Mass spectrometric differentiation of linear peptides composed of L-amino acids from isomers containing one D-amino acid residue.

Science.gov (United States)

Serafin, Scott V; Maranan, Rhonda; Zhang, Kangling; Morton, Thomas Hellman

2005-09-01

MS/MS of electrosprayed ions is shown to have the capacity to discriminate between peptides that differ by configuration about their alpha-carbons. It is not necessary for the peptides to possess tertiary structures that are affected by stereochemistry, since five epimers of the pentapeptide, H2N-Gly-Leu-Ser-Phe-Ala-OH (GLSFA) all display different collisionally activated dissociation (CAD) patterns of their protonated parent ions. The figure of merit, r, is a ratio of ratios of fragment ion abundances between stereoisomers, where r = 1 corresponds to no stereochemical effect. Values of r as high as 3.8 are seen for diastereomer pairs. Stereochemical effects are also seen for the diprotonated dodecapeptide H2N-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Ser-Asn-Lys-OH (LVFFAEDVGSNK), a tryptic fragment from the amyloid beta-protein. Triply charged complexes of the protonated dodecapeptide with cobalt(II) ions undergo CAD at lower collision energies than do doubly protonated LVFFAEDVGSNK ions. Statistically significant (p < 0.01) differences between the all-L-dodecapeptide and the ones containing a d-serine or a D-aspartic acid are observed.

48 CFR 31.205-11 - Depreciation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Depreciation. 31.205-11....205-11 Depreciation. (a) Depreciation on a contractor's plant, equipment, and other capital facilities... method of depreciation or the class life asset depreciation range system is used, the residual value need...

Side chain and backbone contributions of Phe508 to CFTR folding

Energy Technology Data Exchange (ETDEWEB)

Thibodeau, Patrick H.; Brautigam, Chad A.; Machius, Mischa; Thomas, Philip J. (U. of Texas-SMED)

2010-12-07

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an integral membrane protein, cause cystic fibrosis (CF). The most common CF-causing mutant, deletion of Phe508, fails to properly fold. To elucidate the role Phe508 plays in the folding of CFTR, missense mutations at this position were generated. Only one missense mutation had a pronounced effect on the stability and folding of the isolated domain in vitro. In contrast, many substitutions, including those of charged and bulky residues, disrupted folding of full-length CFTR in cells. Structures of two mutant nucleotide-binding domains (NBDs) reveal only local alterations of the surface near position 508. These results suggest that the peptide backbone plays a role in the proper folding of the domain, whereas the side chain plays a role in defining a surface of NBD1 that potentially interacts with other domains during the maturation of intact CFTR.

VAL

DEFF Research Database (Denmark)

Winge, Kristoffer; Haugaard, Rune; Merritt, Timothy Robert

2014-01-01

creative practices. We interview and observe laser cutter users to identify issues and concerns in the shared work context of a design school and describe the design process for our prototype, which aims to address these problems and unmet needs. Initial evaluation suggests VAL reduces complexity......) proposes a novel system utilizing spatial augmented reality techniques to provide visual augmentation directly on the work surface. VAL involves projection of the user's model prior to and during laser cutting providing key benefits including minimizing idle time, reduction of errors, and support for new...

Aromatic residues located close to the active center are essential for the catalytic reaction of flap endonuclease-1 from hyperthermophilic archaeon Pyrococcus horikoshii.

Science.gov (United States)

Matsui, Eriko; Abe, Junko; Yokoyama, Hideshi; Matsui, Ikuo

2004-04-16

Flap endonuclease-1 (FEN-1) possessing 5'-flap endonuclease and 5'-->3' exonuclease activity plays important roles in DNA replication and repair. In this study, the kinetic parameters of mutants at highly conserved aromatic residues, Tyr33, Phe35, Phe79, and Phe278-Phe279, in the vicinity of the catalytic centers of FEN-1 were examined. The substitution of these aromatic residues with alanine led to a large reduction in kcat values, although these mutants retained Km values similar to that of the wild-type enzyme. Notably, the kcat of Y33A and F79A decreased 333-fold and 71-fold, respectively, compared with that of the wild-type enzyme. The aromatic residues Tyr33 and Phe79, and the aromatic cluster Phe278-Phe279 mainly contributed to the recognition of the substrates without the 3' projection of the upstream strand (the nick, 5'-recess-end, single-flap, and pseudo-Y substrates) for the both exo- and endo-activities, but played minor roles in recognizing the substrates with the 3' projection (the double flap substrate and the nick substrate with the 3' projection). The replacement of Tyr33, Phe79, and Phe278-Phe279, with non-charged aromatic residues, but not with aliphatic hydrophobic residues, recovered the kcat values almost fully for the substrates without the 3' projection of the upstream strand, suggesting that the aromatic groups of Tyr33, Phe79, and Phe278-Phe279 might be involved in the catalytic reaction, probably via multiple stacking interactions with nucleotide bases. The stacking interactions of Tyr33 and Phe79 might play important roles in fixing the template strand and the downstream strand, respectively, in close proximity to the active center to achieve the productive transient state leading to the hydrolysis.

Structural and functional analysis of validoxylamine A 7'-phosphate synthase ValL involved in validamycin A biosynthesis.

Directory of Open Access Journals (Sweden)

Lina Zheng

Full Text Available Validamycin A (Val-A is an effective antifungal agent widely used in Asian countries as crop protectant. Validoxylamine A, the core structure and intermediate of Val-A, consists of two C(7-cyclitol units connected by a rare C-N bond. In the Val-A biosynthetic gene cluster in Streptomyces hygroscopicus 5008, the ORF valL was initially annotated as a validoxylamine A 7'-phosphate(V7P synthase, whose encoded 497-aa protein shows high similarity with trehalose 6-phosphate(T6P synthase. Gene inactivation of valL abolished both validoxylamine A and validamycin A productivity, and complementation with a cloned valL recovered 10% production of the wild-type in the mutant, indicating the involvement of ValL in validoxylamine A biosynthesis. Also we determined the structures of ValL and ValL/trehalose complex. The structural data indicates that ValL adopts the typical fold of GT-B protein family, featuring two Rossmann-fold domains and an active site at domain junction. The residues in the active site are arranged in a manner homologous to that of Escherichia coli (E.coli T6P synthase OtsA. However, a significant discrepancy is found in the active-site loop region. Also noticeable structural variance is found around the active site entrance in the apo ValL structure while the region takes an ordered configuration upon binding of product analog trehalose. Furthermore, the modeling of V7P in the active site of ValL suggests that ValL might have a similar SNi-like mechanism as OtsA.

Conformation of dehydropentapeptides containing four achiral amino acid residues – controlling the role of L-valine

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Michał Jewgiński

2014-03-01

Full Text Available Structural studies of pentapeptides containing an achiral block, built from two dehydroamino acid residues (ΔZPhe and ΔAla and two glycines, as well as one chiral L-Val residue were performed using NMR spectroscopy. The key role of the L-Val residue in the generation of the secondary structure of peptides is discussed. The obtained results suggest that the strongest influence on the conformation of peptides arises from a valine residue inserted at the C-terminal position. The most ordered conformation was found for peptide Boc-Gly-ΔAla-Gly-ΔZPhe-Val-OMe (3, which adopts a right-handed helical conformation.

Structural and Biochemical Characterization of BdsA from Bacillus subtilis WU-S2B, a Key Enzyme in the “4S” Desulfurization Pathway

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Tiantian Su

2018-02-01

Full Text Available Dibenzothiophene (DBT and their derivatives, accounting for the major part of the sulfur components in crude oil, make one of the most significant pollution sources. The DBT sulfone monooxygenase BdsA, one of the key enzymes in the “4S” desulfurization pathway, catalyzes the oxidation of DBT sulfone to 2′-hydroxybiphenyl 2-sulfonic acid (HBPSi. Here, we determined the crystal structure of BdsA from Bacillus subtilis WU-S2B, at the resolution of 2.2 Å, and the structure of the BdsA-FMN complex at 2.4 Å. BdsA and the BdsA-FMN complex exist as tetramers. DBT sulfone was placed into the active site by molecular docking. Seven residues (Phe12, His20, Phe56, Phe246, Val248, His316, and Val372 are found to be involved in the binding of DBT sulfone. The importance of these residues is supported by the study of the catalytic activity of the active site variants. Structural analysis and enzyme activity assay confirmed the importance of the right position and orientation of FMN and DBT sulfone, as well as the involvement of Ser139 as a nucleophile in catalysis. This work combined with our previous structure of DszC provides a systematic structural basis for the development of engineered desulfurization enzymes with higher efficiency and stability.

Tritium labelling of highly selective probes for. delta. -opioid receptors: ( sup 3 H)Tyr-D-Ser(O-t-Bu)-Gly-Phe-Leu-Thr(DSTBULET) and ( sup 3 H)Tyr-D-Ser(O-t-Bu)-Gly-Phe-Leu-Thr(O-t-Bu)(BUBU)

Energy Technology Data Exchange (ETDEWEB)

Fellion, E.; Gacel, G.; Roques, B.P. (Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France)); Roy, J.; Morgat, J.L. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service de Biochimie)

1990-08-01

The introduction of bulky residue(s) in linear enkephalin-related hexapeptides represents a new approach in the design of selective probes for {delta}-opioid receptors, displaying the appropriate criteria to investigate biological and pharmacological properties of the assumed binding site ({delta}) of endogenous enkephalins. The selectivities and high affinities of Tyr-D-Ser(O-t-Bu)-Gly-Phe-Leu-Thr(DSTBULET) and especially Tyr-D-Ser(O-t-Bu)Gly-Phe-Leu-Thr(O-t-Bu) (BUBU) associated with a satisfactory resistance to peptidases, make them the most suitable {delta}-probes reported to date. In the present paper, we report the synthesis of DSTBULET and BUBU under tritiated forms with high specific radioactivities. These radio-labelled probes will enable extensive in vitro and in vivo investigations of {delta}-opioid receptors properties to be carried out. (author).

Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity

DEFF Research Database (Denmark)

Larsen, Lesli H; Echwald, Søren Morgenthaler; Sørensen, Thorkild I A

2005-01-01

)) for mutations in MC4R. A total of 14 different mutations were identified of which two, Ala219Val and Leu325Phe, were novel variants. The variant receptor, Leu325Phe, was unable to bind [Nle4,d-Phe7]-alphaMSH, whereas the Ala219Val variant showed a significantly impaired melanotan II induction of cAMP, compared...

The Roles of Hemagglutinin Phe-95 in Receptor Binding and Pathogenicity of Influenza B Virus

Science.gov (United States)

Ni, Fengyun; Mbawuike, Innocent Nnadi; Kondrashkina, Elena; Wang, Qinghua

2014-01-01

Diverged ~4,000 years ago, influenza B virus has several important differences from influenza A virus, including lower receptor-binding affinity and highly restricted host range. Based on our prior structural studies, we hypothesized that a single-residue difference in the receptor-binding site of hemagglutinin (HA), Phe-95 in influenza B virus versus Tyr-98 in influenza A/H1~H15, is possibly a key determinant for the low receptor-binding affinity. Here we demonstrate that the mutation Phe95→Tyr in influenza B virus HA restores all three hydrogen bonds made by Tyr-98 in influenza A/H3 HA and has the potential to enhance receptor binding. However, the full realization of this potential is influenced by the local environment into which the mutation is introduced. The binding and replication of the recombinant viruses correlate well with the receptor-binding capabilities of HA. These results are discussed in relation to the roles of Phe-95 in receptor binding and pathogenicity of influenza B virus. PMID:24503069

VAL language: description and analysis

International Nuclear Information System (INIS)

McGraw, J.R.

1982-01-01

VAL is a high-level, function-based language designed for use on data flow computers. A data flow computer has many small processors organized to cooperate in the executive of a single computation. A computation is represented by its data flow graph; each operator in a graph is scheduled for execution on one of the processors after all of its operands' values are known. VAL promotes the indentification of concurrency in algorithms and simplifies the mapping into data graphs. This paper presents a detailed introduction to VAL and analyzes its usefulness for programming in a highly concurrent environment. VAL provides implicit concurrency (operations that can execute simultaneously are evident without the need for any explicit language notation). The language uses function- and expression-based features that prohibit all side effects, which simplifies translation to graphs. The salient language features are described and illustrated through examples taken from a complete VAL program for adaptive quadrature. Analysis of the language shows that VAL meets the critical needs for a data flow environment. The language encourages programmers to think in terms of general concurrency, enhances readability (due to the absence of side effects), and possesses a structure amenable to verification techniques. However, VAL is still evolving. The language definition needs refining, and more support tools for programmer use need to be developed. Also, some new kinds of optimization problems should be addressed

Synthesis and Sensory Characteristics of Kokumi γ-[Glu]n-Phe in the Presence of Glutamine and Phenylalanine: Glutaminase from Bacillus amyloliquefaciens or Aspergillus oryzae as the Catalyst.

Science.gov (United States)

Yang, Juan; Sun-Waterhouse, Dongxiao; Cui, Chun; Dong, Keming; Wang, Wei

2017-10-04

The transpeptidase activity of glutaminase from Bacillus amyloliquefaciens (GBA) and Aspergillus oryzae (GAO) to yield γ-[Glu] n -Phe peptides were verified for the first time. In the presence of Gln and Phe, γ-Glu-Phe and γ-Glu-γ-Glu-Phe were synthesized by GAO, and γ-Glu-Phe, γ-Glu-γ-Glu-Phe, γ-Glu-γ-Glu-γ-Glu-Phe, γ-Glu-γ-Glu-γ-Glu-γ-Glu-Phe, and γ-Glu-γ-Glu-γ-Glu-γ-Glu-γ-Glu-Phe were synthesized by GBA. The K m values for the transpeptidation catalyzed by GBA and GAO were 47.88 and 153.92 mM (Phe as the acceptor), 84.89 and 236.47 mM (γ-Glu-Phe as the acceptor), indicating that GBA had a greater affinity than GAO for Phe and γ-Glu-Phe in the transpeptidation reaction. The K m values for the transpeptidation catalyzed by GBA against acceptors, Phe and γ-[Glu] (1≤n<5) -Phe (47.88-206.47 mM), increased with an elevated number of γ-glutamyl residue within the acceptor. The optimal conditions for γ-[Glu] n -Phe synthesis were pH 10 and 37 °C for 3 h, 300 mM Gln, 100 mM Phe, 0.05 U/mL GBA. All the γ-[Glu] (1≤n≤5) -Phe exhibited astringency in water and imparted a kokumi taste to commercial soy sauce and model chicken broth. The astringent threshold values (2.5-3.92 mM) were approximately 3-fold of the kokumi threshold concentrations (0.78-1.53 mM). γ-[Glu] n -Phe or the post-enzymatic reaction mixture enhanced the umami intensity of commercial soy sauce and model chicken broth.

Capsaicin Synthesis Requires in Situ Phenylalanine and Valine Formation in in Vitro Maintained Placentas from Capsicum chinense

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Fray M. Baas-Espinola

2016-06-01

Full Text Available Capsaicinoids (CAP are nitrogenous metabolites formed from valine (Val and phenylalanine (Phe in the placentas of hot Capsicum genotypes. Placentas of Habanero peppers can incorporate inorganic nitrogen into amino acids and have the ability to secure the availability of the required amino acids for CAP biosynthesis. In order to determine the participation of the placental tissue as a supplier of these amino acids, the effects of blocking the synthesis of Val and Phe by using specific enzyme inhibitors were analyzed. Isolated placentas maintained in vitro were used to rule out external sources′ participation. Blocking Phe synthesis, through the inhibition of arogenate dehydratase, significantly decreased CAP accumulation suggesting that at least part of Phe required in this process has to be produced in situ. Chlorsulfuron inhibition of acetolactate synthase, involved in Val synthesis, decreased not only Val accumulation but also that of CAP, pointing out that the requirement for this amino acid can also be fulfilled by this tissue. The presented data demonstrates that CAP accumulation in in vitro maintained placentas can be accomplished through the in situ availability of Val and Phe and suggests that the synthesis of the fatty acid chain moiety may be a limiting factor in the biosynthesis of these alkaloids.

Affinity labeling of Escherichia coli phenylalanyl-tRNA synthetase at the binding site for tRNA

International Nuclear Information System (INIS)

Hountondji, C.; Schmitter, J.M.; Beauvallet, C.; Blanquet, S.

1987-01-01

Periodate-oxidized tRNA/sup Phe/ (tRNA/sub ox//sup Phe/) behaves as a specific affinity label of tetrameric Escherichia coli phenylalanyl-tRNA synthetase (PheRS). Reaction of the α 2 β 2 enzyme with tRNA/sub ox//sup Phe/ results in the loss of tRNA/sup Phe/ aminoacylation activity with covalent attachment of 2 mol of tRNA dialdehyde/mol of enzyme, in agreement with the stoichiometry of tRNA binding. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the PheRS-[ 14 C]tRNA/sub ox//sup Phe/ covalent complex indicates that the large (α, M/sub r/ 87K) subunit of the enzyme interacts with the 3'-adenosine of tRNA/sub ox//sup Phe/. The [ 14 C]tRNA-labeled chymotryptic peptides of PheRS were purified by both gel filtration and reverse-phase high-performance liquid chromatography. The radioactivity was almost equally distributed among three peptides: Met-Lys[Ado]-Phe, Ala-Asp-Lys[Ado]-Leu, and Lys-Ile-Lys[Ado]-Ala. These sequences correspond to residues 1-3, 59-62, and 104-107, respectively, in the N-terminal region of the 795 amino acid sequence of the α subunit. It is noticeable that the labeled peptide Ala-Asp-Lys-Leu is adjacent to residues 63-66 (Arg-Val-Thr-Lys). The latter sequence was just predicted to resemble the proposed consensus tRNA CCA binding region Lys-Met-Ser-Lys-Ser, as deduced from previous affinity labeling studies on E. coli methionyl- and tyrosyl-tRNA synthetases

Synthesis and Pharmacology of α/β(3)-Peptides Based on the Melanocortin Agonist Ac-His-dPhe-Arg-Trp-NH2 Sequence.

Science.gov (United States)

Singh, Anamika; Tala, Srinivasa R; Flores, Viktor; Freeman, Katie; Haskell-Luevano, Carrie

2015-05-14

The melanocortin-3 and -4 receptors are expressed in the brain and play key roles in regulating feeding behavior, metabolism, and energy homeostasis. In the present study, incorporation of β(3)-amino acids into a melanocortin tetrapeptide template was investigated. Four linear α/β(3)-hybrid tetrapeptides were designed with the modifications at the Phe, Arg, and Trp residues in the agonist sequence Ac-His-dPhe-Arg-Trp-NH2. The most potent mouse melanocortin-4 receptor (mMC4R) agonist, Ac-His-dPhe-Arg-β(3)hTrp-NH2 (8) showed 35-fold selectivity versus the mMC3R. The study presented here has identified a new template with heterogeneous backbone for designing potent and selective melanocortin receptor ligands.

Synthesis and Pharmacology of α/β3-Peptides Based on the Melanocortin Agonist Ac-His-dPhe-Arg-Trp-NH2 Sequence

Science.gov (United States)

2015-01-01

The melanocortin-3 and -4 receptors are expressed in the brain and play key roles in regulating feeding behavior, metabolism, and energy homeostasis. In the present study, incorporation of β3-amino acids into a melanocortin tetrapeptide template was investigated. Four linear α/β3-hybrid tetrapeptides were designed with the modifications at the Phe, Arg, and Trp residues in the agonist sequence Ac-His-dPhe-Arg-Trp-NH2. The most potent mouse melanocortin-4 receptor (mMC4R) agonist, Ac-His-dPhe-Arg-β3hTrp-NH2 (8) showed 35-fold selectivity versus the mMC3R. The study presented here has identified a new template with heterogeneous backbone for designing potent and selective melanocortin receptor ligands. PMID:26005535

The Phe105 Loop of Alix Bro1 Domain Plays a Key Role in HIV-1 Release

Energy Technology Data Exchange (ETDEWEB)

Sette, Paola; Mu, Ruiling; Dussupt, Vincent; Jiang, Jiansheng; Snyder, Greg; Smith, Patrick; Xiao, Tsan Sam; Bouamr, Fadila (NIH)

2011-12-07

Alix and cellular paralogs HD-PTP and Brox contain N-terminal Bro1 domains that bind ESCRT-III CHMP4. In contrast to HD-PTP and Brox, expression of the Bro1 domain of Alix alleviates HIV-1 release defects that result from interrupted access to ESCRT. In an attempt to elucidate this functional discrepancy, we solved the crystal structures of the Bro1 domains of HD-PTP and Brox. They revealed typical 'boomerang' folds they share with the Bro1 Alix domain. However, they each contain unique structural features that may be relevant to their specific function(s). In particular, phenylalanine residue in position 105 (Phe105) of Alix belongs to a long loop that is unique to its Bro1 domain. Concurrently, mutation of Phe105 and surrounding residues at the tip of the loop compromise the function of Alix in HIV-1 budding without affecting its interactions with Gag or CHMP4. These studies identify a new functional determinant in the Bro1 domain of Alix.

Mechanisms of the p(He 6,He 5)d, p(He 6,α)t and p(He 6,t)α reactions

International Nuclear Information System (INIS)

Heiberg-Andersen, Henning

2002-07-01

This work was devoted to nucleon induced transfer reactions having the potential to probe the sub-cluster structures of the benchmark halo nucleus He 6, without the question marks the necessarily omitted exchange effects tend to put behind the CRC results when both collision partners are composite systems. Still, the exchange complications entered the analysis in an ironic way: The high Q-value of the p(He 6,α)t and p(He 6, t)α reactions caused sensitivity to the t - α optical potential at small radii, where the one-nucleon exchange effects are strongest. Since the attempt to throw them out of the extracted tau - α potential failed, it was necessary to extend the model space to avoid a too difficult modelling of the local equivalent t - α potential. By this step, all the complications originating from antisymmetrization within a larger model space entered the analysis. However, the persistent failures of the two-channel calculations of this and previous works can hardly be due to incorrect treatment of exchange effects only, so the loss of simplicity is probably illusory. Even at small angles, where the surface processes dominate, none of the two-channel calculations with various choices of t - α optical potentials managed to reproduce the p(He 6, α)t (p(He 6,t)α) data. This motivated inclusion of sequential transfers through the d + He 5 channel, where the sequential triton transfer process, included just for consistency in the coupling scheme of the four-channel calculation, turned out to be more influent than expected. The satisfactory reproduction of both the p(He 6, He 5)d and the p(He 6,α)t (p(He 6,t)α) data by the four-channel approach and the required re-normalization the real part of the p - He 6 optical potential are strong indications of substantial contributions from sequential transfer of the halo neutrons at this energy. The conclusions that can be drawn from this work are limited by the modest amount of available data. This limitation does

Mechanisms of the p(He 6,He 5)d, p(He 6,{alpha})t and p(He 6,t){alpha} reactions

Energy Technology Data Exchange (ETDEWEB)

Heiberg-Andersen, Henning

2002-07-01

This work was devoted to nucleon induced transfer reactions having the potential to probe the sub-cluster structures of the benchmark halo nucleus He 6, without the question marks the necessarily omitted exchange effects tend to put behind the CRC results when both collision partners are composite systems. Still, the exchange complications entered the analysis in an ironic way: The high Q-value of the p(He 6,{alpha})t and p(He 6, t){alpha} reactions caused sensitivity to the t - {alpha} optical potential at small radii, where the one-nucleon exchange effects are strongest. Since the attempt to throw them out of the extracted tau - {alpha} potential failed, it was necessary to extend the model space to avoid a too difficult modelling of the local equivalent t - {alpha} potential. By this step, all the complications originating from antisymmetrization within a larger model space entered the analysis. However, the persistent failures of the two-channel calculations of this and previous works can hardly be due to incorrect treatment of exchange effects only, so the loss of simplicity is probably illusory. Even at small angles, where the surface processes dominate, none of the two-channel calculations with various choices of t - {alpha} optical potentials managed to reproduce the p(He 6, {alpha})t (p(He 6,t){alpha}) data. This motivated inclusion of sequential transfers through the d + He 5 channel, where the sequential triton transfer process, included just for consistency in the coupling scheme of the four-channel calculation, turned out to be more influent than expected. The satisfactory reproduction of both the p(He 6, He 5)d and the p(He 6,{alpha})t (p(He 6,t){alpha}) data by the four-channel approach and the required re-normalization the real part of the p - He 6 optical potential are strong indications of substantial contributions from sequential transfer of the halo neutrons at this energy. The conclusions that can be drawn from this work are limited by the

Mutations at the S1 sites of methionine aminopeptidases from Escherichia coli and Homo sapiens reveal the residues critical for substrate specificity.

Science.gov (United States)

Li, Jing-Ya; Cui, Yong-Mei; Chen, Ling-Ling; Gu, Min; Li, Jia; Nan, Fa-Jun; Ye, Qi-Zhuang

2004-05-14

Methionine aminopeptidase (MetAP) catalyzes the removal of methionine from newly synthesized polypeptides. MetAP carries out this cleavage with high precision, and Met is the only natural amino acid residue at the N terminus that is accepted, although type I and type II MetAPs use two different sets of residues to form the hydrophobic S1 site. Characteristics of the S1 binding pocket in type I MetAP were investigated by systematic mutation of each of the seven S1 residues in Escherichia coli MetAP type I (EcMetAP1) and human MetAP type I (HsMetAP1). We found that Tyr-65 and Trp-221 in EcMetAP1, as well as the corresponding residues Phe-197 and Trp-352 in HsMetAP1, were essential for the hydrolysis of a thiopeptolide substrate, Met-S-Gly-Phe. Mutation of Phe-191 to Ala in HsMetAP1 caused inactivity in contrast to the full activity of EcMetAP1(Y62A), which may suggest a subtle difference between the two type I enzymes. The more striking finding is that mutation of Cys-70 in EcMetAP1 or Cys-202 in HsMetAP1 opens up the S1 pocket. The thiopeptolides Leu-S-Gly-Phe and Phe-S-Gly-Phe, with previously unacceptable Leu or Phe as the N-terminal residue, became efficient substrates of EcMetAP1(C70A) and HsMetAP1(C202A). The relaxed specificity shown in these S1 site mutants for the N-terminal residues was confirmed by hydrolysis of peptide substrates and inhibition by reaction products. The structural features at the enzyme active site will be useful information for designing specific MetAP inhibitors for therapeutic applications.

New cytotoxic cyclic peptides and dianthramide from Dianthus superbus.

Science.gov (United States)

Hsieh, Pei-Wen; Chang, Fang-Rong; Wu, Ching-Chung; Wu, Kuen-Yuh; Li, Chien-Ming; Chen, Su-Li; Wu, Yang-Chang

2004-09-01

Four new cyclic peptides, dianthins C-F (1-4), and a new dianthramide, 4-methoxydianthramide B (5), were isolated from the MeOH extract of the traditional Chinese medicinal plant Dianthus superbus. The sequences of cyclic peptides 1-4 were elucidated as cyclo(Gly(1)-Pro(2)-Phe(3)-Tyr(4)-Val(5)-Ile(6)-), cyclo(Gly(1)-Ser(2)-Leu(3)-Pro(4)-Pro(5)-Ile(6)-Phe(7)-), cyclo(Gly(1)-Pro(2)-Ile(3)-Ser(4)-Phe(5)-Val(6)-), and cyclo(Gly(1)-Pro(2)-Phe(3)-Val(4)-Phe(5)-) on the basis of ESI tandem mass fragmentation analysis, chemical evidence, and extensive 2D NMR methods. The conformation of compound 1 was established as an alpha-helix by CD analysis. Furthermore, compounds 3 and 5 showed cytotoxicities toward the Hep G2 cancer cell line with IC(50) values of 2.37 and 4.08, respectively.

48 CFR 503.570 - Advertising.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Advertising. 503.570 Section 503.570 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION GENERAL IMPROPER BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Other Improper Business Practices 503.570 Advertising. ...

24 CFR 570.507 - Reports.

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2010-04-01

... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Reports. 570.507 Section 570.507... COMMUNITY FACILITIES COMMUNITY DEVELOPMENT BLOCK GRANTS Grant Administration § 570.507 Reports. (a) Performance and evaluation report—(1) Entitlement grant recipients and HUD-administered small cities...

VAL

DEFF Research Database (Denmark)

Winge, Kristoffer; Haugaard, Rune; Merritt, Timothy Robert

2014-01-01

) proposes a novel system utilizing spatial augmented reality techniques to provide visual augmentation directly on the work surface. VAL involves projection of the user's model prior to and during laser cutting providing key benefits including minimizing idle time, reduction of errors, and support for new...

29 CFR 570.72 - Exemptions.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Exemptions. 570.72 Section 570.72 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR... the Employment of Children Below the Age of 16 § 570.72 Exemptions. (a) Student-learners. The findings...

24 CFR 570.426 - Program income.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Program income. 570.426 Section 570... in Hawaii and Insular Areas Programs § 570.426 Program income. (a) The provisions of § 570.504(b) apply to all program income generated by a specific grant and received prior to grant closeout. (b) If...

29 CFR 570.123 - Agriculture.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Agriculture. 570.123 Section 570.123 Labor Regulations... Provisions of the Fair Labor Standards Act of 1938, as Amended Exemptions § 570.123 Agriculture. (a) Section... agriculture outside of school hours for the school district where such employee is living while he is so...

COMT (Val158Met and BDNF (Val66Met Genes Polymorphism in Schizophrenia: A Case-Control Report

Directory of Open Access Journals (Sweden)

ramin saravani

2017-10-01

Full Text Available Objective: The effects of human brain-derived neurotropic factor (BDNF Val66Met (G>A and the human Catechol-O-methylTransferase (COMT Val158Met (G>A polymorphisms on Schizophrenia (SCZ risk were evaluated.Methods: This case control study included 92 SCZ patients and 92 healthy controls (HCs. Genotyping of both variants were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR.Results: The findings showed that BDNF Val66Met (G>A variant increased the risk of SCZ (OR=2.008 95%CI=1.008-4.00, P=0.047, GA vs. GG, OR=3.876 95%CI=1.001-14.925, P=0.049. AA vs. GG, OR=2.272. 95%CI=1.204-4.347, P=0.011, GA+AA vs. GG, OR=2.22 95%CI=1.29-3.82. P=0.005, A vs. G. COMT Val158Met (G>A polymorphism was not associated with the risk/protective of SCZ.Conclusion: The results proposed that BDNF Val66Met (G>A polymorphism may increase the risk of SCZ development and did not support an association between COMT Val158Met (G>A variant and risk/protective of SCZ. Further studies and different ethnicities are recommended to confirm the findings.

Valūtas tirgus. Eiro kā valsts valūta Latvijā

OpenAIRE

Bondarevs, Maksims

2007-01-01

Maksima Bondareva diplomdarba “ Valūtas tirgus. Eiro kā valsts valūta Latvijā”. Diplomdarba mērķis ir: izpētīt tagadnes Latvijas ekonomisko situāciju un noteikt vai tā ir labvēlīga eiro ieviešanai. Lai sasniegtu darba mērķi, tika izvirzīti vairāki uzdevumi: 1.raksturot valūtas sistēmas attīstības posmi un tas pakāpeniskas izmaiņas; 2.raksturot Monetārās sistēmas attistību; 3.izpētīt eiro ieviešanas Latvijā riskus un iespējas; 4.izdarīt secinājumus par Latvijas gatavību ei...

Accurate Determination of Leucine and Valine Side-chain Conformations using U-[15N/13C/2H]/[1H-(methine/methyl)-Leu/Val] Isotope Labeling, NOE Pattern Recognition, and Methine Cγ-Hγ/Cβ-Hβ Residual Dipolar Couplings

International Nuclear Information System (INIS)

Tang, Chun; Iwahara, Junji; Clore, G. Marius

2005-01-01

An isotope labeling scheme is described in which specific protonation of methine and methyl protons of leucine and valine is obtained on a 15 N/ 13 C labeled background with uniform deuteration of all other non-exchangeable protons. The presence of a protonated methine group has little effect on the favorable relaxation properties of the methyl protons of Leu and Val. This labeling scheme permits the rotameric state of leucine side-chains to be readily determined by simple inspection of the pattern of Hγ(i)-H N (i) and Hγ(i)-H N (i+1) NOEs in a 3D 15 N-separated NOE spectrum free of complications arising from spectral overlap and spin-diffusion. In addition, one-bond residual dipolar couplings for the methine 13 C- 1 H bond vectors of Leu and Val can be accurately determined from an intensity J-modulated constant-time HCCH-COSY experiment and used to accurately orient the side-chains of Leu and Val. Incorporation of these data into structure refinement improves the accuracy with which the conformations of Leu and Val side-chains can be established. This is important to ensure optimal packing both within the protein core and at intermolecular interfaces. The impact of the method on protein structure determination is illustrated by application to enzyme IIA Chitobiose , a 34 kDa homotrimeric phosphotransferase protein

48 CFR 570.106 - Publicizing/Advertising.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Publicizing/Advertising. 570.106 Section 570.106 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CONTRACTING PROGRAMS ACQUIRING LEASEHOLD INTERESTS IN REAL PROPERTY General 570.106 Publicizing/Advertising...

ICTR-PHE: converging sciences to corner cancer

CERN Multimedia

Antonella Del Rosso

2014-01-01

Radio chemists, nuclear-medicine physicians, biologists, software developers, accelerator experts, oncologists, and detector physicists: the ICTR-PHE conference is an amazing confluence of experts from a variety of fields. Despite their diversified backgrounds, and their many scientific languages, they all share a common goal: fighting cancer with state-of-the-art techniques from their respective areas of expertise. Thinking outside the box is their speciality.   Head of CERN’s Medical Application Programme, Steve Myers addresses the ICTR-PHE conference. If you are still picturing scientists as secretive people who live locked away in their lab and talk only to their peers, it’s time to upgrade to “Scientist 3.0”. At the ICTR-PHE conference, experts in radiochemistry working in hospitals ask CERN’s accelerator scientists to produce the isotopes they need to make innovative radiopharmaceuticals, and medical doctors in the audience stand up and...

Enabling phenotypic big data with PheNorm.

Science.gov (United States)

Yu, Sheng; Ma, Yumeng; Gronsbell, Jessica; Cai, Tianrun; Ananthakrishnan, Ashwin N; Gainer, Vivian S; Churchill, Susanne E; Szolovits, Peter; Murphy, Shawn N; Kohane, Isaac S; Liao, Katherine P; Cai, Tianxi

2018-01-01

Electronic health record (EHR)-based phenotyping infers whether a patient has a disease based on the information in his or her EHR. A human-annotated training set with gold-standard disease status labels is usually required to build an algorithm for phenotyping based on a set of predictive features. The time intensiveness of annotation and feature curation severely limits the ability to achieve high-throughput phenotyping. While previous studies have successfully automated feature curation, annotation remains a major bottleneck. In this paper, we present PheNorm, a phenotyping algorithm that does not require expert-labeled samples for training. The most predictive features, such as the number of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes or mentions of the target phenotype, are normalized to resemble a normal mixture distribution with high area under the receiver operating curve (AUC) for prediction. The transformed features are then denoised and combined into a score for accurate disease classification. We validated the accuracy of PheNorm with 4 phenotypes: coronary artery disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. The AUCs of the PheNorm score reached 0.90, 0.94, 0.95, and 0.94 for the 4 phenotypes, respectively, which were comparable to the accuracy of supervised algorithms trained with sample sizes of 100-300, with no statistically significant difference. The accuracy of the PheNorm algorithms is on par with algorithms trained with annotated samples. PheNorm fully automates the generation of accurate phenotyping algorithms and demonstrates the capacity for EHR-driven annotations to scale to the next level - phenotypic big data. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

9 CFR 205.205 - Fees.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Fees. 205.205 Section 205.205 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS ADMINISTRATION (PACKERS AND STOCKYARDS... can be set in any manner provided by the law of the State in which such EFS is filed. The basis for...

Reciprocally coupled residues crucial for protein kinase Pak2 activity calculated by statistical coupling analysis.

Directory of Open Access Journals (Sweden)

Yuan-Hao Hsu

2010-03-01

Full Text Available Regulation of Pak2 activity involves at least two mechanisms: (i phosphorylation of the conserved Thr(402 in the activation loop and (ii interaction of the autoinhibitory domain (AID with the catalytic domain. We collected 482 human protein kinase sequences from the kinome database and globally mapped the evolutionary interactions of the residues in the catalytic domain with Thr(402 by sequence-based statistical coupling analysis (SCA. Perturbation of Thr(402 (34.6% suggests a communication pathway between Thr(402 in the activation loop, and Phe(387 (DeltaDeltaE(387F,402T = 2.80 in the magnesium positioning loop, Trp(427 (DeltaDeltaE(427W,402T = 3.12 in the F-helix, and Val(404 (DeltaDeltaE(404V,402T = 4.43 and Gly(405 (DeltaDeltaE(405G,402T = 2.95 in the peptide positioning loop. When compared to the cAMP-dependent protein kinase (PKA and Src, the perturbation pattern of threonine phosphorylation in the activation loop of Pak2 is similar to that of PKA, and different from the tyrosine phosphorylation pattern of Src. Reciprocal coupling analysis by SCA showed the residues perturbed by Thr(402 and the reciprocal coupling pairs formed a network centered at Trp(427 in the F-helix. Nine pairs of reciprocal coupling residues crucial for enzymatic activity and structural stabilization were identified. Pak2, PKA and Src share four pairs. Reciprocal coupling residues exposed to the solvent line up as an activation groove. This is the inhibitor (PKI binding region in PKA and the activation groove for Pak2. This indicates these evolutionary conserved residues are crucial for the catalytic activity of PKA and Pak2.

Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid-binding SCP/TAPS protein that lacks the prototypical CAP motifs

Energy Technology Data Exchange (ETDEWEB)

Kelleher, Alan [Baylor College of Medicine, Houston, TX 77030 (United States); Darwiche, Rabih [University of Fribourg, Chemin du Musée 10, CH 1700 Fribourg (Switzerland); Rezende, Wanderson C. [Baylor College of Medicine, Houston, TX 77030 (United States); Farias, Leonardo P.; Leite, Luciana C. C. [Instituto Butantan, São Paulo, SP (Brazil); Schneiter, Roger [University of Fribourg, Chemin du Musée 10, CH 1700 Fribourg (Switzerland); Asojo, Oluwatoyin A., E-mail: asojo@bcm.edu [Baylor College of Medicine, Houston, TX 77030 (United States)

2014-08-01

The first structure of an S. mansoni venom allergen-like protein is presented. Schistosomiasis is a parasitic disease that affects over 200 million people. Vaccine candidates have been identified, including Schistosoma mansoni venom allergen-like proteins (SmVALs) from the SCP/TAPS (sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. The first SmVAL structure, SmVAL4, was refined to a resolution limit of 2.16 Å. SmVAL4 has a unique structure that could not be predicted from homologous structures, with longer loops and an unusual C-terminal extension. SmVAL4 has the characteristic α/β-sandwich and central SCP/TAPS cavity. Furthermore, SmVAL4 has only one of the signature CAP cavity tetrad amino-acid residues and is missing the histidines that coordinate divalent cations such as Zn{sup 2+} in other SCP/TAPS proteins. SmVAL4 has a cavity between α-helices 1 and 4 that was observed to bind lipids in tablysin-15, suggesting the ability to bind lipids. Subsequently, SmVAL4 was shown to bind cholesterol in vitro. Additionally, SmVAL4 was shown to complement the in vivo sterol-export phenotype of yeast mutants lacking their endogenous CAP proteins. Expression of SmVAL4 in yeast cells lacking endogenous CAP function restores the block in sterol export. These studies suggest an evolutionarily conserved lipid-binding function shared by CAP proteins such as SmVAL4 and yeast CAP proteins such as Pry1.

49 CFR 570.8 - Suspension systems.

Science.gov (United States)

2010-10-01

... 49 Transportation 6 2010-10-01 2010-10-01 false Suspension systems. 570.8 Section 570.8 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... Pounds or Less § 570.8 Suspension systems. (a) Suspension condition. Ball joint seals shall not be cut or...

49 CFR 570.61 - Suspension system.

Science.gov (United States)

2010-10-01

... 49 Transportation 6 2010-10-01 2010-10-01 false Suspension system. 570.61 Section 570.61... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VEHICLE IN USE INSPECTION STANDARDS Vehicles With GVWR of More Than 10,000 Pounds § 570.61 Suspension system. (a) Suspension condition. Ball joint seals shall not be cut...

24 CFR 570.504 - Program income.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Program income. 570.504 Section 570... income. (a) Recording program income. The receipt and expenditure of program income as defined in § 570... of program income received by recipients. (1) Program income received before grant closeout may be...

28 CFR 570.21 - Time-frames.

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2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Time-frames. 570.21 Section 570.21... PROGRAMS Pre-Release Community Confinement § 570.21 Time-frames. (a) Community confinement. Inmates may be... inmate's term of imprisonment or six months. (c) Exceeding time-frames. These time-frames may be exceeded...

49 CFR 570.7 - Steering systems.

Science.gov (United States)

2010-10-01

... 49 Transportation 6 2010-10-01 2010-10-01 false Steering systems. 570.7 Section 570.7... Pounds or Less § 570.7 Steering systems. (a) System play. Lash or free play in the steering system shall... in the steering system. Table 1—Steering System Free Play Values Steering wheel diameter (inches...

Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico

Directory of Open Access Journals (Sweden)

Omar Ramos-Lopez

2016-02-01

Full Text Available Some high-carbohydrate diets may lead to obesity and multiple metabolic disorders, including hypertriglyceridemia (HTG. This lipid abnormality is considered an important risk factor for cardiovascular disease and type 2 diabetes. The sweet taste receptor TAS1R2 polymorphism (Ile191Val has been reported to be associated with carbohydrate intake. The aim of this study was to analyze the association of the TAS1R2 gene polymorphism with carbohydrate intake and HTG among the population of West Mexico. In a cross-sectional study, 441 unrelated subjects were analyzed for TAS1R2 genotypes (Ile/Ile, Ile/Val and Val/Val by an allelic discrimination assay. Biochemical tests and a three-day food record were assessed. The Val/Val genotype carriers had a higher intake of total carbohydrates, fiber and servings of cereals and vegetables than the other genotype carriers. The Val/Val genotype conferred a higher risk for HTG than the Ile/Val and Ile/Ile genotypes (OR = 3.26, 95%CI 1.35–7.86, p = 0.006 and OR = 2.61, 95%CI 1.12–6.07, p = 0.02, respectively. Furthermore, the Val/Val genotype was associated with approximately 30% higher triglycerides compared with Ile/Val and Ile/Ile genotypes (β = 44.09, 95%CI 9.94–78.25, p = 0.01 and β = 45.7, 95%CI 10.85–80.54, p = 0.01, respectively. In conclusion, the Val/Val genotype of TAS1R2 was associated with a higher carbohydrate intake and HTG.

49 CFR 570.10 - Wheel assemblies.

Science.gov (United States)

2010-10-01

... bead through one full wheel revolution and note runout in excess of one-eighth of an inch. (c) Mounting... 49 Transportation 6 2010-10-01 2010-10-01 false Wheel assemblies. 570.10 Section 570.10... Pounds or Less § 570.10 Wheel assemblies. (a) Wheel integrity. A tire rim, wheel disc, or spider shall...

HR-TEM and FT-Raman dataset of the caffeine interacted Phe-Phe peptide nanotube for possible sensing applications.

Science.gov (United States)

Narayanan, A Lakshmi; Dhamodaran, M; Solomon, J Samu; Karthikeyan, B; Govindhan, R

2018-02-01

Sensing ability of caffeine interaction with Phe-Phe annotates (PNTs), is presented (Govindhan et al., 2017; Karthikeyan et al., 2014; Tavagnacco et al., 2013; Kennedy et al., 2011; Wang et al., 2017) [1-5] in this data set. Investigation of synthesized caffeine carrying peptide nanotubes are carried out by FT-Raman spectral analysis and high resolution transmission electron microscopy (HR-TEM). Particle size of the caffeine loaded PNTs is < 40 nm. The FT-Raman spectrum signals are enhanced in the region of 400-1700 cm -1 . These data are ideal tool for the applications like biosensing and drug delivery research (DDS).

Expanding the peptide beta-turn in alphagamma hybrid sequences: 12 atom hydrogen bonded helical and hairpin turns.

Science.gov (United States)

Chatterjee, Sunanda; Vasudev, Prema G; Raghothama, Srinivasarao; Ramakrishnan, Chandrasekharan; Shamala, Narayanaswamy; Balaram, Padmanabhan

2009-04-29

Hybrid peptide segments containing contiguous alpha and gamma amino acid residues can form C(12) hydrogen bonded turns which may be considered as backbone expanded analogues of C(10) (beta-turns) found in alphaalpha segments. Exploration of the regular hydrogen bonded conformations accessible for hybrid alphagamma sequences is facilitated by the use of a stereochemically constrained gamma amino acid residue gabapentin (1-aminomethylcyclohexaneacetic acid, Gpn), in which the two torsion angles about C(gamma)-C(beta) (theta(1)) and C(beta)-C(alpha) (theta(2)) are predominantly restricted to gauche conformations. The crystal structures of the octapeptides Boc-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-OMe (1) and Boc-Leu-Phe-Val-Aib-Gpn-Leu-Phe-Val-OMe (2) reveal two distinct conformations for the Aib-Gpn segment. Peptide 1 forms a continuous helix over the Aib(2)-Aib(6) segment, while the peptide 2 forms a beta-hairpin structure stabilized by four cross-strand hydrogen bonds with the Aib-Gpn segment forming a nonhelical C(12) turn. The robustness of the helix in peptide 1 in solution is demonstrated by NMR methods. Peptide 2 is conformationally fragile in solution with evidence of beta-hairpin conformations being obtained in methanol. Theoretical calculations permit delineation of the various C(12) hydrogen bonded structures which are energetically feasible in alphagamma and gammaalpha sequences.

Bitcoin - alternatīva valūta

OpenAIRE

Liškovska, Eva

2014-01-01

Mūsdienās digitālās valūtas kļūst ar vien izplatītākas, tādēļ autore ir izvēlējusies pētīt digitālo valūtu Bitcoin. Maģistra darba mērķis ir izanalizēt, kādas ir Bitcoin valūtas priekšrocības un trūkumi, lai izdarītu secinājumus un izstrādātu priekšlikumus Bitcoin uzlabošanai, lai nākotnē tā spētu būt tikpat konkurētspējīga kā reālā valūta. Pēc pētījuma veikšanas autore secināja, ka Bitcoin popularitāte gan lietotāju vidū, gan uzņēmumu vidū, kas sāk pieņemt Bitcoin digotālo valūtu, tikai t...

48 CFR 570.402-2 - Publicizing/Advertising.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Publicizing/Advertising. 570.402-2 Section 570.402-2 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION... for Continued Space Requirements 570.402-2 Publicizing/Advertising. Publish a notice if required by...

Rationally designed chimeric peptide of met-enkephalin and FMRFa-[D-Ala2,p-Cl-Phe4]YFa induce multiple opioid receptors mediated antinociception and up-regulate their expression.

Science.gov (United States)

Vats, Ishwar Dutt; Chaudhary, Snehlata; Sharma, Ahuti; Nath, Mahendra; Pasha, Santosh

2010-07-25

The physiological role of NPFF/FMRFa family of peptides appears to be complex and exact mechanism of action of these peptides is not yet completely understood. In same line of scrutiny, another analog of YGGFMKKKFMRFamide (YFa), a chimeric peptide of met-enkephalin and FMRFamide, was rationally designed and synthesized which contain D-alanine and p-Cl-phenylalanine residues at 2nd and 4th positions, respectively i.e., Y-(D-Ala)-G-(p-Cl-Phe)-MKKKFMRFamide ([D-Ala(2), p-Cl-Phe(4)]YFa) in order to achieve improved bioavailability and blood brain barrier penetration. Therefore, present study investigates the possible antinociceptive effect of [D-Ala(2), p-Cl-Phe(4)]YFa on intra-peritoneal (i.p.) administration using tail-flick test in rats followed by its opioid receptor(s) specificity using mu, delta and kappa receptor antagonists. Further, its antinociceptive effect was examined during 6 days of chronic i.p. treatment and assessed effect of this treatment on differential expression of opioid receptors. [D-Ala(2), p-Cl-Phe(4)]YFa in comparison to parent peptide YFa, induce significantly higher dose dependent antinociception in rats which was mediated by all three opioid receptors (mu, delta and kappa). Importantly, it induced comparable antinociception in rats throughout the chronic i.p. treatment and significantly up-regulated the overall expression (mRNA and protein) of mu, delta and kappa opioid receptors. Therefore, pharmacological and molecular behavior of [D-Ala(2), p-Cl-Phe(4)]YFa demonstrate that incorporation of D-alanine and p-Cl-phenylalanine residues at appropriate positions in chimeric peptide leads to altered opioid receptor selectivity and enhanced antinociceptive potency, relative to parent peptide. (c) 2010 Elsevier B.V. All rights reserved.

Experiments and strategies for the assignment of fully13 C/15N-labelled polypeptides by solid state NMR

International Nuclear Information System (INIS)

Straus, Suzana K.; Bremi, Tobias; Ernst, Richard R.

1998-01-01

High-resolution heteronuclear NMR correlation experiments and strategies are proposed for the assignment of fully 13 C/ 15 N-labelled polypeptides in the solid state. By the combination of intra-residue and inter-residue 13 C- 15 N correlation experiments with 13 C- 13 C spin-diffusion studies, it becomes feasible to partially assign backbone and side-chain resonances in solid proteins. The performance of sequences using 15 N instead of 13 C detection is evaluated regarding sensitivity and resolution for a labelled dipeptide (L-Val-L-Phe). The techniques are used for a partial assignment of the 15 N and 13 C resonances in human ubiquitin

PARP1 Val762Ala polymorphism reduces enzymatic activity

International Nuclear Information System (INIS)

Wang Xiaogan; Wang Zhaoqi; Tong Weimin; Shen Yan

2007-01-01

Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K m of PARP1-Ala762 was increased to a 1.2-fold of the K m of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K m . This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding Cancer risk of carriers of the PARP1 Val762Ala polymorphism

Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme.

Science.gov (United States)

Affholter, J A; Cascieri, M A; Bayne, M L; Brange, J; Casaretto, M; Roth, R A

1990-08-21

Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, we have studied the binding of a variety of insulin analogues to the protease in a solid-phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600-fold greater affinity than it does insulin-like growth factor I (25 nM and approximately 16,000 nM, respectively), the first set of analogues studied were hybrid molecules of insulin and IGF I. IGF I mutants [insB1-17,17-70]IGF I, [Tyr55,Gln56]IGF I, and [Phe23,Phe24,Tyr25]IGF I have been synthesized and share the property of having insulin-like amino acids at positions corresponding to primary sites of cleavage of insulin by IDE. Whereas the first two exhibit affinities for IDE similar to that of wild type IGF I, the [Phe23,Phe24,Tyr25]IGF I analogue has a 32-fold greater affinity for the immobilized enzyme. Replacement of Phe-23 by Ser eliminates this increase. Removal of the eight amino acid D-chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants [B25-Asp]insulin and [B25-His]insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of NCAM that interacts with the PHE-CoV spike protein.

Science.gov (United States)

Gao, Wei; He, Wenqi; Zhao, Kui; Lu, Huijun; Ren, Wenzhi; Du, Chongtao; Chen, Keyan; Lan, Yungang; Song, Deguang; Gao, Feng

2010-09-24

The spike proteins of coronaviruses associate with cellular molecules to mediate infection of their target cells. The characterization of cellular proteins required for virus infection is essential for understanding viral life cycles and may provide cellular targets for antiviral therapies. We identified Neural Cell Adhesion Molecule (NCAM) as a novel interacting partner of the PHE-CoV S protein. A T7 phage display cDNA library from N2a cells was constructed, and the library was screened with the soluble PHE-CoV S glycoproteins. We used a coimmunoprecipitation assay to show that only the NCAM was a binding partner of spike protein. We found that a soluble form of anti-NCAM antibody blocked association of the PHE-CoV with N2a cells. Furthermore, double-stranded siRNA targeted against NCAM inhibited PHE-CoV infection. A novel interaction was identified between NCAM and spike protein and this association is critical during PHE-CoV infection.

Identification of NCAM that interacts with the PHE-CoV spike protein

Directory of Open Access Journals (Sweden)

Chen Keyan

2010-09-01

Full Text Available Abstract Background The spike proteins of coronaviruses associate with cellular molecules to mediate infection of their target cells. The characterization of cellular proteins required for virus infection is essential for understanding viral life cycles and may provide cellular targets for antiviral therapies. Results We identified Neural Cell Adhesion Molecule (NCAM as a novel interacting partner of the PHE-CoV S protein. A T7 phage display cDNA library from N2a cells was constructed, and the library was screened with the soluble PHE-CoV S glycoproteins. We used a coimmunoprecipitation assay to show that only the NCAM was a binding partner of spike protein. We found that a soluble form of anti-NCAM antibody blocked association of the PHE-CoV with N2a cells. Furthermore, double-stranded siRNA targeted against NCAM inhibited PHE-CoV infection. Conclusions A novel interaction was identified between NCAM and spike protein and this association is critical during PHE-CoV infection.

48 CFR 803.570 - Commercial advertising.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Commercial advertising. 803.570 Section 803.570 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL... Commercial advertising. ...

29 CFR 570.128 - Good faith defense.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Good faith defense. 570.128 Section 570.128 Labor... Provisions of the Fair Labor Standards Act of 1938, as Amended Enforcement § 570.128 Good faith defense. Link... commerce goods which he acquired in good faith in reliance on written assurance from the producer...

Correction: β-Amyrin synthase from Euphorbia tirucalli L. functional analyses of the highly conserved aromatic residues Phe413, Tyr259 and Trp257 disclose the importance of the appropriate steric bulk, and cation-π and CH-π interactions for the efficient catalytic action of the polyolefin cyclization cascade.

Science.gov (United States)

Ito, Ryousuke; Nakada, Chika; Hoshino, Tsutomu

2017-01-18

Correction for 'β-Amyrin synthase from Euphorbia tirucalli L. functional analyses of the highly conserved aromatic residues Phe413, Tyr259 and Trp257 disclose the importance of the appropriate steric bulk, and cation-π and CH-π interactions for the efficient catalytic action of the polyolefin cyclization cascade' by Ryousuke Ito et al., Org. Biomol. Chem., 2017, 15, 177-188.

29 CFR 570.50 - General.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false General. 570.50 Section 570.50 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS... by the Bureau of Apprenticeship and Training of the United States Department of Labor as employed in...

48 CFR 1403.570 - Restrictions on contractor advertising.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Restrictions on contractor advertising. 1403.570 Section 1403.570 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... 1403.570 Restrictions on contractor advertising. ...

CoalVal-A coal resource valuation program

Science.gov (United States)

Rohrbacher, Timothy J.; McIntosh, Gary E.

2010-01-01

CoalVal is a menu-driven Windows program that produces cost-of-mining analyses of mine-modeled coal resources. Geological modeling of the coal beds and some degree of mine planning, from basic prefeasibility to advanced, must already have been performed before this program can be used. United States Geological Survey mine planning is done from a very basic, prefeasibility standpoint, but the accuracy of CoalVal's output is a reflection of the accuracy of the data entered, both for mine costs and mine planning. The mining cost analysis is done by using mine cost models designed for the commonly employed, surface and underground mining methods utilized in the United States. CoalVal requires a Microsoft Windows? 98 or Windows? XP operating system and a minimum of 1 gigabyte of random access memory to perform operations. It will not operate on Microsoft Vista?, Windows? 7, or Macintosh? operating systems. The program will summarize the evaluation of an unlimited number of coal seams, haulage zones, tax entities, or other area delineations for a given coal property, coalfield, or basin. When the reader opens the CoalVal publication from the USGS website, options are provided to download the CoalVal publication manual and the CoalVal Program. The CoalVal report is divided into five specific areas relevant to the development and use of the CoalVal program: 1. Introduction to CoalVal Assumptions and Concepts. 2. Mine Model Assumption Details (appendix A). 3. CoalVal Project Tutorial (appendix B). 4. Program Description (appendix C). 5. Mine Model and Discounted Cash Flow Formulas (appendix D). The tutorial explains how to enter coal resource and quality data by mining method; program default values for production, operating, and cost variables; and ones own operating and cost variables into the program. Generated summary reports list the volume of resource in short tons available for mining, recoverable short tons by mining method; the seam or property being mined

Roles of the β subunit hinge domain in ATP synthase F1 sector: Hydrophobic network formed by introduced βPhe174 inhibits subunit rotation

International Nuclear Information System (INIS)

Nakanishi-Matsui, Mayumi; Kashiwagi, Sachiko; Kojima, Masaki; Nonaka, Takamasa; Futai, Masamitsu

2010-01-01

The ATP synthase β subunit hinge domain (βPhe148 ∼ βGly186, P-loop/α-helixB/loop/β-sheet4, Escherichia coli residue numbering) dramatically changes in conformation upon nucleotide binding. We previously reported that F 1 with the βSer174 to Phe mutation in the domain lowered the γ subunit rotation speed, and thus decreased the ATPase activity [M. Nakanishi-Matsui, S. Kashiwagi, T. Ubukata, A. Iwamoto-Kihara, Y. Wada, M. Futai, Rotational catalysis of Escherichia coli ATP synthase F 1 sector. Stochastic fluctuation and a key domain of the β subunit, J. Biol. Chem. 282 (2007) 20698-20704.]. Homology modeling indicates that the amino acid replacement induces a hydrophobic network, in which the βMet159, βIle163, and βAla167 residues of the β subunit are involved together with the mutant βPhe174. The network is expected to stabilize the conformation of β DP (nucleotide-bound form of the β subunit), resulting in increased activation energy for transition to β E (empty β subunit). The modeling further predicts that replacement of βMet159 with Ala or Ile weakens the hydrophobic network. As expected, these two mutations experimentally suppressed the ATPase activities as well as subunit rotation of βS174F. Furthermore, the rotation rate decreased with the increase of the strength in the hydrophobic network. These results indicate that the smooth conformational change of the β subunit hinge domain is pertinent for the rotational catalysis.

Comparison of the level of residual coagulant activity in different cheese varieties.

Science.gov (United States)

Bansal, Nidhi; Fox, Patrick F; McSweeney, Paul L H

2009-08-01

The coagulant retained in cheese curd is a major contributor to proteolysis during ripening. The objective of this study was to quantify residual coagulant in 9 cheese varieties by measuring its activity on a synthetic heptapeptide (Pro-Thr-Glu-Phe-[NO2-Phe]-Arg-Leu) assayed using reversed-phase HPLC. The level of residual coagulant activity was highest in Camembert cheese, probably due to its low pH at whey drainage and the high moisture content of the cheese, followed in order by Feta=Port du Salut=Cheddar>Gouda>Emmental=Parmigiano Reggiano=low-moisture part-skim Mozzarella=Mozzarella di Bufala Campana. The high cooking temperature (50-54 degrees C) used during the manufacture of Emmental and Parmigiano Reggiano cheeses and the cooking and stretching step in hot water during the manufacture of Mozzarella cheese may be the reasons for the lowest residual coagulant activity in these cheeses. The level of residual coagulant activity was higher in Feta cheese made from milk concentrated by ultrafiltration than in conventional Feta.

Biosynthetically directed fractional 13C labeling facilitates identification of Phe and Tyr aromatic signals in proteins

International Nuclear Information System (INIS)

Jacob, Jaison; Louis, John M.; Nesheiwat, Issa; Torchia, Dennis A.

2002-01-01

Analysis of 2D [ 13 C, 1 H]-HSQC spectra of biosynthetic fractionally 13 C labeled proteins is a reliable, straightforward means to obtain stereospecific assignments of Val and Leu methyl sites in proteins. Herein we show that the same fractionally labeled protein sample facilitates observation and identification of Phe and Tyr aromatic signals. This is the case, in part, because the fractional 13 C labeling yields aromatic rings in which some of the 13 C- 13 C J-couplings, present in uniformly labeled samples, are absent. Also, the number of homonuclear J-coupling partners differs for the δ-, ε- and ζ-carbons. This enabled us to vary their signal intensities in distinctly different ways by appropriately setting the 13 C constant-time period in 2D [ 13 C, 1 H]-HSQC spectra. We illustrate the application of this approach to an 18 kDa protein, c-VIAF, a modulator of apoptosis. In addition, we show that cancellation of the aromatic 13 C CSA and 13 C- 1 H dipolar interactions can be fruitfully utilized in the case of the fractionally labeled sample to obtain high resolution 13 C constant-time spectra with good sensitivity

NordVal: A Nordic system for validation of alternative microbiological methods

DEFF Research Database (Denmark)

Qvist, Sven

2007-01-01

NordVal was created in 1999 by the Nordic Committee of Senior Officials for Food Issues under the Nordic Council of Ministers. The Committee adopted the following objective for NordVal: NordVal evaluates the performance and field of application of alternative microbiological methods. This includes...... analyses of food, water, feed, animal faeces and food environmental samples in the Nordic countries. NordVal is managed by a steering group, which is appointed by the National Food Administrations in Denmark, Finland, Iceland, Norway and Sweden. The background for creation of NordVal was a Danish...... validation system (DanVal) established in 1995 to cope with a need to validate alternative methods to be used in the Danish Salmonella Action Program. The program attracted considerable attention in the other Nordic countries. NordVal has elaborated a number of documents, which describe the requirements...

Secretion of [Met]enkephalyl-Arg6-Phe7-related peptides and catecholamines from bovine adrenal chromaffin cells: modification by changes in cyclic AMP and by treatment with reserpine.

Science.gov (United States)

Adams, M; Boarder, M R

1987-07-01

Investigations into the effects of culturing bovine adrenal chromaffin cells in the presence (72 h) of dibutyryl cyclic AMP, forskolin, and reserpine on the level and release of [Met]enkephalyl-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline are reported. The assay for [Met]enkephalyl-Arg6-Phe7 immunoreactivity recognises both peptide B, the 31-amino acid carboxy-terminal segment of proenkephalin, and its heptapeptide fragment, [Met]enkephalyl-Arg6-Phe7. Treatments that elevate cyclic AMP increase the amount of peptide immunoreactivity in these cells; this is predominantly peptide B-like immunoreactivity in both control cells and cyclic AMP-elevated cells. Treatment with reserpine gives no change in total immunoreactivity levels, but does not result in increased accumulation of the heptapeptide [Met]enkephalyl-Arg6-Phe7 at the expense of immunoreactivity that elutes with its immediate precursor, peptide B. Cyclic AMP treatment causes either no change or a decrease in levels of accumulated noradrenaline and adrenaline. However, the release of [Met]enkephalin-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline is increased by 72-h pretreatment with forskolin or dibutyryl cyclic AMP, whether release is stimulated by nicotine or elevated potassium. In each case the molecular form of [Met]enkephalyl-Arg6-Phe7 immunoreactivity that is released approximately reflects the cell content. Pretreatment with reserpine has no effect on the total [Met]enkephalyl-Arg6-Phe7 immunoreactivity released, but does result in an increased release of the heptapeptide and a decrease in release of peptide B-like immunoreactivity. The studies suggest that the levels of [Met]enkephalyl-Arg6-Phe7 and peptide B available for release are controlled both at the level of proenkephalin synthesis and at the level of double-basic residue proteolysis.

The conserved Phe GH5 of importance for hemoglobin intersubunit contact is mutated in gadoid fish

Science.gov (United States)

2014-01-01

Background Functionality of the tetrameric hemoglobin molecule seems to be determined by a few amino acids located in key positions. Oxygen binding encompasses structural changes at the interfaces between the α1β2 and α2β1 dimers, but also subunit interactions are important for the oxygen binding affinity and stability. The latter packing contacts include the conserved Arg B12 interacting with Phe GH5, which is replaced by Leu and Tyr in the αA and αD chains, respectively, of birds and reptiles. Results Searching all known hemoglobins from a variety of gnathostome species (jawed vertebrates) revealed the almost invariant Arg B12 coded by the AGG triplet positioned at an exon-intron boundary. Rare substitutions of Arg B12 in the gnathostome β globins were found in pig, tree shrew and scaled reptiles. Phe GH5 is also highly conserved in the β globins, except for the Leu replacement in the β1 globin of five marine gadoid species, gilthead seabream and the Comoran coelacanth, while Cys and Ile were found in burbot and yellow croaker, respectively. Atlantic cod β1 globin showed a Leu/Met polymorphism at position GH5 dominated by the Met variant in northwest-Atlantic populations that was rarely found in northeast-Atlantic cod. Site-specific analyses identified six consensus codons under positive selection, including 122β(GH5), indicating that the amino acid changes identified at this position may offer an adaptive advantage. In fact, computational mutation analysis showed that the replacement of Phe GH5 with Leu or Cys decreased the number of van der Waals contacts essentially in the deoxy form that probably causes a slight increase in the oxygen binding affinity. Conclusions The almost invariant Arg B12 and the AGG codon seem to be important for the packing contacts and pre-mRNA processing, respectively, but the rare mutations identified might be beneficial. The Leu122β1(GH5)Met and Met55β1(D6)Val polymorphisms in Atlantic cod hemoglobin modify the

48 CFR 536.570-8 - Specifications and drawings.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Specifications and drawings. 536.570-8 Section 536.570-8 Federal Acquisition Regulations System GENERAL SERVICES... 536.570-8 Specifications and drawings. Insert the clause at 552.236-77, Specifications and Drawings...

Ressenya a Carme Llanes, L’obrador de Pere Nicolau, L’estil gòtic internacional a València (1390- 1408, València, Publicacions de la Universitat de València, 2014, pp. 312, ISBN: 978-84-370-9561-5

Directory of Open Access Journals (Sweden)

Guillem Chismol

2015-12-01

Full Text Available Review to Carme Llanes, L’obrador de Pere Nicolau, L’estil gòtic internacional a València (1390-1408, València, Publicacions de la Universitat de València, 2014, pp. 312, ISBN: 978-84-370-9561-5

48 CFR 223.570 - Drug-free work force.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Drug-free work force. 223.570 Section 223.570 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... TECHNOLOGIES, OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Drug-Free Workplace 223.570 Drug-free work force. ...

Residues in the alternative reading frame tumor suppressor that influence its stability and p53-independent activities

International Nuclear Information System (INIS)

Tommaso, Anne di; Hagen, Jussara; Tompkins, Van; Muniz, Viviane; Dudakovic, Amel; Kitzis, Alain; Ladeveze, Veronique; Quelle, Dawn E.

2009-01-01

The Alternative Reading Frame (ARF) protein suppresses tumorigenesis through p53-dependent and p53-independent pathways. Most of ARF's anti-proliferative activity is conferred by sequences in its first exon. Previous work showed specific amino acid changes occurred in that region during primate evolution, so we programmed those changes into human p14ARF to assay their functional impact. Two human p14ARF residues (Ala 14 and Thr 31 ) were found to destabilize the protein while two others (Val 24 and Ala 41 ) promoted more efficient p53 stabilization and activation. Despite those effects, all modified p14ARF forms displayed robust p53-dependent anti-proliferative activity demonstrating there are no significant biological differences in p53-mediated growth suppression associated with simian versus human p14ARF residues. In contrast, p53-independent p14ARF function was considerably altered by several residue changes. Val 24 was required for p53-independent growth suppression whereas multiple residues (Val 24 , Thr 31 , Ala 41 and His 60 ) enabled p14ARF to block or reverse the inherent chromosomal instability of p53-null MEFs. Together, these data pinpoint specific residues outside of established p14ARF functional domains that influence its expression and signaling activities. Most intriguingly, this work reveals a novel and direct role for p14ARF in the p53-independent maintenance of genomic stability.

28 CFR 570.45 - Violation of escorted trip.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Violation of escorted trip. 570.45 Section 570.45 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE COMMUNITY PROGRAMS Escorted Trips § 570.45 Violation of escorted trip. (a) Staff shall process as...

48 CFR 570.105-1 - Contracting by negotiation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Contracting by negotiation. 570.105-1 Section 570.105-1 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CONTRACTING PROGRAMS ACQUIRING LEASEHOLD INTERESTS IN REAL PROPERTY General 570.105-1 Contracting by negotiation. Contracting by negotiation...

29 CFR 570.12 - Revoked certificates of age.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Revoked certificates of age. 570.12 Section 570.12 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Certificates of Age § 570.12 Revoked certificates of age...

48 CFR 2009.570 - NRC organizational conflicts of interest.

Science.gov (United States)

2010-10-01

... conflicts of interest. 2009.570 Section 2009.570 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION COMPETITION AND ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Organizational Conflicts of Interest 2009.570 NRC organizational conflicts of interest. ...

Design, chemical synthesis and kinetic studies of trypsin chromogenic substrates based on the proteinase binding loop of Cucurbita maxima trypsin inhibitor (CMTI-III).

Science.gov (United States)

Lesner, A; Brzozowski, K; Kupryszewski, G; Rolka, K

2000-03-05

A series of trypsin chromogenic substrates with formula: Y-Ala-X-Abu-Pro-Lys-pNA, where X = Gly, Ala, Abu, Val, Leu, Phe, Ser, Glu and Y = Ac, H; pNA = p-nitroanilide was synthesized. The Cucurbita maxima trypsin inhibitor CMTI-III molecule was used as a vehicle to design the trypsin substrates. To evaluate the influence of position P(4) on the substrate-enzyme interaction, kinetic parameters of newly synthesized substrates with bovine beta-trypsin were determined. The increasing hydrophobicity of the amino acid residue (Gly, Ala, Abu, Val) introduced in position P(4) significantly enhanced the substrate specificity (k(cat)/K(m)) which was over 8 times higher for the last residue than that for the first one. The introduction of residues with more hydrophilic side chain (Glu, Ser) in this position reduced the value of this parameter. These results correspond well with those obtained using molecular dynamics of bovine beta-trypsin with monosubstituted CMTI-I analogues, indicating that in both trypsin substrate and inhibitor position 4 plays an important role in the interaction with the enzyme. Copyright 2000 Academic Press.

7 CFR 3560.570 - Construction financing.

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Construction financing. 3560.570 Section 3560.570 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF... financing. The requirements established in § 3560.71 apply to all applications involving off-farm labor...

48 CFR 536.570-11 - Heat.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Heat. 536.570-11 Section... OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 536.570-11 Heat. Insert the clause at 552.236-80, Heat, in solicitations and contracts if construction, dismantling...

29 CFR 570.126 - Parental exemption.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Parental exemption. 570.126 Section 570.126 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION General Statements of Interpretation of the Child Labor...

48 CFR 536.570-3 - Specialist.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Specialist. 536.570-3... CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 536.570-3 Specialist. Insert 552.236-72, Specialist, in solicitations and contracts for construction if the technical sections...

24 CFR 241.570 - Insurance endorsement.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Insurance endorsement. 241.570... § 241.570 Insurance endorsement. (a) Initial endorsement. The Commissioner shall indicate his/her insurance of the mortgage by endorsing the original credit instrument and identifying the section of the Act...

48 CFR 570.306 - Evaluating offers.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Evaluating offers. 570.306... Real Property 570.306 Evaluating offers. (a) You must evaluate offers solely in accordance with the... solicitation. The file must include the basis for evaluation, an analysis of each offer, and a summary of...

48 CFR 570.401 - Renewal options.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Renewal options. 570.401... Requirements 570.401 Renewal options. (a) Exercise of options. Before exercising an option to renew, follow the... survey. Before exercising an option to renew a lease, review current market information to ensure the...

Accurate Determination of Leucine and Valine Side-chain Conformations using U-[{sup 15}N/{sup 13}C/{sup 2}H]/[{sup 1}H-(methine/methyl)-Leu/Val] Isotope Labeling, NOE Pattern Recognition, and Methine C{gamma}-H{gamma}/C{beta}-H{beta} Residual Dipolar Couplings

Energy Technology Data Exchange (ETDEWEB)

Tang, Chun; Iwahara, Junji; Clore, G. Marius [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Laboratory of Chemical Physics (United States)], E-mail: mariusc@intra.niddk.nih.gov

2005-10-15

An isotope labeling scheme is described in which specific protonation of methine and methyl protons of leucine and valine is obtained on a {sup 15}N/{sup 13}C labeled background with uniform deuteration of all other non-exchangeable protons. The presence of a protonated methine group has little effect on the favorable relaxation properties of the methyl protons of Leu and Val. This labeling scheme permits the rotameric state of leucine side-chains to be readily determined by simple inspection of the pattern of H{gamma}(i)-H{sub N}(i) and H{gamma}(i)-H{sub N}(i+1) NOEs in a 3D {sup 15}N-separated NOE spectrum free of complications arising from spectral overlap and spin-diffusion. In addition, one-bond residual dipolar couplings for the methine {sup 13}C-{sup 1}H bond vectors of Leu and Val can be accurately determined from an intensity J-modulated constant-time HCCH-COSY experiment and used to accurately orient the side-chains of Leu and Val. Incorporation of these data into structure refinement improves the accuracy with which the conformations of Leu and Val side-chains can be established. This is important to ensure optimal packing both within the protein core and at intermolecular interfaces. The impact of the method on protein structure determination is illustrated by application to enzyme IIA{sup Chitobiose}, a 34 kDa homotrimeric phosphotransferase protein.

Castrelo do Val

Directory of Open Access Journals (Sweden)

Aquilino Santiago Alonso Núñez

2013-01-01

Full Text Available This paper focuses on the study of the dialect of the municipality of Castrelo do Val, Ourense, Spain. The objectives of the paper are to show the particularities of the variety spoken in the municipality and the convergence of varieties within the municipality. Based on a number of dialect markers (pronunciation of sogro, sogra, esterco, medo, novo, and birollo; the evolution of the Latin groups -ŭlt-, -ŭctand -ūct-; presence of viñen, bidueiro and filloas or variants of these elements, among others this paper shows that the varieties spoken in each area studied within the municipality have distinct features that differentiate them from the varieties spoken in other areas, and that four linguistic areas converge at the municipality of Castrelo do Val: the valley, the parish of San Xoán de Servoi, the parish of Santa Eufemia de Piornedo and the north (the former parsih of Santiago de Campobecerros and its annex, the parish of San Miguel de Portocamba. The secondary objective of this paper is to determine the innovative and conservative oral varieties of the municipality. Overall, some innovations are entering the valley, including din as compared to dei in the north. Innovations have also been observed in northern areas, such as viñen in Veiga de Nostre, and some conservative forms have been found in the valley, such as vin in Pepín, Ribas, Gondulfes and Castrelo do Val. Data was collected through two survey questionnaires that contained indirect questions. The survey was conducted among speakers from every area in the municipality with very little or no formal education. Survey data was corroborated or refined using additional data from recordings made in each area in the municipality.

Association of Catechol-O-methyltransferase polymorphism Val158Met and mammographic density: A meta-analysis.

Science.gov (United States)

Kallionpää, Roope A; Uusitalo, Elina; Peltonen, Juha

2017-08-15

The Val158Met polymorphism in catechol-O-methyltransferase (COMT) enzyme reduces the methylation of catechol estrogens, which may affect mammographic density. High mammographic density is a known risk factor of breast cancer. Our aim was to perform meta-analysis of the effect of COMT Val158Met polymorphism on mammographic density. Original studies reporting data on mammographic density, stratified by the presence of COMT Val158Met polymorphism, were identified and combined using genetic models Met/Val vs. Val/Val, Met/Met vs. Val/Val, Val/Met+Met/Met vs. Val/Val (dominant model) and Met/Met vs. Val/Met+Val/Val (recessive model). Subgroup analyses by breast cancer status, menopausal status and use of hormone replacement therapy (HRT) were also performed. Eight studies were included in the meta-analysis. The overall effect in percent mammographic density was -1.41 (CI -2.86 to 0.05; P=0.06) in the recessive model. Exclusion of breast cancer patients increased the effect size to -1.93 (CI -3.49 to -0.37; P=0.02). The results suggested opposite effect of COMT Val158Met for postmenopausal users of HRT versus premenopausal women or postmenopausal non-users of HRT. COMT Val158Met polymorphism may be associated with mammographic density at least in healthy women. Menopausal status and HRT should be taken into account in future studies to avoid masking of the underlying effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Fluorine-18-labeled [Nle4,D-Phe7]-α-MSH, an α-melanocyte stimulating hormone analogue

International Nuclear Information System (INIS)

Vaidyanathan, Ganesan; Zalutsky, Michael R.

1997-01-01

The α-melanocyte stimulating hormone (α-MSH) analogue [N1e 4 ,D-Phe 7 ]-α-MSH was labeled with 18 F using N-succinimidyl 4-[ 18 F]fluorobenzoate ([ 18 F]SFB) in >80% radiochemical yield. The IC 50 values of [N1e 4 ,D-Phe 7 ]-α-MSH and para-fluorobenzoyl-[N1e 4 ,D-Phe 7 ]-α-MSH ([N1e 4 ,D-Phe 7 ,Lys 11 -( 18 F)PFB]-α-MSH) for inhibiting the binding of meta-[ 131 I]iodobenzoyl-[N1e 4 ,D-Phe 7 ]-α-MSH ([N1e 4 ,D-Phe 7 ,Lys 11 -( 131 I)MIB]-α-MSH) to B16-F1 murine melanoma cells were 89 ± 9 pM and 112 ± 22 pM, respectively, suggesting that addition of 4-fluorobenzoate did not compromise α-MSH receptor binding affinity. Binding of [N1e 4 ,D-Phe 7 ,Lys 11 -( 18 F)PFB]-α-MSH was influenced by the specific activity of the preparation (400-1000 Ci/mmol). The normal tissue clearance of [N1e 4 ,D-Phe 7 ,Lys 11 -( 18 F)PFB]-α-MSH in mice was quite rapid, with little evidence for defluorination

G673 could be a novel mutational hot spot for intragenic suppressors of pheS5 lesion in Escherichia coli.

Science.gov (United States)

Ponmani, Thangaraj; Munavar, M Hussain

2014-06-01

The pheS5 Ts mutant of Escherichia coli defined by a G293 → A293 transition, which is responsible for thermosensitive Phenylalanyl-tRNA synthetase has been well studied at both biochemical and molecular level but genetic analyses pertaining to suppressors of pheS5 were hard to come by. Here we have systematically analyzed a spectrum of Temperature-insensitive derivatives isolated from pheS5 Ts mutant and identified two intragenic suppressors affecting the same base pair coordinate G673 (pheS19 defines G673 → T673 ; Gly225 → Cys225 and pheS28 defines G673 → C673 ; Gly225 → Arg225). In fact in the third derivative, the intragenic suppressor originally named pheS43 (G673 → C673 transversion) is virtually same as pheS28. In the fourth case, the very pheS5 lesion itself has got changed from A293 → T293 (named pheS40). Cloning of pheS(+), pheS5, pheS5-pheS19, pheS5-pheS28 alleles into pBR322 and introduction of these clones into pheS5 mutant revealed that excess of double mutant protein is not at all good for the survival of cells at 42°C. These results clearly indicate a pivotal role for Gly225 in the structural/functional integrity of alpha subunit of E. coli PheRS enzyme and it is proposed that G673 might define a hot spot for intragenic suppressors of pheS5. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

48 CFR 570.203-3 - Soliciting offers.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Soliciting offers. 570.203... 570.203-3 Soliciting offers. (a) Solicit offers by providing each prospective offeror a proposed short..., evaluation procedures and submissions of offers. ...

21 CFR 570.18 - Tolerances for related food additives.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tolerances for related food additives. 570.18 Section 570.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES General Provisions § 570.18 Tolerances...

ICTR-PHE: scientists engage with multidisciplinary research

CERN Multimedia

Antonella Del Rosso

2015-01-01

In 2016, the next edition of the unique conference that gathers scientists from a variety of fields will focus on many topics particularly dear to the heart of physicists, clinicians, biologists, and computer specialists. The call for abstracts is open until 16 October.   When detector physicists, radiochemists, nuclear-medicine physicians and other physicists, biologists, software developers, accelerator experts and oncologists think outside the box and get involved in multidisciplinary research, they create innovative healthcare. ICTR-PHE is a biennial event, co-organised by CERN, whose main aim is to foster multidisciplinary research by positioning itself at the crossing of physics, medicine and biology. At the ICTR-PHE conference, physicists, engineers, and computer scientists share their knowledge and technologies while doctors and biologists present their needs and vision for the medical tools of the future, thus triggering breakthrough ideas and technological developments in speci...

48 CFR 2009.570-5 - Contract clauses.

Science.gov (United States)

2010-10-01

... COMPETITION AND ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Organizational Conflicts of Interest 2009.570-5 Contract clauses. (a) General contract clause. All contracts and simplified acquisitions of the types set forth in 2009.570-4(b) must include the clause entitled, “Contractor Organizational Conflicts of...

The role of cysteine residues in the sulphate transporter, SHST1: construction of a functional cysteine-less transporter.

Science.gov (United States)

Howitt, Susan M

2005-05-20

We investigated the role of cysteine residues in the sulphate transporter, SHST1, with the aim of generating a functional cysteine-less variant. SHST1 contains five cysteine residues and none was essential for function. However, replacement of C421 resulted in a reduction in transport activity. Sulphate transport by C205 mutants was dependent on the size of the residue at this position. Alanine at position 205 resulted in a complete loss of function whereas leucine resulted in a 3-fold increase in sulphate transport relative to wild type SHST1. C205 is located in a putative intracellular loop and our results suggest that this loop may be important for sulphate transport. By replacing C205 with leucine and the other four cysteine residues with alanine, we constructed a cysteine-less variant of SHST1 that has transport characteristics indistinguishable from wild type. This construct will be useful for further structure and function studies of SHST1.

21 CFR 570.38 - Determination of food additive status.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Determination of food additive status. 570.38... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES Food Additive Safety § 570.38 Determination of food additive status. (a) The Commissioner may, in accordance with § 570.35 (b)(4) or (c)(5...

48 CFR 536.570-5 - Working hours.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Working hours. 536.570-5... CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 536.570-5 Working hours. Insert 552.236-74, Working Hours, in solicitations and contracts if construction, dismantling...

29 CFR 570.53 - Coal-mine occupations (Order 3).

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Coal-mine occupations (Order 3). 570.53 Section 570.53... § 570.53 Coal-mine occupations (Order 3). (a) Finding and declaration of fact. All occupations in or about any coal mine, except the occupation of slate or other refuse picking at a picking table or...

A new technique of ion beam tritium labelling

International Nuclear Information System (INIS)

Zhang Nianbao; Sheng Shugang; Yao Fuzeng

1990-01-01

In this paper a new technique is reported for tritium labelling of proteins, peptides and other nonvolatile organic compounds. A tritium ion beam is accelerated to bombard solid sample target for producing tritium exchange with hydrogen. The tritium labelling method has been applied to tritiated soybean trypsin inhibitor, ribonuclease A, elastin, pachyman and others totalled 11. After purifying by dialysis, ion exchange chromatography and gel filtration, the tritiated proteins and polysaccharide were obtained with specific activity over 37 GBq/mmol, without decomposition and with biological activity well preserved. By amino acid analysis of tritiated protein it was shown that the relative specific radioactivities for His., Tyr. and Phe. residues were higher while those for Val., Ile. and Ser. residues were lower

28 CFR 570.37 - Violation of furlough.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Violation of furlough. 570.37 Section 570.37 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE.... (a) Staff shall process as an escapee an inmate who absconds from furlough. (b) Staff may take...

14 CFR 121.570 - Airplane evacuation capability.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Airplane evacuation capability. 121.570... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations § 121.570 Airplane evacuation capability. (a) No person may cause an airplane carrying passengers to be moved on the surface, take off, or...

48 CFR 1836.570 - NASA solicitation provisions and contract clause.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true NASA solicitation provisions and contract clause. 1836.570 Section 1836.570 Federal Acquisition Regulations System NATIONAL... CONTRACTS Contract Clauses 1836.570 NASA solicitation provisions and contract clause. (a) The contracting...

The image in print advertising and comments to Val Larsen's research program

DEFF Research Database (Denmark)

Sørensen, Bent; Thellefsen, Torkild Leo; Thellefsen, Martin Muderspach

2017-01-01

In this article, the authors re-visit, with Val Larsen, the use of Peircean icons and symbols in print advertising and thereby find (some) formal conditions concerning its images. Even though they are inspired by Val Larsen's research program the authors are also critical of it. Hence, they set out...... to demonstrate how Val Larsen overlooks crucial parts of the semiotic potential of icons and symbols within print advertising. Furthermore, Val Larsen needs, they argue, the Peircean index within his research program. At the end of the article, and inspired by Val Larsen, the authors put forth nine Peircean...... points they find relevant for a research program concerning the image within print advertising. Here, ontological and methodological deductions are made from Peircean ideas and principles....

24 CFR 570.611 - Conflict of interest.

Science.gov (United States)

2010-04-01

...: (i) A disclosure of the nature of the conflict, accompanied by an assurance that there has been... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Conflict of interest. 570.611... § 570.611 Conflict of interest. (a) Applicability. (1) In the procurement of supplies, equipment...

24 CFR 570.610 - Uniform administrative requirements and cost principles.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Uniform administrative requirements and cost principles. 570.610 Section 570.610 Housing and Urban Development Regulations Relating to... GRANTS Other Program Requirements § 570.610 Uniform administrative requirements and cost principles. The...

24 CFR 570.613 - Eligibility restrictions for certain resident aliens.

Science.gov (United States)

2010-04-01

... certain resident aliens. 570.613 Section 570.613 Housing and Urban Development Regulations Relating to... GRANTS Other Program Requirements § 570.613 Eligibility restrictions for certain resident aliens. (a) Restriction. Certain newly legalized aliens, as described in 24 CFR part 49, are not eligible to apply for...

Data of evolutionary structure change: 1DPZB-2DHTB [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1DPZB-2DHTB 1DPZ 2DHT B B ------------------------MKVAVLPGDGIGPEV...ntryChain> 2DHT B 2DHT...91 HIS CA 345 VAL CA 448 VAL CA 486 2DHT... B 2DHTB YAIEHKRKKVT GLY CA 356 GLU CA 278 PHE CA 317 2DHT

29 CFR 570.11 - Continued acceptability of certificates of age.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Continued acceptability of certificates of age. 570.11 Section 570.11 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Certificates of Age § 570.11...

New construction of the Leis-Gannibach small hydro power station in Vals, Switzerland; Elektrizitaetswerk der Gemeinde Vals, 7132 Vals. Neubau Kleinwasserkraftwerk 'Leis-Gannibach' - Schlussbericht / Vorprojekt

Energy Technology Data Exchange (ETDEWEB)

Mittner, Ch.

2010-03-15

This report for the Swiss Federal Office of Energy (SFOE) presents a project concerning a new small hydro installation in Vals, Switzerland. A system in planning is to provide artificial snow at this ski resort using water from the Gannibach stream. The local utility in Vals intends to use this water during those periods when no artificial snow is needed to drive a small hydro power plant. The paper discusses the current situation, the hydrology of the catchment area and the potential that can be used. The legal and planning situation is examined and details of the project are provided, including water intake, pressurised piping, turbine, generator and control system. Finally, the financial viability of the project is examined.

29 CFR 570.70 - Purpose and scope.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Purpose and scope. 570.70 Section 570.70 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR... “provisions of section 12 [of the Act] relating to child labor shall apply to an employee below the age of 16...

Data of evolutionary structure change: 1DR8A-2DHTB [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1DR8A-2DHTB 1DR8 2DHT A B ------------------------MKVAVLPGDGIGPEV...Chain> 2DHT B 2DHT...50 VAL CA 456 VAL CA 489 SER CA 527 2DHT... B 2DHTB AIEHKRKKVTI GLY CA 352 GLU CA 281 PHE CA 327

Data of evolutionary structure change: 1DR0A-2DHTB [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1DR0A-2DHTB 1DR0 2DHT A B ------------------------MKVAVLPGDGIGPEV...tryChain> 2DHT B 2DHT...95 HIS CA 348 VAL CA 450 VAL CA 478 2DHT... B 2DHTB YAIEHKRKKVT GLY CA 354 GLU CA 281 PHE CA 323 2DHT

High-Temperature Structural Analysis of a Small-Scale PHE Prototype under the Test Condition of a Small-Scale Gas Loop

International Nuclear Information System (INIS)

Song, K.; Hong, S.; Park, H.

2012-01-01

A process heat exchanger (PHE) is a key component for transferring the high-temperature heat generated from a very high-temperature reactor (VHTR) to a chemical reaction for the massive production of hydrogen. The Korea Atomic Energy Research Institute has designed and assembled a small-scale nitrogen gas loop for a performance test on VHTR components and has manufactured a small-scale PHE prototype made of Hastelloy-X alloy. A performance test on the PHE prototype is underway in the gas loop, where different kinds of pipelines connecting to the PHE prototype are tested for reducing the thermal stress under the expansion of the PHE prototype. In this study, to evaluate the high-temperature structural integrity of the PHE prototype under the test condition of the gas loop, a realistic and effective boundary condition imposing the stiffness of the pipelines connected to the PHE prototype was suggested. An equivalent spring stiffness to reduce the thermal stress under the expansion of the PHE prototype was computed from the bending deformation and expansion of the pipelines connected to the PHE. A structural analysis on the PHE prototype was also carried out by imposing the suggested boundary condition. As a result of the analysis, the structural integrity of the PHE prototype seems to be maintained under the test condition of the gas loop.

Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study.

Science.gov (United States)

Saravani, Ramin; Galavi, Hamid Reza; Lotfian Sargazi, Marzieh

2017-10-01

Objective: Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. Method: This case- control study included 92 SCZ patients and 92 healthy controls (HCs). Genotyping of both variants (COMT Val158Met (G>A) and BDNF Val66Met (G>A)) were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Results: The findings revealed that the COMT Val158Met (G>A) polymorphism was not associated with the risk/protective of SCZ in all models (OR=0.630, 95%CI=0.299-1.326, P=0.224, GA vs. GG, OR=1.416, 95%CI=0.719-2.793, P=0.314, AA vs. GG, OR=1.00, 95%CI=0.56-1.79, P=1.00 GA+AA vs. GG, OR=1.667, 95%CI=0.885-3.125, P=0.11, AA vs. GG+GA, OR=1.247, 95%CI=0.825-1.885, P=0.343, A vs. G,). However, BDNF Val66Met (G>A) variant increased the risk of SCZ (OR = 2.008 95%CI = 1.008-4.00, P = 0.047, GA vs. GG, OR = 3.876 95%CI = 1.001-14.925, P = 0.049. AA vs. GG, OR = 2.272. 95%CI = 1.204-4.347, P = 0.011, GA+AA vs. GG, OR = 2.22 95%CI = 1.29-3.82. P = 0.005, A vs. G). Conclusion: The results did not support an association between COMT Val158Met (G>A) variant and risk/protective of SCZ. Moreover, it was found that BDNF Val66Met (G>A) polymorphism may increase the risk of SCZ development. Further studies and different ethnicities are recommended to confirm the findings.

Cathecol-O-methyl transferase Val158Met genotype is not a risk factor for conversion disorder.

Science.gov (United States)

Armagan, E; Almacıoglu, M L; Yakut, T; Köse, A; Karkucak, M; Köksal, O; Görükmez, O

2013-03-19

Alterations in catechol-O-methyltransferase (COMT) activity are involved in various types of neurological disorders. We examined a possible association between the COMT Val158Met polymorphism and conversion disorder in a study of 48 patients with conversion disorder and 48 control patients. In the conversion disorder group, 31 patients were Val/Met heterozygotes, 15 patients were Val/Val homozygotes and 2 patients were Met/Met homozygotes. In the control group, 32 patients were Val/Met heterozygotes and 16 patients were Val/Val homozygotes. There was no significant difference between the groups. We conclude that the COMT Val158Met genotype is quite common in Turkey and that it is not a risk factor for conversion disorder in the Turkish population.

29 CFR 570.71 - Occupations involved in agriculture.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Occupations involved in agriculture. 570.71 Section 570.71... CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION 1-Occupations in Agriculture... agriculture. (a) Findings and declarations of fact as to specific occupations. The following occupations in...

Simple and rapid analytical method for detection of amino acids in blood using blood spot on filter paper, fast-GC/MS and isotope dilution technique.

Science.gov (United States)

Kawana, Shuichi; Nakagawa, Katsuhiro; Hasegawa, Yuki; Yamaguchi, Seiji

2010-11-15

A simple and rapid method for quantitative analysis of amino acids, including valine (Val), leucine (Leu), isoleucine (Ile), methionine (Met) and phenylalanine (Phe), in whole blood has been developed using GC/MS. In this method, whole blood was collected using a filter paper technique, and a 1/8 in. blood spot punch was used for sample preparation. Amino acids were extracted from the sample, and the extracts were purified using cation-exchange resins. The isotope dilution method using ²H₈-Val, ²H₃-Leu, ²H₃-Met and ²H₅-Phe as internal standards was applied. Following propyl chloroformate derivatization, the derivatives were analyzed using fast-GC/MS. The extraction recoveries using these techniques ranged from 69.8% to 87.9%, and analysis time for each sample was approximately 26 min. Calibration curves at concentrations from 0.0 to 1666.7 μmol/l for Val, Leu, Ile and Phe and from 0.0 to 333.3 μmol/l for Met showed good linearity with regression coefficients=1. The method detection limits for Val, Leu, Ile, Met and Phe were 24.2, 16.7, 8.7, 1.5 and 12.9 μmol/l, respectively. This method was applied to blood spot samples obtained from patients with phenylketonuria (PKU), maple syrup urine disease (MSUD), hypermethionine and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), and the analysis results showed that the concentrations of amino acids that characterize these diseases were increased. These results indicate that this method provides a simple and rapid procedure for precise determination of amino acids in whole blood. Copyright © 2010 Elsevier B.V. All rights reserved.

Genetic contribution of catechol-O-methyltransferase polymorphism (Val158Met) in children with chronic tension-type headache.

Science.gov (United States)

Fernández-de-las-Peñas, César; Ambite-Quesada, Silvia; Rivas-Martínez, Inés; Ortega-Santiago, Ricardo; de-la-Llave-Rincón, Ana Isabel; Fernández-Mayoralas, Daniel M; Pareja, Juan A

2011-10-01

Our aim was to investigate the relationship between Val158Met polymorphisms, headache, and pressure hypersensitivity in children with chronic tension-type headache (CTTH). A case-control study with blinded assessor was conducted. Seventy children with CTTH associated with pericranial tenderness and 70 healthy children participated. After amplifying Val158Met polymorphism by polymerase chain reactions, we assessed genotype frequencies and allele distributions. We classified children according to their Val158Met polymorphism: Val/Val, Val/Met, Met/Met. Pressure pain thresholds (PPT) were bilaterally assessed over the temporalis, upper trapezius, second metacarpal, and tibialis anterior muscles. The distribution of Val158Met genotypes was not significantly different (p = 0.335), between children with CTTH and healthy children, and between boys and girls (p = 0.872). Children with CTTH with the Met/Met genotype showed a longer headache history compared with those with Met/Val (p = 0.001) or Val/Val (p = 0.002) genotype. Children with CTTH with Met/Met genotype showed lower PPT over upper trapezius and temporalis muscles than children with CTTH with Met/Val or Val/Val genotype (p < 0.01). The Val158Met catechol-O-methyltransferase (COMT) polymorphism does not appear to be involved in predisposition to suffer from CTTH in children; nevertheless, this genetic factor may be involved in the phenotypic expression, as pressure hypersensitivity was greater in those CTTH children with the Met/Met genotype.

9 CFR 590.570 - Pasteurization of liquid eggs.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Pasteurization of liquid eggs. 590.570..., Processing, and Facility Requirements § 590.570 Pasteurization of liquid eggs. (a) Pasteurization facilities: The facilities for pasteurization of egg products shall be adequate and of approved construction so...

Autophosphorylation of JAK2 on tyrosines 221 and 570 regulates its activity

DEFF Research Database (Denmark)

Argetsinger, Lawrence S; Kouadio, Jean-Louis K; Steen, Hanno

2004-01-01

or which of the 49 tyrosines in JAK2 are autophosphorylated. In this study, mass spectrometry and two-dimensional peptide mapping were used to determine that tyrosines 221, 570, and 1007 in JAK2 are autophosphorylated. Phosphorylation of tyrosine 570 is particularly robust. In response to growth hormone......, JAK2 was rapidly and transiently phosphorylated at tyrosines 221 and 570, returning to basal levels by 60 min. Analysis of the sequences surrounding tyrosines 221 and 570 in JAK2 and tyrosines in other proteins that are phosphorylated in response to ligands that activate JAK2 suggests that the YXX......[L/I/V] motif is one of the motifs recognized by JAK2. Experiments using JAK2 with tyrosines 221 and 570 mutated to phenylalanine suggest that tyrosines 221 and 570 in JAK2 may serve as regulatory sites in JAK2, with phosphorylation of tyrosine 221 increasing kinase activity and phosphorylation of tyrosine 570...

Measuring patient engagement: development and psychometric properties of the Patient Health Engagement (PHE) Scale.

Science.gov (United States)

Graffigna, Guendalina; Barello, Serena; Bonanomi, Andrea; Lozza, Edoardo

2015-01-01

Beyond the rhetorical call for increasing patients' engagement, policy makers recognize the urgency to have an evidence-based measure of patients' engagement and capture its effect when planning and implementing initiatives aimed at sustaining the engagement of consumers in their health. In this paper, authors describe the Patient Health Engagement Scale (PHE-scale), a measure of patient engagement that is grounded in rigorous conceptualization and appropriate psychometric methods. The scale was developed based on our previous conceptualization of patient engagement (the PHE-model). In particular, the items of the PHE-scale were developed based on the findings from the literature review and from interviews with chronic patients. Initial psychometric analysis was performed to pilot test a preliminary version of the items. The items were then refined and administered to a national sample of chronic patients (N = 382) to assess the measure's psychometric performance. A final phase of test-retest reliability was performed. The analysis showed that the PHE Scale has good psychometric properties with good correlation with concurrent measures and solid reliability. Having a valid and reliable measure to assess patient engagement is the first step in understanding patient engagement and its role in health care quality, outcomes, and cost containment. The PHE Scale shows a promising clinical relevance, indicating that it can be used to tailor intervention and assess changes after patient engagement interventions.

Neurotensin analogs [D-TYR11] and [D-PHE11]neurotensin resist degradation by brain peptidases in vitro and in vivo

International Nuclear Information System (INIS)

Checler, F.; Vincent, J.P.; Kitabgi, P.

1983-01-01

The present study was designed to compare the susceptibility of neurotensin (NT), [ 3 H]NT, [D-Tyr11]NT and [D-Phe11]NT to degradation by 1) rat brain synaptic membranes in vitro and 2) after i.c.v. administration in the rat in vivo. Degradation was assessed by purifying the peptides using reverse phase high-performance liquid chromatography and by measuring the amount of radioactive or absorbing (OD 230) material under each peptide peak. In contrast to NT, [D-Tyr11]NT and [D-Phe11]NT were resistant to degradation by brain synaptic peptidases in vitro. Furthermore, NT was rapidly metabolized in brain tissues after i.c.v. administration, whereas [D-Tyr11]NT was metabolically stable. The present data confirm the central role of NT residue Tyr11 in the mechanisms of NT inactivation by brain synaptic peptidases. They account for the higher in vivo potency of [D-Tyr11]NT as compared with its in vitro potency. Finally, they explain, at least in part, the need to administer large doses of NT in the brain in order to observe neurobehavioral and neuropharmacological effects

29 CFR 570.8 - Issuance of a Federal certificate of age.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Issuance of a Federal certificate of age. 570.8 Section 570.8 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Certificates of Age § 570.8...

Animal experiment of 111In-DTPA-D-Phe1-octreotide

International Nuclear Information System (INIS)

Wang Fan; Xiao Lun; Fan Hongqiang; Jin Xiaohai; Wang Yishan; Chen Daming; Bai Hongsheng; Chen Fang; Li Jiaxiu; Liu Lin

1998-01-01

The animal experiments of a novel somatostatin receptor-positive tumors imaging agent, 111 In-DTPA-D-Phe 1 -octreotide, has been described. Biological properties were evaluated by dynamic and static γ images of somatostatin receptor-positive tumors in nude mice bearing pancreatic carcinoma. The radiocomponent of 111 In-DTPA, which came from 111 In-DTPA-D-Phe 1 -octreotide decomposition, showed 50% of radioactivity in blood and 40% in urine at 3h postinjection. Rapid blood and urine clearance, and high T/B ratio (7.92 up to 24 h postinjection) were observed. The images of somatostatin receptor-positive tumors could be obtained during 0.5-24 h after administration but the best one would be at 24 h

A Conserved Proline Triplet in Val-tRNA Synthetase and the Origin of Elongation Factor P

Directory of Open Access Journals (Sweden)

Agata L. Starosta

2014-10-01

Full Text Available Bacterial ribosomes stall on polyproline stretches and require the elongation factor P (EF-P to relieve the arrest. Yet it remains unclear why evolution has favored the development of EF-P rather than selecting against the occurrence of polyproline stretches in proteins. We have discovered that only a single polyproline stretch is invariant across all domains of life, namely a proline triplet in ValS, the tRNA synthetase, that charges tRNAVal with valine. Here, we show that expression of ValS in vivo and in vitro requires EF-P and demonstrate that the proline triplet located in the active site of ValS is important for efficient charging of tRNAVal with valine and preventing formation of mischarged Thr-tRNAVal as well as efficient growth of E. coli in vivo. We suggest that the critical role of the proline triplet for ValS activity may explain why bacterial cells coevolved the EF-P rescue system.

Arg-Phe-amide-like peptides in the primitive nervous systems of coelenterates

DEFF Research Database (Denmark)

Grimmelikhuijzen, C J; Ebbesen, Ditte Graff

1985-01-01

By using immunocytochemistry and radioimmunoassays, several substances resembling vertebrate or invertebrate neuropeptides have been found in the nervous systems of coelenterates. The most abundant neuropeptides were those related to the molluscan neuropeptide Phe-Met-Arg-Phe-amide (FMRFamide......). Of antisera against different fragments of FMRFamide, those against RFamide were superior in recognizing the coelenterate peptide. Incubation of whole mounts with these RFamide antisera visualized the coelenterate nervous system in such a detail as has previously not been possible. By using a radioimmunoassay...

The functional BDNF Val66Met polymorphism affects functions of pre-attentive visual sensory memory processes.

Science.gov (United States)

Beste, Christian; Schneider, Daniel; Epplen, Jörg T; Arning, Larissa

2011-01-01

The brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is involved in nerve growth and survival. Especially, a single nucleotide polymorphism (SNP) in the BDNF gene, Val66Met, has gained a lot of attention, because of its effect on activity-dependent BDNF secretion and its link to impaired memory processes. We hypothesize that the BDNF Val66Met polymorphism may have modulatory effects on the visual sensory (iconic) memory performance. Two hundred and eleven healthy German students (106 female and 105 male) were included in the data analysis. Since BDNF is also discussed to be involved in the pathogenesis of depression, we additionally tested for possible interactions with depressive mood. The BDNF Val66Met polymorphism significantly influenced iconic-memory performance, with the combined Val/Met-Met/Met genotype group revealing less time stability of information stored in iconic memory than the Val/Val group. Furthermore, this stability was positively correlated with depressive mood exclusively in the Val/Val genotype group. Thus, these results show that the BDNF Val66Met polymorphism has an effect on pre-attentive visual sensory memory processes. Copyright © 2010 Elsevier Ltd. All rights reserved.

29 CFR 570.32 - Effect of subpart C.

Science.gov (United States)

2010-07-01

... Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR... (Child Labor Reg. 3) § 570.32 Effect of subpart C. Link to an amendment published at 75 FR 28448, May 20... conditions specified in § 570.35 shall not be deemed to be oppressive child labor within the meaning of the...

Subnanomolar Inhibitor of Cytochrome bc1 Complex Designed via Optimizing Interaction with Conformationally Flexible Residues

Science.gov (United States)

Zhao, Pei-Liang; Wang, Le; Zhu, Xiao-Lei; Huang, Xiaoqin; Zhan, Chang-Guo; Wu, Jia-Wei; Yang, Guang-Fu

2009-01-01

Cytochrome bc1 complex (EC 1.10.2.2, bc1), an essential component of the cellular respiratory chain and the photosynthetic apparatus in photosynthetic bacteria, has been identified as a promising target for new drugs and agricultural fungicides. X-ray diffraction structures of the free bc1 complex and its complexes with various inhibitors revealed that the phenyl group of Phe274 in the binding pocket exhibited significant conformational flexibility upon different inhibitors binding to optimize respective π-π interactions, whereas the side chains of other hydrophobic residues showed conformational stability. Therefore, in the present study, a strategy of optimizing the π-π interaction with conformationally flexible residues was proposed to design and discover new bc1 inhibitors with a higher potency. Eight new compounds were designed and synthesized, among which compound 5c with a Ki value of 570 pM was identified as the most promising drug or fungicide candidate, significantly more potent than the commercially available bc1 inhibitors including azoxystrobin (AZ), kresoxim-methyl (KM), and pyraclostrobin (PY). To our knowledge, this is the first bc1 inhibitor discovered from structure-based design with a potency of subnanomolar Ki value. For all of the compounds synthesized and assayed, the calculated binding free energies correlated reasonably well with the binding free energies derived from the experimental Ki values with a correlation coefficient of r2 = 0.89. The further inhibitory kinetics studies revealed that compound 5c is a non-competitive inhibitor with respect to substrate cytochrome c, but is a competitive inhibitor with respect to substrate ubiquinol. Due to its subnanomolar Ki potency and slow dissociation rate constant (k−0 = 0.00358 s−1), compound 5c could be used as a specific probe for further elucidation of the mechanism of bc1 function and as a new lead compound for future drug discovery. PMID:19928849

Lower baseline performance but greater plasticity of working memory for carriers of the val allele of the COMT Val¹⁵⁸Met polymorphism.

Science.gov (United States)

Bellander, Martin; Bäckman, Lars; Liu, Tian; Schjeide, Brit-Maren M; Bertram, Lars; Schmiedek, Florian; Lindenberger, Ulman; Lövdén, Martin

2015-03-01

Little is known about genetic contributions to individual differences in cognitive plasticity. Given that the neurotransmitter dopamine is critical for cognition and associated with cognitive plasticity, we investigated the effects of 3 polymorphisms of dopamine-related genes (LMX1A, DRD2, COMT) on baseline performance and plasticity of working memory (WM), perceptual speed, and reasoning. One hundred one younger and 103 older adults underwent approximately 100 days of cognitive training, and extensive testing before and after training. We analyzed the baseline and posttest data using latent change score models. For working memory, carriers of the val allele of the COMT polymorphism had lower baseline performance and larger performance gains from training than carriers of the met allele. There was no significant effect of the other genes or on other cognitive domains. We relate this result to available evidence indicating that met carriers perform better than val carriers in WM tasks taxing maintenance, whereas val carriers perform better at updating tasks. We suggest that val carriers may show larger training gains because updating operations carry greater potential for plasticity than maintenance operations. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Pulsational stability of the SX Phe star AE UMa

Science.gov (United States)

Pena, J. H.; Renteria, A.; Villarreal, C.; Pina, D. S.; Soni, A. A.; Guillen, J.; Vargas, K.; Trejo, O.

2016-11-01

From newly determined times of maxima of the SX Phe star AE UMa and a compilation of previous times of maxima, we were able to determine the nature of this star. With uv photometry we determined its physical parameters.

COMT Val158 Met moderates the link between rank and aggression in a non-human primate.

Science.gov (United States)

Gutleb, D R; Roos, C; Noll, A; Ostner, J; Schülke, O

2018-04-01

The COMT Val 158 Met polymorphism is one of the most widely studied genetic polymorphisms in humans implicated in aggression and the moderation of stressful life event effects. We screened a wild primate population for polymorphisms at the COMT Val 158 Met site and phenotyped them for aggression to test whether the human polymorphism exists and is associated with variation in aggressive behavior. Subjects were all adults from 4 study groups (37 males, 40 females) of Assamese macaques (Macaca assamensis) in their natural habitat (Phu Khieo Wildlife Sanctuary, Thailand). We collected focal animal behavioral data (27 males, 36 females, 5964 focal hours) and fecal samples for non-invasive DNA analysis. We identified the human COMT Val 158 Met polymorphism (14 Met/Met, 41 Val/Met and 22 Val/Val). Preliminary results suggest that COMT genotype and dominance rank interact to influence aggression rates. Aggression rates increased with rank in Val/Val, but decreased in Met/Met and Val/Met individuals, with no significant main effect of COMT genotype on aggression. Further support for the interaction effect comes from time series analyses revealing that when changing from lower to higher rank position Val/Val individuals decreased, whereas Met/Met individuals increased their aggression rate. Contradicting the interpretation of earlier studies, we show that the widely studied Val 158 Met polymorphism in COMT is not unique to humans and yields similar behavioral phenotypes in a non-human primate. This study represents an important step towards understanding individual variation in aggression in a wild primate population and may inform human behavioral geneticists about the evolutionary roots of inter-individual variation in aggression. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Effect of site disorder on the electronic properties of Fe2VAl Heusler alloy

International Nuclear Information System (INIS)

Venkatesh, Ch.; Srinivas, V.; Rao, V.V.; Srivastava, S.K.; Babu, P. Sudheer

2013-01-01

Highlights: •The role of site-disorder on physical properties of Fe 2 VAl has been investigated through experiments as well as DFT calculations. •Metal to semiconductor-like behaviour in electrical transport of anti-site disordered Fe 2 VAl was consistently explained. •Both itinerant and localized magnetic behaviours of anti-site disordered Fe 2 VAl are discussed. •Justification of metallic-like transition in site-disordered Fe 2 VAl is given. -- Abstract: Ab initio calculations on ordered L2 1 structure of Fe 2 VAl alloy have been carried out by introducing B2, DO 3 , A2′ and XY–XZ type disorders in order to understand the role of anti-site disorder on magnetic and transport properties. These studies show an enhancement of individual spin moments of anti-site Fe atoms in DO 3 , A2′ and XY–XZ type anti-site disorder, making the Fe 2 VAl alloy magnetically active. These calculations also show that hybridization due to covalent distribution of valance states among the atoms is important in Fe 2 VAl, defining its unusual physical properties. From the density of states spectrum obtained near the Fermi level, we have noticed formation of intermediate defect-like states that couple the edges of the pseudo gap on both sides of the Fermi level, driving the material from semi-metallic to metallic type in electrical transport. We also present experimental results on structural, magnetic and electrical properties of Fe 2 VAl Heusler alloy. A comparison of present experimental data with calculations shows an existence of DO 3 type anti-site disorder due to the Al-deficiency in Fe 2 VAl alloy which causes deviations in theoretical results on the magnetic and transport behaviour of pure Fe 2 VAl. The temperature dependence of electrical transport and magnetic data analysed on the basis of impurity band model which provides convincing evidence for itinerant character of this alloy system with an anti-site disorder

Spanish adaptation of the Patient Health Engagement scale (S.PHE-s)in patients with chronic diseases.

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Magallares, Alejandro; Graffigna, Guendalina; Barello, Serena; Bonanomi, Andrea; Lozza, Edoardo

2017-08-01

The Patient Health Engagement scale is an instrument based on evidence about the experiences and preferences of patients with chronic diseases regarding their engagement with the treatment they receive. The main goal of this study was to adapt the Patient Health Engagement scale to the Spanish population (S.PHE-s) following the guidelines for cross-cultural adaptations. The sample comprised 413 patients with different chronic diseases. The confirmatory factor analysis showed a one factor model corresponding to the structure proposed by the original authors. The factor structure was invariant by gender. Furthermore, a Rasch Model showed that the S.PHE-s was unidimensional. In addition, every polychoric correlation coefficient was higher than .60. The Ordinal Alpha of the S.PHE-s was .85. Finally, the S.PHE-s was found to be positively related to life satisfaction, positive affect, and treatment adherence and negatively correlated to negative affect, depression, and anxiety. In light of these results, it may be concluded that the S.PHE-s has good psychometric properties and it may be used by the Spanish-speaking scientific community to measure patient engagement.

Editoriale – Paul Valéry: strategie del sensibile

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Benedetta Zaccarello

2012-05-01

Full Text Available Sensibilité is in Valéry’s theory the name of a large grasp of functions, involving both perception and creation, and involved both in art and in experience. So far, this key word of Valéry’s aesthetics can be read as the bridge between his conceptions of art and his idea of the self in order to understand the way this author writes and conceives what philosophy can aim to.

570 miljonit Mondriani maali eest

Index Scriptorium Estoniae

1998-01-01

Hollandi maalikunsti fond ostis Piet Modigliani viimase maali ameerika ajakirja-kirjastaja S. I. Newhouse erakogult 80 miljoni kuldna (570 miljoni krooni) eest. 1944. a. valminud 'Victory Boogie Woogie' eksponeeritakse Haagi linnamuuseumis

Residue Phe112 of the Human-Type Corrinoid Adenosyltransferase (PduO) Enzyme of Lactobacillus reuteri Is Critical to the Formation of the Four-Coordinate Co(II) Corrinoid Substrate and to the Activity of the Enzyme

Energy Technology Data Exchange (ETDEWEB)

Mera, Paola E.; St. Maurice, Martin; Rayment, Ivan; Escalante-Semerena, Jorge C.; UW

2009-06-08

ATP:Corrinoid adenosyltransferases (ACAs) catalyze the transfer of the adenosyl moiety from ATP to cob(I)alamin via a four-coordinate cob(II)alamin intermediate. At present, it is unknown how ACAs promote the formation of the four-coordinate corrinoid species needed for activity. The published high-resolution crystal structure of the ACA from Lactobacillus reuteri (LrPduO) in complex with ATP and cob(II)alamin shows that the environment around the alpha face of the corrin ring consists of bulky hydrophobic residues. To understand how these residues promote the generation of the four-coordinate cob(II)alamin, variants of the human-type ACA enzyme from L. reuteri (LrPduO) were kinetically and structurally characterized. These studies revealed that residue Phe112 is critical in the displacement of 5,6-dimethylbenzimidazole (DMB) from its coordination bond with the Co ion of the ring, resulting in the formation of the four-coordinate species. An F112A substitution resulted in a 80% drop in the catalytic efficiency of the enzyme. The explanation for this loss of activity was obtained from the crystal structure of the mutant protein, which showed cob(II)alamin bound in the active site with DMB coordinated to the cobalt ion. The crystal structure of an LrPduO(F112H) variant showed a DMB-off/His-on interaction between the corrinoid and the enzyme, whose catalytic efficiency was 4 orders of magnitude lower than that of the wild-type protein. The analysis of the kinetic parameters of LrPduO(F112H) suggests that the F112H substitution negatively impacts product release. Substitutions of other hydrophobic residues in the Cbl binding pocket did not result in significant defects in catalytic efficiency in vitro; however, none of the variant enzymes analyzed in this work supported AdoCbl biosynthesis in vivo.

Secondary Structures in Phe-Containing Isolated Dipeptide Chains: Laser Spectroscopy vs Quantum Chemistry.

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Loquais, Yohan; Gloaguen, Eric; Habka, Sana; Vaquero-Vara, Vanesa; Brenner, Valérie; Tardivel, Benjamin; Mons, Michel

2015-06-11

The intrinsic conformational landscape of two phenylalanine-containing protein chain models (-Gly-Phe- and -Ala-Phe- sequences) has been investigated theoretically and experimentally in the gas phase. The near UV spectroscopy (first ππ* transition of the Phe ring) is obtained experimentally under jet conditions where the conformational features can be resolved. Single-conformation IR spectroscopy in the NH stretch region is then obtained by IR/UV double resonance in the ground state, leading to resolved vibrational spectra that are assigned in terms of conformation and H-bonding content from comparison with quantum chemistry calculations. For the main conformer, whose UV spectrum exhibits a significant Franck-Condon activity in low frequency modes involving peptide backbone motions relative to the Phe chromophore, excited state IR spectroscopy has also been recorded in a UV/IR/UV experiment. The NH stretch spectral changes observed in such a ππ* labeling experiment enable us to determine those NH bonds that are coupled to the phenyl ring; they are compared to CC2 excited state calculations to quantify the geometry change upon ππ* excitation. The complete and consistent series of data obtained enable us to propose an unambiguous assignment for the gallery of conformers observed and to demonstrate that, in these two sequences, three conceptually important local structural motifs of proteins (β-strands, 27 ribbons, and β-turns) are represented. The satisfactory agreement between the experimental conformational distribution and the predicted landscape anticipated from the DFT-D approach demonstrates the capabilities of a theoretical method that accounts for dispersive interactions. It also shows that the flaws, inherent to a resonant two-photon ionization detection scheme, often evoked for aromatic chromophores, do not seem to be significant in the case of Phe.

N-terminal fatty acylated His-dPhe-Arg-Trp-NH(2) tetrapeptides: influence of fatty acid chain length on potency and selectivity at the mouse melanocortin receptors and human melanocytes.

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Todorovic, Aleksandar; Holder, Jerry Ryan; Bauzo, Rayna M; Scott, Joseph Walker; Kavanagh, Renny; Abdel-Malek, Zalfa; Haskell-Luevano, Carrie

2005-05-05

The melanocortin system is involved in the regulation of a diverse number of physiologically important pathways including pigmentation, feeding behavior, weight and energy homeostasis, inflammation, and sexual function. All the endogenous melanocortin agonist ligands possess the conserved His-Phe-Arg-Trp tetrapeptide sequence that is postulated to be important for melanocortin receptor molecular recognition and stimulation. Previous studies by our laboratory resulted in the discovery that increasing alkyl chain length at the N-terminal "capping" region of the His-dPhe-Arg-Trp-NH(2) tetrapeptide resulted in a 100-fold increased melanocortin receptor agonist potency. This study was undertaken to systematically evaluate the pharmacological effects of increasing N-capping alkyl chain length of the CH(3)(CH(2))(n)CO-His-dPhe-Arg-Trp-NH(2) (n = 6-16) tetrapeptide template. Twelve analogues were synthesized and pharmacologically characterized at the mouse melanocortin receptors MC1R and MC3R-MC5R and human melanocytes known to express the MC1R. These peptides demonstrated melanocortin receptor selectivity profiles different from those of previously published tetrapeptides. The most notable results of enhanced ligand potency (20- to 200-fold) and receptor selectivity were observed at the MC1R. Tetrapeptides that possessed greater than nine alkyl groups were superior to alpha-MSH in terms of the stimulation of human melanocyte tyrosinase activity. Additionally, the n-pentadecanoyl derivative had a residual effect on tyrosinase activity that existed for at least 4 days after the peptide was removed from the human melanocyte culture medium. These data demonstrate the utility, potency, and residual effect of melanocortin tetrapeptides by adding N-terminal fatty acid moieties.

Data of evolutionary structure change: 1BANC-3DA7A [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1BANC-3DA7A 1BAN 3DA7 C A ---------------------------------------...bID> C 1BANC VINTF-DGVAD e-map> ASP ALA VAL GLY ASP PHE T...e> ASP CA e-map> VAL CA 244 ILE CA 298 ASN CA 3...P A 58 3.752 -15.094 16.737 1.00 35.20 C e-map

Polymorphisms at Amino Acid Residues 141 and 154 Influence Conformational Variation in Ovine PrP

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Yang, Sujeong; Thackray, Alana M.; Hopkins, Lee; Monie, Tom P.; Burke, David F.; Bujdoso, Raymond

2014-01-01

Polymorphisms in ovine PrP at amino acid residues 141 and 154 are associated with susceptibility to ovine prion disease: Leu141Arg154 with classical scrapie and Phe141Arg154 and Leu141His154 with atypical scrapie. Classical scrapie is naturally transmissible between sheep, whereas this may not be the case with atypical scrapie. Critical amino acid residues will determine the range or stability of structural changes within the ovine prion protein or its functional interaction with potential cofactors, during conversion of PrPC to PrPSc in these different forms of scrapie disease. Here we computationally identified that regions of ovine PrP, including those near amino acid residues 141 and 154, displayed more conservation than expected based on local structural environment. Molecular dynamics simulations showed these conserved regions of ovine PrP displayed genotypic differences in conformational repertoire and amino acid side-chain interactions. Significantly, Leu141Arg154 PrP adopted an extended beta sheet arrangement in the N-terminal palindromic region more frequently than the Phe141Arg154 and Leu141His154 variants. We supported these computational observations experimentally using circular dichroism spectroscopy and immunobiochemical studies on ovine recombinant PrP. Collectively, our observations show amino acid residues 141 and 154 influence secondary structure and conformational change in ovine PrP that may correlate with different forms of scrapie. PMID:25126555

20 CFR 410.570 - Underpayments.

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2010-04-01

...-BLACK LUNG BENEFITS (1969- ) Payment of Benefits § 410.570 Underpayments. (a) General. As used in this... (ii) In the case of a deceased miner, entitled for the month of death to widow's black lung benefits...

COMT Val158Met polymorphism, cognitive stability and cognitive flexibility: an experimental examination

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Rosa Elise C

2010-09-01

Full Text Available Abstract Background Dopamine in prefrontal cortex (PFC modulates core cognitive processes, notably working memory and executive control. Dopamine regulating genes and polymorphisms affecting PFC - including Catechol-O-Methyltransferase (COMT Val158Met - are crucial to understanding the molecular genetics of cognitive function and dysfunction. A mechanistic account of the COMT Val158Met effect associates the Met allele with increased tonic dopamine transmission underlying maintenance of relevant information, and the Val allele with increased phasic dopamine transmission underlying the flexibility of updating new information. Thus, consistent with some earlier work, we predicted that Val carriers would display poorer performance when the maintenance component was taxed, while Met carriers would be less efficient when rapid updating was required. Methods Using a Stroop task that manipulated level of required cognitive stability and flexibility, we examined reaction time performance of patients with schizophrenia (n = 67 and healthy controls (n = 186 genotyped for the Val/Met variation. Results In both groups we found a Met advantage for tasks requiring cognitive stability, but no COMT effect when a moderate level of cognitive flexibility was required, or when a conflict cost measure was calculated. Conclusions Our results do not support a simple stability/flexibility model of dopamine COMT Val/Met effects and suggest a somewhat different conceptualization and experimental operationalization of these cognitive components.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism affects sympathetic tone in a gender-specific way.

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Chang, Chuan-Chia; Chang, Hsin-An; Chen, Tien-Yu; Fang, Wen-Hui; Huang, San-Yuan

2014-09-01

The Val/Val genotype of the brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) has been reported to affect human anxiety-related phenotypes. Substantial research has demonstrated that anxiety is associated with sympathetic activation, while sex steroid hormones have been shown to exert differential actions in regulating BDNF expression. Thus, we examined whether the BDNF variant modulates autonomic function in a gender-dependent manner. From 708 adults initially screened for medical and psychiatric illnesses, a final cohort of 583 drug-free healthy Han Chinese (355 males, 228 females; age 34.43±8.42 years) was recruited for BDNF genotyping (Val/Val: 136, 23.3%, Val/Met: 294, 50.4%, and Met/Met: 153, 26.2%). Time- and frequency-domain analyses of heart rate variability (HRV) were used to assess autonomic outflow to the heart. Significant genotype-by-gender interaction effects were found on HRV indices. Even after adjusting for possible confounders, male participants bearing the Val/Val genotype had significant increases in low frequency (LF), LF% and LF/high frequency (HF) ratio, indicating altered sympathovagal balance with increased sympathetic modulation, compared to male Met/Met homozygotes. Females, however, showed an opposite but non-significant pattern. These results suggest that the studied BDNF polymorphism is associated with sympathetic control in a gender-specific way. The findings here support the view that male subjects with the Val/Val genotype have increased risk of anxiety by association with sympathetic activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Híbridos de trifoliata como porta-enxertos para a laranjeira 'Valência' Trifoliate hybrids as rootstocks for sweet orange 'Valência'

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Jorgino Pompeu Junior

2009-07-01

Full Text Available O objetivo deste trabalho foi avaliar a produtividade e as características agronômicas de laranjeira 'Valência', enxertadas em porta-enxertos de híbridos de trifoliata (Poncirus trifoliata. A produção de frutos, a de sólidos solúveis totais por planta, as dimensões e a eficiência produtiva de copas de laranjeira 'Valência', enxertadas em 13 híbridos de trifoliata, cultivados sem irrigação, foram avaliados por períodos que variaram de três a oito anos. As plantas também foram avaliadas, visualmente, quanto à manifestação dos sintomas de tristeza (Citrus tristeza virus e de declínio-dos-citros, e foi utilizado o teste diagnóstico "dot immunobinding assay" (DIBA, para detecção da ocorrência do declínio antes do aparecimento dos sintomas. As plantas tinham oito anos de idade, no início das avaliações. Verificou-se que o citrandarin 'Sunki' x 'English' induziu as maiores produções de frutos em oito colheitas, sem diferir significativamente do citrange 'Troyer'. Em três anos de análise, o citrandarin 'Sunki' x 'English', sem diferir dos citranges 'Troyer' e 'Carrizo', também induziu as maiores produções de frutos e sólidos solúveis por planta. O citrentin 'Clementina' x trifoliata, os citrandarins 'Cleópatra' x 'Swingle' (715 e (1.614, 'Cleópatra' x 'Rubidoux' (1.600 e 'Cleópatra' x 'Christian' induziram a formação de laranjeiras da cultivar Valência com alturas iguais ou inferiores a 2,5 m. Nenhuma das plantas apresentou sintomas de tristeza ou declínio-dos-citros. Foi constatada a incompatibilidade entre a cultivar Valência e o trangpur 'Cravo' x 'Carrizo'.The objective of this work was to evaluate the productivity and agronomic traits of 'Valência' sweet orange tree budded onto trifoliate (Poncirus trifoliata hybrids rootstocks. Fruit production, total soluble solids production per plant, canopy production efficiency and dimensions of 'Valência' sweet orange trees budded onto 13 trifoliate hybrids

Central administration of angiotensin IV rapidly enhances novel object recognition among mice.

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Paris, Jason J; Eans, Shainnel O; Mizrachi, Elisa; Reilley, Kate J; Ganno, Michelle L; McLaughlin, Jay P

2013-07-01

Angiotensin IV (Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6)) has demonstrated potential cognitive-enhancing effects. The present investigation assessed and characterized: (1) dose-dependency of angiotensin IV's cognitive enhancement in a C57BL/6J mouse model of novel object recognition, (2) the time-course for these effects, (3) the identity of residues in the hexapeptide important to these effects and (4) the necessity of actions at angiotensin IV receptors for procognitive activity. Assessment of C57BL/6J mice in a novel object recognition task demonstrated that prior administration of angiotensin IV (0.1, 1.0, or 10.0, but not 0.01 nmol, i.c.v.) significantly enhanced novel object recognition in a dose-dependent manner. These effects were time dependent, with improved novel object recognition observed when angiotensin IV (0.1 nmol, i.c.v.) was administered 10 or 20, but not 30 min prior to the onset of the novel object recognition testing. An alanine scan of the angiotensin IV peptide revealed that replacement of the Val(1), Ile(3), His(4), or Phe(6) residues with Ala attenuated peptide-induced improvements in novel object recognition, whereas Tyr(2) or Pro(5) replacement did not significantly affect performance. Administration of the angiotensin IV receptor antagonist, divalinal-Ang IV (20 nmol, i.c.v.), reduced (but did not abolish) novel object recognition; however, this antagonist completely blocked the procognitive effects of angiotensin IV (0.1 nmol, i.c.v.) in this task. Rotorod testing demonstrated no locomotor effects with any angiotensin IV or divalinal-Ang IV dose tested. These data demonstrate that angiotensin IV produces a rapid enhancement of associative learning and memory performance in a mouse model that was dependent on the angiotensin IV receptor. Copyright © 2013 Elsevier Ltd. All rights reserved.

Autophosphorylation of JAK2 on tyrosines 221 and 570 regulates its activity.

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Argetsinger, Lawrence S; Kouadio, Jean-Louis K; Steen, Hanno; Stensballe, Allan; Jensen, Ole N; Carter-Su, Christin

2004-06-01

The tyrosine kinase JAK2 is a key signaling protein for at least 20 receptors in the cytokine/hematopoietin receptor superfamily and is a component of signaling by insulin receptor and several G-protein-coupled receptors. However, there is only limited knowledge of the physical structure of JAK2 or which of the 49 tyrosines in JAK2 are autophosphorylated. In this study, mass spectrometry and two-dimensional peptide mapping were used to determine that tyrosines 221, 570, and 1007 in JAK2 are autophosphorylated. Phosphorylation of tyrosine 570 is particularly robust. In response to growth hormone, JAK2 was rapidly and transiently phosphorylated at tyrosines 221 and 570, returning to basal levels by 60 min. Analysis of the sequences surrounding tyrosines 221 and 570 in JAK2 and tyrosines in other proteins that are phosphorylated in response to ligands that activate JAK2 suggests that the YXX[L/I/V] motif is one of the motifs recognized by JAK2. Experiments using JAK2 with tyrosines 221 and 570 mutated to phenylalanine suggest that tyrosines 221 and 570 in JAK2 may serve as regulatory sites in JAK2, with phosphorylation of tyrosine 221 increasing kinase activity and phosphorylation of tyrosine 570 decreasing kinase activity and thereby contributing to rapid termination of ligand activation of JAK2.

Standardisation of the USGS Volcano Alert Level System (VALS): analysis and ramifications

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Fearnley, C. J.; McGuire, W. J.; Davies, G.; Twigg, J.

2012-11-01

The standardisation of volcano early warning systems (VEWS) and volcano alert level systems (VALS) is becoming increasingly common at both the national and international level, most notably following UN endorsement of the development of globally comprehensive early warning systems. Yet, the impact on its effectiveness, of standardising an early warning system (EWS), in particular for volcanic hazards, remains largely unknown and little studied. This paper examines this and related issues through evaluation of the emergence and implementation, in 2006, of a standardised United States Geological Survey (USGS) VALS. Under this upper-management directive, all locally developed alert level systems or practices at individual volcano observatories were replaced with a common standard. Research conducted at five USGS-managed volcano observatories in Alaska, Cascades, Hawaii, Long Valley and Yellowstone explores the benefits and limitations this standardisation has brought to each observatory. The study concludes (1) that the process of standardisation was predominantly triggered and shaped by social, political, and economic factors, rather than in response to scientific needs specific to each volcanic region; and (2) that standardisation is difficult to implement for three main reasons: first, the diversity and uncertain nature of volcanic hazards at different temporal and spatial scales require specific VEWS to be developed to address this and to accommodate associated stakeholder needs. Second, the plural social contexts within which each VALS is embedded present challenges in relation to its applicability and responsiveness to local knowledge and context. Third, the contingencies of local institutional dynamics may hamper the ability of a standardised VALS to effectively communicate a warning. Notwithstanding these caveats, the concept of VALS standardisation clearly has continuing support. As a consequence, rather than advocating further commonality of a standardised

Novel piperonal 1,3,4-thiadiazolium-2-phenylamines mesoionic derivatives: Synthesis, tyrosinase inhibition evaluation and HSA binding study.

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Lopes, Natália Drumond; Chaves, Otávio Augusto; de Oliveira, Márcia C C; Sant'Anna, Carlos Mauricio R; Sousa-Pereira, Danilo; Netto-Ferreira, José Carlos; Echevarria, Aurea

2018-06-01

A novel series of piperonal mesoionic derivatives (PMI 1-6) was synthesized. Tyrosinase inhibition in the presence of PMI-1, -2, -3, -4, -5 and -6 as well as human serum albumin (HSA) binding studies with PMI-5 and PMI-6 were done by spectroscopic and theoretical methods. The mesoionic compound PMI-5 is the most promising tyrosinase inhibitor with a noncompetitive inhibitory mechanism and an IC 50 =124μmolL -1 . In accordance with the kinetic profile, molecular docking results show that PMI-5 is able to interact favorably with the tyrosinase active site containing the substrate molecule, L-DOPA, interacting with Val-247, Phe-263 and Val-282 residues. The spectroscopic results for the interaction HSA:PMI-5 and HSA:PMI-6 indicated that these mesoionic compounds can associate with HSA in the ground state and energy transfer can occur with high probability. The binding was moderate, spontaneous and can perturb significantly the secondary structure of the albumin. The molecular docking results suggest that PMI-5 and PMI-6 are able to be accommodated inside the Sudlow's site I in HSA, interacting with hydrophobic and hydrophilic amino acid residues. Copyright © 2018 Elsevier B.V. All rights reserved.

24 CFR 570.513 - Lump sum drawdown for financing of property rehabilitation activities.

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2010-04-01

... DEVELOPMENT BLOCK GRANTS Grant Administration § 570.513 Lump sum drawdown for financing of property... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Lump sum drawdown for financing of property rehabilitation activities. 570.513 Section 570.513 Housing and Urban Development Regulations...

Introduction of a unique tryptophan residue into various positions of Bacillus licheniformis DnaK.

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Chen, Bo-En; Lin, Min-Guan; Lo, Huei-Fen; Wang, Tzu-Fan; Chi, Meng-Chun; Lin, Long-Liu

2013-01-01

Site-directed mutagenesis together with biochemical and biophysical techniques were used to probe effects of single-tryptophan-incorporated mutations on a bacterial molecular chaperone, Bacillus licheniformis DnaK (BlDnaK). Specifically, five phenylalanine residues (Phe(120), Phe(174), Phe(186), Phe(378) and Phe(396)) of BlDnaK were individually replaced by single tryptophans, thus creating site-specific probes for the fluorescence analysis of the protein. The steady-state ATPase activity for BlDnaK, F120W, F174W, F186W, F378W, and F396W was determined to be 76.01, 52.82, 25.32, 53.31, 58.84, and 47.53 nmol Pi/min/mg, respectively. Complementation test revealed that the single mutation at codons 120, 186, and 378 of the dnaK gene still allowed an Escherichia coli dnaK756-Ts strain to grow at a stringent temperature of 44°C. Simultaneous addition of co-chaperones and NR-peptide did not synergistically stimulate the ATPase activity of F174W and F396W, and these two proteins were unable to assist the refolding of GdnHCl-denatured luciferase. The heat-induced denaturation of all variants could be fitted adequately to a three-state model, in agreement with the observation for the wild-type protein. By CD spectral analysis, GdnHCl-induced unfolding transition for BlDnaK was 1.51 M corresponding to ΔG(N-U) of 1.69 kcal/mol; however, the transitions for mutant proteins were 1.07-1.55 M equivalent to ΔG(N-U) of 0.94-2.93 kcal/mol. The emission maximum of single-tryptophan-incorporated variants was in the range of 333.2-335.8 nm. Acrylamide quenching analysis showed that the mutant proteins had a dynamic quenching constant of 3.0-4.2 M(-1). Taken together, these results suggest that the molecular properties of BlDnaK have been significantly changed upon the individual replacement of selected phenylalanine residues by tryptophan. Copyright © 2012 Elsevier B.V. All rights reserved.

48 CFR 1403.570-2 - Procedures.

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2010-10-01

... BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Other Improper Business Practices 1403.570-2... response shall be coordinated with the cognizant Public Affairs Office and Ethics Officer. ...

BDNF val66met polymorphism affects aging of multiple types of memory.

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Kennedy, Kristen M; Reese, Elizabeth D; Horn, Marci M; Sizemore, April N; Unni, Asha K; Meerbrey, Michael E; Kalich, Allan G; Rodrigue, Karen M

2015-07-01

The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age×BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (pmemory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory - in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). This article is part of a Special Issue entitled Memory & Aging. Copyright © 2014 Elsevier B.V. All rights reserved.

21 CFR 570.20 - General principles for evaluating the safety of food additives.

Science.gov (United States)

2010-04-01

... food additives. 570.20 Section 570.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES Food Additive Safety § 570.20 General principles for evaluating the safety of food additives. (a) In reaching a...

Paul Valéry’s Theory of Poetic Action

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Anna Maria Brigante

2013-07-01

Full Text Available This article purports to show that Paul Valéry’s poetic art is, in the end, a theory of poeticaction in which the main concern revolves around the work in progress rather than in the final product. Todo so, we follow the poet’s critique (with deep wittgensteinian elements of classic aesthetics’ stance on beauty and taste. In our view, this reflection results in Valéry’s proposal of a poetics which can be explained in three moments: poiein of reception – the recipient as producer; poiein in its proper sense – the produceras creator of the work and him/herself; and artificialist poiein – the creator as opposed to natural creation.Valéry’s emphasis on poiesis and, therefore, on the action exerted upon what is being done, makes his proposal also an ethical assertion: the artist’s action, his/her discipline whilst producing, create both thework and the artist. Thus, the spirit will also be a never-ending work in progress.

The BDNF Val66Met Polymorphism Affects the Vulnerability of the Brain Structural Network

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Chang-hyun Park

2017-08-01

Full Text Available Val66Met, a naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF gene resulting in a valine (Val to methionine (Met substitution at codon 66, plays an important role in neuroplasticity. While the effect of the BDNF Val66Met polymorphism on local brain structures has previously been examined, its impact on the configuration of the graph-based white matter structural networks is yet to be investigated. In the current study, we assessed the effect of the BDNF polymorphism on the network properties and robustness of the graph-based white matter structural networks. Graph theory was employed to investigate the structural connectivity derived from white matter tractography in two groups, Val homozygotes (n = 18 and Met-allele carriers (n = 55. Although there were no differences in the global network measures including global efficiency, local efficiency, and modularity between the two genotype groups, we found the effect of the BDNF Val66Met polymorphism on the robustness properties of the white matter structural networks. Specifically, the white matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygote group. These findings suggest that the central role of the BDNF Val66Met polymorphism in regards to neuroplasticity may be associated with inherent differences in the robustness of the white matter structural network according to the genetic variants. Furthermore, greater susceptibility to brain disorders in Met-allele carriers may be understood as being due to their limited stability in white matter structural connectivity.

19 CFR 10.570 - Goods re-entered after repair or alteration in Singapore.

Science.gov (United States)

2010-04-01

... Singapore. 10.570 Section 10.570 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... States-Singapore Free Trade Agreement Goods Returned After Repair Or Alteration § 10.570 Goods re-entered after repair or alteration in Singapore. (a) General. This section sets forth the rules which apply for...

48 CFR 503.570-1 - Policy.

Science.gov (United States)

2010-10-01

... BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Other Improper Business Practices 503.570-1 Policy. GSA policy precludes contractors from making references to GSA contracts in commercial advertising in...

Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress

Directory of Open Access Journals (Sweden)

Tsuru J

2014-11-01

Full Text Available Jusen Tsuru,1 Yoshihiro Tanaka,1 Yoshinobu Ishitobi,1 Yoshihiro Maruyama,1 Ayako Inoue,1 Aimi Kawano,1 Rie Ikeda,1 Tomoko Ando,1 Harumi Oshita,2 Saeko Aizawa,1 Koji Masuda,1 Haruka Higuma,1 Masayuki Kanehisa,1 Taiga Ninomiya,1 Jotaro Akiyoshi1 1Department of Neuropsychiatry, 2Department of Applied Linguistics, Faculty of Medicine, Oita University, Oita, Japan Background: Decreased expression of brain-derived neurotrophic factor (BDNF is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder.Methods: To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men using a social stress procedure (Trier Social Stress Test [TSST] and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A.Results: A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; P<0.05 was demonstrated that revealed different salivary cortisol responses in the TSST but not in electrical stimulation. Met/Met women had stronger cortisol responses than Val/Met and Val/Val individuals in the TSST. Met/Met men exhibited stronger salivary cortisol responses than Val/Met and Val/Val individuals in the TSST.Conclusion: These results indicate that a common, functionally significant polymorphism in BDNF had different effects on hypothalamic–pituitary–adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests. Keywords: stress, brain-derived neurotrophic factor, cortisol, saliva

Tyrocidine A Analogues Bearing the Planar d-Phe-2-Abz Turn Motif: How Conformation Impacts Bioactivity.

Science.gov (United States)

Cameron, Alan J; Edwards, Patrick J B; Harjes, Elena; Sarojini, Vijayalekshmi

2017-12-14

The d-Phe-Pro β-turn of the cyclic β-hairpin antimicrobial decapeptide tyrocidine A, (Tyrc A) was substituted with the d-Phe-2-aminobenzoic acid (2-Abz) motif in a synthetic analogue (1). The NMR structure of 1 demonstrated that compound 1 retained the β-hairpin structure of Tyrc A with additional planarity, resulting in approximately 30-fold reduced hemolysis than Tyrc A. Although antibacterial activity was partially compromised, a single Gln to Lys substitution (2) restored activity equivalent to Tyrc A against S. aureus, enhanced activity against two Gram negative strains and maintained the reduced hemeloysis of 1. Analysis by transmission electron microscopy (TEM) suggested a membrane lytic mechanism of action for these peptides. Compound 2 also exhibits nanomolar antifungal activity in synergy with amphotericin B. The d-Phe-2-Abz turn may serve as a tool for the synthesis of structurally predictable β-hairpin libraries. Unlike traditional β-turn motifs such as d-Pro-Gly, both the 2-Abz and d-Phe rings may be further functionalized.

e -ech-o / -ech-a na fala de Castrelo do Val

Directory of Open Access Journals (Sweden)

Aquilino Santiago Alonso Núñez

2017-01-01

Full Text Available This paper focuses on the uses of the Galician diminutive nominal suffixes -et-e / -et-a, -uc-o / -uc-a e -ech-o / -ech-a in the Castrelo do Val (Ourense, Spain dialect variety, while also surveying aspects of their use in other Galician dialects, including their occurrence in toponyms and some medieval corpora, and also in Portuguese and Spanish. This information is contrasted with data obtained from our participant observation of a particular variety of Galician while also supplying a historical perspective. The study uses a dynamic approach to word formation taking into account both words in actual use and the possibility of forming new words by means of the same suffixes. This analysis shows that the diminutive suffix -et-e is used as in the most widespread variety of Galician, whereas -uc- only has residual uses; use of -ech- is more restricted in the variety studied than in common Galician.

Association between the catechol-o-methyltransferase val158met polymorphism with susceptibility and severity of carpal tunnel syndrome

Directory of Open Access Journals (Sweden)

Erkol İnal E

2015-12-01

Full Text Available Carpal tunnel syndrome (CTS is the most common entrapment neuropathy of the upper extremity. In this study, we aimed to clarify the relationships between the catechol-O-methyltransferase (COMT gene Val158Met (rs4680 polymorphism and development, functional and clinical status of CTS. Ninety-five women with electro diagnostically confirmed CTS and 95 healthy controls were enrolled in the study. The functional and clinical status of the patients was measured by the Turkish version of the Boston Questionnaire and intensity of pain related to the past 2 weeks was evaluated on a visual analog scale (VAS. The Val158Met polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP, method. We divided patients according to the genotypes of the Val158Met polymorphism as Val/Val, Val/Met and Met/Met. There were not any significant differences in terms of Val158Met polymorphisms between patients and healthy controls (p >0.05. We also did not find any relationships between the Val158Met polymorphism and CTS (p >0.05. In conclusion, although we did not find any relationships between CTS and the Val158Met polymorphism, we could not generalize this result to the general population. Future studies are warranted to conclude precise associations.

20 CFR 663.570 - What is the consumer reports system?

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false What is the consumer reports system? 663.570....570 What is the consumer reports system? The consumer reports system, referred to in WIA as... consumer reports system must contain the information necessary for an adult or dislocated worker customer...

28 CFR 570.43 - Inmates requiring a high degree of control and supervision.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Inmates requiring a high degree of control and supervision. 570.43 Section 570.43 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE COMMUNITY PROGRAMS Escorted Trips § 570.43 Inmates requiring a high degree of control and supervision. Only the...

28 CFR 570.20 - Purpose.

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2010-07-01

..., halfway house, restitution center, mental health facility, alcohol or drug rehabilitation center, or other... Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE COMMUNITY PROGRAMS Pre-Release Community Confinement § 570.20 Purpose. The purpose of this subpart is to provide the procedures...

48 CFR 570.102 - Definitions.

Science.gov (United States)

2010-10-01

... Section 570.102 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CONTRACTING... lease, including option periods and excluding the cost of operational services. Small business means a..., principle, and substance of the FAR or GSAR provision or clause and related coverage on the subject matter. ...

Dipeptidyl peptidase IV inhibitors derived from a mangrove flora Rhizophora mucronata: An in silico approach

Directory of Open Access Journals (Sweden)

Selvaraj Gurudeeban

2012-08-01

Full Text Available Dipeptidyl peptidase IV (DPP IV is responsible for conversion of glucose tolerance (GLP-1, into inactive form. The inhibition of DPP IV would be beneficial in the treatment of diabetes mellitus. Therefore, the aim of the present study was to isolate and evaluate cystine, phenyl acetic acid, acrylamide, caprylone and oleic acid from Rhizophora mucronata inhibitory action on DPP IV inhibitors using in silico approach. In silico analysis of cystine, phenyl acetic acid, acrylamide, caprylone and oleic acid on human apo DPP IV protein was done by using Autodoc 4.0. Among the five compounds cysteine acts as an inhibitor with binding energy -5.89 kcal/mol, seven hydrogen bond interactions at residues VAL459, VAL 459, GLU408, GLU206, ARG358, GLU205 and SER209 to suppresses the action of DPP IV protein.

Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study

OpenAIRE

Saravani, Ramin; Galavi, Hamid Reza; Lotfian Sargazi, Marzieh

2017-01-01

Objective: Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. Method: This case- contro...

Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial.

Science.gov (United States)

Long, Georgina V; Trefzer, Uwe; Davies, Michael A; Kefford, Richard F; Ascierto, Paolo A; Chapman, Paul B; Puzanov, Igor; Hauschild, Axel; Robert, Caroline; Algazi, Alain; Mortier, Laurent; Tawbi, Hussein; Wilhelm, Tabea; Zimmer, Lisa; Switzky, Julie; Swann, Suzanne; Martin, Anne-Marie; Guckert, Mary; Goodman, Vicki; Streit, Michael; Kirkwood, John M; Schadendorf, Dirk

2012-11-01

Brain metastases are common in patients with metastatic melanoma and median overall survival from their diagnosis is typically 17-22 weeks. We assessed dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain. We undertook a multicentre, open-label, phase 2 trial in 24 centres in six countries. We enrolled patients with histologically confirmed Val600Glu or Val600Lys BRAF-mutant melanoma and at least one asymptomatic brain metastasis (≥5 mm and ≤40 mm in diameter). Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had adequate organ function. Patients were split into two cohorts: those in cohort A had not received previous local treatment for brain metastases and those in cohort B had progressive brain metastases after previous local treatments. Patients received 150 mg oral dabrafenib twice a day until disease progression, death, or unacceptable adverse events. The primary endpoint was the proportion of patients with Val600Glu BRAF-mutant melanoma who achieved an overall intracranial response, which was defined as a complete response or partial response assessed with a modified form of Response Evaluation Criteria in Solid Tumors (RECIST 1.1). We included patients who received at least one dose of dabrafenib in efficacy and safety analyses. This study is registered with ClinicalTrials.gov, number NCT01266967. Between Feb 2, 2011, and Aug 5, 2011, we enrolled 172 patients: 89 (52%) in cohort A and 83 (48%) in cohort B. 139 (81%) had Val600Glu BRAF-mutant melanoma. 29 (39·2%, 95% CI 28·0-51·2) of 74 patients with Val600Glu BRAF-mutant melanoma in cohort A achieved an overall intracranial response, as did 20 (30·8%, 19·9-43·4) of 65 in cohort B. One (6·7%, 0·2-31·9) of 15 patients with Val600Lys BRAF-mutant melanoma achieved an overall intracranial response in cohort A, as did four (22·2%, 6·4-47·6) of 18 such patients in cohort B. Treatment

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism interacts with gender to influence cortisol responses to mental stress.

Science.gov (United States)

Jiang, Rong; Babyak, Michael A; Brummett, Beverly H; Siegler, Ilene C; Kuhn, Cynthia M; Williams, Redford B

2017-05-01

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with cortisol responses to stress with gender differences reported, although the findings are not entirely consistent. To evaluate the role of Val66Met genotype and gender on cortisol responses to stress, we conducted a 45-min mental stress protocol including four tasks and four rest periods. Blood cortisol was collected for assay immediately before and after each task and rest period. A significant two-way interaction of Val66Met genotype×gender (P=0.022) was observed on the total area under the curve (AUC), a total cortisol response over time, such that the Val/Val genotype was associated with a larger cortisol response to stress as compared to the Met group in women but not in men. Further contrast analyses between the Val/Val and Met group for each stress task showed a similar increased cortisol pattern among women Val/Val genotype but not among men. The present findings indicate the gender differences in the effect of Val66Met genotype on the cortisol responses to stress protocol, and extend the evidence for the importance of gender and the role of Val66Met in the modulation of stress reactivity and subsequent depression prevalence. Further studies and the underlying mechanism need to be investigated, which may provide an insight for prevention, intervention, and treatment strategies that target those at high risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

21 CFR 570.6 - Opinion letters on food additive status.

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2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Opinion letters on food additive status. 570.6... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES General Provisions § 570.6 Opinion letters on food additive status. (a) Over the years the Food and Drug Administration has given informal...

48 CFR 3036.570 - Special precautions for work at operating airports.

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2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Special precautions for work at operating airports. 3036.570 Section 3036.570 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) SPECIAL CATEGORIES OF...

29 CFR 570.117 - General.

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2010-07-01

... to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION General Statements of Interpretation of the Child Labor Provisions of the Fair Labor Standards Act of 1938, as Amended Oppressive Child Labor § 570.117 General. (a...

BDNF VAL66MET Polymorphism Elevates the Risk of Bladder Cancer via MiRNA-146b in Micro-Vehicles

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Cong Li

2018-01-01

Full Text Available Background/Aims: Emerging studies on brain-derived neurotrophic factor (BDNF have shown that might be novel biomarkers and therapeutic targets for cancer. We explore the role of BDNF in the tumorigenesis of bladder cancer and the underlying molecular mechanism. Methods: 368 patients with diagnosed bladder cancer and 352 healthy controls were enrolled to evaluate the association of BDNF and the miR-146b. Bioinformatics algorithm analysis and luciferase assay were performed to identify the target genes of miR-146b. Real-time PCR and western-blot were carried out to validate the relationship between miR-146b and CRK. MTT assay and FACS were used to evaluated the proliferation and apoptosis of cancer cells. MVs were isolated and transfect into the culture cells to confirm the above observation. Results: The clinical study shows that BDNF Met/Met was significantly associated with the risk of bladder cancer. In addition, comparing with Val/Val and Val/Met, Met/Met has lower miR-146b level. Luciferase assay shows that BDNF Val/Val is apparently enhanced miR-146b promoter-luciferase, but not BDNF Met/Met. Based on luciferase assay, CRK is a direct target gene of miR-146b. MiR-146b mimics significantly inhibited the expression of CRK and activation of AKT level. The expression of CRK and the activation of AKT (p-AKT were significantly inhibited by MV-BDNF Val/Val-miR-146b or MV-BDNF Val/Met-miR-146b, but not MV-BDNF Met/Met-miR-146b. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b obviously inhibited cell proliferation, which eliminated by CRK. Meanwhile, with MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not affect the proliferation. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b enhanced cell apoptosis, which could be eliminated by CRK. Meanwhile, MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not promote apoptosis. Conclusion: BDNF VAL66MET polymorphism is associated with miR-146b and its target gene CRK. MiR-146b and CRK mediated BDNF VAL66

40 CFR 205.55 - Requirements.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Requirements. 205.55 Section 205.55 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.55 Requirements. ...

The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion.

Science.gov (United States)

Moskovitz, Jackob; Walss-Bass, Consuelo; Cruz, Dianne A; Thompson, Peter M; Hairston, Jenaqua; Bortolato, Marco

2015-12-01

The enzyme catechol-O-methyltransferase (COMT) plays a primary role in the metabolism of catecholamine neurotransmitters and is implicated in the modulation of cognitive and emotional responses. The best characterized single nucleotide polymorphism (SNP) of the COMT gene consists of a valine (Val)-to-methionine (Met) substitution at codon 108/158. The Met-containing variant confers a marked reduction in COMT catalytic activity. We recently showed that the activity of recombinant COMT is positively regulated by the enzyme Met sulphoxide reductase (MSR), which counters the oxidation of Met residues of proteins. The current study was designed to assess whether brain COMT activity may be correlated to MSR in an allele-dependent fashion. COMT and MSR activities were measured from post-mortem samples of prefrontal cortices, striata and cerebella of 32 subjects by using catechol and dabsyl-Met sulphoxide as substrates, respectively. Allelic discrimination of COMT Val(108/185) Met SNP was performed using the Taqman 5'nuclease assay. Our studies revealed that, in homozygous carriers of Met, but not Val alleles, the activity of COMT and MSR was significantly correlated throughout all tested brain regions. These results suggest that the reduced enzymatic activity of Met-containing COMT may be secondary to Met sulphoxidation and point to MSR as a key molecular determinant for the modulation of COMT activity. © 2015 British Neuropathological Society.

48 CFR 570.303-3 - Late offers, modifications of offers, and withdrawals of offers.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Late offers, modifications of offers, and withdrawals of offers. 570.303-3 Section 570.303-3 Federal Acquisition Regulations... PROPERTY Contracting Procedures for Leasehold Interests in Real Property 570.303-3 Late offers...

205Tl experiment

International Nuclear Information System (INIS)

Henning, W.; Kutschera, W.; Ernst, H.

1984-01-01

205 Tl has been previously proposed as a geological detector for solar neutrinos, making use of the reaction 205 Tl(nu, e - ) 205 Pb with a neutrino threshold of only approx. = 43 keV. We report on an experiment performed to study the feasibility of detecting radioactive 205 Pb nuclei (T/sub 1/2/ = 15 million years) at very low concentrations using the recently developed technique of accelerator mass spectrometry. Employing the high-energy ion beams of good quality from the UNILAC heavy-ion accelerator at the GSI Darmstadt, we are able to demonstrate a suppression of neighbouring isotopes to better than 1 in 10 16 and of neighbouring elements to about 1 in 10 3 . While these results are very encouraging, the minimum number of atoms detectable is still severely limited by the efficiency of producing multiply-charged ions from present ion sources. Future improvements in ion-source performance are briefly discussed

Suicide attempt, clinical correlates, and BDNF Val66Met polymorphism in chronic patients with schizophrenia.

Science.gov (United States)

Xia, Haisen; Zhang, Guangya; Du, Xiangdong; Zhang, Yingyang; Yin, Guangzhong; Dai, Jing; He, Man-Xi; Soares, Jair C; Li, Xiaosi; Zhang, Xiang Yang

2018-02-01

Recent evidence suggests the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidal behavior. Because schizophrenia patients usually have high suicide rates and numerous studies have suggested that BDNF may contribute to the psychopathology of schizophrenia, we hypothesized that the functional polymorphism of BDNF (Val66Met) was associated with suicide attempts in patients with schizophrenia in a Chinese Han population. This polymorphism was genotyped in 825 chronic schizophrenia patients with (n = 123) and without (n = 702) suicide attempts and 445 healthy controls without a history of suicide attempts using a case-control design. The schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale. There were no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls. However, we found the Val allele (p = .023) and the Val/Val genotypes (p = .058) to be associated with a history of suicide attempts. Moreover, some clinical characteristics, including age and cigarettes smoked each day, interacted with the BDNF gene variant and appeared to play an important role in suicide attempts among schizophrenia patients. The BDNF Val66Met polymorphism itself and its interaction with some clinical variables may influence suicide attempts among schizophrenia patients. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

40 CFR 205.50 - Applicability.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Applicability. 205.50 Section 205.50 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.50 Applicability. (a) Except as otherwise...

The BDNF Val66Met polymorphism moderates the relationship between Posttraumatic Stress Disorder and fear extinction learning.

Science.gov (United States)

Felmingham, Kim L; Zuj, Daniel V; Hsu, Ken Chia Ming; Nicholson, Emma; Palmer, Matthew A; Stuart, Kimberley; Vickers, James C; Malhi, Gin S; Bryant, Richard A

2018-05-01

The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism. Moderation analyses using PROCESS examined whether BDNF genotype (Val-Val vs Met carriers) moderated the relationship between PTSD symptom severity (and diagnostic status) and skin conductance response (SCR) amplitude during fear extinction. The PTSD group displayed significantly slower fear extinction learning compared to TC and NTC in the early extinction phase. The BDNF Val66Met polymorphism moderated the relationship between PTSD and fear extinction learning, such that poorer fear extinction learning was associated with greater PTSD symptom severity (and PTSD diagnostic status) in individuals with the low-expression Met allele, but no relationship was demonstrated in individuals with the Val-Val allele. This study reveals that impaired fear extinction learning is particularly evident in individuals with PTSD who carry the low-expression BDNF Met allele and importantly not in those with the Val-Val allele. This provides novel evidence of a link between BDNF and impaired fear extinction learning in PTSD, which may contribute to poorer response to exposure therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Residues Phe103 and Phe149 are critical for the co-chaperone activity of Bacillus licheniformis GrpE.

Science.gov (United States)

Lin, Min-Guan; Chi, Meng-Chun; Chen, Bo-En; Wang, Tzu-Fan; Lo, Huei-Fen; Lin, Long-Liu

2015-01-01

A tryptophan-free Bacillus licheniformis nucleotide exchange factor (BlGrpE) and its Trp mutants (F70W, F103W, F149W, F70/103W, F70/149W, F103/149W and F70/103/149W) were over-expressed and purified to near homogeneity. Simultaneous addition of B. licheniformis DnaJ, NR-peptide and individual variants synergistically stimulated the ATPase activity of a recombinant DnaK (BlDnaK) from the same bacterium by 3.1-14.7-fold, which are significantly lower than the synergistic stimulation (18.9-fold) of BlGrpE. Protein-protein interaction analysis revealed that Trp mutants relevant to amino acid positions 103 and 149 lost the ability to bind BlDnaK. Circular dichroism measurements indicate that F70W displayed a comparable level of secondary structure to that of BlGrpE, and the wild-type protein and the Trp mutants as well all experienced a reversible behavior of thermal denaturation. Guanidine hydrochloride (GdnHCl)-induced unfolding transition for BlGrpE was calculated to be 1.25 M corresponding to ΔG(N-U) of 4.29 kcal/mol, whereas the unfolding transitions of mutant proteins were in the range of 0.77-1.31 M equivalent to ΔG(N-U) of 2.41-4.14 kcal/mol. Taken together, the introduction of tryptophan residue, especially at positions 103 and 149, into the primary structure of BlGrpE has been proven to be detrimental to structural integrity and proper function of the protein. Copyright © 2014 Elsevier B.V. All rights reserved.

48 CFR 2009.570-4 - Representation.

Science.gov (United States)

2010-10-01

... type required by the organizational conflicts of interest representation provisions has previously been... ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Organizational Conflicts of Interest 2009.570-4 Representation... whether situations or relationships exist which may constitute organizational conflicts of interest with...

29 CFR 570.25 - Effect on laws other than the Federal child labor standards.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Effect on laws other than the Federal child labor standards. 570.25 Section 570.25 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... of Age Provisions of Other Laws § 570.25 Effect on laws other than the Federal child labor standards...

40 CFR 91.205 - Banking.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Banking. 91.205 Section 91.205... EMISSIONS FROM MARINE SPARK-IGNITION ENGINES Averaging, Banking, and Trading Provisions § 91.205 Banking. (a... banking. (i) For outboard engines in model year (MY) 1997, a manufacturer may bank positive emission...

29 CFR 570.122 - General.

Science.gov (United States)

2010-07-01

... newspapers to the consumer; (c) Employment of children as actors or performers in motion pictures or in... 28459, May 20, 2010, § 570.122 was revised, effective July 19, 2010. For the convenience of the user... engaged in the delivery of newspapers to the consumer; (3) Employment of children as actors or performers...

29 CFR 570.1 - Definitions.

Science.gov (United States)

2010-07-01

... to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS...) Oppressive child labor means employment of a minor in an occupation for which he does not meet the minimum age standards of the Act, as set forth in § 570.2 of this subpart. (c) Oppressive child labor age...

Binding of the 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs to tRNA(phe..

Directory of Open Access Journals (Sweden)

Anirban Basu

Full Text Available BACKGROUND: Three new analogs of berberine with aryl/ arylalkyl amino carbonyl methyl substituent at the 9-position of the isoquinoline chromophore along with berberrubine were studied for their binding to tRNA(phe by wide variety of biophysical techniques like spectrophotometry, spectrofluorimetry, circular dichroism, thermal melting, viscosity and isothermal titration calorimetry. METHODOLOGY/ PRINCIPAL FINDINGS: Scatchard binding isotherms revealed that the cooperative binding mode of berberine was propagated in the analogs also. Thermal melting studies showed that all the 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs stabilized the tRNA(phe more in comparison to berberine. Circular dichroism studies showed that these analogs perturbed the structure of tRNA(phe more in comparison to berberine. Ferrocyanide quenching studies and viscosity results proved the intercalative binding mode of these analogs into the helical organization of tRNA(phe. The binding was entropy driven for the analogs in sharp contrast to the enthalpy driven binding of berberine. The introduction of the aryl/arylalkyl amino carbonyl methyl substituent at the 9-position thus switched the enthalpy driven binding of berberine to entropy dominated binding. Salt and temperature dependent calorimetric studies established the involvement of multiple weak noncovalent interactions in the binding process. CONCLUSIONS/ SIGNIFICANCE: The results showed that 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs exhibited almost ten folds higher binding affinity to tRNA(phe compared to berberine whereas the binding of berberrubine was dramatically reduced by about twenty fold in comparison to berberine. The spacer length of the substitution at the 9-position of the isoquinoline chromophore appears to be critical in modulating the binding affinities towards tRNA(phe.

40 CFR 89.205 - Banking.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Banking. 89.205 Section 89.205... EMISSIONS FROM NEW AND IN-USE NONROAD COMPRESSION-IGNITION ENGINES Averaging, Banking, and Trading Provisions § 89.205 Banking. (a) Requirements for Tier 1 engines rated at or above 37 kW. (1) A manufacturer...

40 CFR 90.205 - Banking.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Banking. 90.205 Section 90.205... EMISSIONS FROM NONROAD SPARK-IGNITION ENGINES AT OR BELOW 19 KILOWATTS Certification Averaging, Banking, and Trading Provisions § 90.205 Banking. (a)(1) Beginning August 1, 2007, a manufacturer of a Class I engine...

Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis.

Science.gov (United States)

Lee, Young Ho; Kim, Jae-Hoon; Song, Gwan Gyu

2015-01-01

The aim of this study was to explore whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with susceptibility to fibromyalgia and fibromyalgia impact questionnaire (FIQ) score in fibromyalgia patients. We conducted a meta-analysis of the associations of the COMT Val158Met polymorphism with fibromyalgia risk as well as FIQ score in fibromyalgia patients. A total of 993 fibromyalgia patients and 778 controls from 10 studies on the COMT Val158Met polymorphism and 538 fibromyalgia patients from 5 studies on the COMT Val158Met polymorphism and FIQ score were included in this meta-analysis. The meta-analysis revealed an association between fibromyalgia and the COMT Met/Met + Val/Met genotype in all study subjects (odds ratio (OR) 1.635, 95 % confidence interval (CI) 1.029-2.597, p = 0.037). However, stratification by ethnicity indicated no association between the Met/Met + Val/Met genotype and fibromyalgia in the European and Turkish populations (OR 1.202, 95 % CI 0.876-1.649, p = 0.255; OR 2.132, 95 % CI 0.764-5.949, p = 0.148, respectively). Analysis using other genetic models showed no association between the COMT Val158Met polymorphism and fibromyalgia. The meta-analysis also revealed that the FIQ score was significantly higher in individuals with the COMT Met/Met genotype than in those with the Val/Val genotype [weighted mean difference (WMD) = 14.39, 95 % CI 3.316-25.48, p = 0.011] and the Val/Met genotype (WMD = 5.108, 95 % CI 2.212-4.891, p = 0.021). This meta-analysis identified an association between fibromyalgia risk and the COMT Val158Met polymorphism as well as the FIQ score in fibromyalgia patients.

Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH test results in depressed patients.

Science.gov (United States)

Schüle, Cornelius; Zill, Peter; Baghai, Thomas C; Eser, Daniela; Zwanzger, Peter; Wenig, Nadine; Rupprecht, Rainer; Bondy, Brigitta

2006-09-01

Data suggest that both neurotrophic and hypothalamic-pituitary-adrenocortical (HPA) systems are involved in the pathophysiology of depression. The aim of the present study was to investigate whether the non-conservative brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has an impact on HPA axis activity in depressed patients. At admission, the dexamethasone/CRH (DEX/CRH) test was performed in 187 drug-free in-patients suffering from major depression or depressed state of bipolar disorder (DSM-IV criteria). Moreover, genotyping of BDNF Val66Met polymorphism was carried out using the fluorescence resonance energy transfer method (FRET). Homozygous carriers of the Met/Met genotype showed a significantly higher HPA axis activity during the DEX/CRH test than patients carrying the Val/Val or Val/Met genotype (ACTH, cortisol). Our results further contribute to the hypothesized association between HPA axis dysregulation and reduced neuroplasticity in depression and are consistent with the assumption that BDNF is a stress-responsive intercellular messenger modifying HPA axis activity.

Proposal for the Award of a Contract for the Supply of 13 kA and 20.5 kA, 18 V Switched-Mode Power Converters for the LHC

CERN Document Server

2003-01-01

This document concerns the award of a contract for the supply of 13 kA and 20.5 kA, 18 V switched-mode power converters using sub-converters of 3.25 kA. Following a market survey (MS-2866/SL/LHC) carried out among 81 firms in seventeen Member States and a call for tenders for prototypes (IT-2919/SL/LHC) sent on 11 June 2001, a call for tenders for the supply of the pre-series and series of 13 kA and 20.5 kA, 18 V switched-mode power converters both using sub-converters of 3.25 kA was sent to two firms on 17 September 2002. The Finance Committee is invited to agree to the negotiation of a contract with TRANSTECHNIK (DE), the only firm that has delivered a successfully qualifying prototype, for the supply of eighteen 13 kA and one 20.5 kA, 18 V switched-mode power converters and spares for a total amount of 4 607 731 euros (6 747 300 Swiss francs), not subject to revision. The rate of exchange used is that stipulated in the tender. The firm has indicated the following distribution by country of the contract val...

48 CFR 3009.570-2 - Policy.

Science.gov (United States)

2010-10-01

... ACQUISITION REGULATION (HSAR) ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Organizational and Consultant... took appropriate steps to prevent any organizational conflict of interest in the selection process; or... process over which the entity exercised no control. (c) CONSTRUCTION—Nothing in this section 3009.570...

12 CFR 205.3 - Coverage.

Science.gov (United States)

2010-01-01

... authorizes a financial institution to debit or credit a consumer's account. Generally, this part applies to financial institutions. For purposes of §§ 205.3(b)(2) and (b)(3), 205.10(b), (d), and (e) and 205.13, this..., or magnetic tape for the purpose of ordering, instructing, or authorizing a financial institution to...

Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress.

Science.gov (United States)

Tsuru, Jusen; Tanaka, Yoshihiro; Ishitobi, Yoshinobu; Maruyama, Yoshihiro; Inoue, Ayako; Kawano, Aimi; Ikeda, Rie; Ando, Tomoko; Oshita, Harumi; Aizawa, Saeko; Masuda, Koji; Higuma, Haruka; Kanehisa, Masayuki; Ninomiya, Taiga; Akiyoshi, Jotaro

2014-01-01

Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder. To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A). A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; PBDNF had different effects on hypothalamic-pituitary-adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests.

Depression, the Val66Met polymorphism, age, and gender influence the serum BDNF level

DEFF Research Database (Denmark)

Elfving, Betina; Buttenschøn, Henriette Nørmølle; Foldager, Leslie

2012-01-01

, depression, gender, the Val66Met polymorphism, and the interaction between Val66Met and gender were identified as significant determinants of the serum BDNF level. In conclusion, our data demonstrate that other factors than a diagnosis of depression influence the serum BDNF level and the importance...

10 CFR 205.198 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Discovery. 205.198 Section 205.198 Energy DEPARTMENT OF... of Proposed Disallowance, and Order of Disallowance § 205.198 Discovery. (a) If a person intends to file a Motion for Discovery, he must file it at the same time that he files his Statement of Objections...

48 CFR 803.570-2 - Contract clause.

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2010-10-01

... BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Other Improper Business Practices 803.570-2 Contract clause. The contracting officer shall insert the clause at 852.203-70, Commercial advertising, in...

48 CFR 503.570-2 - Contract clause.

Science.gov (United States)

2010-10-01

... BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Other Improper Business Practices 503.570-2 Contract clause. Insert the clause at 552.203-71, Restriction on Advertising, in solicitations and contracts...

The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese heroin-dependent patients.

Science.gov (United States)

Chen, Shiou-Lan; Lee, Sheng-Yu; Chang, Yun-Hsuan; Wang, Tzu-Yun; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2015-02-02

BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of long-term heroin use. Thus, we investigated the relationships between brain-derived neurotrophic factor (BDNF) plasma concentrations and the BDNF Val66Met nucleotide polymorphism (SNP) in heroin-dependent patients. The pretreatment expression levels of plasma BDNF and the BDNF Val66Met SNP in 172 heroin-dependent patients and 102 healthy controls were checked. BDNF levels were significantly lower in patients (F = 52.28, p BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not affect plasma BDNF levels in our participants. In heroin-dependent patients, plasma BDNF levels were negatively correlated with the length of heroin dependency. Long-term (>15 years) users had significantly lower plasma BDNF levels than did short-term (BDNF concentration in habitual heroin users are not affected by BDNF Val66Met gene variants, but by the length of the heroin dependency.

First principle investigations on Boron doped Fe2VAl Heusler alloy

International Nuclear Information System (INIS)

Venkatesh, Ch.; Srivastava, S.K.; Rao, V.V.

2014-01-01

The role of atomic size of sp-element is investigated through theoretical calculations and basic experiments to understand the physical properties of Boron doped Fe 2 VAl alloy. The results of ab-initio calculations on ordered L2 1 structure of Fe 2 VAl 1-x B x (x=0, 0.5, 1) alloys have been compared to understand the role of sp-element size on the hybridization among their respective valance states. Interestingly, semi-metallic and paramagnetic like ground states were found in the Boron doped alloys in similar to Fe 2 VAl, eliminating the role of size of the doppent sp-atom. These calculations result in hybridization where the covalent distribution of valance states among the atoms is responsible to produce a finite pseudo-gap at the Fermi level. The observed features could be explained on the basis of covalent theory of magnetism in which an amount of spectral weight transfer occurs in the DOS spectrum among the same spin orbitals, leading to symmetric distribution of bonding and anti-bonding states. However, the obtained experimental findings on Boron doped alloys are in contrast with these calculations, indicating that experimentally the alloy formation into an ideal L2 1 lattice does not happen while doping with Boron. Further, the micro structural analysis shows Boron segregation across the grain boundaries that may form magnetic inhomogeneities in the lattice of Boron doped Fe 2 VAl alloys which preferably cause these experimental anomalies

Structural and biochemical studies of a fluoroacetyl-CoA-specific thioesterase reveal a molecular basis for fluorine selectivity.

Science.gov (United States)

Weeks, Amy M; Coyle, Scott M; Jinek, Martin; Doudna, Jennifer A; Chang, Michelle C Y

2010-11-02

We have initiated a broad-based program aimed at understanding the molecular basis of fluorine specificity in enzymatic systems, and in this context, we report crystallographic and biochemical studies on a fluoroacetyl-coenzyme A (CoA) specific thioesterase (FlK) from Streptomyces cattleya. Our data establish that FlK is competent to protect its host from fluoroacetate toxicity in vivo and demonstrate a 10(6)-fold discrimination between fluoroacetyl-CoA (k(cat)/K(M) = 5 × 10⁷ M⁻¹ s⁻¹) and acetyl-CoA (k(cat)/K(M) = 30 M⁻¹ s⁻¹) based on a single fluorine substitution that originates from differences in both substrate reactivity and binding. We show that Thr 42, Glu 50, and His 76 are key catalytic residues and identify several factors that influence substrate selectivity. We propose that FlK minimizes interaction with the thioester carbonyl, leading to selection against acetyl-CoA binding that can be recovered in part by new C═O interactions in the T42S and T42C mutants. We hypothesize that the loss of these interactions is compensated by the entropic driving force for fluorinated substrate binding in a hydrophobic binding pocket created by a lid structure, containing Val 23, Leu 26, Phe 33, and Phe 36, that is not found in other structurally characterized members of this superfamily. We further suggest that water plays a critical role in fluorine specificity based on biochemical and structural studies focused on the unique Phe 36 "gate" residue, which functions to exclude water from the active site. Taken together, the findings from these studies offer molecular insights into organofluorine recognition and design of fluorine-specific enzymes.

Structural characterization of Bacillus subtilis membrane protein Bmr: an in silico approach.

Science.gov (United States)

Nargotra, Amit; Rukmankesh; Ali, Shakir; Koul, Surrinder

2014-01-01

Efflux pump--a membrane protein belonging to Major Facilitator (MF) family and associated with Multi Drug Resistance (MDR) has been a major factor in drug resistance of bacteria. In the era when no new effective antibiotic had been reported for years, the detailed study of these membrane proteins became imperative in order to improve the efficacy of existing drugs. The Bacillus subtilis membrane protein Bmr belongs to the super family of major facilitator proteins and is one of the first-discovered bacterial multidrug-efflux transporters. Development of Bmr inhibitors (B. subtilis) for least resistance, better drug sustainability and effective cellular activity requires three dimensional structure of this protein which has not yet been determined. In this communication structural characterization of this important efflux pump has been attempted using in silico approaches. The modeled structure of Bmr has been found to have 12 main helical segments interspersed by loops of variable lengths at regular intervals with both N- and C-termini on the same side of membrane. Docking of the known inhibitor reserpine on to the predicted structure of Bmr and its mutants signified the importance of the residues Phe143, Val286 and Phe306 in the interaction with the ligand. Besides this, the role of Arg313 and Phe309 in the H-bond formation and π-π interaction respectively, with reserpine was the new significant finding based on the interaction studies. The structure elucidation of Bmr and the role of these residues in binding to the ligand are expected to have a great impact on the efflux pump inhibition studies around the world and hence in the efficiency of the existing antibiotic drugs.

49 CFR 570.59 - Service brake system.

Science.gov (United States)

2010-10-01

... 10,000 Pounds § 570.59 Service brake system. (a) Service brake performance. Compliance with any one of the following performance criteria will satisfy the requirements of this section. Verify that tire...

Corpo, sensibilità ed esperienza: la riflessione di Valéry alla luce dell’estetica pragmatista

Directory of Open Access Journals (Sweden)

Emanuele Crescimanno

2012-05-01

Full Text Available Body, sensibility and experience: Paul Valéry’s reflection and pragmatist aestheticThe pragmatist aesthetic of Dewey and Shusterman can be useful to understand the complexity of the Valéry’s thought: this paper aims to highlight a pragmatist attitude on the Valéry’s aesthetic through the links of the triad Corps, Esprit, Monde and underline the crucial role that the body and the senses play in experience. 

Inhibition of chrysin on xanthine oxidase activity and its inhibition mechanism.

Science.gov (United States)

Lin, Suyun; Zhang, Guowen; Liao, Yijing; Pan, Junhui

2015-11-01

Chrysin, a bioactive flavonoid, was investigated for its potential to inhibit the activity of xanthine oxidase (XO), a key enzyme catalyzing xanthine to uric acid and finally causing gout. The kinetic analysis showed that chrysin possessed a strong inhibition on XO ability in a reversible competitive manner with IC50 value of (1.26±0.04)×10(-6)molL(-1). The results of fluorescence titrations indicated that chrysin bound to XO with high affinity, and the interaction was predominately driven by hydrogen bonds and van der Waals forces. Analysis of circular dichroism demonstrated that chrysin induced the conformational change of XO with increases in α-helix and β-sheet and reductions in β-turn and random coil structures. Molecular simulation revealed that chrysin interacted with the amino acid residues Leu648, Phe649, Glu802, Leu873, Ser876, Glu879, Arg880, Phe1009, Thr1010, Val1011 and Phe1013 located within the active cavity of XO. The mechanism of chrysin on XO activity may be the insertion of chrysin into the active site occupying the catalytic center of XO to avoid the entrance of xanthine and causing conformational changes in XO. Furthermore, the interaction assays indicated that chrysin and its structural analog apigenin exhibited an additive effect on inhibition of XO. Copyright © 2015 Elsevier B.V. All rights reserved.

The catechol-O-methyltransferase (COMT) Val158Met genotype modulates working memory-related dorsolateral prefrontal response and performance in bipolar disorder

DEFF Research Database (Denmark)

Miskowiak, K. W.; Kjærstad, H. L.; Støttrup, M. M.

2017-01-01

prefrontal cortex (dlPFC) (P=.016). Exploratory whole-brain analysis revealed a bilateral decrease in working memory-related dlPFC activity in the ValVal group vs the ValMet group which was not associated with differences in working memory performance during fMRI. Outside the MRI scanner, Val carriers...... performed worse in the CANTAB Spatial Working Memory task than Met homozygotes (P≤.006), with deficits being most pronounced in Val homozygotes. CONCLUSIONS: The association between Val allelic load, dlPFC activity and WM impairment points to a putative role of aberrant PFC dopamine tonus in the cognitive......-O-methyltransferase (COMT) gene is associated with reduced prefrontal cortex dopamine and exaggerated working memory-related prefrontal activity. This functional magnetic resonance imaging (fMRI) study investigated for the first time whether the COMT Val158Met genotype modulates prefrontal activity during spatial working...

The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress.

Science.gov (United States)

Alexander, Nina; Osinsky, Roman; Schmitz, Anja; Mueller, Eva; Kuepper, Yvonne; Hennig, Juergen

2010-07-01

Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date. Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity. Healthy male adults (N=100) were genotyped and exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol and self-reported mood levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Furthermore, heart rate reactivity as an indicator of sympathetic activation was monitored continuously during the experimental procedure. We report a small, but significant effect of the BDNF Val66Met polymorphism on stress reactivity. More precisely, carriers of the met-allele showed a significantly attenuated HPA-axis and cardiovascular reactivity to the psychosocial stressor compared to subjects with the val/val genotype. Furthermore, the diminished physiological response in met-allele carriers was also attended by significantly lower self-reported ratings of perceived stress and nervousness. Our findings of a diminished endocrine and cardiovascular stress response in healthy male adults is consistent with a previously published study and adds further evidence for a crucial role of the BDNF Val66Met polymorphism in the modulation of stress reactivity. Copyright 2010. Published by Elsevier Ltd.

Neironu tīklu pielietošana valūtas cenu prognozēšanai

OpenAIRE

Slavs, Vladimirs

2012-01-01

Šajā bakalaura darbā ir aprakstīta dažāda veida neironu tīklu un apmācības metožu pielietojums un to lietderība valūtas cenu prognozēšanai „forex” tirgos. Darbs mēģina analizēt mākslīga intelekta spējas valūtu tirgošanas sistēmā, kurā tieši nav atrastas simtprocentīgi darbojošās veiksmes formulas, tomēr eksistē likumsakarības. Mākslīgais neironu tīkls vairākslāņu perceptrona veidā ir uzprogrammēts C++ valodā un analizēja Eiro/ASV dolāra valūtu pāri. Atslēgvārdi: neironu tīkli, forex, valūt...

Structural Insights into l-Tryptophan Dehydrogenase from a Photoautotrophic Cyanobacterium, Nostoc punctiforme.

Science.gov (United States)

Wakamatsu, Taisuke; Sakuraba, Haruhiko; Kitamura, Megumi; Hakumai, Yuichi; Fukui, Kenji; Ohnishi, Kouhei; Ashiuchi, Makoto; Ohshima, Toshihisa

2017-01-15

l-Tryptophan dehydrogenase from Nostoc punctiforme NIES-2108 (NpTrpDH), despite exhibiting high amino acid sequence identity (>30%)/homology (>50%) with NAD(P) + -dependent l-Glu/l-Leu/l-Phe/l-Val dehydrogenases, exclusively catalyzes reversible oxidative deamination of l-Trp to 3-indolepyruvate in the presence of NAD + Here, we determined the crystal structure of the apo form of NpTrpDH. The structure of the NpTrpDH monomer, which exhibited high similarity to that of l-Glu/l-Leu/l-Phe dehydrogenases, consisted of a substrate-binding domain (domain I, residues 3 to 133 and 328 to 343) and an NAD + /NADH-binding domain (domain II, residues 142 to 327) separated by a deep cleft. The apo-NpTrpDH existed in an open conformation, where domains I and II were apart from each other. The subunits dimerized themselves mainly through interactions between amino acid residues around the β-1 strand of each subunit, as was observed in the case of l-Phe dehydrogenase. The binding site for the substrate l-Trp was predicted by a molecular docking simulation and validated by site-directed mutagenesis. Several hydrophobic residues, which were located in the active site of NpTrpDH and possibly interacted with the side chain of the substrate l-Trp, were arranged similarly to that found in l-Leu/l-Phe dehydrogenases but fairly different from that of an l-Glu dehydrogenase. Our crystal structure revealed that Met-40, Ala-69, Ile-74, Ile-110, Leu-288, Ile-289, and Tyr-292 formed a hydrophobic cluster around the active site. The results of the site-directed mutagenesis experiments suggested that the hydrophobic cluster plays critical roles in protein folding, l-Trp recognition, and catalysis. Our results provide critical information for further characterization and engineering of this enzyme. In this study, we determined the three-dimensional structure of l-Trp dehydrogenase, analyzed its various site-directed substitution mutants at residues located in the active site, and obtained the

48 CFR 2009.570-2 - Definitions.

Science.gov (United States)

2010-10-01

... ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Organizational Conflicts of Interest 2009.570-2 Definitions... concern or individual controls or has the power to control another, or when a third party controls or has the power to control both. Contract means any contractual agreement or other arrangement with the NRC...

29 CFR 570.115 - Joint applicability.

Science.gov (United States)

2010-07-01

... Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION General Statements of Interpretation of the Child Labor... 12(a) and 12(c) § 570.115 Joint applicability. The child labor coverage provisions contained in...

Association between COMT Polymorphism Val158Met and Opioid Consumption in Patients with Postoperative Pain: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Bo Hu

2018-01-01

Full Text Available Background/Aims: Several factors influencing postoperative pain and the effect of opioid analgesics have been investigated on an individual level. The aim of this study was to clarify the impact of catecholamine-O-methyltransferase (COMT gene Val158Met on opioid consumption in postoperative patients. Methods: A systematic review and meta-analysis of the literature up to September 30, 2017, were performed by using PubMed, Cochrane Library, ISI Web of Science, and Chinese National Knowledge Infrastructure (CNKI database. The meta-analysis examined all studies involving the association between genetic polymorphisms of COMT Val158Met and opioid consumption during the acute postoperative period. Results: Of the 153 identified studies, 23 studies were retrieved for systematic review and 10 studies were retrieved for meta-analysis. However, it was impossible to conduct meta-analysis on the association between COMT Val158Met polymorphism and postoperative pain because of heterogeneity of the data. Overall, meta-analysis showed that COMT Val/Met carriers consumed less opioid for analgesia within the first 24 hours after surgery (SMD = 0.14, 95% CI = [0.03, 0.25], P = 0.01 but not within 48 hours (SMD = 0.14, 95% CI = [0.08, 0.36], P = 0.21. There was no significant difference in opioid consumption between Val/ Val and Met/Met patients. Conclusion: Patients with Val/Met but not Met/Met allele variant consumed less opioid, though larger and better-designed studies are required to obtain an exclusive conclusion about the correlation between postoperative pain and COMT Val158Met polymorphism.

Vad är den främst avgörande faktorn vid privatkundens val av marginalbank? : en studie om hur demografiska skillnader påverkar privatkunders val av marginalbank samt se hur deras val kan användas vid segmentering

OpenAIRE

Lindh, Jenni; Persson, Frida

2012-01-01

Syfte: Syftet med detta examensarbete är att förklara vad som är den främst avgörande faktorn vid privatkundens val av marginalbank, genom att jämföra med demografiska variabler samt hur deras val kan användas vid segmentering. Dessutom vill vi titta på vilka typer av banker privatkunder har. Metod: För att nå fram till resultat för analysen har ett positivistiskt angreppssätt och en deduktiv ansats använts. Det empiriska materialet är baserat på en enkätundersökning gjord på personer i Hässl...

40 CFR 240.205 - Air quality.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Air quality. 240.205 Section 240.205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR THE THERMAL PROCESSING OF SOLID WASTES Requirements and Recommended Procedures § 240.205 Air quality. ...

Amino Acids Inhibitory Effects and Mechanism on 2-Amino-1-Methyl-6-Phenylimidazo [4,5-b]Pyridine (PhIP) Formation in the Maillard Reaction Model Systems.

Science.gov (United States)

Linghu, Ziyi; Karim, Faris; Smith, J Scott

2017-12-01

This study was to investigate the inhibitory effects of amino acids (AAs) on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and to evaluate the inhibition mechanism of PhIP in Maillard model systems. Different AAs were individually added into model systems heat-treated at 180 °C/1 h. The PhIP, phenylacetaldehyde (PheAce), and pyrazines derivatives were determined using HPLC and GC-MS. AAs significantly reduced (P Pro > Leu > Met > Val > Ile > Thr > Phe > Asp, at the highest molar ratio. The PheAce content was gradually reduced with increasing AAs levels, suggesting that AAs may inhibit PhIP formation through scavenging the available PheAce. A correlation between PhIP inhibition and PheAce-scavenging activity of AAs was observed when PheAce and AAs were heated. The variety and quantity of pyrazines formed are highly depending on the type of AAs. © 2017 Institute of Food Technologists®.

The BDNF Val66Met polymorphism: relation to familiar risk of affective disorder, BDNF levels and salivary cortisol

DEFF Research Database (Denmark)

Vinberg, Maj; Trajkovska, Viktorija; Bennike, Bente

2009-01-01

BACKGROUND: Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are considered to play an important role in the pathophysiology of affective disorders. The aim of the present study was to investigate whether the BDNF Val66Met polymorphism is associated...... with a familiar risk of affective disorder and whether these genotypes affect whole blood BDNF level and salivary cortisol. METHOD: In a high-risk study, healthy monozygotic and dizygotic twins with and without a co-twin (high- and low-risk twins, respectively) history of affective disorder were identified...... through nationwide registers. RESULTS: Familiar predisposition to unipolar and bipolar disorder was not associated with any specific genotype pattern of the BDNF Val66Met polymorphism, not in this sample of 124 val/val, 58 val/met and 8 met/met individuals. However, the combination of having a high...

BDNF Val66Met Polymorphism Influences Visuomotor Associative Learning and the Sensitivity to Action Observation

Science.gov (United States)

Taschereau-Dumouchel, Vincent; Hétu, Sébastien; Michon, Pierre-Emmanuel; Vachon-Presseau, Etienne; Massicotte, Elsa; De Beaumont, Louis; Fecteau, Shirley; Poirier, Judes; Mercier, Catherine; Chagnon, Yvon C.; Jackson, Philip L.

2016-01-01

Motor representations in the human mirror neuron system are tuned to respond to specific observed actions. This ability is widely believed to be influenced by genetic factors, but no study has reported a genetic variant affecting this system so far. One possibility is that genetic variants might interact with visuomotor associative learning to configure the system to respond to novel observed actions. In this perspective, we conducted a candidate gene study on the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, a genetic variant linked to motor learning in regions of the mirror neuron system, and tested the effect of this polymorphism on motor facilitation and visuomotor associative learning. In a single-pulse TMS study carried on 16 Met (Val/Met and Met/Met) and 16 Val/Val participants selected from a large pool of healthy volunteers, Met participants showed significantly less muscle-specific corticospinal sensitivity during action observation, as well as reduced visuomotor associative learning, compared to Val homozygotes. These results are the first evidence of a genetic variant tuning sensitivity to action observation and bring to light the importance of considering the intricate relation between genetics and associative learning in order to further understand the origin and function of the human mirror neuron system. PMID:27703276

Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity.

Science.gov (United States)

Ursini, Gianluca; Bollati, Valentina; Fazio, Leonardo; Porcelli, Annamaria; Iacovelli, Luisa; Catalani, Assia; Sinibaldi, Lorenzo; Gelao, Barbara; Romano, Raffaella; Rampino, Antonio; Taurisano, Paolo; Mancini, Marina; Di Giorgio, Annabella; Popolizio, Teresa; Baccarelli, Andrea; De Blasi, Antonio; Blasi, Giuseppe; Bertolino, Alessandro

2011-05-04

DNA methylation at CpG dinucleotides is associated with gene silencing, stress, and memory. The catechol-O-methyltransferase (COMT) Val(158) allele in rs4680 is associated with differential enzyme activity, stress responsivity, and prefrontal activity during working memory (WM), and it creates a CpG dinucleotide. We report that methylation of the Val(158) allele measured from peripheral blood mononuclear cells (PBMCs) of Val/Val humans is associated negatively with lifetime stress and positively with WM performance; it interacts with stress to modulate prefrontal activity during WM, such that greater stress and lower methylation are related to reduced cortical efficiency; and it is inversely related to mRNA expression and protein levels, potentially explaining the in vivo effects. Finally, methylation of COMT in prefrontal cortex and that in PBMCs of rats are correlated. The relationship of methylation of the COMT Val(158) allele with stress, gene expression, WM performance, and related brain activity suggests that stress-related methylation is associated with silencing of the gene, which partially compensates the physiological role of the high-activity Val allele in prefrontal cognition and activity. Moreover, these results demonstrate how stress-related DNA methylation of specific functional alleles impacts directly on human brain physiology beyond sequence variation.

40 CFR 205.54 - Test procedures.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Test procedures. 205.54 Section 205.54 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.54 Test procedures. The procedures described...

Brain-derived neurotrophic factor Val66Met polymorphism and hippocampal activation during episodic encoding and retrieval tasks

OpenAIRE

Dennis, Nancy A.; Cabeza, Roberto; Need, Anna C.; Waters-Metenier, Sheena; Goldstein, David B.; LaBar, Kevin S.

2010-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin which has been shown to regulate cell survival and proliferation, as well as synaptic growth and hippocampal long-term potentiation. A naturally occurring single nucleotide polymorphism in the human BDNF gene (val66met) has been associated with altered intercellular trafficking and regulated secretion of BDNF in met compared to val carriers. Additionally, previous studies have found a relationship between the BDNF val66met genotype an...

3,4-Phenylenedioxythiophene (PheDOT) Based Hole-Transporting Materials for Perovskite Solar Cells.

Science.gov (United States)

Chen, Jian; Chen, Bai-Xue; Zhang, Fang-Shuai; Yu, Hui-Juan; Ma, Shuang; Kuang, Dai-Bin; Shao, Guang; Su, Cheng-Yong

2016-04-05

Two new electron-rich molecules based on 3,4-phenylenedioxythiophene (PheDOT) were synthesized and successfully adopted as hole-transporting materials (HTMs) in perovskite solar cells (PSCs). X-ray diffraction, absorption spectra, photoluminescence spectra, electrochemical properties, thermal stabilities, hole mobilities, conductivities, and photovoltaic parameters of PSCs based on these two HTMs were compared with each other. By introducing methoxy substituents into the main skeleton, the energy levels of PheDOT-core HTM were tuned to match with the perovskite, and its hole mobility was also improved (1.33×10(-4)  cm(2)  V(-1)  s(-1) , being higher than that of spiro-OMeTAD, 2.34×10(-5)  cm(2)  V(-1)  s(-1)). The PSC based on MeO-PheDOT as HTM exhibits a short-circuit current density (Jsc) of 18.31 mA cm(-2) , an open-circuit potential (Voc ) of 0.914 V, and a fill factor (FF) of 0.636, yielding an encouraging power conversion efficiency (PCE) of 10.64 % under AM 1.5G illumination. These results give some insight into how the molecular structures of HTMs affect their performances and pave the way for developing high-efficiency and low-cost HTMs for PSCs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

40 CFR 205.58-2 - Tampering.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Tampering. 205.58-2 Section 205.58-2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.58-2 Tampering. (a) For each configuration...

40 CFR 205.58-1 - Warranty.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Warranty. 205.58-1 Section 205.58-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.58-1 Warranty. (a) The vehicle manufacturer...

Energy Landscape of Pentapeptides in a Higher-Order (ϕ,ψ Conformational Subspace

Directory of Open Access Journals (Sweden)

Karim M. ElSawy

2016-01-01

Full Text Available The potential energy landscape of pentapeptides was mapped in a collective coordinate principal conformational subspace derived from principal component analysis of a nonredundant representative set of protein structures from the PDB. Three pentapeptide sequences that are known to be distinct in terms of their secondary structure characteristics, (Ala5, (Gly5, and Val.Asn.Thr.Phe.Val, were considered. Partitioning the landscapes into different energy valleys allowed for calculation of the relative propensities of the peptide secondary structures in a statistical mechanical framework. The distribution of the observed conformations of pentapeptide data showed good correspondence to the topology of the energy landscape of the (Ala5 sequence where, in accord with reported trends, the α-helix showed a predominant propensity at 298 K. The topography of the landscapes indicates that the stabilization of the α-helix in the (Ala5 sequence is enthalpic in nature while entropic factors are important for stabilization of the β-sheet in the Val.Asn.Thr.Phe.Val sequence. The results indicate that local interactions within small pentapeptide segments can lead to conformational preference of one secondary structure over the other where account of conformational entropy is important in order to reveal such preference. The method, therefore, can provide critical structural information for ab initio protein folding methods.

Analysis list: Su(var)205 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Su(var)205 Adult,Embryo,Larvae + dm3 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3.../target/Su(var)205.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Su(var)205.5.tsv http://dbarc...hive.biosciencedbc.jp/kyushu-u/dm3/target/Su(var)205.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/c...olo/Su(var)205.Adult.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Su(var)205.Embryo.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Su(var)205.Larvae.tsv http://dbarchive

“Der Artist Valéry” nella teoria estetica di Adorno

Directory of Open Access Journals (Sweden)

Giovanni Matteucci

2012-05-01

Full Text Available This paper aims to outline the importance of Valéry with respect to some cornerstones of Adorno’s aesthetic theory as a negative-dialectical thought. Adorno’s concept of aesthetic experience finds in Valéry as an “Artist” (not simply as a “Künstler” a sort of lieutenant: he helps to specify notions like “apparition”, “form”, “configuration”, and above all the idea of the aesthetic as a relation by which something happens in the field of human experience without being a determinate, or determinable, content of it.

Platyhelminth Venom Allergen-Like (VAL) proteins: revealing structural diversity, class-specific features and biological associations across the phylum

Science.gov (United States)

CHALMERS, IAIN W.; HOFFMANN, KARL F.

2012-01-01

SUMMARY During platyhelminth infection, a cocktail of proteins is released by the parasite to aid invasion, initiate feeding, facilitate adaptation and mediate modulation of the host immune response. Included amongst these proteins is the Venom Allergen-Like (VAL) family, part of the larger sperm coating protein/Tpx-1/Ag5/PR-1/Sc7 (SCP/TAPS) superfamily. To explore the significance of this protein family during Platyhelminthes development and host interactions, we systematically summarize all published proteomic, genomic and immunological investigations of the VAL protein family to date. By conducting new genomic and transcriptomic interrogations to identify over 200 VAL proteins (228) from species in all 4 traditional taxonomic classes (Trematoda, Cestoda, Monogenea and Turbellaria), we further expand our knowledge related to platyhelminth VAL diversity across the phylum. Subsequent phylogenetic and tertiary structural analyses reveal several class-specific VAL features, which likely indicate a range of roles mediated by this protein family. Our comprehensive analysis of platyhelminth VALs represents a unifying synopsis for understanding diversity within this protein family and a firm context in which to initiate future functional characterization of these enigmatic members. PMID:22717097

Staphylococcal phosphoenolpyruvate-dependent phosphotransferase system: purification and characterization of the mannitol-specific enzyme III/sup mtl/ of Staphylococcus aureus and Staphylococcus carnosus and homology with the enzyme II/sup mtl/ of Escherichia coli

International Nuclear Information System (INIS)

Reiche, B.; Frank, R.; Deutscher, J.; Meyer, N.; Hengstenberg, W.

1988-01-01

Enzyme III/sup mtl/ is part of the mannitol phosphotransferase system of Staphylococcus aureus and Staphylococcus carnosus and is phosphorylated by phosphoenolpyruvate in a reaction sequence requiring enzyme I (phosphoenolpyruvate-protein phosphotransferase) and the histidine-containing protein HPr. In this paper, the authors report the isolation of III/sup mtl/ from both S. aureus and S. carnosus and the characterization of the active center. After phosphorylation of III/sup mtl/ with [ 32 P]PEP, enzyme I, and HPr, the phosphorylated protein was cleaved with endoproteinase GLu(C). The amino acid sequence of the S. aureus peptide carrying the phosphoryl group was found to be Gln-Val-Val-Ser-Thr-Phe-Met-Gly-Asn-Gly-Leu-Ala-Ile-Pro-His-Gly-Thr-Asp-Asp. The corresponding peptide from S. carnosus shows an equal sequence except that the first residue is Ala instead of Gln. These peptides both contain a single histidyl residue which they assume to carry the phosphoryl group. All proteins of the PTS so far investigated indeed carry the phosphoryl group attached to a histidyl residue. According to sodium dodecyl sulfate gels, the molecular weight of the III/sup mtl/ proteins was found to be 15,000. They have also determined the N-terminal sequence of both proteins. Comparison of the III/sup mtl/ peptide sequences and the C-terminal part of the enzyme II/sup mtl/ of Escherichia coli reveals considerable sequence homology, which supports the suggestion that II/sup mtl/ of E. coli is a fusion protein of a soluble III protein with a membrane-bound enzyme II

20 CFR 655.205 - Recruitment period.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Recruitment period. 655.205 Section 655.205... FOREIGN WORKERS IN THE UNITED STATES Labor Certification Process for Logging Employment and Non-H-2A Agricultural Employment § 655.205 Recruitment period. (a) If the OFLC Administrator determines that the...

24 CFR 570.482 - Eligible activities.

Science.gov (United States)

2010-04-01

... certification from the assisted business that neither it, nor any of its subsidiaries, has plans to relocate... Block Grant Program § 570.482 Eligible activities. (a) General. The choice of activities on which block... accordance with the state's program design and procedures, as to which approach or approaches will best serve...

48 CFR 803.570-1 - Policy.

Science.gov (United States)

2010-10-01

... BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Other Improper Business Practices 803.570-1 Policy. It is VA policy that contractors will not advertise the award of contracts or refer to VA contracts in contractors' commercial advertising in such a manner as to state or imply that VA endorses a...

Both COMT Val158Met single nucleotide polymorphism and sex-dependent differences influence response inhibition

Directory of Open Access Journals (Sweden)

Valentina eMione

2015-05-01

Full Text Available Reactive and proactive control of actions are cognitive abilities that allow to deal with a continuously changing environment by adjusting already programmed actions. They also set forthcoming acts by evaluating the outcome of the previous ones. Earlier studies highlighted sex related differences in the strategies and in the pattern of brain activation during cognitive tasks involving reactive and proactive control. To further identify sex-dependent characteristics in the cognitive control of actions, in this study we have assessed whether/how differences in reactive and proactive control were modulated by the COMT Val158Met single nucleotide polymorphism, a genetic factor known to influence the functionality of the dopaminergic system, in particular at the level of prefrontal cortex. Two groups of male and female participants were further sorted according to their genotype (Val/Met, Val/Val and Met/Met and tested in a stop signal task, a consolidated tool to measure reactive and proactive control in experimental and clinical settings. In each group of participants we estimated both a measure of the capacity to react to unexpected events and the ability of monitoring their performance. The between groups comparison of these measures indicated a poorer ability of male individuals carrying the Val/Val genotype in error-monitoring, suggesting that differences between sexes could be influenced by the efficiency of COMT and that other sex-specific factors have to be considered. The comprehension of inter-groups behavioral and physiological correlates of cognitive control will provide more accurate diagnostic tools for predicting the incidence and the development of pathologies like ADHD or deviant behaviors as drug or alcohol abuse.

22 CFR 20.5 - Survivor benefits.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Survivor benefits. 20.5 Section 20.5 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR CERTAIN FORMER SPOUSES § 20.5 Survivor benefits. (a) Type of benefits. A former spouse who meets the eligibility requirements of § 20.3 is entitled to...

48 CFR 570.110 - Cost or pricing data and information other than cost or pricing data.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Cost or pricing data and information other than cost or pricing data. 570.110 Section 570.110 Federal Acquisition Regulations System... PROPERTY General 570.110 Cost or pricing data and information other than cost or pricing data. (a) The...

Protective Effect of Val129-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

Science.gov (United States)

Fernández-Borges, Natalia; Espinosa, Juan Carlos; Marín-Moreno, Alba; Aguilar-Calvo, Patricia; Asante, Emmanuel A; Kitamoto, Tetsuyuki; Mohri, Shirou; Andréoletti, Olivier; Torres, Juan María

2017-09-01

Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met 129 ) or valine (Val 129 ) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met 129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val 129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met 129 Hu-PrP. In addition, the transmission of vCJD to transgenic mice homozygous for Val 129 Hu-PrP resulted in a prion with distinct strain features. These observations may indicate increased risk for vCJD secondary transmission in Val 129 Hu-PrP-positive humans with the emergence of new strain features.

Deltorphins: a family of naturally occurring peptides with high affinity and selectivity for delta opioid binding sites.

OpenAIRE

Erspamer, V; Melchiorri, P; Falconieri-Erspamer, G; Negri, L; Corsi, R; Severini, C; Barra, D; Simmaco, M; Kreil, G

1989-01-01

Deltorphins are endogenous linear heptapeptides, isolated from skin extracts of frogs belonging to the genus Phyllomedusa, that have a higher affinity and selectivity for delta opioid binding sites than any other natural compound known. Two deltorphins with the sequence Tyr-Ala-Phe-Asp(or Glu)-Val-Val-Gly-NH2 have been isolated from skin extracts of Phyllomedusa bicolor. The alanine in position 2 is in the D configuration. These peptides, [D-Ala2]deltorphins I and II, show an even higher affi...

BDNF Val66Met homozygosity does not influence plasma BDNF levels in healthy human subjects

NARCIS (Netherlands)

Luykx, J.J.; Boks, M.P.M.; Breetvelt, E.J.; Aukes, M.F.; Strengman, E.; da Pozzo, E.; Dell'osso, L.; Marazziti, D.; van Leeuwen, A.; Vreeker, A.; Abramovic, L.; Martini, C.; Numans, M.E.; Kahn, R. S.; Ophoff, R. A.

2013-01-01

A putative pathway by which the BDNF Val66Met polymorphism (rs6265) leads to aberrant phenotypes is its influence on plasma BDNF. Research into the impact of rs6265 on plasma BDNF has given rise to conflicting results. Moreover, most such studies have compared Met-carriers with Val-homozygous

Determination of 13C isotopic enrichment of valine and threonine by GC-C-IRMS after formation of the N(O,S)-ethoxycarbonyl ethyl ester derivatives of the amino acids.

Science.gov (United States)

Godin, Jean-Philippe; Faure, Magali; Breuille, Denis; Hopfgartner, Gérard; Fay, Laurent-Bernard

2007-06-01

We describe a new method of assessing, in a single run, (13)C isotopic enrichment of both Val and Thr by gas chromatography-combustion-isotope-ratio mass spectrometry (GC-C-IRMS). This method characterised by a rapid one-step derivatisation procedure performed at room temperature to form the N(O,S)-ethoxycarbonyl ethyl ester derivatives, and a polar column for GC. The suitability of this method for Val and Thr in in-vivo samples (mucosal hydrolysate) was demonstrated by studying protein metabolism with two tracers ((13)C-valine or (13)C-threonine). The intra-day and inter-day repeatability were both assessed either with standards or with in-vivo samples at natural abundance and at low (13)C isotopic enrichment. For inter-day repeatability CVs were between 0.8 and 1.5% at natural abundance and lower than 5.5% at 0.112 and 0.190 atom% enrichment for Val and Thr, respectively. Overall isotopic precision was studied for eleven standard amino acid derivatives (those of Val, Ala, Leu, Iso, Gly, Pro, Asp, Thr, Ser, Met, and Phe) and was assessed at 0.32 per thousand. The (13)C isotopic measurement was then extended to the other amino acids (Ala, Val, Leu, Iso, Gly, Pro, Thr, and Phe) at natural abundance for in-vivo samples. The isotopic precision was better than 0.002 atom% per amino acid (for n = 4 rats). This analytical method was finally applied to an animal study to measure Thr utilization in protein synthesis.

29 CFR 570.106 - “Ship or deliver for shipment in commerce”.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false âShip or deliver for shipment in commerceâ. 570.106 Section 570.106 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION General Statements of Interpretation of the Child Labor Provisions of...

Association of Polymorphous Markers Ala(-9Val of SOD2 Gene and C(-262T of CAT Gene in Patients with Hashimotos’ Thyroiditis and Hypothyroidism

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A Mkrtumyan

2008-03-01

Full Text Available A comparative analysis of distribution of alleles and genotypes of polymorphous markers Ala(-9Val of SOD2 gene and C(-262T of CAT gene was performed. Eighty six patients with Hashimotos’ thyroiditis (HT were enrolled in the study. Significant deferens were found by comparison of alleles and genotypes incidence of polymorphous marker Ala(-9Val of SOD2 gene in HT-patients and in control group. Significant increase of incidence of Val/Val genotype (OR = 15,6; p = 0.04 in HT-patients may reflect a higher risk of HT in Val/Val individuals. This hypothesis may be confirmed by increase of malonic dialdehyde and antithyroid antibodies in Val/Val carriers.

50 CFR 223.205 - Sea turtles.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Sea turtles. 223.205 Section 223.205... Threatened Marine and Anadromous Species § 223.205 Sea turtles. (a) The prohibitions of section 9 of the Act (16 U.S.C. 1538) relating to endangered species apply to threatened species of sea turtle, except as...

BDNF val66met association with serotonin transporter binding in healthy humans

DEFF Research Database (Denmark)

Fisher, P. M.; Ozenne, B.; Svarer, C.

2017-01-01

The serotonin transporter (5-HTT) is a key feature of the serotonin system, which is involved in behavior, cognition and personality and implicated in neuropsychiatric illnesses including depression. The brain-derived neurotrophic factor (BDNF) val66met and 5-HTTLPR polymorphisms have predicted......-carriers have increased subcortical 5-HTT binding. The small difference suggests limited statistical power may explain previously reported null effects. Our finding adds to emerging evidence that BDNF val66met contributes to differences in the human brain serotonin system, informing how variability in the 5-HTT...

No association of the BDNF val66met polymorphism with implicit associative vocabulary and motor learning.

Directory of Open Access Journals (Sweden)

Nils Freundlieb

Full Text Available Brain-derived neurotrophic factor (BDNF has been suggested to play a major role in plasticity, neurogenesis and learning in the adult brain. The BDNF gene contains a common val66met polymorphism associated with decreased activity-dependent excretion of BDNF and a potential influence on behaviour, more specifically, on motor learning. The objective of this study was to determine the influence of the BDNF val66met polymorphism on short-term implicit associative learning and whether its influence is cognitive domain-specific (motor vs. language. A sample of 38 young healthy participants was genotyped, screened for background and neuropsychological differences, and tested with two associative implicit learning paradigms in two different cognitive domains, i.e., motor and vocabulary learning. Subjects performed the serial reaction time task (SRTT to determine implicit motor learning and a recently established associative vocabulary learning task (AVL for implicit learning of action and object words. To determine the influence of the BDNF polymorphism on domain-specific implicit learning, behavioural improvements in the two tasks were compared between val/val (n = 22 and met carriers (val/met: n = 15 and met/met: n = 1. There was no evidence for an impact of the BDNF val66met polymorphism on the behavioural outcome in implicit short-term learning paradigms in young healthy subjects. Whether this polymorphism plays a relevant role in long-term training paradigms or in subjects with impaired neuronal plasticity or reduced learning capacity, such as aged individuals, demented patients or patients with brain lesions, has to be determined in future studies.

Properties of chymotrypsin bound covalently to dextran.

Science.gov (United States)

Zlateva, T P; Krysteva, M; Balajthy, Z; Elödi, P

1988-01-01

The kinetic properties dextran-chymotrypsin conjugate were studied by means of low molecular weight substrates. It was found that KM, kcat and kcat/KM of dextran chymotrypsin for the hydrolysis of benzoyl-L-tyrosine-ethyl-ester did not differ substantially from those of the free enzyme. However, the data found for kcat of dextran-chymotrypsin and free chymotrypsin assayed for the hydrolysis of three tripeptidyl-p-nitroanilide D-Arg-Val-Trp-pNA, D-Arg-Val-Tyr-pNA, Z-Phe-Pro-Phe-pNA, were definitely different. The inhibition of the modified chymotrypsin with soybean trypsin inhibitor was found to be less pronounced than that with the free enzyme. The effect of potassium and magnesium salts on the inactivation of both enzymes was also studied. The effect of dextran matrix on the catalytic properties and the conformational stability of modified chymotrypsin is discussed.

Val L. Fitch, the CP Violation, and Antimatter

Science.gov (United States)

dropdown arrow Site Map A-Z Index Menu Synopsis Val L. Fitch, the CP Violation, and Antimatter Resources ) 'to verify a fundamental tenet of physics, known as CP [charge-parity] symmetry, by showing that two into two pi mesons. Cronin and Fitch had found an example of CP violation. The discovery's

A Case-Control Study and Meta-Analysis Reveal BDNF Val66Met Is a Possible Risk Factor for PTSD

Directory of Open Access Journals (Sweden)

Dagmar Bruenig

2016-01-01

Full Text Available Posttraumatic stress disorder (PTSD is a debilitating condition that develops in some people after exposure to a traumatic event. Brain-derived neurotrophic factor (BDNF is highly expressed in the mammalian brain and is thought to be involved in learning and memory processes. A nonsynonymous polymorphism in the BDNF gene, rs6265 (Val66Met, has been hypothesised to be associated with PTSD. Association studies examining the Val66Met polymorphism and PTSD have been inconclusive, likely due to the variability in type of trauma exposure analysed. Vietnam veterans (n=257 screened for PTSD and controlled for trauma exposure were genotyped for BDNF Val66Met. The association was not significant so we incorporated our data into a meta-analysis to obtain greater statistical power. A comprehensive search of more than 1237 articles revealed eight additional studies suitable for meta-analysis (n=3625. A random-effects meta-analysis observed a potential protective factor of the Val/Val genotype. After removing two studies with violation of Hardy-Weinberg equilibrium, findings for the Val/Val genotype reached significance. Subgroup analyses confirmed a trend for this finding. Limitations of some studies that inform this meta-analysis include poorly screened controls and a lack of examination of population stratification. Effectively designed studies should inform this line of research in the future.

BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions.

Science.gov (United States)

Shalev, Idan; Lerer, Elad; Israel, Salomon; Uzefovsky, Florina; Gritsenko, Inga; Mankuta, David; Ebstein, Richard P; Kaitz, Marsha

2009-04-01

A key protein in maintaining neuronal integrity throughout the life span is brain-derived neurotrophic factor (BDNF). The BDNF gene is characterized by a functional polymorphism, which has been associated with stress-related disorders such as anxiety-related syndromes and depression, prompting us to examine individual responses by Genotype and Sex to a standardized social stress paradigm. Gender differences in BDNFxstress responses were posited because estrogen induces synthesis of BDNF in several brain regions. 97 university students (51 females and 46 males) participated in a social stress procedure (Trier Social Stress Test, TSST). Indices of stress were derived from repeated measurement of cortisol, blood pressure, and heart rate during the TSST. All subjects were genotyped for the Val66Met polymorphism. Tests of within-subject effects showed a significant three-way interaction (SPSS GLM repeated measures: Time (eight levels)xBDNF (val/val, val/met)xSex: p=0.0002), which reflects gender differences in the pattern of cortisol rise and decline during the social challenge. In male subjects, val/val homozygotes showed a greater rise in salivary cortisol than val/met heterozygotes. In female subjects, there was a trend for the opposite response, which is significant when area under the curve increase (AUCi) was calculated for the val/val homozygotes to show the lowest rise. Overall, the same pattern of results was observed for blood pressure and heart rate. These results indicate that a common, functionally significant polymorphism in the BDNF gene modulates HPA axis reactivity and regulation during the TSST differently in men and women. Findings may be related to gender differences in reactivity and vulnerability to social stress.

Impurity band effects on transport and thermoelectric properties of Fe2 -xNixVAl

Science.gov (United States)

Knapp, I.; Budinska, B.; Milosavljevic, D.; Heinrich, P.; Khmelevskyi, S.; Moser, R.; Podloucky, R.; Prenninger, P.; Bauer, E.

2017-07-01

Full Heusler alloys of the series Fe2 -xNixVAl ,0 ≤x ≤0.2 , were prepared and characterized, and their physical properties, relevant to the thermoelectric performance of such materials, were studied in a wide temperature range. The starting material Fe2VAl is characterized by a pseudogap of the electronic density of states near the Fermi energy, with a gap width of the order of 1 eV. Density functional theory calculations were performed by application of two approaches. In the framework of the local-spin-density approximation and coherent potential approximation, the electronic densities of states of substitutional alloys were calculated, revealing that with increasing Ni content the Fermi energy moves toward the conduction band, and consequently, the nature of electronic transport changes from p type to n type. It appears that Ni, due to its extra electrons, provides a narrow impurity band near the Fermi level. These states can be made responsible for the experimentally observed evolution of transport properties. Furthermore, the Vienna ab initio Simulation package (vasp) was utilized for deriving electronic, structural, and vibrational properties of ordered Fe2VAl and Fe1.75Ni0.25VAl . In particular, it is found that due to Ni substitution there is a general shift to lower phonon frequencies by about 2 THz as compared to the undoped case. Associated to these modifications, the electrical resistivity, ρ (T ) , changes from a semiconducting-like behavior to a nonsimple metallic behavior, while the Seebeck coefficient reaches values of the order of -80 μ V /K around room temperature for the sample x =0.2 . The increase of the Ni content, in addition, goes along with a substantial reduction of the lattice part of the thermal conductivity. This change is analyzed in detail in terms of a disorder parameter Γ , characterizing the derangement of the crystalline lattice due to the substitution of Fe by Ni. Ab initio calculations of the phonon dynamics carried out

BDNF val66met polymorphism is associated with age at onset and intensity of symptoms of paranoid schizophrenia in a Polish population.

Science.gov (United States)

Suchanek, Renata; Owczarek, Aleksander; Paul-Samojedny, Monika; Kowalczyk, Małgorzata; Kucia, Krzysztof; Kowalski, Jan

2013-01-01

The brain-derived neurotrophic factor (BDNF) is one of the candidate genes for schizophrenia. There is evidence that val66met polymorphism may be involved in the pathophysiology of schizophrenia. The authors genotyped val66met (rs6265) polymorphism of the BDNF gene in 208 inpatients with paranoid schizophrenia and 254 control subjects in a Polish population. There was no association between val66met polymorphism and development of paranoid schizophrenia in either men or women. However, an association was found between this polymorphism and age at onset and psychopathology of paranoid schizophrenia. Men with the val/met genotype had an earlier age at onset, and the val/val genotype predisposed to more severe symptoms, particularly on the General Psychopathology Scale of the Positive and Negative Symptoms Scale (PANSS-G). The analysis of PANSS single items has shown that patients with the val/met genotype had higher scores on a hallucinatory behavior item than those with other genotypes.

29 CFR 570.9 - States in which State certificates of age are accepted.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false States in which State certificates of age are accepted. 570.9 Section 570.9 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Certificates of...

CYP1A1 Ile462Val polymorphism contributes to lung cancer susceptibility among lung squamous carcinoma and smokers: a meta-analysis.

Directory of Open Access Journals (Sweden)

Ya-Nan Ji

Full Text Available Many studies have examined the association between the CYP1A1 Ile462Val gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. Ultimately, 43 case-control studies, comprising 19,228 subjects were included. A significantly elevated lung cancer risk was associated with 2 Ile462Val genotype variants (for Val/Val vs Ile/Ile: OR = 1.22, 95% CI = 1.08-1.40; for (Ile/Val +Val/Val vs Ile/Ile: OR = 1.15, 95% CI = 1.07-1.23 in overall population. In the stratified analysis, a significant association was found in Asians, Caucasians and lung SCC, not lung AC and lung SCLC. Additionally, a significant association was found in smoker population and not found in non-smoker populations. This meta-analysis suggests that the Ile462Val polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility in Asian and Caucasian populations and there is an interaction with smoking status, but these associations vary in different histological types of lung caner.

Alkaline transition of pseudoazurin Met16X mutant proteins: protein stability influenced by the substitution of Met16 in the second sphere coordination.

Science.gov (United States)

Abdelhamid, Rehab F; Obara, Yuji; Kohzuma, Takamitsu

2008-01-01

Several blue copper proteins are known to change the active site structure at alkaline pH (alkaline transition). Spectroscopic studies of Met16Phe, Met16Tyr, Met16Trp, and Met16Val pseudoazurin variants were performed to investigate the second sphere role through alkaline transition. The visible electronic absorption and resonance Raman spectra of Met16Phe, Met16Tyr, and Met16Trp variants showed the increasing of axial component at pH approximately 11 like wild-type PAz. The visible electronic absorption and far-UV CD spectra of Met16Val demonstrated that the destabilization of the protein structure was triggered at pH>11. Resonance Raman (RR) spectra of PAz showed that the intensity-weighted averaged Cu-S(Cys) stretching frequency was shifted to higher frequency region at pH approximately 11. The higher frequency shift of Cu-S(Cys) bond is implied the stronger Cu-S(Cys) bond at alkaline transition pH approximately 11. The visible electronic absorption and far-UV CD spectra of Met16X PAz revealed that the Met16Val variant is denatured at pH>11, but Met16Phe, Met16Tyr, and Met16Trp mutant proteins are not denatured even at pH>11. These observations suggest that Met16 is important to maintain the protein structure through the possible weak interaction between methionine -SCH3 part and coordinated histidine imidazole moiety. The introduction of pi-pi interaction in the second coordination sphere may be contributed to the enhancement of protein structure stability.

Ressenya a Rosa Mª Gregori Roig, La impressora Jerònima Galés i els Mey (València, segle XVI, València, Generalitat Valenciana-Biblioteca Valenciana, 2012, 611 pp. ISBN:978-84-482-5722-4

Directory of Open Access Journals (Sweden)

Estefania Ferrer del Río

2013-12-01

Full Text Available Review to Rosa Mª Gregori Roig, La impressora Jerònima Galés i els Mey (València, segle XVI, València, Generalitat Valenciana-Biblioteca Valenciana, 2012, 611 pp. ISBN:978-84-482-5722-4.

29 CFR 570.33 - Prohibited occupations for minors 14 and 15 years of age.

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2010-07-01

... 28448, May 20, 2010, § 570.33 was revised, effective July 19, 2010. For the convenience of the user, the... as permitted by § 570.34(i). (j) Youth peddling, which entails the selling of goods or services to...

The effect of the COMT val(158)met polymorphism on neural correlates of semantic verbal fluency.

Science.gov (United States)

Krug, Axel; Markov, Valentin; Sheldrick, Abigail; Krach, Sören; Jansen, Andreas; Zerres, Klaus; Eggermann, Thomas; Stöcker, Tony; Shah, N Jon; Kircher, Tilo

2009-12-01

Variation in the val(158)met polymorphism of the COMT gene has been found to be associated with cognitive performance. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal areas. Given the complex modulation and functional heterogeneity of frontal lobe systems, further specification of COMT gene-related phenotypes differing in prefrontally mediated cognitive performance are of major interest. Eighty healthy individuals (54 men, 26 women; mean age 23.3 years) performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (fMRI). COMT val(158)met genotype was determined and correlated with brain activation measured with fMRI during the task. Although there were no differences in performance, brain activation in the left inferior frontal gyrus [Brodmann area 10] was positively correlated with the number of val alleles in the COMT gene. COMT val(158)met status modulates brain activation during the language production on a semantic level in an area related to executive functions.

BDNF-Val66Met-Polymorphism Impact on Cortical Plasticity in Schizophrenia Patients: A Proof-of-Concept Study

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Nitsche, Michael A.; Wobrock, Thomas; Bunse, Tilmann; Rein, Bettina; Herrmann, Maximiliane; Schmitt, Andrea; Nieratschker, Vanessa; Witt, Stephanie H.; Rietschel, Marcella; Falkai, Peter; Hasan, Alkomiet

2015-01-01

Background: Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients. Methods: Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied. Results: Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS. Conclusions: These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory

COMT Val(158)Met genotype determines the direction of cognitive effects produced by catechol-O-methyltransferase inhibition.

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Farrell, Sarah M; Tunbridge, Elizabeth M; Braeutigam, Sven; Harrison, Paul J

2012-03-15

Catechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT Val(158)Met polymorphism influences its activity, and multiple neural correlates of this genotype on dopaminergic phenotypes, especially working memory, have been reported. COMT activity can also be regulated pharmacologically by COMT inhibitors. The inverted-U relationship between cortical dopamine signaling and working memory predicts that the effects of COMT inhibition will differ according to COMT genotype. Thirty-four COMT Met(158)Met (Met-COMT) and 33 COMT Val(158)Val (Val-COMT) men were given a single 200-mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a randomized, double-blind, between-subjects design. They completed the N-back task of working memory and a gambling task. In the placebo group, Met-COMT subjects outperformed Val-COMT subjects on the 2- back, and they were more risk averse. Tolcapone had opposite effects in the two genotype groups: it worsened N-back performance in Met-COMT subjects but enhanced it in Val-COMT subjects. Tolcapone made Met-COMT subjects less risk averse but Val-COMT subjects more so. In both tasks, tolcapone reversed the baseline genotype differences. Depending on genotype, COMT inhibition can enhance or impair working memory and increase or decrease risky decision making. To our knowledge, the data are the clearest demonstration to date that the direction of effect of a drug can be influenced by a polymorphism in its target gene. The results support the inverted-U model of dopamine function. The findings are of translational relevance, because COMT inhibitors are used in the adjunctive treatment of Parkinson's disease and are under evaluation in schizophrenia and other disorders. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Coevolution of the Ile1,016 and Cys1,534 Mutations in the Voltage Gated Sodium Channel Gene of Aedes aegypti in Mexico.

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Farah Z Vera-Maloof

2015-12-01

Full Text Available Worldwide the mosquito Aedes aegypti (L. is the principal urban vector of dengue viruses. Currently 2.5 billion people are at risk for infection and reduction of Ae. aegypti populations is the most effective means to reduce the risk of transmission. Pyrethroids are used extensively for adult mosquito control, especially during dengue outbreaks. Pyrethroids promote activation and prolong the activation of the voltage gated sodium channel protein (VGSC by interacting with two distinct pyrethroid receptor sites [1], formed by the interfaces of the transmembrane helix subunit 6 (S6 of domains II and III. Mutations of S6 in domains II and III synergize so that double mutants have higher pyrethroid resistance than mutants in either domain alone. Computer models predict an allosteric interaction between mutations in the two domains. In Ae. aegypti, a Ile1,016 mutation in the S6 of domain II was discovered in 2006 and found to be associated with pyrethroid resistance in field populations in Mexico. In 2010 a second mutation, Cys1,534 in the S6 of domain III was discovered and also found to be associated with pyrethroid resistance and correlated with the frequency of Ile1,016.A linkage disequilibrium analysis was performed on Ile1,016 and Cys1,534 in Ae. aegypti collected in Mexico from 2000-2012 to test for statistical associations between S6 in domains II and III in natural populations. We estimated the frequency of the four dilocus haplotypes in 1,016 and 1,534: Val1,016/Phe1,534 (susceptible, Val1,016/Cys1,534, Ile1,016/Phe1,534, and Ile1,016/Cys1,534 (resistant. The susceptible Val1,016/Phe1,534 haplotype went from near fixation to extinction and the resistant Ile1,016/Cys1,534 haplotype increased in all collections from a frequency close to zero to frequencies ranging from 0.5-0.9. The Val1,016/Cys1,534 haplotype increased in all collections until 2008 after which it began to decline as Ile1,016/Cys1,534 increased. However, the Ile1,016/Phe1

7 CFR 205.406 - Continuation of certification.

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2010-01-01

..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) ORGANIC FOODS PRODUCTION ACT PROVISIONS NATIONAL ORGANIC PROGRAM Certification § 205.406 Continuation of certification. (a) To continue... 7 Agriculture 3 2010-01-01 2010-01-01 false Continuation of certification. 205.406 Section 205.406...

7 CFR 1280.205 - Vacancies.

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2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Vacancies. 1280.205 Section 1280.205 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... INFORMATION ORDER Lamb Promotion, Research, and Information Order Lamb Promotion, Research, and Information...

21 CFR 570.30 - Eligibility for classification as generally recognized as safe (GRAS).

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2010-04-01

...), it may be used in food only within such limitation(s) (including the category of food(s), the... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Eligibility for classification as generally recognized as safe (GRAS). 570.30 Section 570.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

Cal/Val activities for DubaiSat-2 performance assessment

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Bushahab, A.; Al-Mansoori, S.; Al-Suwaidi, K.; Al Matroushi, Hessa; Al-Tunaiji, E.; Al Shamsi, Meera

2014-10-01

Emirates Institution for Advanced Science and Technology (EIAST) was established by the Dubai Government in 2006. After three years of working together with Satrec Initiative (South Korea), EIAST was able to launch DubaiSat-1 on the 29th of July 2009. Building on the success of DubaiSat-1 and the roll out of the knowledge transfer program, UAE engineers were involved in almost 70% of the total build and design of DubaiSat-2. Targeting the commercial market, DubaiSat-2 was launched on the 21st of November 2013 for capturing 1-meter resolution images. The 1st Cal/Val phase was the most critical phase in the satellite life-time, where most of the initial measurements took place. This phase extended over the period of 25/11/2013 till 12/12/2013. Moreover, this phase included most of the relative calibration tasks, color balancing and band matching. 2nd Cal/Val phase included most of the debugging and the pointing accuracy calibration tests. This phase extended over the period of 11/02/2014 till 09/03/2014. This phase emphasized on the calibration of the pointing accuracy. The 3rd Cal/Val phase included fine tuning for the Gyro system to further increase the stability of the satellite and thus improve the pointing accuracy. Moreover, new techniques were implemented to the Pan-Sharpening and to the MTF compensation procedures to enhance the final product. This phase extended over the period of 04/05/2014 till 21/05/2014.

48 CFR 2131.205-3 - Bad debts.

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2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Bad debts. 2131.205-3 Section 2131.205-3 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT, FEDERAL... PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 2131.205-3 Bad debts. Erroneous benefit...

40 CFR 205.57-4 - Testing procedures.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Testing procedures. 205.57-4 Section 205.57-4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.57-4 Testing...

40 CFR 205.55-1 - General requirements.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false General requirements. 205.55-1 Section 205.55-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.55-1 General...

40 CFR 205.55-4 - Labeling-compliance.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Labeling-compliance. 205.55-4 Section 205.55-4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.55-4 Labeling...

40 CFR 205.55-3 - Configuration identification.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Configuration identification. 205.55-3 Section 205.55-3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.55-3 Configuration...

40 CFR 205.58 - In-use requirements.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false In-use requirements. 205.58 Section 205.58 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.58 In-use requirements. ...

40 CFR 205.57-8 - Continued testing.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Continued testing. 205.57-8 Section 205.57-8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.57-8 Continued...

A brain-derived neurotrophic factor polymorphism Val66Met identifies fibromyalgia syndrome subgroup with higher body mass index and C-reactive protein.

Science.gov (United States)

Xiao, Yangming; Russell, I Jon; Liu, Ya-Guang

2012-08-01

A common single nucleotide polymorphism (SNP) in the gene of brain-derived neurotrophic factor (BDNF) results from a substitution at position 66 from valine (Val) to methionine (Met) and may predispose to human neuropsychiatric disorders. We proposed to determine whether these BDNF gene SNPs were associated with fibromyalgia syndrome (FMS) and/or any of its typical phenotypes. Patients with FMS (N = 95) and healthy normal controls (HNC, N = 58) were studied. Serum high-sensitivity C-reactive protein (hsCRP) levels were measured using an enzyme-linked immunosorbent assay (ELISA). The BDNF SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The BDNF SNP distribution was 65 (68%) Val/Val, 28 (30%) Val/Met, and 2 (2%) Met/Met for FMS and 40 (69%), 17(29%), and 1 (2%) for HNC, respectively. The serum high-sensitivity C-reactive protein (hsCRP)and body mass index (BMI) in FMS were higher than in HNC. The FMS with BDNF Val66Val had significantly higher mean BMI (P = 0.0001) and hsCRP (P = 0.02) than did FMS carrying the Val66Met genotype. This pattern was not found in HNC. Phenotypic measures of subjective pain, pain threshold, depression, or insomnia did not relate to either of the BDNF SNPs in FMS. The relative distribution BDNF SNPs did not differ between FMS and HNC. The BDNF Val66Met polymorphism is not selective for FMS. The BDNF Val66Val SNP identifies a subgroup of FMS with elevated hsCRP and higher BMI. This is the first study to associate a BDNF polymorphism with a FMS subgroup phenotype.

7 CFR 205.239 - Livestock living conditions.

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2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Livestock living conditions. 205.239 Section 205.239... PROVISIONS NATIONAL ORGANIC PROGRAM Organic Production and Handling Requirements § 205.239 Livestock living conditions. (a) The producer of an organic livestock operation must establish and maintain livestock living...

7 CFR 205.405 - Denial of certification.

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2010-01-01

... PROVISIONS NATIONAL ORGANIC PROGRAM Certification § 205.405 Denial of certification. (a) When the certifying... organic program. (e) An applicant for certification who has received a written notification of... 7 Agriculture 3 2010-01-01 2010-01-01 false Denial of certification. 205.405 Section 205.405...

7 CFR 205.401 - Application for certification.

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2010-01-01

... PROVISIONS NATIONAL ORGANIC PROGRAM Certification § 205.401 Application for certification. A person seeking... certification to a certifying agent. The application must include the following information: (a) An organic... 7 Agriculture 3 2010-01-01 2010-01-01 false Application for certification. 205.401 Section 205.401...

7 CFR 62.205 - Conflict of interest.

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2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Conflict of interest. 62.205 Section 62.205 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Definitions Service § 62.205 Conflict of interest. No USDA official shall review any program documentation or...

10 CFR 205.371 - Definition of emergency.

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2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Definition of emergency. 205.371 Section 205.371 Energy...; Applications; Administrative Procedures and Sanctions Emergency Interconnection of Electric Facilities and the Transfer of Electricity to Alleviate An Emergency Shortage of Electric Power § 205.371 Definition of...

Brain-derived neurotrophic factor gene val66met polymorphism and executive functioning in patients with bipolar disorder Polimorfismo do gene do fator neurotrófico derivado do cérebro val66met e função executiva em pacientes com transtorno bipolar

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Juliana Fernandes Tramontina

2009-06-01

Full Text Available OBJECTIVE: In the present study, we investigate the association between the val66met polymorphism of the brain-derived neurotrophic factor (BNDF and the performance on the Wisconsin Card Sorting Test in a sample of Caucasian Brazilian patients with bipolar disorder. METHOD: Sixty-four patients with bipolar disorder were assessed and their performance on the Wisconsin Card Sorting Test was compared with the allele frequency and genotype of the val66met polymorphism of the brain-derived neurotrophic factor. RESULTS: The percentage of non-perseverative errors was significantly higher among patients with the val/val genotype. There was no association between (BNDF genotype frequency and other Wisconsin Card Sorting Test domains. CONCLUSION: Our results did not replicate previous descriptions of an association between a worse cognitive performance and the presence of the met allele of the val66met brain-derived neurotrophic factor gene polymorphism.OBJETIVO: O presente estudo tem por objetivo investigar a associação entre o polimorfismo val66met do gene do fator neurotrófico derivado do cérebro (BDNF e o desempenho cognitivo no Teste Wisconsin de Classificação de Cartas em uma amostra de pacientes bipolares brasileiros caucasianos. MÉTODO: Sessenta e quatro pacientes com transtorno bipolar foram avaliados em relação a sua cognição por meio do Teste Wisconsin de Classificação de Cartas que foi comparada com a freqüência alélica e genotípica do polimorfismo val66met do gene do fator neurotrófico derivado do cérebro. RESULTADOS: O percentual de erros não-perseverativos foi significativamente maior nos indivíduos com genótipo val/val. Não foi encontrada diferença significativa entre a freqüência genotípica do polimorfismo do BDNF e os outros domínios do Teste Wisconsin de Classificação de Cartas. CONCLUSÃO: O estudo do polimorfismo val66met em relação ao desempenho executivo em pacientes bipolares caucasianos de uma

24 CFR 570.466 - Additional application submission requirements for Pockets of Poverty-employment opportunities.

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2010-04-01

... requirements for Pockets of Poverty-employment opportunities. 570.466 Section 570.466 Housing and Urban... application submission requirements for Pockets of Poverty—employment opportunities. Applicants for Action Grants under the Pockets of Poverty provision must describe the number and, to the extent possible, the...

Modified melanocortin tetrapeptide Ac-His-dPhe-Arg-Trp-NH at the arginine side chain with ureas and thioureas.

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Joseph, C G; Sorensen, N B; Wood, M S; Xiang, Z; Moore, M C; Haskell-Luevano, C

2005-11-01

The Ac-His-dPhe-Arg-Trp-NH2 tetrapeptide is a nonselective melanocortin agonist and replacement of Arg in the tetrapeptide with acidic, basic or neutral amino acids results in reduced potency at the melanocortin receptor (MCR) isoforms (MC1R and MC3-5R). To determine the importance of the positive charge and the guanidine moiety for melanocortin activity, a series of urea- and thiourea-substituted tetrapeptides were designed. Replacement of Arg with Lys or ornithine reduced agonist activity at the mouse mMC1 and mMC3-5 receptors, thus supporting the hypothesis that the guanidine moiety is important for receptor potency, particularly at the MC3-5 receptors. The Arg side chain-modified tetrapeptides examined in this study include substituted phenyl, naphthyl, and aliphatic urea and thiourea residues using a Lys side-chain template. These ligands elicit full-agonist pharmacology at the mouse MCRs examined in this study.

Frequency of the GPR7 Tyr135Phe allelic variant in lean and obese subjects.

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Pelosini, C; Maffei, M; Ceccarini, G; Marchi, M; Marsili, A; Galli, G; Scartabelli, G; Tamberi, A; Latrofa, F; Fierabracci, P; Vitti, P; Pinchera, A; Santini, F

2013-10-01

GPR7, the endogenous coupled receptor for neuropeptide B and neuropeptide W, is expressed in several regions of the central nervous system, which are involved in the regulation of feeding behavior. GPR7 affects the regulation of energy balance through a mechanism independent of leptin and melanocortin pathways. Aim of this study was to investigate whether GPR7 gene mutations can be detected in human subjects and, in that event, if they are differently distributed among lean and obese subjects. The coding region of GPR7 were sequenced in 150 obese patients and 100 normal-weight unrelated controls. Functional studies of the allelic variants were performed. One genetic GPR7 variant was found (Tyr135Phe - rs33977775) in obese subjects (13.3%) and lean control (25%). Functional studies did not reveal significant differences between the wild type and the Tyr135Phe allelic variants in their NPW-mediated capacity to inhibit forskolin-induced cAMP production. Screening of GPR7 gene mutations among lean and obese subjects revealed a Tyr135Phe allelic variant that was fairly common in the study population. As indicated by in vitro and in silico studies, this variant is unlikely to cause a functional derangement of the receptor.

48 CFR 731.205-46 - Travel costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Travel costs. 731.205-46 Section 731.205-46 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT GENERAL....205-46 Travel costs. It is USAID policy to require prior written approval of international travel by...

33 CFR 107.205 - Purpose and delegation.

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2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Purpose and delegation. 107.205 Section 107.205 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MARITIME... Cuban Territorial Waters § 107.205 Purpose and delegation. The purpose of this subpart is to implement...

42 CFR 50.205 - Consent form requirements.

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Consent form requirements. 50.205 Section 50.205 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS POLICIES OF GENERAL APPLICABILITY Sterilization of Persons in Federally Assisted Family Planning Projects § 50.205 Consent form...

40 CFR 205.57-1 - Test request.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Test request. 205.57-1 Section 205.57-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.57-1 Test request. (a) The...

Comparison of kokumi γ-[Glu](n>1)-Val and γ-[Glu](n>1)-Met synthesized through transpeptidation catalyzed by glutaminase from Bacillus amyloliquefaciens.

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Yang, Juan; Sun-Waterhouse, Dongxiao; Xie, Jin; Wang, Lan; Chen, Hong-Zhang; Cui, Chun; Zhao, Mouming

2018-05-01

A series of γ-[Glu] (n=2,3,4) -Val or γ-[Glu] (n=2,3,4) -Met were synthesized in the presence of donor (Gln) and corresponding acceptor (Val or Met) through transpeptidation catalyzed by the glutaminase from Bacillus amyloliquefaciens. Gln in excess significantly (p n>1) -Val/Met except for γ-Glu-Val/Met. The K m values for transpeptidase activity to yield γ-[Glu] (n=0,1,2,3) -Val increased with an elevated n, but remained essentially the same irrespective of n value for γ-[Glu] (n=0,1,2) -Met (which were 31-44% of that for γ-[Glu] 3 -Met). The highest K m value appearing when n = 3 (γ-[Glu] 3 -Val or γ-[Glu] 3 -Met) suggested the rising difficulty for synthesis when the number of donor increases. All the γ-[Glu] n -Val/Met substances exhibited kokumi properties and enhanced the continuity and umami taste of soy sauce as well as the thickness, mouthfulness and umaminess of model chicken broth. These results indicate the potential of the γ-[Glu] n -Val and γ-[Glu] n -Met as food flavor enhancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structure-function analysis of the OB and latch domains of chlorella virus DNA ligase.

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Samai, Poulami; Shuman, Stewart

2011-06-24

Chlorella virus DNA ligase (ChVLig) is a minimized eukaryal ATP-dependent DNA sealing enzyme with an intrinsic nick-sensing function. ChVLig consists of three structural domains, nucleotidyltransferase (NTase), OB-fold, and latch, that envelop the nicked DNA as a C-shaped protein clamp. The OB domain engages the DNA minor groove on the face of the duplex behind the nick, and it makes contacts to amino acids in the NTase domain surrounding the ligase active site. The latch module occupies the DNA major groove flanking the nick. Residues at the tip of the latch contact the NTase domain to close the ligase clamp. Here we performed a structure-guided mutational analysis of the OB and latch domains. Alanine scanning defined seven individual amino acids as essential in vivo (Lys-274, Arg-285, Phe-286, and Val-288 in the OB domain; Asn-214, Phe-215, and Tyr-217 in the latch), after which structure-activity relations were clarified by conservative substitutions. Biochemical tests of the composite nick sealing reaction and of each of the three chemical steps of the ligation pathway highlighted the importance of Arg-285 and Phe-286 in the catalysis of the DNA adenylylation and phosphodiester synthesis reactions. Phe-286 interacts with the nick 5'-phosphate nucleotide and the 3'-OH base pair and distorts the DNA helical conformation at the nick. Arg-285 is a key component of the OB-NTase interface, where it forms a salt bridge to the essential Asp-29 side chain, which is imputed to coordinate divalent metal catalysts during the nick sealing steps.

Structure-Function Analysis of the OB and Latch Domains of Chlorella Virus DNA Ligase*

Science.gov (United States)

Samai, Poulami; Shuman, Stewart

2011-01-01

Chlorella virus DNA ligase (ChVLig) is a minimized eukaryal ATP-dependent DNA sealing enzyme with an intrinsic nick-sensing function. ChVLig consists of three structural domains, nucleotidyltransferase (NTase), OB-fold, and latch, that envelop the nicked DNA as a C-shaped protein clamp. The OB domain engages the DNA minor groove on the face of the duplex behind the nick, and it makes contacts to amino acids in the NTase domain surrounding the ligase active site. The latch module occupies the DNA major groove flanking the nick. Residues at the tip of the latch contact the NTase domain to close the ligase clamp. Here we performed a structure-guided mutational analysis of the OB and latch domains. Alanine scanning defined seven individual amino acids as essential in vivo (Lys-274, Arg-285, Phe-286, and Val-288 in the OB domain; Asn-214, Phe-215, and Tyr-217 in the latch), after which structure-activity relations were clarified by conservative substitutions. Biochemical tests of the composite nick sealing reaction and of each of the three chemical steps of the ligation pathway highlighted the importance of Arg-285 and Phe-286 in the catalysis of the DNA adenylylation and phosphodiester synthesis reactions. Phe-286 interacts with the nick 5′-phosphate nucleotide and the 3′-OH base pair and distorts the DNA helical conformation at the nick. Arg-285 is a key component of the OB-NTase interface, where it forms a salt bridge to the essential Asp-29 side chain, which is imputed to coordinate divalent metal catalysts during the nick sealing steps. PMID:21527793

29 CFR 570.119 - Fourteen-year minimum.

Science.gov (United States)

2010-07-01

... Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION General Statements of Interpretation of the Child Labor Provisions of the Fair Labor Standards Act of 1938, as Amended Oppressive Child Labor § 570.119 Fourteen-year...

29 CFR 570.118 - Sixteen-year minimum.

Science.gov (United States)

2010-07-01

... Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION General Statements of Interpretation of the Child Labor Provisions of the Fair Labor Standards Act of 1938, as Amended Oppressive Child Labor § 570.118 Sixteen-year...

Influence of COMT Val158Met polymorphism on emotional decision-making: A sex-dependent relationship?

Science.gov (United States)

Costa, Danielle de Souza; Bechara, Antoine; de Paula, Jonas Jardim; Romano-Silva, Marco Aurélio; Correa, Humberto; Lage, Guilherme Menezes; Miranda, Débora Marques de; Malloy-Diniz, Leandro Fernandes

2016-12-30

The biological underpinnings of sex-related differences in decision-making are still under-explored. The COMT gene is related to sexual dimorphism and with different choices made under uncertainty, albeit no study has specifically investigated a moderation effect of sex on the association between the COMT gene and the performance on decision-making paradigms. In this study, we investigated the influence of the COMT Val 158 Met polymorphism on Iowa Gambling Task (IGT) performance depending on sex in a healthy adult sample. Participants were 192 healthy adults (84 men and 108 women). The first 40 choices in the IGT were considered decisions under ambiguity and the last 60 choices decisions under risk. To test our moderation hypothesis we used a separate regressions approach. The results revealed a sex-dependent effect of COMT Va l 158 Met polymorphism on decision-making as measured by the IGT. Val/Val women showed the best performance in the last trials of the IGT. Therefore, the COMT Val 158 Met polymorphism may be considered a genetic marker underlying sex differences in decision-making. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

29 CFR 780.205 - Nursery activities generally.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Nursery activities generally. 780.205 Section 780.205 Labor... as It Relates to Specific Situations Nursery and Landscaping Operations § 780.205 Nursery activities generally. The employees of a nursery who are engaged in the following activities are employed in...

48 CFR 12.205 - Offers.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Offers. 12.205 Section 12... ACQUISITION OF COMMERCIAL ITEMS Special Requirements for the Acquisition of Commercial Items 12.205 Offers. (a) Where technical information is necessary for evaluation of offers, agencies should, as part of market...

Glucosinolate diversity within a phylogenetic framework of the tribe Cardamineae (Brassicaceae) unraveled with HPLC-MS/MS and NMR-based analytical distinction of 70 desulfoglucosinolates

DEFF Research Database (Denmark)

Olsen, Carl Erik; Huang, Xiao-Chen; Hansen, Cecilie Ida Cetti

2016-01-01

. This included glucosinolates apparently derived from Met, Phe, Trp, Val/Leu, Ile and higher homologues. Normal side chain elongation and side chain decoration by oxidation or methylation was observed, as well as rare abnormal side chain decoration (hydroxylation of aliphatics at the δ rather than β...

HR-TEM and FT-Raman dataset of the caffeine interacted Phe–Phe peptide nanotube for possible sensing applications

OpenAIRE

Narayanan, A. Lakshmi; Dhamodaran, M.; Solomon, J. Samu; Karthikeyan, B.; Govindhan, R.

2017-01-01

Sensing ability of caffeine interaction with Phe-Phe annotates (PNTs), is presented (Govindhan et al., 2017; Karthikeyan et al., 2014; Tavagnacco et al., 2013; Kennedy et al., 2011; Wang et al., 2017) [1–5] in this data set. Investigation of synthesized caffeine carrying peptide nanotubes are carried out by FT-Raman spectral analysis and high resolution transmission electron microscopy (HR-TEM). Particle size of the caffeine loaded PNTs is < 40 nm. The FT-Raman spectrum signals are enhanced i...

The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

Directory of Open Access Journals (Sweden)

Kaja K Jasińska

Full Text Available Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265 is associated with children's (age 6-10 neural activation patterns during a reading task (n = 81 using functional magnetic resonance imaging (fMRI, genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

Science.gov (United States)

Jasińska, Kaja K; Molfese, Peter J; Kornilov, Sergey A; Mencl, W Einar; Frost, Stephen J; Lee, Maria; Pugh, Kenneth R; Grigorenko, Elena L; Landi, Nicole

2016-01-01

Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

7 CFR 205.509 - Peer review panel.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Peer review panel. 205.509 Section 205.509 Agriculture... PROVISIONS NATIONAL ORGANIC PROGRAM Accreditation of Certifying Agents § 205.509 Peer review panel. The Administrator shall establish a peer review panel pursuant to the Federal Advisory Committee Act (FACA) (5 U.S.C...

Characterization of molecular determinants of the conformational stability of macrophage migration inhibitory factor: leucine 46 hydrophobic pocket.

Directory of Open Access Journals (Sweden)

Farah El-Turk

Full Text Available Macrophage Migration Inhibitory Factor (MIF is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the β-strand β3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF's trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G, alanine (L46A and phenylalanine (L46F, and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state.

48 CFR 931.205 - Selected costs.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Selected costs. 931.205... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 931.205 Selected costs. ...

48 CFR 1231.205 - Selected costs.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Selected costs. 1231.205... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 1231.205 Selected costs. ...

48 CFR 31.205 - Selected costs.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Selected costs. 31.205... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.205 Selected costs. ...

48 CFR 1331.205 - Selected costs.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Selected costs. 1331.205... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 1331.205 Selected costs. ...

48 CFR 631.205 - Selected costs.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Selected costs. 631.205... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts with Commercial Organizations 631.205 Selected costs. ...

Structural insights into cellulolytic and chitinolytic enzymes revealing crucial residues of insect β-N-acetyl-D-hexosaminidase.

Directory of Open Access Journals (Sweden)

Tian Liu

Full Text Available The chemical similarity of cellulose and chitin supports the idea that their corresponding hydrolytic enzymes would bind β-1,4-linked glucose residues in a similar manner. A structural and mutational analysis was performed for the plant cellulolytic enzyme BGlu1 from Oryza sativa and the insect chitinolytic enzyme OfHex1 from Ostrinia furnacalis. Although BGlu1 shows little amino-acid sequence or topological similarity with OfHex1, three residues (Trp(490, Glu(328, Val(327 in OfHex1, and Trp(358, Tyr(131 and Ile(179 in BGlu1 were identified as being conserved in the +1 sugar binding site. OfHex1 Glu(328 together with Trp(490 was confirmed to be necessary for substrate binding. The mutant E328A exhibited a 8-fold increment in K(m for (GlcNAc(2 and a 42-fold increment in K(i for TMG-chitotriomycin. A crystal structure of E328A in complex with TMG-chitotriomycin was resolved at 2.5 Å, revealing the obvious conformational changes of the catalytic residues (Glu(368 and Asp(367 and the absence of the hydrogen bond between E328A and the C3-OH of the +1 sugar. V327G exhibited the same activity as the wild-type, but acquired the ability to efficiently hydrolyse β-1,2-linked GlcNAc in contrast to the wild-type. Thus, Glu(328 and Val(327 were identified as important for substrate-binding and as glycosidic-bond determinants. A structure-based sequence alignment confirmed the spatial conservation of these three residues in most plant cellulolytic, insect and bacterial chitinolytic enzymes.

29 CFR 570.7 - Documentary evidence required for issuance of a certificate of age.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Documentary evidence required for issuance of a certificate of age. 570.7 Section 570.7 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Certificates...

Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice

Science.gov (United States)

Ieraci, Alessandro; Madaio, Alessandro I; Mallei, Alessandra; Lee, Francis S; Popoli, Maurizio

2016-01-01

Several studies have shown that exercise improves cognitive functions and emotional behaviors. Positive effects of exercise have been associated with enhanced brain plasticity, adult hippocampal neurogenesis, and increased levels of brain-derived neurotrophic factor (BDNF). However, a substantial variability of individual response to exercise has been described, which may be accounted for by individual genetic variants. Here, we have assessed whether and how the common human BDNF Val66Met polymorphism influences the neurobiological effects modulated by exercise in BDNF Val66Met knock-in male mice. Wild-type (BDNFVal/Val) and homozygous BDNF Val66Met (BDNFMet/Met) male mice were housed in cages equipped with or without running wheels for 4 weeks. Changes in behavioral phenotype, hippocampal adult neurogenesis, and gene expression were evaluated in exercised and sedentary control mice. We found that exercise reduced the latency to feed in the novelty suppressed feeding and the immobility time in the forced swimming test in BDNFVal/Val but not in BDNFMet/Met mice. Hippocampal neurogenesis was reduced in BDNFMet/Met mice compared with BDNFVal/Val mice. BDNFMet/Met mice had lower basal BDNF protein levels in the hippocampus, which was not recovered following exercise. Moreover, exercise-induced expression of total BDNF, BDNF splice variants 1, 2, 4, 6 and fibronectin type III domain-containing protein 5 (FNDC5) mRNA levels were absent or reduced in the dentate gyrus of BDNFMet/Met mice. Exercise failed to enhance PGC-1α and FNDC5 mRNA levels in the BDNFMet/Met muscle. Overall these results indicate that, in adult male mice, the BDNF Val66Met polymorphism impairs the beneficial behavioral and neuroplasticity effects induced by physical exercise. PMID:27388329

The BDNF Val66Met polymorphism: relation to familiar risk of affective disorder, BDNF levels and salivary cortisol.

Science.gov (United States)

Vinberg, Maj; Trajkovska, Viktorija; Bennike, Bente; Knorr, Ulla; Knudsen, Gitte M; Kessing, Lars V

2009-10-01

Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are considered to play an important role in the pathophysiology of affective disorders. The aim of the present study was to investigate whether the BDNF Val66Met polymorphism is associated with a familiar risk of affective disorder and whether these genotypes affect whole blood BDNF level and salivary cortisol. In a high-risk study, healthy monozygotic and dizygotic twins with and without a co-twin (high- and low-risk twins, respectively) history of affective disorder were identified through nationwide registers. Familiar predisposition to unipolar and bipolar disorder was not associated with any specific genotype pattern of the BDNF Val66Met polymorphism, not in this sample of 124 val/val, 58 val/met and 8 met/met individuals. However, the combination of having a high familiar risk of affective disorder and the met allele was associated with a higher whole blood BDNF (p=0.02) and a higher evening cortisol level (p=0.01), but not with awakening cortisol. Individuals at high risk of affective disorders and who are carriers of the met allele of the Val66Met polymorphism may present with an enhanced stress response. The presence of a specific genotype alone may not enhance the risk of developing an affective episode. Rather, the altered stress response may be expressed only in combination with other risk variants through interactions with the environment.

Met-enkephalyl-Arg6-Phe7 immunoreactivity in a human neuroblastoma cell line: effect of dibutyryl 3':5'-cyclic AMP and reserpine.

Science.gov (United States)

Boarder, M R; Marriott, D; Adams, M

1986-12-30

The carboxy terminal part of the proenkephalin A sequence is the 31 amino acid peptide B, which has as its final seven amino acids the sequence of the opioid peptide Met-enkephalyl-Arg6-Phe7. Using a radioimmunoassay which recognises both these peptides we have investigated the relative amounts of peptide B and Met-enkephalyl-Arg6-Phe7 in a human neuroblastoma cell line. We show that these cells contain peptide B-like immunoreactivity but not its heptapeptide fragment. This may be due to lack of proteolytic activity cleaving Met-enkephalyl-Arg6-Phe7 from its precursor, peptide B. On treatment with dibutyryl cyclic AMP the level of immunoreactivity approximately doubles, due to increased amounts of peptide B-like immunoreactivity. Treatment with reserpine, which increases conversion of peptide B to the heptapeptide in bovine chromaffin cells in culture does not stimulate the accumulation of Met-enkephalyl-Arg6-Phe7 in the human neuroblastoma cells. The results are discussed with respect to peptide processing.

7 CFR 205.1 - Meaning of words.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Meaning of words. 205.1 Section 205.1 Agriculture... PROVISIONS NATIONAL ORGANIC PROGRAM Definitions § 205.1 Meaning of words. For the purpose of the regulations in this subpart, words in the singular form shall be deemed to impart the plural and vice versa, as...

Effects of Mind-Body Training on Personality and Behavioral Activation and Inhibition System According to BDNF Val66Met Polymorphism.

Science.gov (United States)

Jung, Ye-Ha; Lee, Ul Soon; Jang, Joon Hwan; Kang, Do-Hyung

2016-05-01

It has been known that mind-body training (MBT) can affect personality and behavior system as well as emotional well-being, but different effects of MBT on them has not been reported according to BDNF genetic polymorphism. Healthy subjects consisted of 64 subjects and the MBT group who practiced meditation regularly consisted of 72 practitioners. Participants completed neuroticism-extraversion-openness (NEO) Five-Factor Inventory and Behavioral Activation System/Behavioral Inhibition System (BAS/BIS) scales. All subjects were genotyped for the BDNF Val66Met polymorphism. In the same genotypes of the BDNF Val/Val+Val/Met group, MBT group showed the increased Extraversion (p=0.033) and the increased Openness to Experience (p=0.004) compared to the control group. Also, in the same Met/Met carriers, MBT group exhibited the increase of Extraversion (p=0.008), the reduction of Neuroticism (p=0.002), and the increase of Openness to Experience (p=0.008) compared to the control group. In the same genotypes of the BDNF Val/Val+Val/Met group, MBT group showed the decreased BAS-Reward Responsiveness (p=0.016) and the decrease of BIS (p=0.004) compared to the control group. In the BDNF Met/Met group, MBT group increased BAS-Fun Seeking (p=0.045) and decreased BIS (p=0.013) compared to the control group. MBT would differently contribute to NEO personality and BAS/BIS according to BDNF genetic polymorphism, compensating for different vulnerable traits based on each genotype.

Executive control in schizophrenia: a preliminary study on the moderating role of COMT Val158Met for comorbid alcohol and substance use disorders.

Science.gov (United States)

Carrà, Giuseppe; Nicolini, Gabriella; Crocamo, Cristina; Lax, Annamaria; Amidani, Francesca; Bartoli, Francesco; Castellano, Filippo; Chiorazzi, Alessia; Gamba, Giulia; Papagno, Costanza; Clerici, Massimo

2017-07-01

A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val158Met) appears to influence cognition in people with alcohol/substance use disorders (AUD/SUD) and in those with psychosis. To explore the potential moderating effect of these factors, a cross-sectional study was conducted, randomly recruiting subjects with DSM-IV diagnosis of schizophrenia. AUD/SUD was rigorously assessed, as well as COMT Val158Met polymorphism. Executive control functioning was measured using the Intra-Extra Dimensional Set Shift (IED). The effect of a possible interaction between comorbid AUD/SUD and COMT Val158Met polymorphism on IED scores was explored. Subjects with schizophrenia, comorbid AUD/SUD, and MetMet carriers for SNP rs4680 of the COMT gene showed worse performance on IED completed stages scores, as compared with individuals with ValVal genotype. However, among subjects without AUD/SUD, those with the MetMet variant performed better than people carrying ValVal genotype. This study is the first to date examining the impact of COMT on cognition in a highly representative sample of people with schizophrenia and comorbid AUD/SUD. Differential moderating effects of COMT Val/Met genotype variations may similarly influence executive functions in people with schizophrenia and comorbid AUD/SUD.

40 CFR 205.165 - Definitions.

Science.gov (United States)

2010-07-01

... respect to the parameters listed in § 205.168 of this subpart. (2) Exhaust header pipe means any tube of... be “exhaust header pipes.” (3) Failing exhaust system means that, when installed on any Federally... EQUIPMENT NOISE EMISSION CONTROLS Motorcycle Exhaust Systems § 205.165 Definitions. (a) As used in this...

38 CFR 3.205 - Marriage.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Marriage. 3.205 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.205 Marriage. (a) Proof of marriage. Marriage is established by one of the following types of evidence: (1) Copy or abstract of the...

ICTR-PHE 2016: Strength in numbers

CERN Multimedia

Anaïs Schaeffer

2016-01-01

The third biennial ICTR-PHE medical conference (see here) concluded last Friday, 19 February, once again on a very successful note. More than 400 participants from all over the world met over five days and then returned to their home institutes with new ideas, new collaboration prospects and optimistic visions for the future of cancer therapy.   During the week, the participants had the opportunity to look at the 80 posters presented by young researchers. (Image: Salvatore Fiore) During the five-day conference, a large spectrum of topics was covered – radiobiology, nuclear medicine, detectors and imaging, new technologies etc.– and a large amount of new research was presented. “I’ve been impressed by many wonderful lectures, which promise great progress in the future,” says Jacques Bernier, Chair of the Department of Radio-Oncology at the Genolier Clinic in Geneva and co-chair of the conference with CERN’s Manjit Dosanj...

48 CFR 53.205-1 - Paid advertisements.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Paid advertisements. 53.205-1 Section 53.205-1 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Prescription of Forms 53.205-1 Paid advertisements. SF 1449, prescribed in 53.212, shall be used to place orders for paid...

40 CFR 205.3 - Number and gender.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Number and gender. 205.3 Section 205.3... EQUIPMENT NOISE EMISSION CONTROLS General Provisions § 205.3 Number and gender. As used in this part, words in the -singular shall be deemed to import -the plural, and words in the masculine -gender shall be...

7 CFR 58.205 - Meaning of words.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Meaning of words. 58.205 Section 58.205 Agriculture... Whole Milk, and Dry Buttermilk § 58.205 Meaning of words. For the purpose of the regulations in this subpart, words in the singular form shall be deemed to impart the plural and vice versa, as the case may...

BDNF Val66Met polymorphism moderates the link between child maltreatment and reappraisal ability.

Science.gov (United States)

Miu, A C; Cărnuţă, M; Vulturar, R; Szekely-Copîndean, R D; Bîlc, M I; Chiş, A; Cioară, M; Fernandez, K C; Szentágotai-Tătar, A; Gross, J J

2017-04-01

Child maltreatment is associated with increased risk for virtually all common mental disorders, but it is not yet clear why. One possible mechanism is emotion regulation ability. The present study investigated for the first time the influence of a BDNF Val66Met genotype × child maltreatment interaction on emotion regulation, and compared differential susceptibility and diathesis-stress models. A sample of N = 254 healthy volunteers were genotyped for the BDNF Val66Met polymorphism and underwent an experimental assessment of reappraisal ability (i.e. the success of using reappraisal to downregulate negative affect). A self-report instrument previously validated against a clinical interview was used to investigate child maltreatment. There was a significant BDNF Val66Met genotype × child maltreatment interaction (B = -0.31, P maltreated participants, and the highest level of reappraisal ability in non-maltreated participants. By assessing alternative models, we found that the best fitting model was in line with strong differential susceptibility. As expected, reappraisal ability was negatively correlated with depressive symptoms. Therefore, the BDNF Val66Met polymorphism moderates the link between child maltreatment and emotion regulation ability. Future studies could investigate whether improving reappraisal in maltreated BDNF Met carriers results in reduced risk for mental disorders. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

COMT Val158Met, but not BDNF Val66Met, is associated with white matter abnormalities of the temporal lobe in patients with first-episode, treatment-naïve major depressive disorder: a diffusion tensor imaging study

Directory of Open Access Journals (Sweden)

Hayashi K

2014-06-01

Full Text Available Kenji Hayashi,1 Reiji Yoshimura,1 Shingo Kakeda,2 Taro Kishi,3 Osamu Abe,4 Wakako Umene-Nakano,1 Asuka Katsuki,1 Hikaru Hori,1 Atsuko Ikenouchi-Sugita,1 Keita Watanabe,2 Satoru Ide,2 Issei Ueda,2 Junji Moriya,2 Nakao Iwata,3 Yukunori Korogi,2 Marek Kubicki,5 Jun Nakamura1 1Department of Psychiatry, 2Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Psychiatry, Fujita Health University, Toyoake, Japan; 4Department of Radiology, Nihon University School of Medicine, Tokyo, Japan; 5Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Abstract: We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF gene, and white matter changes in patients with major depressive disorder (MDD and healthy subjects using diffusion tensor imaging (DTI. We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years. Using DTI analysis with a tract-based spatial statistics (TBSS approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects. In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P<0.05. No correlations in fractional anisotropy, axial diffusivity, or radial diffusivity were observed between the MDD patients and the controls, either among those with the BDNF Val/Val genotype or among the BDNF Met-carriers. These results suggest an association

Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson's disease mouse model.

Science.gov (United States)

Zhang, YanFang; Chen, YiMei; Li, Lin; Hölscher, Christian

2015-10-15

Glucagon-like peptide 1 (GLP-1) is a hormone and a growth factor. GLP-1 mimetics are currently on the market as treatments for type 2 diabetes. They also have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a first clinical trial in PD patients showed promising results. (Val8)GLP-1-glu-PAL is a new GLP-1 analogue which has a longer biological half-life than exendin-4. We previously showed that (Val8)GLP-1-glu-PAL has neuroprotective properties. Here we tested the drug in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected (30mg/kg i.p.) along with (Val8)GLP-1-glu-PAL (25nmol/kg i.p.) once-daily for 8 days. (Val8)GLP-1-glu-PAL showed good effects in preventing the MPTP-induced motor impairment (Rotarod, open field locomotion, swim test), reduction in tyrosine hydroxylase levels (dopamine synthesis) in the substantia nigra, a reduction of activated caspase 3 levels, of TUNEL positive cell numbers, of the pro-apoptotic signaling molecule BAX and an increase in the growth signaling molecule Bcl-2. The results demonstrate that (Val8)GLP-1-glu-PAL shows promise as a novel treatment of PD. Copyright © 2015 Elsevier B.V. All rights reserved.

Contribution to the knowledge of the Val le Chico Uruguay formation

International Nuclear Information System (INIS)

Pirelli, H.

1999-01-01

This research has been designed to contribute with Val le Chico Uruguay formation knowledge, taking into the alkaline type tectonic environment, geochronology, granitoid types, lithologies and mineralizations existing in the area

Theoretical calculation of pKa reveals an important role of Arg205 in the activity and stability of Streptomyces sp. N174 chitosanase.

Science.gov (United States)

Fukamizo, T; Juffer, A H; Vogel, H J; Honda, Y; Tremblay, H; Boucher, I; Neugebauer, W A; Brzezinski, R

2000-08-18

Based on the crystal structure of chitosanase from Streptomyces sp. N174, we have calculated theoretical pK(a) values of the ionizable groups of this protein using a combination of the boundary element method and continuum electrostatics. The pK(a) value obtained for Arg(205), which is located in the catalytic cleft, was abnormally high (>20.0), indicating that the guanidyl group may interact strongly with nearby charges. Chitosanases possessing mutations in this position (R205A, R205H, and R205Y), produced by Streptomyces lividans expression system, were found to have less than 0.3% of the activity of the wild type enzyme and to possess thermal stabilities 4-5 kcal/mol lower than that of the wild type protein. In the crystal structure, the Arg(205) side chain is in close proximity to the Asp(145) side chain (theoretical pK(a), -1.6), which is in turn close to the Arg(190) side chain (theoretical pK(a), 17.7). These theoretical pK(a) values are abnormal, suggesting that both of these residues may participate in the Arg(205) interaction network. Activity and stability experiments using Asp(145)- and Arg(190)-mutated chitosanases (D145A and R190A) provide experimental data supporting the hypothesis derived from the theoretical pK(a) data and prompt the conclusion that Arg(205) forms a strong interaction network with Asp(145) and Arg(190) that stabilizes the catalytic cleft.

48 CFR 231.205 - Selected costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Selected costs. 231.205... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 231.205 Selected costs. ...

Data of evolutionary structure change: 1DEAA-2RI1A [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1DEAA-2RI1A 1DEA 2RI1 A A -MRLIPLTTAEQVGKWAARHIVNRINAFKPTADRPFVLG.../line> ASP CA 284 PHE CA 347 SER CA 228 1DEA... A 1DEAA ALVEMHKAGQVSFK 1DEA A 1DEAA GLU CA 160 ASP CA 224 VAL CA 284 1DEA

24 CFR 570.506 - Records to be maintained.

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2010-04-01

... (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES COMMUNITY DEVELOPMENT BLOCK GRANTS Grant Administration § 570.506...) which are projected to become available to low and moderate income persons through job turnover within...

COMT val108/158 met genotype affects neural but not cognitive processing in healthy individuals.

Science.gov (United States)

Dennis, Nancy A; Need, Anna C; LaBar, Kevin S; Waters-Metenier, Sheena; Cirulli, Elizabeth T; Kragel, James; Goldstein, David B; Cabeza, Roberto

2010-03-01

The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496-1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output.

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults.

Science.gov (United States)

Azeredo, Lucas A de; De Nardi, Tatiana; Levandowski, Mateus L; Tractenberg, Saulo G; Kommers-Molina, Julia; Wieck, Andrea; Irigaray, Tatiana Q; Silva, Irênio G da; Grassi-Oliveira, Rodrigo

2017-01-01

Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

The brain-derived neurotrophic factor (BDNF gene Val66Met polymorphism affects memory performance in older adults

Directory of Open Access Journals (Sweden)

Lucas A. de Azeredo

Full Text Available Objective: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Methods: Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR, delayed verbal recall (DVR, and memory retention rate. Results: BDNF Met allele carriers had lower DVR scores (p = 0.004 and a decline in memory retention (p = 0.017 when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088. Conclusion: These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

miRNA-205 affects infiltration and metastasis of breast cancer

International Nuclear Information System (INIS)

Wang, Zhouquan; Liao, Hehe; Deng, Zhiping; Yang, Po; Du, Ning; Zhanng, Yunfeng; Ren, Hong

2013-01-01

Highlights: •We detected expression of miR-205 in breast cancer cell lines and tissue samples. •We suggest miR-205 is downregulated in human breast cancer tissues and MCF7 cells. •We suggest the lower expression of miR-205 play a role in breast cancer onset. •These data suggest that miR-205 directly targets HER3 in human breast cancer. -- Abstract: Background: An increasing number of studies have shown that miRNAs are commonly deregulated in human malignancies, but little is known about the function of miRNA-205 (miR-205) in human breast cancer. The present study investigated the influence of miR-205 on breast cancer malignancy. Methods: The expression level of miR-205 in the MCF7 breast cancer cell line was determined by quantitative (q)RT-PCR. We then analyzed the expression of miR-205 in breast cancer and paired non-tumor tissues. Finally, the roles of miR-205 in regulating tumor proliferation, apoptosis, migration, and target gene expression were studied by MTT assay, flow cytometry, qRT-PCR, Western blotting and luciferase assay. Results: miR-205 was downregulated in breast cancer cells or tissues compared with normal breast cell lines or non-tumor tissues. Overexpression of miR-205 reduced the growth and colony-formation capacity of MCF7 cells by inducing apoptosis. Overexpression of miR-205 inhibited MCF7 cell migration and invasiveness. By bioinformation analysis, miR-205 was predicted to bind to the 3′ untranslated regions of human epidermal growth factor receptor (HER)3 mRNA, and upregulation of miR-205 reduced HER3 protein expression. Conclusion: miR-205 is a tumor suppressor in human breast cancer by post-transcriptional inhibition of HER3 expression

Peptide design using alpha,beta-dehydro amino acids: from beta-turns to helical hairpins.

Science.gov (United States)

Mathur, Puniti; Ramakumar, S; Chauhan, V S

2004-01-01

Incorporation of alpha,beta-dehydrophenylalanine (DeltaPhe) residue in peptides induces folded conformations: beta-turns in short peptides and 3(10)-helices in larger ones. A few exceptions-namely, alpha-helix or flat beta-bend ribbon structures-have also been reported in a few cases. The most favorable conformation of DeltaPhe residues are (phi,psi) approximately (-60 degrees, -30 degrees ), (-60 degrees, 150 degrees ), (80 degrees, 0 degrees ) or their enantiomers. DeltaPhe is an achiral and planar residue. These features have been exploited in designing DeltaPhe zippers and helix-turn-helix motifs. DeltaPhe can be incorporated in both right and left-handed helices. In fact, consecutive occurrence of three or more DeltaPhe amino acids induce left-handed screw sense in peptides containing L-amino acids. Weak interactions involving the DeltaPhe residue play an important role in molecular association. The C--H.O==C hydrogen bond between the DeltaPhe side-chain and backbone carboxyl moiety, pi-pi stacking interactions between DeltaPhe side chains belonging to enantiomeric helices have shown to stabilize folding. The unusual capability of a DeltaPhe ring to form the hub of multicentered interactions namely, a donor in aromatic C--H.pi and C--H.O==C and an acceptor in a CH(3).pi interaction suggests its exploitation in introducing long-range interactions in the folding of supersecondary structures. Copyright 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004

Um novo Kant: homenagem a Valério Rohden

Directory of Open Access Journals (Sweden)

Delamar José Volpato Dutra

2010-05-01

Full Text Available http://dx.doi.org/10.5007/1677-2954.2010v9n2p157 Valério Rohden nasceu em Braço do Norte, SC, em 14 de agosto 1937, e faleceu no dia 19/09/2010 em Curitiba, PR, tendo sido enterrado em Porto Alegre, RS.

40 CFR 300.205 - Planning and coordination structure.

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2010-07-01

... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Planning and coordination structure. 300.205 Section 300.205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... POLLUTION CONTINGENCY PLAN Planning and Preparedness § 300.205 Planning and coordination structure. (a...

7 CFR 205.506 - Granting accreditation.

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2010-01-01

..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) ORGANIC FOODS PRODUCTION ACT PROVISIONS NATIONAL ORGANIC PROGRAM Accreditation of Certifying Agents § 205.506 Granting accreditation. (a... accreditation as provided in § 205.510(c), the certifying agent voluntarily ceases its certification activities...

48 CFR 31.205-8 - Contributions or donations.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contributions or donations. 31.205-8 Section 31.205-8 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... Organizations 31.205-8 Contributions or donations. Contributions or donations, including cash, property and...

28 CFR 16.205 - Closed meetings-Informal procedures.

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2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Closed meetings-Informal procedures. 16.205 Section 16.205 Judicial Administration DEPARTMENT OF JUSTICE PRODUCTION OR DISCLOSURE OF MATERIAL OR INFORMATION Public Observation of Parole Commission Meetings § 16.205 Closed meetings—Informal...

40 CFR 205.59 - Recall of noncomplying vehicles.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Recall of noncomplying vehicles. 205.59 Section 205.59 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.59 Recall...

45 CFR 1230.205 - Professional and technical services.

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2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Professional and technical services. 1230.205 Section 1230.205 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE NEW RESTRICTIONS ON LOBBYING Activities by Own Employees § 1230.205...

45 CFR 604.205 - Professional and technical services.

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2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Professional and technical services. 604.205 Section 604.205 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION NEW RESTRICTIONS ON LOBBYING Activities by Own Employees § 604.205 Professional and technical...

Modification of depression by COMT val158met polymorphism in children exposed to early severe psychosocial deprivation

Science.gov (United States)

Drury, Stacy S; Theall, Katherine P; Smyke, Anna T; Keats, Bronya JB; Egger, Helen L; Nelson, Charles A; Fox, Nathan A; Marshall, Peter J; Zeanah, Charles H

2014-01-01

Objective To examine the impact of the Catechol-O-Methyltransferase (COMT) val158met allele on depressive symptoms in young children exposed to early severe social deprivation as a result of being raised in institutions. Methods 136 children from the Bucharest Early Intervention Project (BEIP) were randomized before 31 months of age to either care as usual (CAU) in institutions or placement in newly created foster care (FCG). At 54 months of age, a psychiatric assessment using the Preschool Age Psychiatric Assessment (PAPA) was completed. DNA was collected and genotyped for the COMT val158met polymorphism. Multivariate analysis examined the relationship between COMT alleles and depressive symptoms. Results Mean level of depressive symptoms was lower among participants with the met allele compared to those with two copies of the val allele (p <0.05). Controlling for group and gender, the rate of depressive symptoms was significantly lower among participants with the met/met or the met/val genotype (adjusted relative risk (aRR) = 0.67, 95% CI = 0.45, 0.99) compared to participants with the val/val genotype, indicating an intermediate impact for heterozygotes consistent with the biological impact of this polymorphism. The impact of genotype within groups differed significantly. There was a significant protective effect of the met allele on depressive symptoms within the CAU group, however there was no relationship seen within the FCG group. Conclusions This is the first study, to our knowledge, to find evidence of a gene × environment interaction in the setting of early social deprivation. These results support the hypothesis that individual genetic differences may explain some of the variability in recovery amongst children exposed to early severe social deprivation. PMID:20403637

41 CFR 101-6.205-3 - Elementary and secondary schools.

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2010-07-01

... schools. 101-6.205-3 Section 101-6.205-3 Public Contracts and Property Management Federal Property...-Nondiscrimination in Programs Receiving Federal Financial Assistance § 101-6.205-3 Elementary and secondary schools. The requirements of §§ 101-6.205-1 and 101-6.205-2 with respect to any elementary or secondary school...

48 CFR 1851.205 - Contract clause.

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2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contract clause. 1851.205 Section 1851.205 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CONTRACT MANAGEMENT USE OF GOVERNMENT SOURCES BY CONTRACTORS Contractor Use of Interagency Fleet Management...

33 CFR 136.205 - Compensation allowable.

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2010-07-01

...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.205 Compensation... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.205...

48 CFR 1631.205-71 - FEHBP bad debts.

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2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true FEHBP bad debts. 1631.205-71 Section 1631.205-71 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL... AND PROCEDURES Contracts With Commercial Organizations 1631.205-71 FEHBP bad debts. Erroneous benefit...

40 CFR 205.56 - Testing by the Administrator.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Testing by the Administrator. 205.56 Section 205.56 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.56 Testing by the...

40 CFR 205.55-5 - Labeling-exterior. [Reserved

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Labeling-exterior. [Reserved] 205.55-5 Section 205.55-5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.55-5 Labeling...

48 CFR 31.205-28 - Other business expenses.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Other business expenses. 31.205-28 Section 31.205-28 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... Organizations 31.205-28 Other business expenses. The following types of recurring costs are allowable (a...

Sensitivities of a Standard Test Method for the Determination of the pHe of Bioethanol and Suggestions for Improvement

Directory of Open Access Journals (Sweden)

Paul J. Brewer

2010-11-01

Full Text Available An assessment of the sensitivities of the critical parameters in the ASTM D6423 documentary standard method for the measurement of pHe in (bioethanol has been undertaken. Repeatability of measurements made using the same glass electrode and reproducibility between different glass electrodes have been identified as the main contributors to the uncertainty of the values produced. Strategies to reduce the uncertainty of the measurement have been identified and tested. Both increasing the time after which the pHe measurement is made following immersion in the sample, and rinsing the glass electrode with ethanol prior to immersion in the sample, have been shown to be effective in reducing the uncertainty of the numerical value produced. However, it is acknowledged that the values produced using these modified approaches may not be directly compared with those obtained using the documentary ASTM method since pHe is defined operationally by the process used to measure it.

COOH-terminal substitutions in the serpin C1 inhibitor that cause loop overinsertion and subsequent multimerization

NARCIS (Netherlands)

Eldering, E.; Verpy, E.; Roem, D.; Meo, T.; Tosi, M.

1995-01-01

The region COOH-terminal to the reactive center loop is highly conserved in the serine protease inhibitor (serpin) family. We have studied the structural consequences of three substitutions (Val451-->Met, Phe455-->Ser, and Pro476-->Ser) found in this region of C1 inhibitor in patients suffering from

A comparison of the nutritional quality of organic and conventional ready-to-eat breakfast cereals based on NuVal scores.

Science.gov (United States)

Woodbury, Nancy J; George, Valerie A

2014-07-01

To identify whether there were differences in nutritional quality between organic and conventional ready-to-eat breakfast cereals of similar types, based on NuVal scores. The current descriptive study analysed NuVal scores for 829 ready-to-eat breakfast cereals and eighteen different cereal types. ANOVA was used to compare the mean NuVal scores of 723 conventional cereals with those of 106 organic cereals. Ready-to-eat breakfast cereals (n 829) with NuVal scores. Not applicable. There was no significant difference in NuVal scores between conventional (mean 28·4 (sd 13·4)) and organic (mean 30·6 (sd 13·2)) cereal types. Consumers who choose the organic version of a ready-to-eat breakfast cereal believing that nutritional quality is superior may not be making a valid assumption. Public health nutrition educators must help consumers understand that organic cereals are not necessarily more nutritious and their consumption could result in excessive intake of undesirable nutrients, such as fat, sugar and sodium.

24 CFR 232.570 - Endorsement of credit instrument.

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2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Endorsement of credit instrument... of Fire Safety Equipment Eligible Security Instruments § 232.570 Endorsement of credit instrument. The Commissioner shall indicate his insurance of the loan by endorsing the credit instrument and...

24 CFR 570.203 - Special economic development activities.

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2010-04-01

... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Special economic development... § 570.203 Special economic development activities. A recipient may use CDBG funds for special economic... part of an economic development project. Guidelines for selecting activities to assist under this...

NMR study of the possible interaction in solution of angiotensin II with a peptide encoded by angiotensin II complementary RNA

International Nuclear Information System (INIS)

Eaton, H.L.; Fesik, S.W.; Austin, R.E.; Martin, S.F.

1989-01-01

The potential binding of angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) (AII) to a peptide encoded by its complementary RNA (Lys-Gly-Val-Asp-Val-Try-Ala-Val) (IIA) has been studied by monitoring the 1 H NMR spectrum of IIA in aqueous phosphate or Tris·HCl buffer ( 2 H 2 O) as it is titrated with AII. For molar ratios of AII/IIA ranging from 0.2 to 1.8, the NMR spectra are unchanged as compared to the spectra of the isolated peptides. Based on these findings, the K d for the putative biomolecular complex of the two peptides under these conditions is calculated to be >10 -4 M. This result does not support the suggestion of Elton et al. that AII and IIA engage in high-affinity binding (K d ∼ 5 x 10 -8 M) with each other

46 CFR 205.5 - Contracts containing disputes article.

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2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Contracts containing disputes article. 205.5 Section 205... AUDIT APPEALS; POLICY AND PROCEDURE § 205.5 Contracts containing disputes article. When a contract contains a disputes article, the disputes article will govern the bases for negotiating disputes regarding...

Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A

Energy Technology Data Exchange (ETDEWEB)

McGinniss, M.J.; Kazazian, H.H. Jr.; Bi, L.; Antonarakis, S.E. (John Hopkins Univ., Baltimore, MD (United States)); Hoyer, L.W. (American Red Cross Blood Services, Rockville, MD (United States)); Inaba, H. (Tokyo Medical College (Japan))

1993-02-01

Hemophilia A is due to the functional deficiency of factor VIII (FVIII, gene locus F8C). Although half the patients have no detectable FVIII protein in their plasma, the more rare patients ([approximately]5%) have normal levels of a dysfunctional FVIII and are termed cross-reacting material (CRM)-positive. More commonly ([approximately]45%), patients have plasma FVIII protein reduced to an extent roughly comparable to the level of FVIII activity and are designated CRM-reduced. We used denaturing gradient gel electrophoresis to screen for mutations within the F8C gene of 11 patients (6CRM-positive, 5 CRM-reduced) and identified 9 different mutations in 9 patients after analyses of all 26 exons, the promoter region, and the polyadenylation site. Six mutations have not been described previously. Five weree missense (Ser289Leu, Ser558Phe, Val634Ala, Val634Met, Asn1441Lys), and the sixth was a 3-bp deletion ([Delta]Phe652). A review of the literature and the assay of FVIII antigen in 5 hemophilia A patients with previously identified missense mutations from this laboratory yielded a total of 20 other unique CRM-reduced and CRM-positive mutations. Almost all CRM-positive/reduced mutations (24/26) were missense, and many (12/26) occurred at CpG dinucleotides. We examined 19 missense mutation for evolutionary conservation using the portions of the porcine and murine F8C sequences that are known, and 18/19 amino acid residue altered by mutation in these patients wer conserved. Almost 50% of mutations (11/26) clustered in the A2 domain, suggesting that this region is critical for the function of FVIII. The results indicate a nonrandom distribution of mutations and suggest that mutations in a limited number of FVIII regions may cause CRM-positive and CRM-reduced heomphilia A. 48 refs., 1 fig., 1 tab.

41 CFR 101-39.205 - [Reserved

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2010-07-01

... FEDERAL PROPERTY MANAGEMENT REGULATIONS AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 39-INTERAGENCY FLEET MANAGEMENT SYSTEMS 39.2-GSA Interagency Fleet Management System Services § 101-39.205 [Reserved] ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true [Reserved] 101-39.205...

Biological findings from the PheWAS catalog: focus on connective tissue-related disorders (pelvic floor dysfunction, abdominal hernia, varicose veins and hemorrhoids).

Science.gov (United States)

Salnikova, Lyubov E; Khadzhieva, Maryam B; Kolobkov, Dmitry S

2016-07-01

Pelvic floor dysfunction, specifically genital prolapse (GP) and stress urinary inconsistency (SUI) presumably co-occur with other connective tissue disorders such as hernia, hemorrhoids, and varicose veins. Observations on non-random coexistence of these disorders have never been summarized in a meta-analysis. The performed meta-analysis demonstrated that varicose veins and hernia are associated with GP. Disease connections on the molecular level may be partially based on shared genetic susceptibility. A unique opportunity to estimate shared genetic susceptibility to disorders is provided by a PheWAS (phenome-wide association study) designed to utilize GWAS data concurrently to many phenotypes. We searched the PheWAS Catalog, which includes the results of the PheWAS study with P value hemorrhoids. We found pronounced signals for the associations of the SLC2A9 gene with SUI (P = 6.0e-05) and the MYH9 gene with varicose veins of lower extremity (P = 0.0001) and hemorrhoids (P = 0.0007). The comparison of the PheWAS Catalog and the NHGRI Catalog data revealed enrichment of genes associated with bone mineral density in GP and with activated partial thromboplastin time in varicose veins of lower extremity. In cross-phenotype associations, genes responsible for peripheral nerve functions seem to predominate. This study not only established novel biologically plausible associations that may warrant further studies but also exemplified an effective use of the PheWAS Catalog data.

A hydrophobic residue in the TALE homeodomain of PBX1 promotes epithelial-to-mesenchymal transition of gastric carcinoma.

Science.gov (United States)

He, Changyu; Wang, Zhenqiang; Zhang, Li; Yang, Liyun; Li, Jianfang; Chen, Xuehua; Zhang, Jun; Chang, Qing; Yu, Yingyan; Liu, Bingya; Zhu, Zhenggang

2017-07-18

Pre-B-cell leukemia homeobox 1 (PBX1) was originally identified as a proto-oncogene in human leukemia. Although this protein has been shown to contribute to cellular development and tumorigenesis, the role of PBX1 in gastric carcinoma (GC) remains unclear. In this study, we observed increased expression of PBX1 in GC tissues compared with adjacent normal tissues. This increase in PBX1 expression levels negatively correlated with HOXB9 mRNA expression and was also associated with malignancy and metastasis. PBX1 promoted proliferation and metastasis of GC cells both in vitro and in vivo.These phenomena were also accompanied by epithelial-to-mesenchymal transition (EMT). Additionally, we observed that PBX1 promotes the expression of tumor growth and angiogenic factors. A structural model of the PBX1-HOX complex revealed that hydrophobic binding between PBX1 and the hexapeptide motif might be required for EMT induction. This analysis also demonstrated that the Phe252 residue in the first helix of the TALE homeodomain is involved in the latter hydrophobic binding reaction. In vitro data from PBX1 mutants suggest that PBX1 cannot promote tumorigenesis of GC cells via EMT induction when Phe252 residues lose hydrophobicity. It is likely that the presence of this residue is essential in facilitating hydrophobic binding with the hexapeptide motif. These findings suggest that PBX1 may be a potential target for GC treatment and this study provides a platform to elucidate the molecular mechanisms that underpin the role of PBX1 in GC tumorigenesis.

21 CFR 111.570 - Under this subpart O, what records must you make and keep?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Under this subpart O, what records must you make and keep? 111.570 Section 111.570 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN...

Photoaffinity labeling of opiate (enkephalin) receptor of rat brain plasma membranes with 125I(D-Ala2, p-N3-Phe4-Met5)-enkephalin

International Nuclear Information System (INIS)

Yeung, C.W.T.

1986-01-01

A photoreactive (D-Ala 2 , p-N 3 -Phe 4 -Met 5 )enkephalin derivative was prepared, iodinated with carrier free 125 I and then purified by high performance liquid chromatography. The purified radioactive photoprobe was monoiodinated at the amino terminal tyrosine residue. This radioactive photoprobe was used to photoaffinity label plasma membranes prepared from rat brain, spinal cord and cerebellum. The photolabeled plasma membranes were analyzed by sodium dodecyl sulfate gel electrophoresis. A 46,000-daltons band was specifically photolabeled in the plasma membranes of brain and spinal cord but not in the plasma membranes from cerebellum. The photolabeling of this band was inhibited by peptides related to enkephalin by not but substance P or gastrin tetrapeptide. These data demonstrate that the labeled 46,000-daltons band is a protein of the opiate (enkephalin)receptor

Identification of a novel amino acid racemase from a hyperthermophilic archaeon Pyrococcus horikoshii OT-3 induced by D-amino acids.

Science.gov (United States)

Kawakami, Ryushi; Ohmori, Taketo; Sakuraba, Haruhiko; Ohshima, Toshihisa

2015-08-01

To date, there have been few reports analyzing the amino acid requirement for growth of hyperthermophilic archaea. We here found that the hyperthermophilic archaeon Pyrococcus horikoshii OT-3 requires Thr, Leu, Val, Phe, Tyr, Trp, His and Arg in the medium for growth, and shows slow growth in medium lacking Met or Ile. This largely corresponds to the presence, or absence, of genes related to amino acid biosynthesis in its genome, though there are exceptions. The amino acid requirements were dramatically lost by addition of D-isomers of Met, Leu, Val, allo-Ile, Phe, Tyr, Trp and Arg. Tracer analysis using (14)C-labeled D-Trp showed that D-Trp in the medium was used as a protein component in the cells, suggesting the presence of D-amino acid metabolic enzymes. Pyridoxal 5'-phosphate (PLP)-dependent racemase activity toward Met, Leu and Phe was detected in crude extract of P. horikoshii and was enhanced in cells grown in the medium supplemented with D-amino acids, especially D-allo-Ile. The gene encoding the racemase was narrowed down to one open reading frame on the basis of enzyme purification from P. horikoshii cells, and the recombinant enzyme exhibited PLP-dependent racemase activity toward several amino acids, including Met, Leu and Phe, but not Pro, Asp or Glu. This is the first report showing the presence in a hyperthermophilic archaeon of a PLP-dependent amino acid racemase with broad substrate specificity that is likely responsible for utilization of D-amino acids for growth.

31 CFR 536.205 - Exempt transactions.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exempt transactions. 536.205 Section 536.205 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... creation of information and informational materials, and payment of royalties to a specially designated...

19 CFR 201.205 - Salary adjustments.

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2010-04-01

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7 CFR 3430.205 - Funding restrictions.

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2010-01-01

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40 CFR 205.153 - Engine displacement.

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2010-07-01

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7 CFR 205.301 - Product composition.

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2010-01-01

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12 CFR 411.205 - Professional and technical services.

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2010-01-01

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48 CFR 1631.205-10 - Cost of money.

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2010-10-01

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Novel essential residues of Hda for interaction with DnaA in the regulatory inactivation of DnaA: unique roles for Hda AAA Box VI and VII motifs.

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Nakamura, Kenta; Katayama, Tsutomu

2010-04-01

Escherichia coli ATP-DnaA initiates chromosomal replication. For preventing extra-initiations, a complex of ADP-Hda and the DNA-loaded replicase clamp promotes DnaA-ATP hydrolysis, yielding inactive ADP-DnaA. However, the Hda-DnaA interaction mode remains unclear except that the Hda Box VII Arg finger (Arg-153) and DnaA sensor II Arg-334 within each AAA(+) domain are crucial for the DnaA-ATP hydrolysis. Here, we demonstrate that direct and functional interaction of ADP-Hda with DnaA requires the Hda residues Ser-152, Phe-118 and Asn-122 as well as Hda Arg-153 and DnaA Arg-334. Structural analyses suggest intermolecular interactions between Hda Ser-152 and DnaA Arg-334 and between Hda Phe-118 and the DnaA Walker B motif region, in addition to an intramolecular interaction between Hda Asn-122 and Arg-153. These interactions likely sustain a specific association of ADP-Hda and DnaA, promoting DnaA-ATP hydrolysis. Consistently, ATP-DnaA and ADP-DnaA interact with the ADP-Hda-DNA-clamp complex with similar affinities. Hda Phe-118 and Asn-122 are contained in the Box VI region, and their hydrophobic and electrostatic features are basically conserved in the corresponding residues of other AAA(+) proteins, suggesting a conserved role for Box VI. These findings indicate novel interaction mechanisms for Hda-DnaA as well as a potentially fundamental mechanism in AAA(+) protein interactions.

10 CFR 205.350 - General purpose.

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2010-01-01

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49 CFR 1560.205 - Redress process.

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2010-10-01

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40 CFR 205.57-3 - Test vehicle preparation.

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2010-07-01

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48 CFR 2103.570 - Misleading, Deceptive, or Unfair Advertising.

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2010-10-01

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Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study

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Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

2012-01-01

Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2. Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most

Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study.

Science.gov (United States)

Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

2012-03-27

Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1-7.2. Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1-7.2 is most promising.

Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction.

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Anastasia, Agustin; Deinhardt, Katrin; Chao, Moses V; Will, Nathan E; Irmady, Krithi; Lee, Francis S; Hempstead, Barbara L; Bracken, Clay

2013-01-01

A common single-nucleotide polymorphism (SNP) in the human brain-derived neurotrophic factor (BDNF) gene results in a Val66Met substitution in the BDNF prodomain region. This SNP is associated with alterations in memory and with enhanced risk to develop depression and anxiety disorders in humans. Here we show that the isolated BDNF prodomain is detected in the hippocampus and that it can be secreted from neurons in an activity-dependent manner. Using nuclear magnetic resonance spectroscopy and circular dichroism, we find that the prodomain is intrinsically disordered, and the Val66Met substitution induces structural changes. Surprisingly, application of Met66 (but not Val66) BDNF prodomain induces acute growth cone retraction and a decrease in Rac activity in hippocampal neurons. Expression of p75(NTR) and differential engagement of the Met66 prodomain to the SorCS2 receptor are required for this effect. These results identify the Met66 prodomain as a new active ligand, which modulates neuronal morphology.

The Role of the Val66Met Polymorphism of the Brain Derived Neurotrophic Factor Gene in Coping Strategies Relevant to Depressive Symptoms.

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Warren Caldwell

Full Text Available Disturbances of brain derived neurotrophic factor (BDNF signalling have been implicated in the evolution of depression, which likely arises, in part, as a result of diminished synaptic plasticity. Predictably, given stressor involvement in depression, BDNF is affected by recent stressors as well as stressors such as neglect experienced in early life. The effects of early life maltreatment in altering BDNF signalling may be particularly apparent among those individuals with specific BDNF polymorphisms. We examined whether polymorphisms of the Val66Met genotype might be influential in moderating how early-life events play out with respect to later coping styles, cognitive flexibility and depressive features. Among male and female undergraduate students (N = 124, childhood neglect was highly related to subsequent depressive symptoms. This outcome was moderated by the BDNF polymorphism in the sense that depressive symptoms appeared higher in Met carriers who reported low levels of neglect than in those with the Val/Val allele. However, under conditions of high neglect depressive symptoms only increased in the Val/Val individuals. In effect, the Met polymorphism was associated with depressive features, but did not interact with early life neglect in predicting later depressive features. It was further observed that among the Val/Val individuals, the relationship between neglect and depression was mediated by emotion-focused styles and diminished perceived control, whereas this mediation was not apparent in Met carriers. In contrast to the more typical view regarding this polymorphism, the data are consistent with the perspective that in the presence of synaptic plasticity presumably associated with the Val/Val genotype, neglect allows for the emergence of specific appraisal and coping styles, which are tied to depression. In the case of the reduced degree of neuroplasticity expected in the Met carriers, early life adverse experiences are not tied

The BDNF-Val66Met polymorphism modulates parental rearing effects on adult psychiatric symptoms: a community twin-based study.

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Ibarra, P; Alemany, S; Fatjó-Vilas, M; Córdova-Palomera, A; Goldberg, X; Arias, B; González-Ortega, I; González-Pinto, A; Nenadic, I; Fañanás, L

2014-06-01

To test whether firstly, different parental rearing components were associated with different dimensions of psychiatric symptoms in adulthood, secondly BDNF-Val66Met polymorphism moderated this association and thirdly, this association was due to genetic confounding. Perceived parental rearing according to Parental Bonding Instrument (PBI), psychiatric symptoms evaluated with the Brief Symptom Inventory (BSI) and the BDNF-Val66Met polymorphism were analyzed in a sample of 232 adult twins from the general population. In the whole sample, paternal care was negatively associated with depression. Maternal overprotection was positively associated with paranoid ideation, obsession-compulsion and somatization. Gene-environment interaction effects were detected between the BDNF-Val66Met polymorphism and maternal care on phobic anxiety, paternal care on hostility, maternal overprotection on somatization and paternal overprotection also in somatization. In the subsample of MZ twins, intrapair differences in maternal care were associated with anxiety, paranoid ideation and somatization. Met carriers were, in general, more sensitive to the effects of parental rearing compared to Val/Val carriers in relation to anxiety and somatization. Contra-intuitively, our findings suggest that high rates of maternal care might be of risk for Met carriers regarding anxiety. Results from analyses controlling for genetic confounding were in line with this finding. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

International Nuclear Information System (INIS)

Helisch, Andreas; Foerster, Gregor J.; Reber, Helmut; Buchholz, Hans-Georg; Bartenstein, Peter; Arnold, Rudolf; Goeke, Burkhard; Weber, Matthias M.; Wiedenmann, Bertram; Pauwels, Stanislas; Haus, Ulrike; Bouterfa, Hakim

2004-01-01

For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90 Y is frequently used [ 90 Y-DOTA-Phe 1 -Tyr 3 -octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86 Y-DOTA-Phe 1 -Tyr 3 -octreotide (considered as the gold standard) and the commercially available 111 In-pentetreotide. The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq 90 Y-DOTA-Phe 1 -Tyr 3 -octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with 90 Y-DOTA-Phe 1 -Tyr 3 -octreotide, in accordance with the directives of the German radiation protection authorities. The range of doses (mGy/MBq 90 Y-DOTA-Phe 1 -Tyr 3 -octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.5-4.2, 0.3-1.3 and 2.1-29.5 ( 86 Y-DOTA-Phe 1 -Tyr 3 -octreotide), respectively, versus 1.3-3.0, 1.8-4.4, 0.2-0.8 and 1.4-19.7 ( 111 In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. Compared with 86 Y-DOTA-Phe 1 -Tyr 3 -octreotide, dosimetry with 111 In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy. (orig.)

Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours.

Science.gov (United States)

Helisch, Andreas; Förster, Gregor J; Reber, Helmut; Buchholz, Hans-Georg; Arnold, Rudolf; Göke, Burkhard; Weber, Matthias M; Wiedenmann, Bertram; Pauwels, Stanislas; Haus, Ulrike; Bouterfa, Hakim; Bartenstein, Peter

2004-10-01

For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90Y is frequently used [90Y-DOTA-Phe1-Tyr3)-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86Y-DOTA-Phe1-Tyr3-octreotide (considered as the gold standard) and the commercially available 111In-pentetreotide. The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq 90Y-DOTA-Phe1-Tyr3-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with 90Y-DOTA-Phe1-Tyr3-octreotide, in accordance with the directives of the German radiation protection authorities. The range of doses (mGy/MBq 90Y-DOTA-Phe1-Tyr3-octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.5-4.2, 0.3-1.3 and 2.1-29.5 (86Y-DOTA-Phe1-Tyr3-octreotide), respectively, versus 1.3-3.0, 1.8-4.4, 0.2-0.8 and 1.4-19.7 (111In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. Compared with 86Y-DOTA-Phe1-Tyr3-octreotide, dosimetry with 111In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy.

Effects of the BDNF Val66Met polymorphism on neural responses to facial emotion.

Science.gov (United States)

Mukherjee, Prerona; Whalley, Heather C; McKirdy, James W; McIntosh, Andrew M; Johnstone, Eve C; Lawrie, Stephen M; Hall, Jeremy

2011-03-31

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with affective disorders, but its role in emotion processing has not been fully established. Due to the clinically heterogeneous nature of these disorders, studying the effect of genetic variation in the BDNF gene on a common attribute such as fear processing may elucidate how the BDNF Val66Met polymorphism impacts brain function. Here we use functional magnetic resonance imaging examine the effect of the BDNF Val66Met genotype on neural activity for fear processing. Forty healthy participants performed an implicit fear task during scanning, where subjects made gender judgments from facial images with neutral or fearful emotion. Subjects were tested for facial emotion recognition post-scan. Functional connectivity was investigated using psycho-physiological interactions. Subjects were genotyped for the BDNF Val66Met polymorphism and the measures compared between genotype groups. Met carriers showed overactivation in the anterior cingulate cortex (ACC), brainstem and insula bilaterally for fear processing, along with reduced functional connectivity from the ACC to the left hippocampus, and impaired fear recognition ability. The results show that during fear processing, Met allele carriers show an increased neural response in regions previously implicated in mediating autonomic arousal. Further, the Met carriers show decreased functional connectivity with the hippocampus, which may reflect differential retrieval of emotional associations. Together, these effects show significant differences in the neural substrate for fear processing with genetic variation in BDNF. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

40 CFR 205.171 - Selective enforcement auditing (SEA) requirements.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Selective enforcement auditing (SEA) requirements. 205.171 Section 205.171 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... § 205.171 Selective enforcement auditing (SEA) requirements. ...

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and post-stroke dementia: a hospital-based study from northern Iran.

Science.gov (United States)

Rezaei, Sajjad; Asgari Mobarake, Karim; Saberi, Alia; Keshavarz, Parvaneh; Leili, Ehsan Kazemnejad

2016-06-01

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with functional and cognitive outcomes of stroke and plays a key role in preventing neuronal death. This study aimed to answer the following question: does BDNF Val66Met polymorphism prognosticate survival status and risk of post-stroke dementia (PSD)? In a retrospective cohort study, 206 patients with ischemic stroke (IS) entered the study. They were consecutively being admitted to the neurology clinic in Poursina Hospital (northern Iran) from 2012 to 2014. The diagnosis of PSD was based on DSM-5 criteria. The current and the premorbid cognitive statuses of the patients were respectively assessed through the third edition of Addenbrooke's Cognitive Examination and the Informant Questionnaire on Cognitive Decline in the Elderly. BDNF Val66Met gene polymorphism was determined by PCR-RFLP. On average, 48 patients (23.3 %) developed PSD 6 months after IS. Log-rank test showed that the survival rate of at least one Val-allele carriers was significantly lower than that of Met/Met homozygotes (P = 0.0005), and the former developed PSD sooner than the latter (375, 492 days, respectively). Cox model showed that heterozygous carriers of Val/Met were at greater risk of PSD over time (HR 2.280, 95 % CI 1.566-4.106, P = 0.006). However, the risk ratio of patients with PSD among different BDNF genotypes decreased after adjusting demographic, clinical, and vascular risk factors, and was no longer statistically significant (AHR 2.434, 95 % CI 0.597-9.926, P = 0.215). Val-allele carriers or Val/Met genotypes were more quickly diagnosed as having dementia after IS. However, this genetic vulnerability became more destructive when it was added to demographic, clinical, and vascular risk factors.

Aqueous Microwave-Assisted Solid-Phase Synthesis Using Boc-Amino Acid Nanoparticles

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Yoshinobu Fukumori

2013-07-01

Full Text Available We have previously developed water-based microwave (MW-assisted peptide synthesis using Fmoc-amino acid nanopaticles. It is an organic solvent-free, environmentally friendly method for peptide synthesis. Here we describe water-based MW-assisted solid-phase synthesis using Boc-amino acid nanoparticles. The microwave irradiation allowed rapid solid-phase reaction of nanoparticle reactants on the resin in water. We also demonstrated the syntheses of Leu-enkephalin, Tyr-Gly-Gly-Phe-Leu-OH, and difficult sequence model peptide, Val-Ala-Val-Ala-Gly-OH, using our water-based MW-assisted protocol with Boc-amino acid nanoparticles.

The A-chain of insulin contacts the insert domain of the insulin receptor. Photo-cross-linking and mutagenesis of a diabetes-related crevice.

Science.gov (United States)

Huang, Kun; Chan, Shu Jin; Hua, Qing-xin; Chu, Ying-Chi; Wang, Run-ying; Klaproth, Birgit; Jia, Wenhua; Whittaker, Jonathan; De Meyts, Pierre; Nakagawa, Satoe H; Steiner, Donald F; Katsoyannis, Panayotis G; Weiss, Michael A

2007-11-30

The contribution of the insulin A-chain to receptor binding is investigated by photo-cross-linking and nonstandard mutagenesis. Studies focus on the role of Val(A3), which projects within a crevice between the A- and B-chains. Engineered receptor alpha-subunits containing specific protease sites ("midi-receptors") are employed to map the site of photo-cross-linking by an analog containing a photoactivable A3 side chain (para-azido-Phe (Pap)). The probe cross-links to a C-terminal peptide (residues 703-719 of the receptor A isoform, KTFEDYLHNVVFVPRPS) containing side chains critical for hormone binding (underlined); the corresponding segment of the holoreceptor was shown previously to cross-link to a Pap(B25)-insulin analog. Because Pap is larger than Val and so may protrude beyond the A3-associated crevice, we investigated analogs containing A3 substitutions comparable in size to Val as follows: Thr, allo-Thr, and alpha-aminobutyric acid (Aba). Substitutions were introduced within an engineered monomer. Whereas previous studies of smaller substitutions (Gly(A3) and Ser(A3)) encountered nonlocal conformational perturbations, NMR structures of the present analogs are similar to wild-type insulin; the variant side chains are accommodated within a native-like crevice with minimal distortion. Receptor binding activities of Aba(A3) and allo-Thr(A3) analogs are reduced at least 10-fold; the activity of Thr(A3)-DKP-insulin is reduced 5-fold. The hormone-receptor interface is presumably destabilized either by a packing defect (Aba(A3)) or by altered polarity (allo-Thr(A3) and Thr(A3)). Our results provide evidence that Val(A3), a site of mutation causing diabetes mellitus, contacts the insert domain-derived tail of the alpha-subunit in a hormone-receptor complex.

Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders

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Shih-Jen Tsai

2018-05-01

Full Text Available Neurotrophins have been implicated in the pathophysiology of many neuropsychiatric diseases. Brain-derived neurotrophic factor (BDNF is the most abundant and widely distributed neurotrophin in the brain. Its Val66Met polymorphism (refSNP Cluster Report: rs6265 is a common and functional single-nucleotide polymorphism (SNP affecting the activity-dependent release of BDNF. BDNF Val66Met transgenic mice have been generated, which may provide further insight into the functional impact of this polymorphism in the brain. Considering the important role of BDNF in brain function, more than 1,100 genetic studies have investigated this polymorphism in the past 15 years. Although these studies have reported some encouraging positive findings initially, most of the findings cannot be replicated in following studies. These inconsistencies in BDNF Val66Met genetic studies may be attributed to many factors such as age, sex, environmental factors, ethnicity, genetic model used for analysis, and gene–gene interaction, which are discussed in this review. We also discuss the results of recent studies that have reported the novel functions of this polymorphism. Because many BDNF polymorphisms and non-genetic factors have been implicated in the complex traits of neuropsychiatric diseases, the conventional genetic association-based method is limited to address these complex interactions. Future studies should apply data mining and machine learning techniques to determine the genetic role of BDNF in neuropsychiatric diseases.

First-principles study of L10 Ti-Al and V-Al alloys

International Nuclear Information System (INIS)

Chubb, S.R.; Papaconstantopoulos, D.A.; Klein, B.M.

1988-01-01

As a first step towards understanding the reduced embrittlement of L1 0 Ti-Al alloys which accompanies the introduction of small concentrations of V, we have determined from first principles, using full-potential linearized--augmented-plane-wave calculations, the equilibrium values of the structural parameters and the associated electronic structure for the stoichiometric (L1 0 ) Ti-Al (tetragonal) compound. Our calculated values of c/a and a are in good agreement with experiment. Using the same method of calculation, we have also studied the electronic structure associated with the (hypothetical) L1 0 V-Al alloy that would form when V is substituted for Ti. We find that (1) the electronic structures of these V-Al alloys are relatively insensitive to variations of c/a and a; (2) near the Ti-Al equilibrium geometry, the electronic structures of the V-Al and Ti-Al alloys are very similar; and (3) that a rigid-band model involving substitution of V for Ti can be used to gain a qualitative understanding of the reduction in c/a which accompanies the introduction of small concentrations of V. We relate the reduction in c/a to important changes in the bonding that accompany the occupation of bands immediately above the Fermi level of the stoichiometric Ti-Al compound

48 CFR 504.570 - Procedures for using the EPS.

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2010-10-01

... GENERAL ADMINISTRATIVE MATTERS Electronic Commerce in Contracting 504.570 Procedures for using the EPS. (a... [Identify address block in the solicitation]. (e) The Electronic Posting System Manual provides detailed... that electronic access to a solicitation will result in adequate competition, distribute the...

Element segregation behavior of aluminum-copper alloy ZL205A

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Fan Li

2014-11-01

Full Text Available In aluminum-copper alloy, the segregation has a severe bad effect on the alloying degree, strength and corrosion resistance. A deeper understanding of element segregation behavior will have a great significance on the prevention of segregation. In the study, the element segregation behavior of ZL205A aluminum-copper alloy was investigated by examining isothermally solidified samples using scanning electron microscopy and energy dispersive spectroscopy. The calculated results of segregation coefficients show that Cu and Mn are negative segregation elements; while Ti, V and Zr are positive segregation elements. The sequence of element segregation degree from the greatest to the least in ZL205A alloy is Cu, Mn, V, Ti, Zr and Al. The density of residual liquid is expected to increase with a decrease in the quenching temperature ranging from 630 ºC to 550 ºC. The calculated results confirm that the quenching temperature has an insignificant effect on the liquid density; and the variation of density is mainly due to element segregation. Consequently, segregations of Al, Cu and Mn lead to an increase in density, but Ti, V and Zr present the opposite effect. The contribution of each element to the variation of the liquid density was analyzed. The sequence of contributions of alloying elements to the variation of total liquid density is Cu﹥Al﹥Mn﹥V﹥Ti﹥Zr.

15 CFR 970.205 - Vessel safety.

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2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Vessel safety. 970.205 Section 970.205... safety. In order to provide a basis for the necessary determinations with respect to the safety of life... Safety of Life at Sea, 1974 (SOLAS 74) possesses current valid SOLAS 74 certificates; (2) That any...

47 CFR 25.205 - Minimum angle of antenna elevation.

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2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Minimum angle of antenna elevation. 25.205 Section 25.205 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Technical Standards § 25.205 Minimum angle of antenna elevation. (a) Earth station...

Un rimedio esasperato dal male. Ovvero i due corpi di Valéry

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Ciro Felice Papparo

2012-05-01

Full Text Available In his Cahiers, Valéry says that writing two of his major dialogues, Eupalinos and L’âme et la danse, was an antidote to his ravaging mood: literature and spirituality are the remedy generated by a necessary and not eliminable evil, particularly the one that shows itself as ‘rage’ in love. The essay investigates thoroughly this contradictory logic and focuses on the problem of sensitiveness in Valéry’s work, pointing out a twofold presence of the ‘body’. Preserving these two presences, the writing incessantly tries to make up “une fureur intelligente et expérimentale” and to give a new form, without deleting it, to sensitiveness’ acute pain.

Bioremediation of piggery slaughterhouse wastewater using the marine protist, Thraustochytrium kinney VAL-B1

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María P. Villarroel Hipp

2018-07-01

Full Text Available Industrial wastewaters from pig slaughtering plants (PSPs generated in the slaughtering process could have an environmental impact, if discharged to a receiving water body without any treatment. In this study, a Chilean Thraustochytrid (TH strain, a class of marine protist, was used for the bioremediation of piggery slaughterhouse wastewater (SWW. According to the physicochemical analysis of the residue, it was characterized by an initial chemical oxygen demand (COD of 9610 mg L−1, 18,625 mg L−1 of oil and grease, 1639 mg L−1 of total nitrogen, 149 mg L−1 of total phosphorus, and 82.41 mg L−1 of total iron. Growth studies were conducted to evaluate the growth and biomass production of the strain on residue-based media and its subsequent bioremediation ability. After 5–7 days of fermentation, the results showed that COD of the medium supernatant was reduced by 56.29% (4200 mg L−1, while oil and grease had a significant decrease about 99% (18 mg L−1, and the content of total nitrogen, total phosphorus, and total iron were also decreased by 63.27% (602 mg L−1, 97.55% (3.65 mg L−1 and 60.35% (30.88 mg L−1, respectively. With these results, it was concluded that VAL-B1 can be used for the bioremediation of industrial wastewater from PSPs, and therefore THs could contribute to regulate the environmental pollution. Keywords: Thraustochytrid, Meat-processing industry, Pig slaughtering plant, Environmental pollution, Chemical oxygen demand, Iron

Association between catechol-O-methyltrasferase Val108/158Met genotype and prefrontal hemodynamic response in schizophrenia.

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Ryu Takizawa

Full Text Available BACKGROUND: "Imaging genetics" studies have shown that brain function by neuroimaging is a sensitive intermediate phenotype that bridges the gap between genes and psychiatric conditions. Although the evidence of association between functional val108/158met polymorphism of the catechol-O-methyltransferase gene (COMT and increasing risk for developing schizophrenia from genetic association studies remains to be elucidated, one of the most topical findings from imaging genetics studies is the association between COMT genotype and prefrontal function in schizophrenia. The next important step in the translational approach is to establish a useful neuroimaging tool in clinical settings that is sensitive to COMT variation, so that the clinician could use the index to predict clinical response such as improvement in cognitive dysfunction by medication. Here, we investigated spatiotemporal characteristics of the association between prefrontal hemodynamic activation and the COMT genotype using a noninvasive neuroimaging technique, near-infrared spectroscopy (NIRS. METHODOLOGY/PRINCIPAL FINDINGS: Study participants included 45 patients with schizophrenia and 60 healthy controls matched for age and gender. Signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions from 52-channel NIRS and compared between two COMT genotype subgroups (Met carriers and Val/Val individuals matched for age, gender, premorbid IQ, and task performance. The [oxy-Hb] increase in the Met carriers during the verbal fluency task was significantly greater than that in the Val/Val individuals in the frontopolar prefrontal cortex of patients with schizophrenia, although neither medication nor clinical symptoms differed significantly between the two subgroups. These differences were not found to be significant in healthy controls. CONCLUSIONS/SIGNIFICANCE: These data suggest that the prefrontal NIRS signals can noninvasively detect the impact

BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses.

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Aas, Monica; Haukvik, Unn K; Djurovic, Srdjan; Bergmann, Ørjan; Athanasiu, Lavinia; Tesli, Martin S; Hellvin, Tone; Steen, Nils Eiel; Agartz, Ingrid; Lorentzen, Steinar; Sundet, Kjetil; Andreassen, Ole A; Melle, Ingrid

2013-10-01

Brain derived neurotrophic factor (BDNF) is important for brain development and plasticity, and here we tested if the functional BDNF val66met variant modulates the association between high levels of childhood abuse, cognitive function, and brain abnormalities in psychoses. 249 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited to the TOP research study (mean±age: 30.7±10.9; gender: 49% males). History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Cognitive function was assessed through a standardized neuropsychological test battery. BDNF val66met was genotyped using standardized procedures. A sub-sample of n=106 Caucasians with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder (mean±age: 32.67±10.85; 49% males) had data on sMRI. Carriers of the Methionine (met) allele exposed to high level of childhood abuse demonstrated significantly poorer cognitive functioning compared to homozygotic Valine (val/val) carriers. Taking in consideration multiple testing, using a more conservative p value, this was still shown for physical abuse and emotional abuse, as well as a trend level for sexual abuse. Further, met carriers exposed to high level of childhood sexual abuse showed reduced right hippocampal volume (r(2)=0.43; p=0.008), and larger right and left lateral ventricles (r(2)=0.37; p=0.002, and r(2)=0.27; p=0.009, respectively). Our findings were independent of age, gender, diagnosis and intracranial volume. Our data demonstrate that in patients with psychoses, met carriers of the BDNF val66met with high level of childhood abuse have more cognitive and brain abnormalities than all other groups. © 2013.

48 CFR 2131.205-71 - Reinsurer administrative expense costs.

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2010-10-01

... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 2131.205-71... as set forth in the contract is an allowable cost when documented through an internal accounting... expense costs. 2131.205-71 Section 2131.205-71 Federal Acquisition Regulations System OFFICE OF PERSONNEL...

9 CFR 113.205 - Newcastle Disease Vaccine, Killed Virus.

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2010-01-01

... Virus. 113.205 Section 113.205 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.205 Newcastle Disease Vaccine, Killed Virus. Newcastle Disease Vaccine...

12 CFR 205.7 - Initial disclosures.

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2010-01-01

... electronic fund transfers or for the right to make transfers. (6) Documentation. A summary of the consumer's... transfers as provided in §§ 205.10(a), and 205.10(d). (7) Stop payment. A summary of the consumer's right to... shall make the disclosures required by this section at the time a consumer contracts for an electronic...

Conopeptide ρ-TIA Defines a New Allosteric Site on the Extracellular Surface of the α1B-Adrenoceptor*♦

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Ragnarsson, Lotten; Wang, Ching-I Anderson; Andersson, Åsa; Fajarningsih, Dewi; Monks, Thea; Brust, Andreas; Rosengren, K. Johan; Lewis, Richard J.

2013-01-01

The G protein-coupled receptor (GPCR) superfamily is an important drug target that includes over 1000 membrane receptors that functionally couple extracellular stimuli to intracellular effectors. Despite the potential of extracellular surface (ECS) residues in GPCRs to interact with subtype-specific allosteric modulators, few ECS pharmacophores for class A receptors have been identified. Using the turkey β1-adrenergic receptor crystal structure, we modeled the α1B-adrenoceptor (α1B-AR) to help identify the allosteric site for ρ-conopeptide TIA, an inverse agonist at this receptor. Combining mutational radioligand binding and inositol 1-phosphate signaling studies, together with molecular docking simulations using a refined NMR structure of ρ-TIA, we identified 14 residues on the ECS of the α1B-AR that influenced ρ-TIA binding. Double mutant cycle analysis and docking confirmed that ρ-TIA binding was dominated by a salt bridge and cation-π between Arg-4-ρ-TIA and Asp-327 and Phe-330, respectively, and a T-stacking-π interaction between Trp-3-ρ-TIA and Phe-330. Water-bridging hydrogen bonds between Asn-2-ρ-TIA and Val-197, Trp-3-ρ-TIA and Ser-318, and the positively charged N terminus and Glu-186, were also identified. These interactions reveal that peptide binding to the ECS on transmembrane helix 6 (TMH6) and TMH7 at the base of extracellular loop 3 (ECL3) is sufficient to allosterically inhibit agonist signaling at a GPCR. The ligand-accessible ECS residues identified provide the first view of an allosteric inhibitor pharmacophore for α1-adrenoceptors and mechanistic insight and a new set of structural constraints for the design of allosteric antagonists at related GPCRs. PMID:23184947

Conopeptide ρ-TIA defines a new allosteric site on the extracellular surface of the α1B-adrenoceptor.

Science.gov (United States)

Ragnarsson, Lotten; Wang, Ching-I Anderson; Andersson, Åsa; Fajarningsih, Dewi; Monks, Thea; Brust, Andreas; Rosengren, K Johan; Lewis, Richard J

2013-01-18

The G protein-coupled receptor (GPCR) superfamily is an important drug target that includes over 1000 membrane receptors that functionally couple extracellular stimuli to intracellular effectors. Despite the potential of extracellular surface (ECS) residues in GPCRs to interact with subtype-specific allosteric modulators, few ECS pharmacophores for class A receptors have been identified. Using the turkey β(1)-adrenergic receptor crystal structure, we modeled the α(1B)-adrenoceptor (α(1B)-AR) to help identify the allosteric site for ρ-conopeptide TIA, an inverse agonist at this receptor. Combining mutational radioligand binding and inositol 1-phosphate signaling studies, together with molecular docking simulations using a refined NMR structure of ρ-TIA, we identified 14 residues on the ECS of the α(1B)-AR that influenced ρ-TIA binding. Double mutant cycle analysis and docking confirmed that ρ-TIA binding was dominated by a salt bridge and cation-π between Arg-4-ρ-TIA and Asp-327 and Phe-330, respectively, and a T-stacking-π interaction between Trp-3-ρ-TIA and Phe-330. Water-bridging hydrogen bonds between Asn-2-ρ-TIA and Val-197, Trp-3-ρ-TIA and Ser-318, and the positively charged N terminus and Glu-186, were also identified. These interactions reveal that peptide binding to the ECS on transmembrane helix 6 (TMH6) and TMH7 at the base of extracellular loop 3 (ECL3) is sufficient to allosterically inhibit agonist signaling at a GPCR. The ligand-accessible ECS residues identified provide the first view of an allosteric inhibitor pharmacophore for α(1)-adrenoceptors and mechanistic insight and a new set of structural constraints for the design of allosteric antagonists at related GPCRs.

Interaction between catechol-O-methyltransferase (COMT) Val158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli.

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Lo Bianco, L; Blasi, G; Taurisano, P; Di Giorgio, A; Ferrante, F; Ursini, G; Fazio, L; Gelao, B; Romano, R; Papazacharias, A; Caforio, G; Sinibaldi, L; Popolizio, T; Bellantuono, C; Bertolino, A

2013-02-01

Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing. A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence. We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing. Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.

Deltorphins: a family of naturally occurring peptides with high affinity and selectivity for delta opioid binding sites.

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Erspamer, V; Melchiorri, P; Falconieri-Erspamer, G; Negri, L; Corsi, R; Severini, C; Barra, D; Simmaco, M; Kreil, G

1989-07-01

Deltorphins are endogenous linear heptapeptides, isolated from skin extracts of frogs belonging to the genus Phyllomedusa, that have a higher affinity and selectivity for delta opioid binding sites than any other natural compound known. Two deltorphins with the sequence Tyr-Ala-Phe-Asp(or Glu)-Val-Val-Gly-NH2 have been isolated from skin extracts of Phyllomedusa bicolor. The alanine in position 2 is in the D configuration. These peptides, [D-Ala2]deltorphins I and II, show an even higher affinity for delta receptors than the previously characterized deltorphin, which contains D-methionine as the second amino acid. These peptides show some similarity to another constituent of Phyllomedusa skin, dermorphin, which is highly selective for mu-opioid receptors. These peptides all have the N-terminal sequence Tyr-D-Xaa-Phe, where D-Xaa is either D-alanine or D-methionine. While this structure seems to be capable of activating both mu and delta opioid receptors, differences in the C-terminal regions of these peptides are probably responsible for the observed high receptor selectivity of dermorphin and deltorphin.

Genetic Correlates of Maladaptive Beliefs: COMT VAL(158)MET and Irrational Cognitions Linked Depending on Distress.

Science.gov (United States)

Podina, Ioana; Popp, Radu; Pop, Ioan; David, Daniel

2015-11-01

Maladaptive/irrational beliefs are significant cognitive vulnerability mechanisms in psychopathology. They are more likely to be associated with a genetic vulnerability marker under conditions of emotional distress when irrational beliefs are more salient. Therefore, in the current study we investigated the COMT Val(158)Met gene variation in relation to irrational beliefs, assuming this relationship depended on the level of emotional distress. Two hundred and sixty-seven genotyped volunteers were assessed for core/general maladaptive beliefs, as well as trait emotional distress. We focused on context-independent measures of irrational beliefs and emotional distress in the absence of a stressor. As expected, the relationship between COMT Val(158)Met and irrational beliefs depended on the level of emotional distress (f(2)=.314). The COMT Val(158)Met-irrationality association was significant only when individuals fell in the average to above average range of emotional distress. Furthermore, within this range the Met allele seemed to relate to higher irrational beliefs. These results were significant for overall irrational beliefs and its subtypes, but not for rational beliefs, the functional counterpart of irrationality. In light of the study's limitations, the results should be considered as preliminary. If replicable, these findings have potential implications for therapygenetics, changing the view that COMT Val(158)Met might be of greater relevance when treatment modality does not rely on cognitive variables. Copyright © 2015. Published by Elsevier Ltd.

40 CFR 205.54-2 - Sound data acquisition system.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Sound data acquisition system. 205.54-2 Section 205.54-2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.54-2 Sound...

On the near UV photophysics of a phenylalanine residue: conformation-dependent ππ* state deactivation revealed by laser spectroscopy of isolated neutral dipeptides.

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Loquais, Yohan; Gloaguen, Eric; Alauddin, Mohammad; Brenner, Valérie; Tardivel, Benjamin; Mons, Michel

2014-10-28

The primary step of the near UV photophysics of a phenylalanine residue is investigated in one- and two-color pump-probe R2PI nanosecond experiments carried out on specific conformers of the Ac-Gly-Phe-NH2 molecule and related neutral compounds isolated in a supersonic expansion. Compared to toluene, whose ππ* state photophysics is dominated by intersystem crossing with a lifetime of ∼80 ns at the origin, the first ππ* state of Phe in the peptide environment is systematically found to be shorter-lived. The lifetime at the origin of transition is found to be significantly shortened in the presence of a primary amide (-CONH2) group (20-60 ns, depending on the conformer considered), demonstrating the existence of an additional non-radiative relaxation channel related to this chemical group. The quenching effect induced by the peptide environment is still more remarkable beyond the origin of the ππ* state, since vibronic bands of one of the 4 conformers observed (the 27-ribbon conformation) become barely detectable in the ns R2PI experiment, suggesting a significant conformer-selective lifetime shortening (below 100 ps). These results on dipeptides, which extend previous investigations on shorter Phe-containing molecules (N-Ac-Phe-NH2 and N-Ac-Phe-NH-Me), confirm the existence of conformer-dependent non-radiative deactivation processes, whose characteristic timescales range from tens of ns down to hundreds of ps or below. This dynamics is assigned to two distinct mechanisms: a first one, consistent with an excitation energy transfer from the optically active ππ* state to low-lying amide nπ* excited states accessed through conical intersections, especially in the presence of a C-terminal primary amide group (-CONH2); a second one, responsible for the short lifetimes in 2(7) ribbon structures, would be more specifically triggered by phenyl ring vibrational excitations. Implications in terms of spectroscopic probing of Phe in a peptide environment, especially

BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF.

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Lim, Yen Ying; Rainey-Smith, Stephanie; Lim, Yoon; Laws, Simon M; Gupta, Veer; Porter, Tenielle; Bourgeat, Pierrick; Ames, David; Fowler, Christopher; Salvado, Olivier; Villemagne, Victor L; Rowe, Christopher C; Masters, Colin L; Zhou, Xin Fu; Martins, Ralph N; Maruff, Paul

2017-11-01

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36-54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months. Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ- or Aβ+. At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ- Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF. While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.

29 CFR 570.58 - Occupations involved in the operation of power-driven hoisting apparatus (Order 7).

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2010-07-01

... hoisting apparatus (Order 7). 570.58 Section 570.58 Labor Regulations Relating to Labor (Continued) WAGE... trucks, or stacking trucks, but shall not mean low-lift trucks or low-lift platform trucks that are... stacking trucks, but shall not mean low-lift trucks or low-lift platform trucks that are designed for the...

29 CFR 570.55 - Occupations involved in the operation of power-driven woodworking machines (Order 5).

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2010-07-01

... woodworking machines (Order 5). 570.55 Section 570.55 Labor Regulations Relating to Labor (Continued) WAGE AND... woodworking machines (Order 5). Link to an amendment published at 75 FR 28455, May 20, 2010. (a) Finding and declaration of fact. The following occupations involved in the operation of power-driven wood-working machines...

48 CFR 31.205-23 - Losses on other contracts.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Losses on other contracts. 31.205-23 Section 31.205-23 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... Organizations 31.205-23 Losses on other contracts. An excess of costs over income under any other contract...

Distribution, utilization structure and potential of biomass resources in rural China: With special references of crop residues

Energy Technology Data Exchange (ETDEWEB)

Liu, H [Laboratory of Quantitative Vegetation Ecology, Institute of Botany, Chinese Academy of Sciences, 20 Nanxincun, Xiangshan, Beijing 100093 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Jiang, G M [Laboratory of Quantitative Vegetation Ecology, Institute of Botany, Chinese Academy of Sciences, 20 Nanxincun, Xiangshan, Beijing 100093 (China); Agronomy Department, Shandong Agricultural University, Tai' an 271018, Shandong Province (China); Zhuang, H Y [National Bio-Energy CO., LTD, No. 26B, Financial Street, Xicheng District, Beijing 100032 (China); Shandong Academy of Sciences, No. 19, Keyuan Road, Ji' nan 250014, Shandong Province (China); Wang, K J [Agronomy Department, Shandong Agricultural University, Tai' an 271018, Shandong Province (China)

2008-06-15

As the largest developing country in the world, China is urgently in short of energy and natural resources. However, biological resources such as crop residues are burnt in the field, which cause serious environmental pollution. Still it is not clear how much storage and potential of these huge crop residues are in China. This paper firstly reported the distribution, utilization structure and potential of crop biomass and provided the tangible information of crop residues in rural China through careful collecting and recalculating data. From 1995 to 2005, China produces some 630 million tons of crop residues per year, 50% of which comes from east and central south of China. The amount of crop residues is 1.3 times of the total yield of crops, 2 times of the total fodder of grassland, which covers 41% of China's territory. Crop residues of corn, wheat and rice amounted to 239, 137 and 116 million tons, respectively, accounting for nearly 80% of the total crop residues. Unfortunately, the utilizing structure is seriously improper for such abundant biomass resources. Although 23% of the crop residues are used for forage, 4% for industry materials and 0.5% for biogas, the large parts are used with lower efficiency or wasted, with 37% being directly combusted by farmers, 15% lost during collection and the rest 20.5% discarded or directly burnt in the field. Reasonable adjustment of the utilizing pattern and popularization of the recycling agriculture are essential out-ways for residues, with the development of the forage industry being the breakthrough point. We suggested that utilizing the abandoned 20.5% of the total residues for forage and combining agriculture and stock raising can greatly improve the farm system and cut down fertilizer pollution. Through the development of forage industries, the use efficiency of crop residues could be largely enhanced. Commercializing and popularizing technologies of biomass gasification and liquefaction might be substitute

40 CFR 205.157-3 - Configuration identification.

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2010-07-01

...-3 Section 205.157-3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycles § 205.157-3 Configuration...) intake ducting; and (iii) air cleaner element. (3) Vehicle drive train: (i) Chain; and (ii) shaft. (4...

The impact of the Catechol-O-methyltransferase Val158Met polymorphism on survival in the general population – the HUNT study

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Skorpen Frank

2007-06-01

Full Text Available Abstract Background The catechol-O-methyltransferase (COMT gene contains a functional polymorphism, Val158Met which has been related to common diseases like cancer, psychiatric illness and myocardial infarction. Whether the Val158Met polymorphism is associated with survival has not been evaluated in the general population. The aim of this prospective study was to evaluate the impact of codon 158 COMT gene polymorphism on survival in a population-based cohort. Methods The sample comprised 2979 non-diabetic individuals who participated in the Nord-Trøndelag Health Study (HUNT in the period 1995–97. The subjects were followed up with respect to mortality throughout year 2004. Results 212 men and 183 women died during the follow up. No association between codon 158 COMT gene polymorphism and survival was found. The unadjusted relative risk of death by non-ischemic heart diseases with Met/Met or Met/Val genotypes was 3.27 (95% confidence interval, 1.19–9.00 compared to Val/Val genotype. When we adjusted for age, gender, smoking, coffee intake and body mass index the relative risk decreased to 2.89 (95% confidence interval, 1.04–8.00. Conclusion During 10 year of follow-up, the Val158Met polymorphism had no impact on survival in a general population. Difference in mortality rates from non-ischemic heart diseases may be incidental and should be evaluated in other studies.

48 CFR 615.205-70 - Use of English language.

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2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Use of English language. 615.205-70 Section 615.205-70 Federal Acquisition Regulations System DEPARTMENT OF STATE CONTRACTING... Information 615.205-70 Use of English language. The requirements of DOSAR 614.201-70 also apply when...

Residue 182 influences the second step of protein-tyrosine phosphatase-mediated catalysis

DEFF Research Database (Denmark)

Pedersen, A.K.; Guo, X.; Møller, K.B.

2004-01-01

Previous enzyme kinetic and structural studies have revealed a critical role for Asp(181) (PTP1B numbering) in PTP (protein-tyrosine phosphatase)-mediated catalysis. In the E-P (phosphoenzyme) formation step, Asp(181) functions as a general acid, while in the E-P hydrolysis step it acts...... as a general base. Most of our understanding of the role of Asp(181). is derived from studies with the Yersinia PTP and the mammalian PTP1B, and to some extent also TC (T-cell)-PTP and, the related PTPalpha and PTPepsilon. The neighbouring residue 182 is a phenylalanine in these four mammalian enzymes...... and a glutamine in Yersinia PTP. Surprisingly, little attention has been paid to the fact that this residue is a histidine in most other mammalian PTPs. Using a reciprocal single-point mutational approach with introduction of His(182) in PTP1B and Phe(182) in PTPH1, we demonstrate here that His(182)-PTPs...

Solvent selection and optimization of α-chymotrypsin-catalyzed synthesis of N-Ac-Phe-Tyr-NH2 using mixture design and response surface methodology.

Science.gov (United States)

Hu, Shih-Hao; Kuo, Chia-Hung; Chang, Chieh-Ming J; Liu, Yung-Chuan; Chiang, Wen-Dee; Shieh, Chwen-Jen

2012-01-01

A peptide, N-Ac-Phe-Tyr-NH(2) , with angiotensin I-converting enzyme (ACE) inhibitor activity was synthesized by an α-chymotrypsin-catalyzed condensation reaction of N-acetyl phenylalanine ethyl ester (N-Ac-Phe-OEt) and tyrosinamide (Tyr-NH(2) ). Three kinds of solvents: a Tris-HCl buffer (80 mM, pH 9.0), dimethylsulfoxide (DMSO), and acetonitrile were employed in this study. The optimum reaction solvent component was determined by simplex centroid mixture design. The synthesis efficiency was enhanced in an organic-aqueous solvent (Tris-HCl buffer: DMSO: acetonitrile = 2:1:1) in which 73.55% of the yield of N-Ac-Phe-Tyr-NH(2) could be achieved. Furthermore, the effect of reaction parameters on the yield was evaluated by response surface methodology (RSM) using a central composite rotatable design (CCRD). Based on a ridge max analysis, the optimum condition for this peptide synthesis included a reaction time of 7.4 min, a reaction temperature of 28.1°C, an enzyme activity of 98.9 U, and a substrate molar ratio (Phe:Tyr) of 1:2.8. The predicted and the actual (experimental) yields were 87.6 and 85.5%, respectively. The experimental design and RSM performed well in the optimization of synthesis of N-Ac-Phe-Tyr-NH(2) , so it is expected to be an effective method for obtaining a good yield of enzymatic peptide. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

COMT Val158Met Polymorphism, Executive Dysfunction, and Sexual Risk Behavior in the Context of HIV Infection and Methamphetamine Dependence

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C. A. Bousman

2010-01-01

Full Text Available Catechol-O-methyltransferease (COMT metabolizes prefrontal cortex dopamine (DA, a neurotransmitter involved in executive behavior; the Val158Met genotype has been linked to executive dysfunction, which might increase sexual risk behaviors favoring HIV transmission. Main and interaction effects of COMT genotype and executive functioning on sexual risk behavior were examined. 192 sexually active nonmonogamous men completed a sexual behavior questionnaire, executive functioning tests, and were genotyped using blood-derived DNA. Main effects for executive dysfunction but not COMT on number of sexual partners were observed. A COMT x executive dysfunction interaction was found for number of sexual partners and insertive anal sex, significant for carriers of the Met/Met and to a lesser extent Val/Met genotypes but not Val/Val carriers. In the context of HIV and methamphetamine dependence, dopaminergic overactivity in prefrontal cortex conferred by the Met/Met genotype appears to result in a liability for executive dysfunction and potentially associated risky sexual behavior.

Amino acids analysis during lactic acid fermentation by single strain ...

African Journals Online (AJOL)

L. salivarius alone showed relatively good assimilation of various amino acids that existed at only a little amounts in MRS media (Asn, Asp, Cit, Cys, Glu, His, Lys, Orn, Phe, Pro, Tyr, Arg, Ile, Leu, Met, Ser, Thr, Trp and Val), whereas Ala and Gly accumulated in L. salivarius cultures. P. acidilactici, in contrast, hydrolyzed the ...

Age-related olfactory decline is associated with the BDNF val66met polymorphism: evidence from a population-based study

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Margareta Hedner

2010-06-01

Full Text Available The present study investigates the effect of the brain-derived neurotrophic factor (BDNF val66met polymorphism on change in olfactory function in a large scale, longitudinal population-based sample (n=836. The subjects were tested on a 13 item force-choice odor identification test on two test occasions over a 5-year-interval. Sex, education, health-related factors, and semantic ability were controlled for in the statistical analyses. Results showed an interaction effect of age and BDNF val66met on olfactory change, such that the magnitude of olfactory decline in the older age cohort (70-90 years old at baseline was larger for the val homozygote carriers than for the met carriers. The older met carriers did not display larger age-related decline in olfactory function compared to the younger group. The BDNF val66met polymorphism did not affect the rate of decline in the younger age cohort (45-65 years. The findings are discussed in the light of the proposed roles of BDNF in neural development and maintenance.

The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: a fMRI study.

Science.gov (United States)

Kempton, Matthew J; Haldane, Morgan; Jogia, Jigar; Christodoulou, Tessa; Powell, John; Collier, David; Williams, Steven C R; Frangou, Sophia

2009-04-01

The functional catechol-O-methyltransferase (COMT Val108/158Met) polymorphism has been shown to have an impact on tasks of executive function, memory and attention and recently, tasks with an affective component. As oestrogen reduces COMT activity, we focused on the interaction between gender and COMT genotype on brain activations during an affective processing task. We used functional MRI (fMRI) to record brain activations from 74 healthy subjects who engaged in a facial affect recognition task; subjects viewed and identified fearful compared to neutral faces. There was no main effect of the COMT polymorphism, gender or genotypexgender interaction on task performance. We found a significant effect of gender on brain activations in the left amygdala and right temporal pole, where females demonstrated increased activations over males. Within these regions, Val/Val carriers showed greater signal magnitude compared to Met/Met carriers, particularly in females. The COMT Val108/158Met polymorphism impacts on gender-related patterns of activation in limbic and paralimbic regions but the functional significance of any oestrogen-related COMT inhibition appears modest.

48 CFR 31.205-32 - Precontract costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Precontract costs. 31.205... CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.205-32 Precontract costs. Precontract costs means costs incurred before the effective date of the...

48 CFR 31.205-27 - Organization costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Organization costs. 31.205... CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.205-27 Organization costs. (a) Except as provided in paragraph (b) of this section, expenditures in...

HR-TEM and FT-Raman dataset of the caffeine interacted Phe–Phe peptide nanotube for possible sensing applications

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A. Lakshmi Narayanan

2018-02-01

Full Text Available Sensing ability of caffeine interaction with Phe-Phe annotates (PNTs, is presented (Govindhan et al., 2017; Karthikeyan et al., 2014; Tavagnacco et al., 2013; Kennedy et al., 2011; Wang et al., 2017 [1–5] in this data set. Investigation of synthesized caffeine carrying peptide nanotubes are carried out by FT-Raman spectral analysis and high resolution transmission electron microscopy (HR-TEM. Particle size of the caffeine loaded PNTs is < 40 nm. The FT-Raman spectrum signals are enhanced in the region of 400–1700 cm−1. These data are ideal tool for the applications like biosensing and drug delivery research (DDS. Keywords: Caffeine, PNTs, Sensing, HR-TEM, FT-Raman data

Comparison of Glycomacropeptide with Phenylalanine Free-Synthetic Amino Acids in Test Meals to PKU Patients: No Significant Differences in Biomarkers, Including Plasma Phe Levels

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Kirsten K. Ahring

2018-01-01

Full Text Available Introduction. Management of phenylketonuria (PKU is achieved through low-phenylalanine (Phe diet, supplemented with low-protein food and mixture of free-synthetic (FS amino acid (AA. Casein glycomacropeptide (CGMP is a natural peptide released in whey during cheese-making and does not contain Phe. Lacprodan® CGMP-20 used in this study contained a small amount of Phe due to minor presence of other proteins/peptides. Objective. The purpose of this study was to compare absorption of CGMP-20 to FSAA with the aim of evaluating short-term effects on plasma AAs as well as biomarkers related to food intake. Methods. This study included 8 patients, who had four visits and tested four drink mixtures (DM1–4, consisting of CGMP, FSAA, or a combination. Plasma blood samples were collected at baseline, 15, 30, 60, 120, and 240 minutes (min after the meal. AA profiles and ghrelin were determined 6 times, while surrogate biomarkers were determined at baseline and 240 min. A visual analogue scale (VAS was used for evaluation of taste and satiety. Results. The surrogate biomarker concentrations and VAS scores for satiety and taste were nonsignificant between the four DMs, and there were only few significant results for AA profiles (not Phe. Conclusion. CGMP and FSAA had the overall same nonsignificant short-term effect on biomarkers, including Phe. This combination of FSAA and CGMP is a suitable supplement for PKU patients.

The COMT Val158Met Polymorphism Is Associated With Response to Add-on Dextromethorphan Treatment in Bipolar Disorder.

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Lee, Sheng-Yu; Chen, Shiou-Lan; Wang, Tzu-Yun; Chang, Yun-Hsuan; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Chen, Kao Ching; Yang, Yen Kuang; Lu, Ru-Band

2017-02-01

We previously conducted a randomized, double-blind, controlled, 12-week study evaluating the effect of add-on dextromethorphan (DM), a noncompetitive N-methyl-D-aspartate receptor antagonist, on patients with bipolar disorder (BD) treated using valproate (VPA), which showed negative clinical differences. The genetic variation between each individual may be responsible for interindividual differences. The catechol-O-methyltransferase (COMT) gene has been a candidate gene for BD. In the current study, we investigated whether the COMT Val158Met polymorphism predicts treatment response to VPA + add-on DM and to VPA + placebo. Patients with BD (n = 309) undergoing regular VPA treatments were randomly assigned to groups given either add-on DM (30 mg/d) (n = 102), DM (60 mg/d) (n = 101), or placebo (n = 106) for 12 weeks. The Hamilton Depression Rating Scale and Young Mania Rating Scale were used to evaluate clinical response during weeks 0, 1, 2, 4, 8, and 12. The genotypes of the COMT Val158Met polymorphism were determined using polymerase chain reaction plus restriction fragment length polymorphism analysis. To adjust for within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used. When stratified by the COMT Val158Met genotypes, significantly greater decreases in Hamilton Depression Rating Scale scores were found in the VPA + DM (30 mg/d) group in patients with the Val/Met genotype (P = 0.008). We conclude that the COMT Val158Met polymorphism may influence responses to DM (30 mg/d) by decreasing depressive symptoms in BD patients.

48 CFR 1823.570 - Drug- and alcohol-free workforce.

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2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Drug- and alcohol-free..., OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Drug-Free Workplace 1823.570 Drug- and alcohol-free workforce. This section sets sets forth NASA requirements for mandatory drug and alcohol testing of certain...

48 CFR 31.205-26 - Material costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Material costs. 31.205-26... CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.205-26 Material costs. (a) Material costs include the costs of such items as raw materials, parts...

48 CFR 31.205-4 - Bonding costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Bonding costs. 31.205-4... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.205-4 Bonding costs. (a) Bonding costs arise when the Government requires assurance against financial loss to itself...

48 CFR 31.205-3 - Bad debts.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Bad debts. 31.205-3... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.205-3 Bad debts. Bad debts, including actual or estimated losses arising from uncollectible accounts receivable due...

Impaired cognitive flexibility during sleep deprivation among carriers of the Brain Derived Neurotrophic Factor (BDNF) Val66Met allele.

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Grant, Leilah K; Cain, Sean W; Chang, Anne-Marie; Saxena, Richa; Czeisler, Charles A; Anderson, Clare

2018-02-15

Accumulating evidence points to a genetic contribution to explain inter-individual vulnerability to sleep deprivation. A functional polymorphism in the BDNF gene, which causes a valine (Val) to methionine (Met) amino acid substitution at Codon 66, has been associated with cognitive impairment, particularly in populations with impaired frontal functioning. We hypothesised that sleep deprivation, which affects frontal function, may lead to cognitive dysfunction in Met allele carriers. To examine this, we investigated, in different BDNF genotypes, the effects of sleep deprivation on cognitive flexibility, as measured by response inhibition using the Stroop Color Naming Task. Thirty healthy, adults of European ancestry, including 12 heterozygous Met allele carriers and 18 Val/Val homozygotes, underwent 30-h of extended wakefulness under constant routine conditions. A computerised Stroop task was administered every 2h. Error rate and reaction times increased with time awake for all individuals. Participants with the Val/Met genotype made more errors on incongruent trials after 20h awake. While Val/Met participants also took significantly longer to respond when inhibiting a prepotent response irrespective of time awake, this was particularly evident during the biological night. Our study shows that carriers of the BDNF Met allele are more vulnerable to the impact of prolonged wakefulness and the biological night on a critical component of executive function, as measured by response inhibition on the Stroop task. Copyright © 2017 Elsevier B.V. All rights reserved.

A case-control study of the HER2 Ile655Val polymorphism in relation to risk of invasive breast cancer

International Nuclear Information System (INIS)

Nelson, Stephanie E; Gould, Michael N; Hampton, John M; Trentham-Dietz, Amy

2005-01-01

Overexpression of the HER2 proto-oncogene in human cancer cells has been associated with a poor prognosis, and survival improves with therapy targeting the HER2 gene. Animal studies and protein modeling suggest that the Ile655Val polymorphism located in the transmembrane domain of the HER2 protein might influence breast cancer development by altering the efficiency of homodimerization. To investigate this genetic polymorphism, incident cases of invasive breast cancer (N = 1,094) and population controls of a similar age (N = 976) were interviewed during 2001 to 2003 regarding their risk factors for breast cancer. By using DNA collected from buccal samples mailed by the participants, the HER2 Ile655Val polymorphism was evaluated with the Applied Biosystems allelic discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression adjusted for numerous breast cancer risk factors. Analysis was restricted to women with self-reported European descent. Prevalence of the Val/Val genotype was 5.6% in cases and 7.1% in controls. In comparison with the Ile/Ile genotype, the Ile/Val genotype was not significantly associated with breast cancer risk (OR 0.97, 95% CI 0.79 to 1.18), whereas the Val/Val genotype was associated with a reduced risk (OR 0.63, 95% CI 0.42 to 0.92). This inverse association seemed strongest in older women (OR 0.51, 95% CI 0.29 to 0.89 for women aged more than 55 years), women without a family history of breast cancer (OR 0.54, 95% CI 0.35 to 0.84), postmenopausal women with greater body mass index (OR 0.43, 95% CI 0.20 to 0.91 for a body mass index of 25.3 kg/m 2 or more), and cases diagnosed with non-localized breast cancer (OR 0.49, 95% CI 0.26 to 0.90). Although results from our population-based case-control study show an inverse association between the HER2 Ile655Val polymorphism and risk of invasive breast cancer, most other studies of this single-nucleotide polymorphism suggest an overall null

Study of new interactions of glitazone's stereoisomers and the endogenous ligand 15d-PGJ2 on six different PPAR gamma proteins.

Science.gov (United States)

Álvarez-Almazán, Samuel; Bello, Martiniano; Tamay-Cach, Feliciano; Martínez-Archundia, Marlet; Alemán-González-Duhart, Diana; Correa-Basurto, José; Mendieta-Wejebe, Jessica Elena

2017-10-15

Diabetes mellitus is a chronic disease characterized by hyperglycemia, insulin resistance and hyperlipidemia. Glitazones or thiazolidinediones (TZD) are drugs that act as insulin-sensitizing agents whose molecular target is the peroxisome proliferator-activated receptor gamma (PPARγ). The euglycemic action of TZD has been linked with the induction of type 4 glucose transporter. However, it has been shown that the effect of TZD depends on the specific stereoisomer that interacts with PPARγ. Therefore, this work is focused on exploring the interactions and geometry adopted by glitazone's stereoisomers and one endogenous ligand on different conformations of the six crystals of the PPARγ protein using molecular docking and molecular dynamics (MD) simulations accompanied by the MMGBSA approach. Specifically, the 2,4-thiazolidinedione ring, pioglitazone (PIO), rosiglitazone (ROSI) and troglitazone (TRO) stereoisomers (exogenous ligands), as well as the endogenous ligand 15d-PGJ2, were evaluated. The six crystallographic structures of PPARγ are available at Protein Data Bank as the PDB entries 2PRG, 4PRG, 3T03, 1I7I, 1FM6, and 4EMA. According to the results, a boomerang shape and a particular location of ligands were found with low variations according to the protein conformations. The 15d-PGJ2, TZD, PIO, ROSI and (S,S)-TRO enantiomers were mostly stabilized by twenty hydrophobic residues: Phe226, Pro227, Leu228, Ile281, Phe282, Cys285, Ala292, Ile296, Ile326, Tyr327, Met329, Leu330, Leu333, Met334, Val339, Ile341, Met348, Leu353, Phe363 and Met364. Most hydrogen bond interactions were found between the polar groups of ligands with Arg288, Ser289, Lys367, Gln286, His323, Glu343 and His449 residues. An energetic analysis revealed binding free energy trends that supported known experimental findings of other authors describing better binding properties for PIO, ROSI and (S,S)-TRO than for 15d-PGJ2 and the TZD ring. Copyright © 2017 Elsevier Inc. All rights reserved.

BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction.

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Zhao, Mingzhe; Chen, Lu; Yang, Jiarun; Han, Dong; Fang, Deyu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Ma, Jingsong; Wang, Lin; Jiang, Shixiang; Song, Xuejia; Zhou, Jiawei; Zhang, Jian; Chen, Mingqi; Qi, Dong; Yang, Yanjie; Pan, Hui

2018-02-01

Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect. Copyright © 2017 Elsevier B.V. All rights reserved.

48 CFR 31.205-36 - Rental costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Rental costs. 31.205-36... CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.205-36 Rental costs. (a) This subsection is applicable to the cost of renting or leasing real or...

37 CFR 205.3 - Waiver of rules.

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2010-07-01

... procedural, enforceable at law by a party against the Copyright Office, the Library of Congress, or the... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Waiver of rules. 205.3 Section 205.3 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT OFFICE...

45 CFR 205.101 - Organization for administration.

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2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false Organization for administration. 205.101 Section... ADMINISTRATION-PUBLIC ASSISTANCE PROGRAMS § 205.101 Organization for administration. (a) A State plan for... description of the organization and functions of the single State agency and an organizational chart of the...

48 CFR 31.205-34 - Recruitment costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Recruitment costs. 31.205....205-34 Recruitment costs. (a) Subject to paragraph (b) of this subsection, the following costs are... positions; or (2) Includes material that is not relevant for recruitment purposes, such as extensive...

Study of association between genetic polymorphisms of phospholipase A2 enzymes and Alzheimer's disease Associação entre polimorfismos das enzimas fosfolipases A2 e doença de Alzheimer

Directory of Open Access Journals (Sweden)

Quirino Cordeiro

2010-04-01

Full Text Available Several genes have been related to late-onset Alzheimer's disease (LOAD. Phospholipases A2 (PLA2 influence the processing and secretion of the amyloid precursor protein, which gives rise to the beta-amyloid peptide, the major component of the amyloid plaque in AD. Hence, in the present study, polymorphisms of three genes encoding PLA2 enzymes group (cytosolic PLA2: BanI cPLA2 polymorphism; calcium-independent PLA2: AvrII iPLA2 polymorphism; PAFAH: Val279Phe PAFAH polymorphism were analysed in a case-control sample using 58 patients with LOAD and 107 matched healthy controls. There was a genotypic association between the BanI cPLA2 polymorphism and LOAD (χ2=6.25, 2df, p=0.04, however there was no allelic association. There were no associations between AvrII iPLA2 and Val279Phe PAFAH polymorphisms and LOAD. These data suggest that the BanI cPLA2 polymorphism may play a role in the susceptibility for LOAD in our Brazilian sample.Vários genes têm sido investigados como fatores de risco para o desenvolvimento da doença de Alzheimer (DA de início tardio. As fosfolipases A2 (PLA2 influenciam o processamento e secreção da proteína precursora do amilóide, que dá origem ao peptídeo meta-amilóide, o principal componente da placa amilóide na DA. Assim, no presente estudo, foram analisados três polimorfismos genéticos que codificam enzimas do grupo das PLA2 (PLA2 citosólica: polimorfismo BanI cPLA2; PLA2 cálcio-independente: polimorfismo AvrII iPLA2; PAFAH: polimorfismo Val279Phe PAFAH em 58 pacientes com DA de início tardio e 107 controles saudáveis pareados. Houve associação genotípica entre o polimorfismo BanI cPLA2 e DA de início tardio (χ2=6,25, 2df, p=0,04; no entanto não foi observada associação alélica. Não houve associação entre os polimorfismos AvrII iPLA2 e Val279Phe PAFAH com a doença. Tais dados sugerem que o polimorfismo BanI cPLA2 pode estar envolvido como fator de susceptibilidade para DA de início tardio em

29 CFR 570.102 - General scope of statutory provisions.

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2010-07-01

... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION General Statements of Interpretation of the Child Labor Provisions of the Fair Labor Standards Act of 1938, as Amended General § 570.... The most important of the child labor provisions are contained in sections 12(a), 12(c), and 3(l) of...

40 CFR 205.57 - Selective enforcement auditing requirements.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Selective enforcement auditing requirements. 205.57 Section 205.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE... Selective enforcement auditing requirements. ...

COMT Val158Met polymorphism influences the susceptibility to framing in decision-making: OFC-amygdala functional connectivity as a mediator.

Science.gov (United States)

Gao, Xiaoxue; Gong, Pingyuan; Liu, Jinting; Hu, Jie; Li, Yue; Yu, Hongbo; Gong, Xiaoliang; Xiang, Yang; Jiang, Changjun; Zhou, Xiaolin

2016-05-01

Individuals tend to avoid risk in a gain frame, in which options are presented in a positive way, but seek risk in a loss frame, in which the same options are presented negatively. Previous studies suggest that emotional responses play a critical role in this "framing effect." Given that the Met allele of COMT Val158Met polymorphism (rs4680) is associated with the negativity bias during emotional processing, this study investigated whether this polymorphism is associated with individual susceptibility to framing and which brain areas mediate this gene-behavior association. Participants were genotyped, scanned in resting state, and completed a monetary gambling task with options (sure vs risky) presented as potential gains or losses. The Met allele carriers showed a greater framing effect than the Val/Val homozygotes as the former gambled more than the latter in the loss frame. Moreover, the gene-behavior association was mediated by resting-state functional connectivity (RSFC) between orbitofrontal cortex (OFC) and bilateral amygdala. Met allele carriers showed decreased RSFC, thereby demonstrating higher susceptibility to framing than Val allele carriers. These findings demonstrate the involvement of COMT Val158Met polymorphism in the framing effect in decision-making and suggest RSFC between OFC and amygdala as a neural mediator underlying this gene-behavior association. Hum Brain Mapp 37:1880-1892, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

New cyclic peptides with osteoblastic proliferative activity from Dianthus superbus.

Science.gov (United States)

Tong, Yun; Luo, Jian-Guang; Wang, Rui; Wang, Xiao-Bing; Kong, Ling-Yi

2012-03-01

Two new cyclic peptides, dianthins G-H (1 and 2), together with the known dianthin E (3), were isolated from the traditional Chinese medicinal plant Dianthus superbus. The sequences of cyclic peptides 1 and 2 were elucidated as cyclo (-Gly(1)-Pro(2)-Leu(3)-Thr(4)-Leu(5)-Phe(6)-) and cyclo (-Gly(1)-Pro(2)-Val(3)-Thr(4)-Ile(5)-Phe(6)-), on the basis of ESI tandem mass fragmentation analysis, extensive 2D NMR methods and X-ray diffraction. The isolated three compounds all increase proliferation of MC3T3-E1 cells in vitro using MTT method. Copyright © 2012 Elsevier Ltd. All rights reserved.

48 CFR 31.205-46 - Travel costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Travel costs. 31.205-46....205-46 Travel costs. (a) Costs for transportation, lodging, meals, and incidental expenses. (1) Costs... at the time of travel as set forth in the— (i) Federal Travel Regulation, prescribed by the General...

7 CFR 205.236 - Origin of livestock.

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2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Origin of livestock. 205.236 Section 205.236... livestock. (a) Livestock products that are to be sold, labeled, or represented as organic must be from livestock under continuous organic management from the last third of gestation or hatching: Except, That: (1...

37 CFR 205.21 - Scope and purpose.

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2010-07-01

... Section 205.21 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT OFFICE... in Which the Office Is Not a Party § 205.21 Scope and purpose. (a) This subpart prescribes policies... opinions of Office employees with Office policy; (4) To avoid spending the time and money of the United...

48 CFR 31.205-20 - Interest and other financial costs.

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2010-10-01

... financial costs. 31.205-20 Section 31.205-20 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.205-20 Interest and other financial costs. Interest on borrowings (however represented), bond...

31 CFR 515.570 - Remittances to Nationals of Cuba.

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2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Remittances to Nationals of Cuba. 515..., Authorizations, and Statements of Licensing Policy § 515.570 Remittances to Nationals of Cuba. (a) Family... older are authorized to make remittances to nationals of Cuba who are close relatives, as defined in...

17 CFR 205.3 - Issuer as client.

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2010-04-01

... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Issuer as client. 205.3... ISSUER § 205.3 Issuer as client. (a) Representing an issuer. An attorney appearing and practicing before...'s clients. (b) Duty to report evidence of a material violation. (1) If an attorney, appearing and...

48 CFR 31.205-30 - Patent costs.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Patent costs. 31.205-30....205-30 Patent costs. (a) The following patent costs are allowable to the extent that they are incurred... patent application where title or royalty-free license is to be conveyed to the Government. (b) General...

Effect of thermal exposure on the residual stress relaxation in a hardened cylindrical sample under creep conditions

Science.gov (United States)

Radchenko, V. P.; Saushkin, M. N.; Tsvetkov, V. V.

2016-05-01

This paper describes the effect of thermal exposure (high-temperature exposure) ( T = 675°C) on the residual creep stress relaxation in a surface hardened solid cylindrical sample made of ZhS6UVI alloy. The analysis is carried out with the use of experimental data for residual stresses after micro-shot peening and exposures to temperatures equal to T = 675°C during 50, 150, and 300 h. The paper presents the technique for solving the boundary-value creep problem for the hardened cylindrical sample with the initial stress-strain state under the condition of thermal exposure. The uniaxial experimental creep curves obtained under constant stresses of 500, 530, 570, and 600 MPa are used to construct the models describing the primary and secondary stages of creep. The calculated and experimental data for the longitudinal (axial) tensor components of residual stresses are compared, and their satisfactory agreement is determined.

Study on the enthalpy of solution and enthalpy of dilution for the ionic liquid [C3mim][Val] (1-propyl-3-methylimidazolium valine)

International Nuclear Information System (INIS)

Guan Wei; Li Long; Ma Xiaoxue; Tong Jing; Fang Dawei; Yang Jiazhen

2012-01-01

Graphical abstract: The thermodynamic cycle for estimation of the hydration enthalpy of ionic liquid [C 3 mim][Val]. Highlights: ► A new amino acid ionic liquid [C 3 mim][Val] was prepared. ► The molar enthalpies of solution of the ionic liquid. ► The hydration enthalpy of the cation [C 3 mim] + was estimated. ► The molar enthalpies of dilution, of aqueous [C 3 mim][Val] were measured. - Abstract: A new amino acid ionic liquid (AAIL) [C 3 mim][Val] (1-propyl-3-methylimidazolium valine) was prepared by the neutralization method. Using the solution-reaction isoperibol calorimeter, molar solution enthalpies of the ionic liquid [C 3 mim][Val] with known amounts of water and with different concentrations in molality were measured at T = 298.15 K. In terms of standard addition method (SAM) and Archer’s method, the standard molar enthalpy of solution for [C 3 mim][Val] without water, Δ s H m ∘ = (−55.7 ± 0.4) kJ · mol −1 , was obtained. The hydration enthalpy of the cation [C 3 mim] + , ΔH + ([C 3 mim] + ) = −226 kJ · mol −1 , was estimated in terms of Glasser’s theory. Using the RD496-III heat conduction microcalorimeter, the molar enthalpies of dilution, Δ D H m (m i → m f ), of aqueous [C 3 mim][Val] with various values of molality were measured. The values of Δ D H m (m i → m f ) were fitted to Pitzer’s ion-interaction model and the values of apparent relative molar enthalpy, φ L, calculated using Pitzer’s ion-interaction model.

The BDNF Val66Met Polymorphism Interacts with Maternal Parenting Influencing Adolescent Depressive Symptoms: Evidence of Differential Susceptibility Model.

Science.gov (United States)

Zhang, Leilei; Li, Zhi; Chen, Jie; Li, Xinying; Zhang, Jianxin; Belsky, Jay

2016-03-01

Although depressive symptoms are common during adolescence, little research has examined gene-environment interaction on youth depression. This study chose the brain-derived neurotrophic factor (BDNF) gene, tested the interaction between a functional polymorphism resulting amino acid substitution of valine (Val) to methionine (Met) in the proBDNF protein at codon 66 (Val66Met), and maternal parenting on youth depressive symptoms in a sample of 780 community adolescents of Chinese Han ethnicity (aged 11-17, M = 13.6, 51.3 % females). Participants reported their depressive symptoms and perceived maternal parenting. Results indicated the BDNF Val66Met polymorphism significantly moderated the influence of maternal warmth-reasoning, but not harshness-hostility, on youth depressive symptoms. Confirmatory model evaluation indicated that the interaction effect involving warmth-reasoning conformed to the differential-susceptibility rather than diathesis-stress model of person-X-environment interaction. Thus, Val carriers experienced less depressive symptoms than Met homozygotes when mothering was more positive but more symptoms when mothering was less positive. The findings provided evidence in support of the differential susceptibility hypothesis of youth depressive symptoms and shed light on the importance of examining the gene-environment interaction from a developmental perspective.

The Val{sup 192}Leu mutation in the {alpha}-subunit of {beta}-hexosaminidase A is not associated with the B1-variant form of Tay-Sachs disease

Energy Technology Data Exchange (ETDEWEB)

Hou, Y.; Vavougios, G.; Hinek, A. [Univ. of Toronto (Canada)] [and others

1996-07-01

Substitution mutations adversely affecting the {alpha}-subunit of {beta}-hexosaminidase A ({alpha}{beta}) (EC 3.2.1.52) result in Tay-Sachs disease. The majority affect the initial folding of the pro-{alpha} chain in the endoplasmic reticulum, resulting in its retention and degradation. A much less common occurrence is a mutation that specifically affects an {open_quotes}active-site{close_quotes} residue necessary for substrate binding and/or catalysis. In this case, hexosaminidase A is present in the lysosome, but it lacks all {alpha}-specific activity. This biochemical phenotype is referred to as the {open_quotes}B1-variant form{close_quotes} of Tay-Sachs disease. Kinetic analysis of suspected B1-variant mutations is complex because hexosaminidase A is heterodimeric and both subunits possess similar active sites. In this report, we examine a previously identified B1-variant mutation, {alpha}-Val{sup 192}Leu. Chinese hamster ovary cells were permanently cotransfected with an {alpha}-cDNA-construct encoding the substitution and a mutant {beta}-cDNA ({beta}-Arg{sup 211}Lys), encoding a {beta}-subunit that is inactive but normal in all other respects. We were surprised to find that the Val{sup 192}Leu substitution produced a pro-{alpha} chain that did not form {alpha}-{beta} dimers and was not transported to the lysosome. Finally, we reexamined the hexosaminidase activity and protein levels in the fibroblasts from the original patient. These data were also not consistent with the biochemical phenotype of the B1 variant of Tay-Sachs disease previously reported to be present. Thus, we conclude that the Val{sup 192}Leu substitution does not specifically affect the {alpha}-active site. 23 refs., 4 figs., 2 tabs.

Ressenya a Sònia Gros, «Aquella dolçor amarga». La tradició amatòria clàssica en el Curial e Güelfa. València, Publicacions de la Universitat de València, 2015, 346 pp. ISBN: 978-84-370-9648-3

Directory of Open Access Journals (Sweden)

Adrià Martí i Badia

2015-12-01

Full Text Available Review to Sònia Gros, «Aquella dolçor amarga». La tradició amatòria clàssica en el Curial e Güelfa. València, Publicacions de laUniversitat de València, 2015, 346 pp, ISBN: 978-84-370-9648-3

40 CFR 205.57-6 - Acceptance and rejection of batches.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Acceptance and rejection of batches. 205.57-6 Section 205.57-6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.57-6...

40 CFR 205.57-5 - Reporting of the test results.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Reporting of the test results. 205.57-5 Section 205.57-5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.57-5...

Solid state NMR of isotope labelled murine fur: a powerful tool to study atomic level keratin structure and treatment effects

Energy Technology Data Exchange (ETDEWEB)

Wong, Wai Ching Veronica; Narkevicius, Aurimas; Chow, Wing Ying; Reid, David G.; Rajan, Rakesh [University of Cambridge, Department of Chemistry (United Kingdom); Brooks, Roger A. [University of Cambridge, Department of Trauma and Orthopaedic Surgery, Addenbrooke’s Hospital (United Kingdom); Green, Maggie [University of Cambridge, Central Biomedical Resources, School of Clinical Medicine (United Kingdom); Duer, Melinda J., E-mail: mjd13@cam.ac.uk [University of Cambridge, Department of Chemistry (United Kingdom)

2016-10-15

We have prepared mouse fur extensively {sup 13}C,{sup 15}N-labelled in all amino acid types enabling application of 2D solid state NMR techniques which establish covalent and spatial proximities within, and in favorable cases between, residues. {sup 13}C double quantum–single quantum correlation and proton driven spin diffusion techniques are particularly useful for resolving certain amino acid types. Unlike 1D experiments on isotopically normal material, the 2D methods allow the chemical shifts of entire spin systems of numerous residue types to be determined, particularly those with one or more distinctively shifted atoms such as Gly, Ser, Thr, Tyr, Phe, Val, Leu, Ile and Pro. Also the partial resolution of the amide signals into two signal envelopes comprising of α-helical, and β-sheet/random coil components, enables resolution of otherwise overlapped α-carbon signals into two distinct cross peak families corresponding to these respective secondary structural regions. The increase in resolution conferred by extensive labelling offers new opportunities to study the chemical fate and structural environments of specific atom and amino acid types under the influence of commercial processes, and therapeutic or cosmetic treatments.

49 CFR 40.205 - How are drug test problems corrected?

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false How are drug test problems corrected? 40.205 Section 40.205 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Drug Tests § 40.205 How are drug test problems...

Feasibility studies of the geochemical Ti-205 solar neutrino experiment

CERN Document Server

Neumaier, S; Nolte, E; Morinaga, H

1991-01-01

New investigations on the signal to background ratio of the geochemical 205Tl( v., e-)205Pb solar neutrino experiment are presented. The neutrino capture rate of 205Tl and a possible reduction of the neutrino signal due to neutrino oscillations in matter are discussed. The contributions of natural radioactivity, stopped negative muons and fast muons to the background of 205Pb are estimated. The production of radioisotopes in the lead region induced by cosmic ray muons was studied at the high energy muon beam (M2) of CERN with 120, 200 and 280 GeV muons. The background contribution of cosmic ray muons is found to be significantly higher than expected by former estimations and restricts the feasibility of the 205Tl solar neutrino experiment.

COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of 'switching on' hallucinations in the flow of daily life.

Science.gov (United States)

Henquet, C; Rosa, A; Delespaul, P; Papiol, S; Fananás, L; van Os, J; Myin-Germeys, I

2009-02-01

A functional polymorphism in the catechol-o-methyltransferase gene (COMT Val(158)Met) may moderate the psychosis-inducing effects of cannabis. In order to extend this finding to dynamic effects in the flow of daily life, a momentary assessment study of psychotic symptoms in response to cannabis use was conducted. The experience sampling technique was used to collect data on cannabis use and occurrence of symptoms in daily life in patients with a psychotic disorder (n = 31) and healthy controls (n = 25). Carriers of the COMT Val(158)Met Val allele, but not subjects with the Met/Met genotype, showed an increase in hallucinations after cannabis exposure, conditional on prior evidence of psychometric psychosis liability. The findings confirm that in people with psychometric evidence of psychosis liability, COMT Val(158)Met genotype moderates the association between cannabis and psychotic phenomena in the flow of daily life.

Isolation and structure elucidation of neuropeptides of the AKH/RPCH family in long-horned grasshoppers (Ensifera).

Science.gov (United States)

Gäde, G

1992-11-01

An identical neuropeptide was isolated by reversed-phase high-performance liquid chromatography from the corpora cardiaca of the king cricket, Libanasidus vittatus, and the two armoured ground crickets, Heterodes namaqua and Acanthoproctus cervinus. The crude gland extracts had adipokinetic activity in migratory locusts, hypertrehalosaemic activity in American cockroaches and a slight hypertrehalosaemic, but no adipokinetic, effect in armoured ground crickets. The primary structure of this neuropeptide was determined by pulsed-liquid phase sequencing employing Edman chemistry after enzymically deblocking the N-terminal 5-oxopyrrolidine-2-carboxylic acid residue. The C-terminus was also blocked, as indicated by the lack of digestion by carboxypeptidase A. The peptide was assigned the structure [symbol: see text]Glu-Leu-Asn-Phe-Ser-Thr-Gly-TrpNH2, previously designated Scg-AKH-II. The corpora cardiaca of the cricket Gryllodes sigillatus contained a neuropeptide which differed in retention time from the one isolated from the king and armoured ground crickets. The structure was assigned as [symbol: see text]Glu-Val-Asn-Phe-Ser-Thr-Gly-TrpNH2, previously designated Grb-AKH. This octapeptide caused hyperlipaemia in its donor species. The presence of the same peptide, Scg-AKH-II, in the two primitive infraorders of Ensifera, and the different peptide, Grb-AKH, in the most advanced infraorder of Ensifera, supports the evolutionary trends assigned formerly from morphological and physiological evidence.

Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease.

Science.gov (United States)

Gomar, Jesus J; Conejero-Goldberg, Concepcion; Huey, Edward D; Davies, Peter; Goldberg, Terry E

2016-03-01

Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e., APOE gene) may influence brain-derived neurotrophic factor (BDNF) val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied 2 cohorts from Alzheimer's Disease Neuroimaging Initiative: 175 healthy subjects and 222 with prodromal and established Alzheimer's disease. Yearly structural magnetic resonance imaging and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers' (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices was detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes, respectively. The mild cognitive impairment/Alzheimer's disease cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. In addition, an effect of BDNF genotype was found in APOE E4 carriers for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers and APOE E4 carriers in healthy and pathological aging. Copyright © 2016 Elsevier Inc. All rights reserved.

Technology Development of an Advanced Small-scale Microchannel-type Process Heat Exchanger (PHE) for Hydrogen Production in Iodine-sulfur Cycle

Energy Technology Data Exchange (ETDEWEB)

Sah, Injin; Kim, Chan Soo; Kim, Yong Wan; Park, Jae-Won; Kim, Eung-Seon; Kim, Min-Hwan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-10-15

In this study, ongoing manufacturing processes of the components employed in an advanced small-scale microchannel-type PHE are presented. The components, such as mechanically machined microchannels and a diffusion-bonded stack are introduced. Also, preliminary studies on surface treatment techniques for improving corrosion resistance from the corrosive sulfuric environment will be covered. Ongoing manufacturing process for an advanced small-size microchannel-type PHE in KAERI is presented. Through the preliminary studies for optimizing diffusion bonding condition of Hastelloy-X, a diffusion-bonded stack, consisting of primary and secondary side layer by layer, is scheduled to be fabricated in a few months. Also, surface treatment for enhancing the corrosion resistance from the sulfuric acid environment is in progress for the plates with microchannels. A massive production of hydrogen with electricity generation is expected in a Process Heat Exchanger (PHE) in a Very High Temperature gas-cooled Reactor (VHTR) system. For the application of hydrogen production, a small-scale gas loop for feasibility testing of a laboratory-scale has constructed and operated in Korea Atomic Energy Research Institute (KAERI) as a precursor to an experimental- and a pilot-scale gas loops.

A novel 13 residue acyclic peptide from the marine snail, Conus monile, targets potassium channels.

Science.gov (United States)

Sudarslal, Sadasivannair; Singaravadivelan, Govindaswamy; Ramasamy, Palanisamy; Ananda, Kuppanna; Sarma, Siddhartha P; Sikdar, Sujit K; Krishnan, K S; Balaram, Padmanabhan

2004-05-07

A novel 13-residue peptide Mo1659 has been isolated from the venom of a vermivorous cone snail, Conus monile. HPLC fractions of the venom extract yielded an intense UV absorbing fraction with a mass of 1659Da. De novo sequencing using both matrix assisted laser desorption and ionization and electrospray MS/MS methods together with analysis of proteolytic fragments successfully yielded the amino acid sequence, FHGGSWYRFPWGY-NH(2). This was further confirmed by comparison with the chemically synthesized peptide and by conventional Edman sequencing. Mo1659 has an unusual sequence with a preponderance of aromatic residues and the absence of apolar, aliphatic residues like Ala, Val, Leu, and Ile. Mo1659 has no disulfide bridges distinguishing it from the conotoxins and bears no sequence similarity with any of the acyclic peptides isolated thus far from the venom of cone snails. Electrophysiological studies on the effect of Mo1659 on measured currents in dorsal root ganglion neurons suggest that the peptide targets non-inactivating voltage-dependent potassium channels.

29 CFR 99.205 - Basis for determining Federal awards expended.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Basis for determining Federal awards expended. 99.205 Section 99.205 Labor Office of the Secretary of Labor AUDITS OF STATES, LOCAL GOVERNMENTS, AND NON-PROFIT ORGANIZATIONS Audits § 99.205 Basis for determining Federal awards expended. (a) Determining Federal awards...

Low-Temperature Thermoelectric Properties of Fe2VAl with Partial Cobalt Doping

Science.gov (United States)

Liu, Chang; Morelli, Donald T.

2012-06-01

Ternary metallic alloy Fe2VAl with a pseudogap in its energy band structure has received intensive scrutiny for potential thermoelectric applications. Due to the sharp change in the density of states profile near the Fermi level, interesting transport properties can be triggered to render possible enhancement in the overall thermoelectric performance. Previously, this full-Heusler-type alloy was partially doped with cobalt at the iron sites to produce a series of compounds with n-type conductivity. Their thermoelectric properties in the temperature range of 300 K to 850 K were reported. In this research, efforts were made to extend the investigation on (Fe1- x Co x )2VAl to the low-temperature range. Alloy samples were prepared by arc-melting and annealing. Seebeck coefficient, electrical resistivity, and thermal conductivity measurements were performed from 80 K to room temperature. The effects of cobalt doping on the material's electronic and thermal properties are discussed.

7 CFR 205.400 - General requirements for certification.

Science.gov (United States)

2010-01-01

...) ORGANIC FOODS PRODUCTION ACT PROVISIONS NATIONAL ORGANIC PROGRAM Certification § 205.400 General requirements for certification. A person seeking to receive or maintain organic certification under the... 7 Agriculture 3 2010-01-01 2010-01-01 false General requirements for certification. 205.400...

Cerebral 5-HT2A receptor and serotonin transporter binding in humans are not affected by the val66met BDNF polymorphism status or blood BDNF levels

DEFF Research Database (Denmark)

Klein, Anders Bue; Trajkovska, Viktorija; Erritzoe, David

2010-01-01

Recent studies have proposed an interrelation between the brain-derived neurotrophic factor (BDNF) val66met polymorphism and the serotonin system. In this study, we investigated whether the BDNF val66met polymorphism or blood BDNF levels are associated with cerebral 5-hydroxytryptamine 2A (5-HT(2A......)) receptor or serotonin transporter (SERT) binding in healthy subjects. No statistically significant differences in 5-HT(2A) receptor or SERT binding were found between the val/val and met carriers, nor were blood BDNF values associated with SERT binding or 5-HT(2A) receptor binding. In conclusion, val66met...... BDNF polymorphism status is not associated with changes in the serotonergic system. Moreover, BDNF levels in blood do not correlate with either 5-HT(2A) or SERT binding....

Combined Role of Two Tryptophane Residues of α-Factor Pheromone

Energy Technology Data Exchange (ETDEWEB)

Hong, Eun Young [Yeungnam Univ., Gyungsan (Korea, Republic of); Hong, Nam Joo [Seoul National Univ., Seoul (Korea, Republic of)

2013-02-15

Amide analogs of tridecapeptide α-factor (WHWLQLKPGQPMYCONH{sub 2}) of Saccharomyces cerevisiae, in which Trp at position 1 and 3 were replaced with other residues, were synthesized to ascertain whether cooperative interactions between two Trp residues occurred upon binding with its receptor. Analogs containing Ala or Aib at position 3 of the peptide [Ala{sup 3}]α-factor amide (2) and [Aib{sup 3}]α-factor amide (5) exhibited greater decreases in bioactivity than analogs with same residue at position one [Ala{sup 1}]α-factor amide (1) and [Aib{sup 1}]α-factor amide (4), reflecting that Trp{sup 3} may plays more important role than Trp{sup 1} for agonist activity. Analogs containing Ala or Aib in both position one and three 3, 6 exhibited complete loss of bioactivity, emphasizing both the essential role and the combined role of two indole rings for triggering cell signaling. In contrast, double substituted analog with D-Trp in both positions 9 exhibited greater activity than single substituted analog with D-Trp 8 or deleted analog 7, reflecting the combined contribution of two tryptophane residues of α-factor ligand to activation of Ste2p through interaction with residue Tyr{sup 266} and importance of the proper parallel orientation of two indole rings for efficient triggering of signal G protein coupled activation. Among ten amide analogs, [Ala{sup 1,3}]α-factor amide (3), [Aib{sup 1,3}]α-factor amide (6), [D-Trp{sup 3}]α-factor amide (8) and [des-Trp{sup 1},Phe{sup 3}]α-factor amide (10) were found to have antagonistic activity. Analogs 3 and 6 showed greater antagonistic activity than analogs 8 and 10.

Combined Role of Two Tryptophane Residues of α-Factor Pheromone

International Nuclear Information System (INIS)

Hong, Eun Young; Hong, Nam Joo

2013-01-01

Amide analogs of tridecapeptide α-factor (WHWLQLKPGQPMYCONH 2 ) of Saccharomyces cerevisiae, in which Trp at position 1 and 3 were replaced with other residues, were synthesized to ascertain whether cooperative interactions between two Trp residues occurred upon binding with its receptor. Analogs containing Ala or Aib at position 3 of the peptide [Ala 3 ]α-factor amide (2) and [Aib 3 ]α-factor amide (5) exhibited greater decreases in bioactivity than analogs with same residue at position one [Ala 1 ]α-factor amide (1) and [Aib 1 ]α-factor amide (4), reflecting that Trp 3 may plays more important role than Trp 1 for agonist activity. Analogs containing Ala or Aib in both position one and three 3, 6 exhibited complete loss of bioactivity, emphasizing both the essential role and the combined role of two indole rings for triggering cell signaling. In contrast, double substituted analog with D-Trp in both positions 9 exhibited greater activity than single substituted analog with D-Trp 8 or deleted analog 7, reflecting the combined contribution of two tryptophane residues of α-factor ligand to activation of Ste2p through interaction with residue Tyr 266 and importance of the proper parallel orientation of two indole rings for efficient triggering of signal G protein coupled activation. Among ten amide analogs, [Ala 1,3 ]α-factor amide (3), [Aib 1,3 ]α-factor amide (6), [D-Trp 3 ]α-factor amide (8) and [des-Trp 1 ,Phe 3 ]α-factor amide (10) were found to have antagonistic activity. Analogs 3 and 6 showed greater antagonistic activity than analogs 8 and 10

The BDNF Val66Met polymorphism has opposite effects on memory circuits of multiple sclerosis patients and controls.

Directory of Open Access Journals (Sweden)

Francesco Fera

Full Text Available Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val(66Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis. Functional magnetic resonance imaging was used to assess how the Brain Derived Neurotrophic Factor Val(66Met polymorphism modulated brain regional activity and functional connectivity in 26 cognitively unimpaired Multiple Sclerosis patients and 25 age- and education-matched healthy controls while performing an episodic memory task that included encoding and retrieving visual scenes. We found a highly significant group by genotype interaction in the left posterior hippocampus, bilateral parahippocampus, and left posterior cingulate cortex. In particular, Multiple Sclerosis patients homozygous for the Val(66 allele, relative to Met(66 carriers, showed greater brain responses during both encoding and retrieval while the opposite was true for healthy controls. Furthermore, a robust group by genotype by task interaction was detected for the functional connectivity between the left posterior hippocampus and the ipsilateral posterior cingulate cortex. Here, greater hippocampus-posterior cingulate cortex connectivity was observed in Multiple Sclerosis Met(66 carriers relative to Val(66 homozygous during retrieval (but not encoding while, again, the reverse was true for healthy controls. The Val(66Met polymorphism has opposite effects on hippocampal circuitry underlying episodic memory in Multiple Sclerosis patients and healthy controls. Enhancing the knowledge of how genetic factors influence cognitive functions may improve the clinical

29 CFR 570.63 - Occupations involved in the operation of paper-products machines, scrap paper balers, and paper...

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Occupations involved in the operation of paper-products machines, scrap paper balers, and paper box compactors (Order 12). 570.63 Section 570.63 Labor Regulations... involved in the operation of paper-products machines, scrap paper balers, and paper box compactors (Order...

Metabolic engineering of Saccharomyces cerevisiae for caffeine and theobromine production.

Directory of Open Access Journals (Sweden)

Lu Jin

Full Text Available Caffeine (1, 3, 7-trimethylxanthine and theobromine (3, 7-dimethylxanthine are the major purine alkaloids in plants, e.g., tea (Camellia sinensis and coffee (Coffea arabica. Caffeine is a major component of coffee and is used widely in food and beverage industries. Most of the enzymes involved in the caffeine biosynthetic pathway have been reported previously. Here, we demonstrated the biosynthesis of caffeine (0.38 mg/L by co-expression of Coffea arabica xanthosine methyltransferase (CaXMT and Camellia sinensis caffeine synthase (TCS in Saccharomyces cerevisiae. Furthermore, we endeavored to develop this production platform for making other purine-based alkaloids. To increase the catalytic activity of TCS in an effort to increase theobromine production, we identified four amino acid residues based on structural analyses of 3D-model of TCS. Two TCS1 mutants (Val317Met and Phe217Trp slightly increased in theobromine accumulation and simultaneously decreased in caffeine production. The application and further optimization of this biosynthetic platform are discussed.

Metabolic engineering of Saccharomyces cerevisiae for caffeine and theobromine production.

Science.gov (United States)

Jin, Lu; Bhuiya, Mohammad Wadud; Li, Mengmeng; Liu, XiangQi; Han, Jixiang; Deng, WeiWei; Wang, Min; Yu, Oliver; Zhang, Zhengzhu

2014-01-01

Caffeine (1, 3, 7-trimethylxanthine) and theobromine (3, 7-dimethylxanthine) are the major purine alkaloids in plants, e.g., tea (Camellia sinensis) and coffee (Coffea arabica). Caffeine is a major component of coffee and is used widely in food and beverage industries. Most of the enzymes involved in the caffeine biosynthetic pathway have been reported previously. Here, we demonstrated the biosynthesis of caffeine (0.38 mg/L) by co-expression of Coffea arabica xanthosine methyltransferase (CaXMT) and Camellia sinensis caffeine synthase (TCS) in Saccharomyces cerevisiae. Furthermore, we endeavored to develop this production platform for making other purine-based alkaloids. To increase the catalytic activity of TCS in an effort to increase theobromine production, we identified four amino acid residues based on structural analyses of 3D-model of TCS. Two TCS1 mutants (Val317Met and Phe217Trp) slightly increased in theobromine accumulation and simultaneously decreased in caffeine production. The application and further optimization of this biosynthetic platform are discussed.

40 CFR 240.205-2 - Recommended procedures: Design.

Science.gov (United States)

2010-07-01

... air pollution control technology. (b) All emissions, including dust from vents, should be controlled. ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Recommended procedures: Design. 240.205-2 Section 240.205-2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID...

CryoSat Land Ice Product Validation within the CryoVal-LI project

DEFF Research Database (Denmark)

Sørensen, Louise Sandberg; Baker, Steven; Csatho, Bea

The main objective of the ESA funded CryoVal-LI project has been to identify and quantify the error sources for the CryoSat-2 mission over land ice. This has been undertaken through the careful documentation of the possible error sources, the identification of suitable validation sites...

Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.

Directory of Open Access Journals (Sweden)

Kathryn T Hall

Full Text Available Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT, an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS. The three treatment arms from this study were: no-treatment ("waitlist", placebo treatment alone ("limited" and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035. The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice.

Science.gov (United States)

Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L; Lee, Francis S; Blendy, Julie A

2015-12-01

Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine withdrawal. Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For

BDNF Val66Met polymorphism is associated with higher anticipatory cortisol stress response, anxiety, and alcohol consumption in healthy adults.

Science.gov (United States)

Colzato, Lorenza S; Van der Does, A J Willem; Kouwenhoven, Coen; Elzinga, Bernet M; Hommel, Bernhard

2011-11-01

The brain-derived neurotrophic factor (BDNF) is a key protein in maintaining neuronal integrity. The BDNF gene is thought to play an important role in the pathophysiology of mood and anxiety disorders. The aim of this study was to investigate, for the first time in a single study, the association between BDNF Val(66)Met polymorphism, anxiety, alcohol consumption, and cortisol stress response. 98 healthy university students (54 females and 44 males), genotyped for the Val(66)Met polymorphism, participated in a physical-stress procedure (cold pressure test, CPT) after having been informed that they would undergo a painful experience. Indices of anxiety and of stress were collected from repeated measurement of salivary cortisol, blood pressure, and heart rate. BDNF Met carriers, were more anxious during the CPT (pBDNF Val(66)Met polymorphism with HPA axis reactivity to stress was not modulated by gender. These results suggest that Met carriers are particularly sensitive in anticipating stressful events, which extends previous findings on the moderating role of the BDNF Val(66)Met polymorphism in the face of stressful life events. Copyright © 2011 Elsevier Ltd. All rights reserved.

20 CFR 422.205 - Review by Appeals Council.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Review by Appeals Council. 422.205 Section 422.205 Employees' Benefits SOCIAL SECURITY ADMINISTRATION ORGANIZATION AND PROCEDURES Procedures of... the Council. In the event of disagreement between a panel composed of only two members, the Chairman...

45 CFR 1158.205 - Professional and technical services.

Science.gov (United States)

2010-10-01

... advice and analysis directly applying any professional or technical discipline. For example, drafting of... 45 Public Welfare 3 2010-10-01 2010-10-01 false Professional and technical services. 1158.205... Own Employees § 1158.205 Professional and technical services. (a) The prohibition on the use of...

7 CFR 3018.205 - Professional and technical services.

Science.gov (United States)

2010-01-01

... and analysis directly applying any professional or technical discipline. For example, drafting of a... 7 Agriculture 15 2010-01-01 2010-01-01 false Professional and technical services. 3018.205 Section....205 Professional and technical services. (a) The prohibition on the use of appropriated funds, in...

20 CFR 438.205 - Professional and technical services.

Science.gov (United States)

2010-04-01

... advice and analysis directly applying any professional or technical discipline. For example, drafting of... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Professional and technical services. 438.205... Own Employees § 438.205 Professional and technical services. (a) The prohibition on the use of...

40 CFR 205.52 - Vehicle noise emission standards.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Vehicle noise emission standards. 205... ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.52 Vehicle noise emission standards. (a) Low Speed Noise Emission Standard. Vehicles which are manufactured after...