HR1b domains may impart greater flexibility, driving their ability to interact with Rho isoforms.

Role of PTP1B in HER2 Signaling in Breast Cancer

DTIC Science & Technology

2011-10-01

AD_________________ Award Number: W81XWH-10-1-1005 TITLE: Role of PTP1B in HER2 Signaling in...AND SUBTITLE 5a. CONTRACT NUMBER Role of PTP1B in HER2 Signaling in Breast Cancer 5b. GRANT NUMBER W81XWH-10-1-1005 5c. PROGRAM ELEMENT...pathways. Recent reports have shown that Protein Tyrosine Phosphatase 1B ( PTP1B ) plays a positive role in ErbB2-induced breast cancer in vitroand

Downregulation of kinin B1 receptor function by B2 receptor heterodimerization and signaling.

PubMed

Zhang, Xianming; Brovkovych, Viktor; Zhang, Yongkang; Tan, Fulong; Skidgel, Randal A

2015-01-01

Signaling through the G protein-coupled kinin receptors B1 (kB1R) and B2 (kB2R) plays a critical role in inflammatory responses mediated by activation of the kallikrein-kinin system. The kB2R is constitutively expressed and rapidly desensitized in response to agonist whereas kB1R expression is upregulated by inflammatory stimuli and it is resistant to internalization and desensitization. Here we show that the kB1R heterodimerizes with kB2Rs in co-transfected HEK293 cells and natively expressing endothelial cells, resulting in significant internalization and desensitization of the kB1R response in cells pre-treated with kB2R agonist. However, pre-treatment of cells with kB1R agonist did not affect subsequent kB2R responses. Agonists of other G protein-coupled receptors (thrombin, lysophosphatidic acid) had no effect on a subsequent kB1R response. The loss of kB1R response after pretreatment with kB2R agonist was partially reversed with kB2R mutant Y129S, which blocks kB2R signaling without affecting endocytosis, or T342A, which signals like wild type but is not endocytosed. Co-endocytosis of the kB1R with kB2R was dependent on β-arrestin and clathrin-coated pits but not caveolae. The sorting pathway of kB1R and kB2R after endocytosis differed as recycling of kB1R to the cell surface was much slower than that of kB2R. In cytokine-treated human lung microvascular endothelial cells, pre-treatment with kB2R agonist inhibited kB1R-mediated increase in transendothelial electrical resistance (TER) caused by kB1R stimulation (to generate nitric oxide) and blocked the profound drop in TER caused by kB1R activation in the presence of pyrogallol (a superoxide generator). Thus, kB1R function can be downregulated by kB2R co-endocytosis and signaling, suggesting new approaches to control kB1R signaling in pathological conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Downregulation of kinin B1 receptor function by B2 receptor heterodimerization and signaling

PubMed Central

Zhang, Xianming; Brovkovych, Viktor; Zhang, Yongkang; Tan, Fulong; Skidgel, Randal A.

2014-01-01

Signaling through the G protein-coupled kinin receptors B1 (kB1R) and B2 (kB2R) plays a critical role in inflammatory responses mediated by activation of the kallikrein-kinin system. The kB2R is constitutively expressed and rapidly desensitized in response to agonist whereas kB1R expression is upregulated by inflammatory stimuli and it is resistant to internalization and desensitization. Here we show that the kB1R heterodimerizes with kB2Rs in co-transfected HEK293 cells and natively expressing endothelial cells, resulting in significant internalization and desensitization of the kB1R response in cells pre-treated with kB2R agonist. However, pre-treatment of cells with kB1R agonist did not affect subsequent kB2R responses. Agonists of other G protein-coupled receptors (thrombin, lysophosphatidic acid) had no effect on a subsequent kB1R response. The loss of kB1R response after pretreatment with kB2R agonist was partially reversed with kB2R mutant Y129S, which blocks kB2R signaling without affecting endocytosis, or T342A, which signals like wild type but is not endocytosed. Co-endocytosis of the kB1R with kB2R was dependent on β-arrestin and clathrin-coated pits but not caveolae. The sorting pathway of kB1R and kB2R after endocytosis differed as recycling of kB1R to the cell surface was much slower than that of kB2R. In cytokine-treated human lung microvascular endothelial cells, pre-treatment with kB2R agonist inhibited kB1R-mediated increase in transendothelial electrical resistance (TER) caused by kB1R stimulation (to generate nitric oxide) and blocked the profound drop in TER caused by kB1R activation in the presence of pyrogallol (a superoxide generator). Thus, kB1R function can be downregulated by kB2R co-endocytosis and signaling, suggesting new approaches to control kB1R signaling in pathological conditions. PMID:25289859

High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia

PubMed Central

2013-01-01

Background The Minangkabau is one of the major ethnic groups in Indonesia. Previous studies with a limited number of samples have shown a different prevalence of HBV/C in the Minangkabau compared to the Indonesian population in general. The aim of this study was to assess the HBV genotype distribution pattern and the prevalence of pre-S, T1753V and A1762T/G1764A mutations among the Minangkabau HBV carriers. The samples were collected from Padang, West Sumatera and from western Java. Mixed primers for specific genotypes were used to determine the HBV genotype. Pre-S or S genes were amplified, sequenced and aligned with reference sequences from GenBank to derive a phylogenetic tree for subgenotyping. Pre-S genes were also analyzed for mutations. The basal core promoter (BCP) region was amplified and directly sequenced to analyze T1753V and A1762T/G1764A mutations. Results The predominant HBV genotype among the Minangkabau HBV carriers (n=117) was C (72.6%) followed by B (24.8%) and co-infection with B and C (2.6%). The prevalence of pre-S mutations, including both the pre-S deletion and pre-S2 start codon mutation, was 41.0%, and the T1753V and A1762T/G1764A mutations were found in 51.9% and 71.2% respectively. HBV/C1 was the predominant HBV subgenotype in the Minangkabau HBV carriers, and was found in 66.2%, followed by B3, B7, C8, B2, B9, C2, and C10 (18.3%, 7.0%, 2.8%, 1.4%, 1.4%, 1.4%, and 1.4% respectively). From samples that were found to be co-infected with HBV B and C, two samples were successfully cloned and subgenotyped, including one with mixed subgenotypes of B3 and C1, and another one with mixed subgenotypes of B7, C1, putative intergenotypic of B/A, and C/A. Furthermore, three samples from donors of non-Minangkabau ethnicity from Padang were found to be infected with an intragenotypic recombination form, including a putative recombinant of B8/B3 and B9/B7. Conclusion HBV/C with subgenotype C1 was the predominant HBV genotype among HBV carriers of

Origin and Evolution of the Unique Hepatitis C Virus Circulating Recombinant Form 2k/1b

PubMed Central

Thomas, Xiomara V.; Koekkoek, Sylvie M.; Schinkel, Janke; Molenkamp, Richard; van de Laar, Thijs J.; Takebe, Yutaka; Tanaka, Yasuhito; Mizokami, Masashi; Rambaut, Andrew

2012-01-01

Since its initial identification in St. Petersburg, Russia, the recombinant hepatitis C virus (HCV) 2k/1b has been isolated from several countries throughout Eurasia. The 2k/1b strain is the only recombinant HCV to have spread widely, raising questions about the epidemiological background in which it first appeared. In order to further understand the circumstances by which HCV recombinants might be formed and spread, we estimated the date of the recombination event that generated the 2k/1b strain using a Bayesian phylogenetic approach. Our study incorporates newly isolated 2k/1b strains from Amsterdam, The Netherlands, and has employed a hierarchical Bayesian framework to combine information from different genomic regions. We estimate that 2k/1b originated sometime between 1923 and 1956, substantially before the first detection of the strain in 1999. The timescale and the geographic spread of 2k/1b suggest that it originated in the former Soviet Union at about the time that the world's first centralized national blood transfusion and storage service was being established. We also reconstructed the epidemic history of 2k/1b using coalescent theory-based methods, matching patterns previously reported for other epidemic HCV subtypes. This study demonstrates the practicality of jointly estimating dates of recombination from flanking regions of the breakpoint and further illustrates that rare genetic-exchange events can be particularly informative about the underlying epidemiological processes. PMID:22114341

Magnetic and superconducting phase diagrams of single-crystal Er0.8R0.2Ni2B2C (R=Tb,Lu) and ErNi1.9Co0.1B2C: Identification of pair-breaking mechanisms

NASA Astrophysics Data System (ADS)

Takeya, H.; El Massalami, M.

2004-01-01

We investigated the magnetism, superconductivity and their interplay in single crystals Er0.8R0.2Ni2B2C (R=Tb,Lu) and ErNi1.9Co0.1B2C. In contrast to Co substitution, R substitutions induce considerable modifications in the magnetism of Er sublattice: e.g., Tb (Lu) substitution enhances (reduces) TN and critical fields. Both R substitutions introduce size effects and pinning centers; the former modifies the magnon specific heat while the latter hinders the formation of a weak ferromagnetism. The superconductivity, on the other hand, is strongly (weakly) influenced by Tb and Co (Lu) substitution. Taking LuNi2B2C as a nonmagnetic superconducting limit, we analyzed their superconductivities, as well as that of ErNi2B2C, in terms of multiple pair breaking theory on dirty superconductors. Based on this analysis, many of their superconducting features can be explained: The breakdown of de Gennes scaling is due to the presence of multiple pair breakers, the anisotropy of Hc2(T) is related to the magnetic anisotropy, the absence of a structure in Hc2(T) at TN of Lu substitution (TN2(T) of Tb and Co substitutions is in part due to a saturation of antiferromagnetic correlations. For Lu substitution, the strength of magnon mediated pair breaking process(es) is substantially reduced.

Bruton's tyrosine kinase regulates B cell antigen receptor-mediated JNK1 response through Rac1 and phospholipase C-gamma2 activation.

PubMed

Inabe, Kazunori; Miyawaki, Toshio; Longnecker, Richard; Matsukura, Hiroyoshi; Tsukada, Satoshi; Kurosaki, Tomohiro

2002-03-13

Bruton's tyrosine kinase (Btk) is essential for B cell development and B cell antigen receptor (BCR) function. Recent studies have shown that Btk plays an important role in BCR-mediated c-Jun NH(2)-terminal kinase (JNK) 1 activation; however, the mechanism by which Btk participates in the JNK1 response remains elusive. Here we show that the BCR-mediated Rac1 activation is significantly inhibited by loss of Btk, while this Rac1 activation is not affected by loss of phospholipase C-gamma2 (PLC-gamma2). Since PLC-gamma2 is also required for BCR-mediated JNK1 response, our results suggest that Btk regulates Rac1 pathway as well as PLC-gamma2 pathway, both of which contribute to the BCR-mediated JNK1 response.

Crystal structures of the coil 2B fragment and the globular tail domain of human lamin B1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruan, Jianbin; Xu, Chao; Bian, Chuanbing

2012-07-18

We present here the crystal structures of human lamin B1 globular tail domain and coiled 2B domain, which adopt similar folds to Ig-like domain and coiled-coil domain of lamin A, respectively. Despite the overall similarity, we found an extra intermolecular disulfide bond in the lamin B1 coil 2B domain, which does not exist in lamin A/C. In addition, the structural analysis indicates that interactions at the lamin B1 homodimer interface are quite different from those of lamin A/C. Thus our research not only reveals the diversely formed homodimers among lamin family members, but also sheds light on understanding the importantmore » roles of lamin B1 in forming the nuclear lamina matrix.« less

Experiences and Future Expectations towards Online Courses--An Empirical Study of the B2C-and B2B-Segments

ERIC Educational Resources Information Center

Krämer, Andreas; Böhrs, Sandra

2016-01-01

This article explores the future potential for the development of online courses. The findings are based on an empirical study with 3 sample groups: (1) B2C segment in Germany, (2) B2C segment in the United States, and (3) B2B segment (international). In the first step the status quo of the use of e-learning in general and online courses in…

75 FR 34062 - Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model AS355 E, F, F1, F2... AS 350 B, BA, B1, B2, B3, and D, and Model AS355 E, F, F1, F2, and N helicopters, with certain main... an unsafe condition for certain Eurocopter France Model AS 350 B, BA, BB, B1, B2, B3, and D, and...

Synthesis, structure and reactivity of rare-earth metallacarborane alkyls [η(1):η(5)-O(CH2)2C2B9H9]Ln(σ:η(1)-CH2C6H4-o-NMe2)(THF)2.

PubMed

Yang, Jingying; Xie, Zuowei

2015-04-14

Rare-earth metallacarborane alkyls can be stabilized by the incorporation of a functional sidearm into both π and σ ligands. Reaction of [Me3NH][7,8-O(CH2)2-7,8-C2B9H10] with one equiv. of Ln(CH2C6H4-o-NMe2)3 gave metallacarborane alkyls [η(1):η(5)-O(CH2)2C2B9H9]Ln(σ:η(1)-CH2C6H4-o-NMe2)(THF)2 (Ln = Y (), Gd (), Er ()) via alkane elimination. They represent the first examples of rare-earth metallacarborane alkyls. Treatment of with RN[double bond, length as m-dash]C[double bond, length as m-dash]NR (R = Cy, (i)Pr) or 2-benzoylpyridine afforded the corresponding mono-insertion products [η(1):η(5)-O(CH2)2C2B9H9]Y[η(2)-(RN)2C(CH2C6H4-o-NMe2)](DME) (R = Cy (), (i)Pr ()) or [η(1):η(5)-O(CH2)2C2B9H9]Y[C5H4NC(Ph)(CH2C6H4-o-NMe2)O](THF)2 (), respectively. Complex also reacted with ArNCO or ArNC (Ar = 2,6-diisopropylphenyl, 2,6-dimethylphenyl) to give di-insertion products [η(1):η(5)-O(CH2)2C2B9H9]Y[OC([double bond, length as m-dash]NC6H3Me2)N(C6H3Me2)C(CH2C6H4-o-NMe2)O](THF)2 () or [η(1):η(5)-O(CH2)2C2B9H9]Y[C([double bond, length as m-dash]NC6H3(i)Pr2)C([double bond, length as m-dash]NC6H3(i)Pr2)(CH2C6H4-o-NMe2)](DME) (). These results showed that the reactivity pattern of the Ln-C σ bond in rare-earth metallacarborane alkyls was dependent on the nature of the unsaturated organic molecules. New complexes were characterized by various spectroscopic techniques and elemental analysis. Some were further confirmed by single-crystal X-ray analysis.

Measurement of sigma Lambda b0/sigma B0 x B(Lambda b0-->Lambda c+pi-)/B(B0-->D+pi-) in pp collisions at square root s=1.96 TeV.

PubMed

Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Budroni, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Cyr, D; DaRonco, S; D'Auria, S; Davies, T; D'Onofrio, M; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; DiTuro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A C; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Le, Y; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Nagano, A; Naganoma, J; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ranjan, N; Rappoccio, S; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sánchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tseng, J; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waschke, S; Waters, D; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

2007-03-23

We present the first observation of the baryon decay Lambda b0-->Lambda c+pi- followed by Lambda c+-->pK-pi+ in 106 pb-1 pp collisions at square root s=1.96 TeV in the CDF experiment. In order to reduce systematic error, the measured rate for Lambda b0 decay is normalized to the kinematically similar meson decay B0-->D+pi- followed by D+-->pi+K-pi+. We report the ratio of production cross sections (sigma) times the ratio of branching fractions (B) for the momentum region integrated above pT>6 GeV/c and pseudorapidity range |eta|<1.3: sigma(pp-->Lambda b0X)/sigma(pp-->B0X)xB(Lambda b0-->Lambda c+pi-)/B(B0-->D+pi-)=0.82+/-0.08(stat)+/-0.11(syst)+/-0.22[B(Lambda c+-->pK-pi+)].

L1-mediated retrotransposition of murine B1 and B2 SINEs recapitulated in cultured cells.

PubMed

Dewannieux, Marie; Heidmann, Thierry

2005-06-03

SINEs are short interspersed nucleotide elements with transpositional activity, present at a high copy number (up to a million) in mammalian genomes. They are 80-400 bp long, non-coding sequences which derive either from the 7SL RNA (e.g. human Alus, murine B1s) or tRNA (e.g. murine B2s) polymerase III-driven genes. We have previously demonstrated that Alus very efficiently divert the enzymatic machinery of the autonomous L1 LINE (long interspersed nucleotide element) retrotransposons to transpose at a high rate. Here we show, using an ex vivo assay for transposition, that both B1 and B2 SINEs can be mobilized by murine LINEs, with the hallmarks of a bona fide retrotransposition process, including target site duplications of varying lengths and integrations into A-rich sequences. Despite different phylogenetic origins, transposition of the tRNA-derived B2 sequences is as efficient as that of the human Alus, whereas that of B1s is 20-100-fold lower despite a similar high copy number of these elements in the mouse genome. We provide evidence, via an appropriate nucleotide substitution within the B1 sequence in a domain essential for its intracellular targeting, that the current B1 SINEs are not optimal for transposition, a feature most probably selected for the host sake in the course of evolution.

Covalent Allosteric Inactivation of Protein Tyrosine Phosphatase 1B (PTP1B) by an Inhibitor-Electrophile Conjugate.

PubMed

Punthasee, Puminan; Laciak, Adrian R; Cummings, Andrea H; Ruddraraju, Kasi Viswanatharaju; Lewis, Sarah M; Hillebrand, Roman; Singh, Harkewal; Tanner, John J; Gates, Kent S

2017-04-11

Protein tyrosine phosphatase 1B (PTP1B) is a validated drug target, but it has proven difficult to develop medicinally useful, reversible inhibitors of this enzyme. Here we explored covalent strategies for the inactivation of PTP1B using a conjugate composed of an active site-directed 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxide inhibitor connected via a short linker to an electrophilic α-bromoacetamide moiety. Inhibitor-electrophile conjugate 5a caused time-dependent loss of PTP1B activity consistent with a covalent inactivation mechanism. The inactivation occurred with a second-order rate constant of (1.7 ± 0.3) × 10 2 M -1 min -1 . Mass spectrometric analysis of the inactivated enzyme indicated that the primary site of modification was C121, a residue distant from the active site. Previous work provided evidence that covalent modification of the allosteric residue C121 can cause inactivation of PTP1B [Hansen, S. K., Cancilla, M. T., Shiau, T. P., Kung, J., Chen, T., and Erlanson, D. A. (2005) Biochemistry 44, 7704-7712]. Overall, our results are consistent with an unusual enzyme inactivation process in which noncovalent binding of the inhibitor-electrophile conjugate to the active site of PTP1B protects the nucleophilic catalytic C215 residue from covalent modification, thus allowing inactivation of the enzyme via selective modification of allosteric residue C121.

Dietary intake of the water-soluble vitamins B1, B2, B6, B12 and C in 10 countries in the European Prospective Investigation into Cancer and Nutrition.

PubMed

Olsen, A; Halkjaer, J; van Gils, C H; Buijsse, B; Verhagen, H; Jenab, M; Boutron-Ruault, M C; Ericson, U; Ocké, M C; Peeters, P H M; Touvier, M; Niravong, M; Waaseth, M; Skeie, G; Khaw, K T; Travis, R; Ferrari, P; Sanchez, M J; Agudo, A; Overvad, K; Linseisen, J; Weikert, C; Sacerdote, C; Evangelista, A; Zylis, D; Tsiotas, K; Manjer, J; van Guelpen, B; Riboli, E; Slimani, N; Bingham, S

2009-11-01

To describe the intake of vitamins thiamine (B1), riboflavin (B2), B6 (pyridoxine), B12 (cobalamine) and C (ascorbic acid) and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Between 1995 and 2000, 36 034 persons aged between 35 and 74 years were administered a standardized 24-h dietary recall using a computerized interview software programme (EPIC-SOFT). Intakes of the four B vitamins and vitamin C were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age and weighted by season and day of recall. Intake of B vitamins did not vary considerably between centres, except in the UK health-conscious cohort, in which substantially higher intakes of thiamine and lower intakes of vitamin B12 were reported compared with other centres. Overall, meat was the most important contributor to the B vitamins in all centres except in the UK health-conscious group. Vitamin C showed a clear geographical gradient, with higher intakes in the southern centres as compared with the northern ones; this was more pronounced in men than in women. Vegetables and fruits were major contributors to vitamin C in all centres, but juices and potatoes were also important sources in the northern centres. This study showed no major differences across centres in the mean intakes of B vitamins (thiamine, riboflavin, B6, B12), whereas a tendency towards a north-south gradient was observed for vitamin C.

Different patterns of supramolecular assembly in constitutionally similar 6-arylimidazo[2,1-b][1,3,4]thiadiazoles.

PubMed

Praveen, Aletti S; Yathirajan, Hemmige S; Kaur, Manpreet; Narayana, Badiadka; Hosten, Eric C; Betz, Richard; Glidewell, Christopher

2014-09-01

Four imidazo[2,1-b][1,3,4]thiadiazoles containing a simply-substituted 6-aryl group have been synthesized by reaction of 2-amino-1,3,4-thiadiazoles with bromoacetylarenes using microwave irradiation and brief reaction times. 6-(2-Chlorophenyl)imidazo[2,1-b][1,3,4]thiadiazole, C(10)H(6)ClN(3)S, (I), 6-(2-chlorophenyl)-2-methylimidazo[2,1-b][1,3,4]thiadiazole, C(11)H(8)ClN(3)S, (II), 6-(3,4-dichlorophenyl)imidazo[2,1-b][1,3,4]thiadiazole, C(10)H(5)Cl(2)N(3)S, (III), and 6-(4-fluoro-3-methoxyphenyl)-2-methylimidazo[2,1-b][1,3,4]thiadiazole, C(12)H(10)FN(3)OS, (IV), crystallize with Z' values of 2, 1, 1 and 2 respectively. The molecular skeletons are all nearly planar and the dihedral angles between the imidazole and aryl rings are 1.51 (8) and 7.28 (8)° in (I), 9.65 (7)° in (II), 10.44 (8)° in (III), and 1.05 (8) and 7.21 (8)° in (IV). The molecules in (I) are linked by three independent C-H...N hydrogen bonds to form ribbons containing alternating R2(2)(8) and R4(4)(18) rings, and these ribbons are linked into a three-dimensional array by three independent π-stacking interactions. Both (II) and (III) contain centrosymmetric dimers formed by π-stacking interactions but hydrogen bonds are absent, and the molecules of (IV) are linked into centrosymmetric R2(2)(8) dimers by C-H...N hydrogen bonds. Comparisons are made with a number of related compounds.

Aldo-keto Reductase 1B15 (AKR1B15)

PubMed Central

Weber, Susanne; Salabei, Joshua K.; Möller, Gabriele; Kremmer, Elisabeth; Bhatnagar, Aruni; Adamski, Jerzy; Barski, Oleg A.

2015-01-01

Aldo-keto reductases (AKRs) comprise a superfamily of proteins involved in the reduction and oxidation of biogenic and xenobiotic carbonyls. In humans, at least 15 AKR superfamily members have been identified so far. One of these is a newly identified gene locus, AKR1B15, which clusters on chromosome 7 with the other human AKR1B subfamily members (i.e. AKR1B1 and AKR1B10). We show that alternative splicing of the AKR1B15 gene transcript gives rise to two protein isoforms with different N termini: AKR1B15.1 is a 316-amino acid protein with 91% amino acid identity to AKR1B10; AKR1B15.2 has a prolonged N terminus and consists of 344 amino acid residues. The two gene products differ in their expression level, subcellular localization, and activity. In contrast with other AKR enzymes, which are mostly cytosolic, AKR1B15.1 co-localizes with the mitochondria. Kinetic studies show that AKR1B15.1 is predominantly a reductive enzyme that catalyzes the reduction of androgens and estrogens with high positional selectivity (17β-hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoA conjugates and exhibits strong cofactor selectivity toward NADP(H). In accordance with its substrate spectrum, the enzyme is expressed at the highest levels in steroid-sensitive tissues, namely placenta, testis, and adipose tissue. Placental and adipose expression could be reproduced in the BeWo and SGBS cell lines, respectively. In contrast, AKR1B15.2 localizes to the cytosol and displays no enzymatic activity with the substrates tested. Collectively, these results demonstrate the existence of a novel catalytically active AKR, which is associated with mitochondria and expressed mainly in steroid-sensitive tissues. PMID:25577493

75 FR 65222 - Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-22

... Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model AS355 E, F, F1, F2... adopting a new airworthiness directive (AD) for the Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D... 14 CFR part 39 to include an AD that would apply to the Eurocopter France Model AS 350 B, BA, B1, B2...

Role of PTP1B in HER2 Signaling in Breast Cancer

DTIC Science & Technology

2012-10-01

AD_________________ Award Number: W81XWH-10-1-1005 TITLE: Role of PTP1B in HER2 Signaling in...AND SUBTITLE 5a. CONTRACT NUMBER Role of PTP1B in HER2 Signaling in Breast Cancer 5b. GRANT NUMBER W81XWH-10-1-1005 5c. PROGRAM ELEMENT NUMBER...2009, Postdoctoral Fellowship Award W81XWH-10-1-1005, “Role of PTP1B in HER2 Signaling in Breast Cancer" INTRODUCTION  The receptor tyrosine

Ubiquitination and sumoylation of the HTLV-2 Tax-2B protein regulate its NF-κB activity: a comparative study with the HTLV-1 Tax-1 protein

PubMed Central

2012-01-01

Background Retroviruses HTLV-1 and HTLV-2 have homologous genomic structures but differ significantly in pathogenicity. HTLV-1 is associated with Adult T cell Leukemia (ATL), whereas infection by HTLV-2 has no association with neoplasia. Transformation of T lymphocytes by HTLV-1 is linked to the capacity of its oncoprotein Tax-1 to alter cell survival and cell cycle control mechanisms. Among these functions, Tax-1-mediated activation of cellular gene expression via the NF-κB pathway depends on Tax-1 post-translational modifications by ubiquitination and sumoylation. The Tax-2 protein of HTLV-2B (Tax-2B) is also modified by ubiquitination and sumoylation and activates the NF-κB pathway to a level similar to that of Tax-1. The present study aims to understand whether ubiquitination and sumoylation modifications are involved in Tax-2B-mediated activation of the NF-κB pathway. Results The comparison of Tax-1 and Tax-2B lysine to arginine substitution mutants revealed conserved patterns and levels of ubiquitination with notable difference in the lysine usage for sumoylation. Neither Tax-1 nor Tax-2B ubiquitination and sumoylation deficient mutants could activate the NF-κB pathway and fusion of ubiquitin or SUMO-1 to the C-terminus of the ubiquitination and sumoylation deficient Tax-2B mutant strikingly restored transcriptional activity. In addition, ubiquitinated forms of Tax-2B colocalized with RelA and IKKγ in prominent cytoplasmic structures associated with the Golgi apparatus, whereas colocalization of Tax-2B with the RelA subunit of NF-κB and the transcriptional coactivator p300 in punctate nuclear structures was dependent on Tax-2B sumoylation, as previously observed for Tax-1. Conclusions Both Tax-1 and Tax-2 activate the NF-κB pathway via similar mechanisms involving ubiquitination and sumoylation. Therefore, the different transforming potential of HTLV-1 and HTLV-2 is unlikely to be related to different modes of activation of the canonical NF-κB pathway

Genotype X/C recombinant (putative genotype I) of hepatitis B virus is rare in Hanoi, Vietnam--genotypes B4 and C1 predominate.

PubMed

Phung, Thi Bich Thuy; Alestig, Erik; Nguyen, Thanh Liem; Hannoun, Charles; Lindh, Magnus

2010-08-01

There are eight known genotypes of hepatitis B virus, A-H, and several subgenotypes, with rather well-defined geographic distributions. HBV genotypes were evaluated in 153 serum samples from Hanoi, Vietnam. Of the 87 samples that could be genotyped, genotype B was found in 67 (77%) and genotype C in 19 (22%). All genotype C strains were of subgenotype C1, and the majority of genotype B strains were B4, while a few were B2. The genotype X/C recombinant strain, identified previously in Swedish patients of indigenous Vietnamese origin, was found in one sample. This variant, proposed to be classified as genotype I, has been found recently also by others in Vietnam and Laos. The current study indicates that the genotype X/C recombinant may represent approximately 1% of the HBV strains circulating in Vietnam. (c) 2010 Wiley-Liss, Inc.

Synthesis, characterization, antimicrobial and enzymatic activity of 4b,9b-dihydroxy-7,8-dihydro-4bH-indeno[1,2-b]benzofuran-9,10(6H,9bH)-dione

NASA Astrophysics Data System (ADS)

Mehdi, Sayed Hasan; Hashim, Rokiah; Ghalib, Raza Murad; Fátima C. Guedes da Silva, M.; Sulaiman, Othman; Rahman, Syed Ziaur; Murugaiyah, Vikneswaran; Marimuthu, Mani Maran

2011-12-01

The crystal structure of the title compound, 4b,9b-dihydroxy-7,8-dihydro-4bH-indeno[1,2-b]benzofuran-9,10(6H,9bH)-dione has been determined by single crystal X-ray diffraction. It crystallizes in the monoclinic space group P2 1/c with Z = 4. The FTIR as well as the 1H and 13C NMR spectra of the compound were also recorded and briefly discussed. The compound showed potential antimicrobial activity comparable to that of clinically used antimicrobial agents against selected microorganisms. It has selective and moderate inhibitory activity on butyryl cholinesterase enzyme and could serve as potential lead compound for synthesis of more bioactive derivatives.

Prognostic Significance of ESR1 Amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 Polymorphisms in Breast Cancer Patients

PubMed Central

Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Jaśkiewicz, Janusz; Szade, Jolanta; Jassem, Jacek; Żaczek, Anna J.

2013-01-01

Introduction Amplification of the ESR1 gene, coding for estrogen receptor alpha, was shown to predict responsiveness to tamoxifen, however its prognostic impact in breast cancer patients has not been thoroughly investigated. Other factors that could contribute to responsiveness to tamoxifen treatment are polymorphisms in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study was to assess the prognostic role of ESR1 gene dosage in a consecutive group of breast cancer patients and to correlate this feature with clinico-pathological factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were analyzed in the tamoxifen-treated subgroup of patients. Materials and Methods Primary tumor samples from 281 stage I-III consecutive breast cancer patients were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed. Results were correlated with clinico-pathological factors and with disease-free survival (DFS) and overall survival (OS). Results ESR1 amplification (with a cut-off level of 2.0) was found in 12% of the entire group of breast cancer patients, and in 18% of the ER-negative subgroup. This feature was associated with decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1 PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. Conclusions ESR1 amplification can occur in ER-negative tumors and may carry poor prognosis. In the tamoxifen-treated subgroup, poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype. PMID:23951298

Prognostic significance of ESR1 amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 polymorphisms in breast cancer patients.

PubMed

Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Jaśkiewicz, Janusz; Szade, Jolanta; Jassem, Jacek; Zaczek, Anna J

2013-01-01

Amplification of the ESR1 gene, coding for estrogen receptor alpha, was shown to predict responsiveness to tamoxifen, however its prognostic impact in breast cancer patients has not been thoroughly investigated. Other factors that could contribute to responsiveness to tamoxifen treatment are polymorphisms in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study was to assess the prognostic role of ESR1 gene dosage in a consecutive group of breast cancer patients and to correlate this feature with clinico-pathological factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were analyzed in the tamoxifen-treated subgroup of patients. Primary tumor samples from 281 stage I-III consecutive breast cancer patients were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed. Results were correlated with clinico-pathological factors and with disease-free survival (DFS) and overall survival (OS). ESR1 amplification (with a cut-off level of 2.0) was found in 12% of the entire group of breast cancer patients, and in 18% of the ER-negative subgroup. This feature was associated with decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1 PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. ESR1 amplification can occur in ER-negative tumors and may carry poor prognosis. In the tamoxifen-treated subgroup, poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype.

Comparison of genetic variations of the SLCO1B1, SLCO1B3, and SLCO2B1 genes among five ethnic groups.

PubMed

Namgoong, Suhg; Cheong, Hyun Sub; Kim, Ji On; Kim, Lyoung Hyo; Na, Han Sung; Koh, In Song; Chung, Myeon Woo; Shin, Hyoung Doo

2015-11-01

Organic anion-transporting polypeptide (OATP; gene symbol, SLCO) transporters are generally involved in the uptake of multiple drugs and their metabolites at most epithelial barriers. The pattern of single-nucleotide polymorphisms (SNPs) in these transporters may be determinants of interindividual variability in drug disposition and response. The objective of this study was to define the distribution of SNPs of three SLCO genes, SLCO1B1, SLCO1B3, and SLCO2B1, in a Korean population and other ethnic groups. The study was screened using the Illumina GoldenGate assay for genomic DNA from 450 interethnic subjects, including 11 pharmacogenetic core variants and 76 HapMap tagging SNPs. The genotype distribution of the Korean population was similar to East Asian populations, but significantly different from African American and European American cohorts. These interethnic differences will be useful information for prospective studies, including genetic association and pharmacogenetic studies of drug metabolism by SLCO families. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced expression of rat hepatic CYP2B1/2B2 and 2E1 by pyridine: differential induction kinetics and molecular basis of expression.

PubMed

Kim, H; Putt, D; Reddy, S; Hollenberg, P F; Novak, R F

1993-11-01

Expression of the cytochrome P450 (CYP) 2B subfamily in rat and rabbit hepatic tissues after pyridine (PY) treatment has been examined, and the molecular basis for enhanced 2B1/2B2 expression has been determined. P450 expression was monitored using metabolic activity, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses, and the identity of the proteins was confirmed through N-terminus microsequence analysis. PY caused a dose-dependent elevation of hepatic CYP2B1/B2B levels in rats, which ranged from 4- to 22-fold over the dosing regimen of 100 to 400 mg PY/kg/day, for 3 days, respectively. PY at low dose failed to induce CYP2B in rabbit hepatic tissue, suggesting a species-dependent response in 2B expression. Anti-2B1 IgG addition to PY-induced microsomes inhibited benzphetamine N-demethylase activity by only approximately 15%, in sharp contrast to the approximately 73% inhibition observed for phenobarbital-induced microsomes, suggesting the induction of other form(s) of P450 having benzphetamine N-demethylase activity. Northern blot analysis revealed that PY treatment increased 2B1 and 2B2 poly(A)+ RNA levels approximately 69- and approximately 34-fold, respectively, whereas the 2E1 poly(A)+ RNA levels failed to increase. The results of this study show that PY induces CYP2B1/2B2 and that induction is species-dependent and kinetically distinguishable from 2E1 induction. Moreover, 2B1/2B2 induction occurs as a result of elevated mRNA levels associated with either transcriptional activation or mRNA stabilization, and it differs from the mechanism of hepatic 2E1 induction by PY.

Synaptotagmin C2B Domain Regulates Ca2+-triggered Fusion in Vitro

PubMed Central

Gaffaney, Jon D.; Dunning, F. Mark; Wang, Zhao; Hui, Enfu; Chapman, Edwin R.

2008-01-01

Synaptotagmin (syt) 1 is localized to synaptic vesicles, binds Ca2+, and regulates neuronal exocytosis. Syt 1 harbors two Ca2+-binding motifs referred to as C2A and C2B. In this study we examine the function of the isolated C2 domains of Syt 1 using a reconstituted, SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor)-mediated, fusion assay. We report that inclusion of phosphatidylethanolamine into reconstituted SNARE vesicles enabled isolated C2B, but not C2A, to regulate Ca2+-triggered fusion. The isolated C2B domain had a 6-fold lower EC for Ca2+ 50-activated fusion than the intact cytosolic domain of Syt 1 (C2AB). Phosphatidylethanolamine increased both the rate and efficiency of C2AB- and C2B-regulated fusion without affecting their abilities to bind membrane-embedded syntaxin-SNAP-25 (t-SNARE) complexes. At equimolar concentrations, the isolated C2A domain was an effective inhibitor of C2B-, but not C2AB-regulated fusion; hence, C2A has markedly different effects in the fusion assay depending on whether it is tethered to C2B. Finally, scanning alanine mutagenesis of C2AB revealed four distinct groups of mutations within the C2B domain that play roles in the regulation of SNARE-mediated fusion. Surprisingly, substitution of Arg-398 with alanine, which lies on the opposite end of C2B from the Ca2+/membrane-binding loops, decreases C2AB t-SNARE binding and Ca2+-triggered fusion in vitro without affecting Ca2+-triggered interactions with phosphatidylserine or vesicle aggregation. In addition, some mutations uncouple the clamping and stimulatory functions of syt 1, suggesting that these two activities are mediated by distinct structural determinants in C2B. PMID:18784080

Comparison of CYP2C9, CYP2C19, CYP2D6, ABCB1, and SLCO1B1 gene-polymorphism frequency in Russian and Nanai populations

PubMed Central

Sychev, Dmitrij Alekseevitch; Shuev, Grigorij Nikolaevich; Suleymanov, Salavat Shejhovich; Ryzhikova, Kristina Anatol’evna; Mirzaev, Karin Badavievich; Grishina, Elena Anatol’evna; Snalina, Natalia Evgenievna; Sozaeva, Zhannet Alimovna; Grabuzdov, Anton Mikhailovich; Matsneva, Irina Andreevna

2017-01-01

Background The efficiency and safety of drug therapy depends on the peculiarities of functioning of the P450 cytochrome group and transporting proteins. There are significant differences for single-nucleotide polymorphism (SNP) frequency. Materials and methods We studied the peculiarities of P450 cytochrome polymorphisms, SLCO1B1 transporting protein, and P-glycoprotein carriage in healthy volunteers in the Nanai ethnic group living in Russia, and compared them to the carriage of SNPs in the Russian population according to literature data. Results After performing the real-time polymerase chain reactions on the samples from 70 healthy volunteers from the Nanai group, for the CYP2C9*2C430T polymorphism we determined 70 CC-genotype carriers. As for the CYP2C9*3A1075C polymorphism, we found 62 AA-genotype carriers and eight AC-genotype carriers. For the CYP2C19*2G681A polymorphism, we determined 39 GG-genotype carriers and 28 GA-genotype carriers, for the CYP2C19*3G636A polymorphism 58 GG-genotype carriers and 12 GA-genotype carriers, and for the CYP2C19*17C806T polymorphism 67 CC-genotype carriers and three CT-genotype carriers. For the CYP2D6*4G1846A polymorphism, the GG genotype had 68 carriers, and the GA genotype two carriers. For the ABCB1*6C3435T polymorphism, there were 19 CC-genotype carriers and 39 CT-genotype carriers. For the SLCO1B1*5T521C polymorphism, the TT genotype had 41 carriers and the CT genotype 25 carriers. The distribution of genotypes fitted the Hardy–Weinberg equilibrium for all the polymorphisms, except those of CYP2C9*2. There were also significant differences in allele frequencies for some polymorphisms between the Nanais and the Russians. Conclusion In the Nanai population, there are polymorphisms connected with the decrease in safety and efficiency of drug therapy. Studying the ethnic differences might influence the determination of priority in the introduction of pharmacogenetic tests in clinical practice in different regions of

Targeting the disordered C-terminus of PTP1B with an allosteric inhibitor

PubMed Central

Krishnan, Navasona; Koveal, Dorothy; Miller, Daniel H.; Xue, Bin; Akshinthala, Sai Dipikaa; Kragelj, Jaka; Jensen, Malene Ringkjøbing; Gauss, Carla-Maria; Page, Rebecca; Blackledge, Martin; Muthuswamy, Senthil K.; Peti, Wolfgang; Tonks, Nicholas K.

2014-01-01

PTP1B, a validated therapeutic target for diabetes and obesity, plays a critical positive role in HER2 signaling in breast tumorigenesis. Efforts to develop therapeutic inhibitors of PTP1B have been frustrated by the chemical properties of the active site. We defined a novel mechanism of allosteric inhibition that targets the C-terminal, non-catalytic segment of PTP1B. We present the first ensemble structure of PTP1B containing this intrinsically disordered segment, within which we identified a binding site for the small molecule inhibitor, MSI-1436. We demonstrate binding to a second site close to the catalytic domain, with cooperative effects between the two sites locking PTP1B in an inactive state. MSI-1436 antagonized HER2 signaling, inhibited tumorigenesis in xenografts and abrogated metastasis in the NDL2 mouse model of breast cancer, validating inhibition of PTP1B as a therapeutic strategy in breast cancer. This new approach to inhibition of PTP1B emphasizes the potential of disordered segments of proteins as specific binding sites for therapeutic small molecules. PMID:24845231

Method 446.0: In Vitro Determination of Chlorophylls a, b, c + c and Pheopigments in 1 2Marine And Freshwater Algae by Visible Spectrophotometry

EPA Science Inventory

This method provides a procedure for determination of chlorophylls a (chl a), b (chl b), c + c 1 2 (chl c + c ) and pheopigments of chlorophyll a (pheo a) 1 2 found in marine and freshwater phytoplankton. Chlorophyllide a is determined as chl a. Visible wavelength spectrophotomet...

Determination of aflatoxins B1, B2, G1 and G2 in spices using a multifunctional column clean-up.

PubMed

Akiyama, H; Goda, Y; Tanaka, T; Toyoda, M

2001-10-12

A rapid and simple method using a multifunctional column, which contains lipophilic and charged active sites, was developed to analyse aflatoxins B1, B2, G1 and G2 in various spices, such as red pepper and nutmeg. After extraction by acetonitrile:water (9:1) and clean-up using MultiSep #228 column, the aflatoxins and aflatoxin-TFA derivatives are determined using LC with fluorescence detection. Recoveries of each aflatoxin B1, B2, G1 and G2 spiked to red pepper, white pepper, black pepper, nutmeg and tear grass at the level of 10 ng/g were over 80-85% in all instances. The minimum detectable concentration for aflatoxins in red pepper was 0.5 ng/g.

SULT2B1b Sulfotransferase: Induction by Vitamin D Receptor and Reduced Expression in Prostate Cancer

PubMed Central

Seo, Young-Kyo; Mirkheshti, Nooshin; Song, Chung S.; Kim, Soyoung; Dodds, Sherry; Ahn, Soon C.; Christy, Barbara; Mendez-Meza, Rosario; Ittmann, Michael M.; Abboud-Werner, Sherry

2013-01-01

An elevated tumor tissue androgen level, which reactivates androgen receptor in recurrent prostate cancer, arises from the intratumor synthesis of 5α-dihydrotestosterone through use of the precursor steroid dehydroepiandrosterone (DHEA) and is fueled by the steroidogenic enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD1), aldoketoreductase (AKR1C3), and steroid 5-alpha reductase, type 1 (SRD5A1) present in cancer tissue. Sulfotransferase 2B1b (SULT2B1b) (in short, SULT2B) is a prostate-expressed hydroxysteroid SULT that converts cholesterol, oxysterols, and DHEA to 3β-sulfates. DHEA metabolism involving sulfonation by SULT2B can potentially interfere with intraprostate androgen synthesis due to reduction of free DHEA pool and, thus, conversion of DHEA to androstenedione. Here we report that in prostatectomy specimens from treatment-naive patients, SULT2B expression is markedly reduced in malignant tissue (P < .001, Mann-Whitney U test) compared with robust expression in adjacent nonmalignant glands. SULT2B was detected in formalin-fixed specimens by immunohistochemistry on individual sections and tissue array. Immunoblotting of protein lysates of frozen cancer and matched benign tissue confirmed immunohistochemistry results. An in-house–developed rabbit polyclonal antibody against full-length human SULT2B was validated for specificity and used in the analyses. Ligand-activated vitamin D receptor induced the SULT2B1 promoter in vivo in mouse prostate and increased SULT2B mRNA and protein levels in vitro in prostate cancer cells. A vitamin D receptor/retinoid X receptor-α–bound DNA element (with a DR7 motif) mediated induction of the transfected SULT2B1 promoter in calcitriol-treated cells. SULT2B knockdown caused an increased proliferation rate of prostate cancer cells upon stimulation by DHEA. These results suggest that the tumor tissue SULT2B level may partly control prostate cancer growth, and its induction in a therapeutic setting may inhibit disease

MIRK/DYRK1B MEDIATES SURVIVAL DURING THE DIFFERENTIATION OF C2C12 MYOBLASTS 1

PubMed Central

Mercer, Stephen E.; Ewton, Daina Z.; Deng, Xiaobing; Lim, Seunghwan; Mazur, Thomas R.; Friedman, Eileen

2005-01-01

The kinase Mirk/dyrk1B is essential for the differentiation of C2C12 myoblasts. Mirk reinforces the G0/G1 arrest state in which differentiation occurs by directly phosphorylating and stabilizing p27kip1 and destabilizing cyclin D1. We now demonstrate that Mirk is anti-apoptotic in myoblasts. Knockdown of endogenous Mirk by RNA interference activated caspase 3 and decreased myoblast survival by 75%, while transient overexpression of Mirk increased cell survival. Mirk exerts its anti-apoptotic effects during muscle differentiation at least in part through effects on the cell cycle inhibitor and pro-survival molecule p21cip1. Overexpression and RNA interference experiments demonstrated that Mirk phosphorylates p21 within its nuclear localization domain at Ser153 causing a portion of the typically nuclear p21 to localize in the cytoplasm. Phosphomimetic GFP-p21-S153D was pancellular in both cycling C2C12 myoblasts and NIH3T3 cells. Endogenous Mirk in myotubes, and overexpressed Mirk in NIH3T3 cells were able to cause the pancellular localization of wild-type GFP-p21, but not the non-phosphorylatable mutant GFP-p21-S153A. Translocation to the cytoplasm enables p21 to block apoptosis through inhibitory interaction with pro-apoptotic molecules. Phosphomimetic p21-S153D was more effective than wild-type p21 in blocking the activation of caspase 3. Transient expression of p21-S153D also increased myoblast viability in colony forming assays, while the p21-S153A mutant had no effect. This Mirk-dependent change in p21 intracellular localization is a natural part of myoblast differentiation. Endogenous p21 localized exclusively to the nuclei of proliferating myoblasts, but was also found in the cytoplasm of post-mitotic multinucleated myotubes and adult human skeletal myofibers. PMID:15851482

Genetic polymorphisms of genes coding to alcohol-metabolizing enzymes in western Mexicans: association of CYP2E1*c2/CYP2E1*5B allele with cirrhosis and liver function.

PubMed

García-Bañuelos, Jesús; Panduro, Arturo; Gordillo-Bastidas, Daniela; Gordillo-Bastidas, Elizabeth; Muñoz-Valle, José Francisco; Gurrola-Díaz, Carmen M; Sánchez-Enríquez, Sergio; Ruiz-Madrigal, Bertha; Bastidas-Ramírez, Blanca Estela

2012-03-01

Alcoholic cirrhosis constitutes a major public health problem in the world where ADH1B, ALDH2, and CYP2E1 polymorphisms could be playing an important role. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy control individuals (C) and patients with alcoholic cirrhosis (AC) from western Mexico. Ninety C and 41 patients with AC were studied. Genotype and allele frequency were determined through polymerase chain reaction-restriction fragment length polymorphisms. Polymorphic allele distribution in AC was 1.6%ADH1B*2, 0.0%ALDH2*2, and 19.5%CYP2E1*c2; in C: 6.1%ADH1B*2, 0%ALDH2*2, and 10.6%CYP2E1*c2. CYP2E1*c2 polymorphic allele and c1/c2 genotype frequency were significantly higher (p < 0.05 and p < 0.01, respectively) in patients with AC when compared to C. Patients with AC, carrying the CYP2E1*c2 allele, exhibited more decompensated liver functioning evaluated by total bilirubin and prothrombin time, than c1 allele carrying patients (p < 0.05). Cirrhosis severity, assessed by Child's Pugh score and mortality, was higher in patients carrying the c2 allele, although not statistically significant. In this study, CYP2E1*c2 allele was associated with susceptibility to AC; meanwhile, ADH1B*2 and ALDH2*2 alleles were not. CYP2E1*c2 allele was associated with AC severity, which could probably be attributed to the oxidative stress promoted by this polymorphic form. Further studies to clearly establish CYP2E1*c2 clinical relevance in the development of alcohol-induced liver damage and its usefulness as a probable prognostic marker, should be performed. Also, increasing the number of patients and including a control group conformed by alcoholic patients free of liver damage may render more conclusive results. These findings contribute to the understanding of the influence of gene variations in AC development among populations, alcohol metabolism, and pharmacogenetics. Copyright © 2011 by the Research Society on Alcoholism.

Genotype and environment effects on the contents of vitamins B1, B2, B3, and B6 in wheat grain.

PubMed

Shewry, Peter R; Van Schaik, Frank; Ravel, Catherine; Charmet, Gilles; Rakszegi, Mariann; Bedo, Zoltan; Ward, Jane L

2011-10-12

The total contents of thiamine (vitamin B1), riboflavin (B2), and pyridoxine (B6) and the bioavailable forms of niacin (B3) were determined on wholemeal flours of 24 winter wheat varieties grown on four sites (United Kingdom, Poland, France, and Hungary) in 2007 and of two spring varieties grown on the same sites with the exception of Poland. The contents of vitamins B1 (5.53-13.55 μg/g dw), B2 (0.77-1.40 μg/g dw), and B6 (1.27-2.97 μg/g dw) were within the ranges reported previously, while the content of bioavailable vitamin B3 (0.16-1.74 μg/g dw) was about 10-15% of the total contents of vitamin B3 reported in previous studies. Strong correlations were observed between the contents of vitamins B1, B3, and B6, and partitioning of the variance in the contents of these three B vitamins showed that between 48 and 70% was accounted for by the environment. By contrast, the content of vitamin B2 was not correlated with the contents of other B vitamins, and 73% of the variance was ascribed to the error term, which suggests that this trait may be influenced by genotype × environment interactions. Whereas the contents of vitamins B1, B3, and B6 were correlated positively with the mean temperature from heading to harvest (r > 0.8), the content of vitamin B2 was positively correlated with precipitation during the 3 months prior to heading. These results are discussed in relation to the development of new wheat varieties with enhanced health benefits.

Observation of the Hadronic transitions chi(b1,2)(2P)-->omegaUpsilon(1S).

PubMed

Cronin-Hennessy, D; Park, C S; Park, W; Thayer, J B; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Stroynowski, R; Artuso, M; Boulahouache, C; Blusk, S; Dambasuren, E; Dorjkhaidav, O; Mountain, R; Muramatsu, H; Nandakumar, R; Skwarnicki, T; Stone, S; Wang, J C; Mahmood, A H; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Bornheim, A; Lipeles, E; Pappas, S P; Shapiro, A; Sun, W M; Weinstein, A J; Briere, R A; Chen, G P; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Adam, N E; Alexander, J P; Berkelman, K; Boisvert, V; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Galik, R S; Gibbons, L; Gittelman, B; Gray, S W; Hartill, D L; Heltsley, B K; Hsu, L; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Magerkurth, A; Mahlke-Krüger, H; Meyer, T O; Mistry, N B; Patterson, J R; Pedlar, T K; Peterson, D; Pivarski, J; Richichi, S J; Riley, D; Sadoff, A J; Schwarthoff, H; Shepherd, M R; Thayer, J G; Urner, D; Wilksen, T; Warburton, A; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Potlia, V; Stoeck, H; Yelton, J; Eisenstein, B I; Gollin, G D; Karliner, I; Lowrey, N; Plager, C; Sedlack, C; Selen, M; Thaler, J J; Williams, J; Edwards, K W; Besson, D; Gao, K Y; Gong, D T; Kubota, Y; Li, S Z; Poling, R; Scott, A W; Smith, A; Stepaniak, C J; Urheim, J; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ernst, J; Arms, K; Eckhart, E; Gan, K K; Gwon, C; Severini, H; Skubic, P; Dytman, S A; Mueller, J A; Nam, S; Savinov, V; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shibata, E I; Shipsey, I P J; Danko, I

2004-06-04

The CLEO Collaboration has made the first observations of hadronic transitions among bottomonium (bbmacr;) states other than the dipion transitions among Upsilon(nS) states. In our study of Upsilon(3S) decays, we find a significant signal for Upsilon(3S)-->gammaomegaUpsilon(1S) that is consistent with radiative decays Upsilon(3S)-->gammachi(b1,2)(2P), followed by chi(b1,2)(2P)-->omegaUpsilon(1S). The branching ratios we obtain are B[chi(b1)(2P)-->omegaUpsilon(1S)]=(1.63(+0.35+0.16)(-0.31-0.15))% and B[chi(b2)(2P)-->omegaUpsilon(1S)]=(1.10(+0.32+0.11)(-0.28-0.10))%, in which the first error is statistical and the second is systematic.

Synthesis of Substituted 2,3,5,6-tetraarylbenzo(1,2-b:5,4-b')difurans

NASA Technical Reports Server (NTRS)

Abdul-Aziz, Mahmoud; Auping, Judith V.; Meador, Michael A.

1995-01-01

A series of substituted 2,3,5,6-tetraarylbenzo(l,2-b:5,4-b')difurans 1 was synthesized. This synthesis is based upon the photocyclization of 2,5-dibenzoylresorcinol dibenzyl ethers to the corresponding tetrahydrobenzo(1,2-b:5,4-b')difurans. Treatment of the photoproducts with methanesulfonyl chloride in pyridine afforded 1 in overall yields ranging from 30-72%. A number of these compounds have high fluorescence quantum yields (of phi(sub f) = 0.76-0.90), and their fluorescence spectra exhibit large solvatochromic shifts. These compounds may be suitable for use as fluorescent probes.

Symbiotic effects of a lipase-secreting bacterium, Burkholderia arboris SL1B1, and a glycerol-assimilating yeast, Candida cylindracea SL1B2, on triacylglycerol degradation.

PubMed

Matsuoka, Hiroshi; Miura, Atsuto; Hori, Katsutoshi

2009-04-01

Although microbial degradation of oils and fats has been developed for application in wastewater treatment, microbial degraders are not always effective in the field, for example, in grease-traps installed for the treatment of wastewater from restaurants and food industries. Wastewater in grease-traps is usually in a pH range of 5.5 to 6.5 due to hydrolysis of triacylglycerol (TAG). Because many microorganisms commercialized for use in grease-traps cannot grow at pH 6.0, we screened oil-degrading microorganisms from the environment by growing in a medium at pH 6.0 containing canola oil as the sole carbon source. We succeeded in isolating the bacterial strain Burkholderia arboris SL1B1, which secretes lipase and assimilates fatty acids, and the yeast strain Candida cylindracea SL1B2, which assimilates glycerol. The former cannot utilize glycerol as a carbon source while the latter shows only faint lipase activity that cannot support its active growth on TAG. Canola oil was degraded rapidly by a pure culture of SL1B1 at pH 6.0. However, the degradation was markedly enhanced by a mixed culture of SL1B1 and SL1B2, although lipase activity during cultivation was similar between the pure and mixed cultures. This suggests that the reversible reaction proceeds in the direction of hydrolysis of TAG due to consumption of the reaction product, glycerol, by the symbiotic yeast strain. The optimum pH and temperature of lipase secreted by B. arboris SL1B1 were 8.0 and 60 degrees C, respectively. This lipase showed highly thermal stability; the residual activity after incubation at 70 degrees C for 2 h did not decline.

Dlx1&2-Dependent Expression of Zfhx1b (Sip1, Zeb2) Regulates the Fate Switch Between Cortical and Striatal Interneurons

PubMed Central

McKinsey, Gabriel L.; Lindtner, Susan; Trzcinski, Brett; Visel, Axel; Pennacchio, Len A.; Huylebroeck, Danny; Higashi, Yujiro; Rubenstein, John L. R.

2013-01-01

Summary Mammalian pallial (cortical and hippocampal) and striatal interneurons are both generated in the embryonic subpallium, including the medial ganglionic eminence (MGE). Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE, directly downstream of Dlx1&2, to generate cortical interneurons that express Cxcr7, MafB and cMaf. In its absence, Nkx2-1 expression is not repressed, and cells that ordinarily would become cortical interneurons appear to transform towards a subtype of GABAeric striatal interneurons. These results show that Zfhx1b is required to generate cortical interneurons, and suggest a mechanism for the epilepsy observed in humans with Zfhx1b mutations (Mowat-Wilson syndrome). PMID:23312518

29 CFR Appendix B to Subpart C of... - Figures C-1 through C-16

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 9 2013-07-01 2013-07-01 false Figures C-1 through C-16 B Appendix B to Subpart C of Part 1928 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR AGRICULTURE Roll-Over Protective...

Control of HIV-1 by an HLA-B*52:01-C*12:02 Protective Haplotype.

PubMed

Chikata, Takayuki; Murakoshi, Hayato; Koyanagi, Madoka; Honda, Kazutaka; Gatanaga, Hiroyuki; Oka, Shinichi; Takiguchi, Masafumi

2017-12-12

HLA-B*52:01-C*12:02, which is found in approximately 20% of all Japanese persons, is well known to be associated with ulcerative colitis and Takayasu arteritis. This haplotype is also known to be protective in individuals infected with human immunodeficiency virus (HIV) type 1. Recent studies showed that HLA-B*52:01-restricted HIV-1-specific T cells suppress HIV-1 and that HLA-C*12:02 together with KIR2DL2 play an important role in natural killer cell-mediated control of HIV-1. However, the role of HLA-C*12:02-restricted cytotoxic T lymphocytes (CTLs) in suppressing HIV-1 replication remains unknown. In the present study, we demonstrated that HLA-C*12:02-restricted CTLs specific for 2 immunodominant epitopes, Pol IY11 and Nef MY9, contributed to the suppression of HIV-1 replication in HIV-1-infected individuals. Further analysis demonstrated that these 2 HLA-C*12:02-restricted CTLs together with 4 HLA-B*52:01-restricted ones effectively suppressed HIV-1 in individuals with the HLA-B*52:01-C*12:02 haplotype. Thus, both HLA-C*12:02 and HLA-B*52:01 alleles contribute to HIV-1 suppression via both HIV-1-specific CTLs and natural killer cells in individuals with this haplotype. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Structure determination of two structural analogs, named 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16F2N4S) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16ClFN4S) by synchrotron X-ray powder diffraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gündoğdu, Gülsüm; Aytaç, Sevim Peri; Müller, Melanie

Two novel compounds, 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C 23H 16F 2N 4S) (1) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C 23H 16ClFN 4S) (2), have been designed and synthesized as cytotoxic agents. The compounds were characterized by infrared, proton nuclear magnetic resonance, mass spectral data, elemental analysis and X-ray powder diffraction. The present study comprises spectral data and crystal structures of these novel compounds determined from synchrotron X-ray powder diffraction data. The structure solutions were obtained by simulated annealing. The final structures were achieved by Rietveld refinement using soft restraints for all bond lengths, bond angles, and planar groups. Both compounds crystallize in space groupmore » $$P\\bar 1$$,Z= 2, with the unit-cell parametersa= 6.37433(9),b= 11.3641(2),c= 14.09115(19) Å,α= 80.1740(8)°,β= 85.1164(8)°,γ= 80.9831(10)°,V= 991.55(3) Å 3of compound (1) anda= 6.53736(6),b= 11.55725(15),c= 14.01373(13) Å,α= 80.3323(7)°,β= 84.8939(6)°,γ= 79.3954(8)°,V= 1024.08(2) Å 3of compound (2). Structural analyses reveal that the title compounds are isostructural.« less

75 FR 79988 - Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, and EC130 B4 Helicopters

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Absence of B1-B2 structural transition in lithium halides under hydrostatic pressure

NASA Astrophysics Data System (ADS)

de Coss, Romeo; Murrieta, Gabriel

2005-03-01

We have investigated the B1-B2 structural transition in LiF, LiCl, LiBr, and LiI under hydrostatic pressure by means of first-principles total-energy calculations using the Full- Potential LAPW method. In order to analyze the gradient effects, we have performed calculations using the local density approximation (LDA) and the generalized gradient approximation (GGA), for the exchange and correlation potential. In agreement with the experimental observations, we find that even for pressures higher than 100 GPa, the Li halides do not present the B1-B2 structural transition. In order to understand this behavior, we have calculated the distribution of the electron densities. From the analysis of the distribution of electron densities for the Li halides in the B1 and B2 phases, we find that for this group of ionic compounds the B1 phase have a distribution of electron densities more homogeneous than in the B2 phase, preventing the B1-B2 structural transition. This work was partially supported by Consejo Nacional de Ciencia y Tecnolog'ia (CONACYT, M'exico) under Grant No. 43830-F.

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[Effect of vitamins B1, B2, B6, folic acid and vitamin C on the motor activity of chicken's intestines in chronic experiments and in vitro].

PubMed

Nagórna-Stasiak, B; Wawrzeńska, M

1987-01-01

The studies were carried out on 33 chickens of the broiler breed in chronic experiments and in vitro. In the chronic experiments the motility of the jejunum under the influence of vitamins of group B and vitamine C was recorded in 8 chickens. The vitamins were used at concentrations from 10 mg/l to 2.5 x 10(3) mg/l. In the experiments in vitro, the motility of the isolated segment of the jejunum was recorded by the method of Magnus. In this part of experiments the chickens were divided into 3 groups, of which group I (15 chickens) were fed with DKA finischer mixture, group II (5 hens) received, besides the mixture, per os 200 mg of vitamin C for 2 weeks, group III (5 hens) received the mixture and for 2 weeks intraperitoneally 200 mg of vitamin C. The effect of vitamins of group B in vitro was determined in chickens of group I, whereas that of vitamin C in chickens of group I, II and III. At the same time the level of vitamin C in the wall of the jejunum was determined by the method of Roe-Kuenther. It was shown that vitamin B2 and folic acid caused stimulation of intestine motility in the chickens, while vitamin B1, B6 and C decreased the motoric activity. Increased level of vitamin C in the intestinal wall resulted in increased intestine sensitivity. Chicken intestines sensitivity to vitamins was 10 times stronger to vitamins than that of the intestines of rabbits.

1H, 15N and 13C NMR Assignments of Mouse Methionine Sulfoxide Reductase B2

PubMed Central

Breivik, Åshild S.; Aachmann, Finn L.; Sal, Lena S.; Kim, Hwa-Young; Del Conte, Rebecca; Gladyshev, Vadim N.; Dikiy, Alexander

2011-01-01

A recombinant mouse methionine-r-sulfoxide reductase 2 (MsrB2ΔS) isotopically labeled with 15N and 15N/13C was generated. We report here the 1H, 15N and 13C NMR assignments of the reduced form of this protein. PMID:19636904

Selective increases in serotonin 5-HT1B/1D and 5-HT2A/2C binding sites in adult rat basal ganglia following lesions of serotonergic neurons.

PubMed

Compan, V; Segu, L; Buhot, M C; Daszuta, A

1998-05-18

Quantitative autoradiography was used to examine possible adaptive changes in serotonin 5-HT1B/1D and 5-HT2A/2C receptor binding sites in adult rat basal ganglia, after partial or severe lesions of serotonergic neurons produced by intraraphe injections of variable amounts of 5,7-dihydroxytryptamine. In controls, the 5-HT1B/1D sites labeled with S-CM-G[125I]TNH2 were evenly distributed in the core and the shell of the nucleus accumbens. The density of 5-HT1B/1D sites was higher in the ventral than dorsal part of the striatum and no regional differences were detected along the rostrocaudal axis of the structure. The 5-HT2A/2C sites labeled with [125I]DOI were preferentially distributed in the mediodorsal striatum and higher densities were detected in the shell than core of the nucleus accumbens. Following 5,7-dihydroxytryptamine injections, there were no changes in binding of either receptor subtype after partial lesions entailing 80-90% 5-HT depletions. After severe 5-HT depletions (over 95%), large increases in 5-HT1B/1D binding were observed in the substantia nigra (78%), but no changes took place in the globus pallidus. Increases in 5-HT1B/1D binding were also detected in the shell of the nucleus accumbens (27%). Similar sized increases in 5-HT2A/2C binding (22%) were restricted to the medial striatum. The present results suggest a preferential association between 5-HT1B/1D receptors and the striatonigral neurons containing substance P, as indicated by the striatal distribution of these receptors and their selective increases in the substantia nigra after severe 5-HT deprivation. We recently proposed a similar relationship between the 5-HT4 receptors and the striatopallidal neurons containing met-enkephalin. Moreover, the increases in 5-HT1B/1D binding in the substantia nigra and in the shell of the nucleus accumbens reinforce the view of an implication of this receptor subtype in motor functions. In contrast, the prominent increases in 5-HT2A/2C binding after

Synthesis, properties, crystal structures, and semiconductor characteristics of naphtho[1,2-b:5,6-b']dithiophene and -diselenophene derivatives.

PubMed

Shinamura, Shoji; Miyazaki, Eigo; Takimiya, Kazuo

2010-02-19

In this paper we present the synthesis, structures, characterization, and applications to field-effect transistors (FETs) of naphtho[1,2-b:5,6-b']dithiophene (NDT) and -diselenophene (NDS) derivatives. Treatment of 1,5-dichloro-2,6-diethynylnaphthalenes, easily derived from commercially available 2,6-dihydroxynaphthalene, with sodium chalcogenide afforded a straightforward access to NDTs and NDSs including the parent and dioctyl and diphenyl derivatives. Physicochemical evaluations of NDT and NDS derivatives showed that these heteroarenes have a similar electronic structure with isomeric [1]benzothieno[2,3-b][1]benzothiophene (BTBT) and [1]benzoselenopheneno[2,3-b][1]benzoselenophene (BSBS) derivatives, respectively. Although attempts to fabricate solution-processed field-effect transistors (FETs) with soluble dioctyl-NDT (C(8)-NDT) and -NDS (C(8)-NDS) failed, diphenyl derivatives (DPh-NDT and DPh-NDS) afforded vapor-processed FETs showing field-effect mobility as high as 0.7 cm(2) V(-1) s(-1). These results indicated that NDT and NDS are new potential heteroarene core structures for organic semiconducting materials.

B1 to B2 structural phase transition in LiF under pressure

NASA Astrophysics Data System (ADS)

Jain, Aayushi; Dixit, R. C.

2018-05-01

In the last few decades the alkali halides emerged as crystals with useful applications and their high-pressure behaviour is the most intensively studied subject in high-pressure physics/chemistry, material science, and geosciences. Most alkali halides follow the B1 (NaCl-type)→B2 (CsCl-type) phase-transition route under pressure. In the present paper, we have investigated the characteristics of structural phase transition that occurred in Lithium Florid compound under high pressure. The transition pressure of B1-B2 was calculated using an effective interionic interaction potential (EIOP). The changes of the characteristics of crystals like, Gibbs free energy, cohesive energy, volume collapse, and lattice constant are calculated for the B1 and B2 structures. These data were compared with the available experimental and theoretical data.

Antitumour effects of PLC-gamma1-(SH2)2-TAT fusion proteins on EGFR/c-erbB-2-positive breast cancer cells.

PubMed

Katterle, Y; Brandt, B H; Dowdy, S F; Niggemann, B; Zänker, K S; Dittmar, T

2004-01-12

Due to its pivotal role in the growth factor-mediated tumour cell migration, the adaptor protein phospholipase C-gamma1 (PLC-gamma1) is an appropriate target to block ultimately the spreading of EGFR/c-erbB-2-positive tumour cells, thereby minimising metastasis formation. Here, we present an approach to block PLC-gamma1 activity by using protein-based PLC-gamma1 inhibitors consisting of PLC-gamma1 SH2 domains, which were fused to the TAT-transduction domain to ensure a high protein transduction efficiency. Two proteins were generated containing one PLC-gamma1-SH2-domain (PS1-TAT) or two PLC-gamma1-SH2 domains (PS2-TAT). PS2-TAT treatment of the EGFR/c-erbB-2-positive cell line MDA-HER2 resulted in a reduction of the EGF-mediated PLC-gamma1 tyrosine phosphorylation of about 30%, concomitant with a complete abrogation of the EGF-driven calcium influx. In addition to this, long-term PS2-TAT treatment both reduces the EGF-mediated migration of about 75% combined with a markedly decreased time locomotion of single MDA-HER2 cells as well as decreases the proliferation of MDA-HER2 cells by about 50%. Due to its antitumoral capacity on EGFR/c-erbB-2-positive breast cancer cells, we conclude from our results that the protein-based PLC-gamma1 inhibitor PS2-TAT may be a means for novel adjuvant antitumour strategies to minimise metastasis formation because of the blockade of cell migration and proliferation.

Hexavalent Chromium Cr(VI) Up-Regulates COX-2 Expression through an NFκB/c-Jun/AP-1–Dependent Pathway

PubMed Central

Zuo, Zhenghong; Cai, Tongjian; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui

2012-01-01

Background: Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation. However, the molecular mechanisms by which Cr(VI) causes cancers are not well understood. Objectives: We evaluated cyclooxygenase-2 (COX-2) expression and the signaling pathway leading to this induction due to Cr(VI) exposure in cultured cells. Methods: We used the luciferase reporter assay and Western blotting to determine COX-2 induction by Cr(VI). We used dominant negative mutant, genetic knockout, gene knockdown, and chromatin immunoprecipitation approaches to elucidate the signaling pathway leading to COX-2 induction. Results: We found that Cr(VI) exposure induced COX-2 expression in both normal human bronchial epithelial cells and mouse embryonic fibroblasts in a concentration- and time-dependent manner. Deletion of IKKβ [inhibitor of transcription factor NFκB (IκB) kinase β; an upstream kinase responsible for nuclear factor κB (NFκB) activation] or overexpression of TAM67 (a dominant-negative mutant of c-Jun) dramatically inhibited the COX-2 induction due to Cr(VI), suggesting that both NFκB and c-Jun/AP-1 pathways were required for Cr(VI)-induced COX-2 expression. Our results show that p65 and c-Jun are two major components involved in NFκB and AP-1 activation, respectively. Moreover, our studies suggest crosstalk between NFκB and c-Jun/AP-1 pathways in cellular response to Cr(VI) exposure for COX-2 induction. Conclusion: We demonstrate for the first time that Cr(VI) is able to induce COX-2 expression via an NFκB/c-Jun/AP-1–dependent pathway. Our results provide novel insight into the molecular mechanisms linking Cr(VI) exposure to lung inflammation and carcinogenesis. PMID:22472290

Phase stability, crystal structure and magnetism in (U1-xNbx)2 Ni21B6 and (UyNb1-y)3Ni20B6

NASA Astrophysics Data System (ADS)

Provino, Alessia; Bhattacharya, Amitava; Dhar, Sudesh K.; Pani, Marcella; Gatti, Flavio; Paudyal, Durga; Manfrinetti, Pietro

Ternary phases with composition T2M21X6 and T3M20X6 (T = transition metal; M = 3 d metal; X = B, C, P) are reported to crystallize with the W2Cr21C6-type and Mg3Ni20B6-type, respectively (ternary ordered derivatives of the cubic Cr23C6-type, cF116). They attract interest due to their refractory, mechanical, and peculiar magnetic properties. Literature data on these compounds only concern apparently stoichiometric 2:21:6 and 3:20:6 phases. Often only nominal composition has been reported, with few structural refinements and no measurements of physical properties. Lack of detailed stoichiometry and crystallographic data does not allow sufficient understanding of the crystal chemistry and properties of these compounds. We studied stability, crystal structure and magnetism of (U1-xNbx)2 Ni21B6 and (UyNb1-y)3Ni20B6; stable phases are U2Ni21B6 and Nb3Ni20B6, as also confirmed by theoretical calculations. The two pristine compounds solubilize Nb and U, respectively, up to a given extent. The substitution of U by Nb leads to a structural change from the W2Cr21C6- to the Mg3Ni20B6-type. While U2Ni21B6 is a Pauli paramagnet (itinerant non-magnetic state of U-5 f electrons), in agreement with literature, magnetization data for (UyNb1-y)3 Ni20B6 show itinerant ferromagnetism with TC >300 K.

Biophysical Analysis of Anopheles gambiae Leucine-Rich Repeat Proteins APL1A1, APL1B and APL1C and Their Interaction with LRIM1

DOE PAGES

Williams, Marni; Summers, Brady J.; Baxter, Richard H. G.; ...

2015-03-16

Natural infection of Anopheles gambiae by malaria-causing Plasmodium parasites is significantly influenced by the APL1 genetic locus. The locus contains three closely related leucine-rich repeat (LRR) genes, APL1A, APL1B and APL1C. Multiple studies have reported the participation of APL1A—C in the immune response of A. gambiae to invasion by both rodent and human Plasmodium isolates. APL1C forms a heterodimer with the related LRR protein LRIM1 via a C-terminal coiled-coil domain that is also present in APL1A and APL1B. The LRIM1/APL1C heterodimer protects A. gambiae from infection by binding the complement-like protein TEP1 to form a stable and active immune complex.more » We report solution x-ray scatting data for the LRIM1/APL1C heterodimer, the oligomeric state of LRIM1/APL1 LRR domains in solution and the crystal structure of the APL1B LRR domain. The LRIM1/APL1C heterodimeric complex has a flexible and extended structure in solution. In contrast to the APL1A, APL1C and LRIM1 LRR domains, the APL1B LRR domain is a homodimer. The crystal structure of APL1B-LRR shows that the homodimer is formed by an N-terminal helix that complements for the absence of an N-terminal capping motif in APL1B, which is a unique distinction within the LRIM1/APL1 protein family. Full-length APL1A 1 and APL1B form a stable complex with LRIM1. Our results support a model in which APL1A 1, APL1B and APL1C can all form an extended, flexible heterodimer with LRIM1, providing a repertoire of functional innate immune complexes to protect A. gambiae from a diverse array of pathogens.« less

Biophysical Analysis of Anopheles gambiae Leucine-Rich Repeat Proteins APL1A1, APL1B and APL1C and Their Interaction with LRIM1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Marni; Summers, Brady J.; Baxter, Richard H. G.

Natural infection of Anopheles gambiae by malaria-causing Plasmodium parasites is significantly influenced by the APL1 genetic locus. The locus contains three closely related leucine-rich repeat (LRR) genes, APL1A, APL1B and APL1C. Multiple studies have reported the participation of APL1A—C in the immune response of A. gambiae to invasion by both rodent and human Plasmodium isolates. APL1C forms a heterodimer with the related LRR protein LRIM1 via a C-terminal coiled-coil domain that is also present in APL1A and APL1B. The LRIM1/APL1C heterodimer protects A. gambiae from infection by binding the complement-like protein TEP1 to form a stable and active immune complex.more » We report solution x-ray scatting data for the LRIM1/APL1C heterodimer, the oligomeric state of LRIM1/APL1 LRR domains in solution and the crystal structure of the APL1B LRR domain. The LRIM1/APL1C heterodimeric complex has a flexible and extended structure in solution. In contrast to the APL1A, APL1C and LRIM1 LRR domains, the APL1B LRR domain is a homodimer. The crystal structure of APL1B-LRR shows that the homodimer is formed by an N-terminal helix that complements for the absence of an N-terminal capping motif in APL1B, which is a unique distinction within the LRIM1/APL1 protein family. Full-length APL1A 1 and APL1B form a stable complex with LRIM1. Our results support a model in which APL1A 1, APL1B and APL1C can all form an extended, flexible heterodimer with LRIM1, providing a repertoire of functional innate immune complexes to protect A. gambiae from a diverse array of pathogens.« less

Production of infectious chimeric hepatitis C virus genotype 2b harboring minimal regions of JFH-1.

PubMed

Murayama, Asako; Kato, Takanobu; Akazawa, Daisuke; Sugiyama, Nao; Date, Tomoko; Masaki, Takahiro; Nakamoto, Shingo; Tanaka, Yasuhito; Mizokami, Masashi; Yokosuka, Osamu; Nomoto, Akio; Wakita, Takaji

2012-02-01

To establish a cell culture system for chimeric hepatitis C virus (HCV) genotype 2b, we prepared a chimeric construct harboring the 5' untranslated region (UTR) to the E2 region of the MA strain (genotype 2b) and the region of p7 to the 3' UTR of the JFH-1 strain (genotype 2a). This chimeric RNA (MA/JFH-1.1) replicated and produced infectious virus in Huh7.5.1 cells. Replacement of the 5' UTR of this chimera with that from JFH-1 (MA/JFH-1.2) enhanced virus production, but infectivity remained low. In a long-term follow-up study, we identified a cell culture-adaptive mutation in the core region (R167G) and found that it enhanced virus assembly. We previously reported that the NS3 helicase (N3H) and the region of NS5B to 3' X (N5BX) of JFH-1 enabled replication of the J6CF strain (genotype 2a), which could not replicate in cells. To reduce JFH-1 content in MA/JFH-1.2, we produced a chimeric viral genome for MA harboring the N3H and N5BX regions of JFH-1, combined with a JFH-1 5' UTR replacement and the R167G mutation (MA/N3H+N5BX-JFH1/R167G). This chimeric RNA replicated efficiently, but virus production was low. After the introduction of four additional cell culture-adaptive mutations, MA/N3H+N5BX-JFH1/5am produced infectious virus efficiently. Using this chimeric virus harboring minimal regions of JFH-1, we analyzed interferon sensitivity and found that this chimeric virus was more sensitive to interferon than JFH-1 and another chimeric virus containing more regions from JFH-1 (MA/JFH-1.2/R167G). In conclusion, we established an HCV genotype 2b cell culture system using a chimeric genome harboring minimal regions of JFH-1. This cell culture system may be useful for characterizing genotype 2b viruses and developing antiviral strategies.

CD22 Promotes B-1b Cell Responses to T Cell-Independent Type 2 Antigens.

PubMed

Haas, Karen M; Johnson, Kristen L; Phipps, James P; Do, Cardinal

2018-03-01

CD22 (Siglec-2) is a critical regulator of B cell activation and survival. CD22 -/- mice generate significantly impaired Ab responses to T cell-independent type 2 (TI-2) Ags, including haptenated Ficoll and pneumococcal polysaccharides, Ags that elicit poor T cell help and activate BCR signaling via multivalent epitope crosslinking. This has been proposed to be due to impaired marginal zone (MZ) B cell development/maintenance in CD22 -/- mice. However, mice expressing a mutant form of CD22 unable to bind sialic acid ligands generated normal TI-2 Ab responses, despite significantly reduced MZ B cells. Moreover, mice treated with CD22 ligand-binding blocking mAbs, which deplete MZ B cells, had little effect on TI-2 Ab responses. We therefore investigated the effects of CD22 deficiency on B-1b cells, an innate-like B cell population that plays a key role in TI-2 Ab responses. B-1b cells from CD22 -/- mice had impaired BCR-induced proliferation and significantly increased intracellular Ca 2+ concentration responses following BCR crosslinking. Ag-specific B-1b cell expansion and plasmablast differentiation following TI-2 Ag immunization was significantly impaired in CD22 -/- mice, consistent with reduced TI-2 Ab responses. We generated CD22 -/- mice with reduced CD19 levels (CD22 -/- CD19 +/- ) to test the hypothesis that augmented B-1b cell BCR signaling in CD22 -/- mice contributes to impaired TI-2 Ab responses. BCR-induced proliferation and intracellular Ca 2+ concentration responses were normalized in CD22 -/- CD19 +/- B-1b cells. Consistent with this, TI-2 Ag-specific B-1b cell expansion, plasmablast differentiation, survival, and Ab responses were rescued in CD22 -/- CD19 +/- mice. Thus, CD22 plays a critical role in regulating TI-2 Ab responses through regulating B-1b cell signaling thresholds. Copyright © 2018 by The American Association of Immunologists, Inc.

Inelastic scattering matrix elements for the nonadiabatic collision B(2P1/2)+H2(1Sigmag+,j)<-->B(2P3/2)+H2(1Sigmag+,j').

PubMed

Weeks, David E; Niday, Thomas A; Yang, Sang H

2006-10-28

Inelastic scattering matrix elements for the nonadiabatic collision B(2P1/2)+H2(1Sigmag+,j)<-->B(2P3/2)+H2(1Sigmag+,j') are calculated using the time dependent channel packet method (CPM). The calculation employs 1 2A', 2 2A', and 1 2A" adiabatic electronic potential energy surfaces determined by numerical computation at the multireference configuration-interaction level [M. H. Alexander, J. Chem. Phys. 99, 6041 (1993)]. The 1 2A' and 2 2A', adiabatic electronic potential energy surfaces are transformed to yield diabatic electronic potential energy surfaces that, when combined with the total B+H2 rotational kinetic energy, yield a set of effective potential energy surfaces [M. H. Alexander et al., J. Chem. Phys. 103, 7956 (1995)]. Within the framework of the CPM, the number of effective potential energy surfaces used for the scattering matrix calculation is then determined by the size of the angular momentum basis used as a representation. Twenty basis vectors are employed for these calculations, and the corresponding effective potential energy surfaces are identified in the asymptotic limit by the H2 rotor quantum numbers j=0, 2, 4, 6 and B electronic states 2Pja, ja=1/2, 3/2. Scattering matrix elements are obtained from the Fourier transform of the correlation function between channel packets evolving in time on these effective potential energy surfaces. For these calculations the H2 bond length is constrained to a constant value of req=1.402 a.u. and state to state scattering matrix elements corresponding to a total angular momentum of J=1/2 are discussed for j=0<-->j'=0,2,4 and 2P1/2<-->2P1/2, 2P3/2 over a range of total energy between 0.0 and 0.01 a.u.

Influence of nanosized amorphous silica on assimilation of vitamins B1, B2 and B6 in rats.

PubMed

Gmoshinsky, I V; Vrzhesinskaya, O A; Shumakova, A A; Shipelin, V A; Kodentsova, V M; Khotimchenko, S A

2016-01-01

Amorphous silica (SiO2) in the form of nanoparticles (NPs) is widely used as a food additive E551 in many enriched foods and food supplements. The aim of this study was to evaluate the effect of oral administration of SiO2 NPs on assimilation and metabolism of vitamins B1, B2 and B6 in laboratory rats. Amorphous SiO2 «Orisil-300 ®» was used with the size of the primary NPs 20-60 nm according to the electronic, atomic force microscopy and dynamic light scattering. The experiment was conducted on 8 groups of growing male Wistar rats (with initial body weight 70-80g) number, respectively, 7, 7, 10, 10, 12, 12, 14 and 16 animals. Animals of the 1st, 3rd, 4th and 5th groups received through­out the experiment balanced semi-synthetic diet. Animals of the 2nd group received a diet depleted of vitamins B1, B2 and B6 until day 21; animals of the 6th, 7th and 8th groups -the same diet from the 1st to the 21th day, and then, before the closure of the experiment, the diet provided with the indicated B vitamins at 100% of normal level. From day 22 of experiment and until the end at day 29 the animals of the 3rd and 6th groups received deionized water (placebo) through intragastric gavage; rat of the 4th and 7th groups -aqueous suspension of SiO2 dose of 1 mg/kg body weight /day, and the 5th and 8th group -100 mg/kg/day. Urinary excretion of thiamine, riboflavin, 4-pyridoxilic acid and liver and brain content of vitamins B1 and B2 (after acid and enzyme hydrolysis) were deter­mined by fluorimetric methods. It was found that rats in group 2 lagged in weight gain at day 21 significantly compared to group 1, and developed a marked deficiency of vitamins B1, B2 and B6 according to studied safety parameters. In groups from 6 to 8 at day 29 par­tial recovery was achieved in vitamin status. Administration of SiO2 to animal of groups 4 and 5, with normal consumption of B vitamins, had no significant effect on any param­eters of vitamin status in comparison to group 3. However

MEASUREMENT OF sin 2φ1 IN b → c And b → s DECAYS AT Belle

NASA Astrophysics Data System (ADS)

Hastings, Nicholas C.

Measurements of time-dependent CP asymmetries in B0 → J/ψK0, φK0, K+K- KS, η' KS, f0 (980) KS and ωKS decays based on 386 × 106 Bbar{B} pairs collected by the Belle detector are presented. With this data sample, the J/ψK0 mode provides a precision measurement of sin2 φ1. The other modes, which proceed via b → s penguin (loop) diagrams are sensitive to new physics phases which may appear within the loop. Differing sin2 φ1 measurements between J/ψK0 and the b → s penguin modes could be a signature of such phases.

Laboratory diagnosis of von Willebrand disease type 1/2E (2A subtype IIE), type 1 Vicenza and mild type 1 caused by mutations in the D3, D4, B1-B3 and C1-C2 domains of the von Willebrand factor gene. Role of von Willebrand factor multimers and the von Willebrand factor propeptide/antigen ratio.

PubMed

Gadisseur, Alain; Berneman, Zwi; Schroyens, Wilfried; Michiels, Jan Jacques

2009-01-01

Autosomal dominant von Willebrand disease (VWD) type 1/2E is a quantitative/qualitative defect in the von Willebrand factor (VWF) caused by heterozygous cysteine and non-cysteine mutations in the D3 domain of the VWF gene and results in a secretion-multimerization-clearance defect in mutant VWF with the loss of large VWF multimers not due to proteolysis. The multimers of patients with dominant VWD type 1/2E due to mutations in the D3 domain show an aberrant triplet structure with lack of outer bands but with pronounced inner bands of the triplet structure combined with a relative decrease in large multimers reflecting heterozygosity for multimerization defects. There is a good response to desmopressin (DDAVP) followed by rapid clearance of VWF:antigen (Ag), factor VIII coagulant activity (FVIII:C) and VWF:ristocetin cofactor activity (RCo) as the main cause of VWD type 1 or 2 with typical 2E multimeric pattern (VWD type 1/2E). Cysteine mutations in the D3 domains (C1130, C1149 and C1190) show pronounced features of VWD 1/2E with the relative loss of large and relative increase in small VWF multimers with abnormal triplet structure in heterozygotes. Such abnormalities are less pronounced in patients with a milder form of VWD type 1 due to non-cysteine mutations W1144G, T1156M and W1120S in the D3 domain. VWD type 1 Vicenza is caused by the R1205H mutation in the D3 domain and characterized by equally low levels of FVIII:C, VWF:Ag and VWF:RCo. The response to DDAVP in VWD Vicenza is good for FVIII:C, VWF:Ag and VWF:RCo, which is followed by a rapid clearance in less than a few hours of FVIII:C and VWF parameters. The ratios for FVIII:C/VWF:Ag, VWF:RCo/Ag and VWF:CB/Ag remain normal before and after DDAVP indicating that VWD Vicenza clearly differs from VWD type 1, 1/2E and 2M. A new set of missense mutations in D4, B1-B3 and C1-C2 domains has been discovered as the cause of a mild VWD type 1 secretion defect with normal VWF multimers or smeary VWF multimeric pattern

75 FR 80293 - Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-22

... Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model AS355 E, F, F1, F2... identified in the Applicability section, Table 1, of the AD. As published, two part numbers shown in Table 1... corrected to read as follows: Table 1 Component Part No. (P/N) Serial No. (S/N) Main rotor servo-control...

Word Frequency Analysis. MOS: 95B. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

uU N D 1 A C P A C K1 ? G .I A 2 1 A’J Kt I S , 1 K L S 1 BaRp IF S I ~t2iIAED 5. 1.T’ 6 BATTERY 9!j 2 BECAUSE 17 67EI 2 BEHIND 13 IL 2 RE l1󈧱 3 b1...T S :t cTt lIION 5 U It :,4t 5 F L 1%T5 &:, JC.L ME NT 5 ESTIMS4EO 5 F -4 U0 . F- "CL5 UJ 7 "S 5 F-.[377 7i (, ID󈧏CAlN5.C1DEINTS 5 I’%SER71NkG .0

Effects of configurational disorder on the elastic properties of icosahedral boron-rich alloys based on B6O, B13C2, and B4C, and their mixing thermodynamics

NASA Astrophysics Data System (ADS)

Ektarawong, A.; Simak, S. I.; Hultman, L.; Birch, J.; Tasnádi, F.; Wang, F.; Alling, B.

2016-04-01

The elastic properties of alloys between boron suboxide (B6O) and boron carbide (B13C2), denoted by (B6O)1-x(B13C2)x, as well as boron carbide with variable carbon content, ranging from B13C2 to B4C are calculated from first-principles. Furthermore, the mixing thermodynamics of (B6O)1-x(B13C2)x is studied. A superatom-special quasirandom structure approach is used for modeling different atomic configurations, in which effects of configurational disorder between the carbide and suboxide structural units, as well as between boron and carbon atoms within the units, are taken into account. Elastic properties calculations demonstrate that configurational disorder in B13C2, where a part of the C atoms in the CBC chains substitute for B atoms in the B12 icosahedra, drastically increase the Young's and shear modulus, as compared to an atomically ordered state, B12(CBC). These calculated elastic moduli of the disordered state are in excellent agreement with experiments. Configurational disorder between boron and carbon can also explain the experimentally observed almost constant elastic moduli of boron carbide as the carbon content is changed from B4C to B13C2. The elastic moduli of the (B6O)1-x(B13C2)x system are also practically unchanged with composition if boron-carbon disorder is taken into account. By investigating the mixing thermodynamics of the alloys, in which the Gibbs free energy is determined within the mean-field approximation for the configurational entropy, we outline the pseudo-binary phase diagram of (B6O)1-x(B13C2)x. The phase diagram reveals the existence of a miscibility gap at all temperatures up to the melting point. Also, the coexistence of B6O-rich as well as ordered or disordered B13C2-rich domains in the material prepared through equilibrium routes is predicted.

26 CFR 1.367(b)-2 - Definitions and special rules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (QBU) (B1) in France, whose functional currency is the euro. FC2, an unrelated foreign corporation... functional currency of the combined operations of B1 and B2 is the euro. (ii) Result. FC2's acquisition of... currency of the combined operations of B1 and B2 after the exchange is the euro, B2 is deemed to have...

26 CFR 1.367(b)-2 - Definitions and special rules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (QBU) (B1) in France, whose functional currency is the euro. FC2, an unrelated foreign corporation... functional currency of the combined operations of B1 and B2 is the euro. (ii) Result. FC2's acquisition of... currency of the combined operations of B1 and B2 after the exchange is the euro, B2 is deemed to have...

26 CFR 1.367(b)-2 - Definitions and special rules.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (QBU) (B1) in France, whose functional currency is the euro. FC2, an unrelated foreign corporation... functional currency of the combined operations of B1 and B2 is the euro. (ii) Result. FC2's acquisition of... currency of the combined operations of B1 and B2 after the exchange is the euro, B2 is deemed to have...

26 CFR 1.367(b)-2 - Definitions and special rules.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (QBU) (B1) in France, whose functional currency is the euro. FC2, an unrelated foreign corporation... functional currency of the combined operations of B1 and B2 is the euro. (ii) Result. FC2's acquisition of... currency of the combined operations of B1 and B2 after the exchange is the euro, B2 is deemed to have...

26 CFR 1.367(b)-2 - Definitions and special rules.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (QBU) (B1) in France, whose functional currency is the euro. FC2, an unrelated foreign corporation... functional currency of the combined operations of B1 and B2 is the euro. (ii) Result. FC2's acquisition of... currency of the combined operations of B1 and B2 after the exchange is the euro, B2 is deemed to have...

Diversity in peptide recognition by the SH2 domain of SH2B1.

PubMed

McKercher, Marissa A; Guan, Xiaoyang; Tan, Zhongping; Wuttke, Deborah S

2018-02-01

SH2B1 is a multidomain protein that serves as a key adaptor to regulate numerous cellular events, such as insulin, leptin, and growth hormone signaling pathways. Many of these protein-protein interactions are mediated by the SH2 domain of SH2B1, which recognizes ligands containing a phosphorylated tyrosine (pY), including peptides derived from janus kinase 2, insulin receptor, and insulin receptor substrate-1 and -2. Specificity for the SH2 domain of SH2B1 is conferred in these ligands either by a hydrophobic or an acidic side chain at the +3 position C-terminal to the pY. This specificity for chemically disparate species suggests that SH2B1 relies on distinct thermodynamic or structural mechanisms to bind to peptides. Using binding and structural strategies, we have identified unique thermodynamic signatures for each peptide binding mode, and several SH2B1 residues, including K575 and R578, that play distinct roles in peptide binding. The high-resolution structure of the SH2 domain of SH2B1 further reveals conformationally plastic protein loops that may contribute to the ability of the protein to recognize dissimilar ligands. Together, numerous hydrophobic and electrostatic interactions, in addition to backbone conformational flexibility, permit the recognition of diverse peptides by SH2B1. An understanding of this expanded peptide recognition will allow for the identification of novel physiologically relevant SH2B1/peptide interactions, which can contribute to the design of obesity and diabetes pharmaceuticals to target the ligand-binding interface of SH2B1 with high specificity. © 2017 Wiley Periodicals, Inc.

Search for excited B c + states

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Alfonso Albero, A.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Archilli, F.; d'Argent, P.; Arnau Romeu, J.; Artamonov, A.; Artuso, M.; Aslanides, E.; Atzeni, M.; Auriemma, G.; Baalouch, M.; Babuschkin, I.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baker, S.; Balagura, V.; Baldini, W.; Baranov, A.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Baryshnikov, F.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Beiter, A.; Bel, L. J.; Beliy, N.; Bellee, V.; Belloli, N.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Beranek, S.; Berezhnoy, A.; Bernet, R.; Berninghoff, D.; Bertholet, E.; Bertolin, A.; Betancourt, C.; Betti, F.; Bettler, M. O.; van Beuzekom, M.; Bezshyiko, Ia.; Bifani, S.; Billoir, P.; Birnkraut, A.; Bizzeti, A.; Bjørn, M.; Blake, T.; Blanc, F.; Blusk, S.; Bocci, V.; Boettcher, T.; Bondar, A.; Bondar, N.; Bordyuzhin, I.; Borghi, S.; Borisyak, M.; Borsato, M.; Bossu, F.; Boubdir, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Brodzicka, J.; Brundu, D.; Buchanan, E.; Burr, C.; Bursche, A.; Buytaert, J.; Byczynski, W.; Cadeddu, S.; Cai, H.; Calabrese, R.; Calladine, R.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D. H.; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Cattaneo, M.; Cavallero, G.; Cenci, R.; Chamont, D.; Chapman, M. G.; Charles, M.; Charpentier, Ph.; Chatzikonstantinidis, G.; Chefdeville, M.; Chen, S.; Cheung, S. F.; Chitic, S.-G.; Chobanova, V.; Chrzaszcz, M.; Chubykin, A.; Ciambrone, P.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collins, P.; Colombo, T.; Comerma-Montells, A.; Contu, A.; Coombs, G.; Coquereau, S.; Corti, G.; Corvo, M.; Costa Sobral, C. M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Cruz Torres, M.; Currie, R.; D'Ambrosio, C.; Da Cunha Marinho, F.; Da Silva, C. L.; Dall'Occo, E.; Dalseno, J.; Davis, A.; De Aguiar Francisco, O.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Serio, M.; De Simone, P.; Dean, C. T.; Decamp, D.; Del Buono, L.; Dembinski, H.-P.; Demmer, M.; Dendek, A.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Nezza, P.; Dijkstra, H.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Douglas, L.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Durante, P.; Durham, J. M.; Dutta, D.; Dzhelyadin, R.; Dziewiecki, M.; Dziurda, A.; Dzyuba, A.; Easo, S.; Ebert, M.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farley, N.; Farry, S.; Fazzini, D.; Federici, L.; Ferguson, D.; Fernandez, G.; Fernandez Declara, P.; Fernandez Prieto, A.; Ferrari, F.; Ferreira Lopes, L.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fini, R. A.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fleuret, F.; Fontana, M.; Fontanelli, F.; Forty, R.; Franco Lima, V.; Frank, M.; Frei, C.; Fu, J.; Funk, W.; Furfaro, E.; Färber, C.; Gabriel, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garcia Martin, L. M.; García Pardiñas, J.; Garra Tico, J.; Garrido, L.; Garsed, P. J.; Gascon, D.; Gaspar, C.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianì, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gizdov, K.; Gligorov, V. V.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorelov, I. V.; Gotti, C.; Govorkova, E.; Grabowski, J. P.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greim, R.; Griffith, P.; Grillo, L.; Gruber, L.; Gruberg Cazon, B. R.; Grünberg, O.; Gushchin, E.; Guz, Yu.; Gys, T.; Göbel, C.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hamilton, B.; Han, X.; Hancock, T. H.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Hasse, C.; Hatch, M.; He, J.; Hecker, M.; Heinicke, K.; Heister, A.; Hennessy, K.; Henrard, P.; Henry, L.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hopchev, P. H.; Hu, W.; Huang, W.; Huard, Z. C.; Hulsbergen, W.; Humair, T.; Hushchyn, M.; Hutchcroft, D.; Ibis, P.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jalocha, J.; Jans, E.; Jawahery, A.; Jiang, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Karacson, M.; Kariuki, J. M.; Karodia, S.; Kazeev, N.; Kecke, M.; Keizer, F.; Kelsey, M.; Kenzie, M.; Ketel, T.; Khairullin, E.; Khanji, B.; Khurewathanakul, C.; Kirn, T.; Klaver, S.; Klimaszewski, K.; Klimkovich, T.; Koliiev, S.; Kolpin, M.; Kopecna, R.; Koppenburg, P.; Kosmyntseva, A.; Kotriakhova, S.; Kozeiha, M.; Kravchuk, L.; Kreps, M.; Kress, F.; Krokovny, P.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; Leflat, A.; Lefrançois, J.; Lefèvre, R.; Lemaitre, F.; Lemos Cid, E.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, P.-R.; Li, T.; Li, Y.; Li, Z.; Liang, X.; Likhomanenko, T.; Lindner, R.; Lionetto, F.; Lisovskyi, V.; Liu, X.; Loh, D.; Loi, A.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Lucio Martinez, M.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Lyu, X.; Machefert, F.; Maciuc, F.; Macko, V.; Mackowiak, P.; Maddrell-Mander, S.; Maev, O.; Maguire, K.; Maisuzenko, D.; Majewski, M. W.; Malde, S.; Malecki, B.; Malinin, A.; Maltsev, T.; Manca, G.; Mancinelli, G.; Marangotto, D.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marinangeli, M.; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurice, E.; Maurin, B.; Mazurov, A.; McCann, M.; McNab, A.; McNulty, R.; Mead, J. V.; Meadows, B.; Meaux, C.; Meier, F.; Meinert, N.; Melnychuk, D.; Merk, M.; Merli, A.; Michielin, E.; Milanes, D. A.; Millard, E.; Minard, M.-N.; Minzoni, L.; Mitzel, D. S.; Mogini, A.; Molina Rodriguez, J.; Mombächer, T.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morello, M. J.; Morgunova, O.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mulder, M.; Müller, D.; Müller, J.; Müller, K.; Müller, V.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, T. D.; Nguyen-Mau, C.; Nieswand, S.; Niet, R.; Nikitin, N.; Nikodem, T.; Nogay, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Oldeman, R.; Onderwater, C. J. G.; Ossowska, A.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pais, P. R.; Palano, A.; Palutan, M.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parker, W.; Parkes, C.; Passaleva, G.; Pastore, A.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Pereima, D.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petrov, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pietrzyk, G.; Pikies, M.; Pinci, D.; Pisani, F.; Pistone, A.; Piucci, A.; Placinta, V.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poli Lener, M.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Pomery, G. J.; Ponce, S.; Popov, A.; Popov, D.; Poslavskii, S.; Potterat, C.; Price, E.; Prisciandaro, J.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Pullen, H.; Punzi, G.; Qian, W.; Qin, J.; Quagliani, R.; Quintana, B.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Ramos Pernas, M.; Rangel, M. S.; Raniuk, I.; Ratnikov, F.; Raven, G.; Ravonel Salzgeber, M.; Reboud, M.; Redi, F.; Reichert, S.; dos Reis, A. C.; Remon Alepuz, C.; Renaudin, V.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Robbe, P.; Robert, A.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Lopez, J. A.; Rogozhnikov, A.; Roiser, S.; Rollings, A.; Romanovskiy, V.; Romero Vidal, A.; Rotondo, M.; Rudolph, M. S.; Ruf, T.; Ruiz Valls, P.; Ruiz Vidal, J.; Saborido Silva, J. J.; Sadykhov, E.; Sagidova, N.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santimaria, M.; Santovetti, E.; Sarpis, G.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schael, S.; Schellenberg, M.; Schiller, M.; Schindler, H.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schreiner, H. F.; Schubiger, M.; Schune, M. H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sepulveda, E. S.; Sergi, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Siddi, B. G.; Silva Coutinho, R.; Silva de Oliveira, L.; Simi, G.; Simone, S.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, I. T.; Smith, J.; Smith, M.; Soares Lavra, l.; Sokoloff, M. D.; Soler, F. J. P.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefko, P.; Stefkova, S.; Steinkamp, O.; Stemmle, S.; Stenyakin, O.; Stepanova, M.; Stevens, H.; Stone, S.; Storaci, B.; Stracka, S.; Stramaglia, M. E.; Straticiuc, M.; Straumann, U.; Sun, J.; Sun, L.; Swientek, K.; Syropoulos, V.; Szumlak, T.; Szymanski, M.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Tellarini, G.; Teubert, F.; Thomas, E.; van Tilburg, J.; Tilley, M. J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Tourinho Jadallah Aoude, R.; Tournefier, E.; Traill, M.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tully, A.; Tuning, N.; Ukleja, A.; Usachov, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagner, A.; Vagnoni, V.; Valassi, A.; Valat, S.; Valenti, G.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vecchi, S.; van Veghel, M.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Venkateswaran, A.; Verlage, T. A.; Vernet, M.; Vesterinen, M.; Viana Barbosa, J. V.; Vieira, D.; Vieites Diaz, M.; Viemann, H.; Vilasis-Cardona, X.; Vitti, M.; Volkov, V.; Vollhardt, A.; Voneki, B.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Vázquez Sierra, C.; Waldi, R.; Walsh, J.; Wang, J.; Wang, Y.; Ward, D. R.; Wark, H. M.; Watson, N. K.; Websdale, D.; Weiden, A.; Weisser, C.; Whitehead, M.; Wicht, J.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Winn, M.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wyllie, K.; Xie, Y.; Xu, M.; Xu, Q.; Xu, Z.; Xu, Z.; Yang, Z.; Yang, Z.; Yao, Y.; Yin, H.; Yu, J.; Yuan, X.; Yushchenko, O.; Zarebski, K. A.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhelezov, A.; Zheng, Y.; Zhu, X.; Zhukov, V.; Zonneveld, J. B.; Zucchelli, S.

2018-01-01

A search is performed in the invariant mass spectrum of the B c + π+π- system for the excited B c + states B c (21 S 0)+ and B c (23 S 1)+ using a data sample of pp collisions collected by the LHCb experiment at the centre-of-mass energy of √{s}=8 TeV, corresponding to an integrated luminosity of 2 fb-1. No evidence is seen for either state. Upper limits on the ratios of the production cross-sections of the B c (21 S 0)+ and B c (23 S 1)+ states times the branching fractions of B c (21 S 0)+ → B c + π+π- and B c (23 S 1)+ → B c * +π+π- over the production cross-section of the B c + state are given as a function of their masses. They are found to be between 0.02 and 0.14 at 95% confidence level for B c (21 S 0)+ and B c (23 S 1)+ in the mass ranges [6830 , 6890] MeV /c 2 and [6795 , 6890] MeV /c 2, respectively. [Figure not available: see fulltext.

76 FR 2930 - International Product Change-Global Plus 1B and 2B Negotiated Service Agreements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-18

... POSTAL SERVICE International Product Change--Global Plus 1B and 2B Negotiated Service Agreements... the Postal Regulatory Commission to add Global Plus 1B and 2B Negotiated Service Agreements to the... United States Postal Service to Add Global Plus 1B and 2B Negotiated Service Agreements to the...

Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages.

PubMed

Xu, Xiaolong; Guo, Yuhong; Zhao, Jingxia; He, Shasha; Wang, Yan; Lin, Yan; Wang, Ning; Liu, Qingquan

2017-09-01

Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC 50 value of 1.04μM. Results from NPOI further showed that the K on and K off of PUN-PTP1B complex were 3.38e2M -1 s -1 and 4.13e-3s -1 , respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation. Moreover, inhibition of PTP1B by PUN promoted an M2c-like macrophage polarization and enhanced anti-inflammatory cytokines expression, including IL-10 and M-CSF. Based on gene expression profile, we elucidated that PUN treatment significantly up-regulated 275 genes and down-regulated 1059 genes. M1-like macrophage marker genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2 marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfα, Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene encoding HO-1 protein, was preferentially expressed with 16-fold change. Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10 secretion. In addition, phosphorylation of both Akt and STAT3 contributed to PUN-induced HO-1 expression. This study provided new insights into the mechanisms of PUN-mediated anti-inflammatory and anti-oxidant activities and provided new therapeutic strategies for inflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

BPAG1a and b associate with EB1 and EB3 and modulate vesicular transport, Golgi apparatus structure, and cell migration in C2.7 myoblasts.

PubMed

Poliakova, Kseniia; Adebola, Adijat; Leung, Conrad L; Favre, Bertrand; Liem, Ronald K H; Schepens, Isabelle; Borradori, Luca

2014-01-01

BPAG1a and BPAG1b (BPAG1a/b) constitute two major isoforms encoded by the dystonin (Dst) gene and show homology with MACF1a and MACF1b. These proteins are members of the plakin family, giant multi-modular proteins able to connect the intermediate filament, microtubule and microfilament cytoskeletal networks with each other and to distinct cell membrane sites. They also serve as scaffolds for signaling proteins that modulate cytoskeletal dynamics. To gain better insights into the functions of BPAG1a/b, we further characterized their C-terminal region important for their interaction with microtubules and assessed the role of these isoforms in the cytoskeletal organization of C2.7 myoblast cells. Our results show that alternative splicing does not only occur at the 5' end of Dst and Macf1 pre-mRNAs, as previously reported, but also at their 3' end, resulting in expression of additional four mRNA variants of BPAG1 and MACF1. These isoform-specific C-tails were able to bundle microtubules and bound to both EB1 and EB3, two microtubule plus end proteins. In the C2.7 cell line, knockdown of BPAG1a/b had no major effect on the organization of the microtubule and microfilament networks, but negatively affected endocytosis and maintenance of the Golgi apparatus structure, which became dispersed. Finally, knockdown of BPAG1a/b caused a specific decrease in the directness of cell migration, but did not impair initial cell adhesion. These data provide novel insights into the complexity of alternative splicing of Dst pre-mRNAs and into the role of BPAG1a/b in vesicular transport, Golgi apparatus structure as well as in migration in C2.7 myoblasts.

BPAG1a and b Associate with EB1 and EB3 and Modulate Vesicular Transport, Golgi Apparatus Structure, and Cell Migration in C2.7 Myoblasts

PubMed Central

Poliakova, Kseniia; Adebola, Adijat; Leung, Conrad L.; Favre, Bertrand; Liem, Ronald K. H.; Schepens, Isabelle; Borradori, Luca

2014-01-01

BPAG1a and BPAG1b (BPAG1a/b) constitute two major isoforms encoded by the dystonin (Dst) gene and show homology with MACF1a and MACF1b. These proteins are members of the plakin family, giant multi-modular proteins able to connect the intermediate filament, microtubule and microfilament cytoskeletal networks with each other and to distinct cell membrane sites. They also serve as scaffolds for signaling proteins that modulate cytoskeletal dynamics. To gain better insights into the functions of BPAG1a/b, we further characterized their C-terminal region important for their interaction with microtubules and assessed the role of these isoforms in the cytoskeletal organization of C2.7 myoblast cells. Our results show that alternative splicing does not only occur at the 5′ end of Dst and Macf1 pre-mRNAs, as previously reported, but also at their 3′ end, resulting in expression of additional four mRNA variants of BPAG1 and MACF1. These isoform-specific C-tails were able to bundle microtubules and bound to both EB1 and EB3, two microtubule plus end proteins. In the C2.7 cell line, knockdown of BPAG1a/b had no major effect on the organization of the microtubule and microfilament networks, but negatively affected endocytosis and maintenance of the Golgi apparatus structure, which became dispersed. Finally, knockdown of BPAG1a/b caused a specific decrease in the directness of cell migration, but did not impair initial cell adhesion. These data provide novel insights into the complexity of alternative splicing of Dst pre-mRNAs and into the role of BPAG1a/b in vesicular transport, Golgi apparatus structure as well as in migration in C2.7 myoblasts. PMID:25244344

Thermodynamic consideration and ground-state search of icosahedral boron subselenide B12(B1-xSex) 2 from a first-principles cluster expansion

NASA Astrophysics Data System (ADS)

Ektarawong, A.

2018-05-01

The phase stability of icosahedral boron subselenide B12(B1-xSex) 2 , where 0.5 ≤x ≤1 , is explored using a first-principles cluster expansion. The results shows that, instead of a continuous solid solution, B12(B1-xSex) 2 is thermodynamically stable as an individual line compound at the composition of B9.5Se . The ground-state configuration of B9.5Se is represented by a mixture of B12(Se-Se), B12(B-Se), and B12(Se-B) with a ratio of 1:1:1, where they form a periodic A B C A B C ⋯ stacking sequence of B12(Se-Se), B12(B-Se), and B12(Se-B) layers along the c axis of the hexagonal conventional unit cell. The structural and electronic properties of the ground-state B9.5Se are also derived and discussed. By comparing the derived ground-state properties of B9.5Se to the existing experimental data of boron subselenide B˜13Se , I proposed that the as-synthesized boron subselenide B˜13Se , as reported in the literature, has the actual composition of B9.5Se .

Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4bp-mediated C3b and C4b degradation

PubMed Central

Wooster, David G; Maruvada, Ravi; Blom, Anna M; Prasadarao, Nemani V

2006-01-01

Meningitis caused by Escherichia coli K1 is a serious illness in neonates with neurological sequelae in up to 50% of survivors. A high degree of bacteremia is required for E. coli K1 to cross the blood–brain barrier, which suggests that the bacterium must evade the host defence mechanisms and survive in the bloodstream. We previously showed that outer membrane protein A (OmpA) of E. coli binds C4b-binding protein (C4bp), an inhibitor of complement activation via the classical pathway. Nevertheless, the exact mechanism by which E. coli K1 survives in serum remains elusive. Here, we demonstrate that log phase (LP) OmpA+E. coli K1 avoids serum bactericidal activity more effectively than postexponential phase bacteria. OmpA–E. coli cannot survive in serum grown to either phase. The increased serum resistance of LP OmpA+E. coli is the result of increased binding of C4bp, with a concomitant decrease in the deposition of C3b and the downstream complement proteins responsible for the formation of the membrane attack complex. C4bp bound to E. coli K1 acts as a cofactor to factor I in the cleavage of both C3b and C4b, which shuts down the ensuing complement cascade. Accordingly, a peptide corresponding to the complement control protein domain 3 of C4bp sequence, was able to compete with C4bp binding to OmpA and cause increased deposition of C3b. Thus, binding of C4bp appears to be responsible for survival of E. coli K1 in human serum. PMID:16556262

7 CFR 301.85-2b - Exempted articles. 1

Code of Federal Regulations, 2014 CFR

2014-01-01

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7 CFR 301.85-2b - Exempted articles. 1

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2011-01-01

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2010-01-01

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2013-01-01

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7 CFR 301.85-2b - Exempted articles. 1

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

C 1Σ+ , A 1Σ+ , and b 3Π0+ states of LiRb

NASA Astrophysics Data System (ADS)

Stevenson, I. C.; Blasing, D. B.; Chen, Y. P.; Elliott, D. S.

2016-12-01

We present the first spectroscopic studies of the C 1Σ+ electronic state and the A 1Σ+ -b 3Π0+ complex in 7Li-85Rb. Using resonantly enhanced, two-photon ionization, we observed v =7 , 9, 12, 13, and 26-45 of the C 1Σ+ state. We augment the REMPI data with a form of depletion spectra in regions of dense spectral lines. The A 1Σ+ -b 3Π0+ complex was observed with depletion spectroscopy, depleting to vibrational levels v =0 →29 of the A 1Σ+ state and v =8 →18 of the b 3Π0+ state. For all three series, we determine the term energy and vibrational constants. Finally, we outline several possible future projects based on the data presented here.

15-HETE "modulates" expression of C3b receptor (CR1) antigen on peripheral blood B-lymphocytes.

PubMed

Cook, J; Delebassée, S; Aldigier, J C; Gualde, N; Kazatchkine, M

1986-08-01

We have studied the effect of the lipoxygenase metabolite, 15-HETE, on the expression of the human C3b receptor (CR1) by a B-lymphocyte enriched population of human peripheral blood leukocytes. The number of CR1 antigenic sites expressed by B-lymphocytes isolated from HLA typed donors was determined by equilibrium binding studies using an 125 I-labelled mouse monoclonal anti CR1 antibody before and after 16 hrs incubation in RPMI alone or containing 10(-6)M, 10(-7)M or 10(-8)M final concentration of 15-HETE. In B44- subjects CR1 expression on B cells increased 63% after incubation in RPMI alone. This increase was inhibited in the presence of 10(-6)M and 10(-7)M 15-HETE (23% and 30% increase respectively). In contrast, B44+ individuals showed a smaller increase in CR1 numbers when incubated in RPMI alone. In the presence of 15-HETE CR1 antigenic sites continued to increase. When B44+ subjects were classified as A29+ or A29-, donors that were A29+ B44+ accounted for the augmentation observed while A29- B44+ individuals did not differ from individuals that were A29- B44-.

The conformations of 13-vertex ML2C2B10 metallacarboranes: experimental and computational studies.

PubMed

Dalby, Kelly J; Ellis, David; Erhardt, Stefan; McIntosh, Ruaraidh D; Macgregor, Stuart A; Rae, Karen; Rosair, Georgina M; Settels, Volker; Welch, Alan J; Hodson, Bruce E; McGrath, Thomas D; Stone, F Gordon A

2007-03-21

The docosahedral metallacarboranes 4,4-(PMe(2)Ph)2-4,1,6-closo-PtC(2)B(10)H(12), 4,4-(PMe(2)Ph)2-4,1,10-closo-PtC(2)B(10)H(12), and [N(PPh(3))2][4,4-cod-4,1,10-closo-RhC(2)B(10)H(12)] were prepared by reduction/metalation of either 1,2-closo-C(2)B(10)H(12) or 1,12-closo-C(2)B(10)H(12). All three species were fully characterized, with a particular point of interest of the latter being the conformation of the {ML2} fragment relative to the carborane ligand face. Comparison with conformations previously established for six other ML(2)C(2)B(10) species of varying heteroatom patterns (4,1,2-MC(2)B(10), 4,1,6-MC(2)B(10), 4,1,10-MC(2)B(10), and 4,1,12-MC(2)B(10)) reveals clear preferences. In all cases a qualitative understanding of these was afforded by simple MO arguments applied to the model heteroarene complexes [(PH3)2PtC(2)B(4)H(6)]2- and [(PH3)2PtCB(5)H(6)]3-. Moreover, DFT calculations on [(PH3)2PtC(2)B(4)H(6)]2- in its various isomeric forms approximately reproduced the observed conformations in the 4,1,2-, 4,1,6-, and 4,1,10-MC(2)B(10) species, although analogous calculations on [(PH3)2PtCB(5)H(6)]3- did not reproduce the conformation observed in the 4,1,12-MC(2)B(10) metallacarborane. DFT calculations on (PH3)2PtC(2)B(10)H(12) yielded good agreement with experimental conformations in all four isomeric cases. Apparent discrepancies between observed and computed Pt-C distances were probed by further refinement of the 4,1,2- model to 1,2-(CH2)3-4,4-(PMe3)2-4,1,2-closo-PtC(2)B(10)H(10). This still has a more distorted structure than measured experimentally for 1,2-(CH2)3-4,4-(PMe(2)Ph)2-4,1,2-closo-PtC(2)B(10)H(10), but the structural differences lie on a very shallow potential energy surface. For the model compound a henicosahedral transition state was located 8.3 kcal mol(-1) above the ground-state structure, consistent with the fluxionality of 1,2-(CH2)3-4,4-(PMe(2)Ph)2-4,1,2-closo-PtC(2)B(10)H(10) in solution.

Software Design Document GT Real-Time Software Host CSCI (9B). Volume 1, Sections 1.0 - 2.12.19.2

DTIC Science & Technology

1991-06-01

78 2.4.2.8 bOsig-frame-rate.c ............................. 79 2.4.2.9 bO- database -info.c.............................. 79...93 2.4.3 Ballistics Database Interaction ......................................... 94 2.4.3.1 bxbvolintc... database -disable................................ 417 2.12.6.11 _handle-.point-lights ............................. 418 2.12.6.12 _-reset~model-Wpinters

Rapid hydrothermal synthesis of VO2 (B) and its conversion to thermochromic VO2 (M1).

PubMed

Popuri, Srinivasa Rao; Miclau, Marinela; Artemenko, Alla; Labrugere, Christine; Villesuzanne, Antoine; Pollet, Michaël

2013-05-06

The present study provides a rapid way to obtain VO2 (B) under economical and environmentally friendly conditions. VO2 (B) is one of the well-known polymorphs of vanadium dioxide and is a promising cathode material for aqueous lithium ion batteries. VO2 (B) was successfully synthesized by rapid single-step hydrothermal process using V2O5 and citric acid as precursors. The present study shows that phase-pure VO2 (B) polytype can be easily obtained at 180 °C for 2 h and 220 °C for 1 h, that is, the lowest combination of temperature and duration reported so far. The obtained VO2 (B) is characterized by X-ray powder diffraction, high-resolution scanning electron microscopy, and Fourier transform infrared spectroscopy. In addition, we present an indirect way to obtain VO2 (M1) by annealing VO2 (B) under vacuum for 1 h.

Asperentin B, a New Inhibitor of the Protein Tyrosine Phosphatase 1B.

PubMed

Wiese, Jutta; Aldemir, Hülya; Schmaljohann, Rolf; Gulder, Tobias A M; Imhoff, Johannes F

2017-06-21

In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillus sydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B ( 1 ) contains an additional phenolic hydroxy function at C-6 and exhibits an IC 50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin. Interestingly, asperentin ( 2 ) did not show any inhibition of this enzymatic activity. Asperentin B ( 1 ) is discussed as possible therapeutic agents for type 2 diabetes and sleeping sickness.

Asperentin B, a New Inhibitor of the Protein Tyrosine Phosphatase 1B

PubMed Central

Wiese, Jutta; Aldemir, Hülya; Schmaljohann, Rolf; Gulder, Tobias A. M.; Imhoff, Johannes F.

2017-01-01

In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillus sydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin. Interestingly, asperentin (2) did not show any inhibition of this enzymatic activity. Asperentin B (1) is discussed as possible therapeutic agents for type 2 diabetes and sleeping sickness. PMID:28635658

Telecom 2-B and 2-C (TC2B and TC2C)

NASA Technical Reports Server (NTRS)

Dulac, J.; Alvarez, H.

1991-01-01

The DSN (Deep Space Network) mission support requirements for Telecom 2-B and 2-C (TC2B and TC2C) are summarized. These Telecom missions will provide high-speed data link applications, telephone, and television service between France and overseas territories as a follow-on to TC2A. Mission objectives are outlined and the DSN support requirements are defined through the presentation of tables and narratives describing the spacecraft flight profile; DSN support coverage; frequency assignments; support parameters for telemetry, command and support systems; and tracking support responsibility.

75 FR 23572 - Airworthiness Directives; Airbus Model A300 B2-1C, B2-203, B2K-3C, B4-103, B4-203, B4-2C...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-04

... cycles 6,700 flight 80A3 or Pratt & Whitney engines. flight cycles \\1\\. flight cycles or \\2\\. cycles or...-200 airplanes with GE CF6- 18,000 total 19,500 total 250 flight cycles 5,800 flight 80C2 engines... flight cycles 6,700 flight Pratt & Whitney JT9D engines. flight cycles \\1\\. flight cycles or \\2\\. cycles...

Protein tyrosine phosphatase 1B (PTP1B) is required for cardiac lineage differentiation of mouse embryonic stem cells.

PubMed

Eshkiki, Zahra Shokati; Ghahremani, Mohammad Hossein; Shabani, Parisa; Firuzjaee, Sattar Gorgani; Sadeghi, Asie; Ghanbarian, Hossein; Meshkani, Reza

2017-01-01

Protein tyrosine phosphatase 1B (PTP1B) has been shown to regulate multiple cellular events such as differentiation, cell growth, and proliferation; however, the role of PTP1B in differentiation of embryonic stem (ES) cells into cardiomyocytes remains unexplored. In the present study, we investigated the effects of PTP1B inhibition on differentiation of ES cells into cardiomyocytes. PTP1B mRNA and protein levels were increased during the differentiation of ES cells into cardiomyocytes. Accordingly, a stable ES cell line expressing PTP1B shRNA was established. In vitro, the number and size of spontaneously beating embryoid bodies were significantly decreased in PTP1B-knockdown cells, compared with the control cells. Decreased expression of cardiac-specific markers Nkx2-5, MHC-α, cTnT, and CX43, as assessed by real-time PCR analysis, was further confirmed by immunocytochemistry of the markers. The results also showed that PTP1B inhibition induced apoptosis in both differentiated and undifferentiated ES cells, as presented by increasing the level of cleaved caspase-3, cytochrome C, and cleaved PARP. Further analyses revealed that PTP1B inhibition did not change proliferation and pluripotency of undifferentiated ES cells. Taken together, the data presented here suggest that PTP1B is essential for proper differentiation of ES cells into cardiomyocytes.

Neuroradiological findings in GM2 gangliosidosis variant B1.

PubMed

Bano, Shahina; Prasad, Akhila; Yadav, Sachchida Nand; Chaudhary, Vikas; Garga, Umesh Chandra

2011-07-01

GM2 gangliosidosis variant B1 is a very rare lysosomal disorder. As per our knowledge, to date, only one article depicting the magnetic resonance imaging (MRI) findings of GM2 gangliosidosis variant B1 is available in the literature. We are the first to describe the neuroradiological findings in an Indian patient diagnosed with GM2 gangliosidosis variant B1.

77 FR 3380 - Airworthiness Directives; Eurocopter France (ECF) Model AS350B, B1, B2, B3, BA, and D; and AS355E...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-24

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[Determination of fumonisins B1 and B2 in corn by high performance liquid chromatography with post-column derivatization method].

PubMed

Zhang, Xiaoxu; Xiao, Zhiyong; Zhang, Hongyan; Yang, Lili; Ma, Liyan

2012-08-01

A high performance liquid chromatography-fluorescence detection with post-column derivatization method was developed to detect fumonisin B1 (FB1) and fumonisin B2 (FB2) in corn. Several factors, such as the pH of derivatization buffer, concentration and flow rate of derivatization reagents, excitation wavelength, emission wavelength, which affected the detection of fumonisins were optimized. The separation was performed on a ZORBAX SB C18 column operated at 40 degrees C with the gradient elution by two mobile phases of 0.1 mol/L sodium dihydrogen phosphate solution (pH 3.3) and methanol at a flow rate of 0.8 mL/min. The derivatization was performed at ambient temperature. The o-phthalaldehyde (OPA) flow rate was 0.4 mL/min. The results showed that the optimum conditions were pH 10.5 of the derivatization reagent, OPA concentration at 2 g/L, and excitation wavelength of 335 nm, emission wavelength of 440 nm. The linear plots of FB1 and FB2 were obtained between 0.2 to 20 mg/L, with the correlation coefficients above 0.999 for both FB1 and FB2. The limits of detection of fumonisins B1 and B2 were 0.02 mg/kg. The mean recoveries at the three spiked levels of 0.1 - 4.0 mg/kg were 82.5% - 89.8%. This method is accurate, simple, rapid and suitable for the determination of fumonisins B1 and B2 in corn.

Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2)*

PubMed Central

Zhou, Gang; Marathe, Gopal K.; Hartiala, Jaana; Hazen, Stanley L.; Allayee, Hooman; Tang, W. H. Wilson; McIntyre, Thomas M.

2013-01-01

Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10−8). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10−17). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation. PMID:23508960

Study of infrared emission spectroscopy for the B{sup 1}Δ{sub g}–A{sup 1}Π{sub u} and B{sup ′1}Σ{sub g}{sup +}–A{sup 1}Π{sub u} systems of C{sub 2}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Wang, E-mail: sc19321@s.okayama-u.ac.jp, E-mail: okakent@okayama-u.ac.jp, E-mail: pbernath@odu.edu; Kawaguchi, Kentarou, E-mail: sc19321@s.okayama-u.ac.jp, E-mail: okakent@okayama-u.ac.jp, E-mail: pbernath@odu.edu; Tang, Jian, E-mail: jtang@okayama-u.ac.jp

Thirteen bands for the B{sup 1}Δ{sub g}–A{sup 1}Π{sub u} system and eleven bands for the B{sup ′1}Σ{sub g}{sup +}–A{sup 1}Π{sub u} system of C{sub 2} were identified in the Fourier transform infrared emission spectra of hydrocarbon discharges. The B{sup ′1}Σ{sub g}{sup +} v = 4 and the B{sup 1}Δ{sub g} v = 6, 7, and 8 vibrational levels involved in nine bands were studied for the first time. A direct global analysis with Dunham parameters was carried out satisfactorily for the B{sup 1}Δ{sub g}–A{sup 1}Π{sub u} system except for a small perturbation in the B{sup 1}Δ{sub g} v = 6more » level. The calculated rovibrational term energies up to B{sup 1}Δ{sub g} v = 12 showed that the level crossing between the B{sup 1}Δ{sub g} and d{sup 3}Π{sub g} states is responsible for many of the prominent perturbations in the Swan system observed previously. Nineteen forbidden transitions of the B{sup 1}Δ{sub g}–a{sup 3}Π{sub u} transition were identified and the off-diagonal spin-orbit interaction constant A{sub dB} between d{sup 3}Π{sub g} and B{sup 1}Δ{sub g} was derived as 8.3(1) cm{sup −1}. For the B{sup ′1}Σ{sub g}{sup +}–A{sup 1}Π{sub u} system, only individual band analyses for each vibrational level in the B′{sup 1}Σ{sub g}{sup +} state could be done satisfactorily and Dunham parameters obtained from these effective parameters showed that the anharmonic vibrational constant ω{sub e}x{sub e} is anomalously small (nearly zero). Inspection of the RKR (Rydberg-Klein-Rees) potential curves for the B{sup ′1}Σ{sub g}{sup +} and X{sup 1}Σ{sub g}{sup +} states revealed that an avoided crossing or nearly avoided crossing may occur around 30 000 cm{sup −1}, which is responsible for the anomalous molecular constants in these two states.« less

Mercury-Bridged Cobaltacarborane Complexes Containing B-Hg-B Three-Center Bonds. Synthesis and Structure of mu, mu’-((n5-C5R5)Co(CH3)2C2B3H4)Hg, mu-(n(5)-C5R5)Co(CH3)2C2B3H4)HgCl, (R=H, CH3) and Related Compounds.

DTIC Science & Technology

1980-11-01

MERCURY-BRIDGED COBALTACARBORANE COMPLEXES CONTAINING B-HG-B TH--ETC(U) NOV 80 D C FINSTER . R N GRIMES N0 0 0 1 4-75-0305 UNCLASSXFIED TR󈧨 NL ILn...C5R5) Co 3)2C2B3 4 2 5 .- -C5R5 )Co(CH3)2C2B3H4 ]HgCl, (R=H, CH3 ) and Related Compounds, David C./ Finster -- Russell N./Grimes ( Department of Chemistry...Compounds 1 \\David C. Finster And Russell N. Grimes* Abstract. Reactions of the nid~p-cobaltacarborane anions 01CR )(C 3 )C BH and [n (H 1oC ihH~5n 5

40 CFR Figure B-1 to Subpart B of... - Example

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40 CFR Figure B-1 to Subpart B of... - Example

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2013-07-01

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40 CFR Figure B-1 to Subpart B of... - Example

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 6 2014-07-01 2014-07-01 false Example B Figure B-1 to Subpart B of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... of Automated Methods for SO2, CO, O3, and NO2 Pt. 53, Subpt. B, Fig. B-1 Figure B-1 to Subpart B of...

SLCO2B1 and SLCO1B3 May Determine Time to Progression for Patients Receiving Androgen Deprivation Therapy for Prostate Cancer

PubMed Central

Yang, Ming; Xie, Wanling; Mostaghel, Elahe; Nakabayashi, Mari; Werner, Lillian; Sun, Tong; Pomerantz, Mark; Freedman, Matthew; Ross, Robert; Regan, Meredith; Sharifi, Nima; Figg, William Douglas; Balk, Steven; Brown, Myles; Taplin, Mary-Ellen; Oh, William K.; Lee, Gwo-Shu Mary; Kantoff, Philip W.

2011-01-01

Purpose Androgen deprivation therapy (ADT), an important treatment for advanced prostate cancer, is highly variable in its effectiveness. We hypothesized that genetic variants of androgen transporter genes, SLCO2B1 and SLCO1B3, may determine time to progression on ADT. Patients and Methods A cohort of 538 patients with prostate cancer treated with ADT was genotyped for SLCO2B1 and SLCO1B3 single nucleotide polymorphisms (SNP). The biologic function of a SLCO2B1 coding SNP in transporting androgen was examined through biochemical assays. Results Three SNPs in SLCO2B1 were associated with time to progression (TTP) on ADT (P < .05). The differences in median TTP for each of these polymorphisms were about 10 months. The SLCO2B1 genotype, which allows more efficient import of androgen, enhances cell growth and is associated with a shorter TTP on ADT. Patients carrying both SLCO2B1 and SLCO1B3 genotypes, which import androgens more efficiently, exhibited a median 2-year shorter TTP on ADT, demonstrating a gene-gene interaction (Pinteraction = .041). Conclusion Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer. PMID:21606417

Vasopressor meets vasodepressor: The AT1-B2 receptor heterodimer.

PubMed

Quitterer, Ursula; AbdAlla, Said

2014-04-01

The AT1 receptor for the vasopressor angiotensin II is one of the most important drug targets for the treatment of cardiovascular diseases. Sensitization of the AT1 receptor system is a common feature contributing to the pathogenesis of many cardiovascular disorders but underlying mechanisms are not fully understood. More than a decade ago, evidence was provided for control of AT1R activation by heterodimerization with the B2 receptor for the vasodepressor peptide, bradykinin, a physiological counterpart of the vasoconstrictor angiotensin II. AT1-B2 receptor heterodimerization was shown to enhance AT1R-stimulated signaling under pathophysiological conditions such as experimental and human pregnancy hypertension. Notably, AT1R signal sensitization of patients with preeclampsia hypertension was attributed to AT1R-B2R heterodimerization. Vice versa, transgenic mice lacking the AT1-B2 receptor heterodimer due to targeted deletion of the B2R gene showed a significantly reduced AT1R-stimulated vasopressor response compared to transgenic mice with abundant AT1R-B2R heterodimerization. Biophysical methods such as BRET and FRET confirmed those data by demonstrating efficient AT1-B2 receptor heterodimerization in transfected cells and transgenic mice. Recently, a study on AT1R-specific biased agonism directed the focus to the AT1-B2 receptor heterodimer again. The β-arrestin-biased [Sar1,Ile4,Ile8]-angiotensin II promoted not only the recruitment of β-arrestin to the AT1R but also stimulated the down-regulation of the AT1R-associated B2 receptor by co-internalization. Thereby specific targeting of the AT1R-B2R heterodimer became feasible and could open the way to a new class of drugs, which specifically interfere with pathological angiotensin II-AT1 receptor system activation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Fate of avermectin B1a on citrus fruits. 1. Distribution and magnitude of the avermectin B sub 1a and sup 14 C residue on citrus fruits from a field study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maynard, M.S.; Iwata, Y.; Wislocki, P.G.

An 8{mu}g/mL solution of ({sup 14}C)avermectin B{sub 1a}, the approximate field application rate, was applied to oranges, lemons, and grapefruit; a 10-fold higher rate was also applied to oranges. Immediately postapplication, {sup 14}C residues were 20-38 ng/g for the fruit treated at the field rate. Most of the residue was recovered in the surface solvent rinse at less than 2 weeks postapplication; however, after this time more of the residue was recovered from the rind fraction. The total recoveries of applied radioactivity were 61-90% and 33-50% at 1 and 12 weeks postapplication, respectively. The level of unextractable rind {sup 14}Cmore » residue from oranges treated at the 10{times} rate and harvested at 12 weeks (a worse case) was 4.9% of the applied dose (<2 ppb at the field rate). The inner pulp samples for all treatments had {sup 14}C residue levels below the detection limit of 0.4-0.8 ppb. The initial depletion half-life of avermectin B{sub 1a} was <1 week, with losses occurring within 30-40 min. For the 1-12-week postapplication period, the avermectin B{sub 1a} and {sup 14}C residue depletion half-lives were 20-38 and 56-98 days, respectively. Differences in the rate of dissipation of avermectin B{sub 1a} due to fruit type and application rate were observed.« less

High-Resolution Synchrotron Infrared Spectroscopy of Thiophosgene: the νb{1}, νb{5}, 2νb{4}, and νb{2} + 2νb{6} bands

NASA Astrophysics Data System (ADS)

McKellar, Bob; Billinghurst, Brant E.

2015-06-01

Thiophosgene (Cl_2CS) is a favorite model system for studies of photophysics, vibrational dynamics, and intersystem interactions. But at high resolution its infrared spectrum is very congested due to hot bands and multiple isotopic species. Previously, we reported the first high resolution IR study of this molecule, analyzing the νb{2} (504 wn) and νb{4} (471 wn) fundamental bands. Here we continue, with analysis of the νb{1} (1139 wn) and νb{5} (820 wn) fundamentals for the two most abundant isotopologues, 35Cl2CS and 35Cl37ClCS, based on spectra with a resolution of about 0.001 wn obtained at the Canadian Light Source far-infrared beamline using synchrotron radiation and a Bruker IFS125 Fourier transform spectrometer. The νb{2} + νb{4} (942 wn) and νb{2} + 2νb{6} (1104 wn) bands are also studied here. But so far the νb{2} + νb{6} combination band (795 wn) resists analysis, as do the weak νb{3} (292.9 wn) and νb{6} (≈300? wn) fundamentals. A.R.W. McKellar, B.E.Billinghurst, J. Mol. Spectrosc. 260, 66 (2010).

Two extreme young objects in Barnard 1-b

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirano, Naomi; Liu, Fang-chun, E-mail: hirano@asiaa.sinica.edu.tw

2014-07-01

Two submillimeter/millimeter sources in the Barnard 1b (B1-b) core, B1-bN and B1-bS, have been studied in dust continuum, H{sup 13}CO{sup +} J = 1-0, CO J = 2-1, {sup 13}CO J = 2-1, and C{sup 18}O J = 2-1. The spectral energy distributions of these sources from the mid-IR to 7 mm are characterized by very cold temperatures of T {sub dust} < 20 K and low bolometric luminosities of 0.15-0.31 L {sub ☉}. The internal luminosities of B1-bN and B1-bS are estimated to be <0.01-0.03 L {sub ☉} and ∼0.1-0.2 L {sub ☉}, respectively. Millimeter interferometric observations have shownmore » that these sources have already formed central compact objects of ∼100 AU sizes. Both B1-bN and B1-bS are driving the CO outflows with low characteristic velocities of ∼2-4 km s{sup –1}. The fractional abundance of H{sup 13}CO{sup +} at the positions of B1-bN and B1-bS is lower than the canonical value by a factor of four to eight. This implies that a significant fraction of CO is depleted onto dust grains in the dense gas surrounding these sources. The observed physical and chemical properties suggest that B1-bN and B1-bS are in an earlier evolutionary stage than most of the known class 0 protostars. In particular, the properties of B1-bN agree with those of the first hydrostatic core predicted by the MHD simulations. The CO outflow was also detected in the mid-IR source located at ∼15'' from B1-bS. Since the dust continuum emission was not detected in this source, the circumstellar material surrounding this source is less than 0.01 M {sub ☉}. It is likely that the envelope of this source was dissipated by the outflow from the protostar that is located to the southwest of B1-b.« less

Hadronic production of the P-wave excited B{sub c} states (B{sub cJ,L=1}*)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, C.-H.; Institute of Theoretical Physics, Chinese Academy of Sciences, P.O. Box 2735, Beijing 100080; Wang, J.-X.

2004-12-01

Adopting the complete {alpha}{sub s}{sup 4} approach of the perturbative QCD and the updated parton distribution functions, we have estimated the hadronic production of the P-wave excited B{sub c} states (B{sub cJ,L=1}*). In the estimate, special care has been paid to the dependence of the production amplitude on the derivative of the wave function at origin which is obtained by the potential model. For experimental references, main theoretical uncertainties are discussed, and the total cross section as well as the distributions of the production with reasonable cuts at the energies of Tevatron and CERN LHC are computed and presented properly.more » The results show that the P-wave production may contribute to the B{sub c}-meson production indirectly by a factor of about 0.5 of the direct production, and according to the estimated cross section, it is further worthwhile to study the possibility of observing the P-wave production itself experimentally.« less

Spreading of hepatitis C virus subtypes 1a and 1b through the central region of Argentina.

PubMed

Culasso, Andrés Carlos Alberto; Farías, Adrián; Di Lello, Federico Alejandro; Golemba, Marcelo Darío; Ré, Viviana; Barbini, Luciana; Campos, Rodolfo

2014-08-01

The recent history of the hepatitis C virus (HCV) subtypes 1a and 1b in the central region of Argentina is hypothesized by phylogeographic reconstruction using coalescent based Bayesian analyses. Direct partial E2 sequences from HCV 1a and 1b infected patients attending different health-care centers of the country were analyzed. The inferred date of the most recent common ancestor (tMRCA) for HCV-1a was: 1962 (between 1943 and 1977) and for HCV-1b was earlier: 1929 (between 1895 and 1953). Diverse ancestral populations were inferred from both subtypes in Córdoba and in Buenos Aires cities and after that, HCV spread within and between larger cities and to other smaller cities. The analyses suggested that HCV-1b was dispersed first and it is currently in a stationary phase whereas HCV-1a was dispersed latter and it is still in a growth phase. Finally, as it was observed in the developed countries, while the transmission of HCV-1b appears to have been somehow prevented, the HCV-1a may still represent a concern in the public health. Further work should be carried out to address their current transmission rate (and its main transmission route) in the Argentinean population. Copyright © 2014 Elsevier B.V. All rights reserved.

Naphtho[1,2-b:5,6-b']dithiophene-Based Conjugated Polymers for Fullerene-Free Inverted Polymer Solar Cells.

PubMed

Jiang, Zhaoyan; Li, Huan; Wang, Zhen; Zhang, Jianqi; Zhang, Yajie; Lu, Kun; Wei, Zhixiang

2018-03-23

Three novel copolymers based on zigzag naphthodithiophene (zNDT) with different aromatic rings as π bridges and different core side substitutions are designed and synthesized (PzNDT-T-1,3-bis(4-(2-ethylhexyl)-thiophen-2-yl)-5,7-bis(2-ethylhexyl)benzo[1,2-c:4,5-c']-dithiophene-4,8-dione (BDD), PzNDT-TT-BDD, and PzNDTP-T-BDD, respectively). The 2D conjugation structure and molecular planarity of the polymers can be effectively altered through the modification of conjugated side chains and π-bridges. These alterations contribute to the variation in energy levels, light absorption capacity, and morphology compatibility of the polymers. When blended with the nonfullerene acceptor (2,2'-[(4,4,9,9-tetrahexyl-4,9-dihydro-sindaceno[1,2-b:5,6-b']dithiophene-2,7-diyl)bis[methylidyne(3-oxo-1H-indene-2,1(3H)-diylidene)

Role of kinin B1 and B2 receptors in memory consolidation during the aging process of mice.

PubMed

Lemos, Mayra Tolentino Resk; Amaral, Fabio Agostini; Dong, Karis Ester; Bittencourt, Maria Fernanda Queiroz Prado; Caetano, Ariadiny Lima; Pesquero, João Bosco; Viel, Tania Araujo; Buck, Hudson Sousa

2010-04-01

Under physiological conditions, elderly people present memory deficit associated with neuronal loss. This pattern is also associated with Alzheimer's disease but, in this case, in a dramatically intensified level. Kinin receptors have been involved in neurodegeneration and increase of amyloid-beta concentration, associated with Alzheimer's disease (AD). Considering these findings, this work evaluated the role of kinin receptors in memory consolidation during the aging process. Male C57Bl/6 (wt), knock-out B1 (koB1) or B2 (koB2) mice (3, 6, 12 and 18-month-old - mo; n=10 per group) were submitted to an acquisition session, reinforcement to learning (24h later: test 1) and final test (7days later: test 2), in an active avoidance apparatus, to evaluate memory. Conditioned avoidance responses (CAR, % of 50 trials) were registered. In acquisition sessions, similar CAR were obtained among age matched animals from all strains. However, a significant decrease in CAR was observed throughout the aging process (3mo: 8.8+/-2.3%; 6mo: 4.1+/-0.6%; 12mo: 2.2+/-0.6%, 18mo: 3.6+/-0.6%, P<0.01), indicating a reduction in the learning process. In test 1, as expected, memory retention increased significantly (P<0.05) in all 3- and 6-month-old animals as well as in 12-month-old-wt and 12-month-old-koB1 (P<0.01), compared to the training session. However, 12-month-old-koB2 and all 18-month-old animals did not show an increase in memory retention. In test 2, 3- and 6-month-old wt and koB1 mice of all ages showed a significant improvement in memory (P<0.05) compared to test 1. However, 12-month-old wt and koB2 mice of all ages showed no difference in memory retention. We suggest that, during the aging process, the B1 receptor could be involved in neurodegeneration and memory loss. Nevertheless, the B2 receptor is apparently acting as a neuroprotective factor. Copyright 2009 Elsevier Ltd. All rights reserved.

Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer.

PubMed

Taskoparan, Betul; Seza, Esin Gulce; Demirkol, Secil; Tuncer, Sinem; Stefek, Milan; Gure, Ali Osmay; Banerjee, Sreeparna

2017-12-01

Aldo-keto reductases (including AKR1B1 and AKR1B10) constitute a family of oxidoreductases that have been implicated in the pathophysiology of diabetes and cancer, including colorectal cancer (CRC). Available data indicate that, despite their similarities in structure and enzymatic functions, their roles in CRC may be divergent. Here, we aimed to determine the expression and functional implications of AKR1B1 and AKR1B10 in CRC. AKR1B1 and AKR1B10 gene expression levels were analyzed using publicly available microarray data and ex vivo CRC-derived cDNA samples. Gene Set Enrichment Analysis (GSEA), The Cancer Genome Atlas (TCGA) RNA-seq data and The Cancer Proteome Atlas (TCPA) proteome data were analyzed to determine the effect of high and low AKR1B1 and AKR1B10 expression levels in CRC patients. Proliferation, cell cycle progression, cellular motility, adhesion and inflammation were determined in CRC-derived cell lines in which these genes were either exogenously overexpressed or silenced. We found that the expression of AKR1B1 was unaltered, whereas that of AKR1B10 was decreased in primary CRCs. GSEA revealed that, while high AKR1B1 expression was associated with increased cell cycle progression, cellular motility and inflammation, high AKR1B10 expression was associated with a weak inflammatory phenotype. Functional studies carried out in CRC-derived cell lines confirmed these data. Microarray data analysis indicated that high expression levels of AKR1B1 and AKR1B10 were significantly associated with shorter and longer disease-free survival rates, respectively. A combined gene expression signature of AKR1B10 (low) and AKR1B1 (high) showed a better prognostic stratification of CRC patients independent of confounding factors. Despite their similarities, the expression levels and functions of AKR1B1 and AKR1B10 are highly divergent in CRC, and they may have prognostic implications.

Hadronic decays of B →a1(1260 )b1(1235 ) in the perturbative QCD approach

NASA Astrophysics Data System (ADS)

Jing, Hao-Yang; Liu, Xin; Xiao, Zhen-Jun

2017-12-01

We calculate the branching ratios and polarization fractions of the B →a1b1 decays in the perturbative QCD(pQCD) approach at leading order, where a1(b1) stands for the axial-vector a1(1260 )[b1(1235 )] state. By combining the phenomenological analyses with the perturbative calculations, we find the following results: (a) the large decay rates around 10-5 to 10-6 of the B →a1b1 decays dominated by the longitudinal polarization(except for the B+→b1+a10 mode) are predicted and basically consistent with those in the QCD factorization(QCDF) within errors, which are expected to be tested by the Large Hadron Collider and Belle-II experiments. The large B0→a10b10 branching ratio could provide hints to help explore the mechanism of the color-suppressed decays. (b) the rather different QCD behaviors between the a1 and b1 mesons result in the destructive(constructive) contributions in the nonfactorizable spectator diagrams with a1(b1) emission. Therefore, an interesting pattern of the branching ratios appears for the color-suppressed B0→a10a10,a10b10, and b10b10 modes in the pQCD approach, BR (B0→b10b10)>BR (B0→a10b10)≳BR (B0→a10a10), which is different from BR (B0→b10b10)˜BR (B0→a10b10)≳BR (B0→a10a10) in the QCDF and would be verified at future experiments. (c) the large naive factorization breaking effects are observed in these B →a1b1 decays. Specifically, the large nonfactorizable spectator(weak annihilation) amplitudes contribute to the B0→b1+a1-(B+→a1+b10andB+→b1+a10) mode(s), which demand confirmations via the precise measurements. Furthermore, the different phenomenologies shown among B →a1b1, B →a1a1, and B →b1b1 decays are also expected to be tested stringently, which could shed light on the typical QCD dynamics involved in these modes, even further distinguish those two popular pQCD and QCDF approaches.

Association of -31T>C and -511 C>T polymorphisms in the interleukin 1 beta (IL1B) promoter in Korean keratoconus patients.

PubMed

Kim, So-Hee; Mok, Jee-Won; Kim, Hyun-Seok; Joo, C K

2008-01-01

To investigate the genetic association between unrelated Korean keratoconus patients and interleukin 1 alpha (IL1A), interleukin 1 beta (IL1B), and IL1 receptor antagonist (IL1RN) gene polymorphisms. We investigated the association between IL1A (rs1800587, rs2071376, and rs17561), IL1B (rs1143627, rs16944, rs1143634, and rs1143633), and IL1RN (rs419598, rs423904, rs424078, and rs315952, variable number tandem repeat [VNTR]) polymorphisms in 100 unrelated Korean keratoconus patients. One hundred control individuals without any corneal disease were selected from the general population. Polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) analysis and direct sequencing were used to screen for genetic variations in the IL1 gene cluster. Haplotypes for the IL1 gene cluster were constructed using Haploview version 4.0. We analyzed a total of 12 polymorphic sites in the IL1 gene cluster. Among them, the -511 (rs16944) and -31 (rs1143627) positions in the promoter region of IL1B were significantly different between patient and control groups. The C allele of rs16944 (-511C>T, p=0.022, odds ratio of risk [OR]=1.46, 95% confidence intervals [CI] 0.94<2.27) and the T allele of rs1143627 (-31T>C, p=0.025, OR=1.43, 95% CI 0.92<2.22) were associated with a significantly increased risk of keratoconus in Korean patients. Linkage of the two alleles, -31*C and -511*T, was associated with an increased risk for keratoconus with OR=2.38 (p=0.012, 95% CI=1.116-5.046). The *C/*A genotype of rs2071376 in IL1A intron 6 was significantly different between the keratoconus patients and control subjects (p=0.034, OR=0.59, 95% CI 0.32<1.11). Other polymorphisms did not show an association with keratoconus risk. This is the first report of IL1 gene cluster mutation screening in Korean keratoconus patients. Significant differences in allelic frequency of IL1B between keratoconus patients and the control group suggest that IL1B polymorphisms may play a role in the

PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice.

PubMed

Zinker, Bradley A; Rondinone, Cristina M; Trevillyan, James M; Gum, Rebecca J; Clampit, Jill E; Waring, Jeffrey F; Xie, Nancy; Wilcox, Denise; Jacobson, Peer; Frost, Leigh; Kroeger, Paul E; Reilly, Regina M; Koterski, Sandra; Opgenorth, Terry J; Ulrich, Roger G; Crosby, Seth; Butler, Madeline; Murray, Susan F; McKay, Robert A; Bhanot, Sanjay; Monia, Brett P; Jirousek, Michael R

2002-08-20

The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide in ob/ob and db/db mice. PTP1B antisense oligonucleotide treatment normalized plasma glucose levels, postprandial glucose excursion, and HbA(1C). Hyperinsulinemia was also reduced with improved insulin sensitivity. PTP1B protein and mRNA were reduced in liver and fat with no effect in skeletal muscle. Insulin signaling proteins, insulin receptor substrate 2 and phosphatidylinositol 3 (PI3)-kinase regulatory subunit p50alpha, were increased and PI3-kinase p85alpha expression was decreased in liver and fat. These changes in protein expression correlated with increased insulin-stimulated protein kinase B phosphorylation. The expression of liver gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, and fructose-1,6-bisphosphatase was also down-regulated. These findings suggest that PTP1B modulates insulin signaling in liver and fat, and that therapeutic modalities targeting PTP1B inhibition may have clinical benefit in type 2 diabetes.

TgrC1 mediates cell-cell adhesion by interacting with TgrB1 via mutual IPT/TIG domains during development of Dictyostelium discoideum.

PubMed

Chen, Gong; Wang, Jun; Xu, Xiaoqun; Wu, Xiangfu; Piao, Ruihan; Siu, Chi-Hung

2013-06-01

Cell-cell adhesion plays crucial roles in cell differentiation and morphogenesis during development of Dictyostelium discoideum. The heterophilic adhesion protein TgrC1 (Tgr is transmembrane, IPT, IG, E-set, repeat protein) is expressed during cell aggregation, and disruption of the tgrC1 gene results in the arrest of development at the loose aggregate stage. We have used far-Western blotting coupled with MS to identify TgrB1 as the heterophilic binding partner of TgrC1. Co-immunoprecipitation and pull-down studies showed that TgrB1 and TgrC1 are capable of binding with each other in solution. TgrB1 and TgrC1 are encoded by a pair of adjacent genes which share a common promoter. Both TgrB1 and TgrC1 are type I transmembrane proteins, which contain three extracellular IPT/TIG (immunoglobulin, plexin, transcription factor-like/transcription factor immunoglobulin) domains. Antibodies raised against TgrB1 inhibit cell reassociation at the post-aggregation stage of development and block fruiting body formation. Ectopic expression of TgrB1 and TgrC1 driven by the actin15 promoter leads to heterotypic cell aggregation of vegetative cells. Using recombinant proteins that cover different portions of TgrB1 and TgrC1 in binding assays, we have mapped the cell-binding regions in these two proteins to Lys(537)-Ala(783) in TgrB1 and Ile(336)-Val(360) in TgrC1, corresponding to their respective TIG3 and TIG2 domain.

The Arrestin-selective Angiotensin AT1 Receptor Agonist [Sar1,Ile4,Ile8]-AngII Negatively Regulates Bradykinin B2 Receptor Signaling via AT1-B2 Receptor Heterodimers*

PubMed Central

Wilson, Parker C.; Lee, Mi-Hye; Appleton, Kathryn M.; El-Shewy, Hesham M.; Morinelli, Thomas A.; Peterson, Yuri K.; Luttrell, Louis M.; Jaffa, Ayad A.

2013-01-01

The renin-angiotensin and kallikrein-kinin systems are key regulators of vascular tone and inflammation. Angiotensin II, the principal effector of the renin-angiotensin system, promotes vasoconstriction by activating angiotensin AT1 receptors. The opposing effects of the kallikrein-kinin system are mediated by bradykinin acting on B1 and B2 bradykinin receptors. The renin-angiotensin and kallikrein-kinin systems engage in cross-talk at multiple levels, including the formation of AT1-B2 receptor heterodimers. In primary vascular smooth muscle cells, we find that the arrestin pathway-selective AT1 agonist, [Sar1,Ile4,Ile8]-AngII, but not the neutral AT1 antagonist, losartan, inhibits endogenous B2 receptor signaling. In a transfected HEK293 cell model that recapitulates this effect, we find that the actions of [Sar1,Ile4, Ile8]-AngII require the AT1 receptor and result from arrestin-dependent co-internalization of AT1-B2 heterodimers. BRET50 measurements indicate that AT1 and B2 receptors efficiently heterodimerize. In cells expressing both receptors, pretreatment with [Sar1,Ile4,Ile8]-AngII blunts B2 receptor activation of Gq/11-dependent intracellular calcium influx and Gi/o-dependent inhibition of adenylyl cyclase. In contrast, [Sar1,Ile4,Ile8]-AngII has no effect on B2 receptor ligand affinity or bradykinin-induced arrestin3 recruitment. Both radioligand binding assays and quantitative microscopy-based analysis demonstrate that [Sar1,Ile4,Ile8]-AngII promotes internalization of AT1-B2 heterodimers. Thus, [Sar1,Ile4,Ile8]-AngII exerts lateral allosteric modulation of B2 receptor signaling by binding to the orthosteric ligand binding site of the AT1 receptor and promoting co-sequestration of AT1-B2 heterodimers. Given the opposing roles of the renin-angiotensin and kallikrein-kinin systems in vivo, the distinct properties of arrestin pathway-selective and neutral AT1 receptor ligands may translate into different pharmacologic actions. PMID:23661707

The arrestin-selective angiotensin AT1 receptor agonist [Sar1,Ile4,Ile8]-AngII negatively regulates bradykinin B2 receptor signaling via AT1-B2 receptor heterodimers.

PubMed

Wilson, Parker C; Lee, Mi-Hye; Appleton, Kathryn M; El-Shewy, Hesham M; Morinelli, Thomas A; Peterson, Yuri K; Luttrell, Louis M; Jaffa, Ayad A

2013-06-28

The renin-angiotensin and kallikrein-kinin systems are key regulators of vascular tone and inflammation. Angiotensin II, the principal effector of the renin-angiotensin system, promotes vasoconstriction by activating angiotensin AT1 receptors. The opposing effects of the kallikrein-kinin system are mediated by bradykinin acting on B1 and B2 bradykinin receptors. The renin-angiotensin and kallikrein-kinin systems engage in cross-talk at multiple levels, including the formation of AT1-B2 receptor heterodimers. In primary vascular smooth muscle cells, we find that the arrestin pathway-selective AT1 agonist, [Sar(1),Ile(4),Ile(8)]-AngII, but not the neutral AT1 antagonist, losartan, inhibits endogenous B2 receptor signaling. In a transfected HEK293 cell model that recapitulates this effect, we find that the actions of [Sar(1),Ile(4), Ile(8)]-AngII require the AT1 receptor and result from arrestin-dependent co-internalization of AT1-B2 heterodimers. BRET50 measurements indicate that AT1 and B2 receptors efficiently heterodimerize. In cells expressing both receptors, pretreatment with [Sar(1),Ile(4),Ile(8)]-AngII blunts B2 receptor activation of Gq/11-dependent intracellular calcium influx and Gi/o-dependent inhibition of adenylyl cyclase. In contrast, [Sar(1),Ile(4),Ile(8)]-AngII has no effect on B2 receptor ligand affinity or bradykinin-induced arrestin3 recruitment. Both radioligand binding assays and quantitative microscopy-based analysis demonstrate that [Sar(1),Ile(4),Ile(8)]-AngII promotes internalization of AT1-B2 heterodimers. Thus, [Sar(1),Ile(4),Ile(8)]-AngII exerts lateral allosteric modulation of B2 receptor signaling by binding to the orthosteric ligand binding site of the AT1 receptor and promoting co-sequestration of AT1-B2 heterodimers. Given the opposing roles of the renin-angiotensin and kallikrein-kinin systems in vivo, the distinct properties of arrestin pathway-selective and neutral AT1 receptor ligands may translate into different pharmacologic

76 FR 63177 - Airworthiness Directives; Airbus Model A300 B2-1C, A300 B2-203, A300 B2K-3C, A300-B4-103, A300 B4...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-12

... available in the AD docket shortly after receipt. List of Subjects in 14 CFR Part 39 Air transportation... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 39 [Docket No. FAA-2011... B4-2C Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT...

Aldo-keto reductases AKR1C1, AKR1C2 and AKR1C3 may enhance progesterone metabolism in ovarian endometriosis.

PubMed

Hevir, N; Vouk, K; Sinkovec, J; Ribič-Pucelj, M; Rižner, T Lanišnik

2011-05-30

Endometriosis is a very common disease that is characterized by increased formation of estradiol and disturbed progesterone action. This latter is usually explained by a lack of progesterone receptor B (PR-B) expression, while the role of pre-receptor metabolism of progesterone is not yet fully understood. In normal endometrium, progesterone is metabolized by reductive 20α-hydroxysteroid dehydrogenases (20α-HSDs), 3α/β-HSDs and 5α/β-reductases. The aldo-keto reductases 1C1 and 1C3 (AKR1C1 and AKR1C3) are the major reductive 20α-HSDs, while the oxidative reaction is catalyzed by 17β-HSD type 2 (HSD17B2). Also, 3α-HSD and 3β-HSD activities have been associated with the AKR1C isozymes. Additionally, 5α-reductase types 1 and 2 (SRD5A1, SRD5A2) and 5β-reductase (AKR1D1) are responsible for the formation of 5α- and 5β-reduced pregnanes. In this study, we examined the expression of PR-AB and the progesterone metabolizing enzymes in 31 specimens of ovarian endometriosis and 28 specimens of normal endometrium. Real-time PCR analysis revealed significantly decreased mRNA levels of PR-AB, HSD17B2 and SRD5A2, significantly increased mRNA levels of AKR1C1, AKR1C2, AKR1C3 and SRD5A1, and negligible mRNA levels of AKR1D1. Immunohistochemistry staining of endometriotic tissue compared to control endometrium showed significantly lower PR-B levels in epithelial cells and no significant differences in stromal cells, there were no significant differences in the expression of AKR1C3 and significantly higher AKR1C2 levels were seen only in stromal cells. Our expression analysis data at the mRNA level and partially at the cellular level thus suggest enhanced metabolism of progesterone by SRD5A1 and the 20α-HSD and 3α/β-HSD activities of AKR1C1, AKR1C2 and AKR1C3. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The HsiB1C1 (TssB-TssC) Complex of the Pseudomonas aeruginosa Type VI Secretion System Forms a Bacteriophage Tail Sheathlike Structure

PubMed Central

Lossi, Nadine S.; Manoli, Eleni; Förster, Andreas; Dajani, Rana; Pape, Tillmann; Freemont, Paul; Filloux, Alain

2013-01-01

Protein secretion systems in Gram-negative bacteria evolved into a variety of molecular nanomachines. They are related to cell envelope complexes, which are involved in assembly of surface appendages or transport of solutes. They are classified as types, the most recent addition being the type VI secretion system (T6SS). The T6SS displays similarities to bacteriophage tail, which drives DNA injection into bacteria. The Hcp protein is related to the T4 bacteriophage tail tube protein gp19, whereas VgrG proteins structurally resemble the gp27/gp5 puncturing device of the phage. The tube and spike of the phage are pushed through the bacterial envelope upon contraction of a tail sheath composed of gp18. In Vibrio cholerae it was proposed that VipA and VipB assemble into a tail sheathlike structure. Here we confirm these previous data by showing that HsiB1 and HsiC1 of the Pseudomonas aeruginosa H1-T6SS assemble into tubules resulting from stacking of cogwheel-like structures showing predominantly 12-fold symmetry. The internal diameter of the cogwheels is ∼100 Å, which is large enough to accommodate an Hcp tube whose external diameter has been reported to be 85 Å. The N-terminal 212 residues of HsiC1 are sufficient to form a stable complex with HsiB1, but the C terminus of HsiC1 is essential for the formation of the tubelike structure. Bioinformatics analysis suggests that HsiC1 displays similarities to gp18-like proteins in its C-terminal region. In conclusion, we provide further structural and mechanistic insights into the T6SS and show that a phage sheathlike structure is likely to be a conserved element across all T6SSs. PMID:23341461

WATER IN COMETS 71P/CLARK AND C/2004 B1 (LINEAR) WITH SPITZER