Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network.

PubMed

Wei, Shu; Gruber, Margaret Y; Yu, Bianyun; Gao, Ming-Jun; Khachatourians, George G; Hegedus, Dwayne D; Parkin, Isobel A P; Hannoufa, Abdelali

2012-09-18

The Arabidopsis microRNA156 (miR156) regulates 11 members of the SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) family by base pairing to complementary target mRNAs. Each SPL gene further regulates a set of other genes; thus, miR156 controls numerous genes through a complex gene regulation network. Increased axillary branching occurs in transgenic Arabidopsis overexpressing miR156b, similar to that observed in loss-of-function max3 and max4 mutants with lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to enhance carotenoid levels and reproductive shoot branching when expressed in Brassica napus, suggesting a link between miR156b expression and carotenoid metabolism. However, details of the miR156 regulatory network of SPL genes related to carotenoid metabolism are not known. In this study, an Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered branching and trichome morphology and increased seed carotenoid levels compared to wild type (WT) ecovar Columbia. Enhanced miR156b expression due to the 35S enhancers present on the T-DNA insert was responsible for these phenotypes. Constitutive and leaf primodium-specific expression of a miR156-insensitive (mutated) SPL15 (SPL15m) largely restored WT seed carotenoid levels and plant morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15 (SPL15n) and SPL15m driven by a native SPL15 promoter did not restore the WT phenotype in sk156. Our findings suggest that SPL15 function is somewhat redundant with other SPL family members, which collectively affect plant phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156 expressing SPL15m, together with the presence of multiple repeats of SPL-binding GTAC core sequence close to the miR156b transcription start site, suggested feedback regulation of miR156b expression by SPL15. This was supported by the demonstration of specific in vitro interaction between DNA-binding SBP domain of SPL15

Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis.

PubMed

Braun, Sandra; Berg, Christoph; Buck, Sandra; Gregor, Michael; Klein, Reinhild

2010-02-28

To search for further immunodominant peptides of the pyruvate dehydrogenase complex E2-component (PDC-E2) recognized by antimitochondrial antibodies (AMA) in primary biliary cirrhosis (PBC). Sera from 95 patients with PBC were tested by enzyme-linked immunosorbent assay against 33 synthetic overlapping peptides (25 amino acids; aa) covering the entire length of the E2-subunit of PDC-E2. Furthermore, the inner lipoyl peptide 167-184 was used in an unlipoylated and a lipoylated form as well as coupled to ovalbumin. Sera from 11 AMA negative/ANA positive PBC patients, 63 patients with other liver disorders and 22 healthy blood donors served as controls. Of the 95 PBC-sera, 74% reacted with the peptide 475-499 and 58% with the peptide 407-431 located within the catalytic domain of PDC-E2. Patients with other disorders or healthy controls were positive in only up to 18%. Antibodies to the unlipoylated and lipoylated peptide 167-184 within the inner lipoyl domain were found in only 5% and 11% of the PBC sera, respectively; using ovalbumin-coupled peptides, the incidence increased up to 57% (unlipoylated form). Peptides within the catalytic site of PDC-E2 rather than the previously reported lipoyl binding peptide 167-184 may represent major immunodominant epitopes recognized by AMA in PBC.

Transit Recovery of Kepler-167e: Providing JWST with an Unprecedented Jupiter-analog Exoplanet Target

NASA Astrophysics Data System (ADS)

Dalba, Paul; Muirhead, Philip; Tamburo, Patrick

2018-05-01

The Kepler Mission has uncovered a handful of long-period transiting exoplanets that orbit in the cold outer reaches of their systems, despite their low transit probabilities. Recent work suggests that cold gas giant exoplanet atmospheres are amenable to transmission spectroscopy (the analysis of the transit depth versus wavelength) enabling novel tests of planetary formation and evolution theories. Of particular scientific interest is Kepler-167e, a low-eccentricity Jupiter-analog exoplanet with a 1,071-day orbital period residing well beyond the snow-line. Transmission spectroscopy of Kepler-167e from JWST can reveal the composition of this planet's atmosphere, constrain its heavy-element abundance, and identify atmospheric photochemical processes. JWST characterization also enables unprecedented direct comparison with Jupiter and Saturn, which show a striking diversity in physical properties that is best investigated through comparative exoplanetology. Since Kepler only observed two transits of Kepler-167e, it is not known if this exoplanet exhibits transit timing variations (TTVs). About half of Kepler's long-period exoplanets have TTVs of up to 40 hours. Such a large uncertainty jeopardizes attempts to characterize the atmosphere of this unique Jovian exoplanet with JWST. To mitigate this risk, the upcoming third transit of Kepler-167e must be observed to test for TTVs. We propose a simple 10-hour, single-channel observation to capture ingress or egress of the next transit of Kepler-167e in December 2018. In the absence of TTVs, our observation will reduce the ephemeris uncertainty from an unknown value to approximately 3 minutes, thereby removing the risk in future transit observations with JWST. The excellent photometric precision of Spitzer is sufficient to identify the transit of Kepler-167e. Given the timing and nature of this program, Spitzer is the only observatory--on the ground or in space--that can make this pivotal observation.

Helicity of short E-R/K peptides.

PubMed

Sommese, Ruth F; Sivaramakrishnan, Sivaraj; Baldwin, Robert L; Spudich, James A

2010-10-01

Understanding the secondary structure of peptides is important in protein folding, enzyme function, and peptide-based drug design. Previous studies of synthetic Ala-based peptides (>12 a.a.) have demonstrated the role for charged side chain interactions involving Glu/Lys or Glu/Arg spaced three (i, i + 3) or four (i, i + 4) residues apart. The secondary structure of short peptides (<9 a.a.), however, has not been investigated. In this study, the effect of repetitive Glu/Lys or Glu/Arg side chain interactions, giving rise to E-R/K helices, on the helicity of short peptides was examined using circular dichroism. Short E-R/K-based peptides show significant helix content. Peptides containing one or more E-R interactions display greater helicity than those with similar E-K interactions. Significant helicity is achieved in Arg-based E-R/K peptides eight, six, and five amino acids long. In these short peptides, each additional i + 3 and i + 4 salt bridge has substantial contribution to fractional helix content. The E-R/K peptides exhibit a strongly linear melt curve indicative of noncooperative folding. The significant helicity of these short peptides with predictable dependence on number, position, and type of side chain interactions makes them an important consideration in peptide design.

A simple and low-cost platform technology for producing pexiganan antimicrobial peptide in E. coli.

PubMed

Zhao, Chun-Xia; Dwyer, Mirjana Dimitrijev; Yu, Alice Lei; Wu, Yang; Fang, Sheng; Middelberg, Anton P J

2015-05-01

Antimicrobial peptides, as a new class of antibiotics, have generated tremendous interest as potential alternatives to classical antibiotics. However, the large-scale production of antimicrobial peptides remains a significant challenge. This paper reports a simple and low-cost chromatography-free platform technology for producing antimicrobial peptides in Escherichia coli (E. coli). A fusion protein comprising a variant of the helical biosurfactant protein DAMP4 and the known antimicrobial peptide pexiganan is designed by joining the two polypeptides, at the DNA level, via an acid-sensitive cleavage site. The resulting DAMP4(var)-pexiganan fusion protein expresses at high level and solubility in recombinant E. coli, and a simple heat-purification method was applied to disrupt cells and deliver high-purity DAMP4(var)-pexiganan protein. Simple acid cleavage successfully separated the DAMP4 variant protein and the antimicrobial peptide. Antimicrobial activity tests confirmed that the bio-produced antimicrobial peptide has the same antimicrobial activity as the equivalent product made by conventional chemical peptide synthesis. This simple and low-cost platform technology can be easily adapted to produce other valuable peptide products, and opens a new manufacturing approach for producing antimicrobial peptides at large scale using the tools and approaches of biochemical engineering. © 2014 Wiley Periodicals, Inc.

A Signal Peptide Derived from hsp60 Binds HLA-E and Interferes with CD94/NKG2A Recognition

PubMed Central

Michaëlsson, Jakob; Teixeira de Matos, Cristina; Achour, Adnane; Lanier, Lewis L.; Kärre, Klas; Söderström, Kalle

2002-01-01

Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical major histocompatibility complex (MHC) class I molecule which presents a restricted set of nonameric peptides, derived mainly from the signal sequence of other MHC class I molecules. It interacts with CD94/NKG2 receptors expressed on the surface of natural killer (NK) cells and T cell subsets. Here we demonstrate that HLA-E also presents a peptide derived from the leader sequence of human heat shock protein 60 (hsp60). This peptide gains access to HLA-E intracellularly, resulting in up-regulated HLA-E/hsp60 signal peptide cell-surface levels on stressed cells. Notably, HLA-E molecules in complex with the hsp60 signal peptide are no longer recognized by CD94/NKG2A inhibitory receptors. Thus, during cellular stress an increased proportion of HLA-E molecules may bind the nonprotective hsp60 signal peptide, leading to a reduced capacity to inhibit a major NK cell population. Such stress induced peptide interference would gradually uncouple CD94/NKG2A inhibitory recognition and provide a mechanism for NK cells to detect stressed cells in a peptide-dependent manner. PMID:12461076

Dynamic Interaction- and Phospho-Proteomics Reveal Lck as a Major Signaling Hub of CD147 in T Cells.

PubMed

Supper, Verena; Hartl, Ingrid; Boulègue, Cyril; Ohradanova-Repic, Anna; Stockinger, Hannes

2017-03-15

Numerous publications have addressed CD147 as a tumor marker and regulator of cytoskeleton, cell growth, stress response, or immune cell function; however, the molecular functionality of CD147 remains incompletely understood. Using affinity purification, mass spectrometry, and phosphopeptide enrichment of isotope-labeled peptides, we examined the dynamic of the CD147 microenvironment and the CD147-dependent phosphoproteome in the Jurkat T cell line upon treatment with T cell stimulating agents. We identified novel dynamic interaction partners of CD147 such as CD45, CD47, GNAI2, Lck, RAP1B, and VAT1 and, furthermore, found 76 CD147-dependent phosphorylation sites on 57 proteins. Using the STRING protein network database, a network between the CD147 microenvironment and the CD147-dependent phosphoproteins was generated and led to the identification of key signaling hubs around the G proteins RAP1B and GNB1, the kinases PKCβ, PAK2, Lck, and CDK1, and the chaperone HSPA5. Gene ontology biological process term analysis revealed that wound healing-, cytoskeleton-, immune system-, stress response-, phosphorylation- and protein modification-, defense response to virus-, and TNF production-associated terms are enriched within the microenvironment and the phosphoproteins of CD147. With the generated signaling network and gene ontology biological process term grouping, we identify potential signaling routes of CD147 affecting T cell growth and function. Copyright © 2017 by The American Association of Immunologists, Inc.

Decreased Sensitivity to Changes in the Concentration of Metal Ions as the Basis for the Hyperactivity of DtxR(E175K)

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

D’Aquino, J. Alejandro; Denninger, Andrew R.; Moulin, Aaron G.

2010-01-12

The metal-ion-activated diphtheria toxin repressor (DtxR) is responsible for the regulation of virulence and other genes in Corynebacterium diphtheriae. A single point mutation in DtxR, DtxR(E175K), causes this mutant repressor to have a hyperactive phenotype. Mice infected with Mycobacterium tuberculosis transformed with plasmids carrying this mutant gene show reduced signs of the tuberculosis infection. Corynebacterial DtxR is able to complement mycobacterial IdeR and vice versa. To date, an explanation for the hyperactivity of DtxR(E175K) has remained elusive. In an attempt to address this issue, we have solved the first crystal structure of DtxR(E175K) and characterized this mutant using circular dichroism,more » isothermal titration calorimetry, and other biochemical techniques. The results show that although DtxR(E175K) and the wild type have similar secondary structures, DtxR(E175K) gains additional thermostability upon activation with metal ions, which may lead to this mutant requiring a lower concentration of metal ions to reach the same levels of thermostability as the wild-type protein. The E175K mutation causes binding site 1 to retain metal ion bound at all times, which can only be removed by incubation with an ion chelator. The crystal structure of DtxR(E175K) shows an empty binding site 2 without evidence of oxidation of Cys102. The association constant for this low-affinity binding site of DtxR(E175K) obtained from calorimetric titration with Ni(II) is K{sub a} = 7.6 {+-} 0.5 x 10{sup 4}, which is very similar to the reported value for the wild-type repressor, K{sub a} = 6.3 x 10{sup 4}. Both the wild type and DtxR(E175K) require the same amount of metal ion to produce a shift in the electrophoretic mobility shift assay, but unlike the wild type, DtxR(E175K) binding to its cognate DNA [tox promoter-operator (toxPO)] does not require metal-ion supplementation in the running buffer. In the timescale of these experiments, the Mn(II)-DtxR(E175K

CD147 Induces Epithelial-to-Mesenchymal Transition by Disassembling Cellular Apoptosis Susceptibility Protein/E-Cadherin/β-Catenin Complex in Human Endometriosis.

PubMed

Wang, Chaoqun; Zhang, Jieting; Fok, Kin Lam; Tsang, Lai Ling; Ye, Mei; Liu, Jianni; Li, Fanghong; Zhao, Allan Zijian; Chan, Hsiao Chang; Chen, Hao

2018-04-06

Epithelial-to-mesenchymal transition (EMT) is postulated to be a prerequisite for the establishment of endometriosis (EMS), a common reproductive disorder in women. Our previous studies have demonstrated the elevated expression of transmembrane glycoprotein CD147 and its prosurvival effect on abnormal cells in endometriosis. Intriguingly, CD147 is known to promote EMT in cancers. However, the involvement of CD147 in EMT during the establishment of endometriosis remains incompletely understood. We found that CD147 promotes EMT in human endometrial adenocarcinoma cell line Ishikawa. We identified a novel CD147-interacting partner, cellular apoptosis susceptibility protein (CAS), which stabilized the interaction between E-cadherin (E-cad) and β-catenin (β-cat) by forming the CAS/E-cad/β-cat complex. Down-regulation of CAS led to the release and nuclear translocation of β-cat from E-cad, resulting in the overexpression of the EMT-promoting gene SNAIL. Interestingly, overexpression of CD147 impaired the interaction between CAS and E-cad and triggered the release of β-cat from the CAS/E-cad/β-cat complex, which in turn led to EMT. Furthermore, CAS was down-regulated in EMS, with elevated levels of CD147 and nuclear β-cat. These findings suggest a previously undefined role of CAS in regulating EMT and reveal the involvement of a CD147-induced EMT signaling pathway in pathogenic progression of EMS. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Clinical Significance of Soluble Hemoglobin Scavenger Receptor CD163 (sCD163) in Sepsis, a Prospective Study

PubMed Central

Feng, Lin; Zhou, Xin; Su, Long-Xiang; Feng, Dan; Jia, Yan-Hong; Xie, Li-Xin

2012-01-01

Objective We investigated serum soluble CD163 (sCD163) levels for use in the diagnosis, severity assessment, and prognosis of sepsis in the critical ill patients and compared sCD163 with other infection-related variables. Methods During july 2010 and April 2011, serum was obtained from 102 sepsis patients (days 1, 3, 5, 7, and 10 after admission to an ICU) and 30 systemic inflammatory response syndrome (SIRS) patients with no sepsis diagnosed. Serum levels of sCD163, procalcitonon (PCT), and C reactive protein (CRP) were determined respectively. Sequential organ failure assessment (SOFA) scores for sepsis patients were also recorded. Then evaluated their roles in sepsis. Results The sCD163 levels were 0.88(0.78–1.00)ug/mL for SIRS patients, 1.50(0.92–2.00)ug/mL for moderate sepsis patients, and 2.95(2.18–5.57)ug/mL for severe sepsis patients on day1. The areas under the ROC curves for sCD163, CRP, and PCT for the diagnosis of sepsis were, respectively, 0.856(95%CI: 0.791–0.921), 0.696(95%CI: 0.595–0.797), and 0.629(95%CI: 0.495–0.763), At the recommended cut-off 1.49 ug/mL for sCD163, the sensitivity is 74.0% with 93.3% specificity. Based on 28-day survivals, sCD163 levels in the surviving group stay constant, while they tended to gradually increase in the non-surviving group.The area under the ROC curve for sCD163 for sepsis prognosis was 0.706(95%CI 0.558–0.804). Levels of sCD163 with cut-off point >2.84 ug/mL have sensitivity of 55.8.0%, specificity 80.4%.Common risk factors for death and sCD163 were included in multivariate logistic regression analysis; the odds ratios (OR) for sCD163 and SOFA scores for sepsis prognosis were 1.173 and 1.396, respectively (P<0.05). Spearman rank correlation analysis showed that sCD163 was weakly, but positively correlated with CRP, PCT, and SOFA scores (0.2< r <0.4, P<0.0001), but not with leukocyte counts (r <0.2, P = 0.450). Conclusion Serum sCD163 is superior to PCT and CRP for the diagnosis of sepsis and

Cross-Section Measurement of the 169Tm(n,3n)167Tm Reaction and Constraining the Branching Ratio of 167Tm

NASA Astrophysics Data System (ADS)

Champine, Brian; Gooden, Matthew; Thomas, Keenan; Krishichayan, F.; Norman, Eric; Scielzo, Nick; Tonchev, Anton; Tornow, Werner

2015-10-01

The cross section of the 169Tm(n,3n)167Tm reaction has been measured from 17.5 to 21.5 MeV using activation technique. This energy region was chosen to resolve the two different trends of the previous (n,3n) cross section measurements on 169Tm. In addition, the branching ratio of the 207.8 keV γ-ray line stemming from electron capture of 167Tm was measured to be 0.419(16). The result of these measurements provide more accurate diagnostic estimation of the so called reaction-in-flight neutrons produced via the internal confinement fusion plasma in deuterium-tritium capsules at the National Ignition Facility.

26 CFR 1.56A-5 - Tax carryovers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 1 2011-04-01 2009-04-01 true Tax carryovers. 1.56A-5 Section 1.56A-5 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Regulations Applicable to Taxable Years Beginning in 1969 and Ending in 1970 § 1.56A-5 Tax carryovers. (a) In general...

HLA-E: Presentation of a Broader Peptide Repertoire Impacts the Cellular Immune Response-Implications on HSCT Outcome.

PubMed

Kraemer, Thomas; Celik, Alexander A; Huyton, Trevor; Kunze-Schumacher, Heike; Blasczyk, Rainer; Bade-Döding, Christina

2015-01-01

The HLA-E locus encodes a nonclassical class Ib molecule that serves many immune functions from inhibiting NK cells to activating CTLs. Structural analysis of HLA-E/NKG2A complexes visualized fine-tuning of protective immune responses through AA interactions between HLA-E, the bound peptide, and NKG2A/CD94. A loss of cellular protection through abrogation of the HLA-E/NKG2A engagement is dependent on the HLA-E bound peptide. The role of HLA-E in posttransplant outcomes is not well understood but might be attributed to its peptide repertoire. To investigate the self-peptide repertoire of HLA-E (∗) 01:01 in the absence of protective HLA class I signal peptides, we utilized soluble HLA technology in class I negative LCL cells in order to characterize HLA-E (∗) 01:01-bound ligands by mass-spectrometry. To understand the immunological impact of these analyzed ligands on NK cell reactivity, we performed cellular assays. Synthesized peptides were loaded onto recombinant T2 cells expressing HLA-E (∗) 01:01 molecules and applied in cytotoxicity assays using the leukemia derived NK cell line (NKL) as effector. HLA-E in complex with the self-peptides demonstrated a shift towards cytotoxicity and a loss of cell protection. Our data highlights the fact that the HLA-E-peptidome is not as restricted as previously thought and support the suggestion of a posttransplant role for HLA-E.

46 CFR 147A.7 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Definitions. 147A.7 Section 147A.7 Shipping COAST GUARD... General § 147A.7 Definitions. As used in this part: (a) Qualified person means a person who has experience... particulate matter may remain in the space that is fumigated. (c) Fumigation means the application of a...

46 CFR 147A.7 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Definitions. 147A.7 Section 147A.7 Shipping COAST GUARD... General § 147A.7 Definitions. As used in this part: (a) Qualified person means a person who has experience... particulate matter may remain in the space that is fumigated. (c) Fumigation means the application of a...

46 CFR 147A.7 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Definitions. 147A.7 Section 147A.7 Shipping COAST GUARD... General § 147A.7 Definitions. As used in this part: (a) Qualified person means a person who has experience... particulate matter may remain in the space that is fumigated. (c) Fumigation means the application of a...

Ultrahigh-resolution γ-ray spectroscopy of 156Gd: a test of tetrahedral symmetry.

PubMed

Jentschel, M; Urban, W; Krempel, J; Tonev, D; Dudek, J; Curien, D; Lauss, B; de Angelis, G; Petkov, P

2010-06-04

Tetrahedral symmetry in strongly interacting systems would establish a new class of quantum effects at subatomic scale. Excited states in 156Gd that could carry the information about the tetrahedral symmetry were populated in the 155Gd(n,γ)156Gd reaction and studied using the GAMS4/5 Bragg spectrometers at the Institut Laue-Langevin. We have identified the 5(1)- → 3(1)- transition of 131.983(12) keV in 156Gd and determined its intensity to be 1.9(3)x10(-6) per neutron capture. The lifetime τ=220(-30)(+180) fs of the 5(1)- state in 156Gd has been measured using the GRID technique. The resulting B(E2)=293(-134)(+6) Weisskopf unit rate of the 131.983 keV transition provides the intrinsic quadrupole moment of the 5(1)- state in 156Gd to be Q0=7.1(-1.6)(+0.7) b. This large value, comparable to the quadrupole moment of the ground state in 156Gd, gives strong evidence against tetrahedral symmetry in the lowest odd-spin, negative-parity band of 156Gd.

75 FR 58012 - 30-Day Notice of Proposed Information Collection: DS-156E Nonimmigrant Treaty Trader/Investor...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-23

... Information Collection: DS-156E Nonimmigrant Treaty Trader/Investor Application ACTION: Notice of request for... Collection: Nonimmigrant Treaty Trader/Investor Application. OMB Control Number: 1405-0101. Type of Request... State (CA/VO). Form Number: DS-156E. Respondents: Nonimmigrant treaty trader/investor visa applicants...

75 FR 25909 - 60-Day Notice of Proposed Information Collection: Form DS-156K, Nonimmigrant Fiancé(e) Visa...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

...-156K, Nonimmigrant Fianc[eacute](e) Visa Application, OMB Control Number 1405-0096 ACTION: Notice of...: Nonimmigrant Fianc[eacute](e) Visa Application. OMB Control Number: 1405-0096. Type of Request: Extension of a... State (CA/VO). Form Number: DS-156K. Respondents: Aliens applying for a nonimmigrant visa to enter the U...

Endothelin-1 stimulates catalase activity through the PKCδ mediated phosphorylation of Serine 167

PubMed Central

Rafikov, Ruslan; Kumar, Sanjiv; Aggarwal, Saurabh; Hou, Yali; Kangath, Archana; Pardo, Daniel; Fineman, Jeffrey R.; Black, Stephen M.

2013-01-01

Our previous studies have shown that endothelin-1 (ET-1) stimulates catalase activity in endothelial cells and lambs with acute increases in pulmonary blood flow (PBF), without altering gene expression. The purpose of this study was to investigate the molecular mechanism by which this occurs. Exposing pulmonary arterial endothelial cells (PAEC) to ET-1 increased catalase activity and decreased cellular hydrogen peroxide (H2O2) levels. These changes correlated with an increase in serine phosphorylated catalase. Using the inhibitory peptide δV1.1, this phosphorylation was shown to be PKCδ dependent. Mass spectrometry identified serine167 as the phosphorylation site. Site-directed mutagenesis was used to generate a phospho-mimic (S167D) catalase. Activity assays using recombinant protein purified from E.coli or transiently transfected COS-7 cells, demonstrated that S167D-catalase had an increased ability to degrade H2O2 compared to the wildtype enzyme. Using a phospho-specific antibody, we were able to verify that pS167 catalase levels are modulated in lambs with acute increases in PBF in the presence and absence of the ET receptor antagonist, tezosentan. S167 is being located on the dimeric interface suggesting it could be involved in regulating the formation of catalase tetramers. To evaluate this possibility we utilized analytical gel-filtration to examine the multimeric structure of recombinant wildtype- and S167D-catalase. We found that recombinant wildtype catalase was present as a mixture of monomers and dimers while S167D catalase was primarily tetrameric. Further, the incubation of wildtype catalase with PKCδ was sufficient to convert wildtype catalase into a tetrameric structure. In conclusion, this is the first report indicating that the phosphorylation of catalase regulates its multimeric structure and activity. PMID:24211614

46 CFR 147A.3 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Applicability. 147A.3 Section 147A.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.3 Applicability. This part prescribes the rules for shipboard fumigation on vessels...

46 CFR 147A.3 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Applicability. 147A.3 Section 147A.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.3 Applicability. This part prescribes the rules for shipboard fumigation on vessels...

46 CFR 147A.3 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Applicability. 147A.3 Section 147A.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.3 Applicability. This part prescribes the rules for shipboard fumigation on vessels...

46 CFR 147A.3 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Applicability. 147A.3 Section 147A.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.3 Applicability. This part prescribes the rules for shipboard fumigation on vessels...

46 CFR 147A.3 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Applicability. 147A.3 Section 147A.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.3 Applicability. This part prescribes the rules for shipboard fumigation on vessels...

46 CFR 147A.25 - Entry.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Entry. 147A.25 Section 147A.25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.25 Entry. (a) No person may enter the spaces that immediately adjoin the space...

46 CFR 147A.25 - Entry.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Entry. 147A.25 Section 147A.25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.25 Entry. (a) No person may enter the spaces that immediately adjoin the space...

46 CFR 147A.25 - Entry.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Entry. 147A.25 Section 147A.25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.25 Entry. (a) No person may enter the spaces that immediately adjoin the space...

46 CFR 147A.1 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Purpose. 147A.1 Section 147A.1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.1 Purpose. The purpose of this part is to prescribe the requirements for shipboard...

46 CFR 147A.1 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Purpose. 147A.1 Section 147A.1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.1 Purpose. The purpose of this part is to prescribe the requirements for shipboard...

46 CFR 147A.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Purpose. 147A.1 Section 147A.1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.1 Purpose. The purpose of this part is to prescribe the requirements for shipboard...

46 CFR 147A.1 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Purpose. 147A.1 Section 147A.1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.1 Purpose. The purpose of this part is to prescribe the requirements for shipboard...

46 CFR 147A.1 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Purpose. 147A.1 Section 147A.1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.1 Purpose. The purpose of this part is to prescribe the requirements for shipboard...

E-Peptides Control Bioavailability of IGF-1

PubMed Central

Piszczek, Agnieszka; Perlas, Emarald; Winn, Nadine; Nastasi, Tommaso; Rosenthal, Nadia

2012-01-01

Insulin-like growth factor 1 (IGF-1) is a potent cytoprotective growth factor that has attracted considerable attention as a promising therapeutic agent. Transgenic over-expression of IGF-1 propeptides facilitates protection and repair in a broad range of tissues, although transgenic mice over-expressing IGF-1 propeptides display little or no increase in IGF-1 serum levels, even with high levels of transgene expression. IGF-1 propeptides are encoded by multiple alternatively spliced transcripts including C-terminal extension (E) peptides, which are highly positively charged. In the present study, we use decellularized mouse tissue to show that the E-peptides facilitate in vitro binding of murine IGF-1 to the extracellular matrix (ECM) with varying affinities. This property is independent of IGF-1, since proteins consisting of the E-peptides fused to relaxin, a related member of the insulin superfamily, bound equally avidly to decellularized ECM. Thus, the E-peptides control IGF-1 bioavailability by preventing systemic circulation, offering a potentially powerful way to tether IGF-1 and other therapeutic proteins to the site of synthesis and/or administration. PMID:23251442

26 CFR 1.56A-1 - Imposition of tax.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Imposition of tax. 1.56A-1 Section 1.56A-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Regulations Applicable to Taxable Years Beginning in 1969 and Ending in 1970 § 1.56A-1 Imposition of tax. (a) In general...

Development of a Targeted Urine Proteome Assay for kidney diseases.

PubMed

Cantley, Lloyd G; Colangelo, Christopher M; Stone, Kathryn L; Chung, Lisa; Belcher, Justin; Abbott, Thomas; Cantley, Jennifer L; Williams, Kenneth R; Parikh, Chirag R

2016-01-01

Since human urine is the most readily available biofluid whose proteome changes in response to disease, it is a logical sample for identifying protein biomarkers for kidney diseases. Potential biomarkers were identified by using a multiproteomics workflow to compare urine proteomes of kidney transplant patients with immediate and delayed graft function. Differentially expressed proteins were identified, and corresponding stable isotope labeled internal peptide standards were synthesized for scheduled MRM. The Targeted Urine Proteome Assay (TUPA) was then developed by identifying those peptides for which there were at least two transitions for which interference in a urine matrix across 156 MRM runs was <30%. This resulted in an assay that monitors 224 peptides from 167 quantifiable proteins. TUPA opens the way for using a robust mass spectrometric technology, MRM, for quantifying and validating biomarkers from among 167 urinary proteins. This approach, while developed using differentially expressed urinary proteins from patients with delayed versus immediate graft function after kidney transplant, can be expanded to include differentially expressed urinary proteins in multiple kidney diseases. Thus, TUPA could provide a single assay to help diagnose, prognose, and manage many kidney diseases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

26 CFR 1.167(a)-1 - Depreciation in general.

Code of Federal Regulations, 2012 CFR

2012-04-01

... salvage value, will, at the end of the estimated useful life of the depreciable property, equal the cost... depreciated below a reasonable salvage value under any method of computing depreciation. However, see section 167(f) and § 1.167(f)-1 for rules which permit a reduction in the amount of salvage value to be taken...

26 CFR 1.167(a)-1 - Depreciation in general.

Code of Federal Regulations, 2011 CFR

2011-04-01

... salvage value, will, at the end of the estimated useful life of the depreciable property, equal the cost... depreciated below a reasonable salvage value under any method of computing depreciation. However, see section 167(f) and § 1.167(f)-1 for rules which permit a reduction in the amount of salvage value to be taken...

26 CFR 1.167(a)-1 - Depreciation in general.

Code of Federal Regulations, 2014 CFR

2014-04-01

... salvage value, will, at the end of the estimated useful life of the depreciable property, equal the cost... depreciated below a reasonable salvage value under any method of computing depreciation. However, see section 167(f) and § 1.167(f)-1 for rules which permit a reduction in the amount of salvage value to be taken...

26 CFR 1.167(a)-1 - Depreciation in general.

Code of Federal Regulations, 2013 CFR

2013-04-01

... salvage value, will, at the end of the estimated useful life of the depreciable property, equal the cost... depreciated below a reasonable salvage value under any method of computing depreciation. However, see section 167(f) and § 1.167(f)-1 for rules which permit a reduction in the amount of salvage value to be taken...

The flexibility of two tropomyosin mutants, D175N and E180G, that cause hypertrophic cardiomyopathy

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

Li, Xiaochuan; Suphamungmee, Worawit; Janco, Miro

2012-08-03

Highlights: Black-Right-Pointing-Pointer Well-known tropomyosin mutants, D175N and E180G are linked to cardiomyopathies. Black-Right-Pointing-Pointer The structural mechanics of D175N and E180G tropomyosins have been investigated. Black-Right-Pointing-Pointer D175N and E180G mutations increase both local and global tropomyosin flexibility. Black-Right-Pointing-Pointer In muscle, this increased flexibility will enhance myosin interactions on actin. Black-Right-Pointing-Pointer Extra myosin interaction can alter cardiac Ca{sup 2+}-switching, leading to dysfunction. -- Abstract: Point mutations targeting muscle thin filament proteins are the cause of a number of cardiomyopathies. In many cases, biological effects of the mutations are well-documented, whereas their structural and mechanical impact on filament assembly and regulatory function ismore » lacking. In order to elucidate molecular defects leading to cardiac dysfunction, we have examined the structural mechanics of two tropomyosin mutants, E180G and D175N, which are associated with hypertrophic cardiomyopathy (HCM). Tropomyosin is an {alpha}-helical coiled-coil dimer which polymerizes end-to-end to create an elongated superhelix that wraps around F-actin filaments of muscle and non-muscle cells, thus modulating the binding of other actin-binding proteins. Here, we study how flexibility changes in the E180G and D175N mutants might affect tropomyosin binding and regulatory motion on F-actin. Electron microscopy and Molecular Dynamics simulations show that E180G and D175N mutations cause an increase in bending flexibility of tropomyosin both locally and globally. This excess flexibility is likely to increase accessibility of the myosin-binding sites on F-actin, thus destabilizing the low-Ca{sup 2+} relaxed-state of cardiac muscle. The resulting imbalance in the on-off switching mechanism of the mutants will shift the regulatory equilibrium towards Ca{sup 2+}-activation of cardiac muscle, as is observed in

Application of E75 peptide vaccine in breast cancer patients: a systematic review and meta-analysis.

PubMed

Chamani, Reyhane; Ranji, Peyman; Hadji, Maryam; Nahvijou, Azin; Esmati, Ebrahim; Alizadeh, Ali Mohammad

2018-05-09

The E75 peptide vaccine, derived from tumor-associated antigen HER2, is the most frequently studied anti-HER2 vaccination strategy for the treatment of breast cancer patients. It has been investigated in the several phases Ι/Π of the clinical trials and is currently being evaluated in a randomized multicenter phase III clinical trial. We conducted a systematic review and meta-analysis to clarify the outcomes of the E75 peptide vaccine including the therapeutic efficacy, the disease recurrence, the survival rate, and the side effects. Three peer-reviewed literature databases including the PubMed, Web of Science, and Scopus were sought. Of 29 trials assessed for eligibility, 16 were considered based on our inclusion criteria. Statistical analyses were performed by The Excel and STATA v.11.0. Meta-analysis of delayed-type hypersensitivity)DTH( reactions and CD8 + -T cell levels, as immune responses, displayed the significant differences in the vaccinated groups compared to their non-vaccinated counterparts. In addition, the recurrence, and the overall and the disease-free survival were significantly different in the vaccinated subjects versus the control. Evaluation of the local and systemic toxicity of the E75 peptide vaccine demonstrated the minimal side effects. It seems that the E75 peptide vaccine is safe and effective, and can be used for further randomized clinical trials. Copyright © 2018. Published by Elsevier B.V.

N-terminal modifications improve the receptor affinity and pharmacokinetics of radiolabeled peptidic gastrin-releasing peptide receptor antagonists: examples of 68Ga- and 64Cu-labeled peptides for PET imaging.

PubMed

Gourni, Eleni; Mansi, Rosalba; Jamous, Mazen; Waser, Beatrice; Smerling, Christiane; Burian, Antje; Buchegger, Franz; Reubi, Jean Claude; Maecke, Helmut R

2014-10-01

Gastrin-releasing peptide receptors (GRPrs) are overexpressed on a variety of human cancers, providing the opportunity for peptide receptor targeting via radiolabeled bombesin-based peptides. As part of our ongoing investigations into the development of improved GRPr antagonists, this study aimed at verifying whether and how N-terminal modulations improve the affinity and pharmacokinetics of radiolabeled GRPr antagonists. The potent GRPr antagonist MJ9, Pip-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH(2) (Pip, 4-amino-1-carboxymethyl-piperidine), was conjugated to 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA), and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and radiolabeled with (68)Ga and (64)Cu. The GRPr affinity of the corresponding metalloconjugates was determined using (125)I-Tyr(4)-BN as a radioligand. The labeling efficiency of (68)Ga(3+) was compared between NODAGA-MJ9 and NOTA-MJ9 in acetate buffer, at room temperature and at 95°C. The (68)Ga and (64)Cu conjugates were further evaluated in vivo in PC3 tumor xenografts by biodistribution and PET imaging studies. The half maximum inhibitory concentrations of all the metalloconjugates are in the high picomolar-low nanomolar range, and these are the most affine-radiolabeled GRPr antagonists we have studied so far in our laboratory. NODAGA-MJ9 incorporates (68)Ga(3+) nearly quantitatively (>98%) at room temperature within 10 min and at much lower peptide concentrations (1.4 × 10(-6) M) than NOTA-MJ9, for which the labeling yield was approximately 45% under the same conditions and increased to 75% at 95°C for 5 min. Biodistribution studies showed high and specific tumor uptake, with a maximum of 23.3 ± 2.0 percentage injected activity per gram of tissue (%IA/g) for (68)Ga-NOTA-MJ9 and 16.7 ± 2.0 %IA/g for (68)Ga-NODAGA-MJ9 at 1 h after injection. The acquisition of PET images with the (64)Cu-MJ9 conjugates at later time points clearly showed the efficient clearance of the accumulated

46 CFR 147A.5 - General requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false General requirement. 147A.5 Section 147A.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.5 General requirement. No person may cause or authorize shipboard...

46 CFR 147A.5 - General requirement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false General requirement. 147A.5 Section 147A.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.5 General requirement. No person may cause or authorize shipboard...

46 CFR 147A.5 - General requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false General requirement. 147A.5 Section 147A.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.5 General requirement. No person may cause or authorize shipboard...

46 CFR 147A.5 - General requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false General requirement. 147A.5 Section 147A.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.5 General requirement. No person may cause or authorize shipboard...

46 CFR 147A.5 - General requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false General requirement. 147A.5 Section 147A.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.5 General requirement. No person may cause or authorize shipboard...

Multiparticle jets from π+/K+/p p collisions at 147 GeV/C compared to e+e- annihilations

NASA Astrophysics Data System (ADS)

Ratti, Sergio P.

1981-02-01

The data presented here have been collected by the International Hybrid Spectrometer Consortium in the 30″ B.C. hybrid spectrometer exposed to a 147 GeV/C positive tagged beam made of 47% π+; 45% p; 8% K+(?s = 16.7 GeV) at Fermilab. The sample consists of 15802 events with at least 4 prongs (11822 events with at least 6 prongs) fully measured and reconstructed with an accuracy Δp/p<0.5%. To account for second-measurements still to be done, the events are weighted according to the measured topological cross sections. The variables used (Sphericity S and thrust T) are evaluated in a 3-dimensional c.m. momentum space defined by the principal axes resulting from the diagonalization of the 3×3 matrix Tαβ = ∑i[p2iδαβ-pαipβi]; α,β = x,y,z; pxi,pyi,pzi are the c.m. momentum components of particle i (x-direction along the beam). Their use in hardron hadron physics was suggested long ago.

Purification and characterization of plantaricin 163, a novel bacteriocin produced by Lactobacillus plantarum 163 isolated from traditional Chinese fermented vegetables.

PubMed

Hu, Meizhong; Zhao, Haizhen; Zhang, Chong; Yu, Jiansheng; Lu, Zhaoxin

2013-11-27

Presumptive lactic acid bacteria (LAB) strains isolated from traditional Chinese fermented vegetables were screened for bacteriocin production. A novel bacteriocin-producing strain, Lactobacillus plantarum 163, was identified on the basis of its physiobiochemical characteristics and characterized by 16S rDNA sequencing. The novel bacteriocin, plantaricin 163, produced by Lb. plantarum 163 was purified by salt precipitation, gel filtration, and reverse-phase high-performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of plantaricin 163 revealed the molecular weight to be 3553.2 Da. The complete amino acid sequence showed VFHAYSARGNYYGNCPANWPSCRNNYKSAGGK, and no similarity to known bacteriocins was found. Plantaricin 163 was highly thermostable (20 min, 121 °C), active in the presence of acidic pH (3-5), sensitive to protease, and exhibited broad-spectrum antimicrobial activity against LAB and other tested Gram-positive and Gram-negative bacteria. The results suggest that plantaricin 163 may be employed as a biopreservative in the food industry.

Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis

PubMed Central

Shin, Byung-Sik; Katoh, Takayuki; Gutierrez, Erik; Kim, Joo-Ran; Suga, Hiroaki

2017-01-01

Abstract Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline. PMID:28637321

Spontaneous adsorption of coiled-coil model peptides K and E to a mixed lipid bilayer.

PubMed

Pluhackova, Kristyna; Wassenaar, Tsjerk A; Kirsch, Sonja; Böckmann, Rainer A

2015-03-26

A molecular description of the lipid-protein interactions underlying the adsorption of proteins to membranes is crucial for understanding, for example, the specificity of adsorption or the binding strength of a protein to a bilayer, or for characterizing protein-induced changes of membrane properties. In this paper, we extend an automated in silico assay (DAFT) for binding studies and apply it to characterize the adsorption of the model fusion peptides E and K to a mixed phospholipid/cholesterol membrane using coarse-grained molecular dynamics simulations. In addition, we couple the coarse-grained protocol to reverse transformation to atomistic resolution, thereby allowing to study molecular interactions with high detail. The experimentally observed differential binding of the peptides E and K to membranes, as well as the increased binding affinity of helical over unstructered peptides, could be well reproduced using the polarizable Martini coarse-grained (CG) force field. Binding to neutral membranes is shown to be dominated by initial binding of the positively charged N-terminus to the phospholipid headgroup region, followed by membrane surface-aligned insertion of the peptide at the interface between the hydrophobic core of the membrane and its polar headgroup region. Both coarse-grained and atomistic simulations confirm a before hypothesized snorkeling of lysine side chains for the membrane-bound state of the peptide K. Cholesterol was found to be enriched in peptide vicinity, which is probably of importance for the mechanism of membrane fusion. The applied sequential multiscale method, using coarse-grained simulations for the slow adsorption process of peptides to membranes followed by backward transformation to atomistic detail and subsequent atomistic simulations of the preformed peptide-lipid complexes, is shown to be a versatile approach to study the interactions of peptides or proteins with biomembranes.

Identification, characterization, immobilization, and mutational analysis of a novel acetylesterase with industrial potential (LaAcE) from Lactobacillus acidophilus.

PubMed

Wang, Ying; Ryu, Bum Han; Yoo, Wanki; Lee, Chang Woo; Kim, Kyeong Kyu; Lee, Jun Hyuck; Kim, T Doohun

2018-01-01

Lactic acid bacteria, which are involved in the fermentation of vegetables, meats, and dairy products, are widely used for the productions of small organic molecules and bioactive peptides. Here, a novel acetylesterase (LaAcE) from Lactobacillus acidophilus NCFM was identified, functionally characterized, immobilized, and subjected to site-directed mutagenesis for biotechnological applications. The enzymatic properties of LaAcE were investigated using biochemical and biophysical methods including native polyacrylamide gel electrophoresis, acetic acid release, biochemical assays, enzyme kinetics, and spectroscopic methods. Interestingly, LaAcE exhibited the ability to act on a broad range of substrates including glucose pentaacetate, glyceryl tributyrate, fish oil, and fermentation-related compounds. Furthermore, immobilization of LaAcE showed good recycling ability and high thermal stability compared with free LaAcE. A structural model of LaAcE was used to guide mutational analysis of hydrophobic substrate-binding region, which was composed of Leu 156 , Phe 164 , and Val 204 . Five mutants (L156A, F164A, V204A, L156A/F164A, and L156A/V204A) were generated and investigated to elucidate the roles of these hydrophobic residues in substrate specificity. This work provided valuable insights into the properties of LaAcE, and demonstrated that LaAcE could be used as a model enzyme of acetylesterase in lactic acid bacteria, making LaAcE a great candidate for industrial applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of critical residues of subunit H in its interaction with subunit E of the A-ATP synthase from Methanocaldococcus jannaschii.

PubMed

Gayen, Shovanlal; Balakrishna, Asha M; Biuković, Goran; Yulei, Wu; Hunke, Cornelia; Grüber, Gerhard

2008-04-01

The boomerang-like H subunit of A(1)A(0) ATP synthase forms one of the peripheral stalks connecting the A(1) and A(0) sections. Structural analyses of the N-terminal part (H1-47) of subunit H of the A(1)A(0) ATP synthase from Methanocaldococcus jannaschii have been performed by NMR spectroscopy. Our initial NMR structural calculations for H1-47 indicate that amino acid residues 7-44 fold into a single alpha-helical structure. Using the purified N- (E1-100) and C-terminal domains (E101-206) of subunit E, NMR titration experiments revealed that the N-terminal residues Met1-6, Lys10, Glu11, Ala15, Val20 and Glu24 of H1-47 interact specifically with the N-terminal domain E1-100 of subunit E. A more detailed picture regarding the residues of E1-100 involved in this association was obtained by titration studies using the N-terminal peptides E1-20, E21-40 and E41-60. These data indicate that the N-terminal tail E41-60 interacts with the N-terminal amino acids of H1-47, and this has been confirmed by fluorescence correlation spectroscopy results. Analysis of (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra of the central stalk subunit F in the presence and absence of E101-206 show no obvious interaction between the C-terminal domain of E and subunit F. The data presented provide, for the first time, structural insights into the interaction of subunits E and H, and their arrangement within A(1)A(0) ATP synthase.

Anti-Alzheimers activity and molecular mechanism of albumin-derived peptides against AChE and BChE.

PubMed

Yu, Zhipeng; Wu, Sijia; Zhao, Wenzhu; Ding, Long; Fan, Yue; Shiuan, David; Liu, Jingbo; Chen, Feng

2018-02-21

Alzheimer's disease (AD) is a global health issue affecting millions of elderly people worldwide. The aim of the present study was to identify novel anti-AD peptides isolated from albumin. Anti-AD activities of the peptides were evaluated via inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Furthermore, the potential molecular mechanisms of the KLPGF/AChE were investigated by CDOCKER of Discovery studio 2017. The results revealed that peptide KLPGF could effectively inhibit AChE with an inhibition rate of 61.23% at a concentration of 50 μg mL -1 . In addition, the peptide KLPGF came in contact with acylation sites and peripheral anion sites of AChE. The present study demonstrates that the peptide KLPGF could become a potential functional food intervention in AD.

Novel T-cell epitopes of ovalbumin in BALB/c mouse: Potential for peptide-immunotherapy

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

Yang, Marie; Mine, Yoshinori

The identification of food allergen T-cell epitopes provides a platform for the development of novel immunotherapies. Despite extensive knowledge of the physicochemical properties of hen ovalbumin (OVA), a major egg allergen, the complete T-cell epitope map of OVA has surprisingly not been defined in the commonly used BALB/c mouse model. In this study, spleen cells obtained from OVA-sensitized mice were incubated in the presence of 12-mer overlapping synthetic peptides, constructed using the SPOTS synthesis method. Proliferative activity was assessed by 72-h in vitro assays with use of the tetrazolium salt WST-1 and led to identification of four mitogenic sequences, i.e.,more » A39R50, S147R158, K263E274, and A329E340. ELISA analyses of interferon (IFN)-{gamma} and interleukin (IL)-4 productions in cell culture supernatants upon stimulation with increasing concentrations of peptides confirmed their immunogenicity. Knowledge of the complete T-cell epitope map of OVA opens the way to a number of experimental investigations, including the exploration of peptide-based immunotherapy.« less

Identification of CD147 (basigin) as a mediator of trophoblast functions.

PubMed

Lee, Cheuk-Lun; Lam, Maggie P Y; Lam, Kevin K W; Leung, Carmen O N; Pang, Ronald T K; Chu, Ivan K; Wan, Tiffany H L; Chai, Joyce; Yeung, William S B; Chiu, Philip C N

2013-11-01

Does CD147 regulate trophoblast functions in vitro? CD147 exists as a receptor complex on human trophoblast and regulates the implantation, invasion and differentiation of trophoblast. CD147 is a membrane protein implicated in a variety of physiological and pathological conditions due to its regulation of cell-cell recognition, cell differentiation and tissue remodeling. Reduced placental CD147 expression is associated with pre-eclampsia, but the mechanism of actions remains unclear. A loss of function approach or functional blocking antibody was used to study the function of CD147 in primary human cytotrophoblasts isolated from first trimester termination of pregnancy and/or in the BeWo cell line, which possesses characteristics of human cytotrophoblasts. CD147 expression was analyzed by immunofluorescence staining and western blotting. CD147-associated protein complex on plasma membrane were separated by blue native gel electrophoresis and identified by reversed-phase liquid chromatography coupled with quadrupole time-of-flight hybrid mass spectrometer. Cell proliferation and invasion were determined by fluorometric cell proliferation assays and transwell invasion assays, respectively. Matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) activities were measured by gelatin gel zymography and uPA assay kits, respectively. Cell migration was determined by wound-healing assays. Cell fusion was analyzed by immunocytochemistry staining of E-cadherin and 4',6-diamidino-2-phenylindole. The transcripts of matrix proteinases and trophoblast lineage markers were measured by quantitative PCR. Extracellular signal-regulated kinase (ERK) activation was analyzed by western blot using antibodies against ERKs. CD147 exists as protein complexes on the plasma membrane of primary human cytotrophoblasts and BeWo cells. Several known CD147-interacting partners, including integrin β1 and monocarboxylate transporter-1, were identified. Suppression of CD147 by si

Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis.

PubMed

Shin, Byung-Sik; Katoh, Takayuki; Gutierrez, Erik; Kim, Joo-Ran; Suga, Hiroaki; Dever, Thomas E

2017-08-21

Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

CD147 is a signaling receptor for cyclophilin B.

PubMed

Yurchenko, V; O'Connor, M; Dai, W W; Guo, H; Toole, B; Sherry, B; Bukrinsky, M

2001-11-09

Cyclophilins A and B (CyPA and CyPB) are cyclosporin A binding proteins that can be secreted in response to inflammatory stimuli. We recently identified CD147 as a cell-surface receptor for CyPA and demonstrated that CD147 is an essential component in the CyPA-initiated signaling cascade that culminates in ERK activation and chemotaxis. Here we demonstrate that CD147 also serves as a receptor for CyPB. CyPB induced Ca(2+) flux and chemotaxis of CD147-transfected, but not control, CHO cells, and the chemotactic response of primary human neutrophils to CyPB was blocked by antibodies to CD147. These results suggest that CD147 serves as a receptor for extracellular cyclophilins. Copyright 2001 Academic Press.

Proven in vitro evolution of protease cathepsin E-inhibitors and -activators at pH 4.5 using a paired peptide method.

PubMed

Kitamura, Koichiro; Komatsu, Masayuki; Biyani, Madhu; Futakami, Masae; Kawakubo, Tomoyo; Yamamoto, Kenji; Nishigaki, Koichi

2012-12-01

Improving a particular function of molecules is often more difficult than identifying such molecules ab initio. Here, a method to acquire higher affinity and/or more functional peptides was developed as a progressive library selection method. The primary library selection products were utilized to build a secondary library composed of blocks of 4 amino acids, of which selection led to peptides with increased activity. These peptides were further converted to randomly generate paired peptides. Cathepsin E-inhibitors thus obtained exhibited the highest activities and affinities (pM order). This was also the case with cathepsin E-activating peptides, proving the methodological effectiveness. The primary, secondary, and tertiary library selections can be regarded as module-finding, module-shuffling, and module-pairing, respectively, which resembles the progression of the natural evolution of proteins. The mode of peptide binding to their target proteins is discussed in analogy to antibodies and epitopes of an antigen. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

Code of Federal Regulations, 2014 CFR

2014-04-01

... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume of...

27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

Code of Federal Regulations, 2013 CFR

2013-04-01

... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume of...

27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

Code of Federal Regulations, 2010 CFR

2010-04-01

... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume of...

27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

Code of Federal Regulations, 2012 CFR

2012-04-01

... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume of...

27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

Code of Federal Regulations, 2011 CFR

2011-04-01

... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume of...

NMR assignment of a PDZ domain in complex with a HPV51 E6 derived N-terminally pyroglutamic acid modified peptide.

PubMed

Mischo, André; Ohlenschläger, Oliver; Ramachandran, Ramadurai; Görlach, Matthias

2013-04-01

The resonance assignment of an amino-terminal pyroglutamic acid containing peptide derived from the E6 protein of human papillomavirus (HPV) type 51 in complex with PDZ domain 2 of hDlg/SAP-97 is reported. The assignments include (1)H, (13)C and (15)N resonances for the protein and peptide in the complex and all of the peptide's pyroglutamic acid nuclei.

A new pro-migratory activity on human myogenic precursor cells for a synthetic peptide within the E domain of the mechano growth factor

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

Mills, Philippe; Lafreniere, Jean-Francois; Benabdallah, Basma Fattouma

2007-02-01

Duchenne muscular dystrophy (DMD) is an inherited disease that leads to progressive muscle wasting. Myogenic precursor cell transplantation is an approach that can introduce the normal dystrophin gene in the muscle fibers of the patients. Unfortunately, these myogenic precursor cells do not migrate well in the muscle and thus many injections have to be done to enable a good graft success. Recent reports have shown that there is extensive splicing of the IGF-1 gene in muscles. The MGF isoform contains a C-terminal 24 amino acids peptide in the E domain (MGF-Ct24E) that has intrinsic properties. It can promote the proliferationmore » while delaying the differentiation of C{sub 2}C{sub 12} cells. Here, we demonstrated that this synthetic peptide is a motogenic factor for human precursor myogenic cells in vitro and in vivo. Indeed, MGF-Ct24E peptide can modulate members of the fibrinolytic and metalloproteinase systems, which are implicated in the migration of myogenic cells. MGF-Ct24E peptide enhances the expression of u-PA, u-PAR and MMP-7 while reducing PAI-1 activity. Moreover, it has no effect on the gelatinases MMP-2 and -9. Those combined effects can favour cell migration. Finally, we present some results suggesting that the MGF-Ct24E peptide induces these cell responses through a mechanism that does not involve the IGF-1 receptor. Thus, this MGF-Ct24E peptide has a new pro-migratory activity on human myogenic precursor cells that may be helpful in the treatment of DMD. Those results reinforce the possibility that the IGF-1Ec isoform may produce an E domain peptide that can act as a cytokine.« less

40 CFR 147.3007 - Application for a permit.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Application for a permit. 147.3007 Section 147.3007 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS..., Ute Mountain Ute, and All Other New Mexico Tribes § 147.3007 Application for a permit. (a...

Repression of miR-17-5p with elevated expression of E2F-1 and c-MYC in non-metastatic hepatocellular carcinoma and enhancement of cell growth upon reversing this expression pattern

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

El Tayebi, H.M.; Omar, K.; Hegy, S.

2013-05-10

Highlights: •The oncogenic miR-17-5p is downregulated in non-metastatic hepatocellular carcinoma patients. •E2F-1 and c-MYC transcripts are upregulated in non-metastatic HCC patients. •miR-17-5p forced overexpression inhibited E2F-1 and c-MYC expression in HuH-7 cells. •miR-17-5p mimicking increased HuH-7 cell growth, proliferation, migration and colony formation. •miR-17-5p is responsible for HCC progression among the c-MYC/E2F-1/miR-17-5p triad members. -- Abstract: E2F-1, c-MYC, and miR-17-5p is a triad of two regulatory loops: a negative and a positive loop, where c-MYC induces the expression of E2F-1 that induces the expression of miR-17-5p which in turn reverses the expression of E2F-1 to close the loop. In thismore » study, we investigated this triad for the first time in hepatocellular carcinoma (HCC), where miR-17-5p showed a significant down-regulation in 23 non-metastatic HCC biopsies compared to 10 healthy tissues; however, E2F-1 and c-MYC transcripts were markedly elevated. Forced over-expression of miR-17-5p in HuH-7 cells resulted in enhanced cell proliferation, growth, migration and clonogenicity with concomitant inhibition of E2F-1 and c-MYC transcripts expressions, while antagomirs of miR-17-5p reversed these events. In conclusion, this study revealed a unique pattern of expression for miR-17-5p in non-metastatic HCC patients in contrast to metastatic HCC patients. In addition we show that miR-17-5p is the key player among the triad that tumor growth and spread.« less

Efficient Subcellular Targeting to the Cell Nucleus of Quantum Dots Densely Decorated with a Nuclear Localization Sequence Peptide.

PubMed

Maity, Amit Ranjan; Stepensky, David

2016-01-27

Organelle-targeted drug delivery can enhance the efficiency of the intracellularly acting drugs and reduce their toxicity. We generated core-shell type CdSe-ZnS quantum dots (QDs) densely decorated with NLS peptidic targeting residues using a 3-stage decoration approach and investigated their endocytosis and nuclear targeting efficiencies. The diameter of the generated QDs increased following the individual decoration stages (16.3, 18.9, and 21.9 nm), the ζ-potential became less negative (-33.2, -17.5, and -11.9 mV), and characteristic changes appeared in the FTIR spectra following decoration with the linker and NLS peptides. Quantitative analysis of the last decoration stage revealed that 37.9% and 33.2% of the alkyne-modified NLS groups that were added to the reaction mix became covalently attached or adsorbed to the QDs surface, respectively. These numbers correspond to 63.6 and 55.7 peptides conjugated or adsorbed to a single QD (the surface density of 42 and 37 conjugated and adsorbed peptides per 1000 nm(2) of the QDs surface), which is higher than in the majority of previous studies that reported decoration efficiencies of formulations intended for nuclear-targeted drug delivery. QDs decorated with NLS peptides undergo more efficient endocytosis, as compared to other investigated QDs formulations, and accumulated to a higher extent in the cell nucleus or in close vicinity to it (11.9%, 14.6%, and 56.1% of the QDs endocytosed by an average cell for the QD-COOH, QD-azide, and QD-NLS formulations, respectively). We conclude that dense decoration of QDs with NLS residues increased their endocytosis and led to their nuclear targeting (preferential accumulation in the cells nuclei or in close vicinity to them). The experimental system and research tools that were used in this study allow quantitative investigation of the mechanisms that govern the QDs nuclear targeting and their dependence on the formulation properties. These findings will contribute to the

46 CFR 147A.6 - Right of appeal.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Right of appeal. 147A.6 Section 147A.6 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.6 Right of appeal. Any person directly affected by a decision or action taken under...

46 CFR 147A.6 - Right of appeal.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Right of appeal. 147A.6 Section 147A.6 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.6 Right of appeal. Any person directly affected by a decision or action taken under...

46 CFR 147A.6 - Right of appeal.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Right of appeal. 147A.6 Section 147A.6 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.6 Right of appeal. Any person directly affected by a decision or action taken under...

46 CFR 147A.6 - Right of appeal.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Right of appeal. 147A.6 Section 147A.6 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.6 Right of appeal. Any person directly affected by a decision or action taken under...

46 CFR 147A.6 - Right of appeal.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Right of appeal. 147A.6 Section 147A.6 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.6 Right of appeal. Any person directly affected by a decision or action taken under...

Direct Measurement of the Mass Difference of 163Ho and 163Dy Solves the Q -Value Puzzle for the Neutrino Mass Determination

NASA Astrophysics Data System (ADS)

Eliseev, S.; Blaum, K.; Block, M.; Chenmarev, S.; Dorrer, H.; Düllmann, Ch. E.; Enss, C.; Filianin, P. E.; Gastaldo, L.; Goncharov, M.; Köster, U.; Lautenschläger, F.; Novikov, Yu. N.; Rischka, A.; Schüssler, R. X.; Schweikhard, L.; Türler, A.

2015-08-01

The atomic mass difference of 163 and 163Dy has been directly measured with the Penning-trap mass spectrometer SHIPTRAP applying the novel phase-imaging ion-cyclotron-resonance technique. Our measurement has solved the long-standing problem of large discrepancies in the Q value of the electron capture in 163Ho determined by different techniques. Our measured mass difference shifts the current Q value of 2555(16) eV evaluated in the Atomic Mass Evaluation 2012 [G. Audi et al., Chin. Phys. C 36, 1157 (2012)] by more than 7 σ to 2833 (30stat)(15sys) eV /c2 . With the new mass difference it will be possible, e.g., to reach in the first phase of the ECHo experiment a statistical sensitivity to the neutrino mass below 10 eV, which will reduce its present upper limit by more than an order of magnitude.

Investigations on the ORF 167L of lymphocystis disease virus (Iridoviridae).

PubMed

Essbauer, Sandra; Fischer, Uwe; Bergmann, Sven; Ahne, Winfried

2004-01-01

The predicted open reading frame 167L (ORF 167L) of lymphocystis disease virus (LCDV, Iridoviridae ) isolated from plaice, dab and flounder was investigated. The ORF 167L corresponding genes of the three LCDV isolates were amplified, cloned and sequenced. A comparison of the LCDV strains showed that the nucleotide sequence of ORF 167L and its deduced amino acid sequence were highly conserved in the genus lymphocystivirus (a homology of 80% in dab and flounder/plaice, 97% in plaice and flounder). The N-terminus protein predicted from the ORF 167L suggests similarities to the tumor necrosis factor receptor (TNFR)-family, and to TNFR-like proteins, which play an important role in various poxvirus species. Further, homology to the CUB-domain was shown at the C-terminus of the LCDV protein. Phylogenetic analyses of partial LCDV protein sequences identified two clusters: one cluster containing the flounder and plaice LCDV isolate (LCDV-1), and another cluster, containing the dab LCDV isolate (LCDV-2). The ORF 167L of plaice LCDV was expressed in Escherichia coli, and in fish cells. The expressed ORF resulted in a 30-kDa cytoplasmic protein lacking a signal peptide. An established monoclonal antibody (mAb 18) was used to detect LCDV proteins in skin explants of flounders and cryosections of dab skin. Specific fluorescence was found in the cytoplasm of intact epitheloid cells of the lymphocystis capsule and in the epidermis skin covering the lymphocystic nodules. LCDV-specific labelling of mAb 18 was also shown in spleen and liver tissue of LCDV-positive flounders. The ORF 167L protein seemed not to have the extracellular receptor function predicted from the usual cellular TNFR. The myxomavirus M-T2 protein, a poxviral TNFR homologue, was also shown not to have TNFR-like functions but to be involved in the apoptosis signal cascade.

75 FR 57543 - 30-Day Notice of Proposed Information Collection: Form DS-156K, Nonimmigrant Fiance(e) Visa...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-21

... DS-156K, Nonimmigrant Fiance(e) Visa Application, OMB Control Number 1405-0096 ACTION: Notice of... Reduction Act of 1995. Title of Information Collection: Nonimmigrant Fiance(e) Visa Application. OMB Control... applying for a nonimmigrant visa to enter the U.S. as the fianc[eacute](e) of a U.S. citizen Estimated...

Recombinant production of antimicrobial peptides in Escherichia coli: a review.

PubMed

Li, Yifeng

2011-12-01

Antimicrobial peptides are of great interest due to their potential application as novel antibiotics. Large quantities of highly purified peptides are required to meet the needs of basic research and clinical trials. Compared with isolation from natural sources and chemical synthesis, recombinant approach offers the most cost-effective means for large-scale peptide manufacture. Among the systems available for heterologous protein production, Escherichia coli has been the most widely used host. Antimicrobial peptides produced in E. coli are often expressed as fusion proteins, a strategy necessary to mask these peptides' lethal effect towards the host and protect them from proteolytic degradation. The present article reviews commonly used fusion partners (e.g., solubility-enhancing, aggregation-promoting and self-cleavable carriers, etc.), cleavage methods and optimization options for antimicrobial peptides production in E. coli. In addition, the various approaches developed to generate recombinant human antimicrobial peptide LL-37, which offer excellent examples demonstrating effective production strategies, were briefly discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

46 CFR 163.003-27 - Production tests and examination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 6 2010-10-01 2010-10-01 false Production tests and examination. 163.003-27 Section 163... examination. (a) General. Each ladder produced under Coast Guard approval must be tested in accordance with... for effective monitoring throughout the production schedule. (e) Visual examination. The visual...

46 CFR 147A.21 - Person in charge of fumigation; during fumigation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Person in charge of fumigation; during fumigation. 147A.21 Section 147A.21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.21 Person in charge of...

46 CFR 147A.21 - Person in charge of fumigation; during fumigation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Person in charge of fumigation; during fumigation. 147A.21 Section 147A.21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.21 Person in charge of...

46 CFR 147A.21 - Person in charge of fumigation; during fumigation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Person in charge of fumigation; during fumigation. 147A.21 Section 147A.21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.21 Person in charge of...

46 CFR 147A.21 - Person in charge of fumigation; during fumigation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Person in charge of fumigation; during fumigation. 147A.21 Section 147A.21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.21 Person in charge of...

Structural evidence for the role of polar core residue Arg175 in arrestin activation

PubMed Central

Granzin, Joachim; Stadler, Andreas; Cousin, Anneliese; Schlesinger, Ramona; Batra-Safferling, Renu

2015-01-01

Binding mechanism of arrestin requires photoactivation and phosphorylation of the receptor protein rhodopsin, where the receptor bound phosphate groups cause displacement of the long C-tail ‘activating’ arrestin. Mutation of arginine 175 to glutamic acid (R175E), a central residue in the polar core and previously predicted as the ‘phosphosensor’ leads to a pre-active arrestin that is able to terminate phototransduction by binding to non-phosphorylated, light-activated rhodopsin. Here, we report the first crystal structure of a R175E mutant arrestin at 2.7 Å resolution that reveals significant differences compared to the basal state reported in full-length arrestin structures. These differences comprise disruption of hydrogen bond network in the polar core, and three-element interaction including disordering of several residues in the receptor-binding finger loop and the C-terminus (residues 361–404). Additionally, R175E structure shows a 7.5° rotation of the amino and carboxy-terminal domains relative to each other. Consistent to the biochemical data, our structure suggests an important role of R29 in the initial activation step of C-tail release. Comparison of the crystal structures of basal arrestin and R175E mutant provide insights into the mechanism of arrestin activation, where binding of the receptor likely induces structural changes mimicked as in R175E. PMID:26510463

Structural evidence for the role of polar core residue Arg175 in arrestin activation.

PubMed

Granzin, Joachim; Stadler, Andreas; Cousin, Anneliese; Schlesinger, Ramona; Batra-Safferling, Renu

2015-10-29

Binding mechanism of arrestin requires photoactivation and phosphorylation of the receptor protein rhodopsin, where the receptor bound phosphate groups cause displacement of the long C-tail 'activating' arrestin. Mutation of arginine 175 to glutamic acid (R175E), a central residue in the polar core and previously predicted as the 'phosphosensor' leads to a pre-active arrestin that is able to terminate phototransduction by binding to non-phosphorylated, light-activated rhodopsin. Here, we report the first crystal structure of a R175E mutant arrestin at 2.7 Å resolution that reveals significant differences compared to the basal state reported in full-length arrestin structures. These differences comprise disruption of hydrogen bond network in the polar core, and three-element interaction including disordering of several residues in the receptor-binding finger loop and the C-terminus (residues 361-404). Additionally, R175E structure shows a 7.5° rotation of the amino and carboxy-terminal domains relative to each other. Consistent to the biochemical data, our structure suggests an important role of R29 in the initial activation step of C-tail release. Comparison of the crystal structures of basal arrestin and R175E mutant provide insights into the mechanism of arrestin activation, where binding of the receptor likely induces structural changes mimicked as in R175E.

Quantitative and functional analysis of PDC-E2–specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis

PubMed Central

Kita, Hiroto; Matsumura, Shuji; He, Xiao-Song; Ansari, Aftab A.; Lian, Zhe-Xiong; Van de Water, Judy; Coppel, Ross L.; Kaplan, Marshall M.; Gershwin, M. Eric

2002-01-01

While the pathologic mechanisms responsible for organ-specific tissue damage in primary biliary cirrhosis (PBC) remain an enigma, it has been suggested that the pathology is mediated by autoreactive T cells infiltrating the intrahepatic bile ducts. Previously, we have documented that there is 100-fold enrichment in the frequency of CD4+ autoreactive T cells in the liver that are specific for peptides encoded by the E2 components of the pyruvate dehydrogenase complexes (PDC-E2). We have also recently characterized the first MHC class I–restricted epitope for PDC-E2, namely amino acid 159–167, a region very similar to the epitope recognized by MHC class II–restricted CD4+ cells and by autoantibodies. The effector functions of these PDC-E2159-167–specific CD8+ cytotoxic T lymphocytes (CTLs) are not well understood. We have taken advantage of tetramer technology and report herein that there is tenfold increase in the frequency of PDC-E2159-167–specific CTLs in the liver as compared with the blood in PBC. In addition, the precursor frequency of the CTLs in blood was significantly higher in early-stage PBC. Of interest was the fact that, upon stimulation with the peptide, the response of PDC-E2159-167 tetramer-positive cells is heterogeneous with respect to IFN-γ synthesis. These data, we believe for the first time, document the enrichment of autoantigen-specific CD8+ T cells in the PBC liver, suggesting that CD8+ T cells play a significant role in the immunopathogenesis of PBC. PMID:11994412

40 CFR 156.78 - Precautionary statements for physical or chemical hazards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... or chemical hazards. 156.78 Section 156.78 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Precautionary Statements § 156.78 Precautionary statements for physical or chemical hazards. (a) Requirement.../chemical hazards (e.g., oxidizing potential, conductivity, chemical reactions leading to production of...

40 CFR 156.78 - Precautionary statements for physical or chemical hazards.

Code of Federal Regulations, 2011 CFR

2011-07-01

.../chemical hazards (e.g., oxidizing potential, conductivity, chemical reactions leading to production of... or chemical hazards. 156.78 Section 156.78 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Precautionary Statements § 156.78 Precautionary statements for physical or chemical hazards. (a) Requirement...

40 CFR 156.78 - Precautionary statements for physical or chemical hazards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... or chemical hazards. 156.78 Section 156.78 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Precautionary Statements § 156.78 Precautionary statements for physical or chemical hazards. (a) Requirement.../chemical hazards (e.g., oxidizing potential, conductivity, chemical reactions leading to production of...

40 CFR 156.78 - Precautionary statements for physical or chemical hazards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... or chemical hazards. 156.78 Section 156.78 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Precautionary Statements § 156.78 Precautionary statements for physical or chemical hazards. (a) Requirement.../chemical hazards (e.g., oxidizing potential, conductivity, chemical reactions leading to production of...

46 CFR 147A.23 - Person in charge of vessel; during fumigation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Person in charge of vessel; during fumigation. 147A.23 Section 147A.23 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.23 Person in charge of vessel...

46 CFR 147A.23 - Person in charge of vessel; during fumigation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Person in charge of vessel; during fumigation. 147A.23 Section 147A.23 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.23 Person in charge of vessel...

46 CFR 147A.23 - Person in charge of vessel; during fumigation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Person in charge of vessel; during fumigation. 147A.23 Section 147A.23 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.23 Person in charge of vessel...

46 CFR 147A.23 - Person in charge of vessel; during fumigation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Person in charge of vessel; during fumigation. 147A.23 Section 147A.23 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION During Fumigation § 147A.23 Person in charge of vessel...

43 CFR 30.175 - When does a purchased interest vest in the purchaser?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false When does a purchased interest vest in the purchaser? 30.175 Section 30.175 Public Lands: Interior Office of the Secretary of the Interior INDIAN PROBATE HEARINGS PROCEDURES Purchase at Probate § 30.175 When does a purchased interest vest in the...

43 CFR 30.175 - When does a purchased interest vest in the purchaser?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false When does a purchased interest vest in the purchaser? 30.175 Section 30.175 Public Lands: Interior Office of the Secretary of the Interior INDIAN PROBATE HEARINGS PROCEDURES Purchase at Probate § 30.175 When does a purchased interest vest in the...

43 CFR 30.175 - When does a purchased interest vest in the purchaser?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false When does a purchased interest vest in the purchaser? 30.175 Section 30.175 Public Lands: Interior Office of the Secretary of the Interior INDIAN PROBATE HEARINGS PROCEDURES Purchase at Probate § 30.175 When does a purchased interest vest in the...

43 CFR 30.175 - When does a purchased interest vest in the purchaser?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false When does a purchased interest vest in the purchaser? 30.175 Section 30.175 Public Lands: Interior Office of the Secretary of the Interior INDIAN PROBATE HEARINGS PROCEDURES Purchase at Probate § 30.175 When does a purchased interest vest in the...

43 CFR 30.175 - When does a purchased interest vest in the purchaser?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true When does a purchased interest vest in the purchaser? 30.175 Section 30.175 Public Lands: Interior Office of the Secretary of the Interior INDIAN PROBATE HEARINGS PROCEDURES Purchase at Probate § 30.175 When does a purchased interest vest in the...

40 CFR 161.175 - Certified limits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... how the certified limits were arrived at (e.g., sample analysis, quantitative estimate based on....175 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR REGISTRATION OF ANTIMICROBIAL PESTICIDES Product Chemistry Data Requirements § 161.175...

Review and retrospective analysis of degenerative lumbosacral stenosis in 156 dogs treated by dorsal laminectomy.

PubMed

Suwankong, N; Meij, B P; Voorhout, G; de Boer, A H; Hazewinkel, H A W

2008-01-01

The medical records of 156 dogs with degenerative lumbosacral stenosis (DLS) that underwent decompressive surgery were reviewed for signalment, history, clinical signs, imaging and surgical findings. The German Shepherd Dog (GSD) was most commonly affected (40/156, 25.6%). Pelvic limb lameness, caudal lumbar pain and pain evoked by lumbosacral pressure were the most frequent clinical findings. Radiography showed lumbosacral step formation in 78.8% (93/118) of the dogs which was associated with elongation of the sacral lamina in 18.6% (22/118). Compression of the cauda equina was diagnosed by imaging (epidurography, CT, or MRI) in 94.2% (147/156) of the dogs. Loss of the bright nucleus pulposus signal of the L7-S1 disc was found on T2-weighted MR images in 73.5% (25/34) of the dogs. The facet joint angle at L7-S1 was significantly smaller, and the tropism greater in GSD than in the other dog breeds. The smaller facet joint angle and higher incidence of tropism seen in the GSD may predispose this breed to DLS. Epidurography, CT, and MRI allow adequate visualization of cauda equina compression. During surgery, disc protrusion was found in 70.5% (110/156) of the dogs. Overall improvement after surgery was recorded in the medical records in 79.0% (83/105) of the dogs. Of the 38 owners that responded to questionnaires up to five years after surgery, 29 (76%) perceived an improvement.

Identification of coeliac disease triggering glutenin peptides in adults.

PubMed

Donnelly, Suzanne C; Šuligoj, Tanja; Ellis, H Julia; Ciclitira, Paul J

2016-07-01

Coeliac disease affects approximately 1% of Northern American and European populations. It is caused by an inappropriate immune response to dietary gluten. Gluten comprises of two major protein fractions: gliadins and glutenins. Glutenins have recently been found to be toxic to coeliac individuals. Proliferation assays suggest in some but not all paediatric coeliac individuals there may be immunological stimulation with high molecular weight (HMW) glutenins. Less evidence pertains to low molecular weight (LMW) glutenins. The aim is to assess adaptive, T-cell driven, and innate immune response in adult coeliac individuals towards HMW glutenin peptide, glut04, and LMW glutenin peptide, glt156. Coeliac patients were recruited attending endoscopy for routine monitoring. Adaptive immune response towards glut04 and glt156 was measured by proliferation assays and measurement of interferon-γ secretion in 28 T-cell lines. The innate immune response was assessed by measurement of enterocyte cell height (ECH) in coeliac small intestinal biopsies following overnight incubation in organ culture chambers in a further nine individuals. There were 3/28 and 2/28 positive proliferation results using gluten-sensitive T-cells with glut04 and glt156, respectively. All coeliac biopsies tested in organ culture chambers demonstrated clear reduction in ECH with peptic-tryptic digest of whole industrial gluten, glut04 and glt156 when compared to negative control ovalbumin (p < 0.005). Three individuals had both T-cell and organ culture study data. Their proliferation assays showed no stimulation of the T-cells. This study demonstrates glutenin epitopes glut04 and glt156, while minor T-cell epitopes, are important in their ability to trigger the innate immune response.

CD147 and glioma: a meta-analysis.

PubMed

Li, Hui; Xi, Zhouhuan; Dai, Xuejiao; Wu, Wenyue; Li, Yanwen; Liu, Yanting; Zhang, Hanwen

2017-08-01

Gliomas are the most common primary brain tumors. This meta-analysis aimed to systematically evaluate the relationship between CD147 expression in tissues and the clinicopathological features of patients with glioma. We searched PubMed (1966-2016), EMBASE (1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and Wan Fang databases (1988-2016). Quality assessment of the literature was performed using the Newcastle-Ottawa Scale, with Revman 5.3 and Stata 14.0 for analysis. In total, 1806 glioma patients from 19 studies were included, and patients with CD147 overexpression had poorer overall survival [hazard ratio (HR) = 2.211, P < 0.0001], a higher risk of recurrence (HR = 2.20, P = 0.0025), and a lower 5-year survival rate [odds ratio (OR) 0.12; 95% CI 0.08-0.19; P < 0.00001]. We observed significant differences in CD147 expression when comparing glioma tissues versus non-cancerous brain tissues (OR 20.42; 95% CI 13.94-29.91; P < 0.00001), tumor grades III-IV versus grades I-II (OR 5.88, 95% CI 4.15-8.34; P < 0.00001), and large versus small tumors (OR 1.58, 95% CI 1.04-2.40; P = 0.03). We also observed a significant correlation with matrix metalloproteinase (MMP) 2 (OR 39.11, 95% CI 11.47-133.34; P < 0.00001) and MMP9 (OR 13.35, 95% CI 4.67-38.18; P < 0.00001). CD147 expression did not differ based on patient's age (young vs. old, P = 0.89) or gender (female vs. male, P = 0.57). CD147 expression may be a potential prognostic biomarker for poorer overall and relapse-free survival, and may affect the 5-year survival rate in glioma patients. CD147 expression is also closely correlated with poor clinical characteristics in glioma patients.

Curvularides A-E: antifungal hybrid peptide-polyketides from the endophytic fungus Curvularia geniculata.

PubMed

Chomcheon, Porntep; Wiyakrutta, Suthep; Aree, Thammarat; Sriubolmas, Nongluksna; Ngamrojanavanich, Nattaya; Mahidol, Chulabhorn; Ruchirawat, Somsak; Kittakoop, Prasat

2010-09-24

Five new hybrid peptide-polyketides, curvularides A-E (1-5), were isolated from the endophytic fungus Curvularia geniculata, which was obtained from the limbs of Catunaregam tomentosa. Structure elucidation for curvularides A-E (1-5) was accomplished by analysis of spectroscopic data, as well as by single-crystal X-ray crystallography. Curvularide B (2) exhibited antifungal activity against Candida albicans, and it also showed synergistic activity with a fluconazole drug.

40 CFR 162.156 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... thereunder: (i) Sec. 12(a)(1) (A) through (E), in accordance with: (A) Sec. 2(q)(1) (A) through (G). (B) Sec... registered by the Administrator in accordance with sec. 7 of FIFRA and 40 CFR part 167. (c) Books and records...

Conformational antigenic determinants generated by interactions between a bacterially expressed recombinant peptide of the hepatitis E virus structural protein.

PubMed

Zhang, J Z; Ng, M H; Xia, N S; Lau, S H; Che, X Y; Chau, T N; Lai, S T; Im, S W

2001-06-01

A 23 kDa peptide locating to amino acid residues 394 to 604 of the major Hepatitis E Virus (HEV) structural protein was expressed in E. coli. This peptide was found to interact naturally with one another to form homodimers and it was recognized strongly and commonly in its dimeric form by HEV reactive human sera. The antigenic activity associated with the dimeric form was abrogated when the dimer was dissociated into monomer and the activity was reconstituted after the monomer was re-associated into dimer again. The dimeric form of the peptide elicited a vigorous antibody response in experimental animals and the resulting antisera were found to cross-react against HEV, effecting an efficient immune capture of the virus. These results attributed the antigenic activity associated with the dimeric form of the peptide to conformational antigenic determinants generated as a result of interaction between the peptide molecules. It is suggested that some of these antigenic determinants may be expressed by the HEV capsid and raised the possibility of this bacterially expressed peptide as an HEV vaccine candidate. Copyright 2001 Wiley-Liss, Inc.

CXCL4 downregulates the atheroprotective hemoglobin receptor CD163 in human macrophages.

PubMed

Gleissner, Christian A; Shaked, Iftach; Erbel, Christian; Böckler, Dittmar; Katus, Hugo A; Ley, Klaus

2010-01-08

CXCL4 is a platelet-derived chemokine that promotes macrophage differentiation from monocytes. Deletion of the PF4 gene that encodes CXCL4 reduces atherosclerotic lesions in ApoE(-/-) mice. We sought to study effects of CXCL4 on macrophage differentiation with possible relevance for atherogenesis. Flow cytometry for expression of surface markers in macrophage colony-stimulating factor (M-CSF)- and CXCL4-induced macrophages demonstrated virtually complete absence of the hemoglobin scavenger receptor CD163 in CXCL4-induced macrophages. mRNA for CD163 was downregulated as early as 2 hours after CXCL4. CD163 protein reached a minimum after 3 days, which was not reversed by treatment of cells with M-CSF. The CXCL4 effect was entirely neutralized by heparin, which bound CXCL4 and prevented CXCL4 surface binding to monocytes. Pretreatment of cells with chlorate, which inhibits glycosaminoglycan synthesis, strongly inhibited CXCL4-dependent downregulation of CD163. Similar to recombinant CXCL4, releasate from human platelets also reduced CD163 expression. CXCL4-differentiated macrophages were unable to upregulate the atheroprotective enzyme heme oxygenase-1 at the RNA and protein level in response to hemoglobin-haptoglobin complexes. Immunofluorescence of human atherosclerotic plaques demonstrated presence of both CD68+CD163+ and CD68+CD163- macrophages. PF4 and CD163 gene expression within human atherosclerotic lesions were inversely correlated, supporting the in vivo relevance of CXCL4-induced downregulation of CD163. CXCL4 may promote atherogenesis by suppressing CD163 in macrophages, which are then unable to upregulate the atheroprotective enzyme heme oxygenase-1 in response to hemoglobin.

40 CFR 14.7 - Where to file a claim.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Where to file a claim. 14.7 Section 14.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL EMPLOYEE PERSONAL PROPERTY CLAIMS § 14.7 Where to file a claim. An employee or his/her representative may file a claim with his/her...

40 CFR 14.7 - Where to file a claim.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Where to file a claim. 14.7 Section 14.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL EMPLOYEE PERSONAL PROPERTY CLAIMS § 14.7 Where to file a claim. An employee or his/her representative may file a claim with his/her...

40 CFR 156.156 - Residue removal instructions for refillable containers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... adequate to protect human health and the environment. (2) Subject to meeting the standard in paragraph (b... (CONTINUED) PESTICIDE PROGRAMS LABELING REQUIREMENTS FOR PESTICIDES AND DEVICES Container Labeling § 156.156 Residue removal instructions for refillable containers. The label of each pesticide product packaged in a...

40 CFR 156.156 - Residue removal instructions for refillable containers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... adequate to protect human health and the environment. (2) Subject to meeting the standard in paragraph (b... (CONTINUED) PESTICIDE PROGRAMS LABELING REQUIREMENTS FOR PESTICIDES AND DEVICES Container Labeling § 156.156 Residue removal instructions for refillable containers. The label of each pesticide product packaged in a...

40 CFR 156.156 - Residue removal instructions for refillable containers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... adequate to protect human health and the environment. (2) Subject to meeting the standard in paragraph (b... (CONTINUED) PESTICIDE PROGRAMS LABELING REQUIREMENTS FOR PESTICIDES AND DEVICES Container Labeling § 156.156 Residue removal instructions for refillable containers. The label of each pesticide product packaged in a...

40 CFR 156.156 - Residue removal instructions for refillable containers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... adequate to protect human health and the environment. (2) Subject to meeting the standard in paragraph (b... (CONTINUED) PESTICIDE PROGRAMS LABELING REQUIREMENTS FOR PESTICIDES AND DEVICES Container Labeling § 156.156 Residue removal instructions for refillable containers. The label of each pesticide product packaged in a...

40 CFR 156.156 - Residue removal instructions for refillable containers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... adequate to protect human health and the environment. (2) Subject to meeting the standard in paragraph (b... (CONTINUED) PESTICIDE PROGRAMS LABELING REQUIREMENTS FOR PESTICIDES AND DEVICES Container Labeling § 156.156 Residue removal instructions for refillable containers. The label of each pesticide product packaged in a...

75 FR 25910 - 60-Day Notice of Proposed Information Collection: DS-156E, Nonimmigrant Treaty Trader/Investor...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

..., Nonimmigrant Treaty Trader/Investor Application, OMB Control Number 1405-0101 ACTION: Notice of request for...: Nonimmigrant Treaty Trader/Investor Application. OMB Control Number: 1405-0101. Type of Request: Extension of a...) Form Number: DS-156E. Respondents: Nonimmigrant treaty trader/investor visa applicants. Estimated...

In vitro and in vivo evaluation of a 64Cu-labeled NOTA-Bn-SCN-Aoc-bombesin analogue in gastrin-releasing peptide receptor expressing prostate cancer.

PubMed

Craft, Jeffrey M; De Silva, Ravindra A; Lears, Kimberly A; Andrews, Rebecca; Liang, Kexian; Achilefu, Samuel; Rogers, Buck E

2012-07-01

Bombesin (BN) is an amphibian peptide that binds to the gastrin-releasing peptide receptor (GRPR). It has been demonstrated that BN analogues can be radiolabeled for potential diagnosis and treatment of GRPR-expressing malignancies. Previous studies have conjugated various chelators to the eight C-terminal amino acids of BN [BN(7-14)] for radiolabeling with 64Cu. Recently, (1,4,7-triazacyclononane-1,4,7-triacetic acid) (NOTA) has been evaluated as the five-coordinate 64Cu complex, with results indicating GRPR-specific tumor uptake. This study aimed to conjugate S-2-(4-isothiocyanatobenzyl)-NOTA (p-SCN-Bn-NOTA) to BN(7-14) such that it could form a six-coordinate complex with 64Cu and to evaluate the resulting peptide. p-SCN-NOTA was conjugated to 8-aminooctanoic acid (Aoc)-BN(7-14) in solution to yield NOTA-Bn-SCN-Aoc-BN(7-14). The unlabeled peptide was evaluated in a cell binding assay using PC-3 prostate cancer cells and 125I-Tyr4-BN to determine the IC50 value. The peptide was radiolabeled with 64Cu and evaluated for internalization into PC-3 cells and for tumor uptake in mice bearing PC-3 xenografts using biodistribution and micro-positron emission tomography imaging studies. The binding assay demonstrated that NOTA-Bn-SCN-Aoc-BN(7-14) bound with high affinity to GRPR with an IC50 of 1.4 nM. The radiolabeled peptide demonstrated time-dependent internalization into PC-3 cells. In vivo, the peptide demonstrated tumor-specific uptake and imaging that were comparable to those of previously reported 64Cu-labeled BN analogues. These studies demonstrate that 64Cu-NOTA-Bn-SCN-Aoc-BN(7-14) binds to GRPR-expressing cells and that it can be used for imaging of GRPR-expressing prostate cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Repressing CD147 is a novel therapeutic strategy for malignant melanoma

PubMed Central

Hu, Xing; Su, Juan; Zhou, Youyou; Xie, Xiaoyun; Peng, Cong; Yuan, Zhimin; Chen, Xiang

2017-01-01

CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR). As a matrix metalloproteinase (MMP) inducer, CD147 could also promote surrounding fibroblasts to secrete abundant MMPs to further stimulate tumor cell invasion. Targeting CD147 has been shown to suppress MM in vitro and in vivo, highlighting the therapeutic potential of CD147 silencing in MM treatment. In this review article, we discuss CD147 and its biological roles, regulatory mechanisms, and potential application as a molecular target for MM. PMID:28445958

Repressing CD147 is a novel therapeutic strategy for malignant melanoma.

PubMed

Hu, Xing; Su, Juan; Zhou, Youyou; Xie, Xiaoyun; Peng, Cong; Yuan, Zhimin; Chen, Xiang

2017-04-11

CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR). As a matrix metalloproteinase (MMP) inducer, CD147 could also promote surrounding fibroblasts to secrete abundant MMPs to further stimulate tumor cell invasion. Targeting CD147 has been shown to suppress MM in vitro and in vivo, highlighting the therapeutic potential of CD147 silencing in MM treatment. In this review article, we discuss CD147 and its biological roles, regulatory mechanisms, and potential application as a molecular target for MM.

46 CFR 147A.13 - Person in charge of the vessel; before fumigation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Person in charge of the vessel; before fumigation. 147A.13 Section 147A.13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION Before Fumigation § 147A.13 Person in charge of the...

46 CFR 147A.13 - Person in charge of the vessel; before fumigation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Person in charge of the vessel; before fumigation. 147A.13 Section 147A.13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION Before Fumigation § 147A.13 Person in charge of the...

46 CFR 147A.13 - Person in charge of the vessel; before fumigation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Person in charge of the vessel; before fumigation. 147A.13 Section 147A.13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION Before Fumigation § 147A.13 Person in charge of the...

A Rice Immunophilin Gene, OsFKBP16-3, Confers Tolerance to Environmental Stress in Arabidopsis and Rice

PubMed Central

Park, Hyun Ji; Lee, Sang Sook; You, Young Nim; Yoon, Dae Hwa; Kim, Beom-Gi; Ahn, Jun Cheul; Cho, Hye Sun

2013-01-01

The putative thylakoid lumen immunophilin, FKBP16-3, has not yet been characterized, although this protein is known to be regulated by thioredoxin and possesses a well-conserved CxxxC motif in photosynthetic organisms. Here, we characterized rice OsFKBP16-3 and examined the role of this gene in the regulation of abiotic stress in plants. FKBP16-3s are well conserved in eukaryotic photosynthetic organisms, including the presence of a unique disulfide-forming CxxxC motif in their N-terminal regions. OsFKBP16-3 was mainly expressed in rice leaf tissues and was upregulated by various abiotic stresses, including salt, drought, high light, hydrogen peroxide, heat and methyl viologen. The chloroplast localization of OsFKBP16-3-GFP was confirmed through the transient expression of OsFKBP16-3 in Nicotiana benthamiana leaves. Transgenic Arabidopsis and transgenic rice plants that constitutively expressed OsFKBP16-3 exhibited increased tolerance to salinity, drought and oxidative stresses, but showed no change in growth or phenotype, compared with vector control plants, when grown under non-stressed conditions. This is the first report to demonstrate the potential role of FKBP16-3 in the environmental stress response, which may be regulated by a redox relay process in the thylakoid lumen, suggesting that artificial regulation of FKBP16-3 expression is a candidate for stress-tolerant crop breeding. PMID:23485991

Activated FGFR2 as a Viable Therapeutic Target in a Subset of Ovarian Cancers

DTIC Science & Technology

2009-07-01

Geneticin 163 in the presence of 5 ng/m l IL-3 for 14 days, a nd then mainta ined un der sele ction in RPMI 164 supplemented with 10% FBS, 50 nM beta...from FGFR2c t o FGFR2b is 214 currently unknown. Functional studi es have shown that a neut ralizing antibody to FGF7 can 215 partially inhibit DNA...and ovarian cancer . Mol Cell Endocrinol 362 l2000;167: 77-87. 363 [26] White KE, Cabral JM, Davi s SI, F ishburn T, E vans W E, Ichi kawa S, Fields

Identification, Characterization, Immunolocalization, and Biological Activity of Lucilin Peptide.

PubMed

Alberto, Tellez German; Alejandra, Zapata Jesica; Johanna, Toro Lily; Carolina, Henao Diana; Pablo, Bedoya Juan; David, Rivera Juan; Valentin, Trujillo Juan; Bruno, Rivas; Lopez, Richard Onalbi Hoyos; Carlos, Castano Jhon

2018-06-08

Maggots from the Lucilia sp. genus are used for debridement of infected and necrotic wounds. Broad-spectrum antimicrobial activity has been described in the excretion/secretions (ES 1 ) of these larvae. This study identifies the genetic sequence of a cecropin-like antimicrobial peptide from Lucilia eximia. Total RNA was extracted and used for PCR-RACE amplification of a cecropin, the native peptide was immunolocalized in the tissues and secretions of the larvae, and a synthetic analog was used to explore its antimicrobial, cytotoxic, LPS neutralizing and wound-healing activities in vitro. The genetic cDNA sequence of a cecropin-like antimicrobial peptide in L. eximia called "Lucilin" was amplified, corresponding to 63 aa completed protein and 40 aa mature peptide; the structure of the mature peptide was predicted as an α-helix. The peptide was immunolocalized in the salivary glands, fat body, the ES, and hemolymph of the maggots. Lucilin synthetic peptide analog was active against E. coli DH10B with a MIC 2 of 7.8 µg/mL, E. coli extended spectrum b-lactamase (ESBL) (MIC: 15.6 µg/mL), and Enterobacter cloacae (MIC: 125 µg/mL), but it was not active against Pseudomonas aeruginosa and Staphylococcus epidermidis; and had no cytotoxic or hemolytic activity. It showed immunomodulatory activity against human peripheral blood mononuclear cells (PBMCs) stimulated with LPS, reducing the TNF-α production when treated at 17 µg/mL and induces cell migration of Hacat at 5 and 50 µg/mL. Lucilin is a cecropin-like peptide from L. eximia with antimicrobial activity against Gram negative bacteria and immunomodulatory activities, decreasing the TNF-α production in PBMCs and inducing cellular migration in human keratinocytes. Copyright © 2018. Published by Elsevier B.V.

E 2 decay strength of the M 1 scissors mode of 156Gd and its first excited rotational state

NASA Astrophysics Data System (ADS)

Beck, T.; Beller, J.; Pietralla, N.; Bhike, M.; Birkhan, J.; Derya, V.; Gayer, U.; Hennig, A.; Isaak, J.; Löher, B.; Ponomarev, V. Yu.; Richter, A.; Romig, C.; Savran, D.; Scheck, M.; Tornow, W.; Werner, V.; Zilges, A.; Zweidinger, M.

2017-05-01

The E 2 /M 1 multipole mixing ratio δ1 →2 of the 1sc+→21+ γ -ray decay in 156Gd and hence the isovector E 2 transition rate of the scissors mode of a well-deformed rotational nucleus has been measured for the first time. It has been obtained from the angular distribution of an artificial quasimonochromatic linearly polarized γ -ray beam of energy 3.07(6) MeV scattered inelastically off an isotopically highly enriched 156Gd target. The data yield first direct support for the deformation dependence of effective proton and neutron quadrupole boson charges in the framework of algebraic nuclear models. First evidence for a low-lying Jπ=2+ member of the rotational band of states on top of the 1+ band head is obtained, too, indicating a significant signature splitting in the K =1 scissors mode rotational band.

E2 decay strength of the M1 scissors mode of ^{156}Gd and its first excited rotational state.

PubMed

Beck, T; Beller, J; Pietralla, N; Bhike, M; Birkhan, J; Derya, V; Gayer, U; Hennig, A; Isaak, J; Löher, B; Ponomarev, V Yu; Richter, A; Romig, C; Savran, D; Scheck, M; Tornow, W; Werner, V; Zilges, A; Zweidinger, M

2017-05-26

The E2/M1 multipole mixing ratio δ_{1→2} of the 1_{sc}^{+}→2_{1}^{+} γ-ray decay in ^{156}Gd and hence the isovector E2 transition rate of the scissors mode of a well-deformed rotational nucleus has been measured for the first time. It has been obtained from the angular distribution of an artificial quasimonochromatic linearly polarized γ-ray beam of energy 3.07(6) MeV scattered inelastically off an isotopically highly enriched ^{156}Gd target. The data yield first direct support for the deformation dependence of effective proton and neutron quadrupole boson charges in the framework of algebraic nuclear models. First evidence for a low-lying J^{π}=2^{+} member of the rotational band of states on top of the 1^{+} band head is obtained, too, indicating a significant signature splitting in the K=1 scissors mode rotational band.

CD147/EMMPRIN overexpression and prognosis in cancer: A systematic review and meta-analysis

PubMed Central

Xin, Xiaoyan; Zeng, Xianqin; Gu, Huajian; Li, Min; Tan, Huaming; Jin, Zhishan; Hua, Teng; Shi, Rui; Wang, Hongbo

2016-01-01

CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) plays an important role in tumor progression and a number of studies have suggested that it is an indicator of tumor prognosis. This current meta-analysis systematically reevaluated the predictive potential of CD147/EMMPRIN in various cancers. We searched PubMed and Embase databases to screen the literature. Fixed-effect and random-effect meta-analytical techniques were used to correlate CD147 expression with outcome measures. A total of 53 studies that included 68 datasets were eligible for inclusion in the final analysis. We found a significant association between CD147/EMMPRIN overexpression and adverse tumor outcomes, such as overall survival, disease-specific survival, progression-free survival, metastasis-free survival or recurrence-free survival, irrespective of the model analysis. In addition, CD147/EMMPRIN overexpression predicted a high risk for chemotherapy drugs resistance. CD147/EMMPRIN is a central player in tumor progression and predicts a poor prognosis, including in patients who have received chemo-radiotherapy. Our results provide the evidence that CD147/EMMPRIN could be a potential therapeutic target for cancers. PMID:27608940

14 CFR 147.38a - Quality of instruction.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Quality of instruction. 147.38a Section 147... Quality of instruction. Each certificated aviation maintenance technician school shall provide instruction of such quality that, of its graduates of a curriculum for each rating who apply for a mechanic...

The Roles of CD147 and/or Cyclophilin A in Kidney Diseases

PubMed Central

Wang, Chunting; Zhang, Jicheng; Qie, Guoqiang

2014-01-01

CD147 is a widely expressed integral plasma membrane glycoprotein and has been involved in a variety of physiological and pathological activities in combination with different partners, including cyclophilins, caveolin-1, monocarboxylate transporters, and integrins. Recent data demonstrate that both CyPA and CD147 significantly contribute to renal inflammation, acute kidney injury, renal fibrosis, and renal cell carcinoma. Here we review the current understanding of cyclophilin A and CD147 expression and functions in kidney diseases and potential implications for treatment of kidney diseases. PMID:25580061

A NEW LARGE SUPER-FAST ROTATOR: (335433) 2005 UW163

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

Chang, Chan-Kao; Lin, Hsing-Wen; Ip, Wing-Huen

2014-08-20

Asteroids of size larger than 150 m generally do not have rotation periods smaller than 2.2 hr. This spin cutoff is believed to be due to the gravitationally bound rubble-pile structures of the asteroids. Rotation with periods exceeding this critical value will cause asteroid breakup. Up until now, only one object, 2001 OE84, has been found to be an exception to this spin cutoff. We report the discovery of a new super-fast rotator, (335433) 2005 UW163, spinning with a period of 1.290 hr and a light curve variation of r' ∼ 0.8 mag from the observations made at the P48 telescope andmore » the P200 telescope of the Palomar Observatory. Its H{sub r{sup ′}}=17.69±0.27 mag and multi-band colors (i.e., g' – r' = 0.68 ± 0.03 mag, r' – i' = 0.19 ± 0.02 mag and SDSS i – z = –0.45 mag) show it is a V-type asteroid with a diameter of 0.6 + 0.3/ – 0.2 km. This indicates (335433) 2005 UW163 is a super-fast rotator beyond the regime of the small monolithic asteroid.« less

25 CFR 163.15 - Advertisement of sales.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false Advertisement of sales. 163.15 Section 163.15 Indians... Management and Operations § 163.15 Advertisement of sales. Except as provided in §§ 163.13, 163.14, 163.16, and 163.26 of this part, sales of forest products shall be made only after advertising. (a) The...

25 CFR 163.15 - Advertisement of sales.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Advertisement of sales. 163.15 Section 163.15 Indians... Management and Operations § 163.15 Advertisement of sales. Except as provided in §§ 163.13, 163.14, 163.16, and 163.26 of this part, sales of forest products shall be made only after advertising. (a) The...

Virtual screening of a milk peptide database for the identification of food-derived antimicrobial peptides.

PubMed

Liu, Yufang; Eichler, Jutta; Pischetsrieder, Monika

2015-11-01

Milk provides a wide range of bioactive substances, such as antimicrobial peptides and proteins. Our study aimed to identify novel antimicrobial peptides naturally present in milk. The components of an endogenous bovine milk peptide database were virtually screened for charge, amphipathy, and predicted secondary structure. Thus, 23 of 248 screened peptides were identified as candidates for antimicrobial effects. After commercial synthesis, their antimicrobial activities were determined against Escherichia coli NEB5α, E. coli ATCC25922, and Bacillus subtilis ATCC6051. In the tested concentration range (<2 mM), bacteriostatic activity of 14 peptides was detected including nine peptides inhibiting both Gram-positive and Gram-negative bacteria. The most effective fragment was TKLTEEEKNRLNFLKKISQRYQKFΑLPQYLK corresponding to αS2 -casein151-181 , with minimum inhibitory concentration (MIC) of 4.0 μM against B. subtilis ATCC6051, and minimum inhibitory concentrations of 16.2 μM against both E. coli strains. Circular dichroism spectroscopy revealed conformational changes of most active peptides in a membrane-mimic environment, transitioning from an unordered to α-helical structure. Screening of food peptide databases by prediction tools is an efficient method to identify novel antimicrobial food-derived peptides. Milk-derived antimicrobial peptides may have potential use as functional food ingredients and help to understand the molecular mechanisms of anti-infective milk effects. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asparagine 175 of connexin32 is a critical residue for docking and forming functional heterotypic gap junction channels with connexin26.

PubMed

Nakagawa, So; Gong, Xiang-Qun; Maeda, Shoji; Dong, Yuhua; Misumi, Yuko; Tsukihara, Tomitake; Bai, Donglin

2011-06-03

The gap junction channel is formed by proper docking of two hemichannels. Depending on the connexin(s) in the hemichannels, homotypic and heterotypic gap junction channels can be formed. Previous studies suggest that the extracellular loop 2 (E2) is an important molecular domain for heterotypic compatibility. Based on the crystal structure of the Cx26 gap junction channel and homology models of heterotypic channels, we analyzed docking selectivity for several hemichannel pairs and found that the hydrogen bonds between E2 domains are conserved in a group of heterotypically compatible hemichannels, including Cx26 and Cx32 hemichannels. According to our model analysis, Cx32N175Y mutant destroys three hydrogen bonds in the E2-E2 interactions due to steric hindrance at the heterotypic docking interface, which makes it unlikely to dock with the Cx26 hemichannel properly. Our experimental data showed that Cx26-red fluorescent protein (RFP) and Cx32-GFP were able to traffic to cell-cell interfaces forming gap junction plaques and functional channels in transfected HeLa/N2A cells. However, Cx32N175Y-GFP exhibited mostly intracellular distribution and was occasionally observed in cell-cell junctions. Double patch clamp analysis demonstrated that Cx32N175Y did not form functional homotypic channels, and dye uptake assay indicated that Cx32N175Y could form hemichannels on the cell surface similar to wild-type Cx32. When Cx32N175Y-GFP- and Cx26-RFP-transfected cells were co-cultured, no colocalization was found at the cell-cell junctions between Cx32N175Y-GFP- and Cx26-RFP-expressing cells; also, no functional Cx32N175Y-GFP/Cx26-RFP heterotypic channels were identified. Both our modeling and experimental data suggest that Asn(175) of Cx32 is a critical residue for heterotypic docking and functional gap junction channel formation between the Cx32 and Cx26 hemichannels.

WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia

PubMed Central

Patel-King, Ramila S.; Gilberti, Renée M.; Hom, Erik F. Y.; King, Stephen M.

2013-01-01

Retrograde intraflagellar transport (IFT) is required for assembly of cilia. We identify a Chlamydomonas flagellar protein (flagellar-associated protein 163 [FAP163]) as being closely related to the D1bIC(FAP133) intermediate chain (IC) of the dynein that powers this movement. Biochemical analysis revealed that FAP163 is present in the flagellar matrix and is actively trafficked by IFT. Furthermore, FAP163 copurified with D1bIC(FAP133) and the LC8 dynein light chain, indicating that it is an integral component of the retrograde IFT dynein. To assess the functional role of FAP163, we generated an RNA interference knockdown of the orthologous protein (WD60) in planaria. The Smed-wd60(RNAi) animals had a severe ciliary assembly defect that dramatically compromised whole-organism motility. Most cilia were present as short stubs that had accumulated large quantities of IFT particle–like material between the doublet microtubules and the membrane. The few remaining approximately full-length cilia had a chaotic beat with a frequency reduced from 24 to ∼10 Hz. Thus WD60/FAP163 is a dynein IC that is absolutely required for retrograde IFT and ciliary assembly. PMID:23864713

Parity-Doublet Structure in the $$147\\atop{57}$$La 90 nucleus

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

Wisniewski, J.; Urban, W.; Rzaca-Urban, T.

Excited states in 147La, populated in spontaneous fission of 252Cf have been reinvestigated by means of γ spectroscopy, using high-fold γ coincidences measured with Gammasphere array of Ge detectors. The 229.5-keV level, which has been assigned spin-parity 9/2 - in a recent evaluation, is shown to have spin-parity 11/2 -. Consequently, the ground state has spin-parity 5/2 +. Excited levels in 147La have been arranged into a parity-doublet structure, showing that at medium excitation energy the 147La nucleus may have octupole deformation. In conclusion, the B( E1) rates in 147La, which are factor four lower than in 145La, suggest thatmore » the electric dipole moment in 147La is depresses by an extra mechanism, probably connected with the population of particular neutron orbitals.« less

Parity-Doublet Structure in the $$147\\atop{57}$$La 90 nucleus

DOE PAGES

Wisniewski, J.; Urban, W.; Rzaca-Urban, T.; ...

2017-12-01

Excited states in 147La, populated in spontaneous fission of 252Cf have been reinvestigated by means of γ spectroscopy, using high-fold γ coincidences measured with Gammasphere array of Ge detectors. The 229.5-keV level, which has been assigned spin-parity 9/2 - in a recent evaluation, is shown to have spin-parity 11/2 -. Consequently, the ground state has spin-parity 5/2 +. Excited levels in 147La have been arranged into a parity-doublet structure, showing that at medium excitation energy the 147La nucleus may have octupole deformation. In conclusion, the B( E1) rates in 147La, which are factor four lower than in 145La, suggest thatmore » the electric dipole moment in 147La is depresses by an extra mechanism, probably connected with the population of particular neutron orbitals.« less

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture.

PubMed

Lee, Changkeun; Guo, Jiangtao; Zeng, Weizhong; Kim, Sunghoon; She, Ji; Cang, Chunlei; Ren, Dejian; Jiang, Youxing

2017-07-27

TMEM175 is a lysosomal K + channel that is important for maintaining the membrane potential and pH stability in lysosomes. It contains two homologous copies of a six-transmembrane-helix (6-TM) domain, which has no sequence homology to the canonical tetrameric K + channels and lacks the TVGYG selectivity filter motif found in these channels. The prokaryotic TMEM175 channel, which is present in a subset of bacteria and archaea, contains only a single 6-TM domain and functions as a tetramer. Here, we present the crystal structure of a prokaryotic TMEM175 channel from Chamaesiphon minutus, CmTMEM175, the architecture of which represents a completely different fold from that of canonical K + channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TM1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TM1 helices form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Mutagenesis analysis suggests that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K + channel family.

Soluble expression and purification of the recombinant bioactive peptide precursor BPP-1 in Escherichia coli using a cELP-SUMO dual fusion system.

PubMed

Rao, Shengqi; Zang, Xiangyu; Yang, Zhenquan; Gao, Lu; Yin, Yongqi; Fang, Weiming

2016-02-01

A bioactive peptide precursor (BPP-1, 14.3 kDa/115AA), a newly designed polypeptide that may exert a potential antihypertensive effect in vivo, is composed of many different ACE inhibitory peptides and antioxidant peptides tandemly linked according to the restriction sites of gastrointestinal proteases. In this report, we present a novel method to obtain soluble BPP-1 in Escherichia coli using cationic elastin-like polypeptide and SUMO (cELP-SUMO) tags. The cELP-SUMO-tagged fusion protein was expressed in soluble form at 20 °C for 20 h. After purification based on the inverse transition cycling (ITC) method, the purified cELP-SUMO-CFPP fusion protein was subsequently cleaved by a SUMO protease to release the mature BPP-1. After a subsequent simple salt precipitation process, approximately 167.2 mg of recombinant BPP-1 was obtained from 1 l of bacterial culture with at least 92% purity. The molecular mass (Mr) of the recombinant BPP-1 was confirmed by MALDI-TOF MS to equal 14,347. The purified BPP-1 was subjected to simulated gastrointestinal digestion, and the resulting hydrolysates exhibited notable ACE inhibitory and antioxidant activities in vitro. This report provides the first description of the soluble production of a bioactive peptide multimer with potential ACE inhibitory and antioxidant activities in E. coli using a cELP-SUMO tag. Copyright © 2015 Elsevier Inc. All rights reserved.

Human HLA-Ev (147) Expression in Transgenic Animals.

PubMed

Matsuura, R; Maeda, A; Sakai, R; Eguchi, H; Lo, P-C; Hasuwa, H; Ikawa, M; Nakahata, K; Zenitani, M; Yamamichi, T; Umeda, S; Deguchi, K; Okuyama, H; Miyagawa, S

2016-05-01

In our previous study, we reported on the development of substituting S147C for HLA-E as a useful gene tool for xenotransplantation. In this study we exchanged the codon of HLA-Ev (147), checked its function, and established a line of transgenic mice. A new construct, a codon exchanging human HLA-Ev (147) + IRES + human beta 2-microgloblin, was established. The construct was subcloned into pCXN2 (the chick beta-actin promoter and cytomegalovirus enhancer) vector. Natural killer cell- and macrophage-mediated cytotoxicities were performed using the established the pig endothelial cell (PEC) line with the new gene. Transgenic mice with it were next produced using a micro-injection method. The expression of the molecule on PECs was confirmed by the transfection of the plasmid. The established molecules on PECs functioned well in regulating natural killer cell-mediated cytotoxicity and macrophage-mediated cytotoxicity. We have also successfully generated several lines of transgenic mice with this plasmid. The expression of HLA-Ev (147) in each mouse organ was confirmed by assessing the mRNA. The chick beta-actin promoter and cytomegalovirus enhancer resulted in a relatively broad expression of the gene in each organ, and a strong expression in the cases of the heart and lung. A synthetic HLA-Ev (147) gene with a codon usage optimized to a mammalian system represents a critical factor in the development of transgenic animals for xenotransplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

26 CFR 1.167(a)-10 - When depreciation deduction is allowable.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false When depreciation deduction is allowable. 1.167... Corporations § 1.167(a)-10 When depreciation deduction is allowable. (a) A taxpayer should deduct the proper depreciation allowance each year and may not increase his depreciation allowances in later years by reason of...

An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine pulmonary fibrosis model.

PubMed

Nishimoto, Tetsuya; Mlakar, Logan; Takihara, Takahisa; Feghali-Bostwick, Carol

2015-10-01

Pulmonary fibrosis causes high morbidity and mortality in affected individuals. Recently, we showed that parenteral or intratracheal administration of a peptide derived from endostatin, called E4, prevents and ameliorates fibrosis using different models of dermal and pulmonary disease. No marketed orally delivered peptide drugs are currently available for progressive pulmonary fibrosis; however oral delivery of drugs is the preferred route for treating most chronic diseases. Thus, we investigated whether oral administration of E4 peptide exerted anti-fibrotic activity in a murine pulmonary fibrosis model. Bleomycin (1.2mU/g body weight) was intratracheally administrated to male 6-8-week-old C57BL/6J mice. E4 peptide (20, 10, 5, and 1 μg/mouse) or scrambled control peptide (20 μg/mouse) was orally administered on the same day as bleomycin. In some experiments, E4 peptide (10 and 5 μg/mouse) was orally administered three times on days 0, 3, and 6 post-bleomycin treatment. Lungs were harvested on day 21 for histological analysis and hydroxyproline assay. Histological analysis and hydroxyproline assay revealed that bleomycin successfully induced pulmonary fibrosis, and that 20 μg of oral E4 peptide ameliorated the fibrosis. The lower doses of E4 peptide (10, 5, and 1 μg) were insufficient to exert anti-fibrotic activity when given as a single dose. Multiple doses of E4 peptide efficiently exerted anti-fibrotic activity even at lower doses. E4 peptide shows oral bioavailability and exerts anti-fibrotic activity in a bleomycin-induced pulmonary fibrosis model. We suggest that E4 peptide is a novel oral drug for fibroproliferative disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine pulmonary fibrosis model

PubMed Central

Nishimoto, Tetsuya; Mlakar, Logan; Takihara, Takahisa; Feghali-Bostwick, Carol

2016-01-01

Objective Pulmonary fibrosis causes high morbidity and mortality in affected individuals. Recently, we showed that parenteral or intratracheal administration of a peptide derived from endostatin, called E4, prevents and ameliorates fibrosis using different models of dermal and pulmonary disease. No marketed orally delivered peptide drugs are currently available for progressive pulmonary fibrosis; however oral delivery of drugs is the preferred route for treating most chronic diseases. Thus, we investigated whether oral administration of E4 peptide exerted anti-fibrotic activity in a murine pulmonary fibrosis model. Methods Bleomycin (1.2mU/g body weight) was intratracheally administrated to male 6–8-week-old C57BL/6J mice. E4 peptide (20, 10, 5, and 1 μg/mouse) or scrambled control peptide (20 μg/mouse) were orally administered on the same day as bleomycin. In some experiments, E4 peptide (10 and 5 μg/mouse) was orally administered three times on days 0, 3, and 6 post-bleomycin treatment. Lungs were harvested on day 21 for histological analysis and hydroxyproline assay. Results Histological analysis and hydroxyproline assay revealed that bleomycin successfully induced pulmonary fibrosis, and that 20μg of oral E4 peptide ameliorated the fibrosis. The lower doses of E4 peptide (10, 5, and 1 μg) were insufficient to exert anti-fibrotic activity when given as a single dose. Multiple doses of E4 peptide efficiently exerted anti-fibrotic activity even at lower doses. Conclusion E4 peptide shows oral bioavailability and exerts anti-fibrotic activity in a bleomycin-induced pulmonary fibrosis model. We suggest that E4 peptide is a novel oral drug for fibroproliferative disorders. PMID:26315492

45 CFR 156.915 - Intervention.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Intervention. 156.915 Section 156.915 Public... Administrative Review of QHP Issuer Sanctions in Federally-Facilitated Exchanges § 156.915 Intervention. (a) The... intervention will not unduly delay or prejudice the adjudication of the rights of the existing parties. (b) A...

The clinical relevance of plasma CD147/basigin in biopsy-proven kidney diseases.

PubMed

Mori, Yoshiko; Masuda, Tomohiro; Kosugi, Tomoki; Yoshioka, Tomoki; Hori, Mayuko; Nagaya, Hiroshi; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Kato, Noritoshi; Ishimoto, Takuji; Katsuno, Takayuki; Yuzawa, Yukio; Kadomatsu, Kenji; Maruyama, Shoichi

2017-12-12

Precise understanding of kidney disease activity is needed to design therapeutic strategies. CD147/basigin is involved in the pathogenesis of acute kidney injury and renal fibrosis through inflammatory cell infiltration. The present study examined the clinical relevance of CD147 in biopsy-proven kidney diseases that lead to the progression of chronic kidney disease. Kidney biopsy specimens and plasma and urine samples were obtained from patients with kidney diseases, including IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), who underwent renal biopsy between 2011 and 2014. Plasma and urinary CD147 levels were measured and evaluated for their ability to reflect histological features. Disease activity of IgAN tissues was evaluated according to the Oxford classification and the Japanese histological grading system. In biopsy tissues, CD147 induction was detected in injured lesions representing renal inflammation. Plasma CD147 values correlated with eGFR in patients with inflammation-related kidney diseases such as IgAN, HSPN, and DKD. Particularly in IgAN patients, plasma CD147 levels were correlated with injured regions comprising more than 50% of glomeruli or with tubular atrophy/interstitial injury in biopsy tissues. Proteinuria showed a closer correlation with urinary values of CD147 and L-FABP. Of note, plasma and urinary CD147 levels showed a strong correlation with eGFR or proteinuria, respectively, only in DKD patients. Evaluation of plasma and urinary CD147 levels might provide key insights for the understanding of the activity of various kidney diseases.

46 CFR 147A.9 - Persons in charge of fumigation and the vessel; designation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Persons in charge of fumigation and the vessel; designation. 147A.9 Section 147A.9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.9 Persons in charge of fumigation and...

46 CFR 147A.9 - Persons in charge of fumigation and the vessel; designation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Persons in charge of fumigation and the vessel; designation. 147A.9 Section 147A.9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.9 Persons in charge of fumigation and...

46 CFR 147A.9 - Persons in charge of fumigation and the vessel; designation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Persons in charge of fumigation and the vessel; designation. 147A.9 Section 147A.9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.9 Persons in charge of fumigation and...

46 CFR 147A.9 - Persons in charge of fumigation and the vessel; designation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Persons in charge of fumigation and the vessel; designation. 147A.9 Section 147A.9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.9 Persons in charge of fumigation and...

46 CFR 147A.9 - Persons in charge of fumigation and the vessel; designation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Persons in charge of fumigation and the vessel; designation. 147A.9 Section 147A.9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.9 Persons in charge of fumigation and...

46 CFR 163.002-15 - Performance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 6 2012-10-01 2012-10-01 false Performance. 163.002-15 Section 163.002-15 Shipping...: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Hoist § 163.002-15 Performance. (a) Each pilot hoist must have sufficient performance capability to pass the approval tests in § 163.002-21. (b) [Reserved] ...

46 CFR 163.002-15 - Performance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Performance. 163.002-15 Section 163.002-15 Shipping...: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Hoist § 163.002-15 Performance. (a) Each pilot hoist must have sufficient performance capability to pass the approval tests in § 163.002-21. (b) [Reserved] ...

46 CFR 163.002-15 - Performance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 6 2011-10-01 2011-10-01 false Performance. 163.002-15 Section 163.002-15 Shipping...: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Hoist § 163.002-15 Performance. (a) Each pilot hoist must have sufficient performance capability to pass the approval tests in § 163.002-21. (b) [Reserved] ...

46 CFR 163.002-15 - Performance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Performance. 163.002-15 Section 163.002-15 Shipping...: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Hoist § 163.002-15 Performance. (a) Each pilot hoist must have sufficient performance capability to pass the approval tests in § 163.002-21. (b) [Reserved] ...

46 CFR 163.002-15 - Performance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 6 2010-10-01 2010-10-01 false Performance. 163.002-15 Section 163.002-15 Shipping...: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Hoist § 163.002-15 Performance. (a) Each pilot hoist must have sufficient performance capability to pass the approval tests in § 163.002-21. (b) [Reserved] ...

14 CFR 406.163 - Record.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Record. 406.163 Section 406.163 Aeronautics... Transportation Adjudications § 406.163 Record. (a) Exclusive record. The transcript of all testimony in the..., applications, and requests, and responses thereto; and all rulings constitute the exclusive record for decision...

14 CFR 406.163 - Record.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Record. 406.163 Section 406.163 Aeronautics... Transportation Adjudications § 406.163 Record. (a) Exclusive record. The transcript of all testimony in the..., applications, and requests, and responses thereto; and all rulings constitute the exclusive record for decision...

14 CFR 406.163 - Record.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Record. 406.163 Section 406.163 Aeronautics... Transportation Adjudications § 406.163 Record. (a) Exclusive record. The transcript of all testimony in the..., applications, and requests, and responses thereto; and all rulings constitute the exclusive record for decision...

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture

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

Lee, Changkeun; Guo, Jiangtao; Zeng, Weizhong

TMEM175 is a lysosomal K+ channel that is important for maintaining the membrane potential and pH stability in lysosomes1. It contains two homologous copies of a six-transmembrane-helix (6-TM) domain, which has no sequence homology to the canonical tetrameric K+ channels and lacks the TVGYG selectivity filter motif found in these channels2, 3, 4. The prokaryotic TMEM175 channel, which is present in a subset of bacteria and archaea, contains only a single 6-TM domain and functions as a tetramer. Here, we present the crystal structure of a prokaryotic TMEM175 channel from Chamaesiphon minutus, CmTMEM175, the architecture of which represents a completelymore » different fold from that of canonical K+ channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TM1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TM1 helices form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Mutagenesis analysis suggests that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K+ channel family.« less

Small molecule non-peptide inhibitors of botulinum neurotoxin serotype E: Structure–activity relationship and a pharmacophore model

DOE PAGES

Kumar, Gyanendra; Agarwal, Rakhi; Swaminathan, Subramanyam

2016-06-18

Botulinum neurotoxins (BoNTs) are the most poisonous biological substance known to humans. They cause flaccid paralysis by blocking the release of acetylcholine at the neuromuscular junction. Here, we report a number of small molecule non-peptide inhibitors of BoNT serotype E. In addition, the structure–activity relationship and a pharmacophore model are presented. Although non-peptidic in nature, these inhibitors mimic key features of the uncleavable substrate peptide Arg-Ile-Met-Glu (RIME) of the SNAP-25 protein. Among the compounds tested, most of the potent inhibitors bear a zinc-chelating moiety connected to a hydrophobic and aromatic moiety through a carboxyl or amide linker. All of themmore » show low micromolar IC 50 values.« less

EtpE Binding to DNase X Induces Ehrlichial Entry via CD147 and hnRNP-K Recruitment, Followed by Mobilization of N-WASP and Actin.

PubMed

Mohan Kumar, Dipu; Lin, Mingqun; Xiong, Qingming; Webber, Mathew James; Kural, Comert; Rikihisa, Yasuko

2015-11-03

Obligate intracellular bacteria, such as Ehrlichia chaffeensis, perish unless they can enter eukaryotic cells. E. chaffeensis is the etiological agent of human monocytic ehrlichiosis, an emerging infectious disease. To infect cells, Ehrlichia uses the C terminus of the outer membrane invasin entry-triggering protein (EtpE) of Ehrlichia (EtpE-C), which directly binds the mammalian cell surface glycosylphosphatidyl inositol-anchored protein, DNase X. How this binding drives Ehrlichia entry is unknown. Here, using affinity pulldown of host cell lysates with recombinant EtpE-C (rEtpE-C), we identified two new human proteins that interact with EtpE-C: CD147 and heterogeneous nuclear ribonucleoprotein K (hnRNP-K). The interaction of CD147 with rEtpE-C was validated by far-Western blotting and coimmunoprecipitation of native EtpE with endogenous CD147. CD147 was ubiquitous on the cell surface and also present around foci of rEtpE-C-coated-bead entry. Functional neutralization of surface-exposed CD147 with a specific antibody inhibited Ehrlichia internalization and infection but not binding. Downregulation of CD147 by short hairpin RNA (shRNA) impaired E. chaffeensis infection. Functional ablation of cytoplasmic hnRNP-K by a nanoscale intracellular antibody markedly attenuated bacterial entry and infection but not binding. EtpE-C also interacted with neuronal Wiskott-Aldrich syndrome protein (N-WASP), which is activated by hnRNP-K. Wiskostatin, which inhibits N-WASP activation, and cytochalasin D, which inhibits actin polymerization, inhibited Ehrlichia entry. Upon incubation with host cell lysate, EtpE-C but not an EtpE N-terminal fragment stimulated in vitro actin polymerization in an N-WASP- and DNase X-dependent manner. Time-lapse video images revealed N-WASP recruitment at EtpE-C-coated bead entry foci. Thus, EtpE-C binding to DNase X drives Ehrlichia entry by engaging CD147 and hnRNP-K and activating N-WASP-dependent actin polymerization. Ehrlichia chaffeensis, an

C-Peptide Is a Sensitive Indicator for the Diagnosis of Metabolic Syndrome in Subjects from Central Mexico.

PubMed

Gonzalez-Mejia, M Elba; Porchia, Leonardo M; Torres-Rasgado, Enrique; Ruiz-Vivanco, Guadalupe; Pulido-Pérez, Patricia; Báez-Duarte, Blanca G; Pérez-Fuentes, Ricardo

2016-05-01

Metabolic Syndrome (MetS) is associated with elevated risk for developing diabetes and cardiovascular disease. A key component of MetS is the development of insulin resistance (IR). The homeostatic model assessment (HOMA) model can determine IR by using insulin or C-peptide concentrations; however, the efficiency of insulin and C-peptide to determine MetS has not been compared. The aim of the study was to compare the efficiency of C-peptide and insulin to determine MetS in Mexicans. Anthropometrics, glucose, insulin, C-peptide, triglycerides, and high-density lipoproteins were determined in 156 nonpregnant females and 114 males. Subjects were separated into normal or positive for MetS. IR was determined by the HOMA2 calculator using insulin or C-peptide. Correlations were calculated using the Spearman correlation coefficient (ρ). Differences between correlations were determined by calculating Steiger's Z. The sensitivity was determined by the area under receiver operating characteristics curve (AUC) analysis. Independent of the MetS definition [Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF), or World Health Organization (WHO)], C-peptide and insulin were significantly higher in MetS subjects (P < 0.05). C-peptide and insulin correlated with all components of MetS; however, for waist circumference, waist-to-hip ratio, and fasting plasma glucose, C-peptide correlated better than insulin (P < 0.05). Moreover, C-peptide (AUC = 0.72-0.78) was a better marker than insulin (AUC = 0.62-0.72) for MetS (P < 0.05). Finally, HOMA2-IR calculated with C-peptide (AUC = 0.80-0.84) was more accurate than HOMA2-IR calculated with insulin (AUC = 0.68-0.75, P < 0.05) at determining MetS. C-peptide is a strong indicator of MetS. Since C-peptide has recently emerged as a biomolecule with significant importance for inflammatory diseases, monitoring C-peptide levels will aid clinicians in preventing MetS.

Angiostatic, tumor inflammatory and anti-tumor effects of CXCL447–70 and CXCL4L147–70 in an EGF-dependent breast cancer model

PubMed Central

Van Raemdonck, Katrien; Berghmans, Nele; Vanheule, Vincent; Bugatti, Antonella; Proost, Paul; Opdenakker, Ghislain; Presta, Marco; Van Damme, Jo; Struyf, Sofie

2014-01-01

CXCL4 and CXCL4L1, platelet-derived CXC chemokines, and their carboxy-terminal peptides CXCL447–70 and CXCL4L147–70 previously displayed angiostatic and anti-tumoral activity in a melanoma model. Here, we found CXCL447–70 and CXCL4L147–70 to inhibit lymphatic endothelial cell proliferation in vitro. Furthermore, the angiostatic potential of CXCL447–70 and CXCL4L147–70 was tested against different angiogenic stimuli (FGF1, FGF2, FGF8, EGF and VEGF). Besides reducing FGF2-induced vascular endothelial cell growth, CXCL447–70 and CXCL4L147–70 efficiently counteracted EGF. Consequently, we considered their anti-tumoral potential in EGF-dependent MDA-MB-231 breast tumors. In tumor-bearing mice, CXCL447–70 reduced tumor growth better than CXCL4L147–70. In CXCL447–70-treated tumors significantly more intratumoral monocytes/macrophages and dendritic cells were present and higher expression levels of CCL5 and IFN-γ were detected by qPCR on tumor lysates. Because neither peptide was able to specifically bind CXCR3A or CXCR3B, differential glycosaminoglycan binding and direct interaction with cytokines (EGF and CCL5) might explain any differences in anti-tumoral effects. Notably, CCL5-induced monocyte chemotaxis in vitro was increased by addition of CXCL447–70 or CXCL4L147–70. Finally, CXCL447–70 and CXCL4L147–70 inhibited proliferation of MDA-MB-231 cells. Our results suggest a tumor type-dependent responsiveness to either CXCL447–70 or CXCL4L147–70 treatment, defined by anti-proliferative, angiostatic and inflammatory actions, and substantiate their therapeutic potential. PMID:25373734

45 CFR 156.510 - Eligibility.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Eligibility. 156.510 Section 156.510 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS HEALTH... Operated and Oriented Plan Program § 156.510 Eligibility. (a) General. In addition to the eligibility...

Seizure outcome in 175 patients with juvenile myoclonic epilepsy--a long-term observational study.

PubMed

Höfler, Julia; Unterberger, Iris; Dobesberger, Judith; Kuchukhidze, Giorgi; Walser, Gerald; Trinka, Eugen

2014-12-01

Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome. Under appropriate antiepileptic drugs (AED) up to 85% of patients become seizure-free, but many may have a relapse after AED withdrawal. We retrospectively studied 242 patients with JME at the Department of Neurology, Medical University Innsbruck, Austria (1975-2006). We analyzed age at seizure onset, age at last follow up, seizure types, photosensitivity, seizure outcome and neuroimaging findings; inclusion criterion was a medical treatment period of >2 years; exclusion criteria were traumatic or infectious brain injury before the onset of JME and/or gross structural pathology on neuroimaging. We identified 175 patients (111 women) with a median age at seizure onset of 15 years, (range 3-46) and a median age at follow-up (FU) of 38 years (range 14-87; median FU 8 years, range 2-38). Fourteen percent showed (24/175) photosensitivity on routine EEG. Seizure outcome: 62% (109/175) were seizure-free of myoclonic seizures (MS), generalized tonic clonic seizures (GTCS) and absence seizures (AS) for >1 year, and 53% (94/175) for >2 years, including 16 patients (9%) without AEDs. Thirty-one percent (54/175) were seizure-free between 2 and 5 years, 15% (26/175) between 6 and 10, and 8% (14/175) >10 years; 38% (66/175) were not seizure-free. Not seizure-free patients had more often MS, AS and GTCS within the first year of epilepsy than those who were seizure-free at last FU (11% vs. 3%, Chi(2)=4.679, df=1, p=0.043). Seizure-free patients had more often MS and GTCS as last seizure types in the year before becoming seizure-free (37% vs. 15%, p=0.003), whereas in not seizure-free group MS only and GTCS only persisted. JME does not always need lifelong treatment, as a substantial minority of patients remain seizure-free without AEDs. AS, MS and GTCS at onset of the disease are indicators of poor long-term seizure control. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

26 CFR 1.163-11T - Allocation of certain prepaid qualified mortgage insurance premiums (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... insurance premiums (temporary). 1.163-11T Section 1.163-11T Internal Revenue INTERNAL REVENUE SERVICE... insurance premiums (temporary). (a) Allocation—(1) In general. As provided in section 163(h)(3)(E), premiums... section applies whether the qualified mortgage insurance premiums are paid in cash or are financed...

26 CFR 1.163-11T - Allocation of certain prepaid qualified mortgage insurance premiums (temporary).

Code of Federal Regulations, 2011 CFR

2011-04-01

... insurance premiums (temporary). 1.163-11T Section 1.163-11T Internal Revenue INTERNAL REVENUE SERVICE... insurance premiums (temporary). (a) Allocation—(1) In general. As provided in section 163(h)(3)(E), premiums... section applies whether the qualified mortgage insurance premiums are paid in cash or are financed...

Small molecule non-peptide inhibitors of botulinum neurotoxin serotype E: Structure-activity relationship and a pharmacophore model.

PubMed

Kumar, Gyanendra; Agarwal, Rakhi; Swaminathan, Subramanyam

2016-09-15

Botulinum neurotoxins (BoNTs) are the most poisonous biological substance known to humans. They cause flaccid paralysis by blocking the release of acetylcholine at the neuromuscular junction. Here, we report a number of small molecule non-peptide inhibitors of BoNT serotype E. The structure-activity relationship and a pharmacophore model are presented. Although non-peptidic in nature, these inhibitors mimic key features of the uncleavable substrate peptide Arg-Ile-Met-Glu (RIME) of the SNAP-25 protein. Among the compounds tested, most of the potent inhibitors bear a zinc-chelating moiety connected to a hydrophobic and aromatic moiety through a carboxyl or amide linker. All of them show low micromolar IC50 values. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association of the FAM167A-BLK region with systemic sclerosis.

PubMed

Ito, Ikue; Kawaguchi, Yasushi; Kawasaki, Aya; Hasegawa, Minoru; Ohashi, Jun; Kawamoto, Manabu; Fujimoto, Manabu; Takehara, Kazuhiko; Sato, Shinichi; Hara, Masako; Tsuchiya, Naoyuki

2010-03-01

An association of single-nucleotide polymorphisms (SNPs) in the FAM167A (previously referred to as C8orf13)-BLK region with systemic lupus erythematosus (SLE) has been demonstrated in Caucasians and in Asians. Recent studies have shown that many genes, including IRF5, STAT4, and PTPN22, are shared susceptibility genes in multiple autoimmune diseases. We undertook the current study to examine whether the FAM167A-BLK region is also associated with susceptibility to systemic sclerosis (SSc). Japanese patients with SSc (n = 309) and healthy controls (n = 769) were enrolled in a 2-tiered case-control association study. In tier 1, 124 patients and 412 controls were tested to determine association of 16 tag SNPs encompassing the FAM167A-BLK region with SSc. In tier 2, an additional 185 patients and 357 controls were analyzed for SNP rs13277113. Two haplotype blocks that correspond approximately to FAM167A and BLK were observed. In tier 1 of the study, the rs13277113A allele in the BLK block exhibited the most significant association with SSc after correction for multiple testing (permutated P = 0.024). Two SNP haplotypes formed by rs13277113 and the most significant SNP in the FAM167A block did not exhibit stronger association. When samples from tier 1 and tier 2 were combined, the rs13277113A allele was significantly associated with SSc (odds ratio 1.45 [95% confidence interval 1.17-1.79], P = 6.1 x 10(-4)). Association or a tendency toward association of rs13277113A with SSc was observed regardless of a patient's autoantibody profile or whether a patient had diffuse cutaneous or limited cutaneous SSc. Our findings indicate that the rs13277113A allele is associated not only with SLE but also with SSc and that the FAM167A-BLK region is a common genetic risk factor for both SLE and SSc.

4p16.3 microdeletions and microduplications detected by chromosomal microarray analysis: New insights into mechanisms and critical regions.

PubMed

Bi, Weimin; Cheung, Sau-Wai; Breman, Amy M; Bacino, Carlos A

2016-10-01

Deletions in the 4p16.3 region cause Wolf-Hirschhorn syndrome, a well known contiguous microdeletion syndrome with the critical region for common phenotype mapped in WHSCR2. Recently, duplications in 4p16.3 were reported in three patients with developmental delay and dysmorphic features. Through chromosomal microarray analysis, we identified 156 patients with a deletion (n = 109) or duplication (n = 47) in 4p16.3 out of approximately 60,000 patients analyzed by Baylor Miraca Genetics Laboratories. Seventy-five of the postnatally detected deletions encompassed the entire critical region, 32 (43%) of which were associated with other chromosome rearrangements, including six patients (8%) that had a duplication adjacent to the terminal deletion. Our data indicate that Wolf-Hirschhorn syndrome deletions with an adjacent duplication occur at a higher frequency than previously appreciated. Pure deletions (n = 14) or duplications (n = 15) without other copy number changes distal to or inside the WHSCR2 were identified for mapping of critical regions. Our data suggest that deletion of the segment from 0.6 to 0.9 Mb from the terminus of 4p causes a seizure phenotype and duplications of a region distal to the previously defined smallest region of overlap for 4p16.3 microduplication syndrome are associated with neurodevelopmental problems. We detected seven Wolf-Hirschhorn syndrome deletions and one 4p16.3 duplication prenatally; all of the seven are either >8 Mb in size and/or associated with large duplications. In conclusion, our study provides deeper insight into the molecular mechanisms, the critical regions and effective prenatal diagnosis for 4p16.3 deletions/ duplications. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

CD147 as a Novel Prognostic Biomarker for Hepatocellular Carcinoma: A Meta-Analysis.

PubMed

Peng, Fei; Li, Hui; You, Qian; Li, Hongru; Wu, Dongwen; Jiang, Chunxiang; Deng, Guangtong; Li, Yan; Li, Yuyan; Wu, Yi

2017-01-01

We conducted a meta-analysis to investigate the controversial association of CD147 expression with HCC prognosis and clinicopathological characteristics. Eight studies from PubMed (1966-2016), EMBASE (1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and Wanfang databases (1988-2016) were considered. The associations between CD147 expression and clinicopathological parameters and overall survival (OS) or DFS/RFS were reassessed using the meta-analysis for odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI). CD147 expression was associated with DFS/RFS (HR = 3.26; 95% CI: 1.82-5.83; P < 0.0001) but not with OS (HR = 1.35; 95% CI: 0.56-3.29; P = 0.51). We also delved deeper into the association between median survival time and CD147 expression owing to significant heterogeneity and found significant differences between high and low CD147 expression groups with respect to median survival time. CD147 expression was closely associated with the TNM stage (OR = 0.18; 95% CI: 0.04-0.85; P = 0.03) and venous invasion (OR = 6.29; 95% CI: 1.70-23.20; P = 0.006). In contrast, there was no association between CD147 expression and tumor stage, cirrhosis, differentiation, lymph node metastasis, HBsAg, and serum AFP levels. Thus, CD147 expression is potentially closely related to HCC survival and associated clinicopathological parameters, paving the way for further research.

46 CFR 147A.11 - Person in charge of fumigation; before fumigation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Person in charge of fumigation; before fumigation. 147A.11 Section 147A.11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS... Introduction of the International Maritime Dangerous Goods Code. The word “unit” on the warning sign may be...

46 CFR 147A.11 - Person in charge of fumigation; before fumigation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Person in charge of fumigation; before fumigation. 147A.11 Section 147A.11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS... Introduction of the International Maritime Dangerous Goods Code. The word “unit” on the warning sign may be...

46 CFR 147A.11 - Person in charge of fumigation; before fumigation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Person in charge of fumigation; before fumigation. 147A.11 Section 147A.11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS... Introduction of the International Maritime Dangerous Goods Code. The word “unit” on the warning sign may be...

Design and heterologous expression of dengue virus envelope protein (E) peptides and their use for serological diagnosis.

PubMed

Honda, Eduardo R; Zanchi, Fernando; Rios, Katiuscia; Lira, Ednaldo; DeusileneVieira; da Silva, Luiz H P; De Paula, Sergio O

2012-12-01

Viruses belonging to the Flaviviridae family are found and distributed in most of the tropical and sub-tropical regions of the world. The genus has more than 56 members, most of which cause clinical symptoms in humans. The clinical diagnosis of dengue requires laboratory confirmation because of the similarity of symptoms with a series of other acute fevers and the primary use antibodies or antigens for detection. In this work, peptides E(1) and E(2) of the envelope protein (E) of the dengue virus were mapped using bioinformatics methods. These peptides were then expressed in a prokaryotic system and purified. An indirect ELISA for antibodies IgG and IgM from laboratory samples previously characterised was then used with the peptides to detect anti-dengue antibodies. For IgG using the peptide E(1), the sensitivity of the indirect ELISA was 88.3% and the specificity was 56%; using the peptide E(2), the sensitivity was 90% and the specificity was 59%; and using a combination of both peptides, the sensitivity was 93.3% and the specificity was 78%. For IgM using the peptide E(1), the sensitivity was 88% and the specificity was 66%; using the peptide E(2), the sensitivity was 88% and the specificity was 69%; and when used in combination, the peptides E(1)/E(2) demonstrated a sensitivity of 90% and a specificity of 86%. These results indicate that the use of the E(1) and E(2) peptides of the E protein are an alternative for serological diagnosis of dengue fever. Copyright © 2012 Elsevier B.V. All rights reserved.

26 CFR 1.167(a)-6 - Depreciation in special cases.

Code of Federal Regulations, 2010 CFR

2010-04-01

....167(a)-6 Depreciation in special cases. (a) Depreciation of patents or copyrights. The cost or other basis of a patent or copyright shall be depreciated over its remaining useful life. Its cost to the patentee includes the various Government fees, cost of drawings, models, attorneys' fees, and similar...

CD147 and AGR2 expression promote cellular proliferation and metastasis of head and neck squamous cell carcinoma

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

Sweeny, Larissa, E-mail: larissasweeny@gmail.com; Liu, Zhiyong; Bush, Benjamin D.

2012-08-15

The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis. -- Highlights: Black-Right-Pointing-Pointer We investigated AGR2more » in head and neck squamous cell carcinoma for the first time. Black-Right-Pointing-Pointer We explored the relationship between AGR2 and CD147 for the first time. Black-Right-Pointing-Pointer AGR2 and CD147 appear to co-localize in head and squamous cell carcinoma samples. Black-Right-Pointing-Pointer Knockdown of both AGR2 and CD147 reduced migration and invasion in vitro. Black-Right-Pointing-Pointer Knockdown of both AGR2 and CD147 decreased metastasis in vivo.« less

Glucuronidation of OTS167 in Humans Is Catalyzed by UDP-Glucuronosyltransferases UGT1A1, UGT1A3, UGT1A8, and UGT1A10

PubMed Central

Ramírez, Jacqueline; Mirkov, Snezana; House, Larry K.

2015-01-01

OTS167 is a potent maternal embryonic leucine zipper kinase inhibitor undergoing clinical testing as antineoplastic agent. We aimed to identify the UDP-glucuronosyltransferases (UGTs) involved in OTS167 metabolism, study the relationship between UGT genetic polymorphisms and hepatic OTS167 glucuronidation, and investigate the inhibitory potential of OTS167 on UGTs. Formation of a single OTS167-glucuronide (OTS167-G) was observed in pooled human liver (HLM) (Km = 3.4 ± 0.2 µM), intestinal microsomes (HIM) (Km = 1.7 ± 0.1 µM), and UGTs. UGT1A1 (64 µl/min/mg) and UGT1A8 (72 µl/min/mg) exhibited the highest intrinsic clearances (CLint) for OTS167, followed by UGT1A3 (51 µl/min/mg) and UGT1A10 (47 µl/min/mg); UGT1A9 was a minor contributor. OTS167 glucuronidation in HLM was highly correlated with thyroxine glucuronidation (r = 0.91, P < 0.0001), SN-38 glucuronidation (r = 0.79, P < 0.0001), and UGT1A1 mRNA (r = 0.72, P < 0.0001). Nilotinib (UGT1A1 inhibitor) and emodin (UGT1A8 and UGT1A10 inhibitor) exhibited the highest inhibitory effects on OTS167-G formation in HLM (68%) and HIM (47%). We hypothesize that OTS167-G is an N-glucuronide according to mass spectrometry. A significant association was found between rs6706232 and reduced OTS167-G formation (P = 0.03). No or weak UGT inhibition (range: 0–21%) was observed using clinically relevant OTS167 concentrations (0.4–2 µM). We conclude that UGT1A1 and UGT1A3 are the main UGTs responsible for hepatic formation of OTS167-G. Intestinal UGT1A1, UGT1A8, and UGT1A10 may contribute to first-pass OTS167 metabolism after oral administration. PMID:25870101

Glucuronidation of OTS167 in Humans Is Catalyzed by UDP-Glucuronosyltransferases UGT1A1, UGT1A3, UGT1A8, and UGT1A10.

PubMed

Ramírez, Jacqueline; Mirkov, Snezana; House, Larry K; Ratain, Mark J

2015-07-01

OTS167 is a potent maternal embryonic leucine zipper kinase inhibitor undergoing clinical testing as antineoplastic agent. We aimed to identify the UDP-glucuronosyltransferases (UGTs) involved in OTS167 metabolism, study the relationship between UGT genetic polymorphisms and hepatic OTS167 glucuronidation, and investigate the inhibitory potential of OTS167 on UGTs. Formation of a single OTS167-glucuronide (OTS167-G) was observed in pooled human liver (HLM) (Km = 3.4 ± 0.2 µM), intestinal microsomes (HIM) (Km = 1.7 ± 0.1 µM), and UGTs. UGT1A1 (64 µl/min/mg) and UGT1A8 (72 µl/min/mg) exhibited the highest intrinsic clearances (CLint) for OTS167, followed by UGT1A3 (51 µl/min/mg) and UGT1A10 (47 µl/min/mg); UGT1A9 was a minor contributor. OTS167 glucuronidation in HLM was highly correlated with thyroxine glucuronidation (r = 0.91, P < 0.0001), SN-38 glucuronidation (r = 0.79, P < 0.0001), and UGT1A1 mRNA (r = 0.72, P < 0.0001). Nilotinib (UGT1A1 inhibitor) and emodin (UGT1A8 and UGT1A10 inhibitor) exhibited the highest inhibitory effects on OTS167-G formation in HLM (68%) and HIM (47%). We hypothesize that OTS167-G is an N-glucuronide according to mass spectrometry. A significant association was found between rs6706232 and reduced OTS167-G formation (P = 0.03). No or weak UGT inhibition (range: 0-21%) was observed using clinically relevant OTS167 concentrations (0.4-2 µM). We conclude that UGT1A1 and UGT1A3 are the main UGTs responsible for hepatic formation of OTS167-G. Intestinal UGT1A1, UGT1A8, and UGT1A10 may contribute to first-pass OTS167 metabolism after oral administration. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

26 CFR 1.167(a)-8 - Retirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... income. Such distortion would result from the fact that the use of average useful life (and, accordingly... Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations § 1.167(a)-8 Retirements...

45 CFR 156.935 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Discovery. 156.935 Section 156.935 Public Welfare... QHP Issuer Sanctions in Federally-Facilitated Exchanges § 156.935 Discovery. (a) The parties must identify any need for discovery from the opposing party as soon as possible, but no later than the time for...

CD147 blockade as a potential and novel treatment of graft rejection

PubMed Central

Luan, Jing; Zhao, Yu; Zhang, Yang; Miao, Jinlin; Li, Jia; Chen, Zhi-Nan; Zhu, Ping

2017-01-01

Cluster of differentiation (CD)147 is highly involved in the T cell activation process. High CD147 expression is observed on the surfaces of activated T cells, particularly CD4+ T cells. In organ transplantation, it is important to prevent graft rejection resulting from the excessive activation of T cells, particularly CD4+ T cells, which exhibit a key role in amplifying the immune response. The present study aimed to investigate the effects of CD147 blockade in vitro and in vivo and used a transplant rejection system to assess the feasibility of utilizing CD147 antibody-based immunosuppressant drugs for the treatment of graft rejection. The effects of CD147 antibodies were evaluated on lymphocyte proliferation stimulated by phytohemagglutinin or CD3/CD28 magnetic beads and in a one-way mixed lymphocyte reaction (MLR) system in vitro. For the in vivo analysis, an allogeneic skin transplantation mouse model was used. CD147 antibodies were effective against lymphocytes, particularly CD4+T lymphocytes, and were additionally effective in the one-way MLR system. In the allogeneic skin transplantation mouse model, the survival of transplanted skin was extended in the CD147 antibody-treated group. Furthermore, the level of inflammatory cell infiltration in transplanted skin was reduced. CD147 blockade decreased the serum levels of interleukin (IL)-17 and the proportions of peripheral blood CD4+ and CD8+ memory T cells. The data demonstrated that CD147 blockade suppressed skin graft rejection, primarily by suppressing CD4+T and memory T cell proliferation, indicating that CD147 exhibits great potential as a target of immunosuppressant drugs. PMID:28849101

CD147 blockade as a potential and novel treatment of graft rejection.

PubMed

Luan, Jing; Zhao, Yu; Zhang, Yang; Miao, Jinlin; Li, Jia; Chen, Zhi-Nan; Zhu, Ping

2017-10-01

Cluster of differentiation (CD)147 is highly involved in the T cell activation process. High CD147 expression is observed on the surfaces of activated T cells, particularly CD4+ T cells. In organ transplantation, it is important to prevent graft rejection resulting from the excessive activation of T cells, particularly CD4+ T cells, which exhibit a key role in amplifying the immune response. The present study aimed to investigate the effects of CD147 blockade in vitro and in vivo and used a transplant rejection system to assess the feasibility of utilizing CD147 antibody‑based immunosuppressant drugs for the treatment of graft rejection. The effects of CD147 antibodies were evaluated on lymphocyte proliferation stimulated by phytohemagglutinin or CD3/CD28 magnetic beads and in a one‑way mixed lymphocyte reaction (MLR) system in vitro. For the in vivo analysis, an allogeneic skin transplantation mouse model was used. CD147 antibodies were effective against lymphocytes, particularly CD4+T lymphocytes, and were additionally effective in the one‑way MLR system. In the allogeneic skin transplantation mouse model, the survival of transplanted skin was extended in the CD147 antibody‑treated group. Furthermore, the level of inflammatory cell infiltration in transplanted skin was reduced. CD147 blockade decreased the serum levels of interleukin (IL)‑17 and the proportions of peripheral blood CD4+ and CD8+ memory T cells. The data demonstrated that CD147 blockade suppressed skin graft rejection, primarily by suppressing CD4+T and memory T cell proliferation, indicating that CD147 exhibits great potential as a target of immunosuppressant drugs.

Impedance based detection of pathogenic E. coli O157:H7 using a ferrocene-antimicrobial peptide modified biosensor.

PubMed

Li, Yongxin; Afrasiabi, Rouzbeh; Fathi, Farkhondeh; Wang, Nan; Xiang, Cuili; Love, Ryan; She, Zhe; Kraatz, Heinz-Bernhard

2014-08-15

Escherichia coli O157:H7 can cause life-threatening gastrointestinal diseases and has been a severe public health problem worldwide in recent years. A novel biosensor for the detection of E. coli O157:H7 is described here using a film composed of ferrocene-peptide conjugates, in which the antimicrobial peptide magainin I has been incorporated as the biorecognition element. Electrochemical impedance spectroscopy was employed to investigate the surface characteristics of the newly developed biosensor and to monitor the interactions between the peptide film and the pathogenic bacteria. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were employed to confirm the immobilization of ferrocene-conjugate onto the gold surface. Non-pathogenic E. coli K12, Staphylococcus epidermidis and Bacillus subtilis were used in this study to evaluate the selectivity of the proposed biosensor. The results have shown the order of the preferential selectivity of the method is E. coli O157:H7>non-pathogenic E. coli>gram positive species. The detection of E. coli O157:H7 with a sensitivity of 10(3)cfu/mL is enabled by the biosensor. The experimental conditions have been optimized and the plot of changes of charge transfer resistance (ΔRCT) and the logarithm of the cell concentration of E. coli O157:H7 shows a linear correlation in the range of 10(3)-10(7)cfu/mL with a correlation coefficient of 0.983. Copyright © 2014 Elsevier B.V. All rights reserved.

Pharmacological evidences for DFK167-sensitive presenilin-independent gamma-secretase-like activity.

PubMed

Sevalle, Jean; Ayral, Erwan; Hernandez, Jean-François; Martinez, Jean; Checler, Frédéric

2009-07-01

Amyloid-beta (Abeta) peptides production is thought to be a key event in the neurodegenerative process ultimately leading to Alzheimer's disease (AD) pathology. A bulk of studies concur to propose that the C-terminal moiety of Abeta is released from its precursor beta-amyloid precursor protein by a high molecular weight enzymatic complex referred to as gamma-secretase, that is composed of at least, nicastrin (NCT), Aph-1, Pen-2, and presenilins (PS) 1 or 2. They are thought to harbor the gamma-secretase catalytic activity. However, several lines of evidence suggest that additional gamma-secretase-like activities could potentially contribute to Abeta production. By means of a quenched fluorimetric substrate (JMV2660) mimicking the beta-amyloid precursor protein sequence targeted by gamma-secretase, we first show that as expected, this probe allows monitoring of an activity detectable in several cell systems including the neuronal cell line telencephalon specific murine neurons (TSM1). This activity is reduced by DFK167, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), and LY68458, three inhibitors known to functionally interact with PS. Interestingly, JMV2660 but not the unrelated peptide JMV2692, inhibits Abeta production in an in vitrogamma-secretase assay as expected from a putative substrate competitor. This activity is enhanced by PS1 and PS2 mutations known to be responsible for familial forms of AD and reduced by aspartyl mutations inactivating PS or in cells devoid of PS or NCT. However, we clearly establish that residual JMV2660-hydrolysing activity could be recovered in PS- and NCT-deficient fibroblasts and that this activity remained inhibited by DFK167. Overall, our study describes the presence of a proteolytic activity displaying gamma-secretase-like properties but independent of PS and still blocked by DFK167, suggesting that the PS-dependent complex could not be the unique gamma-secretase activity responsible for Abeta

16 CFR 16.3 - Policy.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Policy. 16.3 Section 16.3 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ADVISORY COMMITTEE MANAGEMENT § 16.3 Policy. (a) The Commission's policy shall be to: (1) Establish an advisory committee only...

MRUniNovo: an efficient tool for de novo peptide sequencing utilizing the hadoop distributed computing framework.

PubMed

Li, Chuang; Chen, Tao; He, Qiang; Zhu, Yunping; Li, Kenli

2017-03-15

Tandem mass spectrometry-based de novo peptide sequencing is a complex and time-consuming process. The current algorithms for de novo peptide sequencing cannot rapidly and thoroughly process large mass spectrometry datasets. In this paper, we propose MRUniNovo, a novel tool for parallel de novo peptide sequencing. MRUniNovo parallelizes UniNovo based on the Hadoop compute platform. Our experimental results demonstrate that MRUniNovo significantly reduces the computation time of de novo peptide sequencing without sacrificing the correctness and accuracy of the results, and thus can process very large datasets that UniNovo cannot. MRUniNovo is an open source software tool implemented in java. The source code and the parameter settings are available at http://bioinfo.hupo.org.cn/MRUniNovo/index.php. s131020002@hnu.edu.cn ; taochen1019@163.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

33 CFR 175.113 - Launchers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Launchers. 175.113 Section 175... SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.113 Launchers. (a) When a visual distress signal carried to meet the requirements of § 175.110 requires a launcher to activate, then a launcher...

33 CFR 175.113 - Launchers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Launchers. 175.113 Section 175... SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.113 Launchers. (a) When a visual distress signal carried to meet the requirements of § 175.110 requires a launcher to activate, then a launcher...

33 CFR 175.113 - Launchers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Launchers. 175.113 Section 175... SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.113 Launchers. (a) When a visual distress signal carried to meet the requirements of § 175.110 requires a launcher to activate, then a launcher...

33 CFR 175.113 - Launchers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Launchers. 175.113 Section 175... SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.113 Launchers. (a) When a visual distress signal carried to meet the requirements of § 175.110 requires a launcher to activate, then a launcher...

33 CFR 175.113 - Launchers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Launchers. 175.113 Section 175... SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.113 Launchers. (a) When a visual distress signal carried to meet the requirements of § 175.110 requires a launcher to activate, then a launcher...

Structural basis for NKG2A/CD94 recognition of HLA-E

PubMed Central

Kaiser, Brett K.; Pizarro, Juan Carlos; Kerns, Julie; Strong, Roland K.

2008-01-01

The NKG2x/CD94 (x = A, C, E) natural killer-cell receptors perform an important role in immunosurveillance by binding to HLA-E complexes that exclusively present peptides derived from MHC class I leader sequences, thereby monitoring MHC class I expression. We have determined the crystal structure of the NKG2A/CD94/HLA-E complex at 4.4-Å resolution, revealing two critical aspects of this interaction. First, the C-terminal region of the peptide, which displays the most variability among class I leader sequences, interacts entirely with CD94, the invariant component of these receptors. Second, residues 167–170 of NKG2A/C account for the ≈6-fold-higher affinity of the inhibitory NKG2A/CD94 receptor compared to its activating NKG2C/CD94 counterpart. These residues do not contact HLA-E or peptide directly but instead form part of the heterodimer interface with CD94. An evolutionary analysis across primates reveals that whereas CD94 is evolving under purifying selection, both NKG2A and NKG2C are evolving under positive selection. Specifically, residues at the CD94 interface have evolved under positive selection, suggesting that the evolution of these genes is driven by an interaction with pathogen-derived ligands. Consistent with this possibility, we show that NKG2C/CD94, but not NKG2A/CD94, weakly but specifically binds to the CMV MHC-homologue UL18. Thus, the evolution of the NKG2x/CD94 family of receptors has likely been shaped both by the need to bind the invariant HLA-E ligand and the need to avoid subversion by pathogen-derived decoys. PMID:18448674

46 CFR 147A.10 - Notice to Captain of the Port.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Notice to Captain of the Port. 147A.10 Section 147A.10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.10 Notice to Captain of the Port. Unless otherwise authorized by the...

46 CFR 147A.10 - Notice to Captain of the Port.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Notice to Captain of the Port. 147A.10 Section 147A.10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.10 Notice to Captain of the Port. Unless otherwise authorized by the...

46 CFR 147A.10 - Notice to Captain of the Port.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Notice to Captain of the Port. 147A.10 Section 147A.10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.10 Notice to Captain of the Port. Unless otherwise authorized by the...

46 CFR 147A.10 - Notice to Captain of the Port.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Notice to Captain of the Port. 147A.10 Section 147A.10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.10 Notice to Captain of the Port. Unless otherwise authorized by the...

46 CFR 147A.10 - Notice to Captain of the Port.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Notice to Captain of the Port. 147A.10 Section 147A.10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.10 Notice to Captain of the Port. Unless otherwise authorized by the...

16 CFR 16.3 - Policy.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Policy. 16.3 Section 16.3 Commercial... MANAGEMENT § 16.3 Policy. (a) The Commission's policy shall be to: (1) Establish an advisory committee only... making policy decisions and determining action to be taken with respect to any matter considered by an...

32 CFR 16.3 - Available sentences.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Available sentences. 16.3 Section 16.3 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS SENTENCING § 16.3 Available sentences. (a) General. 32 CFR part 9 permits a military commission wide latitude in sentencing...

32 CFR 16.3 - Available sentences.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false Available sentences. 16.3 Section 16.3 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS SENTENCING § 16.3 Available sentences. (a) General. 32 CFR part 9 permits a military commission wide latitude in sentencing...

32 CFR 16.3 - Available sentences.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false Available sentences. 16.3 Section 16.3 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS SENTENCING § 16.3 Available sentences. (a) General. 32 CFR part 9 permits a military commission wide latitude in sentencing...

32 CFR 16.3 - Available sentences.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Available sentences. 16.3 Section 16.3 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS SENTENCING § 16.3 Available sentences. (a) General. 32 CFR part 9 permits a military commission wide latitude in sentencing...

Structural and pharmacological characteristics of chimeric peptides derived from peptide E and beta-endorphin reveal the crucial role of the C-terminal YGGFL and YKKGE motifs in their analgesic properties.

PubMed

Condamine, Eric; Courchay, Karine; Rego, Jean-Claude Do; Leprince, Jérôme; Mayer, Catherine; Davoust, Daniel; Costentin, Jean; Vaudry, Hubert

2010-05-01

Peptide E (a 25-amino acid peptide derived from proenkephalin A) and beta-endorphin (a 31-amino acid peptide derived from proopiomelanocortin) bind with high affinity to opioid receptors and share structural similarities but induce analgesic effects of very different intensity. Indeed, whereas they possess the same N-terminus Met-enkephalin message sequence linked to a helix by a flexible spacer and a C-terminal part in random coil conformation, in contrast with peptide E, beta-endorphin produces a profound analgesia. To determine the key structural elements explaining this very divergent opioid activity, we have compared the structural and pharmacological characteristics of several chimeric peptides derived from peptide E and beta-endorphin. Structures were obtained under the same experimental conditions using circular dichroism, computational estimation of helical content and/or nuclear magnetic resonance spectroscopy (NMR) and NMR-restrained molecular modeling. The hot-plate and writhing tests were used in mice to evaluate the antinociceptive effects of the peptides. Our results indicate that neither the length nor the physicochemical profile of the spacer plays a fundamental role in analgesia. On the other hand, while the functional importance of the helix cannot be excluded, the last 5 residues in the C-terminal part seem to be crucial for the expression or absence of the analgesic activity of these peptides. These data raise the question of the true function of peptides E in opioidergic systems. Copyright (c) 2010 Elsevier Inc. All rights reserved.

25 CFR 163.29 - Trespass.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Trespass. 163.29 Section 163.29 Indians BUREAU OF INDIAN... Operations § 163.29 Trespass. (a) Trespassers will be liable for civil penalties and damages to the enforcement agency and the beneficial Indian owners, and will be subject to prosecution for acts of trespass...

25 CFR 163.29 - Trespass.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true Trespass. 163.29 Section 163.29 Indians BUREAU OF INDIAN... Operations § 163.29 Trespass. (a) Trespassers will be liable for civil penalties and damages to the enforcement agency and the beneficial Indian owners, and will be subject to prosecution for acts of trespass...

25 CFR 163.29 - Trespass.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false Trespass. 163.29 Section 163.29 Indians BUREAU OF INDIAN... Operations § 163.29 Trespass. (a) Trespassers will be liable for civil penalties and damages to the enforcement agency and the beneficial Indian owners, and will be subject to prosecution for acts of trespass...

25 CFR 163.29 - Trespass.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Trespass. 163.29 Section 163.29 Indians BUREAU OF INDIAN... Operations § 163.29 Trespass. (a) Trespassers will be liable for civil penalties and damages to the enforcement agency and the beneficial Indian owners, and will be subject to prosecution for acts of trespass...

25 CFR 163.29 - Trespass.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Trespass. 163.29 Section 163.29 Indians BUREAU OF INDIAN... Operations § 163.29 Trespass. (a) Trespassers will be liable for civil penalties and damages to the enforcement agency and the beneficial Indian owners, and will be subject to prosecution for acts of trespass...

21 CFR 163.113 - Cocoa.

Code of Federal Regulations, 2010 CFR

2010-04-01

... CONSUMPTION CACAO PRODUCTS Requirements for Specific Standardized Cacao Products § 163.113 Cocoa. (a) Description. Cocoa is the food that conforms to the definition and standard of identity, and is subject to the... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Cocoa. 163.113 Section 163.113 Food and Drugs FOOD...

VUV action spectroscopy of protonated leucine-enkephalin peptide in the 6-14 eV range

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

Ranković, M. Lj.; Canon, F.; Nahon, L.

2015-12-28

We have studied the Vacuum Ultraviolet (VUV) photodissociation of gas-phase protonated leucine-enkephalin peptide ion in the 5.7 to 14 eV photon energy range by coupling a linear quadrupole ion trap with a synchrotron radiation source. We report VUV activation tandem mass spectra at 6.7, 8.4, and 12.8 eV photon energies and photodissociation yields for a number of selected fragments. The obtained results provide insight into both near VUV radiation damage and electronic properties of a model peptide. We could distinguish several absorption bands and assign them to particular electronic transitions, according to previous theoretical studies. The photodissociation yields appear tomore » be very different for the various observed fragmentation channels, depending on both the types of fragments and their position along the peptide backbone. The present results are discussed in light of recent gas-phase spectroscopic data on peptides.« less

VUV action spectroscopy of protonated leucine-enkephalin peptide in the 6-14 eV range

DOE PAGES

Ranković, M. Lj.; Canon, F.; Nahon, L.; ...

2015-12-29

We have studied the VUV photodissociation of gas-phase protonated leucine-enkephalin peptide ion in the 5.7 to 14 eV photon energy range by coupling a linear quadrupole ion trap with a synchrotron radiation source. We report VUV activation tandem mass spectra at 6.7, 8.4 and 12.8 eV photon energies and photodissociation yields for a number of selected fragments. The obtained results provide insights into both near VUV radiation damage and electronic properties of a model peptide. We could distinguish several absorption bands and assign them to particular electronic transitions, according to previous theoretical studies. Furthermore, the photodissociation yields appear to bemore » very different for the various observed fragmentation channels, depending both on the type of fragments and their position along the peptide backbone. The present results are discussed in light of recent gas-phase spectroscopic data on peptides.« less

46 CFR 147A.13 - Person in charge of the vessel; before fumigation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... fumigation of the spaces that are determined to be safe for occupancy under § 147A.11(b)(1)(i). (b) If no spaces are determined to be safe for occupancy under § 147A.11 (b)(1)(i), the person in charge of the...

46 CFR 147A.13 - Person in charge of the vessel; before fumigation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... fumigation of the spaces that are determined to be safe for occupancy under § 147A.11(b)(1)(i). (b) If no spaces are determined to be safe for occupancy under § 147A.11 (b)(1)(i), the person in charge of the...

21 CFR 163.113 - Cocoa.

Code of Federal Regulations, 2011 CFR

2011-04-01

... CONSUMPTION CACAO PRODUCTS Requirements for Specific Standardized Cacao Products § 163.113 Cocoa. (a... requirements for label declaration of ingredients for breakfast cocoa in § 163.112, except that the cacao fat...

33 CFR 156.160 - Supervision by person in charge.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Supervision by person in charge. 156.160 Section 156.160 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Operations § 156.160 Supervision by person in charge. (a) No person may connect or disconnect a hose, top off...

33 CFR 156.160 - Supervision by person in charge.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Supervision by person in charge. 156.160 Section 156.160 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Operations § 156.160 Supervision by person in charge. (a) No person may connect or disconnect a hose, top off...

33 CFR 156.160 - Supervision by person in charge.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Supervision by person in charge. 156.160 Section 156.160 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Operations § 156.160 Supervision by person in charge. (a) No person may connect or disconnect a hose, top off...

33 CFR 156.160 - Supervision by person in charge.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Supervision by person in charge. 156.160 Section 156.160 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Operations § 156.160 Supervision by person in charge. (a) No person may connect or disconnect a hose, top off...

33 CFR 156.160 - Supervision by person in charge.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Supervision by person in charge. 156.160 Section 156.160 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Operations § 156.160 Supervision by person in charge. (a) No person may connect or disconnect a hose, top off...

26 CFR 1.56A-4 - Certain taxpayers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Applicable to Taxable Years Beginning in 1969 and Ending in 1970 § 1.56A-4 Certain taxpayers. For application of the minimum tax in the case of estates and trusts, electing small business corporations, common....58-2 through 1.58-6. [T.D. 7564, 43 FR 40468, Sept. 12, 1978. Redesignated by T.D. 8138, 52 FR 15309...

25 CFR 163.81 - Assessment guidelines.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Assessment guidelines. 163.81 Section 163.81 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Program Assessment § 163.81 Assessment guidelines. Assessments shall be national in scope and shall include: (a) An...

25 CFR 163.21 - Bonds required.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and Operations § 163.21 Bonds required. (a) Performance bonds will be required in connection with all sales of forest products, except they may or may not be required, as determined by the approving officer... part in § 163.13 or in timber cutting permits issued pursuant to § 163.26 of this part. (1) In sales in...

25 CFR 163.21 - Bonds required.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and Operations § 163.21 Bonds required. (a) Performance bonds will be required in connection with all sales of forest products, except they may or may not be required, as determined by the approving officer... part in § 163.13 or in timber cutting permits issued pursuant to § 163.26 of this part. (1) In sales in...

Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy.

PubMed

Woitek, Felix; Zentilin, Lorena; Hoffman, Nicholas E; Powers, Jeffery C; Ottiger, Isabel; Parikh, Suraj; Kulczycki, Anna M; Hurst, Marykathryn; Ring, Nadja; Wang, Tao; Shaikh, Farah; Gross, Polina; Singh, Harinder; Kolpakov, Mikhail A; Linke, Axel; Houser, Steven R; Rizzo, Victor; Sabri, Abdelkarim; Madesh, Muniswamy; Giacca, Mauro; Recchia, Fabio A

2015-07-14

Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis. This study evaluated VEGF-B gene therapy in a canine model of tachypacing-induced dilated cardiomyopathy. Chronically instrumented dogs underwent cardiac tachypacing for 28 days. Adeno-associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at the beginning of the pacing protocol or during compensated heart failure. Moreover, we tested a novel VEGF-B167 transgene controlled by the atrial natriuretic factor promoter. Compared with control subjects, VEGF-B167 markedly preserved diastolic and contractile function and attenuated ventricular chamber remodeling, halting the progression from compensated to decompensated heart failure. Atrial natriuretic factor-VEGF-B167 expression was low in normally functioning hearts and stimulated by cardiac pacing; it thus functioned as an ideal therapeutic transgene, active only under pathological conditions. Our results, obtained with a standard technique of interventional cardiology in a clinically relevant animal model, support VEGF-B167 gene transfer as an affordable and effective new therapy for nonischemic heart failure. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Mapping a Noncovalent Protein-Peptide Interface by Top-Down FTICR Mass Spectrometry Using Electron Capture Dissociation

NASA Astrophysics Data System (ADS)

Clarke, David J.; Murray, Euan; Hupp, Ted; Mackay, C. Logan; Langridge-Smith, Pat R. R.

2011-08-01

Noncovalent protein-ligand and protein-protein complexes are readily detected using electrospray ionization mass spectrometry (ESI MS). Furthermore, recent reports have demonstrated that careful use of electron capture dissociation (ECD) fragmentation allows covalent backbone bonds of protein complexes to be dissociated without disruption of noncovalent protein-ligand interactions. In this way the site of protein-ligand interfaces can be identified. To date, protein-ligand complexes, which have proven tractable to this technique, have been mediated by ionic electrostatic interactions, i.e., ion pair interactions or salt bridging. Here we extend this methodology by applying ECD to study a protein-peptide complex that contains no electrostatics interactions. We analyzed the complex between the 21 kDa p53-inhibitor protein anterior gradient-2 and its hexapeptide binding ligand (PTTIYY). ECD fragmentation of the 1:1 complex occurs with retention of protein-peptide binding and analysis of the resulting fragments allows the binding interface to be localized to a C-terminal region between residues 109 and 175. These finding are supported by a solution-phase competition assay, which implicates the region between residues 108 and 122 within AGR2 as the PTTIYY binding interface. Our study expands previous findings by demonstrating that top-down ECD mass spectrometry can be used to determine directly the sites of peptide-protein interfaces. This highlights the growing potential of using ECD and related top-down fragmentation techniques for interrogation of protein-protein interfaces.

Development of a peptide conjugate vaccine for inducing therapeutic anti-IgE antibodies.

PubMed

Licari, Amelia; Castagnoli, Riccardo; De Sando, Elisabetta; Marseglia, Gian Luigi

2017-04-01

Given the multifaceted effector functions of IgE in immediate hypersensitivity, late-phase reactions, regulation of IgE receptor expression and immune modulation, IgE antibodies have long represented an attractive target for therapeutic agents in asthma and other allergic diseases. Effective pharmacologic blockade of the binding of IgE to its receptors has become one of most innovative therapeutic strategies in the field of allergic diseases in the last 10 years. Areas covered: The latest strategies targeting IgE include the development of a therapeutic vaccine, able to trigger our own immune systems to produce therapeutic anti-IgE antibodies, potentially providing a further step forward in the treatment of allergic diseases. The aim of this review is to discuss the discovery strategy, preclinical and early clinical development of a peptide conjugate vaccine for inducing therapeutic anti-IgE antibodies. Expert opinion: Outside the area of development of humanized anti-IgE monoclonal antibodies, the research field of therapeutic IgE-targeted vaccines holds potential benefits for the treatment of allergic diseases. However, most of the experimental observations in animal models have not yet been translated into new treatments and evidence of human efficacy and safety of this new therapeutic strategy are still lacking.

25 CFR 1000.163 - Can a Tribe/Consortium negotiate other terms and conditions not contained in the model compact?

Code of Federal Regulations, 2010 CFR

2010-04-01

... conditions not contained in the model compact? 1000.163 Section 1000.163 Indians OFFICE OF THE ASSISTANT SECRETARY, INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ANNUAL FUNDING AGREEMENTS UNDER THE TRIBAL SELF... Funding Agreements Negotiating A Self-Governance Compact § 1000.163 Can a Tribe/Consortium negotiate other...

25 CFR 163.15 - Advertisement of sales.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Advertisement of sales. 163.15 Section 163.15 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Forest Management and Operations § 163.15 Advertisement of sales. Except as provided in §§ 163.13, 163.14, 163.16, and 163.26 of this part, sales of forest...

Buwchitin: a ruminal peptide with antimicrobial potential against Enterococcus faecalis

NASA Astrophysics Data System (ADS)

Oyama, Linda B.; Crochet, Jean-Adrien; Edwards, Joan E.; Girdwood, Susan E.; Cookson, Alan R.; Fernandez-Fuentes, Narcis; Hilpert, Kai; Golyshin, Peter N.; Golyshina, Olga V.; Privé, Florence; Hess, Matthias; Mantovani, Hilario C.; Creevey, Christopher J.; Huws, Sharon A.

2017-07-01

Antimicrobial peptides (AMPs) are gaining popularity as alternatives for treatment of bacterial infections and recent advances in omics technologies provide new platforms for AMP discovery. We sought to determine the antibacterial activity of a novel antimicrobial peptide, buwchitin, against Enterococcus faecalis. Buwchitin was identified from a rumen bacterial metagenome library, cloned, expressed and purified. The antimicrobial activity of the recombinant peptide was assessed using a broth microdilution susceptibility assay to determine the peptide's killing kinetics against selected bacterial strains. The killing mechanism of buwchitin was investigated further by monitoring its ability to cause membrane depolarization (diSC3(5) method) and morphological changes in E. faecalis cells. Transmission electron micrographs of buwchitin treated E. faecalis cells showed intact outer membranes with blebbing, but no major damaging effects and cell morphology changes. Buwchitin had negligible cytotoxicity against defibrinated sheep erythrocytes. Although no significant membrane leakage and depolarization was observed, buwchitin at minimum inhibitory concentration (MIC) was bacteriostatic against E. faecalis cells and inhibited growth in vitro by 70% when compared to untreated cells. These findings suggest that buwchitin, a rumen derived peptide, has potential for antimicrobial activity against E. faecalis.

Identification and characterization of a peptide affinity reagent for detection of noroviruses in clinical samples.

PubMed

Rogers, Jennifer D; Ajami, Nadim J; Fryszczyn, Bartlomiej G; Estes, Mary K; Atmar, Robert L; Palzkill, Timothy

2013-06-01

Norovirus (NoV) is the most common agent of nonbacterial epidemic gastroenteritis and is estimated to cause 21 million cases of the disease in the United States annually. The antigen enzyme-linked immunosorbent assays (ELISAs) currently available for NoV diagnosis detect only certain strains and are approved for use in the United States only in epidemics where NoV is suspected. There is a clear need for simpler, more rapid, and more reliable diagnostic tools for the detection of NoV. In this study, phage display technology was used to screen a library of phage displaying random 12-mer peptides for those that bind to Norwalk virus virus-like particles (NV VLPs). Three phage clones displaying unique peptides were identified, and both the peptide-displaying phages and the peptides were confirmed to bind specifically to NV VLPs. The peptide displayed on phage clone NV-N-R5-1 was determined to bind to the protruding domain of the VP1 capsid protein. This phage also bound to NV VLPs seeded into NoV-negative stool with a limit of detection of 1.56 ng NV VLP. This value was comparable to monoclonal antibody (MAb) 3912, which is currently used in commercially available assays. Furthermore, the NV-N-R5-1 phage exhibited high specificity by detecting NV only in previously characterized NV-positive stool samples in contrast to no detection in NV-negative stool samples. These data demonstrate that the further development of NV-N-R5-1 phage as a diagnostic reagent is possible and might offer several distinct advantages over antibodies, such as decreases in the time and cost of production and ease of isolating phage against other epidemic strains currently circulating as well as those that are emerging.

Plant proteases for bioactive peptides release: A review.

PubMed

Mazorra-Manzano, M A; Ramírez-Suarez, J C; Yada, R Y

2017-04-10

Proteins are a potential source of health-promoting biomolecules with medical, nutraceutical, and food applications. Nowadays, bioactive peptides production, its isolation, characterization, and strategies for its delivery to target sites are a matter of intensive research. In vitro and in vivo studies regarding the bioactivity of peptides has generated strong evidence of their health benefits. Dairy proteins are considered the richest source of bioactive peptides, however proteins from animal and vegetable origin also have been shown to be important sources. Enzymatic hydrolysis has been the process most commonly used for bioactive peptide production. Most commercial enzymatic preparations frequently used are from animal (e.g., trypsin and pepsin) and microbial (e.g., Alcalase® and Neutrase®) sources. Although the use of plant proteases is still relatively limited to papain and bromelain from papaya and pineapple, respectively, the application of new plant proteases is increasing. This review presents the latest knowledge in the use and diversity of plant proteases for bioactive peptides release from food proteins including both available commercial plant proteases as well as new potential plant sources. Furthermore, the properties of peptides released by plant proteases and health benefits associated in the control of disorders such as hypertension, diabetes, obesity, and cancer are reviewed.

Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis.

PubMed

Grønbaek, H; Sandahl, T D; Mortensen, C; Vilstrup, H; Møller, H J; Møller, S

2012-07-01

Activation of Kupffer cells may be involved in the pathogenesis of portal hypertension by release of vasoconstrictive substances and fibrosis due to co-activation of hepatic stellate cells. To study soluble plasma (s) CD163, a specific marker of activated macrophages, as a biomarker for portal hypertension in patients with liver cirrhosis. We measured sCD163 concentration and the hepatic venous pressure gradient (HVPG) by liver vein catheterisation in 81 cirrhosis patients (Child-Pugh CP-A: n = 26, CP-B: n = 29, CP-C: n = 26) and 22 healthy subjects. We also measured their cardiac output (CO), cardiac index and systemic vascular resistance (SVR). Liver status was examined by Child-Pugh and MELD-score. In cirrhosis, sCD163 concentration was nearly three times higher than in controls (4.7 ± 2.5 vs. 1.6 ± 0.5 mg/L, P < 0.001). sCD163 was also higher, as measured in steps by CP-score (P < 0.001). The HVPG rose steeply to an asymptote of 22 mmHg with sCD163 up to about 5 mg/L and not to higher values with higher sCD163. In a multivariate analysis, sCD163 was the only independent predictor of the HVPG but did not predict any of the systemic circulatory findings. sCD163 > 3.95 mg/L (upper normal limit) predicted HVPG ≥ 10 mmHg with a positive predictive value of 0.99. Circulating sCD163 originating from activated Kupffer cells is increased in cirrhosis with increasing Child-Pugh score and with increasing HVPG, and it is an independent predictor for HVPG. These findings support a primary role of macrophage activation in portal hypertension, and may indicate a target for biological intervention. © 2012 Blackwell Publishing Ltd.

25 CFR 163.26 - Forest product harvesting permits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Forest product harvesting permits. 163.26 Section 163.26... Forest Management and Operations § 163.26 Forest product harvesting permits. (a) Except as provided in §§ 163.13 and 163.27 of this part, removal of forest products that are not under formal contract...

The property distance index PD predicts peptides that cross-react with IgE antibodies

PubMed Central

Ivanciuc, Ovidiu; Midoro-Horiuti, Terumi; Schein, Catherine H.; Xie, Liping; Hillman, Gilbert R.; Goldblum, Randall M.; Braun, Werner

2009-01-01

Similarities in the sequence and structure of allergens can explain clinically observed cross-reactivities. Distinguishing sequences that bind IgE in patient sera can be used to identify potentially allergenic protein sequences and aid in the design of hypo-allergenic proteins. The property distance index PD, incorporated in our Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/), may identify potentially cross-reactive segments of proteins, based on their similarity to known IgE epitopes. We sought to obtain experimental validation of the PD index as a quantitative predictor of IgE cross-reactivity, by designing peptide variants with predetermined PD scores relative to three linear IgE epitopes of Jun a 1, the dominant allergen from mountain cedar pollen. For each of the three epitopes, 60 peptides were designed with increasing PD values (decreasing physicochemical similarity) to the starting sequence. The peptides synthesized on a derivatized cellulose membrane were probed with sera from patients who were allergic to Jun a 1, and the experimental data were interpreted with a PD classification method. Peptides with low PD values relative to a given epitope were more likely to bind IgE from the sera than were those with PD values larger than 6. Control sequences, with PD values between 18 and 20 to all the three epitopes, did not bind patient IgE, thus validating our procedure for identifying negative control peptides. The PD index is a statistically validated method to detect discrete regions of proteins that have a high probability of cross-reacting with IgE from allergic patients. PMID:18950868

24 CFR 35.175 - Records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Records. 35.175 Section 35.175... and Definitions for All Programs. § 35.175 Records. The designated party, as specified in subparts C... records applicable to a portion of a residential property for which ongoing lead-based paint maintenance...

24 CFR 35.175 - Records.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Records. 35.175 Section 35.175... and Definitions for All Programs. § 35.175 Records. The designated party, as specified in subparts C... records applicable to a portion of a residential property for which ongoing lead-based paint maintenance...

24 CFR 35.175 - Records.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Records. 35.175 Section 35.175... and Definitions for All Programs. § 35.175 Records. The designated party, as specified in subparts C... records applicable to a portion of a residential property for which ongoing lead-based paint maintenance...

24 CFR 35.175 - Records.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Records. 35.175 Section 35.175... and Definitions for All Programs. § 35.175 Records. The designated party, as specified in subparts C... records applicable to a portion of a residential property for which ongoing lead-based paint maintenance...

24 CFR 35.175 - Records.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Records. 35.175 Section 35.175... and Definitions for All Programs. § 35.175 Records. The designated party, as specified in subparts C... records applicable to a portion of a residential property for which ongoing lead-based paint maintenance...

46 CFR 147A.31 - Removal of fumigation material and warning signs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Removal of fumigation material and warning signs. 147A.31 Section 147A.31 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION After Ventilation § 147A.31 Removal of fumigation...

46 CFR 147A.31 - Removal of fumigation material and warning signs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Removal of fumigation material and warning signs. 147A.31 Section 147A.31 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION After Ventilation § 147A.31 Removal of fumigation...

20 CFR 655.156 - Recruitment report.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Recruitment report. 655.156 Section 655.156... the United States (H-2A Workers) Post-Acceptance Requirements § 655.156 Recruitment report. (a) Requirements of a recruitment report. The employer must prepare, sign, and date a written recruitment report...

46 CFR 147A.25 - Entry.

Code of Federal Regulations, 2010 CFR

2010-10-01

... During Fumigation § 147A.25 Entry. (a) No person may enter the spaces that immediately adjoin the space that is fumigated during fumigation unless entry is for emergency purposes or the space is tested and declared safe for human occupancy by a marine chemist or other qualified person and is inspected under...

46 CFR 147A.25 - Entry.

Code of Federal Regulations, 2011 CFR

2011-10-01

... During Fumigation § 147A.25 Entry. (a) No person may enter the spaces that immediately adjoin the space that is fumigated during fumigation unless entry is for emergency purposes or the space is tested and declared safe for human occupancy by a marine chemist or other qualified person and is inspected under...

M1 distributions for 163Dy and 157Gd in the SUBFsdg(3) and SUBFsd(3) × 1g limits of pn-sdgIBFM

NASA Astrophysics Data System (ADS)

Devi, Y. D.; Kota, V. K. B.

1996-02-01

The SU sdgBF(3) limit of pn-sdgIBFM, which was developed earlier, is applied with success in analyzing the recently observed M1 data in the 163Dy nucleus. As new experiments are being planned for 157Gd nucleus and that 156Gd is known to be a good SU sd(3)×1g nucleus, in the second part of the paper a formalism for M1 distributions in the SU sdBF(3)×1g limit is developed. In both these analytically solvable limiting situations, predictions are made for M1 distributions in the 157Gd nucleus.

46 CFR 163.003-11 - Materials.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 6 2011-10-01 2011-10-01 false Materials. 163.003-11 Section 163.003-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-11 Materials. (a) Suspension members. Each...

46 CFR 163.003-11 - Materials.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Materials. 163.003-11 Section 163.003-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-11 Materials. (a) Suspension members. Each...

46 CFR 163.003-11 - Materials.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 6 2012-10-01 2012-10-01 false Materials. 163.003-11 Section 163.003-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-11 Materials. (a) Suspension members. Each...

46 CFR 163.003-11 - Materials.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Materials. 163.003-11 Section 163.003-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-11 Materials. (a) Suspension members. Each...

A microbially derived tyrosine-sulfated peptide mimics a plant peptide hormone.

PubMed

Pruitt, Rory N; Joe, Anna; Zhang, Weiguo; Feng, Wei; Stewart, Valley; Schwessinger, Benjamin; Dinneny, José R; Ronald, Pamela C

2017-07-01

The biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo) produces a sulfated peptide named RaxX, which shares similarity to peptides in the PSY (plant peptide containing sulfated tyrosine) family. We hypothesize that RaxX mimics the growth-stimulating activity of PSY peptides. Root length was measured in Arabidopsis and rice treated with synthetic RaxX peptides. We also used comparative genomic analyses and reactive oxygen species burst assays to evaluate the activity of RaxX and PSY peptides. Here we found that a synthetic sulfated RaxX derivative comprising 13 residues (RaxX13-sY), highly conserved between RaxX and PSY, induces root growth in Arabidopsis and rice in a manner similar to that triggered by PSY. We identified residues that are required for activation of immunity mediated by the rice XA21 receptor but that are not essential for root growth induced by PSY. Finally, we showed that a Xanthomonas strain lacking raxX is impaired in virulence. These findings suggest that RaxX serves as a molecular mimic of PSY peptides to facilitate Xoo infection and that XA21 has evolved the ability to recognize and respond specifically to the microbial form of the peptide. © 2017 UT-Battelle LLC. New Phytologist © 2017 New Phytologist Trust.

A microbially derived tyrosine-sulfated peptide mimics a plant peptide hormone

PubMed Central

Pruitt, Rory N.; Joe, Anna; Zhang, Weiguo; Feng, Wei; Stewart, Valley; Schwessinger, Benjamin; Dinneny, José R.; Ronald, Pamela C.

2018-01-01

Summary The biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo) produces a sulfated peptide named RaxX, which shares similarity to peptides in the PSY (plant peptide containing sulfated tyrosine) family. We hypothesize that RaxX mimics the growth-stimulating activity of PSY peptides.Root length was measured in Arabidopsis and rice treated with synthetic RaxX peptides. We also used comparative genomic analyses and reactive oxygen species burst assays to evaluate the activity of RaxX and PSY peptides.Here we found that a synthetic sulfated RaxX derivative comprising 13 residues (RaxX13-sY), highly conserved between RaxX and PSY, induces root growth in Arabidopsis and rice in a manner similar to that triggered by PSY. We identified residues that are required for activation of immunity mediated by the rice XA21 receptor but that are not essential for root growth induced by PSY. Finally, we showed that a Xanthomonas strain lacking raxX is impaired in virulence.These findings suggest that RaxX serves as a molecular mimic of PSY peptides to facilitate Xoo infection and that XA21 has evolved the ability to recognize and respond specifically to the microbial form of the peptide. PMID:28556915

46 CFR 163.003-13 - Construction.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Construction. 163.003-13 Section 163.003-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-13 Construction. (a) General. Each pilot ladder...

46 CFR 163.003-13 - Construction.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 6 2012-10-01 2012-10-01 false Construction. 163.003-13 Section 163.003-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-13 Construction. (a) General. Each pilot ladder...

46 CFR 163.003-13 - Construction.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 6 2011-10-01 2011-10-01 false Construction. 163.003-13 Section 163.003-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-13 Construction. (a) General. Each pilot ladder...

46 CFR 163.003-13 - Construction.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Construction. 163.003-13 Section 163.003-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-13 Construction. (a) General. Each pilot ladder...

46 CFR 163.003-17 - Strength.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 6 2010-10-01 2010-10-01 false Strength. 163.003-17 Section 163.003-17 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-17 Strength. (a) Each pilot ladder must be...

46 CFR 163.003-17 - Strength.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 6 2011-10-01 2011-10-01 false Strength. 163.003-17 Section 163.003-17 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-17 Strength. (a) Each pilot ladder must be...

46 CFR 163.003-15 - Performance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 6 2012-10-01 2012-10-01 false Performance. 163.003-15 Section 163.003-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-15 Performance. (a) Each pilot ladder must be...

46 CFR 163.003-15 - Performance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Performance. 163.003-15 Section 163.003-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-15 Performance. (a) Each pilot ladder must be...

46 CFR 163.003-15 - Performance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Performance. 163.003-15 Section 163.003-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-15 Performance. (a) Each pilot ladder must be...

46 CFR 163.003-15 - Performance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 6 2011-10-01 2011-10-01 false Performance. 163.003-15 Section 163.003-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-15 Performance. (a) Each pilot ladder must be...

46 CFR 163.003-15 - Performance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 6 2010-10-01 2010-10-01 false Performance. 163.003-15 Section 163.003-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Ladder § 163.003-15 Performance. (a) Each pilot ladder must be...

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation.

PubMed

Jin, Rong; Xiao, Adam Y; Chen, Rui; Granger, D Neil; Li, Guohong

2017-12-01

Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147 (cluster of differentiation 147), also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown. In this study, we show that CD147 acts as a key player in ischemic stroke by driving thrombotic and inflammatory responses. Focal cerebral ischemia was induced in C57BL/6 mice by a 60-minute transient middle cerebral artery occlusion. Animals were treated with anti-CD147 function-blocking antibody (αCD147) or isotype control antibody. Blood-brain barrier permeability, thrombus formation, and microvascular patency were assessed 24 hours after ischemia. Infarct size, neurological deficits, and inflammatory cells invaded in the brain were assessed 72 hours after ischemia. CD147 expression was rapidly increased in ischemic brain endothelium after transient middle cerebral artery occlusion. Inhibition of CD147 reduced infarct size and improved functional outcome on day 3 after transient middle cerebral artery occlusion. The neuroprotective effects were associated with (1) prevented blood-brain barrier damage, (2) decreased intravascular fibrin and platelet deposition, which in turn reduced thrombosis and increased cerebral perfusion, and (3) reduced brain inflammatory cell infiltration. The underlying mechanism may include reduced NF-κB (nuclear factor κB) activation, MMP-9 (matrix metalloproteinase-9) activity, and PAI-1 (plasminogen activator inhibitor-1) expression in brain microvascular endothelial cells. Inhibition of CD147 ameliorates acute ischemic stroke by reducing thromboinflammation. CD147 might represent a novel and promising therapeutic target for ischemic stroke and possibly other thromboinflammatory disorders. © 2017 American Heart

46 CFR 167.15-15 - Application for inspection of a new nautical school ship or a conversion of a vessel to a...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Application for inspection of a new nautical school ship or a conversion of a vessel to a nautical school ship. 167.15-15 Section 167.15-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS PUBLIC NAUTICAL SCHOOL SHIPS Inspections § 167.15-15 Application for inspection of...

13 CFR 147.640 - Employee.

Code of Federal Regulations, 2013 CFR

2013-01-01

... are directly engaged in the performance of work under the award and who are on the recipient's payroll. (b) This definition does not include workers not on the payroll of the recipient (e.g., volunteers... WORKPLACE (NONPROCUREMENT) Definitions § 147.640 Employee. (a) Employee means the employee of a recipient...

13 CFR 147.640 - Employee.

Code of Federal Regulations, 2012 CFR

2012-01-01

... are directly engaged in the performance of work under the award and who are on the recipient's payroll. (b) This definition does not include workers not on the payroll of the recipient (e.g., volunteers... WORKPLACE (NONPROCUREMENT) Definitions § 147.640 Employee. (a) Employee means the employee of a recipient...

13 CFR 147.640 - Employee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... are directly engaged in the performance of work under the award and who are on the recipient's payroll. (b) This definition does not include workers not on the payroll of the recipient (e.g., volunteers... WORKPLACE (NONPROCUREMENT) Definitions § 147.640 Employee. (a) Employee means the employee of a recipient...

13 CFR 147.640 - Employee.

Code of Federal Regulations, 2014 CFR

2014-01-01

... are directly engaged in the performance of work under the award and who are on the recipient's payroll. (b) This definition does not include workers not on the payroll of the recipient (e.g., volunteers... WORKPLACE (NONPROCUREMENT) Definitions § 147.640 Employee. (a) Employee means the employee of a recipient...

10 CFR 501.163 - OFE evaluation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false OFE evaluation. 501.163 Section 501.163 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS ADMINISTRATIVE PROCEDURES AND SANCTIONS Enforcement § 501.163 OFE evaluation. (a) The record shall consist of the complaint and any supporting documents and all...

Star formation histories in NGC 147 and NGC 185

NASA Astrophysics Data System (ADS)

Hamedani Golshan, R.; Javadi, A.; van Loon, J. Th

2017-06-01

NGC 147 and NGC 185 are two of the most massive satellites of the Andromeda galaxy (M 31). With similar mass and morphological type dE, they possess different amounts of interstellar gas and tidal distortion. The question therefore is, how do their histories compare? We present the first reconstruction of the star formation histories of NGC 147 and NGC 185 using long-period variable stars (LPVs). LPVs are low- to intermediate-mass stars at the asymptotic giant branch, which their luminosity is related to their birth mass. Combining near-infrared photometry with stellar evolution models, we construct the mass function and hence the star formation history. For NGC 185 we found that the main epoch of star formation occurred 8.3 Gyr ago, followed by a much lower, but relatively constant star formation rate. In the case of NGC 147, the star formation rate peaked only 7 Gyr ago, staying intense until ∼ 3 Gyr ago, but no star formation has occurred for at least 300 Myr. Despite their similar masses, NGC 147 has evolved more slowly than NGC 185 initially, but more dramatically in more recent times.

Serum soluble CD163 levels in patients with influenza-associated encephalopathy.

PubMed

Hasegawa, Shunji; Matsushige, Takeshi; Inoue, Hirofumi; Takahara, Midori; Kajimoto, Madoka; Momonaka, Hiroshi; Ishida, Chiemi; Tanaka, Saya; Morishima, Tsuneo; Ichiyama, Takashi

2013-08-01

Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin-haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients. We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects. Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases. Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

21 CFR 163.111 - Chocolate liquor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Chocolate liquor. 163.111 Section 163.111 Food and... CONSUMPTION CACAO PRODUCTS Requirements for Specific Standardized Cacao Products § 163.111 Chocolate liquor. (a) Description. (1) Chocolate liquor is the solid or semiplastic food prepared by finely grinding...

21 CFR 163.111 - Chocolate liquor.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Chocolate liquor. 163.111 Section 163.111 Food and... CONSUMPTION CACAO PRODUCTS Requirements for Specific Standardized Cacao Products § 163.111 Chocolate liquor. (a) Description. (1) Chocolate liquor is the solid or semiplastic food prepared by finely grinding...

21 CFR 163.111 - Chocolate liquor.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Chocolate liquor. 163.111 Section 163.111 Food and... CONSUMPTION CACAO PRODUCTS Requirements for Specific Standardized Cacao Products § 163.111 Chocolate liquor. (a) Description. (1) Chocolate liquor is the solid or semiplastic food prepared by finely grinding...

Association Study between an SNP in CD147 and Its Expression With Acute Coronary Syndrome in a Jiangsu Chinese Population.

PubMed

Yan, Jinchuan; Mao, Yu; Wang, Cuiping; Wang, Zhongqun

2015-10-01

CD147 is an important molecule in the inflammation and proteolysis process. This molecule crucially contributes to the initial and progression of atherosclerotic lesions. A single nucleotide polymorphism in CD147 gene, the rs8259 T/A in the 3'-untranslated region, is responsible for its expression in various cells. This study assessed whether the genetic variation rs8259 is associated with acute coronary syndrome (ACS) and CD147. A total of 943 ACS subjects and 439 stable angina subjects, and 851 controls were genotyped for rs8259 polymorphism by polymerase chain reaction restriction fragment length polymorphism and DNA-sequencing method. Plasma soluble CD147 (sCD147) level was measured by enzyme-linked immunosorbent assay. CD147 mRNA and protein expression in peripheral blood mononuclear cells were tested by real-time quantitative polymerase chain reaction and western blot, respectively. We found that TT genotype and T-allele frequency of CD147 rs8259 in ACS patients were much lower than the other patient groups. Significant difference was not observed between stable angina and controls. CD147 T allele was negatively related to ACS. ACS patients exhibited the highest CD147 expression in peripheral blood mononuclear cells and plasma sCD147 level. The plasma sCD147 levels in the culprit vessel were higher than those in the radial artery. In ACS patients, AA gene carriers had the highest CD147 levels, whereas TT gene carriers had the lowest CD147 levels. Linear regression analysis showed that genotypes and disease conditions contributed 49% to the change of the plasma CD147 level. These results suggested that the single nucleotide polymorphism of CD147 gene rs8259 T/A was associated with ACS susceptibility. Allele T gene may decrease the relative risk of suffering from ACS through downregulation of CD147 expression.

30 CFR 206.156 - Transportation allowances-general.

Code of Federal Regulations, 2010 CFR

2010-07-01

... of this subpart. For purposes of this section, natural gas liquids will be considered one product. (3... MANAGEMENT PRODUCT VALUATION Federal Gas § 206.156 Transportation allowances—general. (a) Where the value of gas has been determined pursuant to § 206.152 or § 206.153 of this subpart at a point (e.g., sales...

Isolation of 163Ho from dysprosium target material by HPLC for neutrino mass measurements

DOE PAGES

Mocko, Veronika; Taylor, Wayne  A.; Nortier, Francois M.; ...

2015-04-29

The rare earth isotope 163Ho is of interest for neutrino mass measurements. This report describes the isolation of 163Ho from a proton-irradiated dysprosium target and its purification. A Dy metal target was irradiated with 16 MeV protons for 10 h. After target dissolution, 163Ho was separated from the bulk Dy via cation-exchange high performance liquid chromatography using 70 mmol dm –3 α-hydroxyisobutyric acid as the mobile phase. Subsequent purification of the collected Ho fraction was performed to remove the α-hydroxyisobutyrate chelating agent and to concentrate the Ho in a low ionic strength aqueous matrix. The final solution was characterized bymore » MC-ICP-MS to determine the 163Ho/ 165Ho ratio, 163Ho and the residual Dy content. The HPLC purification process resulted in a decontamination factor 1.4E5 for Dy. As a result, the isolated Ho fraction contained 24.8 ±1.3 ng of 163Ho corresponding to holmium recovery of 72 ± 3%.« less

Isolation of 163Ho from dysprosium target material by HPLC for neutrino mass measurements

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

Mocko, Veronika; Taylor, Wayne  A.; Nortier, Francois M.

The rare earth isotope 163Ho is of interest for neutrino mass measurements. This report describes the isolation of 163Ho from a proton-irradiated dysprosium target and its purification. A Dy metal target was irradiated with 16 MeV protons for 10 h. After target dissolution, 163Ho was separated from the bulk Dy via cation-exchange high performance liquid chromatography using 70 mmol dm –3 α-hydroxyisobutyric acid as the mobile phase. Subsequent purification of the collected Ho fraction was performed to remove the α-hydroxyisobutyrate chelating agent and to concentrate the Ho in a low ionic strength aqueous matrix. The final solution was characterized bymore » MC-ICP-MS to determine the 163Ho/ 165Ho ratio, 163Ho and the residual Dy content. The HPLC purification process resulted in a decontamination factor 1.4E5 for Dy. As a result, the isolated Ho fraction contained 24.8 ±1.3 ng of 163Ho corresponding to holmium recovery of 72 ± 3%.« less

Study of the peptide length and amino acid specific substitution in the antigenic activity of the chimeric synthetic peptides, containing the p19 core and gp46 envelope proteins of the HTLV-I virus.

PubMed

Marin, Milenen Hernández; Rodríguez-Tanty, Chryslaine; Higginson-Clarke, David; Bocalandro, Yadaris Márquez; Peña, Lilliam Pozo

2005-10-28

Four chimeric synthetic peptides (Q5, Q6, Q7(multiply sign in circle), and Q8(multiply sign in circle)), incorporating immunodominant epitopes of the core p19 (105-124 a.a.) and envelope gp46 proteins (175-205 a.a.), of HTLV-I were obtained. Also, two gp46 monomeric peptides M4 and M5(multiply sign in circle) (Ser at position 192) were synthesized. The analysis of the influence of the peptide lengths and the proline to serine substitution on the chimeric and monomeric peptides' antigenicity, with regard to the chimeric peptides Q1, Q2, Q3(multiply sign in circle), and Q4(multiply sign in circle), reported previously, for HTLV-I was carried out. The peptides' antigenicity was evaluated in an ultramicroenzyme-linked immunosorbent assay (UMELISA) using sera of HTLV-I/II. The peptides' antigenicity was affected appreciably by the change of the peptide length and amino acid substitutions into the immunodominant sequence of gp46 peptide.

40 CFR 205.156 - [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false [Reserved] 205.156 Section 205.156 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycles § 205.156 [Reserved] ...

40 CFR 205.156 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false [Reserved] 205.156 Section 205.156 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycles § 205.156 [Reserved] ...

21 CFR 163.114 - Lowfat cocoa.

Code of Federal Regulations, 2010 CFR

2010-04-01

... CONSUMPTION CACAO PRODUCTS Requirements for Specific Standardized Cacao Products § 163.114 Lowfat cocoa. (a) Description. Lowfat cocoa is the food that conforms to the definition and standard of identity, and is subject... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Lowfat cocoa. 163.114 Section 163.114 Food and...

Novel ZnO-binding peptides obtained by the screening of a phage display peptide library

NASA Astrophysics Data System (ADS)

Golec, Piotr; Karczewska-Golec, Joanna; Łoś, Marcin; Węgrzyn, Grzegorz

2012-11-01

Zinc oxide (ZnO) is a semiconductor compound with a potential for wide use in various applications, including biomaterials and biosensors, particularly as nanoparticles (the size range of ZnO nanoparticles is from 2 to 100 nm, with an average of about 35 nm). Here, we report isolation of novel ZnO-binding peptides, by screening of a phage display library. Interestingly, amino acid sequences of the ZnO-binding peptides reported in this paper and those described previously are significantly different. This suggests that there is a high variability in sequences of peptides which can bind particular inorganic molecules, indicating that different approaches may lead to discovery of different peptides of generally the same activity (e.g., binding of ZnO) but having various detailed properties, perhaps crucial under specific conditions of different applications.

17 CFR 1.67 - Notification of final disciplinary action involving financial harm to a customer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... disciplinary action involving financial harm to a customer. 1.67 Section 1.67 Commodity and Securities... Miscellaneous § 1.67 Notification of final disciplinary action involving financial harm to a customer. (a) Definitions. For purposes of this section: (1) Final disciplinary action means any decision by or settlement...

7 CFR 457.156 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false [Reserved] 457.156 Section 457.156 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.156 [Reserved] ...

40 CFR 156.64 - Signal word.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Signal word. 156.64 Section 156.64... REQUIREMENTS FOR PESTICIDES AND DEVICES Human Hazard and Precautionary Statements § 156.64 Signal word. (a... signal word, reflecting the highest Toxicity Category (Category I is the highest toxicity category) to...

40 CFR 156.64 - Signal word.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Signal word. 156.64 Section 156.64... REQUIREMENTS FOR PESTICIDES AND DEVICES Human Hazard and Precautionary Statements § 156.64 Signal word. (a... signal word, reflecting the highest Toxicity Category (Category I is the highest toxicity category) to...

40 CFR 156.64 - Signal word.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Signal word. 156.64 Section 156.64... REQUIREMENTS FOR PESTICIDES AND DEVICES Human Hazard and Precautionary Statements § 156.64 Signal word. (a... signal word, reflecting the highest Toxicity Category (Category I is the highest toxicity category) to...

40 CFR 156.64 - Signal word.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Signal word. 156.64 Section 156.64... REQUIREMENTS FOR PESTICIDES AND DEVICES Human Hazard and Precautionary Statements § 156.64 Signal word. (a... signal word, reflecting the highest Toxicity Category (Category I is the highest toxicity category) to...

40 CFR 156.64 - Signal word.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Signal word. 156.64 Section 156.64... REQUIREMENTS FOR PESTICIDES AND DEVICES Human Hazard and Precautionary Statements § 156.64 Signal word. (a... signal word, reflecting the highest Toxicity Category (Category I is the highest toxicity category) to...

43 CFR 15.6 - Markers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Markers. 15.6 Section 15.6 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.6 Markers. No person shall willfully mark, deface or injure in any way, or displace, remove or tamper with any Preserve signs...

43 CFR 15.6 - Markers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Markers. 15.6 Section 15.6 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.6 Markers. No person shall willfully mark, deface or injure in any way, or displace, remove or tamper with any Preserve signs...

43 CFR 15.6 - Markers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Markers. 15.6 Section 15.6 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.6 Markers. No person shall willfully mark, deface or injure in any way, or displace, remove or tamper with any Preserve signs...

43 CFR 15.6 - Markers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Markers. 15.6 Section 15.6 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.6 Markers. No person shall willfully mark, deface or injure in any way, or displace, remove or tamper with any Preserve signs...

43 CFR 15.6 - Markers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Markers. 15.6 Section 15.6 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.6 Markers. No person shall willfully mark, deface or injure in any way, or displace, remove or tamper with any Preserve signs...

Promethium-147 capacitor.

PubMed

Kavetskiy, A; Yakubova, G; Lin, Q; Chan, D; Yousaf, S M; Bower, K; Robertson, J D; Garnov, A; Meier, D

2009-06-01

Beta particle surface fluxes for tritium, Ni-63, Pm-147, and Sr-90 sources were calculated in this work. High current density was experimentally achieved from Pm-147 oxide in silica-titana glass. A 96 GBq (2.6 Ci) Pm-147 4pi-source with flux efficiency greater than 50% was used for constructing a direct charge capacitor with a polyimide coated collector and vacuum as electrical insulation. The capacitor connected to high resistance (TOmega) loads produced up to 35 kV. Overall conversion efficiency was over 10% (on optimal load).

30 CFR 1206.156 - Transportation allowances-general.

Code of Federal Regulations, 2012 CFR

2012-07-01

... under § 1206.153 of this subpart. For purposes of this section, natural gas liquids will be considered... RESOURCES REVENUE PRODUCT VALUATION Federal Gas § 1206.156 Transportation allowances—general. (a) Where the value of gas has been determined pursuant to § 1206.152 or § 1206.153 of this subpart at a point (e.g...

30 CFR 1206.156 - Transportation allowances-general.

Code of Federal Regulations, 2014 CFR

2014-07-01

... under § 1206.153 of this subpart. For purposes of this section, natural gas liquids will be considered... RESOURCES REVENUE PRODUCT VALUATION Federal Gas § 1206.156 Transportation allowances—general. (a) Where the value of gas has been determined pursuant to § 1206.152 or § 1206.153 of this subpart at a point (e.g...

30 CFR 1206.156 - Transportation allowances-general.

Code of Federal Regulations, 2013 CFR

2013-07-01

... under § 1206.153 of this subpart. For purposes of this section, natural gas liquids will be considered... RESOURCES REVENUE PRODUCT VALUATION Federal Gas § 1206.156 Transportation allowances—general. (a) Where the value of gas has been determined pursuant to § 1206.152 or § 1206.153 of this subpart at a point (e.g...

Development of a (147)Pm source for beta-backscatter thickness gauge applications.

PubMed

Kumar, Manoj; Udhayakumar, J; Nuwad, J; Shukla, Rakesh; Pillai, C G S; Dash, Ashutosh; Venkatesh, Meera

2011-03-01

This paper describes a method for the preparation of (147)Pm sources, utilized in the determination of graphite coating thickness on the inner surface of the zircaloy cladding tube of nuclear fuels. (147)Pm was adsorbed on a limited surface area [1.5mm (ϕ)×2mm (l)] of a cylindrical aluminum rod [1.5mm (ϕ)×10mm (l)]. In brief, the selected tip area [1.5mm (ϕ)×2mm (l)] was anodized at a current density of 15mA/cm(2) at 15°C in 3M·H(2)SO(4) for 2h followed by immersion of this area in 10μL of (147)Pm solution containing 37MBq (1mCi) of activity at pH 6.0 for 24h. The radioactive area was subsequently covered with a thin layer of Polymethyl Methacrylate (PMMA) to prevent leaching of (147)Pm from the source. The quantity of incorporated (147)Pm activity was assayed in a calibrated ion chamber. Quality control tests were carried out to ensure nonleachability, uniform distribution of activity and stability of the sources. Copyright © 2010 Elsevier Ltd. All rights reserved.

32 CFR 147.23 - Breaks in service.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Breaks in service. 147.23 Section 147.23... Standards § 147.23 Breaks in service. If a person who requires access has been retired or separated from U.S... current, the agency regranting the access will, as a minimum, review an updated Standard Form 86 and...

Purification of a polyclonal antibody against CD147 for ELISA using antigen-immunoaffinity chromatography

PubMed Central

Liu, Shuangshuang; Li, Shasha; Zhang, Yang; Wang, Ye; Zhu, Yumeng; Wang, Bin; Chen, Zhi-Nan

2017-01-01

The immunoglobulin superfamily member CD147 is a widely expressed glycoprotein that occurs in both a membrane-spanning and soluble form. Sandwich ELISA is a powerful tool for analyzing soluble antigens. The aim of the present study was to obtain a highly specific polyclonal antibody against human CD147 that can be used for sandwich ELISA analysis. Expression of recombinant CD147 by a eukaryotic expression system was used to immunize rabbits to obtain antiserum. A highly specific polyclonal antibody that was able to detect soluble CD147 in sandwich ELISA was obtained by antigen-immunoaffinity chromatography purification. The purity of rabbit anti-CD147 polyclonal antibodies was ~99%, and ELISA analysis was able to determine the titer of the rabbit anti-CD147 polyclonal antibodies at 1:512,000. The lowest concentration of the standard CD147 antigen that the sandwich ELISA was able to detect was 31.25 pg/ml. The sandwich ELISA system was composed of anti-hepatoma HAb18 monoclonal antibodies and purified rabbit anti-CD147 polyclonal antibodies. The present study demonstrated that antigen-immunoaffinity chromatography may be a good technique for the purification of polyclonal antibodies, which may be used to detect antigen in sandwich ELISAs. PMID:28487989

27 CFR 28.156 - Losses.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Losses. 28.156 Section 28... Exportation or Transfer to a Foreign-Trade Zone § 28.156 Losses. Where there has been a loss of specially... or a foreign-trade zone, the exporter shall file claim for allowance of the loss in accordance with...

miR156 modulates rhizosphere acidification in response to phosphate limitation in Arabidopsis.

PubMed

Lei, Kai Jian; Lin, Ya Ming; An, Guo Yong

2016-03-01

Rhizosphere acidification is a general response to Pi deficiency, especially in dicotyledonous plants. However, the signaling pathway underlying this process is still unclear. Here, we demonstrate that miR156 is induced in the shoots and roots of wild type Arabidopsis plants during Pi starvation. The rhizosphere acidification capacity was increased in 35S:MIR156 (miR156 overexpression) plants, but was completely inhibited in 35S:MIM156 (target mimicry) plants. Both 35S:MIR156 and 35S:MIM156 plants showed altered proton efflux and H(+)-ATPase activity. In addition, significant up-regulation of H(+)-ATPase activity in 35S:MIR156 roots coupled with increased citric acid and malic acid exudates was observed. qRT-PCR results showed that most H(+)-ATPase and PPCK gene transcript levels were decreased in 35S:MIM156 plants, which may account for the decreased H(+)-ATPase activity in 35S:MIM156 plants. MiR156 also affect the root architecture system. Collectively, our results suggest that miR156 regulates the process of rhizosphere acidification in plants.

12 CFR 163.27 - Advertising.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 1 2014-01-01 2014-01-01 false Advertising. 163.27 Section 163.27 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY SAVINGS ASSOCIATIONS-OPERATIONS Operation and Structure § 163.27 Advertising. No Federal savings association shall use advertising (which...

12 CFR 163.27 - Advertising.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Advertising. 163.27 Section 163.27 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY SAVINGS ASSOCIATIONS-OPERATIONS Operation and Structure § 163.27 Advertising. No Federal savings association shall use advertising (which...

12 CFR 163.27 - Advertising.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Advertising. 163.27 Section 163.27 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY SAVINGS ASSOCIATIONS-OPERATIONS Operation and Structure § 163.27 Advertising. No Federal savings association shall use advertising (which...

29 CFR 15.6 - Administrative action.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Administrative action. 15.6 Section 15.6 Labor Office of the... Against the Government Under the Federal Tort Claims Act § 15.6 Administrative action. (a) Investigation... such harm, it has the responsibility to fully investigate the incident and to take all actions...

46 CFR 163.002-21 - Approval tests.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Approval tests. 163.002-21 Section 163.002-21 Shipping...: SPECIFICATIONS AND APPROVAL CONSTRUCTION Pilot Hoist § 163.002-21 Approval tests. (a) General. If a pilot hoist fails one of the tests in this section the cause of the failure must be identified and any needed design...

Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions.

PubMed

Alvarado-Vazquez, Perla Abigail; Bernal, Laura; Paige, Candler A; Grosick, Rachel L; Moracho Vilrriales, Carolina; Ferreira, David Wilson; Ulecia-Morón, Cristina; Romero-Sandoval, E Alfonso

2017-08-01

M1 macrophages release proinflammatory factors during inflammation. They transit to an M2 phenotype and release anti-inflammatory factors to resolve inflammation. An imbalance in the transition from M1 to M2 phenotype in macrophages contributes to the development of persistent inflammation. CD163, a member of the scavenger receptor cysteine-rich family, is an M2 macrophage marker. The functional role of CD163 during the resolution of inflammation is not completely known. We postulate that CD163 contributes to the transition from M1 to M2 phenotype in macrophages. We induced CD163 gene in THP-1 and primary human macrophages using polyethylenimine nanoparticles grafted with a mannose ligand (Man-PEI). This nanoparticle specifically targets cells of monocytic origin via mannose receptors. Cells were challenged with a single or a double stimulation of lipopolysaccharide (LPS). A CD163 or empty plasmid was complexed with Man-PEI nanoparticles for cell transfections. Quantitative RT-PCR, immunocytochemistry, and ELISAs were used for molecular assessments. CD163-overexpressing macrophages displayed reduced levels of tumor necrosis factor-alpha (TNF)-α and monocytes chemoattractant protein (MCP)-1 after a single stimulation with LPS. Following a double stimulation paradigm, CD163-overexpressing macrophages showed an increase of interleukin (IL)-10 and IL-1ra and a reduction of MCP-1. This anti-inflammatory phenotype was partially blocked by an anti-CD163 antibody (effects on IL-10 and IL-1ra). A decrease in the release of TNF-α, IL-1β, and IL-6 was observed in CD163-overexpressing human primary macrophages. The release of IL-6 was blocked by an anti-CD163 antibody in the CD163-overexpressing group. Our data show that the induction of the CD163 gene in human macrophages under inflammatory conditions produces changes in cytokine secretion in favor of an anti-inflammatory phenotype. Targeting macrophages to induce CD163 using cell-directed nanotechnology is an attractive

40 CFR 97.175 - Petitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Petitions. 97.175 Section 97.175... BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS Monitoring and Reporting § 97.175 Petitions. The CAIR designated representative of a CAIR NOX unit may submit a petition under § 75.66 of this...

45 CFR 156.122 - Prescription drug benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Prescription drug benefits. 156.122 Section 156... Essential Health Benefits Package § 156.122 Prescription drug benefits. (a) A health plan does not provide... at least the greater of: (i) One drug in every United States Pharmacopeia (USP) category and class...

45 CFR 156.122 - Prescription drug benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Prescription drug benefits. 156.122 Section 156... Essential Health Benefits Package § 156.122 Prescription drug benefits. (a) A health plan does not provide... at least the greater of: (i) One drug in every United States Pharmacopeia (USP) category and class...

9 CFR 156.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Definitions. 156.2 Section 156.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VOLUNTARY INSPECTION AND CERTIFICATION SERVICE VOLUNTARY INSPECTION AND CERTIFICATION SERVICE § 156.2...

33 CFR 167.1701 - In Prince William Sound: Precautionary areas.

Code of Federal Regulations, 2011 CFR

2011-07-01