The dominant role of side chains in supramolecular double helical organisation in synthetic tripeptides

Science.gov (United States)

Sharma, Ankita; Tiwari, Priyanka; Dutt Konar, Anita

2018-06-01

Peptide self-assembled nanostructures have attracted attention recently owing to their promising applications in diversified avenues. To validate the importance of sidechains in supramolecular architectural stabilization, herein this report describes the self-assembly propensities involving weak interactions in a series of model tripeptides Boc-Xaa-Aib-Yaa-OMe I-IV, (where Xaa = 4-F-Phe/NMeSer/Ile & Yaa = Tyr in peptide I-III respectively and Xaa = 4-F-Phe & Yaa = Ile in peptide IV) differing in terminal side chains. The solid state structural analysis reveals that tripeptide (I) displays supramolecular preference for double helical architecture. However, when slight modification has been introduced in the N-terminal side chains disfavour the double helical organisation (Peptide II and III). Indeed the peptides display sheet like ensemble within the framework. Besides replacement of C-terminal Tyr by Ile in peptide I even do not promote the architecture, emphasizing the dominant role of balance of side chains in stabilizing double helical organisation. The CD measurements, concentration dependant studies, NMR titrations and ROESY spectra are well in agreement with the solid state conformational investigation. Moreover the morphological experiments utilizing FE-SEM, support the heterogeneity present in the peptides. Thus this work may not only hold future promise in understanding the structure and function of neurodegenerative diseases but also assist in rational design of protein modification in biologically active peptides.

Administration of liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) and diclofenac in the combination attenuates their anti-tumor activities

Czech Academy of Sciences Publication Activity Database

Fedoročko, P.; Hoferová, Zuzana; Hofer, Michal; Brezáni, P.

2003-01-01

Roč. 50, č. 3 (2003), s. 176-184 ISSN 0028-2685 R&D Projects: GA AV ČR IBS5004009; GA AV ČR KSK5011112 Grant - others:VEGA MŠ SR(SK) 1/9211/02 Institutional research plan: CEZ:AV0Z5004920 Keywords : muramyl tripeptide * diclofenac * NSAIDs Subject RIV: BO - Biophysics Impact factor: 0.782, year: 2003

Involvement of T cells in enhanced resistance to Klebsiella pneumoniae septicemia in mice treated with liposome-encapsulated muramyl tripeptide phosphatidylethanolamine or gamma interferon

NARCIS (Netherlands)

Hagen, ten T.L.; Vianen, van W.; Savelkoul, H.F.J.; Heremans, H.; Buurman, W.A.; Bakker-Woudenberg, I.A.

1998-01-01

We have previously shown that prophylactic administration of the liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine (MTPPE) and gamma interferon (IFN-) results in strongly increased survival of mice from a normally lethal septicemia with Klebsiella pneumoniae.

Synthesis, characterization and in vitro biocompatibility assessment of a novel tripeptide hydrogelator, as a promising scaffold for tissue engineering applications.

Science.gov (United States)

Pospišil, Tihomir; Ferhatović Hamzić, Lejla; Brkić Ahmed, Lada; Lovrić, Marija; Gajović, Srećko; Frkanec, Leo

2016-10-20

We have synthesized and characterized a self-assembling tripeptide hydrogelator Ac-l-Phe-l-Phe-l-Ala-NH2. A series of experiments showed that the hydrogel material could serve as a stabile and biocompatible physical support as it improves the survival of HEK293T cells in vitro, thus being a promising biomaterial for use in tissue engineering applications.

The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid (AMB is made from glutamate and two alanine residues via a thiotemplate-linked tripeptide precursor

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Nelson eRojas Murcia

2015-03-01

Full Text Available The Pseudomonas aeruginosa toxin L-2-amino-4-methoxy-trans-3-butenoic acid (AMB is a non-proteinogenic amino acid which is toxic for prokaryotes and eukaryotes. Production of AMB requires a five-gene cluster encoding a putative LysE-type transporter (AmbA, two nonribosomal peptide synthetases (AmbB and AmbE, and two iron(II/α-ketoglutarate-dependent oxygenases (AmbC and AmbD. Bioinformatics analysis predicts one thiolation (T domain for AmbB and two T domains (T1 and T2 for AmbE, suggesting that AMB is generated by a processing step from a precursor tripeptide assembled on a thiotemplate. Using a combination of ATP-PPi exchange assays, aminoacylation assays, and mass spectrometry-based analysis of enzyme-bound substrates and pathway intermediates, the AmbB substrate was identified to be L-alanine (L-Ala, while the T1 and T2 domains of AmbE were loaded with L-glutamate (L-Glu and L-Ala, respectively. Loading of L-Ala at T2 of AmbE occurred only in the presence of AmbB, indicative of a trans loading mechanism. In vitro assays performed with AmbB and AmbE revealed the dipeptide L-Glu-L-Ala at T1 and the tripeptide L-Ala-L-Glu-L-Ala attached at T2. When AmbC and AmbD were included in the assay, these peptides were no longer detected. Instead, an L-Ala-AMB-L-Ala tripeptide was found at T2. These data are in agreement with a biosynthetic model in which L-Glu is converted into AMB by the action of AmbC, AmbD and tailoring domains of AmbE. The importance of the flanking L-Ala residues in the precursor tripeptide is discussed.

Spin-trapping and ESR studies of the direct photolysis of aromatic amino acids, dipeptides, tripeptides and polypeptides in aqueous solutions-II. Tyrosine and related compounds

Energy Technology Data Exchange (ETDEWEB)

Lion, Y; Kuwabara, M; Riesz, P [National Cancer Inst., Bethesda, MD (USA)

1982-01-01

The UV-photolysis of peptides containing tyrosine (Tyr) was investigated in aqueous solutions at room temperature at 220 and 265 nm. The short-lived free radicals formed during photolysis were spin-trapped by t-nitrosobutane and identified by electron spin resonance. For N-acetyl-and N-formyl-L-Tyr and for peptides containing L-Tyr as the middle residue, photolysis at 265 nm under neutral conditions produced mainly spin-adducts due to the scission between the alpha carbon and the methylene group attached to the aromatic ring, while at 220 nm decarboxylation radicals were spin-trapped. Photolysis of di- and tripeptides at 275 nm in alkaline solutions predominantly generated deamination radicals. The radicals produced in the photolysis of the oxidized A chain of insulin were tentatively characterized by comparison with the results for di- and tripeptides.

The Human Tripeptide GHK-Cu in Prevention of Oxidative Stress and Degenerative Conditions of Aging: Implications for Cognitive Health

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Loren Pickart

2012-01-01

Full Text Available Oxidative stress, disrupted copper homeostasis, and neuroinflammation due to overproduction of proinflammatory cytokines are considered leading causative factors in development of age-associated neurodegenerative conditions. Recently, a new mechanism of aging—detrimental epigenetic modifications—has emerged. Thus, compounds that possess antioxidant, anti-inflammatory activity as well as compounds capable of restoring copper balance and proper gene functioning may be able to prevent age-associated cognitive decline and ward off many common neurodegenerative conditions. The aim of this paper is to bring attention to a compound with a long history of safe use in wound healing and antiaging skin care. The human tripeptide GHK was discovered in 1973 as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue. It has high affinity for copper ions and easily forms a copper complex or GHK-Cu. In addition, GHK possesses a plethora of other regenerative and protective actions including antioxidant, anti-inflammatory, and wound healing properties. Recent studies revealed its ability to up- and downregulate a large number of human genes including those that are critical for neuronal development and maintenance. We propose GHK tripeptide as a possible therapeutic agent against age-associated neurodegeneration and cognitive decline.

NMR studies of the influence of dodecyl sulfate on the amide hydrogen exchange kinetics of a micelle-solubilized hydrophobic tripeptide

International Nuclear Information System (INIS)

O'Neil, J.D.J.; Sykes, B.D.

1989-01-01

Backbone amide hydrogen exchange measurements are an important source of information about the internal dynamics of proteins. Before such measurements can be interpreted unambiguously, contributions to hydrogen exchange rates from the chemical and physical environment of the amides must be taken into account. Membrane proteins are often solubilized in detergents, yet there have not been any systematic investigations of the possible effects detergents may have on the amide hydrogen exchange rates of proteins. To address this question, the authors have measured individual backbone and carboxyl-terminal amide exchange rates for the amphipathic tripeptide Leu-Val-Ile-amide dissolved in water and dodecyl sulfate micelles. Proton NMR spectroscopy was used to measure exchange using the direct exchange-out into D 2 O technique at 5 degree C and using an indirect steady-state saturation-transfer technique at 25 degree C. The broadening effect of micelle-incorporated spin-labeled fatty acid (12-doxylsterate) on the 1 H NMR spectra of both the detergent and the peptide resonances was used to demonstrate that the tripeptide is intimately associated with the micelle. These experiments help to explain the elevated pH min observed for backbone amides in the sodium dodecyl sulfate solubilized M13 coat protein

SVMTriP: a method to predict antigenic epitopes using support vector machine to integrate tri-peptide similarity and propensity.

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Bo Yao

Full Text Available Identifying protein surface regions preferentially recognizable by antibodies (antigenic epitopes is at the heart of new immuno-diagnostic reagent discovery and vaccine design, and computational methods for antigenic epitope prediction provide crucial means to serve this purpose. Many linear B-cell epitope prediction methods were developed, such as BepiPred, ABCPred, AAP, BCPred, BayesB, BEOracle/BROracle, and BEST, towards this goal. However, effective immunological research demands more robust performance of the prediction method than what the current algorithms could provide. In this work, a new method to predict linear antigenic epitopes is developed; Support Vector Machine has been utilized by combining the Tri-peptide similarity and Propensity scores (SVMTriP. Applied to non-redundant B-cell linear epitopes extracted from IEDB, SVMTriP achieves a sensitivity of 80.1% and a precision of 55.2% with a five-fold cross-validation. The AUC value is 0.702. The combination of similarity and propensity of tri-peptide subsequences can improve the prediction performance for linear B-cell epitopes. Moreover, SVMTriP is capable of recognizing viral peptides from a human protein sequence background. A web server based on our method is constructed for public use. The server and all datasets used in the current study are available at http://sysbio.unl.edu/SVMTriP.

Phe-Gly dipeptidomimetics designed for the di-/tripeptide transporters PEPT1 and PEPT2

DEFF Research Database (Denmark)

Våbenø, Jon; Lejon, Tore; Nielsen, Carsten Uhd

2004-01-01

A series of five Phe-Gly dipeptidomimetics containing different amide bond replacements have been synthesized in a facile way from the readily available unsaturated ketoester 1, and their affinities for the di-/tripeptide transporters hPEPT1 (Caco-2 cells) and rPEPT2 (SKPT cells) were tested...... information about the importance of flexibility and of the stereochemistry at the C(4)-position for this class of compounds. Furthermore, the intracellular uptake of 2a-4a in Caco-2 cells was investigated, showing a 3-fold reduction of the uptake of 2a in the presence of the competetive inhibitor Gly......-Pro, indicating contribution from an active transport component. No active uptake of 3a and 4a was observed. Transepithelial transport studies also indicated active transport of 2a across Caco-2 monolayers....

Vitamin C-linker-conjugated tripeptide AHK stimulates BMP-2-induced osteogenic differentiation of mouse myoblast C2C12 cells.

Science.gov (United States)

Jung, Jung-Il; Park, Kyeong-Yong; Lee, Yura; Park, Mira; Kim, Jiyeon

2018-03-15

Vitamin C-linker-conjugated Ala-His-Lys tripeptide (Vit C-AHK) is a derivative of Vitamin C-conjugated tripeptides, which were originally developed as a component of a product for collagen synthesis enhancement or human dermal fibroblast growth. Here, we investigated the effect of Vit C-AHK on bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Vit C-AHK enhanced proliferation of C2C12 cells and induction of BMP-2-induced alkaline phosphatase, a typical marker of osteoblast differentiation. Vit C-AHK also stimulated the phosphorylation and translocation of Smad1/5/8 to the nucleus and phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2 and p38. In addition, Vit C-AHK enhanced the BMP-2-induced mRNA expression of osteoblast differentiation-related genes such as ALP, BMP-2, Osteocalcin, and Runx2. Our results suggest that Vit C-AHK exerts an enhancing effect on osteoblast proliferation and differentiation through activation of Smad1/5/8 and MAPK ERK1/2 and p38 signaling and without significant cytotoxicity. These results provide important data for the development of peptide-based bone-regenerative agents and treatment of bone-related disorders. Copyright © 2018 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Metabolism of 125I-atrial natriuretic factor by vascular smooth muscle cells. Evidence for a peptidase that specifically removes the COOH-terminal tripeptide

International Nuclear Information System (INIS)

Johnson, G.R.; Arik, L.; Foster, C.J.

1989-01-01

The addition of 200 pM monoiodinated human atrial natriuretic factor-(99-126) (125I-hANF) to cultured bovine aortic smooth muscle cells at 37 degree C resulted in a rapid clearance from the medium (t1/2 approximately 7.5 min). Within 5 min, [125I]iodotyrosine126 (125I-Y), Arg125-[125I]iodotyrosine126 (125I-RY) and Phe124-Arg-[125]iodotyrosine126 (125I-FRY) appeared in the medium. The identities of these degradation products were confirmed by (1) retention time on high performance liquid chromatography (HPLC) relative to standards, (2) products generated by digestion with aminopeptidase M, and (3) the absence of the Met110. Preincubation of the cells with ammonium chloride or chloroquine resulted in a significant increase in the intracellular accumulation of radiolabel, indicative of endocytosis and rapid delivery of 125I-hANF to an acidic intracellular compartment (endosome and/or lysosome). Neither ammonium chloride, chloroquine, nor excess unlabeled hANF blocked the rapid appearance in the medium of 125I-RY or 125I-FRY. Bestatin inhibited the generation of 125I-RY, with a concomitant increase in 125I-FRY, suggesting that the 125I-RY is produced by aminopeptidase action on 125I-FRY. The endopeptidase 24.11 (enkephalinase) inhibitor, SCH 39370, did not inhibit the formation of 125I-FRY. These results provide evidence of a peptidase capable of specifically removing the COOH-terminal tripeptide from 125I-hANF. The COOH-terminal tripeptide, Phe124-Arg-Tyr126, was also isolated from cell digests of hANF by HPLC and its identity confirmed by amino acid analysis. Since it is generally believed that the COOH-terminal tripeptide is critical to many of atrial natriuretic factor-(99-126)'s bioactivities, this enzyme may be involved in the inactivation of atrial natriuretic factor-(99-126) in target tissues

Tripeptide tyroserleutide plus doxorubicin: therapeutic synergy and side effect attenuation

International Nuclear Information System (INIS)

Zhu, Zhi-feng; Yao, Zhi; Chen, Li-juan; Lu, Rong; Jia, Jing; Liang, Yu; Xu, Qiong; Zhou, Chun-lei; Wang, Li; Wang, Song

2008-01-01

Tripeptide tyroserleutide (YSL) is a novel small molecule anti-tumor polypeptide that has been shown to inhibit the growth of human liver cancer cells. In this study, we investigated the effects of YSL plus doxorubicin on the growth of human hepatocellular carcinoma BEL-7402 cells that had been transplanted into nude mice. Nude mice bearing human hepatocellular carcinoma BEL-7402 tumors were treated with successive intraperitoneal injections of saline; low-, mid-, or high-dose doxorubicin; or low-, mid-, or high-dose doxorubicin plus YSL. Effects on the weight and volume of the tumors were evaluated. Co-administration of YSL and high-dose doxorubicin (6 mg/kg every other day) prolonged the survival time of tumor-bearing mice as compared to high-dose doxorubicin alone. As well, the anti-tumor effects of mid- and low-dose doxorubicin (2 and 0.7 mg/kg every other day, respectively) were enhanced when supplemented with YSL; the tumor growth inhibition rates for YSL plus doxorubicin were greater than the inhibition rates for the same dosages of doxorubicin alone. The combination of YSL and doxorubicin decreased chemotherapy-associated weight loss, leukocyte depression, and heart, liver, and kidney damage as compared to doxorubicin alone. The combination of YSL plus doxorubicin enhances the anti-tumor effect and reduces the side effects associated with doxorubicin chemotherapy

The Napoleon Complex: When Shorter Men Take More.

Science.gov (United States)

Knapen, Jill E P; Blaker, Nancy M; Van Vugt, Mark

2018-05-01

Inspired by an evolutionary psychological perspective on the Napoleon complex, we hypothesized that shorter males are more likely to show indirect aggression in resource competitions with taller males. Three studies provide support for our interpretation of the Napoleon complex. Our pilot study shows that men (but not women) keep more resources for themselves when they feel small. When paired with a taller male opponent (Study 1), shorter men keep more resources to themselves in a game in which they have all the power (dictator game) versus a game in which the opponent also has some power (ultimatum game). Furthermore, shorter men are not more likely to show direct, physical aggression toward a taller opponent (Study 2). As predicted by the Napoleon complex, we conclude that (relatively) shorter men show greater behavioral flexibility in securing resources when presented with cues that they are physically less competitive. Theoretical and practical implications are discussed.

Driving for shorter outages

International Nuclear Information System (INIS)

Tritch, S.

1996-01-01

Nuclear plant outages are necessary to complete activities that cannot be completed during the operating cycle, such as steam generator inspection and testing, refueling, installing modifications, and performing maintenance tests. The time devoted to performing outages is normally the largest contributor to plant unavailability. Similarly, outage costs are a sizable portion of the total plant budget. The scope and quality of work done during outages directly affects operating reliability and the number of unplanned outages. Improved management and planning of outages enhances the margin of safety during the outage and results in increased plant reliability. The detailed planning and in-depth preparation that has become a necessity for driving shorter outage durations has also produced safer outages and improved post-outage reliability. Short outages require both plant and vendor management to focus on all aspects of the outage. Short outage durations, such as 26 days at South Texas or 29 days at North Anna, require power plant inter-department and intra-department teamwork and communication and vendor participation. In this paper shorter and safer outage at the 3-loop plants in the United States are explained. (J.P.N.)

Tetrahydrofuran Calpha-tetrasubstituted amino acids: two consecutive beta-turns in a crystalline linear tripeptide.

Science.gov (United States)

Maity, Prantik; Zabel, Manfred; König, Burkhard

2007-10-12

The synthesis of tetrahydrofuran Calpha-tetrasubstituted amino acids (TAAs) and their effect on the conformation in small peptides are reported. The synthesis starts from the protein amino acid methionine, which is protected at the C and N terminus and converted into the corresponding sulfonium salt by alkylation. Simple base treatment in the presence of an aryl aldehyde leads to the formation of tetrahydrofuran tetrasubstituted Calpha-amino acids in a highly diastereoselective (trans/cis ratio up to 97:3) reaction with moderate to good yields (35-78%) depending on the aldehyde used. Palladium-catalyzed coupling reactions allow a subsequent further functionalization of the TAA. The R,S,S-TAA-Ala dipeptide amide adopts a beta-turn type I conformation, whereas its S,R,S isomer does not. The R,S,S-Gly-TAA-Ala tripeptide amide shows in the solid state and in solution a conformation of two consecutive beta-turn type III structures, stabilized by i+3-->i intramolecular hydrogen bonds.

Antitumor and Antimicrobial Activity of Some Cyclic Tetrapeptides and Tripeptides Derived from Marine Bacteria

Directory of Open Access Journals (Sweden)

Subrata Chakraborty

2015-05-01

Full Text Available Marine derived cyclo(Gly-l-Ser-l-Pro-l-Glu was selected as a lead to evaluate antitumor-antibiotic activity. Histidine was chosen to replace the serine residue to form cyclo(Gly-l-His-l-Pro-l-Glu. Cyclic tetrapeptides (CtetPs were then synthesized using a solution phase method, and subjected to antitumor and antibiotic assays. The benzyl group protected CtetPs derivatives, showed better activity against antibiotic-resistant Staphylococcus aureus in the range of 60–120 μM. Benzyl group protected CtetPs 3 and 4, exhibited antitumor activity against several cell lines at a concentration of 80–108 μM. However, shortening the size of the ring to the cyclic tripeptide (CtriP scaffold, cyclo(Gly-l-Ser-l-Pro, cyclo(Ser-l-Pro-l-Glu and their analogues showed no antibiotic or antitumor activity. This phenomenon can be explained from their backbone structures.

Determination of accurate 1H positions of an alanine tripeptide with anti-parallel and parallel β-sheet structures by high resolution 1H solid state NMR and GIPAW chemical shift calculation.

Science.gov (United States)

Yazawa, Koji; Suzuki, Furitsu; Nishiyama, Yusuke; Ohata, Takuya; Aoki, Akihiro; Nishimura, Katsuyuki; Kaji, Hironori; Shimizu, Tadashi; Asakura, Tetsuo

2012-11-25

The accurate (1)H positions of alanine tripeptide, A(3), with anti-parallel and parallel β-sheet structures could be determined by highly resolved (1)H DQMAS solid-state NMR spectra and (1)H chemical shift calculation with gauge-including projector augmented wave calculations.

36 CFR 223.81 - Shorter advertising periods in emergencies.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Shorter advertising periods... OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Sale Contracts Advertisement and Bids § 223.81 Shorter advertising periods in emergencies. In emergency situations where prompt...

Molecular modeling studies of novel retro-binding tripeptide active-site inhibitors of thrombin.

Science.gov (United States)

Lau, W F; Tabernero, L; Sack, J S; Iwanowicz, E J

1995-08-01

A novel series of retro-binding tripeptide thrombin active-site inhibitors was recently developed (Iwanowicz, E. I. et al. J. Med. Chem. 1994, 37, 2111(1)). It was hypothesized that the binding mode for these inhibitors is similar to that of the first three N-terminal residues of hirudin. This binding hypothesis was subsequently verified when the crystal structure of a member of this series, BMS-183,507 (N-[N-[N-[4-(Aminoiminomethyl)amino[-1-oxobutyl]-L- phenylalanyl]-L-allo-threonyl]-L-phenylalanine, methyl ester), was determined (Taberno, L.J. Mol. Biol. 1995, 246, 14). The methodology for developing the binding models of these inhibitors, the structure-activity relationships (SAR) and modeling studies that led to the elucidation of the proposed binding mode is described. The crystal structure of BMS-183,507/human alpha-thrombin is compared with the crystal structure of hirudin/human alpha-thrombin (Rydel, T.J. et al. Science 1990, 249,227; Rydel, T.J. et al. J. Mol Biol. 1991, 221, 583; Grutter, M.G. et al. EMBO J. 1990, 9, 2361) and with the computational binding model of BMS-183,507.

Structural analysis of alanine tripeptide with antiparallel and parallel beta-sheet structures in relation to the analysis of mixed beta-sheet structures in Samia cynthia ricini silk protein fiber using solid-state NMR spectroscopy.

Science.gov (United States)

Asakura, Tetsuo; Okonogi, Michi; Nakazawa, Yasumoto; Yamauchi, Kazuo

2006-05-10

The structural analysis of natural protein fibers with mixed parallel and antiparallel beta-sheet structures by solid-state NMR is reported. To obtain NMR parameters that can characterize these beta-sheet structures, (13)C solid-state NMR experiments were performed on two alanine tripeptide samples: one with 100% parallel beta-sheet structure and the other with 100% antiparallel beta-sheet structure. All (13)C resonances of the tripeptides could be assigned by a comparison of the methyl (13)C resonances of Ala(3) with different [3-(13)C]Ala labeling schemes and also by a series of RFDR (radio frequency driven recoupling) spectra observed by changing mixing times. Two (13)C resonances observed for each Ala residue could be assigned to two nonequivalent molecules per unit cell. Differences in the (13)C chemical shifts and (13)C spin-lattice relaxation times (T(1)) were observed between the two beta-sheet structures. Especially, about 3 times longer T(1) values were obtained for parallel beta-sheet structure as compared to those of antiparallel beta-sheet structure, which could be explicable by the difference in the hydrogen-bond networks of both structures. This very large difference in T(1) becomes a good measure to differentiate between parallel or antiparallel beta-sheet structures. These differences in the NMR parameters found for the tripeptides may be applied to assign the parallel and antiparallel beta-sheet (13)C resonances in the asymmetric and broad methyl spectra of [3-(13)C]Ala silk protein fiber of a wild silkworm, Samia cynthia ricini.

Tripeptide GGH as the Inhibitor of Copper-Amyloid-β-Mediated Redox Reaction and Toxicity.

Science.gov (United States)

Hu, Xiaoyu; Zhang, Qian; Wang, Wei; Yuan, Zhi; Zhu, Xushan; Chen, Bing; Chen, Xingyu

2016-09-21

The Aβ complexes of some redox-active species, such as Cu, cause oxidative stress and induce severe toxicity by generating reactive oxygen species (ROS). Thus, Cu chelation therapy should be considered as a valuable strategy for the treatment of Alzheimer's disease (AD). However, more attention should be paid to the specific chelating ability of these chelating agents. Herein, a tripeptide GGH was used to selectively chelate the Cu(2+) in Aβ-Cu complex in the presence of other metal ions (e.g., K(+), Ca(2+), Ni(2+), Mg(2+), and Zn(2+)) as shown by isothermal titration calorimetry results. GGH decreased the level of HO(•) radicals by preventing the formation of intermediate Cu(I) ion. Thus, the Cu species completely lost its catalytic activity at a superequimolar GGH/Cu(II) ratio (4:1) as observed by UV-visible spectroscopy, coumarin-3-carboxylic acid fluorescence, and BCA assay. Moreover, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay indicates that GGH increased PC-12 cell viability from 36% to 63%, and neurotoxicity partly triggered by ROS decreased. These results indicate potential development of peptide chelation therapy for AD treatment.

Thermodynamic properties of peptide solutions 20. Partial molar volumes and isothermal compressions for some tripeptides of sequence gly-X-gly (X = gly, ala, leu, asn, thr, and tyr) in aqueous solution at T = 298.15 K and p = (10–120) MPa

International Nuclear Information System (INIS)

Hedwig, Gavin R.; Høiland, Harald

2016-01-01

Highlights: • Sound speeds were measured for aqueous solutions of some tripeptides at high pressures. • Partial molar volumes and isothermal compressions were derived for T = 298.15 K and p = (10–120) MPa. • The partial molar volumes for non-polar amino acid side-chains decrease with increasing pressure. • The partial molar volumes for polar side-chains do not change significantly with increasing pressure. - Abstract: Sound speeds have been measured for aqueous solutions of six tripeptides of sequence glycyl-X-glycine, where X is one of the amino acids glycine, alanine, leucine, asparagine, threonine, and tyrosine at T = 298.15 K and at the pressures p = (10, 20, 40, 60, 80, 100, and 120) MPa. Using methods described in previous work, these sound speeds were used to derive the partial molar volumes at infinite dilution, V_2"o, the partial molar isentropic compressions at infinite dilution, K_S_,_2"o, and the partial molar isothermal compressions at infinite dilution, K"o_T_,_2 {K"o_T_,_2 = −(∂V_2"o/∂p)_T}, for the tripeptides in aqueous solution at the elevated pressures. The results were used to calculate the partial molar volumes and partial molar isothermal compressions for the various amino acid side-chains over the pressure range p = (10–120) MPa.

Discrepancies between conformational distributions of a polyalanine peptide in solution obtained from molecular dynamics force fields and amide I' band profiles.

Science.gov (United States)

Verbaro, Daniel; Ghosh, Indrajit; Nau, Werner M; Schweitzer-Stenner, Reinhard

2010-12-30

overestimated distance between terminal carbonyl groups. In order to more accurately account for the experimental data, we changed the distribution parameters based on results recently obtained for the alanine-based tripeptides. The final model, which satisfactorily reproduced amide I' profiles, J-coupling constant, and the end-to-end distance of A(5)W, reinforces alanine's high structural preference for polyproline II. Our results suggest that distributions obtained from MD simulations suggesting a statistical coil-like distribution for alanine are still based on insufficiently accurate force fields.

Progesterone receptor (PR) polyproline domain (PPD) mediates inhibition of epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer cells.

Science.gov (United States)

Kawprasertsri, Sornsawan; Pietras, Richard J; Marquez-Garban, Diana C; Boonyaratanakornkit, Viroj

2016-05-01

Recent evidence has suggested a possible role for progesterone receptor (PR) in the progression of non-small cell lung cancer (NSCLC). However, little is known concerning roles of PR in NSCLC. PR contains a polyproline domain (PPD), which directly binds to the SH3 domain of signaling molecules. Because PPD-SH3 interactions are essential for EGFR signaling, we hypothesized that the presence of PR-PPD interfered with EGFR-mediated signaling and cell proliferation. We examined the role of PR-PPD in cell proliferation and signaling by stably expressing PR-B, or PR-B with disrupting mutations in the PPD (PR-BΔSH3), from a tetracycline-regulated promoter in A549 NSCLC cells. PR-B dose-dependently inhibited cell growth in the absence of ligand, and progestin (R5020) treatment further suppressed the growth. Treatment with RU486 abolished PR-B- and R5020-mediated inhibition of cell proliferation. Expression of PR-BΔSH3 and treatment with R5020 or RU486 had no effect on cell proliferation. Furthermore, PR-B expression but not PR-BΔSH3 expression reduced EGF-induced A549 proliferation and activation of ERK1/2, in the absence of ligand. Taken together, our data demonstrated the significance of PR extranuclear signaling through PPD interactions in EGFR-mediated proliferation and signaling in NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Macrophages inhibit human osteosarcoma cell growth after activation with the bacterial cell wall derivative liposomal muramyl tripeptide in combination with interferon-γ.

Science.gov (United States)

Pahl, Jens H W; Kwappenberg, Kitty M C; Varypataki, Eleni M; Santos, Susy J; Kuijjer, Marieke L; Mohamed, Susan; Wijnen, Juul T; van Tol, Maarten J D; Cleton-Jansen, Anne-Marie; Egeler, R Maarten; Jiskoot, Wim; Lankester, Arjan C; Schilham, Marco W

2014-03-10

In osteosarcoma, the presence of tumor-infiltrating macrophages positively correlates with patient survival in contrast to the negative effect of tumor-associated macrophages in patients with other tumors. Liposome-encapsulated muramyl tripeptide (L-MTP-PE) has been introduced in the treatment of osteosarcoma patients, which may enhance the potential anti-tumor activity of macrophages. Direct anti-tumor activity of human macrophages against human osteosarcoma cells has not been described so far. Hence, we assessed osteosarcoma cell growth after co-culture with human macrophages. Monocyte-derived M1-like and M2-like macrophages were polarized with LPS + IFN-γ, L-MTP-PE +/- IFN-γ or IL-10 and incubated with osteosarcoma cells. Two days later, viable tumor cell numbers were analyzed. Antibody-dependent effects were investigated using the therapeutic anti-EGFR antibody cetuximab. M1-like macrophages inhibited osteosarcoma cell growth when activated with LPS + IFN-γ. Likewise, stimulation of M1-like macrophages with liposomal muramyl tripeptide (L-MTP-PE) inhibited tumor growth, but only when combined with IFN-γ. Addition of the tumor-reactive anti-EGFR antibody cetuximab did not further improve the anti-tumor activity of activated M1-like macrophages. The inhibition was mediated by supernatants of activated M1-like macrophages, containing TNF-α and IL-1β. However, specific blockage of these cytokines, nitric oxide or reactive oxygen species did not inhibit the anti-tumor effect, suggesting the involvement of other soluble factors released upon macrophage activation. While LPS + IFN-γ-activated M2-like macrophages had low anti-tumor activity, IL-10-polarized M2-like macrophages were able to reduce osteosarcoma cell growth in the presence of the anti-EGFR cetuximab involving antibody-dependent tumor cell phagocytosis. This study demonstrates that human macrophages can be induced to exert direct anti-tumor activity against osteosarcoma cells. Our

Extending 3D near-cloud corrections from shorter to longer wavelengths

International Nuclear Information System (INIS)

Marshak, Alexander; Evans, K. Frank; Várnai, Tamás; Wen, Guoyong

2014-01-01

Satellite observations have shown a positive correlation between cloud amount and aerosol optical thickness (AOT) that can be explained by the humidification of aerosols near clouds, and/or by cloud contamination by sub-pixel size clouds and the cloud adjacency effect. The last effect may substantially increase reflected radiation in cloud-free columns, leading to overestimates in the retrieved AOT. For clear-sky areas near boundary layer clouds the main contribution to the enhancement of clear sky reflectance at shorter wavelengths comes from the radiation scattered into clear areas by clouds and then scattered to the sensor by air molecules. Because of the wavelength dependence of air molecule scattering, this process leads to a larger reflectance increase at shorter wavelengths, and can be corrected using a simple two-layer model [18]. However, correcting only for molecular scattering skews spectral properties of the retrieved AOT. Kassianov and Ovtchinnikov [9] proposed a technique that uses spectral reflectance ratios to retrieve AOT in the vicinity of clouds; they assumed that the cloud adjacency effect influences the spectral ratio between reflectances at two wavelengths less than it influences the reflectances themselves. This paper combines the two approaches: It assumes that the 3D correction for the shortest wavelength is known with some uncertainties, and then it estimates the 3D correction for longer wavelengths using a modified ratio method. The new approach is tested with 3D radiances simulated for 26 cumulus fields from Large-Eddy Simulations, supplemented with 40 aerosol profiles. The results showed that (i) for a variety of cumulus cloud scenes and aerosol profiles over ocean the 3D correction due to cloud adjacency effect can be extended from shorter to longer wavelengths and (ii) the 3D corrections for longer wavelengths are not very sensitive to unbiased random uncertainties in the 3D corrections at shorter wavelengths. - Highlights: �

Natural abundant solid state NMR studies in designed tripeptides for differentiation of multiple conformers.

Science.gov (United States)

Jayanthi, S; Chatterjee, Bhaswati; Raghothama, S

2009-10-01

Solid state NMR (SSNMR) experiments on heteronuclei in natural abundance are described for three synthetically designed tripeptides Piv-(L)Pro-(L)Pro-(L)Phe-OMe (1), Piv-(D)Pro-(L)Pro-(L)Phe-OMe (2), and Piv-(D)Pro-(L)Pro-(L)Phe-NHMe (3). These peptides exist in different conformation as shown by solution state NMR and single crystal X-ray analysis (Chatterjee et al., Chem Eur J 2008, 14, 6192). In this study, SSNMR has been used to probe the conformations of these peptides in their powder form. The (13)C spectrum of peptide (1) showed doubling of resonances corresponding to cis/cis form, unlike in solution where the similar doubling is attributed to cis/trans form. This has been confirmed by the chemical shift differences of C(beta) and C(gamma) carbon of Proline in peptide (1) both in solution and SSNMR. Peptide (2) and (3) provided single set of resonances which represented all trans form across the di-Proline segment. The results are in agreement with the X-ray analysis. Solid state (15)N resonances, especially from Proline residues provided additional information, which is normally not observable in solution state NMR. (1)H chemical shifts are also obtained from a two-dimensional heteronuclear correlation experiment between (1)H--(13)C. The results confirm the utility of NMR as a useful tool for identifying different conformers in peptides in the solid state. (c) 2009 Wiley Periodicals, Inc. Biopolymers 91: 851-860, 2009.

Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.

Science.gov (United States)

Xiao, Bo; Xu, Zhigang; Viennois, Emilie; Zhang, Yuchen; Zhang, Zhan; Zhang, Mingzhen; Han, Moon Kwon; Kang, Yuejun; Merlin, Didier

2017-07-05

Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (∼272.3 nm) and a slightly negative zeta potential (∼-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and downregulate TNF-α, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC. Copyright © 2016 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Shorter height is related to lower cardiovascular disease risk – A narrative review

Directory of Open Access Journals (Sweden)

Thomas T. Samaras

2013-01-01

Full Text Available Numerous Western studies have shown a negative correlation between height and cardiovascular disease. However, these correlations do not prove causation. This review provides a variety of studies showing short people have little to no cardiovascular disease. When shorter people are compared to taller people, a number of biological mechanisms evolve favoring shorter people, including reduced telomere shortening, lower atrial fibrillation, higher heart pumping efficiency, lower DNA damage, lower risk of blood clots, lower left ventricular hypertrophy and superior blood parameters. The causes of increased heart disease among shorter people in the developed world are related to lower income, excessive weight, poor diet, lifestyle factors, catch-up growth, childhood illness and poor environmental conditions. For short people in developed countries, the data indicate that a plant-based diet, leanness and regular exercise can substantially reduce the risk of cardiovascular disease.

SHORTER MENSTRUAL CYCLES ASSOCIATED WITH CHLORINATION BY-PRODUCTS IN DRINKING WATER

Science.gov (United States)

Shorter Menstrual Cycles Associated with Chlorination by-Products in Drinking Water. Gayle Windham, Kirsten Waller, Meredith Anderson, Laura Fenster, Pauline Mendola, Shanna Swan. California Department of Health Services.In previous studies of tap water consumption we...

YAOPBM-II: extension to higher degrees and to shorter time series

Energy Technology Data Exchange (ETDEWEB)

Korzennik, S G [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA (United States)], E-mail: skorzennik@cfa.harvard.edu

2008-10-15

In 2005, I presented a new fitting methodology (Yet AnOther Peak Bagging Method -YAOPBM), derived for very-long time series (2088-day-long) and applied it to low degree modes, {iota} {<=} 25. That very-long time series was also sub-divided into shorter segments (728-day-long) that were each fitted over the same range of degrees, to estimate changes with solar activity levels. I present here the extension of this method in several 'directions': a) to substantially higher degrees ({iota} {<=} 125); b) to shorter time series (364- and 182-day-long); and c) to additional 728-day-long segments, covering now some 10 years of observations. I discuss issues with the fitting, namely the leakage matrix, and the f- and p1 mode at very low frequencies, and I present some of the characteristics of the observed temporal changes.

Discovery and Early Clinical Evaluation of BMS-605339, a Potent and Orally Efficacious Tripeptidic Acylsulfonamide NS3 Protease Inhibitor for the Treatment of Hepatitis C Virus Infection

Energy Technology Data Exchange (ETDEWEB)

Scola, Paul M.; Wang, Alan Xiangdong; Good, Andrew C.; Sun, Li-Qiang; Combrink, Keith D.; Campbell, Jeffrey A.; Chen, Jie; Tu, Yong; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D’Andrea, Stanley; Zheng, Barbara; Hewawasam, Piyasena; Ding, Min; Thuring, Jan; Li, Jianqing; Hernandez, Dennis; Yu, Fei; Falk, Paul; Zhai, Guangzhi; Sheaffer, Amy K.; Chen, Chaoqun; Lee, Min S.; Barry, Diana; Knipe, Jay O.; Li, Wenying; Han, Yong-Hae; Jenkins, Susan; Gesenberg, Christoph; Gao, Qi; Sinz, Michael W.; Santone, Kenneth S.; Zvyaga, Tatyana; Rajamani, Ramkumar; Klei, Herbert E.; Colonno, Richard J.; Grasela, Dennis M.; Hughes, Eric; Chien, Caly; Adams, Stephen; Levesque, Paul C.; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona

2014-03-13

The discovery of BMS-605339 (35), a tripeptidic inhibitor of the NS3/4A enzyme, is described. This compound incorporates a cyclopropylacylsulfonamide moiety that was designed to improve the potency of carboxylic acid prototypes through the introduction of favorable nonbonding interactions within the S1' site of the protease. The identification of 35 was enabled through the optimization and balance of critical properties including potency and pharmacokinetics (PK). This was achieved through modulation of the P2* subsite of the inhibitor which identified the isoquinoline ring system as a key template for improving PK properties with further optimization achieved through functionalization. A methoxy moiety at the C6 position of this isoquinoline ring system proved to be optimal with respect to potency and PK, thus providing the clinical compound 35 which demonstrated antiviral activity in HCV-infected patients.

Partial molar volumes of proteins: amino acid side-chain contributions derived from the partial molar volumes of some tripeptides over the temperature range 10-90 degrees C.

Science.gov (United States)

Häckel, M; Hinz, H J; Hedwig, G R

1999-11-15

The partial molar volumes of tripeptides of sequence glycyl-X-glycine, where X is one of the amino acids alanine, leucine, threonine, glutamine, phenylalanine, histidine, cysteine, proline, glutamic acid, and arginine, have been determined in aqueous solution over the temperature range 10-90 degrees C using differential scanning densitometry . These data, together with those reported previously, have been used to derive the partial molar volumes of the side-chains of all 20 amino acids. The side-chain volumes are critically compared with literature values derived using partial molar volumes for alternative model compounds. The new amino acid side-chain volumes, along with that for the backbone glycyl group, were used to calculate the partial specific volumes of several proteins in aqueous solution. The results obtained are compared with those observed experimentally. The new side-chain volumes have also been used to re-determine residue volume changes upon protein folding.

Implications of shorter cells in PEP

International Nuclear Information System (INIS)

Wiedemann, H.

1975-01-01

Further studies on the beam-stay-clear requirements in PEP led to the conclusion that the vertical aperture needed to be enlarged. There are two main reasons for that: Observations at SPEAR indicate that the aperture should be large enough for a fully coupled beam. Full coupling of the horizontal and vertical betatron oscillations occurs not only occasionally when the energy, tune or betatron function at the interaction point is changed but also due to the beam/endash/beam effect of two strong colliding beams. The second reason for an increased aperture requirement is the nonlinear perturbation of the particle trajectories by the sextupoles. This perturbation increases a fully coupled beam by another 50% to 80%. Both effects together with a +-5 mm allowance for closed orbit perturbation result in a vertical beam-stay-clear in the bending magnets of +-4.8 to +-5.6 cm, compared to the present +-2.0 cm. This beam-stay-clear, together with additional space for vacuum chamber, etc., leads to very costly bending magnets. In this note, a shorter cell length is proposed which would reduce considerably the vertical beam-stay-clear requirements in the bending magnets. 7 figs

Antiaging effects of a novel facial serum containing L-ascorbic acid, proteoglycans, and proteoglycan-stimulating tripeptide: ex vivo skin explant studies and in vivo clinical studies in women

Directory of Open Access Journals (Sweden)

Garre A

2018-05-01

Full Text Available Aurora Garre,1 Mridvika Narda,1 Palmira Valderas-Martinez,1 Jaime Piquero,2 Corinne Granger1 1Innovation and Development, ISDIN SA, Barcelona, Spain; 2Dermik Clinic, Barcelona, Spain Background: With age, decreasing dermal levels of proteoglycans, collagen, and elastin lead to the appearance of aged skin. Oxidation, largely driven by environmental factors, plays a central role.Aim: The aim of this study was to assess the antiaging efficacy of a topical serum containing l-ascorbic acid, soluble proteoglycans, low molecular weight hyaluronic acid, and a tripeptide in ex vivo and in vivo clinical studies.Methods: Photoaging and photo-oxidative damage were induced in human skin explants by artificial solar radiation. Markers of oxidative stress – reactive oxygen species (ROS, total glutathione (GSH, and cyclobutane pyrimidine dimers (CPDs – were measured in serum-treated explants and untreated controls. Chronological aging was simulated using hydrocortisone. In both ex vivo studies, collagen, elastin, and proteoglycans were determined as measures of dermal matrix degradation. In women aged 21–67 years, hydration was measured up to 24 hours after a single application of serum, using Corneometer and hygrometer. Subjects’ perceptions of efficacy and acceptability were assessed via questionnaire after once-daily serum application for 4 weeks. Studies were performed under the supervision of a dermatologist.Results: In the photoaging study, irradiation induced changes in ROS, CPD, GSH, collagen, and elastin levels; these changes were reversed by topical serum application. The serum also protected against hydrocortisone-induced reduction in collagen, elastin, and proteoglycan levels, which were significantly higher in the serum-treated group vs untreated hydrocortisone-control explants. In clinical studies, serum application significantly increased skin moisture for 6 hours. Healthy volunteers perceived the product as efficient in making the

One long chain among shorter chains : the Flory approach revisited

OpenAIRE

Raphaël , E.; Fredrickson , G.; Pincus , P.

1992-01-01

We consider the mean square end-to-end distance of a long chain immersed in a monodisperse, concentrated solution of shorter, chemically identical chains. In contrast with the earlier work of Flory, no simplifying assumption on the wave vector dependence of the effective potential between segments is made. In order to obtain a closed form expression for the dimension of the long chain, we first derive a general expression for the mean square end-to-end distance of a flexible chain with arbitr...

The tripeptide feG regulates the production of intracellular reactive oxygen species by neutrophils

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Davison Joseph S

2006-06-01

Full Text Available Abstract Background The D-isomeric form of the tripeptide FEG (feG is a potent anti-inflammatory agent that suppresses type I hypersensitivity (IgE-mediated allergic reactions in several animal species. One of feG's primary actions is to inhibit leukocyte activation resulting in loss of their adhesive and migratory properties. Since activation of neutrophils is often associated with an increase in respiratory burst with the generation of reactive oxygen species (ROS, we examined the effect of feG on the respiratory burst in neutrophils of antigen-sensitized rats. A role for protein kinase C (PKC in the actions of feG was evaluated by using selective isoform inhibitors for PKC. Results At 18h after antigen (ovalbumin challenge of sensitized Sprague-Dawley rats a pronounced neutrophilia occurred; a response that was reduced in animals treated with feG (100 μg/kg. With antigen-challenged animals the protein kinase C (PKC activator, PMA, significantly increased intracellular ROS of circulating neutrophils, as determined by flow cytometry using the fluorescent probe dihydrorhodamine-123. This increase was prevented by treatment with feG at the time of antigen challenge. The inhibitor of PKCδ, rottlerin, which effectively prevented intracellular ROS production by circulating neutrophils of animals receiving a naïve antigen, failed to inhibit PMA-stimulated ROS production if the animals were challenged with antigen. feG treatment, however, re-established the inhibitory effects of the PKCδ inhibitor on intracellular ROS production. The extracellular release of superoxide anion, evaluated by measuring the oxidative reduction of cytochrome C, was neither modified by antigen challenge nor feG treatment. However, hispidin, an inhibitor of PKCβ, inhibited the release of superoxide anion from circulating leukocytes in all groups of animals. feG prevented the increased expression of the β1-integrin CD49d on the circulating neutrophils elicited by antigen

Physical activity during video capsule endoscopy correlates with shorter bowel transit time.

Science.gov (United States)

Stanich, Peter P; Peck, Joshua; Murphy, Christopher; Porter, Kyle M; Meyer, Marty M

2017-09-01

 Video capsule endoscopy (VCE) is limited by reliance on bowel motility for propulsion, and lack of physical activity has been proposed as a cause of incomplete studies. Our aim was to prospectively investigate the association between physical activity and VCE bowel transit.  Ambulatory outpatients receiving VCE were eligible for the study. A pedometer was attached at the time of VCE ingestion and step count was recorded at the end of the procedure. VCE completion was assessed by logistic regression models, which included step count (500 steps as one unit). Total transit time was analyzed by Cox proportional hazards models. The hazard ratios (HR) with 95 % confidence interval (CI) indicated the "hazard" of completion, such that HRs > 1 indicated a reduced transit time.  A total of 100 patients were included. VCE was completed in 93 patients (93 %). The median step count was 2782 steps. Step count was not significantly associated with VCE completion (odds ratio 1.45, 95 %CI 0.84, 2.49). Pedometer step count was significantly associated with shorter total, gastric, and small-bowel transit times (HR 1.09, 95 %CI 1.03, 1.16; HR 1.05, 95 %CI 1.00, 1.11; HR 1.07, 95 %CI 1.01, 1.14, respectively). Higher body mass index (BMI) was significantly associated with VCE completion (HR 1.87, 95 %CI 1.18, 2.97) and shorter bowel transit times (HR 1.05, 95 %CI 1.02, 1.08).  Increased physical activity during outpatient VCE was associated with shorter bowel transit times but not with study completion. In addition, BMI was a previously unreported clinical characteristic associated with VCE completion and should be included as a variable of interest in future studies.

Do shorter wavelengths improve contrast in optical mammography?

International Nuclear Information System (INIS)

Taroni, P; Pifferi, A; Torricelli, A; Spinelli, L; Danesini, G M; Cubeddu, R

2004-01-01

The detection of tumours with time-resolved transmittance imaging relies essentially on blood absorption. Previous theoretical and phantom studies have shown that both contrast and spatial resolution of optical images are affected by the optical properties of the background medium, and high absorption and scattering are generally beneficial. Based on these observations, wavelengths shorter than presently used (680-780 nm) could be profitable for optical mammography. A study was thus performed analysing time-resolved transmittance images at 637, 656, 683 and 785 nm obtained from 26 patients bearing 16 tumours and 15 cysts. The optical contrast proved to increase upon decreasing wavelengths for the detection of cancers in late-gated intensity images, with higher gain in contrast for lesions of smaller size (<1.5 cm diameter). For cysts either a progressive increase or decrease in contrast with wavelength was observed in scattering images

A tripeptide Diapin effectively lowers blood glucose levels in male type 2 diabetes mice by increasing blood levels of insulin and GLP-1.

Directory of Open Access Journals (Sweden)

Jifeng Zhang

Full Text Available The prevalence of type 2 diabetes (T2D is rapidly increasing worldwide. Effective therapies, such as insulin and Glucagon-like peptide-1 (GLP-1, require injections, which are costly and result in less patient compliance. Here, we report the identification of a tripeptide with significant potential to treat T2D. The peptide, referred to as Diapin, is comprised of three natural L-amino acids, GlyGlyLeu. Glucose tolerance tests showed that oral administration of Diapin effectively lowered blood glucose after oral glucose loading in both normal C57BL/6J mice and T2D mouse models, including KKay, db/db, ob/ob mice, and high fat diet-induced obesity/T2D mice. In addition, Diapin treatment significantly reduced casual blood glucose in KKay diabetic mice in a time-dependent manner without causing hypoglycemia. Furthermore, we found that plasma GLP-1 and insulin levels in diabetic models were significantly increased with Diapin treatment compared to that in the controls. In summary, our findings establish that a peptide with minimum of three amino acids can improve glucose homeostasis and Diapin shows promise as a novel pharmaceutical agent to treat patients with T2D through its dual effects on GLP-1 and insulin secretion.

The risk of shorter fasting time for pediatric deep sedation.

Science.gov (United States)

Clark, Mathew; Birisci, Esma; Anderson, Jordan E; Anliker, Christina M; Bryant, Micheal A; Downs, Craig; Dalabih, Abdallah

2016-01-01

Current guidelines adopted by the American Academy of Pediatrics calls for prolonged fasting times before performing pediatric procedural sedation and analgesia (PSA). PSA is increasingly provided to children outside of the operating theater by sedation trained pediatric providers and does not require airway manipulation. We investigated the safety of a shorter fasting time compared to a longer and guideline compliant fasting time. We tried to identify the association between fasting time and sedation-related complications. This is a prospective observational study that included children 2 months to 18 years of age and had an American Society of Anesthesiologists physical status classification of I or II, who underwent deep sedation for elective procedures, performed by pediatric critical care providers. Procedures included radiologic imaging studies, electroencephalograms, auditory brainstem response, echocardiograms, Botox injections, and other minor surgical procedures. Subjects were divided into two groups depending on the length of their fasting time (4-6 h and >6 h). Complication rates were calculated and compared between the three groups. In the studied group of 2487 subjects, 1007 (40.5%) had fasting time of 4-6 h and the remaining 1480 (59.5%) subjects had fasted for >6 h. There were no statistically significant differences in any of the studied complications between the two groups. This study found no difference in complication rate in regard to the fasting time among our subjects cohort, which included only healthy children receiving elective procedures performed by sedation trained pediatric critical care providers. This suggests that using shorter fasting time may be safe for procedures performed outside of the operating theater that does not involve high-risk patients or airway manipulation.

Tripeptide amide L-pyroglutamyl-histidyl-L-prolineamide (L-PHP-thyrotropin-releasing hormone, TRH) promotes insulin-producing cell proliferation.

Science.gov (United States)

Luo, LuGuang; Luo, John Z Q; Jackson, Ivor

2013-02-01

A very small tripeptide amide L-pyroglutamyl-L-histidyl-L-prolineamide (L-PHP, Thyrotropin-Releasing Hormone, TRH), was first identified in the brain hypothalamus area. Further studies found that L-PHP was expressed in pancreas. The biological role of pancreatic L-PHP is still not clear. Growing evidence indicates that L-PHP expression in the pancreas may play a pivotal role for pancreatic development in the early prenatal period. However, the role of L-PHP in adult pancreas still needs to be explored. L-PHP activation of pancreatic β cell Ca2+ flow and stimulation of β-cell insulin synthesis and release suggest that L-PHP involved in glucose metabolism may directly act on the β cell separate from any effects via the central nervous system (CNS). Knockout L-PHP animal models have shown that loss of L-PHP expression causes hyperglycemia, which cannot be reversed by administration of thyroid hormone, suggesting that the absence of L-PHP itself is the cause. L-PHP receptor type-1 has been identified in pancreas which provides a possibility for L-PHP autocrine and paracrine regulation in pancreatic function. During pancreatic damage in adult pancreas, L-PHP may protect beta cell from apoptosis and initiate its regeneration through signal pathways of growth hormone in β cells. L-PHP has recently been discovered to affect a broad array of gene expression in the pancreas including growth factor genes. Signal pathways linked between L-PHP and EGF receptor phosphorylation suggest that L-PHP may be an important factor for adult β-cell regeneration, which could involve adult stem cell differentiation. These effects suggest that L-PHP may benefit pancreatic β cells and diabetic therapy in clinic.

The Change of the Family Life Affected by the Shorter Working Time : From the Point of View of the Home Management

OpenAIRE

平田, 道憲

1994-01-01

In Japan, the working time has been decreasing. However, Japanese working people spend more hours per year to work than those in Western countries. The policy of the shorter working time is conducted by the Japanese Government in order that the working people get more free time. This paper examines whether the shorter working time of working members in the family enrich the time use of the other members of the family. Especially, the effect of the shorter working time of husbands to wives...

Representativeness of shorter measurement sessions in long-term indoor air monitoring.

Science.gov (United States)

Maciejewska, M; Szczurek, A

2015-02-01

Indoor air quality (IAQ) considerably influences health, comfort and the overall performance of people who spend most of their lives in confined spaces. For this reason, there is a strong need to develop methods for IAQ assessment. The fundamental issue in the quantitative determination of IAQ is the duration of measurements. Its inadequate choice may result in providing incorrect information and this potentially leads to wrong conclusions. The most complete information may be acquired through long-term monitoring. However it is typically perceived as impractical due to time and cost load. The aim of this study was to determine whether long-term monitoring can be adequately represented by a shorter measurement session. There were considered three measurable quantities: temperature, relative humidity and carbon dioxide concentration. They are commonly recognized as indicatives for IAQ and may be readily monitored. Scaled Kullback-Leibler divergence, also called relative entropy, was applied as a measure of data representativeness. We considered long-term monitoring in a range from 1 to 9 months. Based on our work, the representative data on CO2 concentration may be acquired while performing measurements during 20% of time dedicated to long-term monitoring. In the case of temperature and relative humidity the respective time demand was 50% of long-term monitoring. From our results, in indoor air monitoring strategies, there could be considered shorter measurement sessions, while still collecting data which are representative for long-term monitoring.

The role of romantic attraction and conflict resolution in predicting shorter and longer relationship maintenance among adolescents.

Science.gov (United States)

Appel, Israel; Shulman, Shmuel

2015-04-01

This study examined the role of romantic attraction and conflict resolution patterns in shorter and longer relationship maintenance among adolescent couples. Data were used from 55 couples aged 15-18 years. Partners completed the Romantic Attraction scale and were observed negotiating a disagreement. Three and 6 months later, they were asked to report whether they were still together. Findings indicated that partners' romantic attraction and the tendency to minimize disagreements during interaction predicted shorter relationship maintenance. In contrast, longer relationship maintenance was predicted by partners' capability to resolve conflicts constructively in a positive atmosphere. Findings are embedded and discussed within Fisher's (2004) evolutionary theory of love.

Shorter Decentralized Attribute-Based Encryption via Extended Dual System Groups

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Jie Zhang

2017-01-01

Full Text Available Decentralized attribute-based encryption (ABE is a special form of multiauthority ABE systems, in which no central authority and global coordination are required other than creating the common reference parameters. In this paper, we propose a new decentralized ABE in prime-order groups by using extended dual system groups. We formulate some assumptions used to prove the security of our scheme. Our proposed scheme is fully secure under the standard k-Lin assumption in random oracle model and can support any monotone access structures. Compared with existing fully secure decentralized ABE systems, our construction has shorter ciphertexts and secret keys. Moreover, fast decryption is achieved in our system, in which ciphertexts can be decrypted with a constant number of pairings.

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

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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.

ATM/RB1 mutations predict shorter overall survival in urothelial cancer.

Science.gov (United States)

Yin, Ming; Grivas, Petros; Emamekhoo, Hamid; Mendiratta, Prateek; Ali, Siraj; Hsu, JoAnn; Vasekar, Monali; Drabick, Joseph J; Pal, Sumanta; Joshi, Monika

2018-03-30

Mutations of DNA repair genes, e.g. ATM/RB1 , are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS). ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.

The effect of shorter exposure versus prolonged exposure on treatment outcome in Tourette syndrome and chronic tic disorders - an open trial.

Science.gov (United States)

van de Griendt, Jolande M T M; van Dijk, Maarten K; Verdellen, Cara W J; Verbraak, Marc J P M

2018-01-11

Exposure and response prevention has shown to be an effective strategy and is considered a first-line intervention in the behavioural treatment of tic disorders. Prior research demonstrated significant tic reduction after 12 two hour sessions. In this open trial, the question is addressed whether, relative to these prolonged sessions, exposure sessions of shorter duration yield differential outcome for patients with tic disorders. A total of 29 patients diagnosed with Tourette syndrome (TS) or chronic tic disorder were treated with shorter exposure sessions (1 h), and these data were compared to the data from a study about prolonged exposure (2 h, n = 21). Outcome was measured by the Yale Global Tic Severity Scale (YGTSS). Results suggest that after taking the difference in illness duration between the two groups into account, the effectiveness of shorter exposure sessions is not inferior to that of prolonged exposure. Results suggest that treatment with shorter exposure might be more efficient and more patients can be reached. Future research is needed to gain more insight into the mechanisms underlying the efficacy of behavioural treatments for tics.

N-Terminal Domains in Two-Domain Proteins Are Biased to Be Shorter and Predicted to Fold Faster Than Their C-Terminal Counterparts

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Etai Jacob

2013-04-01

Full Text Available Computational analysis of proteomes in all kingdoms of life reveals a strong tendency for N-terminal domains in two-domain proteins to have shorter sequences than their neighboring C-terminal domains. Given that folding rates are affected by chain length, we asked whether the tendency for N-terminal domains to be shorter than their neighboring C-terminal domains reflects selection for faster-folding N-terminal domains. Calculations of absolute contact order, another predictor of folding rate, provide additional evidence that N-terminal domains tend to fold faster than their neighboring C-terminal domains. A possible explanation for this bias, which is more pronounced in prokaryotes than in eukaryotes, is that faster folding of N-terminal domains reduces the risk for protein aggregation during folding by preventing formation of nonnative interdomain interactions. This explanation is supported by our finding that two-domain proteins with a shorter N-terminal domain are much more abundant than those with a shorter C-terminal domain.

How do shorter working hours affect employee wellbeing? : Shortening working time in Finland

OpenAIRE

Lahdenperä, Netta

2017-01-01

The way work is done is dramatically changing due to digital breakthroughs. Generation Y is entering the workforce with a changed attitude towards work as organizations are increasing their focus towards employee wellbeing. Organizations who adopt the new model of work and understand the importance of the wellbeing of their staff are leading the transition to a more efficient business, better working life and a healthier planet. The thesis explores the numerous effects of shorter working...

Applicability of the shorter ‘Bangladesh regimen’ in high multidrug-resistant tuberculosis settings

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Giovanni Sotgiu

2017-03-01

Full Text Available In spite of the recent introduction of two new drugs (delamanid and bedaquiline and a few repurposed compounds to treat multidrug-resistant and extensively drug-resistant tuberculosis (MDR- and XDR-TB, clinicians are facing increasing problems in designing effective regimens in severe cases. Recently a 9 to 12-month regimen (known as the ‘Bangladesh regimen’ proved to be effective in treating MDR-TB cases. It included an initial phase of 4 to 6 months of kanamycin, moxifloxacin, prothionamide, clofazimine, pyrazinamide, high-dose isoniazid, and ethambutol, followed by 5 months of moxifloxacin, clofazimine, pyrazinamide, and ethambutol. However, recent evidence from Europe and Latin America identified prevalences of resistance to the first-line drugs in this regimen (ethambutol and pyrazinamide exceeding 60%, and of prothionamide exceeding 50%. Furthermore, the proportions of resistance to the two most important pillars of the regimen – quinolones and kanamycin – were higher than 40%. Overall, only 14 out of 348 adult patients (4.0% were susceptible to all of the drugs composing the regimen, and were therefore potentially suitable for the ‘shorter regimen’. A shorter, cheaper, and well-tolerated MDR-TB regimen is likely to impact the number of patients treated and improve adherence if prescribed to the right patients through the systematic use of rapid MTBDRsl testing.

SM50 repeat-polypeptides self-assemble into discrete matrix subunits and promote appositional calcium carbonate crystal growth during sea urchin tooth biomineralization.

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Mao, Yelin; Satchell, Paul G; Luan, Xianghong; Diekwisch, Thomas G H

2016-01-01

The two major proteins involved in vertebrate enamel formation and echinoderm sea urchin tooth biomineralization, amelogenin and SM50, are both characterized by elongated polyproline repeat domains in the center of the macromolecule. To determine the role of polyproline repeat polypeptides in basal deuterostome biomineralization, we have mapped the localization of SM50 as it relates to crystal growth, conducted self-assembly studies of SM50 repeat polypeptides, and examined their effect on calcium carbonate and apatite crystal growth. Electron micrographs of the growth zone of Strongylocentrotus purpuratus sea urchin teeth documented a series of successive events from intravesicular mineral nucleation to mineral deposition at the interface between tooth surface and odontoblast syncytium. Using immunohistochemistry, SM50 was detected within the cytoplasm of cells associated with the developing tooth mineral, at the mineral secreting front, and adjacent to initial mineral deposits, but not in muscles and ligaments. Polypeptides derived from the SM50 polyproline alternating hexa- and hepta-peptide repeat region (SM50P6P7) formed highly discrete, donut-shaped self-assembly patterns. In calcium carbonate crystal growth studies, SM50P6P7 repeat peptides triggered the growth of expansive networks of fused calcium carbonate crystals while in apatite growth studies, SM50P6P7 peptides facilitated the growth of needle-shaped and parallel arranged crystals resembling those found in developing vertebrate enamel. In comparison, SM50P6P7 surpassed the PXX24 polypeptide repeat region derived from the vertebrate enamel protein amelogenin in its ability to promote crystal nucleation and appositional crystal growth. Together, these studies establish the SM50P6P7 polyproline repeat region as a potent regulator in the protein-guided appositional crystal growth that occurs during continuous tooth mineralization and eruption. In addition, our studies highlight the role of species

Exploration of peptides that fit into the thermally vibrating active site of cathepsin K protease by alternating artificial intelligence and molecular simulation

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Nishiyama, Katsuhiko

2017-08-01

Eighteen tripeptides that fit into the thermally vibrating active site of cathepsin K were discovered by alternating artificial intelligence and molecular simulation. The 18 tripeptides fit the active site better than the cysteine protease inhibitor E64, and a better inhibitor of cathepsin K could be designed considering these tripeptides. Among the 18 tripeptides, Phe-Arg-Asp and Tyr-Arg-Asp fit the active site the best and their structural similarity should be considered in the design process. Interesting factors emerged from the structure of the decision tree, and its structural information will guide exploration of potential inhibitor molecules for proteases.

High lung cancer surgical procedure volume is associated with shorter length of stay and lower risks of re-admission and death

DEFF Research Database (Denmark)

Møller, Henrik; Riaz, Sharma P; Holmberg, Lars

2016-01-01

It is debated whether treating cancer patients in high-volume surgical centres can lead to improvement in outcomes, such as shorter length of hospital stay, decreased frequency and severity of post-operative complications, decreased re-admission, and decreased mortality. The dataset for this anal......It is debated whether treating cancer patients in high-volume surgical centres can lead to improvement in outcomes, such as shorter length of hospital stay, decreased frequency and severity of post-operative complications, decreased re-admission, and decreased mortality. The dataset...... to their geographical population. Higher volume hospitals had shorter length of stay and the odds of re-admission were 15% lower in the highest hospital volume quintile compared with the lowest quintile. Mortality risks were 1% after 30 d and 3% after 90 d. Patients from hospitals in the highest volume quintile had...

Hereditary angioedema attacks resolve faster and are shorter after early icatibant treatment.

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Marcus Maurer

Full Text Available BACKGROUND: Attacks of hereditary angioedema (HAE are unpredictable and, if affecting the upper airway, can be lethal. Icatibant is used for physician- or patient self-administered symptomatic treatment of HAE attacks in adults. Its mode of action includes disruption of the bradykinin pathway via blockade of the bradykinin B(2 receptor. Early treatment is believed to shorten attack duration and prevent severe outcomes; however, evidence to support these benefits is lacking. OBJECTIVE: To examine the impact of timing of icatibant administration on the duration and resolution of HAE type I and II attacks. METHODS: The Icatibant Outcome Survey is an international, prospective, observational study for patients treated with icatibant. Data on timings and outcomes of icatibant treatment for HAE attacks were collected between July 2009-February 2012. A mixed-model of repeated measures was performed for 426 attacks in 136 HAE type I and II patients. RESULTS: Attack duration was significantly shorter in patients treated <1 hour of attack onset compared with those treated ≥ 1 hour (6.1 hours versus 16.8 hours [p<0.001]. Similar significant effects were observed for <2 hours versus ≥ 2 hours (7.2 hours versus 20.2 hours [p<0.001] and <5 hours versus ≥ 5 hours (8.0 hours versus 23.5 hours [p<0.001]. Treatment within 1 hour of attack onset also significantly reduced time to attack resolution (5.8 hours versus 8.8 hours [p<0.05]. Self-administrators were more likely to treat early and experience shorter attacks than those treated by a healthcare professional. CONCLUSION: Early blockade of the bradykinin B(2 receptor with icatibant, particularly within the first hour of attack onset, significantly reduced attack duration and time to attack resolution.

Investigations of model polymers: Dynamics of melts and statics of a long chain in a dilute melt of shorter chains

International Nuclear Information System (INIS)

Bishop, M.; Ceperley, D.; Frisch, H.L.; Kalos, M.H.

1982-01-01

We report additional results on a simple model of polymers, namely the diffusion in concentrated polymer systems and the static properties of one long chain in a dilute melt of shorter chains. It is found, for the polymer sizes and time scales amenable to our computer calculations, that there is as yet no evidence for a ''reptation'' regime in a melt. There is some indication of reptation in the case of a single chain moving through fixed obstacles. No statistically significant effect of the change, from excluded volume behavior of the long chain to ideal behavior as the shorter chains grow, is observed

Association of mutations in the hemochromatosis gene with shorter life expectancy

DEFF Research Database (Denmark)

Bathum, L; Christiansen, L; Nybo, H

2001-01-01

BACKGROUND: To investigate whether the frequency of carriers of mutations in the HFE gene associated with hereditary hemochromatosis diminishes with age as an indication that HFE mutations are associated with increased mortality. It is of value in the debate concerning screening for hereditary...... hemochromatosis to determine the significance of heterozygosity. METHODS: Genotyping for mutations in exons 2 and 4 of the HFE gene using denaturing gradient gel electrophoresis in 1784 participants aged 45 to 100 years from 4 population-based studies: all 183 centenarians from the Danish Centenarian Study, 601...... in the distribution of mutations in exon 2 in the different age groups. CONCLUSIONS: In a high-carrier frequency population like Denmark, mutations in HFE show an age-related reduction in the frequency of heterozygotes for C282Y, which suggests that carrier status is associated with shorter life expectancy....

Is equity confined to the shorter term projects - and if not, what does it need?

International Nuclear Information System (INIS)

Cryan, T.

1996-01-01

There are two types of equity investor generally found in shorter term energy projects: energy project developers or sponsors who view a given project as buying or building a business; and financial investors who have viewed an investment as buying a stream of cash flows. This article examines the objectives and needs of these two investor groups, and discusses the principal issues which govern their respective decision-making process. (author)

Shorter preschool, leukocyte telomere length is associated with obesity at age 9 in Latino children.

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Kjaer, T W; Faurholt-Jepsen, D; Mehta, K M; Christensen, V B; Epel, E; Lin, J; Blackburn, E; Wojcicki, J M

2018-04-01

The aim of this study was to determine the potential role of leukocyte telomere length as a biomarker for development of childhood obesity in a low-income Latino population. A birth cohort of Latino children (N = 201) in San Francisco (recruited May 2006-May 2007) was followed until age 9 and assessed annually for obesity and dietary intake. Leukocyte telomere length was measured at 4 and 5 years (n = 102) and assessed as a predictor for obesity at age 9, adjusting for known risk factors. Furthermore, leukocyte telomere length at age 4 and 5 was evaluated as a possible mediator of the relationship between excessive sugar-sweetened beverage consumption and obesity at age 9. Shorter leukocyte telomere length in preschoolers was associated with obesity at age 9 (adjusted odds ratio 0.35, 95% confidence interval 0.13-0.94) after adjustment for known risk factors. Telomere length mediated 11% of the relationship between excessive sugar-sweetened beverage consumption and obesity. Shorter leukocyte telomere length may be an indicator of future obesity risk in high-risk populations as it is particularly sensitive to damage from oxidative stress exposure, including those from sugar-sweetened beverages. © 2017 World Obesity Federation.

Are Shorter Versions of the Positive and Negative Syndrome Scale (PANSS) Doable? A Critical Review.

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Lindenmayer, Jean-Pierre

2017-12-01

The Positive and Negative Syndrome Scale (PANSS) is a well-established assessment tool for measuring symptom severity in schizophrenia. Researchers and clinicians have been interested in the development of a short version of the PANSS that could reduce the burden of its administration for patients and raters. The author presents a comprehensive overview of existing brief PANSS measures, including their strengths and limitations, and discusses some possible next steps. There are two available scales that offer a reduced number of original PANSS items: PANSS-14 and PANSS-19; and two shorter versions that include six items: Brief PANSS and PANSS-6. The PANSS-6 has been tested quite extensively in established trials and appears to demonstrate high sensitivity to change and an established cut off definition for remission. Prospective testing in new antipsychotic treatment trials is still required for these shorter versions of PANSS. In addition, they need to be supplemented with interview guides, as well as provide conversion formulas to translate total scores from the short PANSS versions to the PANSS-30. Both short versions of the PANSS are essentially designed to evaluate response to antipsychotic treatment. Future PANSS scale development needs to address specific measurement of treatment-responsive positive symptoms by including treatment-sensitive items, as well as illness-phase specific PANSS tools.

Minimally invasive oesophagectomy more expensive than open despite shorter length of stay.

Science.gov (United States)

Dhamija, Anish; Dhamija, Ankit; Hancock, Jacquelyn; McCloskey, Barbara; Kim, Anthony W; Detterbeck, Frank C; Boffa, Daniel J

2014-05-01

The minimally invasive oesophagectomy (MIO) approach offers a number of advantages over open approaches including reduced discomfort, shorter length of stay and a faster recovery to baseline status. On the other hand, minimally invasive procedures typically are longer and consume greater disposable instrumentation, potentially resulting in a greater overall cost. The objective of this study was to compare costs associated with various oesophagectomy approaches for oesophageal cancer. An institutional Resource Information Management System (RIMS) was queried for cost data relating to hospital expenditures (as opposed to billings or collections). The RIMS was searched for patients undergoing oesophagectomy for oesophageal cancer between 2003 and 2012 via minimally invasive, open transthoracic (OTT) (including Ivor Lewis, modified McKeown or thoracoabdominal) or transhiatal approaches. Patients that were converted from minimally invasive to open, or involved hybrid procedures, were excluded. A total of 160 oesophagectomies were identified, including 61 minimally invasive, 35 open transthoracic and 64 transhiatal. Costs on the day of surgery averaged higher in the MIO group ($12 476 ± 2190) compared with the open groups, OTT ($8202 ± 2512, P < 0.0001) or OTH ($5809 ± 2575, P < 0.0001). The median costs associated with the entire hospitalization also appear to be higher in the MIO group ($25 935) compared with OTT ($24 440) and OTH ($15 248). The average length of stay was lowest in the MIO group (11 ± 9 days) compared with OTT (19 ± 18 days, P = 0.006) and OTH (18 ± 28 days P = 0.07). The operative mortality was similar in the three groups (MIO = 3%, OTT = 9% and OTH = 3%). The operating theatre costs associated with minimally invasive oesophagectomy are significantly higher than OTT or OTH approaches. Unfortunately, a shorter hospital stay after MIO does not consistently offset higher surgical expense, as total hospital costs trend higher in the MIO patients. In

Shorter telomeres in peripheral blood mononuclear cells from older persons with sarcopenia: results from an exploratory study

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Emanuele eMarzetti

2014-08-01

Full Text Available Background. Telomere shortening in peripheral blood mononuclear cells (PBMCs has been associated with biological age and several chronic degenerative diseases. However, the relationship between telomere length and sarcopenia, a hallmark of the aging process, is unknown. The aim of the present study was therefore to determine whether PBMC telomeres obtained from sarcopenic older persons were shorter relative to non-sarcopenic peers. We further explored if PBMC telomere length was associated with frailty, a major clinical correlate of sarcopenia.Methods. Analyses were conducted in 142 persons aged >/= 65 years referred to a geriatric outpatient clinic (University Hospital. The presence of sarcopenia was established according to the European Working Group on Sarcopenia in Older People criteria, with bioelectrical impedance analysis used for muscle mass estimation. The frailty status was determined by both the Fried’s criteria (physical frailty, PF and a modified Rockwood’s frailty index (FI. Telomere length was measured in PBMCs by quantitative real-time polymerase chain reaction according to the Telomere/Single copy gene ratio (T/S method.Results. Among 142 outpatients (mean age 75.0 ± 6.5 years, 59.2% women, sarcopenia was diagnosed in 23 individuals (19.3%. The PF phenotype was detected in 74 participants (52.1%. The average FI score was 0.46 ± 0.17. PBMC telomeres were shorter in sarcopenic subjects (T/S = 0.21; 95% CI: 0.18 – 0.24 relative to non-sarcopenic individuals (T/S = 0.26; 95%: CI: 0.24 – 0.28; p = 0.01, independent of age, gender, smoking habit, or comorbidity. No significant associations were determined between telomere length and either PF or FI.Conclusion. PBMC telomere length, expressed as T/S values, is shorter in older outpatients with sarcopenia. The cross-sectional assessment of PBMC telomere length is not sufficient at capturing the complex, multidimensional syndrome of frailty.

Optimization of a shorter variable-acquisition time for legs to achieve true whole-body PET/CT images.

Science.gov (United States)

Umeda, Takuro; Miwa, Kenta; Murata, Taisuke; Miyaji, Noriaki; Wagatsuma, Kei; Motegi, Kazuki; Terauchi, Takashi; Koizumi, Mitsuru

2017-12-01

The present study aimed to qualitatively and quantitatively evaluate PET images as a function of acquisition time for various leg sizes, and to optimize a shorter variable-acquisition time protocol for legs to achieve better qualitative and quantitative accuracy of true whole-body PET/CT images. The diameters of legs to be modeled as phantoms were defined based on data derived from 53 patients. This study analyzed PET images of a NEMA phantom and three plastic bottle phantoms (diameter, 5.68, 8.54 and 10.7 cm) that simulated the human body and legs, respectively. The phantoms comprised two spheres (diameters, 10 and 17 mm) containing fluorine-18 fluorodeoxyglucose solution with sphere-to-background ratios of 4 at a background radioactivity level of 2.65 kBq/mL. All PET data were reconstructed with acquisition times ranging from 10 to 180, and 1200 s. We visually evaluated image quality and determined the coefficient of variance (CV) of the background, contrast and the quantitative %error of the hot spheres, and then determined two shorter variable-acquisition protocols for legs. Lesion detectability and quantitative accuracy determined based on maximum standardized uptake values (SUV max ) in PET images of a patient using the proposed protocols were also evaluated. A larger phantom and a shorter acquisition time resulted in increased background noise on images and decreased the contrast in hot spheres. A visual score of ≥ 1.5 was obtained when the acquisition time was ≥ 30 s for three leg phantoms, and ≥ 120 s for the NEMA phantom. The quantitative %errors of the 10- and 17-mm spheres in the leg phantoms were ± 15 and ± 10%, respectively, in PET images with a high CV (scan mean SUV max of three lesions using the current fixed-acquisition and two proposed variable-acquisition time protocols in the clinical study were 3.1, 3.1 and 3.2, respectively, which did not significantly differ. Leg acquisition time per bed position of even 30-90�

Shorter Leukocyte Telomere Length in Relation to Presumed Nonalcoholic Fatty Liver Disease in Mexican-American Men in NHANES 1999–2002

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Janet M. Wojcicki

2017-01-01

Full Text Available Leukocyte telomere length is shorter in response to chronic disease processes associated with inflammation such as diabetes mellitus and coronary artery disease. Data from the National Health and Nutrition Examination Survey (NHANES from 1999 to 2002 was used to explore the relationship between leukocyte telomere length and presumed NAFLD, as indicated by elevated serum alanine aminotransferase (ALT levels, obesity, or abdominal obesity. Logistic regression models were used to evaluate the relationship between telomere length and presumed markers of NAFLD adjusting for possible confounders. There was no relationship between elevated ALT levels, abdominal obesity, or obesity and telomere length in adjusted models in NHANES (OR 1.13, 95% CI 0.48–2.65; OR 1.17, 95% CI 0.52–2.62, resp.. Mexican-American men had shorter telomere length in relation to presumed NAFLD (OR 0.07, 95% CI 0.006–0.79 and using different indicators of NAFLD (OR 0.012, 95% CI 0.0006–0.24. Mexican origin with presumed NAFLD had shorter telomere length than men in other population groups. Longitudinal studies are necessary to evaluate the role of telomere length as a potential predictor to assess pathogenesis of NALFD in Mexicans.

Cost-effectiveness of longer-term versus shorter-term provision of antibiotics in patients with persistent symptoms attributed to Lyme disease

NARCIS (Netherlands)

Berende, A.; Nieuwenhuis, L.; Hofstede, H.J.M. ter; Vos, F.J.; Vogelaar, M.L.; Tromp, M.A.; Middendorp, H. van; Donders, A.R.T.; Evers, A.W.M.; Kullberg, B.J.; Adang, E.M.M.

2018-01-01

BACKGROUND: The treatment of persistent symptoms attributed to Lyme disease remains controversial. Recently, the PLEASE study did not demonstrate any additional clinical benefit of longer-term versus shorter-term antibiotic treatment. However, the economic impact of the antibiotic strategies has not

Homework schedule: an important factor associated with shorter sleep duration among Chinese school-aged children.

Science.gov (United States)

Li, Shenghui; Yang, Qian; Chen, Zhe; Jin, Xingming; Jiang, Fan; Shen, Xiaoming

2014-09-03

This study was designed to examine the hypothesis that homework schedule has adverse impacts on Chinese children's sleep-wake habits and sleep duration. A random sample of 19,299 children aged 5.08 to 11.99 years old participated in a large, cross-sectional survey. A parent-administered questionnaire was completed to quantify children's homework schedule and sleep behaviors. Generally, it was demonstrated that more homework schedule was significantly associated with later bedtime, later wake time, and shorter sleep duration. Among all sleep variables, bedtime and sleep duration during weekdays appeared to be most affected by homework schedule, especially homework schedule during weekdays.

Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

Energy Technology Data Exchange (ETDEWEB)

Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Cardarella, Stephanie [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Dahlberg, Suzanne E. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Araki, Tetsuro [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Lydon, Christine; Jackman, David M.; Rabin, Michael S. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Hatabu, Hiroto [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Johnson, Bruce E. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States)

2015-05-15

Highlights: • Interstitial lung abnormalities were present in 14% of stage IV NSCLC patients. • ILA was more common in older patients with heavier smoking history. • ILA was associated with shorter survival after adjusting for smoking and therapy. • ILA could be an additional independent marker for survival in advanced NSCLC. - Abstract: Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and method: The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results: ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9–9.4] compared to 14.8 months [95%CI: 11.1–18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40). Conclusion: Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC.

Orchestration of Structural, Stereoelectronic, and Hydrogen-Bonding Effects in Stabilizing Triplexes from Engineered Chimeric Collagen Peptides (Pro(X)-Pro(Y)-Gly)6 Incorporating 4(R/S)-Aminoproline.

Science.gov (United States)

Umashankara, Muddegowda; Sonar, Mahesh V; Bansode, Nitin D; Ganesh, Krishna N

2015-09-04

Collagens are an important family of structural proteins found in the extracellular matrix with triple helix as the characteristic structural motif. The collagen triplex is made of three left-handed polyproline II (PPII) helices with each PPII strand consisting of repetitive units of the tripeptide motif X-Y-Gly, where the amino acids X and Y are most commonly proline (Pro) and 4R-hydroxyproline (Hyp), respectively. A C4-endo pucker at X-site and C4-exo pucker at Y-site have been proposed to be the key for formation of triplex, and the nature of pucker is dependent on both the electronegativity and stereochemistry of the substituent. The present manuscript describes a new class of collagen analogues-chimeric cationic collagens-wherein both X- and Y-sites in collagen triad are simultaneously substituted by a combination of 4(R/S)-(OH/NH2/NH3(+)/NHCHO)-prolyl units and triplex stabilities measured at different pHs and in EG:H2O. Based on the results a model has been proposed with the premise that any factors which specifically favor the ring puckers of C4-endo at X-site and C4-exo at Y-site stabilize the PPII conformation and hence the derived triplexes. The pH-dependent triplex stability uniquely observed with ionizable 4-amino substituent on proline enables one to define the critical combination of factors C4-(exo/endo), intraresidue H-bonding, stereoelectronic (R/S) and n → π* interactions in dictating the triplex strength. The ionizable NH2 substituent at C4 in R/S configuration is thus a versatile probe for delineating the triplex stabilizing factors and the results have potential for designing of collagen analogues with customized properties for material and biological applications.

Systemic lupus erythematosus and vitamin D deficiency are associated with shorter telomere length among African Americans: a case-control study.

Directory of Open Access Journals (Sweden)

Brett M Hoffecker

Full Text Available Systemic lupus erythematosus (SLE is a chronic systemic autoimmune disease that disproportionately affects African American females. The causes of SLE are unknown but postulated to be a combination of genetic predisposition and environmental triggers. Vitamin D deficiency is one of the possible environmental triggers. In this study we evaluated relationships between vitamin D status, cellular aging (telomere length and anti-telomere antibodies among African American Gullah women with SLE. The study population included African American female SLE patients and unaffected controls from the Sea Island region of South Carolina. Serum 25-hydroxyvitamin D levels were measured using a nonchromatographic radioimmunoassay. Telomere length was measured in genomic DNA of peripheral blood mononuclear cells (PBMCs by monochrome multiplex quantitative PCR. Anti-telomere antibody levels were measured by enzyme-linked immunosorbent assay (ELISA. Patients with SLE had significantly shorter telomeres and higher anti-telomere antibody titers compared to age- and gender-matched unaffected controls. There was a positive correlation between anti-telomere antibody levels and disease activity among patients and a significant correlation of shorter telomeres with lower 25-hydroxyvitamin D levels in both patients and controls. In follow-up examination of a subset of the patients, the patients who remained vitamin D deficient tended to have shorter telomeres than those patients whose 25-hydroxyvitamin D levels were repleted. Increasing 25-hydroxyvitamin D levels in African American patients with SLE may be beneficial in maintaining telomere length and preventing cellular aging. Moreover, anti-telomere antibody levels may be a promising biomarker of SLE status and disease activity.

Smoking Topography among Korean Smokers: Intensive Smoking Behavior with Larger Puff Volume and Shorter Interpuff Interval.

Science.gov (United States)

Kim, Sungroul; Yu, Sol

2018-05-18

The difference of smoker's topography has been found to be a function many factors, including sex, personality, nicotine yield, cigarette type (i.e., flavored versus non-flavored) and ethnicity. We evaluated the puffing behaviors of Korean smokers and its association with smoking-related biomarker levels. A sample of 300 participants was randomly recruited from metropolitan areas in South Korea. Topography measures during a 24-hour period were obtained using a CReSS pocket device. Korean male smokers smoked two puffs less per cigarette compared to female smokers (15.0 (13.0⁻19.0) vs. 17.5 (15.0⁻21.0) as the median (Interquartile range)), but had a significantly larger puff volume (62.7 (52.7⁻75.5) mL vs. 53.5 (42.0⁻64.2) mL); p = 0.012). The interpuff interval was similar between men and women (8.9 (6.5⁻11.2) s vs. 8.3 (6.2⁻11.0) s; p = 0.122) but much shorter than other study results. A dose-response association ( p = 0.0011) was observed between daily total puff volumes and urinary cotinine concentrations, after controlling for sex, age, household income level and nicotine addiction level. An understanding of the difference of topography measures, particularly the larger puff volume and shorter interpuff interval of Korean smokers, may help to overcome a potential underestimation of internal doses of hazardous byproducts of smoking.

Synthesis and evaluation of {sup 99m}Tc-labeled folate-tripeptide conjugate as a folate receptor-targeeted imaging agent in a tumor-bearing mouse model

Energy Technology Data Exchange (ETDEWEB)

Kim, Myoung Hyoun; Kim, Chang Guhn; Kim, Dae Weung [Dept. of Nuclear Medicine, Wonkwang University School of Medicine, Iksan (Korea, Republic of); Kim, Woo Hyoung [Dept. of Nuclear Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

2015-09-15

The folate receptor (FR) is an attractive molecular target since it is overexpressed in a variety of human tumors. The purpose of the present study was to synthesize and evaluate the feasibility of a novel {sup 99m}Tc-ECG-EDA (Glu-Cys-Gly-ethylenediamine)-folate as an FR-positive tumor imaging agent in a mouse tumor model. ECG-EDA-folate was synthesized using solid phase peptide synthesis (SPPS) and radiolabeled with {sup 99m}Tc using tripeptide ECG as a chelator. FR-positive KB cells were inoculated in athymic nude mice. Following injection of {sup 99m}Tc-ECG-EDA-folate, serial scintigraphy and micro-SPECT/CT imaging were performed at various time points with and without pre-administration of excess free folate. Mean count densities (MCD) for regions of interest drawn on KB tumors and major normal organs at each time point were measured, and uptake ratios of tumor to normal organs were calculated. ECG-EDA-folate was labeled with {sup 99m}Tc with high radiolabeling efficiency and stability (>96 %). FR-positive tumors were clearly visualized on both scintigraphy and micro-SPECT/CT images and the tumor uptake of {sup 99m}Tc-ECG-EDA-folate was markedly suppressed with faint visualization of tumors by pre-administration of excess free folate on serial planar scintigraphy, indicating FR-specific binding of the agent. Furthermore, semiquantitative analysis of MCD data showed again that both tumor MCD and tumor-to-normal organ ratios decreased considerably by pre-administration of excess free folate, supporting FR-specific tumor uptake. Tumor-to-normal organ ratios approximately increased with time after injection until 4 h. The present study demonstrated that 9{sup 99m}Tc-ECG-EDA-folate can bind specifically to FR with clear visualization of FR-positive tumors in a mouse tumor model.

At least 10% shorter C–H bonds in cryogenic protein crystal structures than in current AMBER forcefields

Energy Technology Data Exchange (ETDEWEB)

Pang, Yuan-Ping, E-mail: pang@mayo.edu

2015-03-06

High resolution protein crystal structures resolved with X-ray diffraction data at cryogenic temperature are commonly used as experimental data to refine forcefields and evaluate protein folding simulations. However, it has been unclear hitherto whether the C–H bond lengths in cryogenic protein structures are significantly different from those defined in forcefields to affect protein folding simulations. This article reports the finding that the C–H bonds in high resolution cryogenic protein structures are 10–14% shorter than those defined in current AMBER forcefields, according to 3709 C–H bonds in the cryogenic protein structures with resolutions of 0.62–0.79 Å. Also, 20 all-atom, isothermal–isobaric, 0.5-μs molecular dynamics simulations showed that chignolin folded from a fully-extended backbone formation to the native β-hairpin conformation in the simulations using AMBER forcefield FF12SB at 300 K with an aggregated native state population including standard error of 10 ± 4%. However, the aggregated native state population with standard error reduced to 3 ± 2% in the same simulations except that C–H bonds were shortened by 10–14%. Furthermore, the aggregated native state populations with standard errors increased to 35 ± 3% and 26 ± 3% when using FF12MC, which is based on AMBER forcefield FF99, with and without the shortened C–H bonds, respectively. These results show that the 10–14% bond length differences can significantly affect protein folding simulations and suggest that re-parameterization of C–H bonds according to the cryogenic structures could improve the ability of a forcefield to fold proteins in molecular dynamics simulations. - Highlights: • Cryogenic crystal structures are commonly used in computational studies of proteins. • C–H bonds in the cryogenic structures are shorter than those defined in forcefields. • A survey of 3709 C–H bonds shows that the cryogenic bonds are 10–14% shorter. • The

A shorter and more specific oral sensitization-based experimental model of food allergy in mice.

Science.gov (United States)

Bailón, Elvira; Cueto-Sola, Margarita; Utrilla, Pilar; Rodríguez-Ruiz, Judith; Garrido-Mesa, Natividad; Zarzuelo, Antonio; Xaus, Jordi; Gálvez, Julio; Comalada, Mònica

2012-07-31

Cow's milk protein allergy (CMPA) is one of the most prevalent human food-borne allergies, particularly in children. Experimental animal models have become critical tools with which to perform research on new therapeutic approaches and on the molecular mechanisms involved. However, oral food allergen sensitization in mice requires several weeks and is usually associated with unspecific immune responses. To overcome these inconveniences, we have developed a new food allergy model that takes only two weeks while retaining the main characters of allergic response to food antigens. The new model is characterized by oral sensitization of weaned Balb/c mice with 5 doses of purified cow's milk protein (CMP) plus cholera toxin (CT) for only two weeks and posterior challenge with an intraperitoneal administration of the allergen at the end of the sensitization period. In parallel, we studied a conventional protocol that lasts for seven weeks, and also the non-specific effects exerted by CT in both protocols. The shorter protocol achieves a similar clinical score as the original food allergy model without macroscopically affecting gut morphology or physiology. Moreover, the shorter protocol caused an increased IL-4 production and a more selective antigen-specific IgG1 response. Finally, the extended CT administration during the sensitization period of the conventional protocol is responsible for the exacerbated immune response observed in that model. Therefore, the new model presented here allows a reduction not only in experimental time but also in the number of animals required per experiment while maintaining the features of conventional allergy models. We propose that the new protocol reported will contribute to advancing allergy research. Copyright © 2012 Elsevier B.V. All rights reserved.

Reemission spectra and inelastic processes at interaction of attosecond and shorter duration electromagnetic pulses with atoms

International Nuclear Information System (INIS)

Makarov, D.N.; Matveev, V.I.

2017-01-01

Inelastic processes and the reemission of attosecond and shorter electromagnetic pulses by atoms have been considered within the analytical solution of the Schrödinger equation in the sudden perturbation approximation. A method of calculations with the exact inclusion of spatial inhomogeneity of the field of an ultrashort pulse and the momenta of photons in the reemission processes has been developed. The probabilities of inelastic processes and spectra of reemission of ultrashort electromagnetic pulses by one- and many-electron atoms have been calculated. The results have been presented in the form of analytical formulas.

Use of a novel shorter minimum caliber needle for creating endoscopic tattoos for preoperative localization: a comparative ex vivo study.

Science.gov (United States)

Imai, Kenichiro; Hotta, Kinichi; Ito, Sayo; Yamaguchi, Yuichiro; Kawakami, Takeshi; Wada, Takuya; Igarashi, Kimihiro; Kishida, Yoshihiro; Kinugasa, Yusuke; Kawata, Noboru; Tanaka, Masaki; Kakushima, Naomi; Takizawa, Kohei; Ishiwatari, Hirotoshi; Matsubayashi, Hiroyuki; Ono, Hiroyuki

2017-06-01

In colorectal cancer surgery, inadvertent deep injections during endoscopic tattooing can cause India ink leakage into the peritoneum, leading to complications or to poor visualization of the surgical plane. This ex vivo animal study compared the use of novel shorter, minimum caliber needles versus conventional injection needles for endoscopic tattooing. Four endoscopists used the novel needles and conventional needles to make ten endoscopic tattoos (five tattoos/needle type/endoscopist) in harvested porcine rectum using a saline test-injection method. India ink leakage and the success of the tattoo (i. e. visible, tattoos but for none of the novel needle tattoos ( P  = 0.02). Tattoos created using the novel needles were more successful than those made with the conventional needles: 18/20 (90 %) vs. 11/20 (55 %); P  = 0.01. The use of novel shorter minimum caliber needles may be safe and effective for endoscopic tattooing for preoperative localization prior to colorectal cancer surgery.

Towards shorter wavelength x-ray lasers using a high power, short pulse pump laser

International Nuclear Information System (INIS)

Tighe, W.; Krushelnick, K.; Valeo, E.; Suckewer, S.

1991-05-01

A near-terawatt, KrF* laser system, focussable to power densities >10 18 W/cm 2 has been constructed for use as a pump laser in various schemes aimed at the development of x-ray lasing below 5nm. The laser system along with output characteristics such as the pulse duration, the focal spot size, and the percentage of amplified spontaneous emission (ASE) emitted along with the laser pulse will be presented. Schemes intended to lead to shorter wavelength x-ray emission will be described. The resultant requirements on the pump laser characteristics and the target design will be outlined. Results from recent solid target experiments and two-laser experiments, showing the interaction of a high-power, short pulse laser with a preformed plasma, will be presented. 13 refs., 5 figs

Long-Term Costs and Health Consequences of Issuing Shorter Duration Prescriptions for Patients with Chronic Health Conditions in the English NHS.

Science.gov (United States)

Martin, Adam; Payne, Rupert; Wilson, Edward Cf

2018-06-01

The National Health Service (NHS) in England spends over £9 billion on prescription medicines dispensed in primary care, of which over two-thirds is accounted for by repeat prescriptions. Recently, GPs in England have been urged to limit the duration of repeat prescriptions, where clinically appropriate, to 28 days to reduce wastage and hence contain costs. However, shorter prescriptions will increase transaction costs and thus may not be cost saving. Furthermore, there is evidence to suggest that shorter prescriptions are associated with lower adherence, which would be expected to lead to lower clinical benefit. The objective of this study is to estimate the cost-effectiveness of 3-month versus 28-day repeat prescriptions from the perspective of the NHS. We adapted three previously developed UK policy-relevant models, incorporating transaction (dispensing fees, prescriber time) and drug wastage costs associated with 3-month and 28-day prescriptions in three case studies: antihypertensive medications for prevention of cardiovascular events; drugs to improve glycaemic control in patients with type 2 diabetes; and treatments for depression. In all cases, 3-month prescriptions were associated with lower costs and higher QALYs than 28-day prescriptions. This is driven by assumptions that higher adherence leads to improved disease control, lower costs and improved QALYs. Longer repeat prescriptions may be cost-effective compared with shorter ones. However, the quality of the evidence base on which this modelling is based is poor. Any policy rollout should be within the context of a trial such as a stepped-wedge cluster design.

Discrimination of Urban Spaces with Different Level of Restorativeness Based on the Original and on a Shorter Version of Hartig et al.’s Perceived Restorativeness Scale

Directory of Open Access Journals (Sweden)

Fátima Negrín

2017-10-01

Full Text Available Restorativeness is defined as the potential of the environment to re-establish certain cognitive capacities related to human information processing. The most frequently used instrument for evaluating the restorativeness of places is the Perceived Restorativeness Scale, proposed by Hartig et al. (1991. Later on, shorter versions of the Perceived Restorativeness Scale were proposed. The aim of this work is to evaluate the discriminatory capacity of the original and of a shorter Spanish version of the PRS, considering urban settings previously selected for having different level of restorativeness, according to expert’s criteria. The study involved 244 students and used a 3 × 2 mixed experimental design, with two independent variables: Restorativeness of a place (between-subjects, which was manipulated by showing pictures of settings selected with varying levels of restorativeness (high, medium, low, and length of the scale (within-subjects, which was manipulated by asking subjects to fill in both the original and a shorter version of the PRS. The order of presentation of the two scales was counterbalanced. Results show an appropriate reliability for both version of the scale. Items of being-away, fascination, and coherence of the shorter scale correlate more strongly with the corresponding factor of the original scale, compared to the others factors. Both scales produce similar values for the perceived restorativeness of the different places, except for places with low restorativeness.

Marital disruption is associated with shorter salivary telomere length in a probability sample of older adults.

Science.gov (United States)

Whisman, Mark A; Robustelli, Briana L; Sbarra, David A

2016-05-01

Marital disruption (i.e., marital separation, divorce) is associated with a wide range of poor mental and physical health outcomes, including increased risk for all-cause mortality. One biological intermediary that may help explain the association between marital disruption and poor health is accelerated cellular aging. This study examines the association between marital disruption and salivary telomere length in a United States probability sample of adults ≥50 years of age. Participants were 3526 individuals who participated in the 2008 wave of the Health and Retirement Study. Telomere length assays were performed using quantitative real-time polymerase chain reaction (qPCR) on DNA extracted from saliva samples. Health and lifestyle factors, traumatic and stressful life events, and neuroticism were assessed via self-report. Linear regression analyses were conducted to examine the associations between predictor variables and salivary telomere length. Based on their marital status data in the 2006 wave, people who were separated or divorced had shorter salivary telomeres than people who were continuously married or had never been married, and the association between marital disruption and salivary telomere length was not moderated by gender or neuroticism. Furthermore, the association between marital disruption and salivary telomere length remained statistically significant after adjusting for demographic and socioeconomic variables, neuroticism, cigarette use, body mass, traumatic life events, and other stressful life events. Additionally, results revealed that currently married adults with a history of divorce evidenced shorter salivary telomeres than people who were continuously married or never married. Accelerated cellular aging, as indexed by telomere shortening, may be one pathway through which marital disruption is associated with morbidity and mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risky family processes prospectively forecast shorter telomere length mediated through negative emotions.

Science.gov (United States)

Brody, Gene H; Yu, Tianyi; Shalev, Idan

2017-05-01

This study was designed to examine prospective associations of risky family environments with subsequent levels of negative emotions and peripheral blood mononuclear cell telomere length (TL), a marker of cellular aging. A second purpose was to determine whether negative emotions mediate the hypothesized link between risky family processes and diminished telomere length. Participants were 293 adolescents (age 17 years at the first assessment) and their primary caregivers. Caregivers provided data on risky family processes when the youths were age 17 years, youths reported their negative emotions at age 18 years, and youths' TL was assayed from a blood sample at age 22 years. The results revealed that (a) risky family processes forecast heightened negative emotions (β = .316, p emotions forecast shorter TL (β = -.187, p = .012), and (c) negative emotions served as a mediator connecting risky family processes with diminished TL (indirect effect = -0.012, 95% CI [-0.036, -0.002]). These findings are consistent with the hypothesis that risky family processes presage premature cellular aging through effects on negative emotions, with potential implications for lifelong health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Fulltext PDF

Indian Academy of Sciences (India)

tion, DCM was evaporated and the residue was purified by silica gel chromatography using a mixture of chlo- roform and methanol (99:1) to yield linear tripeptide with unsaturated fused ring as a foam which on cat- alytic hydrogenation in presence of Pd-C (0.100 g) in acetic acid (10 mL) yield both side protected tripeptide.

Urdu translation and validation of shorter version of Positive Affect and Negative Affect Schedule (PANAS) on Pakistani bank employees.

Science.gov (United States)

Akhter, Noreen

2017-10-01

To translate, adapt and validate shorter version of positive affect and negative affect scale on Pakistani corporate employees. This cross-sectional study was conducted in the twin cities of Islamabad and Rawalpindi from October 2014 to December 2015. The study was completed into two independent parts. In part one, the scale was translated by forward translation. Then it was pilot-tested and administered on customer services employees from commercial banks and the telecommunication sector. Data of the pilot study was analysed by using exploratory factor analysis to extract the initial factor of positive affect and negative affect scale. Part two comprised the main study. Commercial bank employees were included in the sample using convenient sampling technique. Data of the main study was analysed using confirmatory factor analysis in order to establish construct validity of positive affect and negative affect scale. There were145 participants in the first part of the study and 495 in the second. Results of confirmatory factor analysis confirmed the two-factor structure of positive affect and negative affect scale suggesting that the scale has two distinct domains, i.e. positive affect and negative affect. The shorter version of positive affect and negative affect scale was found to be a valid and reliable measure.

42 CFR 137.78 - May a Self-Governance Tribe negotiate a funding agreement for a term longer or shorter than one...

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false May a Self-Governance Tribe negotiate a funding agreement for a term longer or shorter than one year? 137.78 Section 137.78 Public Health PUBLIC HEALTH... SERVICES TRIBAL SELF-GOVERNANCE Funding General § 137.78 May a Self-Governance Tribe negotiate a funding...

"Taller and Shorter": Human 3-D Spatial Memory Distorts Familiar Multilevel Buildings.

Directory of Open Access Journals (Sweden)

Thomas Brandt

Full Text Available Animal experiments report contradictory findings on the presence of a behavioural and neuronal anisotropy exhibited in vertical and horizontal capabilities of spatial orientation and navigation. We performed a pointing experiment in humans on the imagined 3-D direction of the location of various invisible goals that were distributed horizontally and vertically in a familiar multilevel hospital building. The 21 participants were employees who had worked for years in this building. The hypothesis was that comparison of the experimentally determined directions and the true directions would reveal systematic inaccuracy or dimensional anisotropy of the localizations. The study provides first evidence that the internal representation of a familiar multilevel building was distorted compared to the dimensions of the true building: vertically 215% taller and horizontally 51% shorter. This was not only demonstrated in the mathematical reconstruction of the mental model based on the analysis of the pointing experiments but also by the participants' drawings of the front view and the ground plan of the building. Thus, in the mental model both planes were altered in different directions: compressed for the horizontal floor plane and stretched for the vertical column plane. This could be related to human anisotropic behavioural performance of horizontal and vertical navigation in such buildings.

"Taller and Shorter": Human 3-D Spatial Memory Distorts Familiar Multilevel Buildings.

Science.gov (United States)

Brandt, Thomas; Huber, Markus; Schramm, Hannah; Kugler, Günter; Dieterich, Marianne; Glasauer, Stefan

2015-01-01

Animal experiments report contradictory findings on the presence of a behavioural and neuronal anisotropy exhibited in vertical and horizontal capabilities of spatial orientation and navigation. We performed a pointing experiment in humans on the imagined 3-D direction of the location of various invisible goals that were distributed horizontally and vertically in a familiar multilevel hospital building. The 21 participants were employees who had worked for years in this building. The hypothesis was that comparison of the experimentally determined directions and the true directions would reveal systematic inaccuracy or dimensional anisotropy of the localizations. The study provides first evidence that the internal representation of a familiar multilevel building was distorted compared to the dimensions of the true building: vertically 215% taller and horizontally 51% shorter. This was not only demonstrated in the mathematical reconstruction of the mental model based on the analysis of the pointing experiments but also by the participants' drawings of the front view and the ground plan of the building. Thus, in the mental model both planes were altered in different directions: compressed for the horizontal floor plane and stretched for the vertical column plane. This could be related to human anisotropic behavioural performance of horizontal and vertical navigation in such buildings.

TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10min or shorter.

Science.gov (United States)

Durukan Tolvanen, A; Tatlisumak, E; Pedrono, E; Abo-Ramadan, U; Tatlisumak, T

2017-05-15

Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30min, n=6-8pergroup) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10min of ischemia followed up to 1week after reperfusion remained free of infarction and any MRI signal change. Thus, 10min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA. Copyright © 2017 Elsevier B.V. All rights reserved.

Shorter epilepsy duration is associated with better seizure outcome in temporal lobe epilepsy surgery

Directory of Open Access Journals (Sweden)

Lucas Crociati Meguins

2015-03-01

Full Text Available Objective To investigate the influence of patient’s age and seizure onset on surgical outcome of temporal lobe epilepsy (TLE. Method A retrospective observational investigation performed from a cohort of patients from 2000 to 2012. Results A total of 229 patients were included. One-hundred and eleven of 179 patients (62% were classified as Engel I in the group with < 50 years old, whereas 33 of 50 (66% in the group with ≥ 50 years old group (p = 0.82. From those Engel I, 88 (61% reported epilepsy duration inferior to 10 years and 56 (39% superior to 10 years (p < 0.01. From the total of patients not seizure free, 36 (42% reported epilepsy duration inferior to 10 years and 49 (58% superior to 10 years (p < 0.01. Conclusion Patients with shorter duration of epilepsy before surgery had better postoperative seizure control than patients with longer duration of seizures.

Shorter Versus Longer Shift Durations to Mitigate Fatigue and Fatigue-Related Risks in Emergency Medical Services Personnel and Related Shift Workers: A Systematic Review

Science.gov (United States)

2018-01-11

Background: This study comprehensively reviewed the literature on the impact of shorter versus longer shifts on critical and important outcomes for Emergency Medical Services (EMS) personnel and related shift worker groups. Methods: Six databases (e....

Spindle assembly checkpoint protein expression correlates with cellular proliferation and shorter time to recurrence in ovarian cancer.

LENUS (Irish Health Repository)

McGrogan, Barbara

2014-07-01

Ovarian carcinoma (OC) is the most lethal of the gynecological malignancies, often presenting at an advanced stage. Treatment is hampered by high levels of drug resistance. The taxanes are microtubule stabilizing agents, used as first-line agents in the treatment of OC that exert their apoptotic effects through the spindle assembly checkpoint. BUB1-related protein kinase (BUBR1) and mitotic arrest deficient 2 (MAD2), essential spindle assembly checkpoint components, play a key role in response to taxanes. BUBR1, MAD2, and Ki-67 were assessed on an OC tissue microarray platform representing 72 OC tumors of varying histologic subtypes. Sixty-one of these patients received paclitaxel and platinum agents combined; 11 received platinum alone. Overall survival was available for all 72 patients, whereas recurrence-free survival (RFS) was available for 66 patients. Increased BUBR1 expression was seen in serous carcinomas, compared with other histologies (P = .03). Increased BUBR1 was significantly associated with tumors of advanced stage (P = .05). Increased MAD2 and BUBR1 expression also correlated with increased cellular proliferation (P < .0002 and P = .02, respectively). Reduced MAD2 nuclear intensity was associated with a shorter RFS (P = .03), in ovarian tumors of differing histologic subtype (n = 66). In this subgroup, for those women who received paclitaxel and platinum agents combined (n = 57), reduced MAD2 intensity also identified women with a shorter RFS (P < .007). For the entire cohort of patients, irrespective of histologic subtype or treatment, MAD2 nuclear intensity retained independent significance in a multivariate model, with tumors showing reduced nuclear MAD2 intensity identifying patients with a poorer RFS (P = .05).

The association between post-traumatic stress disorder and shorter telomere length: A systematic review and meta-analysis.

Science.gov (United States)

Li, Xuemei; Wang, Jiang; Zhou, Jianghua; Huang, Pan; Li, Jiping

2017-08-15

Post-traumatic stress disorder (PTSD) is a common psychiatric disorder, which may accelerate aging. Many study have investigated the association between telomeres length and PTSD, but results from published studies are contradictory. Therefore, Meta-analysis approaches were conducted to give more precise estimate of relationship between telomere length and PTSD. We systematically reviewed the databases of PUBMED, PsycINFO, Medline(Ovid SP) and EMBASE for all articles on the association between telomere length and PTSD. Data were summarized by using random-effects in the meta-analysis. The heterogeneity among studies were examined by using Cochrane's Q statistic and I-squared. Five eligible studies containing 3851 participants were included in our meta-analysis. Shorten telomere length was significantly associated with PTSD with mean difference of -0.19( 95% CI: -0.27, -0.01; P<0.001) with I-square of 96%. The results from subgroup analysis demonstrated that shorter telomere length was significantly associated with PTSD across all gender groups, with mean difference of -0.15( 95% CI: -0.29, -0.01; P=0.04) for female, mean difference of -0.17( 95% CI: -0.19, -0.15; P<0.001) for male. Meanwhile, shorten telomere length was significantly associated with sexual assault(mean difference =-0.15, 95% CI: -0.29, -0.01), childhood trauma (mean difference =-0.08, 95% CI: -0.19, -0.07), but not combat (mean difference =-0.39, 95% CI: -0.83, 0.05). Compared to the individuals without PTSD, individuals with PTSD have shorter telomere length, which has implications for early intervention and timely treatment to prevent future adverse health outcomes. Copyright © 2017. Published by Elsevier B.V.

Prenatal paracetamol exposure is associated with shorter anogenital distance in male infants

Science.gov (United States)

Fisher, B.G.; Thankamony, A.; Hughes, I.A.; Ong, K.K.; Dunger, D.B.; Acerini, C.L.

2016-01-01

STUDY QUESTION What is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8–14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW? SUMMARY ANSWER Intrauterine paracetamol exposure during 8–14 weeks of gestation is associated with shorter AGD from birth to 24 months of age. WHAT IS ALREADY KNOWN The increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism. STUDY DESIGN, SIZE, DURATION Prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHOD Mothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8–14 weeks. AGD measurements were available for 434 male infants. MAIN RESULTS AND THE ROLE OF CHANCE Paracetamol exposure during 8–14

Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis

Energy Technology Data Exchange (ETDEWEB)

Khan, Atif J., E-mail: atif.j.khan@rutgers.edu [Department of Radiation Oncology, Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Rafique, Raza [Suleman Dawood School of Business, Lahore University of Management Sciences, Lahore (Pakistan); Zafar, Waleed [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Shah, Chirag [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Haffty, Bruce G. [Department of Radiation Oncology, Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Vicini, Frank [Michigan HealthCare Professionals, Farmington Hills, Michigan (United States); Jamshed, Arif [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Zhao, Yao [Rutgers University School of Business, Newark, New Jersey (United States)

2017-02-01

Purpose: Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. Methods and Materials: We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. Results: The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Conclusions: Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis

International Nuclear Information System (INIS)

Khan, Atif J.; Rafique, Raza; Zafar, Waleed; Shah, Chirag; Haffty, Bruce G.; Vicini, Frank; Jamshed, Arif; Zhao, Yao

2017-01-01

Purpose: Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. Methods and Materials: We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. Results: The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Conclusions: Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

Insights into Unfolded Proteins from the Intrinsic phi/psi Propensities of the AAXAA Host-Guest Series

Czech Academy of Sciences Publication Activity Database

Towse, C. L.; Vymětal, Jiří; Vondrášek, Jiří; Daggett, V.

2016-01-01

Roč. 110, č. 2 (2016), s. 348-361 ISSN 0006-3495 R&D Projects: GA MŠk(CZ) LH11020 Institutional support: RVO:61388963 Keywords : polyproline-II helix * beta-sheet protein * random-coil behavior Subject RIV: BO - Biophysics Impact factor: 3.656, year: 2016

The Glycated Albumin (GA) to HbA1c Ratio Reflects Shorter-Term Glycemic Control than GA: Analysis of Patients with Fulminant Type 1 Diabetes.

Science.gov (United States)

Koga, Masafumi; Inada, Shinya; Nakao, Taisei; Kawamori, Ryuzo; Kasayama, Soji

2017-01-01

Glycated albumin (GA) reflects shorter-term glycemic control than HbA1c. We have reported that HbA1c is paradoxically increased in diabetic patients whose glycemic control deteriorated before ameliorating. In this study, we analyzed paradoxical increases of glycemic control indicators after treatment in patients with fulminant type 1 diabetes (FT1D). We also investigated whether the GA/HbA1c ratio may reflect shorter-term glycemic control than GA. Five FT1D patients whose post-treatment HbA1c and GA levels were measured were enrolled. We also used a formula to estimate HbA1c and GA from the fictitious models of changes in plasma glucose in FT1D patients. In this model, the periods during which HbA1c, GA, and the GA/HbA1c ratio were higher than at the first visit were compared. In addition, the half-life for the GA/HbA1c ratio was calculated in accordance with the half-lives for HbA1c and GA (36 and 14 days, respectively). In all FT1D patients, HbA1c levels 2-4 weeks after treatment were increased, with three patients (60%) experiencing an increase of GA levels. In contrast, an increase of the GA/HbA1c ratio was observed in only one patient. In all of the different models of changes in plasma glucose in FT1D patients, the length of time during which the values were higher than at the first visit was in the order of HbA1c > GA > GA/HbA1c ratio. The half-life for the GA/HbA1c ratio was 9 days, shorter than GA. These findings suggest that the GA/HbA1c ratio reflects shorter-term glycemic control than GA. © 2016 Wiley Periodicals, Inc.

Shorter preschool, leukocyte telomere length is associated with obesity at age 9 in Latino children

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Kjaer, Thora Wesenberg; Faurholt-Jepsen, D; Mehta, K M

2018-01-01

The aim of this study was to determine the potential role of leukocyte telomere length as a biomarker for development of childhood obesity in a low-income Latino population. A birth cohort of Latino children (N = 201) in San Francisco (recruited May 2006-May 2007) was followed until age 9...... and assessed annually for obesity and dietary intake. Leukocyte telomere length was measured at 4 and 5 years (n = 102) and assessed as a predictor for obesity at age 9, adjusting for known risk factors. Furthermore, leukocyte telomere length at age 4 and 5 was evaluated as a possible mediator...... of the relationship between excessive sugar-sweetened beverage consumption and obesity at age 9. Shorter leukocyte telomere length in preschoolers was associated with obesity at age 9 (adjusted odds ratio 0.35, 95% confidence interval 0.13-0.94) after adjustment for known risk factors. Telomere length mediated 11...

Critical Role of PepT1 in Promoting Colitis-Associated Cancer and Therapeutic Benefits of the Anti-inflammatory PepT1-Mediated Tripeptide KPV in a Murine ModelSummary

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Emilie Viennois

2016-05-01

Full Text Available Background & Aims: The human intestinal peptide transporter 1 (hPepT1, is expressed in the small intestine at low levels in the healthy colon and up-regulated during inflammatory bowel disease. hPepT1 plays a role in mouse colitis and human studies have shown that chronic intestinal inflammation leads to colorectal cancer (colitis-associated cancer; CAC. Hence, we assessed here the role of PepT1 in CAC. Methods: Mice with hPepT1 overexpression in intestinal epithelial cells (transgenic [TG] or PepT1 (PepT1-knockout [KO] deletion were used and CAC was induced by azoxymethane/dextran sodium sulfate. Results: TG mice had larger tumor sizes, increased tumor burdens, and increased intestinal inflammation compared with wild-type (WT mice. Conversely, tumor number and size and intestinal inflammation were decreased significantly in PepT1-KO mice. Proliferating crypt cells were increased in TG mice and decreased in PepT1-KO mice. Analysis of human colonic biopsy specimens showed increased expression of PepT1 in patients with colorectal cancer, suggesting that PepT1 might be targeted for the treatment of CAC. The use of an anti-inflammatory tripeptide Lys-Pro-Val (KPV transported by PepT1 was able to prevent carcinogenesis in WT mice. When administered to PepT1-KO mice, KPV did not trigger any of the inhibitory effect on tumorigenesis observed in WT mice. Conclusions: The observations that PepT1 was highly expressed in human colorectal tumor and that its overexpression and deletion in mice increased and decreased colitis-associated tumorigenesis, respectively, suggest that PepT1 is a potential therapeutic target for the treatment of colitis-associated tumorigenesis. Keywords: Colitis-Associated Cancer, Intestinal Inflammation, PepT1, KPV Peptide

Systematic Moiety Variations of Ultrashort Peptides Produce Profound Effects on Self-Assembly, Nanostructure Formation, Hydrogelation, and Phase Transition

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Chan, Kiat Hwa

2017-10-04

Self-assembly of small biomolecules is a prevalent phenomenon that is increasingly being recognised to hold the key to building complex structures from simple monomeric units. Small peptides, in particular ultrashort peptides containing up to seven amino acids, for which our laboratory has found many biomedical applications, exhibit immense potential in this regard. For next-generation applications, more intricate control is required over the self-assembly processes. We seek to find out how subtle moiety variation of peptides can affect self-assembly and nanostructure formation. To this end, we have selected a library of 54 tripeptides, derived from systematic moiety variations from seven tripeptides. Our study reveals that subtle structural changes in the tripeptides can exert profound effects on self-assembly, nanostructure formation, hydrogelation, and even phase transition of peptide nanostructures. By comparing the X-ray crystal structures of two tripeptides, acetylated leucine-leucine-glutamic acid (Ac-LLE) and acetylated tyrosine-leucine-aspartic acid (Ac-YLD), we obtained valuable insights into the structural factors that can influence the formation of supramolecular peptide structures. We believe that our results have major implications on the understanding of the factors that affect peptide self-assembly. In addition, our findings can potentially assist current computational efforts to predict and design self-assembling peptide systems for diverse biomedical applications.

Adjuvant therapy for melanoma in dogs: results of randomized clinical trials using surgery, liposome-encapsulated muramyl tripeptide, and granulocyte macrophage colony-stimulating factor.

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MacEwen, E G; Kurzman, I D; Vail, D M; Dubielzig, R R; Everlith, K; Madewell, B R; Rodriguez, C O; Phillips, B; Zwahlen, C H; Obradovich, J; Rosenthal, R C; Fox, L E; Rosenberg, M; Henry, C; Fidel, J

1999-12-01

Spontaneous canine oral melanoma (COM) is a highly metastatic cancer, resistant to chemotherapy, and can serve as a model for cancer immunotherapy. Liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) can activate the tumoricidal activity of the monocyte-macrophage system following i.v. injection. The objective of these studies was to evaluate the therapeutic effectiveness of L-MTP-PE administered alone and combined with recombinant canine granulocyte macrophage colony-stimulating factor (rcGM-CSF) in dogs undergoing surgery for oral melanoma. Ninety-eight dogs with histologically confirmed, clinically staged, oral melanoma were entered into two randomized, double-blind, surgical adjuvant trials. In trial 1, 50 dogs were stratified based on clinical stage and randomized to once a week L-MTP-PE or lipid equivalent (control). When all of the clinical stages were combined, no difference in disease-free survival or in survival time (ST) were detected. However, within stage I, dogs receiving L-MTP-PE had a significant increase in ST compared with control, with 80% of the dogs treated with L-MTP-PE still alive at >2 years. Within each stage II and stage III, there was no difference detected between the treatment groups. In trial 2, 48 dogs were stratified on the basis of clinical stage and extent of surgery (simple resection or radical excision), treated with L-MTP-PE two times a week, and randomized to rcGM-CSF or saline (placebo) given s.c. daily for 9 weeks. Within each stage and when all of the stages were combined, there was no difference between the treatment groups. In both studies, stage I COM is associated with a better prognosis. No effect on survival was observed with regard to tumor location in the oral cavity, sex, type/extent of surgery, or age. In a subset of dogs tested, pulmonary alveolar macrophage cytotoxicity was enhanced with combined rcGM-CSF and L-MTP-PE but not in dogs treated with L-MTP-PE alone. The present study

Greater reproductive investment, but shorter lifespan, in agrosystem than in natural-habitat toads

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Francisco Javier Zamora-Camacho

2017-09-01

Full Text Available Global amphibian decline is due to several factors: habitat loss, anthropization, pollution, emerging diseases, and global warming. Amphibians, with complex life cycles, are particularly susceptible to habitat alterations, and their survival may be impaired in anthropized habitats. Increased mortality is a well-known consequence of anthropization. Life-history theory predicts higher reproductive investment when mortality is increased. In this work, we compared age, body size, and different indicators of reproductive investment, as well as prey availability, in natterjack toads (Epidalea calamita from agrosystems and adjacent natural pine groves in Southwestern Spain. Mean age was lower in agrosystems than in pine groves, possibly as a consequence of increased mortality due to agrosystem environmental stressors. Remarkably, agrosystem toads were larger despite being younger, suggesting accelerated growth rate. Although we detected no differences in prey availability between habitats, artificial irrigation could shorten aestivation in agrosystems, thus increasing energy trade. Moreover, agrosystem toads exhibited increased indicators of reproductive investment. In the light of life-history theory, agrosystem toads might compensate for lesser reproductive events—due to shorter lives—with a higher reproductive investment in each attempt. Our results show that agrosystems may alter demography, which may have complex consequences on both individual fitness and population stability.

A Kinetic Model Explains Why Shorter and Less Affine Enzyme-recruiting Oligonucleotides Can Be More Potent

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Lykke Pedersen

2014-01-01

Full Text Available Antisense oligonucleotides complementary to RNA targets promise generality and ease of drug design. The first systemically administered antisense drug was recently approved for treatment and others are in clinical development. Chemical modifications that increase the hybridization affinity of oligonucleotides are reasoned to confer higher potency, i.e., modified oligonucleotides can be dosed at lower concentrations to achieve the same effect. Surprisingly, shorter and less affine oligonucleotides sometimes display increased potency. To explain this apparent contradiction, increased uptake or decreased propensity to form structures have been suggested as possible mechanisms. Here, we provide an alternative explanation that invokes only the kinetics behind oligonucleotide-mediated cleavage of RNA targets. A model based on the law of mass action predicts, and experiments support, the existence of an optimal binding affinity. Exaggerated affinity, and not length per se, is detrimental to potency. This finding clarifies how to optimally apply high-affinity modifications in the discovery of potent antisense oligonucleotide drugs.

Effects of shorter versus longer storage time of transfused red blood cells in adult ICU patients

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Rygård, Sofie L; Jonsson, Andreas B; Madsen, Martin B

2018-01-01

on the effects of shorter versus longer storage time of transfused RBCs on outcomes in ICU patients. METHODS: We conducted a systematic review with meta-analyses and trial sequential analyses (TSA) of randomised clinical trials including adult ICU patients transfused with fresher versus older or standard issue...... blood. RESULTS: We included seven trials with a total of 18,283 randomised ICU patients; two trials of 7504 patients were judged to have low risk of bias. We observed no effects of fresher versus older blood on death (relative risk 1.04, 95% confidence interval (CI) 0.97-1.11; 7349 patients; TSA......-adjusted CI 0.93-1.15), adverse events (1.26, 0.76-2.09; 7332 patients; TSA-adjusted CI 0.16-9.87) or post-transfusion infections (1.07, 0.96-1.20; 7332 patients; TSA-adjusted CI 0.90-1.27). The results were unchanged by including trials with high risk of bias. TSA confirmed the results and the required...

Shorter Fallow Cycles Affect the Availability of Noncrop Plant Resources in a Shifting Cultivation System

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Sarah Paule. Dalle

2006-12-01

Full Text Available Shifting cultivation systems, one of the most widely distributed forms of agriculture in the tropics, provide not only crops of cultural significance, but also medicinal, edible, ritual, fuel, and forage resources, which contribute to the livelihoods, health, and cultural identity of local people. In many regions across the globe, shifting cultivation systems are undergoing important changes, one of the most pervasive being a shortening of the fallow cycle. Although there has been much attention drawn to declines in crop yields in conjunction with reductions in fallow times, little if any research has focused on the dynamics of noncrop plant resources. In this paper, we use a data set of 26 fields of the same age, i.e., ~1.5 yr, but differing in the length and frequency of past fallow cycles, to examine the impact of shorter fallow periods on the availability of noncrop plant resources. The resources examined are collected in shifting cultivation fields by the Yucatec Maya in Quintana Roo, Mexico. These included firewood, which is cut from remnant trees and stumps spared at the time of felling, and 17 forage species that form part of the weed vegetation. Firewood showed an overall decrease in basal area with shorter fallow cycles, which was mostly related to the smaller diameter of the spared stumps and trees in short-fallow milpas. In contrast, forage species showed a mixed response. Species increasing in abundance in short-fallow milpas tended to be short-lived herbs and shrubs often with weedy habits, whereas those declining in abundance were predominantly pioneer trees and animal-dispersed species. Coppicing tree species showed a neutral response to fallow intensity. Within the cultural and ecological context of our study area, we expect that declines in firewood availability will be most significant for livelihoods because of the high reliance on firewood for local fuel needs and the fact that the main alternative source of firewood, forest

Hypermetabolism in ALS is associated with greater functional decline and shorter survival.

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Steyn, Frederik J; Ioannides, Zara A; van Eijk, Ruben P A; Heggie, Susan; Thorpe, Kathryn A; Ceslis, Amelia; Heshmat, Saman; Henders, Anjali K; Wray, Naomi R; van den Berg, Leonard H; Henderson, Robert D; McCombe, Pamela A; Ngo, Shyuan T

2018-04-29

To determine the prevalence of hypermetabolism, relative to body composition, in amyotrophic lateral sclerosis (ALS) and its relationship with clinical features of disease and survival. Fifty-eight patients with clinically definite or probable ALS as defined by El Escorial criteria, and 58 age and sex-matched control participants underwent assessment of energy expenditure. Our primary outcome was the prevalence of hypermetabolism in cases and controls. Longitudinal changes in clinical parameters between hypermetabolic and normometabolic patients with ALS were determined for up to 12 months following metabolic assessment. Survival was monitored over a 30-month period following metabolic assessment. Hypermetabolism was more prevalent in patients with ALS than controls (41% vs 12%, adjusted OR=5.4; pALS. Mean lower motor neuron score (SD) was greater in hypermetabolic patients when compared with normometabolic patients (4 (0.3) vs 3 (0.7); p=0.04). In the 12 months following metabolic assessment, there was a greater change in Revised ALS Functional Rating Scale score in hypermetabolic patients when compared with normometabolic patients (-0.68 points/month vs -0.39 points/month; p=0.01). Hypermetabolism was inversely associated with survival. Overall, hypermetabolism increased the risk of death during follow-up to 220% (HR 3.2, 95% CI 1.1 to 9.4, p=0.03). Hypermetabolic patients with ALS have a greater level of lower motor neuron involvement, faster rate of functional decline and shorter survival. The metabolic index could be important for informing prognosis in ALS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Regulation of immune responsiveness in vivo by disrupting an early T-cell signaling event using a cell-permeable peptide.

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David M Guimond

Full Text Available The inducible T cell kinase (ITK regulates type 2 (Th2 cytokines that provide defense against certain parasitic and bacterial infections and are involved in the pathogenesis of lung inflammation such as allergic asthma. Activation of ITK requires the interaction of its SH3 domain with the poly-proline region of its signaling partner, the SH2 domain containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76. The specific disruption of the ITK-SH3/SLP-76 poly-proline interaction in vitro by a cell-permeable competitive inhibitor peptide (R9-QQP interferes with the activation of ITK and the transduction of its cellular functions in T lymphocytes. In the present investigation, we assessed the effects of R9-QQP treatment on the induction of an in vivo immune response as represented by lung inflammation in a murine model of allergic asthma. We found that mice treated with R9-QQP and sensitized and challenged with the surrogate allergen ovalbumin (OVA display significant inhibition of lung inflammation in a peptide-specific manner. Thus, parameters of the allergic response, such as airway hyper-responsiveness, suppression of inflammatory cell infiltration, reduction of bronchial mucus accumulation, and production of relevant cytokines from draining lymph nodes were significantly suppressed. These findings represent the first demonstration of the biological significance of the interaction between ITK and SLP-76 in the induction of an immune response in a whole animal model and specifically underscore the significance of the ITK-SH3 domain interaction with the poly-proline region of SLP-76 in the development of an inflammatory response. Furthermore, the experimental approach of intracellular peptide-mediated inhibition might be applicable to the study of other important intracellular interactions thus providing a paradigm for dissecting signal transduction pathways.

SHORTER, Aylward. African recruits and missionary conscripts: the White Fathers and the Great War (1914 – 1922. London: Missionaries of Africa History Project, 2007. 270 p. ISBN: 9780955523502

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Jefferson Olivatto da Silva

2011-09-01

Full Text Available Resenha do livroSHORTER, Aylward. African recruits and missionary conscripts: the White Fathers and the Great War (1914 – 1922. London: Missionaries of Africa History Project, 2007. 270 p. ISBN: 9780955523502

Shorter Ground Contact Time and Better Running Economy: Evidence From Female Kenyan Runners.

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Mooses, Martin; Haile, Diresibachew W; Ojiambo, Robert; Sang, Meshack; Mooses, Kerli; Lane, Amy R; Hackney, Anthony C

2018-06-25

Mooses, M, Haile, DW, Ojiambo, R, Sang, M, Mooses, K, Lane, AR, and Hackney, AC. Shorter ground contact time and better running economy: evidence from female Kenyan runners. J Strength Cond Res XX(X): 000-000, 2018-Previously, it has been concluded that the improvement in running economy (RE) might be considered as a key to the continued improvement in performance when no further increase in V[Combining Dot Above]O2max is observed. To date, RE has been extensively studied among male East African distance runners. By contrast, there is a paucity of data on the RE of female East African runners. A total of 10 female Kenyan runners performed 3 × 1,600-m steady-state run trials on a flat outdoor clay track (400-m lap) at the intensities that corresponded to their everyday training intensities for easy, moderate, and fast running. Running economy together with gait characteristics was determined. Participants showed moderate to very good RE at the first (202 ± 26 ml·kg·km) and second (188 ± 12 ml·kg·km) run trials, respectively. Correlation analysis revealed significant relationship between ground contact time (GCT) and RE at the second run (r = 0.782; p = 0.022), which represented the intensity of anaerobic threshold. This study is the first to report the RE and gait characteristics of East African female athletes measured under everyday training settings. We provided the evidence that GCT is associated with the superior RE of the female Kenyan runners.

High Numbers of Stromal Cancer-Associated Fibroblasts Are Associated With a Shorter Survival Time in Cats With Oral Squamous Cell Carcinoma.

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Klobukowska, H J; Munday, J S

2016-11-01

Cancer-associated fibroblasts (CAFs) are fibroblastic cells that express α-smooth muscle actin and have been identified in the stroma of numerous epithelial tumors. The presence of CAFs within the tumor stroma has been associated with a poorer prognosis in some human cancers, including oral squamous cell carcinomas (SCCs). Cats frequently develop oral SCCs, and although these are generally highly aggressive neoplasms, there is currently a lack of prognostic markers for these tumors. The authors investigated the prognostic value of the presence of CAFs within the stroma of oral SCC biopsy specimens from 47 cats. In addition, several epidemiologic, clinical, and histologic variables were also assessed for prognostic significance. A CAF-positive stroma was identified in 35 of 47 SCCs (74.5%), and the median survival time (ST) of cats with CAF-positive SCCs (35 days) was significantly shorter than that of cats with CAF-negative SCCs (48.5 days) (P = .031). ST was also associated with the location of the primary tumor (P = .0018): the median ST for oropharyngeal SCCs (179 days) was significantly longer than for maxillary (43.5 days; P = .047), mandibular (42 days; P = .022), and sublingual SCCs (22.5 days; P = .0005). The median ST of sublingual SCCs was also shorter compared with maxillary SCCs (P = .0017). Furthermore, a significant association was identified between site and the presence of stromal CAFs (P = .025). On the basis of this retrospective study, evaluating the tumor stroma for CAFs in feline oral SCC biopsy specimens may be of potential prognostic value. © The Author(s) 2016.

The introduction of hydrogen bond and hydrophobicity effects into the rotational isomeric states model for conformational analysis of unfolded peptides

Science.gov (United States)

Engin, Ozge; Sayar, Mehmet; Erman, Burak

2009-03-01

Relative contributions of local and non-local interactions to the unfolded conformations of peptides are examined by using the rotational isomeric states model which is a Markov model based on pairwise interactions of torsion angles. The isomeric states of a residue are well described by the Ramachandran map of backbone torsion angles. The statistical weight matrices for the states are determined by molecular dynamics simulations applied to monopeptides and dipeptides. Conformational properties of tripeptides formed from combinations of alanine, valine, tyrosine and tryptophan are investigated based on the Markov model. Comparison with molecular dynamics simulation results on these tripeptides identifies the sequence-distant long-range interactions that are missing in the Markov model. These are essentially the hydrogen bond and hydrophobic interactions that are obtained between the first and the third residue of a tripeptide. A systematic correction is proposed for incorporating these long-range interactions into the rotational isomeric states model. Preliminary results suggest that the Markov assumption can be improved significantly by renormalizing the statistical weight matrices to include the effects of the long-range correlations.

The introduction of hydrogen bond and hydrophobicity effects into the rotational isomeric states model for conformational analysis of unfolded peptides

International Nuclear Information System (INIS)

Engin, Ozge; Sayar, Mehmet; Erman, Burak

2009-01-01

Relative contributions of local and non-local interactions to the unfolded conformations of peptides are examined by using the rotational isomeric states model which is a Markov model based on pairwise interactions of torsion angles. The isomeric states of a residue are well described by the Ramachandran map of backbone torsion angles. The statistical weight matrices for the states are determined by molecular dynamics simulations applied to monopeptides and dipeptides. Conformational properties of tripeptides formed from combinations of alanine, valine, tyrosine and tryptophan are investigated based on the Markov model. Comparison with molecular dynamics simulation results on these tripeptides identifies the sequence-distant long-range interactions that are missing in the Markov model. These are essentially the hydrogen bond and hydrophobic interactions that are obtained between the first and the third residue of a tripeptide. A systematic correction is proposed for incorporating these long-range interactions into the rotational isomeric states model. Preliminary results suggest that the Markov assumption can be improved significantly by renormalizing the statistical weight matrices to include the effects of the long-range correlations

Efficient Absorption of X-Hydroxyproline (Hyp)-Gly after Oral Administration of a Novel Gelatin Hydrolysate Prepared Using Ginger Protease.

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Taga, Yuki; Kusubata, Masashi; Ogawa-Goto, Kiyoko; Hattori, Shunji

2016-04-13

Recent studies have reported that oral intake of gelatin hydrolysate has various beneficial effects, such as reduction of joint pain and lowering of blood sugar levels. In this study, we produced a novel gelatin hydrolysate using a cysteine-type ginger protease having unique substrate specificity with preferential peptide cleavage with Pro at the P2 position. Substantial amounts of X-hydroxyproline (Hyp)-Gly-type tripeptides were generated up to 2.5% (w/w) concomitantly with Gly-Pro-Y-type tripeptides (5%; w/w) using ginger powder. The in vivo absorption of the ginger-degraded gelatin hydrolysate was estimated using mice. The plasma levels of collagen-derived oligopeptides, especially X-Hyp-Gly, were significantly high (e.g., 2.3-fold for Glu-Hyp-Gly, p < 0.05) compared with those of the control gelatin hydrolysate, which was prepared using gastrointestinal proteases and did not contain detectable X-Hyp-Gly. This study demonstrated that orally administered X-Hyp-Gly was effectively absorbed into the blood, probably due to the high protease resistance of this type of tripeptide.

Elevated CD147 expression is associated with shorter overall survival in non-small cell lung cancer.

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Zhang, Xiaojun; Tian, Tian; Zhang, Xiaofeng; Liu, Changting; Fang, Xiangqun

2017-06-06

A number of studies have reported on the prognostic role of CD147 expression in non-small cell lung cancer (NSCLC); however, the results remain controversial. This study aims to investigate the impact of CD147 on the prognosis of NSCLC by means of a meta-analysis. A literature search was performed for relevant studies published before October 29, 2016. The hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated as effective measures. Sensitivity analysis and publication bias examination were also conducted. Ten eligible studies with a total of 1605 patients were included in this meta-analysis. CD147 overexpression was correlated with poor overall survival (OS) (HR=1.59, 95% CI=1.32-1.91, pCD147 expression was associated with the presence of lymph node metastasis (OR=2.31, 95% CI=1.74-3.07, pCD147 and sex, age, differentiation, or histology was found. No evidence of significant publication bias was identified. This meta-analysis revealed that overexpression of CD147 was associated with shorter OS, the presence of lymph node metastasis and advanced TNM stage in NSCLC. Therefore, CD147 could serve as a potential prognostic marker for NSCLC.

C-terminal motif prediction in eukaryotic proteomes using comparative genomics and statistical over-representation across protein families

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Cutler Sean R

2007-06-01

Full Text Available Abstract Background The carboxy termini of proteins are a frequent site of activity for a variety of biologically important functions, ranging from post-translational modification to protein targeting. Several short peptide motifs involved in protein sorting roles and dependent upon their proximity to the C-terminus for proper function have already been characterized. As a limited number of such motifs have been identified, the potential exists for genome-wide statistical analysis and comparative genomics to reveal novel peptide signatures functioning in a C-terminal dependent manner. We have applied a novel methodology to the prediction of C-terminal-anchored peptide motifs involving a simple z-statistic and several techniques for improving the signal-to-noise ratio. Results We examined the statistical over-representation of position-specific C-terminal tripeptides in 7 eukaryotic proteomes. Sequence randomization models and simple-sequence masking were applied to the successful reduction of background noise. Similarly, as C-terminal homology among members of large protein families may artificially inflate tripeptide counts in an irrelevant and obfuscating manner, gene-family clustering was performed prior to the analysis in order to assess tripeptide over-representation across protein families as opposed to across all proteins. Finally, comparative genomics was used to identify tripeptides significantly occurring in multiple species. This approach has been able to predict, to our knowledge, all C-terminally anchored targeting motifs present in the literature. These include the PTS1 peroxisomal targeting signal (SKL*, the ER-retention signal (K/HDEL*, the ER-retrieval signal for membrane bound proteins (KKxx*, the prenylation signal (CC* and the CaaX box prenylation motif. In addition to a high statistical over-representation of these known motifs, a collection of significant tripeptides with a high propensity for biological function exists

Selective binding of carotenoids with a shorter conjugated chain to the LH2 antenna complex and those with a longer conjugated chain to the reaction center from Rubrivivax gelatinosus.

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Kakitani, Yoshinori; Fujii, Ritsuko; Hayakawa, Yoshihiro; Kurahashi, Masahiro; Koyama, Yasushi; Harada, Jiro; Shimada, Keizo

2007-06-19

Rubrivivax gelatinosus having both the spheroidene and spirilloxanthin biosynthetic pathways produces carotenoids (Cars) with a variety of conjugated chains, which consist of different numbers of conjugated double bonds (n), including the C=C (m) and C=O (o) bonds. When grown under anaerobic conditions, the wild type produces Cars for which n = m = 9-13, whereas under semiaerobic conditions, it additionally produces Cars for which n = m + o = 10 + 1, 13 + 1, and 13 + 2. On the other hand, a mutant, in which the latter pathway is genetically blocked, produces only Cars for which n = 9 and 10 under anaerobic conditions and n = 9, 10, and 10 + 1 under semianaerobic conditions. Those Cars that were extracted from the LH2 complex (LH2) and the reaction center (RC), isolated from the wild-type and the mutant Rvi. gelatinosus, were analyzed by HPLC, and their structures were determined by mass spectrometry and 1H NMR spectroscopy. The selective binding of Cars to those pigment-protein complexes has been characterized as follows. (1) Cars with a shorter conjugated chain are selectively bound to LH2 whereas Cars with a longer conjugated chain to the RC. (2) Shorter chain Cars with a hydroxyl group are bound to LH2 almost exclusively. This rule holds either in the absence or in the presence of the keto group. The natural selection of shorter chain Cars by LH2 and longer chain Cars by the RC is discussed, on the basis of the results now available, in relation to the light-harvesting and photoprotective functions of Cars.

Dyslexics' faster decay of implicit memory for sounds and words is manifested in their shorter neural adaptation.

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Jaffe-Dax, Sagi; Frenkel, Or; Ahissar, Merav

2017-01-24

Dyslexia is a prevalent reading disability whose underlying mechanisms are still disputed. We studied the neural mechanisms underlying dyslexia using a simple frequency-discrimination task. Though participants were asked to compare the two tones in each trial, implicit memory of previous trials affected their responses. We hypothesized that implicit memory decays faster among dyslexics. We tested this by increasing the temporal intervals between consecutive trials, and by measuring the behavioral impact and ERP responses from the auditory cortex. Dyslexics showed a faster decay of implicit memory effects on both measures, with similar time constants. Finally, faster decay of implicit memory also characterized the impact of sound regularities in benefitting dyslexics' oral reading rate. Their benefit decreased faster as a function of the time interval from the previous reading of the same non-word. We propose that dyslexics' shorter neural adaptation paradoxically accounts for their longer reading times, since it reduces their temporal window of integration of past stimuli, resulting in noisier and less reliable predictions for both simple and complex stimuli. Less reliable predictions limit their acquisition of reading expertise.

Is Alcohol Use Disorder Identification Test (AUDIT or its shorter versions more useful to identify risky drinkers in a Chinese population? A diagnostic study.

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Benjamin H K Yip

Full Text Available To examine the diagnostic performance of shorter versions of Alcohol Use Disorder Identification Test (AUDIT, including Alcohol Consumption (AUDIT-C, in identifying risky drinkers in primary care settings using conventional performance measures, supplemented by decision curve analysis and reclassification table.A cross-sectional study of adult males in general outpatient clinics in Hong Kong. The study included only patients who reported at least sometimes drinking alcoholic beverages. Timeline follow back alcohol consumption assessment method was used as the reference standard. A Chinese translated and validated 10-item AUDIT (Ch-AUDIT was used as a screening tool of risky drinking.Of the participants, 21.7% were classified as risky drinkers. AUDIT-C has the best overall performance among the shorter versions of Ch-AUDIT. The AUC of AUDIT-C was comparable to Ch-AUDIT (0.898 vs 0.901, p-value = 0.959. Decision curve analysis revealed that when the threshold probability ranged from 15-30%, the AUDIT-C had a higher net-benefit than all other screens. AUDIT-C improved the reclassification of risky drinking when compared to Ch-AUDIT (net reclassification improvement = 0.167. The optimal cut-off of AUDIT-C was at ≥5.Given the rising levels of alcohol consumption in the Chinese regions, this Chinese translated 3-item instrument provides convenient and time-efficient risky drinking screening and may become an increasingly useful tool.

MO-E-BRD-02: Accelerated Partial Breast Irradiation in Brachytherapy: Is Shorter Better?

International Nuclear Information System (INIS)

Todor, D.

2015-01-01

Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant. A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current

MO-E-BRD-02: Accelerated Partial Breast Irradiation in Brachytherapy: Is Shorter Better?

Energy Technology Data Exchange (ETDEWEB)

Todor, D. [Virginia Commonwealth University (United States)

2015-06-15

Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant. A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current

Quantitative structure-activity relationship study of antioxidative peptide by using different sets of amino acids descriptors

Science.gov (United States)

Li, Yao-Wang; Li, Bo; He, Jiguo; Qian, Ping

2011-07-01

A database consisting of 214 tripeptides which contain either His or Tyr residue was applied to study quantitative structure-activity relationships (QSAR) of antioxidative tripeptides. Partial Least-Squares Regression analysis (PLSR) was conducted using parameters individually of each amino acid descriptor, including Divided Physico-chemical Property Scores (DPPS), Hydrophobic, Electronic, Steric, and Hydrogen (HESH), Vectors of Hydrophobic, Steric, and Electronic properties (VHSE), Molecular Surface-Weighted Holistic Invariant Molecular (MS-WHIM), isotropic surface area-electronic charge index (ISA-ECI) and Z-scale, to describe antioxidative tripeptides as X-variables and antioxidant activities measured with ferric thiocyanate methods were as Y-variable. After elimination of outliers by Hotelling's T 2 method and residual analysis, six significant models were obtained describing the entire data set. According to cumulative squared multiple correlation coefficients ( R2), cumulative cross-validation coefficients ( Q2) and relative standard deviation for calibration set (RSD c), the qualities of models using DPPS, HESH, ISA-ECI, and VHSE descriptors are better ( R2 > 0.6, Q2 > 0.5, RSD c 0.44). Furthermore, the predictive ability of models using DPPS descriptor is best among the six descriptors systems (cumulative multiple correlation coefficient for predict set ( Rext2) > 0.7). It was concluded that the DPPS is better to describe the amino acid of antioxidative tripeptides. The results of DPPS descriptor reveal that the importance of the center amino acid and the N-terminal amino acid are far more than the importance of the C-terminal amino acid for antioxidative tripeptides. The hydrophobic (positively to activity) and electronic (negatively to activity) properties of the N-terminal amino acid are suggested to play the most important significance to activity, followed by the hydrogen bond (positively to activity) of the center amino acid. The N-terminal amino acid

Molecular dynamics simulations and in silico peptide ligand screening of the Elk-1 ETS domain

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Hussain Abrar

2011-11-01

Full Text Available Abstract Background The Elk-1 transcription factor is a member of a group of proteins called ternary complex factors, which serve as a paradigm for gene regulation in response to extracellular signals. Its deregulation has been linked to multiple human diseases including the development of tumours. The work herein aims to inform the design of potential peptidomimetic compounds that can inhibit the formation of the Elk-1 dimer, which is key to Elk-1 stability. We have conducted molecular dynamics simulations of the Elk-1 ETS domain followed by virtual screening. Results We show the ETS dimerisation site undergoes conformational reorganisation at the α1β1 loop. Through exhaustive screening of di- and tri-peptide libraries against a collection of ETS domain conformations representing the dynamics of the loop, we identified a series of potential binders for the Elk-1 dimer interface. The di-peptides showed no particular preference toward the binding site; however, the tri-peptides made specific interactions with residues: Glu17, Gln18 and Arg49 that are pivotal to the dimer interface. Conclusions We have shown molecular dynamics simulations can be combined with virtual peptide screening to obtain an exhaustive docking protocol that incorporates dynamic fluctuations in a receptor. Based on our findings, we suggest experimental binding studies to be performed on the 12 SILE ranked tri-peptides as possible compounds for the design of inhibitors of Elk-1 dimerisation. It would also be reasonable to consider the score-ranked tri-peptides as a comparative test to establish whether peptide size is a determinant factor of binding to the ETS domain.

Shorter duration of non-rapid eye movement sleep slow waves in EphA4 knockout mice.

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Freyburger, Marlène; Poirier, Gaétan; Carrier, Julie; Mongrain, Valérie

2017-10-01

Slow waves occurring during non-rapid eye movement sleep have been associated with neurobehavioural performance and memory. In addition, the duration of previous wakefulness and sleep impacts characteristics of these slow waves. However, molecular mechanisms regulating the dynamics of slow-wave characteristics remain poorly understood. The EphA4 receptor regulates glutamatergic transmission and synaptic plasticity, which have both been linked to sleep slow waves. To investigate if EphA4 regulates slow-wave characteristics during non-rapid eye movement sleep, we compared individual parameters of slow waves between EphA4 knockout mice and wild-type littermates under baseline conditions and after a 6-h sleep deprivation. We observed that, compared with wild-type mice, knockout mice display a shorter duration of positive and negative phases of slow waves under baseline conditions and after sleep deprivation. However, the mutation did not change slow-wave density, amplitude and slope, and did not affect the sleep deprivation-dependent changes in slow-wave characteristics, suggesting that EphA4 is not involved in the response to elevated sleep pressure. Our present findings suggest a role for EphA4 in shaping cortical oscillations during sleep that is independent from sleep need. © 2017 European Sleep Research Society.

Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom

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Khin Than Yee

2016-12-01

Full Text Available Russell’s viper bites are potentially fatal from severe bleeding, renal failure and capillary leakage. Snake venom metalloproteinases (SVMPs are attributed to these effects. In addition to specific antivenom therapy, endogenous inhibitors from snakes are of interest in studies of new treatment modalities for neutralization of the effect of toxins. Two major snake venom metalloproteinases (SVMPs: RVV-X and Daborhagin were purified from Myanmar Russell’s viper venom using a new purification strategy. Using the Next Generation Sequencing (NGS approach to explore the Myanmar RV venom gland transcriptome, mRNAs of novel tripeptide SVMP inhibitors (SVMPIs were discovered. Two novel endogenous tripeptides, pERW and pEKW were identified and isolated from the crude venom. Both purified SVMPs showed caseinolytic activity. Additionally, RVV-X displayed specific proteolytic activity towards gelatin and Daborhagin showed potent fibrinogenolytic activity. These activities were inhibited by metal chelators. Notably, the synthetic peptide inhibitors, pERW and pEKW, completely inhibit the gelatinolytic and fibrinogenolytic activities of respective SVMPs at 5 mM concentration. These complete inhibitory effects suggest that these tripeptides deserve further study for development of a therapeutic candidate for Russell’s viper envenomation.

Comparison of Predicted pKa Values for Some Amino-Acids, Dipeptides and Tripeptides, Using COSMO-RS, ChemAxon and ACD/Labs Methods Comparaison des valeurs de pKa de quelques acides aminés, dipeptides et tripeptides, prédites en utilisant les méthodes COSMO-RS, ChemAxon et ACD/Labs

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Toure O.

2013-05-01

Full Text Available Liquid-phase pKa values play a key role in food science. Chemical properties of molecules depend largely on whether they are ionized or not. Most organic molecules are capable of gaining and/or losing a proton in aqueous solutions. Proton transfer most. frequently occurs between water and any ionizable atom of the organic molecule. The molecule’s response to profanation or deprotonation depends significantly on the site that was disturbed by proton transfer. Partial charge distribution in the molecule also varies with protonation of the acidlbase active sites. Then it can he used to determine the pKa of a molecule. First, we use the COSMO-RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment fin- more Realistic Solvation (RS simulations, for the direct prediction of pKa constants of about 50 molecules (amino-acids, dipeptides and tripeptides. Then, we compare our results with experimental data and the pKa values predicted using two other methods. We used respectively the ChemAxon method using a program based on the calculation of partial charge of atoms in the molecule and the ACD/Labs method that enables to calculate single pKa values. for all possible dissociation centers when the rest of the molecule is considered neutral, using an internal database containing chemical structures and their experimental pKa values. The averaged Root Mean Square Error (RMSE of the predicted pKa values for each method compared to experimental results were respectively 0.596 for COSMO-RS, 0.445 for ChemAxon and 0.490 for ACD/Labs. While ACDILabs and ChemAxon are parameterized using a large set ofexperimental data (including several of the studied molecules, the COSMO- RS method was used in a fully predictive way. Regarding these results, COSMO-RS appears as a promising method to predict the pKa values of molecules of interest in food science with scarce available pKa values such

Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival.

LENUS (Irish Health Repository)

2012-02-01

Aims: Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Post-operative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods: 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas.

Self-produced Time Intervals Are Perceived as More Variable and/or Shorter Depending on Temporal Context in Subsecond and Suprasecond Ranges

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Keita eMitani

2016-06-01

Full Text Available The processing of time intervals is fundamental for sensorimotor and cognitive functions. Perceptual and motor timing are often performed concurrently (e.g., playing a musical instrument. Although previous studies have shown the influence of body movements on time perception, how we perceive self-produced time intervals has remained unclear. Furthermore, it has been suggested that the timing mechanisms are distinct for the sub- and suprasecond ranges. Here, we compared perceptual performances for self-produced and passively presented time intervals in random contexts (i.e., multiple target intervals presented in a session across the sub- and suprasecond ranges (Experiment 1 and within the sub- (Experiment 2 and suprasecond (Experiment 3 ranges, and in a constant context (i.e., a single target interval presented in a session in the sub- and suprasecond ranges (Experiment 4. We show that self-produced time intervals were perceived as shorter and more variable across the sub- and suprasecond ranges and within the suprasecond range but not within the subsecond range in a random context. In a constant context, the self-produced time intervals were perceived as more variable in the suprasecond range but not in the subsecond range. The impairing effects indicate that motor timing interferes with perceptual timing. The dependence of impairment on temporal contexts suggests multiple timing mechanisms for the subsecond and suprasecond ranges. In addition, violation of the scalar property (i.e., a constant variability to target interval ratio was observed between the sub- and suprasecond ranges. The violation was clearer for motor timing than for perceptual timing. This suggests that the multiple timing mechanisms for the sub- and suprasecond ranges overlap more for perception than for motor. Moreover, the central tendency effect (i.e., where shorter base intervals are overestimated and longer base intervals are underestimated disappeared with subsecond

Shorter exposures to harder X-rays trigger early apoptotic events in Xenopus laevis embryos.

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JiaJia Dong

Full Text Available BACKGROUND: A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems. METHODOLOGY/PRINCIPAL FINDINGS: We explored how the energy of individual X-ray photons and exposure time, both factors that determine the total dose, influence the occurrence of cell death in early Xenopus embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time. CONCLUSIONS/SIGNIFICANCE: Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system. In particular, for embryos exposed under identical conditions and delivered the same absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and

The prosurvival activity of ascites against TRAIL is associated with a shorter disease-free interval in patients with ovarian cancer

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Lane Denis

2010-01-01

associated with shorter disease-free interval. Conclusions The prosurvival activity of ascites against TRAIL is associated with shorter disease-free interval, which may be explained, at least in part, by ascites-induced cisplatin/paclitaxel resistance. Our findings suggest that ascites may contain prosurvival factors that protect against TRAIL and chemotherapy and consequently affect disease progression.

Cleavage of SNAP25 and its shorter versions by the protease domain of serotype A botulinum neurotoxin.

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Rahman M Mizanur

Full Text Available Various substrates, catalysts, and assay methods are currently used to screen inhibitors for their effect on the proteolytic activity of botulinum neurotoxin. As a result, significant variation exists in the reported results. Recently, we found that one source of variation was the use of various catalysts, and have therefore evaluated its three forms. In this paper, we characterize three substrates under near uniform reaction conditions using the most active catalytic form of the toxin. Bovine serum albumin at varying optimum concentrations stimulated enzymatic activity with all three substrates. Sodium chloride had a stimulating effect on the full length synaptosomal-associated protein of 25 kDa (SNAP25 and its 66-mer substrates but had an inhibitory effect on the 17-mer substrate. We found that under optimum conditions, full length SNAP25 was a better substrate than its shorter 66-mer or 17-mer forms both in terms of kcat, Km, and catalytic efficiency kcat/Km. Assay times greater than 15 min introduced large variations and significantly reduced the catalytic efficiency. In addition to characterizing the three substrates, our results identify potential sources of variations in previous published results, and underscore the importance of using well-defined reaction components and assay conditions.

Shorter time since inflammatory bowel disease diagnosis in children is associated with lower mental health in parents.

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Werner, H; Braegger, Cp; Buehr, P; Koller, R; Nydegger, A; Spalinger, J; Heyland, K; Schibli, S; Landolt, Ma

2015-01-01

This study assessed the mental health of parents of children with inflammatory bowel disease (IBD), compared their mental health with age-matched and gender-matched references and examined parental and child predictors for mental health problems. A total of 125 mothers and 106 fathers of 125 children with active and inactive IBD from the Swiss IBD multicentre cohort study were included. Parental mental health was assessed by the Symptom Checklist 27 and child behaviour problems by the Strengths and Difficulties Questionnaire. Child medical data were extracted from hospital records. While the mothers reported lower mental health, the fathers' mental health was similar, or even better, than in age-matched and gender-matched community controls. In both parents, shorter time since the child's diagnosis was associated with poorer mental health. In addition, the presence of their own IBD diagnosis and child behaviour problems predicted maternal mental health problems. Parents of children with IBD may need professional support when their child is diagnosed, to mitigate distress. This, in turn, may help the child to adjust better to IBD. Particular attention should be paid to mothers who have their own IBD diagnosis and whose children display behaviour problems. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Focused Screening of ECM-Selective Adhesion Peptides on Cellulose-Bound Peptide Microarrays.

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Kanie, Kei; Kondo, Yuto; Owaki, Junki; Ikeda, Yurika; Narita, Yuji; Kato, Ryuji; Honda, Hiroyuki

2016-11-19

The coating of surfaces with bio-functional proteins is a promising strategy for the creation of highly biocompatible medical implants. Bio-functional proteins from the extracellular matrix (ECM) provide effective surface functions for controlling cellular behavior. We have previously screened bio-functional tripeptides for feasibility of mass production with the aim of identifying those that are medically useful, such as cell-selective peptides. In this work, we focused on the screening of tripeptides that selectively accumulate collagen type IV (Col IV), an ECM protein that accelerates the re-endothelialization of medical implants. A SPOT peptide microarray was selected for screening owing to its unique cellulose membrane platform, which can mimic fibrous scaffolds used in regenerative medicine. However, since the library size on the SPOT microarray was limited, physicochemical clustering was used to provide broader variation than that of random peptide selection. Using the custom focused microarray of 500 selected peptides, we assayed the relative binding rates of tripeptides to Col IV, collagen type I (Col I), and albumin. We discovered a cluster of Col IV-selective adhesion peptides that exhibit bio-safety with endothelial cells. The results from this study can be used to improve the screening of regeneration-enhancing peptides.

Focused Screening of ECM-Selective Adhesion Peptides on Cellulose-Bound Peptide Microarrays

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Kei Kanie

2016-11-01

Full Text Available The coating of surfaces with bio-functional proteins is a promising strategy for the creation of highly biocompatible medical implants. Bio-functional proteins from the extracellular matrix (ECM provide effective surface functions for controlling cellular behavior. We have previously screened bio-functional tripeptides for feasibility of mass production with the aim of identifying those that are medically useful, such as cell-selective peptides. In this work, we focused on the screening of tripeptides that selectively accumulate collagen type IV (Col IV, an ECM protein that accelerates the re-endothelialization of medical implants. A SPOT peptide microarray was selected for screening owing to its unique cellulose membrane platform, which can mimic fibrous scaffolds used in regenerative medicine. However, since the library size on the SPOT microarray was limited, physicochemical clustering was used to provide broader variation than that of random peptide selection. Using the custom focused microarray of 500 selected peptides, we assayed the relative binding rates of tripeptides to Col IV, collagen type I (Col I, and albumin. We discovered a cluster of Col IV-selective adhesion peptides that exhibit bio-safety with endothelial cells. The results from this study can be used to improve the screening of regeneration-enhancing peptides.

Effect of Group Exercising and Adjusting the Brace at Shorter Intervals on Cobb Angle and Quality of Life of Patients with Idiopathic Scoliosis

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Zahra Hedayati

2016-01-01

Full Text Available Objective: Bracing along with exercising is the most effective protocol in patients with idiopathic scoliosis which have Cobb angles of 25 to 45 degrees. However, since the psychological aspects of scoliosis treatment may affect the quality of life, and the exact time for adjusting the pads of Milwaukee brace is unknown; Therefore the aim of this study was evaluating the effect of exercising in a group, with adjusting the brace in shorter intervals, in compare to routine protocol, in the treatment of idiopathic scoliosis. Matterials & Methods: Thirty-four patients with idiopathic scoliosis which had Cobb angles of 50 to 15 degrees were included in this study and were divided into experimental and control groups. The patients of two groups participated in an eleven-week treatment program, differ between the two groups. Quality of life scores of both groups were evaluated before and after intervention using SRS-22 questionnaire, as well as scoliosis angles before and after the intervention according to the primary and secondary radiographic X-rays. Results: Statistical analysis was performed using Paired T-Test in each group, and Independent T-Test between the two groups before and after treatment. The severity of scoliosis curvature and satisfaction domain of the experimental group was reduced significantly in compared with the control group, after intervention (P=0.04. Moreover in the case of  the quality of life in patients with Cobb angles less than 30 degrees, compared with patients with Cobb angles greater than 31 degrees, in the domains of self-image, satisfaction, and total score, the difference was significant (P<0.05. Conclusion: Adjusting the brace at shorter intervals along with exercising as a group, during the eleven weeks of treatment, has increased satisfaction and reduced the scoliosis Cobb angles of patients.

Alternative promoter usage generates novel shorter MAPT mRNA transcripts in Alzheimer's disease and progressive supranuclear palsy brains.

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Huin, Vincent; Buée, Luc; Behal, Hélène; Labreuche, Julien; Sablonnière, Bernard; Dhaenens, Claire-Marie

2017-10-03

Alternative promoter usage is an important mechanism for transcriptome diversity and the regulation of gene expression. Indeed, this alternative usage may influence tissue/subcellular specificity, protein translation and function of the proteins. The existence of an alternative promoter for MAPT gene was considered for a long time to explain differential tissue specificity and differential response to transcription and growth factors between mRNA transcripts. The alternative promoter usage could explain partly the different tau proteins expression patterns observed in tauopathies. Here, we report on our discovery of a functional alternative promoter for MAPT, located upstream of the gene's second exon (exon 1). By analyzing genome databases and brain tissue from control individuals and patients with Alzheimer's disease or progressive supranuclear palsy, we identified novel shorter transcripts derived from this alternative promoter. These transcripts are increased in patients' brain tissue as assessed by 5'RACE-PCR and qPCR. We suggest that these new MAPT isoforms can be translated into normal or amino-terminal-truncated tau proteins. We further suggest that activation of MAPT's alternative promoter under pathological conditions leads to the production of truncated proteins, changes in protein localization and function, and thus neurodegeneration.

Induction of a shorter compression phase is correlated with a deeper chest compression during metronome-guided cardiopulmonary resuscitation: a manikin study.

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Chung, Tae Nyoung; Bae, Jinkun; Kim, Eui Chung; Cho, Yun Kyung; You, Je Sung; Choi, Sung Wook; Kim, Ok Jun

2013-07-01

Recent studies have shown that there may be an interaction between duty cycle and other factors related to the quality of chest compression. Duty cycle represents the fraction of compression phase. We aimed to investigate the effect of shorter compression phase on average chest compression depth during metronome-guided cardiopulmonary resuscitation. Senior medical students performed 12 sets of chest compressions following the guiding sounds, with three down-stroke patterns (normal, fast and very fast) and four rates (80, 100, 120 and 140 compressions/min) in random sequence. Repeated-measures analysis of variance was used to compare the average chest compression depth and duty cycle among the trials. The average chest compression depth increased and the duty cycle decreased in a linear fashion as the down-stroke pattern shifted from normal to very fast (pmetronome-guided cardiopulmonary resuscitation.

Access to Electric Light Is Associated with Shorter Sleep Duration in a Traditionally Hunter-Gatherer Community.

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de la Iglesia, Horacio O; Fernández-Duque, Eduardo; Golombek, Diego A; Lanza, Norberto; Duffy, Jeanne F; Czeisler, Charles A; Valeggia, Claudia R

2015-08-01

Access to electric light might have shifted the ancestral timing and duration of human sleep. To test this hypothesis, we studied two communities of the historically hunter-gatherer indigenous Toba/Qom in the Argentinean Chaco. These communities share the same ethnic and sociocultural background, but one has free access to electricity while the other relies exclusively on natural light. We fitted participants in each community with wrist activity data loggers to assess their sleep-wake cycles during one week in the summer and one week in the winter. During the summer, participants with access to electricity had a tendency to a shorter daily sleep bout (43 ± 21 min) than those living under natural light conditions. This difference was due to a later daily bedtime and sleep onset in the community with electricity, but a similar sleep offset and rise time in both communities. In the winter, participants without access to electricity slept longer (56 ± 17 min) than those with access to electricity, and this was also related to earlier bedtimes and sleep onsets than participants in the community with electricity. In both communities, daily sleep duration was longer during the winter than during the summer. Our field study supports the notion that access to inexpensive sources of artificial light and the ability to create artificially lit environments must have been key factors in reducing sleep in industrialized human societies. © 2015 The Author(s).

Are Shorter Article Titles More Attractive for Citations? Cross-sectional Study of 22 Scientific Journals

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Habibzadeh, Farrokh; Yadollahie, Mahboobeh

2010-01-01

Aim To investigate the correlation between the length of the title of a scientific article and the number of citations it receives, in view of the common editorial call for shorter titles. Methods Title and the number of citations to all articles published in 2005 in 22 arbitrarily chosen English-language journals (n = 9031) were retrieved from citation database Scopus. The 2008 journal impact factors of these 22 journals were also retrieved from Thomson Reuters’ Journal Citation Report (JCR). Assuming the article title length as the independent variable, and the number of citations to the article as the dependent variable, a linear regression model was applied. Results The slope of the regression line for some journals (n = 6, when titles were measured in characters but 7 when titles were measured in words) was negative – none was significantly different from 0. The overall slope for all journals was 0.140 (when titles were measured in characters) and 0.778 (when titles were measured in words), significantly different from 0 (P articles with longer titles received more citations – Spearman ρ = 0.266 – when titles were measured in characters, and ρ = 0.244 when titles were measured in words (P 10 and for 2 out of 14 journals with impact factor <10 (P < 0.001, Fisher exact test). Conclusion Longer titles seem to be associated with higher citation rates. This association is more pronounced for journals with high impact factors. Editors who insist on brief and concise titles should perhaps update the guidelines for authors of their journals and have more flexibility regarding the length of the title. PMID:20401960

Cationic ferritin uptake by cultured anterior pituitary cells treated with the proteinase inhibitor, BOC-DPhe-Phe-Lys-H.

Science.gov (United States)

Gaál, G; Bácsy, E; Rappay, G

1988-01-01

Cultured cells from the anterior pituitary glands of adult rats were treated with the tripeptide aldehyde proteinase inhibitor, BOC-DPhe-Phe-Lys-H. The addition of this tripeptide aldehyde decreased the in vitro release of prolactin to 25% of the control value, while the release of growth hormone in the same cultures decreased to 33% of the control value. Prolactin immunostaining was stronger in semithin sections of proteinase-inhibitor-treated cultures than in control sections. After 2 h treatment with the inhibitor, prolactin- and growth hormone-containing secretory granules were numerous, and the number of crinophagic vacuoles had increased. In the presence of the inhibitor, the overall cytoarchitecture of parenchymal cells was well preserved, and the pathway of the uptake of cationic ferritin appeared to be unaffected.

Progesterone-releasing devices for cattle estrus induction and synchronization: Device optimization to anticipate shorter treatment durations and new device developments.

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de Graaff, W; Grimard, B

2018-05-01

Synchronization programs using progesterone-releasing intravaginal devices that allow for fixed time artificial insemination are still finding increasing application in bovine reproduction. This practice is useful for rationalizing livestock management because an increased number of cows can be inseminated in one session without the need for estrus detection. Although much of the innovation related to the design and development of intravaginal devices for use in cattle took place in the previous century, progress in understanding the physiology of the bovine estrous cycle resulted in shorter treatment durations, a trend which is still continuing. In this competitive market, with little functional differentiation between the existing devices, the shorter treatment duration prompted for optimization of the progesterone content in the device, as the cost of the drug significantly contributes to the price per unit. For CIDR ® a reduction of the progesterone content of about 30 per cent was realized. Price reduction remained an important target for further device development. Next to reduction of progesterone content, cheaper and easier to process materials like polyethylene vinyl acetate (EVA) copolymers have been explored to replace the commonly used silicone elastomers. The reengineering effort of CIDR ® demonstrated that knowledge of release kinetics and insight into gradual depletion patterns in the device is critical for optimization of drug content without compromising performance (blood levels). More recent publications related to the use of alternative polymers like EVA and polyisoprene (IP) indicated encouraging results regarding further reduction of progesterone content. The use of EVA seems most promising, because it is in principle a low-cost polymer available in many grades and this thermoplastic polymer can be processed easily by means of commonly used techniques like injection molding and extrusion. The use of thermoplastic polymers, however, requires

Mecanismos de absorção de aminoácidos e oligopeptídios. Controle e implicações na dietoterapia humana Mechanisms of amino acids and oligopeptides absorption in humans

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Patrícia Baston FRENHANI

1999-12-01

bactérias para produção de energia e aminoácidos, respectivamente.The mechanisms involved in the absorption of amino acids and oligopeptides are reviewed regarding their implications in human feedings. Brush border and basolateral membranes are crossed by amino acids and di-tripeptides by passive (facilitated or simple diffusion or active (Na+ or H+ co-transporters pathways. Active Na+-dependent system accurs mainly at brush border and simple diffusion at basolateral, both membranes have the passive facilitated transport. Free-amino acids use either passive or active transport systems whereas di-tripeptides do mainly active (H+ co-transporter. Brush border have distinctive transport system for amino acids and di-tripeptides. The former occurs mainly by active Na+ dependently whereas the later is active H+-dependent with little affinity for tetra or higher peptides. Free amino acids are transported at different speed by saturable, competitive carriers with specificity for basic, acidic or neutral amino acids. Di and tripeptides have at least two carriers both electrogenic and H+-dependent. The basolateral membrane transport of amino acids is mostly by facilitated diffusion while for di-tripeptides it is an active anion exchange associated process. The main regulation of amino acids and di-tripeptide transport is the presence o substrate at the mucosal membrane with higher the substrate higher the absorption. Di and tripeptides are more efficiently absorbed than free amino acids which in turns are better absorbed than oligopeptides. So di-tripeptides result in better N-retention and is particularly useful in cases of lower intestinal absorption capacity. The non-absorbed peptides are digested and fermented by colonic bacteria resulting short-chain fatty acids, dicarboxylic acids, phenolic compounds and ammonia. Short-chain fatty acid provides energy for colonocytes and bacteria and the ammonia not fixed by bacteria returns to the liver for ureagenesis.

The Effect of Shorter Treatment Regimens for Hepatitis C on Population Health and Under Fixed Budgets.

Science.gov (United States)

Morgan, Jake R; Kim, Arthur Y; Naggie, Susanna; Linas, Benjamin P

2018-01-01

Direct acting antiviral hepatitis C virus (HCV) therapies are highly effective but costly. Wider adoption of an 8-week ledipasvir/sofosbuvir treatment regimen could result in significant savings, but may be less efficacious compared with a 12-week regimen. We evaluated outcomes under a constrained budget and cost-effectiveness of 8 vs 12 weeks of therapy in treatment-naïve, noncirrhotic, genotype 1 HCV-infected black and nonblack individuals and considered scenarios of IL28B and NS5A resistance testing to determine treatment duration in sensitivity analyses. We developed a decision tree to use in conjunction with Monte Carlo simulation to investigate the cost-effectiveness of recommended treatment durations and the population health effect of these strategies given a constrained budget. Outcomes included the total number of individuals treated and attaining sustained virologic response (SVR) given a constrained budget and incremental cost-effectiveness ratios. We found that treating eligible (treatment-naïve, noncirrhotic, HCV-RNA budget among both black and nonblack individuals, and our results suggested that NS5A resistance testing is cost-effective. Eight-week therapy provides good value, and wider adoption of shorter treatment could allow more individuals to attain SVR on the population level given a constrained budget. This analysis provides an evidence base to justify movement of the 8-week regimen to the preferred regimen list for appropriate patients in the HCV treatment guidelines and suggests expanding that recommendation to black patients in settings where cost and relapse trade-offs are considered.

Less is more: latent learning is maximized by shorter training sessions in auditory perceptual learning.

Science.gov (United States)

Molloy, Katharine; Moore, David R; Sohoglu, Ediz; Amitay, Sygal

2012-01-01

The time course and outcome of perceptual learning can be affected by the length and distribution of practice, but the training regimen parameters that govern these effects have received little systematic study in the auditory domain. We asked whether there was a minimum requirement on the number of trials within a training session for learning to occur, whether there was a maximum limit beyond which additional trials became ineffective, and whether multiple training sessions provided benefit over a single session. We investigated the efficacy of different regimens that varied in the distribution of practice across training sessions and in the overall amount of practice received on a frequency discrimination task. While learning was relatively robust to variations in regimen, the group with the shortest training sessions (∼8 min) had significantly faster learning in early stages of training than groups with longer sessions. In later stages, the group with the longest training sessions (>1 hr) showed slower learning than the other groups, suggesting overtraining. Between-session improvements were inversely correlated with performance; they were largest at the start of training and reduced as training progressed. In a second experiment we found no additional longer-term improvement in performance, retention, or transfer of learning for a group that trained over 4 sessions (∼4 hr in total) relative to a group that trained for a single session (∼1 hr). However, the mechanisms of learning differed; the single-session group continued to improve in the days following cessation of training, whereas the multi-session group showed no further improvement once training had ceased. Shorter training sessions were advantageous because they allowed for more latent, between-session and post-training learning to emerge. These findings suggest that efficient regimens should use short training sessions, and optimized spacing between sessions.

Model Prebiotic Iron-Sulfur Peptides

Science.gov (United States)

Bonfio, C.; Scintilla, S.; Shah, S.; Evans, D. J.; Jin, L.; Szostak, J. W.; Sasselov, D. D.; Sutherland, J. D.; Mansy, S. S.

2017-07-01

Iron-sulfur clusters form easily in aqueous solution in the presence of thiolates and iron ions. Polymerization of short, iron-sulfur binding tripeptide sequences leads to ferredoxin-like ligand spacing and activity.

In vitro evaluation of N-methyl amide tripeptidomimetics as substrates for the human intestinal di-/tri-peptide transporter hPEPT1

DEFF Research Database (Denmark)

Andersen, Rikke; Nielsen, Carsten Uhd; Begtrup, Mikael

2006-01-01

application of N-methyl amide bioisosteres as peptide bond replacements in tripeptides in order to decrease degradation by peptidases and yet retain affinity for and transport via hPEPT1. Seven structurally diverse N-methyl amide tripeptidomimetics were selected based on a principal component analysis...... of structural properties of 6859 N-methyl amide tripeptidomimetics. In vitro extracellular degradation of the selected tripeptidomimetics as well as affinity for and transepithelial transport via hPEPT1 were investigated in Caco-2 cells. Decreased apparent degradation was observed for all tripeptidomimetics...... to be substrates for hPEPT1 than tripeptidomimetics with charged side chains. The results of the present study indicate that the N-methyl amide peptide bond replacement approach for increasing bioavailability of tripeptidomimetic drug candidates is not generally applicable to all tripeptides. Nevertheless...

Identification of the mpl gene encoding UDP-N-acetylmuramate: L-alanyl-gamma-D-glutamyl-meso-diaminopimelate ligase in Escherichia coli and its role in recycling of cell wall peptidoglycan.

Science.gov (United States)

Mengin-Lecreulx, D; van Heijenoort, J; Park, J T

1996-01-01

A gene, mpl, encoding UDP-N-acetylmuramate:L-alanyl-gamma-D-glutamyl-meso-diaminopimelat e ligase was recognized by its amino acid sequence homology with murC as the open reading frame yjfG present at 96 min on the Escherichia coli map. The existence of such an enzymatic activity was predicted from studies indicating that reutilization of the intact tripeptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelate occurred and accounted for well over 30% of new cell wall synthesis. Murein tripeptide ligase activity could be demonstrated in crude extracts, and greatly increased activity was produced when the gene was cloned and expressed under control of the trc promoter. A null mutant totally lacked activity but was viable, showing that the enzyme is not essential for growth. PMID:8808921

Déjà-vu all over again: using simulation to evaluate the impact of shorter shelf life for red blood cells at Héma-Québec.

Science.gov (United States)

Blake, John T; Hardy, Matthew; Delage, Gilles; Myhal, Geneviève

2013-07-01

Since the 1970s red blood cells (RBCs) have had a rated shelf life of 42 days. Recently, studies have suggested poorer patient outcomes when older blood is transfused. However, shortening the shelf life of RBCs may increase costs and lead to greater instances of outdates and shortages. A simulation method to evaluate the impact of a shorter shelf life for RBCs on a regional blood network was developed. A network model of the production and distribution system in the province of Quebec was built and validated. The model suggests that a shelf life of 21 or 28 days will have modest impact on outdate and shortage rates. A shelf life of 14 days will create significant challenges for both blood suppliers and hospitals and will result in systemwide outdate rates of 6.64% and shortage rates of 2.75%. The impact of a shorter shelf life for RBCs will disproportionately affect smaller and midsize hospitals. A shelf life of 28 or 21 days is feasible without excessive increases to systemwide outdate, shortage, or emergency ordering rates. Large hospitals will see minimal impact; smaller hospitals will see larger increases and may be unable to find inventory policies that maintain both low outdate and shortage rates. Reducing the shelf life to 14 days, or lower, results in significant challenges for suppliers and hospitals of all sizes. All hospitals will see an impact on outdate and shortage rates; overall systemwide outdate rates (6% or more) will reach levels that would currently be considered unacceptably high. © 2012 American Association of Blood Banks.

GenBank blastx search result: AK062185 [KOME

Lifescience Database Archive (English)

Full Text Available AK062185 001-046-E03 AF080002.1 Heliobacillus mobilis exopolyphosphatase Ppx (ppx) gene, partial cds; cobyric acid synthase CobQ (cobQ), UDP-N-acetylmuramyl tripeptide synthetase MurC (murC),

Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice.

Science.gov (United States)

Andziak, Blazej; Buffenstein, Rochelle

2006-12-01

A key tenet of the oxidative stress theory of aging is that levels of accrued oxidative damage increase with age. Differences in damage generation and accumulation therefore may underlie the natural variation in species longevity. We compared age-related profiles of whole-organism lipid peroxidation (urinary isoprostanes) and liver lipid damage (malondialdehyde) in long living naked mole-rats [maximum lifespan (MLS) > 28.3 years] and shorter-living CB6F1 hybrid mice (MLS approximately 3.5 years). In addition, we compared age-associated changes in liver non-heme iron to assess how intracellular conditions, which may modulate oxidative processes, are affected by aging. Surprisingly, even at a young age, concentrations of both markers of lipid peroxidation, as well as of iron, were at least twofold (P naked mole tats than in mice. This refutes the hypothesis that prolonged naked mole-rat longevity is due to superior protection against oxidative stress. The age-related profiles of all three parameters were distinctly species specific. Rates of lipid damage generation in mice were maintained throughout adulthood, while accrued damage in old animals was twice that of young mice. In naked mole-rats, urinary isoprostane excretion declined by half with age (P naked mole-rats is independent of oxidative stress parameters.

The return trip is felt shorter only postdictively: A psychophysiological study of the return trip effect [corrected].

Directory of Open Access Journals (Sweden)

Ryosuke Ozawa

Full Text Available The return trip often seems shorter than the outward trip even when the distance and actual time are identical. To date, studies on the return trip effect have failed to confirm its existence in a situation that is ecologically valid in terms of environment and duration. In addition, physiological influences as part of fundamental timing mechanisms in daily activities have not been investigated in the time perception literature. The present study compared round-trip and non-round-trip conditions in an ecological situation. Time estimation in real time and postdictive estimation were used to clarify the situations where the return trip effect occurs. Autonomic nervous system activity was evaluated from the electrocardiogram using the Lorenz plot to demonstrate the relationship between time perception and physiological indices. The results suggest that the return trip effect is caused only postdictively. Electrocardiographic analysis revealed that the two experimental conditions induced different responses in the autonomic nervous system, particularly in sympathetic nervous function, and that parasympathetic function correlated with postdictive timing. To account for the main findings, the discrepancy between the two time estimates is discussed in the light of timing strategies, i.e., prospective and retrospective timing, which reflect different emphasis on attention and memory processes. Also each timing method, i.e., the verbal estimation, production or comparative judgment, has different characteristics such as the quantification of duration in time units or knowledge of the target duration, which may be responsible for the discrepancy. The relationship between postdictive time estimation and the parasympathetic nervous system is also discussed.

Structural Studies on Intact Clostridium Botulinum Neurotoxins Complexed with Inhibitors Leading to Drug Design

National Research Council Canada - National Science Library

Swaminathan, Subramanyam

2005-01-01

.... While one is common to botulinum toxins, the other is unique for tetanus. The second unique site also binds a tri-peptide which suggests that this peptide could be used as an inhibitor for tetanus, at least...

Genetic and biochemical analysis of peptide transport in Escherichia coli

International Nuclear Information System (INIS)

Andrews, J.C.

1986-01-01

E. coli peptide transport mutants have been isolated based on their resistance to toxic tripeptides. These genetic defects were found to map in two distinct chromosomal locations. The transport systems which require expression of the trp-linked opp genes and the oppE gene(s) for activity were shown to have different substrate preferences. Growth of E. coli in medium containing leucine results in increased entry of exogenously supplied tripeptides into the bacterial cell. This leucine-mediated elevation of peptide transport required expression of the trp-linked opp operon and was accompanied by increased sensitivity to toxic tripeptides, by an enhanced capacity to utilize nutritional peptides, and by an increase in both the velocity and apparent steady-state level of L-(U- 14 C)alanyl-L-alanyl-L-alanine accumulation for E. coli grown in leucine-containing medium relative to these parameters of peptide transport measured with bacteria grown in media lacking leucine. Direct measurement of opp operon expression by pulse-labeling experiments demonstrated that growth of E. coli in the presence of leucine resulted in increased synthesis of the oppA-encoded periplasmic binding protein. The transcriptional regulation of the trp-linked opp operon of E. coli was investigated using λ placMu51-generated lac operon fusions. Synthesis of β-galactosidase by strains harboring oppA-lac, oppB-lac, and oppD-lac fusions occurred at a basal level when the fusion-containing strains were grown in minimal medium

Functionalized polypyrrole nanotube arrays as electrochemical biosensor for the determination of copper ions

International Nuclear Information System (INIS)

Lin Meng; Hu Xiaoke; Ma Zhaohu; Chen Lingxin

2012-01-01

Highlights: ► PPy nanotube arrays were electropolymerized using ZnO nanowire arrays as templates. ► PPy nanotube arrays were anchored onto ITO glass without any chemical linker. ► Using SWV, the biosensor was found to be highly sensitive and selective to Cu 2+ . ► The biosensor was successfully applied for the determination of Cu 2+ in drinking water. - Abstract: A novel electrochemical biosensor based on functionalized polypyrrole (PPy) nanotube arrays modified with a tripeptide (Gly-Gly-His) proved to be highly effective for electrochemical analysis of copper ions (Cu 2+ ). The vertically oriented PPy nanotube arrays were electropolymerized by using modified zinc oxide (ZnO) nanowire arrays as templates which were electrodeposited on indium–tin oxide (ITO) coated glass substrates. The electrodes were functionalized by appending pyrrole-α-carboxylic acid onto the surface of polypyrrole nanotube arrays by electrochemical polymerization. The carboxylic groups of the polymer were covalently coupled with the amine groups of the tripeptide, and its structural features were confirmed by attenuated total reflection infrared (ATR-IR) spectroscopy. The tripeptide modified PPy nanotube arrays electrode was used for the electrochemical analysis of various trace copper ions by square wave voltammetry. The electrode was found to be highly sensitive and selective to Cu 2+ in the range of 0.1–30 μM. Furthermore, the developed biosensor exhibited a high stability and reproducibility, despite the repeated use of the biosensor electrode.

Omnipresence of the polyproline II helix in fibrous and globular proteins.

Science.gov (United States)

Esipova, Natalia G; Tumanyan, Vladimir G

2017-02-01

Left-handed helical conformation of a polypeptide chain (PPII) is the third type of the protein backbone structure. This conformation universally exists in fibrous, globular proteins, and biologically active peptides. It has unique physical and chemical properties determining a wide range of biological functions, from the protein folding to the tissue differentiation. New examples of the structure have been appearing in spite of difficulties in their detection and investigation. The annotation and prediction of the PPII was also a challenging task. Recently, many PPII motifs with new and/or unexpected functions are being accumulated in databases. In this review we describe the major structural and dynamic forms of PPII, the diversity of its functions, and the role in different biological processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhancement of nonspecific resistance by liposome-encapsulated immunomodulators does not affect skin graft rejection in mice

NARCIS (Netherlands)

Hagen, ten T.L.M.; Vossen, A.C.T.M.; Vianen, van W.; Tibbe, G.J.M.; Savelkoul, H.F.J.; Heremans, H.; Bakker-Woudenberg, I.A.J.M.

1995-01-01

Administration of liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidyl ethanolamine (LE-MTPPE) or interferon-gamma (LE-IFN-gamma), or co-encapsulated MTPPE and IFN-gamma (LE-(MTPPE/IFN-gamma)) resulted in a dramatic increase of the nonspecific antimicrobial resistance in

Modified peptides as potent inhibitors of the postsynaptic density-95/N-methyl-D-aspartate receptor interaction

DEFF Research Database (Denmark)

Bach, Anders; Chi, Celestine N.; Olsen, Thomas B.

2008-01-01

and unnatural amino acids, which disclosed a tripeptide with micromolar affinity and N-methylated tetrapeptides with improved affinities. Molecular modeling studies guided further N-terminal modifications and introduction of a range of N-terminal substitutions dramatically improved affinity. The best compound...

Urban blackbirds have shorter telomeres

NARCIS (Netherlands)

Ibanez-Alamo, Juan Diego; Pineda-Pampliega, Javier; Thomson, Robert L.; Aguirre, Jose I.; Diez-Fernandez, Alazne; Faivre, Bruno; Figuerola, Jordi; Verhulst, Simon

Urbanization, one of the most extreme human-induced environmental changes, represents a major challenge for many organisms. Anthropogenic habitats can have opposing effects on different fitness components, for example, by decreasing starvation risk but also health status. Assessment of the net

Shorter Exciton Lifetimes via an External Heavy-Atom Effect: Alleviating the Effects of Bimolecular Processes in Organic Light-Emitting Diodes.

Science.gov (United States)

Einzinger, Markus; Zhu, Tianyu; de Silva, Piotr; Belger, Christian; Swager, Timothy M; Van Voorhis, Troy; Baldo, Marc A

2017-10-01

Multiexcited-state phenomena are believed to be the root cause of two exigent challenges in organic light-emitting diodes; namely, efficiency roll-off and degradation. The development of novel strategies to reduce exciton densities under heavy load is therefore highly desirable. Here, it is shown that triplet exciton lifetimes of thermally activated delayed-fluorescence-emitter molecules can be manipulated in the solid state by exploiting intermolecular interactions. The external heavy-atom effect of brominated host molecules leads to increased spin-orbit coupling, which in turn enhances intersystem crossing rates in the guest molecule. Wave function overlap between the host and the guest is confirmed by combined molecular dynamics and density functional theory calculations. Shorter triplet exciton lifetimes are observed, while high photoluminescence quantum yields and essentially unaltered emission spectra are maintained. A change in the intersystem crossing rate ratio due to increased dielectric constants leads to almost 50% lower triplet exciton densities in the emissive layer in the steady state and results in an improved onset of the photoluminescence quantum yield roll-off at high excitation densities. Efficient organic light-emitting diodes with better roll-off behavior based on these novel hosts are fabricated, demonstrating the suitability of this concept for real-world applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Specific β-turns precede PPIIL structures binding to allele-specific HLA-DRβ1* PBRs in fully-protective malaria vaccine components

Science.gov (United States)

Bermudez, Adriana; Alba, Martha P.; Vanegas, Magnolia; Patarroyo, Manuel A.; Patarroyo, Manuel E.

2018-04-01

The 3D structural analysis of 62 peptides derived from highly pathogenic Plasmodium falciparum malaria parasite proteins involved in host cell invasion led to finding a striking association between particular β-turn types located in the N-terminal peripheral flanking residue region (preceding the polyproline II left-handed structures fitting into the HLA-DRβ* allele family) and modified immune protection-inducing protein structure induced long-lasting protective immunity. This is the first time association between two different secondary structures associated with a specific immunological function has been described: full, long-lasting protective immunity.

Kinetic enantioselectivity of a protonated bis(diamido)-bridged basket resorcin[4]arene towards alanine peptides.

Science.gov (United States)

Fraschetti, C; Montagna, M; Crestoni, M E; Calcaterra, A; Aiello, F; Santi, L; Filippi, A

2017-02-01

Efficient enantiodiscrimination of some alanine-containing di- and tri-peptides by using chiral protonated bis(diamido)-bridged basket resorcin[4]arenes depends on several factors, including the basicity of the amino acid residues at the C- and N-termini of the peptide.

Retrospective detection of exposure to sulfur mustard: Improvements on an assay for liquid chromatography-tandem mass spectrometry analysis of albumin/sulfur mustard adducts

NARCIS (Netherlands)

Noort, D.; Fidder, A.; Hulst, A.G.; Woolfitt, A.R.; Ash, D.; Barr, J.R.

2004-01-01

We here report on the further development of the method comprising the pronase digestion of albumin alkylated by sulfur mustard and the subsequent mass spectrometric analysis of an adducted tripeptide. This includes significant improvements in both the albumin isolation procedure and the automation

Pulmonary Embolism Inpatients Treated With Rivaroxaban Had Shorter Hospital Stays and Lower Costs Compared With Warfarin.

Science.gov (United States)

Margolis, Jay M; Deitelzweig, Steven; Kline, Jeffrey; Tran, Oth; Smith, David M; Crivera, Concetta; Bookhart, Brahim; Schein, Jeff

2016-11-01

Using real-world data, this study compares inpatient length of stay (LOS) and costs for patients with a primary diagnosis of pulmonary embolism (PE) initiating treatment with oral anticoagulation with rivaroxaban versus warfarin. Hospitalizations from MarketScan's Hospital Drug Database were selected from November 1, 2012, through December 31, 2013, for adults with a primary diagnosis of PE initiating treatment with rivaroxaban or warfarin. Warfarin patients were matched 1:1 to rivaroxaban patients using exact and propensity score matching. Hospital LOS, treatment patterns, and hospitalization costs were evaluated. Matched cohorts included 751 rivaroxaban-treated patients and 751 warfarin-treated patients. Adjusted mean LOS was 3.77 days for rivaroxaban patients (95% CI, 3.66-3.87 days) and 5.48 days for warfarin patients (95% CI, 5.33-5.63 days; P < .001). Mean (SD) LOS was shorter for patients taking rivaroxaban whether admission was for provoked PE (rivaroxaban: 5.2 [5.1] days; warfarin: 7.0 [6.5] days; P < .001) or unprovoked PE (rivaroxaban: 3.4 [2.3] days; warfarin: 5.1 [2.7] days; P < .001). Mean (SD) days from first dose to discharge were 2.5 (1.7) (rivaroxaban) and 4.0 (2.9) (warfarin) when initiated with parenteral anticoagulants (P < .001) and 2.7 (1.7) (rivaroxaban) and 4.0 (2.2) (warfarin) without parenteral anticoagulants (P < .001). The rivaroxaban cohort incurred significantly lower unadjusted mean (SD) hospitalization costs (rivaroxaban: $8473 [$9105]; warfarin: $10,291 [$9185]; P < .001), confirmed by covariate adjustment with generalized linear modeling estimating predicted mean hospitalization costs of $8266 for rivaroxaban patients (95% CI, $7851-$8681) and $10,511 for warfarin patients (95% CI, $10,031-$10,992; P < .001). patients with PE treated with rivaroxaban incurred significantly lower hospitalization costs by $2245 per admission compared with patients treated with warfarin, which was attributable to cost offsets from 1.71 fewer days of

Synthesis of aldehyde-linked nucleotides and DNA and their bioconjugations with lysine and peptides through reductive amination.

Science.gov (United States)

Raindlová, Veronika; Pohl, Radek; Hocek, Michal

2012-03-26

5-(5-Formylthienyl)-, 5-(4-formylphenyl)- and 5-(2-fluoro-5-formylphenyl)cytosine 2'-deoxyribonucleoside mono- (dC(R)MP) and triphosphates (dC(R)TP) were prepared by aqueous Suzuki-Miyaura cross-coupling of 5-iodocytosine nucleotides with the corresponding formylarylboronic acids. The dC(R)TPs were excellent substrates for DNA polymerases and were incorporated into DNA by primer extension or PCR. Reductive aminations of the model dC(R)MPs with lysine or lysine-containing tripeptide were studied and optimized. In aqueous phosphate buffer (pH 6.7) the yields of the reductive aminations with tripeptide III were up to 25 %. Bioconjugation of an aldehyde-containing DNA with a lysine-containing tripeptide was achieved through reductive amination in yields of up to 90 % in aqueous phosphate buffer. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cells by the peptides related to bacterial cell wall mucopeptide precursors: quantitative structure-activity relationships

International Nuclear Information System (INIS)

Kim, K.H.; Martin, Y.; Otis, E.; Mao, J.

1989-01-01

Quantitative structure-activity relationships (QSAR) of N-Ac amino acids, N-Ac dipeptides, and N-Ac tripeptides in inhibition of 125 I-labeled ristocetin binding to Micrococcus luteus cell wall have been developed to probe the details of the binding between ristocetin and N-acetylated peptides. The correlation equations indicate that (1) the binding is stronger for peptides in which the side chain of the C-terminal amino acid has a large molar refractivity (MR) value, (2) the binding is weaker for peptides with polar than for those with nonpolar C-terminal side chains, (3) the N-terminal amino acid in N-Ac dipeptides contributes 12 times that of the C-terminal amino acid to binding affinity, and (4) the interactions between ristocetin and the N-terminal amino acid of N-acetyl tripeptides appear to be much weaker than those with the first two amino acids

Impaired absorption of marked oligopeptide Glycine-I Tyrosine-Glycine after successful autologous-allotopic ileal mucosa transplantation in beagles.

Science.gov (United States)

Beiler, H A; Steinorth, J; Witt, A; Mier, W; Mohammed, A; Waag, K L; Zachariou, Z

2004-10-01

After establishing a method for ileal mucosa transplantation in an animal model, the authors investigated the absorptive capacity for oligopeptides of the transplanted mucosa. In 14 beagle dogs the authors transplanted ileal mucosa in a vascularized demucosed segment of the transverse colon. The colonic wall-ileal mucosa complex then was integrated in the ileal continuity. Six animals were lost owing to operative complications. Absorptive capacity for oligopeptides was measured in the remaining 8 animals with the iodine 131 (131I)-marked tripeptide glycine-tyrosine-glycine before and 4 weeks after transplantation. The results were compared and analyzed with the Student's t test for matched pairs. Blood concentrations of the marked tripeptide with P value less than .05 were considered as a significant reduction in the absorptive capacity of the transplanted ileal mucosa. After fixation with glutaraldehyd graft, uptake of the colonic wall-ileal mucosa complex was evaluated histologically in 8 animals. In all 8 animals, a 100% graft uptake was verified in all sections. Fifteen minutes after application of 15 MBc Glycine-131I-Tyrosine-Glycine there was no significant difference in the absorption between normal and transplanted ileal mucosa. After 30 minutes, the absorption of the transplanted ileal mucosa showed a tendency (P < .1) for an impaired uptake of the marked tripeptide. However, 60 minutes after application the difference in the absorptive capacity of the transplanted ileal mucosa was significant (P < .05). Autologous allotopic ileal mucosa transplantation is feasible; however, an impaired absorption of oligopeptides of the transplanted mucosa 4 weeks after transplantation could be observed.

High affinity recognition of a Phytophthora protein by Arabidopsis via an RGD motif

NARCIS (Netherlands)

Senchou, V.; Weide, R.L.; Carrasco, A.; Bouyssou, H.; Pont-Lezica, R.; Govers, F.; Canut, H.

2004-01-01

The RGD tripeptide sequence, a cell adhesion motif present in several extracellular matrix proteins of mammalians, is involved in numerous plant processes. In plant-pathogen interactions, the RGD motif is believed to reduce plant defence responses by disrupting adhesions between the cell wall and

Hypothalamic regulation of thyroid-stimulating hormone and prolactin release : the role of thyrotrophin-releasing hormone

NARCIS (Netherlands)

G.A.C. van Haasteren (Goedele)

1995-01-01

textabstractThyrotrophin-releasing-hormone (TRH), a tripeptide, is produced by hypothalamic neurons and transported along their axons to the median eminence (ME). From there it is released at nerve terminals into hypophyseal portal blood. It is then transported to the anterior pituitary gland where

Ligand binding analyses of the putative peptide transporter YjdL from E. coli display a significant selectivity towards dipeptides

DEFF Research Database (Denmark)

Ernst, Heidi Asschenfeldt; Pham, Antony; Hald, Helle

2009-01-01

Proton-dependent oligopeptide transporters (POTs) are secondary active transporters that couple the inwards translocation of di- and tripeptides to inwards proton translocation. Escherichia coli contains four genes encoding the putative POT proteins YhiP, YdgR, YjdL and YbgH. We have over-express...

Shorter Hospital Stays and Lower Costs for Rivaroxaban Compared With Warfarin for Venous Thrombosis Admissions.

Science.gov (United States)

Margolis, Jay M; Deitelzweig, Steven; Kline, Jeffrey; Tran, Oth; Smith, David M; Bookhart, Brahim; Crivera, Concetta; Schein, Jeff

2016-10-06

% confidence interval, $8035-$8739]; warfarin $10 275 [95% confidence interval, $9842-$10 708]). Rivaroxaban was associated with significantly shorter hospital LOS and lower hospitalization costs compared with warfarin. © 2016 The Authors, Janssen Scientific Affairs, LLC, and Truven Health Analytics. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Basolateral glycylsarcosine (Gly-Sar) transport in Caco-2 cell monolayers is pH dependent

DEFF Research Database (Denmark)

Berthelsen, Ragna; Nielsen, Carsten Uhd; Brodin, Birger

2013-01-01

Transepithelial di/tripeptide transport in enterocytes occurs via the apical proton-coupled peptide transporter, hPEPT1 (SLC15A1) and a basolateral peptide transporter, which has only been characterized functionally. In this study we examined the pH dependency, substrate uptake kinetics and subst...

The prototypical proton-coupled oligopeptide transporter YdgR from Escherichia coli facilitates chloramphenicol uptake into bacterial cells

DEFF Research Database (Denmark)

Prabhala, Bala K; Aduri, Nanda G; Sharma, Neha

2018-01-01

. However, to date no report exists on any specific transport protein that facilitates Cam uptake. The proton-coupled oligopeptide transporter (POT) YdgR from Escherichia coli is a prototypical member of the POT family, functioning in proton-coupled uptake of di- and tripeptides. By following bacterial...

Transport of peptidomimetic drugs by the intestinal Di/tri-peptide transporter, PepT1

DEFF Research Database (Denmark)

Brodin, Birger; Nielsen, Carsten Uhd; Steffansen, Bente

2002-01-01

The apical membrane of small intestinal enterocytes possess an uptake system for di- and tripeptides. The physiological function of the system is to transport small peptides resulting from digestion of dietary protein. Moreover, due to the broad substrate specificity of the system, it is also cap...

A Bayesian-probability-based method for assigning protein backbone dihedral angles based on chemical shifts and local sequences

Energy Technology Data Exchange (ETDEWEB)

Wang Jun; Liu Haiyan [University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at the Microscale, and Key Laboratory of Structural Biology, School of Life Sciences (China)], E-mail: hyliu@ustc.edu.cn

2007-01-15

Chemical shifts contain substantial information about protein local conformations. We present a method to assign individual protein backbone dihedral angles into specific regions on the Ramachandran map based on the amino acid sequences and the chemical shifts of backbone atoms of tripeptide segments. The method uses a scoring function derived from the Bayesian probability for the central residue of a query tripeptide segment to have a particular conformation. The Ramachandran map is partitioned into representative regions at two levels of resolution. The lower resolution partitioning is equivalent to the conventional definitions of different secondary structure regions on the map. At the higher resolution level, the {alpha} and {beta} regions are further divided into subregions. Predictions are attempted at both levels of resolution. We compared our method with TALOS using the original TALOS database, and obtained comparable results. Although TALOS may produce the best results with currently available databases which are much enlarged, the Bayesian-probability-based approach can provide a quantitative measure for the reliability of predictions.

Planar integrated optical waveguide used as a transducer to yield chemical information: detection of the activity of proteolytic enzymes e.g. serine-proteases

Science.gov (United States)

Zhylyak, Gleb; Ramoz-Perez, Victor; Linnhoff, Michael; Hug, Thomas; Citterio, Daniel; Spichiger-Keller, Ursula E.

2005-03-01

The paper shows the very first results of a feasibility study where the activity of proteolytic enzymes towards dye-labelled artificial substrates immobilized on the surface of planar optical Ta2O5 waveguide was investigated. Within this project, a chromophore label was developed, synthesized and attached to the carboxy-terminus of specific tripeptides. The goal was to develop a highly sensitive optical assay in order to monitor the activity of serine-proteases by cleavage of the amide bond between peptide and chromophore. On the one hand, a strategy was developed to immobilize the labeled tripeptide unto integrated planar waveguides. On the other hand, an instrument, the so-called "chip-reader" was developed to detect the biological process on the surface of the integrated planar optical waveguide. Surface characteristics were analyzed by XPS, TOF-SIMS and contact angle measurements. A comparison between the effectivity of ATR-photometry on chip using TE0 mode and photometry in transmission mode is discussed.

Feasibility of a shorter Goal Attainment Scaling method for a pediatric spasticity clinic - The 3-milestones GAS.

Science.gov (United States)

Krasny-Pacini, A; Pauly, F; Hiebel, J; Godon, S; Isner-Horobeti, M-E; Chevignard, M

2017-07-01

Goal Attainment Scaling (GAS) is a method for writing personalized evaluation scales to quantify progress toward defined goals. It is useful in rehabilitation but is hampered by the experience required to adequately "predict" the possible outcomes relating to a particular goal before treatment and the time needed to describe all 5 levels of the scale. Here we aimed to investigate the feasibility of using GAS in a clinical setting of a pediatric spasticity clinic with a shorter method, the "3-milestones" GAS (goal setting with 3 levels and goal rating with the classical 5 levels). Secondary aims were to (1) analyze the types of goals children's therapists set for botulinum toxin treatment and (2) compare the score distribution (and therefore the ability to predict outcome) by goal type. Therapists were trained in GAS writing and prepared GAS scales in the regional spasticity-management clinic they attended with their patients and families. The study included all GAS scales written during a 2-year period. GAS score distribution across the 5 GAS levels was examined to assess whether the therapist could reliably predict outcome and whether the 3-milestones GAS yielded similar distributions as the original GAS method. In total, 541 GAS scales were written and showed the expected score distribution. Most scales (55%) referred to movement quality goals and fewer (29%) to family goals and activity domains. The 3-milestones GAS method was feasible within the time constraints of the spasticity clinic and could be used by local therapists in cooperation with the hospital team. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Psoralen-mediated virus photoinactivation in platelet concentrates: enhanced specificity of virus kill in the absence of shorter UVA wavelengths

International Nuclear Information System (INIS)

Margolis-Nunno, Henrietta; Robinson, Richard; Horowitz, Bernard; Ben-Hur, Ehud; Geacintov, N.E.

1995-01-01

Treatments with psoralens and long-wavelength ultraviolet radiation (UVA, 320-400 nm; PUVA) have shown efficacy for virus sterilization of platelet concentrates (PC). We have employed the psoralen derivative 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT), and have found that platelet integrity is best preserved when rutin, a flavonoid that quenches multiple reactive oxygen species, is present during AMT/UVA treatment of PC. In this report, we examine the effects of different UVA spectra under our standard PC treatment conditions (i.e. 50 μg/mL AMT, 0.35 mM rutin and 38 J/cm 2 UVA). Added vesicular stomatitis virus (VSV; ≥ 5.5 log 10 ) was completely inactivated with the simultaneous maintenance of the platelet aggregation response (> 90% of control) when a UVA light source with transmission mainly between 360 and 370 nm (narrow UVA1) was used. In contrast, with a broad-band UVA (320-400 nm; broad UVA) light source, the aggregation response was greatly compromised (< 50% of control) with only a minor increase in the rate of VSV kill. With this lamp, platelet function could be improved to about 75% of the control by adding a long-pass filter, which reduced the transmission of shorter (≤ 345 nm) UVA wavelengths (340-400 nm; UVA1). At equivalent levels of virus kill, aggregation function was always best preserved when narrow UVA1 was used for PUVA treatment. Even in the absence of AMT, and with or without rutin present, narrow UVA1 irradiation was better tolerated by platelets than was broad UVA. (author)

Elucidating Key Motifs Required for Arp2/3-Dependent and Independent Actin Nucleation by Las17/WASP

Science.gov (United States)

Urbanek, Agnieszka N.; Smaczynska-de Rooij, Iwona I.

2016-01-01

Actin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. Arp2/3 is a well-characterised protein complex that can promote nucleation of new filaments, though its activity requires additional nucleation promotion factors (NPFs). The best recognized of these factors are the WASP family of proteins that contain binding motifs for both monomeric actin and for Arp2/3. Previously we demonstrated that the yeast WASP homologue, Las17, in addition to activating Arp2/3 can also nucleate actin filaments de novo, independently of Arp2/3. This activity is dependent on its polyproline rich region. Through biochemical and in vivo analysis we have now identified key motifs within the polyproline region that are required for nucleation and elongation of actin filaments, and have addressed the role of the WH2 domain in the context of actin nucleation without Arp2/3. We have also demonstrated that full length Las17 is able to bind liposomes giving rise to the possibility of direct linkage of nascent actin filaments to specific membrane sites to which Las17 has been recruited. Overall, we propose that Las17 functions as the key initiator of de novo actin filament formation at endocytic sites by nucleating, elongating and tethering nascent filaments which then serve as a platform for Arp2/3 recruitment and function. PMID:27637067

Self-assembled peptides for coating of active sulfur nanoparticles in lithium–sulfur battery

International Nuclear Information System (INIS)

Jewel, Yead; Yoo, Kisoo; Liu, Jin; Dutta, Prashanta

2016-01-01

Development of lithium–sulfur (Li–S) battery is hindered by poor cyclability due to the loss of sulfur, although Li–S battery can provide high energy density. Coating of sulfur nanoparticles can help maintain active sulfur in the cathode of Li–S battery, and hence increase the cyclability. Among myriad of coating materials, synthetic peptides are very attractive because of their spontaneous self-assembly as well as electrical conductive characteristics. In this study, we explored the use of various synthetic peptides as a coating material for sulfur nanoparticles. Atomistic simulations were carried out to identify optimal peptide structure and density for coating sulfur nanoparticles. Three different peptide models, poly-proline, poly(leucine–lysine) and poly-histidine, are selected for this study based on their peptide–peptide and peptide-sulfur interactions. Simulation results show that both poly-proline and poly(leucine–lysine) can form self-assembled coating on sulfur nanoparticles (2–20 nm) in pyrrolidinone, a commonly used solvent for cathode slurry. We also studied the structural integrity of these synthetic peptides in organic [dioxolane (DOL) and dimethoxyethane (DME)] electrolyte used in Li–S battery. Both peptides show stable structures in organic electrolyte (DOL/DME) used in Li–S battery. Furthermore, the dissolution of sulfur molecules in organic electrolyte is investigated in the absence and presence of these peptide coatings. It was found that only poly(leucine–lysine)-based peptide can most effectively suppress the sulfur loss in electrolyte, suggesting its potential applications in Li–S battery as a coating material.Graphical abstract

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

Science.gov (United States)

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

2017-08-21

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

Conditional inactivation of TNFα-converting enzyme in chondrocytes results in an elongated growth plate and shorter long bones.

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Kenta Saito

Full Text Available TNFα-converting enzyme (TACE is a membrane-bound proteolytic enzyme with essential roles in the functional regulation of TNFα and epidermal growth factor receptor (EGFR ligands. Previous studies have demonstrated critical roles for TACE in vivo, including epidermal development, immune response, and pathological neoangiogenesis, among others. However, the potential contribution of TACE to skeletal development is still unclear. In the present study, we generated a Tace mutant mouse in which Tace is conditionally disrupted in chondrocytes under the control of the Col2a1 promoter. These mutant mice were fertile and viable but all exhibited long bones that were approximately 10% shorter compared to those of wild-type animals. Histological analyses revealed that Tace mutant mice exhibited a longer hypertrophic zone in the growth plate, and there were fewer osteoclasts at the chondro-osseous junction in the Tace mutant mice than in their wild-type littermates. Of note, we found an increase in osteoprotegerin transcripts and a reduction in Rankl and Mmp-13 transcripts in the TACE-deficient cartilage, indicating that dysregulation of these genes is causally related to the skeletal defects in the Tace mutant mice. Furthermore, we also found that phosphorylation of EGFR was significantly reduced in the cartilage tissue lacking TACE, and that suppression of EGFR signaling increases osteoprotegerin transcripts and reduces Rankl and Mmp-13 transcripts in primary chondrocytes. In accordance, chondrocyte-specific abrogation of Egfr in vivo resulted in skeletal defects nearly identical to those observed in the Tace mutant mice. Taken together, these data suggest that TACE-EGFR signaling in chondrocytes is involved in the turnover of the growth plate during postnatal development via the transcriptional regulation of osteoprotegerin, Rankl, and Mmp-13.

The tandem chain extension aldol reaction used for synthesis of ketomethylene tripeptidomimetics targeting hPEPT1

DEFF Research Database (Denmark)

Thorn, Karina; Nielsen, Carsten Uhd; Jakobsen, Palle

2011-01-01

The rationale for targeting the human di-/tripeptide transporter hPEPT1 for oral drug delivery has been well established by several drug and prodrug cases. The aim of this study was to synthesize novel ketomethylene modified tripeptidomimetics and to investigate their binding affinity for hPEPT1....

The relevance of the non-canonical PTS1 of peroxisomal catalase

NARCIS (Netherlands)

Williams, Chris; Aksam, Eda Bener; Gunkel, Katja; Veenhuis, Marten; van der Klei, Ida J.

Catalase is sorted to peroxisomes via a C-terminal peroxisomal targeting signal 1 (PTS1), which binds to the receptor protein Pex5. Analysis of the C-terminal sequences of peroxisomal catalases from various species indicated that catalase never contains the typical C-terminal PTS1 tripeptide-SKL,

Characterization of rPEPT2-mediated Gly-Sar transport parameters in the rat kidney proximal tubule cell line SKPT-0193 cl.2 cultured in basic growth media

DEFF Research Database (Denmark)

Bravo, Silvina A; Nielsen, Carsten Uhd; Frokjaer, Sven

2005-01-01

The rat proximal kidney tubule cell line SKPT-0193 cl.2 (SKPT) expresses the di-/tripeptide transporter PEPT2 (rPEPT2) and has been used to study PEPT2-mediated transport. Traditionally, SKPT cells have been cultured in growth media supplemented with epidermal growth factor (EGF), apotransferrin,...

Uranyl complexes of glutathione

Energy Technology Data Exchange (ETDEWEB)

Marzotto, A [Consiglio Nazionale delle Ricerche, Padua (Italy). Lab. di Chimica e Tecnologia dei Radioelementi

1977-01-01

Dioxouranium(VI) complexes of the tripeptide glutathione having different molar ratios were prepared and studied by IR, PMR, electronic absorption and circular dichroism spectra. The results indicate that coordination occurs at the carboxylato groups, acting as monodentate ligands, whereas no significant interaction with the amino and sulfhydrylic groups takes place.

Aiming for a shorter rheumatoid arthritis MRI protocol: can contrast-enhanced MRI replace T2 for the detection of bone marrow oedema?

Energy Technology Data Exchange (ETDEWEB)

Stomp, Wouter; Bloem, Johan L.; Reijnierse, Monique [Leiden University Medical Center, Department of Radiology, P.O. Box 9600, Leiden (Netherlands); Krabben, Annemarie; Heijde, Desiree van der; Huizinga, Tom W.J.; Helm-van Mil, Annette H.M. van der [Leiden University Medical Center, Department of Rheumatology, P.O. Box 9600, Leiden (Netherlands)

2014-10-15

To determine whether T1 post-gadolinium chelate images (T1Gd) can replace T2-weighted images (T2) for evaluating bone marrow oedema (BME), thereby allowing a shorter magnetic resonance imaging (MRI) protocol in rheumatoid arthritis (RA). In 179 early arthritis patients and 43 advanced RA patients, wrist and metacarpophalangeal joints were examined on a 1.5-T extremity MRI system with a standard protocol (coronal T1, T2 fat-saturated and coronal and axial T1 fat-saturated after Gd). BME was scored according to OMERACT RAMRIS by two observers with and without T2 images available. Agreement was assessed using intraclass correlation coefficients (ICCs) for semi-quantitative scores and test characteristics with T2 images as reference. Agreement between scores based on T2 and T1Gd images was excellent ICC (0.80-0.99). At bone level, sensitivity and specificity of BME on T1Gd compared to T2 were high for both patient groups and both readers (all ≥80 %). T1Gd and T2 images are equally suitable for evaluating BME. Because contrast is usually administered to assess (teno)synovitis, a short MRI protocol of T1 and T1Gd is sufficient in RA. (orig.)

Aiming for a shorter rheumatoid arthritis MRI protocol: can contrast-enhanced MRI replace T2 for the detection of bone marrow oedema?

International Nuclear Information System (INIS)

Stomp, Wouter; Bloem, Johan L.; Reijnierse, Monique; Krabben, Annemarie; Heijde, Desiree van der; Huizinga, Tom W.J.; Helm-van Mil, Annette H.M. van der

2014-01-01

To determine whether T1 post-gadolinium chelate images (T1Gd) can replace T2-weighted images (T2) for evaluating bone marrow oedema (BME), thereby allowing a shorter magnetic resonance imaging (MRI) protocol in rheumatoid arthritis (RA). In 179 early arthritis patients and 43 advanced RA patients, wrist and metacarpophalangeal joints were examined on a 1.5-T extremity MRI system with a standard protocol (coronal T1, T2 fat-saturated and coronal and axial T1 fat-saturated after Gd). BME was scored according to OMERACT RAMRIS by two observers with and without T2 images available. Agreement was assessed using intraclass correlation coefficients (ICCs) for semi-quantitative scores and test characteristics with T2 images as reference. Agreement between scores based on T2 and T1Gd images was excellent ICC (0.80-0.99). At bone level, sensitivity and specificity of BME on T1Gd compared to T2 were high for both patient groups and both readers (all ≥80 %). T1Gd and T2 images are equally suitable for evaluating BME. Because contrast is usually administered to assess (teno)synovitis, a short MRI protocol of T1 and T1Gd is sufficient in RA. (orig.)

Fluorescence analysis of the Hansenula polymorpha peroxisomal targeting signal-1 receptor, Pex5p

NARCIS (Netherlands)

Boteva, R.; Koek, A.; Visser, N.V.; Visser, A.J.W.G.; Krieger, E.; Zlateva, T.; Veenhuis, M.; Klei, van der I.

2003-01-01

Correct sorting of newly synthesized peroxisomal matrix proteins is dependent on a peroxisomal targeting signal (PTS). So far two PTSs are known. PTS1 consists of a tripeptide that is located at the extreme C terminus of matrix proteins and is specifically recognized by the PTS1-receptor Pex5p. We

ATLAS: Adjuvant Tamoxifen Longer Against Shorter

Science.gov (United States)

1998-09-01

largely tunaffected by other these 30 000 women during about 10 years of follow-up patient characteristics or treatments. were 21% (SD 3), 29% (SD 2...for both types of mosted to stop part of the eduon y epatient . most of them did stop, part of the reduction in the The right side of figure 4...patient characteristics (e.g. high/ low-risk, ER+/ER-, pre/post-menopausal) recorded at entry. Other trials of tamoxifen duration The Atlas collaboration

Movement and touch make plants shorter

NARCIS (Netherlands)

Heuvelink, E.; Kierkels, T.

2017-01-01

Plants in the greenhouse are increasingly on the move. More attention is being paid to air circulation and mobile cultivation is on the rise. Research shows that movement and touch (also as plants rub against each other) slow down growth. That can be frustrating but you can also use it to your

Wear Fast, Die Young: More Worn Teeth and Shorter Lives in Iberian Compared to Scottish Red Deer.

Science.gov (United States)

Pérez-Barbería, F J; Carranza, J; Sánchez-Prieto, C

2015-01-01

Teeth in Cervidae are permanent structures that are not replaceable or repairable; consequently their rate of wear, due to the grinding effect of food and dental attrition, affects their duration and can determine an animal's lifespan. Tooth wear is also a useful indicator of accumulative life energy investment in intake and mastication and their interactions with diet. Little is known regarding how natural and sexual selection operate on dental structures within a species in contrasting environments and how these relate to life history traits to explain differences in population rates of tooth wear and longevity. We hypothesised that populations under harsh environmental conditions should be selected for more hypsodont teeth while sexual selection may maintain similar sex differences within different populations. We investigated the patterns of tooth wear in males and females of Iberian red deer (Cervus elaphus hispanicus) in Southern Spain and Scottish red deer (C. e. scoticus) across Scotland, that occur in very different environments, using 10343 samples from legal hunting activities. We found higher rates of both incisor and molar wear in the Spanish compared to Scottish populations. However, Scottish red deer had larger incisors at emergence than Iberian red deer, whilst molars emerged at a similar size in both populations and sexes. Iberian and Scottish males had earlier tooth depletion than females, in support of a similar sexual selection process in both populations. However, whilst average lifespan for Iberian males was 4 years shorter than that for Iberian females and Scottish males, Scottish males only showed a reduction of 1 year in average lifespan with respect to Scottish females. More worn molars were associated with larger mandibles in both populations, suggesting that higher intake and/or greater investment in food comminution may have favoured increased body growth, before later loss of tooth efficiency due to severe wear. These results

Do Dysphagic Patients with an Absent Pharyngeal Swallow Have a Shorter Survival than Dysphagic Patients with Pharyngeal Swallow? Prognostic Importance of a Therapeutic Videoradiographic Swallowing Study (TVSS)

International Nuclear Information System (INIS)

Buelow, M.; Olsson, R.; Ekberg, O.

2005-01-01

Purpose: To study survival in two groups of dysphagic patients - one group unable to elicit the pharyngeal stage of swallow (APS) and another group with pharyngeal swallow (WPS) - and to compare recommendations regarding nutrition and therapeutic strategies based on the therapeutic swallowing study. Material and Methods: In this retrospective study, the records of dysphagic patients who have undergone a therapeutic videoradiographic swallowing study (TVSS) were reviewed. Forty patients without pharyngeal swallow were matched for age and gender with 40 patients with pharyngeal swallow; altogether 80 patients were included in the study. Survival was registered at 3, 12, and 72 months after the TVSS. Results: In this study, the APS group had a significantly shorter survival time compared to the WPS group when followed-up at 12 months. In the APS group, most patients (37.5% (15/40)) died within the 3 months after TVSS. At 72 months, 62.5% (25/40) of the patients in the APS group had died. In the WPS group, 5% (2/40) had died within 3 months and 47.4% (19/40) after 12 months. At 72 months, 52.5% (21/40) of the patients in the WPS group had died. Regarding nutritional and therapeutic recommendations based on TVSS, 34/40 in the APS group were recommended no oral intake. Eighteen naso-gastric tubes were placed directly after TVSS. The therapeutic strategies recommended were head-positioning, thermal tactile stimulation, and tongue exercises (in 8 patients). In the WPS group, all patients were recommended oral intake. Diet modification was recommended in 29 patients. The therapeutic strategies recommended were head-positioning, thermal tactile stimulation, tongue exercises, supraglottic swallow, and effortful swallow (in 24 patients). Conclusion: Patients unable to elicit the pharyngeal stage of swallow had a shorter survival time than patients with pharyngeal swallow, probably due to a more severe underlying disease. Tube feeding was more frequent in the APS group. Fewer

Harnessing natural diversity to probe metabolic pathways.

Directory of Open Access Journals (Sweden)

Oliver R Homann

2005-12-01

Full Text Available Analyses of cellular processes in the yeast Saccharomyces cerevisiae rely primarily upon a small number of highly domesticated laboratory strains, leaving the extensive natural genetic diversity of the model organism largely unexplored and unexploited. We asked if this diversity could be used to enrich our understanding of basic biological processes. As a test case, we examined a simple trait: the utilization of di/tripeptides as nitrogen sources. The capacity to import small peptides is likely to be under opposing selective pressures (nutrient utilization versus toxin vulnerability and may therefore be sculpted by diverse pathways and strategies. Hitherto, dipeptide utilization in S. cerevisiae was solely ascribed to the activity of a single protein, the Ptr2p transporter. Using high-throughput phenotyping and several genetically diverse strains, we identified previously unknown cellular activities that contribute to this trait. We find that the Dal5p allantoate/ureidosuccinate permease is also capable of facilitating di/tripeptide transport. Moreover, even in the absence of Dal5p and Ptr2p, an additional activity--almost certainly the periplasmic asparaginase II Asp3p--facilitates the utilization of dipeptides with C-terminal asparagine residues by a different strategy. Another, as-yet-unidentified activity enables the utilization of dipeptides with C-terminal arginine residues. The relative contributions of these activities to the utilization of di/tripeptides vary among the strains analyzed, as does the vulnerability of these strains to a toxic dipeptide. Only by sampling the genetic diversity of multiple strains were we able to uncover several previously unrecognized layers of complexity in this metabolic pathway. High-throughput phenotyping facilitates the rapid exploration of the molecular basis of biological complexity, allowing for future detailed investigation of the selective pressures that drive microbial evolution.

Carrier-mediated transport of peptides by the kidney

International Nuclear Information System (INIS)

Skopicki, H.A.

1988-01-01

Small peptide transport was characterized to determine if: (1) Multiple carriers are present in the luminal membrane of renal proximal tubular cells; (2) Carrier-mediated peptide transport is limited by size; and (3) Gentamicin inhibits carrier-mediated reabsorption of peptides. Uptake of glycyl-[ 3 H]proline (Gly-Pro) into renal brush border membrane vesicles demonstrated a dual affinity carrier system. Whether multiple carriers are present was further investigated by characterizing the uptake of [ 3 H]pyroglutamyl-histidine. To determine if carrier-mediated transport of peptides is limited by size of the molecule, uptake of the hydrolytically resistant tripeptide, [ 3 H]pryroglutamyl-histidyl-tryptophan (pGlu-His-Trp), and tetrapeptide, [ 3 H]pyroglutamyl-histidyl-tryptophyl-serine (pGlu-His-Trp-Ser) were assessed. These data indicate: multiple carriers exist on the luminal membrane of renal proximal tubular cells for the transport of dipeptides, and tripeptide pGlu-His-Trp and the tetrapeptide pGlu-His-Trp-Ser are not taken up by a carrier-mediated mechanism, suggesting that the carrier may be limited by the size of the substrate

Testis-expressed profilins 3 and 4 show distinct functional characteristics and localize in the acroplaxome-manchette complex in spermatids

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Rothkegel Martin

2009-05-01

Full Text Available Abstract Background Multiple profilin isoforms exist in mammals; at least four are expressed in the mammalian testis. The testis-specific isoforms profilin-3 (PFN3 and profilin-4 (PFN4 may have specialized roles in spermatogenic cells which are distinct from known functions fulfilled by the "somatic" profilins, profilin-1 (PFN1 and profilin-2 (PFN2. Results Ligand interactions and spatial distributions of PFN3 and PFN4 were compared by biochemical, molecular and immunological methods; PFN1 and PFN2 were employed as controls. β-actin, phosphoinositides, poly-L-proline and mDia3, but not VASP, were confirmed as in vitro interaction partners of PFN3. In parallel experiments, PFN4 bound to selected phosphoinositides but not to poly-L-proline, proline-rich proteins, or actin. Immunofluorescence microscopy of PFN3 and PFN4 revealed distinct subcellular locations in differentiating spermatids. Both were associated first with the acroplaxome and later with the transient manchette. Predicted 3D structures indicated that PFN3 has the actin-binding site conserved, but retains only approximately half of the common poly-L-proline binding site. PFN4, in comparison, has lost both, polyproline and actin binding sites completely, which is well in line with the experimental data. Conclusion The testis-specific isoform PFN3 showed major hallmarks of the well characterized "somatic" profilin isoforms, albeit with distinct binding affinities. PFN4, on the other hand, did not interact with actin or polyproline in vitro. Rather, it seemed to be specialized for phospholipid binding, possibly providing cellular functions which are distinct from actin dynamics regulation.

Genome-wide analyses and functional classification of proline repeat-rich proteins: potential role of eIF5A in eukaryotic evolution.

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Ajeet Mandal

Full Text Available The eukaryotic translation factor, eIF5A has been recently reported as a sequence-specific elongation factor that facilitates peptide bond formation at consecutive prolines in Saccharomyces cerevisiae, as its ortholog elongation factor P (EF-P does in bacteria. We have searched the genome databases of 35 representative organisms from six kingdoms of life for PPP (Pro-Pro-Pro and/or PPG (Pro-Pro-Gly-encoding genes whose expression is expected to depend on eIF5A. We have made detailed analyses of proteome data of 5 selected species, Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, Mus musculus and Homo sapiens. The PPP and PPG motifs are low in the prokaryotic proteomes. However, their frequencies markedly increase with the biological complexity of eukaryotic organisms, and are higher in newly derived proteins than in those orthologous proteins commonly shared in all species. Ontology classifications of S. cerevisiae and human genes encoding the highest level of polyprolines reveal their strong association with several specific biological processes, including actin/cytoskeletal associated functions, RNA splicing/turnover, DNA binding/transcription and cell signaling. Previously reported phenotypic defects in actin polarity and mRNA decay of eIF5A mutant strains are consistent with the proposed role for eIF5A in the translation of the polyproline-containing proteins. Of all the amino acid tandem repeats (≥3 amino acids, only the proline repeat frequency correlates with functional complexity of the five organisms examined. Taken together, these findings suggest the importance of proline repeat-rich proteins and a potential role for eIF5A and its hypusine modification pathway in the course of eukaryotic evolution.

Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism.

Science.gov (United States)

Alvarado, John J; Betts, Laurie; Moroco, Jamie A; Smithgall, Thomas E; Yeh, Joanne I

2010-11-12

Most mammalian cell types depend on multiple Src family kinases (SFKs) to regulate diverse signaling pathways. Strict control of SFK activity is essential for normal cellular function, and loss of kinase regulation contributes to several forms of cancer and other diseases. Previous x-ray crystal structures of the SFKs c-Src and Hck revealed that intramolecular association of their Src homology (SH) 3 domains and SH2 kinase linker regions has a key role in down-regulation of kinase activity. However, the amino acid sequence of the Hck linker represents a suboptimal ligand for the isolated SH3 domain, suggesting that it may form the polyproline type II helical conformation required for SH3 docking only in the context of the intact structure. To test this hypothesis directly, we determined the crystal structure of a truncated Hck protein consisting of the SH2 and SH3 domains plus the linker. Despite the absence of the kinase domain, the structures and relative orientations of the SH2 and SH3 domains in this shorter protein were very similar to those observed in near full-length, down-regulated Hck. However, the SH2 kinase linker adopted a modified topology and failed to engage the SH3 domain. This new structure supports the idea that these noncatalytic regions work together as a "conformational switch" that modulates kinase activity in a manner unique to the SH3 domain and linker topologies present in the intact Hck protein. Our results also provide fresh structural insight into the facile induction of Hck activity by HIV-1 Nef and other Hck SH3 domain binding proteins and implicate the existence of innate conformational states unique to individual Src family members that "fine-tune" their sensitivities to activation by SH3-based ligands.

Dipeptide transporters in Fusarium graminearum

DEFF Research Database (Denmark)

Droce, Aida; Giese, Henriette; Søndergaard, Teis

Fungi have evolved different transport mechanisms in order to utilize both inorganic and organic nitrogen sources because nitrogen availability often is one of the limiting factors in pathogenic processes. In this study we have characterized four di/tripeptide transporters in the necrotrophic plant...... pathogen Fusarium graminearum Fusarium that causes head blight (FHB) in wheat and barley....

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor.

Science.gov (United States)

Zhang, Hao; Jing, Xigang; Shi, Yang; Xu, Hao; Du, Jianhai; Guan, Tongju; Weihrauch, Dorothee; Jones, Deron W; Wang, Weiling; Gourlay, David; Oldham, Keith T; Hillery, Cheryl A; Pritchard, Kirkwood A

2013-11-01

Myeloperoxidase (MPO) plays important roles in disease by increasing oxidative and nitrosative stress and oxidizing lipoproteins. Here we report N-acetyl lysyltyrosylcysteine amide (KYC) is an effective inhibitor of MPO activity. We show KYC inhibits MPO-mediated hypochlorous acid (HOCl) formation and nitration/oxidation of LDL. Disulfide is the major product of MPO-mediated KYC oxidation. KYC (≤4,000 μM) does not induce cytotoxicity in bovine aortic endothelial cells (BAECs). KYC inhibits HOCl generation by phorbol myristate acetate (PMA)-stimulated neutrophils and human promyelocytic leukemia (HL-60) cells but not superoxide generation by PMA-stimulated HL-60 cells. KYC inhibits MPO-mediated HOCl formation in BAEC culture and protects BAECs from MPO-induced injury. KYC inhibits MPO-mediated lipid peroxidation of LDL whereas tyrosine (Tyr) and tryptophan (Trp) enhance oxidation. KYC is unique as its isomers do not inhibit MPO activity, or are much less effective. Ultraviolet-visible spectral studies indicate KYC binds to the active site of MPO and reacts with compounds I and II. Docking studies show the Tyr of KYC rests just above the heme of MPO. Interestingly, KYC increases MPO-dependent H₂O₂ consumption. These data indicate KYC is a novel and specific inhibitor of MPO activity that is nontoxic to endothelial cell cultures. Accordingly, KYC may be useful for treating MPO-mediated vascular disease.

Safety evaluation of an IPP tripeptide-containing milk protein hydrolysate

NARCIS (Netherlands)

Ponstein-Simarro Doorten, A.Y.; Wiel, J.A.G. van de; Jonker, D.

2009-01-01

Tensguard™ is a milk protein hydrolysate containing the lactotripeptide IPP. It is derived from cow's milk, which is present in the human diet and has a safe history of consumption. The final Tensguard™ product, a supplement or a functional food ingredient, is intended for use by people who want to

Areca nut is associated with younger age of diagnosis, poor chemoradiotherapy response, and shorter overall survival in esophageal squamous cell carcinoma.

Directory of Open Access Journals (Sweden)

Chang-Han Chen

Full Text Available Areca nut chewing is carcinogenic to humans. However, little is known about the impact of areca nut chewing on esophageal squamous cell carcinoma (ESCC.We retrospectively reviewed 286 ESCC patients who received surgery or preoperative chemoradiotherapy followed by surgery at our institution. Background characteristics including areca nut chewing history were analyzed. The 4-nitroquinoline 1-oxide (4-NQO-induced murine ESCC model was used to test the impact of arecoline, a main constituent of areca nut, on ESCC.Compared to patients without areca nut chewing history, patients with areca nut chewing history had overall a younger age of onset (Mean age: 56.75 versus 52.68 yrs, P<0.001 and significantly worse overall survival than those without areca nut chewing history (P = 0.026. Among patients who received surgery, the overall survival rates were not significantly different between those with or without areca nut chewing history. Among patients who received preoperative chemoradiotherapy followed by surgery, those with areca nut chewing history had a significantly lower pathologic complete response rate (P = 0.002 and lower overall survival rate (P = 0.002 than those without. In the murine ESCC model, the incidence of esophageal invasive squamous cell carcinoma was 40% in mice exposed to concomitant 4-NQO and arecoline treatment for 8 weeks and 6% in mice exposed to 4-NQO only for 8 weeks (P = 0.037.Our results indicate that areca nut chewing history is significantly associated with younger age of onset, poor response to chemoradiotherapy, and shorter overall survival in ESCC patients. Arecoline, a main constituent of areca nut, accelerates esophageal tumorigenesis in the 4-NQO-induced murine ESCC model.

Domain cooperativity in the β1a subunit is essential for dihydropyridine receptor voltage sensing in skeletal muscle.

Science.gov (United States)

Dayal, Anamika; Bhat, Vinayakumar; Franzini-Armstrong, Clara; Grabner, Manfred

2013-04-30

The dihydropyridine receptor (DHPR) β1a subunit is crucial for enhancement of DHPR triad expression, assembly of DHPRs in tetrads, and elicitation of DHPRα1S charge movement--the three prerequisites of skeletal muscle excitation-contraction coupling. Despite the ability to fully target α1S into triadic junctions and tetradic arrays, the neuronal isoform β3 was unable to restore considerable charge movement (measure of α1S voltage sensing) upon expression in β1-null zebrafish relaxed myotubes, unlike the other three vertebrate β-isoforms (β1a, β2a, and β4). Thus, we used β3 for chimerization with β1a to investigate whether any of the five distinct molecular regions of β1a is dominantly involved in inducing the voltage-sensing function of α1S. Surprisingly, systematic domain swapping between β1a and β3 revealed a pivotal role of the src homology 3 (SH3) domain and C terminus of β1a in charge movement restoration. More interestingly, β1a SH3 domain and C terminus, when simultaneously engineered into β3 sequence background, were able to fully restore charge movement together with proper intracellular Ca(2+) release, suggesting cooperativity of these two domains in induction of the α1S voltage-sensing function in skeletal muscle excitation-contraction coupling. Furthermore, substitution of a proline by alanine in the putative SH3-binding polyproline motif in the proximal C terminus of β1a (also of β2a and β4) fully obstructed α1S charge movement. Consequently, we postulate a model according to which β subunits, probably via the SH3-C-terminal polyproline interaction, adapt a discrete conformation required to modify the α1S conformation apt for voltage sensing in skeletal muscle.

One Gene and Two Proteins: a Leaderless mRNA Supports the Translation of a Shorter Form of the Shigella VirF Regulator

Directory of Open Access Journals (Sweden)

Maria Letizia Di Martino

2016-11-01

Full Text Available VirF, an AraC-like activator, is required to trigger a regulatory cascade that initiates the invasive program of Shigella spp., the etiological agents of bacillary dysentery in humans. VirF expression is activated upon entry into the host and depends on many environmental signals. Here, we show that the virF mRNA is translated into two proteins, the major form, VirF30 (30 kDa, and the shorter VirF21 (21 kDa, lacking the N-terminal segment. By site-specific mutagenesis and toeprint analysis, we identified the translation start sites of VirF30 and VirF21 and showed that the two different forms of VirF arise from differential translation. Interestingly, in vitro and in vivo translation experiments showed that VirF21 is also translated from a leaderless mRNA (llmRNA whose 5′ end is at position +309/+310, only 1 or 2 nucleotides upstream of the ATG84 start codon of VirF21. The llmRNA is transcribed from a gene-internal promoter, which we identified here. Functional analysis revealed that while VirF30 is responsible for activation of the virulence system, VirF21 negatively autoregulates virF expression itself. Since VirF21 modulates the intracellular VirF levels, this suggests that transcription of the llmRNA might occur when the onset of the virulence program is not required. We speculate that environmental cues, like stress conditions, may promote changes in virF mRNA transcription and preferential translation of llmRNA.

Rigidity of the polypeptide backbone in the triple-stranded collagen molecule.

Science.gov (United States)

Nemethy, G

1981-02-01

Conformational energy computations were carried out on collagen-like triple-stranded conformations of several polytripeptides with the structure CH3CO(GXY)3NHCH3, where X and Y can be Pro, Ala, or Gly. The computed minimum-energy conformations for various sequences are compared with that computed earlier for poly(Gly-Pro-Pro). Usually, substitution of Ala or Gly residues for Pro does not cause any strain or distortion of the conformation of the triple-stranded complex. Thus, the structure is a very stable and essentially rigid one. Unfavorable interactions were found only in the case of CH3CO(Gly-Ala-Pro)NHCH3. These interactions are a consequence of differences between the residue geometry of Ala and Pro. They result in small changes of some backbone dihedral angles and in an increase of intra- and interchain energies. The presence of a single Gly-Ala-Pro tripeptide within a sequence of Gly-Pro-Pro tripeptides is not sufficient, however, to cause even a small distoration of the triple strand. No deviation of the peptide groups from planarity is required to stabilize the triple-stranded structure.

Biochemical characterisation of the chlamydial MurF ligase, and possible sequence of the chlamydial peptidoglycan pentapeptide stem.

Science.gov (United States)

Patin, Delphine; Bostock, Julieanne; Chopra, Ian; Mengin-Lecreulx, Dominique; Blanot, Didier

2012-06-01

Chlamydiaceae are obligate intracellular bacteria that do not synthesise detectable peptidoglycan although they possess an almost complete arsenal of genes encoding peptidoglycan biosynthetic activities. In this paper, the murF gene from Chlamydia trachomatis was shown to be capable of complementing a conditional Escherichia coli mutant impaired in UDP-MurNAc-tripeptide:D-Ala-D-Ala ligase activity. Recombinant MurF from C. trachomatis was overproduced and purified from E. coli. It exhibited ATP-dependent UDP-MurNAc-X-γ-D-Glu-meso-A(2)pm:D-Ala-D-Ala ligase activity in vitro. No significant difference of kinetic parameters was seen when X was L-Ala, L-Ser or Gly. The L-Lys-containing UDP-MurNAc-tripeptide was a poorer substrate as compared to the meso-A(2)pm-containing one. Based on the respective substrate specificities of the chlamydial MurC, MurE, MurF and Ddl enzymes, a sequence L-Ala/L-Ser/Gly-γ-D-Glu-meso-A(2)pm-D-Ala-D-Ala is expected for the chlamydial pentapeptide stem, with Gly at position 1 being less likely.

Harrap's shorter dictionary English-French, French-English

CERN Document Server

2004-01-01

Maîtrisez parfaitement l'Anglais et l'Américain modernes. Les évolutions les plus récentes du vocabulaire. 350 000 mots et expressions 600 000 traductions. Nouveau : des centaines de mots nouveaux issus des grands thèmes de l'actualité (altermondialisme, bioterrorisme, coparentalité, bibande...). Une couverture complète du vocabulaire technique et idiomatique des deux langues. Un traitement détaillé des variantes régionales (irlandaises, australiennes, québécoises, belges, etc.). Les sigles, abréviations et noms propres. De nombreuses aides à la traduction : nouveau, 400 entrées longues introduites par des menus pour accéder sans ambiguïté à la bonne traduction ; nouveau, des notes culturelles pour comprendre mots et expressions liés à la civilisation anglo-saxonne ; des centaines de notes d'usage pour éviter les pièges de la traduction : faux amis, mots difficiles à traduire... Des milliers d'exemples pour illustrer les différents sens des mots. L'indication des niveaux de langue : ...

Hypofractionated Breast Radiation: Shorter Scheme, Lower Toxicity.

Science.gov (United States)

Linares, Isabel; Tovar, María Isabel; Zurita, Mercedes; Guerrero, Rosario; Expósito, Manuela; Del Moral, Rosario

2016-08-01

We analyzed the toxicity and cosmetic outcomes for patients who had undergone 3-dimensional conformal radiotherapy with a hypofractionated schedule and identified the risk factors associated with such a schedule. A total of 143 patients were treated for breast cancer (stage 0-III) with a hypofractionated radiation schedule after breast-conserving surgery from 2006 to 2011. Most patients received 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction to the whole breast plus an additional simultaneous integrated or sequential boost to the tumor bed. The median follow-up period was 36 months. Mild acute skin toxicity was observed in 62%; 7% of the patients developed moderate skin toxicity, but no grade 4 toxicity was observed. The prevalence of fibrosis within the boost area was 5%, but no grade ≥ 2 was observed. The prevalence of fibrosis of any grade was greater in the nonboost (23%) than in the boost area. Of all the patients, 91% had good or excellent cosmetic outcomes. From the multivariate analysis, the incidence of epithelitis correlated with the patient's treated volume (P = .044). The incidence of acute toxicity correlated with the boost type to the tumor bed and the total treatment dose (P = .012 and P = .002, respectively). Also, a poor to fair cosmetic outcome was significantly associated statistically with the surgery type (P = .05), boost type (P = .004), and total dose (P = .001). Delivering whole-breast irradiation with a hypofractionated schedule of 42.4 Gy plus a simultaneous integrated boost to the tumor bed appears to be a safe and effective technique, with good cosmetic results and lower toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment.

Science.gov (United States)

Munier, Francis L; Mosimann, Pascal; Puccinelli, Francesco; Gaillard, Marie-Claire; Stathopoulos, Christina; Houghton, Susan; Bergin, Ciara; Beck-Popovic, Maja

2017-08-01

The introduction of intra-arterial chemotherapy (IAC) as salvage treatment has improved the prognosis for eye conservation in group D retinoblastoma. The aim of this study was to compare the outcomes of consecutive patients with advanced unilateral disease treated with either first-line intravenous chemotherapy (IVC) or first-line IAC. This is a retrospective mono-centric comparative review of consecutive patients. Sporadic unilateral retinoblastoma group D cases treated conservatively at Jules-Gonin Eye Hospital and CHUV between 1997 and 2014. From January 1997 to August 2008, IVC, combined with focal treatments, was the primary treatment approach. From September 2008 to October 2014, IAC replaced IVC as first-line therapy. 48 patients met the inclusion criteria, receiving only either IAC or IVC as primary treatment modality. Outcomes of 23 patients treated by IVC were compared with those of 25 treated by IAC; mean follow-up was 105.3 months (range 29.2-218.6) and 41.7 months (range 19.6-89.5), respectively. Treatment duration was significantly shorter in the IAC group (pchemotherapy treatment. Despite this, the results reported here imply that eyes treated with first-line IAC will have shorter treatment period, better ocular survival and visual acuity than first-line IVC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

In Vitro Comparison of Holmium Lasers: Evidence for Shorter Fragmentation Time and Decreased Retropulsion Using a Modern Variable-pulse Laser.

Science.gov (United States)

Bell, John Roger; Penniston, Kristina L; Nakada, Stephen Y

2017-09-01

To compare the performance of variable- and fixed-pulse lasers on stone phantoms in vitro. Seven-millimeter stone phantoms were made to simulate calcium oxalate monohydrate stones using BegoStone plus. The in vitro setting was created with a clear polyvinyl chloride tube. For each trial, a stone phantom was placed at the open end of the tubing. The Cook Rhapsody H-30 variable-pulse laser was tested on both long- and short-pulse settings and was compared to the Dornier H-20 fixed-pulse laser; 5 trials were conducted for each trial arm. Fragmentation was accomplished with the use of a flexible ureteroscope and a 273-micron holmium laser fiber using settings of 1 J × 12 Hz. The treatment time (in minute) for complete fragmentation was recorded as was the total retropulsion distance (in centimeter) during treatment. Laser fibers were standardized for all repetitions. The treatment time was significantly shorter with the H-30 vs the H-20 laser (14.3 ± 2.5 vs 33.1 ± 8.9 minutes, P = .008). There was no difference between the treatment times using the long vs short pulse widths of the H-30 laser (14.4 ± 3.4 vs 14.3 ± 1.7 minutes, P = .93). Retropulsion differed by laser type and pulse width, H-30 long pulse (15.8 ± 5.7 cm), H-30 short pulse (54.8 ± 7.1 cm), and H-20 (33.2 ± 12.5 cm) (P laser fragmented stone phantoms in half the time of the H-20 laser regardless of the pulse width. Retropulsion effects differed between the lasers, with the H-30 causing the least retropulsion. Longer pulse widths result in less stone retropulsion. Copyright © 2017 Elsevier Inc. All rights reserved.

Highly efficient pulsed power supply system with a two-stage LC generator and a step-up transformer for fast capillary discharge soft x-ray laser at shorter wavelength

International Nuclear Information System (INIS)

Sakai, Yusuke; Takahashi, Shnsuke; Komatsu, Takanori; Song, Inho; Watanabe, Masato; Hotta, Eiki

2010-01-01

Highly efficient and compact pulsed power supply system for a capillary discharge soft x-ray laser (SXRL) has been developed. The system consists of a 2.2 μF two-stage LC inversion generator, a 2:54 step-up transformer, a 3 nF water capacitor, and a discharge section with a few tens of centimeter length capillary. Adoption of the pulsed transformer in combination with the LC inversion generator enables us to use only one gap switch in the circuit for charging the water capacitor up to about 0.5 MV. Furthermore, step-up ratio of a water capacitor voltage to a LC inversion generator initial charging voltage is about 40 with energy transfer efficiency of about 50%. It also leads to good reproducibility of a capillary discharge which is necessary for lasing a SXRL stably. For the study of the possibility of lasing a SXRL at shorter wavelength in a small laboratory scale, high-density and high-temperature plasma column suitable for the laser can be generated relatively easily with this system.

A Macrocyclic Agouti-Related Protein/[Nle4, DPhe7]α-Melanocyte Stimulating Hormone Chimeric Scaffold Produces Sub-nanomolar Melanocortin Receptor Ligands

OpenAIRE

Ericson, Mark D.; Freeman, Katie T.; Schnell, Sathya M.; Haskell-Luevano, Carrie

2017-01-01

The melanocortin system consists of five receptor subtypes, endogenous agonists, and naturally occurring antagonists. These receptors and ligands have been implicated in numerous biological pathways including processes linked to obesity and food intake. Herein, a truncation structure-activity relationship study of chimeric agouti-related protein (AGRP)/[Nle4, DPhe7]α-Melanocyte Stimulating Hormone (NDP-MSH) ligands is reported. The tetrapeptide His-DPhe-Arg-Trp or tripeptide DPhe-Arg-Trp repl...

Thermodynamics of grape and wine tannin interaction with polyproline: implications for red wine astringency.

Science.gov (United States)

McRae, Jacqui M; Falconer, Robert J; Kennedy, James A

2010-12-08

The astringency of red wine is largely due to the interaction between wine tannins and salivary proline-rich proteins and is known to change as wine ages. To further understand the mechanisms behind wine astringency change over time, thermodynamics of the interactions between poly(l-proline) (PLP) and grape seed and skin tannins (preveraison (PV) and commercially ripe) or Shiraz wine tannins (2 years old and 9-10 years old) was analyzed using isothermal titration calorimetry (ITC). The nature of these interactions varied with changes to the tannin structure that are associated with maturation. The change in enthalpy associated with hydrophobic interaction and hydrogen bonding decreased with tannin age and the stoichiometry of binding indicated that grape tannins associated with more proline residues than wine tannins, irrespective of molecular size. These results could provide an explanation for the observed change in wine astringency quality with age.

Data describing the solution structure of the WW3* domain from human Nedd4-1

Directory of Open Access Journals (Sweden)

Vineet Panwalkar

2016-09-01

Full Text Available The third WW domain (WW3* of human Nedd4-1 (Neuronal precursor cell expressed developmentally down-regulated gene 4-1 interacts with the poly-proline (PY motifs of the human epithelial Na+ channel (hENaC subunits at micromolar affinity. This data supplements the article (Panwalkar et al., 2015 [1]. We describe the NMR experiments used to solve the solution structure of the WW3* domain. We also present NOE network data for defining the rotameric state of side chains of peptide binding residues, and complement this data with χ1 dihedral angles derived from 3J couplings and molecular dynamics simulations data. Keywords: Chemical shift, Neuronal precursor cell expressed developmentally down-regulated gene 4-1, NMR, NOE distance restraints, WW domain

Targeting PEPT1: a novel strategy to improve the antitumor efficacy of doxorubicin in human hepatocellular carcinoma therapy.

Science.gov (United States)

Gong, Yanxia; Wu, Xiang; Wang, Tao; Zhao, Jia; Liu, Xi; Yao, Zhi; Zhang, Qingyu; Jian, Xu

2017-06-20

Proton coupled oligopeptide transporter 1 (PEPT1) is a member of the peptide transporter superfamily and plays important role in the absorption of oligopeptide and peptidomimetic drugs. Our previous research verified that PEPT1 expressed specifically in human Hepatocellular carcinoma (HCC) tissue and cell lines and showed potential transport activity to be a new candidate of the tumor therapeutic target. In this study, we aim to explore the feasibility of a novel tumor target therapeutic strategy: Targeting PEPT1 to improve the antitumor efficacy of Doxorubicin in human HCC therapy. First, Doxorubicin was conjugated with Glycylglycylglycine (Gly-Gly-Gly) - a tripeptide which was known as the substrate of PEPT1 and characterized by HPLC and MS successfully. Doxorubicin-tripeptide conjugate was then observed to clarify the target delivery by PEPT1 and the antitumor effect on human hepatocarcinoma in vivo and in vitro. Furthermore, the improvement of the toxic and side effect of Doxorubicin after conjugation was also evaluated by some biochemical tests. Our results reveal that targeting PEPT1 may contribute to the efficient delivery of Doxorubicin to hepatocarcinoma cells and the reduction of drug toxicity. PEPT1 has the prospect to be a novel target of HCC therapy.

What are the ideal properties for functional food peptides with antihypertensive effect? A computational peptidology approach.

Science.gov (United States)

Zhou, Peng; Yang, Chao; Ren, Yanrong; Wang, Congcong; Tian, Feifei

2013-12-01

Peptides with antihypertensive potency have long been attractive to the medical and food communities. However, serving as food additives, rather than therapeutic agents, peptides should have a good taste. In the present study, we explore the intrinsic relationship between the angiotensin I-converting enzyme (ACE) inhibition and bitterness of short peptides in the framework of computational peptidology, attempting to find out the appropriate properties for functional food peptides with satisfactory bioactivities. As might be expected, quantitative structure-activity relationship modeling reveals a significant positive correlation between the ACE inhibition and bitterness of dipeptides, but this correlation is quite modest for tripeptides and, particularly, tetrapeptides. Moreover, quantum mechanics/molecular mechanics analysis of the structural basis and energetic profile involved in ACE-peptide complexes unravels that peptides of up to 4 amino acids long are sufficient to have efficient binding to ACE, and more additional residues do not bring with substantial enhance in their ACE-binding affinity and, thus, antihypertensive capability. All of above, it is coming together to suggest that the tripeptides and tetrapeptides could be considered as ideal candidates for seeking potential functional food additives with both high antihypertensive activity and low bitterness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structure of a retro-binding peptide inhibitor complexed with human alpha-thrombin.

Science.gov (United States)

Tabernero, L; Chang, C Y; Ohringer, S L; Lau, W F; Iwanowicz, E J; Han, W C; Wang, T C; Seiler, S M; Roberts, D G; Sack, J S

1995-02-10

The crystallographic structure of the ternary complex between human alpha-thrombin, hirugen and the peptidyl inhibitor Phe-alloThr-Phe-O-CH3, which is acylated at its N terminus with 4-guanidino butanoic acid (BMS-183507), has been determined at 2.6 A resolution. The structure reveals a unique "retro-binding" mode for this tripeptide active site inhibitor. The inhibitor binds with its alkyl-guanidine moiety in the primary specificity pocket and its two phenyl rings occupying the hydrophobic proximal and distal pockets of the thrombin active site. In this arrangement the backbone of the tripeptide forms a parallel beta-strand to the thrombin main-chain at the binding site. This is opposite to the orientation of the natural substrate, fibrinogen, and all the small active site-directed thrombin inhibitors whose bound structures have been previously reported. BMS-183507 is the first synthetic inhibitor proved to bind in a retro-binding fashion to thrombin, in a fashion similar to that of the N-terminal residues of the natural inhibitor hirudin. Furthermore, this new potent thrombin inhibitor (Ki = 17.2 nM) is selective for thrombin over other serine proteases tested and may be a template to be considered in designing hirudin-based thrombin inhibitors with interactions at the specificity pocket.

Patients with Duchenne muscular dystrophy are significantly shorter than those with Becker muscular dystrophy, with the higher incidence of short stature in Dp71 mutated subgroup.

Science.gov (United States)

Matsumoto, Masaaki; Awano, Hiroyuki; Lee, Tomoko; Takeshima, Yasuhiro; Matsuo, Masafumi; Iijima, Kazumoto

2017-11-01

Duchenne and Becker muscular dystrophy (DMD/BMD) are caused by mutations in the dystrophin gene and are characterized by severe and mild progressive muscle wasting, respectively. Short stature has been reported as a feature of DMD in the Western hemisphere, but not yet confirmed in Orientals. Height of young BMD has not been fully characterized. Here, height of ambulant and steroid naive Japanese 179 DMD and 42 BMD patients between 4 and 10 years of age was retrospectively examined using height standard deviation score (SDS). The mean height SDS of DMD was -1.08 SD that was significantly smaller than normal (p < 0.001), indicating short stature of Japanese DMD. Furthermore, the mean height SDS of BMD was -0.27 SD, suggesting shorter stature than normal. Remarkably, the mean height SDS of DMD was significantly smaller than that of BMD (p < 0.0001). In DMD higher incidence of short stature (height SDS < -2.5 SD) was observed in Dp71 subgroup having mutations in dystrophin exons 63-79 than others having mutations in exons 1-62 (27.8% vs. 7.5%, p = 0.017). These suggested that height is influenced by dystrophin in not only DMD but also BMD and that dystrophin Dp71 has a role in height regulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Glutathione Metabolism and Parkinson’s Disease

OpenAIRE

Smeyne, Michelle; Smeyne, Richard Jay

2013-01-01

It has been established that oxidative stress, defined as the condition when the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson’s disease. Glutathione is a ubiquitous thiol tripeptide that acts alone, or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals and peroxynitrites. In this review, we examine the synthesis, metabolism and functional interactions of glutathione, and discuss how...

Total Synthesis of Ustiloxin D Utilizing an Ammonia-Ugi Reaction.

Science.gov (United States)

Brown, Aaron L; Churches, Quentin I; Hutton, Craig A

2015-10-16

Total synthesis of the highly functionalized cyclic peptide natural product, ustiloxin D, has been achieved in a convergent manner. Our strategy incorporates an asymmetric allylic alkylation to construct the tert-alkyl aryl ether linkage between the dopa and isoleucine residues. The elaborated β-hydroxydopa derivative is rapidly converted to a linear tripeptide through an ammonia-Ugi reaction. Subsequent cyclization and global deprotection affords ustiloxin D in six steps from a known β-hydroxydopa derivative.

Identification and characterization of Iporin as a novel interaction partner for rab1

Directory of Open Access Journals (Sweden)

Konczal Magdalena

2005-03-01

Full Text Available Abstract Background The small GTPase rab1a and its isoform rab1b are essential regulating components in the vesicle transport between the ER and the Golgi apparatus. Rab1 is thought to act as a molecular switch and can change between an active GTP-bound and an inactive GDP-bound conformation. To elucidate the function of rab1, several approaches have been established to isolate effector proteins, which interact with the activated conformation of rab1. To date p115, GM130, golgin-84 and MICAL have been identified as direct interacting partners. Together with rab1, these molecules are components of a protein complex, which mediates and regulates intracellular vesicle transport. Results Here, we report the characterization of Iporin, which is similar to KIAA0375 as a novel rab1-interacting protein. It was initially identified by yeast two-hybrid screening experiments with the active mutant of rab1b (rab1b Q67R as bait. Iporin contains a SH3 domain and two polyproline stretches, which are known to play a role in protein/protein interactions. In addition, Iporin encloses a RUN domain, which seems to be a major part of the rab1binding domain (R1BD. Iporin is ubiquitously expressed and immunofluorescence staining displays a cytosolic punctual distribution. Interestingly, we also show that Iporin interacts with another rab1 interacting partner, the GM130 protein. Conclusion Our results demonstrate that Iporin is a potential new interacting partner of rab1. Iporin is different from already identified rab1 interacting proteins concerning protein structure and cellular localization. We conclude that Iporin might function as a link between the targeting of ER derived vesicles, triggered by the rab1 GTPase and a signaling pathway regulated by molecules containing SH3 and/or poly-proline regions. The characterization of this novel intermolecular relation could help to elucidate how vesicles find their way from ER to the Golgi apparatus.

New fat suppression RF pulse with shorter duration

International Nuclear Information System (INIS)

Yamaguchi, Kojiro; Ukai, Hiroyuki

2010-01-01

The fat suppression radio frequency pulse currently employed for MRI, which selectively saturates the frequency of the fat, has the narrow-band frequency characteristics. Therefore, the application duration for the pulse employed tends to be prolonged. In the present study, we designed a new fat suppression radiofrequency (RF) pulse using the Laguerre function in order to shorten the duration for fat suppression RF pulse and conducted an evaluation with the clinical equipment. The length of the RF pulse that we created allowed to reduce the duration by 47.3% compared with that employed for the clinical equipment. In addition, in the MR imaging evaluation, the new pulse was confirmed to have the fat suppression effect equivalent to that employed for the clinical equipment. (author)

Shorter lines facilitate reading in those who struggle.

Directory of Open Access Journals (Sweden)

Matthew H Schneps

Full Text Available People with dyslexia, who ordinarily struggle to read, sometimes remark that reading is easier when e-readers are used. Here, we used eye tracking to observe high school students with dyslexia as they read using these devices. Among the factors investigated, we found that reading using a small device resulted in substantial benefits, improving reading speeds by 27%, reducing the number of fixations by 11%, and importantly, reducing the number of regressive saccades by more than a factor of 2, with no cost to comprehension. Given that an expected trade-off between horizontal and vertical regression was not observed when line lengths were altered, we speculate that these effects occur because sluggish attention spreads perception to the left as the gaze shifts during reading. Short lines eliminate crowded text to the left, reducing regression. The effects of attention modulation by the hand, and of increased letter spacing to reduce crowding, were also found to modulate the oculomotor dynamics in reading, but whether these factors resulted in benefits or costs depended on characteristics, such as visual attention span, that varied within our sample.

Effect of inhaled formyl-methionyl-leucyl-phenylalanine on airway function.

OpenAIRE

Berend, N; Peters, M J; Armour, C L; Black, J L; Ward, H E

1988-01-01

Formyl-methionyl-leucyl-phenylalanine (FMLP), a synthetic, acylated tripeptide analogous to bacterial chemotactic factors, has been shown to cause bronchoconstriction in guinea pig, rabbit, and human airways in vitro. To determine whether FMLP causes bronchoconstriction in man in vivo, a preliminary study was undertaken in which five non-smokers (mean age 35 years, FEV1 94% (SEM 5%) predicted) and five smokers (mean age 34 years, FEV1 93% (6%) predicted) inhaled aerosols of FMLP. None of the ...

Synthesis and Biological Evaluation of New Mannose Derived Immunomodulating Adamantyltripeptides

OpenAIRE

Ribić, Rosana; Habjanec, Lidija; Vranešić, Branka; Frkanec, Ruža; Tomić, Srđanka

2011-01-01

A novel class of mannosylated adamantyltripeptides, general formula of which is α-Man- OCH2CH(CH3)CO-AdGly-L-Ala-D-isoGln, were prepared, characterized, and their possible immunomodulatory properties investigated in some preliminary tests in vivo. All newly synthesized glycopeptides comprise in their structure the adamantylglycyl moiety linked to the dipeptide L-Ala-D-isoGln, as well as mannose. Adjuvant activity of mannosylated adamant-2-yl tripeptides was tested in the mouse mod...

Topical Peptide Treatments with Effective Anti-Aging Results

OpenAIRE

Silke Karin Schagen

2017-01-01

In the last two decades, many new peptides have been developed, and new knowledge on how peptides improve the skin has been uncovered. The spectrum of peptides in the field of cosmetics is continuously growing. This review summarizes some of the effective data on cosmeceutical peptides that work against intrinsic and extrinsic aging. Some peptides have been proven in their efficacy through clinical skin trials. Well-known and documented peptides like copper tripeptide are still under research...

Protein hydrolysates in sports nutrition

Directory of Open Access Journals (Sweden)

Manninen Anssi H

2009-09-01

Full Text Available Abstract It has been suggested that protein hydrolysates providing mainly di- and tripeptides are superior to intact (whole proteins and free amino acids in terms of skeletal muscle protein anabolism. This review provides a critical examination of protein hydrolysate studies conducted in healthy humans with special reference to sports nutrition. The effects of protein hydrolysate ingestion on blood amino acid levels, muscle protein anabolism, body composition, exercise performance and muscle glycogen resynthesis are discussed.

The development and validation of a shorter version of the Canadian Health Care Evaluation Project Questionnaire (CANHELP Lite): a novel tool to measure patient and family satisfaction with end-of-life care.

Science.gov (United States)

Heyland, Daren K; Jiang, Xuran; Day, Andrew G; Cohen, S Robin

2013-08-01

The recently developed Canadian Health Care Evaluation Project (CANHELP) questionnaire, which can be used to assess both patient and family satisfaction with end-of-life care, takes 40-60 minutes to complete. The length of the interview may limit its uptake and clinical utility; a shorter version would make its use more feasible. The purpose of this study was to develop and validate a shorter version of the CANHELP questionnaire. Data were collected using a cross-sectional survey of patients with advanced medical diseases and their family members. Participants completed the long version of CANHELP, a global rating of satisfaction with care (GRS), the FAMCARE scale (family members only), and a quality-of-life (QOL) questionnaire. We reduced the items on the long version based on their relationship to the GRS, the frequency of missing data, the distribution of responses, the redundancy of the items, and focus groups with frontline users. With the remaining items, we assessed internal consistency using Cronbach's alpha, and evaluated construct validity by describing the correlation of the new CANHELP Lite with the full version of CANHELP, GRS, FAMCARE, and the QOL questionnaire scores. A total of 363 patients and 193 family members participated in this study. The patient version was reduced from 37 items to 20 items and the caregiver version was reduced from 38 items to 21 items. Cronbach's alphas ranged from 0.68 to 0.93 for all domains of both the patient and caregiver questionnaires. We observed a high degree of correlation between CANHELP Lite domains and overall scores and the same domains and overall scores for the full version of CANHELP. In addition, we observed moderate to strong correlation between the CANHELP Lite overall satisfaction scores and the GRS questions. There was moderate correlation between the overall family member CANHELP Lite score and overall FAMCARE score (r = 0.45) and this was similar to the correlation between the full version of

Probing spatial heterogeneity in supercooled glycerol and temporal heterogeneity with single-molecule FRET in polyprolines

NARCIS (Netherlands)

Xia, Ted

2010-01-01

This thesis presents two lines of research. On the one hand, we investigate heterogeneity in supercooled glycerol by means of rheometry, small-angle neutron scattering, and fluorescence imaging. We find from the rheological experiments that supercooled glycerol can behave like weak solids at

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor1[S

OpenAIRE

Zhang, Hao; Jing, Xigang; Shi, Yang; Xu, Hao; Du, Jianhai; Guan, Tongju; Weihrauch, Dorothee; Jones, Deron W.; Wang, Weiling; Gourlay, David; Oldham, Keith T.; Hillery, Cheryl A.; Pritchard, Kirkwood A.

2013-01-01

Myeloperoxidase (MPO) plays important roles in disease by increasing oxidative and nitrosative stress and oxidizing lipoproteins. Here we report N-acetyl lysyltyrosylcysteine amide (KYC) is an effective inhibitor of MPO activity. We show KYC inhibits MPO-mediated hypochlorous acid (HOCl) formation and nitration/oxidation of LDL. Disulfide is the major product of MPO-mediated KYC oxidation. KYC (⩽4,000 μM) does not induce cytotoxicity in bovine aortic endothelial cells (BAECs). KYC inhibits HO...

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor1[S

Science.gov (United States)

Zhang, Hao; Jing, Xigang; Shi, Yang; Xu, Hao; Du, Jianhai; Guan, Tongju; Weihrauch, Dorothee; Jones, Deron W.; Wang, Weiling; Gourlay, David; Oldham, Keith T.; Hillery, Cheryl A.; Pritchard, Kirkwood A.

2013-01-01

Myeloperoxidase (MPO) plays important roles in disease by increasing oxidative and nitrosative stress and oxidizing lipoproteins. Here we report N-acetyl lysyltyrosylcysteine amide (KYC) is an effective inhibitor of MPO activity. We show KYC inhibits MPO-mediated hypochlorous acid (HOCl) formation and nitration/oxidation of LDL. Disulfide is the major product of MPO-mediated KYC oxidation. KYC (⩽4,000 μM) does not induce cytotoxicity in bovine aortic endothelial cells (BAECs). KYC inhibits HOCl generation by phorbol myristate acetate (PMA)-stimulated neutrophils and human promyelocytic leukemia (HL-60) cells but not superoxide generation by PMA-stimulated HL-60 cells. KYC inhibits MPO-mediated HOCl formation in BAEC culture and protects BAECs from MPO-induced injury. KYC inhibits MPO-mediated lipid peroxidation of LDL whereas tyrosine (Tyr) and tryptophan (Trp) enhance oxidation. KYC is unique as its isomers do not inhibit MPO activity, or are much less effective. Ultraviolet-visible spectral studies indicate KYC binds to the active site of MPO and reacts with compounds I and II. Docking studies show the Tyr of KYC rests just above the heme of MPO. Interestingly, KYC increases MPO-dependent H2O2 consumption. These data indicate KYC is a novel and specific inhibitor of MPO activity that is nontoxic to endothelial cell cultures. Accordingly, KYC may be useful for treating MPO-mediated vascular disease. PMID:23883583

Identification of the ubiquitous antioxidant tripeptide glutathione as a fruit fly semiochemical

Science.gov (United States)

Many insects mark their oviposition sites with a host marking pheromone (HMP) to deter other females from over-exploiting these sites for egg-laying. Previous studies have identified and used HMPs to manage certain fruit fly species. However, few examples are known for African indigenous fruit flie...

Investigating the inclusion properties of aromatic amino acids complexing beta-cyclodextrins in model peptides.

Science.gov (United States)

Caso, Jolanda Valentina; Russo, Luigi; Palmieri, Maddalena; Malgieri, Gaetano; Galdiero, Stefania; Falanga, Annarita; Isernia, Carla; Iacovino, Rosa

2015-10-01

Cyclodextrins are commonly used as complexing agents in biological, pharmaceutical, and industrial applications since they have an effect on protein thermal and proteolytic stability, refolding yields, solubility, and taste masking. β-cyclodextrins (β-CD), because of their cavity size are a perfectly suited complexing agent for many common guest moieties. In the case of peptide-cyclodextrin and protein-cyclodextrin host-guest complexes the aromatic amino acids are reported to be the principal responsible of the interaction. For these reasons, we have investigated the inclusion properties of nine designed tripeptides, obtained permuting the position of two L-alanines (Ala, A) with that of one L-tryptophan (Trp, W), L-phenylalanine (Phe, F), or L-tyrosine (Tyr, Y), respectively. Interestingly, the position of the aromatic side-chain in the sequence appears to modulate the β-CD:peptide binding constants, determined via UV-Vis and NMR spectroscopy, which in turn assumes values higher than those reported for the single amino acid. The tripeptides containing a tyrosine showed the highest binding constants, with the central position in the Ac-AYA-NH2 peptide becoming the most favorite for the interaction. A combined NMR and Molecular Docking approach permitted to build detailed complex models, highlighting the stabilizing interactions of the neighboring amino acids backbone atoms with the upper rim of the β-CD.

Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects

Directory of Open Access Journals (Sweden)

Sofia Pavanello

2018-06-01

Full Text Available Background/objectivesThe pathologic relationship linking obesity and lipid dismetabolism with earlier onset of aging-related disorders, including cardiovascular disease (CVD and type-2 diabetes (T2D, is not fully elucidate. Chronic inflammatory state, in obese individuals, may accelerate cellular aging. However, leukocyte telomere length (LTL, the cellular biological aging indicator, is elusively linked with obesity. Recent studies indicate that sterol 27-hydroxylase (CYP27A1 is an emerging antiatherogenic enzyme, that, by converting extrahepatic cholesterol to 27-hydroxycholesterol, facilitates cholesterol removal via high-density lipoprotein-cholesterol (HDL-C. We tested the hypothesis that obese subjects who carry at least three copies of CYP27A1 low-hydroxylation (LH activity genome-wide-validated alleles (rs4674345A, rs1554622A, and rs4674338G present premature aging, as reflected in shorter LTL and higher levels of CVD/T2D risk factors, including reduced HDL-C.Subjects/methodsObese subjects from SPHERE project {n = 1,457; overweight [body mass index (BMI 25–30 kg/m2] 65.8% and severe-obese (BMI > 30 kg/m2 34.2%} were characterized for the presence from 0 to 6 LH-CYP27A1 allele copy number. Univariate and multivariable sex–age–smoking-adjusted linear-regression models were performed to compare CVD/T2D risk factors and biological aging (LTL in relation to the combined BMI-LH groups: overweight-LH: 0–2, overweight-LH: 3–6, severe-obese-LH: 0–2, and severe-obese-LH: 3–6.ResultsHigher LTL attrition was found in severe-obese than overweight individuals (p < 0.001. Multivariable model reveals that among severe-obese patients those with LH: 3–6 present higher LTL attrition than LH: 0–2 (p < 0.05. Univariate and multivariable models remarkably show that insulin resistance is higher both in overweight-LH: 3–6 vs overweight-LH: 0–2 (p < 0.001 and in severe-obese-LH: 3–6 vs severe-obese-LH: 0–2 (p�

Correlation between fibroin amino acid sequence and physical silk properties.

Science.gov (United States)

Fedic, Robert; Zurovec, Michal; Sehnal, Frantisek

2003-09-12

The fiber properties of lepidopteran silk depend on the amino acid repeats that interact during H-fibroin polymerization. The aim of our research was to relate repeat composition to insect biology and fiber strength. Representative regions of the H-fibroin genes were sequenced and analyzed in three pyralid species: wax moth (Galleria mellonella), European flour moth (Ephestia kuehniella), and Indian meal moth (Plodia interpunctella). The amino acid repeats are species-specific, evidently a diversification of an ancestral region of 43 residues, and include three types of regularly dispersed motifs: modifications of GSSAASAA sequence, stretches of tripeptides GXZ where X and Z represent bulky residues, and sequences similar to PVIVIEE. No concatenations of GX dipeptide or alanine, which are typical for Bombyx silkworms and Antheraea silk moths, respectively, were found. Despite different repeat structure, the silks of G. mellonella and E. kuehniella exhibit similar tensile strength as the Bombyx and Antheraea silks. We suggest that in these latter two species, variations in the repeat length obstruct repeat alignment, but sufficiently long stretches of iterated residues get superposed to interact. In the pyralid H-fibroins, interactions of the widely separated and diverse motifs depend on the precision of repeat matching; silk is strong in G. mellonella and E. kuehniella, with 2-3 types of long homogeneous repeats, and nearly 10 times weaker in P. interpunctella, with seven types of shorter erratic repeats. The high proportion of large amino acids in the H-fibroin of pyralids has probably evolved in connection with the spinning habit of caterpillars that live in protective silk tubes and spin continuously, enlarging the tubes on one end and partly devouring the other one. The silk serves as a depot of energetically rich and essential amino acids that may be scarce in the diet.

An exit cavity was crucial to the polymerase activity of the early ribosome.

Science.gov (United States)

Fox, George E; Tran, Quyen; Yonath, Ada

2012-01-01

The emergence of an RNA entity capable of synthesizing peptides was a key prebiotic development. It is hypothesized that a precursor of the modern ribosomal exit tunnel was associated with this RNA entity (e.g., "protoribosome" or "bonding entity") from the earliest time and played an essential role. Various compounds that can bind and activate amino acids, including extremely short RNA chains carrying amino acids, and possibly di- or tripeptides, would have associated with the internal cavity of the protoribosome. This cavity hosts the site for peptide bond formation and adjacent to it a relatively elongated feature that could have evolved to the modern ribosomal exit tunnel, as it is wide enough to allow passage of an oligopeptide. When two of the compounds carrying amino acids or di- or tripeptides (to which we refer, for simplicity, as small aminoacylated RNAs) were in proximity within the heart of the protoribosome, a peptide bond could form spontaneously. The growing peptide would enter the nearby cavity and would not disrupt the attachment of the substrates to the protoribosome or interfere with the subsequent attachment of additional small aminoacylated RNAs. Additionally, the presence of the peptide in the cavity would increase the lifetime of the oligopeptide in the protoribosome. Thus, subsequent addition of another amino acid would be more likely than detachment from the protoribosome, and synthesis could continue. The early ability to synthesize peptides may have resulted in an abbreviated RNA World.

Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency

Directory of Open Access Journals (Sweden)

Anderson Dik Wai Luk

2017-07-01

Full Text Available BackgroundSevere combined immunodeficiency (SCID is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH has been associated with earlier diagnosis.ObjectiveThe aim of this study was to identify the clinical features that affect age at diagnosis (AD and time to the diagnosis of SCID.MethodsFrom 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP, and AD were selected for study.ResultsA total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57. A total of 29 patients had a positive FH. Candidiasis (n = 27 and bacillus Calmette–Guérin (BCG vaccine infection (n = 19 were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002 and diagnosis by 2 months (p = 0.008, but not shorter time to diagnosis (p = 0.494. Candidiasis was associated with later AD by 2 months (p = 0.008 and longer time to diagnosis by 0.55 months (p = 0.003. BCG infections were not associated with age or time to diagnosis.ConclusionFH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of

A shorter fractionation schedule for postlumpectomy breast cancer patients

International Nuclear Information System (INIS)

Shelley, Wendy; Brundage, Michael; Hayter, Charles; Paszat, Lawrence; Zhou, Sam; Mackillop, William

2000-01-01

Purpose: The purpose of this retrospective review was to determine the effectiveness of 40 Gy in 16 daily fractions in preventing local recurrence in postlumpectomy invasive breast cancer patients whose margins of resection were clear of tumor by at least 2 mm. Methods: Between September 1989 and December 1993, 294 breasts were treated with this regimen. The entire breast was treated, using a tangential parallel pair, with wedges as necessary, to a dose of 40 Gy in 16 daily fractions. No additional boost was given. The median duration of follow-up of surviving patients is 5.5 years. Recently, the patients' assessment of the cosmetic outcome of their treatment was obtained, using a mailed questionnaire. Results: The 5-year actuarial breast-relapse rate was 3.5%, with an overall 5-year survival and disease-specific survival of 87.8% and 92.1%, respectively. In response to the cosmesis questionnaire, 77% of patients stated they were either extremely or very satisfied with the overall appearance of the breast, 19.5% moderately satisfied, and 3.5% either slightly or not at all satisfied. The corresponding responses for overall level of comfort of the breast were 79%, 16.5%, and 4.5% respectively. Conclusion: This regimen is very effective at preventing recurrent breast cancer in this group of patients, and it provides a high level of patient satisfaction with cosmetic outcome. Its short duration offers the added advantage of a more efficient use of resources and greater patient convenience

Introductory Business Textbook Revision Cycles: Are They Getting Shorter?

Science.gov (United States)

Zinser, Brian; Brunswick, Gary

2010-01-01

The rate of textbook revision cycles is examined in light of the recent trend towards more rapid revisions (and adoptions of textbooks). The authors conduct background research to better understand the context for textbook revision cycles and the environmental forces that have been influencing what appears to be more rapid textbook revisions. A…

Less snow and shorter snow season in the future

International Nuclear Information System (INIS)

Vikhamar-Schuler, Dagrun; Beldring, Stein; Foerland, Eirik J.; Roald, Lars A.; Engen-Skaugen, Torill

2006-01-01

The article presents some results from the studies of changes in the Norwegian climate made by the project RegClim. Some regional and yearly tendencies are mentioned as well as some macro economical consequences

Cannabis use predicts shorter duration of untreated psychosis and ...

African Journals Online (AJOL)

Objective: Cannabis use/abuse is a common co-morbid problem in patients experiencing a first episode of psychotic illness (FEP). The relationship between the clinical presentation of FEP and cannabis abuse is complex and warrants further investigation, especially within the South African context. Method: We tested ...

Chemosensitivity of walking legs of the lobster Homarus americanus: neurophysiological response spectrum and thresholds

Energy Technology Data Exchange (ETDEWEB)

Derby, C D; Atema, J

1982-01-01

Responses of chemoreceptors in the walking legs of the lobster Homarus americanus to 35 individual compounds and 3 mixtures (prey odours and extracts) were studied using extracellular recording techniques. Compared against a standard mussel (Mytilus edulis) extract, these receptors were most sensitive to the amino acids L-glutamate, hydroxy-L-proline, L-aspartate, L-arginine, glycine, taurine, and L-alanine, as well as such other compounds as ammonium chloride, betaine, and the tripeptide glutathione. Most of these excitants are among those compounds most prevalent in the prey of lobsters.

Investigation of the substrate specificity of the proton coupled peptide transporter PepT_So from Shewanella oneidensis

DEFF Research Database (Denmark)

Prabhala, Bala Krishna; Aduri, Nanda Gowtham; Hald, Helle

2015-01-01

a strikingly high sequence identity, can be used to rationalize its mechanism and substrate preference. However, very little is known about the substrate specificity of PepTSo. To elaborate on this, the natural peptide specificity of PepTSo was investigated. Di and tri-peptides were found to be substrates...... for PepTSo in contrast to mono- and tetrapeptides as was indicated by previous competition studies. Interestingly, a negatively charged side chain was better accommodated on the dipeptide N- than the C-terminus position. Inversely, a positive charged side chain appeared to be tolerated better...

Radioprotective preparation

International Nuclear Information System (INIS)

Stefanova, D.; Frattadochi, A.; Gattavecchia, E.; Ferri, E.; Tonnelli, D.

1988-01-01

The invention is intended for radiation injuries prophylaxis in mammals. It has an well expressed radioprotective effect against acute gamma irradiation on cellular level as well as a prolonged action when applied up to 48 hours before the acute irradiation. The preparation is a coprecipitate of the natural tripeptide glutathione (reduced form) and polyvinyl pyrrolidone (pvp) in ratio 30-60/70-40. It is obtained by incubation method with subsequent lyophilization from water solution of the initial components. The molecular mass of the pvp is 20 till 360.10 3 . 2 claims

Click Chemistry for the Synthesis of RGD-Containing Integrin Ligands

Directory of Open Access Journals (Sweden)

Matteo Colombo

2010-01-01

Full Text Available In the last few years click chemistry reactions, and in particular coppercatalyzed cycloadditions, have been used intensively for the preparation of new bioconjugate molecules and materials applicable to biomedical and pharmaceutical areas. This review will be focused on conjugates of the tripeptide Arg-Gly-Asp formed by means of click chemistry reactions. This sequence is a well known binding motif for specific transmembrane proteins and is involved in cellular adhesion to the extracellular matrix, allowing the selective recognition of the biomolecule or polymer in which it is incorporated.

Synthesis of Structures Related to Antifreeze Glycoproteins

OpenAIRE

Fyrner, Timmy

2005-01-01

In this thesis, synthesis of structures related to antifreeze glycoproteins (AFGPs) are presented. Synthetic routes to a protected carbohydrate derivative, 2,3,4,6-tetra-O-benzyl-β-galactopyranosyl-(1→3)-2-deoxy-2-azido-4,6-di-O-benzyl-β-D-thio-1-galactopyranoside, and a tBu-Ala-Thr-Ala-Fmoc tripeptide, are described. These compounds are meant to be used in the assembly of AFGPs and analogues thereof. A Gal-GlcN disaccharide was synthesized via glycosylation between the donor, bromo-2-O-benzo...

The power of the kashrut: older but shorter. The impact of religious nutritional and hygienic rules on stature and life expectancy of Jewish conscripts in the early 19th century.

Science.gov (United States)

Tassenaar, V; Karel, E H

2016-06-01

We test the impact of several demographic, economic and social factors on stature in an early nineteenth century environment. We use a database of conscripts from the period 1818-1860 of a rural province in The Netherlands (Drenthe). This area had a rather high biological standard of living. This database of 413 conscripts contains information about family structure, family rank order, height, tax income, occupation and age of death. Conscripts came from two communities: one from a particular village (Oosterhesselen) and the other was Jewish conscripts that came from the countryside of the province. Our statistical analysis shows a positive significant relationship between family size and height, which confirms the resource dilution theory. Remarkably, the sign of the relation between family size and life expectancy is inverse. Other factors such as the potato crisis and income had the expected effect on conscript heights. The community effect was strong. Jewish conscripts were much shorter than their counterparts. Access to nutrition, the specific food laws and other factors can explain this difference. An increasing sibship size had a negative impact on body height but positive effects on life expectancy when adulthood was reached. Specifically for the Jewish community was the positive effect of the death of the father on conscript height. The mechanisms behind this phenomenon are unclear and open for further research.

Impact of Dose Reductions, Delays Between Chemotherapy Cycles, and/or Shorter Courses of Adjuvant Chemotherapy in Stage II and III Colorectal Cancer Patients: a Single-Center Retrospective Study.

Science.gov (United States)

Sgouros, Joseph; Aravantinos, Gerasimos; Kouvatseas, George; Rapti, Anna; Stamoulis, George; Bisvikis, Anastasios; Res, Helen; Samantas, Epameinondas

2015-12-01

Most stage II or III colorectal cancer patients are receiving nowadays a 4 to 6-month course of adjuvant chemotherapy. However, delays between cycles, reductions in the doses of chemotherapy drugs, or even permanent omissions of chemotherapy cycles might take place due to side effects or patient's preference. We examined the impact of these treatment modifications on recurrence-free survival (RFS) and overall survival (OS). We retrospectively collected data from colorectal cancer patients who had received adjuvant chemotherapy in our Department. Patients were categorized in five groups based on whether they had or not delays between chemotherapy cycles, dose reductions, and permanent omissions of chemotherapy cycles. Three-year RFS and OS of the five different groups were compared using the log-rank test and the Sidak approach. Five hundred and eight patients received treatment. Twenty seven percent of the patients had the full course of chemotherapy; the others had delays, dose reductions, or early termination of the treatment. No statistically significant differences were observed in 3-year RFS and OS between the five groups. A trend for worse RFS was noticed with early termination of treatment. A similar trend was also noticed for OS but only for stage II patients. In colorectal cancer patients, receiving adjuvant chemotherapy, delays between chemotherapy cycles, dose reductions of chemotherapy drugs, or even early termination of the treatment course do not seem to have a negative impact in 3-year RFS and OS; however, due to the trend of worse RFS in patients receiving shorter courses of chemotherapy, further studies are needed.

Sequential assignment of proline-rich regions in proteins: Application to modular binding domain complexes

International Nuclear Information System (INIS)

Kanelis, Voula; Donaldson, Logan; Muhandiram, D.R.; Rotin, Daniela; Forman-Kay, Julie D.; Kay, Lewis E.

2000-01-01

Many protein-protein interactions involve amino acid sequences containing proline-rich motifs and even poly-proline stretches. The lack of amide protons in such regions complicates assignment, since 1 HN-based triple-resonance assignment strategies cannot be employed. Two such systems that we are currently studying include an SH2 domain from the protein Crk with a region containing 9 prolines in a 14 amino acid sequence, as well as a WW domain that interacts with a proline-rich target. A modified version of the HACAN pulse scheme, originally described by Bax and co-workers [Wang et al. (1995) J. Biomol. NMR, 5, 376-382], and an experiment which correlates the intra-residue 1 H α , 13 C α / 13 C β chemical shifts with the 15 N shift of the subsequent residue are presented and applied to the two systems listed above, allowing sequential assignment of the molecules

One Gene and Two Proteins: a Leaderless mRNA Supports the Translation of a Shorter Form of the Shigella VirF Regulator.

Science.gov (United States)

Di Martino, Maria Letizia; Romilly, Cédric; Wagner, E Gerhart H; Colonna, Bianca; Prosseda, Gianni

2016-11-08

VirF, an AraC-like activator, is required to trigger a regulatory cascade that initiates the invasive program of Shigella spp., the etiological agents of bacillary dysentery in humans. VirF expression is activated upon entry into the host and depends on many environmental signals. Here, we show that the virF mRNA is translated into two proteins, the major form, VirF 30 (30 kDa), and the shorter VirF 21 (21 kDa), lacking the N-terminal segment. By site-specific mutagenesis and toeprint analysis, we identified the translation start sites of VirF 30 and VirF 21 and showed that the two different forms of VirF arise from differential translation. Interestingly, in vitro and in vivo translation experiments showed that VirF 21 is also translated from a leaderless mRNA (llmRNA) whose 5' end is at position +309/+310, only 1 or 2 nucleotides upstream of the ATG84 start codon of VirF 21 The llmRNA is transcribed from a gene-internal promoter, which we identified here. Functional analysis revealed that while VirF 30 is responsible for activation of the virulence system, VirF 21 negatively autoregulates virF expression itself. Since VirF 21 modulates the intracellular VirF levels, this suggests that transcription of the llmRNA might occur when the onset of the virulence program is not required. We speculate that environmental cues, like stress conditions, may promote changes in virF mRNA transcription and preferential translation of llmRNA. Shigella spp. are a major cause of dysentery in humans. In bacteria of this genus, the activation of the invasive program involves a multitude of signals that act on all layers of the gene regulatory hierarchy. By controlling the essential genes for host cell invasion, VirF is the key regulator of the switch from the noninvasive to the invasive phenotype. Here, we show that the Shigella virF gene encodes two proteins of different sizes, VirF 30 and VirF 21 , that are functionally distinct. The major form, VirF 30 , activates the genes

Oxidative diversification of amino acids and peptides by small-molecule iron catalysis.

Science.gov (United States)

Osberger, Thomas J; Rogness, Donald C; Kohrt, Jeffrey T; Stepan, Antonia F; White, M Christina

2016-09-08

Secondary metabolites synthesized by non-ribosomal peptide synthetases display diverse and complex topologies and possess a range of biological activities. Much of this diversity derives from a synthetic strategy that entails pre- and post-assembly oxidation of both the chiral amino acid building blocks and the assembled peptide scaffolds. The vancomycin biosynthetic pathway is an excellent example of the range of oxidative transformations that can be performed by the iron-containing enzymes involved in its biosynthesis. However, because of the challenges associated with using such oxidative enzymes to carry out chemical transformations in vitro, chemical syntheses guided by these principles have not been fully realized in the laboratory. Here we report that two small-molecule iron catalysts are capable of facilitating the targeted C-H oxidative modification of amino acids and peptides with preservation of α-centre chirality. Oxidation of proline to 5-hydroxyproline furnishes a versatile intermediate that can be transformed to rigid arylated derivatives or flexible linear carboxylic acids, alcohols, olefins and amines in both monomer and peptide settings. The value of this C-H oxidation strategy is demonstrated in its capacity for generating diversity: four 'chiral pool' amino acids are transformed to twenty-one chiral unnatural amino acids representing seven distinct functional group arrays; late-stage C-H functionalizations of a single proline-containing tripeptide furnish eight tripeptides, each having different unnatural amino acids. Additionally, a macrocyclic peptide containing a proline turn element is transformed via late-stage C-H oxidation to one containing a linear unnatural amino acid.

H{sup +}/peptide transporter (PEPT2) is expressed in human epidermal keratinocytes and is involved in skin oligopeptide transport

Energy Technology Data Exchange (ETDEWEB)

Kudo, Michiko; Katayoshi, Takeshi; Kobayashi-Nakamura, Kumiko [DHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba 261-0025 (Japan); Akagawa, Mitsugu [Department of Biological Chemistry, Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531 (Japan); Tsuji-Naito, Kentaro, E-mail: knaito@dhc.co.jp [DHC Corporation Laboratories, Division 2, 2-42 Hamada, Mihama-ku, Chiba 261-0025 (Japan)

2016-07-08

Peptide transporter 2 (PEPT2) is a member of the proton-coupled oligopeptide transporter family, which mediates the cellular uptake of oligopeptides and peptide-like drugs. Although PEPT2 is expressed in many tissues, its expression in epidermal keratinocytes remains unclear. We investigated PEPT2 expression profile and functional activity in keratinocytes. We confirmed PEPT2 mRNA expression in three keratinocyte lines (normal human epidermal keratinocytes (NHEKs), immortalized keratinocytes, and malignant keratinocytes) by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. In contrast to PEPT1, PEPT2 expression in the three keratinocytes was similar or higher than that in HepG2 cells, used as PEPT2-positive cells. Immunolocalization analysis using human skin showed epidermal PEPT2 localization. We studied keratinocyte transport function by measuring the oligopeptide content using liquid chromatography/tandem mass spectrometry. Glycylsarcosine uptake in NHEKs was pH-dependent, suggesting that keratinocytes could absorb small peptides in the presence of an inward H{sup +} gradient. We also performed a skin-permeability test of several oligopeptides using skin substitute, suggesting that di- and tripeptides pass actively through the epidermis. In conclusion, PEPT2 is expressed in keratinocytes and involved in skin oligopeptide uptake. -- Highlights: •PEPT2 is expressed in keratinocytes, which are more common than other skin cells. •Immunolocalization analysis using human skin revealed epidermal PEPT2 localization. •Keratinocytes could absorb small peptides in the presence of an inward H{sup +} gradient. •Di- and tripeptide pass actively through the epidermis.

In-vivo study of adhesion and bone growth around implanted laser groove/RGD-functionalized Ti-6Al-4V pins in rabbit femurs

Energy Technology Data Exchange (ETDEWEB)

Chen, J., E-mail: jianboc@gmail.com [Princeton Institute of Science and Technology of Materials and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Bly, R.A. [Princeton Institute of Science and Technology of Materials and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Saad, M.M.; AlKhodary, M.A.; El-Backly, R.M. [Tissue Engineering laboratories, Faculty of Dentistry, Alexandria University, Alexandria (Egypt); Cohen, D.J.; Kattamis, N. [Princeton Institute of Science and Technology of Materials and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Fatta, M.M.; Moore, W.A. [Tissue Engineering laboratories, Faculty of Dentistry, Alexandria University, Alexandria (Egypt); Arnold, C.B. [Princeton Institute of Science and Technology of Materials and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Marei, M.K. [Tissue Engineering laboratories, Faculty of Dentistry, Alexandria University, Alexandria (Egypt); Soboyejo, W.O. [Princeton Institute of Science and Technology of Materials and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States)

2011-07-20

Titanium surfaces were designed, produced, and evaluated for levels of osseointegration into the femurs of rabbits. A total of 36 Ti-6Al-4V pins (15 mm length, 1.64 mm diameter) were prepared into three experimental groups. These were designed to test the effects of osseointegration on laser grooved, RGD coated, and polished control surfaces, as well as combined effects. Circumferential laser grooves were introduced onto pin surfaces (40 {mu}m spacing) using a UV laser ({lambda} = 355 nm). The tripeptide sequence, Arginine-Glycine-Aspartic acid (RGD), was functionalized onto laser grooved surfaces. Of the prepared samples, surface morphology and chemistry were analyzed using scanning electron microscopy (SEM) and Immunoflourescence (IF) spectroscopy, respectively. The experimental pin surfaces were surgically implanted into rabbit femurs. The samples were then harvested and evaluated histologically. Sections of the sample were preserved in a methylmethacralate mold, sliced via a hard microtome, and polished systematically. In the case of the RGD coated and laser grooved surfaces, histological results showed accelerated bone growth into the implant, pull-out tests were also used to compare the adhesion between bone and the titanium pins with/without laser textures and/or RGD coatings. - Research highlights: {yields} Circumferential laser grooves were introduced onto pin surfaces using a UV laser. {yields} The tripeptide sequence, RGD, was functionalized onto laser grooved surfaces. {yields} The experimental pin surfaces were surgically implanted into rabbit femurs. {yields} RGD coated laser groove surfaces accelerated bone growth into the implant. {yields} RGD coated laser grooved surfaces enhanced the adhesion between the bone and implant.

Multipolar electrostatics for proteins: atom-atom electrostatic energies in crambin.

Science.gov (United States)

Yuan, Yongna; Mills, Matthew J L; Popelier, Paul L A

2014-02-15

Accurate electrostatics necessitates the use of multipole moments centered on nuclei or extra point charges centered away from the nuclei. Here, we follow the former alternative and investigate the convergence behavior of atom-atom electrostatic interactions in the pilot protein crambin. Amino acids are cut out from a Protein Data Bank structure of crambin, as single amino acids, di, or tripeptides, and are then capped with a peptide bond at each side. The atoms in the amino acids are defined through Quantum Chemical Topology (QCT) as finite volume electron density fragments. Atom-atom electrostatic energies are computed by means of a multipole expansion with regular spherical harmonics, up to a total interaction rank of L = ℓA+ ℓB + 1 = 10. The minimum internuclear distance in the convergent region of all the 15 possible types of atom-atom interactions in crambin that were calculated based on single amino acids are close to the values calculated from di and tripeptides. Values obtained at B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVTZ levels are only slightly larger than those calculated at HF/6-31G(d,p) level. This convergence behavior is transferable to the well-known amyloid beta polypeptide Aβ1-42. Moreover, for a selected central atom, the influence of its neighbors on its multipole moments is investigated, and how far away this influence can be ignored is also determined. Finally, the convergence behavior of AMBER becomes closer to that of QCT with increasing internuclear distance. Copyright © 2013 Wiley Periodicals, Inc.

Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment.

Science.gov (United States)

Holroyd, K J; Buhl, R; Borok, Z; Roum, J H; Bokser, A D; Grimes, G J; Czerski, D; Cantin, A M; Crystal, R G

1993-10-01

Concentrations of glutathione, a ubiquitous tripeptide with immune enhancing and antioxidant properties, are decreased in the blood and lung epithelial lining fluid of human immunodeficiency virus (HIV) seropositive individuals. Since the lung is the most common site of infection in those who progress to AIDS it is rational to consider whether it is possible to safely augment glutathione levels in the epithelial lining fluid of HIV seropositive individuals, thus potentially improving local host defence. Purified reduced glutathione was delivered by aerosol to HIV seropositive individuals (n = 14) and the glutathione levels in lung epithelial lining fluid were compared before and at one, two, and three hours after aerosol administration. Before treatment total glutathione concentrations in the epithelial lining fluid were approximately 60% of controls. After three days of twice daily doses each of 600 mg reduced glutathione, total glutathione levels in the epithelial lining fluid increased and remained in the normal range for at least three hours after treatment. Strikingly, even though > 95% of the glutathione in the aerosol was in its reduced form, the percentage of oxidised glutathione in epithelial lining fluid increased from 5% before treatment to about 40% three hours after treatment, probably reflecting the use of glutathione as an antioxidant in vivo. No adverse effects were observed. It is feasible and safe to use aerosolised reduced glutathione to augment the deficient glutathione levels of the lower respiratory tract of HIV seropositive individuals. It is rational to evaluate further the efficacy of this tripeptide in improving host defence in HIV seropositive individuals.

Parallel β-Sheet Structure of Alanine Tetrapeptide in the Solid State As Studied by Solid-State NMR Spectroscopy.

Science.gov (United States)

Asakura, Tetsuo; Horiguchi, Kumiko; Aoki, Akihiro; Tasei, Yugo; Naito, Akira

2016-09-01

The structural analysis of alanine oligopeptides is important for understanding the crystalline region in silks from spiders and wild silkworms and also the mechanism of cellular toxicity of human diseases arising from expansion in polyalanine sequences. The atomic-level structures of alanine tripeptide and tetrapeptide with antiparallel β-sheet structures (AP-Ala3 and AP-Ala4, respectively) together with alanine tripeptide with parallel β-sheet structures (P-Ala3) have been determined, but alanine tetrapeptide with a parallel β-sheet structure (P-Ala4) has not been reported yet. In this article, first, we established the preparation protocol of P-Ala4 from more stable AP-Ala4. Second, complete assignments of the (13)C, (15)N, and (1)H solid-state NMR spectra were performed with (13)C- and (15)N-labeled Ala4 samples using several solid-state NMR techniques. Then, the structural constraints were obtained, for example, the amide proton peaks of P-Ala4 in the (1)H double-quantum magic-angle spinning NMR spectrum were heavily overlapped and observed at about 7.4 ppm, which was a much higher field than that of 8.7-9.1 ppm observed for AP-Ala4, indicating that the intermolecular hydrogen-bond lengths across strands (N-H···O═C) were considerably longer for P-Ala4, that is, 2.21-2.34 Å, than those reported for AP-Ala4, that is, 1.8-1.9 Å. The structural model was proposed for P-Ala4 by NMR results and MD calculations.

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.

In-vivo study of adhesion and bone growth around implanted laser groove/RGD-functionalized Ti-6Al-4V pins in rabbit femurs

International Nuclear Information System (INIS)

Chen, J.; Bly, R.A.; Saad, M.M.; AlKhodary, M.A.; El-Backly, R.M.; Cohen, D.J.; Kattamis, N.; Fatta, M.M.; Moore, W.A.; Arnold, C.B.; Marei, M.K.; Soboyejo, W.O.

2011-01-01

Titanium surfaces were designed, produced, and evaluated for levels of osseointegration into the femurs of rabbits. A total of 36 Ti-6Al-4V pins (15 mm length, 1.64 mm diameter) were prepared into three experimental groups. These were designed to test the effects of osseointegration on laser grooved, RGD coated, and polished control surfaces, as well as combined effects. Circumferential laser grooves were introduced onto pin surfaces (40 μm spacing) using a UV laser (λ = 355 nm). The tripeptide sequence, Arginine-Glycine-Aspartic acid (RGD), was functionalized onto laser grooved surfaces. Of the prepared samples, surface morphology and chemistry were analyzed using scanning electron microscopy (SEM) and Immunoflourescence (IF) spectroscopy, respectively. The experimental pin surfaces were surgically implanted into rabbit femurs. The samples were then harvested and evaluated histologically. Sections of the sample were preserved in a methylmethacralate mold, sliced via a hard microtome, and polished systematically. In the case of the RGD coated and laser grooved surfaces, histological results showed accelerated bone growth into the implant, pull-out tests were also used to compare the adhesion between bone and the titanium pins with/without laser textures and/or RGD coatings. - Research highlights: → Circumferential laser grooves were introduced onto pin surfaces using a UV laser. → The tripeptide sequence, RGD, was functionalized onto laser grooved surfaces. → The experimental pin surfaces were surgically implanted into rabbit femurs. → RGD coated laser groove surfaces accelerated bone growth into the implant. → RGD coated laser grooved surfaces enhanced the adhesion between the bone and implant.

Surface control of blastospore attachment and ligand-mediated hyphae adhesion of Candida albicans.

Science.gov (United States)

Varghese, Nisha; Yang, Sijie; Sejwal, Preeti; Luk, Yan-Yeung

2013-11-14

Adhesion on a surface via nonspecific attachment or multiple ligand-receptor interactions is a critical event for fungal infection by Candida albicans. Here, we find that the tri(ethylene glycol)- and d-mannitol-terminated monolayers do not resist the blastospore attachment, but prevent the hyphae adhesion of C. albicans. The hyphae adhesion can be facilitated by tripeptide sequences of arginine-glycine-aspartic acid (RGD) covalently decorated on a background of tri(ethylene glycol)-terminated monolayers. This adhesion mediated by selected ligands is sensitive to the scrambling of peptide sequences, and is inhibited by the presence of cyclic RGD peptides in the solution.

Raman spectra studies of dipeptides

International Nuclear Information System (INIS)

Blanchard, Simone.

1977-10-01

This work deals with the homogenous and heterogeneous dipeptides derived from alanine and glycine, in the solid state or in aqueous solutions, in the zwitterions or chlorhydrates form. The Raman spectra comparative study of these various forms of hydrogenated or deuterated compounds allows to specify some of the attributions which are necessary in the conformational study of the like tripeptides. These compounds contain only one peptidic group; therefore there is no possibility of intramolecular hydrogen bond which caracterise vibrations of non bonded peptidic groups and end groups. Infrared spectra of solid dipeptides will be presented and discussed in the near future [fr

PQN-75 is expressed in the pharyngeal gland cells of Caenorhabditis elegans and is dispensable for germline development

Directory of Open Access Journals (Sweden)

Jesse D. Rochester

2017-09-01

Full Text Available In Caenorhabditis elegans, five pharyngeal gland cells reside in the terminal bulb of the pharynx and extend anterior processes to five contact points in the pharyngeal lumen. Pharyngeal gland cells secrete mucin-like proteins thought to facilitate digestion, hatching, molting and assembly of the surface coat of the cuticle, but supporting evidence has been sparse. Here we show pharyngeal gland cell expression of PQN-75, a unique protein containing an N-terminal signal peptide, nucleoporin (Nup-like phenylalanine/glycine (FG repeats, and an extensive polyproline repeat domain with similarities to human basic salivary proline-rich pre-protein PRB2. Imaging of C-terminal tagged PQN-75 shows localization throughout pharyngeal gland cell processes but not the pharyngeal lumen; instead, aggregates of PQN-75 are occasionally found throughout the pharynx, suggesting secretion from pharyngeal gland cells into the surrounding pharyngeal muscle. PQN-75 does not affect fertility and brood size in C. elegans but confers some degree of stress resistance and thermotolerance through unknown mechanisms.

On the length dependence of bridge-mediated electron transfer reactions

International Nuclear Information System (INIS)

Petrov, E.G.; Shevchenko, Ye.V.; May, V.

2003-01-01

Bridge-mediated nonadiabatic donor-acceptor (D-A) electron transfer (ET) is studied for the case of a regular molecular bridge of N identical units. It is shown that the multi-exponential ET kinetics reduces to a single-exponential transfer if, and only if, the integral population of the bridge remains small (less than 10 -2 ). An analytical expression for the overall D-A ET rate is derived and the necessary and sufficient conditions are formulated at which the rate is given as a sum of a superexchange and a sequential contribution. To describe experimental data on the N-dependence of ET reactions an approximate form of the overall transfer rate is derived. This expression is used to reproduce experimental data on distant ET through polyproline chains. Finally it is noted that the obtained analytical results can also be used for the description of more complex two-electron transfer reactions if the latter comprises separate single-electron pathways

Sampling the Denatured State of Polypeptides in Water, Urea, and Guanidine Chloride to Strict Equilibrium Conditions with the Help of Massively Parallel Computers.

Science.gov (United States)

Meloni, Roberto; Camilloni, Carlo; Tiana, Guido

2014-02-11

The denatured state of polypeptides and proteins, stabilized by chemical denaturants like urea and guanidine chloride, displays residual secondary structure when studied by nuclear-magnetic-resonance spectroscopy. However, these experimental techniques are weakly sensitive, and thus molecular-dynamics simulations can be useful to complement the experimental findings. To sample the denatured state, we made use of massively-parallel computers and of a variant of the replica exchange algorithm, in which the different branches, connected with unbiased replicas, favor the formation and disruption of local secondary structure. The algorithm is applied to the second hairpin of GB1 in water, in urea, and in guanidine chloride. We show with the help of different criteria that the simulations converge to equilibrium. It results that urea and guanidine chloride, besides inducing some polyproline-II structure, have different effect on the hairpin. Urea disrupts completely the native region and stabilizes a state which resembles a random coil, while guanidine chloride has a milder effect.

Women want taller men more than men want shorter women

NARCIS (Netherlands)

Stulp, G.; Buunk, A.P.; Pollet, T.V.

2013-01-01

Physical characteristics, such as height, play an important role in human mate preferences. Satisfaction with one's own height and one's partner height seem likely to be related to these preferences. Using a student sample (N= 650), we show that women are not only more selective, but also more

Women want taller men more than men want shorter women

NARCIS (Netherlands)

Stulp, Gert; Buunk, Abraham P.; Pollet, Thomas V.

Physical characteristics, such as height, play an important role in human mate preferences. Satisfaction with ones own height and one's partner height seem likely to be related to these preferences. Using a student sample (N = 650), we show that women are not only more selective, but also more

Medical necessity for shorter lived radionuclides, specifically pure Iodine-123

International Nuclear Information System (INIS)

DeNardo, G.L.; DeNardo, S.J.; Hines, H.H.; Lagunas-Solar, M.C.; Jungerman, J.A.

1985-01-01

Iodine-123 has physical and radiochemical characteristics ideal for most tracer procedures performed in patients. Its use is generally preferable to the use of 131 I for diagnosis. The potential for 123 I can be realized only if a radiopharmaceutical of lesser radionuclide contamination is generally and economically available. Iodine-123 produced by direct methods has significant disadvantages relative to quality of procedure and radiation dosimetry. Our experience with 123 I(p,5n) during the past 12 years causes us to vigorously encourage general availability of an 123 I radiopharmaceutical of this quality. Using this product, the authors have prepared radiopharmaceuticals for use in the study of cancer, coagulation, and renal and thyroid diseases

Shorter duration of breastfeeding at elevated exposures to perfluoroalkyl substances

DEFF Research Database (Denmark)

Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Petersen, Maria Skaalum

2017-01-01

. Duration of breastfeeding was assessed by questionnaire and clinical interview. In adjusted linear regression models, a doubling of maternal serum PFASs was associated with a reduction in duration of both total and exclusive breastfeeding, most pronounced for perfluorooctane sulfonic acid (PFOS) where...... a doubling was associated with a reduction in total breastfeeding of 1.4 (95% CI: 0.6; 2.1) months and perfluorooctanoic acid (PFOA) where a doubling was associated with a reduction in exclusive breastfeeding of 0.5 (0.3; 0.7) months. The associations were evident among both primiparous and multiparous women......, and thus cannot be explained by confounding from previous breastfeeding....

Shorter dialysis session length was not associated with lower mental health and physical functioning in elderly hemodialysis patients: Results from the Japan Dialysis Outcome and Practice Patterns Study (J-DOPPS.

Directory of Open Access Journals (Sweden)

Masashi Kitagawa

Full Text Available Health-related quality of life (HRQOL is often prioritized over long-term survival in elderly patients. Although a longer dialysis session length (DSL has been shown to reduce mortality, its effects on improving the HRQOL are unknown.Using data from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS, patients aged ≥ 65 years on maintenance hemodialysis were enrolled. DSL was categorized as short (240 minutes. The primary outcomes were changes in mental health (ΔMH and physical functioning (ΔPF scores assessed using the Japanese version of SF-12, in one year. The differences in the ΔMH and ΔPF among the three groups were assessed via regression (beta coefficients derived using a linear regression model.Of 1,187 patients at baseline, 319 (26.9% had a short length, 686 (57.8% a medium length, and 182 (15.3% a long length. We assessed the ΔMH data from 793 patients and the ΔPF data from 738. No significant differences in the ΔMH were noted for the short or long groups compared with the medium group (score difference: 0.26, 95% confidence interval [CI]: -4.17 to 4.69 for short; score difference: -1.15, 95% CI: -6.17 to 3.86 for long. Similarly, no significant differences were noted for these groups versus the medium group in ΔPF either (score difference: -1.43, 95% CI: -6.73 to 3.87 for short; score difference: -1.71, 95% CI: -7.63 to 4.22 for long.A shorter DSL might have no adverse effects on MH or PF for elderly patients.

Synthesis and characterization of DNA minor groove binding alkylating agents.

Science.gov (United States)

Iyer, Prema; Srinivasan, Ajay; Singh, Sreelekha K; Mascara, Gerard P; Zayitova, Sevara; Sidone, Brian; Fouquerel, Elise; Svilar, David; Sobol, Robert W; Bobola, Michael S; Silber, John R; Gold, Barry

2013-01-18

Derivatives of methyl 3-(1-methyl-5-(1-methyl-5-(propylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl)-1H-pyrrol-3-ylamino)-3-oxopropane-1-sulfonate (1), a peptide-based DNA minor groove binding methylating agent, were synthesized and characterized. In all cases, the N-terminus was appended with an O-methyl sulfonate ester, while the C-terminus group was varied with nonpolar and polar side chains. In addition, the number of pyrrole rings was varied from 2 (dipeptide) to 3 (tripeptide). The ability of the different analogues to efficiently generate N3-methyladenine was demonstrated as was their selectivity for minor groove (N3-methyladenine) versus major groove (N7-methylguanine) methylation. Induced circular dichroism studies were used to measure the DNA equilibrium binding properties of the stable sulfone analogues; the tripeptide binds with affinity that is >10-fold higher than that of the dipeptide. The toxicities of the compounds were evaluated in alkA/tag glycosylase mutant E. coli and in human WT glioma cells and in cells overexpressing and under-expressing N-methylpurine-DNA glycosylase, which excises N3-methyladenine from DNA. The results show that equilibrium binding correlates with the levels of N3-methyladenine produced and cellular toxicity. The toxicity of 1 was inversely related to the expression of MPG in both the bacterial and mammalian cell lines. The enhanced toxicity parallels the reduced activation of PARP and the diminished rate of formation of aldehyde reactive sites observed in the MPG knockdown cells. It is proposed that unrepaired N3-methyladenine is toxic due to its ability to directly block DNA polymerization.

Analogues of Cucurbita maxima trypsin inhibitor III (CMTI-III) with elastase inhibitory activity.

Science.gov (United States)

Rózycki, J; Kupryszewski, G; Rolka, K; Ragnarsson, U; Zbyryt, T; Krokoszyńska, I; Wilusz, T

1994-04-01

Three new CMTI-III analogues containing the Val residue in the reactive site (position 5) were synthesized by the solid-phase method. The analogues displayed an elastase inhibitory activity. It is shown that the removal of the N-terminal Arg residue and the introduction of the Gly-Pro-Gln tripeptide in the region 23-25 decreases the antielastase activity by two orders of magnitude. The removal of the disulfide bridge in positions 16-28 and the substitution of Ala for Cys16 and Gly for Cys28 decreases the activity (measured as Ka with HLE) by five orders of magnitude as compared with [Val5]CMTI-III.

Changes Of Hydration Level In Type I Collagen And Glycosaminoglycans Synthesized In The Rat’s Skin Under The Mechanical Stress

Directory of Open Access Journals (Sweden)

Alexandr M. Ponomarenko

2013-01-01

Full Text Available Changes of Hydratation Level Of Type I Collagen And Glycosaminoglycans That Are Synthesized In The Rat’s Skin Under The Mechanical Stress. The effect of the mechanical stress on the levels of hydratation of type I collagen and glycosaminoglycans that are synthesized in it, has been studied in vitro using the rats’ skin. The measured hydration of isotherms has shown that mechanical stress in the skin increases and decreases the amount of absorbed water in glycosaminoglycans and in collagen, respectively. Сalculated the average amounts of water molecules in collagen tripeptide and glycosaminoglycans disaccharide unit in the inside and outside layers of their hydrate shells

Synthèse d’un dérivé du fragment glutamique du glutathion

OpenAIRE

CHIBI, Nadjet

2016-01-01

Le glutathion (GSH) est un tripeptide, formé par la condensation d'acide glutamique, de cystéine et de glycine, connu pour ses propriétés thérapeutiques intéressantes : Anti-vieillissement. Prévention et lutte contre le cancer. Prévention et réduction des symptômes des maladies dégénératives. Prévention et contrôle de l'artériosclérose. Diminution des effets dégénérateurs du diabète. Mais puisqu’il est impossible d’avoir le glutathion, car il est instable en deh...

Competitor analogs for defined T cell antigens: peptides incorporating a putative binding motif and polyproline or polyglycine spacers.

Science.gov (United States)

Maryanski, J L; Verdini, A S; Weber, P C; Salemme, F R; Corradin, G

1990-01-12

We describe a new approach for modeling antigenic peptides recognized by T cells. Peptide A24 170-182 can compete with other antigenic peptides that are recognized by H-2kd-restricted cytolytic T cells, presumably by binding to the Kd molecule. By comparing substituted A24 peptides as competitors in a functional competition assay, the A24 residues Tyr-171, Thr-178, and Leu-179 were identified as possible contact residues for Kd. A highly active competitor peptide analog was synthesized in which Tyr was separated from the Thr-Leu pair by a pentaproline spacer. The choice of proline allowed the prediction of a probable conformation for the analog when bound to the Kd molecule. The simplest conformation of the A24 peptide that allows the same spacing and orientation of the motif as in the analog would be a nearly extended polypeptide chain incorporating a single 3(10) helical turn or similar structural kink.

Potential-energy and free-energy surfaces of glycyl-phenylalanyl-alanine (GFA) tripeptide: Experiment and theory

Czech Academy of Sciences Publication Activity Database

Valdes, Haydee; Spiwok, V.; Řezáč, Jan; Reha, D.; Abo-Riziq, A.; de Vries, M. S.; Hobza, Pavel

2008-01-01

Roč. 14, č. 16 (2008), s. 4886-4898 ISSN 0947-6539 R&D Projects: GA MŠk LC512; GA AV ČR IAA400550510 Institutional research plan: CEZ:AV0Z40550506 Keywords : ab initio calculations * IR-UV spectra * metadynamics Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.454, year: 2008

Shorter leukocyte telomere length is associated with higher risk of infections

DEFF Research Database (Denmark)

Helby, Jens; Nordestgaard, Børge G; Benfield, Thomas

2017-01-01

In the general population, older age is associated with short leukocyte telomere length and with high risk of infections. In a recent study of allogeneic hematopoietic cell transplantation for severe aplastic anemia, long donor leukocyte telomere length was associated with improved survival...

Do shorter lengths of stay increase readmissions after total joint replacements?

Directory of Open Access Journals (Sweden)

Udai S. Sibia, MD, MBA

2017-03-01

Conclusions: Early discharge does not increase readmissions and may help attenuate costs associated with TJRs. Further refinement of protocols may allow for more patients to be safely discharged on postoperative day 1.

Shorter or longer text in Ezekiel 6: The role of genre

Directory of Open Access Journals (Sweden)

Godwin Mushayabasa

2014-08-01

Full Text Available The text of Ezekiel continues to present some challenges to students studying it. This is in view of what one school of thought identify in the Ezekiel text as extensive redactions and revisions, whilst another school of thought is hesitant to subject the Masoretic Text (MT to such critical analysis. Amidst these differing viewpoints, I have discussed by means of literary analysis, the possibility that chapter 6 of Ezekiel may have been intended as a prophetic poetic message, or was later edited to conform to the genre of prophetic poetry. This is in the light of the so-called repetitions or ‘additions’ reflected in the MT if compared against the LXX, as well as the general problems associated with the Hebrew text of Ezekiel. The findings indicate that the text of Ezekiel 6 probably already had a complete theological corpus when it left the hand of the prophet Ezekiel or those who penned his words down. However, scribes saw it necessary to restructure, organise and colour the prophetic oracle in a literary form and structure they thought was necessary. This finding could be vital for solving literary and text critical problems in Ezekiel.

Shorter or longer text in Ezekiel 6: The role of genre

Directory of Open Access Journals (Sweden)

Godwin Mushayabasa

2014-08-01

Full Text Available The text of Ezekiel continues to present some challenges to students studying it. This is in view of what one school of thought identify in the Ezekiel text as extensive redactions and revisions, whilst another school of thought is hesitant to subject the Masoretic Text (MT to such critical analysis. Amidst these differing viewpoints, I have discussed by means of literary analysis, the possibility that chapter 6 of Ezekiel may have been intended as a prophetic poetic message, or was later edited to conform to the genre of prophetic poetry. This is in the light of the so-called repetitions or ‘additions’ reflected in the MT if compared against the LXX, as well as the general problems associated with the Hebrew text of Ezekiel. The findings indicate that the text of Ezekiel 6 probably already had a complete theological corpus when it left the hand of the prophet Ezekiel or those who penned his words down. However, scribes saw it necessary to restructure, organise and colour the prophetic oracle in a literary form and structure they thought was necessary. This finding could be vital for solving literary and text critical problems in Ezekiel.

Moderate Exercise Allows for shorter Recovery Time in Critical Limb Ischemia

Directory of Open Access Journals (Sweden)

Anne Lejay

2017-07-01

Full Text Available Whether and how moderate exercise might allow for accelerated limb recovery in chronic critical limb ischemia (CLI remains to be determined. Chronic CLI was surgically induced in mice, and the effect of moderate exercise (training five times per week over a 3-week period was investigated. Tissue damages and functional scores were assessed on the 4th, 6th, 10th, 20th, and 30th day after surgery. Mice were sacrificed 48 h after the last exercise session in order to assess muscle structure, mitochondrial respiration, calcium retention capacity, oxidative stress and transcript levels of genes encoding proteins controlling mitochondrial functions (PGC1α, PGC1β, NRF1 and anti-oxidant defenses markers (SOD1, SOD2, catalase. CLI resulted in tissue damages and impaired functional scores. Mitochondrial respiration and calcium retention capacity were decreased in the ischemic limb of the non-exercised group (Vmax = 7.11 ± 1.14 vs. 9.86 ± 0.86 mmol 02/min/g dw, p < 0.001; CRC = 7.01 ± 0.97 vs. 11.96 ± 0.92 microM/mg dw, p < 0.001, respectively. Moderate exercise reduced tissue damages, improved functional scores, and restored mitochondrial respiration and calcium retention capacity in the ischemic limb (Vmax = 9.75 ± 1.00 vs. 9.82 ± 0.68 mmol 02/min/g dw; CRC = 11.36 ± 1.33 vs. 12.01 ± 1.24 microM/mg dw, respectively. Exercise also enhanced the transcript levels of PGC1α, PGC1β, NRF1, as well as SOD1, SOD2, and catalase. Moderate exercise restores mitochondrial respiration and calcium retention capacity, and it has beneficial functional effects in chronic CLI, likely by stimulating reactive oxygen species-induced biogenesis and anti-oxidant defenses. These data support further development of exercise therapy even in advanced peripheral arterial disease.

Shorter Perceived Outpatient MRI Wait Times Associated With Higher Patient Satisfaction.

Science.gov (United States)

Holbrook, Anna; Glenn, Harold; Mahmood, Rabia; Cai, Qingpo; Kang, Jian; Duszak, Richard

2016-05-01

The aim of this study was to assess differences in perceived versus actual wait times among patients undergoing outpatient MRI examinations and to correlate those times with patient satisfaction. Over 15 weeks, 190 patients presenting for outpatient MR in a radiology department in which "patient experience" is one of the stated strategic priorities were asked to (1) estimate their wait times for various stages in the imaging process and (2) state their satisfaction with their imaging experience. Perceived times were compared with actual electronic time stamps. Perceived and actual times were compared and correlated with standardized satisfaction scores using Kendall τ correlation. The mean actual wait time between patient arrival and examination start was 53.4 ± 33.8 min, whereas patients perceived a mean wait time of 27.8 ± 23.1 min, a statistically significant underestimation of 25.6 min (P perceived wait times at all points during patient encounters were correlated with higher satisfaction scores (P perceived and actual wait times were both correlated with higher satisfaction scores. As satisfaction surveys play a larger role in an environment of metric transparency and value-based payments, better understanding of such factors will be increasingly important. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Performance of Batteries for electric vehicles on shorter and longer term

NARCIS (Netherlands)

Gerssen-Gondelach, S.J.; Faaij, A.P.C.

2012-01-01

In this work, the prospects of available and new battery technologies for battery electric vehicles (BEVs) are examined. Five selected battery technologies are assessed on battery performance and cost in the short, medium and long term. Driving cycle simulations are carried out to assess the

Characterization of melanocortin NDP-MSH agonist peptide fragments at the mouse central and peripheral melanocortin receptors.

Science.gov (United States)

Haskell-Luevano, C; Holder, J R; Monck, E K; Bauzo, R M

2001-06-21

The central melanocortin receptors, melanocortin-4 (MC4R) and melanocortin-3 (MC3R), are involved in the regulation of satiety and energy homeostasis. The MC4R in particular has become a pharmaceutical industry drug target due to its direct involvement in the regulation of food intake and its potential therapeutic application for the treatment of obesity-related diseases. The melanocortin receptors are stimulated by the native ligand, alpha-melanocyte stimulating hormone (alpha-MSH). The potent and enzymatically stable analogue NDP-MSH (Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH(2)) is a lead peptide for the identification of melanocortin amino acids important for receptor molecular recognition and stimulation. We have synthesized nine peptide fragments of NDP-MSH, deleting N- and C-terminal amino acids to determine the "minimally active" sequence of NDP-MSH. Additionally, five peptides were synthesized to study stereochemical inversion at the Phe 7 and Trp 9 positions in attempts to increase tetra- and tripeptide potencies. These peptide analogues were pharmacologically characterized at the mouse melanocortin MC1, MC3, MC4, and MC5 receptors. This study has identified the Ac-His-DPhe-Arg-Trp-NH(2) tetrapeptide as possessing 10 nM agonist activity at the brain MC4R. The tripeptide Ac-DPhe-Arg-Trp-NH(2) possessed micromolar agonist activities at the MC1R, MC4R, and MC5R but only slight stimulatory activity was observed at the MC3R (at up to 100 microM concentration). This study has also examined to importance of both N- and C-terminal NDP-MSH amino acids at the different melanocortin receptors, providing information for drug design and identification of putative ligand-receptor interactions.

Adsorption mechanisms of L-Glutathione on Au and controlled nano-patterning through Dip Pen Nanolithography

Energy Technology Data Exchange (ETDEWEB)

Calborean, A., E-mail: adrian.calborean@gmail.com [National Institute for Research and Development of Isotopic and Molecular Technologies, Donat 67-103, 400293 Cluj-Napoca (Romania); Martin, F.; Marconi, D.; Turcu, R.; Kacso, I.E.; Buimaga-Iarinca, L. [National Institute for Research and Development of Isotopic and Molecular Technologies, Donat 67-103, 400293 Cluj-Napoca (Romania); Graur, F. [Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Babeş 8, 400012 Cluj-Napoca (Romania); Turcu, I. [National Institute for Research and Development of Isotopic and Molecular Technologies, Donat 67-103, 400293 Cluj-Napoca (Romania)

2015-12-01

Dip Pen Nanolithography technique has been employed for patterning L-Glutathione tripeptide (L-y-glutamyl-L-cysteinyl-glycine) nanostructures at specific locations on metallic Au(111) substrate. The formed supramolecular architectures were designed through straight lines and dots serving as precursors for building blocks assemblies in nano-bio-electronics applications or as template structures for functionalized particles in the form of host–guest networks. Tween 20 polyoxyethylene surfactant concentrations ranging from 0.005 to 0.1% (v/v) into initial L-Glutathione tripeptide (2 mg mL{sup −1}) ink solutions were sequentially tested for the improvement of the ink delivery process and to assure an optimum uniformity and homogeneity over the patterned space. A strong relationship was found between the coated atomic force microscope (AFM) cantilever within the highly effective Tween 20 activator adjuvant and the molecular diffusion along concentration gradients. An increase in the driving force for ink transport from the AFM tip has been demonstrated within the highest 0.1% (v/v) TW 20 surfactant concentration, favoring the patterning of GSH molecules routinely with sub-100 nm resolution. Self-assembled monolayers of GSH were also fabricated and characterized in the light of X-ray photoemission spectroscopy (XPS) and ellipsometric optical measurements. Adsorption from water of L-Glutathione to the gold substrate is proven to be made by the thiol group of cysteine. Theoretical DFT approaches were applied for quantum chemical studies dedicated to electronic processes underneath molecular GSH/Au(111) systems. - Highlights: • Controlled nano-patterning of L-Glutathione was performed on Au by DPN. • Tween 20 was used for increasing driving force of molecular ink transport. • SAM's formation has described the adsorption mechanisms of L-Glutathione on Au. • Electronic properties of hybrid GSH/Au(111) structures were investigated by DFT. • Validation of

Assistant in design of tissue targeting leads with radio-combinatorial screening vivo

International Nuclear Information System (INIS)

Liu Ciyi; Zeng Jun; Xie Wenhui; Hu Silong; Jin Muxiu

2004-01-01

The diagnostic and therapeutic efficiency of drug depends highly on the drug distribution in target tissues (tumor for example) both specifically and accumulatively. We report here a powerful approach in design of tissue targeting leads with the assistant of radio-combinatorial screening technique developed in our laboratory. Methods: The C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin in the OXX aO1OXaO1O2O positional scanning format and iterative protoco. A technetium (V) oxo core[(TcO)3+] was bound to the N4-triligands of tripeptide libraries via four deprotonated anfide nitrogen atoms to form a structure of 99Tcm-tripeptoid libraries. The radio-combinatorial screening (RCS) in vivo was then carried out after SD rats and A549 tumor bearing mice received i.v. with 99Tcm-tripeptoid libraries. Results: Signals of tissue distribution and metabolism of libraries were recorded by g counting or imaging. From library of 8,000 99Tcm-tripeptoid members, the tissue targeting leads had been identified by RCS. Those included 99Tcm-DSG (RES), 99Tcm-VAA, and 99Tcm-VIG that had specific tissue targeting in kidney, stomach, and liver respectively. The percent injected dose per gram tissue (%ID/g) of 99Tcm labeled leads in their target tissues was highly structure-dependent The discovery of 99Tcm-VAA and 99Tcm-VIG indicates that side chain methyl at positionl and 2 are crucial for stomach and liver accumulating 99Tcm-tripeptoids. In the case of kidney targeting, Ser in the position 2 and 3 is crucial for 99Tcm-tripeptoids renal excretion and accumulation characteristics respectively. Conclusion: RCS in vivo is a powerful tool for design of tissue targeting leads. (authors)

Structure and function of the first full-length murein peptide ligase (Mpl) cell wall recycling protein.

Science.gov (United States)

Das, Debanu; Hervé, Mireille; Feuerhelm, Julie; Farr, Carol L; Chiu, Hsiu-Ju; Elsliger, Marc-André; Knuth, Mark W; Klock, Heath E; Miller, Mitchell D; Godzik, Adam; Lesley, Scott A; Deacon, Ashley M; Mengin-Lecreulx, Dominique; Wilson, Ian A

2011-03-18

Bacterial cell walls contain peptidoglycan, an essential polymer made by enzymes in the Mur pathway. These proteins are specific to bacteria, which make them targets for drug discovery. MurC, MurD, MurE and MurF catalyze the synthesis of the peptidoglycan precursor UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-diaminopimelyl-D-alanyl-D-alanine by the sequential addition of amino acids onto UDP-N-acetylmuramic acid (UDP-MurNAc). MurC-F enzymes have been extensively studied by biochemistry and X-ray crystallography. In gram-negative bacteria, ∼30-60% of the bacterial cell wall is recycled during each generation. Part of this recycling process involves the murein peptide ligase (Mpl), which attaches the breakdown product, the tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, to UDP-MurNAc. We present the crystal structure at 1.65 Å resolution of a full-length Mpl from the permafrost bacterium Psychrobacter arcticus 273-4 (PaMpl). Although the Mpl structure has similarities to Mur enzymes, it has unique sequence and structure features that are likely related to its role in cell wall recycling, a function that differentiates it from the MurC-F enzymes. We have analyzed the sequence-structure relationships that are unique to Mpl proteins and compared them to MurC-F ligases. We have also characterized the biochemical properties of this enzyme (optimal temperature, pH and magnesium binding profiles and kinetic parameters). Although the structure does not contain any bound substrates, we have identified ∼30 residues that are likely to be important for recognition of the tripeptide and UDP-MurNAc substrates, as well as features that are unique to Psychrobacter Mpl proteins. These results provide the basis for future mutational studies for more extensive function characterization of the Mpl sequence-structure relationships.

Structure and function of the first full-length murein peptide ligase (Mpl cell wall recycling protein.

Directory of Open Access Journals (Sweden)

Debanu Das

2011-03-01

Full Text Available Bacterial cell walls contain peptidoglycan, an essential polymer made by enzymes in the Mur pathway. These proteins are specific to bacteria, which make them targets for drug discovery. MurC, MurD, MurE and MurF catalyze the synthesis of the peptidoglycan precursor UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-diaminopimelyl-D-alanyl-D-alanine by the sequential addition of amino acids onto UDP-N-acetylmuramic acid (UDP-MurNAc. MurC-F enzymes have been extensively studied by biochemistry and X-ray crystallography. In gram-negative bacteria, ∼30-60% of the bacterial cell wall is recycled during each generation. Part of this recycling process involves the murein peptide ligase (Mpl, which attaches the breakdown product, the tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, to UDP-MurNAc. We present the crystal structure at 1.65 Å resolution of a full-length Mpl from the permafrost bacterium Psychrobacter arcticus 273-4 (PaMpl. Although the Mpl structure has similarities to Mur enzymes, it has unique sequence and structure features that are likely related to its role in cell wall recycling, a function that differentiates it from the MurC-F enzymes. We have analyzed the sequence-structure relationships that are unique to Mpl proteins and compared them to MurC-F ligases. We have also characterized the biochemical properties of this enzyme (optimal temperature, pH and magnesium binding profiles and kinetic parameters. Although the structure does not contain any bound substrates, we have identified ∼30 residues that are likely to be important for recognition of the tripeptide and UDP-MurNAc substrates, as well as features that are unique to Psychrobacter Mpl proteins. These results provide the basis for future mutational studies for more extensive function characterization of the Mpl sequence-structure relationships.

Preparation, Characterization and Activity of a Peptide-Cellulosic Aerogel Protease Sensor from Cotton

Directory of Open Access Journals (Sweden)

J. Vincent Edwards

2016-10-01

Full Text Available Nanocellulosic aerogels (NA provide a lightweight biocompatible material with structural properties, like interconnected high porosity and specific surface area, suitable for biosensor design. We report here the preparation, characterization and activity of peptide-nanocellulose aerogels (PepNA made from unprocessed cotton and designed with protease detection activity. Low-density cellulosic aerogels were prepared from greige cotton by employing calcium thiocyanate octahydrate/lithium chloride as a direct cellulose dissolving medium. Subsequent casting, coagulation, solvent exchange and supercritical carbon dioxide drying afforded homogeneous cellulose II aerogels of fibrous morphology. The cotton-based aerogel had a porosity of 99% largely dominated by mesopores (2–50 nm and an internal surface of 163 m2·g−1. A fluorescent tripeptide-substrate (succinyl-alanine-proline-alanine-4-amino-7-methyl-coumarin was tethered to NA by (1 esterification of cellulose C6 surface hydroxyl groups with glycidyl-fluorenylmethyloxycarbonyl (FMOC, (2 deprotection and (3 coupling of the immobilized glycine with the tripeptide. Characterization of the NA and PepNA included techniques, such as elemental analysis, mass spectral analysis, attenuated total reflectance infrared imaging, nitrogen adsorption, scanning electron microscopy and bioactivity studies. The degree of substitution of the peptide analog attached to the anhydroglucose units of PepNA was 0.015. The findings from mass spectral analysis and attenuated total reflectance infrared imaging indicated that the peptide substrate was immobilized on to the surface of the NA. Nitrogen adsorption revealed a high specific surface area and a highly porous system, which supports the open porous structure observed from scanning electron microscopy images. Bioactivity studies of PepNA revealed a detection sensitivity of 0.13 units/milliliter for human neutrophil elastase, a diagnostic biomarker for inflammatory

Genomics of glycopeptidolipid biosynthesis in Mycobacterium abscessus and M. chelonae

Directory of Open Access Journals (Sweden)

Etienne Gilles

2007-05-01

Full Text Available Abstract Background The outermost layer of the bacterial surface is of crucial importance because it is in constant interaction with the host. Glycopeptidolipids (GPLs are major surface glycolipids present on various mycobacterial species. In the fast-grower model organism Mycobacterium smegmatis, GPL biosynthesis involves approximately 30 genes all mapping to a single region of 65 kb. Results We have recently sequenced the complete genomes of two fast-growers causing human infections, Mycobacterium abscessus (CIP 104536T and M. chelonae (CIP 104535T. We show here that these two species contain genes corresponding to all those of the M. smegmatis "GPL locus", with extensive conservation of the predicted protein sequences consistent with the production of GPL molecules indistinguishable by biochemical analysis. However, the GPL locus appears to be split into several parts in M. chelonae and M. abscessus. One large cluster (19 genes comprises all genes involved in the synthesis of the tripeptide-aminoalcohol moiety, the glycosylation of the lipopeptide and methylation/acetylation modifications. We provide evidence that a duplicated acetyltransferase (atf1 and atf2 in M. abscessus and M. chelonae has evolved through specialization, being able to transfer one acetyl at once in a sequential manner. There is a second smaller and distant (M. chelonae, 900 kb; M. abscessus, 3 Mb cluster of six genes involved in the synthesis of the fatty acyl moiety and its attachment to the tripeptide-aminoalcohol moiety. The other genes are scattered throughout the genome, including two genes encoding putative regulatory proteins. Conclusion Although these three species produce identical GPL molecules, the organization of GPL genes differ between them, thus constituting species-specific signatures. An hypothesis is that the compact organization of the GPL locus in M. smegmatis represents the ancestral form and that evolution has scattered various pieces throughout the

Phi (Φ) and psi (Ψ) angles involved in malarial peptide bonds determine sterile protective immunity.

Science.gov (United States)

Patarroyo, Manuel E; Moreno-Vranich, Armando; Bermúdez, Adriana

2012-12-07

Modified HABP (mHABP) regions interacting with HLA-DRβ1(∗) molecules have a more restricted conformation and/or sequence than other mHABPs which do not fit perfectly into their peptide binding regions (PBR) and do not induce an acceptable immune response due to the critical role of their Φ and Ψ torsion angles. These angle's critical role was determined in such highly immunogenic, protection-inducing response against experimental malaria using the conformers (mHABPs) obtained by (1)H-NMR and superimposed into HLA-DRβ1(∗)-like Aotus monkey molecules; their phi (Φ) and psi (Ψ) angles were measured and the H-bond formation between these molecules was evaluated. The aforementioned mHABP propensity to assume a regular conformation similar to a left-handed polyproline type II helix (PPII(L)) led to suggesting that favouring these conformations according to their amino acid sequence would lead to high antibody titre production and sterile protective immunity induction against malaria, thereby adding new principles or rules for vaccine development, malaria being one of them. Copyright © 2012 Elsevier Inc. All rights reserved.

High-Temperature unfolding of a trp-Cage mini-protein: a molecular dynamics simulation study

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Seshasayee Aswin Sai Narain

2005-03-01

Full Text Available Abstract Background Trp cage is a recently-constructed fast-folding miniprotein. It consists of a short helix, a 3,10 helix and a C-terminal poly-proline that packs against a Trp in the alpha helix. It is known to fold within 4 ns. Results High-temperature unfolding molecular dynamics simulations of the Trp cage miniprotein have been carried out in explicit water using the OPLS-AA force-field incorporated in the program GROMACS. The radius of gyration (Rg and Root Mean Square Deviation (RMSD have been used as order parameters to follow the unfolding process. Distributions of Rg were used to identify ensembles. Conclusion Three ensembles could be identified. While the native-state ensemble shows an Rg distribution that is slightly skewed, the second ensemble, which is presumably the Transition State Ensemble (TSE, shows an excellent fit. The denatured ensemble shows large fluctuations, but a Gaussian curve could be fitted. This means that the unfolding process is two-state. Representative structures from each of these ensembles are presented here.

Synthesis and conformational analysis of linear homo- and heterooligomers from novel 2-C-branched sugar amino acids (SAAs).

Science.gov (United States)

Tian, Guang-Zong; Hu, Jing; Zhang, Heng-Xi; Rademacher, Christoph; Zou, Xiao-Peng; Zheng, Hong-Ning; Xu, Fei; Wang, Xiao-Li; Linker, Torsten; Yin, Jian

2018-04-26

Sugar amino acids (SAAs), as biologically interesting structures bearing both amino and carboxylic acid functional groups represent an important class of multifunctional building blocks. In this study, we develop an easy access to novel SAAs in only three steps starting from nitro compounds in high yields in analytically pure form, easily available by ceric (IV) mediated radical additions. Such novel SAAs have been applied in the assembly of total nine carbopeptoids with the form of linear homo- and heterooligomers for the structural investigations employing circular dichroism (CD) spectroscopy, which suggest that the carbopeptoids emerge a well-extended, left (or right)-handed conformation similar to polyproline II (PPII) helices. NMR studies also clearly demonstrated the presence of ordered secondary structural elements. 2D-ROESY spectra were acquired to identify i+1 NH ↔  i C 1 H, i C 2 H correlations which support the conformational analysis of tetramers by CD spectroscopy. These findings provide interesting information of SAAs and their oligomers as potential scaffolds for discovering new drugs and materials.

Sequestration of Sup35 by aggregates of huntingtin fragments causes toxicity of [PSI+] yeast.

Science.gov (United States)

Zhao, Xiaohong; Park, Yang-Nim; Todor, Horia; Moomau, Christine; Masison, Daniel; Eisenberg, Evan; Greene, Lois E

2012-07-06

Expression of huntingtin fragments with 103 glutamines (HttQ103) is toxic in yeast containing either the [PIN(+)] prion, which is the amyloid form of Rnq1, or [PSI(+)] prion, which is the amyloid form of Sup35. We find that HttQP103, which has a polyproline region at the C-terminal end of the polyQ repeat region, is significantly more toxic in [PSI(+)] yeast than in [PIN(+)], even though HttQP103 formed multiple aggregates in both [PSI(+)] and [PIN(+)] yeast. This toxicity was only observed in the strong [PSI(+)] variant, not the weak [PSI(+)] variant, which has more soluble Sup35 present than the strong variant. Furthermore, expression of the MC domains of Sup35, which retains the C-terminal domain of Sup35, but lacks the N-terminal prion domain, almost completely rescued HttQP103 toxicity, but was less effective in rescuing HttQ103 toxicity. Therefore, the toxicity of HttQP103 in yeast containing the [PSI(+)] prion is primarily due to sequestration of the essential protein, Sup35.

Refining Markov state models for conformational dynamics using ensemble-averaged data and time-series trajectories

Science.gov (United States)

Matsunaga, Y.; Sugita, Y.

2018-06-01

A data-driven modeling scheme is proposed for conformational dynamics of biomolecules based on molecular dynamics (MD) simulations and experimental measurements. In this scheme, an initial Markov State Model (MSM) is constructed from MD simulation trajectories, and then, the MSM parameters are refined using experimental measurements through machine learning techniques. The second step can reduce the bias of MD simulation results due to inaccurate force-field parameters. Either time-series trajectories or ensemble-averaged data are available as a training data set in the scheme. Using a coarse-grained model of a dye-labeled polyproline-20, we compare the performance of machine learning estimations from the two types of training data sets. Machine learning from time-series data could provide the equilibrium populations of conformational states as well as their transition probabilities. It estimates hidden conformational states in more robust ways compared to that from ensemble-averaged data although there are limitations in estimating the transition probabilities between minor states. We discuss how to use the machine learning scheme for various experimental measurements including single-molecule time-series trajectories.

Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor.

Science.gov (United States)

McDonald, Caleb B; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C; Deegan, Brian J; Seldeen, Kenneth L; Lednev, Igor K; Farooq, Amjad

2013-01-01

Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. Copyright © 2013 Elsevier B.V. All rights reserved.

Glicoalcaloides antifúngicos, flavonoides e outros constituintes químicos de Solanum asperum

Directory of Open Access Journals (Sweden)

Francisco das Chagas L. Pinto

2011-01-01

Full Text Available Two glycoalkaloids: solamargine and solasonine; three flavonoids: tiliroside, 7-O-α-L-ramnopyranosyl-kaempferol and 3-O-[ß-D-glucopyranosyl-(1→6-α-L-ramnopyranosyl]-7- O-α-L-ramnopyranosyl-kaempferol, in addition to the tripeptide Leu-Ile-Val, the aminoacid proline and the eicosanoic acid were isolated from Solanum asperum (Solanaceae. The structures of all compounds were determined by interpretation of their spectra (IR, MS, ¹H and 13C NMR and comparison with the literature data. All compounds, except the glycoalkaloids, are being reported for the first time for S. asperum. Solasonine showed strong activity (MIC < 0.24 μg/mL against four filamentous fungi species of the genera Microsporum and Trichophyton.

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP) and maintenance of normal blood pressure pursuant to Article 13(5) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

to isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP) and maintenance of normal blood pressure (BP). The tripeptides IPP and VPP are sufficiently characterised. Maintenance of normal blood pressure is a beneficial physiological effect. The applicant identified a total of 20 published intervention......Following an application from Valio Ltd submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Finland, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related...... relationship has not been established between the consumption of IPP and VPP and maintenance of normal blood pressure. © European Food Safety Authority, 2011...

Beneficial effects of protein hydrolysates in exercise and sports nutrition.

Science.gov (United States)

Yuan, J; Jiang, B; Li, K; Shen, W; Tang, J L

2017-01-01

Protein hydrolysates (PH) are rich sources of proteins that supply the need of exercising muscles. PHs are enriched in di- and tripeptides and are better than free amino acids or intact proteins when muscle anabolic effect is considered. Digestion, absorption and muscle uptake of amino acids are faster and more efficient when PH is ingested in comparison to the respective intact protein. PHs not only enhance endurance in high intensity exercise regimen, but also help in faster post-exercise recovery of muscle by promoting glycogen synthesis, although the latter effect requires more convincing evidence. PHs have been shown to exhibit insulinotrophic effect as it enhances the secretion of insulin and the hormone, in turn, exerts muscle anabolic effect.

Antifungal glycoalkaloids, flavonoids and other chemical constituents of Solanum asperum Rich (Solanaceae)

International Nuclear Information System (INIS)

Pinto, Francisco das Chagas L.; Uchoa, Daniel Esdras de A.; Silveira, Edilberto R.; Pessoa, Otilia Deusdenia L.; Braz-Filho, Raimundo; Silva, Fernanda M. e; Theodoro, Phellipe N.E.T.; Espindola, Laila S.

2011-01-01

Two glycoalkaloids: solamargine and solasonine; three flavonoids: tiliroside, 7-O-alpha-L-ramnopyranosyl-kaempferol and 3-O-[beta-D-glucopyranosyl-(1->6)-alpha-L-ramnopyranosyl ]-7-O-alpha-L-ramnopyranosyl-kaempferol, in addition to the tripeptide Leu-Ile-Val, the aminoacid proline and the eicosanoic acid were isolated from Solanum asperum (Solanaceae). The structures of all compounds were determined by interpretation of their spectra (IR, MS, 1 H and 13 C NMR) and comparison with the literature data. All compounds, except the glycoalkaloids, are being reported for the first time for S. asperum. Solasonine showed strong activity (MIC < 0.24 mug/mL) against four filamentous fungi species of the genera Microsporum and Trichophyton. (author)

Antifungal glycoalkaloids, flavonoids and other chemical constituents of Solanum asperum Rich (Solanaceae); Glicoalcaloides antifugincos, flavonoides e outros constituintes quimicos de Solanum asperum

Energy Technology Data Exchange (ETDEWEB)

Pinto, Francisco das Chagas L.; Uchoa, Daniel Esdras de A.; Silveira, Edilberto R.; Pessoa, Otilia Deusdenia L.; Braz-Filho, Raimundo, E-mail: opessoa@ufc.b [Universidade Federal do Ceara (DQOI/UFC), Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica; Silva, Fernanda M. e; Theodoro, Phellipe N.E.T.; Espindola, Laila S. [Universidade de Brasilia (FCS/UnB), DF (Brazil). Fac. de Ciencias da Saude

2011-07-01

Two glycoalkaloids: solamargine and solasonine; three flavonoids: tiliroside, 7-O-alpha-L-ramnopyranosyl-kaempferol and 3-O-[beta-D-glucopyranosyl-(1->6)-alpha-L-ramnopyranosyl ]-7-O-alpha-L-ramnopyranosyl-kaempferol, in addition to the tripeptide Leu-Ile-Val, the aminoacid proline and the eicosanoic acid were isolated from Solanum asperum (Solanaceae). The structures of all compounds were determined by interpretation of their spectra (IR, MS, {sup 1}H and {sup 13}C NMR) and comparison with the literature data. All compounds, except the glycoalkaloids, are being reported for the first time for S. asperum. Solasonine showed strong activity (MIC < 0.24 mug/mL) against four filamentous fungi species of the genera Microsporum and Trichophyton. (author)

Effects of long-term intraperitoneal injection of thyrotropin-releasing hormone (TRH) on aging- and obesity-related changes in body weight, lipid metabolism, and thyroid functions.

Science.gov (United States)

Pierpaoli, Walter; Lesnikov, Vladimir A

2011-02-01

Adult adipose mice, high fat diet-fed (HFD) mice, anterior hypothalamus-lesioned obese mice and genetically obese mice, were injected daily with thyrotropin releasing hormone (TRH). The treatment provoked a mobilization of triglycerides in the peripheral blood, a decrease of leptin and a loss of body weight. The weight loss did not depend on TSH-mediated stimulation of thyroid hormone secretion with consequent metabolic hyperthyroidism. The levels of blood cholesterol were not affected or even suppressed. Even at a very high dosage TRH did not affect the obesity of genetically obese mice. The ubiquitous tripeptide TRH may thus constitute a key element in the hormone-controlled regulation of body weight and fat stores in the adult and aging body.

Production of a novel wheat gluten hydrolysate containing dipeptidyl peptidase-IV inhibitory tripeptides using ginger protease.

Science.gov (United States)

Taga, Yuki; Hayashida, Osamu; Kusubata, Masashi; Ogawa-Goto, Kiyoko; Hattori, Shunji

2017-09-01

Wheat gluten is a Pro-rich protein complex comprising glutenins and gliadins. Previous studies have reported that oral intake of enzymatic hydrolysates of gluten has beneficial effects, such as suppression of muscle injury and improvement of hepatitis. Here, we utilized ginger protease that preferentially cleaves peptide bonds with Pro at the P 2 position to produce a novel type of wheat gluten hydrolysate. Ginger protease efficiently hydrolyzed gluten, particularly under weak acidic conditions, to peptides with an average molecular weight of ginger protease can be used as a functional food for patients with type 2 diabetes.

A rapid and convenient method for specific 11C-labelling of synthetic polypeptides containing methionine

International Nuclear Information System (INIS)

Laengstroem, B.; Sjoeberg, S.; Ragnarsson, U.

1981-01-01

11 C-labelling of methionine residues in a synthetic peptide via the preparation of the corresponding protected, pure homocysteine peptide has been investigated. Complete deprotection of the peptide and specific methylation of the homocysteine residue can be performed in one step in liquid ammonia. As a first application of this method the synthesis of the tripeptide, Z-Gly-L-Hcy(Bzl)-Gly-O-Bzl, and its conversion to Gly-Met-Gly and the corresponding labelled Gly-([ 11 C]-methyl)-Met-Gly, is reported. Starting with the protected peptide the labelling was performed in 20 +- 5 min (starting with 11 CO 2 ), yielding the labelled peptide in 92 +- 5 % radiochemical yield. Analyses and preparative LC can be performed within 6 min. (author)

Polymeric peptide pigments with sequence-encoded properties

Energy Technology Data Exchange (ETDEWEB)

Lampel, Ayala; McPhee, Scott A.; Park, Hang-Ah; Scott, Gary G.; Humagain, Sunita; Hekstra, Doeke R.; Yoo, Barney; Frederix, Pim W. J. M.; Li, Tai-De; Abzalimov, Rinat R.; Greenbaum, Steven G.; Tuttle, Tell; Hu, Chunhua; Bettinger, Christopher J.; Ulijn, Rein V.

2017-06-08

Melanins are a family of heterogeneous polymeric pigments that provide ultraviolet (UV) light protection, structural support, coloration, and free radical scavenging. Formed by oxidative oligomerization of catecholic small molecules, the physical properties of melanins are influenced by covalent and noncovalent disorder. We report the use of tyrosine-containing tripeptides as tunable precursors for polymeric pigments. In these structures, phenols are presented in a (supra-)molecular context dictated by the positions of the amino acids in the peptide sequence. Oxidative polymerization can be tuned in a sequence-dependent manner, resulting in peptide sequence–encoded properties such as UV absorbance, morphology, coloration, and electrochemical properties over a considerable range. Short peptides have low barriers to application and can be easily scaled, suggesting near-term applications in cosmetics and biomedicine.

Romania’s economic contribution to making a Long World War II shorter

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Stefan GHEORGHE

2006-10-01

Full Text Available Romania’s participation in World War II was brought about by political reasons and strategic needs that resulted from the internationalpolitical situation at the middle of the twentieth century. One can hardly say that Romania did not do its best to avoid becoming involved in the war.From September 1939 to June 1941, the foreign policy laid focus on non-belligerency and neutrality. But eventually Romania was drawn in, too,right after the series of unfortunate events in the summer of 1940

A shorter snowfall season associated with higher air temperatures over northern Eurasia

International Nuclear Information System (INIS)

Ye Hengchun; Cohen, Judah

2013-01-01

The temperature sensitivity of the snowfall season (start, end, duration) over northern Eurasia (the former USSR) is analyzed from synoptic records of 547 stations from 1966 to 2000. The results find significant correlations between temperature and snowfall season at approximately 56% of stations (61% for the starting date and 56% for the ending date) with a mean snowfall season duration temperature sensitivity of −6.2 days °C −1 split over the start (2.8 days) and end periods (−3.4 days). Temperature sensitivity was observed to increase with stations’ mean seasonal air temperature, with the strongest relationships at locations of around 6 °C temperature. This implies that increasing air temperature in fall and spring will delay the onset and hasten the end of snowfall events, and reduces the snowfall season length by 6.2 days for each degree of increase. This study also clarifies that the increasing trend in snowfall season length during 1936/37–1994 over northern European Russia and central Siberia revealed in an earlier study is unlikely to be associated with warming in spring and fall seasons. (letter)

Poorer Health – Shorter Hours? Health and Flexibility of Hours of Work

OpenAIRE

Geyer, Johannes; Myck, Michal

2010-01-01

We analyse the role of health in determining the difference between desired and actual hours of work in a sample of German men using the Socio-Economic Panel Data for years 1996-2007. The effects of both self-assessed health and legal disability status are examined. About 60% of employees report working more than they would wish with the mean difference of -3.9 hours/week. We estimate static and dynamic model specifications allowing for auto-regressive nature of the dependent variable and tes...

Shorter sleep duration is associated with social impairment and comorbidities in ASD.

Science.gov (United States)

Veatch, Olivia J; Sutcliffe, James S; Warren, Zachary E; Keenan, Brendan T; Potter, Melissa H; Malow, Beth A

2017-07-01

Sleep disturbance, particularly insomnia, is common in children with autism spectrum disorders (ASD). Furthermore, disturbed sleep affects core symptoms and other related comorbidities. Understanding the causes and consequences of sleep disturbances in children with ASD is an important step toward mitigating these symptoms. To better understand the connection between sleep duration and ASD severity, we analyzed ASD-related symptoms using the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), IQ scores, and parent reports of the average amount of time slept per night that were available in the medical histories of 2,714 children with ASD in the Simons Simplex Collection (SSC). The mean (SD) sleep duration was 555 minutes. Sleep duration and severity of core ASD symptoms were negatively correlated, and sleep duration and IQ scores were positively correlated. Regression results indicated that more severe social impairment, primarily a failure to develop peer relationships, is the core symptom most strongly associated with short sleep duration. Furthermore, increased severity for numerous maladaptive behaviors assessed on the Child Behavior Checklist, as well as reports of attention deficit disorder, depressive disorder, and obsessive compulsive disorder were associated with short sleep duration. Severity scores for social/communication impairment and restricted and repetitive behaviors (RRB) were increased, and IQ scores were decreased, for children reported to sleep ≤420 minutes per night (lower 5th percentile) compared to children sleeping ≥660 minutes (upper 95th percentile). Our results indicate that reduced amounts of sleep are related to more severe symptoms in children with ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1221-1238. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Binding of the cSH3 domain of Grb2 adaptor to two distinct RXXK motifs within Gab1 docker employs differential mechanisms.

Science.gov (United States)

McDonald, Caleb B; Seldeen, Kenneth L; Deegan, Brian J; Bhat, Vikas; Farooq, Amjad

2011-01-01

A ubiquitous component of cellular signaling machinery, Gab1 docker plays a pivotal role in routing extracellular information in the form of growth factors and cytokines to downstream targets such as transcription factors within the nucleus. Here, using isothermal titration calorimetry (ITC) in combination with macromolecular modeling (MM), we show that although Gab1 contains four distinct RXXK motifs, designated G1, G2, G3, and G4, only G1 and G2 motifs bind to the cSH3 domain of Grb2 adaptor and do so with distinct mechanisms. Thus, while the G1 motif strictly requires the PPRPPKP consensus sequence for high-affinity binding to the cSH3 domain, the G2 motif displays preference for the PXVXRXLKPXR consensus. Such sequential differences in the binding of G1 and G2 motifs arise from their ability to adopt distinct polyproline type II (PPII)- and 3(10) -helical conformations upon binding to the cSH3 domain, respectively. Collectively, our study provides detailed biophysical insights into a key protein-protein interaction involved in a diverse array of signaling cascades central to health and disease. Copyright © 2010 John Wiley & Sons, Ltd.

Reciprocal carbonyl-carbonyl interactions in small molecules and proteins.

Science.gov (United States)

Rahim, Abdur; Saha, Pinaki; Jha, Kunal Kumar; Sukumar, Nagamani; Sarma, Bani Kanta

2017-07-19

Carbonyl-carbonyl n→π* interactions where a lone pair (n) of the oxygen atom of a carbonyl group is delocalized over the π* orbital of a nearby carbonyl group have attracted a lot of attention in recent years due to their ability to affect the 3D structure of small molecules, polyesters, peptides, and proteins. In this paper, we report the discovery of a "reciprocal" carbonyl-carbonyl interaction with substantial back and forth n→π* and π→π* electron delocalization between neighboring carbonyl groups. We have carried out experimental studies, analyses of crystallographic databases and theoretical calculations to show the presence of this interaction in both small molecules and proteins. In proteins, these interactions are primarily found in polyproline II (PPII) helices. As PPII are the most abundant secondary structures in unfolded proteins, we propose that these local interactions may have implications in protein folding.Carbonyl-carbonyl π* non covalent interactions affect the structure and stability of small molecules and proteins. Here, the authors carry out experimental studies, analyses of crystallographic databases and theoretical calculations to describe an additional type of carbonyl-carbonyl interaction.

Engineering D-Amino Acid Containing Collagen Like Peptide at the Cleavage Site of Clostridium histolyticum Collagenase for Its Inhibition.

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Punitha Velmurugan

Full Text Available Collagenase is an important enzyme which plays an important role in degradation of collagen in wound healing, cancer metastasis and even in embryonic development. However, the mechanism of this degradation has not yet been completely understood. In the field of biomedical and protein engineering, the design and development of new peptide based materials is of main concern. In the present work an attempt has been made to study the effect of DAla in collagen like peptide (imino-poor region of type I collagen on the structure and stability of peptide against enzyme hydrolysis. Effect of replacement of DAla in the collagen like peptide has been studied using circular dichroic spectroscopy (CD. Our findings suggest that, DAla substitution leads to conformational changes in the secondary structure and favours the formation of polyproline II conformation than its L-counterpart in the imino-poor region of collagen like peptides. Change in the chirality of alanine at the cleavage site of collagenase in the imino-poor region inhibits collagenolytic activity. This may find application in design of peptides and peptidomimics for enzyme-substrate interaction, specifically with reference to collagen and other extra cellular matrix proteins.

A molecular quantum spin network controlled by a single qubit.

Science.gov (United States)

Schlipf, Lukas; Oeckinghaus, Thomas; Xu, Kebiao; Dasari, Durga Bhaktavatsala Rao; Zappe, Andrea; de Oliveira, Felipe Fávaro; Kern, Bastian; Azarkh, Mykhailo; Drescher, Malte; Ternes, Markus; Kern, Klaus; Wrachtrup, Jörg; Finkler, Amit

2017-08-01

Scalable quantum technologies require an unprecedented combination of precision and complexity for designing stable structures of well-controllable quantum systems on the nanoscale. It is a challenging task to find a suitable elementary building block, of which a quantum network can be comprised in a scalable way. We present the working principle of such a basic unit, engineered using molecular chemistry, whose collective control and readout are executed using a nitrogen vacancy (NV) center in diamond. The basic unit we investigate is a synthetic polyproline with electron spins localized on attached molecular side groups separated by a few nanometers. We demonstrate the collective readout and coherent manipulation of very few (≤ 6) of these S = 1/2 electronic spin systems and access their direct dipolar coupling tensor. Our results show that it is feasible to use spin-labeled peptides as a resource for a molecular qubit-based network, while at the same time providing simple optical readout of single quantum states through NV magnetometry. This work lays the foundation for building arbitrary quantum networks using well-established chemistry methods, which has many applications ranging from mapping distances in single molecules to quantum information processing.

The amide III vibrational circular dichroism band as a probe to detect conformational preferences of alanine dipeptide in water.

Science.gov (United States)

Mirtič, Andreja; Merzel, Franci; Grdadolnik, Jože

2014-07-01

The conformational preferences of blocked alanine dipeptide (ADP), Ac-Ala-NHMe, in aqueous solution were studied using vibrational circular dichroism (VCD) together with density functional theory (DFT) calculations. DFT calculations of three most representative conformations of ADP surrounded by six explicit water molecules immersed in a dielectric continuum have proven high sensitivity of amide III VCD band shape that is characteristic for each conformation of the peptide backbone. The polyproline II (PII ) and αR conformation of ADP are associated with a positive VCD band while β conformation has a negative VCD band in amide III region. Knowing this spectral characteristic of each conformation allows us to assign the experimental amide III VCD spectrum of ADP. Moreover, the amide III region of the VCD spectrum was used to determine the relative populations of conformations of ADP in water. Based on the interpretation of the amide III region of VCD spectrum we have shown that dominant conformation of ADP in water is PII which is stabilized by hydrogen bonded water molecules between CO and NH groups on the peptide backbone. Copyright © 2014 Wiley Periodicals, Inc.

Identification of novel dipeptidyl peptidase-IV and angiotensin-I-converting enzyme inhibitory peptides from meat proteins using in silico analysis.

Science.gov (United States)

Lafarga, Tomas; O'Connor, Paula; Hayes, Maria

2014-09-01

Angiotensin-I-converting enzyme (ACE-I, EC 3.4.15.1), renin (EC 3.4.23.15), and dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) play key roles in the control of hypertension and the development of type-2 diabetes and other diseases associated with metabolic syndrome. The aim of this work was to utilize known in silico methodologies, peptide databases and software including ProtParam (http://web.expasy.org/protparam/), Basic Local Alignment Tool (BLAST), ExPASy PeptideCutter (http://web.expasy.org/peptide_cutter/) and BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/pl/biopep) to assess the release of potentially bioactive DPP-IV, renin and ACE-I inhibitory peptides from bovine and porcine meat proteins including hemoglobin, collagen and serum albumin. These proteins were chosen as they are found commonly in meat by-products such as bone, blood and low-value meat cuts. In addition, the bioactivities of identified peptides were confirmed using chemical synthesis and in vitro bioassays. The concentration of peptide required to inhibit the activity of ACE-I and DPP-IV by 50% was determined for selected, active peptides. Novel ACE-I and DPP-IV inhibitory peptides were identified in this study using both in silico analysis and a literature search to streamline enzyme selection for peptide production. These novel peptides included the ACE-I inhibitory tri-peptide Ile-Ile-Tyr and the DPP-IV inhibitory tri-peptide Pro-Pro-Leu corresponding to sequences f (182-184) and f (326-328) of both porcine and bovine serum albumin which can be released following hydrolysis with the enzymes papain and pepsin, respectively. This work demonstrates that meat proteins are a suitable resource for the generation of bioactive peptides and further demonstrates the usefulness of in silico methodologies to streamline identification and generation of bioactive peptides. Copyright © 2014 Elsevier Inc. All rights reserved.

Transport Deficiency Is the Molecular Basis of Candida albicans Resistance to Antifungal Oligopeptides

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Marta Schielmann

2017-11-01

Full Text Available Oligopeptides incorporating N3-(4-methoxyfumaroyl-L-2,3-diaminopropanoic acid (FMDP, an inhibitor of glucosamine-6-phosphate synthase, exhibited growth inhibitory activity against Candida albicans, with minimal inhibitory concentration values in the 0.05–50 μg mL-1 range. Uptake by the peptide permeases was found to be the main factor limiting an anticandidal activity of these compounds. Di- and tripeptide containing FMDP (F2 and F3 were transported by Ptr2p/Ptr22p peptide transporters (PTR and FMDP-containing hexa-, hepta-, and undecapeptide (F6, F7, and F11 were taken up by the oligopeptide transporters (OPT oligopeptide permeases, preferably by Opt2p/Opt3p. A phenotypic, apparent resistance of C. albicans to FMDP-oligopeptides transported by OPT permeases was triggered by the environmental factors, whereas resistance to those taken up by the PTR system had a genetic basis. Anticandidal activity of longer FMDP-oligopeptides was strongly diminished in minimal media containing easily assimilated ammonium sulfate or L-glutamine as the nitrogen source, both known to downregulate expression of the OPT genes. All FMDP-oligopeptides tested were more active at lower pH and this effect was slightly more remarkable for peptides F6, F7, and F11, compared to F2 and F3. Formation of isolated colonies was observed inside the growth inhibitory zones induced by F2 and F3 but not inside those induced by F6, F7, and F11. The vast majority (98% of those colonies did not originate from truly resistant cells. The true resistance of 2% of isolates was due to the impaired transport of di- and to a lower extent, tripeptides. The resistant cells did not exhibit a lower expression of PTR2, PTR22, or OPT1–3 genes, but mutations in the PTR2 gene resulting in T422H, A320S, D119V, and A320S substitutions in the amino acid sequence of Ptr2p were found.

Thromboelastometric and platelet responses to silk biomaterials.

Science.gov (United States)

Kundu, Banani; Schlimp, Christoph J; Nürnberger, Sylvia; Redl, Heinz; Kundu, S C

2014-05-13

Silkworm's silk is natural biopolymer with unique properties including mechanical robustness, all aqueous base processing and ease in fabrication into different multifunctional templates. Additionally, the nonmulberry silks have cell adhesion promoting tri-peptide (RGD) sequences, which make it an immensely potential platform for regenerative medicine. The compatibility of nonmulberry silk with human blood is still elusive; thereby, restricts its further application as implants. The present study, therefore, evaluate the haematocompatibility of silk biomaterials in terms of platelet interaction after exposure to nonmulberry silk of Antheraea mylitta using thromboelastometry (ROTEM). The mulberry silk of Bombyx mori and clinically used Uni-Graft W biomaterial serve as references. Shortened clotting time, clot formation times as well as enhanced clot strength indicate the platelet mediated activation of blood coagulation cascade by tested biomaterials; which is comparable to controls.

Comparison of some peptidic and proteic ovine pineal fractions with a bovine pineal E5 fraction

Energy Technology Data Exchange (ETDEWEB)

Noteborn, H P; Ebels, I; Salemink, C A [State Univ. of Utrecht, Utrecht (Netherlands). Department of Organic Chemistry; Pevet, P [The Netherlands Institute for Brain Research, Amsterdam (Netherlands).; Reinharz, A C [Hopital Cantonal, Geneva (Switzerland). Department of Medicine, Division of Endocrinology; Neacsu, C [Institute of Cellular Biology and Pathology, Bucharest (Romania).

1982-01-01

Using rather simple and mild extraction and separation methods, three ovine pineal fractions (XM 300R - PP 7.2, PP 7.2' and PP 7.2S) were obtained, which contain peptidic/proteic substances and which show fluorescence characteristics of indoles. The ovine fractions were compared with the bovine pineal E5-fraction. The ovine fractions are chemically sensitive to normal laboratory light and stable in red light (..lambda.. > 600 nm). Immunologically, these fractions and the bovine E5 fraction are stable. From the results of radioimmunological experiments it was concluded that the bovine pineal E5 fraction as well as the ovine pineal fraction XM 300R - PP 7.2 and PP 7.2S may contain (a) peptide(s) ending by the same carboxy terminal tripeptide Pro-Arg-Gly(NH/sub 2/).

Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).

Science.gov (United States)

Zask, Arie; Birnberg, Gary; Cheung, Katherine; Kaplan, Joshua; Niu, Chuan; Norton, Emily; Suayan, Ronald; Yamashita, Ayako; Cole, Derek; Tang, Zhilian; Krishnamurthy, Girija; Williamson, Robert; Khafizova, Gulnaz; Musto, Sylvia; Hernandez, Richard; Annable, Tami; Yang, Xiaoran; Discafani, Carolyn; Beyer, Carl; Greenberger, Lee M; Loganzo, Frank; Ayral-Kaloustian, Semiramis

2004-09-09

Hemiasterlin, a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286, an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent antitumor effects, 2 has the advantage of circumventing the P-glycoprotein-mediated resistance that hampers the efficacy of other antimicrotubule agents such as paclitaxel and vincristine in animal models. This paper describes an in-depth study of the structure--activity relationships of analogues of 2, their effects on microtubule polymerization, and their in vitro and in vivo anticancer activity. Regions of the molecule necessary for potent activity are identified. Groups tolerant of modification, leading to novel analogues, are reported. Potent analogues identified through in vivo studies in tumor xenograft models include one superior analogue, HTI-042.

Total Synthesis and Stereochemical Assignment of Nostosin B

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Xiaoji Wang

2017-02-01

Full Text Available Nostosins A and B were isolated from a hydrophilic extract of Nostoc sp. strain from Iran, which exhibits excellent tryps inhibitory activity. Nostosin A was the most potent natural tripeptide aldehyde as trypsin inhibitor up to now. Both R‐ and S‐2‐hydroxy‐4‐(4‐hydroxy‐phenyl butanoic acid (Hhpba were prepared and incorporated into the total synthesis of nostosin B, respectively. Careful comparison of the NMR spectra and optical rotation data of synthetic nostosin B (1a and 1b with the natural product led to the unambiguous identification of the R‐configuration of the Hhpba fragment, which was further confirmed by co‐injection with the authentic sample on HPLC using both reversed phase column and the chiral AD‐RH column.

Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters

DEFF Research Database (Denmark)

Lyons, Joseph A.; Parker, Joanne L.; Solcan, Nicolae

2014-01-01

An enigma in the field of peptide transport is the structural basis for ligand promiscuity, as exemplified by PepT1, the mammalian plasma membrane peptide transporter. Here, we present crystal structures of di‐ and tripeptide‐bound complexes of a bacterial homologue of PepT1, which reveal at least...... two mechanisms for peptide recognition that operate within a single, centrally located binding site. The dipeptide was orientated laterally in the binding site, whereas the tripeptide revealed an alternative vertical binding mode. The co‐crystal structures combined with functional studies reveal...... that biochemically distinct peptide‐binding sites likely operate within the POT/PTR family of proton‐coupled symporters and suggest that transport promiscuity has arisen in part through the ability of the binding site to accommodate peptides in multiple orientations for transport...

Requirements for superoxide-dependent tyrosine hydroperoxide formation in peptides

DEFF Research Database (Denmark)

Winterbourn, Christine C; Parsons-Mair, Helena N; Gebicki, Silvia

2004-01-01

Superoxide reacts rapidly with other radicals, but these reactions have received little attention in the context of oxidative stress. For tyrosyl radicals, reaction with superoxide is 3-fold faster than dimerization, and forms the addition product tyrosine hydroperoxide. We have explored structural...... requirements for hydroperoxide formation using tyrosine analogues and di- and tri-peptides. Superoxide and phenoxyl radicals were generated using xanthine oxidase, peroxidase and the respective tyrosine derivative, or by gamma-radiation. Peroxides were measured using FeSO4/Xylenol Orange. Tyrosine and tyramine...... formed stable hydroperoxides, but N-acetyltyrosine and p-hydroxyphenylacetic acid did not, demonstrating a requirement for a free amino group. Using [14C]tyrosine, the hydroperoxide and dityrosine were formed at a molar ratio of 1.8:1. Studies with pre-formed hydroperoxides, and measurements of substrate...

Determination of glutathione and glutathione disulfide in biological samples: an in-depth review.

Science.gov (United States)

Monostori, Péter; Wittmann, Gyula; Karg, Eszter; Túri, Sándor

2009-10-15

Glutathione (GSH) is a thiol-containing tripeptide, which plays central roles in the defence against oxidative damage and in signaling pathways. Upon oxidation, GSH is transformed to glutathione disulfide (GSSG). The concentrations of GSH and GSSG and their molar ratio are indicators of cell functionality and oxidative stress. Assessment of redox homeostasis in various clinical states and medical applications for restoration of the glutathione status are of growing importance. This review is intended to provide a state-of-the-art overview of issues relating to sample pretreatment and choices for the separation and detection of GSH and GSSG. High-performance liquid chromatography, capillary electrophoresis and gas chromatography (as techniques with a separation step) with photometric, fluorimetric, electrochemical and mass spectrometric detection are discussed, stress being laid on novel approaches.

The tripeptide aldehyde, Boc-DPhe-Phe-Lysinal, is a novel Ca2+ channel inhibitor in pituitary cells.

Science.gov (United States)

Makara, G B; Rappay, G; Garamvölgyi, V; Nagy, I; Dankó, S; Bajusz, S

1988-06-22

The effect of Boc-DPhe-Phe-Lysinal (Boc-DPPL) on the 45Ca2+ uptake of rat anterior pituitary monolayer cultures was investigated. The compound decreased the basal Ca2+ uptake at 3 x 10(-4) mol/l. The 45Ca2+ uptake stimulated by potassium-induced depolarization was more sensitive to Boc-DPPL inhibition, a slight decrease was seen with 3 x 10(-6) mol/l and there was a half maximal inhibition at 3 x 10(-5) mol/l. Boc-DPPL is known to inhibit pituitary hormone release in similar concentrations, an effect might also be due to its calcium antagonist property.

Pre-hospital electrocardiogram triage with tele-cardiology support is associated with shorter time-to-balloon and higher rates of timely reperfusion even in rural areas: data from the Bari- Barletta/Andria/Trani public emergency medical service 118 registry on primary angioplasty in ST-elevation myocardial infarction.

Science.gov (United States)

Brunetti, Natale Daniele; Di Pietro, Gaetano; Aquilino, Ambrogio; Bruno, Angela I; Dellegrottaglie, Giulia; Di Giuseppe, Giuseppe; Lopriore, Claudio; De Gennaro, Luisa; Lanzone, Saverio; Caldarola, Pasquale; Antonelli, Gianfranco; Di Biase, Matteo

2014-09-01

We report the preliminary data from a regional registry on ST-elevation myocardial infarction (STEMI) patients treated with primary angioplasty in Apulia, Italy; the region is covered by a single public health-care service, a single public emergency medical service (EMS), and a single tele-medicine service provider. Two hundred and ninety-seven consecutive patients with STEMI transferred by regional free public EMS 1-1-8 for primary-PCI were enrolled in the study; 123 underwent pre-hospital electrocardiograms (ECGs) triage by tele-cardiology support and directly referred for primary-PCI, those remaining were just transferred by 1-1-8 ambulances for primary percutaneous coronary intervention (PCI) (diagnosis not based on tele-medicine ECG; already hospitalised patients, emergency-room without tele-medicine support). Time from first ECG diagnostic for STEMI to balloon was recorded; a time-to-balloon primary-PCI). Pre-hospital triage with tele-cardiology ECG in an EMS registry from an area with more than one and a half million inhabitants was associated with shorter time-to-balloon and higher rates of timely treated patients, even in 'rural' areas. © The European Society of Cardiology 2014.

Imidacloprid impairs shorter-term and longer-term learning in honey bees (Apis mellifera)

OpenAIRE

Zhang, Erica

2014-01-01

Even at sublethal doses, neonicotinoids, commonly used insecticides can affect neurons involved in learning and memory, cognitive features that play a key role in colony fitness because they facilitate foraging. The commonly used neonicotinoid, imidacloprid, impairs the ability of bees to associate floral odors with a nectar reward. However, no studies, to date, have examined how if imidacloprid impairs negative associative learning. Sit- and-wait predators like spiders can attack foraging be...

Why shorter half-times of repair lead to greater damage in pulsed brachytherapy

International Nuclear Information System (INIS)

Fowler, J.F.

1993-01-01

Pulsed brachytherapy consists of replacing continuous irradiation at low dose-rate with a series of medium dose-rate fractions in the same overall time and to the same total dose. For example, pulses of 1 Gy given every 2 hr or 2 Gy given every 4 hr would deliver the same 70 Gy in 140 hr as continuous irradiation at 0.5 Gy/hr. If higher dose-rates are used, even with gaps between the pulses, the biological effects are always greater. Provided that dose rates in the pulse do not exceed 3 Gy/hr, and provided that pulses are given as often as every 2 hr, the inevitable increases of biological effect are no larger than a few percent (of biologically effective dose or extrapolated response dose). However, these increases are more likely to exceed 10% (and thus become clinically significant) if the half-time of repair of sublethal damage is short (less than 1 hr) rather than long. This somewhat unexpected finding is explained in detail here. The rise and fall of Biologically Effective Dose (and hence of Relative Effectiveness, for a constant dose in each pulse) is calculated during and after single pulses, assuming a range of values of T 1/2 , the half-time of sublethal damage repair. The area under each curve is proportional to Biologically Effective Dose and therefore to log cell kill. Pulses at 3 Gy/hr do yield greater biological effect (dose x integrated Relative Effectiveness) than lower dose-rate pulses or continuous irradiation at 0.5 Gy/hr. The contrast is greater for the short T 1/2 of 0.5 hr than for the longer T 1/2 of 1.5 hr. More biological damage will be done (compared with traditional low dose rate brachytherapy) in tissues with short T 1/2 (0.1-1 hr) than in tissues with longer T 1/2 values. 8 refs., 3 figs

Assessing the reliability and validity of a shorter version of RIASEC in Turkish

Directory of Open Access Journals (Sweden)

Süerdem Ahmet

2016-01-01

Full Text Available Holland’s RIASEC types are being frequently utilized in commercial vocational profiling tools for various human resources purposes. On the other hand, the length of the RIASEC scale and the copyright restrictions put by the publishers, are important barriers to application. In the present study, a RIASEC scale consisting of 41 items and adapted to Turkish language and culture, was developed. Each RIASEC type was represented with 6 or 7 items. Responses were obtained from a sample of 364 business professionals. Survey results indicated a good reliability for the scale, with a Cronbach’s alpha of 0.889. However, reliability analysis pointed out to the need for revision of certain scale items when each RIASEC facet was separately analysed. Then, feedback regarding scale composition, wording and structure were gathered from 20 PhD students. Lastly, feedback of 7 HR professionals were sought, regarding scale items’ expression and application of the scale in regular HR processes of companies. Results from face and content validity have been that for some items of the scale, more descriptive and specific expressions in Turkish are required. Moreover, some of the items would need to be reallocated to another facet where they would be more relevant. In line with findings from face and content validity, construct validity through confirmatory factor analysis also indicated that the short version of RIASEC must be revised substantially in order to become a valid tool for vocational profiling in Turkish context.

Making tomorrow's mistakes today: Evolutionary prototyping for risk reduction and shorter development time

Science.gov (United States)

Friedman, Gary; Schwuttke, Ursula M.; Burliegh, Scott; Chow, Sanguan; Parlier, Randy; Lee, Lorrine; Castro, Henry; Gersbach, Jim

1993-01-01

In the early days of JPL's solar system exploration, each spacecraft mission required its own dedicated data system with all software applications written in the mainframe's native assembly language. Although these early telemetry processing systems were a triumph of engineering in their day, since that time the computer industry has advanced to the point where it is now advantageous to replace these systems with more modern technology. The Space Flight Operations Center (SFOC) Prototype group was established in 1985 as a workstation and software laboratory. The charter of the lab was to determine if it was possible to construct a multimission telemetry processing system using commercial, off-the-shelf computers that communicated via networks. The staff of the lab mirrored that of a typical skunk works operation -- a small, multi-disciplinary team with a great deal of autonomy that could get complex tasks done quickly. In an effort to determine which approaches would be useful, the prototype group experimented with all types of operating systems, inter-process communication mechanisms, network protocols, packet size parameters. Out of that pioneering work came the confidence that a multi-mission telemetry processing system could be built using high-level languages running in a heterogeneous, networked workstation environment. Experience revealed that the operating systems on all nodes should be similar (i.e., all VMS or all PC-DOS or all UNIX), and that a unique Data Transport Subsystem tool needed to be built to address the incompatibilities of network standards, byte ordering, and socket buffering. The advantages of building a telemetry processing system based on emerging industry standards were numerous: by employing these standards, we would no longer be locked into a single vendor. When new technology came to market which offered ten times the performance at one eighth the cost, it would be possible to attach the new machine to the network, re-compile the application code, and run. In addition, we would no longer be plagued with lack of manufacturer support when we encountered obscure bugs. And maybe, hopefully, the eternal elusive goal of software portability across different vendors' platforms would finally be available. Some highlights of our prototyping efforts are described.

Comprehensive borehole management for shorter drilling time; Umfassendes Bohrfortschrittsmanagement zur Verkuerzung der Bohrprojektdauer

Energy Technology Data Exchange (ETDEWEB)

Roehrlich, M. [ExxonMobil Production Deutschland GmbH, Hannover (Germany)

2007-09-13

In 2006, the trademarked ExxonMobil Fast Drill Process (FDP) was introduced also in the German ExxonMobil boreholes. The process is to maximize the drilling speed for every meter drilled. The process makes it possible to ensure borehole management on the basis of quantitative data and in consideration of all phases that are relevant for sinking a borehole. The FDP is used world-wide in all ExxonMobil drilling departments. More than 1.35 million meters are drilled annually in many different boreholes with different geological conditions, drilling profiles and international sites. The results were similar in many cases, with a significant increase in ROP and drill bit life, and with less damage caused by vibrations. FDP was developed on the basis of real time monitoring of the specific mechanical energy (MSE) required for drilling. MSE monitoring was found to be an effective tool dor detecting inefficient functioning of the drill bit and the overall system. To make operation more efficient, the causes must be identified and measures must be taken accordingly, taking into account the potential risks involved in such measures. MSE monitoring is a tool while FDPL is a broad management process ensuring that MSE and many other data sources are used effectively for optimisation of the ROP. Consequent implementation of the process resulted in a significant increase of the ROP. The major elements required for achieving this goal are discussed. (orig.)

Time to punishment: the effects of a shorter criminal procedure on crime rates

Czech Academy of Sciences Publication Activity Database

Dušek, Libor

2015-01-01

Roč. 43, August (2015), s. 134-147 ISSN 0144-8188 Institutional support: PRVOUK-P23 Keywords : criminal procedure * deterrence * law enforcement Subject RIV: AH - Economics Impact factor: 0.543, year: 2015

Time to punishment: the effects of a shorter criminal procedure on crime rates

Czech Academy of Sciences Publication Activity Database

Dušek, Libor

2015-01-01

Roč. 43, August (2015), s. 134-147 ISSN 0144-8188 Institutional support: RVO:67985998 Keywords : criminal procedure * deterrence * law enforcement Subject RIV: AH - Economics Impact factor: 0.543, year: 2015

Accuracy of rate coding: When shorter time window and higher spontaneous activity help

Czech Academy of Sciences Publication Activity Database

Leváková, Marie; Tamborrino, M.; Košťál, Lubomír; Lánský, Petr

2017-01-01

Roč. 95, č. 2 (2017), č. článku 022310. ISSN 2470-0045 R&D Projects: GA ČR(CZ) GA15-08066S; GA MŠk(CZ) 7AMB17AT048 Institutional support: RVO:67985823 Keywords : rate coding * observation window * spontaneous activity * Fisher information * perfect integrate- and -fire model * Wiener process Subject RIV: BB - Applied Statistics, Operational Research OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 2.366, year: 2016

Making tomorrow's mistakes today: Evolutionary prototyping for risk reduction and shorter development time

Science.gov (United States)

Friedman, Gary; Schwuttke, Ursula M.; Burliegh, Scott; Chow, Sanguan; Parlier, Randy; Lee, Lorrine; Castro, Henry; Gersbach, Jim

1993-03-01

In the early days of JPL's solar system exploration, each spacecraft mission required its own dedicated data system with all software applications written in the mainframe's native assembly language. Although these early telemetry processing systems were a triumph of engineering in their day, since that time the computer industry has advanced to the point where it is now advantageous to replace these systems with more modern technology. The Space Flight Operations Center (SFOC) Prototype group was established in 1985 as a workstation and software laboratory. The charter of the lab was to determine if it was possible to construct a multimission telemetry processing system using commercial, off-the-shelf computers that communicated via networks. The staff of the lab mirrored that of a typical skunk works operation -- a small, multi-disciplinary team with a great deal of autonomy that could get complex tasks done quickly. In an effort to determine which approaches would be useful, the prototype group experimented with all types of operating systems, inter-process communication mechanisms, network protocols, packet size parameters. Out of that pioneering work came the confidence that a multi-mission telemetry processing system could be built using high-level languages running in a heterogeneous, networked workstation environment. Experience revealed that the operating systems on all nodes should be similar (i.e., all VMS or all PC-DOS or all UNIX), and that a unique Data Transport Subsystem tool needed to be built to address the incompatibilities of network standards, byte ordering, and socket buffering. The advantages of building a telemetry processing system based on emerging industry standards were numerous: by employing these standards, we would no longer be locked into a single vendor. When new technology came to market which offered ten times the performance at one eighth the cost, it would be possible to attach the new machine to the network, re-compile the application code, and run. In addition, we would no longer be plagued with lack of manufacturer support when we encountered obscure bugs. And maybe, hopefully, the eternal elusive goal of software portability across different vendors' platforms would finally be available. Some highlights of our prototyping efforts are described.

Shorter Psychiatry Clerkship Length Is Associated with Lower NBME Psychiatry Shelf Exam Performance

Science.gov (United States)

Bostwick, J. Michael; Alexander, Cara

2012-01-01

Objective: The goal of this study was to evaluate a recent medical school curriculum change at our institution 3 years ago; specifically: shortening the Psychiatry core clerkship from 4 to 3 weeks and adding an optional 6-week core/elective combination rotation in lieu of the 3-week core. The authors aimed to determine whether clerkship length was…

Conformational Effects through Hydrogen Bonding in a Constrained γ-Peptide Template: From Intraresidue Seven-Membered Rings to a Gel-Forming Sheet Structure.

Science.gov (United States)

Awada, Hawraà; Grison, Claire M; Charnay-Pouget, Florence; Baltaze, Jean-Pierre; Brisset, François; Guillot, Régis; Robin, Sylvie; Hachem, Ali; Jaber, Nada; Naoufal, Daoud; Yazbeck, Ogaritte; Aitken, David J

2017-05-05

A series of three short oligomers (di-, tri-, and tetramers) of cis-2-(aminomethyl)cyclobutane carboxylic acid, a γ-amino acid featuring a cyclobutane ring constraint, were prepared, and their conformational behavior was examined spectroscopically and by molecular modeling. In dilute solutions, these peptides showed a number of low-energy conformers, including ribbonlike structures pleated around a rarely observed series of intramolecular seven-membered hydrogen bonds. In more concentrated solutions, these interactions defer to an organized supramolecular assembly, leading to thermoreversible organogel formation notably for the tripeptide, which produced fibrillar xerogels. In the solid state, the dipeptide adopted a fully extended conformation featuring a one-dimensional network of intermolecularly H-bonded molecules stacked in an antiparallel sheet alignment. This work provides unique insight into the interplay between inter- and intramolecular H-bonded conformer topologies for the same peptide template.

Design of a new peptidomimetic agonist for the melanocortin receptors based on the solution structure of the peptide ligand, Ac-Nle-cyclo[Asp-Pro-DPhe-Arg-Trp-Lys]-NH(2).

Science.gov (United States)

Fotsch, Christopher; Smith, Duncan M; Adams, Jeffrey A; Cheetham, Janet; Croghan, Michael; Doherty, Elizabeth M; Hale, Clarence; Jarosinski, Mark A; Kelly, Michael G; Norman, Mark H; Tamayo, Nuria A; Xi, Ning; Baumgartner, James W

2003-07-21

The solution structure of a potent melanocortin receptor agonist, Ac-Nle-cyclo[Asp-Pro-DPhe-Arg-Trp-Lys]-NH(2) (1) was calculated using distance restraints determined from 1H NMR spectroscopy. Eight of the lowest energy conformations from this study were used to identify non-peptide cores that mimic the spatial arrangement of the critical tripeptide region, DPhe-Arg-Trp, found in 1. From these studies, compound 2a, containing the cis-cyclohexyl core, was identified as a functional agonist of the melanocortin-4 receptor (MC4R) with an IC(50) and EC(50) below 10 nM. Compound 2a also showed 36- and 7-fold selectivity over MC3R and MC1R, respectively, in the binding assays. Subtle changes in cyclohexane stereochemistry and removal of functional groups led to analogues with lower affinity for the MC receptors.

Cryochemistry: freezing effect on peptide coupling in different organic solutions.

Science.gov (United States)

Vajda, T; Szókán, G; Hollósi, M

1998-06-01

The freezing effect on peptide coupling in organic solutions of different polarity has been investigated and compared with the results obtained in liquid phase. The model reaction of DCC-activated coupling of Boc-Ala-Phe-OH with H-Ala-OBu(t) has been carried out in dioxane, dimethylsulfoxide and formamide, as well as in mixtures (90%/10%, v/v) of dioxane with acetonitrile, dimethylformamide, dimethylsulfoxide and formamide. The reactions have been traced and evaluated by RP-HPLC analysis. Freezing the reaction mixture resulted in all cases in a significant suppression of the N-dipeptidylurea side-product formation together with a slight decrease of tripeptide epimerization. The coupling yields and the side effects depended on the solvent, with the dioxane and dioxane/acetonitrile mixture produced the best results. The role of freezing and solvent in the improved results is discussed.

Sensing pH via p-cyanophenylalanine fluorescence: Application to determine peptide pKa and membrane penetration kinetics.

Science.gov (United States)

Pazos, Ileana M; Ahmed, Ismail A; Berríos, Mariana I León; Gai, Feng

2015-08-15

We expand the spectroscopic utility of a well-known infrared and fluorescence probe, p-cyanophenylalanine, by showing that it can also serve as a pH sensor. This new application is based on the notion that the fluorescence quantum yield of this unnatural amino acid, when placed at or near the N-terminal end of a polypeptide, depends on the protonation status of the N-terminal amino group of the peptide. Using this pH sensor, we are able to determine the N-terminal pKa values of nine tripeptides and also the membrane penetration kinetics of a cell-penetrating peptide. Taken together, these examples demonstrate the applicability of using this unnatural amino acid fluorophore to study pH-dependent biological processes or events that accompany a pH change. Copyright © 2015 Elsevier Inc. All rights reserved.

Topical Peptide Treatments with Effective Anti-Aging Results

Directory of Open Access Journals (Sweden)

Silke Karin Schagen

2017-05-01

Full Text Available In the last two decades, many new peptides have been developed, and new knowledge on how peptides improve the skin has been uncovered. The spectrum of peptides in the field of cosmetics is continuously growing. This review summarizes some of the effective data on cosmeceutical peptides that work against intrinsic and extrinsic aging. Some peptides have been proven in their efficacy through clinical skin trials. Well-known and documented peptides like copper tripeptide are still under research to obtain more details on their effectiveness, and for the development of new treatments. Palmitoyl pentapeptide-4 and Carnosine are other well-researched cosmeceuticals. Additionally, there are many more peptides that are used in cosmetics. However, study results for some are sparse, or have not been published in scientific journals. This article summarizes topical peptides with proven efficacy in controlled in vivo studies.

Local Order in the Unfolded State: Conformational Biases and Nearest Neighbor Interactions

Directory of Open Access Journals (Sweden)

Siobhan Toal

2014-07-01

Full Text Available The discovery of Intrinsically Disordered Proteins, which contain significant levels of disorder yet perform complex biologically functions, as well as unwanted aggregation, has motivated numerous experimental and theoretical studies aimed at describing residue-level conformational ensembles. Multiple lines of evidence gathered over the last 15 years strongly suggest that amino acids residues display unique and restricted conformational preferences in the unfolded state of peptides and proteins, contrary to one of the basic assumptions of the canonical random coil model. To fully understand residue level order/disorder, however, one has to gain a quantitative, experimentally based picture of conformational distributions and to determine the physical basis underlying residue-level conformational biases. Here, we review the experimental, computational and bioinformatic evidence for conformational preferences of amino acid residues in (mostly short peptides that can be utilized as suitable model systems for unfolded states of peptides and proteins. In this context particular attention is paid to the alleged high polyproline II preference of alanine. We discuss how these conformational propensities may be modulated by peptide solvent interactions and so called nearest-neighbor interactions. The relevance of conformational propensities for the protein folding problem and the understanding of IDPs is briefly discussed.

Minicollagen-15, a novel minicollagen isolated from Hydra, forms tubule structures in nematocysts.

Science.gov (United States)

Adamczyk, Patrizia; Meier, Sebastian; Gross, Thomas; Hobmayer, Bert; Grzesiek, Stephan; Bächinger, Hans Peter; Holstein, Thomas W; Ozbek, Suat

2008-02-29

Minicollagens constitute a family of unusually short collagen molecules isolated from cnidarians. They are restricted to the nematocyst, a cylindrical explosive organelle serving in defense and capture of prey. The nematocyst capsule contains a long tubule inside of its matrix, which is expelled and everted during an ultrafast discharge process. Here, we report the cloning and characterization of a novel minicollagen in Hydra, designated minicollagen-15 (NCol-15). NCol-15, like NCol-3 and NCol-4, shows deviations from the canonical cysteine pattern in its terminal cysteine-rich domains (CRDs). Minicollagens share common domain architectures with a central collagen sequence flanked by polyproline stretches and short N- and C-terminal CRDs. The CRDs are involved in the formation of a highly resistant cysteine network, which constitutes the basic structure of the nematocyst capsule. Unlike NCol-1, which is part of the capsule wall, NCol-15 is localized to tubules, arguing for a functional differentiation of minicollagens within the nematocyst architecture. NMR analysis of the altered C-terminal CRD of NCol-15 showed a novel disulfide-linked structure within the cysteine-containing region exhibiting similar folding kinetics and stability as the canonical CRDs. Our data provide evidence for evolutionary diversification among minicollagens, which probably facilitated alterations in the morphology of the nematocyst wall and tubule.

Integrating solid-state NMR and computational modeling to investigate the structure and dynamics of membrane-associated ghrelin.

Directory of Open Access Journals (Sweden)

Gerrit Vortmeier

Full Text Available The peptide hormone ghrelin activates the growth hormone secretagogue receptor 1a, also known as the ghrelin receptor. This 28-residue peptide is acylated at Ser3 and is the only peptide hormone in the human body that is lipid-modified by an octanoyl group. Little is known about the structure and dynamics of membrane-associated ghrelin. We carried out solid-state NMR studies of ghrelin in lipid vesicles, followed by computational modeling of the peptide using Rosetta. Isotropic chemical shift data of isotopically labeled ghrelin provide information about the peptide's secondary structure. Spin diffusion experiments indicate that ghrelin binds to membranes via its lipidated Ser3. Further, Phe4, as well as electrostatics involving the peptide's positively charged residues and lipid polar headgroups, contribute to the binding energy. Other than the lipid anchor, ghrelin is highly flexible and mobile at the membrane surface. This observation is supported by our predicted model ensemble, which is in good agreement with experimentally determined chemical shifts. In the final ensemble of models, residues 8-17 form an α-helix, while residues 21-23 and 26-27 often adopt a polyproline II helical conformation. These helices appear to assist the peptide in forming an amphipathic conformation so that it can bind to the membrane.

Solution structure and dynamics of melanoma inhibitory activity protein

International Nuclear Information System (INIS)

Lougheed, Julie C.; Domaille, Peter J.; Handel, Tracy M.

2002-01-01

Melanoma inhibitory activity (MIA) is a small secreted protein that is implicated in cartilage cell maintenance and melanoma metastasis. It is representative of a recently discovered family of proteins that contain a Src Homologous 3 (SH3) subdomain. While SH3 domains are normally found in intracellular proteins and mediate protein-protein interactions via recognition of polyproline helices, MIA is single-domain extracellular protein, and it probably binds to a different class of ligands.Here we report the assignments, solution structure, and dynamics of human MIA determined by heteronuclear NMR methods. The structures were calculated in a semi-automated manner without manual assignment of NOE crosspeaks, and have a backbone rmsd of 0.38 A over the ordered regions of the protein. The structure consists of an SH3-like subdomain with N- and C-terminal extensions of approximately 20 amino acids each that together form a novel fold. The rmsd between the solution structure and our recently reported crystal structure is 0.86 A over the ordered regions of the backbone, and the main differences are localized to the most dynamic regions of the protein. The similarity between the NMR and crystal structures supports the use of automated NOE assignments and ambiguous restraints to accelerate the calculation of NMR structures

Disintegrins from Hematophagous Sources

Directory of Open Access Journals (Sweden)

Ivo M. B. Francischetti

2012-04-01

Full Text Available Bloodsucking arthropods are a rich source of salivary molecules (sialogenins which inhibit platelet aggregation, neutrophil function and angiogenesis. Here we review the literature on salivary disintegrins and their targets. Disintegrins were first discovered in snake venoms, and were instrumental in our understanding of integrin function and also for the development of anti-thrombotic drugs. In hematophagous animals, most disintegrins described so far have been discovered in the salivary gland of ticks and leeches. A limited number have also been found in hookworms and horseflies, and none identified in mosquitoes or sand flies. The vast majority of salivary disintegrins reported display a RGD motif and were described as platelet aggregation inhibitors, and few others as negative modulator of neutrophil or endothelial cell functions. This notably low number of reported disintegrins is certainly an underestimation of the actual complexity of this family of proteins in hematophagous secretions. Therefore an algorithm was created in order to identify the tripeptide motifs RGD, KGD, VGD, MLD, KTS, RTS, WGD, or RED (flanked by cysteines in sialogenins deposited in GenBank database. The search included sequences from various blood-sucking animals such as ticks (e.g., Ixodes sp., Argas sp., Rhipicephalus sp., Amblyomma sp., tabanids (e.g., Tabanus sp., bugs (e.g., Triatoma sp., Rhodnius prolixus, mosquitoes (e.g., Anopheles sp., Aedes sp., Culex sp., sand flies (e.g., Lutzomyia sp., Phlebotomus sp., leeches (e.g., Macrobdella sp., Placobdella sp. and worms (e.g., Ancylostoma sp.. This approach allowed the identification of a remarkably high number of novel putative sialogenins with tripeptide motifs typical of disintegrins (>450 sequences whose biological activity remains to be verified. This database is accessible

Inhibition of growth hormone and prolactin secretion by a serine proteinase inhibitor

International Nuclear Information System (INIS)

Rappay, G.; Nagy, I.; Makara, G.B.; Horvath, G.; Karteszi, M.; Bacsy, E.; Stark, E.

1984-01-01

The action of the tripeptide aldehyde t-butyloxycarbonyl-DPhe-Pro-Arg-H (boc-fPR-H), belonging to a family of serine proteinase inhibitors, on the release of immunoreactive prolactin (iPRL) and growth hormone (iGH) has been studied. In rat anterior pituitary cell cultures and pituitary quarters 1 mM boc-fPR-H inhibited basal iPRL and iGH release. Thyroliberin-induced iPRL release by cultured cells was also markedly inhibited with a concomitant accumulation of intracellular iPRL. During the short- and long-term exposure of cells to boc-fPR-H there were no changes in total cell protein contents and in activities of some lysosomal marker enzymes. The marked inhibition of basal as well as stimulated hormone release in the presence of the enzyme inhibitor might suggest that at least a portion of the hormones is released via a proteolytic enzyme-dependent process

Amide proton exchange rates of a bound pepsin inhibitor determined by isotope-edited proton NMR experiments

International Nuclear Information System (INIS)

Fesik, S.W.; Luly, J.R.; Stein, H.H.; BaMaung, N.

1987-01-01

From a series of isotope-edited proton NMR spectra, amide proton exchange rates were measured at 20 C, 30 C, and 40 0 C for a tightly bound 15 N-labeled tripeptide inhibitor of porcine pepsin (IC50 = 1.7 X 10(-) M). Markedly different NH exchange rates were observed for the three amide protons of the bound inhibitor. The P1 NH exchanged much more slowly than the P2 NH and P3 NH. These results are discussed in terms of the relative solvent accessibility in the active site and the role of the NH protons of the inhibitor for hydrogen bonding to the enzyme. In this study a useful approach is demonstrated for obtaining NH exchange rates on ligands bound to biomacromolecules, the knowledge of which could be of potential utility in the design of therapeutically useful nonpeptide enzyme inhibitors from peptide leads

Assessment of contamination of the Svitava and Svratka rivers in the Czech Republic using selected biochemical markers.

Science.gov (United States)

Blahová, Jana; Havelková, Marcela; Kruzíková, Kamila; Hilscherová, Klára; Halouzka, Roman; Modrá, Helena; Grabic, Roman; Halírová, Jarmila; Jurcíková, Jana; Ocelka, Tomás; Harustiaková, Danka; Svobodová, Zdenka

2010-03-01

The aim of the present study is to assess aquatic ecosystem contamination using selected biochemical markers: cytochrome P450, ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), tripeptide glutathione, vitellogenin, and 11-ketotestosterone in chub (Leuciscus cephalus L.). Seven locations on the Svitava and Svratka rivers (in the Brno conurbation, Czech Republic) were assessed. The results were compared with the levels of the most important inductors of these biomarkers: organic pollutants hexachlorocyclohexane (HCH), hexachlorobenzene (HCB), DDT and its metabolites, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons in bottom sediment, fish muscle, and semipermeable membrane devices (SPMDs) and metals in sediment. The highest levels of pollutants were observed at sites situated downstream from Brno, especially at Modrice and Rajhradice. Significant positive correlations (p < 0.05) were found between EROD activity and HCH concentration in SPMDs, and also between GST and EROD activity with HCB concentration in muscle, after adjusting for age.

Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York

DEFF Research Database (Denmark)

Mendiola, Jaime; Stahlhut, Richard W; Jørgensen, Niels

2011-01-01

count (p-values, 0.002-0.048). Men with AGD(AS) below (vs. above) the median were 7.3 times more likely (95% confidence interval, 2.5-21.6) to have a low sperm concentration (... percentiles of (adjusted) AGD(AS). CONCLUSIONS: In our population, AGD(AS) was a strong correlate of all semen parameters and a predictor of low sperm concentration. In animals, male AGD at birth reflects androgen levels during the masculinization programming window and predicts adult AGD and reproductive...

A COMPARISON OF GOLF SHOE DESIGNS HIGHLIGHTS GREATER GROUND REACTION FORCES WITH SHORTER IRONS

Directory of Open Access Journals (Sweden)

Paul Worsfold

2007-12-01

Full Text Available In an effort to reduce golf turf damage the traditional metal spike golf shoe has been redesigned, but shoe-ground biomechanical evaluations have utilised artificial grass surfaces. Twenty-four golfers wore three different golf shoe traction designs (traditional metal spikes, alternative spikes, and a flat-soled shoe with no additional traction when performing shots with a driver, 3 iron and 7 iron. Ground action forces were measured beneath the feet by two natural grass covered force platforms. The maximum vertical force recorded at the back foot with the 3 iron and 7 iron was 0.82 BW (body weight and at the front foot 1.1 BW approximately in both the metal spike and alternative spike golf shoe designs. When using the driver these maximal vertical values were 0.49 BW at the back foot and 0.84 BW at the front foot. Furthermore, as performance of the backswing and then downswing necessitates a change in movement direction the range of force generated during the complete swing was calculated. In the metal spike shoe the vertical force generated at the back foot with both irons was 0.67 BW and at the front foot 0.96 BW with the 3 iron and 0.92 BW with the 7 iron. The back foot vertical force generated with the driver was 0.33 BW and at the front foot 0.83 BW wearing the metal spike shoe. Results indicated the greater force generation with the irons. When using the driver the more horizontal swing plane associated with the longer club reduced vertical forces at the back and front foot. However, the mediolateral force generated across each foot in the metal and alternative spike shoes when using the driver was greater than when the irons were used. The coefficient of friction was 0. 62 at the back and front foot whichever shoe was worn or club used

Snake Venomics and Antivenomics of Bothrops diporus, a Medically Important Pitviper in Northeastern Argentina

Science.gov (United States)

Gay, Carolina; Sanz, Libia; Calvete, Juan J.; Pla, Davinia

2015-01-01

Snake species within genus Bothrops are responsible for more than 80% of the snakebites occurring in South America. The species that cause most envenomings in Argentina, B. diporus, is widely distributed throughout the country, but principally found in the Northeast, the region with the highest rates of snakebites. The venom proteome of this medically relevant snake was unveiled using a venomic approach. It comprises toxins belonging to fourteen protein families, being dominated by PI- and PIII-SVMPs, PLA2 molecules, BPP-like peptides, L-amino acid oxidase and serine proteinases. This toxin profile largely explains the characteristic pathophysiological effects of bothropic snakebites observed in patients envenomed by B. diporus. Antivenomic analysis of the SAB antivenom (Instituto Vital Brazil) against the venom of B. diporus showed that this pentabothropic antivenom efficiently recognized all the venom proteins and exhibited poor affinity towards the small peptide (BPPs and tripeptide inhibitors of PIII-SVMPs) components of the venom. PMID:26712790

Deep-Red Fluorescent Gold Nanoclusters for Nucleoli Staining: Real-Time Monitoring of the Nucleolar Dynamics in Reverse Transformation of Malignant Cells.

Science.gov (United States)

Wang, Xiaojuan; Wang, Yanan; He, Hua; Ma, Xiqi; Chen, Qi; Zhang, Shuai; Ge, Baosheng; Wang, Shengjie; Nau, Werner M; Huang, Fang

2017-05-31

Nucleoli are important subnuclear structures inside cells. We report novel fluorescent gold nanoclusters (K-AuNCs) that are able to stain the nucleoli selectively and make it possible to explore the nucleolar morphology with fluorescence imaging technique. This novel probe is prepared through an easy synthesis method by employing a tripeptide (Lys-Cys-Lys) as the surface ligand. The properties, including deep-red fluorescence emission (680 nm), large Stocks shift, broad excitation band, low cytotoxicity, and good photostability, endow this probe with potential for bioanalytical applications. Because of their small size and their positively charged surface, K-AuNCs are able to accumulate efficiently at the nucleolar regions and provide precise morphological information. K-AuNCs are also used to monitor the nucleolar dynamics along the reverse-transformation process of malignant cells, induced by the agonist of protein A, 8-chloro-cyclic adenosine monophosphate. This gives a novel approach for investigating the working mechanism of antitumor drugs.

Electrochemical behavior of phytochelatins and related peptides at the hanging mercury drop electrode in the presence of cobalt(II) ions.

Science.gov (United States)

Dorcák, Vlastimil; Sestáková, Ivana

2006-01-01

Direct current voltammetry and differential pulse voltammetry have been used to investigate the electrochemical behaviour of two phytochelatins: heptapeptide (gamma-Glu-Cys)3-Gly and pentapeptide (gamma-Glu-Cys)2-Gly, tripeptide glutathione gamma-Glu-Cys-Gly and its fragments: dipeptides Cys-Gly and gamma-Glu-Cys at the hanging mercury drop electrode in the presence of cobalt(II) ions. Most interesting results were obtained with direct current voltammetry in the potential region of -0.80 V up to -1.80 V. Differential pulse voltammetry of the same solutions of Co(II) with peptides gives more complicated voltammograms with overlapping peaks, probably in connection with the influence of adsorption at slow scan rates necessarily used in this method. However, in using Brdicka catalytic currents for analytical purposes, differential pulse voltammograms seem to be more helpful. Presented investigations have shown that particularly the prewave of cobalt(II) allows distinguishing among phytochelatins, glutathione, and its fragments.

EH domain of EHD1

Energy Technology Data Exchange (ETDEWEB)

Kieken, Fabien; Jovic, Marko; Naslavsky, Naava; Caplan, Steve, E-mail: scaplan@unmc.edu; Sorgen, Paul L. [University of Nebraska Medical Center, Department of Biochemistry and Molecular Biology and Eppley Cancer Center (United States)], E-mail: psorgen@unmc.edu

2007-12-15

EHD1 is a member of the mammalian C-terminal Eps15 homology domain (EH) containing protein family, and regulates the recycling of various receptors from the endocytic recycling compartment to the plasma membrane. The EH domain of EHD1 binds to proteins containing either an Asn-Pro-Phe or Asp-Pro-Phe motif, and plays an important role in the subcellular localization and function of EHD1. Thus far, the structures of five N-terminal EH domains from other proteins have been solved, but to date, the structure of the EH domains from the four C-terminal EHD family paralogs remains unknown. In this study, we have assigned the 133 C-terminal residues of EHD1, which includes the EH domain, and solved its solution structure. While the overall structure resembles that of the second of the three N-terminal Eps15 EH domains, potentially significant differences in surface charge and the structure of the tripeptide-binding pocket are discussed.

EH domain of EHD1

International Nuclear Information System (INIS)

Kieken, Fabien; Jovic, Marko; Naslavsky, Naava; Caplan, Steve; Sorgen, Paul L.

2007-01-01

EHD1 is a member of the mammalian C-terminal Eps15 homology domain (EH) containing protein family, and regulates the recycling of various receptors from the endocytic recycling compartment to the plasma membrane. The EH domain of EHD1 binds to proteins containing either an Asn-Pro-Phe or Asp-Pro-Phe motif, and plays an important role in the subcellular localization and function of EHD1. Thus far, the structures of five N-terminal EH domains from other proteins have been solved, but to date, the structure of the EH domains from the four C-terminal EHD family paralogs remains unknown. In this study, we have assigned the 133 C-terminal residues of EHD1, which includes the EH domain, and solved its solution structure. While the overall structure resembles that of the second of the three N-terminal Eps15 EH domains, potentially significant differences in surface charge and the structure of the tripeptide-binding pocket are discussed

A redox responsive, fluorescent supramolecular metallohydrogel consists of nanofibers with single-molecule width

KAUST Repository

Zhang, Ye

2013-04-03

The integration of a tripeptide derivative, which is a versatile self-assembly motif, with a ruthenium(II)tris(bipyridine) complex affords the first supramolecular metallo-hydrogelator that not only self assembles in water to form a hydrogel but also exhibits gel-sol transition upon oxidation of the metal center. Surprisingly, the incorporation of the metal complex in the hydrogelator results in the nanofibers, formed by the self-assembly of the hydrogelator in water, to have the width of a single molecule of the hydrogelator. These results illustrate that metal complexes, besides being able to impart rich optical, electronic, redox, or magnetic properties to supramolecular hydrogels, also offer a unique geometrical control to prearrange the self-assembly motif prior to self-assembling. The use of metal complexes to modulate the dimensionality of intermolecular interactions may also help elucidate the interactions of the molecular nanofibers with other molecules, thus facilitating the development of supramolecular hydrogel materials for a wide range of applications. © 2013 American Chemical Society.

Protein Hydrolysates as Promoters of Non-Haem Iron Absorption

Science.gov (United States)

Li, Yanan; Jiang, Han; Huang, Guangrong

2017-01-01

Iron (Fe) is an essential micronutrient for human growth and health. Organic iron is an excellent iron supplement due to its bioavailability. Both amino acids and peptides improve iron bioavailability and absorption and are therefore valuable components of iron supplements. This review focuses on protein hydrolysates as potential promoters of iron absorption. The ability of protein hydrolysates to chelate iron is thought to be a key attribute for the promotion of iron absorption. Iron-chelatable protein hydrolysates are categorized by their absorption forms: amino acids, di- and tri-peptides and polypeptides. Their structural characteristics, including their size and amino acid sequence, as well as the presence of special amino acids, influence their iron chelation abilities and bioavailabilities. Protein hydrolysates promote iron absorption by keeping iron soluble, reducing ferric iron to ferrous iron, and promoting transport across cell membranes into the gut. We also discuss the use and relative merits of protein hydrolysates as iron supplements. PMID:28617327

The E1 mechanism in photo-induced beta-elimination reactions for green-to-red conversion of fluorescent proteins.

Science.gov (United States)

Tsutsui, Hidekazu; Shimizu, Hideaki; Mizuno, Hideaki; Nukina, Nobuyuki; Furuta, Toshiaki; Miyawaki, Atsushi

2009-11-25

KikGR is a fluorescent protein engineered to display green-to-red photoconvertibility that is induced by irradiation with ultraviolet or violet light. Similar to Kaede and EosFP, two naturally occurring photoconvertible proteins, KikGR contains a His(62)-Tyr(63)-Gly(64) tripeptide sequence, which forms a green chromophore that can be photoconverted to a red one via formal beta-elimination and subsequent extension of a pi-conjugated system. Using a crystallizable variant of KikGR, we determined the structures of both the green and red state at 1.55 A resolution. The double bond between His(62)-C(alpha) and His(62)-C(beta) in the red chromophore is in a cis configuration, indicating that rotation along the His(62) C(alpha)-C(beta) bond occurs following cleavage of the His(62) N(alpha)-C(alpha) bond. This structural rearrangement provides evidence that the beta-elimination reaction governing the green-to-red photoconversion of KikGR follows an E1 (elimination, unimolecular) mechanism.

Proteomic and metabolomic profiles of marine Vibrio sp. 010 in response to an antifoulant challenge

KAUST Repository

Chandramouli, Kondethimmanahalli; Dash, Swagatika; Zhang, Yu; Ravasi, Timothy; Qian, Peiyuan

2013-01-01

Vibrio spp. have the ability to form biofilms, which may contribute to the subsequent successful colonization by microfouling and macrofouling organisms. The effects of an antifouling compound, poly-ether B, on Vibrio sp. 010 were investigated using flow cytometry, proteomics, and metabolomics. A 2-D gel-based proteomic analysis was used to identify proteins responsive to poly-ether B treatment. The profiles of biofilm metabolites were analyzed by ultra-performance liquid chromatography-mass spectrometry. Poly-ether B caused a significant reduction in viability. The proteins affected by the treatment were related to nucleotide metabolism, the glyoxylate cycle, and stress responses. Metabolites such as tripeptides, fatty acids, and quorum-sensing molecules were regulated differentially. Down-regulation of proteins and metabolites potentially led to a loss in colonisation ability, thereby affecting the structure of the biofilm. These results suggest that the proteins and metabolites identified may serve as target molecules for potent antifouling compounds. © 2013 Copyright Taylor and Francis Group, LLC.

[Alpha-melanocyte-stimulating hormone. From bench to bedside].

Science.gov (United States)

Böhm, M; Luger, T A

2010-06-01

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide that is produced by the skin itself from the precursor proopiomelanocortin. It crucially mediates ultraviolet light-induced tanning after binding to melanocortin-1 receptors (MC-1R) expressed on the surface of epidermal melanocytes. The potent pigment-inducing and also cytoprotective actions of alpha-MSH are the rationale for the performance of first phase II clinical trials with Nle4-D-Phe7-alpha-MSH (NDP-alpha-MSH), a subcutaneously administered synthetic and superpotent alpha-MSH analogue, in patients with photodermatoses such as erythropoietic protoporphyria. Since alpha-MSH has shown promising anti-inflammatory and antifibrotic properties in numerous preclinical studies, it will be most interesting to evaluate these effects in further clinical pilot studies with NDP-alpha-MSH. In addition to alpha-MSH analogues, truncated tripeptides such as KDPT which do not bind to MC-1R but have sustained anti-inflammatory properties are currently emerging as another novel therapeutic strategy in dermatology.

Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2.

Science.gov (United States)

Murphy, Jane E; Vohra, Ravinder S; Dunn, Sarah; Holloway, Zoe G; Monaco, Anthony P; Homer-Vanniasinkam, Shervanthi; Walker, John H; Ponnambalam, Sreenivasan

2008-07-01

The LOX-1 scavenger receptor recognises pro-atherogenic oxidised low-density lipoprotein (OxLDL) particles and is implicated in atherosclerotic plaque formation, but this mechanism is not well understood. Here we show evidence for a novel clathrin-independent and cytosolic-signal-dependent pathway that regulates LOX-1-mediated OxLDL internalisation. Cell surface labelling in the absence or presence of OxLDL ligand showed that LOX-1 is constitutively internalised from the plasma membrane and its half-life is not altered upon ligand binding and trafficking. We show that LOX-1-mediated OxLDL uptake is disrupted by overexpression of dominant-negative dynamin-2 but unaffected by CHC17 or mu2 (AP2) depletion. Site-directed mutagenesis revealed a conserved and novel cytoplasmic tripeptide motif (DDL) that regulates LOX-1-mediated endocytosis of OxLDL. Taken together, these findings indicate that LOX-1 is internalised by a clathrin-independent and dynamin-2-dependent pathway and is thus likely to mediate OxLDL trafficking in vascular tissues.

Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms.

LENUS (Irish Health Repository)

Corvin, Aiden P

2012-06-27

Insulin-like growth factor-1 (IGF1) and its active peptide (1-3)IGF1 modulate brain growth and plasticity and are candidate molecules for treatment of brain disorders. IGF1 N-terminal portion is naturally cleaved to generate the tri-peptide (1-3)IGF1 (glycine-praline-glutamate). IGF1 and (1-3)IGF have been proposed as treatment for neuropathologies, yet their effect on nerve cells has not been directly compared. In this study we examine the effects of IGF1 and (1-3)IGF1 in primary cortical cultures and measure the expression levels of markers for intracellular pathways and synaptic function. We find that both treatments activate the IGF1 receptor and enhance the expression of synaptic markers, however, they activate different intracellular pathways. Furthermore, (1-3)IGF1 administration increases the expression of endogenous IGF1, suggesting a direct interaction between the two molecules. The results show that the two molecules increase the expression of synaptic proteins through activating different cellular mechanisms.

Protein Hydrolysates as Promoters of Non-Haem Iron Absorption

Directory of Open Access Journals (Sweden)

Yanan Li

2017-06-01

Full Text Available Iron (Fe is an essential micronutrient for human growth and health. Organic iron is an excellent iron supplement due to its bioavailability. Both amino acids and peptides improve iron bioavailability and absorption and are therefore valuable components of iron supplements. This review focuses on protein hydrolysates as potential promoters of iron absorption. The ability of protein hydrolysates to chelate iron is thought to be a key attribute for the promotion of iron absorption. Iron-chelatable protein hydrolysates are categorized by their absorption forms: amino acids, di- and tri-peptides and polypeptides. Their structural characteristics, including their size and amino acid sequence, as well as the presence of special amino acids, influence their iron chelation abilities and bioavailabilities. Protein hydrolysates promote iron absorption by keeping iron soluble, reducing ferric iron to ferrous iron, and promoting transport across cell membranes into the gut. We also discuss the use and relative merits of protein hydrolysates as iron supplements.

Discovery of Nanomolar Desmuramylpeptide Agonists of the Innate Immune Receptor Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Possessing Immunostimulatory Properties.

Science.gov (United States)

Gobec, Martina; Tomašič, Tihomir; Štimac, Adela; Frkanec, Ruža; Trontelj, Jurij; Anderluh, Marko; Mlinarič-Raščan, Irena; Jakopin, Žiga

2018-04-12

Muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, has long been known as the smallest fragment possessing adjuvant activity, on the basis of its agonistic action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). There is a pressing need for novel adjuvants, and NOD2 agonists provide an untapped source of potential candidates. Here, we report the design, synthesis, and characterization of a series of novel acyl tripeptides. A pivotal structural element for molecular recognition by NOD2 has been identified, culminating in the discovery of compound 9, the most potent desmuramylpeptide NOD2 agonist to date. Compound 9 augmented pro-inflammatory cytokine release from human peripheral blood mononuclear cells in synergy with lipopolysaccharide. Furthermore, it was able to induce ovalbumin-specific IgG titers in a mouse model of adjuvancy. These findings provide deeper insights into the structural requirements of desmuramylpeptides for NOD2-activation and highlight the potential use of NOD2 agonists as adjuvants for vaccines.

Transport of glutathione into the nucleus.

Science.gov (United States)

Queval, Guillaume; Foyer, Christine

2014-10-01

The tripeptide thiol glutathione (GSH) is present in the nucleus of plant and animal cells. However, the functions of GSH in the nucleus remain poorly characterised. GSH appears to become sequestered in the nucleus at the early stages of the cell cycle. As part of our search for proteins that may be involved in GSH transport into the nucleus, we studied the functions of the nucleoporin called Alacrima Achalasia aDrenal Insufficiency Neurologic disorder (ALADIN). ALADIN is encoded by the Achalasia-Addisonianism-Alacrimia (AAAS) gene in mammalian cells. Defects in ALADIN promote adrenal disorders and lead to the triple A syndrome in humans. The ALADIN protein localizes to the nuclear envelope in Arabidopsis thaliana and interacts with other components of the nuclear pore complex (NPC). We characterised the functions of the ALADIN protein in an Arabidopsis thaliana T-DNA insertion knockout mutant, which shows slow growth compared to the wild type. Copyright © 2014. Published by Elsevier Inc.

Proteomic and metabolomic profiles of marine Vibrio sp. 010 in response to an antifoulant challenge

KAUST Repository

Chandramouli, Kondethimmanahalli

2013-08-01

Vibrio spp. have the ability to form biofilms, which may contribute to the subsequent successful colonization by microfouling and macrofouling organisms. The effects of an antifouling compound, poly-ether B, on Vibrio sp. 010 were investigated using flow cytometry, proteomics, and metabolomics. A 2-D gel-based proteomic analysis was used to identify proteins responsive to poly-ether B treatment. The profiles of biofilm metabolites were analyzed by ultra-performance liquid chromatography-mass spectrometry. Poly-ether B caused a significant reduction in viability. The proteins affected by the treatment were related to nucleotide metabolism, the glyoxylate cycle, and stress responses. Metabolites such as tripeptides, fatty acids, and quorum-sensing molecules were regulated differentially. Down-regulation of proteins and metabolites potentially led to a loss in colonisation ability, thereby affecting the structure of the biofilm. These results suggest that the proteins and metabolites identified may serve as target molecules for potent antifouling compounds. © 2013 Copyright Taylor and Francis Group, LLC.

Transient erythromycin resistance phenotype associated with peptidyl-tRNA drop-off on early UGG and GGG codons

DEFF Research Database (Denmark)

Macvanin, Mirjana; Gonzalez de Valdivia, Ernesto I; Ardell, David H

2007-01-01

-peptide-encoding sequence, we asked whether the codons UGG and GGG, which are known to promote peptidyl-tRNA drop-off at early positions in mRNA, would result in a phenotype of erythromycin resistance if located after this sequence. We find that UGG or GGG, at either position +4 or +5, without a following stop codon......, is associated with an erythromycin resistance phenotype upon gene induction. Our results suggest that, while a stop codon at +4 gives a tripeptide product (MIL) and erythromycin sensitivity, UGG or GGG codons at the same position give a tetrapeptide product (MILW or MILG) and phenotype of erythromycin...... resistance. Thus, the drop-off event on GGG or UGG codons occurs after incorporation of the corresponding amino acid into the growing peptide chain. Drop-off gives rise to a peptidyl-tRNA where the peptide moiety functionally mimics a minigene peptide product of the type previously associated...

Integrating Solid-State NMR and Computational Modeling to Investigate the Structure and Dynamics of Membrane-Associated Ghrelin

Science.gov (United States)

Els-Heindl, Sylvia; Chollet, Constance; Scheidt, Holger A.; Beck-Sickinger, Annette G.; Meiler, Jens; Huster, Daniel

2015-01-01

The peptide hormone ghrelin activates the growth hormone secretagogue receptor 1a, also known as the ghrelin receptor. This 28-residue peptide is acylated at Ser3 and is the only peptide hormone in the human body that is lipid-modified by an octanoyl group. Little is known about the structure and dynamics of membrane-associated ghrelin. We carried out solid-state NMR studies of ghrelin in lipid vesicles, followed by computational modeling of the peptide using Rosetta. Isotropic chemical shift data of isotopically labeled ghrelin provide information about the peptide’s secondary structure. Spin diffusion experiments indicate that ghrelin binds to membranes via its lipidated Ser3. Further, Phe4, as well as electrostatics involving the peptide’s positively charged residues and lipid polar headgroups, contribute to the binding energy. Other than the lipid anchor, ghrelin is highly flexible and mobile at the membrane surface. This observation is supported by our predicted model ensemble, which is in good agreement with experimentally determined chemical shifts. In the final ensemble of models, residues 8–17 form an α-helix, while residues 21–23 and 26–27 often adopt a polyproline II helical conformation. These helices appear to assist the peptide in forming an amphipathic conformation so that it can bind to the membrane. PMID:25803439

Miscoding-induced stalling of substrate translocation on the bacterial ribosome.

Science.gov (United States)

Alejo, Jose L; Blanchard, Scott C

2017-10-10

Directional transit of the ribosome along the messenger RNA (mRNA) template is a key determinant of the rate and processivity of protein synthesis. Imaging of the multistep translocation mechanism using single-molecule FRET has led to the hypothesis that substrate movements relative to the ribosome resolve through relatively long-lived late intermediates wherein peptidyl-tRNA enters the P site of the small ribosomal subunit via reversible, swivel-like motions of the small subunit head domain within the elongation factor G (GDP)-bound ribosome complex. Consistent with translocation being rate-limited by recognition and productive engagement of peptidyl-tRNA within the P site, we now show that base-pairing mismatches between the peptidyl-tRNA anticodon and the mRNA codon dramatically delay this rate-limiting, intramolecular process. This unexpected relationship between aminoacyl-tRNA decoding and translocation suggests that miscoding antibiotics may impact protein synthesis by impairing the recognition of peptidyl-tRNA in the small subunit P site during EF-G-catalyzed translocation. Strikingly, we show that elongation factor P (EF-P), traditionally known to alleviate ribosome stalling at polyproline motifs, can efficiently rescue translocation defects arising from miscoding. These findings help reveal the nature and origin of the rate-limiting steps in substrate translocation on the bacterial ribosome and indicate that EF-P can aid in resuming translation elongation stalled by miscoding errors.

Predicting the denitrification capacity of sandy aquifers from shorter-term incubation experiments and sediment properties

Directory of Open Access Journals (Sweden)

W. Eschenbach

2013-02-01

Full Text Available Knowledge about the spatial variability of denitrification rates and the lifetime of denitrification in nitrate-contaminated aquifers is crucial to predict the development of groundwater quality. Therefore, regression models were derived to estimate the measured cumulative denitrification of aquifer sediments after one year of incubation from initial denitrification rates and several sediment parameters, namely total sulphur, total organic carbon, extractable sulphate, extractable dissolved organic carbon, hot water soluble organic carbon and potassium permanganate labile organic carbon.

For this purpose, we incubated aquifer material from two sandy Pleistocene aquifers in Northern Germany under anaerobic conditions in the laboratory using the ¹⁵N tracer technique. The measured amount of denitrification ranged from 0.19 to 56.2 mg N kg⁻¹ yr⁻¹. The laboratory incubations exhibited high differences between non-sulphidic and sulphidic aquifer material in both aquifers with respect to all investigated sediment parameters. Denitrification rates and the estimated lifetime of denitrification were higher in the sulphidic samples. For these samples, the cumulative denitrification measured during one year of incubation (D_cum(365 exhibited distinct linear regressions with the stock of reduced compounds in the investigated aquifer samples. D_cum(365 was predictable from sediment variables within a range of uncertainty of 0.5 to 2 (calculated D_cum(365/measured D_cum(365 for aquifer material with a D_cum(365 > 20 mg N kg⁻¹ yr⁻¹. Predictions were poor for samples with lower D_cum(365, such as samples from the NO₃⁻ bearing groundwater zone, which includes the non-sulphidic samples, from the upper part of both aquifers where denitrification is not sufficient to protect groundwater from anthropogenic NO₃⁻ input. Calculation of D_cum(365 from initial denitrification rates was only successful for samples from the NO₃⁻-bearing zone, whereas a lag-phase of denitrification in samples from deeper zones of NO₃⁻ free groundwater caused imprecise predictions.

In our study, D_cum(365 of two sandy Pleistocene aquifers was predictable using a combination of short-term incubations and analysis of sediment parameters. Moreover, the protective lifetime of denitrification sufficient to remove NO₃⁻ from groundwater in the investigated aquifers is limited, which demonstrates the need to minimise anthropogenic NO₃⁻ input.

Shorter CAG repeat in the AR gene is associated with atypical hyperplasia and breast carcinoma

DEFF Research Database (Denmark)

De Abreu, Francine Blumental; Pirolo, Leandro Júnior; Canevari, Renata de Azevedo

2007-01-01

BACKGROUND: Previous reports into the role of [CAG]n repeat lengths in the androgen receptor (AR) gene indicate that these may play an important part in the development and progression of breast cancer, however, knowledge regarding benign breast lesions is limited. PATIENTS AND METHODS: PCR-based...

Designing of peptides with desired half-life in intestine-like environment

KAUST Repository

Sharma, Arun

2014-08-20

Background: In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life.Results: In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides.Conclusion: In summary, this study describes a web server \\'HLP\\' that has been developed for assisting scientific

Biophysical properties of intrinsically disordered p130Cas substrate domain--implication in mechanosensing.

Directory of Open Access Journals (Sweden)

Kinya Hotta

2014-04-01

Full Text Available Mechanical stretch-induced tyrosine phosphorylation in the proline-rich 306-residue substrate domain (CasSD of p130Cas (or BCAR1 has eluded an experimentally validated structural understanding. Cellular p130Cas tyrosine phosphorylation is shown to function in areas without internal actomyosin contractility, sensing force at the leading edge of cell migration. Circular dichroism shows CasSD is intrinsically disordered with dominant polyproline type II conformations. Strongly conserved in placental mammals, the proline-rich sequence exhibits a pseudo-repeat unit with variation hotspots 2-9 residues before substrate tyrosine residues. Atomic-force microscopy pulling experiments show CasSD requires minimal extension force and exhibits infrequent, random regions of weak stability. Proteolysis, light scattering and ultracentrifugation results show that a monomeric intrinsically disordered form persists for CasSD in solution with an expanded hydrodynamic radius. All-atom 3D conformer sampling with the TraDES package yields ensembles in agreement with experiment when coil-biased sampling is used, matching the experimental radius of gyration. Increasing β-sampling propensities increases the number of prolate conformers. Combining the results, we conclude that CasSD has no stable compact structure and is unlikely to efficiently autoinhibit phosphorylation. Taking into consideration the structural propensity of CasSD and the fact that it is known to bind to LIM domains, we propose a model of how CasSD and LIM domain family of transcription factor proteins may function together to regulate phosphorylation of CasSD and effect machanosensing.

Empirical isotropic chemical shift surfaces

International Nuclear Information System (INIS)

Czinki, Eszter; Csaszar, Attila G.

2007-01-01

A list of proteins is given for which spatial structures, with a resolution better than 2.5 A, are known from entries in the Protein Data Bank (PDB) and isotropic chemical shift (ICS) values are known from the RefDB database related to the Biological Magnetic Resonance Bank (BMRB) database. The structures chosen provide, with unknown uncertainties, dihedral angles φ and ψ characterizing the backbone structure of the residues. The joint use of experimental ICSs of the same residues within the proteins, again with mostly unknown uncertainties, and ab initio ICS(φ,ψ) surfaces obtained for the model peptides For-(l-Ala) n -NH 2 , with n = 1, 3, and 5, resulted in so-called empirical ICS(φ,ψ) surfaces for all major nuclei of the 20 naturally occurring α-amino acids. Out of the many empirical surfaces determined, it is the 13C α ICS(φ,ψ) surface which seems to be most promising for identifying major secondary structure types, α-helix, β-strand, left-handed helix (α D ), and polyproline-II. Detailed tests suggest that Ala is a good model for many naturally occurring α-amino acids. Two-dimensional empirical 13C α - 1 H α ICS(φ,ψ) correlation plots, obtained so far only from computations on small peptide models, suggest the utility of the experimental information contained therein and thus they should provide useful constraints for structure determinations of proteins

Difficulties in applying pure Kohn-Sham density functional theory electronic structure methods to protein molecules

Science.gov (United States)

Rudberg, Elias

2012-02-01

Self-consistency-based Kohn-Sham density functional theory (KS-DFT) electronic structure calculations with Gaussian basis sets are reported for a set of 17 protein-like molecules with geometries obtained from the Protein Data Bank. It is found that in many cases such calculations do not converge due to vanishing HOMO-LUMO gaps. A sequence of polyproline I helix molecules is also studied and it is found that self-consistency calculations using pure functionals fail to converge for helices longer than six proline units. Since the computed gap is strongly correlated to the fraction of Hartree-Fock exchange, test calculations using both pure and hybrid density functionals are reported. The tested methods include the pure functionals BLYP, PBE and LDA, as well as Hartree-Fock and the hybrid functionals BHandHLYP, B3LYP and PBE0. The effect of including solvent molecules in the calculations is studied, and it is found that the inclusion of explicit solvent molecules around the protein fragment in many cases gives a larger gap, but that convergence problems due to vanishing gaps still occur in calculations with pure functionals. In order to achieve converged results, some modeling of the charge distribution of solvent water molecules outside the electronic structure calculation is needed. Representing solvent water molecules by a simple point charge distribution is found to give non-vanishing HOMO-LUMO gaps for the tested protein-like systems also for pure functionals.

Synthesis and characterization of recombinant abductin-based proteins.

Science.gov (United States)

Su, Renay S-C; Renner, Julie N; Liu, Julie C

2013-12-09

Recombinant proteins are promising tools for tissue engineering and drug delivery applications. Protein-based biomaterials have several advantages over natural and synthetic polymers, including precise control over amino acid composition and molecular weight, modular swapping of functional domains, and tunable mechanical and physical properties. In this work, we describe recombinant proteins based on abductin, an elastomeric protein that is found in the inner hinge of bivalves and functions as a coil spring to keep shells open. We illustrate, for the first time, the design, cloning, expression, and purification of a recombinant protein based on consensus abductin sequences derived from Argopecten irradians . The molecular weight of the protein was confirmed by mass spectrometry, and the protein was 94% pure. Circular dichroism studies showed that the dominant structures of abductin-based proteins were polyproline II helix structures in aqueous solution and type II β-turns in trifluoroethanol. Dynamic light scattering studies illustrated that the abductin-based proteins exhibit reversible upper critical solution temperature behavior and irreversible aggregation behavior at high temperatures. A LIVE/DEAD assay revealed that human umbilical vein endothelial cells had a viability of 98 ± 4% after being cultured for two days on the abductin-based protein. Initial cell spreading on the abductin-based protein was similar to that on bovine serum albumin. These studies thus demonstrate the potential of abductin-based proteins in tissue engineering and drug delivery applications due to the cytocompatibility and its response to temperature.

SH3 domain tyrosine phosphorylation--sites, role and evolution.

Directory of Open Access Journals (Sweden)

Zuzana Tatárová

Full Text Available BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains. RESULTS: To explore the incidence of the tyrosine phosphorylation within SH3 domains we queried the PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine phosphorylations occurring on 20 different SH3 domain positions were identified. The tyrosine corresponding to c-Src Tyr-90 was by far the most frequently identified SH3 domain phosphorylation site. A comparison of sequences around this tyrosine led to delineation of a preferred sequence motif ALYD(Y/F. This motif is present in about 15% of human SH3 domains and is structurally well conserved. We further observed that tyrosine phosphorylation is more abundant than serine or threonine phosphorylation within SH3 domains and other adaptor domains, such as SH2 or WW domains. Tyrosine phosphorylation could represent an important regulatory mechanism of adaptor domains. CONCLUSIONS: While tyrosine phosphorylation typically promotes signaling protein interactions via SH2 or PTB domains, its role in SH3 domains is the opposite - it blocks or prevents interactions. The regulatory function of tyrosine phosphorylation is most likely achieved by the phosphate moiety and its charge interfering with binding of polyproline helices of SH3 domain interacting partners.

Difficulties in applying pure Kohn-Sham density functional theory electronic structure methods to protein molecules

International Nuclear Information System (INIS)

Rudberg, Elias

2012-01-01

Self-consistency-based Kohn-Sham density functional theory (KS-DFT) electronic structure calculations with Gaussian basis sets are reported for a set of 17 protein-like molecules with geometries obtained from the Protein Data Bank. It is found that in many cases such calculations do not converge due to vanishing HOMO-LUMO gaps. A sequence of polyproline I helix molecules is also studied and it is found that self-consistency calculations using pure functionals fail to converge for helices longer than six proline units. Since the computed gap is strongly correlated to the fraction of Hartree-Fock exchange, test calculations using both pure and hybrid density functionals are reported. The tested methods include the pure functionals BLYP, PBE and LDA, as well as Hartree-Fock and the hybrid functionals BHandHLYP, B3LYP and PBE0. The effect of including solvent molecules in the calculations is studied, and it is found that the inclusion of explicit solvent molecules around the protein fragment in many cases gives a larger gap, but that convergence problems due to vanishing gaps still occur in calculations with pure functionals. In order to achieve converged results, some modeling of the charge distribution of solvent water molecules outside the electronic structure calculation is needed. Representing solvent water molecules by a simple point charge distribution is found to give non-vanishing HOMO-LUMO gaps for the tested protein-like systems also for pure functionals. (fast track communication)

Potassium-chloride cotransporter 3 interacts with Vav2 to synchronize the cell volume decrease response with cell protrusion dynamics.

Directory of Open Access Journals (Sweden)

Adèle Salin-Cantegrel

Full Text Available Loss-of-function of the potassium-chloride cotransporter 3 (KCC3 causes hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC, a severe neurodegenerative disease associated with defective midline crossing of commissural axons in the brain. Conversely, KCC3 over-expression in breast, ovarian and cervical cancer is associated with enhanced tumor cell malignancy and invasiveness. We identified a highly conserved proline-rich sequence within the C-terminus of the cotransporter which when mutated leads to loss of the KCC3-dependent regulatory volume decrease (RVD response in Xenopus Laevis oocytes. Using SH3 domain arrays, we found that this poly-proline motif is a binding site for SH3-domain containing proteins in vitro. This approach identified the guanine nucleotide exchange factor (GEF Vav2 as a candidate partner for KCC3. KCC3/Vav2 physical interaction was confirmed using GST-pull down assays and immuno-based experiments. In cultured cervical cancer cells, KCC3 co-localized with the active form of Vav2 in swelling-induced actin-rich protruding sites and within lamellipodia of spreading and migrating cells. These data provide evidence of a molecular and functional link between the potassium-chloride co-transporters and the Rho GTPase-dependent actin remodeling machinery in RVD, cell spreading and cell protrusion dynamics, thus providing new insights into KCC3's involvement in cancer cell malignancy and in corpus callosum agenesis in HMSN/ACC.

pmx Webserver: A User Friendly Interface for Alchemistry.

Science.gov (United States)

Gapsys, Vytautas; de Groot, Bert L

2017-02-27

With the increase of available computational power and improvements in simulation algorithms, alchemical molecular dynamics based free energy calculations have developed into routine usage. To further facilitate the usability of alchemical methods for amino acid mutations, we have developed a web based infrastructure for obtaining hybrid protein structures and topologies. The presented webserver allows amino acid mutation selection in five contemporary molecular mechanics force fields. In addition, a complete mutation scan with a user defined amino acid is supported. The output generated by the webserver is directly compatible with the Gromacs molecular dynamics engine and can be used with any of the alchemical free energy calculation setup. Furthermore, we present a database of input files and precalculated free energy differences for tripeptides approximating a disordered state of a protein, of particular use for protein stability studies. Finally, the usage of the webserver and its output is exemplified by performing an alanine scan and investigating thermodynamic stability of the Trp cage mini protein. The webserver is accessible at http://pmx.mpibpc.mpg.de.

Effect of wine inhibitors on the proteolytic activity of papain from Carica papaya L. latex.

Science.gov (United States)

Benucci, Ilaria; Esti, Marco; Liburdi, Katia

2015-01-01

The influence of potential inhibitors naturally present in wine on the proteolytic activity of papain from Carica papaya latex was investigated to evaluate its applicability in white wine protein haze stabilization. Enzymatic activity was tested against a synthetic tripeptide chromogenic substrate in wine-like acidic medium that consisted of tartaric buffer (pH 3.2) supplemented with ethanol, free sulfur dioxide (SO2 ), grape skin and seed tannins within the average ranges of concentrations that are typical in wine. The diagnosis of inhibition type, performed with the graphical method, demonstrated that all of tested wine constituents were reversible inhibitors of papain. The strongest inhibition was exerted by free SO2 , which acted as a mixed-type inhibitor, similar to grape skin and seed tannins. Finally, when tested in table white wines, the catalytic activity of papain, even when if it was ascribable to the hyperbolic behavior of Michaelis-Menten equation, was determined to be strongly affected by free SO2 and total phenol level. © 2014 American Institute of Chemical Engineers.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

International Nuclear Information System (INIS)

Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P.; Gelman, Andrew E.; Jarzembowski, Jason A.; Zhang, Hao; Pritchard, Kirkwood A. Jr.; Vikis, Haris G.

2014-01-01

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting

The role of neutrophil myeloperoxidase in models of lung tumor development.

Science.gov (United States)

Rymaszewski, Amy L; Tate, Everett; Yimbesalu, Joannes P; Gelman, Andrew E; Jarzembowski, Jason A; Zhang, Hao; Pritchard, Kirkwood A; Vikis, Haris G

2014-05-09

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

Energy Technology Data Exchange (ETDEWEB)

Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P. [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Gelman, Andrew E. [Department of Surgery, Washington University in St. Louis, St. Louis, MO 63130 (United States); Jarzembowski, Jason A. [Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Zhang, Hao; Pritchard, Kirkwood A. Jr. [Department of Surgery and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Vikis, Haris G., E-mail: hvikis@mcw.edu [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

2014-05-09

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

Directory of Open Access Journals (Sweden)

Amy L. Rymaszewski

2014-05-01

Full Text Available Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA-initiated, butylated hydroxytoluene (BHT-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC, a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

Electronic structure, dielectric response, and surface charge distribution of RGD (1FUV) peptide.

Science.gov (United States)

Adhikari, Puja; Wen, Amy M; French, Roger H; Parsegian, V Adrian; Steinmetz, Nicole F; Podgornik, Rudolf; Ching, Wai-Yim

2014-07-08

Long and short range molecular interactions govern molecular recognition and self-assembly of biological macromolecules. Microscopic parameters in the theories of these molecular interactions are either phenomenological or need to be calculated within a microscopic theory. We report a unified methodology for the ab initio quantum mechanical (QM) calculation that yields all the microscopic parameters, namely the partial charges as well as the frequency-dependent dielectric response function, that can then be taken as input for macroscopic theories of electrostatic, polar, and van der Waals-London dispersion intermolecular forces. We apply this methodology to obtain the electronic structure of the cyclic tripeptide RGD-4C (1FUV). This ab initio unified methodology yields the relevant parameters entering the long range interactions of biological macromolecules, providing accurate data for the partial charge distribution and the frequency-dependent dielectric response function of this peptide. These microscopic parameters determine the range and strength of the intricate intermolecular interactions between potential docking sites of the RGD-4C ligand and its integrin receptor.

Vinegar Metabolomics: An Explorative Study of Commercial Balsamic Vinegars Using Gas Chromatography-Mass Spectrometry

Directory of Open Access Journals (Sweden)

Farhana R. Pinu

2016-07-01

Full Text Available Balsamic vinegar is a popular food condiment produced from cooked grape must by two successive fermentation (anaerobic and aerobic processes. Although many studies have been performed to determine the composition of major metabolites, including sugars and aroma compounds, no study has been undertaken yet to characterize the comprehensive metabolite composition of balsamic vinegars. Here, we present the first metabolomics study of commercial balsamic vinegars by gas chromatography coupled to mass spectrometry (GC-MS. The combination of three GC-MS methods allowed us to detect >1500 features in vinegar samples, of which 123 metabolites were accurately identified, including 25 amino acids, 26 carboxylic acids, 13 sugars and sugar alcohols, four fatty acids, one vitamin, one tripeptide and over 47 aroma compounds. Moreover, we identified for the first time in vinegar five volatile metabolites: acetin, 2-methylpyrazine, 2-acetyl-1-pyroline, 4-anisidine and 1,3-diacetoxypropane. Therefore, we demonstrated the capability of metabolomics for detecting and identifying large number of metabolites and some of them could be used to distinguish vinegar samples based on their origin and potentially quality.

Metabolic profile modifications in milk after enrofloxacin administration studied by liquid chromatography coupled with high resolution mass spectrometry.

Science.gov (United States)

Junza, A; Saurina, J; Barrón, D; Minguillón, C

2016-08-19

High resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was used in the search and identification of metabolites in raw milk from cows medicated with enrofloxacin. Data consisting of m/z features were taken throughout the entire chromatogram of milk samples from medicated animals and were compared with blank samples. Twenty six different compounds were identified. Some of them were attributed to structures related to enrofloxacin while others were dipeptides or tripeptides. Additionally, enrofloxacin was administered in a controlled treatment for three days. Milk was collected daily from the first day of treatment and until four days after in the search for the identified compounds. The obtained data were chemometrically treated by Principal Component Analysis. Samples were classified by this method into three different groups corresponding to days 1-2, day 3 and days 4-7 considering the different concentration profile evolution of metabolites during the days studied. Tentative metabolic pathways were designed to rationalize the presence of the newly identified compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Hybrid Metaheuristic Approach for Nonlocal Optimization of Molecular Systems.

Science.gov (United States)

Dresselhaus, Thomas; Yang, Jack; Kumbhar, Sadhana; Waller, Mark P

2013-04-09

Accurate modeling of molecular systems requires a good knowledge of the structure; therefore, conformation searching/optimization is a routine necessity in computational chemistry. Here we present a hybrid metaheuristic optimization (HMO) algorithm, which combines ant colony optimization (ACO) and particle swarm optimization (PSO) for the optimization of molecular systems. The HMO implementation meta-optimizes the parameters of the ACO algorithm on-the-fly by the coupled PSO algorithm. The ACO parameters were optimized on a set of small difluorinated polyenes where the parameters exhibited small variance as the size of the molecule increased. The HMO algorithm was validated by searching for the closed form of around 100 molecular balances. Compared to the gradient-based optimized molecular balance structures, the HMO algorithm was able to find low-energy conformations with a 87% success rate. Finally, the computational effort for generating low-energy conformation(s) for the phenylalanyl-glycyl-glycine tripeptide was approximately 60 CPU hours with the ACO algorithm, in comparison to 4 CPU years required for an exhaustive brute-force calculation.

Protective Activity of N-acetyl-L-cysteine (NAC) against Cellular Oxidative Stress Induced by Radiation

Energy Technology Data Exchange (ETDEWEB)

Han, Min; Hyun, Kyung Man; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain); Aroutiounian, Rouben [Yerevan State University, Yerevan (Armenia)

2009-10-15

Oxidative stress occurs due to numerous factors such as irradiation, redox decomposition by ions of hydroperoxides or hydrogen peroxide, and thermal decomposition of free radical initiators including peroxides and hyponitrites. The antioxidant and free-radical scavenger N-acetyl- L-cysteine (NAC) is used extensively as a conditional nutrient. NAC acts as a cysteine donor and maintains or even increases the intracellular levels of glutathione (GSH), a tripeptide which protects cells from toxins such as free-radicals. With regard to the radioprotective effects of NAC, the majority of studies have been performed in vitro. NAC were used to protect the Chinese hamster ovary (CHO) cells from radiationinduced apoptosis by controlling the enzyme that triggers programmed cell death. Some studies have successfully demonstrated sporadic radioprotection following low-level chronic administration of NAC, though the mode and optimal dose of NAC are yet to be fully determined. This study was designed to evaluate the effects of NAC in different doses on the activity levels of GSH and the cell viability in the fish cell line against ionizing radiation.

Constants and thermodynamics of the acid-base equilibria of triglycine in water-ethanol solutions containing sodium perchlorate at 298 K

Science.gov (United States)

Pham Tkhi, L.; Usacheva, T. R.; Tukumova, N. V.; Koryshev, N. E.; Khrenova, T. M.; Sharnin, V. A.

2016-02-01

The acid-base equilibrium constants for glycyl-glycyl-glycine (triglycine) in water-ethanol solvents containing 0.0, 0.1, 0.3, and 0.5 mole fractions of ethanol are determined by potentiometric titration at 298.15 K and an ionic strength of 0.1, maintained with sodium perchlorate. It is established that an increase in the ethanol content in the solvent reduces the dissociation constant of the carboxyl group of triglycine (increases p K 1) and increases the dissociation constant of the amino group of triglycine (decreases p K 2). It is noted that the weakening of the acidic properties of a triglycinium ion upon an increase of the ethanol content in the solvent is due to the attenuation of the solvation shell of the zwitterionic form of triglycine, and to the increased solvation of triglycinium ions. It is concluded that the acid strength of triglycine increases along with a rise in the EtOH content in the solvent, due to the desolvation of the tripeptide zwitterion and the enhanced solvation of protons.

In vitro preparation and assessment of radical reducing peptide from Octopus aegina using digestive proteases.

Science.gov (United States)

Sudhakar, Sekar; Nazeer, Rasool Abdul

2017-07-01

Antioxidant peptides protect biological macromolecules against radical damages. The use of these peptides was evaluated using free radicals scavenging assays [2,2-diphenyl-1 picrylhydrazyl (DPPH) and hydroxyl] with the help of UV-visible and electron spin resonance (ESR) spectroscopy methods. The Octopus aegina mantle protein were tested upon hydrolysis using gastrointestinal enzymes up to 12 h, where pepsin hydrolysate exhibited superior properties (DPPH: 44.39±0.67% and hydroxyl: 38.84±1.07%) compared with trypsin and α-chymotrypsin. Consequently, the antioxidant activity of the purified hydrolysate increased on a successive purification, and the peptide sequence was determined to be 368.9 Da with Gly-Glu-Tyr amino acids. Tripeptide exerted free radical scavenging efficiency in DNA damage, lipid peroxidation and cellular destruction (MCF7 cells) under stress condition. The results obtained with octopus antioxidant peptide suggested its role as an adjunct in food and pharmaceutical industries. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Alanine scan of the peptide antibiotic feglymycin: assessment of amino acid side chains contributing to antimicrobial activity.

Science.gov (United States)

Hänchen, Anne; Rausch, Saskia; Landmann, Benjamin; Toti, Luigi; Nusser, Antje; Süssmuth, Roderich D

2013-03-18

The antibiotic feglymycin is a linear 13-mer peptide synthesized by the bacterium Streptomyces sp. DSM 11171. It mainly consists of the nonproteinogenic amino acids 4-hydroxyphenylglycine and 3,5-dihydroxyphenylglycine. An alanine scan of feglymycin was performed by solution-phase peptide synthesis in order to assess the significance of individual amino acid side chains for biological activity. Hence, 13 peptides were synthesized from di- and tripeptide building blocks, and subsequently tested for antibacterial activity against Staphylococcus aureus strains. Furthermore we tested the inhibition of peptidoglycan biosynthesis enzymes MurA and MurC, which are inhibited by feglymycin. Whereas the antibacterial activity is significantly based on the three amino acids D-Hpg1, L-Hpg5, and L-Phe12, the inhibitory activity against MurA and MurC depends mainly on L-Asp13. The difference in the position dependence for antibacterial activity and enzyme inhibition suggests multiple molecular targets in the modes of action of feglymycin. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In Vitro Reactivity of Carboxylic Acid-CoA Thioesters with Glutathione

DEFF Research Database (Denmark)

Sidenius, Ulrik; Skonberg, Christian; Olsen, Jørgen

2004-01-01

was to investigate whether a correlation could be found between the structure of acyl-CoA thioesters and their reactivities toward the tripeptide, glutathione (ç- Glu-Cys-Gly).  The  acyl-CoA  thioesters  of  eight  carboxylic  acids  (ibuprofen,  clofibric  acid, indomethacin,  fenbufen,  tolmetin,  salicylic  acid......The chemical reactivity of acyl-CoA thioesters toward nucleophiles has been demonstrated in several recent studies. Thus, intracellularly formed acyl-CoAs of xenobiotic carboxylic acids may react covalently with endogenous proteins and potentially lead to adverse effects. The purpose of this study......,  2-phenoxypropionic  acid,  and  (4-chloro-2-methyl-phenoxy)acetic  acid  (MCPA))  were  synthesized,  and  each  acyl-CoA  (0.5  mM)  was incubated with glutathione (5.0 mM) in 0.1 M potassium phosphate (pH 7.4, 37 °C). All of the acyl-CoAs reacted with glutathione to form the respective acyl...

Reinforced dynamics for enhanced sampling in large atomic and molecular systems

Science.gov (United States)

Zhang, Linfeng; Wang, Han; E, Weinan

2018-03-01

A new approach for efficiently exploring the configuration space and computing the free energy of large atomic and molecular systems is proposed, motivated by an analogy with reinforcement learning. There are two major components in this new approach. Like metadynamics, it allows for an efficient exploration of the configuration space by adding an adaptively computed biasing potential to the original dynamics. Like deep reinforcement learning, this biasing potential is trained on the fly using deep neural networks, with data collected judiciously from the exploration and an uncertainty indicator from the neural network model playing the role of the reward function. Parameterization using neural networks makes it feasible to handle cases with a large set of collective variables. This has the potential advantage that selecting precisely the right set of collective variables has now become less critical for capturing the structural transformations of the system. The method is illustrated by studying the full-atom explicit solvent models of alanine dipeptide and tripeptide, as well as the system of a polyalanine-10 molecule with 20 collective variables.

Applications of snake venom components to modulate integrin activities in cell-matrix interactions

Science.gov (United States)

Marcinkiewicz, Cezary

2013-01-01

Snake venom proteins are broadly investigated in the different areas of life science. Direct interaction of these compounds with cells may involve a variety of mechanisms that result in diverse cellular responses leading to the activation or blocking of physiological functions of the cell. In this review, the snake venom components interacting with integrins will be characterized in context of their effect on cellular response. Currently, two major families of snake venom proteins are considered as integrin-binding molecules. The most attention has been devoted to the disintegrin family, which binds certain types of integrins through specific motifs recognized as a tri-peptide structurally localized on an integrin-binding loop. Other snake venom integrin-binding proteins belong to the C-type lectin family. Snake venom molecules bind to the cellular integrins resulting in a modulation of cell signaling and in consequence, the regulation of cell proliferation, migration and apoptosis. Therefore, snake venom research on the integrin-binding molecules may have significance in biomedicine and basic cell biology. PMID:23811033

FY 1998 annual report on the exploration and production of functional peptide from unutilized protein resources; 1998 nendo miriyo tanpakushitsugen kara no kinosei pepuchido no tansaku to seisan ni kansuru kenkyu hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

This project is aimed at promotion of effective utilization of unutilized resources by transforming histidine-containing peptide (anserine), enzymatically hydrolyzed muscle protein present in lean salmon swimming off the Sanriku District in the spawning season, into functional peptide. A reactor system, comprising an enzyme-immobilized column and rotary bioreactor, is investigated to efficiently produce peptide by enzymatically hydrolyzing the water-insoluble muscle protein. Anserine is isolated by ethanol extraction, ion-exchanging and partition chromatography. The TPTZ and ABTS methods are developed for speeding up measurement of the antioxidant activity. The salmon muscle protein is hydrolyzed by 3 types of enzymes, to measure the free radical erasing activity by the ABTS method. The enzymatically hydrolyzed protein is fractionated by gel permeation chromatography. The fractions having a molecular weight of 10,000 or less show strong antioxidant activity. The hydrolyzed protein shows improved activity by the iron rhodanide method when it has histidine at the center of tripeptide, and strong radical erasing function when it has thyrosine or tryptophan at the carboxyl terminal. (NEDO)

Low intensity shear stress increases endothelial ELR+ CXC chemokine production via a focal adhesion kinase-p38{beta} MAPK-NF-{kappa}B pathway.

Science.gov (United States)

Shaik, Sadiq S; Soltau, Thomas D; Chaturvedi, Gaurav; Totapally, Balagangadhar; Hagood, James S; Andrews, William W; Athar, Mohammad; Voitenok, Nikolai N; Killingsworth, Cheryl R; Patel, Rakesh P; Fallon, Michael B; Maheshwari, Akhil

2009-02-27

CXC chemokines with a glutamate-leucine-arginine (ELR) tripeptide motif (ELR(+) CXC chemokines) play an important role in leukocyte trafficking into the tissues. For reasons that are not well elucidated, circulating leukocytes are recruited into the tissues mainly in small vessels such as capillaries and venules. Because ELR(+) CXC chemokines are important mediators of endothelial-leukocyte interaction, we compared chemokine expression by microvascular and aortic endothelium to investigate whether differences in chemokine expression by various endothelial types could, at least partially, explain the microvascular localization of endothelial-leukocyte interaction. Both in vitro and in vivo models indicate that ELR(+) CXC chemokine expression is higher in microvascular endothelium than in aortic endothelial cells. These differences can be explained on the basis of the preferential activation of endothelial chemokine production by low intensity shear stress. Low shear activated endothelial ELR(+) CXC chemokine production via cell surface heparan sulfates, beta(3)-integrins, focal adhesion kinase, the mitogen-activated protein kinase p38beta, mitogen- and stress-associated protein kinase-1, and the transcription factor.

A novel Alaska pollack-derived peptide, which increases glucose uptake in skeletal muscle cells, lowers the blood glucose level in diabetic mice.

Science.gov (United States)

Ayabe, Tatsuhiro; Mizushige, Takafumi; Ota, Wakana; Kawabata, Fuminori; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kanamoto, Ryuhei; Ohinata, Kousaku

2015-08-01

We found that the tryptic digest of Alaska pollack protein exhibits a glucose-lowering effect in KK-Ay mice, a type II diabetic model. We then searched for glucose-lowering peptides in the digest. Ala-Asn-Gly-Glu-Val-Ala-Gln-Trp-Arg (ANGEVAQWR) was identified from a peak of the HPLC fraction selected based on the glucose-lowering activity in an insulin resistance test using ddY mice. ANGEVAQWR (3 mg kg(-1)) decreased the blood glucose level after intraperitoneal administration. Among its fragment peptides, the C-terminal tripeptide, Gln-Trp-Arg (QWR, 1 mg kg(-1)), lowered the blood glucose level, suggesting that the C-terminal is critical for glucose-lowering activity. QWR also enhanced glucose uptake into C2C12, a mouse skeletal muscle cell line. QWR did not induce the phosphorylation of serine/threonine protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK). We also demonstrated that QWR lowered the blood glucose level in NSY and KK-Ay, type II diabetic models.

Identification of ace inhibitory cryptides in Tilapia protein hydrolysate by UPLC-MS/MS coupled to database analysis.

Science.gov (United States)

Yesmine, Ben Henda; Antoine, Bonnet; da Silva Ortência Leocádia, Nunes Gonzalez; Rogério, Boscolo Wilson; Ingrid, Arnaudin; Nicolas, Bridiau; Thierry, Maugard; Jean-Marie, Piot; Frédéric, Sannier; Stéphanie, Bordenave-Juchereau

2017-05-01

An ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry method was developed and applied to identify short angiotensin-I-converting enzyme (ACE) inhibitory cryptides in Tilapia (Oreochromis Niloticus) protein hydrolyzate. A database was created with previously identified ACE-inhibitory di- and tripeptides and the lowest molecular weight fraction of Tilapia hydrolysate was analysed for coincidences. Only VW and VY were identified. Further analysis of collected fractions conducted to the identification of 51 different peptides in major fractions. 19 peptides selected were synthesised and tested for their ACE inhibitory potential. TL, TI, IK, LR, LD, IQ, DI, AILE, ALLE, ALIE and AIIE were identified as new ACE inhibitors. The findings from this study point UPLC-MS/MS combined with the creation of a database as an efficient technique to identify specific short peptides within a complex hydrolysate, in addition with de novo sequencing. This efficient characterisation of bioactive factors like cryptides in protein hydrolysates will extend their use as functional foods. Copyright © 2017 Elsevier B.V. All rights reserved.

Ultrahigh and High Resolution Structures and Mutational Analysis of Monomeric Streptococcus pyogenes SpeB Reveal a Functional Role for the Glycine-rich C-terminal Loop

Energy Technology Data Exchange (ETDEWEB)

González-Páez, Gonzalo E.; Wolan, Dennis W. (Scripps)

2012-09-05

Cysteine protease SpeB is secreted from Streptococcus pyogenes and has been studied as a potential virulence factor since its identification almost 70 years ago. Here, we report the crystal structures of apo mature SpeB to 1.06 {angstrom} resolution as well as complexes with the general cysteine protease inhibitor trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane and a novel substrate mimetic peptide inhibitor. These structures uncover conformational changes associated with maturation of SpeB from the inactive zymogen to its active form and identify the residues required for substrate binding. With the use of a newly developed fluorogenic tripeptide substrate to measure SpeB activity, we determined IC{sub 50} values for trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane and our new peptide inhibitor and the effects of mutations within the C-terminal active site loop. The structures and mutational analysis suggest that the conformational movements of the glycine-rich C-terminal loop are important for the recognition and recruitment of biological substrates and release of hydrolyzed products.

Milk-derived angiotensin-I-converting enzymeinhibitory peptides generated by Lactobacillus delbrueckii subsp. lactis CRL 581

Directory of Open Access Journals (Sweden)

Villegas Josefina M.

2014-01-01

Full Text Available Several strains of Lactobacillus helveticus and Lactobacillus delbrueckii subsp. lactis were evaluated for their ability to release angiotensin-I-converting enzyme (ACE inhibitory peptides from α-casein (α-CN and β-casein (β-CN. Casein peptides resulting from L. delbrueckii subsp. lactis CRL 581-mediated hydrolysis exhibited the highest ACE-inhibitory (ACEI activities, with values of 53 and 40% for α-CN and β-CN, respectively. The casein hydrolysates were fractionated by reversedphase high pressure liquid chromatography and some of the active peptides were identified by mass spectrometry. The fraction with the highest ACEI activity arose from β-CN and contained a mixture of the β-CN f194-206 (QEPVLGPVRGPFP and f198-206 (LGPVRGPFP peptides. Furthermore, the ACEI tripeptide IPP was identified in all β-CN hydrolysates; L. delbrueckii subsp. lactis CRL 581 produced the highest amount of this peptide. The bioactive peptides released by CRL 581 strain may be used in the formulation of functional foods and nutraceuticals, representing a healthier and natural alternative for regulating blood pressure.

Shorter HBIG administration is not associated to HBV recurrence when receiving combined prophylaxis after liver transplantation.

Science.gov (United States)

Lens, Sabela; García-Eliz, María; Fernández, Inmaculada; Castells, Lluis; Bonacci, Martin; Mas, Antoni; Crespo, Gonzalo; Buti, María; Prieto, Martín; Forns, Xavier

2018-04-16

The combination of hepatitis B immunoglobulin (HBIG) and a nucleos(t)ide analogs (NA) has markedly reduced the rate of hepatitis B (HBV) recurrence after liver transplantation (LT); however, the optimal duration of HBIG has not been clarified. This lack of consensus perpetuates the use of different strategies. The aim of this study was to evaluate the risk factors associated to HBV recurrence after LT in a large cohort of patients under different HBIG regimens. Retrospective multicenter analysis of HBV-related LT recipients receiving combined prophylaxis (HBIG+NA). The strategy of short-term HBIG was compared to life-long administration. HBV recurrence was defined as positive HBsAg after LT. 338 patients were analyzed. After a median follow-up period of 72 months, 37 patients (11%) developed HBV recurrence. Hepatocellular carcinoma (HCC) recurrence and lamivudine resistance after LT were the only factors independently associated to HBV recurrence (HR 5.4[2.3-12] and 9.3[4.2-20], respectively pHBV recurrence was transient (16 patients), persistent (15) or alternant (6). The HBIG regimen did not have an impact on the rate or evolution of HBV recurrence. Overall, patient survival was good and not influenced by HBV recurrence (82% at 5 years). Fulminant liver failure, hepatitis C coinfection or HCC at LT were independent risk factors for lower survival. LT is an effective treatment for HBV-related liver disease. Since the introduction of combined prophylaxis the rate of HBV recurrence is very low. However, life-long HBIG administration does not seem necessary to reduce HBV recurrence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Changing patterns of working time in Germany - from shorter working hours to more flexible work schedules

OpenAIRE

Seifert, Hartmut

2010-01-01

La reducción del tiempo de trabajo promete sustanciales efectos sobre el empleo. La reducción del tiempo de trabajo, combinada con la flexibilización del tiempo de trabajo se ha mostrado como una buena experiencia porque permite reducir los costes laborales, mejorar la productividad y mantener el empleo. Los incentivos sobre las contribuciones sociales pueden contribuir no sólo a la mejora del empleo, sino también a reducir la carga del gasto público por desempleo. Sin embar...

Diurnal lamotrigine plasma level fluctuations: clinical significance and indication of shorter half-life with chronic administration

DEFF Research Database (Denmark)

Nielsen, K.A.; Dahl, M.; Tommerup, E.

2008-01-01

-daily regimens without pharmacokinetic interactions exhibited C(min)/C(max) ratios between 0.62 and 0.69. Fluctuations were smaller in those co-medicated with valproate, and reached a ratio of 0.55 in those co-medicated with phenobarbital. The C(max) was as much as 58% above the MTL. Therefore, verification...

Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells

Science.gov (United States)

2014-01-01

Background Peritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored. Methods To investigate the parameters impacting EMT during PD therapy, 53 clinical stable PD patients were enrolled. EMT assessments were conducted through human peritoneal MCs cultured from dialysate effluent with one consistent standard criterion (MC morphology and the expression of an epithelial marker, cytokeratin 18). The factors potentially associated with EMT were analyzed using logistic regression analysis. Primary MCs derived from the omentum were isolated for the in vitro study. Results Forty-seven percent of the patients presented with EMT, 28% with non-EMT, and 15% with a mixed presentation. Logistic regression analysis showed that patients who received persistent PD therapy (dwelling time of 24 h/day) had significantly higher EMT tendency. These results were consistent in vitro. Conclusions Dwelling time had a significant effect on the occurrence of EMT on MCs. PMID:24555732

An Aero-Acoustic Tool for Terminal Area Operations, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — In this highly interconnected world, transportation systems must feature increased flexibility and shorter door-to-door trip times to be successful. Shorter...

Tender frequency and market concentration in balancing power markets

International Nuclear Information System (INIS)

Knaut, Andreas; Obermueller, Frank; Weiser, Florian

2017-01-01

Balancing power markets ensure the short-term balance of supply and demand in electricity markets and their importance may increase with a higher share of fluctuating renewable electricity production. While it is clear that shorter tender frequencies, e.g. daily or hourly, are able to increase the efficiency compared to a weekly procurement, it remains unclear in which respect market concentration will be affected. Against this background, we develop a numerical electricity market model to quantify the possible effects of shorter tender frequencies on costs and market concentration. We find that shorter time spans of procurement are able to lower the costs by up to 15%. While market concentration decreases in many markets, we - surprisingly - identify cases in which shorter time spans lead to higher concentration.

Tender frequency and market concentration in balancing power markets

Energy Technology Data Exchange (ETDEWEB)

Knaut, Andreas; Obermueller, Frank; Weiser, Florian

2017-01-15

Balancing power markets ensure the short-term balance of supply and demand in electricity markets and their importance may increase with a higher share of fluctuating renewable electricity production. While it is clear that shorter tender frequencies, e.g. daily or hourly, are able to increase the efficiency compared to a weekly procurement, it remains unclear in which respect market concentration will be affected. Against this background, we develop a numerical electricity market model to quantify the possible effects of shorter tender frequencies on costs and market concentration. We find that shorter time spans of procurement are able to lower the costs by up to 15%. While market concentration decreases in many markets, we - surprisingly - identify cases in which shorter time spans lead to higher concentration.

Two new species of nematodes (Nematoda) from highly mineralized rivers of Lake El'ton basin, Russia.

Science.gov (United States)

Gusakov, Vladimir A; Gagarin, Vladimir G

2016-09-05

Two new nematode species, Mesodorylaimus rivalis sp. n. and Allodiplogaster media sp. n., from the highly mineralized rivers of the El'ton Lake basin (Russia) are described and illustrated from numerous mature females and males. Mesodorylaimus rivalis sp. n. is similar to M. vulvapapillatus Bagaturia & Eliava, 1966, but differs from it in the longer body, shorter spicules and longer female prerectum. Allodiplogaster media sp. n. resembles A. lupata (Shoshin, 1989) Kanzaki, Ragsdale & Giblin-Davis, 2014 and A. mordax (Shoshin, 1989) Kanzaki, Ragsdale & Giblin-Davis, 2014, but differs from the first species in having a shorter pharynx, shorter outer labial setae, longer spicules and different ratio between anterior and posterior pharynx sections, and from A. mordax in the thinner body, shorter pharynx and longer spicules.

Urinary Tract Infections (For Kids)

Medline Plus

Full Text Available ... Urinary Tract Troubles Girls are more likely than boys to get a UTI. That's because their urethras are much shorter than boys' urethras. The shorter urethra means bacteria can get ...

Hyperactivity and sugar

Science.gov (United States)

... movement, impulsive actions, being easily distracted, and shorter attention span . Some people believe that children are more likely ... most often more active, and has a shorter attention span, than a 10-year old. A child's attention ...

Urinary Tract Infections (For Kids)

Medline Plus

Full Text Available ... Your pee smells bad. These things happen because bacteria have caused an infection somewhere in your urinary ... shorter than boys' urethras. The shorter urethra means bacteria can get up into the bladder more easily ...

Height-income association in developing countries: Evidence from 14 countries.

Science.gov (United States)

Patel, Pankaj C; Devaraj, Srikant

2017-12-28

The purpose of this study was to assess whether the height-income association is positive in developing countries, and whether income differences between shorter and taller individuals in developing countries are explained by differences in endowment (ie, taller individuals have a higher income than shorter individuals because of characteristics such as better social skills) or due to discrimination (ie, shorter individuals have a lower income despite having comparable characteristics). Instrumental variable regression, Oaxaca-Blinder decomposition, quantile regression, and quantile decomposition analyses were applied to a sample of 45 108 respondents from 14 developing countries represented in the Research on Early Life and Aging Trends and Effects (RELATE) study. For a one-centimeter increase in country- and sex-adjusted median height, real income adjusted for purchasing power parity increased by 1.37%. The income differential between shorter and taller individuals was explained by discrimination and not by differences in endowments; however, the effect of discrimination decreased at higher values of country- and sex-adjusted height. Taller individuals in developing countries may realize higher income despite having characteristics similar to those of shorter individuals. © 2017 Wiley Periodicals, Inc.

Innovative E/E developments with enhanced quality requirements along the process chain; Innovative E/E Entwicklungen mit hohen Qualitaetsanforderungen entlang der Prozesskette

Energy Technology Data Exchange (ETDEWEB)

Tappe, Robert [Audi AG, Ingolstadt (Germany)

2010-07-01

The proportion of electronics in motor vehicles is still steadily increasing and is constantly creating new challenges for the Technical Development departments. They must generate innovative products while the product cycles are getting shorter and shorter. The new developments, in turn, are also making great demands on the production - the construction process must be efficient, the cycle times are getting shorter and shorter and the quality standards are rising. In addition, our after-sales service staff must increasingly face the challenges of servicing vehicles from very different generations of electronics quickly and reliably while at the same time keeping the costs low for our customers. And above all this, we are all facing the challenge that we must inspire customer confidence in our products for many years and all over the world - by offering reliability, functionality and top-level design. (orig.)

Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality.

Directory of Open Access Journals (Sweden)

Kendra N Iskander

Full Text Available Antimicrobial therapy for sepsis has beneficial effects, but prolonged use fosters emergence of resistant microorganisms, increases cost, and secondary infections. We tested whether 3 days versus 5 days of antibiotics in the murine model of cecal ligation and puncture (CLP negatively influences outcomes. Following CLP mice were randomized to receive the antibiotic imipenem-cilastatin (25mg/kg in dextrose 5% in Lactated Ringer's solution every 12 hours for either three or five days. Serial monitoring over 28 days included body weight, temperature, pulse oximetry, and facial vein sampling for hematological analysis and glucose. A separate group of mice were euthanized on post-CLP day 5 to measure cytokines and peritoneal bacterial counts. The first study examined no antimicrobial therapy and demonstrated that antibiotics significantly improved survival compared to fluids only (p = 0.004. We next tested imipenem-cilastatin therapy for 3 days versus 5 days. Body weight, temperature, glucose, and pulse oximetry measurements remained generally consistent between both groups as did the hematological profile. Pro-inflammatory plasma cytokines were comparable between both groups for IL-6, IL-1β, MIP-2 and anti-inflammatory cytokines IL-10, and TNF SRI. At 5 days post-CLP, i.e. 2 days after the termination of antibiotics in the 3 day group, there were no differences in the number of peritoneal bacteria. Importantly, shortening the course of antibiotics by 40% (from 5 days to 3 days did not decrease survival. Our results indicate that reducing the duration of broad-spectrum antibiotics in murine sepsis did not increase inflammation or mortality.

Measuring single constructs by single items: Constructing an even shorter version of the "Short Five" personality inventory.

Directory of Open Access Journals (Sweden)

Kenn Konstabel

Full Text Available The aim of this study was to construct a short, 30-item personality questionnaire that would be, in terms of content and meaning of the scores, as comparable as possible with longer, well-established inventories such as NEO PI-R and its clones. To do this, we shortened the formerly constructed 60-item "Short Five" (S5 by half so that each subscale would be represented by a single item. We compared all possibilities of selecting 30 items (preserving balanced keying within each domain of the five-factor model in terms of correlations with well-established scales, self-peer correlations, and clarity of meaning, and selected an optimal combination for each domain. The resulting shortened questionnaire, XS5, was compared to the original S5 using data from student samples in 6 different countries (Estonia, Finland, UK, Germany, Spain, and China, and a representative Finnish sample. The correlations between XS5 domain scales and their longer counterparts from well-established scales ranged from 0.74 to 0.84; the difference from the equivalent correlations for full version of S5 or from meta-analytic short-term dependability coefficients of NEO PI-R was not large. In terms of prediction of external criteria (emotional experience and self-reported behaviours, there were no important differences between XS5, S5, and the longer well-established scales. Controlling for acquiescence did not improve the prediction of criteria, self-peer correlations, or correlations with longer scales, but it did improve internal reliability and, in some analyses, comparability of the principal component structure. XS5 can be recommended as an economic measure of the five-factor model of personality at the level of domain scales; it has reasonable psychometric properties, fair correlations with longer well-established scales, and it can predict emotional experience and self-reported behaviours no worse than S5. When subscales are essential, we would still recommend using the full version of S5.

Robot-Assisted Hybrid Esophagectomy Is Associated with a Shorter Length of Stay Compared to Conventional Transthoracic Esophagectomy

DEFF Research Database (Denmark)

Rolff, Hans C; Ambrus, Rikard B; Belmouhand, Mohammed

2017-01-01

Aim: To compare the peri- and postoperative data between a hybrid minimally invasive esophagectomy (HMIE) and the conventional Ivor Lewis esophagectomy. Methods: Retrospective comparison of perioperative characteristics, postoperative complications, and survival between HMIE and Ivor Lewis esopha...

Transition Metal Donor-Peptide-Acceptor Complexes: From Intramolecular Electron Transfer Reactions to the Study of Reactive Intermediates

Energy Technology Data Exchange (ETDEWEB)

Isied, Stephan S.

2003-03-11

The trans-polyproline (PII) oligomers (Figure 1) are unusually rigid peptide structures which have been extensively studied by our group for peptide mediated intramolecular electron transfer (ET) at long distances. We have previously studied ET across a series of metal ion donor (D) acceptor (A) oligoproline peptides with different distances, driving forces and reorganizational energies. The majority of these experiments involve generating the ET intermediate using pulse radiolysis methods, although more recently photochemical methods are also used. Results of these studies showed that ET across peptides can vary by more than twelve orders of magnitude. Using ruthenium bipyridine donors, ET reaction rate constants across several proline residues (n = 4 - 9) occurred in the millisecond (ms) to {micro}s timescale, thus limiting the proline peptide conformational motions to only minor changes (far smaller than the large changes that occur on the ms to sec timescale, such as trans to cis proline isomerization). The present report describes our large data base of experimental results for D-peptide-A complexes in terms of a model where the involvement of both superexchange and hopping (hole and electron) mechanisms account for the long range ET rate constants observed. Our data shows that the change from superexchange to hopping mechanisms occurs at different distances depending on the type of D and A and their interactions with the peptides. Our model is also consistent with generalized models for superexchange and hopping which have been put forward by a number of theoretical groups to account for long range ET phenomena.

Phi ({Phi}) and psi ({Psi}) angles involved in malarial peptide bonds determine sterile protective immunity

Energy Technology Data Exchange (ETDEWEB)

Patarroyo, Manuel E., E-mail: mepatarr@gmail.com [Fundacion Instituto de Inmunologia de Colombia (FIDIC), Bogota (Colombia); Universidad Nacional de Colombia, Bogota (Colombia); Moreno-Vranich, Armando; Bermudez, Adriana [Fundacion Instituto de Inmunologia de Colombia (FIDIC), Bogota (Colombia)

2012-12-07

Highlights: Black-Right-Pointing-Pointer Phi ({Phi}) and psi ({Psi}) angles determine sterile protective immunity. Black-Right-Pointing-Pointer Modified peptide's tendency to assume a regular conformation related to a PPII{sub L}. Black-Right-Pointing-Pointer Structural modifications in mHABPs induce Ab and protective immunity. Black-Right-Pointing-Pointer mHABP backbone atom's interaction with HLA-DR{beta}1{sup Asterisk-Operator} is stabilised by H-bonds. -- Abstract: Modified HABP (mHABP) regions interacting with HLA-DR{beta}1{sup Asterisk-Operator} molecules have a more restricted conformation and/or sequence than other mHABPs which do not fit perfectly into their peptide binding regions (PBR) and do not induce an acceptable immune response due to the critical role of their {Phi} and {Psi} torsion angles. These angle's critical role was determined in such highly immunogenic, protection-inducing response against experimental malaria using the conformers (mHABPs) obtained by {sup 1}H-NMR and superimposed into HLA-DR{beta}1{sup Asterisk-Operator }-like Aotus monkey molecules; their phi ({Phi}) and psi ({Psi}) angles were measured and the H-bond formation between these molecules was evaluated. The aforementioned mHABP propensity to assume a regular conformation similar to a left-handed polyproline type II helix (PPII{sub L}) led to suggesting that favouring these conformations according to their amino acid sequence would lead to high antibody titre production and sterile protective immunity induction against malaria, thereby adding new principles or rules for vaccine development, malaria being one of them.

A rare polyglycine type II-like helix motif in naturally occurring proteins.

Science.gov (United States)

Warkentin, Eberhard; Weidenweber, Sina; Schühle, Karola; Demmer, Ulrike; Heider, Johann; Ermler, Ulrich

2017-11-01

Common structural elements in proteins such as α-helices or β-sheets are characterized by uniformly repeating, energetically favorable main chain conformations which additionally exhibit a completely saturated hydrogen-bonding network of the main chain NH and CO groups. Although polyproline or polyglycine type II helices (PP II or PG II ) are frequently found in proteins, they are not considered as equivalent secondary structure elements because they do not form a similar self-contained hydrogen-bonding network of the main chain atoms. In this context our finding of an unusual motif of glycine-rich PG II -like helices in the structure of the acetophenone carboxylase core complex is of relevance. These PG II -like helices form hexagonal bundles which appear to fulfill the criterion of a (largely) saturated hydrogen-bonding network of the main-chain groups and therefore may be regarded in this sense as a new secondary structure element. It consists of a central PG II -like helix surrounded by six nearly parallel PG II -like helices in a hexagonal array, plus an additional PG II -like helix extending the array outwards. Very related structural elements have previously been found in synthetic polyglycine fibers. In both cases, all main chain NH and CO groups of the central PG II -helix are saturated by either intra- or intermolecular hydrogen-bonds, resulting in a self-contained hydrogen-bonding network. Similar, but incomplete PG II -helix patterns were also previously identified in a GTP-binding protein and an antifreeze protein. © 2017 Wiley Periodicals, Inc.

Drastic Effect of the Peptide Sequence on the Copper-Binding Properties of Tripeptides and the Electrochemical Behaviour of Their Copper(II) Complexes.

Science.gov (United States)

Mena, Silvia; Mirats, Andrea; Caballero, Ana B; Guirado, Gonzalo; Barrios, Leoní A; Teat, Simon J; Rodriguez-Santiago, Luis; Sodupe, Mariona; Gamez, Patrick

2018-04-06

The binding and electrochemical properties of the complexes Cu II -HAH, Cu II -HWH, Cu II -Ac-HWH, Cu II -HHW, and Cu II -WHH have been studied by using NMR and UV/Vis spectroscopies, CV, and density functional calculations. The results obtained highlight the importance of the peptidic sequence on the coordination properties and, consequently, on the redox properties of their Cu II complexes. For Cu II -HAH and Cu II -HWH, no cathodic processes are observed up to -1.2 V; that is, the complexes exhibit very high stability towards copper reduction. This behaviour is associated with the formation of very stable square-planar (5,5,6)-membered chelate rings (ATCUN motif), which enclose two deprotonated amides. In contrast, for non-ATCUN Cu II -Ac-HWH, Cu II -HHW complexes, simulations seem to indicate that only one deprotonated amide is enclosed in the coordination sphere. In these cases, the main electrochemical feature is a reductive irreversible one electron-transfer process from Cu II to Cu I , accompanied with structural changes of the metal coordination sphere and reprotonation of the amide. Finally, for Cu II -WHH, two major species have been detected: one at low pH (10) with an ATCUN motif, both species coexisting at intermediate pH. The present study shows that the use of CV, using glassy carbon as a working electrode, is an ideal and rapid tool for the determination of the redox properties of Cu II metallopeptides. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Physicochemical characterization of native glycyl-l-histidyl-l-lysine tripeptide for wound healing and anti-aging: a preformulation study for dermal delivery.

Science.gov (United States)

Badenhorst, Travis; Svirskis, Darren; Wu, Zimei

2016-03-01

This study investigates the physicochemical properties of glycyl-histidyl-lysine-copper (GHK-Cu) to support the development of a formulation for effective topical delivery. The solubility and distribution coefficients (log D) were investigated using conventional methods and GHK concentrations were quantified with a validated stability-indicating reversed phase high performance liquid chromatography (RP-HPLC) method. In addition, the stability of GHK-Cu under stressed conditions and the compatibility with some potential formulation components were assessed. The peptide was susceptible to hydrolytic cleavage under basic and oxidative stressors and to a lesser extent acidic stress with first-order degradation profiles. Surprisingly, the peptide was stable in water and in pH (4.5-7.4) buffers for at least two weeks at 60  °C. The HPLC in conjunction with mass spectrometry identified three key degradation products, one of which was the constituent amino acid histidine. The distribution coefficients in octanol-phosphate buffered saline indicated the highly hydrophilic nature of GHK-Cu with log D values between -2.38 and -2.49 at pH range of 4.5-7.4. Furthermore, GHK-Cu was compatible with Span 60 based niosomes but less stable in the presence of the negatively charged lipid dicetyl phosphate. In summary, the preformulation studies provided information useful to deliver the GHK-Cu complex by carrier.

The Pet Connection. Use of pets as sentinels to better integrate data on endocrine health effects of persistent environmental contaminants.

Science.gov (United States)

Many pets, cats in particular, spend virtually all their lives within the family domicile, thus paralleling their owner’s low-level but chronic exposure to a variety of indoor contaminants. Owing to their shorter life-spans and shorter latency periods, associations between contam...

Postoperative radiotherapy in squamous cell carcinoma of the oral cavity: the importance of the overall treatment time

NARCIS (Netherlands)

Langendijk, J. A.; de Jong, M. A.; Leemans, C. R.; de Bree, R.; Smeele, L. E.; Doornaert, P.; Slotman, B. J.

2003-01-01

To test the hypothesis that (1) the distinction between intermediate- and high-risk patients by clustering different prognostic factors results in a significant difference in treatment outcome and (2) a shorter interval between surgery and radiotherapy and shorter overall treatment times of

Telomere length is associated with oppositional defiant behavior and maternal clinical depression in Latino preschool children.

Science.gov (United States)

Wojcicki, J M; Heyman, M B; Elwan, D; Shiboski, S; Lin, J; Blackburn, E; Epel, E

2015-06-16

Exposure to psychological stress and depression are associated with shorter white blood cell telomere length (TL) in adults, possibly via associated lifelong oxidative stressors. Exposure to maternal depression increases risk for future depression and behavior problems in children, and Latino youth are at high risk. Few studies have evaluated the role of exposure to maternal depression or child behavior in relation to TL in children. We assessed early-childhood exposures to maternal depression from birth to the age of 5 years and child behavior from ages 3-5 years in a cohort of Latino children in relation to child leukocyte TL at ages 4 and 5 years. Children who had oppositional defiant behavior at 3, 4 or 5 years had shorter TL than those without by ~450 base pairs (P maternal clinical depression at 3 years of age (β = -363.99, 95% CI -651.24 to 764.74; P = 0.01), shorter maternal TL (β = 502.92, 95% CI 189.21-816.63) and younger paternal age at the child's birth (β = 24.63, 95% CI 1.14-48.12). Thus, exposure to maternal clinical depression (versus depressive symptoms) in early childhood was associated with deleterious consequences on child cellular health as indicated by shorter TL at 4 and 5 years of age. Similarly, children with oppositional defiant behavior also had shorter TL, possibly related to early exposures to maternal clinical depression. Our study is the first to link maternal clinical depression and oppositional defiant behavior with shorter TL in the preschool years in a relatively homogenous population of low-income Latino children.

A new Amblycephalus from Sumatra

NARCIS (Netherlands)

Lidth de Jeude, van Th.W.

1923-01-01

Amblycephalus tropidonotus nov. spec. Rostral slightly broader than long scarcely visible from above; internasals much shorter than the praefrontals, latter entering the eye; frontal hexagonal, more long than broad, nearly twice as long as its distance from the tip of the snout, a little shorter

The exposure of bacteria to CdTe-core quantum dots: the importance of surface chemistry on cytotoxicity

Energy Technology Data Exchange (ETDEWEB)

Schneider, Raphael [DCPR, Departement de Chimie Physique de Reactions, Nancy Universite, CNRS, 1 rue Grandville, BP 20451, F-54001 Nancy (France); Wolpert, Cecile; Guilloteau, Helene; Lambert, Jacques; Merlin, Christophe [LCPME, Laboratoire de Chimie Physique et Microbiologie pour l' Environnement, Nancy-Universite, CNRS, 405 rue de Vandoeuvre, F-54600 Villers-les-Nancy (France); Balan, Lavinia [DPG, Departement de Photochimie Generale, UMR CNRS 7525, Universite de Haute Alsace, ENSCMu, 3 rue Alfred Werner, F-68093 Mulhouse (France)], E-mail: Christophe.Merlin@pharma.uhp-nancy.fr

2009-06-03

A series of water-soluble CdTe-core quantum dots (QDs) with diameters below 5.0 nm and functionalized at their surface with polar ligands such as thioglycolic acid (TGA) or the tripeptide glutathione (GSH) were synthesized and characterized by UV-vis absorption spectroscopy, their photoluminescence measurements, atomic force microscopy (AFM) and transmission electron microscopy (TEM). Because cell elongations and growth inhibitions were observed during labeling experiments, the cytotoxicity of CdTe-core QDs was investigated. Using growth inhibition tests combining different bacterial strains with different CdTe-core QDs, it was possible to demonstrate that the cytotoxicity of QDs towards bacteria depends on exposure concentrations, surface chemistry and coating, and that it varied with the strain considered. Growth inhibition tests carried out with heavy-metal-resistant bacteria, as well as ICP-AES analyses of cadmium species released by CdTe-TGA QDs, demonstrated that the leakage of Cd{sup 2+} is not the main source of QD toxicity. Our study suggests that QD cytotoxicity is rather due to the formation of TeO{sub 2} and probably the existence of CdO formed by surface oxidation. In this respect, QDs possessing a CdO shell appeared very toxic.

Extracting Markov Models of Peptide Conformational Dynamics from Simulation Data.

Science.gov (United States)

Schultheis, Verena; Hirschberger, Thomas; Carstens, Heiko; Tavan, Paul

2005-07-01

A high-dimensional time series obtained by simulating a complex and stochastic dynamical system (like a peptide in solution) may code an underlying multiple-state Markov process. We present a computational approach to most plausibly identify and reconstruct this process from the simulated trajectory. Using a mixture of normal distributions we first construct a maximum likelihood estimate of the point density associated with this time series and thus obtain a density-oriented partition of the data space. This discretization allows us to estimate the transfer operator as a matrix of moderate dimension at sufficient statistics. A nonlinear dynamics involving that matrix and, alternatively, a deterministic coarse-graining procedure are employed to construct respective hierarchies of Markov models, from which the model most plausibly mapping the generating stochastic process is selected by consideration of certain observables. Within both procedures the data are classified in terms of prototypical points, the conformations, marking the various Markov states. As a typical example, the approach is applied to analyze the conformational dynamics of a tripeptide in solution. The corresponding high-dimensional time series has been obtained from an extended molecular dynamics simulation.

Impact of glutathione-enriched inactive dry yeast preparations on the stability of terpenes during model wine aging.

Science.gov (United States)

Rodríguez-Bencomo, Juan José; Andújar-Ortiz, Inmaculada; Moreno-Arribas, M Victoria; Simó, Carolina; González, Javier; Chana, Antonio; Dávalos, Juan; Pozo-Bayón, M Ángeles

2014-02-12

The impact of the addition of glutathione-enriched Inactive dry yeast preparations (g-IDYs) on the stability of some typical wine terpenes (linalool, α-terpineol, β-citronellol, and nerol) stored under accelerated oxidative conditions was evaluated in model wines. Additionally, the effects of a second type of IDY preparation with a different claim (fermentative nutrient) and the sole addition of commercial glutathione into the model wines were also assessed. Model wines were spiked with the low molecular weight fraction (loss of typical wine terpenes in model wines submitted to accelerated aging conditions. The g-IDY preparation did indeed release reduced GSH into the model wines, although this compound did not seem exclusively related to the protective effect on some aroma compounds determined in both model wines. The presence of other sulfur-containing compounds from yeast origin in g-IDY, and also the presence of small yeast peptides, such as methionine/tryptophan/tyrosine-containing tripeptide in both types of IDYs, seemed to be related to the antioxidant activity determined in the two permeates and to the minor loss of some terpenes in the model wines spiked with them.

Molecular mechanism of the intramembrane cleavage of the β-carboxyl terminal fragment of amyloid precursor protein by γ-secretase

Directory of Open Access Journals (Sweden)

Maho eMorishima-Kawashima

2014-11-01

Full Text Available Amyloid β-protein (Aβ plays a central role in the pathogenesis of Alzheimer’s disease, the most common age-associated neurodegenerative disorder. Aβ is generated through intramembrane proteolysis of the β-carboxyl terminal fragment (βCTF of β-amyloid precursor protein (APP by γ-secretase. The initial cleavage by γ-secretase occurs in the membrane/cytoplasm boundary of the βCTF, liberating the APP intracellular domain (AICD. The remaining βCTFs, which are truncated at the C-terminus (longer Aβs, are then cropped sequentially in a stepwise manner, predominantly at three residue intervals, to generate Aβ. There are two major Aβ product lines which generate Aβ40 and Aβ42 with concomitant release of three and two tripeptides, respectively. Additionally, many alternative cleavages occur, releasing peptides with three to six residues. These modulate the Aβ product lines and define the species and quantity of Aβ generated. Here, we review our current understanding of the intramembrane cleavage of the βCTF by γ-secretase, which may contribute to the future goal of developing an efficient therapeutic strategy for Alzheimer’s disease.

Photo-crosslinking induced geometric restriction controls the self-assembly of diphenylalanine based peptides

International Nuclear Information System (INIS)

Tie Zuoxiu; Qin Meng; Zou Dawei; Cao Yi; Wang Wei

2011-01-01

The diphenylalanine (FF) motif has been widely used in the design of peptides that are capable of forming various ordered structures, such as nanotubes, nanospheres and hydrogels. In these assemblies, FF based peptides adopt an antiparallel structure and are stabilized by π-π stacking among the phenyl groups. Here we show that assembly of FF-based peptides can be controlled by their geometric restrictions. Using tripeptide FFY (L-Phe-L-Phe-L-Tyr) as an example, we demonstrate that photo-crosslinking of C-terminal tyrosine can impose a geometric restriction to the formation of an antiparallel structure, leading to a structural change of the assemblies from nanosphere to amorphous. This finding is confirmed using far-UV circular dichroism, Fourier transform infrared spectroscopy and atomic force microscopy. Based on such a mechanism, we are able to control the gel-sol transition of Fmoc-FFY using the geometric restriction induced by photo-crosslinking of C-terminal tyrosine groups. We believe that geometric restriction should be considered as an important factor in the design of peptide-based materials. It can also be implemented as a useful strategy for the construction of environment-responsive 'smart' materials. (authors)

Paenilarvins: Iturin family lipopeptides from the honey bee pathogen Paenibacillus larvae.

Science.gov (United States)

Sood, Sakshi; Steinmetz, Heinrich; Beims, Hannes; Mohr, Kathrin I; Stadler, Marc; Djukic, Marvin; von der Ohe, Werner; Steinert, Michael; Daniel, Rolf; Müller, Rolf

2014-09-05

The bacterium Paenibacillus larvae has been extensively studied as it is an appalling honey bee pathogen. In the present work, we screened crude extracts derived from fermentations of P. larvae genotypes ERIC I and II for antimicrobial activity, following the detection of four putative secondary metabolite gene clusters that show high sequence homology to known biosynthetic gene clusters for the biosynthesis of antibiotics. Low molecular weight metabolites produced by P. larvae have recently been shown to have toxic effects on honey bee larvae. Moreover, a novel tripeptide, sevadicin, was recently characterized from laboratory cultures of P. larvae. In this study, paenilarvins, which are iturinic lipopeptides exhibiting strong antifungal activities, were obtained by bioassay-guided fractionation from cultures of P. larvae, genotype ERIC II. Their molecular structures were determined by extensive 2D NMR spectroscopy, high resolution mass spectrometry, and other methods. Paenilarvins are the first antifungal secondary metabolites to be identified from P. larvae. In preliminary experiments, these lipopeptides also affected honey bee larvae and might thus play a role in P. larvae survival and pathogenesis. However, further studies are needed to investigate their function. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron-dependent formation of reactive oxygen species and glutathione depletion after accumulation of magnetic iron oxide nanoparticles by oligodendroglial cells

International Nuclear Information System (INIS)

Hohnholt, Michaela C.; Dringen, Ralf

2011-01-01

Magnetic iron oxide nanoparticles (IONP) are currently used for various neurobiological applications. To investigate the consequences of a treatment of brain cells with such particles, we have applied dimercaptosuccinate (DMSA)-coated IONP that had an average hydrodynamic diameter of 60 nm to oligodendroglial OLN-93 cells. After exposure to 4 mM iron applied as DMSA–IONP, these cells increased their total specific iron content within 8 h 600-fold from 7 to 4,200 nmol/mg cellular protein. The strong iron accumulation was accompanied by a change in cell morphology, although the cell viability was not compromized. DMSA–IONP treatment caused a concentration-dependent increase in the iron-dependent formation of reactive oxygen species and a decrease in the specific content of the cellular antioxidative tripeptide glutathione. During a 16 h recovery phase in IONP-free culture medium following exposure to DMSA–IONP, OLN-93 cells maintained their high iron content and replenished their cellular glutathione content. These data demonstrate that viable OLN-93 cells have a remarkable potential to deal successfully with the consequences of an accumulation of large amounts of iron after exposure to DMSA–IONP.

Calculation of Relative Binding Free Energy in the Water-Filled Active Site of Oligopeptide-Binding Protein A.

Science.gov (United States)

Maurer, Manuela; de Beer, Stephanie B A; Oostenbrink, Chris

2016-04-15

The periplasmic oligopeptide binding protein A (OppA) represents a well-known example of water-mediated protein-ligand interactions. Here, we perform free-energy calculations for three different ligands binding to OppA, using a thermodynamic integration approach. The tripeptide ligands share a high structural similarity (all have the sequence KXK), but their experimentally-determined binding free energies differ remarkably. Thermodynamic cycles were constructed for the ligands, and simulations conducted in the bound and (freely solvated) unbound states. In the unbound state, it was observed that the difference in conformational freedom between alanine and glycine leads to a surprisingly slow convergence, despite their chemical similarity. This could be overcome by increasing the softness parameter during alchemical transformations. Discrepancies remained in the bound state however, when comparing independent simulations of the three ligands. These difficulties could be traced to a slow relaxation of the water network within the active site. Fluctuations in the number of water molecules residing in the binding cavity occur mostly on a timescale larger than the simulation time along the alchemical path. After extensive simulations, relative binding free energies that were converged to within thermal noise could be obtained, which agree well with available experimental data.

Hydrogen bond strengths in phosphorylated and sulfated amino acid residues.

Directory of Open Access Journals (Sweden)

Chaya Rapp

Full Text Available Post-translational modification by the addition of an oxoanion functional group, usually a phosphate group and less commonly a sulfate group, leads to diverse structural and functional consequences in protein systems. Building upon previous studies of the phosphoserine residue (pSer, we address the distinct nature of hydrogen bonding interactions in phosphotyrosine (pTyr and sulfotyrosine (sTyr residues. We derive partial charges for these modified residues and then study them in the context of molecular dynamics simulation of model tripeptides and sulfated protein complexes, potentials of mean force for interacting residue pairs, and a survey of the interactions of modified residues among experimental protein structures. Overall, our findings show that for pTyr, bidentate interactions with Arg are particularly dominant, as has been previously demonstrated for pSer. sTyr interactions with Arg are significantly weaker, even as compared to the same interactions made by the Glu residue. Our work sheds light on the distinct nature of these modified tyrosine residues, and provides a physical-chemical foundation for future studies with the goal of understanding their roles in systems of biological interest.

Relative telomere length is associated with a functional ...

Indian Academy of Sciences (India)

ated with several neuropsychiatric disorders, such as major depression ... with shorter telomeres in white blood cells of healthy indi- viduals (Starkweather et al. 2014). Recently, a systematic review identified a possible association between shorter TL and high levels of ... MAOA protein plays an important role in the regula-.

Telomere length differences between subcutaneous and visceral adipose tissue in humans

Energy Technology Data Exchange (ETDEWEB)

Lakowa, Nicole; Trieu, Nhu; Flehmig, Gesine [Department of Medicine, University of Leipzig, Leipzig (Germany); Lohmann, Tobias [Municipal Clinic Dresden-Neustadt, Dresden (Germany); Schön, Michael R. [Städtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, Karlsruhe (Germany); Dietrich, Arne [Department of Surgery, University of Leipzig, Leipzig (Germany); IFB AdiposityDiseases, University of Leipzig, Leipzig (Germany); Zeplin, Philip Helge; Langer, Stefan [Department of Orthopaedics, Traumatology and Plastic Surgery, University of Leipzig, Leipzig (Germany); Stumvoll, Michael; Blüher, Matthias [Department of Medicine, University of Leipzig, Leipzig (Germany); Klöting, Nora, E-mail: nora.kloeting@medizin.uni-leipzig.de [IFB AdiposityDiseases, Junior Research Group 2 “Animal Models of Obesity”, University of Leipzig, Leipzig (Germany)

2015-02-13

Adipocyte hypertrophy and hyperplasia have been shown to be associated with shorter telomere length, which may reflect aging, altered cell proliferation and adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat distribution and AT cellular composition may contribute to obesity related metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are different between: (1) abdominal subcutaneous and omental fat depots, (2) superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and cells of the stromal vascular fraction (SVF). We further asked whether AT TL is related to age, anthropometric and metabolic traits. TL was analyzed by quantitative PCR in total human genomic DNA isolated from paired subcutaneous and visceral AT of 47 lean and 50 obese individuals. In subgroups, we analyzed TL in isolated small and large adipocytes and SVF cells. We find significantly shorter TL in subcutaneous compared to visceral AT (P < 0.001) which is consistent in men and subgroups of lean and obese, and individuals with or without type 2 diabetes (T2D). Shorter TL in SAT is entirely due to shorter TL in the SVF compared to visceral AT (P < 0.01). SAT TL is most strongly correlated with age (r = −0.205, P < 0.05) and independently of age with HbA1c (r = −0.5, P < 0.05). We found significant TL differences between superficial SAT of lean and obese as well as between individuals with our without T2D, but not between the two layers of SAT. Our data indicate that fat depot differences in TL mainly reflect shorter TL of SVF cells. In addition, we found an age and BMI-independent relationship between shorter TL and HbA1c suggesting that chronic hyperglycemia may impair the regenerative capacity of AT more strongly than obesity alone. - Highlights: • Telomere lengths (TL) differ between fat depots mainly due to different lengths in SVF. • TL is not associated with gender, BMI and T2D. • The tendency for

Telomere length differences between subcutaneous and visceral adipose tissue in humans

International Nuclear Information System (INIS)

Lakowa, Nicole; Trieu, Nhu; Flehmig, Gesine; Lohmann, Tobias; Schön, Michael R.; Dietrich, Arne; Zeplin, Philip Helge; Langer, Stefan; Stumvoll, Michael; Blüher, Matthias; Klöting, Nora

2015-01-01

Adipocyte hypertrophy and hyperplasia have been shown to be associated with shorter telomere length, which may reflect aging, altered cell proliferation and adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat distribution and AT cellular composition may contribute to obesity related metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are different between: (1) abdominal subcutaneous and omental fat depots, (2) superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and cells of the stromal vascular fraction (SVF). We further asked whether AT TL is related to age, anthropometric and metabolic traits. TL was analyzed by quantitative PCR in total human genomic DNA isolated from paired subcutaneous and visceral AT of 47 lean and 50 obese individuals. In subgroups, we analyzed TL in isolated small and large adipocytes and SVF cells. We find significantly shorter TL in subcutaneous compared to visceral AT (P < 0.001) which is consistent in men and subgroups of lean and obese, and individuals with or without type 2 diabetes (T2D). Shorter TL in SAT is entirely due to shorter TL in the SVF compared to visceral AT (P < 0.01). SAT TL is most strongly correlated with age (r = −0.205, P < 0.05) and independently of age with HbA1c (r = −0.5, P < 0.05). We found significant TL differences between superficial SAT of lean and obese as well as between individuals with our without T2D, but not between the two layers of SAT. Our data indicate that fat depot differences in TL mainly reflect shorter TL of SVF cells. In addition, we found an age and BMI-independent relationship between shorter TL and HbA1c suggesting that chronic hyperglycemia may impair the regenerative capacity of AT more strongly than obesity alone. - Highlights: • Telomere lengths (TL) differ between fat depots mainly due to different lengths in SVF. • TL is not associated with gender, BMI and T2D. • The tendency for

Length of Maternity Leave and Quality of Mother-Infant Interactions.

Science.gov (United States)

Clark, Roseanne; And Others

1997-01-01

Assessed association between length of maternity leave and quality of mother-infant interaction. Found a direct association between shorter leave and more negative affect and behavior; mothers with more depressive symptoms or who perceived their infant as having a difficult temperament, and with shorter leaves expressed less positive affect,…

Translation, modification and cellular distribution of two AC4 variants of African cassava mosaic virus in yeast and their pathogenic potential in plants

International Nuclear Information System (INIS)

Hipp, Katharina; Rau, Peter; Schäfer, Benjamin; Pfannstiel, Jens; Jeske, Holger

2016-01-01

Plant infecting geminiviruses encode a small (A)C4 protein within the open reading frame of the replication-initiator protein. In African cassava mosaic virus, two in-frame start codons may be used for the translation of a longer and a shorter AC4 variant. Both were fused to green fluorescent protein or glutathione-S-transferase genes and expressed in fission yeast. The longer variant accumulated in discrete spots in the cytoplasm, whereas the shorter variant localized to the plasma membrane. A similar expression pattern was found in plants. A myristoylation motif may promote a targeting of the shorter variant to the plasma membrane. Mass spectrometry analysis of the yeast-expressed shorter variant detected the corresponding myristoylation. The biological relevance of the second start codon was confirmed using mutated infectious clones. Whereas mutating the first start codon had no effect on the infectivity in Nicotiana benthamiana plants, the second start codon proved to be essential. -- Highlights: •The ACMV AC4 may be translated from one or the other in-frame start codon. •Both AC4 variants are translated in fission yeast. •The long AC4 protein localizes to the cytoplasm, the short to the plasma membrane. •The short variant is myristoylated in yeast and may promote membrane localization. •Only the shorter AC4 variant has an impact on viral infections in plants.

Translation, modification and cellular distribution of two AC4 variants of African cassava mosaic virus in yeast and their pathogenic potential in plants

Energy Technology Data Exchange (ETDEWEB)

Hipp, Katharina, E-mail: katharina.hipp@bio.uni-stuttgart.de [University of Stuttgart, Institute of Biomaterials and biomolecular Systems, Department of Molecular Biology and Plant Virology, Pfaffenwaldring 57, 70550 Stuttgart (Germany); Rau, Peter; Schäfer, Benjamin [University of Stuttgart, Institute of Biomaterials and biomolecular Systems, Department of Molecular Biology and Plant Virology, Pfaffenwaldring 57, 70550 Stuttgart (Germany); Pfannstiel, Jens [University of Hohenheim, Mass Spectrometry Core Facility, August-von-Hartmann-Straße 3, 70599 Stuttgart (Germany); Jeske, Holger [University of Stuttgart, Institute of Biomaterials and biomolecular Systems, Department of Molecular Biology and Plant Virology, Pfaffenwaldring 57, 70550 Stuttgart (Germany)

2016-11-15

Plant infecting geminiviruses encode a small (A)C4 protein within the open reading frame of the replication-initiator protein. In African cassava mosaic virus, two in-frame start codons may be used for the translation of a longer and a shorter AC4 variant. Both were fused to green fluorescent protein or glutathione-S-transferase genes and expressed in fission yeast. The longer variant accumulated in discrete spots in the cytoplasm, whereas the shorter variant localized to the plasma membrane. A similar expression pattern was found in plants. A myristoylation motif may promote a targeting of the shorter variant to the plasma membrane. Mass spectrometry analysis of the yeast-expressed shorter variant detected the corresponding myristoylation. The biological relevance of the second start codon was confirmed using mutated infectious clones. Whereas mutating the first start codon had no effect on the infectivity in Nicotiana benthamiana plants, the second start codon proved to be essential. -- Highlights: •The ACMV AC4 may be translated from one or the other in-frame start codon. •Both AC4 variants are translated in fission yeast. •The long AC4 protein localizes to the cytoplasm, the short to the plasma membrane. •The short variant is myristoylated in yeast and may promote membrane localization. •Only the shorter AC4 variant has an impact on viral infections in plants.

Chromosome Connections: Compelling Clues to Common Ancestry

Science.gov (United States)

Flammer, Larry

2013-01-01

Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

Accelerated stress testing in a time-driven product development process

NARCIS (Netherlands)

Lu, Y.; Loh, H.T.; Brombacher, A.C.; Ouden, den P.H.

2000-01-01

In order to compete in the market, companies have to produce the right products with a shorter time to market and at lower costs than before. Shorter time to market requires the product development process (PDP) to change the way of working from the classical ‘wait and react’ to anticipating and

On the Use of Writing Assignments in Intermediate Microeconomic Theory

Science.gov (United States)

O'Neill, Patrick B.

2009-01-01

A typical writing assignment in upper level required courses is a term paper. However many economics majors, particularly those in business schools, need to develop skill at writing shorter pieces. In this paper I describe numerous examples of shorter writing assignments that I have incorporated into an Intermediate Microeconomic Theory course.…

76 FR 44633 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Science.gov (United States)

2011-07-26

... opportunity to manipulate this product and disrupt the underlying market that a lower position limit may... the date on which it was filed, or such shorter time as the Commission may designate, if consistent... five business days prior to the date of filing of the proposed rule change or such shorter time as...

Should we use the shorter Thai-version quality of life and symptoms questionnaires in women with overactive bladder?

Science.gov (United States)

Bunyavejchevin, Suvit; Liao, Limin; Lu, Shing-Hwa; Choo, Myung-Soo; Rabbani, Khalid Javed; Havanond, Piyalamporn

2015-08-01

The aim of this study was to test: (i) the validation and reliability of the Thai versions of overactive bladder (OAB) questionnaires (the 8-item and 3-item Overactive Bladder Symptoms Score questionnaires [OAB-v8 and OAB-v3, respectively] and the Overactive Bladder Questionnaire [OAB-q]); and (ii) the correlation of the OAB-v8, OAB-v3, and the single-question Quality of Life Questionnaire (1-QoL) to the OAB-q in Thai women with OAB. During January to March 2011, 36 Thai women with OAB attending a urogynecology clinic at Chulalongkorn Hospital, Bangkok, Thailand were recruited. All questionnaires were given as a psychometric test twice, 2 weeks apart. Cronbach's alpha of the OAB-v8 was higher (and above 0.7) than OAB-v3 at both week 0 and week 2. The intraclass correlations (ricc ) were 0.64, 0.85, and 0.97 for the OABV8, OAB-v3, and OAB-q, respectively. The correlation coefficient (r) of OAB-v3 and OAB-q at weeks 0 and 2 (0.40 and 0.49) were lower than those for OAB-v8 and OAB-q at weeks 0 and 2 (0.62 and 0.62). All questions on the OAB-v3 had a lower weighted kappa than OAB-v8. There was no statistically significant difference in the OAB-q score in each level of 1-QoL score at week 0 (P = 0.12) and at week 2 (P = 0.29). The reliability of the OAB-v3 is poorer than that of the OAB-v8. The OAB-v3 is poorer correlated to the OAB-q than to the OAB-v8. A short questionnaire, such as the OAB-v3 and the 1-QoL, has poor reliability and is poorly correlated to the OAB-q and is not recommended as a replacement for the standard questionnaires, such as the OAB-q and the OAB-v8. The OAB-v3 should only be used in large screening populations where there are time limits. © 2015 The Authors Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

Shorter CAG repeat length in the AR gene is associated with poor outcome in head and neck cancer

DEFF Research Database (Denmark)

Rosa, Fabíola Encinas; dos Santos, Rodrigo Mattos; Poli-Frederico, Regina Célia

2007-01-01

microsatellite instability (MSI) and loss of heterozygosity (LOH) in these tumors. DESIGN: Matched samples of blood and head and neck tumors were evaluated using two methodologies, silver-stained gels to perform the analyses of MSI and LOH, and automated analysis to confirm these results and for genotyping...... of the AR [CAG](n) repeat length. Sixty-nine individuals without cancer were used as a control group for both procedures. The Log-rank test was used to compare overall survival and disease-free survival curves. The Cox proportional hazards regression models were performed to determine the [CAG](n) repeats......: These results suggest that short [CAG](n) repeat length (poor prognosis in a subset of male patients with head and neck cancer and that AR gene microsatellite instability is uncommon in these tumors....

Toward Shorter Hospitalization After Endoscopic Transsphenoidal Pituitary Surgery: Day-by-Day Analysis of Early Postoperative Complications and Interventions.

Science.gov (United States)

Shimanskaya, Viktoria E; Wagenmakers, Margreet A E M; Bartels, Ronald H M A; Boogaarts, Hieronymus D; Grotenhuis, J André; Hermus, Ad R M M; van de Ven, Annenienke C; van Lindert, Erik J

2018-03-01

It is unclear which patients have the greatest risk of developing complications in the first days after endoscopic transsphenoidal pituitary surgery (ETS) and how long patients should stay hospitalized after surgery. The objective of this study is to identify which patients are at risk for early postoperative medical and surgical reinterventions to optimize the length of hospitalization. The medical records of 146 patients who underwent ETS for a pituitary adenoma between January 2013 and July 2016 were reviewed retrospectively. Data were collected on baseline patient-related characteristics, characteristics of the pituitary adenoma, perioperative complications and interventions, and postoperative outcomes. Patients who underwent additional interventions on days 2, 3, and 4 after ETS were identified as cases, and patients who did not have any interventions after day 1 postoperatively were identified as controls. Diabetes mellitus (odds ratio [OR], 4.279; 95% confidence interval [CI], 1.149-15.933; P = 0.03), incomplete adenoma resection (OR, 2.840; 95% CI, 1.228-6.568; P = 0.02) and increased morning sodium concentration on day 2 after surgery (OR, 5.211; 95% CI, 2.158-12.579; P surgery have an increased chance on reinterventions. In addition, patients without any interventions on day 1 and 2 are at low risk for later reinterventions. These patients could be suitable candidates for early hospital discharge. Copyright © 2018 Elsevier Inc. All rights reserved.

Measuring single constructs by single items: Constructing an even shorter version of the “Short Five” personality inventory

Science.gov (United States)

Konstabel, Kenn; Lönnqvist, Jan-Erik; Leikas, Sointu; García Velázquez, Regina; Qin, Hiaying; Verkasalo, Markku; Walkowitz, Gari

2017-01-01

The aim of this study was to construct a short, 30-item personality questionnaire that would be, in terms of content and meaning of the scores, as comparable as possible with longer, well-established inventories such as NEO PI-R and its clones. To do this, we shortened the formerly constructed 60-item “Short Five” (S5) by half so that each subscale would be represented by a single item. We compared all possibilities of selecting 30 items (preserving balanced keying within each domain of the five-factor model) in terms of correlations with well-established scales, self-peer correlations, and clarity of meaning, and selected an optimal combination for each domain. The resulting shortened questionnaire, XS5, was compared to the original S5 using data from student samples in 6 different countries (Estonia, Finland, UK, Germany, Spain, and China), and a representative Finnish sample. The correlations between XS5 domain scales and their longer counterparts from well-established scales ranged from 0.74 to 0.84; the difference from the equivalent correlations for full version of S5 or from meta-analytic short-term dependability coefficients of NEO PI-R was not large. In terms of prediction of external criteria (emotional experience and self-reported behaviours), there were no important differences between XS5, S5, and the longer well-established scales. Controlling for acquiescence did not improve the prediction of criteria, self-peer correlations, or correlations with longer scales, but it did improve internal reliability and, in some analyses, comparability of the principal component structure. XS5 can be recommended as an economic measure of the five-factor model of personality at the level of domain scales; it has reasonable psychometric properties, fair correlations with longer well-established scales, and it can predict emotional experience and self-reported behaviours no worse than S5. When subscales are essential, we would still recommend using the full version of S5. PMID:28800630

Plasma shifts of C VI Lyman lines to shorter wavelengths. Final report, November 4, 1981-September 30, 1983

International Nuclear Information System (INIS)

Griem, H.R.

1984-07-01

The first two years of this ongoing research program were devoted to experimental observations of shifts and widths of hydrogenic ion lines emitted by very dense plasmas. This search is an essential step in the general study of the properties of bound states of multiply charged ions in dense plasmas. This research is of importance in a number of areas, notably equilibrium statistical mechanics (equation of state), plasma radiation physics (energy transport and diagnostics) and calibration of wavelengths in the extreme vacuum uv region (10 A < lambda < 200 A). In the latter case, the wavelengths of lines from one-electron ions are generally accepted to be well known theoretically and are considered as standards for plate calibration. The question nevertheless arises whether or not significant changes in wavelength can occur, e.g., in low-inductance sparks or laser produced plasma which are often used as line sources

Potchefstroom Electronic Law Journal/Potchefstroomse Elektroniese ...

African Journals Online (AJOL)

The editors reserve the right to make such changes to a contribution that are in their judgment desirable for the purposes of conforming to the PELJ/PER Standard for Style and ... For notes, case notes and reviews, the same rigour is required, though they may be shorter contributions on material of shorter-term topicality.

Initiation points for cellular deoxyribonucleic acid replication in human lymphoid cells converted by Epstein-Barr virus

International Nuclear Information System (INIS)

Oppenheim, A.; Shlomai, Z.; Ben-Bassat, H.

1981-01-01

Replicon size was estimated in two Epstein-Barr virus (EBV)-negative human lymphoma lines, BJAB and Ramos, and four EBV-positive lines derived from the former ones by infection (conversion) with two viral strains, B95-8 and P3HR-1. Logarithmic cultures were pulse-labeled with [/sup -3/H]thymidine, and the deoxyribonucleic acid was spread on microscopic slides and autoradiographed by the method of Huberman and Riggs. Three of the four EBV-converted cell lines, BJAB/B95-8, Ra/B95-8, and Ra/HRIK, were found to have significantly shorter replicons (41, 21, 54% shorter, respectively), i.e., more initiation points, than their EBV-negative parents. BJAB/HRIK had replicons which were only slightly shorter (11%) than those of BJAB. However, analysis of track length demonstrated that extensive track fusion occurred during the labeling of BJAB/HRIK, implying that its true average replicon size is shorter than the observed value. The results indicate that in analogy to simian virus 40, EBV activates new initiation points for cellular DNA replication in EBV-transformed cells

Morphological Responses Explain Tolerance of the Bamboo Yushania microphylla to Grazing

Directory of Open Access Journals (Sweden)

Kesang Wangchuk

2014-01-01

Full Text Available Mechanisms of tolerance of the bamboo Y. microphylla to ungulate herbivory were investigated by measuring above- and belowground morphogenetic traits and biomass allocation patterns of the bamboo Y. microphylla under grazed and ungrazed conditions in a Himalayan mixed conifer forest. Data were collected from 5 populations consisting of 10 ramets each in adjacent grazed and ungrazed plots. Compared with ungrazed ramets, the aboveground morphological modifications of grazed ramets were higher culm density, shorter and thinner culms, shorter internode, and shorter top leaf. The belowground morphological modifications for the grazed ramets were thinner rhizomes, lower rhizome biomass and dry matter, more nodes, and shorter internodes. Despite the lower biomass and dry matter, the root-to-shoot ratio was higher for grazed ramets. Results suggest that Y. microphylla subjected to herbivory shows aboveground overcompensation in terms of densification at the cost of belowground biomass, but at the same time maintains a higher proportion of belowground reserves, as compared to ungrazed conditions. These responses provide adequate evidence to conclude that Y. microphylla tolerates ungulate herbivory through above- and belowground morphological modifications.

Association Between Leukocyte Telomere Length and the Risk of Incident Atrial Fibrillation

DEFF Research Database (Denmark)

Staerk, Laila; Wang, Biqi; Lunetta, Kathryn L

2017-01-01

BACKGROUND: Advancing age is a prominent risk factor for atrial fibrillation (AF). Shorter telomere length is a biomarker of biological aging, but the link between shorter telomere length and increased risk of AF remains unclear. We examined the association between shorter leukocyte telomere length...... at baseline was 6.95±0.57 kb. During 15.1±4.2 years mean follow-up, 184 participants (64 women) developed AF. Chronological age was associated with increased risk of AF (hazard ratio per 10-year increase, 2.16; 95% confidence interval, 1.71-2.72). There was no significant association between LTL and incident...... evidence for a significant association between LTL and risk of incident AF....

Selection pressure on human STR loci and its relevance in repeat expansion disease

KAUST Repository

Shimada, Makoto K.

2016-06-11

Short Tandem Repeats (STRs) comprise repeats of one to several base pairs. Because of the high mutability due to strand slippage during DNA synthesis, rapid evolutionary change in the number of repeating units directly shapes the range of repeat-number variation according to selection pressure. However, the remaining questions include: Why are STRs causing repeat expansion diseases maintained in the human population; and why are these limited to neurodegenerative diseases? By evaluating the genome-wide selection pressure on STRs using the database we constructed, we identified two different patterns of relationship in repeat-number polymorphisms between DNA and amino-acid sequences, although both patterns are evolutionary consequences of avoiding the formation of harmful long STRs. First, a mixture of degenerate codons is represented in poly-proline (poly-P) repeats. Second, long poly-glutamine (poly-Q) repeats are favored at the protein level; however, at the DNA level, STRs encoding long poly-Qs are frequently divided by synonymous SNPs. Furthermore, significant enrichments of apoptosis and neurodevelopment were biological processes found specifically in genes encoding poly-Qs with repeat polymorphism. This suggests the existence of a specific molecular function for polymorphic and/or long poly-Q stretches. Given that the poly-Qs causing expansion diseases were longer than other poly-Qs, even in healthy subjects, our results indicate that the evolutionary benefits of long and/or polymorphic poly-Q stretches outweigh the risks of long CAG repeats predisposing to pathological hyper-expansions. Molecular pathways in neurodevelopment requiring long and polymorphic poly-Q stretches may provide a clue to understanding why poly-Q expansion diseases are limited to neurodegenerative diseases. © 2016, Springer-Verlag Berlin Heidelberg.

Experimental conformational energy maps of proteins and peptides.

Science.gov (United States)

Balaji, Govardhan A; Nagendra, H G; Balaji, Vitukudi N; Rao, Shashidhar N

2017-06-01

We have presented an extensive analysis of the peptide backbone dihedral angles in the PDB structures and computed experimental Ramachandran plots for their distributions seen under a various constraints on X-ray resolution, representativeness at different sequence identity percentages, and hydrogen bonding distances. These experimental distributions have been converted into isoenergy contour plots using the approach employed previously by F. M. Pohl. This has led to the identification of energetically favored minima in the Ramachandran (ϕ, ψ) plots in which global minima are predominantly observed either in the right-handed α-helical or the polyproline II regions. Further, we have identified low energy pathways for transitions between various minima in the (ϕ,ψ) plots. We have compared and presented the experimental plots with published theoretical plots obtained from both molecular mechanics and quantum mechanical approaches. In addition, we have developed and employed a root mean square deviation (RMSD) metric for isoenergy contours in various ranges, as a measure (in kcal.mol -1 ) to compare any two plots and determine the extent of correlation and similarity between their isoenergy contours. In general, we observe a greater degree of compatibility with experimental plots for energy maps obtained from molecular mechanics methods compared to most quantum mechanical methods. The experimental energy plots we have investigated could be helpful in refining protein structures obtained from X-ray, NMR, and electron microscopy and in refining force field parameters to enable simulations of peptide and protein structures that have higher degree of consistency with experiments. Proteins 2017; 85:979-1001. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Alanine and proline content modulate global sensitivity to discrete perturbations in disordered proteins.

Science.gov (United States)

Perez, Romel B; Tischer, Alexander; Auton, Matthew; Whitten, Steven T

2014-12-01

Molecular transduction of biological signals is understood primarily in terms of the cooperative structural transitions of protein macromolecules, providing a mechanism through which discrete local structure perturbations affect global macromolecular properties. The recognition that proteins lacking tertiary stability, commonly referred to as intrinsically disordered proteins (IDPs), mediate key signaling pathways suggests that protein structures without cooperative intramolecular interactions may also have the ability to couple local and global structure changes. Presented here are results from experiments that measured and tested the ability of disordered proteins to couple local changes in structure to global changes in structure. Using the intrinsically disordered N-terminal region of the p53 protein as an experimental model, a set of proline (PRO) and alanine (ALA) to glycine (GLY) substitution variants were designed to modulate backbone conformational propensities without introducing non-native intramolecular interactions. The hydrodynamic radius (R(h)) was used to monitor changes in global structure. Circular dichroism spectroscopy showed that the GLY substitutions decreased polyproline II (PP(II)) propensities relative to the wild type, as expected, and fluorescence methods indicated that substitution-induced changes in R(h) were not associated with folding. The experiments showed that changes in local PP(II) structure cause changes in R(h) that are variable and that depend on the intrinsic chain propensities of PRO and ALA residues, demonstrating a mechanism for coupling local and global structure changes. Molecular simulations that model our results were used to extend the analysis to other proteins and illustrate the generality of the observed PRO and alanine effects on the structures of IDPs. © 2014 Wiley Periodicals, Inc.

A unified conformational selection and induced fit approach to protein-peptide docking.

Directory of Open Access Journals (Sweden)

Mikael Trellet

Full Text Available Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II, flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking.

A polymorphism in a transporter of testosterone is a determinant of androgen independence in prostate cancer.

Science.gov (United States)

Sharifi, Nima; Hamada, Akinobu; Sissung, Tristan; Danesi, Romano; Venzon, David; Baum, Caitlin; Gulley, James L; Price, Douglas K; Dahut, William L; Figg, William D

2008-08-05

To determine if patients with advanced prostate cancer carrying a polymorphism that codes for a more active testosterone transporter have less durable responses to androgen-deprivation therapy (ADT) than patients not carrying this polymorphism. We previously determined that a polymorphism in SLCO1B3 affects testosterone transport and that those men who have at least one wild-type T allele at the 334 T > G polymorphism in this gene have a shorter survival. We hypothesized that the T allele which increases testosterone transport would be associated with a shorter interval from ADT to androgen independence. We examined the association between this SLCO1B3 polymorphism and time from ADT to androgen independence, ADT to prostate-specific antigen (PSA) nadir and PSA nadir to androgen independence in 68 Caucasian patients with advanced prostate cancer who were treated with ADT with metastatic disease (D2) or biochemical failure with no metastatic disease (D0). When examined separately, patients in the individual stages tended to have a shorter time to androgen independence with the T allele in the D0 (P = 0.11) and D2 (P = 0.18) groups. Combining these groups and stratifying by stage yielded a statistically significant shorter time to androgen independence with the T allele (P = 0.048). A polymorphism in a transporter that increases testosterone import is associated with a shorter time to androgen independence in patients with prostate cancer who are treated with ADT.

Effect of deformation on the continuous cooling transformation (CCT diagram of steel 32CRB4

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R. Kawulok

2015-07-01

Full Text Available CCT and DCCT steel diagrams of the steel 32CrB4 were determined by the universal plastometer GLEEBLE 3 800 on the basis of dilatometric tests. Dilatometric analysis showed that compared to the diagram provided by the software QTSteel th e noses of individual curves are in fact shifted towards shorter times. Preceding deformation significantly affected the decay diagram of the investigated steel. Shorter times, which were available for recovery of the deformed structure during more rapid cooling, resulted in a significant shift of the curves in the DCCT diagram towards shorter times. At low cooling rates the effect of deformation was practically negligible, since recrystallization took place between the deformation and beginning of the phase transformation.

Comparative Characterization of Multiscale Carbon Fiber Composite with Long and Short MWCNTs at Higher Weight Fractions

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Michael Zimmer

2012-01-01

Full Text Available There are documented advantages to using carbon nanotubes (CNTs in composites for various property enhancements. However, to date, only limited studies have been conducted on using of longer CNTs over 1 mm in length. This study used long multiwalled carbon nanotubes (LMWCNTs and their longer extended networks to test multiple properties in thermal conductivity, electrical conductivity, mechanical strength, and modulus and then compared these properties to those of shorter multi-walled carbon nanotubes (SMWCNTs. For carbon fiber-reinforced composites, the longer graphite paths from LMWCNTs in the matrix were expected to improve all properties. The longer networks were expected to allow for more undisturbed phonon transportation to improve thermal conductivity. This in turn relates to improved electrical conductivity and better mechanical properties. However, results have shown that the LMWCNTs do not improve or decrease thermal conductivity, whereas the shorter MWCNTs provide mixed results. LMWCNTs did show improvements in electrical, mechanical, and physical properties, but compared to shorter MWCNTs, the results in other certain properties varied. This perplexing outcome resides in the functioning of the networks made by both the LMWCNTs and shorter MWCNTs.

A comparative study of craniofacial morphology of cleft lip children with or without palate

Energy Technology Data Exchange (ETDEWEB)

Cho, Su Beom; Kim, Young Ju; Koh, Kwang Joon [Dept. of Oral Radiology, College of Dentistry, Chonbuk National University, Chonju (Korea, Republic of)

1995-08-15

The purpose of this study was to determine whether any difference existed in craniofacial morphology between cleft children and normal subjects. Thirty three measurements of the various regions of cranium and face were obtained from lateral cephalometric radiograms in 40 cleft children (27 males, 13 females) and 40 normal subjects (23 males, 17 females) in our dental hospital from Jan. 1988 to Dec. 1995. The measurements were compared with those in control subjects who had no history of craniofacial abnormalities.. The obtained results were as follows; l. In the cranium, the cleft children had significantly shorter posterior cranial base length (S-Ba) and total antero-posterior cranial base length (N-Ba) (P<0.05). 2. In the upper face, the cleft children had significantly shorter upper anterior facial height (N-ANS) and upper posterior facial height (Ptm'-SNL) (P<0.05). 3. In the lower face, the cleft children had significantly shorter antero-posterior mandibular length (Pog-Ar) and antero-posterior mandibular body length (Pog-Go) (P<0.05). 4. In the facial profile, the cleft children had significantly shorter total facial height (N-Me) and posterior facial height (S-Go) (P<0.05).

A comparative study of craniofacial morphology of cleft lip children with or without palate

International Nuclear Information System (INIS)

Cho, Su Beom; Kim, Young Ju; Koh, Kwang Joon

1995-01-01

The purpose of this study was to determine whether any difference existed in craniofacial morphology between cleft children and normal subjects. Thirty three measurements of the various regions of cranium and face were obtained from lateral cephalometric radiograms in 40 cleft children (27 males, 13 females) and 40 normal subjects (23 males, 17 females) in our dental hospital from Jan. 1988 to Dec. 1995. The measurements were compared with those in control subjects who had no history of craniofacial abnormalities.. The obtained results were as follows; l. In the cranium, the cleft children had significantly shorter posterior cranial base length (S-Ba) and total antero-posterior cranial base length (N-Ba) (P<0.05). 2. In the upper face, the cleft children had significantly shorter upper anterior facial height (N-ANS) and upper posterior facial height (Ptm'-SNL) (P<0.05). 3. In the lower face, the cleft children had significantly shorter antero-posterior mandibular length (Pog-Ar) and antero-posterior mandibular body length (Pog-Go) (P<0.05). 4. In the facial profile, the cleft children had significantly shorter total facial height (N-Me) and posterior facial height (S-Go) (P<0.05).

Kinetic study of the interaction of glutathione with four antitumor disulfides: possible mechanism for cellular glutathione depletion.

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Kirkpatrick, D L

1989-01-01

The reactions between the cellular tripeptide, glutathione (GSH) and four disulfide derivatives of 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) (compounds 1-4) were studied kinetically. The decyl and phenyl derivatives of 6-MP and 6-TG were reacted with GSH in phosphate buffer (pH 7.4 or 6.0) at 25.0 degrees C and were monitored spectrophotometrically by observing the release of 6-MP and 6-TG. Second order kinetics were observed, with rate constants of 142, 564, 4174 and 429 M-1 s-1 being measured for compounds 1-4, respectively. When the reactions were carried out in the presence of GSH-S-transferase the rates were enhanced 1.3-5.4 times those observed in the absence of enzyme. Products of the reactions were isolated by chromatography and tentatively identified by TLC or fast atom bombardment mass spectrometry. It was observed that GSH reacted with each disulfide in a 1:1 manner, forming a mixed disulfide between GSH and decanethiol or thiophenol while releasing 6-MP or 6-TG. It was concluded that the reported depletion of GSH from EMT6 cells after exposure to these disulfides could be due to their reaction with GSH, and the formation of the mixed disulfides.

Photo-oxidation of 6-thioguanine by UVA: the formation of addition products with low molecular weight thiol compounds.

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Ren, Xiaolin; Xu, Yao-Zhong; Karran, Peter

2010-01-01

The thiopurine, 6-thioguanine (6-TG) is present in the DNA of patients treated with the immunosuppressant and anticancer drugs azathioprine or mercaptopurine. The skin of these patients is selectively sensitive to UVA radiation-which comprises >90% of the UV light in incident sunlight-and they suffer high rates of skin cancer. UVA irradiation of DNA 6-TG produces DNA lesions that may contribute to the development of cancer. Antioxidants can protect 6-TG against UVA but 6-TG oxidation products may undergo further reactions. We characterize some of these reactions and show that addition products are formed between UVA-irradiated 6-TG and N-acetylcysteine and other low molecular weight thiol compounds including β-mercaptoethanol, cysteine and the cysteine-containing tripeptide glutathione (GSH). GSH is also adducted to 6-TG-containing oligodeoxynucleotides in an oxygen- and UVA-dependent nucleophilic displacement reaction that involves an intermediate oxidized 6-TG, guanine sulfonate (G(SO3) ). These photochemical reactions of 6-TG, particularly the formation of a covalent oligodeoxynucleotide-GSH complex, suggest that crosslinking of proteins or low molecular weight thiol compounds to DNA may be a previously unrecognized hazard in sunlight-exposed cells of thiopurine-treated patients. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

Fermentation characteristics and angiotensin I-converting enzyme-inhibitory activity of Lactobacillus helveticus isolate H9 in cow milk, soy milk, and mare milk.

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Wang, Jicheng; Li, Changkun; Xue, Jiangang; Yang, Jie; Zhang, Qing; Zhang, Heping; Chen, Yongfu

2015-06-01

Lactobacillus helveticus isolate H9 demonstrated high angiotensin I-converting enzyme (ACE)-inhibitory activity in previous research. Here, we evaluated the fermentation characteristics (pH, titratable acidity, free amino nitrogen, and viable bacterial counts), ACE-inhibitory activity, and contents of Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) peptides of stored yogurt (4°C for 28 d) fermented by L. helveticus isolate H9 (initially inoculated at 4 concentrations), from cow, mare, and soy milks. During storage, the pH and titratable acidity remained stable in yogurts produced from all milk types and all inoculation concentrations. The viable bacterial counts in all stored yogurts ranged between 10(6.72) and 10(8.59) cfu/g. The highest ACE-inhibitory activity (70.9-74.5%) was achieved at inoculation concentrations of 5×10(6) cfu/mL. The ACE-inhibitory tripeptides VPP and IPP as determined by ultra-performance liquid chromatography-tandem mass spectrometry were not produced in yogurt made from soy milk or mare milk. These evaluations indicate that L. helveticus H9 has good probiotic properties and would be a promising candidate for production of fermented food with probiotic properties. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A Macrocyclic Agouti-Related Protein/[Nle4,DPhe7]α-Melanocyte Stimulating Hormone Chimeric Scaffold Produces Subnanomolar Melanocortin Receptor Ligands.

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Ericson, Mark D; Freeman, Katie T; Schnell, Sathya M; Haskell-Luevano, Carrie

2017-01-26

The melanocortin system consists of five receptor subtypes, endogenous agonists, and naturally occurring antagonists. These receptors and ligands have been implicated in numerous biological pathways including processes linked to obesity and food intake. Herein, a truncation structure-activity relationship study of chimeric agouti-related protein (AGRP)/[Nle4,DPhe7]α-melanocyte stimulating hormone (NDP-MSH) ligands is reported. The tetrapeptide His-DPhe-Arg-Trp or tripeptide DPhe-Arg-Trp replaced the Arg-Phe-Phe sequence in the AGRP active loop derivative c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro], where Xxx was the native Asn of AGRP or a diaminopropionic (Dap) acid residue previously shown to increase antagonist potency at the mMC4R. The Phe, Ala, and Dap/Asn residues were successively removed to generate a 14-member library that was assayed for agonist activity at the mouse MC1R, MC3R, MC4R, and MC5R. Two compounds possessed nanomolar agonist potency at the mMC4R, c[Pro-His-DPhe-Arg-Trp-Asn-Ala-Phe-DPro] and c[Pro-His-DPhe-Arg-Trp-Dap-Ala-DPro], and may be further developed to generate novel melanocortin probes and ligands for understanding and treating obesity.

Transition-state characterization: a new approach combining inhibitor analogues and variation in enzyme structure.

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Phillips, M A; Kaplan, A P; Rutter, W J; Bartlett, P A

1992-02-04

A new strategy of potentially broad application for probing transition-state (TS) analogy in enzymatic systems is described in this paper. The degree to which a series of phosphonate inhibitors act as TS analogues of rat carboxypeptidase A1 has been determined for the wild-type enzyme, for the R127K, R127M, and R127A mutants, and for the R127A mutant in the presence of 0.5 M guanidine hydrochloride. The impact that the mutations have on the inverse second-order rate constants (Km/kcat) for substrate hydrolysis is mirrored by the effect on the inhibition constants (Ki) for the corresponding phosphonate inhibitors. These results demonstrate that the phosphonate moiety mimics some of the electronic as well as the geometric characteristics of the TS. A similar but distinctly separate correlation is observed for tripeptide analogues in comparison to analogues of the dipeptide Cbz-Gly-Phe, reflecting an anomalous mode of binding for the latter system. The selective rate increases and corresponding enhancement in inhibitor binding observed on addition of 0.5 M guanidine hydrochloride to the R127A mutant indicate that the exogenous cation can assume the role played by Arg-127 in stabilizing the TS and in providing substrate selectivity at the P2 position.

Randomized, Split-Face/Décolleté Comparative Trial of Procedure Enhancement System for Fractional non-Ablative Laser Resurfacing Treatment.

Science.gov (United States)

Robinson, Deanne Mraz; Frulla, Ashton P

2017-07-01

INTRODUCTION: A topical proprietary procedural enhancement system (PES) containing a combination of active ingredients including a tripeptide and hexapeptide (TriHex Technology™, Alastin Procedure Enhancement Invasive System, ALASTIN Skincare™, Inc., Carlsbad, CA) has been used successfully to aid in healing and improve symptomatology following resurfacing procedures. METHODS: PES (Gentle Cleanser, Regenerating Skin Nectar with TriHex Technology™, Ultra Nourishing Moisturizer with TriHex Technology™, Soothe + Protect Recovery Balm, Broad Spectrum 30+ Sunscreen) was compared to a basic regimen (Aquaphor™, Cerave™ cleanser, Vanicream™, Alastin Broad Spectrum 30+ Sunscreen) in a split face/ décolleté trial following fractional non-ablative thulium-doped resurfacing treatment to the face or décolleté. The skin was pre-conditioned and treated during and after the procedure using the two regimens. RESULTS: A blinded investigator rated the PES statistically superior to the basic regimen on healing post-laser treatment on day 4 based on lentigines, texture, and Global Skin Quality. Subjects also reported 'better looking and feeling' skin on the PES side. CONCLUSION: PES appears to improve healing post-non ablative thulium-doped resurfacing treatment to the face/décolleté in comparison with standard of care. J Drugs Dermatol. 2017;16(7):707-710..

Preparation and comparative evaluation of 99m Tc-HYNIC-cNGR and 99m Tc-HYNIC-PEG2 -cNGR as tumor-targeting molecular imaging probes.

Science.gov (United States)

Vats, Kusum; Satpati, Drishty; Sharma, Rohit; Kumar, Chandan; Sarma, Haladhar Dev; Banerjee, Sharmila

2018-02-01

The tripeptide sequence asparagine-glycine-arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC-c(NGR) and HYNIC-PEG 2 -c(NGR), were synthesized, radiolabeled with 99m Tc, and evaluated in CD13-positive human fibrosarcoma HT-1080 tumor xenografts. The radiotracers, 99m Tc-HYNIC-c(NGR) and 99m Tc-HYNIC-PEG 2 -c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being -2.33 ± 0.05 and -2.61 ± 0.08. The uptake of 2 radiotracers 99m Tc-HYNIC-c(NGR) and 99m Tc-HYNIC-PEG 2 -c(NGR) was similar in nude mice bearing human fibrosarcoma HT-1080 tumor xenografts, which was significantly reduced (P Tc-labeled HYNIC peptide could not be modulated through introduction of PEG 2 unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention. Copyright © 2017 John Wiley & Sons, Ltd.

The mechanism of cysteine detection in biological media by means of vanadium oxide nanoparticles

International Nuclear Information System (INIS)

Bezerra, A. G.; Barison, A.; Oliveira, V. S.; Foti, L.; Krieger, M. A.; Dhalia, R.; Viana, I. F. T.; Schreiner, W. H.

2012-01-01

We report on the interaction of vanadate nanoparticles, produced using the laser ablation in liquids synthesis, with cysteine in biological molecules. Cysteine is a very important amino acid present in most proteins, but also because cysteine and the tripeptide glutathione are the main antioxidant molecules in our body system. Detailed UV–Vis absorption spectra and dynamic light scattering measurements were done to investigate the detection of cysteine in large biological molecules. The intervalence band of the optical absorption spectra shows capability for quantitative cysteine sensing in the μM range in biological macromolecules. Tests included cytoplasmic repetitive antigen and flagellar repetitive antigen proteins of the Trypanosoma cruzi protozoa, as well as the capsid p24 proteins from Human Immunodeficiency Virus type 1 and type 2. Detailed NMR measurements for hydrogen, carbon, and vanadium nuclei show that cysteine in contact with the vanadate looses hydrogen of the sulphydryl side chain, while the vanadate is reduced. The subsequent detachment of two deprotonated molecules to form cystine and the slow return to the vanadate complete the oxidation–reduction cycle. Therefore, the vanadate acts as a charge exchanging catalyst on cysteine to form cystine. The NMR results also indicate that the nanoparticles are not formed by the common orthorhombic V 2 O 5 form.

GHK-Cu may Prevent Oxidative Stress in Skin by Regulating Copper and Modifying Expression of Numerous Antioxidant Genes

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Loren Pickart

2015-07-01

Full Text Available The copper binding tripeptide GHK (glycyl-l-histidyl-l-lysine is a naturally occurring plasma peptide that significantly declines during human aging. It has been established that GHK:Copper(2+ improves wound healing and tissue regeneration and stimulates collagen and decorin production. GHK-Cu also supports angiogenesis and nerve outgrowth, improves the condition of aging skin and hair, and possesses antioxidant and anti-inflammatory effects. In addition, it increases cellular stemness and secretion of trophic factors by mesenchymal stem cells. GHK’s antioxidant actions have been demonstrated in vitro and in animal studies. They include blocking the formation of reactive oxygen and carbonyl species, detoxifying toxic products of lipid peroxidation such as acrolein, protecting keratinocytes from lethal Ultraviolet B (UVB radiation, and blocking hepatic damage by dichloromethane radicals. In recent studies, GHK has been found to switch gene expression from a diseased state to a healthier state for certain cancers and for chronic obstructive pulmonary disease (COPD. The Broad Institute’s Connectivity Map indicated that GHK induces a 50% or greater change of expression in 31.2% of human genes. This paper reviews biological data demonstrating positive effects of GHK in skin and proposes interaction with antioxidant-related genes as a possible explanation of its antioxidant activity.

Molecular characterization of amino acid deletion in VP1 (1D) protein and novel amino acid substitutions in 3D polymerase protein of foot and mouth disease virus subtype A/Iran87.

Science.gov (United States)

Esmaelizad, Majid; Jelokhani-Niaraki, Saber; Hashemnejad, Khadije; Kamalzadeh, Morteza; Lotfi, Mohsen

2011-12-01

The nucleotide sequence of the VP1 (1D) and partial 3D polymerase (3D(pol)) coding regions of the foot and mouth disease virus (FMDV) vaccine strain A/Iran87, a highly passaged isolate (~150 passages), was determined and aligned with previously published FMDV serotype A sequences. Overall analysis of the amino acid substitutions revealed that the partial 3D(pol) coding region contained four amino acid alterations. Amino acid sequence comparison of the VP1 coding region of the field isolates revealed deletions in the highly passaged Iranian isolate (A/Iran87). The prominent G-H loop of the FMDV VP1 protein contains the conserved arginine-glycine-aspartic acid (RGD) tripeptide, which is a well-known ligand for a specific cell surface integrin. Despite losing the RGD sequence of the VP1 protein and an Asp(26)→Glu substitution in a beta sheet located within a small groove of the 3D(pol) protein, the virus grew in BHK 21 suspension cell cultures. Since this strain has been used as a vaccine strain, it may be inferred that the RGD deletion has no critical role in virus attachment to the cell during the initiation of infection. It is probable that this FMDV subtype can utilize other pathways for cell attachment.

Metabolic fate of lactoferricin-based antimicrobial peptides: effect of truncation and incorporation of amino acid analogs on the in vitro metabolic stability.

Science.gov (United States)

Svenson, Johan; Vergote, Valentijn; Karstad, Rasmus; Burvenich, Christian; Svendsen, John S; De Spiegeleer, Bart

2010-03-01

A series of promising truncated antibacterial tripeptides derived from lactoferricin has been prepared, and their in vitro metabolic stability in the main metabolic compartments, plasma, liver, kidney, stomach, duodenum, and brain, has been investigated for the first time. The potential stabilizing effect of truncation, C-terminal capping, and introduction of the bulky synthetic amino acid biphenylalanine is also investigated. The drug-like peptides displayed large differences in half-lives in the different matrixes ranging from 4.2 min in stomach and duodenum to 355.9 min in liver. Kinetic analysis of the metabolites revealed that several different degrading enzymes simultaneously target the different peptide bonds and that the outcome of the tested strategies to increase the stability is clearly enzyme-specific. Some of the metabolic enzymes even prefer the synthetic modifications incorporated over the natural counterparts. Collectively, it is shown that the necessary antibacterial pharmacophore generates compounds that are not only potent antibacterial peptides, but excellent substrates for the main degrading enzymes. All the amide bonds are thus rapidly targeted by different enzymes despite the short peptidic sequences of the tested compounds. Hence, our results illustrate that several structural changes are needed before these compounds can be considered for oral administration. Strategies to overcome such metabolic challenges are discussed.

Triazole RGD antagonist reverts TGFβ1-induced endothelial-to-mesenchymal transition in endothelial precursor cells.

Science.gov (United States)

Bianchini, Francesca; Peppicelli, Silvia; Fabbrizzi, Pierangelo; Biagioni, Alessio; Mazzanti, Benedetta; Menchi, Gloria; Calorini, Lido; Pupi, Alberto; Trabocchi, Andrea

2017-01-01

Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident. In this study, we present a class of triazole-derived RGD antagonists that interact with αvβ3 integrin. Above different compounds, the RGD-2 specifically interferes with integrin-dependent TGFβ1 EndoMT in Endothelial Colony-Forming Cells (ECPCs) derived from circulating Endothelial Precursor Cells (ECPCs). The RGD-2 decreases the amount of membrane-associated TGFβ1, and reduces both ALK5/TGFβ1 type I receptor expression and Smad2 phosphorylation in ECPCs. We found that RGD-2 antagonist reverts EndoMT, reducing α-smooth muscle actin (α-SMA) and vimentin expression in differentiated ECPCs. Our results outline the critical role of integrin in fibrosis progression and account for the opportunity of using integrins as target for anti-fibrotic therapeutic treatment.

Quantitative autoradiography of TRH receptors and radioimmunoassay of TRH in the cat central nervous system

International Nuclear Information System (INIS)

Bogin, R.M.; Kreider, M.S.; Caine, S.B.; Pack, A.I.; Winokur, A.

1986-01-01

In the cat, microinjection of Thyrotropin-Releasing Hormone (TRH) into certain areas of the central nervous system (CNS) changes ventilation and cardiovascular variables. To initiate a more systematic investigation of these effects, they undertook a study to determine the location of TRH and its receptors in the cat CNS. Using techniques previously described from the laboratory, quantitative autoradiograms for TRH receptors of the cat brain were produced; additional specimens were dissected, and radioimmunoassay for TRH was performed. Heterogeneous distribution of receptors was observed in the cat brain. In the forebrain, large quantities of TRH receptors were found in amygdala, hippocampus, claustrum, pyriform nucleus, and tuberculum olfactorium. In the brainstem, high concentrations were localized to the dorsal motor nucleus of the vagus, the hypoglossal nucleus, and the periaqueductal grey. The cerebellum contained few receptors. The largest quantities of the TRH tripeptide were noted in the hypothalamus and septum, with substantial amounts also obtained from the olfactory bulb, corpus striatum, and thalamus. The results demonstrate that the distribution of TRH and TRH receptors in the cat brain is very similar to that previously described in the rat and human brain. They provide a basis for exploring the physiological and pharmacological effects of TRH in cats

Photo-Crosslinking Induced Geometric Restriction Controls the Self-Assembly of Diphenylalanine Based Peptides

International Nuclear Information System (INIS)

Tie Zuo-Xiu; Qin Meng; Zou Da-Wei; Cao Yi; Wang Wei

2011-01-01

The diphenylalanine (FF) motif has been widely used in the design of peptides that are capable of forming various ordered structures, such as nanotubes, nanospheres and hydrogels. In these assemblies, FF based peptides adopt an antiparallel structure and are stabilized by π — π stacking among the phenyl groups. Here we show that assembly of FF-based peptides can be controlled by their geometric restrictions. Using tripeptide FFY (L-Phe-L-Phe-L-Tyr) as an example, we demonstrate that photo-crosslinking of C-terminal tyrosine can impose a geometric restriction to the formation of an antiparallel structure, leading to a structural change of the assemblies from nanosphere to amorphous. This finding is confirmed using far-UV circular dichroism, Fourier transform infrared spectroscopy and atomic force microscopy. Based on such a mechanism, we are able to control the gel-sol transition of Fmoc-FFY using the geometric restriction induced by photo-crosslinking of C-terminal tyrosine groups. We believe that geometric restriction should be considered as an important factor in the design of peptide-based materials. It can also be implemented as a useful strategy for the construction of environment-responsive 'smart' materials. (cross-disciplinary physics and related areas of science and technology)

Importance of asparagine on the conformational stability and chemical reactivity of selected anti-inflammatory peptides

Energy Technology Data Exchange (ETDEWEB)

Soriano-Correa, Catalina, E-mail: csorico@comunidad.unam.mx [Química Computacional, Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Autónoma de México (UNAM), Iztapalapa, C.P. 09230 México, D.F. (Mexico); Barrientos-Salcedo, Carolina [Laboratorio de Química Médica y Quimiogenómica, Facultad de Bioanálisis Campus Veracruz-Boca del Río, Universidad Veracruzana, C.P. 91700 Veracruz (Mexico); Campos-Fernández, Linda; Alvarado-Salazar, Andres [Química Computacional, Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Autónoma de México (UNAM), Iztapalapa, C.P. 09230 México, D.F. (Mexico); Esquivel, Rodolfo O. [Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa (UAM-Iztapalapa), C.P. 09340 México, D.F. (Mexico)

2015-08-18

Highlights: • Asparagine plays an important role to anti-inflammatory effect of peptides. • The electron-donor substituent groups favor the formation of the hydrogen bonds, which contribute in the structural stability of peptides. • Chemical reactivity and the physicochemical features are crucial in the biological functions of peptides. - Abstract: Inflammatory response events are initiated by a complex series of molecular reactions that generate chemical intermediaries. The structure and properties of peptides and proteins are determined by the charge distribution of their side chains, which play an essential role in its electronic structure and physicochemical properties, hence on its biological functionality. The aim of this study was to analyze the effect of changing one central amino acid, such as substituting asparagine for aspartic acid, from Cys–Asn–Ser in aqueous solution, by assessing the conformational stability, physicochemical properties, chemical reactivity and their relationship with anti-inflammatory activity; employing quantum-chemical descriptors at the M06-2X/6-311+G(d,p) level. Our results suggest that asparagine plays a more critical role than aspartic acid in the structural stability, physicochemical features, and chemical reactivity of these tripeptides. Substituent groups in the side chain cause significant changes on the conformational stability and chemical reactivity, and consequently on their anti-inflammatory activity.

Poly-Ub-substrate-degradative activity of 26S proteasome is not impaired in the aging rat brain.

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Carolin Giannini

Full Text Available Proteostasis is critical for the maintenance of life. In neuronal cells an imbalance between protein synthesis and degradation is thought to be involved in the pathogenesis of neurodegenerative diseases during aging. Partly, this seems to be due to a decrease in the activity of the ubiquitin-proteasome system, wherein the 20S/26S proteasome complexes catalyse the proteolytic step. We have characterised 20S and 26S proteasomes from cerebrum, cerebellum and hippocampus of 3 weeks old (young and 24 month old (aged rats. Our data reveal that the absolute amount of the proteasome is not dfferent between both age groups. Within the majority of standard proteasomes in brain the minute amounts of immuno-subunits are slightly increased in aged rat brain. While this goes along with a decrease in the activities of 20S and 26S proteasomes to hydrolyse synthetic fluorogenic tripeptide substrates from young to aged rats, the capacity of 26S proteasomes for degradation of poly-Ub-model substrates and its activation by poly-Ub-substrates is not impaired or even slightly increased in brain of aged rats. We conclude that these alterations in proteasome properties are important for maintaining proteostasis in the brain during an uncomplicated aging process.

Fractionation of yeast extract by nanofiltration process to assess key compounds involved in CHO cell culture improvement.

Science.gov (United States)

Mosser, Mathilde; Kapel, Romain; Chevalot, Isabelle; Olmos, Eric; Marc, Ivan; Marc, Annie; Oriol, Eric

2015-01-01

Yeast extract (YE) is known to greatly enhance mammalian cell culture performances, but its undefined composition decreases process reliability. Accordingly, in the present study, the nature of YE compounds involved in the improvement of recombinant CHO cell growth and IgG production was investigated. First, the benefits of YE were verified, revealing that it increased maximal concentrations of viable cells and IgG up to 73 and 60%, respectively compared to a reference culture. Then, the analyses of YE composition highlighted the presence of molecules such as amino acids, vitamins, salts, nucleobase, and glucose that were contained in reference medium, while others including peptides, trehalose, polysaccharides, and nucleic acids were not. Consequently, YE was fractionated by a nanofiltration process to deeper evaluate its effects on CHO cell cultures. The YE molecules already contained in reference medium were mainly isolated in the permeate fraction together with trehalose and short peptides, while other molecules were concentrated in the retentate. Permeate, which was free of macromolecules, exhibited a similar positive effect than raw YE on maximal concentrations. Additional studies on cell energetic metabolism underlined that dipeptides and tripeptides in permeate were used as an efficient source of nitrogenous substrates. © 2015 American Institute of Chemical Engineers.

Individual variability in the venom proteome of juvenile Bothrops jararaca specimens.

Science.gov (United States)

Dias, Gabriela S; Kitano, Eduardo S; Pagotto, Ana H; Sant'anna, Sávio S; Rocha, Marisa M T; Zelanis, André; Serrano, Solange M T

2013-10-04

Snake venom proteomes/peptidomes are highly complex and subject to ontogenetic changes. Individual variation in the venom proteome of juvenile snakes is poorly known. We report the proteomic analysis of venoms from 21 juvenile specimens of Bothrops jararaca of different geographical origins and correlate it with the evaluation of important venom features. Individual venoms showed similar caseinolytic activities; however, their amidolytic activities were significantly different. Rather intriguingly, plasma coagulant activity showed remarkable variability among the venoms but not the prothrombin-activating activity. LC-MS analysis showed significant differences between venoms; however, an interesting finding was the ubiquitous presence of the tripeptide ZKW, an endogenous inhibitor of metalloproteinases. Electrophoretic profiles of proteins submitted to reduction showed significant variability in total proteins, glycoproteins, and in the subproteomes of proteinases. Moreover, identification of differential bands revealed variation in most B. jararaca toxin classes. Profiles of venoms analyzed under nonreducing conditions showed less individual variability and identification of proteins in a conserved band revealed the presence of metalloproteinases and l-amino acid oxidase as common components of these venoms. Taken together, our findings suggest that individual venom proteome variability in B. jararaca exists from a very early animal age and is not a result of ontogenetic and diet changes.

The mechanism of cysteine detection in biological media by means of vanadium oxide nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Bezerra, A. G. [Universidade Tecnologica Federal do Parana, Departamento Academico de Fisica (Brazil); Barison, A. [Universidade Federal do Parana, Departamento de Quimica (Brazil); Oliveira, V. S. [Universidade Federal do Parana, Departamento de Fisica (Brazil); Foti, L.; Krieger, M. A. [Fundacao Oswaldo Cruz, Instituto de Biologia Molecular do Parana (Brazil); Dhalia, R.; Viana, I. F. T. [Fundacao Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhaes (Brazil); Schreiner, W. H., E-mail: wido@fisica.ufpr.br [Universidade Federal do Parana, Departamento de Fisica (Brazil)

2012-09-15

We report on the interaction of vanadate nanoparticles, produced using the laser ablation in liquids synthesis, with cysteine in biological molecules. Cysteine is a very important amino acid present in most proteins, but also because cysteine and the tripeptide glutathione are the main antioxidant molecules in our body system. Detailed UV-Vis absorption spectra and dynamic light scattering measurements were done to investigate the detection of cysteine in large biological molecules. The intervalence band of the optical absorption spectra shows capability for quantitative cysteine sensing in the {mu}M range in biological macromolecules. Tests included cytoplasmic repetitive antigen and flagellar repetitive antigen proteins of the Trypanosoma cruzi protozoa, as well as the capsid p24 proteins from Human Immunodeficiency Virus type 1 and type 2. Detailed NMR measurements for hydrogen, carbon, and vanadium nuclei show that cysteine in contact with the vanadate looses hydrogen of the sulphydryl side chain, while the vanadate is reduced. The subsequent detachment of two deprotonated molecules to form cystine and the slow return to the vanadate complete the oxidation-reduction cycle. Therefore, the vanadate acts as a charge exchanging catalyst on cysteine to form cystine. The NMR results also indicate that the nanoparticles are not formed by the common orthorhombic V{sub 2}O{sub 5} form.

Detecting the formation of products of radiolysis of tryptophan in foods rich in protein and irradiated with γ rays

International Nuclear Information System (INIS)

Kleeberg, K.K.; Wickern, B. van; Simat, T.J.; Steinhart, H.

1999-01-01

N-formyl kynurenine (NFK), OIA and the four hydroxytryptophan isomers (4-, 5-, 6- and 7-OH-TRP) were found as the major radiolysis products in γ-ray irradiated solutions containing tryptophan, in tripeptides and lysozyme. Their identification was achieved by enzymatic hydrolysis with pronase E under mild conditions (40 C, 30-60 min), applying electrochemical methods and RP-HPLC and uv fluroscence methods. Highly significant dissimilarity of results was shown for all the radiolysis products found in the specimens irradiated with 1.3 or 5 kGy and in non-irradiated samples. For release of the radiolysis products from protein-rich foods (egg white, white chicken meat, North Sea shrimps), a two-stage enzymatic hydrolytic process was developed, using proteinase K and carboxypeptidase A for egg white and chicken meat, and proteinase K and pronase E for the shrimps. The four OH-TRP isomers could be detected and quantified in all specimens. The contents varied from 0.02 to 1.97 mg/kg of proteine. Significant deviation of results between irradiated and non-irradiated specimens of egg white and chicken meat could be detected as from an applied dose of 3 kGy. In the shrimps, deviations were evident only at applied doses of 5 kGy. (orig./CB) [de