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

Changes in FGFR2 amino-acid residue Asn549 lead to Crouzon and Pfeiffer syndrome with hydrocephalus

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Caroline Apra

2016-10-01

Full Text Available Mutations in Fibroblast Growth Factor Receptor II (FGFR2 have been identified in patients with Crouzon and Pfeiffer syndrome, among which rare mutations of the intracellular tyrosine kinase domain. Correlating subtle phenotypes with each rare mutation is still in progress. In Necker-Enfants Malades Hospital, we identified three patients harboring three different pathogenic variants of the same amino acid residue Asn-549 located in this domain: in addition to a very typical crouzonoid appearance, they all developed clinically relevant hydrocephalus, which is an inconstant feature of Crouzon and Pfeiffer syndrome. Overall, FGFR2 tyrosine kinase domain mutations account for 5/67 (7.4% cases in our hospital. We describe a novel mutation, p.Asn549Ser, and new cases of p.Asn549His and p.Asn549Thr mutations, each reported once before. Our three cases of Asn-549 mutations, alongside with rare previously reported cases, show that these patients are at higher risk of hydrocephalus. Clinical and imaging follow-up, with possible early surgery, may help prevent secondary intellectual disability.

Residues at a Single Site Differentiate Animal Cryptochromes from Cyclobutane Pyrimidine Dimer Photolyases by Affecting the Proteins' Preferences for Reduced FAD.

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Xu, Lei; Wen, Bin; Wang, Yuan; Tian, Changqing; Wu, Mingcai; Zhu, Guoping

2017-06-19

Cryptochromes (CRYs) and photolyases belong to the cryptochrome/photolyase family (CPF). Reduced FAD is essential for photolyases to photorepair UV-induced cyclobutane pyrimidine dimers (CPDs) or 6-4 photoproducts in DNA. In Drosophila CRY (dCRY, a type I animal CRY), FAD is converted to the anionic radical but not to the reduced state upon illumination, which might induce a conformational change in the protein to relay the light signal downstream. To explore the foundation of these differences, multiple sequence alignment of 650 CPF protein sequences was performed. We identified a site facing FAD (Ala377 in Escherichia coli CPD photolyase and Val415 in dCRY), hereafter referred to as "site 377", that was distinctly conserved across these sequences: CPD photolyases often had Ala, Ser, or Asn at this site, whereas animal CRYs had Ile, Leu, or Val. The binding affinity for reduced FAD, but not the photorepair activity of E. coli photolyase, was dramatically impaired when replacing Ala377 with any of the three CRY residues. Conversely, in V415S and V415N mutants of dCRY, FAD was photoreduced to its fully reduced state after prolonged illumination, and light-dependent conformational changes of these mutants were severely inhibited. We speculate that the residues at site 377 play a key role in the different preferences of CPF proteins for reduced FAD, which differentiate animal CRYs from CPD photolyases. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Importance of Terminal Amino Acid Residues to the Transport of Oligopeptides across the Caco-2 Cell Monolayer.

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Ding, Long; Wang, Liying; Yu, Zhipeng; Ma, Sitong; Du, Zhiyang; Zhang, Ting; Liu, Jingbo

2017-09-06

The objective of this paper was to investigate the effects of terminal amino acids on the transport of oligopeptides across the Caco-2 cell monolayer. Ala-based tetra- and pentapeptides were designed, and the N- or C-terminal amino acid residues were replaced by different amino acids. The results showed that the oligopeptides had a wide range of transport permeability across the Caco-2 cell monolayer and could be divided into four categories: non-/poor permeability, low permeability, intermediate permeability, and good permeability. Tetrapeptides with N-terminal Leu, Pro, Ile, Cys, Met, and Val or C-terminal Val showed the highest permeability, with apparent permeability coefficient (P app ) values over 10 × 10 -6 cm/s (p transport of tetrapeptides. Pentapeptides with N- or C-terminal Tyr also showed high permeability levels, with P app values of about 10 × 10 -6 cm/s. The amino acids Glu, Asn, and Thr at the N terminus or Lys, Asp, and Arg at the C terminus were also beneficial for the transport of tetra- and pentapeptides, with P app values ranging from 1 × 10 -6 to 10 × 10 -6 cm/s. In addition, peptides with amino acids replaced at the N terminus generally showed higher permeability than those with amino acids replaced at the C terminus (p transport of oligopeptides across the Caco-2 cell monolayer.

Backbone and sidechain methyl Ile (δ1), Leu and Val chemical shift assignments of RDE-4 (1-243), an RNA interference initiation protein in C. elegans.

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Chiliveri, Sai Chaitanya; Kumar, Sonu; Marelli, Udaya Kiran; Deshmukh, Mandar V

2012-10-01

The RNAi pathway of several organisms requires presence of double stranded RNA binding proteins for functioning of Dicer in gene regulation. In C. elegans, a double stranded RNA binding protein, RDE-4 (385 aa, 44 kDa) recognizes long exogenous dsRNA and initiates the RNAi pathway. We have achieved complete backbone and stereospecific methyl sidechain Ile (δ1), Leu and Val chemical shifts of first 243 amino acids of RDE-4, namely RDE-4ΔC.

[Conformation analysis of the N-glycosylation site Asn-X-Thr/Ser in glycoproteins].

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Avanov, A Ia; Lipkind, G M

1990-03-01

Theoretical conformational analysis of oligopeptides CH3CO-Asn-X-Thr-NHCH3 (X = Gly, Ala, Pro), modelling N-glycosylation site, and their glycosylated derivatives CH3CO-(GlcNAc beta 1-4GlcNAc beta 1) Asn-X-Thr-NHCH3 has been carried out. Active conformations of the site are found, corresponding to structural prerequisities of N-glycosylation: Asn residue's position in beta-turn and hydrogen bond formation between side chains of Asn and Thr/Ser residues. In this case the L conformation of the central residue X is most probable. Since Pro residue does not possess this conformation, sequences with X = Pro are not glycosylated. It is shown that glycosylation of the above-mentioned sites is accompanied by reorientation of the Asn residue's side chains.

Flexible xxx-asp/asn and gly-xxx residues of equine cytochrome C in matrix-assisted laser desorption/ionization in-source decay mass spectrometry.

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Takayama, Mitsuo

2012-01-01

The backbone flexibility of a protein has been studied from the standpoint of the susceptibility of amino acid residues to in-source decay (ISD) in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Residues more susceptible to MALDI-ISD, namely Xxx-Asp/Asn and Gly-Xxx, were identified from the discontinuous intense peak of c'-ions originating from specific cleavage at N-Cα bonds of the backbone of equine cytochrome c. The identity of the residues susceptible to ISD was consistent with the known flexible backbone amides as estimated by hydrogen/deuterium exchange (HDX) experiments. The identity of these flexible amino acid residues (Asp, Asn, and Gly) is consistent with the fact that these residues are preferred in flexible secondary structure free from intramolecular hydrogen-bonded structures such as α-helix and β-sheet. The MALDI-ISD spectrum of equine cytochrome c gave not only intense N-terminal side c'-ions originating from N-Cα bond cleavage at Xxx-Asp/Asn and Gly-Xxx residues, but also C-terminal side complement z'-ions originating from the same cleavage sites. The present study implies that MALDI-ISD can give information about backbone flexibility of proteins, comparable with the protection factors estimated by HDX.

Flexible Xxx–Asp/Asn and Gly–Xxx Residues of Equine Cytochrome c in Matrix-Assisted Laser Desorption/Ionization In-Source Decay Mass Spectrometry

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Takayama, Mitsuo

2012-01-01

The backbone flexibility of a protein has been studied from the standpoint of the susceptibility of amino acid residues to in-source decay (ISD) in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Residues more susceptible to MALDI-ISD, namely Xxx–Asp/Asn and Gly–Xxx, were identified from the discontinuous intense peak of c′-ions originating from specific cleavage at N–Cα bonds of the backbone of equine cytochrome c. The identity of the residues susceptible to ISD was consistent with the known flexible backbone amides as estimated by hydrogen/deuterium exchange (HDX) experiments. The identity of these flexible amino acid residues (Asp, Asn, and Gly) is consistent with the fact that these residues are preferred in flexible secondary structure free from intramolecular hydrogen-bonded structures such as α-helix and β-sheet. The MALDI-ISD spectrum of equine cytochrome c gave not only intense N-terminal side c′-ions originating from N–Cα bond cleavage at Xxx–Asp/Asn and Gly–Xxx residues, but also C-terminal side complement z′-ions originating from the same cleavage sites. The present study implies that MALDI-ISD can give information about backbone flexibility of proteins, comparable with the protection factors estimated by HDX. PMID:24349908

The role of a second-shell residue in modifying substrate and inhibitor interactions in the SHV beta-lactamase: a study of ambler position Asn276.

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Drawz, Sarah M; Bethel, Christopher R; Hujer, Kristine M; Hurless, Kelly N; Distler, Anne M; Caselli, Emilia; Prati, Fabio; Bonomo, Robert A

2009-06-02

Inhibitor-resistant class A beta-lactamases of the TEM and SHV families that arise by single amino acid substitutions are a significant threat to the efficacy of beta-lactam/beta-lactamase inhibitor combinations. To better understand the basis of the inhibitor-resistant phenotype in SHV, we performed mutagenesis to examine the role of a second-shell residue, Asn276. Of the 19 variants expressed in Escherichia coli, only the Asn276Asp enzyme demonstrated reduced susceptibility to ampicillin/clavulanate (MIC increased from 50/2 --> 50/8 microg/mL) while maintaining high-level resistance to ampicillin (MIC = 8192 microg/mL). Steady-state kinetic analyses of Asn276Asp revealed slightly diminished k(cat)/K(m) for all substrates tested. In contrast, we observed a 5-fold increase in K(i) for clavulanate (7.4 +/- 0.9 microM for Asn276Asp vs 1.4 +/- 0.2 microM for SHV-1) and a 40% reduction in k(inact)/K(I) (0.013 +/- 0.002 microM(-1 )s(-1) for Asn276Asp vs 0.021 +/- 0.004 microM(-1) s(-1) for SHV-1). Timed electrospray ionization mass spectrometry of clavulanate-inhibited SHV-1 and SHV Asn276Asp showed nearly identical mass adducts, arguing for a similar pathway of inactivation. Molecular modeling shows that novel electrostatic interactions are formed between Arg244Neta2 and both 276AspOdelta1 and Odelta2; these new forces restrict the spatial position of Arg244, a residue important in the recognition of the C(3)/C(4) carboxylate of beta-lactam substrates and inhibitors. Testing the functional consequences of this interaction, we noted considerable free energy costs (+DeltaDeltaG) for substrates and inhibitors. A rigid carbapenem (meropenem) was most affected by the Asn276Asp substitution (46-fold increase in K(i) vs SHV-1). We conclude that residue 276 is an important second-shell residue in class A beta-lactamase-mediated resistance to substrates and inhibitors, and only Asn is able to precisely modulate the conformational flexibility of Arg244 required for successful

Asn12 and Asn278: Critical Residues for In Vitro Biological Activity of Reteplase

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Naganath Mandi

2010-01-01

Full Text Available Reteplase (rPA is a thrombolytic agent used for the treatment of acute myocardial infarction. We studied the expression of rPA and its selected asparagine mutants after integration into the Pichia genome. Though methanol induction of the native and the rPA mutants showed similar expression levels (~200–250 mg/L, the mutants displayed significant loss of protease activity. Strikingly, the clot lysis activities of these mutants were considerably different. While mutation of Asn12 (N12P of the Kringle 2 domain showed delayed clot lysis activity (1/2=38 min compared to the native rPA (1/2=33 min, a faster rate of clot lysis (1/2=27 min was observed when the Asn278 (N278S of the serine protease domain was mutated. Interestingly, the slowest clot lysis activity (1/2=49 min demonstrated by the double mutant (N12P, N278S suggests the dominant role of Asn12 in regulating the fibrinolytic activity of rPA. The results presented in this paper indicate that the fibrinolytic and the proteolytic activities of rPA are independent of each other.

Selective backbone labelling of ILV methyl labelled proteins

International Nuclear Information System (INIS)

Sibille, Nathalie; Hanoulle, Xavier; Bonachera, Fanny; Verdegem, Dries; Landrieu, Isabelle; Wieruszeski, Jean-Michel; Lippens, Guy

2009-01-01

Adding the 13 C labelled 2-keto-isovalerate and 2-oxobutanoate precursors to a minimal medium composed of 12 C labelled glucose instead of the commonly used ( 2 D, 13 C) glucose leads not only to the 13 C labelling of (I, L, V) methyls but also to the selective 13 C labelling of the backbone C α and CO carbons of the Ile and Val residues. As a result, the backbone ( 1 H, 15 N) correlations of the Ile and Val residues and their next neighbours in the (i + 1) position can be selectively identified in HN(CA) and HN(CO) planes. The availability of a selective HSQC spectrum corresponding to the sole amide resonances of the Ile and Val residues allows connecting them to their corresponding methyls by the intra-residue NOE effect, and should therefore be applicable to larger systems

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 ...

Bioethanol Production from Iles-Iles (Amorphopallus campanulatus Flour by Fermentation using Zymomonas mobilis

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Kusmiyati Kusmiyati

2016-02-01

Full Text Available Due to the depletion of fossil oil sources, Indonesia attempts to search new source of bioenergy including bioethanol. One of this sources is Iles-iles tubers (Amorphophallus campanulatus, which is abundantly available in Java Indonesia. The carbohydrate content in Iles-Iles tuber flour was 77% and it can be converted to ethanol by three consecutive steps methods consist of liquefaction-saccharification using α and β-amylase, respectively and then followed by fermentation by using Z. mobilis. The objective of this research was to convert the Iles-iles flour to bioethanol by fermentation process with Z.mobilis. The ethanol production process was studied at various starch concentration 15-30% g/L, Z. mobilis concentration (10-40% and pH fermentation of (4-6. The result showed that the yield of bioethanol (10.33% was the highest at 25% starch concentration and 25% of Z.mobilis concentration. The optimum conditions was found at 4.5, 30°C, 10%, 120 h for pH, temperature, Z. mobilis concentration and fermentation time, respectively  at which  ACT tuber flour produced a maximum ethanol of 10.33 % v/v.Article History: Received November 12nd 2015; Received in revised form January 25th 2016; Accepted January 29th 2016; Available online How to Cite This Article: Kusmiyati , Hadiyanto,H  and Kusumadewi, I (2016. Bioethanol Production from Iles-Iles (Amorphopallus campanulatus Flour by Fermentation using Zymomonas mobilis. Int. Journal of Renewable Energy Development, 9(1, 9-14 http://dx.doi.org/10.14710/ijred.5.1.9-14 

Utilization of Iles-Iles and Sorghum Starch for Bioethanol Production

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Kusmiyati Kusmiyati

2014-05-01

Full Text Available The aims of this study were to convert the starches from iles-iles tubers (Amorphophalus campanulatus and sorghum grains (Sorghum bicolor L into bioethanol as an alternative energy. Both of these agricultural products contains a high content starches and they do not use as the major foods in Indonesia. To find out the maximum ethanol concentration and yield, both the raw materials were converted to ethanol on various process variables including the concentration of flour substrate solution (100-300 g/L, β-amylase enzyme concentration (0.8 - 6.4 ml/kg of flour , the  concentration of dry yeast S. cerevisiae (2-15 g, and fermentation time (72-168 hours. The results showed that at the flour substrate concentration of 250 g/L produced the maximum ethanol contents of 100.29 g/L and 95.11 g/L   for iles-iles and sorghum, respectively. Effect of β-amylase enzyme in the saccharification process showed that at concentration  of 3.2 ml/kg  the maximum reducing sugar content of 204.94 g/L and 193.15 g/L  for iles-iles and sorghum substrate, respectively were generated therefore it was corresponding to the maximum ethanol production. The concentration effect of dry yeast S. cerevisiae in the fermentation stage for the iles-iles and sorghum substrate revealed that the maximum ethanol obtained at 5 g yeast activated in 100 ml medium starter resulted the highest ethanol content 100.29 g/L 95.11 g/L for iles-iles and sorghum substrate, respectively. To determine the effect of fermentation time on ethanol yield from iles-iles and sorghum substrate, the fermentation process were performed at 3, 5, and 7 days. The maximum ethanol fermentation was obtained at 5 days fermentation. The ethanol yield is calculated by weight of ethanol is formed (g divided by the weight of flour (g. Based on the experiment results, conducted, generally the highest ethanol yield of iles-iles was higher than that of sorghum flour. The highest yield (g/g iles-iles and sorghum

Dependence of α-helical and β-sheet amino acid propensities on the overall protein fold type

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Fujiwara Kazuo

2012-08-01

Full Text Available Abstract Background A large number of studies have been carried out to obtain amino acid propensities for α-helices and β-sheets. The obtained propensities for α-helices are consistent with each other, and the pair-wise correlation coefficient is frequently high. On the other hand, the β-sheet propensities obtained by several studies differed significantly, indicating that the context significantly affects β-sheet propensity. Results We calculated amino acid propensities for α-helices and β-sheets for 39 and 24 protein folds, respectively, and addressed whether they correlate with the fold. The propensities were also calculated for exposed and buried sites, respectively. Results showed that α-helix propensities do not differ significantly by fold, but β-sheet propensities are diverse and depend on the fold. The propensities calculated for exposed sites and buried sites are similar for α-helix, but such is not the case for the β-sheet propensities. We also found some fold dependence on amino acid frequency in β-strands. Folds with a high Ser, Thr and Asn content at exposed sites in β-strands tend to have a low Leu, Ile, Glu, Lys and Arg content (correlation coefficient = −0.90 and to have flat β-sheets. At buried sites in β-strands, the content of Tyr, Trp, Gln and Ser correlates negatively with the content of Val, Ile and Leu (correlation coefficient = −0.93. "All-β" proteins tend to have a higher content of Tyr, Trp, Gln and Ser, whereas "α/β" proteins tend to have a higher content of Val, Ile and Leu. Conclusions The α-helix propensities are similar for all folds and for exposed and buried residues. However, β-sheet propensities calculated for exposed residues differ from those for buried residues, indicating that the exposed-residue fraction is one of the major factors governing amino acid composition in β-strands. Furthermore, the correlations we detected suggest that amino acid composition is related to folding

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

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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.

Expression and mutagenesis of the sea anemone toxin Av2 reveals key amino acid residues important for activity on voltage-gated sodium channels.

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Moran, Yehu; Cohen, Lior; Kahn, Roy; Karbat, Izhar; Gordon, Dalia; Gurevitz, Michael

2006-07-25

Type I sea anemone toxins are highly potent modulators of voltage-gated Na-channels (Na(v)s) and compete with the structurally dissimilar scorpion alpha-toxins on binding to receptor site-3. Although these features provide two structurally different probes for studying receptor site-3 and channel fast inactivation, the bioactive surface of sea anemone toxins has not been fully resolved. We established an efficient expression system for Av2 (known as ATX II), a highly insecticidal sea anemone toxin from Anemonia viridis (previously named A. sulcata), and mutagenized it throughout. Each toxin mutant was analyzed in toxicity and binding assays as well as by circular dichroism spectroscopy to discern the effects derived from structural perturbation from those related to bioactivity. Six residues were found to constitute the anti-insect bioactive surface of Av2 (Val-2, Leu-5, Asn-16, Leu-18, and Ile-41). Further analysis of nine Av2 mutants on the human heart channel Na(v)1.5 expressed in Xenopus oocytes indicated that the bioactive surfaces toward insects and mammals practically coincide but differ from the bioactive surface of a structurally similar sea anemone toxin, Anthopleurin B, from Anthopleura xanthogrammica. Hence, our results not only demonstrate clear differences in the bioactive surfaces of Av2 and scorpion alpha-toxins but also indicate that despite the general conservation in structure and importance of the Arg-14 loop and its flanking residues Gly-10 and Gly-20 for function, the surface of interaction between different sea anemone toxins and Na(v)s varies.

Structure-guided modification of Rhizomucor miehei lipase for production of structured lipids.

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Jun-Hui Zhang

Full Text Available To improve the performance of yeast surface-displayed Rhizomucor miehei lipase (RML in the production of human milk fat substitute (HMFS, we mutated amino acids in the lipase substrate-binding pocket based on protein hydrophobicity, to improve esterification activity. Five mutants: Asn87Ile, Asn87Ile/Asp91Val, His108Leu/Lys109Ile, Asp256Ile/His257Leu, and His108Leu/Lys109Ile/Asp256Ile/His257Leu were obtained and their hydrolytic and esterification activities were assayed. Using Discovery Studio 3.1 to build models and calculate the binding energy between lipase and substrates, compared to wild-type, the mutant Asp256Ile/His257Leu was found to have significantly lower energy when oleic acid (3.97 KJ/mol decrease and tripalmitin (7.55 KJ/mol decrease were substrates. This result was in accordance with the esterification activity of Asp256Ile/His257Leu (2.37-fold of wild-type. The four mutants were also evaluated for the production of HMFS in organic solvent and in a solvent-free system. Asp256Ile/His257Leu had an oleic acid incorporation of 28.27% for catalyzing tripalmitin and oleic acid, and 53.18% for the reaction of palm oil with oleic acid. The efficiency of Asp256Ile/His257Leu was 1.82-fold and 1.65-fold that of the wild-type enzyme for the two reactions. The oleic acid incorporation of Asp256Ile/His257Leu was similar to commercial Lipozyme RM IM for palm oil acidolysis with oleic acid. Yeast surface-displayed RML mutant Asp256Ile/His257Leu is a potential, economically feasible catalyst for the production of structured lipids.

Structure-guided modification of Rhizomucor miehei lipase for production of structured lipids.

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Zhang, Jun-Hui; Jiang, Yu-Yan; Lin, Ying; Sun, Yu-Fei; Zheng, Sui-Ping; Han, Shuang-Yan

2013-01-01

To improve the performance of yeast surface-displayed Rhizomucor miehei lipase (RML) in the production of human milk fat substitute (HMFS), we mutated amino acids in the lipase substrate-binding pocket based on protein hydrophobicity, to improve esterification activity. Five mutants: Asn87Ile, Asn87Ile/Asp91Val, His108Leu/Lys109Ile, Asp256Ile/His257Leu, and His108Leu/Lys109Ile/Asp256Ile/His257Leu were obtained and their hydrolytic and esterification activities were assayed. Using Discovery Studio 3.1 to build models and calculate the binding energy between lipase and substrates, compared to wild-type, the mutant Asp256Ile/His257Leu was found to have significantly lower energy when oleic acid (3.97 KJ/mol decrease) and tripalmitin (7.55 KJ/mol decrease) were substrates. This result was in accordance with the esterification activity of Asp256Ile/His257Leu (2.37-fold of wild-type). The four mutants were also evaluated for the production of HMFS in organic solvent and in a solvent-free system. Asp256Ile/His257Leu had an oleic acid incorporation of 28.27% for catalyzing tripalmitin and oleic acid, and 53.18% for the reaction of palm oil with oleic acid. The efficiency of Asp256Ile/His257Leu was 1.82-fold and 1.65-fold that of the wild-type enzyme for the two reactions. The oleic acid incorporation of Asp256Ile/His257Leu was similar to commercial Lipozyme RM IM for palm oil acidolysis with oleic acid. Yeast surface-displayed RML mutant Asp256Ile/His257Leu is a potential, economically feasible catalyst for the production of structured lipids.

N-Glycosylation analysis of yeast Carboxypeptidase Y reveals the ultimate removal of phosphate from glycans at Asn368.

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B S, Gnanesh Kumar; Surolia, Avadhesha

2017-05-01

Carboxypeptidase Y from Saccharomyces cerivisiae was characterized for its site specific N-glycosylation through mass spectrometry. The N-glycopeptides were derived using non specific proteases and are analysed directly on liquid chromatography coupled to ion trap mass spectrometer in tandem mode. The evaluation of glycan fragment ions and the Y 1 ions (peptide+HexNAc) +n revealed the glycan sequence and the corresponding site of attachment. We observed the microheterogeneity in N-glycans such as Man 11-15 GlcNAc 2 at Asn 13 , Man 8-12 GlcNAc 2 at Asn 87 , Man 9-14 GlcNAc 2 at Asn 168 and phosphorylated Man 12-17 GlcNAc 2 as well as Man 11-16 GlcNAc 2 at Asn 368 . The presence of N-glycans with Man <18 GlcNAc 2 indicated that in vacuoles the steady release of mannose/phospho mannose residues from glycans occurs initially at Asn 13 or Asn 168 followed by at Asn 368 . However, glycans at Asn 87 which comprises Man 8-12 residues as reported earlier remain intact suggesting its inaccessibility for a similar processing. This in turn indicates the interaction of the glycan at Asn 87 with the polypeptide chain implicating it in the folding of the protein. Copyright © 2017 Elsevier B.V. All rights reserved.

Solution structure of tRNA{sup Val} from refinement of homology model against residual dipolar coupling and SAXS data

Energy Technology Data Exchange (ETDEWEB)

Grishaev, Alexander, E-mail: AlexanderG@intra.niddk.nih.gov; Ying, Jinfa [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Canny, Marella D.; Pardi, Arthur [University of Colorado, Boulder, Department of Chemistry and Biochemistry, 215 UCB (United States)], E-mail: Arthur.Pardi@Colorado.edu; Bax, Ad [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)], E-mail: bax@nih.gov

2008-10-15

A procedure is presented for refinement of a homology model of E. coli tRNA{sup Val}, originally based on the X-ray structure of yeast tRNA{sup Phe}, using experimental residual dipolar coupling (RDC) and small angle X-ray scattering (SAXS) data. A spherical sampling algorithm is described for refinement against SAXS data that does not require a globbic approximation, which is particularly important for nucleic acids where such approximations are less appropriate. Substantially higher speed of the algorithm also makes its application favorable for proteins. In addition to the SAXS data, the structure refinement employed a sparse set of NMR data consisting of 24 imino N-H{sup N} RDCs measured with Pf1 phage alignment, and 20 imino N-H{sup N} RDCs obtained from magnetic field dependent alignment of tRNA{sup Val}. The refinement strategy aims to largely retain the local geometry of the 58% identical tRNA{sup Phe} by ensuring that the atomic coordinates for short, overlapping segments of the ribose-phosphate backbone and the conserved base pairs remain close to those of the starting model. Local coordinate restraints are enforced using the non-crystallographic symmetry (NCS) term in the XPLOR-NIH or CNS software package, while still permitting modest movements of adjacent segments. The RDCs mainly drive the relative orientation of the helical arms, whereas the SAXS restraints ensure an overall molecular shape compatible with experimental scattering data. The resulting structure exhibits good cross-validation statistics (jack-knifed Q{sub free} = 14% for the Pf1 RDCs, compared to 25% for the starting model) and exhibits a larger angle between the two helical arms than observed in the X-ray structure of tRNA{sup Phe}, in agreement with previous NMR-based tRNA{sup Val} models.

ASN annual report 2004; ASN Rapport annuel 2004

Energy Technology Data Exchange (ETDEWEB)

NONE

2005-07-01

The Nuclear Safety Authority (ASN) groups the Directorate General for Nuclear Safety and Radiation Protection (DGSNR), reporting to the Ministries for Health, Environment and Industry, and the devolved services of the State on which it relies for nuclear safety and radiation protection supervision, primarily DRIRE, DRASS and DDASS. The main topic of 2004, discussed in this report are: nuclear Safety and Transparency bill, shaping the new ASN, setting up inspection of non-BNI nuclear activities, Radiation protection and monitoring of patients, the safety of the EPR reactor project, the national plan for radioactive waste management, the future of high-level long-lived waste, harmonizing nuclear safety in Europe and ASN international involvement. (A.L.B.)

[Association between HRE-2 gene polymorphism at codon 655 and genetic susceptibility of colorectal cancer].

Science.gov (United States)

Liang, Xia; Zhang, Yong-jing; Liu, Bing; Ni, Qin; Jin, Ming-juan; Ma, Xin-yuan; Yao, Kai-yan; Li, Qi-long; Chen, Kun

2009-06-01

To explore the distribution of HER-2 genetic polymorphism at codon 655 and its association with susceptibility of colorectal cancer in Chinese. A population-based case-control study was carried out. 292 patients with colorectal cancer and 842 healthy controls were interviewed. Meanwhile, the genetic polymorphism of HRE-2 was detected using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of Ile/Val+Val/Val genotypes and Val allele were both higher in cases (25.34% and 13.36%) than those in controls (18.41% and 9.74%) (P<0.05). Compared with Ile/Ile genotype, Ile/Val+Val/Val genotypes were significantly associated with colorectal cancer [ORadjusted=1.54, 95% CI: 1.11-2.14]. The adjusted odds ratio of interactions between this polymorphism and smoking, alcohol drinking were 1.43 (95%CI: 0.88-2.30) and 1.29 (95%CI: 0.73-2.29), respectively. The present findings suggest that HER-2 genetic polymorphism at codon 655 may be associated with the risk of colorectal cancer in Chinese. In addition, there are no interactions between this polymorphism and smoking, alcohol drinking, respectively.

Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family

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Fazakas Ferenc

2008-04-01

Full Text Available Abstract Von Hippel-Lindau disease (VHL is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult.

The milk-derived peptides Val-Pro-Pro and Ile-Pro-Pro attenuate arterial dysfunction in L-NAME-treated rats.

Science.gov (United States)

Nonaka, Atsuko; Nakamura, Teppei; Hirota, Tatsuhiko; Matsushita, Akiko; Asakura, Masanori; Ohki, Kohji; Kitakaze, Masafumi

2014-08-01

Both endothelial dysfunction and arterial stiffness are surrogate markers of atherosclerosis and thus cardiovascular (CV) events. The milk-derived peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) inhibit angiotensin-converting enzyme, dilate blood vessels ex vivo and stimulate nitric oxide (NO) production in cells. In this study, we investigated the effects of either VPP or IPP on arterial function and on target organ damage in vivo. Male Wistar rats were treated with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 g l(-1)), L-NAME+VPP (0.3 g l(-1)) or L-NAME+IPP (0.3 g l(-1)) in their drinking water for 8 weeks. Plasma nitrite and nitrate (NOx) levels were significantly increased in normal Wistar rats after supplementation with either VPP or IPP but not in rats that were chronically treated with L-NAME. Acetylcholine-induced vasorelaxation in the thoracic aorta ring was impaired by L-NAME, whereas vasorelaxation was significantly greater in mice treated with L-NAME+VPP for 1 or 4 weeks or L-NAME+IPP for 4 weeks than in mice treated with L-NAME alone. Four weeks of treatment with either VPP or IPP attenuated the increase in pulse wave velocity (PWV) that was induced by L-NAME. Cardiac and renal damage were observed after 8 weeks of treatment with L-NAME, and either VPP or IPP attenuated this damage. These results show that VPP or IPP attenuates arterial dysfunction and suggest that milk-derived peptides might prevent CV damage.

Role of a cysteine residue in the active site of ERK and the MAPKK family

International Nuclear Information System (INIS)

Ohori, Makoto; Kinoshita, Takayoshi; Yoshimura, Seiji; Warizaya, Masaichi; Nakajima, Hidenori; Miyake, Hiroshi

2007-01-01

Kinases of mitogen-activated protein kinase (MAPK) cascades, including extracellular signal-regulated protein kinase (ERK), represent likely targets for pharmacological intervention in proliferative diseases. Here, we report that FR148083 inhibits ERK2 enzyme activity and TGFβ-induced AP-1-dependent luciferase expression with respective IC 50 values of 0.08 and 0.05 μM. FR265083 (1'-2' dihydro form) and FR263574 (1'-2' and 7'-8' tetrahydro form) exhibited 5.5-fold less and no activity, respectively, indicating that both the α,β-unsaturated ketone and the conformation of the lactone ring contribute to this inhibitory activity. The X-ray crystal structure of the ERK2/FR148083 complex revealed that the compound binds to the ATP binding site of ERK2, involving a covalent bond to Sγ of ERK2 Cys166, hydrogen bonds with the backbone NH of Met108, Nζ of Lys114, backbone C=O of Ser153, Nδ2 of Asn154, and hydrophobic interactions with the side chains of Ile31, Val39, Ala52, and Leu156. The covalent bond motif in the ERK2/FR148083 complex assures that the inhibitor has high activity for ERK2 and no activity for other MAPKs such as JNK1 and p38MAPKα/β/γ/δ which have leucine residues at the site corresponding to Cys166 in ERK2. On the other hand, MEK1 and MKK7, kinases of the MAPKK family which also can be inhibited by FR148083, contain a cysteine residue corresponding to Cys166 of ERK2. The covalent binding to the common cysteine residue in the ATP-binding site is therefore likely to play a crucial role in the inhibitory activity for these MAP kinases. These findings on the molecular recognition mechanisms of FR148083 for kinases with Cys166 should provide a novel strategy for the pharmacological intervention of MAPK cascades

Organochlorine pesticide residues in dried cocoa beans obtained from cocoa stores at Ondo and Ile-Ife, Southwestern Nigeria

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J.A.O. Oyekunle

Full Text Available Levels of organochlorine pesticides (OCPs were determined in dried cocoa beans obtained from cocoa produce stores at Ondo and Ile-Ife, Southwestern Nigeria. Cocoa beans samples were sun dried to a constant weight, pulverized and soxhlet extracted with dichloromethane to obtain the OCPs. Qualitative identification and quantitative evaluation of the extracted OCPs after clean-up on silica gel were accomplished with the aid of a Gas Chromatography coupled with an Electron Capture Detector (GC-ECD. Levels of OCPs in cocoa beans from Ondo had a mean range of ND (p, p’-DDE to 82.17 ± 54.53 ng/g (p, p’-DDT were higher than the OCPs levels in cocoa beans from Ile-Ife with a mean range of 0.37 ± 0.63 ng/g (Endrin to 57.76 ± 81.48 ng/g (p, p’-DDT. The higher levels of OCPs detected in the cocoa beans from Ondo could be an indication of higher volume of OCPs application by cocoa farmers in Ondo and its environs since cocoa plantations were more concentrated than Ile-Ife environs. Levels of OCPs determined in the cocoa beans were within the Maximum Residue Limit (MRLs for OCPs set by the World Health Organization/Food and Agricultural Organization. The study established the presence of OCPs in an important crop of Nigeria. Hence, there is the need to keep monitoring ecotoxicological chemical substances in agricultural food products of Nigeria so as to take steps that ensure health safety of end users. Keywords: Pesticides, Organochlorine, Cocoa beans, Ondo, Ile-Ife, Nigeria

ASN reputation system model

Science.gov (United States)

Hutchinson, Steve; Erbacher, Robert F.

2015-05-01

Network security monitoring is currently challenged by its reliance on human analysts and the inability for tools to generate indications and warnings for previously unknown attacks. We propose a reputation system based on IP address set membership within the Autonomous System Number (ASN) system. Essentially, a metric generated based on the historic behavior, or misbehavior, of nodes within a given ASN can be used to predict future behavior and provide a mechanism to locate network activity requiring inspection. This will provide reinforcement of notifications and warnings and lead to inspection for ASNs known to be problematic even if initial inspection leads to interpretation of the event as innocuous. We developed proof of concept capabilities to generate the IP address to ASN set membership and analyze the impact of the results. These results clearly show that while some ASNs are one-offs with individual or small numbers of misbehaving IP addresses, there are definitive ASNs with a history of long term and wide spread misbehaving IP addresses. These ASNs with long histories are what we are especially interested in and will provide an additional correlation metric for the human analyst and lead to new tools to aid remediation of these IP address blocks.

Data of evolutionary structure change: 1ANCA-2HNTE [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1ANCA-2HNTE 1ANC 2HNT A E IVGGYTCQENSVPYQVSLNSGYHFCGGSLINDQWVVSAA...> 0 1ANC A 1ANC...1 1.00 16.75 C e-map> ILE ASP ASN ASN LEU THR LYS ARG ASP PHE ASN CA 5.65 3.82 ASP CA 3.82 ILE CA ...21.33 C e-map> ILE ASP ARG ASP LEU ASN

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

Isolation and structural analysis of antihypertensive peptides that exist naturally in Gouda cheese.

Science.gov (United States)

Saito, T; Nakamura, T; Kitazawa, H; Kawai, Y; Itoh, T

2000-07-01

Seven kinds of ripened cheeses (8-mo-aged and 24-mo-aged Gouda, Emmental, Blue, Camembert, Edam, and Havarti) were homogenized with distilled water, and water-soluble peptides were prepared by C-18 hydrophobic chromatography. The inhibitory activity to angiotensin I-converting enzyme and decrease in the systolic blood pressure in spontaneously hypertensive rats were measured before and after oral administration of each peptide sample. The strongest depressive effect in the systolic blood pressure (-24.7 mm Hg) and intensive inhibitory activity to angiotensin I-converting enzyme (75.7%) were detected in the peptides from 8-mo-aged Gouda cheese. Four peptides were isolated by HPLC with reverse-phase and gel filtration modes. Their chemical structures and origins, clarified by combination analyses of protein sequencing, amino acid composition, and mass spectrometry, were as follows: peptide A, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln [alpha(s1)-casein (CN), B-8P; f 1-9]; peptide B, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln-Gly-Leu-Pro-Gln (alpha(s1)-CN, B-8P; f 1-13); peptide F, Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn (beta-CN, A2-5P; f 60-68); and peptide G, Met-Pro-Phe-Pro-Lys-Tyr-Pro-Val-Gln-Pro-Phe (beta-CN, A2-5P; f 109-119). Peptides A and F, which were chemically synthesized, showed potent angiotensin I-converting enzyme inhibitory activity with little antihypertensive effects.

OPDA-Ile a new JA-Ile-independent signal?

Czech Academy of Sciences Publication Activity Database

Wasternack, Claus; Hause, B.

2016-01-01

Roč. 11, č. 11 (2016), č. článku e1253646. ISSN 1559-2316 R&D Projects: GA MŠk(CZ) LO1204; GA ČR GA14-34792S Institutional support: RVO:61389030 Keywords : allene oxide cyclase * 12-oxo-phytodienoic acid * arabidopsis -thaliana * stress responses * jasmonic acid * cyclopentenones * perception * coronatine * repressors * oxylipins * 12-oxo-phytodienoic acid (OPDA) * JA-Ile perception * jasmonic acid (JA) * jasmonoyl-isoleucine (JA-Ile) * OPDA-Ile-induced gene expression * SCFCOI1-JAZ coreceptor complex Subject RIV: EB - Genetics ; Molecular Biology

CYP1A1 gene polymorphisms increase lung cancer risk in a high-incidence region of Spain: a case control study

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San Jose Carmen

2010-08-01

Full Text Available Abstract Background A rural region in south-west Spain has one of the highest lung cancer incidence rates of the country, as revealed by a previous epidemiological 10-year follow-up study. The present work was undertaken to ascertain the role of CYP1A1 gene polymorphisms and their interaction with tobacco smoking in the development of the disease in this location. Methods One-hundred-and-three cases of lung cancer and 265 controls participated in the study. The participants were screened for the presence of four CYP1A1 polymorphisms, namely MspI, Ile462Val, T3205C, and Thr461Asn. Lung cancer risk was estimated as odds ratios (OR and 95% confidence intervals (CI using unconditional logistic regression models adjusting for age, sex, and smoking. Results The distribution of the variant CYP1A1 alleles was different from that described for other Caucasian populations, with CYP1A1*2A showing an uncommonly high frequency (p CYP1A1*2B allele (carrying MspI and Ile462Val mutations was strongly associated with high lung cancer risk (OR = 4.59, CI:1.4-12.6, p p p = 0.04. Moreover, the Thr461Asn polymorphism was found to be associated with SCLC in a Caucasian population for the first time to our knowledge (OR = 8.33, CI: 1.3-15.2, p = 0.04. Conclusion The results suggest that CYP1A1 polymorphisms contribute to increase lung cancer susceptibility in an area with an uncommon high incidence rate.

Structure of the Yersinia pestis tip protein LcrV refined to 1.65 Å resolution

International Nuclear Information System (INIS)

Chaudhury, Sukanya; Battaile, Kevin P.; Lovell, Scott; Plano, Gregory V.; De Guzman, Roberto N.

2013-01-01

Here, the crystal structure of Yersinia pestis tip protein LcrV is reported at a resolution of 1.65 Å. The human pathogen Yersinia pestis requires the assembly of the type III secretion system (T3SS) for virulence. The structural component of the T3SS contains an external needle and a tip complex, which is formed by LcrV in Y. pestis. The structure of an LcrV triple mutant (K40A/D41A/K42A) in a C273S background has previously been reported to 2.2 Å resolution. Here, the crystal structure of LcrV without the triple mutation in a C273S background is reported at a higher resolution of 1.65 Å. Overall the two structures are similar, but there are also notable differences, particularly near the site of the triple mutation. The refined structure revealed a slight shift in the backbone positions of residues Gly28–Asn43 and displayed electron density in the loop region consisting of residues Ile46–Val63, which was disordered in the original structure. In addition, the helical turn region spanning residues Tyr77–Gln95 adopts a different orientation

VCD Robustness of the Amide-I and Amide-II Vibrational Modes of Small Peptide Models.

Science.gov (United States)

Góbi, Sándor; Magyarfalvi, Gábor; Tarczay, György

2015-09-01

The rotational strengths and the robustness values of amide-I and amide-II vibrational modes of For(AA)n NHMe (where AA is Val, Asn, Asp, or Cys, n = 1-5 for Val and Asn; n = 1 for Asp and Cys) model peptides with α-helix and β-sheet backbone conformations were computed by density functional methods. The robustness results verify empirical rules drawn from experiments and from computed rotational strengths linking amide-I and amide-II patterns in the vibrational circular dichroism (VCD) spectra of peptides with their backbone structures. For peptides with at least three residues (n ≥ 3) these characteristic patterns from coupled amide vibrational modes have robust signatures. For shorter peptide models many vibrational modes are nonrobust, and the robust modes can be dependent on the residues or on their side chain conformations in addition to backbone conformations. These robust VCD bands, however, provide information for the detailed structural analysis of these smaller systems. © 2015 Wiley Periodicals, Inc.

Neurospora tryptophan synthase: N-terminal analysis and the sequence of the pyridoxal phosphate active site peptide

International Nuclear Information System (INIS)

Pratt, M.L.; Hsu, P.Y.; DeMoss, J.A.

1986-01-01

Tryptophan synthase (TS), which catalyzes the final step of tryptophan biosynthesis, is a multifunctional protein requiring pyridoxal phosphate (B6P) for two of its three distinct enzyme activities. TS from Neurospora has a blocked N-terminal, is a homodimer of 150 KDa and binds one mole of B6P per mole of subunit. The authors shown the N-terminal residue to be acyl-serine. The B6P-active site of holoenzyme was labelled by reduction of the B6P-Schiff base with [ 3 H]-NaBH 4 , and resulted in a proportionate loss of activity in the two B6P-requiring reactions. SDS-polyacrylamide gel electrophoresis of CNBr-generated peptides showed the labelled, active site peptide to be 6 KDa. The sequence of this peptide, purified to apparent homogeneity by a combination of C-18 reversed phase and TSK gel filtration HPLC is: gly-arg-pro-gly-gln-leu-his-lys-ala-glu-arg-leu-thr-glu-tyr-ala-gly-gly-ala-gln-ile-xxx-leu-lys-arg-glu-asp-leu-asn-his-xxx-gly-xxx-his-/sub ***/-ile-asn-asn-ala-leu. Although four residues (xxx, /sub ***/) are unidentified, this peptide is minimally 78% homologous with the corresponding peptide from yeast TS, in which residue (/sub ***/) is the lysine that binds B6P

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.

ASN annual report 2004

International Nuclear Information System (INIS)

2005-01-01

The Nuclear Safety Authority (ASN) groups the Directorate General for Nuclear Safety and Radiation Protection (DGSNR), reporting to the Ministries for Health, Environment and Industry, and the devolved services of the State on which it relies for nuclear safety and radiation protection supervision, primarily DRIRE, DRASS and DDASS. The main topic of 2004, discussed in this report are: nuclear Safety and Transparency bill, shaping the new ASN, setting up inspection of non-BNI nuclear activities, Radiation protection and monitoring of patients, the safety of the EPR reactor project, the national plan for radioactive waste management, the future of high-level long-lived waste, harmonizing nuclear safety in Europe and ASN international involvement. (A.L.B.)

Enhancement of the thermostability of Hydrogenobacter thermophilus cytochrome c(552) through introduction of an extra methylene group into its hydrophobic protein interior.

Science.gov (United States)

Tai, Hulin; Irie, Kiyofumi; Mikami, Shin-ichi; Yamamoto, Yasuhiko

2011-04-19

Careful scrutiny of the protein interior of Hydrogenobacter thermophilus cytochrome c(552) (HT) on the basis of its X-ray structure [Travaglini-Allocatelli, C., Gianni, S., Dubey, V. K., Borgia, A., Di Matteo, A., Bonivento, D., Cutruzzola, F., Bren, K. L., and Brunori, M. (2005) J. Biol. Chem. 280, 25729-25734] indicated that a void space, which is large enough to accommodate a methyl group, exists in the hydrophobic protein interior near the heme. We tried to reduce the void space through the replacement of a Val by Ile or Leu (Val/Ile or Val/Leu mutation), and then the structural and functional consequences of these two mutations were characterized in order to elucidate the relationship between the nature of the packing of hydrophobic residues and the functional properties of the protein. The study demonstrated striking differences in the structural and functional consequences between the two mutations. The Val/Ile mutation was found to cause further enhancement of the thermostability of the oxidized HT, as reflected in the increase of the denaturation temperature (T(m)) value by ∼ 3 deg, whereas the thermostability of the reduced form was essentially unaffected. As a result, the redox potential (E(m)) of the Val/Ile mutant exhibited a negative shift of ∼ 50 mV relative to that of the wild-type protein in an enthalpic manner, this being consistent with our previous finding that a protein with higher stability in its oxidized form exhibits a lower E(m) value [Terui, N., Tachiiri, N., Matsuo, H., Hasegawa, J., Uchiyama, S., Kobayashi, Y., Igarashi, Y., Sambongi, Y., and Yamamoto, Y. (2003) J. Am. Chem. Soc. 125, 13650-13651]. In contrast, the Val/Leu mutation led to a decrease in thermostability of both the redox forms of the protein, as reflected in the decreases of the T(m) values of the oxidized and reduced proteins by ∼ 3 and ∼ 5 deg, respectively, and the E(m) value of the Val/Leu mutant happened to be similar to that of the Val/Ile one. The E

Impact of the Ile105Val Polymorphism of the Glutathione S-transferase P1 (GSTP1) Gene on Obesity and Markers of Cardiometabolic Risk in Young Adult Population.

Science.gov (United States)

Chielle, E O; Trott, A; da Silva Rosa, B; Casarin, J N; Fortuna, P C; da Cruz, I B M; Moretto, M B; Moresco, R N

2017-05-01

The aim of the study was to investigate the association between Glutathione S-transferase P1 (GSTP1) gene polymorphism with obesity and markers of cardiometabolic risk. A cross-sectional study was carried out in individuals aged≥18 and ≤30 years. The study included 54 normal weight, 27 overweight and 68 obese volunteers. Anthropometric measurements and biochemical parameters were evaluated, the DNA was extracted from blood samples and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 Ile 105 Val gene polymorphism of the study participants. Also, biochemical analysis and hormone assays were carried out. A positive association between GSTP1 polymorphism and obesity was observed on subjects carrying at least one G allele (AG and GG). GG genotype was found only in the obese group. The G allele carriers presented 2.4 times higher chance of obesity when compared to those with the AA genotype. These results were independent of sex and age. We suggest that despite a study in population regional (south of Brazil), the GSTP1 gene polymorphism may play a significant role in the increase of susceptibility of obesity and contribute to identify the cardiovascular risk in young adults. © Georg Thieme Verlag KG Stuttgart · New York.

The French Nuclear Safety Authority - ASN

International Nuclear Information System (INIS)

2013-01-01

The ASN (Nuclear Safety Authority) was created by the act of 13 June 2006 concerning the transparency and safety of nuclear activities. The ASN is an independent administrative body that is in charge of controlling nuclear activities in France. The ASN has a workforce of 471 people and a budget of about 76 millions euros. This article details its missions and how it is organized to cover all the French territory. (A.C.)

The isolation and amino acid sequence of an adrenocorticotrophin from the pars distalis and a corticotrophin-like intermediate-lobe peptide from the neurointermediate lobe of the pituitary of the dogfish Squalus acanthias

Science.gov (United States)

Lowry, Philip J.; Bennett, Hugh P. J.; McMartin, Colin; Scott, Alexander P.

1974-01-01

An adrenocorticotrophic hormone (ACTH) was isolated from extracts of the pars distalis of the pituitary of the dogfish Squalus acanthias by gel filtration and ion-exchange chromatography. It had 15% of the potency of human ACTH in promoting cortico-steroidogenesis in isolated rat adrenal cells. Sequence analysis revealed it to be a nonatria-contapeptide with the following primary structure: Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Met-Gly-Arg-Lys-Arg-Arg-Pro-Ile-Lys-Val-Tyr-Pro-Asn-Ser-Phe-Glu-Asp-Glu-Ser-Val-Glu-Asn-Met-Gly-Pro-Glu-Leu. The N-terminal tridecapeptide sequence was identical with the proposed structure of dogfish α-melanocyte-stimulating hormone (α-MSH). On comparison with human ACTH eleven amino acid differences were seen, nine of which are in the 20–39 region of the molecule which is not essential for the steroidogenic activity of ACTH. A peptide identical with the 18–39 portion of this new ACTH was similarly isolated from the neurointermediate lobe of the pituitary where considerable amounts of dogfish α-MSH were found. This supported our view that ACTH as well as having a distinct biological role of its own is also the precursor of α-MSH. PMID:4375977

Inhibitory effects of a novel Val to Thr mutation on the distal heme of human catalase.

Science.gov (United States)

Mashhadi, Zahra; Boeglin, William E; Brash, Alan R

2014-11-01

True catalases efficiently breakdown hydrogen peroxide, whereas the catalase-related enzyme allene oxide synthase (cAOS) is completely unreactive and instead metabolizes a fatty acid hydroperoxide. In cAOS a Thr residue adjacent to the distal His restrains reaction with H2O2 (Tosha et al. (2006) J. Biol. Chem. 281:12610; De Luna et al. (2013) J. Phys. Chem. B 117: 14635) and its mutation to the consensus Val of true catalases permits the interaction. Here we investigated the effects of the reciprocal experiment in which the Val74 of human catalase is mutated to Thr, Ser, Met, Pro, or Ala. The Val74Thr substitution decreased catalatic activity by 3.5-fold and peroxidatic activity by 3-fold. Substitution with Ser had similar negative effects (5- and 3-fold decreases). Met decreased catalatic activity 2-fold and eliminated peroxidatic activity altogether, whereas the Val74Ala substitution was well tolerated. (The Val74Pro protein lacked heme). We conclude that the conserved Val74 of true catalases helps optimize catalysis. There are rare substitutions of Val74 with Ala, Met, or Pro, but not with Ser of Thr, possibly due their hydrogen bonding affecting the conformation of His75, the essential distal heme residue for activity in catalases. Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

Enhanced resistance to fluoroquinolones in laboratory-grown mutants & clinical isolates of Shigella due to synergism between efflux pump expression & mutations in quinolone resistance determining region

Directory of Open Access Journals (Sweden)

Neelam Taneja

2015-01-01

Full Text Available Background & objectives: There is a worldwide emergence of fluoroquinolone resistance in Shigella species. To understand the molecular mechanisms associated with fluoroquinolone resistance, naturally occurring fluoroquinolone-resistant strains and laboratory-induced spontaneous mutants of Shigella spp. were used and the relative contributions of acrAB-tolC efflux pumps, gyrase and topoisomerase target gene mutations towards fluoroquinolone resistance were determined. Methods: Eight Shigella flexneri and six S. dysenteriae clinical isolates were studied. Three consecutive mutants resistant to ciprofloxacin for S. flexneri SFM1 (≥0.25 µg/ml, SFM2 (≥4 µg/ml and SFM3 (≥32 µg/ml were selected in 15 steps from susceptible isolates by serial exposure to increasing concentrations of nalidixic acid and ciprofloxacin. Similarly, two mutants for S. dysenteriae SDM1 (≥0.25 µg/ml and SDM2 (≥4 µg/ml were selected in eight steps. After PCR amplification sequence analyses of gyrase and topoisomerase target genes were performed. Expression of efflux genes acrA, acrB, acrR and tolC was measured using real-time PCR. Results: Mutations were observed in gyrA Ser [83]→Leu, Asp [87]→Asn/Gly, Val [196]→Ala and in parC Phe [93]→Val, Ser [80]→Ile, Asp [101]→Glu and Asp [110]→Glu. Overall, acrA and acrB overexpression was associated with fluoroquinolone resistance ( p0 <0.05; while tolC and acrR expression levels did not. Interpretation & conclusions: Fluoroquinolone resistance in Shigella spp. is the end product of either a single or a combination of mutations in QRDRs and/ or efflux activity. Novel polymorphisms were observed at Val [196]→Ala in gyrA in clinical isolates and Phe [93]→Val, Asp [101]→Glu, Asp [110]→Glu and in parC in majority of laboratory-grown mutants.

Comparasion of iles-iles and cassava tubers as a Saccharomyces cerevisiae substrate fermentation for bioethanol production

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KUSMIYATI

2010-01-01

Full Text Available Kusmiyati (2010 Comparasion of iles-iles and cassava tubers as a Saccharomyces cerevisiae substrate fermentation for bioethanol production. Nusantara Bioscience 2: 7-13. The production of bioethanol increase rapidly because it is renewable energy that can be used to solve energy crisis caused by the depleting of fossil oil. The large scale production bioethanol in industry generally use feedstock such as sugarcane, corn, and cassava that are also required as food resouces. Therefore, many studies on the bioethanol process concerned with the use raw materials that were not competing with food supply. One of the alternative feedstock able to utilize for bioethanol production is the starchy material that available locally namely iles-iles (Amorphophallus mueller Blum. The contain of carbohydrate in the iles-iles tubers is around 71.12 % which is slightly lower as compared to cassava tuber (83,47%. The effect of various starting material, starch concentration, pH, fermentation time were studied. The conversion of starchy material to ethanol have three steps, liquefaction and saccharification were conducted using α-amylase and amyloglucosidase then fermentation by yeast S.cerevisiaie. The highest bioethanol was obtained at following variables starch:water ratio=1:4 ;liquefaction with 0.40 mL α-amylase (4h; saccharification with 0.40 mL amyloglucosidase (40h; fermentation with 10 mL S.cerevisiae (72h producing bioethanol 69,81 g/L from cassava while 53,49 g/L from iles-iles tuber. At the optimum condition, total sugar produced was 33,431 g/L from cassava while 16,175 g/L from iles-iles tuber. The effect of pH revealed that the best ethanol produced was obtained at pH 5.5 during fermentation occurred for both cassava and iles-iles tubers. From the results studied shows that iles-iles tuber is promising feedstock because it is producing bioethanol almost similarly compared to cassava.

Regulation of taste-active components of meat by dietary branched-chain amino acids; effects of branched-chain amino acid antagonism.

Science.gov (United States)

Imanari, M; Kadowaki, M; Fujimura, S

2008-05-01

1. The effects of dietary branched-chain amino acids (BCAAs) including leucine (Leu), isoleucine (Ile) and valine (Val) on taste-active components, especially free glutamate (Glu), in meat were investigated. 2. Broiler chickens (28 d old) were given varied dietary BCAA levels for 10 d before marketing. Dietary BCAA content ratios were either 100:100:100 (Low Leu group), 150:100:100 (Control group) or 150:150:150 (High Ile + Val group) for Leu:Ile:Val (% of each BCAA requirement according to NRC, 1994). Taste-related components of meat (free amino acids and ATP metabolites) and sensory scores of meat soup were estimated. 3. Free Glu content, the main taste-active component of meat, was significantly increased by dietary BCAA. Compared to the Control group, free Glu content increased by 30% in the High Ile + Val group. However, the inosine monophosphate (IMP) content in meat did not change among groups. 4. Sensory evaluation of meat soups showed that Control and High Ile + Val groups had different meat flavours. The sensory score of overall taste intensity was significantly higher in the High Ile + Val group. 5. These results suggest that dietary BCAA concentrations regulate free Glu in meat. Increasing dietary Ile + Val induces an increase in free Glu content of meat, improves meat taste and is more effective for increasing free Glu content in meat than decreasing dietary Leu level.

Kinetic proofreading at single molecular level: aminoacylation of tRNA(Ile and the role of water as an editor.

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Mantu Santra

Full Text Available Proofreading/editing in protein synthesis is essential for accurate translation of information from the genetic code. In this article we present a theoretical investigation of efficiency of a kinetic proofreading mechanism that employs hydrolysis of the wrong substrate as the discriminatory step in enzyme catalytic reactions. We consider aminoacylation of tRNA(Ile which is a crucial step in protein synthesis and for which experimental results are now available. We present an augmented kinetic scheme and then employ methods of stochastic simulation algorithm to obtain time dependent concentrations of different substances involved in the reaction and their rates of formation. We obtain the rates of product formation and ATP hydrolysis for both correct and wrong substrates (isoleucine and valine in our case, respectively, in single molecular enzyme as well as ensemble enzyme kinetics. The present theoretical scheme correctly reproduces (i the amplitude of the discrimination factor in the overall rates between isoleucine and valine which is obtained as (1.8×10(2.(4.33×10(2 = 7.8×10(4, (ii the rates of ATP hydrolysis for both Ile and Val at different substrate concentrations in the aminoacylation of tRNA(Ile. The present study shows a non-michaelis type dependence of rate of reaction on tRNA(Ile concentration in case of valine. The overall editing in steady state is found to be independent of amino acid concentration. Interestingly, the computed ATP hydrolysis rate for valine at high substrate concentration is same as the rate of formation of Ile-tRNA(Ile whereas at intermediate substrate concentration the ATP hydrolysis rate is relatively low. We find that the presence of additional editing domain in class I editing enzyme makes the kinetic proofreading more efficient through enhanced hydrolysis of wrong product at the editing CP1 domain.

Modeling and experimental assessment of a buried Leu–Ile mutation in dengue envelope domain III

Energy Technology Data Exchange (ETDEWEB)

Kulkarni, Manjiri R. [Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16, Nakamachi, Koganei-shi, Tokyo, 184-8588 (Japan); Numoto, Nobutaka; Ito, Nobutoshi [Department of Structural Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima Bunkyo-ku, Tokyo, 113-8510 (Japan); Kuroda, Yutaka, E-mail: ykuroda@cc.tuat.ac.jp [Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16, Nakamachi, Koganei-shi, Tokyo, 184-8588 (Japan)

2016-02-26

Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4-L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile{sup 387} conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype’s ED3 is used as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile{sup 387} confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4-L387I at 2 Å resolution. Ile{sup 387} indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task. - Highlights: • We mutated L387I of DEN4 ED3 and examined its effects on structure and stability. • We modeled the side-chain of Ile{sup 387} using DEN4 ED3's structure as a template. • We determined the crystal structure of DEN4-L387I and confirmed the modeling. • Side-chain repacking occurring around Ile{sup 387} involved >3 inter-connected residues. • These results explained why L387I mutation in DEN4 ED3 conserves thermostability.

Modeling and experimental assessment of a buried Leu–Ile mutation in dengue envelope domain III

International Nuclear Information System (INIS)

Kulkarni, Manjiri R.; Numoto, Nobutaka; Ito, Nobutoshi; Kuroda, Yutaka

2016-01-01

Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4-L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile"3"8"7 conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype’s ED3 is used as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile"3"8"7 confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4-L387I at 2 Å resolution. Ile"3"8"7 indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task. - Highlights: • We mutated L387I of DEN4 ED3 and examined its effects on structure and stability. • We modeled the side-chain of Ile"3"8"7 using DEN4 ED3's structure as a template. • We determined the crystal structure of DEN4-L387I and confirmed the modeling. • Side-chain repacking occurring around Ile"3"8"7 involved >3 inter-connected residues. • These results explained why L387I mutation in DEN4 ED3 conserves thermostability.

Association between Two Common Missense Substitutions, Thr6Lys and Val81Ile, in MC3R Gene and Childhood Obesity: A Meta-Analysis.

Science.gov (United States)

Koya, Charita; Yu, Tsung; Strong, Carol; Tsai, Meng-Che

2018-04-24

Two common missense variants in the melanocortin-3 receptor (MC3R) gene, Thr6Lys (T6K) and Val81Ile (V81I), are presumably correlated with pediatric obesity. This meta-analysis aimed to examine and synthesize evidence on the association between these two common MC3R polymorphisms and the development of childhood obesity. A combination of words relevant to the research question was searched on PubMed, EMBASE, Scopus, and the Cochrane database. Results were restricted to human studies, specifically child and adolescent populations. Articles were excluded based on accessibility of full online texts and availability of pertinent data. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model to determine the association of the polymorphisms with obesity. Searches on the databases using the keywords identified 65 potentially relevant reports. Among them, 32 studies were excluded due to irrelevance, and 28 studies excluded due to lack of access, insufficient data, and investigation of other variants. A final set of five studies included in this meta-analysis found that the risk of overweight/obesity increased by 46.1% per K allele and 21.7% per I allele. Only homozygous genotypes for T6K were associated with a 3.10-fold (95% CI: 1.29-7.43) increased risk of overweight/obesity in children. Data were insufficient to examine if homozygosity for both rare alleles further increases risk. Our results supported a recessive inheritance model for MC3R gene as a potential cause of childhood obesity. High clinical heterogeneity existed among studies and thus requires more research of larger participation for future integration of data.

A conformational switch in the inhibitory gamma-subunit of PDE6 upon enzyme activation by transducin.

Science.gov (United States)

Granovsky, A E; Artemyev, N O

2001-11-06

In response to light, a photoreceptor G protein, transducin, activates cGMP-phosphodiesterase (PDE6) by displacing the inhibitory gamma-subunits (Pgamma) from the enzyme's catalytic sites. Evidence suggests that the activation of PDE6 involves a conformational change of the key inhibitory C-terminal domain of Pgamma. In this study, the C-terminal region of Pgamma, Pgamma-73-85, has been targeted for Ala-scanning mutagenesis to identify the point-to-point interactions between Pgamma and the PDE6 catalytic subunits and to probe the nature of the conformational change. Pgamma mutants were tested for their ability to inhibit PDE6 and a chimeric PDE5-conePDE6 enzyme containing the Pgamma C-terminus-binding site of cone PDE. This analysis has revealed that in addition to previously characterized Ile86 and Ile87, important inhibitory contact residues of Pgamma include Asn74, His75, and Leu78. The patterns of mutant PDE5-conePDE6 enzyme inhibition suggest the interaction between the PgammaAsn74/His75 sequence and Met758 of the cone PDE6alpha' catalytic subunit. This interaction, and the interaction between the PgammaIle86/Ile87 and PDE6alpha'Phe777/Phe781 residues, is most consistent with an alpha-helical structure of the Pgamma C-terminus. The analysis of activation of PDE6 enzymes containing Pgamma mutants with Ala-substituted transducin-contact residues demonstrated the critical role of PgammaLeu76. Accordingly, we hypothesize that the initial step in PDE6 activation involves an interaction of transducin-alpha with PgammaLeu76. This interaction introduces a bend into the alpha-helical structure of the Pgamma C-terminus, allowing transducin-alpha to further twist the C-terminus thereby uncovering the catalytic pocket of PDE6.

ASN annual report 2007 - ASN report abstracts on the state of Nuclear Safety and Radiation Protection in France in 2007; ASN rapport annuel 2007

Energy Technology Data Exchange (ETDEWEB)

NONE

2008-07-01

The 2007 annual report of the French nuclear safety authority (ASN) presents the highlights of the year in the domain of nuclear safety and radiation protection in France. The year 2007 was marked by the implementation of a new legislative and regulatory framework created by the 13 June 2006 Act on transparency and security in the nuclear field (TSN) and the 28 June Act on the sustainable management of radioactive materials and wastes. As in the previous two years, the year was relatively satisfactory from the nuclear safety viewpoint and slightly less so with regard to small-scale nuclear activities. For two years now, the medical field has been marked by the declaration to ASN of a number of serious radiotherapy accidents which have led to several deaths or the need for extensive surgery. The following main topics are reviewed in the document: 1 - the decrees implementing the 'TSN' act and the 'Waste' act; 2 - the new ASN, one year on; 3 - ASN regulatory actions in the field of radiotherapy; 4 - regulation of new installations; 5 - the key issues for regulation of existing installations; 6 - nuclear safety and radiation protection research; 7 - policy for management of the post-accident phase of a radiological emergency; 8 - sites and soils polluted by radioactive materials; 9 - international harmonization of nuclear safety and radiation protection.

ASN annual report 2007 - ASN report abstracts on the state of Nuclear Safety and Radiation Protection in France in 2007; ASN rapport annuel 2007

Energy Technology Data Exchange (ETDEWEB)

NONE

2008-07-01

The 2007 annual report of the French nuclear safety authority (ASN) presents the highlights of the year in the domain of nuclear safety and radiation protection in France. The year 2007 was marked by the implementation of a new legislative and regulatory framework created by the 13 June 2006 Act on transparency and security in the nuclear field (TSN) and the 28 June Act on the sustainable management of radioactive materials and wastes. As in the previous two years, the year was relatively satisfactory from the nuclear safety viewpoint and slightly less so with regard to small-scale nuclear activities. For two years now, the medical field has been marked by the declaration to ASN of a number of serious radiotherapy accidents which have led to several deaths or the need for extensive surgery. The following main topics are reviewed in the document: 1 - the decrees implementing the 'TSN' act and the 'Waste' act; 2 - the new ASN, one year on; 3 - ASN regulatory actions in the field of radiotherapy; 4 - regulation of new installations; 5 - the key issues for regulation of existing installations; 6 - nuclear safety and radiation protection research; 7 - policy for management of the post-accident phase of a radiological emergency; 8 - sites and soils polluted by radioactive materials; 9 - international harmonization of nuclear safety and radiation protection.

Energetics and Structure Prediction of the Network of Homo- and Hetero-Oligomers Formed by the Transmembrane Domains of the ErbReceptor Family of Proteins

Science.gov (United States)

2006-06-01

amino acid residue motif, Small-x-x-Large-G/A, consist- ing of a small residue (Gly, Ala , Ser, Thr, or Pro) in the zero position, a large aliphatic...residue ( Ala , Val, Leu, or Ile) in position 3, followed by Gly or Ala in position four.15 This motif was identified in a large number of receptor tyrosine...M. A., Codony-Servat, J., Albanell, J., Rojo, F., Arribas , J. & Baselga, J. (2001). Trastuzumab (her- ceptin), a humanized anti-Her2 receptor

Publication of the inspection follow-up letters of the ASN on its site web asn.gouv.fr; Publication des lettres de suite d'inspection de l'ASN sur son site web asn.gouv.fr

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-07-01

Since February 2002, the French authority of nuclear safety (ASN) publishes on its web site (http://www.asn.gouv.fr) the letters addressed to the operators of nuclear facilities at the end of its inspections. The ASN carries out about 700 inspections every year which concern the French nuclear facilities, the central services of nuclear operators or of their suppliers, and the transports of nuclear materials. Each inspection is followed by a follow-up letter which mentions all anomalies noticed during the inspection and eventually asks for some remedial actions or for some complements of information. This document brings together the letters published between february and May 2002 and concerning the on-site inspections of nuclear facilities (EdF nuclear power plants, CEA centers, Cogema facilities, other sites) and the off-site inspections (Andra, transports of nuclear materials). (J.S.)

ASN report abstracts on the state of Nuclear Safety and Radiation Protection in France in 2008. ASN annual report 2008

International Nuclear Information System (INIS)

2009-01-01

ASN is an independent administrative authority tasked, on behalf of the state, with regulating nuclear safety and radiation protection in order to protect workers, patients and the environment from the hazards involved in nuclear activities. It also contributes to informing the public. ASN, run by a five-member commission, regulates the whole of the sector, acting in a completely impartial manner. The ASN Commission presents its report on the state of nuclear safety and radiation protection in France in 2008. Contents: A - Introduction: The year 2008. B - Key topics: 1. ASN actions to promote greater transparency; 2. EDF nuclear power plant ageing and operating life: the conditions for continued operation; 3. The prevention of malicious acts; 4. ASN regulation of the radiotherapy sector; 5. Regulating and monitoring the construction of the Flamanville 3 EPR reactor; 6. ASN's international nuclear safety responsibilities; 7. The new nuclear countries; 8. Decommissioning of basic nuclear installations and the low-level, long-lived waste disposal project. C - Overview: 1 - Nuclear activities: ionising radiations and health risks; 2 - Principles and stakeholders in the regulation of nuclear safety and radiation protection; 3 - Regulation; 4 - Regulation of nuclear activities and exposure to ionising radiations; 5 - Environmental protection; 6 - Public information and transparency; 7 - International relations; 8 - Radiological emergencies; 9 - Medical uses of ionising radiations; 10 - Industrial and research activities; 11 - Transport of radioactive materials; 12 - EDF nuclear power plants; 13 - Nuclear fuel cycle installations; 14 - Nuclear research facilities and various nuclear installations; 15 - Safe decommissioning of basic nuclear installations; 16 - Radioactive waste and polluted sites. D - Appendices: List of basic nuclear installations; ASN decisions and opinions published in 2008 in its Official Bulletin; Acronyms, abbreviations and names

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...

Effects of Asn318 and Asp87Asn318 mutations on signal transduction by the gonadotropin-releasing hormone receptor and receptor regulation.

Science.gov (United States)

Awara, W M; Guo, C H; Conn, P M

1996-02-01

GnRH receptor (GnRH-R) contains Asn87 and Asp318 instead of the more frequently observed Asp87 and Asn318 found in other G protein-coupled receptors. In the present study, site-directed mutagenesis was used to introduce Asn318 and Asp87Asn318 into GnRH-R. The effect on coupling and regulation of GnRH-R was studied by stable expression of wild and mutant mouse GnRH-R in the lactotropic GH3 cells; these normally release PRL in response to TRH stimulation. The responses to Buserelin (a metabolically stable GnRH analog) in three different cell lines, M1, N8, and ND1 (expressing wild-type, Asn318 mutant, and Asp87Asn318 mutant mouse GnRH-R, respectively) were compared with that observed in the previously characterized GGH3-1' cells, which stably express rat GnRH-R. The Asn318 and Asp87Asn318 mutations had no measurable effect on ligand binding, but abolished the initial down-regulation of receptor that was observed in M1 and GGH3-1' cells, suggesting that the normal location of Asn87 and Asp318 in GnRH-R is involved in the regulation of GnRH-R. In N8 and ND1 cells, Buserelin-stimulated inositol phosphate (IP) production was attenuated, but the release of both cAMP and PRL was stimulated in a dose- and time-dependent manner. These mutations apparently impaired the coupling between GnRH-R and G proteins involved in IP production, but not those involved in cAMP release. In M1 cells, Buserelin stimulation produced a significant increase in IP production, but neither cAMP nor PRL release was significantly stimulated. These findings are consistent with the previous suggestion that GnRH-stimulated PRL release is mediated by a cAMP second messenger system in transfected GGH3 cells.

The French Nuclear Safety Authority (ASN)

International Nuclear Information System (INIS)

Alloso, Ph.

2011-01-01

This article presents the statutes, the organization and the missions of the Nuclear Safety Authority (ASN) whose scope includes radiation protection since 2002. Globally ASN is in charge of: -) participating to the making of laws and regulations, -) delivering administrative authorizations, -) controlling the conformity of nuclear installations and activities with the laws and regulations, -) informing the public, and -) reporting on the state of nuclear safety and radiation protection each year. (A.C.)

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.

Mutation of Asn28 Disrupts the Dimerization and Enzymatic Activity of SARS 3CL

Energy Technology Data Exchange (ETDEWEB)

Barrila, J.; Gabelli, S; Bacha, U; Amzel, M; Freire, E

2010-01-01

Coronaviruses are responsible for a significant proportion of annual respiratory and enteric infections in humans and other mammals. The most prominent of these viruses is the severe acute respiratory syndrome coronavirus (SARS-CoV) which causes acute respiratory and gastrointestinal infection in humans. The coronavirus main protease, 3CL{sup pro}, is a key target for broad-spectrum antiviral development because of its critical role in viral maturation and high degree of structural conservation among coronaviruses. Dimerization is an indispensable requirement for the function of SARS 3CL{sup pro} and is regulated through mechanisms involving both direct and long-range interactions in the enzyme. While many of the binding interactions at the dimerization interface have been extensively studied, those that are important for long-range control are not well-understood. Characterization of these dimerization mechanisms is important for the structure-based design of new treatments targeting coronavirus-based infections. Here we report that Asn28, a residue 11 {angstrom} from the closest residue in the opposing monomer, is essential for the enzymatic activity and dimerization of SARS 3CLpro. Mutation of this residue to alanine almost completely inactivates the enzyme and results in a 19.2-fold decrease in the dimerization K{sub d}. The crystallographic structure of the N28A mutant determined at 2.35 {angstrom} resolution reveals the critical role of Asn28 in maintaining the structural integrity of the active site and in orienting key residues involved in binding at the dimer interface and substrate catalysis. These findings provide deeper insight into complex mechanisms regulating the activity and dimerization of SARS 3CL{sup pro}.

Determination of amino acids in industrial effluents contaminated soil

International Nuclear Information System (INIS)

Mahar, M.T.; Khuhawar, M.Y.

2014-01-01

38 samples of soil for 19 locations partially irrigated on the effluents of sugar mill and oil andghee mill, bottom sediments of evaporation ponds of sugar and fertilizer industries were collected and analyzed for amino acids after acid digestion by gas chromatography using pre column derivatization with trifluroacetyleacetone and ethyl chloroformate. The results obtained were compared with the soil samples irrigated with fresh water. The soil samples were also analyzed for pH, total nitrogen contents and organic carbon. Nine essential (leucine (Leu), threonine (Thr), lysine (Lys), L-phenylalanine (Phe), tryptophan (Trp), histadine (His), L-valine (Val), methionine (Met) and isoleucine Ile) and ten non-essential ( alanine (Ala), cysteine (Cys), asparagine (Asn), glutamic acid (Glu), serine (Ser), glycine (Gly), proline (Pro), Glutamine (Gln), aspartic acid (Asp), tyrosine (Tyr)) amino acids were analyzed 13-15 amino acids were identified and determined quantitatively from soil samples. Amino acids Met, Asn, Gln and Trp were observed absent from all the samples. The variation in the amino acids contents in soil with the industrial effluents added and total nitrogen and organic carbon is discussed. (author)

Skin peptide tyrosine-tyrosine, a member of the pancreatic polypeptide family: isolation, structure, synthesis, and endocrine activity.

Science.gov (United States)

Mor, A; Chartrel, N; Vaudry, H; Nicolas, P

1994-10-25

Pancreatic polypeptide, peptide tyrosine-tyrosine (PYY), and neuropeptide tyrosine (NPY), three members of a family of structurally related peptides, are mainly expressed in the endocrine pancreas, in endocrine cells of the gut, and in the brain, respectively. In the present study, we have isolated a peptide of the pancreatic polypeptide family from the skin of the South American arboreal frog Phyllomedusa bicolor. The primary structure of the peptide was established as Tyr-Pro-Pro-Lys-Pro-Glu-Ser-Pro-Gly-Glu10-Asp-Ala-Ser-Pro-Glu-Glu- Met-Asn- Lys-Tyr20-Leu-Thr-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu30-Val-Thr- Arg-Gln-Arg-Tyr-NH2 . This unusual peptide, named skin peptide tyrosine-tyrosine (SPYY), exhibits 94% similarity with PYY from the frog Rana ridibunda. A synthetic replicate of SPYY inhibits melanotropin release from perifused frog neurointermediate lobes in very much the same way as NPY. These results demonstrate the occurrence of a PYY-like peptide in frog skin. Our data also suggest the existence of a pituitary-skin regulatory loop in amphibians.

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

Directory of Open Access Journals (Sweden)

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.

A 19-kDa C-terminal tryptic fragment of the α chain of Na/K-ATPase is essential for occlusion and transport of cations

International Nuclear Information System (INIS)

Karlish, S.J.D.; Goldshleger, R.; Stein, W.D.

1990-01-01

Tryptic digestion of pig renal Na/K-ATPase in the presence of Rb and absence of Ca ions removes about half of the protein but leaves a stable 19-kDa membrane-embedded fragment derived from the α chain, a largely intact β chain, and essentially normal Rb- and Na-occlusion capacity. Subsequent digestion with trypsin in the presence of Ca or absence of Rb ions leads to rapid loss of the 19-kDa fragment and a parallel loss of Rb occlusion, demonstrating that the fragment is essential for occlusion. The N-terminal sequence of the 19-kDa fragment is Asn-Pro-Lys-Thr-Asp-Lys-Leu-Val-Asn-Glu-Arg-Leu-Ile-Ser-Met-Ala, beginning at residue 830 and extending toward the C terminus. Membranes containing the 19-kDa fragment have the following functional properties. (i) ATP-dependent functions are absent. (ii) The apparent affinity for occluding Rb is unchanged, the affinity for Na is lower than in the control enzyme, and activation is now strongly sigmoidal rather than hyperbolic. (iii) Membranes containing the 19-kDa fragment can be reconstituted into phospholipid vesicles and sustain slow Rb-Rb exchange. Thus the transport pathway is retained. The authors conclude that cation occlusion sites and the transport pathway within transmembrane segments are quite separate from the ATP binding sites, located on the cytoplasmic domain of the α chain. Interactions between cation and ATP sites, the heart of active transport, must be indirect - mediated, presumably, by conformational changes of the protein

A 19-kDa C-terminal tryptic fragment of the. alpha. chain of Na/K-ATPase is essential for occlusion and transport of cations

Energy Technology Data Exchange (ETDEWEB)

Karlish, S.J.D.; Goldshleger, R. (Weizmann Institute of Science, Rehovot (Israel)); Stein, W.D. (Hebrew Univ. Jerusalem (Israel))

1990-06-01

Tryptic digestion of pig renal Na/K-ATPase in the presence of Rb and absence of Ca ions removes about half of the protein but leaves a stable 19-kDa membrane-embedded fragment derived from the {alpha} chain, a largely intact {beta} chain, and essentially normal Rb- and Na-occlusion capacity. Subsequent digestion with trypsin in the presence of Ca or absence of Rb ions leads to rapid loss of the 19-kDa fragment and a parallel loss of Rb occlusion, demonstrating that the fragment is essential for occlusion. The N-terminal sequence of the 19-kDa fragment is Asn-Pro-Lys-Thr-Asp-Lys-Leu-Val-Asn-Glu-Arg-Leu-Ile-Ser-Met-Ala, beginning at residue 830 and extending toward the C terminus. Membranes containing the 19-kDa fragment have the following functional properties. (i) ATP-dependent functions are absent. (ii) The apparent affinity for occluding Rb is unchanged, the affinity for Na is lower than in the control enzyme, and activation is now strongly sigmoidal rather than hyperbolic. (iii) Membranes containing the 19-kDa fragment can be reconstituted into phospholipid vesicles and sustain slow Rb-Rb exchange. Thus the transport pathway is retained. The authors conclude that cation occlusion sites and the transport pathway within transmembrane segments are quite separate from the ATP binding sites, located on the cytoplasmic domain of the {alpha} chain. Interactions between cation and ATP sites, the heart of active transport, must be indirect - mediated, presumably, by conformational changes of the protein.

(DDT) and hexachlorohexane (HCH) pesticide residues in foodstuffs ...

African Journals Online (AJOL)

Dichloro-diphenyl-trichloro-ethane (DDT) and hexachlorohexane (HCH) pesticide residues in foodstuffs from markets in Ile-Ife, Nigeria. ... International Journal of Biological and Chemical Sciences ... Keywords: Dichlorodiphenyltrichloroethane, hexachlorocyclohexane, pesticide, residue, cowpea grain, yam chip.

Distribution of stable free radicals among amino acids of isolated soy proteins.

Science.gov (United States)

Lei, Qingxin; Liebold, Christopher M; Boatright, William L; Shah Jahan, M

2010-09-01

Application of deuterium sulfide to powdered isolated soy proteins (ISP) was used to quench stable free radicals and produce a single deuterium label on amino acids where free radicals reside. The deuterium labels rendered increases of isotope ratio for the specific ions of radical-bearing amino acids. Isotope ratio measurements were achieved by gas chromatography/mass spectrometry (GC/MS) analyses after the amino acids were released by acidic hydrolysis and converted to volatile derivatives with propyl chloroformate. The isotope enrichment data showed the stable free radicals were located on Ala, Gly, Leu, Ile, Asx (Asp+Asn), Glx (Glu+Gln), and Trp but not on Val, Pro, Met, Phe, Lys, and His. Due to the low abundance of Ser, Thr, and Cys derivatives and the impossibility to accurately measure their isotope ratios, the radical bearing status for these amino acids remained undetermined even though their derivatives were positively identified from ISP hydrolysates. The relative isotope enrichment for radical-bearing amino acids Ala, Gly, Leu, Ile, Asx (Asp+Asn), Glx (Glu+Gln), and Trp were 8.67%, 2.96%, 2.90%, 3.94%, 6.03%, 3.91%, and 21.48%, respectively. Isotope ratio increase for Tyr was also observed but further investigation revealed such increase was mainly from nonspecific deuterium-hydrogen exchange not free radical quenching. The results obtained from the present study provide important information for a better understanding of the mechanisms of free radical formation and stabilization in "dry" ISP.

Enhanced delivery of hydrophilic peptides in vitro by transdermal microneedle pretreatment.

Science.gov (United States)

Zhang, Suohui; Qiu, Yuqin; Gao, Yunhua

2014-02-01

The aims of this study were to investigate the utility of solid microneedle arrays (150 µm in length) in enhancing transdermal delivery of peptides and to examine the relationship between peptide permeation rates and D2O flux. Four model peptides were used (Gly-Gln-Pro-Arg [tetrapeptide-3, 456.6 Da], Val-Gly-Val-Ala-Pro-Gly [hexapeptide, 498.6 Da], AC-Glu-Glu-Met-Gln-Arg-Arg-NH2 [acetyl hexapeptide-3, 889 Da] and Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2 [oxytocin, 1007.2 Da]). The influence of microneedle pretreatment on skin permeation was evaluated using porcine ear skin with Franze diffusion cell. Peptide permeation across the skin was significantly enhanced by microneedle pretreatment, and permeation rates were dependent on peptide molecular weights. A positive correlation between D2O flux and acetyl hexapeptide-3 clearances suggests that convective solvent flow contributes to the enhanced transdermal peptide delivery. It is concluded that solid microneedle arrays are effective devices to enhance skin delivery of peptides.

A.S.N. regulation of Flamanville 3 EPR construction

International Nuclear Information System (INIS)

Limousin, S.

2009-01-01

The EPR authorization decree for Flamanville 3 was issued by the French government (decree no. 2007-534) on the 10 April 2007. The construction activities are going on in the manufacturer workshops and at Flamanville site. The decree published in November 2007, and related to the so called TSN law (the nuclear transparency and safety nuclear law published in 2006), specifies that the commissioning licence (the agreement for first fuel load) has to be granted by an ASN decision on the basis of the assessment of the demonstration of the plant safety. In this aim, one part of ASN's work is to review, with its technical sup-port organisation (IRSN), the reactor construction in order to appreciate the safety level of the construction activities. This paper describes ASN's strategy for the regulation of Flamanville 3 EPR construction activities, endorsed by ASN commission at the end of November 2007, and the main events which have occurred on Flamanville site since the beginning of the construction. The article presents the main ASN conclusions of this regulation at this time. (author)

Asn563Ser polymorphism of CD31/PECAM-1 is associated with atherosclerotic cerebral infarction in a southern Han population

Directory of Open Access Journals (Sweden)

Song YM

2014-12-01

Full Text Available Yanmin Song, Qunfang Li, Lili Long, Ning Zhang, Yunhai Liu Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China Background: CD31, also called platelet endothelial cell adhesion molecule-1 (PECAM-1, is thought to play a role in the pathological mechanisms of atherosclerosis. Leu125Val polymorphism and elevated plasma levels of soluble PECAM-1 (sPECAM-1 were found to be associated with cerebral infarction. Our aim was to investigate the association between the Asn563Ser polymorphism of CD31/PECAM-1, plasma level of sPECAM-1, and the risk of atherosclerotic cerebral infarction (ACI in the southern Han population of the People’s Republic of China.Subjects and methods: A total of 147 subjects with ACI and 114 controls were enrolled in the study. The Asn563Ser CD31/PECAM-1 polymorphism was detected using the polymerase chain reaction–restriction fragment length polymorphism method. The plasma spECAM-1 level was measured using the enzyme-linked immunosorbent assay method.Results: In this study, statistically significant differences in Asn563Ser genotype and allele distribution were found between the cases and controls (P<0.05. Furthermore, logistic regression analysis showed that the GG genotype is associated with increase in ACI risk (odds ratio =4.862, P<0.001. The plasma level of sPECAM-1 was associated with ACI (odds ratio =1.431, P=0.038. In both the ACI and the control groups, the plasma sPECAM-1 level in subjects with the GG genotype was higher than that in subjects carrying the AA or GA genotype (P<0.05.Conclusion: Our study showed that the Asn563Ser polymorphism of CD31/PECAM-1 gene and elevated plasma sPECAM-1 level are related to ACI risk in the southern Han population of People’s Republic of China. Keywords: genetic polymorphism, CD31, platelet endothelial cell adhesion molecule-1 (PECAM-1

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

Impact of the Disruption of ASN3-Encoding Asparagine Synthetase on Arabidopsis Development

Directory of Open Access Journals (Sweden)

Laure Gaufichon

2016-02-01

Full Text Available The aim of this study was to investigate the role of ASN3-encoded asparagine synthetase (AS, EC 6.3.5.4 during vegetative growth, seed development and germination of Arabidopsis thaliana. Phenotypic analysis of knockout (asn3-1 and knockdown (asn3-2 T-DNA insertion mutants for the ASN3 gene (At5g10240 demonstrated wild-type contents of asparagine synthetase protein, chlorophyll and ammonium in green leaves at 35 days after sowing. In situ hybridization localized ASN3 mRNA to phloem companion cells of vasculature. Young siliques of the asn3-1 knockout line showed a decrease in asparagine but an increase in glutamate. The seeds of asn3-1 and asn3-2 displayed a wild-type nitrogen status expressed as total nitrogen content, indicating that the repression of ASN3 expression had only a limited effect on mature seeds. An analysis of amino acid labeling of seeds imbibed with (15N ammonium for 24 h revealed that asn3-1 seeds contained 20% less total asparagine while 15N-labeled asparagine ((2-15Nasparagine, (4-15Nasparagine and (2,4-15Nasparagine increased by 12% compared to wild-type seeds. The data indicate a fine regulation of asparagine synthesis and hydrolysis in Arabidopsis seeds.

Skills of Asn inspectors responsible for inspecting pressurised equipment

International Nuclear Information System (INIS)

Colonna, F.

2010-01-01

ASN relies on the unique competencies of its staff to assure that it can complete its mission of maintaining public health and safety. Since 1975, personnel at ASN Nuclear Pressure Equipment Department have played a major role in the oversight of pressure boundary equipment by verifying that equipment is manufactured in compliance with regulatory requirements. This has called for highly competent individuals trained in a variety of technical and regulatory backgrounds. ASN is meeting the challenge of keeping its staff trained and prepared to continue its oversight of nuclear boilers. This has included ensuring that its organization is welt suited to meet the demands, and relying on third-party experts when necessary. With the implementation of the 2006 transparency law, ASN has taken necessary steps to ensure that it will maintain its high level of expertise going forward. (author)

Novel nucleotide and amino acid covariation between the 5'UTR and the NS2/NS3 proteins of hepatitis C virus: bioinformatic and functional analyses.

Directory of Open Access Journals (Sweden)

Hung-Yu Sun

Full Text Available Molecular covariation of highly polymorphic viruses is thought to have crucial effects on viral replication and fitness. This study employs association rule data mining of hepatitis C virus (HCV sequences to search for specific evolutionary covariation and then tests functional relevance on HCV replication. Data mining is performed between nucleotides in the untranslated regions 5' and 3'UTR, and the amino acid residues in the non-structural proteins NS2, NS3 and NS5B. Results indicate covariance of the 243(rd nucleotide of the 5'UTR with the 14(th, 41(st, 76(th, 110(th, 211(th and 212(th residues of NS2 and with the 71(st, 175(th and 621(st residues of NS3. Real-time experiments using an HCV subgenomic system to quantify viral replication confirm replication regulation for each covariant pair between 5'UTR₂₄₃ and NS2-41, -76, -110, -211, and NS3-71, -175. The HCV subgenomic system with/without the NS2 region shows that regulatory effects vanish without NS2, so replicative modulation mediated by HCV 5'UTR₂₄₃ depends on NS2. Strong binding of the NS2 variants to HCV RNA correlates with reduced HCV replication whereas weak binding correlates with restoration of HCV replication efficiency, as determined by RNA-protein immunoprecipitation assay band intensity. The dominant haplotype 5'UTR₂₄₃-NS2-41-76-110-211-NS3-71-175 differs according to the HCV genotype: G-Ile-Ile-Ile-Gly-Ile-Met for genotype 1b and A-Leu-Val-Leu-Ser-Val-Leu for genotypes 1a, 2a and 2b. In conclusion, 5'UTR₂₄₃ co-varies with specific NS2/3 protein amino acid residues, which may have significant structural and functional consequences for HCV replication. This unreported mechanism involving HCV replication possibly can be exploited in the development of advanced anti-HCV medication.

Exchanging a single amino acid residue generates or weakens a +2 cellooligosaccharide binding subsite in rice β-glucosidases.

Science.gov (United States)

Sansenya, Sompong; Maneesan, Janjira; Cairns, James R Ketudat

2012-04-01

Os3BGlu6, Os3BGlu7, and Os4BGlu12 are rice glycoside hydrolase family 1 β-glucosidases, the structures of which have been solved by X-ray crystallography. In complex structures, Os3BGlu7 residue Asn245 hydrogen bonds to the second sugar in the +1 subsite for laminaribiose and the third sugar in the +2 subsite for cellotetraose and cellopentaose. The corresponding Os3BGlu6 residue, Met251, appears to block the binding of cellooligosaccharides at the +2 subsite, whereas His252 in this position in Os4BGlu12 could hydrogen bond to oligosaccharides. Mutation of Os3BGlu6 Met251 to Asn resulted in a 15-fold increased k(cat)/K(m) value for hydrolysis of laminaribiose compared to wild type Os3BGlu6 and 9 to 24-fold increases for cellooligosaccharides with degrees of polymerization (DP) of 2-5. On the other hand, mutation of Os3BGlu7 Asn245 to Met decreased the k(cat)/K(m) of hydrolysis by 6.5-fold for laminaribiose and 17 to 30-fold for cellooligosaccharides with DP >2, while mutation of Os4BGlu12 His252 to Met decreased the corresponding k(cat)/K(m) values 2 to 6-fold. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Bacillus subtilis and Bacillus halodurans Aspartyl-tRNA Synthetases Retain Recognition of tRNA(Asn).

Science.gov (United States)

Nair, Nilendra; Raff, Hannah; Islam, Mohammed Tarek; Feen, Melanie; Garofalo, Denise M; Sheppard, Kelly

2016-02-13

Synthesis of asparaginyl-tRNA (Asn-tRNA(Asn)) in bacteria can be formed either by directly ligating Asn to tRNA(Asn) using an asparaginyl-tRNA synthetase (AsnRS) or by synthesizing Asn on the tRNA. In the latter two-step indirect pathway, a non-discriminating aspartyl-tRNA synthetase (ND-AspRS) attaches Asp to tRNA(Asn) and the amidotransferase GatCAB transamidates the Asp to Asn on the tRNA. GatCAB can be similarly used for Gln-tRNA(Gln) formation. Most bacteria are predicted to use only one route for Asn-tRNA(Asn) formation. Given that Bacillus halodurans and Bacillus subtilis encode AsnRS for Asn-tRNA(Asn) formation and Asn synthetases to synthesize Asn and GatCAB for Gln-tRNA(Gln) synthesis, their AspRS enzymes were thought to be specific for tRNA(Asp). However, we demonstrate that the AspRSs are non-discriminating and can be used with GatCAB to synthesize Asn. The results explain why B. subtilis with its Asn synthetase genes knocked out is still an Asn prototroph. Our phylogenetic analysis suggests that this may be common among Firmicutes and 30% of all bacteria. In addition, the phylogeny revealed that discrimination toward tRNA(Asp) by AspRS has evolved independently multiple times. The retention of the indirect pathway in B. subtilis and B. halodurans likely reflects the ancient link between Asn biosynthesis and its use in translation that enabled Asn to be added to the genetic code. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Obnova bývalé prádelny pod hradem Veveří pro účely enviromentálních aktivit

OpenAIRE

Vrtek, Tomáš

2014-01-01

Cílem bakalářské práce bylo navržení obnovy objektu bývalé hradní prádelny hradu Veveří, při ulici Rakovecká v městské části Brno-Bystrc. Záměr k obnově vzešel od současných majitelů a spočíval v návrhu nového programu využití s environmentální tématikou a poté samotné rekonstrukce objektu. Navržen byl objekt s rekreačním ubytováním se specializovanými dílnami zaměřenými převážně na výuku a provozování tradičních řemesel. Vzhledem k špatnému technickému stavu objektu a novému plánovanému využ...

Comparisons of Prostate Cancer Inhibitors Abiraterone and TOK-001 Binding with CYP17A1 through Molecular Dynamics

Directory of Open Access Journals (Sweden)

Fei Xiao

2015-01-01

However, biology-driven inhibitor development of prostate cancer is poorly elucidated. The aims of this study are to address structural differences at atomic-level between CYP17A1 and inhibitors i.e., abiraterone and TOK-001, and further investigate the effect of point mutation of CYP17A1 on the active site stability and the local interactions that are hydrophobic interaction and hydrogen bonding throughout molecular dynamics (MD simulation. After performing multiple comparisons among four different complexes across CYP17A1 and inhibitors, interestingly TOK-001 oriented toward the active pocket and formed larger volume with I-helix of CYP17A1 than abiraterone, whereas abiraterone showed tighter binding and more active site stability. Considering on the effect of hydrophobic interaction and hydrogen bonding between abiraterone and CYP17A1, the key residues of Phe114, Ile371, Val482, and Asn202 were identified. This contributes into tight binding interactions; however abiraterone is effectively weakened along with the global conformation mobility increased in A105L mutation. Surprisingly, overall conformation of the CYP17A1 remained stable when bound to TOK-001. This basic knowledge can guide future experiments on design of efficient inhibitors for CYP17A1, which provides theoretical basis of androgen-dependent disease therapy.

14 CFR 380.26 - Discrimination.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Discrimination. 380.26 Section 380.26... REGULATIONS PUBLIC CHARTERS Requirements Applicable to Charter Operators § 380.26 Discrimination. No charter... unjust discrimination or any undue or unreasonable prejudice or disadvantage in any respect whatsoever. ...

Ethnic disparity in 21-hydroxylase gene mutations identified in Pakistani congenital adrenal hyperplasia patients

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Jabbar Abdul

2011-02-01

Full Text Available Abstract Background Congenital adrenal hyperplasia (CAH is a group of autosomal recessive disorders caused by defects in the steroid 21 hydroxylase gene (CYP21A2. We studied the spectrum of mutations in CYP21A2 gene in a multi-ethnic population in Pakistan to explore the genetics of CAH. Methods A cross sectional study was conducted for the identification of mutations CYP21A2 and their phenotypic associations in CAH using ARMS-PCR assay. Results Overall, 29 patients were analyzed for nine different mutations. The group consisted of two major forms of CAH including 17 salt wasters and 12 simple virilizers. There were 14 phenotypic males and 15 females representing all the major ethnic groups of Pakistan. Parental consanguinity was reported in 65% cases and was equally distributed in the major ethnic groups. Among 58 chromosomes analyzed, mutations were identified in 45 (78.6% chromosomes. The most frequent mutation was I2 splice (27% followed by Ile173Asn (26%, Arg 357 Trp (19%, Gln319stop, 16% and Leu308InsT (12%, whereas Val282Leu was not observed in this study. Homozygosity was seen in 44% and heterozygosity in 34% cases. I2 splice mutation was found to be associated with SW in the homozygous. The Ile173Asn mutation was identified in both SW and SV forms. Moreover, Arg357Trp manifested SW in compound heterozygous state. Conclusion Our study showed that CAH exists in our population with ethnic difference in the prevalence of mutations examined.

46 CFR 380.21 - Reproduction.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Reproduction. 380.21 Section 380.21 Shipping MARITIME... Reproduction. (a) The records described in § 380.24 may be microfilmed or otherwise reproduced in lieu of their retention in original form: Provided, That such reproductions shall not be made prior to completion of the...

ASN annual report 2007 - ASN report abstracts on the state of Nuclear Safety and Radiation Protection in France in 2007

International Nuclear Information System (INIS)

2008-01-01

The 2007 annual report of the French nuclear safety authority (ASN) presents the highlights of the year in the domain of nuclear safety and radiation protection in France. The year 2007 was marked by the implementation of a new legislative and regulatory framework created by the 13 June 2006 Act on transparency and security in the nuclear field (TSN) and the 28 June Act on the sustainable management of radioactive materials and wastes. As in the previous two years, the year was relatively satisfactory from the nuclear safety viewpoint and slightly less so with regard to small-scale nuclear activities. For two years now, the medical field has been marked by the declaration to ASN of a number of serious radiotherapy accidents which have led to several deaths or the need for extensive surgery. The following main topics are reviewed in the document: 1 - the decrees implementing the 'TSN' act and the 'Waste' act; 2 - the new ASN, one year on; 3 - ASN regulatory actions in the field of radiotherapy; 4 - regulation of new installations; 5 - the key issues for regulation of existing installations; 6 - nuclear safety and radiation protection research; 7 - policy for management of the post-accident phase of a radiological emergency; 8 - sites and soils polluted by radioactive materials; 9 - international harmonization of nuclear safety and radiation protection

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...

ASN 2009 annual report

International Nuclear Information System (INIS)

2010-01-01

After a presentation of the roles, missions and organization of the ASN (the French Nuclear safety Authority), this document presents and reports its actions in various domains: ionizing radiations and health and environmental risks (knowledge on these risks and hazards, nuclear activities controlled by the ASN, surveillance of exposures to ionizing radiations), principles and actors of nuclear safety, radioprotection and environment protection control, regulation (general framework, proximity nuclear regulation, nuclear installation legal regime, radioactive material transport regulation, arrangements associated with some risks and some specific activities), control of nuclear activities and exposures to ionizing radiations, situations of radiological emergency, public information, international relationships (objectives in Europe and in the world, relationships within the EU and multilateral relationships, bilateral relationships, international convention, international conferences), regional overview of nuclear safety and radioprotection, medical and non medical uses of ionizing radiations, transport of radioactive materials, EDF nuclear plants, nuclear fuel cycle installations, nuclear research installations and other installations, basic nuclear installation dismantling safety, radioactive wastes and polluted sites. This report also provides presentations of incident and accident classification scales and law texts

Identification of dipeptidyl peptidase-IV inhibitory peptides from mare whey protein hydrolysates.

Science.gov (United States)

Song, J J; Wang, Q; Du, M; Ji, X M; Mao, X Y

2017-09-01

Inhibition of dipeptidyl peptidase-IV (DPP-IV) activity is a promising strategy for treatment of type 2 diabetes. In the current study, DPP-IV inhibitory peptides were identified from mare whey protein hydrolysates obtained by papain. The results showed that all the mare whey protein hydrolysates obtained at various hydrolysis durations possessed more potent DPP-IV inhibitory activity compared with intact whey protein. The 4-h hydrolysates showed the greatest DPP-IV inhibitory activity with half-maximal inhibitory concentration of 0.18 mg/mL. The 2 novel peptides from 4-h hydrolysate fractions separated by successive chromatographic steps were characterized by liquid chromatography-electrospray ionization tandem mass spectrometry. The novel peptides Asn-Leu-Glu-Ile-Ile-Leu-Arg and Thr-Gln-Met-Val-Asp-Glu-Glu-Ile-Met-Glu-Lys-Phe-Arg, which corresponded to β-lactoglobulin 1 f(71-77) and β-lactoglobulin 1 f(143-155), demonstrated DPP-IV inhibitory activity with half-maximal inhibitory concentrations of 86.34 and 69.84 μM, respectively. The DPP-IV inhibitory activity of the 2 peptides was retained or even improved after simulated gastrointestinal digestion in vitro. Our findings indicate that mare whey protein-derived peptides may possess potential as functional food ingredients in the management of type 2 diabetes. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Detecção de resistência às fluoroquinolonas em Campylobacter isolados de frangos de criação orgânica

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Beatriz S. Frasão

2015-07-01

Full Text Available Resumo Estudos têm revelado que a resistência às quinolonas em cepas de Campylobacter está relacionada à presença da mutação Treonina-86 para Isoleucina. Com o objetivo de investigar a presença dessa mutação em cepas de Campylobacter sensíveis e resistentes à ciprofloxacina e enrofloxacina, o conteúdo cecal de 80 frangos de corte de criação orgânica, abatidos sob Serviço de Inspeção Estadual (S.I.E. do Estado do Rio de Janeiro, foram coletados e investigados para a presença de Campylobacter. A determinação da resistência à ciprofloxacina e enrofloxacina foi feita pela técnica de difusão em disco e de diluição em ágar para determinação da Concentração Inibitória Mínima (CIM. A detecção da mutação na Região Determinante de Resistencia às Quinolonas (RDRQ no gene gyrA foi realizada através de sequenciamento. Campylobacter foi isolado a partir de 100% das amostras avaliadas, sendo 68,75% correspondente à C. jejuni e 31,25% à C. coli. No teste de difusão em disco, 100% das cepas foram resistentes à ciprofloxacina e 56,25% das cepas foram resistentes à enrofloxacina. No teste de diluição em ágar, todas as cepas foram resistentes à ciprofloxacina apresentando CIM variando de ≥ 16-64μg/mL, e resistência ou resistência intermediaria à enrofloxacina foi detectada em 42,50% (CIM ≥ 4-32μg/mL e 38,75% (CIM = 2μg/mL das cepas, respectivamente. A mutação Tre-86-Ile, foi observada em 100% das cepas analisadas. Além dessa mutação, foram observadas outras mutações não silenciosas (Val-73-Glu, Ser-114-Leu, Val-88-Asp, Ala-75-Asp, Ser-119-Gli, Arg-79-Lis e mutações silenciosas (His-81-His, Ser-119-Ser, Ala-120-Ala, Fen-99-Fen, Ala-122-Ala, Gli-74-Gli, Ile-77-Ile, Ala-91-Ala, Leu-92-Leu, Val-93-Val, Ile-106-Ile, Tre-107-Tre, Gli-113-Gli, Ile-115-Ile, Gli-110-Gli. A observação de que cepas sensíveis à enrofloxacina pelos testes fenotípicos apresentavam a substituição Tre-86 para Ile sugere

Polyethylene glycol promotes autoxidation of cytochrome c.

Science.gov (United States)

Sato, Wataru; Uchida, Takeshi; Saio, Tomohide; Ishimori, Koichiro

2018-06-01

Cytochrome c (Cyt c) was rapidly oxidized by molecular oxygen in the presence, but not absence of PEG. The redox potential of heme c was determined by the potentiometric titration to be +236 ± 3 mV in the absence of PEG, which was negatively shifted to +200 ± 4 mV in the presence of PEG. The underlying the rapid oxidation was explored by examining the structural changes in Cyt c in the presence of PEG using UV-visible absorption, circular dichroism, resonance Raman, and fluorescence spectroscopies. These spectroscopic analyses suggested that heme oxidation was induced by a modest tertiary structural change accompanied by a slight shift in the heme position (c, which triggered heme displacement. The primary dehydration site was estimated to be around surface-exposed hydrophobic residues near the heme center: Ile81 and Val83. These findings and our previous studies, which showed that hydrated water molecules around Ile81 and Val83 are expelled when Cyt c forms a complex with CcO, proposed that dehydration of these residues is functionally significant to electron transfer from Cyt c to CcO. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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

Protein changes associated with reprotonation of the Schiff base in the photocycle of Asp96-->Asn bacteriorhodopsin. The MN intermediate with unprotonated Schiff base but N-like protein structure

Science.gov (United States)

Sasaki, J.; Shichida, Y.; Lanyi, J. K.; Maeda, A.

1992-01-01

The difference Fourier transform infrared spectrum for the N intermediate in the photoreaction of the light-adapted form of bacteriorhodopsin can be recorded at pH 10 at 274 K (Pfefferle, J.-M., Maeda, A., Sasaki, J., and Yoshizawa, T. (1991) Biochemistry 30, 6548-6556). Under these conditions, Asp96-->Asn bacteriorhodopsin gives a photoproduct which shows changes in protein structure similar to those observed in N of wild-type bacteriorhodopsin. However, decreased intensity of the chromophore bands and the single absorbance maximum at about 400 nm indicate that the Schiff base is unprotonated, as in the M intermediate. This photoproduct was named MN. At pH 7, where the supply of proton is not as restricted as at pH 10, Asp96-->Asn bacteriorhodopsin yields N with a protonated Schiff base. The Asn96 residue, which cannot deprotonate as Asp96 in wild-type bacteriorhodopsin, is perturbed upon formation of both MN at pH 10 and N at pH 7. We suggest that the reprotonation of the Schiff base is preceded by a large change in the protein structure including perturbation of the residue at position 96.

Study of the interactions of PAMAM-NH2 G4 dendrimer with selected natural amino acids in aqueous solutions

International Nuclear Information System (INIS)

Buczkowski, Adam; Palecz, Bartlomiej

2014-01-01

Highlights: • Calorimetric titration and dilution calorimetry show strong interactions between PAMAM-NH 2 G4 dendrimer and amino acids. • The more polar the amino acid side chain, the more exothermic the effects of the direct interactions with dendrimer. • Macromolecule of PAMAM-NH 2 G4 dendrimer can coordinate 20 to 40 molecules of amino acid. -- Abstract: The interactions of PAMAM-NH 2 G4 dendrimer with selected natural amino acids (Gly, Ala, Val, Leu, Ile, Phe, Ser, Thr, Met, Asn, Gln, Pro and Trp) in aqueous solutions were measured with the use of the techniques of calorimetric titration and dilution calorimetry. The results of calorimetric measurements show strong interactions between PAMAM-NH 2 G4 dendrimer and amino acids with polar substituents. A macromolecule of PAMAM-NH 2 G4 dendrimer can coordinate 20 to 40 molecules of amino acid

Structural characterization of V57D and V57P mutants of human cystatin C, an amyloidogenic protein

Energy Technology Data Exchange (ETDEWEB)

Orlikowska, Marta; Szymańska, Aneta [University of Gdansk, Sobieskiego 18/19, 80-952 Gdansk (Poland); Borek, Dominika; Otwinowski, Zbyszek [University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816 (United States); Skowron, Piotr; Jankowska, Elżbieta, E-mail: elaj@chem.univ.gda.pl [University of Gdansk, Sobieskiego 18/19, 80-952 Gdansk (Poland)

2013-04-01

Val57 point mutants of human cystatin C, which were designed to assess the influence of changes in the properties of the L1 loop on the dimerization propensity, were structurally characterized. Wild-type human cystatin C (hCC wt) is a low-molecular-mass protein (120 amino-acid residues, 13 343 Da) that is found in all nucleated cells. Physiologically, it functions as a potent regulator of cysteine protease activity. While the biologically active hCC wt is a monomeric protein, all crystallization efforts to date have resulted in a three-dimensional domain-swapped dimeric structure. In the recently published structure of a mutated hCC, the monomeric fold was preserved by a stabilization of the conformationally constrained loop L1 caused by a single amino-acid substitution: Val57Asn. Additional hCC mutants were obtained in order to elucidate the relationship between the stability of the L1 loop and the propensity of human cystatin C to dimerize. In one mutant Val57 was substituted by an aspartic acid residue, which is favoured in β-turns, and in the second mutant proline, a residue known for broadening turns, was substituted for the same Val57. Here, 2.26 and 3.0 Å resolution crystal structures of the V57D andV57P mutants of hCC are reported and their dimeric architecture is discussed in terms of the stabilization and destabilization effects of the introduced mutations.

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

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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.

ASN report on nuclear safety and radioprotection status in France in 2010

International Nuclear Information System (INIS)

2011-01-01

After a general overview of the activity of the ASN (the French nuclear safety authority), of its missions and organisation, this activity report indicates the main events of 2010 concerning the actions performed by the ASN and the activities controlled by the ASN. These both aspects are then detailed. The actions performed by the ASN are dealing with nuclear activities (ionizing radiations and risks for health and for the environment), principles and actors of nuclear safety control, radioprotection and environment protection, regulation, control of nuclear activities and exposures to ionizing radiations, emergency situations, public information, international relationship, regional overview of nuclear safety and radioprotection. The activities controlled by the ASN are the medical uses of ionizing radiations, their non medical uses, the transport of radioactive materials, electronuclear plants, installations related to nuclear fuel cycle, nuclear research installations and other nuclear installations, the safety of nuclear installation dismantling, radioactive wastes and polluted sites

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

Review: Kandungan Mannan pada Tanaman Iles-iles (Amorphophallus muelleri Blume.

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SUMARWOTO

2007-05-01

Full Text Available Mannan is a kind of polysaccharide that shaped from mannose and glucose with molar ratio 3:2. Sum of total mannan have a variation rate, influenced by the age, kind of plant, beginning treatment before drying and many other reason. This kind of carbohydrate is important for the plant, it self, and for human, it can be used for many industries. This polysaccharide produced most by a tuber like iles-iles (Amorphophallus muelleri Blume. mannan polymer has a special character which have an attitude between cellulose and galactomannan, so have and ability to crystallize and shaping soft patterns. Besides Amorphophallus, mannan can be found in a small number of another plant, like Ivory nut, and some of Orchidaceae and some in subdivision Gymnosperm. The way to isolate can be in physically and chemically. And the benefits are for the development of many industries, like food, medical, paper, laboratory, etc.

Phosphoenolpyruvate-dependent protein kinase enzyme I of Streptococcus faecalis: purification and properties of the enzyme and characterization of its active center

International Nuclear Information System (INIS)

Alpert, C.A.; Frank, R.; Stueber, K.D.; Deutscher, J.; Hengstenberg, W.

1985-01-01

Enzyme I, the phosphoenolpyruvate:protein phosphotransferase (EC 2.7.3.9), which is part of the bacterial phosphoenolpyruvate-(PEP) dependent phosphotransferase system, has been purified from Streptococcus faecalis by using a large-scale preparation. Size exclusion chromatography revealed a molecular weight of 140,000. On sodium dodecyl sulfate gels, enzyme I gave one band with a molecular weight of 70,000, indicating that enzyme I consists of two identical subunits. The first 59 amino acids of the amino-terminal part of the protein have been sequenced. It showed some similarities with enzyme I of Salmonella typhimurium. The active center of enzyme I has also been determined. After phosphorylation with [ 32 P]PEP, the enzyme was cleaved by using different proteases. Labeled peptides were isolated by high-performance liquid chromatography on a reversed-phase column. The amino acid composition or amino acid sequence of the peptides has been determined. The largest labeled peptide was obtained with Lys-C protease and had the following sequence: -Ala-Phe-Val-Thr-Asp-Ile-Gly- Gly-Arg-Thr-Ser-His*-Ser-Ala-Ile-Met-Ala-Arg-Ser-Leu-Glu-Ile-Pro-Ala- Ile-Val-Gly-Thr-Lys-. It has previously been shown that the phosphoryl group is bound to the N-3 position of a histidyl residue in phosphorylated enzyme I. The single His in position 12 of the above peptide must therefore carry the phosphoryl group

Functional discrimination of membrane proteins using machine learning techniques

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Yabuki Yukimitsu

2008-03-01

Full Text Available Abstract Background Discriminating membrane proteins based on their functions is an important task in genome annotation. In this work, we have analyzed the characteristic features of amino acid residues in membrane proteins that perform major functions, such as channels/pores, electrochemical potential-driven transporters and primary active transporters. Results We observed that the residues Asp, Asn and Tyr are dominant in channels/pores whereas the composition of hydrophobic residues, Phe, Gly, Ile, Leu and Val is high in electrochemical potential-driven transporters. The composition of all the amino acids in primary active transporters lies in between other two classes of proteins. We have utilized different machine learning algorithms, such as, Bayes rule, Logistic function, Neural network, Support vector machine, Decision tree etc. for discriminating these classes of proteins. We observed that most of the algorithms have discriminated them with similar accuracy. The neural network method discriminated the channels/pores, electrochemical potential-driven transporters and active transporters with the 5-fold cross validation accuracy of 64% in a data set of 1718 membrane proteins. The application of amino acid occurrence improved the overall accuracy to 68%. In addition, we have discriminated transporters from other α-helical and β-barrel membrane proteins with the accuracy of 85% using k-nearest neighbor method. The classification of transporters and all other proteins (globular and membrane showed the accuracy of 82%. Conclusion The performance of discrimination with amino acid occurrence is better than that with amino acid composition. We suggest that this method could be effectively used to discriminate transporters from all other globular and membrane proteins, and classify them into channels/pores, electrochemical and active transporters.

NMR structure determination of a synthetic analogue of bacillomycin Lc reveals the strategic role of L-Asn1 in the natural iturinic antibiotics

Science.gov (United States)

Volpon, Laurent; Tsan, Pascale; Majer, Zsuzsa; Vass, Elemer; Hollósi, Miklós; Noguéra, Valérie; Lancelin, Jean-Marc; Besson, Françoise

2007-08-01

Iturins are a group of antifungal produced by Bacillus subtilis. All are cyclic lipopeptides with seven α-amino acids of configuration LDDLLDL and one β-amino fatty acid. The bacillomycin L is a member of this family and its NMR structure was previously resolved using the sequence Asp-Tyr-Asn-Ser-Gln-Ser-Thr. In this work, we carefully examined the NMR spectra of this compound and detected an error in the sequence. In fact, Asp1 and Gln5 need to be changed into Asn1 and Glu5, which therefore makes it identical to bacillomycin Lc. As a consequence, it now appears that all iturinic peptides with antibiotic activity share the common β-amino fatty acid 8- L-Asn1- D-Tyr2- D-Asn3 sequence. To better understand the conformational influence of the acidic residue L-Asp1, present, for example in the inactive iturin C, the NMR structure of the synthetic analogue SCP [cyclo ( L-Asp1- D-Tyr2- D-Asn3- L-Ser4- L-Gln5- D-Ser6- L-Thr7-β-Ala8)] was determined and compared with bacillomycin Lc recalculated with the corrected sequence. In both cases, the conformers obtained were separated into two families of similar energy which essentially differ in the number and type of turns. A detailed analysis of both cyclopeptide structures is presented here. In addition, CD and FTIR spectra were performed and confirmed the conformational differences observed by NMR between both cyclopeptides.

14 CFR 380.14 - Unused space.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Unused space. 380.14 Section 380.14 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS PUBLIC CHARTERS Conditions and Limitations § 380.14 Unused space. Noting contained in this part...

Flexibility of the myosin heavy chain: direct evidence that the region containing SH/sub 1/ and SH/sub 2/ can move 10 /Angstrom/ under the influence of nucleotide binding

Energy Technology Data Exchange (ETDEWEB)

Huston, E.E.; Grammer, J.C.; Yount, R.G.

1988-12-13

Previous experiments demonstrated that two thiols of skeletal myosin subfragment 1 (SF/sub 1/) could be oxidized to a disulfide bond by treatment with a 2-fold excess of 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) in the presence of MgADP. The resulting characteristic changes in the ATPase activities of SF/sub 1/ and the fact that MgADP was stably trapped at the active site, suggested that the two thiols cross-linked were SH/sub 1/ (Cys-707) and SH/sub 2/ (Cys-697) from the myosin heavy chain. To verify this suggestion, SF/sub 1/, after DTNB treatment as above, was treated with an excess of N-ethylmaleimide to block all accessible thiols. The single protein disulfide produced by DTNB oxidation was reduced with dithioerythritol and the modified SF/sub 1/ internally cross-linked with equimolar (/sup 14/C)p-phenylenedimaleimide (pPDM) in the presence of MgADP. After extensive trypsinization, the major /sup 14/C-labeled peptide was isolated, characterized, and shown to be Cys-Asn-Gly-Val-Leu-Gly-Ile-Arg-Ile-Cys-Arg, in which the two cysteines were cross-linked by pPDM. This peptide is known to contain SH/sub 2/ and SH/sub 1/ in this order and to come from residues 697-708 in the rabbit skeletal myosin heavy chain. Parallel experiments with (/sup 14/C)pPDM and unmodified SF/sub 1/ similar to those above gave an identical SH/sub 1/, SH/sub 2/ tryptic peptide, verifying earlier labeling results. These combined results demonstrate that SH/sub 1/ and SH/sub 2/ cross-linked by pPDM (12-13 /Angstrom/, S to S) or by oxidation with DTNB (2 /Angstrom/, S to S) can move a minimum of 10 /Angstrom/ under the influence of nucleotide binding. Because these residues are separated by only nine amino acids in the primary sequence, this small section of the heavy chain must possess extraordinary flexibility.

ASN report on nuclear safety and radiation protection in France in 2006, excerpts

International Nuclear Information System (INIS)

Lacoste, A.C.

2007-01-01

The main topics for the Nuclear Safety Authority (ASN) in 2006 were the following ones. 1) the 2006-686 bill on transparency and security in the nuclear field. This law constitutes an overhaul of the legislative framework applicable to nuclear activities. It creates the Nuclear Safety Authority as an independent administrative authority and defines its tasks. It contains significant advances in terms of transparency. 2) The 2006-739 bill concerning sustainable management of radioactive materials and waste. This law clearly states that the disposal in deep geological formations is the reference solution for high-level, long-lived radioactive wastes. 3) The EPR reactor project safety in which ASN completed technical examination of the preliminary safety case. In November 2006, ASN produced to French Authorities a draft decree concerning the EPR project on the Flamanville site. 4) An international audit of ASN was performed in 2006 by IAEA in order to assess the extent to which the standards IAEA recommends are taken into account and implemented. 5) ASN has contributed to the harmonization of nuclear safety in Europe and at world scale through its contribution to the work of the WENRA association. 6) In 2005 and 2006 4 serious radiotherapy accidents were reported in France. Cancer radiotherapy is a fully justified practice that demands a vigilant supervision of ASN. 7) ASN has amplified its means for informing the public about nuclear safety and radiation protection. And 8) ASN considers that people and organizations are fundamental factors in safety and radiation protection and that significant progress is still to be made in taking into account these factors in nuclear activities. (A.C.)

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.

Prediction of beta-turns at over 80% accuracy based on an ensemble of predicted secondary structures and multiple alignments.

Science.gov (United States)

Zheng, Ce; Kurgan, Lukasz

2008-10-10

beta-turn is a secondary protein structure type that plays significant role in protein folding, stability, and molecular recognition. To date, several methods for prediction of beta-turns from protein sequences were developed, but they are characterized by relatively poor prediction quality. The novelty of the proposed sequence-based beta-turn predictor stems from the usage of a window based information extracted from four predicted three-state secondary structures, which together with a selected set of position specific scoring matrix (PSSM) values serve as an input to the support vector machine (SVM) predictor. We show that (1) all four predicted secondary structures are useful; (2) the most useful information extracted from the predicted secondary structure includes the structure of the predicted residue, secondary structure content in a window around the predicted residue, and features that indicate whether the predicted residue is inside a secondary structure segment; (3) the PSSM values of Asn, Asp, Gly, Ile, Leu, Met, Pro, and Val were among the top ranked features, which corroborates with recent studies. The Asn, Asp, Gly, and Pro indicate potential beta-turns, while the remaining four amino acids are useful to predict non-beta-turns. Empirical evaluation using three nonredundant datasets shows favorable Q total, Q predicted and MCC values when compared with over a dozen of modern competing methods. Our method is the first to break the 80% Q total barrier and achieves Q total = 80.9%, MCC = 0.47, and Q predicted higher by over 6% when compared with the second best method. We use feature selection to reduce the dimensionality of the feature vector used as the input for the proposed prediction method. The applied feature set is smaller by 86, 62 and 37% when compared with the second and two third-best (with respect to MCC) competing methods, respectively. Experiments show that the proposed method constitutes an improvement over the competing prediction

Prediction of beta-turns at over 80% accuracy based on an ensemble of predicted secondary structures and multiple alignments

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Kurgan Lukasz

2008-10-01

Full Text Available Abstract Background β-turn is a secondary protein structure type that plays significant role in protein folding, stability, and molecular recognition. To date, several methods for prediction of β-turns from protein sequences were developed, but they are characterized by relatively poor prediction quality. The novelty of the proposed sequence-based β-turn predictor stems from the usage of a window based information extracted from four predicted three-state secondary structures, which together with a selected set of position specific scoring matrix (PSSM values serve as an input to the support vector machine (SVM predictor. Results We show that (1 all four predicted secondary structures are useful; (2 the most useful information extracted from the predicted secondary structure includes the structure of the predicted residue, secondary structure content in a window around the predicted residue, and features that indicate whether the predicted residue is inside a secondary structure segment; (3 the PSSM values of Asn, Asp, Gly, Ile, Leu, Met, Pro, and Val were among the top ranked features, which corroborates with recent studies. The Asn, Asp, Gly, and Pro indicate potential β-turns, while the remaining four amino acids are useful to predict non-β-turns. Empirical evaluation using three nonredundant datasets shows favorable Qtotal, Qpredicted and MCC values when compared with over a dozen of modern competing methods. Our method is the first to break the 80% Qtotal barrier and achieves Qtotal = 80.9%, MCC = 0.47, and Qpredicted higher by over 6% when compared with the second best method. We use feature selection to reduce the dimensionality of the feature vector used as the input for the proposed prediction method. The applied feature set is smaller by 86, 62 and 37% when compared with the second and two third-best (with respect to MCC competing methods, respectively. Conclusion Experiments show that the proposed method constitutes an

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

Assessment of MC1R and α-MSH gene sequences in Iranian vitiligo patients

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Eskandani M

2010-01-01

Full Text Available Background: Vitiligo is an acquired pigmentary disorder of the skin that is caused by unknown factors and is characterized by white and depigmented patches that enlarge and become more numerous with time. Genetic factors, oxidative stress, autoimmunity, and neurochemical agents, such as catecholamines might also contribute to vitiligo. Cutaneous pigmentation is determined by the amounts of eumelanin and pheomelanin synthesized by the epidermal melanocytes and interference of melanocortin-1 receptor (MC1R, a G-protein coupled receptor, its normal agonist, alpha-melanocyte stimulating hormone (α-MSH, and key enzymes, such as tyrosinase, to protect against sun-induced DNA damage. The MC1R, a 7 pass trans-membrane G-protein coupled receptor, is a key control point in melanogenesis. Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to pheomelanin production, resulting in a red or yellow coat color. Aim: In this research, we aim to examine the genetic variety of MC1R and α-MSH gene in 20 Iranian vitiligo patients and 20 healthy controls. Materials and Methods: Analysis of the MC1R coding gene was performed with direct sequencing. Results: We found the following 9 MC1R coding region variants: Arg163Gl (G488A, Arg227Leu (G680A, Val 97Phe (G289T, Asp184Asn (G550A, Arg227Lys (G680A, Arg142His (G425A, Val60Leu (G178T, Val247Met (C739A, and Val174Ile (G520A. We also found 2 frameshift changes: one of them was the Insertion of C (frameshift in Pro136, stop at Trp148 and the other, Insertion of G (frameshift in Pro256, stop at Trp 333. Of all the changes, the most common was Val60Leu at 5% in patients vs 20% in controls, Val247Met at 15% in patients vs 0% in controls and Val174Ile at 15% in controls and 0% in patients. The other variants showed a frequency <5% in both patients and controls. Also in this study, we have examined the frequency of single nucleotide polymorphisms within the α-MSH genes with direct sequencing in

Süt Proteinlerinin RP-HPLC ile Saptanması (İngilizce

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Zerrin Yüksel

2015-02-01

Full Text Available Bu çalışmada, κ-, α- and β-kazein ile α-laktalbumin and β-laktoglobulin, bir RP kolonunun kullanıldığı HPLC-UV ile basit ve hızlı bir yöntem geliştirilerek saptanmıştır. Gradient elüsyonu, 1 ml/dk akış hızında ve 25 oC sıcaklıkta iki çözücü karışımı kullanılarak yürütülmüştür. A çözücüsü asetonitril: su:trifloroasetik asit (100:900:1 ve B çözücüsü asetonitril: su: trifloroasetik asit (100:900:1 karışımlarından oluşmaktadır. Akış, bir UV dedektörü kullanılarak 220 nm’de kaydedilmiştir. Farklı yöntemler kullanılarak RP-HPLC analizi için hazırlanan örneklerde, süt proteinlerine ait farklı kromatografik profiller elde edilmiştir. Diğer örnek hazırlama yöntemlerine kıyasla, enjeksiyondan önce belirtilen oranlarda A ve B çözücülerinin kullanıldığı örnek hazırlama yöntemi ile separasyonun daha keskin ve efektif olduğu ortaya konulmuştur. Bu çalışmada ortaya konulan örnek hazırlama tekniği ve elusyon pratiği ile, süt proteinlerinin analizi basit, hızlı ve duyarlı bir şekilde gerçekleştirilmiştir.

Enhancing the intestinal absorption of molecules containing the polar guanidino functionality: a double-targeted prodrug approach.

Science.gov (United States)

Sun, Jing; Dahan, Arik; Amidon, Gordon L

2010-01-28

A prodrug strategy was applied to guanidino-containing analogues to increase oral absorption via hPEPT1 and hVACVase. l-Valine, l-isoleucine, and l-phenylalanine esters of [3-(hydroxymethyl)phenyl]guanidine (3-HPG) were synthesized and evaluated for transport and activation. In HeLa/hPEPT1 cells, Val-3-HPG and Ile-3-HPG exhibited high affinity to hPEPT1 (IC(50): 0.65 and 0.63 mM, respectively), and all three l-amino acid esters showed higher uptake (2.6- to 9-fold) than the parent compound 3-HPG. Val-3-HPG and Ile-3-HPG demonstrated remarkable Caco-2 permeability enhancement, and Val-3-HPG exhibited comparable permeability to valacyclovir. In rat perfusion studies, Val-3-HPG and Ile-3-HPG permeabilities were significantly higher than 3-HPG and exceeded/matched the high-permeability standard metoprolol, respectively. All the l-amino acid 3-HPG esters were effectively activated in HeLa and Caco-2 cell homogenates and were found to be good substrates of hVACVase (k(cat)/K(m) in mM(-1) x s(-1): Val-3-HPG, 3370; Ile-3-HPG, 1580; Phe-3-HPG, 1660). In conclusion, a prodrug strategy is effective at increasing the intestinal permeability of polar guanidino analogues via targeting hPEPT1 for transport and hVACVase for activation.

An integrated palaeoenvironmental investigation of a 6200 year old peat sequence from Ile de la Possession, Iles Crozet, sub-Antarctica

NARCIS (Netherlands)

Van der Putten, N.; Hébrard, J. P.; Verbruggen, C.; Van de Vijver, B.; Disnar, J. R.; Spassov, S.; de Beaulieu, J. L.; De Dapper, M.; Keravis, D.; Hus, J.; Thouveny, N.; Frenot, Y.

2008-01-01

A 6200 year old peat sequence, cored in a volcanic crater on the sub-Antarctic Ile de la Possession (Iles Crozet), has been investigated, based on a multi-proxy approach. The methods applied are macrobotanical (mosses, seeds and fruits) and diatom analyses, complemented by geochemical (Rock-Eval6)

Ser95, Asn97, and Thr78 are important for the catalytic function of porcine NADP-dependent isocitrate dehydrogenase

OpenAIRE

Kim, Tae-Kang; Colman, Roberta F.

2005-01-01

The mammalian mitochondrial NADP-dependent isocitrate dehydrogenase is a citric acid cycle enzyme and an important contributor to cellular defense against oxidative stress. The Mn2+-isocitrate complex of the porcine enzyme was recently crystallized; its structure indicates that Ser95, Asn97, and Thr78 are within hydrogen-bonding distance of the γ-carboxylate of enzyme-bound isocitrate. We used site-directed mutagenesis to replace each of these residues by Ala and Asp. The wild-type and mutant...

Primary structure of pancreatic polypeptide from four species of Perissodactyla (Przewalski's horse, zebra, rhino, tapir).

Science.gov (United States)

Henry, J S; Lance, V A; Conlon, J M

1991-12-01

Pancreatic polypeptide (PP) has been purified from extracts of the pancreas of four species of odd-toed ungulates (Perissodactyla): Przewalski's horse, mountain zebra, white rhinoceros, and mountain tapir. The amino acid sequence of Przewalski's horse pancreatic polypeptide was established as Ala-Pro-Met-Glu-Pro-Val-Tyr-Pro-Gly-Asp10-Asn- Ala-Thr-Pro-Glu-Gln-Met-Ala-Gln-Tyr20-Ala-Ala-Glu-Leu-Arg-Arg-Tyr- Ile-Asn-Met30 - Leu-Thr-Arg-Pro-Arg-Tyr.NH2. Zebra PP was identical to Przewalski's horse PP, rhinoceros PP contained three substitutions relative to the horse (Ser for Ala1, Leu for Met3, and Glu for Gln16), and tapir PP contained one substitution relative to the horse (Leu for Met3). On the basis of morphological characteristics and the fossil record, the rhinocerotids are classified with the tapirids in the suborder Ceratomorpha, whereas the horse and zebra belong to a separate suborder, Hippomorpha. On the basis of structural similarity of the PP molecules, however, it would appear that the tapir is more closely related to the horse than to the rhinoceros. These observations provide a further example of the need for extreme caution when inferring taxonomic or phylogenetic relationships between species from the structures of homologous peptides.

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...

Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor

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Guodong Hu

2016-05-01

Full Text Available Drug resistance of mutations in HIV-1 protease (PR is the most severe challenge to the long-term efficacy of HIV-1 PR inhibitor in highly active antiretroviral therapy. To elucidate the molecular mechanism of drug resistance associated with mutations (D30N, I50V, I54M, and V82A and inhibitor (GRL-0519 complexes, we have performed five molecular dynamics (MD simulations and calculated the binding free energies using the molecular mechanics Poisson–Boltzmann surface area (MM-PBSA method. The ranking of calculated binding free energies is in accordance with the experimental data. The free energy spectra of each residue and inhibitor interaction for all complexes show a similar binding model. Analysis based on the MD trajectories and contribution of each residues show that groups R2 and R3 mainly contribute van der Waals energies, while groups R1 and R4 contribute electrostatic interaction by hydrogen bonds. The drug resistance of D30N can be attributed to the decline in binding affinity of residues 28 and 29. The size of Val50 is smaller than Ile50 causes the residue to move, especially in chain A. The stable hydrophobic core, including the side chain of Ile54 in the wild type (WT complex, became unstable in I54M because the side chain of Met54 is flexible with two alternative conformations. The binding affinity of Ala82 in V82A decreases relative to Val82 in WT. The present study could provide important guidance for the design of a potent new drug resisting the mutation inhibitors.

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.

Prion protein gene analysis in three kindreds with fatal familial insomnia (FFI): Codon 178 mutation and codon 129 polymorphism

Energy Technology Data Exchange (ETDEWEB)

Medori, R.; Tritschler, H.J. (Universita di Bologna (Italy))

1993-10-01

Fatal familial insomnia (FFI) is a disease linked to a GAC(Asp) [yields] AAC(Asn) mutation in codon 178 of the prion protein (PrP) gene. FFI is characterized clinically by untreatable progressive insomnia, dysautonomia, and motor dysfunctions and is characterized pathologically by selective thalamic atrophy. The authors confirmed the 178[sup Asn] mutation in the PrP gene of a third FFI family of French ancestry. Three family members who are under 40 years of age and who inherited the mutation showed only reduced perfusion in the basal ganglia on single photon emission computerized tomography. Some FFI features differ from the clinical and neuropathologic findings associated with 178[sup Asn] reported elsewhere. However, additional intragenic mutations accounting for the phenotypic differences were not observed in two affected individuals. In other sporadic and familial forms of Creutzfeldt-Jakob disease and Gerstmann-Straeussler syndrome, Met or Val homozygosity at polymorphic codon 129 is associated with a more severe phenotype, younger age at onset, and faster progression. In FFI, young and old individuals at disease onset had 129[sup Met/Val]. Moreover, of five 178[sup Asn] individuals who are above age-at-onset range and who are well, two have 129[sup Met] and three have 129[sup Met/Val], suggesting that polymorphic site 129 does not modulate FFI phenotypic expression. Genetic heterogeneity and environment may play an important role in inter- and intrafamilial variability of the 178[sup Asn] mutation. 32 refs., 5 figs., 1 tab.

Statistical Characterization of the Charge State and Residue Dependence of Low-Energy CID Peptide Dissociation Patterns

International Nuclear Information System (INIS)

Huang, Yingying; Triscari, Joseph M.; Tseng, George C.; Pasa-Tolic, Ljiljana; Lipton, Mary S.; Smith, Richard D.; Wysocki, Vicki H.

2005-01-01

Data mining was performed on 28 330 unique peptide tandem mass spectra for which sequences were assigned with high confidence. By dividing the spectra into different sets based on structural features and charge states of the corresponding peptides, chemical interactions involved in promoting specific cleavage patterns in gas-phase peptides were characterized. Pairwise fragmentation maps describing cleavages at all Xxx-Zzz residue combinations for b and y ions reveal that the difference in basicity between Arg and Lys results in different dissociation patterns for singly charged Arg- and Lys-ending tryptic peptides. While one dominant protonation form (proton localized) exists for Arg-ending peptides, a heterogeneous population of different protonated forms or more facile interconversion of protonated forms (proton partially mobile) exists for Lys-ending peptides. Cleavage C-terminal to acidic residues dominates spectra from peptides that have a localized proton and cleavage N-terminal to Pro dominates those that have a mobile or partially mobile proton. When Pro is absent from peptides that have a mobile or partially mobile proton, cleavage at each peptide bond becomes much more prominent. Whether the above patterns can be found in b ions, y ions, or both depends on the location of the proton holder(s). Enhanced cleavages C-terminal to branched aliphatic residues (Ile, Val, Leu) are observed in both b and y ions from peptides that have a mobile proton, as well as in y ions from peptides that have a partially mobile proton; enhanced cleavages N-terminal to these residues are observed in b ions from peptides that have a partially mobile proton. Statistical tools have been designed to visualize the fragmentation maps and measure the similarity between them. The pairwise cleavage patterns observed expand our knowledge of peptide gas-phase fragmentation behaviors and should be useful in algorithm development that employs improved models to predict fragment ion

Weight reductions for the airbus A380; postbuckling of the A380 VTP skin panels

NARCIS (Netherlands)

Kroese, R.

2014-01-01

The skin panels of the Vertical Tail Plane (VTP) are the largest single piece composite components assembled on the Airbus A380. By allowing postbuckling to these skin panels might result in severe weight reductions for the VTP of the A380. The goal of the study is to give an indication of possible

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

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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.

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

Human Islet Amyloid Polypeptide Fibril Binding to Catalase: A Transmission Electron Microscopy and Microplate Study

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Nathaniel G. N. Milton

2010-01-01

Full Text Available The diabetes-associated human islet amyloid polypeptide (IAPP is a 37-amino-acid peptide that forms fibrils in vitro and in vivo. Human IAPP fibrils are toxic in a similar manner to Alzheimer's amyloid-β (Aβ and prion protein (PrP fibrils. Previous studies have shown that catalase binds to Aβ fibrils and appears to recognize a region containing the Gly-Ala-Ile-Ile sequence that is similar to the Gly-Ala-Ile-Leu sequence found in human IAPP residues 24-27. This study presents a transmission electron microscopy (TEM—based analysis of fibril formation and the binding of human erythrocyte catalase to IAPP fibrils. The results show that human IAPP 1-37, 8-37, and 20-29 peptides form fibrils with diverse and polymorphic structures. All three forms of IAPP bound catalase, and complexes of IAPP 1-37 or 8-37 with catalase were identified by immunoassay. The binding of biotinylated IAPP to catalase was high affinity with a KD of 0.77nM, and could be inhibited by either human or rat IAPP 1-37 and 8-37 forms. Fibrils formed by the PrP 118-135 peptide with a Gly-Ala-Val-Val sequence also bound catalase. These results suggest that catalase recognizes a Gly-Ala-Ile-Leu—like sequence in amyloid fibril-forming peptides. For IAPP 1-37 and 8-37, the catalase binding was primarily directed towards fibrillar rather than ribbon-like structures, suggesting differences in the accessibility of the human IAPP 24-27 Gly-Ala-Ile-Leu region. This suggests that catalase may be able to discriminate between different structural forms of IAPP fibrils. The ability of catalase to bind IAPP, Aβ, and PrP fibrils demonstrates the presence of similar accessible structural motifs that may be targets for antiamyloid therapeutic development.

34 CFR 380.9 - What definitions apply?

Science.gov (United States)

2010-07-01

... compensated at or above the minimum wage, but not less than the customary or usual wage paid by the employer... 34 Education 2 2010-07-01 2010-07-01 false What definitions apply? 380.9 Section 380.9 Education... General § 380.9 What definitions apply? (a) The following term used in this part is defined in 34 CFR part...

Protection of hydrophobic amino acids against moisture-induced deterioration in the aerosolization performance of highly hygroscopic spray-dried powders.

Science.gov (United States)

Yu, Jiaqi; Chan, Hak-Kim; Gengenbach, Thomas; Denman, John A

2017-10-01

Inhalable particles containing amorphous form of drugs or excipients may absorb atmospheric moisture, causing powder aggregation and recrystallization, adversely affecting powder dispersion and lung deposition. The present study aims to explore hydrophobic amino acids for protection against moisture in spray-dried amorphous powders, using disodium cromoglycate (DSCG) as a model drug. DSCG powders were produced by co-spray drying with isoleucine (Ile), valine (Val) and methionine (Met) in various concentrations (10, 20 and 40%w/w). Particle size distribution and morphology were measured by laser diffraction and scanning electron microscopy (SEM). Physiochemical properties of the powders were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and dynamic vapor sorption (DVS). Particle surface chemistry was analyzed by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In vitro aerosolization performance was evaluated by a next generation impactor (NGI) after the powders were stored at 60% or 75% relative humidity (RH) for one month and three months. Ile, Val and Met significantly reduced the deleterious effect of moisture on aerosol performance, depending on the amount of amino acids in the formulation. Formulations containing 10% or 20% of Ile, Val and Met showed notable deterioration in aerosol performance, with fine particle fraction (FPF) reduced by 6-15% after one-month storage at both 60% and 75% RH. However, 40% Ile was able to maintain the aerosol performance of DSCG stored at 75% RH for one month, while the FPF dropped by 7.5% after three months of storage. In contrast, 40% Val or Met were able to maintain the aerosol performance at 60% RH storage but not at 75% RH. At 40%w/w ratio, these formulations had particle surface coverage of 94.5% (molar percent) of Ile, 87.1% of Val and 84.6% of Met, respectively, which may explain their

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

Functional Characterization of Rare RAB12 Variants and Their Role in Musician’s and Other Dystonias

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Eva Hebert

2017-10-01

Full Text Available Mutations in RAB (member of the Ras superfamily genes are increasingly recognized as cause of a variety of disorders including neurological conditions. While musician’s dystonia (MD and writer’s dystonia (WD are task-specific movement disorders, other dystonias persistently affect postures as in cervical dystonia. Little is known about the underlying etiology. Next-generation sequencing revealed a rare missense variant (c.586A>G; p.Ile196Val in RAB12 in two of three MD/WD families. Next, we tested 916 additional dystonia patients; 512 Parkinson’s disease patients; and 461 healthy controls for RAB12 variants and identified 10 additional carriers of rare missense changes among dystonia patients (1.1% but only one carrier in non-dystonic individuals (0.1%; p = 0.005. The detected variants among index patients comprised p.Ile196Val (n = 6; p.Ala174Thr (n = 3; p.Gly13Asp; p.Ala148Thr; and p.Arg181Gln in patients with MD; cervical dystonia; or WD. Two relatives of MD patients with WD also carried p.Ile196Val. The two variants identified in MD patients (p.Ile196Val; p.Gly13Asp were characterized on endogenous levels in patient-derived fibroblasts and in two RAB12-overexpressing cell models. The ability to hydrolyze guanosine triphosphate (GTP, so called GTPase activity, was increased in mutants compared to wildtype. Furthermore, subcellular distribution of RAB12 in mutants was altered in fibroblasts. Soluble Transferrin receptor 1 levels were reduced in the blood of all three tested p.Ile196Val carriers. In conclusion, we demonstrate an enrichment of missense changes among dystonia patients. Functional characterization revealed altered enzyme activity and lysosomal distribution in mutants suggesting a contribution of RAB12 variants to MD and other dystonias.

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...

External PCR, ASN's decision

International Nuclear Information System (INIS)

Anon.

2012-01-01

The French law imposes in some situations the presence of a person skilled in radiation protection (PCR). This article describes the cases when this person must belong to the staff of the enterprise or when this person may be sub-contracted. For instance in most nuclear facilities the PCR must be on the payroll, for enterprises dedicated to nuclear transport the PCR's job can be sub-contracted. A decision given by the ASN (French Nuclear Safety Authority) sets the minimal requests (in terms of training, job contract, activities) of the sub-contracted PCR. (A.C.)

Ectoparasites and endoparasites of peridomestic house-rats in ile-ife, Nigeria and implication on human health.

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Titus Ogunniyi

2014-03-01

Full Text Available There has never been a single case report of any parasitic zoonosis in Ile-Ife while just a case of human Acanthocephalan infection in Nigeria is available.Fifty (house-rats Rattus rattus (Linnaeus, 1758 were caught in houses and raw food sellers' stalls in a market in Ile-Ife. A caught rat was removed from the cage and sacrificed by cervical jerking. A rat was weighed, measured, quickly following which thick and thin blood films on microscope slides were made from blood collected from the tail vein. The rat was examined for ectoparasites then dissected to check for endoparasites.Two ectoparasites (Xenopsylla cheopis and Laelaptid mite were recovered from 19 (38.0% of the rats. Five genera of helminthes (Moniliformis, Hymenolepis, Taenia, Trichuris and Trichinella were recovered from 29 (58.0% of the rats while seven genera of protozoa organisms (Amoeba, Dientamoeba, Entamoeba, Retortamonas, Trichomonas, Chilomastix and Trypanosoma were recovered from 48 (96.0% of them. There was no correlation (Spearman's correlation coefficient = -0.111 between the weight of the individual rat and the total number of alimentary canal acquired parasites.In relation to human health, implications of the rats serving as reservoir hosts for the different pathogens are highlighted. In view of the possibility of unexpected zoonosis arising from the parasites found in the peridomestic rats in this investigation and others not found, and in view of the difficulties that may be associated with diagnosing such ailment, especially by a clinician who trained locally, this report should be like raising awareness to these salient facts.

Squeeze casting of aluminum alloy A380: Microstructure and tensile behavior

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Li Fang

2015-09-01

Full Text Available A380 alloy with a relatively thick cross-section of 25 mm was squeeze cast using a hydraulic press with an applied pressure of 90 MPa. Microstructure and tensile properties of the squeeze cast A380 were characterized and evaluated in comparison with the die cast counterpart. Results show that the squeeze cast A380 possesses a porosity level much lower than the die cast alloy, which is disclosed by both optical microscopy and the density measurement technique. The results of tensile testing indicate the improved tensile properties, specifically ultimate tensile strength (UTS: 215.9 MPa and elongation (Ef: 5.4%, for the squeeze cast samples over those of the conventional high-pressure die cast part (UTS: 173.7 MPa, Ef: 1.0%. The analysis of tensile behavior shows that the squeeze cast A380 exhibits a high tensile toughness (8.5 MJ·m-3 and resilience (179.3 kJ·m-3 compared with the die cast alloy (toughness: 1.4 MJ·m-3, resilience: 140.6 kJ·m-3, despite that, during the onset of plastic deformation, the strain-hardening rate of the die cast specimen is higher than that of the squeeze cast specimens. The microstructure analyzed by the scanning electron microscopy (SEM shows that both the squeeze and die cast specimens contain the primary α-Al, Al2Cu, Al5FeSi phase and the eutectic Si phase. But, the Al2Cu phase present in the squeeze cast alloy is relatively large in size and quantity. The SEM fractography evidently reveals the ductile fracture features of the squeeze cast A380 alloy.

The core of Ure2p prion fibrils is formed by the N-terminal segment in a parallel cross-β structure: evidence from solid-state NMR.

Science.gov (United States)

Kryndushkin, Dmitry S; Wickner, Reed B; Tycko, Robert

2011-06-03

Intracellular fibril formation by Ure2p produces the non-Mendelian genetic element [URE3] in Saccharomyces cerevisiae, making Ure2p a prion protein. We show that solid-state NMR spectra of full-length Ure2p fibrils, seeded with infectious prions from a specific [URE3] strain and labeled with uniformly (15)N-(13)C-enriched Ile, include strong, sharp signals from Ile residues in the globular C-terminal domain (CTD) with both helical and nonhelical (13)C chemical shifts. Treatment with proteinase K eliminates these CTD signals, leaving only nonhelical signals from the Gln-rich and Asn-rich N-terminal segment, which are also observed in the solid-state NMR spectra of Ile-labeled fibrils formed by residues 1-89 of Ure2p. Thus, the N-terminal segment, or "prion domain" (PD), forms the fibril core, while CTD units are located outside the core. We additionally show that, after proteinase K treatment, Ile-labeled Ure2p fibrils formed without prion seeding exhibit a broader set of solid-state NMR signals than do prion-seeded fibrils, consistent with the idea that structural variations within the PD core account for prion strains. Measurements of (13)C-(13)C magnetic dipole-dipole couplings among (13)C-labeled Ile carbonyl sites in full-length Ure2p fibrils support an in-register parallel β-sheet structure for the PD core of Ure2p fibrils. Finally, we show that a model in which CTD units are attached rigidly to the parallel β-sheet core is consistent with steric constraints. Published by Elsevier Ltd.

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

Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?

Science.gov (United States)

Procopio, V; Manti, S; Bianco, G; Conti, G; Romeo, A; Maimone, F; Arrigo, T; Cutrupi, M C; Salpietro, C; Cuppari, C

2018-01-30

Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype-phenotype correlation of FMF disease. To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model. A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3. 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met680Ile/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680Ile/wt genotype reported the most severe clinical phenotype. p.Ala744Ser/wt, p.Glu148Gln/Met680Ile, p.Met680Ile/Met680Ile, p.Met680Ile/Met694Val, p.Pro369Ser/wt, p.Met694Ile/wt, p.Glu148Gln/Glu148Gln, p.Lys695Arg/wt resulted in 100% pathogenicity. The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Cyclodipeptides from metagenomic library of a japanese marine sponge

Energy Technology Data Exchange (ETDEWEB)

He, Rui; Wang, Bochu; Zhub, Liancai, E-mail: wangbc2000@126.com [Bioengineering College, Chongqing University, Chongqing, (China); Wang, Manyuan [School of Traditional Chinese Medicine, Capital University of Medical Sciences, Beijing (China); Wakimoto, Toshiyuki; Abe, Ikuro, E-mail: abei@mol.f.u-tokyo.ac.jp [Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo (Japan)

2013-12-01

Culture-independent metagenomics is an attractive and promising approach to explore unique bioactive small molecules from marine sponges harboring uncultured symbiotic microbes. Therefore, we conducted functional screening of the metagenomic library constructed from the Japanese marine sponge Discodermia calyx. Bioassay-guided fractionation of plate culture extract of antibacterial clone pDC113 afforded eleven cyclodipeptides: Cyclo(l-Thr-l-Leu) (1), Cyclo(l-Val-d-Pro) (2), Cyclo(l-Ile-d-Pro) (3), Cyclo(l-Leu-l-Pro) (4), Cyclo(l-Val-l-Leu) (5), Cyclo(l-Leu-l-Ile) (6), Cyclo(l-Leu-l-Leu) (7), Cyclo(l-Phe-l-Tyr) (8), Cyclo(l-Trp-l-Pro) (9), Cyclo(l-Val-l-Trp) (10) and Cyclo(l-Ile-l-Trp) (11). To the best of our knowledge, these are first cyclodepeptides isolated from metagenomic library. Sequence analysis suggested that isolated cyclodipeptides were not synthesized by nonribosomal peptide synthetases and there was no significant indication of cyclodipeptide synthetases. (author)

Cyclodipeptides from metagenomic library of a japanese marine sponge

International Nuclear Information System (INIS)

He, Rui; Wang, Bochu; Zhub, Liancai; Wang, Manyuan; Wakimoto, Toshiyuki; Abe, Ikuro

2013-01-01

Culture-independent metagenomics is an attractive and promising approach to explore unique bioactive small molecules from marine sponges harboring uncultured symbiotic microbes. Therefore, we conducted functional screening of the metagenomic library constructed from the Japanese marine sponge Discodermia calyx. Bioassay-guided fractionation of plate culture extract of antibacterial clone pDC113 afforded eleven cyclodipeptides: Cyclo(l-Thr-l-Leu) (1), Cyclo(l-Val-d-Pro) (2), Cyclo(l-Ile-d-Pro) (3), Cyclo(l-Leu-l-Pro) (4), Cyclo(l-Val-l-Leu) (5), Cyclo(l-Leu-l-Ile) (6), Cyclo(l-Leu-l-Leu) (7), Cyclo(l-Phe-l-Tyr) (8), Cyclo(l-Trp-l-Pro) (9), Cyclo(l-Val-l-Trp) (10) and Cyclo(l-Ile-l-Trp) (11). To the best of our knowledge, these are first cyclodepeptides isolated from metagenomic library. Sequence analysis suggested that isolated cyclodipeptides were not synthesized by nonribosomal peptide synthetases and there was no significant indication of cyclodipeptide synthetases. (author)

Polymorphisms of cytochrome P450 1A1, glutathione s-transferases M1 and T1 genes in ouangolodougou (Northern Ivory Coast

Directory of Open Access Journals (Sweden)

Alfredo Santovito

2010-01-01

Full Text Available In this study, the frequencies of CYP1A1, GSTM1, and GSTT1 gene polymorphisms were determined in 133 healthy individuals from Ouangolodougou, a small rural town situated in the north of the Ivory Coast. As appeared in several published studies, ethnic differences in these frequencies have been found to play an important role in the metabolism of a relevant number of human carcinogens. In the studied sample, the frequencies of Ile/Ile (wild type, Ile/Val (heterozygous variant, and Val/Val (homozygous variant CYP1A1 genotypes were 0.271, 0.692, and 0.037, respectively. Frequencies of GSTM1 and GSTT1 null genotypes were 0.361 and 0.331, respectively. No significant differences were noted between men and women. In contrast to published data for Africans, CYP1A1 *Val Allele frequency (0.383 was significantly high (p < 0.001 in this specific population. For the GSTT1 null genotype, no differences were found between the studied and other African populations, the contrary to what occurred for the GSTM1 null genotype in relation to Gambia and Egypt.

Genetic Variation in GSTP1, Lung Function, Risk of Lung Cancer, and Mortality

DEFF Research Database (Denmark)

Nørskov, Marianne S.; Dahl, Morten; Tybjærg-Hansen, Anne

2017-01-01

66,069 individuals from the white general population for two common functional variants in the glutathione S-transferase pi 1 gene (GSTP1)—amino acid isoleucine 105 changed to a valine (Ile105Val) and amino acid alanine 114 changed to a valine (Ala114Val)—and recorded lung function, lung cancer......Introduction Glutathione S-transferase pi 1 metabolizes carcinogens from tobacco smoke in the lung. We tested whether genetically altered glutathione S-transferase pi 1 activity affects lung function and risk for tobacco-related cancer and mortality in the general population. Methods We genotyped......, tobacco-related cancer, and death as outcomes. Results Lung function was increased stepwise with the Ile105Val genotype overall (p

A Common Structural Component for β-Subunit Mediated Modulation of Slow Inactivation in Different KV Channels

DEFF Research Database (Denmark)

Strutz-Seebohm, Nathalie; Henrion, Ulrike; Schmitt, Nicole

2013-01-01

Background/Aims: Potassium channels are tetrameric proteins providing potassium selective passage through lipid embedded proteinaceous pores with highest fidelity. The selectivity results from binding to discrete potassium binding sites and stabilization of a hydrated potassium ion in a central...... internal cavity. The four potassium binding sites, generated by the conserved TTxGYGD signature sequence are formed by the backbone carbonyls of the amino acids TXGYG. Residues KV1.5-Val481, KV4.3-Leu368 and KV7.1- Ile 313 represent the amino acids in the X position of the respective channels. Methods...

Cal/Val activities for DubaiSat-2 performance assessment

Science.gov (United States)

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.

A Quantitative Tool to Distinguish Isobaric Leucine and Isoleucine Residues for Mass Spectrometry-Based De Novo Monoclonal Antibody Sequencing

Science.gov (United States)

Poston, Chloe N.; Higgs, Richard E.; You, Jinsam; Gelfanova, Valentina; Hale, John E.; Knierman, Michael D.; Siegel, Robert; Gutierrez, Jesus A.

2014-07-01

De novo sequencing by mass spectrometry (MS) allows for the determination of the complete amino acid (AA) sequence of a given protein based on the mass difference of detected ions from MS/MS fragmentation spectra. The technique relies on obtaining specific masses that can be attributed to characteristic theoretical masses of AAs. A major limitation of de novo sequencing by MS is the inability to distinguish between the isobaric residues leucine (Leu) and isoleucine (Ile). Incorrect identification of Ile as Leu or vice versa often results in loss of activity in recombinant antibodies. This functional ambiguity is commonly resolved with costly and time-consuming AA mutation and peptide sequencing experiments. Here, we describe a set of orthogonal biochemical protocols, which experimentally determine the identity of Ile or Leu residues in monoclonal antibodies (mAb) based on the selectivity that leucine aminopeptidase shows for n-terminal Leu residues and the cleavage preference for Leu by chymotrypsin. The resulting observations are combined with germline frequencies and incorporated into a logistic regression model, called Predictor for Xle Sites (PXleS) to provide a statistical likelihood for the identity of Leu at an ambiguous site. We demonstrate that PXleS can generate a probability for an Xle site in mAbs with 96% accuracy. The implementation of PXleS precludes the expression of several possible sequences and, therefore, reduces the overall time and resources required to go from spectra generation to a biologically active sequence for a mAb when an Ile or Leu residue is in question.

Substrate recognition and catalysis by GH47 α-mannosidases involved in Asn-linked glycan maturation in the mammalian secretory pathway

Energy Technology Data Exchange (ETDEWEB)

Xiang, Yong; Karaveg, Khanita; Moremen, Kelley W.

2016-11-17

Asn-linked glycosylation of newly synthesized polypeptides occurs in the endoplasmic reticulum of eukaryotic cells. Glycan structures are trimmed and remodeled as they transit the secretory pathway, and processing intermediates play various roles as ligands for folding chaperones and signals for quality control and intracellular transport. Key steps for the generation of these trimmed intermediates are catalyzed by glycoside hydrolase family 47 (GH47) α-mannosidases that selectively cleave α1,2-linked mannose residues. Despite the sequence and structural similarities among the GH47 enzymes, the molecular basis for residue-specific cleavage remains obscure. The present studies reveal enzyme–substrate complex structures for two related GH47 α-mannosidases and provide insights into how these enzymes recognize the same substrates differently and catalyze the complementary glycan trimming reactions necessary for glycan maturation.

Zefiro 380. The new very high speed train for China; Zefiro 380. Der neue Hochgeschwindigkeitszug fuer China

Energy Technology Data Exchange (ETDEWEB)

Hoefler, Werner; Niklass, Ralf [Bombardier Transportation GmbH, Hennigsdorf (Germany)

2013-04-01

The Bombardier Zefiro 380 comprehensively redefines very high speed (VHS) travel by harmonizing the often-conflicting demands of economy and ecology. In China's visionary development of a national very high speed rail system, the Zefiro 380 train plays a key role: 70 of these train sets were ordered by the Ministry of Railways in September 2009. The world's fastest series-production train is also the world's most eco-friendly and one of the most economical VHS trains. Bombardier's energy-saving EC04 technologies and an advanced aerodynamic design that benefits from Bombardier's aviation know-how ensure that the Zefiro 380 train runs with an unprecedented degree of energy efficiency.

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

Science.gov (United States)

BANERJI, JULIAN

2015-01-01

The present treatment of childhood T-cell leukemias involves the systemic administration of prokary-otic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity. PMID:26178806

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis).

Science.gov (United States)

Banerji, Julian

2015-09-01

The present treatment of childhood T-cell leukemias involves the systemic administration of prokaryotic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity.

PheVI:09 (Phe6.44) as a sliding microswitch in seven-transmembrane (7TM) G protein-coupled receptor activation

DEFF Research Database (Denmark)

Valentin-Hansen, Louise; Holst, Birgitte; Frimurer, Thomas M

2012-01-01

In seven-transmembrane (7TM), G protein-coupled receptors, highly conserved residues function as microswitches, which alternate between different conformations and interaction partners in an extended allosteric interface between the transmembrane segments performing the large scale conformational......-V into a tight pocket generated by five hydrophobic residues protruding from TM-III and TM-V. Of these, the residue in position III:16 (3.40) (often an Ile or Val) appears to function as a barrier or gate for the transition between inactive and active conformation. Mutational analysis showed that PheVI:09...... an aromatic microswitch that stabilizes the active, outward tilted conformation of TM-VI relative to TM-III by sliding into a tight hydrophobic pocket between TM-III and TM-V and that the hydrophobic residue in position III:16 constitutes a gate for this transition....

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.

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.

Metabolism of chlorobiphenyls by a variant biphenyl dioxygenase exhibiting enhanced activity toward dibenzofuran

International Nuclear Information System (INIS)

Viger, Jean-François; Mohammadi, Mahmood; Barriault, Diane; Sylvestre, Michel

2012-01-01

Highlights: ► Burkholderia xenovorans LB400 biphenyl dioxygenase (BphAE LB400 ) metabolizes PCBs. ► Asn338Gln/Leu409Phe double mutation speeds up electron transfer of enzyme reaction. ► We tested how the mutations affect the PCB-degrading abilities of BphAE LB400 variants. ► The same mutations also broaden the PCB substrate range of BphAE LB400 variants. -- Abstract: The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAE LB400 ) catalyzes the dihydroxylation of biphenyl and of several polychlorinated biphenyls (PCBs) but it poorly oxidizes dibenzofuran. In this work we showed that BphAE RR41 , a variant which was previously found to metabolize dibenzofuran more efficiently than its parent BphAE LB400 , metabolized a broader range of PCBs than BphAE LB400 . Hence, BphAE RR41 was able to metabolize 2,6,2′,6′-, 3,4,3′,5′- and 2,4,3′,4′-tetrachlorobiphenyl that BphAE LB400 is unable to metabolize. BphAE RR41 was obtained by changing Thr335Phe336Asn338Ile341Leu409 of BphAE LB400 to Ala335Met336Gln338Val341Phe409. Site-directed mutagenesis was used to create combinations of each substitution, in order to assess their individual contributions. Data show that the same Asn338Glu/Leu409Phe substitution that enhanced the ability to metabolize dibenzofuran resulted in a broadening of the PCB substrates range of the enzyme. The role of these substitutions on regiospecificities toward selected PCBs is also discussed.

ASN report of the status of nuclear safety and radiation protection in France in 2012

International Nuclear Information System (INIS)

Chevet, Pierre-Franck; Delmestre, Alain; Bardet, Marie-Christine; Covard, Fabienne; Landrin, Sophie

2013-01-01

After a presentation of the French Nuclear Safety Authority (ASN), its missions, some key figures illustrating its activities and its organisation, this report proposes an overview of marking events and of actions undertaken by the ASN after the Fukushima accident. Then, the report proposes a detailed and commented overview of actions undertaken by the ASN in different fields and domains: nuclear activities, principles and actors of nuclear safety and radiation protection control, regulation, control of nuclear activities and of exposures to ionizing radiations, radiological and post-accidental emergency situations, public information and transparency, international relationships, regional overview of nuclear safety and radiation protection. The last part addresses activities controlled by the ASN: medical use of ionizing radiations, industrial, research and veterinary uses and source safety, transport of radioactive materials, electronuclear plants, installations related to nuclear fuel cycle, nuclear research and other nuclear installations, safety of dismantling of base nuclear installations, radioactive wastes and polluted sites

Energies in Ile de France - state of the art

International Nuclear Information System (INIS)

2003-01-01

Because of the area of Ile de France, depends for 94% of outside for its energy needs, a local energy policy is a priority for the region. This document provides recommendations for the next SDRIF (Directory Scheme for the Ile De France Region) publication. After a recall of some definitions, it presents the main characteristics of the regional energy production and of the consumption. In the next chapters it analyses the final regional energy consumption per energy types and per economic activities sector and presents the organization of the energy supply of the region. Five domains of thought complete this analysis by an evaluation of the next energy policy approach: the tomorrow energy needs, the energy supply security, the place of the renewable energies in Ile de France, the transports problem, the minimization of the natural, industrial and social risks. (A.L.B.)

Structural insight into gene transcriptional regulation and effector binding by the Lrp/AsnC family

NARCIS (Netherlands)

Thaw, P.; Sedelnikova, S.E.; Muranova, T.; Wiese, S.; Ayora, S.; Alonso, J.C.; Brinkman, A.B.; Akerboom, A.P.; Oost, van der J.; Rafferty, J.B.

2006-01-01

The Lrp/AsnC family of transcriptional regulatory proteins is found in both archaea and bacteria. Members of the family influence cellular metabolism in both a global (Lrp) and specific (AsnC) manner, often in response to exogenous amino acid effectors. In the present study we have determined both

Penis Ödemi ile Kendini Gösteren Henoch-Schönlein Purpurası

OpenAIRE

UZUN, Hakan; ALAGÖZ, Demet; ?ENSES, Dursun Ali; D?K?C?, Bünyamin; KOCABAY, Kenan

2015-01-01

Henoch Schonlein purpurası artrit/artralji, gastrointestinal sistem ve renal tutulumun e?lik etti?i nontrombositopenik purpura ile karakterize bir sendromdur. Burada penis ödemi ile ba?vuran 3 ya??ndaki bir erkek hasta sunulmuştur. Bu ?ekilde nadir olan bağlangıç bulguları nedeni ile Henoch Schonlein purpurası tanıs?nda zorluk çekilebilmektedir.

Evaluation of the association between the TAS1R2 and TAS1R3 variants and food intake and nutritional status in children.

Science.gov (United States)

Melo, Silvia V; Agnes, Grasiela; Vitolo, Márcia R; Mattevi, Vanessa S; Campagnolo, Paula D B; Almeida, Silvana

2017-01-01

Taste perception plays a key role in determining individual food preferences and dietary habits and may influence nutritional status. This study aimed to investigate the association of TAS1R2 (Ile191Val - rs35874116) and TAS1R3 (-1266 C/T - rs35744813) variants with food intake and nutritional status in children followed from birth until 7.7 years old. The nutritional status and food intake data of 312 children were collected at three developmental stages (1, 3.9 and 7.7 years old). DNA was extracted from blood samples and the polymorphisms were analyzed by real-time polymerase chain reactions (qPCR) using hydrolysis probes as the detection method. Food intake and nutritional status were compared among individuals with different single nucleotide polymorphism (SNP) genotypes. At 3.9 years old, children homozygous (Val/Val) for the TAS1R2 Ile191Val polymorphism ingested less sugar and sugar-dense foods than children who were *Ile carriers. This finding demonstrated that a genetic variant of the T1R2 taste receptor is associated with the intake of different amounts of high sugar-content foods in childhood. This association may provide new perspectives for studying dietary patterns and nutritional status in childhood.

Transposon mutagenesis of probiotic Lactobacillus casei identifies asnH, an asparagine synthetase gene involved in its immune-activating capacity.

Science.gov (United States)

Ito, Masahiro; Kim, Yun-Gi; Tsuji, Hirokazu; Takahashi, Takuya; Kiwaki, Mayumi; Nomoto, Koji; Danbara, Hirofumi; Okada, Nobuhiko

2014-01-01

Lactobacillus casei ATCC 27139 enhances host innate immunity, and the J1 phage-resistant mutants of this strain lose the activity. A transposon insertion mutant library of L. casei ATCC 27139 was constructed, and nine J1 phage-resistant mutants out of them were obtained. Cloning and sequencing analyses identified three independent genes that were disrupted by insertion of the transposon element: asnH, encoding asparagine synthetase, and dnaJ and dnaK, encoding the molecular chaperones DnaJ and DnaK, respectively. Using an in vivo mouse model of Listeria infection, only asnH mutant showed deficiency in their ability to enhance host innate immunity, and complementation of the mutation by introduction of the wild-type asnH in the mutant strain recovered the immuno-augmenting activity. AsnH protein exhibited asparagine synthetase activity when the lysozyme-treated cell wall extracts of L. casei ATCC 27139 was added as substrate. The asnH mutants lost the thick and rigid peptidoglycan features that are characteristic to the wild-type cells, indicating that AsnH of L. casei is involved in peptidoglycan biosynthesis. These results indicate that asnH is required for the construction of the peptidoglycan composition involved in the immune-activating capacity of L. casei ATCC 27139.

Transposon mutagenesis of probiotic Lactobacillus casei identifies asnH, an asparagine synthetase gene involved in its immune-activating capacity.

Directory of Open Access Journals (Sweden)

Masahiro Ito

Full Text Available Lactobacillus casei ATCC 27139 enhances host innate immunity, and the J1 phage-resistant mutants of this strain lose the activity. A transposon insertion mutant library of L. casei ATCC 27139 was constructed, and nine J1 phage-resistant mutants out of them were obtained. Cloning and sequencing analyses identified three independent genes that were disrupted by insertion of the transposon element: asnH, encoding asparagine synthetase, and dnaJ and dnaK, encoding the molecular chaperones DnaJ and DnaK, respectively. Using an in vivo mouse model of Listeria infection, only asnH mutant showed deficiency in their ability to enhance host innate immunity, and complementation of the mutation by introduction of the wild-type asnH in the mutant strain recovered the immuno-augmenting activity. AsnH protein exhibited asparagine synthetase activity when the lysozyme-treated cell wall extracts of L. casei ATCC 27139 was added as substrate. The asnH mutants lost the thick and rigid peptidoglycan features that are characteristic to the wild-type cells, indicating that AsnH of L. casei is involved in peptidoglycan biosynthesis. These results indicate that asnH is required for the construction of the peptidoglycan composition involved in the immune-activating capacity of L. casei ATCC 27139.

Assessment of cumulative evidence for the association between glutathione S-transferase polymorphisms and lung cancer: application of the Venice interim guidelines.

Science.gov (United States)

Langevin, Scott M; Ioannidis, John P A; Vineis, Paolo; Taioli, Emanuela

2010-10-01

There is an overwhelming abundance of genetic association studies available in the literature, which can often be collectively difficult to interpret. To address this issue, the Venice interim guidelines were established for determining the credibility of the cumulative evidence. The objective of this report is to evaluate the literature on the association of common glutathione S-transferase (GST) variants (GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphism) and lung cancer, and to assess the credibility of the associations using the newly proposed cumulative evidence guidelines. Information from the literature was enriched with an updated meta-analysis and a pooled analysis using data from the Genetic Susceptibility to Environmental Carcinogens database. There was a significant association between GSTM1 null and lung cancer for the meta-analysis (meta odds ratio=1.17, 95% confidence interval: 1.10-1.25) and pooled analysis (adjusted odds ratio=1.10, 95% confidence interval: 1.04-1.16), although substantial heterogeneity was present. No overall association between lung cancer and GSTT1 null or GSTP1 Ile105Val was found. When the Venice criteria was applied, cumulative evidence for all associations were considered 'weak', with the exception of East Asian carriers of the G allele of GSTP1 Ile105Val, which was graded as 'moderate' evidence. Despite the large amounts of studies, and several statistically significant summary estimates produced by meta-analyses, the application of the Venice criteria suggests extensive heterogeneity and susceptibility to bias for the studies on association of common genetic polymorphisms, such as with GST variants and lung cancer.

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.

How a regulator is preparing for reviewing a license application file: The case of ASN

International Nuclear Information System (INIS)

Tanguy, Loic

2014-01-01

The French Nuclear Safety Authority (ASN) is an independent administrative authority. It prepares regulation pertaining to the management of radioactive waste, monitors the control of safety of basic nuclear installations that produce or treat waste or are involved in their disposal and performs inspections of waste producers (EDF, AREVA, CEA, hospitals, research centres, etc.) and Andra, the French National Radioactive Waste Management Agency. It regulates the overall system set up by Andra for accepting waste from producers and assesses waste management policy and the practices of radioactive waste producers. It reviews license applications and authorises commissioning of nuclear installations. In order to review technical documents, ASN benefits from the expertise of technical support organisations. The French Institute for Radiation Protection and Nuclear Safety (IRSN) is the main such organisation. ASN has been making efforts to diversify its experts for several years. In preparing its decisions, ASN also calls on the opinions and recommendations of seven Advisory Committees of Experts (GPE), with expert knowledge in the areas of waste, nuclear pressure equipment, medical exposure, non-medical radiation protection, reactors, transport, and laboratories and nuclear plants. ASN consults the GPEs in preparing its main decisions. In particular, they review the preliminary, provisional and final safety analysis reports for each nuclear installation. They can also be consulted about changes in regulations or doctrine. (authors)

40 CFR 436.380 - Applicability; description of the graphite subcategory.

Science.gov (United States)

2010-07-01

... graphite subcategory. 436.380 Section 436.380 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS MINERAL MINING AND PROCESSING POINT SOURCE CATEGORY Graphite Subcategory § 436.380 Applicability; description of the graphite subcategory. The provisions of this subpart...

Data of evolutionary structure change: 1SPXA-1WNTA [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1SPXA-1WNTA 1SPX 1WNT A A --TRFAEKVAIITGSSNGIGRATAVLFAREGAKVTITGR...LY CA 434 GLU CA 516 ILE CA 572 VAL CA 575 1WNT A 1WNTA GLIAR.../line> GLY CA 185 VAL CA 211 1WNT... A 1WNTA KTMLNRIPLGK

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

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....

An Eleven Year Review of Failed Female Sterilisation in Ile-Ife, Nigeria

African Journals Online (AJOL)

An Eleven Year Review of Failed Female Sterilisation in Ile-Ife, Nigeria. ... Teaching Hospitals Complex, Ile-Ife, Nigeria from October 1 1987 to September 30 1998. ... (Tropical Journal of Obstetrics and Gynaecology, 2001, 18(1): 8-11) ...

29 CFR Appendix B to Part 825 - Certification of Health Care Provider (Forms WH-380E & WH-380F)

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Certification of Health Care Provider (Forms WH-380E & WH-380F) B Appendix B to Part 825 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Pt. 825, App. B Appendix B to Part...

A Novel β-Globin Chain Hemoglobin Variant, Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp], Associated with Low Oxygen Saturation, Intermittent Aplastic Crises and Splenomegaly.

Science.gov (United States)

Collier, Anderson B; Coon, Lea M; Monteleone, Philip; Umaru, Samuel; Swanson, Kenneth C; Hoyer, James D; Oliveira, Jennifer L

2016-01-01

Hemoglobin (Hb) variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable β-globin variant that we have named Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb variants characterized by a single method is discouraged, as the Hb variant was misclassified as Hb S-South End or β6(A3)Glu→Val;β132(H10)Lys→Asn (HBB: c.[20A > T;399A > C]) by the initial laboratory.

ARGOS PHWR 380

International Nuclear Information System (INIS)

Gonzalez, A.J.; Vanzulli, R.C.

1987-01-01

This paper introduces the design of a nuclear power plant of 380 MWe, equipped with a preassure-vessel heavy-water reactor. An explanation is given of the technical, economical and financial factors that led to the design of this medium sized nuclear power plant, which is compatible with the latest advances in the field of nuclear safety. (Author) [es

Rapid degradation of D- and L-succinimide-containing peptides by a post-proline endopeptidase from human erythrocytes

Energy Technology Data Exchange (ETDEWEB)

Momand, J.; Clarke, S.

1987-12-01

The authors have been interested in the metabolic fate of proteins containing aspartyl succinimide (Asu) residues. These residues can be derived from the spontaneous rearrangement of Asp and Asn residues and from the spontaneous demethylation of enzymatically methylated L-isoAsp and D-Asp residues. Incubation of the synthetic hexapeptide N-Ac-Val-Tyr-Pro-Asu-Gly-Ala with the cytosolic fraction of human erythrocytes resulted in rapid cleavage of the prolyl-aspartyl succinimide bond producing the tripeptide N-Ac-Val-Try-Pro. The rate of this reaction is equal for both L- and D-Asu-containing peptides and is 10-fold greater that the rate of cleavage of a corresponding peptide containing a normal Pro-Asp linkage. When the aspartyl succinimide ring was replaced with an isoaspartyl residue, the cleavage rate was about 5 times that of the normal Pro-Asp peptide. The tripeptide-producing activity copurified on DEAE-cellulose chromatography with an activity that cleaves N-carbobenzoxy-Gly-Pro-4-methylcoumarin-7-amide, a post-proline endopeptidase substrate. These two activities were both inhibited by an antiserum to rat brain post-proline endopeptidase, and it appears that they are catalyzed by the same enzyme. This enzyme has a molecular weight of approximately 80,000 and is covalently labeled and inhibited by (/sup 3/H) diisopropyl fluorophosphate. The facile cleavage of the succinimide- and isoaspartyl-containing peptides by this post-proline endopeptidase suggests that it may play a role in the metabolism of peptides containing altered aspartyl residues.

Management of long-lived radioactive waste: stakes and ASN actions

International Nuclear Information System (INIS)

Dandrieux, G.

2011-01-01

Due to the length of time it takes to decay, long-lived radioactive waste will remain a hazard on a timescale beyond the length of a human life, and even of several generations. In the case of this waste, long-term management solutions must be implemented to protect human health and the environment without requiring human intervention. In accordance with requirements under the Law, ANDRA (national agency for the management of radioactive waste) is carrying out research on disposal solutions in deep or subsurface geological formations. Nonetheless, until such repositories become available, ASN (authority for nuclear safety) has a duty to ensure safety at current and future interim storage facilities, as well as the safety of operations to retrieve and package this type of waste. To this end, ASN acts on several levels: it is involved in drawing up regulations and reference texts, at national and international level, it examines safety analysis reports related to radioactive waste management at basic nuclear installations, by means of inspections that it performs at every step in radioactive waste management. In its capacity as joint coordinator of the national plan for the management of nuclear waste and materials (PNGMDR) working group, ASN also plays a very active role in drawing up the provisions of the PNGMDR aimed at improving and optimising radioactive waste management. (author)

Ethanol Production from Non-Food Tubers of Iles-iles (Amorphophallus campanulatus by Using Separated Hydrolysis and Fermentation

Directory of Open Access Journals (Sweden)

Kusmiyati Kusmiyati

2014-07-01

Full Text Available The decrease in production and the raise in needs have led to the rise in oil prices. This work investigated the possibility of Iles-iles (Amorphophallus campanulatus tuber flour, which is rich in carbohydrate con-tent, as a raw material to produce bioethanol. To obtain the maximum ethanol concentration, several parameters had been studied, such as: the concentration of α-amylase and β-amylase in liquefaction and sac-charification processes, respectively, the type of S. cerevisiae enzyme (pure, dry, wet and instant and weight of Diammonium phosphate (DAP as a nutrient for S. cerevisiae in fermentation. The result shows that the highest reducing sugar content (12.5% was achieved when 3.2 ml α-amylase/kg flour and 6.4 ml β-amylase/kg flour were used during liquefaction and saccharification processes. Since the concentration of α- and β-amylase increased, the reducing sugar obtained also increased. The higher sugar content resulted the higher the ethanol concentration in the fermentation broth. Furthermore, the highest concentration of ethanol (9 %v/v was obtained at 72 h fermentation using the dry S. cerevisiae, at 3.2 ml and 6.4 ml /kg flour of α-amylase and β-amylase enzymes, respectively. From the study of the effect of S. cerevisiae type, it was shown that dry S. cereviseae produced the highest ethanol concentration 10.2% (v/v at 72 h fermentation. The DAP was used as a nitrogen supply required by S. cerevisiae to growth and as a results can increase the ethanol concentration. The addition of DAP in the fermentation proved that 8.45% (v/v of ethanol was obtained. This result shows that the proposed tuber flour has the potential a raw material for bioethanol production. © 2014 BCREC UNDIP. All rights reservedReceived: 7th January 2014; Revised: 10th March 2014; Accepted: 18th March 2014[How to Cite: Kusmiyati, K. (2014. Ethanol Production from Non-Food Tubers of Iles-iles (Amorphophallus campanulatus by using Separated Hydrolysis and

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.

CAREM-25: Residual heat removal system

International Nuclear Information System (INIS)

Arvia, Roberto P.; Coppari, Norberto R.; Gomez de Soler, Susana M.; Ramilo, Lucia B.

2000-01-01

The objective of this work was the definition and consolidation of the residual heat removal system for the CAREM 25 reactor. The function of this system is cool down the primary circuit, removing the core decay heat from hot stand-by to cold shutdown and during refueling. In addition, this system heats the primary water from the cold shutdown condition to hot stand-by condition during the reactor start up previous to criticality. The system has been designed according to the requirements of the standards: ANSI/ANS 51.1 'Nuclear safety criteria for the design of stationary PWR plants'; ANSI/ANS 58.11 'Design criteria for safe shutdown following selected design basis events in light water reactors' and ANSI/ANS 58.9 'Single failure criteria for light water reactor safety-related fluid systems'. The suggested design fulfills the required functions and design criteria standards. (author)

Effects of the glucagon-like polypeptide-1 analogue (Val8)GLP-1 on learning, progenitor cell proliferation and neurogenesis in the C57B/16 mouse brain.

Science.gov (United States)

McGovern, Stephen F J; Hunter, Kerry; Hölscher, Christian

2012-09-14

Type 2 diabetes (T2DM) has been identified as a risk factor for Alzheimer's disease. Here, we tested the properties of the glucagon-like polypetide-1 (GLP-1) analogue (Val8)GLP-1, a drug originally developed as a treatment for T2DM at a range of doses (2.5 nmol; 25 nmol; 100 nmol; or 250 nmol/kg bw ip.) in an acute memory study in wild type C57B/l6 mice. We also tested (Val8)GLP-1 and the GLP-1 receptor antagonist exendin (9-39) in a chronic study (3 weeks at 25 nmol/kg bw ip. once-daily). We found that (Val8)GLP-1 crossed the blood brain barrier readily and that peripheral injection increased levels in the brain 30 min post-injection ip. but not 2h post-injection in rats. In the acute study, the low dose of 2.5 nmol/kg ip. enhanced motor activity in the open field task, while total distance travelled, exploratory behaviour and anxiety was not affected at any dose. Learning an object recognition task was not affected either. In the chronic study, no effect was observed in the open field assessment. The antagonist exendin (9-39) impaired object recognition learning and spatial learning in a water maze task, demonstrating the importance of GLP-1 signalling in memory formation. Locomotor activity was also affected in some cases. Blood sugar levels and insulin sensitivity was not affected in chronically treated mice. Neuronal stem cells and neurogenesis was enhanced by (Val8)GLP-1 in the dentate gyrus of wild type mice. The results demonstrate that (Val8)GLP-1 is safe in a range of doses, crosses the BBB and has potentially beneficial effects in the CNS by enhancing neurogenesis. Copyright © 2012 Elsevier B.V. All rights reserved.

18 CFR 380.13 - Compliance with the Endangered Species Act.

Science.gov (United States)

2010-04-01

... Endangered Species Act. 380.13 Section 380.13 Conservation of Power and Water Resources FEDERAL ENERGY... ENVIRONMENTAL POLICY ACT § 380.13 Compliance with the Endangered Species Act. (a) Definitions. For purposes of... Species Act of 1973, as amended (ESA). (2) Consultation requirement. (i) Prior to the filing of the...

18 CFR 380.7 - Format of an environmental impact statement.

Science.gov (United States)

2010-04-01

... environmental impact statement. 380.7 Section 380.7 Conservation of Power and Water Resources FEDERAL ENERGY... ENVIRONMENTAL POLICY ACT § 380.7 Format of an environmental impact statement. In addition to the requirements for an environmental impact statement prescribed in 40 CFR 1502.10 of the regulations of the Council...

Penicillium sp. mitigates Fusarium-induced biotic stress in sesame plants.

Science.gov (United States)

Radhakrishnan, Ramalingam; Pae, Suk-Bok; Shim, Kang-Bo; Baek, In-Youl

2013-07-01

Fusarium-infected sesame plants have significantly higher contents of amino acids (Asp, Thr, Ser, Asn, Glu, Gly, Ala, Val, Met, Ile, Leu, Tyr, Phe, Lys, His, Try, Arg, and Pro), compared with their respective levels in the healthy control. These higher levels of amino acids induced by Fusarium infection were decreased when Penicillium was co-inoculated with Fusarium. Compared with the control, Fusarium-infected plants showed higher contents of palmitic (8%), stearic (8%), oleic (7%), and linolenic acids (4%), and lower contents of oil (4%) and linoleic acid (11%). Co-inoculation with Penicillium mitigated the Fusarium-induced changes in fatty acids. The total chlorophyll content was lower in Fusarium- and Penicillium-infected plants than in the healthy control. The accumulation of carotenoids and γ-amino butyric acid in Fusarium-infected plants was slightly decreased by co-inoculation with Penicillium. Sesamin and sesamolin contents were higher in Penicillium- and Fusarium- infected plants than in the control. To clarify the mechanism of the biocontrol effect of Penicillium against Fusarium by evaluating changes in primary and secondary metabolite contents in sesame plants.

Study of the Mn-binding sites in photosystem II using antibodies raised against lumenal regions of the D1 and D2 reaction center proteins

Energy Technology Data Exchange (ETDEWEB)

Dalmasso, Enrique Agustin [Univ. of California, Berkeley, CA (United States)

1992-04-01

The experiments discussed in this thesis focus on identifying the protein segments or specific amino acids which provide ligands to the Mn cluster of photosystem II (PS II). This Mn cluster plays a central role in the oxygen-evolving complex (OEC) of PS II. The Mn cluster is thought to be bound by lumenal regions of the PS II reaction center proteins known as D1 and D2. First, several peptides were synthesized which correspond to specific lumenal segments of the D1 and D2 proteins. Next, polyclonal antibodies were successfully elicited using three of these peptides. The peptides recognized by these antibodies correspond to protein segments of the spinach reaction center proteins: Ile-321 to Ala-344 of D1 (D1-a), Asp-319 to Arg-334 of D1 (D1-b), and Val-300 to Asn-319 of D2 (D2-a). These antibodies were then used in assays which were developed to structurally or functionally probe the potential Mn-binding regions of the D1 and D2 proteins.

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.

Assessment of ASN inspections apart from BNI (Greater South West)

International Nuclear Information System (INIS)

Menechal, Ph.

2008-01-01

After having recalled recent evolutions of the ASN's organization (the French nuclear safety authority) and its basic missions (regulation elaboration, decisions, control of nuclear activities and installations, public information), the author presents the Bordeaux ASN's department which is in charge of the south-western part of France. He indicates and comments some data illustrating the performed actions and missions. He describes the objectives and procedures of inspection which may depend on the activity (external radiotherapy, interventional radiology, research laboratories). He assesses theses inspections in terms of radioprotection organization, of risk assessment and of definition of regulated areas, of personnel classification and dosimetric follow-on, of training of exposed personnel, of medical follow-on, of radioprotection control, of training of patients to radioprotection, of source management, and of waste and effluent management

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

Science.gov (United States)

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.

The Active Jasmonate JA-Ile Regulates a Specific Subset of Plant Jasmonate-Mediated Resistance to Herbivores in Nature

Directory of Open Access Journals (Sweden)

Meredith C. Schuman

2018-06-01

Full Text Available The jasmonate hormones are essential regulators of plant defense against herbivores and include several dozen derivatives of the oxylipin jasmonic acid (JA. Among these, the conjugate jasmonoyl isoleucine (JA-Ile has been shown to interact directly with the jasmonate co-receptor complex to regulate responses to jasmonate signaling. However, functional studies indicate that some aspects of jasmonate-mediated defense are not regulated by JA-Ile. Thus, it is not clear whether JA-Ile is best characterized as the master jasmonate regulator of defense, or if it regulates more specific aspects. We investigated possible functions of JA-Ile in anti-herbivore resistance of the wild tobacco Nicotiana attenuata, a model system for plant-herbivore interactions. We first analyzed the soluble and volatile secondary metabolomes of irJAR4xirJAR6, asLOX3, and WT plants, as well as an RNAi line targeting the jasmonate co-receptor CORONATINE INSENSITIVE 1 (irCOI1, following a standardized herbivory treatment. irJAR4xirJAR6 were the most similar to WT plants, having a ca. 60% overlap in differentially regulated metabolites with either asLOX3 or irCOI1. In contrast, while at least 25 volatiles differed between irCOI1 or asLOX3 and WT plants, there were few or no differences in herbivore-induced volatile emission between irJAR4xirJAR6 and WT plants, in glasshouse- or field-collected samples. We then measured the susceptibility of jasmonate-deficient vs. JA-Ile-deficient plants in nature, in comparison to wild-type (WT controls, and found that JA-Ile-deficient plants (irJAR4xirJAR6 are much better defended even than a mildly jasmonate-deficient line (asLOX3. The differences among lines could be attributed to differences in damage from specific herbivores, which appeared to prefer either one or the other jasmonate-deficient phenotype. We further investigated the elicitation of one herbivore-induced volatile known to be jasmonate-regulated and to mediate resistance to

Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions.

Science.gov (United States)

McCarty, Kathleen M; Smith, Thomas J; Zhou, Wei; Gonzalez, Ernesto; Quamruzzaman, Quazzi; Rahman, Mahmuder; Mahiuddin, Golam; Ryan, Louise; Su, Li; Christiani, David C

2007-08-01

Single-nucleotide polymorphisms in genes related to DNA repair capacity and ultraviolet exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case-control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh, in 2001-2002, investigated the association and potential effect modification between polymorphisms in Xeroderma Pigmentosum complementation group D (XPD) (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic-related skin lesions. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). No significant association was observed between skin lesions and the XPD 312 Asp/Asn (adjusted OR = 0.87, 95% CI = 0.65-1.15) Asn/Asn (adjusted OR = 0.76, 95% CI = 0.50-1.15) (referent Asp/Asp); XPD 751 Lys/Gln (adjusted OR = 0.92, 95% CI = 0.69-1.23) Gln/Gln (adjusted OR = 0.98, 95% CI = 0.66-1.45) (referent Lys/Lys). While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions, we did observe effect modification between these polymorphisms and sunburn tendency and arsenic-related skin lesions. Individuals with the heterozygote or homozygote variant forms (Asp/Asn or Asn/Asn) had half the risk of skin lesions (OR = 0.45, 95% CI = 0.29-0.68) compared with those with the wild-type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) had half the risk of skin lesions (OR = 0.47, 95% CI = 0.31-0.72) compared with those with the wild-type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312. XPD polymorphisms modified the relationship between tendency to sunburn and skin lesions in an arsenic exposed population. Further study is necessary

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.

Metabolism of chlorobiphenyls by a variant biphenyl dioxygenase exhibiting enhanced activity toward dibenzofuran

Energy Technology Data Exchange (ETDEWEB)

Viger, Jean-Francois; Mohammadi, Mahmood; Barriault, Diane [Institut National de la Recherche Scientifique, INRS-Institut Armand-Frappier, Laval, Quebec, Canada H4K 1C2 (Canada); Sylvestre, Michel, E-mail: Michel.Sylvestre@iaf.inrs.ca [Institut National de la Recherche Scientifique, INRS-Institut Armand-Frappier, Laval, Quebec, Canada H4K 1C2 (Canada)

2012-03-09

Highlights: Black-Right-Pointing-Pointer Burkholderia xenovorans LB400 biphenyl dioxygenase (BphAE{sub LB400}) metabolizes PCBs. Black-Right-Pointing-Pointer Asn338Gln/Leu409Phe double mutation speeds up electron transfer of enzyme reaction. Black-Right-Pointing-Pointer We tested how the mutations affect the PCB-degrading abilities of BphAE{sub LB400} variants. Black-Right-Pointing-Pointer The same mutations also broaden the PCB substrate range of BphAE{sub LB400} variants. -- Abstract: The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAE{sub LB400}) catalyzes the dihydroxylation of biphenyl and of several polychlorinated biphenyls (PCBs) but it poorly oxidizes dibenzofuran. In this work we showed that BphAE{sub RR41}, a variant which was previously found to metabolize dibenzofuran more efficiently than its parent BphAE{sub LB400}, metabolized a broader range of PCBs than BphAE{sub LB400}. Hence, BphAE{sub RR41} was able to metabolize 2,6,2 Prime ,6 Prime -, 3,4,3 Prime ,5 Prime - and 2,4,3 Prime ,4 Prime -tetrachlorobiphenyl that BphAE{sub LB400} is unable to metabolize. BphAE{sub RR41} was obtained by changing Thr335Phe336Asn338Ile341Leu409 of BphAE{sub LB400} to Ala335Met336Gln338Val341Phe409. Site-directed mutagenesis was used to create combinations of each substitution, in order to assess their individual contributions. Data show that the same Asn338Glu/Leu409Phe substitution that enhanced the ability to metabolize dibenzofuran resulted in a broadening of the PCB substrates range of the enzyme. The role of these substitutions on regiospecificities toward selected PCBs is also discussed.

14 CFR 380.33a - Operator's option plan.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Operator's option plan. 380.33a Section 380... option plan. (a) For the purposes of this part, an operator's option plan contract that states... flight leg. (b) Operator's option plan contracts shall state, in addition to the information required by...

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.

Synthesis and antioxidant activity of peptide-based ebselen analogues.

Science.gov (United States)

Satheeshkumar, Kandhan; Mugesh, Govindasamy

2011-04-18

A series of di- and tripeptide-based ebselen analogues has been synthesized. The compounds were characterized by (1)H, (13)C, and (77)Se NMR spectroscopy and mass spectral techniques. The glutathione peroxidase (GPx)-like antioxidant activity has been studied by using H(2)O(2) , tert-butyl hydroperoxide (tBuOOH), and cumene hydroperoxide (Cum-OOH) as substrates, and glutathione (GSH) as a cosubstrate. Although all the peptide-based compounds have a selenazole ring similar to that of ebselen, the GPx activity of these compounds highly depends on the nature of the peptide moiety attached to the nitrogen atom of the selenazole ring. It was observed that the introduction of a phenylalanine (Phe) amino acid residue in the N-terminal reduces the activity in all three peroxide systems. On the other hand, the introduction of aliphatic amino acid residues such as valine (Val) significantly enhances the GPx activity of the ebselen analogues. The difference in the catalytic activity of dipeptide-based ebselen derivatives can be ascribed mainly to the change in the reactivity of these compounds toward GSH and peroxide. Although the presence of the Val-Ala-CO(2) Me moiety facilitates the formation of a catalytically active selenol species, the reaction of ebselen analogues that has a Phe-Ile-CO(2) Me residue with GSH does not generate the corresponding selenol. To understand the antioxidant activity of the peptide-based ebselen analogues in the absence of GSH, these compounds were studied for their ability to inhibit peroxynitrite (PN)-mediated nitration of bovine serum albumin (BSA) and oxidation of dihydrorhodamine 123. In contrast to the GPx activity, the PN-scavenging activity of the Phe-based peptide analogues was found to be comparable to that of the Val-based compounds. However, the introduction of an additional Phe residue to the ebselen analogue that had a Val-Ala dipeptide significantly reduced the potency of the parent compound in PN-mediated nitration. Copyright �

18 CFR 380.6 - Actions that require an environmental impact statement.

Science.gov (United States)

2010-04-01

... environmental impact statement. 380.6 Section 380.6 Conservation of Power and Water Resources FEDERAL ENERGY... ENVIRONMENTAL POLICY ACT § 380.6 Actions that require an environmental impact statement. (a) Except as provided in paragraph (b) of this section, an environmental impact statement will normally be prepared first...

14 CFR 380.65 - Notification of change of operations or ownership.

Science.gov (United States)

2010-01-01

... ownership. 380.65 Section 380.65 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS PUBLIC CHARTERS Registration of Foreign Charter Operators § 380... in at least 10 percent of the operator or of the operator's stock reduces its holding to below 10...

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.

Modeling of pollution aerosols in Ile-de-France; Modelisation des aerosols de pollution en Ile-de-France

Energy Technology Data Exchange (ETDEWEB)

Hodzic, A

2005-10-15

The modeling of aerosols is a major stake in the understanding of the emission processes and evolution of particulates in the atmosphere. However, the parameterizations used in today's aerosol models still comprise many uncertainties. This work has been motivated by the need of better identifying the weaknesses of aerosols modeling tools and by the necessity of having new validation methods for a 3D evaluation of models. The studies have been carried out using the CHIMERE chemistry-transport model, which allows to simulate the concentrations and physico-chemical characteristics of pollution aerosols at the European scale and in Ile-de-France region. The validation approach used is based on the complementarity of the measurements performed on the ground by monitoring networks with those acquired during the ESQUIF campaign (study and simulation of air quality in Ile-de-France), with lidar and photometric measurements and with satellite observations. The comparison between the observations and the simulations has permitted to identify and reduce the modeling errors, and to characterize the aerosol properties in the vicinity of an urban area. (J.S.)

Modeling of pollution aerosols in Ile-de-France; Modelisation des aerosols de pollution en Ile-de-France

Energy Technology Data Exchange (ETDEWEB)

Hodzic, A

2005-10-15

The modeling of aerosols is a major stake in the understanding of the emission processes and evolution of particulates in the atmosphere. However, the parameterizations used in today's aerosol models still comprise many uncertainties. This work has been motivated by the need of better identifying the weaknesses of aerosols modeling tools and by the necessity of having new validation methods for a 3D evaluation of models. The studies have been carried out using the CHIMERE chemistry-transport model, which allows to simulate the concentrations and physico-chemical characteristics of pollution aerosols at the European scale and in Ile-de-France region. The validation approach used is based on the complementarity of the measurements performed on the ground by monitoring networks with those acquired during the ESQUIF campaign (study and simulation of air quality in Ile-de-France), with lidar and photometric measurements and with satellite observations. The comparison between the observations and the simulations has permitted to identify and reduce the modeling errors, and to characterize the aerosol properties in the vicinity of an urban area. (J.S.)

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.

"Minulost je bitevním polem současníků". Konference k osmdesátinám Viléma Prečana

Czech Academy of Sciences Publication Activity Database

Hoppe, Jiří

2013-01-01

Roč. 20, 1/2 (2013), s. 236-241 ISSN 1210-7050. ["Minulost je bitevním polem současníků". Konference k osmdesátinám Viléma Prečana. Praha, 24.01.2013-25.01.2013] Institutional support: RVO:68378114 Keywords : Vilém Prečan Subject RIV: AB - History

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.

Estimation of the Binding Free Energy of AC1NX476 to HIV-1 Protease Wild Type and Mutations Using Free Energy Perturbation Method.

Science.gov (United States)

Ngo, Son Tung; Mai, Binh Khanh; Hiep, Dinh Minh; Li, Mai Suan

2015-10-01

The binding mechanism of AC1NX476 to HIV-1 protease wild type and mutations was studied by the docking and molecular dynamics simulations. The binding free energy was calculated using the double-annihilation binding free energy method. It is shown that the binding affinity of AC1NX476 to wild type is higher than not only ritonavir but also darunavir, making AC1NX476 become attractive candidate for HIV treatment. Our theoretical results are in excellent agreement with the experimental data as the correlation coefficient between calculated and experimentally measured binding free energies R = 0.993. Residues Asp25-A, Asp29-A, Asp30-A, Ile47-A, Gly48-A, and Val50-A from chain A, and Asp25-B from chain B play a crucial role in the ligand binding. The mutations were found to reduce the receptor-ligand interaction by widening the binding cavity, and the binding propensity is mainly driven by the van der Waals interaction. Our finding may be useful for designing potential drugs to combat with HIV. © 2015 John Wiley & Sons A/S.

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.

N-linked glycosylation at Asn152 on CD147 affects protein folding and stability: promoting tumour metastasis in hepatocellular carcinoma.

Science.gov (United States)

Li, Jiang-Hua; Huang, Wan; Lin, Peng; Wu, Bo; Fu, Zhi-Guang; Shen, Hao-Miao; Jing, Lin; Liu, Zhen-Yu; Zhou, Yang; Meng, Yao; Xu, Bao-Qing; Chen, Zhi-Nan; Jiang, Jian-Li

2016-11-21

Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer, is a transmembrane glycoprotein that mediates oncogenic processes partly through N-glycosylation modifications. N-glycosylation has been demonstrated to be instrumental for the regulation of CD147 function during malignant transformation. However, the role that site-specific glycosylation of CD147 plays in its defective function in hepatocellular carcinomacells needs to be determined. Here, we demonstrate that the modification of N-glycosylation at Asn152 on CD147 strongly promotes hepatocellular carcinoma (HCC) invasion and migration. After the removal of N-glycans at Asn152, CD147 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated endoplasmic reticulum-associated degradation (ERAD). Furthermore, N-linked glycans at Asn152 were required for CD147 to acquire and maintain proper folding in the ER. Moreover, N-linked glycans at Asn152 functioned as a recognition motif that was directly mediated by the CNX quality control system. Two phases in the retention-based ER chaperones system drove ER-localized CD147 trafficking to degradation. Deletion of N-linked glycosylation at Asn152 on CD147 significantly suppressed in situ tumour metastasis. These data could potentially shed light on the molecular regulation of CD147 through glycosylation and provide a valuable means of developing drugs that target N-glycans at Asn152 on CD147.

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

Unraveling Brazilian Indian population prostate good health: clinical, anthropometric and genetic features

Directory of Open Access Journals (Sweden)

Mario M. de Lima Junior

2015-04-01

Full Text Available Purpose To compare dietary, lifestyle, clinical, anthropometric, genetic and prostatic features of Brazilian Indians and non-Indians (Amazon. Methods 315 men, 228 Indians and 89 non-Indians, ≥40 years old were submitted to digital rectal examination, serum prostate specific antigen (PSA, testosterone, TP53 and GSTP1 genotyping, anthropometric, lifestyle, dietary, personal and familial medical history. Prostatic symptoms were evaluated with the International Prostate Symptom Score (IPSS. Results Macuxis and Yanomamis represented 43.6% and 14.5% of Indians respectively who spontaneously referred no prostate symptoms. Mean IPSS was 7, range 3-19, with only 15% of moderate symptoms (score 8-19; Mean age was 54.7 years, waist circumference 86.6 cm, BMI 23.9 kg/m2. Yanomamis presented both lower BMI (21.4 versus 24.8 and 23.3, p=0,001 and prostate volume than Macuxis and “other ethnic groups” (15 versus 20, p=0.001. Testosterone (414 versus 502 and 512, p=0.207 and PSA (0.48 versus 0.6 and 0.41, p=0.349 were similar with progressive PSA increase with aging. Val/Val correlated with lower PSA (p=0.0361. Indians compared to control population presented: - TP53 super representation of Arg/Arg haplotype, 74.5% versus 42.5%, p<0.0001. -GSTP1 Ile/Ile 35.3% versus 60.9%; Ile/Val 45.9% versus 28.7%; Val/Val 18.8% versus 10.3%; p=0.0003. Conclusions Observed specific dietary, lifestyle, anthropometric and genetic profile for TP53 and GSTP1 may contribute to Brazilian Indian population prostate good health.

Unraveling Brazilian Indian population prostate good health: clinical, anthropometric and genetic features

Science.gov (United States)

de Lima, Mario M.; Reis, Leonardo O.; Ferreira, Ubirajara; Cardoso, Ulieme Oliveira; Barbieri, Raquel Bueno; de Mendonça, Gustavo B.; Ward, Laura S.

2015-01-01

Purpose To compare dietary, lifestyle, clinical, anthropometric, genetic and prostatic features of Brazilian Indians and non-Indians (Amazon). Methods 315 men, 228 Indians and 89 non-Indians, ≥40 years old were submitted to digital rectal examination, serum prostate specific antigen (PSA), testosterone, TP53 and GSTP1 genotyping, anthropometric, lifestyle, dietary, personal and familial medical history. Prostatic symptoms were evaluated with the International Prostate Symptom Score (IPSS). Results Macuxis and Yanomamis represented 43.6% and 14.5% of Indians respectively who spontaneously referred no prostate symptoms. Mean IPSS was 7, range 3-19, with only 15% of moderate symptoms (score 8-19); Mean age was 54.7 years, waist circumference 86.6 cm, BMI 23.9 kg/m2. Yanomamis presented both lower BMI (21.4 versus 24.8 and 23.3, p=0,001) and prostate volume than Macuxis and “other ethnic groups” (15 versus 20, p=0.001). Testosterone (414 versus 502 and 512, p=0.207) and PSA (0.48 versus 0.6 and 0.41, p=0.349) were similar with progressive PSA increase with aging. Val/Val correlated with lower PSA (p=0.0361). Indians compared to control population presented: - TP53 super representation of Arg/Arg haplotype, 74.5% versus 42.5%, p<0.0001. -GSTP1 Ile/Ile 35.3% versus 60.9%; Ile/Val 45.9% versus 28.7%; Val/Val 18.8% versus 10.3%; p=0.0003. Conclusions Observed specific dietary, lifestyle, anthropometric and genetic profile for TP53 and GSTP1 may contribute to Brazilian Indian population prostate good health. PMID:26005978

Role of Metabolic Genes in Blood Aluminum Concentrations of Jamaican Children with and without Autism Spectrum Disorder

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Mohammad H. Rahbar

2016-11-01

Full Text Available Aluminum is a neurotoxic metal with known health effects in animals and humans. Glutathione-S-transferase (GST genes and enzymes play a major role in detoxification of several heavy metals. Besides a direct relationship with oxidative stress; aluminum decreases GST enzyme activities. Using data from 116 Jamaican children; age 2–8 years; with Autism Spectrum Disorder (ASD and 116 sex- and age-matched typically developing (TD children; we investigated the association of polymorphisms in three GST genes (GSTP1; GSTM1; and GSTT1 with mean blood aluminum concentrations in children with and without ASD. Using log-transformed blood aluminum concentration as the dependent variable in a linear regression model; we assessed the additive and interactive effects of ASD status and polymorphisms in the three aforementioned GST genes in relation to blood aluminum concentrations. Although none of the additive effects were statistically significant (all p > 0.16; we observed a marginally significant interaction between GSTP1 Ile105Val (rs1695 and ASD status (p = 0.07; even after controlling for parental education level and consumption of avocado; root vegetables; and tuna (canned fish. Our findings indicate a significantly lower (p < 0.03 adjusted geometric mean blood aluminum concentration for TD children who had the Val/Val genotype (14.57 µg/L; compared with those with Ile/Ile or Ile/Val genotypes who had an adjusted geometric mean of 23.75 µg/L. However; this difference was not statistically significant among the ASD cases (p = 0.76. Our findings indicate that ASD status may be a potential effect modifier when assessing the association between GSTP1 rs1695 and blood aluminum concentrations among Jamaican children. These findings require replication in other populations.

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.

Cyclization of the N-Terminal X-Asn-Gly Motif during Sample Preparation for Bottom-Up Proteomics

DEFF Research Database (Denmark)

Zhang, Xumin; Højrup, Peter

2010-01-01

We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N-terminal ......We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N......-terminal cyclizations, cyclization of N-terminal glutamine and S-carbamoylmethylcysteine, it is dependent on pH instead of [NH(4)(+)]. The data set from our recent study on large-scale N(α)-modified peptides revealed a sequence requirement for the cyclization event similar to the well-known deamidation of Asn to iso...

Significant event of patient radiation protection in radiotherapy (criterion 2.1): declaration and rating on the ASN-SFRO scale - ASN guide nr 16 - Release of the 01/01/2010

International Nuclear Information System (INIS)

2010-01-01

This document brings together all the tools for the management of a significant event in radiation protection concerning a patient in radiotherapy. It contains the declaration form, a model for the reporting of significant events, and the ASN-SFRO scale which allows the event to be rated. After a presentation of the regulatory context and references, of the scope of application, this guide addresses the declaration of a significant event: general principles, definition of the 2.1 criterion, examples, delays and modalities of declaration, addressees of a declaration. It addresses the reporting of a significant event: general principles, sending delays and modalities. It addresses the rating on the ASN-SFRO scale: general principles, scale, and rating process. The last part deals with public information

Significant event of patient radiation protection in radiotherapy (criterion 2.1): declaration and rating on the ASN-SFRO scale - ASN guide no. 16 - Release of 17/07/2015

International Nuclear Information System (INIS)

2015-01-01

This document is an update of the previous version from October 2010. It brings together all the tools for the management of a significant event in radiation protection concerning a patient in radiotherapy. It contains the declaration form, a model for the reporting of significant events, and the ASN-SFRO scale which allows the event to be rated. After a presentation of the regulatory context and references, of the scope of application, this guide addresses the declaration of a significant event: general principles, definition of the 2.1 criterion, examples, delays and modalities of declaration, addressees of a declaration. It addresses the reporting of a significant event: general principles, sending delays and modalities. It addresses the rating on the ASN-SFRO scale: general principles, scale, and rating process. The last part deals with public information

β2-adrenergic receptor Thr164Ile polymorphism, obesity, and diabetes

DEFF Research Database (Denmark)

Thomsen, Mette; Dahl, Morten; Tybjærg-Hansen, Anne

2012-01-01

The β(2)-adrenergic receptor (ADRB2) influences regulation of energy balance by stimulating catecholamine-induced lipolysis in adipose tissue. The rare functional ADRB2rs1800888(Thr164Ile) polymorphism could therefore influence risk of obesity and subsequently diabetes.......The β(2)-adrenergic receptor (ADRB2) influences regulation of energy balance by stimulating catecholamine-induced lipolysis in adipose tissue. The rare functional ADRB2rs1800888(Thr164Ile) polymorphism could therefore influence risk of obesity and subsequently diabetes....

The BDNF Val66Met polymorphism has opposite effects on memory circuits of multiple sclerosis patients and controls.

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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

Redox-active tyrosine residue in the microcin J25 molecule

International Nuclear Information System (INIS)

Chalon, Miriam C.; Wilke, Natalia; Pedersen, Jens; Rufini, Stefano; Morero, Roberto D.; Cortez, Leonardo; Chehin, Rosana N.; Farias, Ricardo N.; Vincent, Paula A.

2011-01-01

Research highlights: → Cyclic voltammetry measurements showed irreversible oxidation of MccJ25 and MccJ25 (Y9F). → Infrared spectroscopy studies showed that only Tyr9 could be deprotonated upon chemical oxidation. → Formation of a long-lived tyrosyl radical in the native MccJ25 oxidized by H 2 O 2 was demonstrated. → Tyr9 but not Tyr20 can be easily oxidized and form a tyrosyl radical. -- Abstract: Microcin J25 (MccJ25) is a 21 amino acid lasso-peptide antibiotic produced by Escherichia coli and composed of an 8-residues ring and a terminal 'tail' passing through the ring. We have previously reported two cellular targets for this antibiotic, bacterial RNA polymerase and the membrane respiratory chain, and shown that Tyr9 is essential for the effect on the membrane respiratory chain which leads to superoxide overproduction. In the present paper we investigated the redox behavior of MccJ25 and the mutant MccJ25 (Y9F). Cyclic voltammetry measurements showed irreversible oxidation of both Tyr9 and Tyr20 in MccJ25, but infrared spectroscopy studies demonstrated that only Tyr9 could be deprotonated upon chemical oxidation in solution. Formation of a long-lived tyrosyl radical in the native MccJ25 oxidized by H 2 O 2 was demonstrated by Electron Paramagnetic Resonance Spectroscopy; this radical was not detected when the reaction was carried out with the MccJ25 (Y9F) mutant. These results show that the essential Tyr9, but not Tyr20, can be easily oxidized and form a tyrosyl radical.

Redox-active tyrosine residue in the microcin J25 molecule

Energy Technology Data Exchange (ETDEWEB)

Chalon, Miriam C. [Departamento de Bioquimica de la Nutricion, Instituto Superior de Investigaciones Biologicas (Consejo Nacional de Investigaciones Cientificas y Tecnicas-Universidad Nacional de Tucuman) and Instituto de Quimica Biologica ' Dr Bernabe Bloj' , Chacabuco 461, 4000 San Miguel de Tucuman, Tucuman (Argentina); Wilke, Natalia [CIQUIBIC, Dpto. de Quimica Biologica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Pabellon Argentina, Ciudad Universitaria, X5000HUA, Cordoba (Argentina); Pedersen, Jens; Rufini, Stefano [Department of Biology, University of Rome Tor Vergata 00133, Rome (Italy); Morero, Roberto D.; Cortez, Leonardo; Chehin, Rosana N.; Farias, Ricardo N. [Departamento de Bioquimica de la Nutricion, Instituto Superior de Investigaciones Biologicas (Consejo Nacional de Investigaciones Cientificas y Tecnicas-Universidad Nacional de Tucuman) and Instituto de Quimica Biologica ' Dr Bernabe Bloj' , Chacabuco 461, 4000 San Miguel de Tucuman, Tucuman (Argentina); Vincent, Paula A., E-mail: pvincent@fbqf.unt.edu.ar [Departamento de Bioquimica de la Nutricion, Instituto Superior de Investigaciones Biologicas (Consejo Nacional de Investigaciones Cientificas y Tecnicas-Universidad Nacional de Tucuman) and Instituto de Quimica Biologica ' Dr Bernabe Bloj' , Chacabuco 461, 4000 San Miguel de Tucuman, Tucuman (Argentina)

2011-03-18

Research highlights: {yields} Cyclic voltammetry measurements showed irreversible oxidation of MccJ25 and MccJ25 (Y9F). {yields} Infrared spectroscopy studies showed that only Tyr9 could be deprotonated upon chemical oxidation. {yields} Formation of a long-lived tyrosyl radical in the native MccJ25 oxidized by H{sub 2}O{sub 2} was demonstrated. {yields} Tyr9 but not Tyr20 can be easily oxidized and form a tyrosyl radical. -- Abstract: Microcin J25 (MccJ25) is a 21 amino acid lasso-peptide antibiotic produced by Escherichia coli and composed of an 8-residues ring and a terminal 'tail' passing through the ring. We have previously reported two cellular targets for this antibiotic, bacterial RNA polymerase and the membrane respiratory chain, and shown that Tyr9 is essential for the effect on the membrane respiratory chain which leads to superoxide overproduction. In the present paper we investigated the redox behavior of MccJ25 and the mutant MccJ25 (Y9F). Cyclic voltammetry measurements showed irreversible oxidation of both Tyr9 and Tyr20 in MccJ25, but infrared spectroscopy studies demonstrated that only Tyr9 could be deprotonated upon chemical oxidation in solution. Formation of a long-lived tyrosyl radical in the native MccJ25 oxidized by H{sub 2}O{sub 2} was demonstrated by Electron Paramagnetic Resonance Spectroscopy; this radical was not detected when the reaction was carried out with the MccJ25 (Y9F) mutant. These results show that the essential Tyr9, but not Tyr20, can be easily oxidized and form a tyrosyl radical.

EFEK POLIMORFISME GENA GSTP-1 TERHADAP AKTIVITAS GLUTATION S-TRANSFERASE (GST PADA INDIVIDU TERPAPAR LOGAM BERAT TIMBAL (Effect of GSTP-1 Gene Polymorphismson Glutation S- Transferase (GST Activity in Heavy Metals Lead-Exposed Individual

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Hernayanti Hernayanti

2015-11-01

Full Text Available ABSTRAK Gena GSTP-1 merupakan penghasil enzim glutation S- transferase (GST, yang berfungsi dalam proses detoksifikasi senyawa toksik di hati. Faktor keberadaan polimorfisme gena GSTP-1 akan menyebabkan penurunan ekspresi GST, sehingga proses detoksifikasi terhadap senyawa toksik akan terhambat. Kerentanan terhadap paparan senyawa toksik pada manusia akan meningkat apabila dijumpai polimorfisme gena. Salah satu senyawa toksik yang dapat menghambat aktivitas GST adalah timbal (Pb, terutama dalam bentuk tetra ethyl lead (TEL. Tujuan penelitian adalah untuk mengetahui pengaruh polimorfisme gena GSTP-1 terhadap aktivitas GST pada individu terpapar Pb, yang diwakili pekerja bengkel mobil. Faktor keberadaan polimorfisme gena individu ditentukan dengan metode PCR-RFLP dan enzim restriksi BsmA1. Parameter yang diukur adalah kadar Pb dan aktivitas GST. Analisis molekuler gena GSTP-1 dilakukan secara deskriptif. Data kadar Pb dan aktivitas GST dianalisis dengan uji t independent. Hasil analisis gena GSTP-1 dari 40 orang subyek kasus setelah dilakukan digesti dengan enzim BsmA1, ditemukan sebanyak 10 orang individu dengan polimorfisme Ile105Val gena GSTP 1 atau sekitar 25% dengan genotip Ile-Val, sedangkan 30 orang atau 75% ditemukan tanpa polimorfisme dengan genotip Ile-Ile. Pita DNA individu dengan polimorfisme terpotong menjadi 3 fragmen sepanjang 176, 91 dan 85 pp (mutan heterozygot, sedangkan tanpa polimorfisme terletak pada 176 bp. Subyek kasus dengan polimorfisme gena GSTP-1 memiliki kadar Pb lebih tinggi dan aktivitas GST lebih rendah dibandingkan individu non polimorfisme. Telah terbukti bahwa polimorfisme gena GSTP-1 menyebabkan penurunan ekspresi enzim GST. Pada individu terpapar Pb dengan polimorfisme gena GSTP-1 memiliki aktivitas GST lebih rendah dibandingkan individu tanpa polimorfisme. ABSTRACT GSTP-1 gene regulates the expression of gluthation S-transferase enzyme, which role in detoxification of toxicant on liver. If the polymorphisms

Structural investigations of the active-site mutant Asn156Ala of outer membrane phospholipase A: Function of the Asn-His interaction in the catalytic triad

NARCIS (Netherlands)

Snijder, H.J.; van Eerde, J.H.; Kalk, K.H.; Dekker, N.; Egmond, M.R.; Dijkstra, B.W.

2010-01-01

Outer membrane phospholipase A (OMPLA) from Escherichia coli is an integral-membrane enzyme with a unique His-Ser-Asn catalytic triad. In serine proteases and serine esterases usually an Asp occurs in the catalytic triad; its role has been the subject of much debate. Here the role of the uncharged

Scale-free behaviour of amino acid pair interactions in folded proteins

DEFF Research Database (Denmark)

Petersen, Steffen B.; Neves-Petersen, Maria Teresa; Mortensen, Rasmus J.

2012-01-01

The protein structure is a cumulative result of interactions between amino acid residues interacting with each other through space and/or chemical bonds. Despite the large number of high resolution protein structures, the ‘‘protein structure code’’ has not been fully identified. Our manuscript...... presents a novel approach to protein structure analysis in order to identify rules for spatial packing of amino acid pairs in proteins. We have investigated 8706 high resolution non-redundant protein chains and quantified amino acid pair interactions in terms of solvent accessibility, spatial and sequence...... which amino acid paired residues contributed to the cells with a population above 50, pairs of Ala, Ile, Leu and Val dominate the results. This result is statistically highly significant. We postulate that such pairs form ‘‘structural stability points’’ in the protein structure. Our data shows...

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.

Science.gov (United States)

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.

Comparisons of Prostate Cancer Inhibitors Abiraterone and TOK-001 Binding with CYP17A1 through Molecular Dynamics.

Science.gov (United States)

Xiao, Fei; Yang, Maohua; Xu, Youjun; Vongsangnak, Wanwipa

2015-01-01

Cytochrome P450 17A1 (CYP17A1) is associated in the steroid hormone biosynthesis in human. As cell proliferation of prostate cancer in response to androgen steroid, an inhibition of CYP17A1 becomes an alternative approach to inhibit biosynthesis of androgen and support treatment of prostate cancer. However, biology-driven inhibitor development of prostate cancer is poorly elucidated. The aims of this study are to address structural differences at atomic-level between CYP17A1 and inhibitors i.e., abiraterone and TOK-001, and further investigate the effect of point mutation of CYP17A1 on the active site stability and the local interactions that are hydrophobic interaction and hydrogen bonding throughout molecular dynamics (MD) simulation. After performing multiple comparisons among four different complexes across CYP17A1 and inhibitors, interestingly TOK-001 oriented toward the active pocket and formed larger volume with I-helix of CYP17A1 than abiraterone, whereas abiraterone showed tighter binding and more active site stability. Considering on the effect of hydrophobic interaction and hydrogen bonding between abiraterone and CYP17A1, the key residues of Phe114, Ile371, Val482, and Asn202 were identified. This contributes into tight binding interactions; however abiraterone is effectively weakened along with the global conformation mobility increased in A105L mutation. Surprisingly, overall conformation of the CYP17A1 remained stable when bound to TOK-001. This basic knowledge can guide future experiments on design of efficient inhibitors for CYP17A1, which provides theoretical basis of androgen-dependent disease therapy.

Perdeuteration and methyl-selective 1H, 13C-labeling by using a Kluyveromyces lactis expression system

International Nuclear Information System (INIS)

Miyazawa-Onami, Mayumi; Takeuchi, Koh; Takano, Toshiaki; Sugiki, Toshihiko; Shimada, Ichio; Takahashi, Hideo

2013-01-01

The production of stable isotope-labeled proteins is critical in structural analyses of large molecular weight proteins using NMR. Although prokaryotic expression systems using Escherichia coli have been widely used for this purpose, yeast strains have also been useful for the expression of functional eukaryotic proteins. Recently, we reported a cost-effective stable isotope-labeled protein expression using the hemiascomycete yeast Kluyveromyces lactis (K. lactis), which allow us to express exogenous proteins at costs comparable to prokaryotic expression systems. Here, we report the successful production of highly deuterated (>90 %) protein in the K. lactis system. We also examined the methyl-selective 1 H, 13 C-labeling of Ile, Leu, and Val residues using commonly used amino acid precursors. The efficiency of 1 H- 13 C-incorporation varied significantly based on the amino acid. Although a high level of 1 H- 13 C-incorporation was observed for the Ile δ1 position, 1 H, 13 C-labeling rates of Val and Leu methyl groups were limited due to the mitochondrial localization of enzymes involved in amino acid biosynthesis and the lack of transporters for α-ketoisovalerate in the mitochondrial membrane. In line with this notion, the co-expression with branched-chain-amino-acid aminotransferase in the cytosol significantly improved the incorporation rates of amino acid precursors. Although it would be less cost-effective, addition of 13 C-labeled valine can circumvent problems associated with precursors and achieve high level 1 H, 13 C-labeling of Val and Leu. Taken together, the K. lactis system would be a good alternative for expressing large eukaryotic proteins that need deuteration and/or the methyl-selective 1 H, 13 C-labeling for the sensitive detection of NMR resonances

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

Science.gov (United States)

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.

Reports by the Parliamentary Office for scientific and technological assessment. Wednesday, March 30, 2011. 2010 activity report - Hearing of the Nuclear Safety Authority (ASN) college

International Nuclear Information System (INIS)

2011-03-01

Members of the French Parliament and representatives of the French nuclear safety authority (ASN) discuss the content of the ASN 2010 activity report, the missions and responsibilities of the ASN in the different fields of exploitation of radioactive materials: nuclear energy and medical care. As far as nuclear energy is concerned, the representatives of the ASN evoke the decennial inspection of the French nuclear reactors, the control of the EPR construction, activities related to fuel cycle, the issue of waste management. As far as medical care is concerned, they address activities in the medical sector, the evolution of the number of events, and the commitment of the ASN in regulation elaboration. These issues are discussed with the members of Parliament

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

Science.gov (United States)

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

Reflection groups established by the ASN

International Nuclear Information System (INIS)

Fournier, M.

2009-01-01

Recent observations about tritium bio-kinetics in aquatic organisms might change our usual consideration about its radio-toxicity. In order to analyse these observations more thoroughly, the French nuclear safety authority (ASN) decided at the end of the year 2007 to create two independent reflection groups gathering scientists, nuclear operators and associations: the group 'tritium impact' has in charge the establishment of a status of the scientific knowledge relative to tritium sanitary impact, while the group 'defense in depth' has in charge the examination of the technical possibilities of tritium reprocessing and the establishment of a knowledge status of its environmental impact. First meetings of both groups took place in May 2008. Abstract only. (J.S.)

Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids.

Science.gov (United States)

Ji, L L; Miller, R H; Nagle, F J; Lardy, H A; Stratman, F W

1987-08-01

The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.

ASN report on the status of nuclear safety and radiation protection in France in 2015. Extracts

International Nuclear Information System (INIS)

2016-01-01

After a recall of ASN missions, key figures and organisation, an overview of main events for 2015, and a presentation of the French law related to energy transition for a green growth, a first part of this huge document presents actions undertaken by the ASN in 2015 in different fields: ionizing radiations and risks for health and the environment, principles and actors of control of nuclear safety and radiation protection, regulation, control of nuclear activities and of exposures to ionizing radiations, emergency radiological and post-accidental situations, public information transparency and participation, international relationships, regional overview of nuclear safety and radiation protection. The second part addresses activities controlled by the ASN: medical uses of ionizing radiations, industrial, research and veterinary uses and source safety, transportation of radioactive materials, EDF nuclear power plants, installations related to nuclear fuel cycle, various industrial and research installations, safety of basic nuclear installation dismantling, radioactive wastes and polluted sites and soils

Pharmacogenetic Study in Rectal Cancer Patients Treated With Preoperative Chemoradiotherapy: Polymorphisms in Thymidylate Synthase, Epidermal Growth Factor Receptor, GSTP1, and DNA Repair Genes

International Nuclear Information System (INIS)

Páez, David; Salazar, Juliana; Paré, Laia; Pertriz, Lourdes; Targarona, Eduardo; Rio, Elisabeth del; Barnadas, Agusti; Marcuello, Eugenio; Baiget, Montserrat

2011-01-01

Purpose: Several studies have been performed to evaluate the usefulness of neoadjuvant treatment using oxaliplatin and fluoropyrimidines for locally advanced rectal cancer. However, preoperative biomarkers of outcome are lacking. We studied the polymorphisms in thymidylate synthase, epidermal growth factor receptor, glutathione S-transferase pi 1 (GSTP1), and several DNA repair genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 128 rectal cancer patients treated with preoperative chemoradiotherapy. Methods and Materials: Blood samples were obtained from 128 patients with Stage II-III rectal cancer. DNA was extracted from the peripheral blood nucleated cells, and the genotypes were analyzed by polymerase chain reaction amplification and automated sequencing techniques or using a 48.48 dynamic array on the BioMark system. The germline polymorphisms studied were thymidylate synthase, (VNTR/5′UTR, 2R G>C single nucleotide polymorphism [SNP], 3R G>C SNP), epidermal growth factor receptor (Arg497Lys), GSTP1 (Ile105val), excision repair cross-complementing 1 (Asn118Asn, 8092C>A, 19716G>C), X-ray repair cross-complementing group 1 (XRCC1) (Arg194Trp, Arg280His, Arg399Gln), and xeroderma pigmentosum group D (Lys751Gln). The pathologic response, pathologic regression, progression-free survival, and overall survival were evaluated according to each genotype. Results: The ∗3/∗3 thymidylate synthase genotype was associated with a greater response rate (pathologic complete remission and microfoci residual tumor, 59% in ∗3/∗3 vs. 35% in ∗2/∗2 and ∗2/∗3; p = .013). For the thymidylate synthase genotype, the median progression-free survival was 103 months for the ∗3/∗3 patients and 84 months for the ∗2/∗2 and ∗2/∗3 patients (p = .039). For XRCC1 Arg399Gln SNP, the median progression-free survival was 101 months for the G/G, 78 months for the G/A, and 31 months for the A/A patients (p = .048). Conclusions: The thymidylate

Pharmacogenetic Study in Rectal Cancer Patients Treated With Preoperative Chemoradiotherapy: Polymorphisms in Thymidylate Synthase, Epidermal Growth Factor Receptor, GSTP1, and DNA Repair Genes

Energy Technology Data Exchange (ETDEWEB)

Paez, David, E-mail: dpaez@santpau.cat [Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona (Spain); Salazar, Juliana; Pare, Laia [Centre for Biomedical Network Research on Rare Diseases, Barcelona (Spain); Department of Genetics, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona (Spain); Pertriz, Lourdes [Department of Radiotherapy, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona (Spain); Targarona, Eduardo [Department of Surgery, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona (Spain); Rio, Elisabeth del [Centre for Biomedical Network Research on Rare Diseases, Barcelona (Spain); Department of Genetics, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona (Spain); Barnadas, Agusti; Marcuello, Eugenio [Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona (Spain); Baiget, Montserrat [Centre for Biomedical Network Research on Rare Diseases, Barcelona (Spain); Department of Genetics, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona (Spain)

2011-12-01

Purpose: Several studies have been performed to evaluate the usefulness of neoadjuvant treatment using oxaliplatin and fluoropyrimidines for locally advanced rectal cancer. However, preoperative biomarkers of outcome are lacking. We studied the polymorphisms in thymidylate synthase, epidermal growth factor receptor, glutathione S-transferase pi 1 (GSTP1), and several DNA repair genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 128 rectal cancer patients treated with preoperative chemoradiotherapy. Methods and Materials: Blood samples were obtained from 128 patients with Stage II-III rectal cancer. DNA was extracted from the peripheral blood nucleated cells, and the genotypes were analyzed by polymerase chain reaction amplification and automated sequencing techniques or using a 48.48 dynamic array on the BioMark system. The germline polymorphisms studied were thymidylate synthase, (VNTR/5 Prime UTR, 2R G>C single nucleotide polymorphism [SNP], 3R G>C SNP), epidermal growth factor receptor (Arg497Lys), GSTP1 (Ile105val), excision repair cross-complementing 1 (Asn118Asn, 8092C>A, 19716G>C), X-ray repair cross-complementing group 1 (XRCC1) (Arg194Trp, Arg280His, Arg399Gln), and xeroderma pigmentosum group D (Lys751Gln). The pathologic response, pathologic regression, progression-free survival, and overall survival were evaluated according to each genotype. Results: The Asterisk-Operator 3/ Asterisk-Operator 3 thymidylate synthase genotype was associated with a greater response rate (pathologic complete remission and microfoci residual tumor, 59% in Asterisk-Operator 3/ Asterisk-Operator 3 vs. 35% in Asterisk-Operator 2/ Asterisk-Operator 2 and Asterisk-Operator 2/ Asterisk-Operator 3; p = .013). For the thymidylate synthase genotype, the median progression-free survival was 103 months for the Asterisk-Operator 3/ Asterisk-Operator 3 patients and 84 months for the Asterisk-Operator 2/ Asterisk-Operator 2 and Asterisk-Operator 2/ Asterisk

BDNF val66met polymorphism affects aging of multiple types of memory.

Science.gov (United States)

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.

Study synthesis: which place for the methanation of wastes in Ile de France; Synthese de l'etude: quelle place pour la methanisation des dechets en Ile de France

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-07-01

In order to complete the studies realized on the methanation topic, a growing channel of bio-wastes treatment in Europe, the Arene and Ordif decided to realize this document of information, for deciders, on the evaluation of the household, industrial and agricultural wastes valorization by the methane. It presents the methanation principle, the situation in Europe and France, the Ile de France installation, the possible development and capacities in Ile de France and the perspectives. (A.L.B.)

Paul Valéry’s Theory of Poetic Action

Directory of Open Access Journals (Sweden)

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.

Affinity labeling and characterization of the active site histidine of glucosephosphate isomerase

International Nuclear Information System (INIS)

Gibson, D.R.; Gracy, R.W.; Hartman, F.C.

1980-01-01

N-bromoacetylethanolamine phosphate was found to act as a specific affinity label for the active center of glucosephosphate isomerase. The inactivation process followed pseudo-first order kinetics, was irreversible, and exhibited rate saturation kinetics with minimal half-lives of inactivation of 4.5 and 6.3 min for the enzyme isolated from human placenta and rabbit muscle, respectively. The pH dependence of the inactivation process closely paralleled the pH dependence of the overall catalytic process with pK/sub a/ values at pH 6.4 and 9.0. The stoichiometry of labeling of either enzyme, as determined with N-bromo[ 14 C 2 ]acetylethanolamine phosphate, was 1 eq of the affinity label/subunit of enzyme. After acid hydrolysis and amino acid analysis of the radioactive affinity-labeled human enzyme, only radioactive 3-carboxymethyl histidine was found. In the case of the rabbit enzyme, the only radioactive derivative obtained was 1-carboxymethyl histidine. Active site tryptic peptides were isolated by solvent extraction, thin layer peptide fingerprinting, and ion exchange chromatography before and after removal of the phosphate from the active site peptide. Amino acid analysis of the labeled peptides from the two species were very similar. Using high sensitivity methods for sequence analysis, the primary structure of the active site was established as Val-Leu-His-Ala-Glu-Asn-Val-Asp (Gly,Thr,Ser) Glu-Ile (Thr-Gly-His-Lys-Glx)-Tyr-Phe. Apparent sequence homology between the catalytic center of glucosephosphate isomerase and triosephosphate isomerase suggest that the two enzymes may have evolved from a common ancestral gene

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

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

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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.

Characterization of an endoprotease from rat small intestinal mucosal secretory granules which generates somatostatin-28 from prosomatostatin by cleavage after a single arginine residue

NARCIS (Netherlands)

Beinfeld, M. C.; Bourdais, J.; Kuks, P.; Morel, A.; Cohen, P.

1989-01-01

We have extracted, characterized, and partially purified an enzyme from secretory granules from rat small intestinal mucosa which cleaves a synthetic prosomatostatin substrate on the carboxyl side of a single arginine residue. This substrate Leu-Gln-Arg-Ser-Ala-Asn-Ser-NH2 contains the monobasic

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.

Carcaça de borregos Ile de France inteiros ou castrados e Hampshire down castrados abatidos aos doze meses de idade Carcass of intact or castrated Ile de France and castrated Hampshire down lambs slaughtered at twelve months of age

Directory of Open Access Journals (Sweden)

Edson Luis de Azambuja Ribeiro

2001-06-01

Full Text Available Um total de 24 borregos, sendo oito Ile de France inteiros, oito Ile de France castrados e oito Hampshire Down castrados, foram utilizados com o objetivo de avaliar características qualitativas e quantitativas da carcaça. Os animais foram mantidos exclusivamente em pastagem de grama Coast-Cross, sendo abatidos aos 12 meses de idade. As carcaças provenientes de animais inteiros da raça Ile de France apresentaram significativamente maior percentagem de pescoço do que as de animais castrados da mesma raça, sendo essa a única diferença encontrada entre esses dois grupos. Porém, foram observadas diferenças na composição tecidual da paleta entre as raças, sendo que os animais da raça Ile de France (inteiros ou castrados apresentaram maior percentual de músculo e maior relação músculo/osso do que os animais da raça Hampshire Down. Os resultados indicam que, por não haver diferenças importantes entre carcaças e carnes de animais inteiros e castrados abatidos aos 12 meses de idade, o uso da castração pode ser dispensado em sistemas intensivos de produção de carne ovinaA total of 24 lambs, eight intact Ile de France, eight castrated Ile de France and eight castrated Hampshire Down, were used in this experiment with the main objective of evaluating quantitative and qualitative carcass traits. The animals were raised on a Coast-Cross pasture and slaughtered at 12 months of age. Carcasses from intact Ile de France lambs had significantly more neck than carcasses from castrated Ile de France lambs. No other differences were observed between carcasses from intact or castrated Ile de France. However, differences between breeds were observed for tissue composition of the shoulder. Shoulders from Ile de France carcasses (intact or castrated presented greater percentage of muscles and greater relation of muscles/bones than shoulders from Hampshire Down lambs. Results indicate that intact males can be recommended for sheep meat production

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

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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.

The Amoco CadizOil Spill: Evolution of Petroleum Hydrocarbons in the Ile Grande Salt Marshes (Brittany) after a 13-year Period

Science.gov (United States)

Mille, G.; Munoz, D.; Jacquot, F.; Rivet, L.; Bertrand, J.-C.

1998-11-01

The Ile Grande salt marshes (Brittany coast) were polluted by petroleum hydrocarbons after theAmoco Cadizgrounding in 1978. Thirteen years after the oil spill, sediments were analysed for residual hydrocarbons in order to monitor the aliphatic and aromatic hydrocarbon signatures and to assess both qualitatively and quantitatively the changes in composition of theAmoco Cadizoil. Six stations were selected in the Ile Grande salt marshes and sediments were sampled to a depth of 20 cm. For each sample, the hydrocarbon compositions were determined for alkanes, alkenes, aromatics and biomarkers (terpanes, steranes, diasteranes). Hydrocarbon levels drastically decreased between 1978 and 1991, but to different extents according to the initial degree of contamination. In 1991, hydrocarbon concentrations never exceeded 1·7 g kg-1sediment dry weight, and in most cases were less than 0·1 g kg-1sediment dry weight. Even though petroleum hydrocarbons are still present, natural hydrocarbons were also detected at several stations. Changes in some biomarker distributions were observed 13 years after the oil spill. Nevertheless, most of the biomarkers are very stable in the salt marsh environment and remain unaltered even after a 13-year period.

Role of the transmembrane domain of FXYD7 in structural and functional interactions with Na,K-ATPase.

Science.gov (United States)

Li, Ciming; Crambert, Gilles; Thuillard, Delphine; Roy, Sophie; Schaer, Danièle; Geering, Käthi

2005-12-30

Members of the FXYD family are tissue-specific regulators of the Na,K-ATPase. Here, we have investigated the contribution of amino acids in the transmembrane (TM) domain of FXYD7 to the interaction with Na,K-ATPase. Twenty amino acids of the TM domain were replaced individually by tryptophan, and combined mutations and alanine insertion mutants were constructed. Wild type and mutant FXYD7 were expressed in Xenopus oocytes with Na,K-ATPase. Mutational effects on the stable association with Na,K-ATPase and on the functional regulation of Na,K-ATPase were determined by co-immunoprecipitation and two-electrode voltage clamp techniques, respectively. Most residues important for the structural and functional interaction of FXYD7 are clustered in a face of the TM helix containing the two conserved glycine residues, but others are scattered over two-thirds of the FXYD TM helix. Ile-35, Ile-43, and Ile-44 are only involved in the stable association with Na,K-ATPase. Glu-26, Met-30, and Ile-44 are important for the functional effect and/or the efficient association of FXYD7 with Na,K-ATPase, consistent with the prediction that these amino acids contact TM domain 9 of the alpha subunit (Li, C., Grosdidier, A., Crambert, G., Horisberger, J.-D., Michielin, O., and Geering, K. (2004) J. Biol. Chem. 279, 38895-38902). Several amino acids that are not implicated in the efficient association of FXYD7 with the Na,K-ATPase are specifically involved in the functional effect of FXYD7. Leu-32 and Phe-37 influence the apparent affinity for external K+, whereas Val-28 and Ile-42 are implicated in the apparent affinity for both external K+ and external Na+. These amino acids act in a synergistic way. These results highlight the important structural and functional role of the TM domain of FXYD7 and delineate the determinants that mediate the complex interactions of FXYD7 with Na,K-ATPase.

Langmuir-Blodgett (LB) yöntemi ile elde edilen çeşitli CdS ve Pb ince filmlerinin fiziksel özelliklerinin elektrik kuvvet mikroskobu (EKM) ile incelenmesi

OpenAIRE

ARSLAN, Melike

2011-01-01