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Sample records for tetra-trico peptide repeat

  1. Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs

    International Nuclear Information System (INIS)

    Shi Weiguo; Qi Zhi; Pan Chungen; Xue Na; Debnath, Asim K.; Qie Jiankun; Jiang Shibo; Liu Keliang

    2008-01-01

    The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins

  2. Nephrotoxicity in mice after repeated imaging using 111In- labeled peptides

    NARCIS (Netherlands)

    M.L. Melis (Marleen); E. Vegt (Erik); M.W. Konijnenberg (Mark); M. de Visser (Monique); M. Bijster (Magda); M. Vermeij (Marcel); E.P. Krenning (Eric); O.C. Boerman (Otto); M. de Jong (Marion)

    2010-01-01

    textabstractWe determined the renal radiation dose of a series of111Inlabeled peptides using animal SPECT. Because the animals' health deteriorated, renal toxicity was assessed. Methods: Wild-type and megalin-deficient mice were imaged repeatedly at 3- to 6-wk intervals to quantify renal retention

  3. Characterisation and evaluation of antiviral recombinant peptides based on the heptad repeat regions of NDV and IBV fusion glycoproteins

    International Nuclear Information System (INIS)

    Wang Xiaojia; Li Chuangen; Chi Xiaojing; Wang Ming

    2011-01-01

    Mixed virus infections can cause livestock losses that are more devastating than those caused by single virus infections. Newcastle disease virus (NDV) and infectious bronchitis virus (IBV), serious threats to the poultry industry, can give rise to complex mixed infections that hinder diagnosis and prevention. In this study, we show that newly designed peptides, which are based on the heptad repeat (HR) region of the fusion glycoproteins from NDV and IBV, have more potent antiviral activity than the mother HR peptides. Plaque formation and chicken embryo infectivity assays confirmed these results. The novel peptides completely inhibited single virus infections and mixed infections caused by NDV and IBV. Furthermore, we assessed cell toxicity and possible targets for the peptides, thereby strengthening the notion that HR2 is an attractive site for therapeutic intervention. These results suggest the possibility of designing a relatively broad-spectrum class of antiviral peptides that can reduce the effects of mixed-infections.

  4. Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides.

    NARCIS (Netherlands)

    B.J. Bosch (Berend Jan); B.E.E. Martina (Byron); R. van der Zee (Ruurd); J. Lepault (Jean); B.J. Haijema; C. Versluis (Cees); A.J.R. Heck (Albert); R. de Groot (Ronald); A.D.M.E. Osterhaus (Albert); P.J.M. Rottier (Peter)

    2004-01-01

    textabstractThe coronavirus SARS-CoV is the primary cause of the life-threatening severe acute respiratory syndrome (SARS). With the aim of developing therapeutic agents, we have tested peptides derived from the membrane-proximal (HR2) and membrane-distal (HR1) heptad repeat region of the spike

  5. Mutations in the fusion peptide and heptad repeat regions of the Newcastle disease virus fusion protein block fusion.

    OpenAIRE

    Sergel-Germano, T; McQuain, C; Morrison, T

    1994-01-01

    Nonconservative mutations were introduced by site-specific mutagenesis into the fusion peptide and the adjacent heptad repeat region of the fusion protein of Newcastle disease virus in order to determine the role of both regions in the fusion activity of the protein. Mutations in both regions that allowed for proper folding and intracellular transport of the protein blocked the fusion activity of the protein when assayed in the presence of the hemagglutinin-neuraminidase protein.

  6. The central repeat domain 1 of Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) prevents cis MHC class I peptide presentation

    International Nuclear Information System (INIS)

    Kwun, Hyun Jin; Ramos da Silva, Suzane; Qin Huilian; Ferris, Robert L.; Tan Rusung; Chang Yuan; Moore, Patrick S.

    2011-01-01

    KSHV LANA1, a latent protein expressed during chronic infection to maintain a viral genome, inhibits major histocompatibility complex class I (MHC I) peptide presentation in cis as a means of immune evasion. Through deletional cloning, we localized this function to the LANA1 central repeat 1 (CR1) subregion. Other CR subregions retard LANA1 translation and proteasomal processing but do not markedly inhibit LANA1 peptide processing by MHC I. Inhibition of proteasomal processing ablates LANA1 peptide presentation. Direct expression of LANA1 within the endoplasmic reticulum (ER) overcomes CR1 inhibition suggesting that CR1 acts prior to translocation of cytoplasmic peptides into the ER. By physically separating CR1 from other subdomains, we show that LANA1 evades MHC I peptide processing by a mechanism distinct from other herpesviruses including Epstein-Barr virus (EBV). Although LANA1 and EBV EBNA1 are functionally similar, they appear to use different mechanisms to evade host cytotoxic T lymphocyte surveillance.

  7. Coronavirus escape from heptad repeat 2 (HR2)-derived peptide entry inhibition as a result of mutations in the HR1 domain of the spike fusion protein

    NARCIS (Netherlands)

    Bosch, Berend Jan; Rossen, John W. A.; Bartelink, Willem; Zuurveen, Stephanie J.; de Haan, Cornelis A. M.; Duquerroy, Stephane; Boucher, Charles A. B.; Rottier, Peter J. M.

    Peptides based on heptad repeat (HR) domains of class I viral fusion proteins are considered promising antiviral drugs targeting virus cell entry. We have analyzed the evolution of the mouse hepatitis coronavirus during multiple passaging in the presence of an HR2-based fusion inhibitor.

  8. B-type natriuretic peptide (BNP serum levels in rats after forced repeated swimming stress

    Directory of Open Access Journals (Sweden)

    Almira Hadžovic-Džuvo

    2011-02-01

    Full Text Available Aim To estimate the effects of forced repeated swimming stress on BNP serum levels in rats. Methods Adult male Wistar rats weighting between 280-330 g were divided into two groups: control group (n =8 and stress group (n =8. Rats in the stress group were exposed to forced swimming stress daily, for 7 days. The rats were forced to swim in plastic tanks (90 cm wide, 120 cm deep containing tap water (temperature ca. 25°C. The depth of water was 40 cm. Duration of each swimming session progressively increased from 10 minutes on the irst day to 40 minutes on days 6 and 7. Rats were sacriiced and blood was drawn from abdominal aorta for BNP analysis immediately after the last swimming session. B-type natriuretic serum level was determined by ELISA method using RAT BNP-32 kit (Phoenix Pharmaceutical Inc.. Results There was no statistically signiicant difference between mean BNP serum level in the stress group after the swimming period (0.81±0.14 ng/ml as compared to the unstressed group of rats (0.8 ±0.08ng/ml. After the swimming period mean body weight slightly decreased in the stress group in comparison with values before stress period (296.3 g vs.272.8 g, but this difference was not statistically signiicant. The stress period had no inluence on food intake in the stress rat group. Conclusion The workload consisting of 40-minutes long swimming session is not suficient to provoke BNP release from myocardium in rats.

  9. Peptide YY Causes Apathy-Like Behavior via the Dopamine D2 Receptor in Repeated Water-Immersed Mice.

    Science.gov (United States)

    Yamada, Chihiro; Mogami, Sachiko; Kanno, Hitomi; Hattori, Tomohisa

    2018-02-10

    Apathy is observed across several neurological and psychiatric conditions; however, its pathogenesis remains unclear. We clarified the involvement of brain-gut signaling in the disruption of goal-directed behavior. Male C57BL/6J mice were exposed to water immersion (WI) stress for 3 days. Food intake and nesting behavior were measured as indexes of motivation. Repeated WI caused decrease in food intake and nesting behavior. Plasma levels of peptide YY (PYY), IL-6, and ratio of dopamine metabolites in the striatum were significantly elevated after WI. PYY and IL-6 administration significantly decreased nesting behavior. The reductions in feeding and nesting behavior were blocked by PYY receptor (Y2R) antagonist or dopamine agonist. The ameliorative effect of the Y2R antagonist was diminished by the dopamine D2 receptor (D2R) antagonist. The reduction in goal-directed behavior is associated with dysfunction of D2R signaling via increased peripheral PYY, suggesting that PYY antagonism is a novel candidate for decline of motivation in several depressive diseases.

  10. Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex

    Directory of Open Access Journals (Sweden)

    Craig ePrzysiecki

    2012-11-01

    Full Text Available Antibodies that neutralize infectivity of malaria sporozoites target the central repeat region of the circumsporozoite (CS protein, which in Plasmodium falciparum is comprised primarily of 30-40 tandem NANP tetramer repeats. We evaluated immunogenicity of an alum-adsorbed (NANP6 peptide conjugated to an outer membrane protein complex (OMPC derived from Neisseria meningitidis, a carrier protein used in a licensed H. influenzae pediatric vaccine. Mice immunized with alum-adsorbed (NANP6-OMPC, with or without Iscomatrix© as co-adjuvant, developed high levels of anti-repeat peptide antibody that inhibited in vitro invasion of human hepatoma cells by transgenic P. berghei sporozoites that express P. falciparum CS repeats (PfPb. Inhibition of sporozoite invasion in vitro correlated with in vivo resistance to challenge by the bites of PfPb infected mosquitoes. Challenged mice had > 90% reduction of hepatic stage parasites as measured by real-time PCR, and either sterile immunity, i.e. no detectable blood stage parasites, or delayed prepatent periods which indicate neutralization of a majority, but not all, sporozoites. Rhesus macaques immunized with two doses of (NANP6-OMPC/MAA formulated with Iscomatrix© developed anti-repeat antibodies that persisted for ~2 years. A third dose of (NANP6-OMPC/MAA+ Iscomatrix© at that time elicited strong anamnestic antibody responses. Rhesus macaque immune sera obtained post second and third dose of vaccine displayed high levels of sporozoite neutralizing activity in vitro that correlated with presence of high anti-repeat antibody titers. These preclinical studies in mice of different MHC haplotypes and a non-human primate support use of CS peptide-OMPC conjugates as a highly immunogenic platform to evaluate CS protective epitopes. Potential pre-erythrocytic vaccines can be combined with sexual blood stage vaccines as a multi-antigen malaria vaccine to block invasion and transmission of Plasmodium parasites

  11. Repeated agouti related peptide (83-132) injections inhibit cocaine-induced locomotor sensitisation, but not via the nucleus accumbens.

    Science.gov (United States)

    Alserda, Edwin; Adan, Roger A H; Ramakers, Geert M J

    2013-11-05

    Drug addiction is a chronic relapsing brain disease for which many of the underlying neuronal mechanisms are yet to be unravelled. There seems to be an interaction between the melanocortin system and drugs of abuse. For instance, infusion of the melanocortin MC4 receptor antagonist SHU9119 (Ac-Nle-cyclo(-Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2) into the nucleus accumbens results in conditioned place avoidance, reduces the amount of lever presses for cocaine and blocks development of cocaine-induced locomotor sensitisation. The aim of this study is to determine whether the induction of locomotor sensitisation to repeated cocaine is inhibited by the melanocortin MC4 receptor inverse agonist Agouti Related Peptide (AgRP83-132). Rats were sensitised to daily cocaine injections for 5 consecutive days and 30 min prior to every daily cocaine injection, rats received an intracerebroventricular (i.c.v.) or intra nucleus accumbens injection with AgRP(83-132) or saline, to determine whether we could inhibit cocaine-induced locomotor sensitisation. We show that i.c.v. injections of AgRP(83-132) inhibit cocaine-induced locomotor sensitisation. This effect is not regulated via the nucleus accumbens, since injecting the melanocortin receptor inverse agonist AgRP(83-132) directly into the nucleus accumbens was unable to inhibit the cocaine-induced locomotor sensitisation. This implicates that the nucleus accumbens is an unlikely site to inhibit the induction of locomotor sensitisation via the melanocortin MC4 receptor. This is in contrast to other studies that show an effect of the melanocortin MC4 receptor antagonist SHU9119 on locomotor sensitisation when injected into the nucleus accumbens. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Peptides corresponding to the predicted heptad repeat 2 domain of the feline coronavirus spike protein are potent inhibitors of viral infection.

    Directory of Open Access Journals (Sweden)

    I-Jung Liu

    Full Text Available BACKGROUND: Feline infectious peritonitis (FIP is a lethal immune-mediated disease caused by feline coronavirus (FCoV. Currently, no therapy with proven efficacy is available. In searching for agents that may prove clinically effective against FCoV infection, five analogous overlapping peptides were designed and synthesized based on the putative heptad repeat 2 (HR2 sequence of the spike protein of FCoV, and the antiviral efficacy was evaluated. METHODS: Plaque reduction assay and MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide cytotoxicity assay were performed in this study. Peptides were selected using a plaque reduction assay to inhibit Feline coronavirus infection. RESULTS: The results demonstrated that peptide (FP5 at concentrations below 20 μM inhibited viral replication by up to 97%. The peptide (FP5 exhibiting the most effective antiviral effect was further combined with a known anti-viral agent, human interferon-α (IFN-α, and a significant synergistic antiviral effect was observed. CONCLUSION: Our data suggest that the synthetic peptide FP5 could serve as a valuable addition to the current FIP prevention methods.

  13. Potent and Broad Inhibition of HIV-1 by a Peptide from the gp41 Heptad Repeat-2 Domain Conjugated to the CXCR4 Amino Terminus

    Science.gov (United States)

    Haggarty, Beth S.; Duong, Jennifer; Jordon, Andrea P. O.; Romano, Josephine; DeClercq, Joshua J.; Gregory, Philip D.; Riley, James L.; Holmes, Michael C.

    2016-01-01

    HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4. C34-conjugated coreceptors were expressed on the surface of T cell lines and primary CD4 T cells, retained the ability to mediate chemotaxis in response to cognate chemokines, and were highly resistant to HIV-1 utilization for entry. Notably, C34-conjugated CCR5 and CXCR4 each exhibited potent and broad inhibition of HIV-1 isolates from diverse clades irrespective of tropism (i.e., each could inhibit R5, X4 and dual-tropic isolates). This inhibition was highly specific and dependent on positioning of the peptide, as HIV-1 infection was poorly inhibited when C34 was conjugated to the amino terminus of CD4. C34-conjugated coreceptors could also inhibit HIV-1 isolates that were resistant to the soluble HR2 peptide inhibitor, enfuvirtide. When introduced into primary cells, CD4 T cells expressing C34-conjugated coreceptors exhibited physiologic responses to T cell activation while inhibiting diverse HIV-1 isolates, and cells containing C34-conjugated CXCR4 expanded during HIV-1 infection in vitro and in a humanized mouse model. Notably, the C34-conjugated peptide exerted greater HIV-1 inhibition when conjugated to CXCR4 than to CCR5. Thus, antiviral effects of HR2 peptides can be specifically directed to the site of viral entry where they provide potent and broad inhibition of HIV-1. This approach to engineer HIV-1 resistance in functional CD4 T cells may provide a novel cell-based therapeutic for controlling HIV infection in humans. PMID:27855210

  14. Synthetic antifreeze peptide

    OpenAIRE

    1991-01-01

    A synthetic antifreeze peptide and a synthetic gene coding for the antifreeze peptide have been produced. The antifreeze peptide has a greater number of repeating amino acid sequences than is present in the native antifreeze peptides from winter flounder upon which the synthetic antifreeze peptide was modeled. Each repeating amino acid sequence has two polar amino acid residues which are spaced a controlled distance apart so that the antifreeze peptide may inhibit ice formation. The synthetic...

  15. Signal peptide cleavage is essential for surface expression of a regulatory T cell surface protein, leucine rich repeat containing 32 (LRRC32

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    Sugiyama Hideaki

    2011-05-01

    Full Text Available Abstract Background Elevated numbers of regulatory T cells (Tregs have been implicated in certain cancers. Depletion of Tregs has been shown to increase anti-tumor immunity. Tregs also play a critical role in the suppression of autoimmune responses. The study of Tregs has been hampered by a lack of adequate surface markers. Leucine Rich Repeat Containing 32 (LRRC32, also known as Glycoprotein A Repetitions Predominant (GARP, has been postulated as a novel surface marker of activated Tregs. However, there is limited information regarding the processing of LRRC32 or the regulatory phenotype and functional activity of Tregs expressing LRRC32. Results Using naturally-occurring freshly isolated Tregs, we demonstrate that low levels of LRRC32 are present intracellularly prior to activation and that freshly isolated LRRC32+ Tregs are distinct from LRRC32- Tregs with respect to the expression of surface CD62L. Using LRRC32 transfectants of HEK cells, we demonstrate that the N-terminus of LRRC32 is cleaved prior to expression of the protein at the cell surface. Furthermore, we demonstrate using a construct containing a deleted putative signal peptide region that the presence of a signal peptide region is critical to cell surface expression of LRRC32. Finally, mixed lymphocyte assays demonstrate that LRRC32+ Tregs are more potent suppressors than LRRC32- Tregs. Conclusions A cleaved signal peptide site in LRRC32 is necessary for surface localization of native LRRC32 following activation of naturally-occurring freshly-isolated regulatory T cells. LRRC32 expression appears to alter the surface expression of activation markers of T cells such as CD62L. LRRC32 surface expression may be useful as a marker that selects for more potent Treg populations. In summary, understanding the processing and expression of LRRC32 may provide insight into the mechanism of action of Tregs and the refinement of immunotherapeutic strategies aimed at targeting these cells.

  16. Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice

    Directory of Open Access Journals (Sweden)

    Wang YW

    2014-10-01

    Full Text Available You-Wei Wang, Kai Yang, Hong Tang, Dan Chen, Yun-Long Bai Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Nanotechnology-based near-infrared quantum dots (NIR QDs have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvß3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine–glycine–aspartic acid (RGD sequence (NIR QDs-RGD can specifically target integrin αvß3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo.Materials and methods: A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800 to the RGD peptide (QD800-RGD. QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection. phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen. The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including

  17. Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C-reactive protein do not predict future allograft rejection in heart transplant recipients.

    Science.gov (United States)

    Battes, Linda C; Caliskan, Kadir; Rizopoulos, Dimitris; Constantinescu, Alina A; Robertus, Jan L; Akkerhuis, Martijn; Manintveld, Olivier C; Boersma, Eric; Kardys, Isabella

    2015-03-01

    Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 ± 4 (mean ± standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. The mean age of the patients at HTx was 49 ± 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ∼ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.

  18. Ten tandem repeats of β-hCG 109-118 enhance immunogenicity and anti-tumor effects of β-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65

    International Nuclear Information System (INIS)

    Zhang Yankai; Yan Rong; He Yi; Liu Wentao; Cao Rongyue; Yan Ming; Li Taiming; Liu Jingjing; Wu Jie

    2006-01-01

    The β-subunit of human chorionic gonadotropin (β-hCG) is secreted by many kinds of tumors and it has been used as an ideal target antigen to develop vaccines against tumors. In view of the low immunogenicity of this self-peptide,we designed a method based on isocaudamer technique to repeat tandemly the 10-residue sequence X of β-hCG (109-118), then 10 tandemly repeated copies of the 10-residue sequence combined with β-hCG C-terminal 37 peptides were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-X10-βhCGCTP37 as an immunogen. In this study, we examined the effect of the tandem repeats of this 10-residue sequence in eliciting an immune by comparing the immunogenicity and anti-tumor effects of the two immunogens, HSP65-X10-βhCGCTP37 and HSP65-βhCGCTP37 (without the 10 tandem repeats). Immunization of mice with the fusion protein HSP65-X10-βhCGCTP37 elicited much higher levels of specific anti-β-hCG antibodies and more effectively inhibited the growth of Lewis lung carcinoma (LLC) in vivo than with HSP65-βhCGCTP37, which should suggest that HSP65-X10-βhCGCTP37 may be an effective protein vaccine for the treatment of β-hCG-dependent tumors and multiple tandem repeats of a certain epitope are an efficient method to overcome the low immunogenicity of self-peptide antigens

  19. N-Terminal Pro-B-Type Natriuretic Peptide-Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations-Results From TIME-CHF.

    Science.gov (United States)

    Davarzani, Nasser; Sanders-van Wijk, Sandra; Karel, Joël; Maeder, Micha T; Leibundgut, Gregor; Gutmann, Marc; Pfisterer, Matthias E; Rickenbacher, Peter; Peeters, Ralf; Brunner-la Rocca, Hans-Peter

    2017-05-01

    Although heart failure (HF) patients are known to experience repeated hospitalizations, most studies evaluated only time to first event. N-Terminal B-type natriuretic peptide (NT-proBNP)-guided therapy has not convincingly been shown to improve HF-specific outcomes, and effects on recurrent all-cause hospitalization are uncertain. Therefore, we investigated the effect of NT-proBNP-guided therapy on recurrent events in HF with the use of a time-between-events approach in a hypothesis-generating analysis. The Trial of Intensified Versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized 499 HF patients, aged ≥60 years, left ventricular ejection fraction ≤45%, New York Heart Association functional class ≥I,I to NT-proBNP-guided versus symptom-guided therapy for 18 months, with further follow-up for 5.5 years. The effect of NT-proBNP-guided therapy on recurrent HF-related and all-cause hospitalizations and/or all-cause death was explored. One hundred four patients (49 NT-proBNP-guided, 55 symptom-guided) experienced 1 and 275 patients (133 NT-proBNP-guided, 142 symptom-guided) experienced ≥2 all-cause hospitalization events. Regarding HF hospitalization, 132 patients (57 NT-proBNP-guided, 75 symptom-guided) experienced 1 and 122 patients (57 NT-proBNP-guided, 65 symptom-guided) experienced ≥2 events. NT-proBNP-guided therapy was significant in preventing 2nd all-cause hospitalizations (hazard ratio [HR] 0.83; P = .01), in contrast to nonsignificant results in preventing 1st all-cause hospitalization events (HR 0.91; P = .35). This was not the case regarding HF hospitalization events (HR 0.85 [P = .14] vs HR 0.73 [P = .01]) The beneficial effect of NT-proBNP-guided therapy was seen only in patients aged <75 years, and not in those aged ≥75 years (interaction terms with P = .01 and P = .03 for all-cause hospitalization and HF hospitalization events, respectively). NT-proBNP-guided therapy

  20. A Novel Variable Number of Tandem Repeat of the Natriuretic Peptide Precursor B gene's 5'-Flanking Region is Associated with Essential Hypertension among Japanese Females

    OpenAIRE

    Kosuge, Kotoko; Soma, Masayoshi; Nakayama, Tomohiro; Aoi, Noriko; Sato, Mikano; Izumi, Yoichi; Matsumoto, Koichi

    2007-01-01

    Background: Brain natriuretic peptide (BNP) acts primarily as a cardiac hormone; it is produced by the ventricle and has both vasodilatory and natriuretic actions. Therefore, the BNP gene is thought to be a candidate gene for essential hypertension (EH). The present study identified variants in the 5'-flanking region of natriuretic peptide precursor B (NPPB) gene and assessed the relationship between gene variants and EH. Methods: The polymerase chain reaction-single strand conformation polym...

  1. Improved efficacy of DNA vaccination against breast cancer by boosting with the repeat beta-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65.

    Science.gov (United States)

    Yi, He; Rong, Yan; Yankai, Zhang; Wentao, Liu; Hongxia, Zhou; Jie, Wu; Rongyue, Cao; Taiming, Li; Jingjing, Liu

    2006-03-24

    Studies have demonstrated that active-specific immunotherapy has potential for controlling mammary tumor progression. Human chorionic gonadotropin (hCG) is expressed and extremely sensitive, easily detectable and highly correlated with breast cancer. We developed a gene vaccine using a plasmid vector to deliver the six copies of 10-amino acid residues of beta-hCG 109-118 and beta hCG C-terminal 37-amino acid (CTP37). BALB/c female mice were immunized with a combination of pCR-HBc-X6-betahCGCTP37 DNA vaccine and HSP-X6-betahCGCTP37 protein vaccine. pCR-HBc-X6-betahCGCTP37 DNA vaccine were injected intramuscularly three times, on days -46,-25 and -11 and HSP-X6-betahCGCTP37 protein were applied two times, 21 and 14 days before tumor cell challenge. We assessed a combined DNA and protein vaccine for its effect of against murine EMT6 mammary tumor cells. In this study, animals vaccinated DNA vaccination boosting with the repeat beta-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65 induced higher avidity antibodies and effectively inhibited the growth of tumor, compared with treatment using DNA alone or BCG priming HSP-X6-betahCGCTP37 protein boosting. The data presented demonstrate that improve immunogenicity of DNA vaccination by boosting with the repeat beta-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65, which should prove useful in the development of new DNA vaccine against growth factors for cancer immunotherapy.

  2. A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA

    Science.gov (United States)

    Zeng, Zhengyang; Han, Shisong; Hong, Wei; Lang, Yange; Li, Fangfang; Liu, Yongxiang; Li, Zeyong; Wu, Yingliang; Li, Wenxin; Zhang, Xianzheng; Cao, Zhijian

    2016-01-01

    Hepatitis B virus (HBV) infection is a major cause of chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma, all of which are severe threats to human health. However, current clinical therapies for HBV are limited by potential side effects, toxicity, and drug-resistance. In this study, a cell-penetrating peptide-conjugated peptide nucleic acid (PNA), Tat-PNA-DR, was designed to target the direct repeat (DR) sequences of HBV. Tat-PNA-DR effectively inhibited HBV replication in HepG2.2.15 cells. Its anti-HBV effect relied on the binding of Tat-PNA-DR to the DR, whereby it suppressed the translation of hepatitis B e antigen (HBeAg), HBsAg, HBV core, hepatitis B virus x protein, and HBV reverse transcriptase (RT) and the reverse transcription of the HBV genome. Furthermore, Tat-PNA-DR administered by intravenous injection efficiently cleared HBeAg and HBsAg in an acute hepatitis B mouse model. Importantly, it induced an 80% decline in HBV DNA in mouse serum, which was similar to the effect of the widely used clinical drug Lamivudine (3TC). Additionally, a long-term hydrodynamics HBV mouse model also demonstrated Tat-PNA-DR's antiviral effect. Interestingly, Tat-PNA-DR displayed low cytotoxicity, low mouse acute toxicity, low immunogenicity, and high serum stability. These data indicate that Tat-PNA-DR is a unique PNA and a promising drug candidate against HBV. PMID:26978579

  3. Synthetic antifreeze peptide and synthetic gene coding for its production

    OpenAIRE

    1991-01-01

    A synthetic antifreeze peptide and a synthetic gene coding for the antifreeze peptide have been produced. The antifreeze peptide has a greater number of repeating amino acid sequences than is present in the native antifreeze peptides from winter flounder upon which the synthetic antifreeze peptide was modeled. Each repeating amino acid sequence has two polar amino acid residues which are spaced a controlled distance apart so that the antifreeze peptide may inhibit ice formation. The synthetic...

  4. Repeated Miscarriage

    Science.gov (United States)

    ... treated? • What treatment is available if I have antiphospholipid syndrome? • What are my chances of having a successful ... may have an increased risk of repeated miscarriages. Antiphospholipid syndrome (APS) is an autoimmune disorder in which a ...

  5. Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407-426 and OK-432.

    Science.gov (United States)

    Ge, Chiyu; Xing, Yun; Wang, Qi; Xiao, Wen; Lu, Yong; Hu, Xiangbing; Gao, Zhenqiu; Xu, Maolei; Ma, Yanjun; Cao, Rongyue; Liu, Jingjing

    2011-12-01

    Therapeutic vaccination with dendritic cells (DCs) pulsed with tumor cell lysate vaccine (H-D) represents an attractive approach for hepatocellular carcinoma (HCC) treatment. However, the efficacy of this approach is not most satisfactory for the low levels of T helper 1 (Th1)-type cytokines secretion and weak T cell responses. In this study, in order to increase the potency of H-D, two tandem repeats of microbial HSP70 peptide epitope 407-426 (2mHSP70(407-426), M2) which has been demonstrated to be effective in enhancing DC maturation were applied. The DC vaccine (HM-D) which was HCC tumor cell lysate pulsed with M2 was developed. Nevertheless, the immunotherapeutic effect was still not satisfactory enough even some promotion was obtained. Therefore, OK-432 (OK), which is a useful anti-cancer agent and effectively in stimulating DC maturation, was introduced to HM-D. Our results demonstrated that treatment with the improved DC vaccine which was tumor cell lysate pulsed with M2 and OK (HMO-D), compared with H-D and HM-D, significantly increased cell surface markers (MHC-I and II, CD40, CD80, CD86 and CD11c) expression on DCs, enhanced Th1-type cytokines (IL-12, TNF-α and IFN-γ) production but not Th2-type cytokine (IL-5) production, induced remarkable high levels of lymphocytes proliferation and CD8(+) cytotoxic T-lymphocyte (CTL). Furthermore, immunization with HMO-D effectively reduced tumor progression and enhanced the survival of mice with H22 tumors. Besides, we also found that the capability of M2 in inducing the Th1 cytokines was stronger than OK. In view of these results, HMO-D vaccination provided a novel immunotherapeutic approach for the treatment of HCC. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Deployment Repeatability

    Science.gov (United States)

    2016-08-31

    Deployment repeatability Olive Stohlman (NASA Langley), Mark Silver (Lincoln Labs), and Dave Waller (Ball Aerospace) Abstract Every time a...of motors or deployment drivers  Loss or redistribution of lubrication Hysteresis errors  Material creep due to time in storage and time in the...controlled or where friction changes unreliably in vacuum or thermal conditions (where these affect the deployment, and not only postdeployment stability

  7. Peptide dendrimers

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2005-01-01

    Roč. 11, - (2005), 757-788 ISSN 1075-2617 R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : multiple antigen peptides * peptide dendrimers * synthetic vaccine * multipleantigenic peptides Subject RIV: CC - Organic Chemistry Impact factor: 1.803, year: 2005

  8. Differentiation of Positional Isomers of Hybrid Peptides Containing Repeats of β-Nucleoside Derived Amino Acid (β-Nda-) and L-Amino Acids by Positive and Negative Ion Electrospray Ionization Tandem Mass Spectrometry (ESI-MS n )

    Science.gov (United States)

    Raju, B.; Ramesh, M.; Srinivas, R.; Chandrasekhar, S.; Kiranmai, N.; Sarma, V. U. M.

    2011-04-01

    A new class of positional isomeric pairs of -Boc protected oligopeptides comprised of alternating nucleoside derived β-amino acid (β-Nda-) and L-amino acid residues (alanine, valine, and phenylalanine) have been differentiated by both positive and negative ion electrospray ionization ion-trap tandem mass spectrometry (ESI-MS n ). The protonated dipeptide positional isomers with β-Nda- at the N-terminus lose CH3OH, NH3, and C2H4O2, whereas these processes are absent for the peptides with L-amino acids at the N-terminus. Instead, the presence of L-amino acids at the N-terminus results in characteristic retro-Mannich reaction involving elimination of imine. A good correlation has been observed between the conformational structure of the peptides and the abundance of y{n/+} and b{n/+} ions in MS n spectra. In the case of tetrapeptide isomers that are reported to form helical structures in solution phase, no y{n/+} and b{n/+} ions are observed when the corresponding amide -NH- participates in the helical structures. In contrast, significant y{n/+} and b{n/+} ions are formed when the amide -NH- is not involved in the H-bonding. In the case of tetra- and hexapeptides, it is observed that abundant b{n/+} ions are formed, presumably with stable oxazolone structures when the C-terminus of the b{n/+} ions possessed L-amino acid and the β-Nda- at the C-terminus appears to prevent the cyclization process leading to the absence of corresponding b{n/+} ions.

  9. Synthesis of peptide-grafted comb polypeptides via polymerisation of NCA-peptides.

    Science.gov (United States)

    Enomoto, Hiroshi; Nottelet, Benjamin; Halifa, Soultan Al; Enjalbal, Christine; Dupré, Mathieu; Tailhades, Julien; Coudane, Jean; Subra, Gilles; Martinez, Jean; Amblard, Muriel

    2013-01-14

    A straightforward synthesis of comb-polypeptides of repeated peptide sequences was developed. These polypeptides were obtained by ROP of defined NCA without any post-polymerization grafting. The key to this strategy relies on the preparation of pure NCA bearing a peptide sequence on its side chain, by an original solid supported methodology.

  10. A Repeat Look at Repeating Patterns

    Science.gov (United States)

    Markworth, Kimberly A.

    2016-01-01

    A "repeating pattern" is a cyclical repetition of an identifiable core. Children in the primary grades usually begin pattern work with fairly simple patterns, such as AB, ABC, or ABB patterns. The unique letters represent unique elements, whereas the sequence of letters represents the core that is repeated. Based on color, shape,…

  11. Method for predicting peptide detection in mass spectrometry

    Science.gov (United States)

    Kangas, Lars [West Richland, WA; Smith, Richard D [Richland, WA; Petritis, Konstantinos [Richland, WA

    2010-07-13

    A method of predicting whether a peptide present in a biological sample will be detected by analysis with a mass spectrometer. The method uses at least one mass spectrometer to perform repeated analysis of a sample containing peptides from proteins with known amino acids. The method then generates a data set of peptides identified as contained within the sample by the repeated analysis. The method then calculates the probability that a specific peptide in the data set was detected in the repeated analysis. The method then creates a plurality of vectors, where each vector has a plurality of dimensions, and each dimension represents a property of one or more of the amino acids present in each peptide and adjacent peptides in the data set. Using these vectors, the method then generates an algorithm from the plurality of vectors and the calculated probabilities that specific peptides in the data set were detected in the repeated analysis. The algorithm is thus capable of calculating the probability that a hypothetical peptide represented as a vector will be detected by a mass spectrometry based proteomic platform, given that the peptide is present in a sample introduced into a mass spectrometer.

  12. Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ali Adem Bahar

    2013-11-01

    Full Text Available The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs, a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics.

  13. Repeatability and Reproducibility in Proteomic Identifications by Liquid Chromatography—Tandem Mass Spectrometry

    Science.gov (United States)

    Tabb, David L.; Vega-Montoto, Lorenzo; Rudnick, Paul A.; Variyath, Asokan Mulayath; Ham, Amy-Joan L.; Bunk, David M.; Kilpatrick, Lisa E.; Billheimer, Dean D.; Blackman, Ronald K.; Cardasis, Helene L.; Carr, Steven A.; Clauser, Karl R.; Jaffe, Jacob D.; Kowalski, Kevin A.; Neubert, Thomas A.; Regnier, Fred E.; Schilling, Birgit; Tegeler, Tony J.; Wang, Mu; Wang, Pei; Whiteaker, Jeffrey R.; Zimmerman, Lisa J.; Fisher, Susan J.; Gibson, Bradford W.; Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry; Stein, Steven E.; Tempst, Paul; Paulovich, Amanda G.; Liebler, Daniel C.; Spiegelman, Cliff

    2009-01-01

    The complexity of proteomic instrumentation for LC-MS/MS introduces many possible sources of variability. Data-dependent sampling of peptides constitutes a stochastic element at the heart of discovery proteomics. Although this variation impacts the identification of peptides, proteomic identifications are far from completely random. In this study, we analyzed interlaboratory data sets from the NCI Clinical Proteomic Technology Assessment for Cancer to examine repeatability and reproducibility in peptide and protein identifications. Included data spanned 144 LC-MS/MS experiments on four Thermo LTQ and four Orbitrap instruments. Samples included yeast lysate, the NCI-20 defined dynamic range protein mix, and the Sigma UPS 1 defined equimolar protein mix. Some of our findings reinforced conventional wisdom, such as repeatability and reproducibility being higher for proteins than for peptides. Most lessons from the data, however, were more subtle. Orbitraps proved capable of higher repeatability and reproducibility, but aberrant performance occasionally erased these gains. Even the simplest protein digestions yielded more peptide ions than LC-MS/MS could identify during a single experiment. We observed that peptide lists from pairs of technical replicates overlapped by 35–60%, giving a range for peptide-level repeatability in these experiments. Sample complexity did not appear to affect peptide identification repeatability, even as numbers of identified spectra changed by an order of magnitude. Statistical analysis of protein spectral counts revealed greater stability across technical replicates for Orbitraps, making them superior to LTQ instruments for biomarker candidate discovery. The most repeatable peptides were those corresponding to conventional tryptic cleavage sites, those that produced intense MS signals, and those that resulted from proteins generating many distinct peptides. Reproducibility among different instruments of the same type lagged behind

  14. Facilitation of peptide fibre formation by arginine-phosphate ...

    Indian Academy of Sciences (India)

    WINTEC

    The process of peptide self-assembly, leading to fibre formation, critically .... an ice bath. After sometime ether was decanted and this process repeated till the gummy compound be- comes solid. This solid compound was dissolved in. 50% aqueous ..... charge neutralization, would further control emergence of peptide fibres ...

  15. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  16. Expansion and Function of Repeat Domain Proteins During Stress and Development in Plants

    Directory of Open Access Journals (Sweden)

    Manisha eSharma

    2016-01-01

    Full Text Available The recurrent repeats having conserved stretches of amino acids exists across all domains of life. Subsequent repetition of single sequence motif and the number and length of the minimal repeating motifs are essential characteristics innate to these proteins. The proteins with tandem peptide repeats are essential for providing surface to mediate protein-protein interactions for fundamental biological functions. Plants are enriched in tandem repeat containing proteins typically distributed into various families. This has been assumed that the occurrence of multigene repeats families in plants enable them to cope up with adverse environmental conditions and allow them to rapidly acclimatize to these conditions. The evolution, structure and function of repeat proteins have been studied in all kingdoms of life. The presence of repeat proteins is particularly profuse in multicellular organisms in comparison to prokaryotes. The precipitous expansion of repeat proteins in plants is presumed to be through internal tandem duplications. Several repeat protein gene families have been identified in plants. Such as Armadillo (ARM, Ankyrin (ANK, HEAT, Kelch-like repeats, Tetratricopeptide (TPR, Leucine rich repeats (LRR, WD40, and Pentatricopeptide repeats (PPR. The structure and functions of these repeat proteins have been extensively studied in plants suggesting a critical role of these repeating peptides in plant cell physiology, stress and development. In this review, we illustrate the structural, functional and evolutionary prospects of prolific repeat proteins in plants.

  17. Quantum repeated games revisited

    International Nuclear Information System (INIS)

    Frąckiewicz, Piotr

    2012-01-01

    We present a scheme for playing quantum repeated 2 × 2 games based on Marinatto and Weber’s approach to quantum games. As a potential application, we study the twice repeated Prisoner’s Dilemma game. We show that results not available in the classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games proposed by Iqbal and Toor. We point out the drawbacks that make their results unacceptable. (paper)

  18. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2, wh...

  19. [SYNTHETIC PEPTIDE VACCINES].

    Science.gov (United States)

    Sergeyev, O V; Barinsky, I F

    2016-01-01

    An update on the development and trials of synthetic peptide vaccines is reviewed. The review considers the successful examples of specific protection as a result of immunization with synthetic peptides using various protocols. The importance of conformation for the immunogenicity of the peptide is pointed out. An alternative strategy of the protection of the organism against the infection using synthetic peptides is suggested.

  20. Repeat migration and disappointment.

    Science.gov (United States)

    Grant, E K; Vanderkamp, J

    1986-01-01

    This article investigates the determinants of repeat migration among the 44 regions of Canada, using information from a large micro-database which spans the period 1968 to 1971. The explanation of repeat migration probabilities is a difficult task, and this attempt is only partly successful. May of the explanatory variables are not significant, and the overall explanatory power of the equations is not high. In the area of personal characteristics, the variables related to age, sex, and marital status are generally significant and with expected signs. The distance variable has a strongly positive effect on onward move probabilities. Variables related to prior migration experience have an important impact that differs between return and onward probabilities. In particular, the occurrence of prior moves has a striking effect on the probability of onward migration. The variable representing disappointment, or relative success of the initial move, plays a significant role in explaining repeat migration probabilities. The disappointment variable represents the ratio of actural versus expected wage income in the year after the initial move, and its effect on both repeat migration probabilities is always negative and almost always highly significant. The repeat probabilities diminish after a year's stay in the destination region, but disappointment in the most recent year still has a bearing on the delayed repeat probabilities. While the quantitative impact of the disappointment variable is not large, it is difficult to draw comparisons since similar estimates are not available elsewhere.

  1. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  2. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  3. Designer Natriuretic Peptides

    Science.gov (United States)

    Lee, Candace Y. W.; Lieu, Hsiao; Burnett, John C.

    2011-01-01

    Designer natriuretic peptides (NPs) are novel hybrid peptides that are engineered from the native NPs through addition, deletion, or substitution of amino acid(s) with a goal toward optimization of pharmacological actions while minimizing undesirable effects. In this article, selected peptides that were designed in our laboratory are reviewed, and future directions for research and development of designer NPs are discussed. PMID:19158603

  4. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  5. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  6. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  7. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  8. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  9. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  10. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  11. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  12. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    to the harsh and selective gastrointestinal system, and development has lacked far behind injection therapy. Peptide acylation is a powerful tool to alter the pharmacokinetics, biophysical properties and chemical stability of injectable peptide drugs, primarily used to prolong blood circulation....... This work aims to characterize acylated analogues of two therapeutic peptides by systematically increasing acyl chain length in order to elucidate its influence on membrane interaction and intestinal cell translocation in vitro. The studied peptides are the 33 amino acid Glucagon-like peptide-2 (GLP-2...... peptides can increase in vitro intestinal permeability, modestly for GLP-2 and drastically for sCT, and might benefit oral delivery. GLP-2 results provide a well-founded predictive power for future peptide analogues, whereas sCT results hold great promise for future analogues, albeit with a larger...

  13. Repeated cycles of peptide receptor radionuclide therapy (PRRT)--results and side-effects of the radioisotope 90Y-DOTA TATE, 177Lu-DOTA TATE or 90Y/177Lu-DOTA TATE therapy in patients with disseminated NET.

    Science.gov (United States)

    Pach, Dorota; Sowa-Staszczak, Anna; Kunikowska, Jolanta; Królicki, Leszek; Trofimiuk, Małgorzata; Stefańska, Agnieszka; Tomaszuk, Monika; Głowa, Bogusław; Mikołajczak, Renata; Pawlak, Dariusz; Jabrocka-Hybel, Agata; Hubalewska-Dydejczyk, Alicja B

    2012-01-01

    PRRT is a known tool in the management of patients with disseminated and inoperable NETs. The aim of study was to assess the effectiveness of the repeated cycles of PRRT in patients with disseminated and inoperable NETs. Eighty nine patients were included in the PRRT. Among them 16 patients (18%) were qualified for a repeated PRRT cycle due to progression of the disease. In one of the patients qualified for the repeated cycle, PRRT was used as neoadjuvant therapy. The results and side-effects of the repeated cycles of PRRT were analyzed. Disease stabilization was observed in 10 patients 6 months after the repeated PRRT cycle and in 5 patients after 12 and 18 months. Ten of the patients who had received repeated PRRT cycles died. In the case of neoadjuvant therapy, further reduction of the tumor size was observed, enabling qualification for surgery. Clinically significant reduction in the mean values of morphological parameters was not observed. Only after 12 and 18 months the mean values of creatinine levels were higher than the normal range (only in 2 patients). The repeated cycles of PRRT did not cause a clinically significant increase of the toxicity of PRRT. The changes in kidney and blood morphology parameters were transient. The repeated cycles of PRRT enabled stabilization of the disease. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Cell Penetrating Peptides and Cationic Antibacterial Peptides

    Science.gov (United States)

    Rodriguez Plaza, Jonathan G.; Morales-Nava, Rosmarbel; Diener, Christian; Schreiber, Gabriele; Gonzalez, Zyanya D.; Lara Ortiz, Maria Teresa; Ortega Blake, Ivan; Pantoja, Omar; Volkmer, Rudolf; Klipp, Edda; Herrmann, Andreas; Del Rio, Gabriel

    2014-01-01

    Cell penetrating peptides (CPP) and cationic antibacterial peptides (CAP) have similar physicochemical properties and yet it is not understood how such similar peptides display different activities. To address this question, we used Iztli peptide 1 (IP-1) because it has both CPP and CAP activities. Combining experimental and computational modeling of the internalization of IP-1, we show it is not internalized by receptor-mediated endocytosis, yet it permeates into many different cell types, including fungi and human cells. We also show that IP-1 makes pores in the presence of high electrical potential at the membrane, such as those found in bacteria and mitochondria. These results provide the basis to understand the functional redundancy of CPPs and CAPs. PMID:24706763

  15. Class of cyclic ribosomal peptide synthetic genes in filamentous fungi.

    Science.gov (United States)

    Nagano, Nozomi; Umemura, Myco; Izumikawa, Miho; Kawano, Jin; Ishii, Tomoko; Kikuchi, Moto; Tomii, Kentaro; Kumagai, Toshitaka; Yoshimi, Akira; Machida, Masayuki; Abe, Keietsu; Shin-Ya, Kazuo; Asai, Kiyoshi

    2016-01-01

    Ustiloxins were found recently to be the first example of cyclic peptidyl secondary metabolites that are ribosomally synthesized in filamentous fungi. In this work, two function-unknown genes (ustYa/ustYb) in the gene cluster for ustiloxins from Aspergillus flavus were found experimentally to be involved in cyclization of the peptide. Their homologous genes are observed mainly in filamentous fungi and mushrooms. They have two "HXXHC" motifs that might form active sites. Computational genome analyses showed that these genes are frequently located near candidate genes for ribosomal peptide precursors, which have signal peptides at the N-termini and repeated sequences with core peptides for the cyclic portions, in the genomes of filamentous fungi, particularly Aspergilli, as observed in the ustiloxin gene cluster. Based on the combination of the ustYa/ustYb homologous genes and the nearby ribosomal peptide precursor candidate genes, 94 ribosomal peptide precursor candidates that were identified computationally from Aspergilli genome sequences were classified into more than 40 types including a wide variety of core peptide sequences. A set of the predicted ribosomal peptide biosynthetic genes was experimentally verified to synthesize a new cyclic peptide compound, designated as asperipin-2a, which comprises the amino acid sequence in the corresponding precursor gene, distinct from the ustiloxin precursors. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Hydroxyapatite-binding peptides for bone growth and inhibition

    Science.gov (United States)

    Bertozzi, Carolyn R [Berkeley, CA; Song, Jie [Shrewsbury, MA; Lee, Seung-Wuk [Walnut Creek, CA

    2011-09-20

    Hydroxyapatite (HA)-binding peptides are selected using combinatorial phage library display. Pseudo-repetitive consensus amino acid sequences possessing periodic hydroxyl side chains in every two or three amino acid sequences are obtained. These sequences resemble the (Gly-Pro-Hyp).sub.x repeat of human type I collagen, a major component of extracellular matrices of natural bone. A consistent presence of basic amino acid residues is also observed. The peptides are synthesized by the solid-phase synthetic method and then used for template-driven HA-mineralization. Microscopy reveal that the peptides template the growth of polycrystalline HA crystals .about.40 nm in size.

  17. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-12-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation (MLI) has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five Glenn Research Center (GRC) provided coupons with 25 layers was shown to be +/- 8.4% whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0%. A second group of 10 coupons has been fabricated by Yetispace and tested by Florida State University, the repeatability between coupons has been shown to be +/- 15-25%. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  18. Plant peptide hormone signalling.

    Science.gov (United States)

    Motomitsu, Ayane; Sawa, Shinichiro; Ishida, Takashi

    2015-01-01

    The ligand-receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone-receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions. © 2015 Authors; published by Portland Press Limited.

  19. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-08-01

    The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques for duct leakage using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards. The three duct leak measurement methods assessed in this report are the two duct pressurization methods that are commonly used by many practitioners and the DeltaQ technique. These are methods B, C and A, respectively of the ASTM E1554 standard. Although it would be useful to evaluate other duct leak test methods, this study focused on those test methods that are commonly used and are required in various test standards, such as BPI (2010), RESNET (2014), ASHRAE 62.2 (2013), California Title 24 (CEC 2012), DOE Weatherization and many other energy efficiency programs.

  20. Discovery of a polystyrene binding peptide isolated from phage display library and its application in peptide immobilization.

    Science.gov (United States)

    Qiang, Xu; Sun, Keyong; Xing, Lijun; Xu, Yifeng; Wang, Hong; Zhou, Zhengpin; Zhang, Juan; Zhang, Fang; Caliskan, Bilgen; Wang, Min; Qiu, Zheng

    2017-06-01

    Phage peptide display is a powerful technique for discovery of various target-specific ligands. However, target-unrelated peptides can often be obtained and cause ambiguous results. Peptide PB-TUP has been isolated repeatedly in our laboratory on different targets and we conducted a research on PB-TUP phage to investigate their binding properties and rate of propagation. ELISA and phage recovery assay demonstrated that PB-TUP phage had a significant superior affinity to polystyrene solid surface compared with control phage clones. In this study, some incidental bindings are excluded like blocking agents and non-specific binding of secondary antibodies. Propagation rate assays of the selected phage clones showed that the growth rate of PB-TUP phage was not superior to the control phages. Furthermore, the binding of PB-TUB to polystyrene was concentration dependent and varied with solution pH. Molecular modeling revealed that stable structures of α-helix and β-turn may contribute to the binding of PB-TUP to polystyrene plate. The PB-TUP sequence was fused to the N-terminus of peptide P2 and the fusion peptide significantly increased the binding affinity to polystyrene. The fusion peptide also enhanced the cell adhesion ability of peptide P2 with human umbilical vein endothelial cell (HUVEC). The addition of the polystyrene binding peptide provided a convenient method for peptide immobilization.

  1. Repeat Customer Success in Extension

    Science.gov (United States)

    Bess, Melissa M.; Traub, Sarah M.

    2013-01-01

    Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

  2. Antimicrobial Peptides in Reptiles

    Science.gov (United States)

    van Hoek, Monique L.

    2014-01-01

    Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867

  3. Peptide specific expansion of CD8(+) T cells by recombinant plate bound MHC/peptide complexes

    DEFF Research Database (Denmark)

    Schmidt, Esben G W; Buus, Soren; Thorn, Mette

    2009-01-01

    Development of methods for efficient in vitro stimulation and expansion of peptide specific CD8(+) T cells is compelling not only with respect to adoptive T cell therapy but also regarding analysis of T cell responses and search for new immunogenic peptides. In the present study, a new approach...... cells (NA-PBMCs) with PB-MHC/CMVp resulted in significant expansion of CMVp specific CD8(+) T cells, which was comparable to that achieved by CMVp pulsed mature dendritic cells (DCs). By repeated exposure of NA-PBMCs to PB-MHC/CMVp more than 60% CMVp specific CD8(+) T cells, representing a 240-fold...... expansion, were reached after only two stimulations. Although stimulation with PB-MHC/CMVp clearly demonstrated efficient peptide specific expansion of CD8(+) T cells, there was a tendency to proliferative exhaustion of the cells after 3-4 stimulations. Thus, it will be of interest to examine the effect...

  4. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  5. REPEAT KIDNEY TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    A. I. Sushkov

    2016-01-01

    Full Text Available Nowadays, kidney transplantation is the best approach of renal replacement therapy for the majority of patients with end-stage renal disease that significantly improves the quality and length of life. Advances in the field of organ donation, immunosuppression, transplant surgery and immunology have improved short-term graft and patient survival. But the long-term graft survival remains static over last two decades. The disparity between low graft and high patient long-term survival led to increasing number of transplant recipients with failed grafts. Repeat renal transplant is presumed to be a good option for many patients losing their grafts, but it is associated with higher complication rates. Unfortunately, there are no evidence-based recommendations or guidelines for renal retransplantation procedure. This review is based on 100 scientifi c publications related to various aspects of the kidney retransplantation and provides the recent data on this matter.

  6. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  7. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    Introduction: A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class...... of antimicrobial drugs, and computational methods utilizing molecular descriptors can significantly accelerate the development of new peptide drug candidates. Areas covered: This paper gives a broad overview of peptide and amino-acid scale descriptors available for AMP modeling and highlights which...

  8. 78 FR 65594 - Vehicular Repeaters

    Science.gov (United States)

    2013-11-01

    ... comment on Industrial/ Business licensees' usage of mobile repeaters. Telemetry Channels We seek comment... mobile repeater applications, e.g., by listing active, co-channel incumbent call signs and associated... Rulemaking, including this IRFA, to the Chief Counsel for Advocacy of the Small Business Administration (SBA...

  9. Review: Production and functionality of active peptides from milk.

    Science.gov (United States)

    Muro Urista, C; Álvarez Fernández, R; Riera Rodriguez, F; Arana Cuenca, A; Téllez Jurado, A

    2011-08-01

    In recent years, research on the production of active peptides obtained from milk and their potential functionality has grown, to a great extent. Bioactive peptides have been defined as specific protein fragments that have a positive impact on body functions or conditions, and they may ultimately have an influence on health. Individual proteins of casein or milk-derived products such as cheese and yogurt have been used as a protein source to study the isolation and activity of peptides with several applications. Currently, the milk whey waste obtained in the production of cheese also represents a protein source from which active peptides could be isolated with potential industrial applications. The active properties of milk peptides and the results found with regard to their physiological effects have led to the classification of peptides as belonging to the group of ingredients of protein nature, appropriate for use in functional foods or pharmaceutical formulations. In this study, the main peptides obtained from milk protein and the past research studies about its production and biological activities will be explained. Second, an analysis will be made on the methods to determinate the biological activities, the separation of bioactive peptides and its structure identification. All of these form the base required to obtain synthetic peptides. Finally, we explain the experimental animal and human trials done in the past years. Nevertheless, more research is required on the design and implementation of equipment for the industrial production and separation of peptides. In addition, different authors suggest that more emphasis should therefore be given to preclinical studies, proving that results are consistent and that effects are demonstrated repeatedly by several research human groups.

  10. Repeatability of visual acuity measurement.

    Science.gov (United States)

    Raasch, T W; Bailey, I L; Bullimore, M A

    1998-05-01

    This study investigates features of visual acuity chart design and acuity testing scoring methods which affect the validity and repeatability of visual acuity measurements. Visual acuity was measured using the Sloan and British Standard letter series, and Landolt rings. Identifiability of the different letters as a function of size was estimated, and expressed in the form of frequency-of-seeing curves. These functions were then used to simulate acuity measurements with a variety of chart designs and scoring criteria. Systematic relationships exist between chart design parameters and acuity score, and acuity score repeatability. In particular, an important feature of a chart, that largely determines the repeatability of visual acuity measurement, is the amount of size change attributed to each letter. The methods used to score visual acuity performance also affect repeatability. It is possible to evaluate acuity score validity and repeatability using the statistical principles discussed here.

  11. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  12. Tevatron serial data repeater system

    International Nuclear Information System (INIS)

    Ducar, R.J.

    1981-01-01

    A ten megabit per second serial data repeater system has been developed for the 6.28km Tevatron accelerator. The repeaters are positioned at each of the thirty service buildings and accommodate control and abort system communications as well as distribution of the Tevatron time and energy clocks. The repeaters are transparent to the particular protocol of the transmissions. Serial data are encoded locally as unipolar two volt signals employing the self-clocking Manchester Bi-Phase code. The repeaters modulate the local signals to low-power bursts of 50 MHz rf carrier for the 260m transmission between service buildings. The repeaters also demodulate the transmission and restructure the data for local utilization. The employment of frequency discrimination techniques yields high immunity to the characteristic noise spectrum

  13. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  14. Tumor-Penetrating Peptides

    Science.gov (United States)

    Teesalu, Tambet; Sugahara, Kazuki N.; Ruoslahti, Erkki

    2013-01-01

    Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC), contains the integrin-binding RGD motif. RGD mediates tumor-homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR) motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular “zip code” of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies, and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is present in the

  15. Novel Endogenous Antimicrobial Peptides

    OpenAIRE

    Nordahl, Emma

    2009-01-01

    Antimicrobial peptides serve as a first line of defence against invading microorganisms and are an essential part of our fast innate immune system. They are ancient molecules found in all classes of life. Antimicrobial peptides rapidly kill a broad spectrum of microbes and are immunomodulatory, i.e. having additional actions influencing inflammation and other innate immune responses. Results presented in this thesis demonstrate that proteases of common human pathogens degrade and inactivate t...

  16. Peptide aldehyde inhibitors of bacterial peptide deformylases.

    Science.gov (United States)

    Durand, D J; Gordon Green, B; O'Connell, J F; Grant, S K

    1999-07-15

    Bacterial peptide deformylases (PDF, EC 3.5.1.27) are metalloenzymes that cleave the N-formyl groups from N-blocked methionine polypeptides. Peptide aldehydes containing a methional or norleucinal inhibited recombinant peptide deformylase from gram-negative Escherichia coli and gram-positive Bacillus subtilis. The most potent inhibitor was calpeptin, N-CBZ-Leu-norleucinal, which was a competitive inhibitor of the zinc-containing metalloenzymes, E. coli and B. subtilis PDF with Ki values of 26.0 and 55.6 microM, respectively. Cobalt-substituted E. coli and B. subtilis deformylases were also inhibited by these aldehydes with Ki values for calpeptin of 9.5 and 12.4 microM, respectively. Distinct spectral changes were observed upon binding of calpeptin to the Co(II)-deformylases, consistent with the noncovalent binding of the inhibitor rather than the formation of a covalent complex. In contrast, the chelator 1,10-phenanthroline caused the time-dependent inhibition of B. subtilis Co(II)-PDF activity with the loss of the active site metal. The fact that calpeptin was nearly equipotent against deformylases from both gram-negative and gram-positive bacterial sources lends further support to the idea that a single deformylase inhibitor might have broad-spectrum antibacterial activity. Copyright 1999 Academic Press.

  17. α-Peptide/ß-Peptoid Chimeras

    DEFF Research Database (Denmark)

    Olsen, Christian Adam; Bonke, Gitte; Vedel, Line

    2007-01-01

    We describe the synthesis and characterization of the first generation of oligomers consisting of alternating repeats of a-amino acids and chiral N-alkyl-ß-alanine (ß-peptoid) residues. These chimeras are stable toward proteolysis, non-hemolytic, and possess antibacterial activity comparable...... to well-known antimicrobial agents. Moreover, the chimeras exhibit length-dependent, concentration-dependent, solvent-dependent, and ion-strength-dependent ellipticity, indicating the presence of a secondary structure in solution. Thus, a-peptide/ß-peptoid oligomers represent a promising novel...

  18. Coding repeats and evolutionary "agility".

    Science.gov (United States)

    Caburet, Sandrine; Cocquet, Julie; Vaiman, Daniel; Veitia, Reiner A

    2005-06-01

    The rapid generation of new shapes observed in the living world is the result of genetic variation, especially in "morphological" developmental genes. Many of these genes contain coding tandem repeats. Fondon and Garner have shown that expansions and contractions of these repeats are associated with the great diversity of morphologies observed in the domestic dog, Canis familiaris. In particular, they found that the repeat variations in two genes were significantly associated with changes in limb and skull morphology. These results open the possibility that such a mechanism contributes to the diversity of life.

  19. Granin-derived peptides.

    Science.gov (United States)

    Troger, Josef; Theurl, Markus; Kirchmair, Rudolf; Pasqua, Teresa; Tota, Bruno; Angelone, Tommaso; Cerra, Maria C; Nowosielski, Yvonne; Mätzler, Raphaela; Troger, Jasmin; Gayen, Jaur R; Trudeau, Vance; Corti, Angelo; Helle, Karen B

    2017-07-01

    The granin family comprises altogether 7 different proteins originating from the diffuse neuroendocrine system and elements of the central and peripheral nervous systems. The family is dominated by three uniquely acidic members, namely chromogranin A (CgA), chromogranin B (CgB) and secretogranin II (SgII). Since the late 1980s it has become evident that these proteins are proteolytically processed, intragranularly and/or extracellularly into a range of biologically active peptides; a number of them with regulatory properties of physiological and/or pathophysiological significance. The aim of this comprehensive overview is to provide an up-to-date insight into the distribution and properties of the well established granin-derived peptides and their putative roles in homeostatic regulations. Hence, focus is directed to peptides derived from the three main granins, e.g. to the chromogranin A derived vasostatins, betagranins, pancreastatin and catestatins, the chromogranin B-derived secretolytin and the secretogranin II-derived secretoneurin (SN). In addition, the distribution and properties of the chromogranin A-derived peptides prochromacin, chromofungin, WE14, parastatin, GE-25 and serpinins, the CgB-peptide PE-11 and the SgII-peptides EM66 and manserin will also be commented on. Finally, the opposing effects of the CgA-derived vasostatin-I and catestatin and the SgII-derived peptide SN on the integrity of the vasculature, myocardial contractility, angiogenesis in wound healing, inflammatory conditions and tumors will be discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Peptide Optical waveguides.

    Science.gov (United States)

    Handelman, Amir; Apter, Boris; Shostak, Tamar; Rosenman, Gil

    2017-02-01

    Small-scale optical devices, designed and fabricated onto one dielectric substrate, create integrated optical chip like their microelectronic analogues. These photonic circuits, based on diverse physical phenomena such as light-matter interaction, propagation of electromagnetic waves in a thin dielectric material, nonlinear and electro-optical effects, allow transmission, distribution, modulation, and processing of optical signals in optical communication systems, chemical and biological sensors, and more. The key component of these optical circuits providing both optical processing and photonic interconnections is light waveguides. Optical confinement and transmitting of the optical waves inside the waveguide material are possible due to the higher refractive index of the waveguides in comparison with their surroundings. In this work, we propose a novel field of bionanophotonics based on a new concept of optical waveguiding in synthetic elongated peptide nanostructures composed of ordered peptide dipole biomolecules. New technology of controllable deposition of peptide optical waveguiding structures by nanofountain pen technique is developed. Experimental studies of refractive index, optical transparency, and linear and nonlinear waveguiding in out-of-plane and in-plane diphenylalanine peptide nanotubes have been conducted. Optical waveguiding phenomena in peptide structures are simulated by the finite difference time domain method. The advantages of this new class of bio-optical waveguides are high refractive index contrast, wide spectral range of optical transparency, large optical nonlinearity, and electro-optical effect, making them promising for new applications in integrated multifunctional photonic circuits. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  1. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul

    2017-01-01

    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  2. Diversity-oriented peptide stapling

    DEFF Research Database (Denmark)

    Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias

    2017-01-01

    The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged as a power......The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged...... incorporating two azide-modified amino acids with 1,3,5-triethynylbenzene efficiently provides (i, i+7)- and (i, i+9)-stapled peptides with a single free alkyne positioned on the staple, that can be further conjugated or dimerised. A unique feature of the present method is that it provides easy access...

  3. Antibody reactivities to glutamate-rich peptides of Plasmodium falciparum parasites in humans from areas of different malaria endemicity

    DEFF Research Database (Denmark)

    Jakobsen, P H; Theander, T G; Hviid, L

    1996-01-01

    Synthetic P. falciparum peptides were evaluated as tools in epidemiological investigations of malaria. Plasma IgM and IgG antibody reactivities against synthetic peptides covering sequences of glutamate-rich protein (GLURP) and acidic-basic repeat antigen (ABRA) were measured by ELISA...

  4. Peptide Integrated Optics.

    Science.gov (United States)

    Handelman, Amir; Lapshina, Nadezda; Apter, Boris; Rosenman, Gil

    2018-02-01

    Bio-nanophotonics is a wide field in which advanced optical materials, biomedicine, fundamental optics, and nanotechnology are combined and result in the development of biomedical optical chips. Silk fibers or synthetic bioabsorbable polymers are the main light-guiding components. In this work, an advanced concept of integrated bio-optics is proposed, which is based on bioinspired peptide optical materials exhibiting wide optical transparency, nonlinear and electrooptical properties, and effective passive and active waveguiding. Developed new technology combining bottom-up controlled deposition of peptide planar wafers of a large area and top-down focus ion beam lithography provides direct fabrication of peptide optical integrated circuits. Finding a deep modification of peptide optical properties by reconformation of biological secondary structure from native phase to β-sheet architecture is followed by the appearance of visible fluorescence and unexpected transition from a native passive optical waveguiding to an active one. Original biocompatibility, switchable regimes of waveguiding, and multifunctional nonlinear optical properties make these new peptide planar optical materials attractive for application in emerging technology of lab-on-biochips, combining biomedical photonic and electronic circuits toward medical diagnosis, light-activated therapy, and health monitoring. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Synthetic antibiofilm peptides.

    Science.gov (United States)

    de la Fuente-Núñez, César; Cardoso, Marlon Henrique; de Souza Cândido, Elizabete; Franco, Octavio Luiz; Hancock, Robert E W

    2016-05-01

    Bacteria predominantly exist as multicellular aggregates known as biofilms that are associated with at least two thirds of all infections and exhibit increased adaptive resistance to conventional antibiotic therapies. Therefore, biofilms are major contributors to the global health problem of antibiotic resistance, and novel approaches to counter them are urgently needed. Small molecules of the innate immune system called host defense peptides (HDPs) have emerged as promising templates for the design of potent, broad-spectrum antibiofilm agents. Here, we review recent developments in the new field of synthetic antibiofilm peptides, including mechanistic insights, synergistic interactions with available antibiotics, and their potential as novel antimicrobials against persistent infections caused by biofilms. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  7. Peptide Vaccine Against Paracoccidioidomycosis.

    Science.gov (United States)

    Taborda, Carlos P; Travassos, Luiz R

    2017-01-01

    The chapter reviews methods utilized for the isolation and characterization of a promising immunogen candidate, aiming at a human vaccine against paracoccidioidomycosis. Peptide P10 carries a T-CD4+ epitope and was identified as an internal sequence of the major diagnostic antigen known as gp43 glycoprotein. It successfully treated massive intratracheal infections by virulent Paracoccidioides brasiliensis in combination with chemotherapy.An introduction about the systemic mycosis was found essential to understand the various options that were considered to design prophylactic and therapeutic vaccine protocols using peptide P10.

  8. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    Science.gov (United States)

    Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

    2014-02-01

    The Gd5Ge2Si2 alloy and the off-stoichiometric Ni50Mn35In15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd5Ge2Si2 and Ni50Mn35In15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  9. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    International Nuclear Information System (INIS)

    Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

    2014-01-01

    The Gd 5 Ge 2 Si 2 alloy and the off-stoichiometric Ni 50 Mn 35 In 15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd 5 Ge 2 Si 2 and Ni 50 Mn 35 In 15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis

  10. NCAM Mimetic Peptides: An Update

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    of combinatorial peptide libraries. The C3 and NBP10 peptides target the first Ig module whereas the ENFIN2 and ENFIN11 peptides target fibronectin type III (FN3) modules of NCAM. A number of NCAM mimetics can induce neurite outgrowth and exhibit neuroprotective and synaptic plasticity modulating properties...

  11. brain natriuretic peptide

    African Journals Online (AJOL)

    Background: Recently brain natriuretic peptide (BNP) level has been introduced as a screening test for congestive heart failure (CHF) in children. The current CHF assessment scores are not satisfactory as they use a large number of variables. Objective: To evaluate two CHF scores: a modified clinical score and an echo-.

  12. Brain Peptides and Psychopharmacology

    Science.gov (United States)

    Arehart-Treichel, Joan

    1976-01-01

    Proteins isolated from the brain and used as drugs can improve and apparently even transfer mental states and behavior. Much of the pioneering work and recent research with humans and animals is reviewed and crucial questions that are being posed about the psychologically active peptides are related. (BT)

  13. [Biosynthesis of opioid peptides].

    Science.gov (United States)

    Rossier, J

    1988-01-01

    The endogenous opioid peptides all contain the enkephalin sequence Tyr-Gly-Gly-Phe-Met and Tyr-Gly-Gly-Phe-Leu at their aminoterminus. Three distinct families of these peptides (endorphins, enkephalins and dynorphins) are present in different neuronal pathways within the central nervous system. Molecular genetics have shown that these three families of opioid peptides are derived from three distinct precursors. Pro-opiomelanocortin gives rise to the endorphins, as well as adrenocorticotropic hormone (ACTH) and the melanotropic hormones (MSH's). [Met] enkephalin, [Leu] enkephalin and the related heptapeptide [Met] enkephalin-Arg6-Phe7 and octapeptide [Met] enkephalin-Arg6-Gly7-Leu8 are derived from proenkephalin. The third family is derived from prodynorphin and includes dynorphin A, dynorphin B (also known as rimorphin) and alpha- and beta-neo-endorphin. The structure of the genes coding for these precursors are similar, suggesting the possibility of one common ancestral gene. The most common scheme for enzymatic maturation of precursors proposes the action of a trypsin-like endopeptidase followed by a carboxypeptidase B-like exopeptidase. However, we have provided evidence that this combination of trypsin-like and carboxypeptidase B-like enzymes may not be the only mechanism for liberating enkephalin from low molecular weight enkephalin-containing peptides. Indeed, endo-oligopeptidase A, an enzyme, known to hydrolyze the Phe5-Ser6 bond of bradykinin and the Arg8-Arg9 bond of neurotensin, has been shown to produce, by a single cleavage, [Leu] enkephalin or [Met] enkephalin from small enkephalin-containing peptides, (Camargo et al., 1987, J. Neurochem. 48, 1258-1263).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  15. Chromosomal rearrangements occurred repeatedly and ...

    African Journals Online (AJOL)

    Furthermore, molecular and/or chromosomal data indicate that Paroedura is a monophyletic genus, in which chromosome rearrangements occurred repeatedly and independently during the specific diversification. Moreover both P. bastardi and P. gracilis in current definitions are paraphyletic assemblages of several ...

  16. Sequencing Games with Repeated Players

    NARCIS (Netherlands)

    Estevez Fernandez, M.A.; Borm, P.; Calleja, P.; Hamers, H.

    2008-01-01

    Two classes of one machine sequencing situations are considered in which each job corresponds to exactly one player but a player may have more than one job to be processed, so called RP(repeated player) sequencing situations. In max-RP sequencing situations it is assumed that each player's cost

  17. Pentapeptide Repeat Proteins and Cyanobacteria

    Energy Technology Data Exchange (ETDEWEB)

    Buchko, Garry W.

    2009-10-16

    Cyanobacteria are unique in many ways and one unusual feature is the presence of a suite of proteins that contain at least one domain with a minimum of eight tandem repeated five-residues (Rfr) of the general consensus sequence A[N/D]LXX. The function of such pentapeptide repeat proteins (PRPs) are still unknown, however, their prevalence in cyanobacteria suggests that they may play some role in the unique biological activities of cyanobacteria. As part of an inter-disciplinary Membrane Biology Grand Challenge at the Environmental Molecular Sciences Laboratory (Pacific Northwest National Laboratory) and Washington University in St. Louis, the genome of Cyanothece 51142 was sequenced and its molecular biology studied with relation to circadian rhythms. The genome of Cyanothece encodes for 35 proteins that contain at least one PRP domain. These proteins range in size from 105 (Cce_3102) to 930 (Cce_2929) kDa with the PRP domains ranging in predicted size from 12 (Cce_1545) to 62 (cce_3979) tandem pentapeptide repeats. Transcriptomic studies with 29 out of the 35 genes showed that at least three of the PRPs in Cyanothece 51142 (cce_0029, cce_3083, and cce_3272) oscillated with repeated periods of light and dark, further supporting a biological function for PRPs. Using X-ray diffraction crystallography, the structure for two pentapeptide repeat proteins from Cyanothece 51142 were determined, cce_1272 (aka Rfr32) and cce_4529 (aka Rfr23). Analysis of their molecular structures suggests that all PRP may share the same structural motif, a novel type of right-handed quadrilateral β-helix, or Rfr-fold, reminiscent of a square tower with four distinct faces. Each pentapeptide repeat occupies one face of the Rfr-fold with four consecutive pentapeptide repeats completing a coil that, in turn, stack upon each other to form “protein skyscrapers”. Details of the structural features of the Rfr-fold are reviewed here together with a discussion for the possible role of end

  18. The P42 peptide and Peptide-based therapies for Huntington's disease.

    Science.gov (United States)

    Marelli, Cecilia; Maschat, Florence

    2016-03-17

    Huntington's disease (HD) is a progressive neurodegenerative hereditary disease clinically characterised by the presence of involuntary movements, behavioural problems and cognitive decline. The disease-onset is usually between 30 and 50 years of age. HD is a rare disorder affecting approximately 1.3 in 10,000 people in the European Union. It is caused by an expanded CAG repeat in the first exon of the Huntingtin (HTT) gene, leading to an abnormal form of the Huntingtin protein (Htt) (polyQHtt), containing N-terminus, enlarged polyglutamine strands of variable length that stick together to form aggregates and nuclear inclusions in the damaged brain cells. Treatments currently used for Huntington's disease are symptomatic and aimed at temporally relieving the symptoms of the disease; although some promising therapies are on study, there is no drug capable of stopping disease progression either in the form of delaying onset or slowing disability progression. The utilization of peptides interacting with polyQ stretches or with Htt protein to prevent misfolding and aggregation of the expanded polyQ protein is a fascinating idea, because of low potential toxicity and ability to target very initial steps in the pathophysiological cascade of the disease, such as aggregation or cleavage process. Indeed, several therapeutic peptides have been developed and were found to significantly slow down the progression of symptoms in experimental models of Huntington's disease. This review is essentially focusing on the latest development concerning peptide strategy. In particular, we focused on a 23aa peptide P42, which is a part of the Htt protein. It is expected to work principally by preventing the abnormal Htt protein from sticking together, thereby preventing pathological consequences of aggregation and improving the symptoms of the disease. In the meantime, as P42 is part of the Htt protein, some therapeutic properties might be linked to the physiological actions of the

  19. Antibody Production with Synthetic Peptides.

    Science.gov (United States)

    Lee, Bao-Shiang; Huang, Jin-Sheng; Jayathilaka, Lasanthi P; Lee, Jenny; Gupta, Shalini

    2016-01-01

    Peptides (usually 10-20 amino acid residues in length) can be used as effectively as proteins in raising antibodies producing both polyclonal and monoclonal antibodies routinely with titers higher than 20,000. Peptide antigens do not function as immunogens unless they are conjugated to proteins. Production of high quality antipeptide antibodies is dependent upon peptide sequence selection, the success of peptide synthesis, peptide-carrier protein conjugation, the humoral immune response in the host animal, the adjuvant used, the peptide dose administered, the injection method, and the purification of the antibody. Peptide sequence selection is probably the most critical step in the production of antipeptide antibodies. Although the process for designing peptide antigens is not exact, several guidelines and computational B-cell epitope prediction methods can help maximize the likelihood of producing antipeptide antibodies that recognize the protein. Antibodies raised by peptides have become essential tools in life science research. Virtually all phospho-specific antibodies are now produced using phosphopeptides as antigens. Typically, 5-20 mg of peptide is enough for antipeptide antibody production. It takes 3 months to produce a polyclonal antipeptide antibody in rabbits that yields ~100 mL of serum which corresponds to ~8-10 mg of the specific antibody after affinity purification using a peptide column.

  20. Synthetic cationic amphiphilic α-helical peptides as antimicrobial agents.

    Science.gov (United States)

    Wiradharma, Nikken; Khoe, Ulung; Hauser, Charlotte A E; Seow, See Voon; Zhang, Shuguang; Yang, Yi-Yan

    2011-03-01

    Antimicrobial peptides (AMPs) secreted by the innate immune system are prevalent as the effective first-line of defense to overcome recurring microbial invasions. They have been widely accepted as the blueprints for the development of new antimicrobial agents for the treatment of drug resistant infections. However, there is also a growing concern that AMPs with a sequence that is too close to the host organism's AMP may inevitably compromise its own natural defense. In this study, we design a series of synthetic (non-natural) short α-helical AMPs to expand the arsenal of the AMP families and to gain further insights on their antimicrobial activities. These cationic and amphiphilic peptides have a general sequence of (XXYY)(n) (X: hydrophobic residue, Y: cationic residue, and n: the number of repeat units), and are designed to mimic the folding behavior of the naturally-occurring α-helical AMPs. The synthetic α-helical AMPs with 3 repeat units, (FFRR)(3), (LLRR)(3), and (LLKK)(3), are found to be more selective towards microbial cells than rat red blood cells, with minimum inhibitory concentration (MIC) values that are more than 10 times lower than their 50% hemolytic concentrations (HC(50)). They are effective against Gram-positive B. subtilis and yeast C. albicans; and the studies using scanning electron microscopy (SEM) have elucidated that these peptides possess membrane-lytic activities against microbial cells. Furthermore, non-specific immune stimulation assays of a typical peptide shows negligible IFN-α, IFN-γ, and TNF-α inductions in human peripheral blood mononuclear cells, which implies additional safety aspects of the peptide for both systemic and topical use. Therefore, the peptides designed in this study can be promising antimicrobial agents against the frequently-encountered Gram-positive bacteria- or yeast-induced infections. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. A GBP 130 derived peptide from Plasmodium falciparum binds to human erythrocytes and inhibits merozoite invasion in vitro

    Directory of Open Access Journals (Sweden)

    Jorge E Suarez

    2000-08-01

    Full Text Available The malarial GBP 130 protein binds weakly to intact human erythrocytes; the binding sites seem to be located in the repeat region and this region's antibodies block the merozoite invasion. A peptide from this region (residues from 701 to 720 which binds to human erythrocytes was identified. This peptide named 2220 did not bind to sialic acid; the binding site on human erythrocyte was affected by treatment with trypsin but not by chymotrypsin. The peptide was able to inhibit Plasmodium falciparum merozoite invasion of erythrocytes. The residues F701, K703, L705, T706, E713 (FYKILTNTDPNDEVERDNAD were found to be critical for peptide binding to erythrocytes.

  2. Antimicrobial Peptides (AMPs

    Directory of Open Access Journals (Sweden)

    Mehrzad Sadredinamin

    2016-04-01

    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  3. Side chain packing below the fusion peptide strongly modulates triggering of the Hendra virus F protein.

    Science.gov (United States)

    Smith, Everett Clinton; Dutch, Rebecca Ellis

    2010-10-01

    Triggering of the Hendra virus fusion (F) protein is required to initiate the conformational changes which drive membrane fusion, but the factors which control triggering remain poorly understood. Mutation of a histidine predicted to lie near the fusion peptide to alanine greatly reduced fusion despite wild-type cell surface expression levels, while asparagine substitution resulted in a moderate restoration in fusion levels. Slowed kinetics of six-helix bundle formation, as judged by sensitivity to heptad repeat B-derived peptides, was observed for all H372 mutants. These data suggest that side chain packing beneath the fusion peptide is an important regulator of Hendra virus F triggering.

  4. Enhancing Motivation through Repeated Listening

    OpenAIRE

    Brown, R. A.

    2007-01-01

    Listening in a foreign language is difficult. Previous research has identified a number of strategies that can result in increased comprehension. One such is repeated listening. The present article describes a study in which 98 Japanese college students of English as a foreign language viewed five videos, rating their comprehension of each video after an initial viewing and again after a second viewing. Self-reported comprehension was found to be significantly better after the second viewing....

  5. Learning in repeated visual search

    OpenAIRE

    Hout, Michael C.; Goldinger, Stephen D.

    2010-01-01

    Visual search (e.g., finding a specific object in an array of other objects) is performed most effectively when people are able to ignore distracting nontargets. In repeated search, however, incidental learning of object identities may facilitate performance. In three experiments, with over 1,100 participants, we examined the extent to which search could be facilitated by object memory and by memory for spatial layouts. Participants searched for new targets (real-world, nameable objects) embe...

  6. Radiolabelled peptides vs. nanoparticle-peptide complexes for medical applications

    International Nuclear Information System (INIS)

    Ferro F, G.

    2007-01-01

    Full text: The principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been provided and the peptide-receptor radionuclide therapy for malignant tumors is a real treatment option. Targeted entry into cells is an increasingly important area of research. The diagnoses and treatment of disease by novel methods would be enhanced greatly by the efficient transport of materials to living cell nuclei. Membrane-trans locating peptides complexed to nanoparticles are small enough (30 nm) to cross the nuclear membrane and to enter the cell via receptor-mediated endocytosis, emerging as a new type of pharmaceuticals. Pharmacokinetic properties and molecular specificity of iron or gold nanoparticle-peptide complexes that do not induce biological toxicity is a topic of world interest in current and future medical investigations. Some perspectives and achievements on the preparation, pharmacokinetics and dosimetry of radiolabelled peptides versus nanoparticle-peptide complexes for medical applications are presented. (Author)

  7. Preventing repeat pregnancy in adolescents.

    Science.gov (United States)

    Milne, Dona; Glasier, Anna

    2008-10-01

    Teenage pregnancy is on a decline, but there are wide inequalities in those who are still becoming pregnant at an early age. Teenage pregnancy remains a public health concern. Numbers of repeat pregnancy in adolescence are small but contribute to poor health outcomes for young women and their children. A number of studies have demonstrated the impact that low levels of educational attainment, lack of aspiration, low socioeconomic status, dislike of school, lack of family connectedness and poor parental monitoring can have on early sexual activity and, in some cases, pregnancy among adolescents. Risks for repeat pregnancy in adolescence would appear to be linked to whether the pregnancy was intended or not, and what incentives or motivations, if any, existed to prevent subsequent early pregnancies. There would appear to be two options available to those who wish to reduce the negative health outcomes associated with repeat pregnancy in adolescence. First, to increase the life choices available to young women, which improve their social and economic circumstances. Secondly, to develop a clear understanding of pregnancy intentions within this group to ensure the provision of appropriate services which deliver the best possible outcomes for them and their child.

  8. THERMAL STABILITY OF SYNTHETIC PEPTIDES MIMICKING THE SEQUENCE OF THE REGION CONTAINING THE SKIP RESIDUES IN SQUID MYOSIN ROD

    Directory of Open Access Journals (Sweden)

    Yoshihiro Ochiai

    2017-08-01

    Full Text Available Myosin is the major protein in skeletal muscles including those of fish and shellfish. The characteristics of this protein are closely related to the biological function and the quality and physical properties of musclefood. In the myosin rod (the coiled-coil region of myosin, several amino acid residues, known as skip residues, seem to destabilize the ordered structure (heptad repeat. These residues might be responsible for reducing thermal stability. Attempts were thus made to examine the role of these residues in the rod of squid myosin, based on the thermodynamic properties of synthetic peptides which have been designed to mimic the partial sequence of myosin heavy chain from the squid Todarodes pacificus mantle muscle. Five peptides, namely, with the sequence of Trp1343 -Ala1372  having the skip residue Glu1357 at the center (Peptide WT, without the skip residue (Peptide Δ, with the replacements of the skip residue (Glu by Ile, Gln and Pro (Peptides E/I, E/Q, and E/P, respectively to modify the helix forming propensity, were synthesized. The results obtained showed that the stability of the peptides as measured by circular dichroism spectrometry was in the order of Peptide Δ > Peptide WT > Peptide E/Q > Peptide E/P > Peptide E/I. It is suggested that the presence of the skip residues dexterously tunes the stability or flexibility of the coiled-coil structure, thus possibly regulating thick filament formation and further gel formation ability of myosin.

  9. Peptide-enhanced oral delivery of therapeutic peptides and proteins

    DEFF Research Database (Denmark)

    Kristensen, Mie; Foged, Camilla; Berthelsen, Jens

    2013-01-01

    Systemic therapy upon oral delivery of biologics, such as peptide and protein drugs is limited due to their large molecular size, their low enzymatic stability and their inability to cross the intestinal epithelium. Ways to overcome the epithelial barrier include the use of peptide-based excipients...... throughout the gastrointestinal (GI) tract, chemical stability is an inherent challenge when employing amino acid-based excipients for oral delivery, and multiple approaches have been investigated to improve this. The exact mechanisms of transepithelial translocation are discussed, and it is believed...... for oral delivery of peptide and protein drugs highlighting recent studies and the most promising compounds from these classes of peptide excipients....

  10. Peptide Signals Encode Protein Localization▿

    OpenAIRE

    Russell, Jay H.; Keiler, Kenneth C.

    2007-01-01

    Many bacterial proteins are localized to precise intracellular locations, but in most cases the mechanism for encoding localization information is not known. Screening libraries of peptides fused to green fluorescent protein identified sequences that directed the protein to helical structures or to midcell. These peptides indicate that protein localization can be encoded in 20-amino-acid peptides instead of complex protein-protein interactions and raise the possibility that the location of a ...

  11. The Equine PeptideAtlas

    DEFF Research Database (Denmark)

    Bundgaard, Louise; Jacobsen, Stine; Sorensen, Mette A.

    2014-01-01

    Equine PeptideAtlas encompassing high-resolution tandem MS analyses of 51 samples representing a selection of equine tissues and body fluids from healthy and diseased animals. The raw data were processed through the Trans-Proteomic Pipeline to yield high quality identification of proteins and peptides...... analyses, and emphasizes the value of the Equine PeptideAtlas as a resource for the design of targeted quantitative proteomic studies....

  12. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery...

  13. One Hundred Years of Peptide Chemistry

    Indian Academy of Sciences (India)

    thus a chiral center. Today, 20 amino acids are known as genetically encoded as building blocks of peptides and proteins. Almost all of them present in peptides have L-configura- tion. D-amino acids have been found only in small peptides of bacterial cell walls, peptide antibiotics and peptides in South American frog skin.

  14. Improving repeatability by improving quality

    Energy Technology Data Exchange (ETDEWEB)

    Ronen, Shuki; Ackers, Mark; Schlumberger, Geco-Prakla; Brink, Mundy

    1998-12-31

    Time lapse (4-D) seismic is a promising tool for reservoir characterization and monitoring. The method is apparently simple: to acquire data repeatedly over the same reservoir, process and interpret the data sets, then changes between the data sets indicate changes in the reservoir. A problem with time lapse seismic data is that reservoirs are a relatively small part of the earth and important reservoir changes may cause very small differences to the time lapse data. The challenge is to acquire and process economical time lapse data such that reservoir changes can be detected above the noise of varying acquisition and environment. 7 refs., 9 figs.

  15. Coordinated hybrid automatic repeat request

    KAUST Repository

    Makki, Behrooz

    2014-11-01

    We develop a coordinated hybrid automatic repeat request (HARQ) approach. With the proposed scheme, if a user message is correctly decoded in the first HARQ rounds, its spectrum is allocated to other users, to improve the network outage probability and the users\\' fairness. The results, which are obtained for single- and multiple-antenna setups, demonstrate the efficiency of the proposed approach in different conditions. For instance, with a maximum of M retransmissions and single transmit/receive antennas, the diversity gain of a user increases from M to (J+1)(M-1)+1 where J is the number of users helping that user.

  16. Accumulate Repeat Accumulate Coded Modulation

    Science.gov (United States)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative coded modulation scheme called 'Accumulate Repeat Accumulate Coded Modulation' (ARA coded modulation). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes that are combined with high level modulation. Thus at the decoder belief propagation can be used for iterative decoding of ARA coded modulation on a graph, provided a demapper transforms the received in-phase and quadrature samples to reliability of the bits.

  17. Peptide Vaccines for Cancer

    Directory of Open Access Journals (Sweden)

    Kono K

    2013-10-01

    Full Text Available Background: In general, the preferable characteristic of the target molecules for development of cancer vaccines are high immunogenicity, very common expression in cancer cells, specific expression in cancer cells and essential molecules for cell survival (to avoid loss of expression. We previously reported that three novel HLA-A24-restricted immunodominant peptides, which were derived from three different oncoantigens, TTK, LY6K, and IMP-3,were promising targets for cancer vaccination for esophageal squamous cell carcinoma (ESCCpatients. Then, we had performed a phase I clinical trial using three HLA-A24-binding peptides and the results had been shown to be promising for ESCC. Therefore, we further performed a multicenter, non-randomized phase II clinical trial. Patients and Methods: Sixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLA-A type, and the HLA types were key-opened at the analysis point. Hence, the endpoints were set to evaluate differences between HLA-A*2402-positive (24(+ and -negative (24(- groups. Results: The OS in the 24 (+ group (n=35 tended to be better than that in the 24(- group (n=25 (MST 4.6 vs. 2.6 month, respectively, p = 0.121, although the difference was not statistically significant. However, the PFS in the 24(+ group was significantly better than that in the 24(- group (p = 0.032. In the 24(+ group, ELISPOT assay indicated that the LY6K-, TTK-, and IMP3-specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+ group, respectively. The patients having LY6K-, TTK-, and IMP3-specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses. Conclusion: The immune response induced

  18. Comparison of marmoset and human FSH using synthetic peptides of the β-subunit L2 loop region and anti-peptide antibodies.

    Science.gov (United States)

    Kutteyil, Susha S; Kulkarni, Bhalchandra J; Mojidra, Rahul; Joseph, Shaini; Pathak, Bhakti R; Mahale, Smita D

    2016-06-01

    Follicle stimulating hormone (FSH) is a glycoprotein hormone required for female and male gametogenesis in vertebrates. Common marmoset (Callithrix jacchus) is a New World primate monkey, used as animal model in biomedical research. Observations like, requirement of extremely high dose of human FSH in marmosets for superovulation compared to other primates and generation of antibodies in marmoset against human FSH after repeated superovulation cycles, point towards the possibility that FSH-FSH receptor (FSHR) interaction in marmosets might be different than in the humans. In this study we attempted to understand some of these structural differences using FSH peptides and anti-peptide antibody approach. Based on sequence alignment, in silico modeling and docking studies, L2 loop of FSH β-subunit (L2β) was found to be different between marmoset and human. Hence, peptides corresponding to region 32-50 of marmoset and human L2β loop were synthesized, purified and characterized. The peptides displayed dissimilarity in terms of molecular mass, predicted isoelectric point, predicted charge and in the ability to inhibit hormone-receptor interaction. Polyclonal antibodies generated against both the peptides were found to exhibit specific binding for the corresponding peptide and parent FSH in ELISA and Western blotting respectively and exhibited negligible reactivity to cross-species peptide and FSH in ELISA. The anti-peptide antibody against marmoset FSH was also able to detect native FSH in marmoset plasma samples and pituitary sections. In summary, the L2β loop of marmoset and human FSH has distinct receptor interaction ability and immunoreactivity indicating possibility of subtle conformational and biochemical differences between the two regions which may affect the FSH-FSHR interaction in these two primates. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  19. Natriuretic peptides in cardiometabolic regulation and disease

    DEFF Research Database (Denmark)

    Zois, Nora E; Bartels, Emil D; Hunter, Ingrid

    2014-01-01

    these conditions can coexist and potentially lead to heart failure, a syndrome associated with a functional natriuretic peptide deficiency despite high circulating concentrations of immunoreactive peptides. Therefore, dysregulation of the natriuretic peptide system, a 'natriuretic handicap', might be an important...

  20. Radiolabeling of methionine containing proteins and peptides

    International Nuclear Information System (INIS)

    Garlick, R.K.; Jirousek, L.

    1986-01-01

    A process for radiolabeling methionine-containing peptides and proteins is disclosed. The process comprises the steps of oxidizing the protein or peptide, radiolabeling and reducing the radiolabeled protein or peptide. (author)

  1. CDC Vital Signs: Preventing Repeat Teen Births

    Science.gov (United States)

    ... MB] Read the MMWR Science Clips Preventing Repeat Teen Births Recommend on Facebook Tweet Share Compartir On ... live birth before age 20. Problem Too many teens, ages 15–19, have repeat births. Nearly 1 ...

  2. Peptide radiopharmaceuticals in nuclear medicine

    International Nuclear Information System (INIS)

    Blok, D.; Vermeij, P.; Feitsma, R.I.J.; Pauwels, E.J.K.

    1999-01-01

    This article reviews the labelling of peptides that are recognised to be of interest for nuclear medicine or are the subject of ongoing nuclear medicine research. Applications and approaches to the labelling of peptide radiopharmaceuticals are discussed, and drawbacks in their development considered. (orig.)

  3. Antimicrobial peptides in the airway.

    Science.gov (United States)

    Laube, D M; Yim, S; Ryan, L K; Kisich, K O; Diamond, G

    2006-01-01

    The airway provides numerous defense mechanisms to prevent microbial colonization by the large numbers of bacteria and viruses present in ambient air. An important component of this defense is the antimicrobial peptides and proteins present in the airway surface fluid (ASF), the mucin-rich fluid covering the respiratory epithelium. These include larger proteins such as lysozyme and lactoferrin, as well as the cationic defensin and cathelicidin peptides. While some of these peptides, such as human beta-defensin (hBD)-1, are present constitutively, others, including hBD2 and -3 are inducible in response to bacterial recognition by Toll-like receptor-mediated pathways. These peptides can act as microbicides in the ASF, but also exhibit other activities, including potent chemotactic activity for cells of the innate and adaptive immune systems, suggesting they play a complex role in the host defense of the airway. Inhibition of antimicrobial peptide activity or gene expression can result in increased susceptibility to infections. This has been observed with cystic fibrosis (CF), where the CF phenotype leads to reduced antimicrobial capacity of peptides in the airway. Pathogenic virulence factors can inhibit defensin gene expression, as can environmental factors such as air pollution. Such an interference can result in infections by airway-specific pathogens including Bordetella bronchiseptica, Mycobacterium tuberculosis, and influenza virus. Research into the modulation of peptide gene expression in animal models, as well as the optimization of peptide-based therapeutics shows promise for the treatment and prevention of airway infectious diseases.

  4. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper...

  5. Chemical Synthesis of Antimicrobial Peptides.

    Science.gov (United States)

    Münzker, Lena; Oddo, Alberto; Hansen, Paul R

    2017-01-01

    Solid-phase peptide synthesis (SPPS) is the method of choice for chemical synthesis of peptides. In this nonspecialist review, we describe commonly used resins, linkers, protecting groups, and coupling reagents in 9-fluorenylmethyloxycarbonyl (Fmoc) SPPS. Finally, a detailed protocol for manual Fmoc SPPS is presented.

  6. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    N.D. Zegers (Netty)

    1995-01-01

    textabstractSynthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps

  7. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the

  8. Urinary Peptides in Rett Syndrome.

    Science.gov (United States)

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  9. Solid-phase peptide synthesis

    DEFF Research Database (Denmark)

    Jensen, Knud Jørgen

    2013-01-01

    This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective....

  10. Topological characteristics of helical repeat proteins

    NARCIS (Netherlands)

    Groves, M R; Barford, D

    The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem

  11. Simple sequence repeats in mycobacterial genomes

    Indian Academy of Sciences (India)

    Prakash

    J. Biosci. 32(1), January 2007. The list of microsatellite rich as well as poor regions in the five mycobacterial genomes. Local GC%. Repeat rich(+)/. Repeat poor(-). Total ORFs. Number of ... Simple sequence repeats in mycobacterial genomes. VATTIPALLY .... heat shock protein (grpE) (15839737), heat shock protein (dnaJ) ...

  12. Repeated Reading. What Works Clearinghouse Intervention Report

    Science.gov (United States)

    What Works Clearinghouse, 2014

    2014-01-01

    "Repeated reading" is an academic practice that aims to increase oral reading fluency. "Repeated reading" can be used with students who have developed initial word reading skills but demonstrate inadequate reading fluency for their grade level. During "repeated reading," a student sits in a quiet location with a…

  13. Maize Bioactive Peptides against Cancer

    Science.gov (United States)

    Díaz-Gómez, Jorge L.; Castorena-Torres, Fabiola; Preciado-Ortiz, Ricardo E.; García-Lara, Silverio

    2017-06-01

    Cancer is one of the main chronic degenerative diseases worldwide. In recent years, consumption of whole-grain cereals and their derived food products has been associated with reduction risks of various types of cancer. Cereals main biomolecules includes proteins, peptides, and amino acids present in different quantities within the grain. The nutraceutical properties associated with peptides exerts biological functions that promote health and prevent this disease. In this review, we report the current status and advances on maize peptides regarding bioactive properties that have been reported such as antioxidant, antihypertensive, hepatoprotective, and anti-tumour activities. We also highlighted its biological potential through which maize bioactive peptides exert anti-cancer activity. Finally, we analyse and emphasize the possible areas of application for maize peptides.

  14. Digital storage of repeated signals

    International Nuclear Information System (INIS)

    Prozorov, S.P.

    1984-01-01

    An independent digital storage system designed for repeated signal discrimination from background noises is described. The signal averaging is performed off-line in the real time mode by means of multiple selection of the investigated signal and integration in each point. Digital values are added in a simple summator and the result is recorded the storage device with the volume of 1024X20 bit from where it can be output on an oscillograph, a plotter or transmitted to a compUter for subsequent processing. The described storage is reliable and simple device on one base of which the systems for the nuclear magnetic resonapce signal acquisition in different experiments are developed

  15. Learning in repeated visual search.

    Science.gov (United States)

    Hout, Michael C; Goldinger, Stephen D

    2010-07-01

    Visual search (e.g., finding a specific object in an array of other objects) is performed most effectively when people are able to ignore distracting nontargets. In repeated search, however, incidental learning of object identities may facilitate performance. In three experiments, with over 1,100 participants, we examined the extent to which search could be facilitated by object memory and by memory for spatial layouts. Participants searched for new targets (real-world, nameable objects) embedded among repeated distractors. To make the task more challenging, some participants performed search for multiple targets, increasing demands on visual working memory (WM). Following search, memory for search distractors was assessed using a surprise two-alternative forced choice recognition memory test with semantically matched foils. Search performance was facilitated by distractor object learning and by spatial memory; it was most robust when object identity was consistently tied to spatial locations and weakest (or absent) when object identities were inconsistent across trials. Incidental memory for distractors was better among participants who searched under high WM load, relative to low WM load. These results were observed when visual search included exhaustive-search trials (Experiment 1) or when all trials were self-terminating (Experiment 2). In Experiment 3, stimulus exposure was equated across WM load groups by presenting objects in a single-object stream; recognition accuracy was similar to that in Experiments 1 and 2. Together, the results suggest that people incidentally generate memory for nontarget objects encountered during search and that such memory can facilitate search performance.

  16. Quality control during repeated fryings

    Directory of Open Access Journals (Sweden)

    Cuesta, C.

    1998-08-01

    Full Text Available Most of the debate ¡s about how the slow or frequent turnover of fresh fat affects the deterioration, of fat used in frying. Then, the modification of different oils used in repeated fryings of potatoes without or with turnover of fresh oil, under similar frying conditions, was evaluated by two criteria: by measuring the total polar component isolated by column chromatography and by the evaluation of the specific compounds related to thermoxidative and hydrolytic alteration by High Performance Size Exclusion Chromatography (HPSEC. The results indicate that with frequent turnover of fresh oil, the critical level of 25% of polar material is rarely reached, and there are fewer problems with fat deterioration because the frying tended to increase the level of polar material and thermoxidative compounds (polymers and dimers of triglycerides and oxidized triglycerides in the fryer oil during the first fryings, followed by minor changes and a tendency to reach a near-steady state in successive fryings. However, in repeated frying of potatoes using a null turnover the alteration rate was higher being linear the relationship found between polar material or the different thermoxidative compounds and the number of fryings. On the other hand chemical reactions produced during deep-fat frying can be minimized by using proper oils. In addition the increased level of consumers awareness toward fat composition and its impact on human health could had an impact on the selection of fats for snacks and for industry. In this way monoenic fats are the most adequate from a nutritional point of view and for its oxidative stability during frying.

  17. Immunologically active peptides capable of inducing immunization against malaria and genes encoding therefor

    Energy Technology Data Exchange (ETDEWEB)

    Dame, J.B.; Williams, J.L.; McCutchan, T.F.; Schneider, I.

    1987-11-17

    An antimalarial immunogenic stimulant is described comprising an immunogenic carrier and a peptide sequence of between 2 and 1000 consecutive repeats of a sequence Asn-X-Y-Pro, wherein X is Ala or Val and Y is Asn or Asp.

  18. Highly selective end-tagged antimicrobial peptides derived from PRELP.

    Directory of Open Access Journals (Sweden)

    Martin Malmsten

    Full Text Available BACKGROUND: Antimicrobial peptides (AMPs are receiving increasing attention due to resistance development against conventional antibiotics. Pseudomonas aeruginosa and Staphylococcus aureus are two major pathogens involved in an array of infections such as ocular infections, cystic fibrosis, wound and post-surgery infections, and sepsis. The goal of the study was to design novel AMPs against these pathogens. METHODOLOGY AND PRINCIPAL FINDINGS: Antibacterial activity was determined by radial diffusion, viable count, and minimal inhibitory concentration assays, while toxicity was evaluated by hemolysis and effects on human epithelial cells. Liposome and fluorescence studies provided mechanistic information. Protease sensitivity was evaluated after subjection to human leukocyte elastase, staphylococcal aureolysin and V8 proteinase, as well as P. aeruginosa elastase. Highly active peptides were evaluated in ex vivo skin infection models. C-terminal end-tagging by W and F amino acid residues increased antimicrobial potency of the peptide sequences GRRPRPRPRP and RRPRPRPRP, derived from proline arginine-rich and leucine-rich repeat protein (PRELP. The optimized peptides were antimicrobial against a range of gram-positive S. aureus and gram-negative P. aeruginosa clinical isolates, also in the presence of human plasma and blood. Simultaneously, they showed low toxicity against mammalian cells. Particularly W-tagged peptides displayed stability against P. aeruginosa elastase, and S. aureus V8 proteinase and aureolysin, and the peptide RRPRPRPRPWWWW-NH(2 was effective against various "superbugs" including vancomycin-resistant enterococci, multi-drug resistant P. aeruginosa, and methicillin-resistant S. aureus, as well as demonstrated efficiency in an ex vivo skin wound model of S. aureus and P. aeruginosa infection. CONCLUSIONS/SIGNIFICANCE: Hydrophobic C-terminal end-tagging of the cationic sequence RRPRPRPRP generates highly selective AMPs with potent

  19. Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Acar, Handan [Institute; Department; Samaeekia, Ravand [Institute; Department; Schnorenberg, Mathew R. [Institute; Department; Medical; Sasmal, Dibyendu K. [Institute; Huang, Jun [Institute; Tirrell, Matthew V. [Institute; Institute; LaBelle, James L. [Department

    2017-08-24

    Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are two major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a resonance energy transfer (FRET)-based tracking system. Using this platform, components in real time using a Forster we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.

  20. Purification and use of E. coli peptide deformylase for peptide deprotection in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia; Sonke, Theo; Quaedflieg, Peter J.; Janssen, Dick B.

    Peptide deformylases (PDFs) catalyze the removal of the formyl group from the N-terminal methionine residue in nascent polypeptide chains in prokaryotes. Its deformylation activity makes PDF an attractive candidate for the biocatalytic deprotection of formylated peptides that are used in

  1. The leucine-rich repeat structure.

    Science.gov (United States)

    Bella, J; Hindle, K L; McEwan, P A; Lovell, S C

    2008-08-01

    The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures.

  2. Delivery systems for antimicrobial peptides

    DEFF Research Database (Denmark)

    Nordström, Randi; Malmsten, Martin

    2017-01-01

    on the identification such peptides, as well as on their optimization to reach potent antimicrobial and anti-inflammatory effects at simultaneously low toxicity against human cells. In comparison, delivery systems for antimicrobial peptides have attracted considerably less interest. However, such delivery systems......, or through achieving co-localization with intracellular pathogens. Here, an overview is provided of the current understanding of delivery systems for antimicrobial peptides, with special focus on AMP-carrier interactions, as well as consequences of these interactions for antimicrobial and related biological...

  3. CLE peptides regulate lateral root development in response to nitrogen nutritional status of plants.

    Science.gov (United States)

    Araya, Takao; von Wirén, Nicolaus; Takahashi, Hideki

    2014-01-01

    CLE (CLAVATA3/embryo surrounding region (ESR)) peptides control meristem functions in plants. Our recent study highlights the critical role of a peptide-receptor signaling module composed of nitrogen (N)-responsive CLE peptides and the CLAVATA1 (CLV1) leucine-rich repeat receptor-like kinase in controlling lateral root development in Arabidopsis thaliana. CLE1, -3, -4 and -7 are expressed in root pericycle cells in Arabidopsis roots under N-limited growth conditions. Overexpression of these CLE genes inhibits lateral root emergence from the primary root. The inhibitory action of N-responsive CLE peptides on lateral root development requires the function of CLV1 expressed in phloem companion cells in roots, suggesting that downstream signals are transferred through phloem for systemic regulation of root system architecture. An additional mechanism downstream of CLV1 feedback-regulates transcript levels of N-responsive CLE genes in roots for fine-tuning the signal amplitude.

  4. Biophysical Properties and Antiviral Activities of Measles Fusion Protein Derived Peptide Conjugated with 25-Hydroxycholesterol.

    Science.gov (United States)

    Gomes, Bárbara; Santos, Nuno C; Porotto, Matteo

    2017-10-31

    Measles virus (MV) infection is re-emerging, despite the availability of an effective vaccine. The mechanism of MV entry into a target cell relies on coordinated action between the MV hemagglutinin (H) receptor binding protein and the fusion envelope glycoprotein (F) which mediates fusion between the viral and cell membranes. Peptides derived from the C -terminal heptad repeat (HRC) of F can interfere with this process, blocking MV infection. As previously described, biophysical properties of HRC-derived peptides modulate their antiviral potency. In this work, we characterized a MV peptide fusion inhibitor conjugated to 25-hydroxycholesterol (25HC), a cholesterol derivative with intrinsic antiviral activity, and evaluated its interaction with membrane model systems and human blood cells. The peptide (MV.

  5. Repeats and EST analysis for new organisms

    Directory of Open Access Journals (Sweden)

    Jonassen Inge

    2008-01-01

    Full Text Available Abstract Background Repeat masking is an important step in the EST analysis pipeline. For new species, genomic knowledge is scarce and good repeat libraries are typically unavailable. In these cases it is common practice to mask against known repeats from other species (i.e., model organisms. There are few studies that investigate the effectiveness of this approach, or attempt to evaluate the different methods for identifying and masking repeats. Results Using zebrafish and medaka as example organisms, we show that accurate repeat masking is an important factor for obtaining a high quality clustering. Furthermore, we show that masking with standard repeat libraries based on curated genomic information from other species has little or no positive effect on the quality of the resulting EST clustering. Library based repeat masking which often constitutes a computational bottleneck in the EST analysis pipeline can therefore be reduced to species specific repeat libraries, or perhaps eliminated entirely. In contrast, substantially improved results can be achived by applying a repeat library derived from a partial reference clustering (e.g., from mapping sequences against a partially sequenced genome. Conclusion Of the methods explored, we find that the best EST clustering is achieved after masking with repeat libraries that are species specific. In the absence of such libraries, library-less masking gives results superior to the current practice of using cross-species, genome-based libraries.

  6. Novel peptides with tyrosinase inhibitory activity

    NARCIS (Netherlands)

    Schurink, M.; Berkel, van W.J.H.; Wichers, H.J.; Boeriu, C.G.

    2007-01-01

    Tyrosinase inhibition by peptides may find its application in food, cosmetics or medicine. In order to identify novel tyrosinase inhibitory peptides, protein-based peptide libraries made by SPOT synthesis were used to screen for peptides that show direct interaction with tyrosinase. One of the

  7. Characterization of Synthetic Peptides by Mass Spectrometry.

    Science.gov (United States)

    Prabhala, Bala K; Mirza, Osman; Højrup, Peter; Hansen, Paul R

    2015-01-01

    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI-TOF-MS and LC-MS of synthetic peptides.

  8. Synthetic molecular evolution of pore–forming peptides by Iterative combinatorial library screening

    Science.gov (United States)

    Krauson, Aram J.; He, Jing; Wimley, Andrew W.; Hoffmann, Andrew R.; Wimley, William C

    2013-01-01

    We previously reported the de novo design of a combinatorial peptide library that was subjected to high–throughput screening to identify membrane permeabilizing antimicrobial peptides that have β–sheet–like secondary structure. Those peptides do not form discreet pores in membranes but instead partition into membrane interfaces and cause transient permeabilization by membrane disruption, but only when present at high concentration. In this work, we used a consensus sequence from that initial screen as a template to design an iterative, second generation library. In the 24–26–residue, 16,200 member second generation library we varied six residues. Two diad repeat motifs of alternating polar and nonpolar amino acids were preserved to maintain a propensity for non–helical secondary structure. We used a new high–throughput assay to identify members that self–assemble into equilibrium pores in synthetic lipid bilayers. This screen was done at a very stringent peptide to lipid ratio of 1:1000 where most known membrane permeabilizing peptides, including the template peptide, are not active. In a screen of 10,000 library members we identified 16 (~0.2%) that are equilibrium pore–formers at this high stringency. These rare and highly active peptides, which share a common sequence motif, are as potent as the most active pore–forming peptides known. Furthermore, they are not α–helical, which makes them unusual, as most of the highly potent pore–forming peptides are amphipathic α–helices. Here we demonstrate that this synthetic molecular evolution–based approach, taken together with the new high–throughput tools we have developed, enables the identification, refinement and optimization of unique membrane active peptides. PMID:23394375

  9. Synthetic molecular evolution of pore-forming peptides by iterative combinatorial library screening.

    Science.gov (United States)

    Krauson, Aram J; He, Jing; Wimley, Andrew W; Hoffmann, Andrew R; Wimley, William C

    2013-04-19

    We previously reported the de novo design of a combinatorial peptide library that was subjected to high-throughput screening to identify membrane-permeabilizing antimicrobial peptides that have β-sheet-like secondary structure. Those peptides do not form discrete pores in membranes but instead partition into membrane interfaces and cause transient permeabilization by membrane disruption, but only when present at high concentration. In this work, we used a consensus sequence from that initial screen as a template to design an iterative, second generation library. In the 24-26-residue, 16,200-member second generation library we varied six residues. Two diad repeat motifs of alternating polar and nonpolar amino acids were preserved to maintain a propensity for non-helical secondary structure. We used a new high-throughput assay to identify members that self-assemble into equilibrium pores in synthetic lipid bilayers. This screen was done at a very stringent peptide to lipid ratio of 1:1000 where most known membrane-permeabilizing peptides, including the template peptide, are not active. In a screen of 10,000 library members we identified 16 (~0.2%) that are equilibrium pore-formers at this high stringency. These rare and highly active peptides, which share a common sequence motif, are as potent as the most active pore-forming peptides known. Furthermore, they are not α-helical, which makes them unusual, as most of the highly potent pore-forming peptides are amphipathic α-helices. Here we demonstrate that this synthetic molecular evolution-based approach, taken together with the new high-throughput tools we have developed, enables the identification, refinement, and optimization of unique membrane active peptides.

  10. Recognition of phage-expressed peptides containing Asx-Pro sequences by monoclonal antibodies produced against Plasmodium falciparum circumsporozoite protein.

    Science.gov (United States)

    Wilson, D R; Wirtz, R A; Finlay, B B

    1997-05-01

    The immunodominant region of the Plasmodium falciparum circumsporozoite protein is comprised mainly of a series of tetrapeptide repeats that can, depending on the starting cadence chosen, be described as (NANP)n, (ANPN)n, (NPNA)n or (PNAN)n in one-letter amino acid code. Data from several studies suggest that the NPNA cadence alone is structurally correct, in that each NPNA tetrapeptide effectively forms a structural unit initiated by an Asx-Pro turn. To explore this idea further and to assess the immunological relevance of peptide conformation as it relates to the cadence of these tetrapeptide repeats, we used ELISA to compare the abilities of monoclonal antibodies (MAbs) produced against P. falciparum sporozoites to recognize repeat-related heptapeptides expressed on the surface of filamentous bacteriophage. Having included representatives of both NANP and NPNA cadences and other peptides in which the number and location of Asx-Pro sequences varied, we provide evidence that Asx-Pro sequences play an important role in peptide conformation and antibody recognition, that peptide conformation is influenced by the cadence of the tetrapeptide repeats and that peptide conformation is important to the abilities of these MAbs to recognize their epitopes.

  11. Neoglycolipidation for modulating peptide properties

    DEFF Research Database (Denmark)

    van Witteloostuijn, Søren Blok

    regulation of appetite, food intake, and glucose homeostasis, and many of these peptides display a signicant potential for treatment of obesity and/or type 2 diabetes. This Ph.D. thesis describes three novel approaches for utilizing gut peptides as the starting point for developing obesity and diabetes drugs....... Subsequent stereological analyses of the pancreata showed that chronic treatment with GUB06-046 led to increased cell mass in db/db mice. The results of projects I and II clearly illustrate how chemical modications can improve the pharmacological properties of native peptides. Collectively, the ndings...... of this thesis contribute to emphasize the tremendous therapeutic potential of gut peptides for treatment of obesity and diabetes....

  12. New vasoactive peptides in cirrhosis

    DEFF Research Database (Denmark)

    Kimer, Nina; Goetze, Jens Peter; Bendtsen, Flemming

    2014-01-01

    BACKGROUND: Patients with cirrhosis have substantial circulatory imbalance between vasoconstrictive and vasodilating forces. The study of circulatory vasoactive peptides may provide important pathophysiological information. This study aimed to assess concentrations, organ extraction and relations...

  13. Moonlighting peptides with emerging function.

    Directory of Open Access Journals (Sweden)

    Jonathan G Rodríguez Plaza

    Full Text Available Hunter-killer peptides combine two activities in a single polypeptide that work in an independent fashion like many other multi-functional, multi-domain proteins. We hypothesize that emergent functions may result from the combination of two or more activities in a single protein domain and that could be a mechanism selected in nature to form moonlighting proteins. We designed moonlighting peptides using the two mechanisms proposed to be involved in the evolution of such molecules (i.e., to mutate non-functional residues and the use of natively unfolded peptides. We observed that our moonlighting peptides exhibited two activities that together rendered a new function that induces cell death in yeast. Thus, we propose that moonlighting in proteins promotes emergent properties providing a further level of complexity in living organisms so far unappreciated.

  14. Matrix-assisted peptide synthesis on nanoparticles.

    Science.gov (United States)

    Khandadash, Raz; Machtey, Victoria; Weiss, Aryeh; Byk, Gerardo

    2014-09-01

    We report a new method for multistep peptide synthesis on polymeric nanoparticles of differing sizes. Polymeric nanoparticles were functionalized via their temporary embedment into a magnetic inorganic matrix that allows multistep peptide synthesis. The matrix is removed at the end of the process for obtaining nanoparticles functionalized with peptides. The matrix-assisted synthesis on nanoparticles was proved by generating various biologically relevant peptides. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

  15. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  16. RepSeq – A database of amino acid repeats present in lower eukaryotic pathogens

    Directory of Open Access Journals (Sweden)

    Smith Deborah F

    2007-04-01

    Full Text Available Abstract Background Amino acid repeat-containing proteins have a broad range of functions and their identification is of relevance to many experimental biologists. In human-infective protozoan parasites (such as the Kinetoplastid and Plasmodium species, they are implicated in immune evasion and have been shown to influence virulence and pathogenicity. RepSeq http://repseq.gugbe.com is a new database of amino acid repeat-containing proteins found in lower eukaryotic pathogens. The RepSeq database is accessed via a web-based application which also provides links to related online tools and databases for further analyses. Results The RepSeq algorithm typically identifies more than 98% of repeat-containing proteins and is capable of identifying both perfect and mismatch repeats. The proportion of proteins that contain repeat elements varies greatly between different families and even species (3–35% of the total protein content. The most common motif type is the Sequence Repeat Region (SRR – a repeated motif containing multiple different amino acid types. Proteins containing Single Amino Acid Repeats (SAARs and Di-Peptide Repeats (DPRs typically account for 0.5–1.0% of the total protein number. Notable exceptions are P. falciparum and D. discoideum, in which 33.67% and 34.28% respectively of the predicted proteomes consist of repeat-containing proteins. These numbers are due to large insertions of low complexity single and multi-codon repeat regions. Conclusion The RepSeq database provides a repository for repeat-containing proteins found in parasitic protozoa. The database allows for both individual and cross-species proteome analyses and also allows users to upload sequences of interest for analysis by the RepSeq algorithm. Identification of repeat-containing proteins provides researchers with a defined subset of proteins which can be analysed by expression profiling and functional characterisation, thereby facilitating study of pathogenicity

  17. A rapid and clean synthetic approach to cyclic peptides via micro-flow peptide chain elongation and photochemical cyclization: synthesis of a cyclic RGD peptide.

    Science.gov (United States)

    Mifune, Yuto; Nakamura, Hiroyuki; Fuse, Shinichiro

    2016-11-29

    A cyclic RGD peptide was efficiently synthesized based on micro-flow, triphosgene-mediated peptide chain elongation and micro-flow photochemical macrolactamization. Our approach enabled a rapid (amidation for peptide chain elongation peptide.

  18. Implications of Neuroinvasive Bacterial Peptides on Rodents Behaviour and Neurotransmission

    Directory of Open Access Journals (Sweden)

    Aneela Taj

    2017-07-01

    Full Text Available Neuroinvasive microbes are capable of applying their influences on the autonomic nervous system (ANS of the host followed by the involvement of central nervous system (CNS by releasing extracellular metabolites that may cause alterations in the biochemical and neurophysiological environment. Consequently synaptic, neuroendocrine, peripheral immune, neuro-immune, and behavioural responses of the host facilitate the progression of infection. The present study was designed to extrapolate the effects of crude and purified extracellular peptides of neuropathogenic bacteria on behavioural responses and neurotransmission of Sprague Dawley (SD models. Listeria monocytogenes (Lm and Neisseria meningitides (Nm were isolated from the 92 cerebrospinal fluid (CSF samples collected from mentally compromised patients. Bacillus cereus (Bc and Clostridium tetani (Ct were also included in the study. All bacterial strains were identified by the standard biochemical procedures. Filter sterilized cell free cultural broths (SCFBs were prepared of different culture media. Behavioural study and neurotransmitter analysis were performed by giving an intraperitoneal (i.p. injection of each bacterial SCFB to four groups (Test; n = 7 of SD rats, whereas two groups each (Control; n = 7 received a nutrient broth (NB control and sterile physiological saline control, respectively. Extracellular bioactive peptides of these bacteria were screened and purified. All experiments were repeated using purified bacterial peptides on SD rat cohorts. Our study indicated promising behavioural changes, including fever, swelling, and hind paw paralysis, in SD rat cohorts. Purified bacterial peptides of all bacteria used in the present study elicited marked changes in behaviour through the involvement of the autonomic nervous system. Furthermore, these peptides of meningitis bacteria were found to potently affect the dopaminergic neurotransmission in CNS.

  19. Automated solid-phase peptide synthesis to obtain therapeutic peptides

    Directory of Open Access Journals (Sweden)

    Veronika Mäde

    2014-05-01

    Full Text Available The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.

  20. Peptides and Food Intake

    Directory of Open Access Journals (Sweden)

    Carmen Sobrino Crespo

    2014-04-01

    Full Text Available Nutrients created by the digestion of food are proposed to active G protein coupled receptors on the luminal side of enteroendocrine cells e.g. the L-cell. This stimulates the release of gut hormones. Hormones released from the gut and adipose tissue play an important rol in the regulation of food intake and energy expenditure (1.Many circulating signals, including gut hormones, can influence the activity of the arcuate nucleus (ARC neurons directly, after passing across the median eminence. The ARC is adjacent to the median eminence, a circumventricular organ with fenestrated capillaries and hence an incomplete blood-brain barrier (2. The ARC of the hypothalamus is believed to play a crucial role in the regulation of food intake and energy homeostasis. The ARC contains two populations of neurons with opposing effect on food intake (3. Medially located orexigenic neurons (i.e those stimulating appetite express neuropeptide Y (NPY and agouti-related protein (AgRP (4-5. Anorexigenic neurons (i.e. those inhibiting appetite in the lateral ARC express alpha-melanocyte stimulating hormone (α-MSH derived from pro-opiomelanocortin (POMC and cocaine and amphetamine-regulated transcript (CART (6. The balance between activities of these neuronal circuits is critical to body weight regulation.In contrast, other peripheral signals influence the hypothalamus indirectly via afferent neuronal pathway and brainstem circuits. In this context gastrointestinal’s vagal afferents are activated by mechanoreceptors and chemoreceptors, and converge in the nucleus of the tractus solitaries (NTS of the brainstem. Neuronal projections from the NTS, in turn, carry signals to the hypotalamus (1, 7. Gut hormones also alter the activity of the ascending vagal pathway from the gut to the brainstem. In the cases of ghrelin and Peptide tyrosine tyrosine (PYY, there are evidences for both to have a direct action on the arcuate nucleus and an action via the vagus nerve a

  1. Fibronectin peptides that bind PDGF-BB enhance survival of cells and tissue under stress

    Science.gov (United States)

    Lin, Fubao; Zhu, Jia; Tonnesen, Marcia G.; Taira, Breena R.; McClain, Steve A.; Singer, Adam J.; Clark, Richard A.F.

    2013-01-01

    Stressors after injury from a multitude of factors can lead to cell death. We have identified four fibronectin (FN) peptides, two from the first FN type III repeat (FNIII1), one from the 13th FN type III repeat (FNIII13), and one from FN variable region (IIICS), that when tethered to a surface acted as platelet-derived growth factor-BB (PDGF-BB) enhancers to promote cell survival. One of the FNIII1 peptides and its smallest (14mer) bioactive form (P12) were also active in solution. Specifically, P12 bound PDGF-BB (KD = 200nM), enhanced adult human dermal fibroblast (AHDF) survival under serum starvation, oxidative or endoplasmic reticulum (ER) stressors, and limited burn injury progression in a rat hot comb model. Furthermore, P12 inhibited ER stress-induced c-Jun N-terminal kinase (JNK) activation. Although many growth factors have been found to bind FN directly or indirectly, this is the first report to identify peptide sequences of growth factor-binding sites in FN. The finding of these novel peptides further delineated how the extracellular matrix protein FN can support cell survival. Since the peptide P12 is active in either soluble form or tethered to a substrate, it will have multifactorial uses as a bioactive in tissue engineering. PMID:24126844

  2. simple sequence repeats (EST-SSR)

    African Journals Online (AJOL)

    Yomi

    2012-01-19

    Jan 19, 2012 ... 212 primer pairs selected, based on repeat patterns of n≥8 for di-, tri-, tetra- and penta-nucleotide repeat ... Cluster analysis revealed a high genetic similarity among the sugarcane (Saccharum spp.) breeding lines which could reduce the genetic gain in ..... The multiple allele characteristic of SSR com-.

  3. Repeatability & Workability Evaluation of SIGMOD 2009

    KAUST Repository

    Manegold, Stefan

    2010-12-15

    SIGMOD 2008 was the first database conference that offered to test submitters\\' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

  4. (SSR) and inter simple sequence repeat (ISSR)

    African Journals Online (AJOL)

    Finally, they were washed 3 to 4 times with sterile distilled water and inoculated aseptically on Murashige and Skoog (MS) basal medium free hormones. Single nodes resulted from seedlings cultured as explants. Inter simple sequence repeat (ISSR) and simple sequence repeat (SSR) primers used produced different ...

  5. Exploration of the Medicinal Peptide Space.

    Science.gov (United States)

    Gevaert, Bert; Stalmans, Sofie; Wynendaele, Evelien; Taevernier, Lien; Bracke, Nathalie; D'Hondt, Matthias; De Spiegeleer, Bart

    2016-01-01

    The chemical properties of peptide medicines, known as the 'medicinal peptide space' is considered a multi-dimensional subset of the global peptide space, where each dimension represents a chemical descriptor. These descriptors can be linked to biofunctional, medicinal properties to varying degrees. Knowledge of this space can increase the efficiency of the peptide-drug discovery and development process, as well as advance our understanding and classification of peptide medicines. For 245 peptide drugs, already available on the market or in clinical development, multivariate dataexploration was performed using peptide relevant physicochemical descriptors, their specific peptidedrug target and their clinical use. Our retrospective analysis indicates that clusters in the medicinal peptide space are located in a relatively narrow range of the physicochemical space: dense and empty regions were found, which can be explored for the discovery of novel peptide drugs.

  6. Cyclic peptide therapeutics: past, present and future.

    Science.gov (United States)

    Zorzi, Alessandro; Deyle, Kaycie; Heinis, Christian

    2017-06-01

    Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics. Over 40 cyclic peptide drugs are currently in clinical use and around one new cyclic peptide drug enters the market every year on average. The vast majority of clinically approved cyclic peptides are derived from natural products, such as antimicrobials or human peptide hormones. New powerful techniques based on rational design and in vitro evolution have enabled the de novo development of cyclic peptide ligands to targets for which nature does not offer solutions. A look at the cyclic peptides currently under clinical evaluation shows that several have been developed using such techniques. This new source for cyclic peptide ligands introduces a freshness to the field, and it is likely that de novo developed cyclic peptides will be in clinical use in the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Perspectives and Peptides of the Next Generation

    Science.gov (United States)

    Brogden, Kim A.

    Shortly after their discovery, antimicrobial peptides from prokaryotes and eukaryotes were recognized as the next potential generation of pharmaceuticals to treat antibiotic-resistant bacterial infections and septic shock, to preserve food, or to sanitize surfaces. Initial research focused on identifying the spectrum of antimicrobial agents, determining the range of antimicrobial activities against bacterial, fungal, and viral pathogens, and assessing the antimicrobial activity of synthetic peptides versus their natural counterparts. Subsequent research then focused on the mechanisms of antimicrobial peptide activity in model membrane systems not only to identify the mechanisms of antimicrobial peptide activity in microorganisms but also to discern differences in cytotoxicity for prokaryotic and eukaryotic cells. Recent, contemporary work now focuses on current and future efforts to construct hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates, and immobilized peptides for unique and specific applications to control the growth of microorganisms in vitro and in vivo.

  8. UK 2009-2010 repeat station report

    Directory of Open Access Journals (Sweden)

    Thomas J.G. Shanahan

    2013-03-01

    Full Text Available The British Geological Survey is responsible for conducting the UK geomagnetic repeat station programme. Measurements made at the UK repeat station sites are used in conjunction with the three UK magnetic observatories: Hartland, Eskdalemuir and Lerwick, to produce a regional model of the local field each year. The UK network of repeat stations comprises 41 stations which are occupied at approximately 3-4 year intervals. Practices for conducting repeat station measurements continue to evolve as advances are made in survey instrumentation and as the usage of the data continues to change. Here, a summary of the 2009 and 2010 UK repeat station surveys is presented, highlighting the measurement process and techniques, density of network, reduction process and recent results.

  9. Thermodynamics of engineered gold binding peptides: establishing the structure-activity relationships.

    Science.gov (United States)

    Seker, Urartu Ozgur Safak; Wilson, Brandon; Kulp, John L; Evans, John S; Tamerler, Candan; Sarikaya, Mehmet

    2014-07-14

    Adsorption behavior of a gold binding peptide was experimentally studied to achieve kinetics and thermodynamics parameters toward understanding of the binding of an engineered peptide onto a solid metal surface. The gold-binding peptide, GBP1, was originally selected using a cell surface display library and contains 14 amino acid residues. In this work, single- and three-repeats of GBP1 were used to assess the effects of two parameters: molecular architecture versus secondary structure on adsorption on to gold substrate. The adsorption measurements were carried out using surface plasmon resonance (SPR) spectroscopy at temperatures ranging from 10 to 55 °C. At all temperatures, two different regimes of peptide adsorption were observed, which, based on the model, correspond to two sets of thermodynamics values. The values of enthalpy, ΔH(ads), and entropy, ΔS(ads), in these two regimes were determined using the van't Hoff approach and Gibbs-Helmholtz relationship. In general, the values of enthalpy for both peptides are negative indicating GBP1 binding to gold is an exothermic phenomenon and that the binding of three repeat gold binding peptide (3l-GBP1) is almost 5 times tighter than that for the single repeat (l-GBP1). More intriguing result is that the entropy of adsorption for the 3l-GBP1 is negative (-43.4 ± 8.5 cal/(mol K)), while that for the l-GBP1 is positive (10.90 ± 1.3 cal/(mol K)). Among a number of factors that synergistically contribute to the decrease of entropy, long-range ordered self-assembly of the 3l-GBP1 on gold surface is the most effective, probably through both peptide-solid and peptide-peptide intermolecular interactions. Additional adsorption experiments were conducted in the presence of 2,2,2-trifluoroethanol (TFE) to determine how the conformational structures of the biomolecules responded to the environmental perturbation. We found that the peptides differ in their conformational responses to the change in solution conditions; while

  10. Microstructure and nanomechanical properties of enamel remineralized with asparagine-serine-serine peptide

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hsiu-Ying, E-mail: hychung@mail.fcu.edu.tw; Li, Cheng Che

    2013-03-01

    A highly biocompatible peptide, triplet repeats of asparagine-serine-serine (3NSS) was designed to regulate mineral deposition from aqueous ions in saliva for the reconstruction of enamel lesions. Healthy human enamel was sectioned and acid demineralized to create lesions, then exposed to the 3NSS peptide solution, and finally immersed in artificial saliva for 24 h. The surface morphology and roughness were examined using scanning electron microscopy (SEM) and atomic force microscopy (AFM), respectively. X-ray diffraction (XRD) was used to identify the phases and crystallinity of the deposited minerals observed on the enamel surface. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to quantitatively analyze the mineral variation by calculating the relative integrated-area of characteristic bands. Nanohardness and elastic modulus measured by nanoindentation at various treatment stages were utilized to evaluate the degree of recovery. Biomimetic effects were accessed according to the degree of nanohardness recovery and the amount of hydroxyapatite deposition. The charged segments in the 3NSS peptide greatly attracted aqueous ions from artificial saliva to form hydroxyapatite crystals to fill enamel caries, in particular the interrod areas, resulting in a slight reduction in overall surface roughness. Additionally, the deposited hydroxyapatites were of a small crystalline size in the presence of the 3NSS peptide, which effectively restrained the plastic deformations and thus resulted in greater improvements in nanohardness and elastic modulus. The degree of nanohardness recovery was 5 times greater for remineralized enamel samples treated with the 3NSS peptide compared to samples without peptide treatment. - Highlights: Black-Right-Pointing-Pointer The degree of nanohardness recovery of enamel was 4 times greater with the aid of 3NSS peptide. Black-Right-Pointing-Pointer 3NSS peptide promoted the formation of hydroxyapatites with

  11. Secretion of Acid Sphingomyelinase is Affected by its Polymorphic Signal Peptide

    Directory of Open Access Journals (Sweden)

    Cosima Rhein

    2014-10-01

    Full Text Available Background: Acid sphingomyelinase (ASM catalyses the hydrolysis of sphingomyelin into ceramide, which acts as a lipid messenger that regulates important cellular functions. Deregulated ASM activity has been reported for different common diseases, but the mechanisms regulating ASM activity are still debated. ASM contains an exceptional signal peptide which is polymorphic due to a variable number of a hexanucleotide sequence that determines the length of the hydrophobic core. We investigated the impact of the signal peptide polymorphism on the regulation of ASM activity and secretion in vivo and in vitro. Methods and Results: Subjects homozygous for the rare 4-repeat allele displayed significantly lower secreted ASM activity than subjects homozygous for the common 6-repeat allele. In vitro, overexpression of ASM variants encoded by 2, 8 or 9 repeats resulted in a significantly lowered ASM secretion rate. Treatment of ASM-overexpressing cells with tumour necrosis factor α induced secretion of ASM, and the secretion rate was highest for the most common ASM variant encoding 6 repeats compared to other naturally occurring variants. Conclusion: We provide evidence that the polymorphic ASM signal peptide regulates ASM secretion. It might be an evolutionary mechanism to increase ASM secretion potential, whereas an increase in lysosomal ASM activity is limited due to deleterious cellular effects.

  12. Characterization of Synthetic Peptides by Mass Spectrometry

    DEFF Research Database (Denmark)

    Prabhala, Bala K; Mirza, Osman; Højrup, Peter

    2015-01-01

    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI-TOF-MS an......Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI...

  13. Preliminary screening and identification of the hepatocarcinoma cell-binding peptide

    International Nuclear Information System (INIS)

    Zhu Xiaohua; Wu Hua

    2004-01-01

    Objective: To explore the feasibility of screening and isolating homing peptides that bind specifically, or preferentially, to hepatocarcinoma cells using phage display random peptide library and to develop a new peptide which may be potentially used as targeting delivery carrier in the biological targeted diagnosis or therapy for liver cancer. Methods: A 12-mer peptide phage display library was used to screen and isolate peptides that bind to human hepatocarcinoma cells, and four rounds of subtractive panning were carried out with the human hepatocarcinoma cell line HepG2 as the target. The affinities of selected phage clones for human hepatocarcinoma cells were determined with enzyme-linked immunosorbent assay (ELISA) and compared with that to human liver cell and other tumor cells of different tissue origins, respectively. In addition, the binding site in the tumor cells was observed with immunofluorescence analysis under confocal light microscopy. The amino acid sequences of phages that bind HepG2 specifically were deduced through DNA sequencing. Based on the results of DNA sequence, a 16-mer peptide (WH16) was designed and synthesized. Binding ability of the new peptide, WH16, was determined with competitive inhibition test. Results: After four rounds of panning, the phages that were bound to and internalized in human hepatocarcinoma cells were isolated. ELISA and immunofluorescence analysis confirmed the affinity of these phages for hepatocarcinoma cells. 56.67%(17/30) of the isolated phages displayed repeated sequence FLLEPHLMDTSM, and FLEP was defined as conservative motif . Binding of the selected phage to HepG2 cells was inhibited by synthesized peptide WH16, that strongly support that cellular binding of the phage is mediated through its displayed peptide, and WH16 can also bind to HepG2. Conclusions: It is feasible to screen and isolate homing peptides that bind specifically, or preferentially, to hepatocarcinoma cells using phage display random peptide

  14. Preliminary screening and identification of the peptide binding to hepatocarcinoma cell

    International Nuclear Information System (INIS)

    Zhu Xiaohua; Wu Ha

    2004-01-01

    Objective: The present study was performed to screen and isolate homing peptides that bind specifically, or preferentially, to hepatocarcinoma cells using phage display of random peptide library with the purpose of developing a new peptide which may be potentially used as target delivery carrier in the biological target diagnosis or therapy for liver cancer. Methods: A peptide 12-mer phage display library was used to screen and isolate peptide that bind to human hepatocarcinoma cell, and four rounds subtractive panning were carried out with the human hepatocarcinoma cell line HepG2 as the target. The affinities of selected phage clones to human hepatocarcinoma cell were determined with ELISA and compared with human liver cell and other tumor cells of different tissue origins respectively. In addition, the binding site in the tumor cells was observed with immunofluorescence analysis under confocal light microscopy. The amino acid sequences of phages that bind HepG2 specifically were deduced though DNA sequencing. Based on the results of DNA sequence, a 16-mer peptide (WH16) was designed and synthesized. Binding ability of the new peptide WH16 was determined with competitive inhibition test. Results: After four rounds panning, the phages that bound to and internalized in human hepatocarcinoma cell were isolated. ELISA and immunofluorescence analysis confirmed the affinity of these phages to hepatpcarcinoma cells 56.57%(17/30) of the isolated phages displayed repeated sequence FLLEPHLMDTSM, and FLEP was defined as conservative motif. Binding of the selected phage to HepG2 cells was inhibited by synthesized peptide WH16, which strongly support that cellular binding of phage is mediated though its displayed peptide and WH16 can also bind to HepG2. Conclusion: It is feasible to screen and isolate homing peptides that bind specifically, or preferentially, to hepatocarcinoma cells using phage display of random peptide libraries. The sequence of peptide that can bind to

  15. Boron-doped diamond electrodes for the electrochemical oxidation and cleavage of peptides.

    Science.gov (United States)

    Roeser, Julien; Alting, Niels F A; Permentier, Hjalmar P; Bruins, Andries P; Bischoff, Rainer

    2013-07-16

    Electrochemical oxidation of peptides and proteins is traditionally performed on carbon-based electrodes. Adsorption caused by the affinity of hydrophobic and aromatic amino acids toward these surfaces leads to electrode fouling. We compared the performance of boron-doped diamond (BDD) and glassy carbon (GC) electrodes for the electrochemical oxidation and cleavage of peptides. An optimal working potential of 2000 mV was chosen to ensure oxidation of peptides on BDD by electron transfer processes only. Oxidation by electrogenerated OH radicals took place above 2500 mV on BDD, which is undesirable if cleavage of a peptide is to be achieved. BDD showed improved cleavage yield and reduced adsorption for a set of small peptides, some of which had been previously shown to undergo electrochemical cleavage C-terminal to tyrosine (Tyr) and tryptophan (Trp) on porous carbon electrodes. Repeated oxidation with BDD electrodes resulted in progressively lower conversion yields due to a change in surface termination. Cathodic pretreatment of BDD at a negative potential in an acidic environment successfully regenerated the electrode surface and allowed for repeatable reactions over extended periods of time. BDD electrodes are a promising alternative to GC electrodes in terms of reduced adsorption and fouling and the possibility to regenerate them for consistent high-yield electrochemical cleavage of peptides. The fact that OH-radicals can be produced by anodic oxidation of water at elevated positive potentials is an additional advantage as they allow another set of oxidative reactions in analogy to the Fenton reaction, thus widening the scope of electrochemistry in protein and peptide chemistry and analytics.

  16. Antiviral active peptide from oyster

    Science.gov (United States)

    Zeng, Mingyong; Cui, Wenxuan; Zhao, Yuanhui; Liu, Zunying; Dong, Shiyuan; Guo, Yao

    2008-08-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster ( Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10 5 kDa, 5 1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10 5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  17. Dietary bioactive peptides: Human studies.

    Science.gov (United States)

    Bouglé, Dominique; Bouhallab, Saïd

    2017-01-22

    Current opinion strongly links nutrition and health. Among nutrients, proteins, and peptides which are encrypted in their sequences and released during digestion could play a key role in improving health. These peptides have been claimed to be active on a wide spectrum of biological functions or diseases, including blood pressure and metabolic risk factors (coagulation, obesity, lipoprotein metabolism, and peroxidation), gut and neurological functions, immunity, cancer, dental health, and mineral metabolism. A majority of studies involved dairy peptides, but the properties of vegetal, animal, and sea products were also assessed. However, these allegations are mainly based on in vitro and experimental studies which are seldom confirmed in humans. This review focused on molecules which were tested in humans, and on the mechanisms explaining discrepancies between experimental and human studies.

  18. Removing Cross-Linked Telopeptides Enhances the Production of Low-Molecular-Weight Collagen Peptides from Spent Hens.

    Science.gov (United States)

    Hong, Hui; Chaplot, Shreyak; Chalamaiah, Meram; Roy, Bimol C; Bruce, Heather L; Wu, Jianping

    2017-08-30

    The low-molecular-weight (LMW) peptides derived from collagen have shown a potential for various nutritional and pharmaceutical applications. However, production of LMW peptides from vertebrate collagen remains a challenge. Herein, we report a new method to produce LMW collagen peptides using pepsin pretreatment that removed cross-linked telopeptides in collagen molecules. After the pretreatment, the proportion of LMW collagen peptides (collagen increased to 32.59% compared to heat-soluble collagen peptides (16.10%). Fourier transform infrared spectroscopy results indicated that telopeptide cleavage retained the triple-helical conformation of collagen. Liquid chromatography-tandem mass spectrometry analysis suggested that Gly-X-Y (X is often proline, while Y is either hydroxyproline or hydroxylysine) repeats were not the main factors that hindered the enzymatic hydrolysis of collagen molecules. However, cross-link quantification demonstrated that trivalent cross-links that included pyridinolines and pyrroles were the primary obstacles to producing small peptides from collagen of spent hens. This study demonstrated for the first time that removing cross-linked telopeptides could enhance the production of LMW peptides from spent hen collagen, which is also of interest to manufacturers who produce LMW collagen peptides from other vertebrate animals, such as bovids and porcids.

  19. Inhibitory peptides of the sulfotransferase domain of the heparan sulfate enzyme, N-deacetylase-N-sulfotransferase-1.

    Science.gov (United States)

    Gesteira, Tarsis F; Coulson-Thomas, Vivien J; Taunay-Rodrigues, Alessandro; Oliveira, Vitor; Thacker, Bryan E; Juliano, Maria A; Pasqualini, Renata; Arap, Wadih; Tersariol, Ivarne L S; Nader, Helena B; Esko, Jeffrey D; Pinhal, Maria A S

    2011-02-18

    N-Deacetylase-N-sulfotransferase 1 (Ndst1) catalyzes the initial modification of heparan sulfate and heparin during their biosynthesis by removal of acetyl groups from subsets of N-acetylglucosamine units and subsequent sulfation of the resulting free amino groups. In this study, we used a phage display library to select peptides that interact with Ndst1, with the aim of finding inhibitors of the enzyme. The phage library consisted of cyclic random 10-mer peptides expressed in the phage capsid protein pIII. Selection was based on the ability of engineered phage to bind to recombinant murine Ndst1 (mNdst1) and displacement with heparin. Peptides that were enriched through multiple cycles of binding and disassociation displayed two specific sequences, CRGWRGEKIGNC and CNMQALSMPVTC. Both peptides inhibited mNdst1 activity in vitro, however, by distinct mechanisms. The peptide CRGWRGEKIGNC presents a chemokine-like repeat motif (BXX, where B represents a basic amino acid and X is a noncharged amino acid) and binds to heparan sulfate, thus blocking the binding of substrate to the enzyme. The peptide NMQALSMPVT inhibits mNdst1 activity by direct interaction with the enzyme near the active site. The discovery of inhibitory peptides in this way suggests a method for developing peptide inhibitors of heparan sulfate biosynthesis.

  20. The Plant Leucine-Rich Repeat Receptor-Like Kinase PSY1R from Head to Toe

    DEFF Research Database (Denmark)

    Oehlenschlæger, Christian Berg

    PSY1R belongs to the family of plant leucine-rich repeat receptor-like kinases that play important roles in processes such as growth regulation and plant immunity response. PSY1R was proposed to be the receptor of the plant peptide hormone PSY1 which promotes cell expansion. PSY1R was furthermore...... are conserved among related plant leucine-rich repeat receptor-like kinases whereas Ser951 is unique for PSY1R which suggests that it may serve a specialized function in regulation of PSY1R kinase activity....

  1. Natriuretic peptides and cerebral hemodynamics

    DEFF Research Database (Denmark)

    Guo, Song; Barringer, Filippa; Zois, Nora Elisabeth

    2014-01-01

    in decompensated disease. In contrast, their biological effects on the cerebral hemodynamics are poorly understood. In this mini-review, we summarize the hemodynamic effects of the natriuretic peptides with a focus on the cerebral hemodynamics. In addition, we will discuss its potential implications in diseases...... where alteration of the cerebral hemodynamics plays a role such as migraine and acute brain injury including stroke. We conclude that a possible role of the peptides is feasible as evaluated from animal and in vitro studies, but more research is needed in humans to determine the precise response...

  2. Novel Formulations for Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2014-10-01

    Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  3. Biodegradable Peptide-Silica Nanodonuts.

    Science.gov (United States)

    Maggini, Laura; Travaglini, Leana; Cabrera, Ingrid; Castro-Hartmann, Pablo; De Cola, Luisa

    2016-03-07

    We report hybrid organosilica toroidal particles containing a short peptide sequence as the organic component of the hybrid systems. Once internalised in cancer cells, the presence of the peptide allows for interaction with peptidase enzymes, which attack the nanocarrier effectively triggering its structural breakdown. Moreover, these biodegradable nanovectors are characterised by high cellular uptake and exocytosis, showing great potential as biodegradable drug carriers. To demonstrate this feature, doxorubicin was employed and its delivery in HeLa cells investigated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. The Plant Leucine-Rich Repeat Receptor-Like Kinase PSY1R from Head to Toe

    DEFF Research Database (Denmark)

    Oehlenschlæger, Christian Berg

    PSY1R belongs to the family of plant leucine-rich repeat receptor-like kinases that play important roles in processes such as growth regulation and plant immunity response. PSY1R was proposed to be the receptor of the plant peptide hormone PSY1 which promotes cell expansion. PSY1R was furthermore...... are conserved among related plant leucine-rich repeat receptor-like kinases whereas Ser951 is unique for PSY1R which suggests that it may serve a specialized function in regulation of PSY1R kinase activity....... shown to phosphorylate and regulate the activity of the plasma membrane localized H+-ATPase, AHA2. While the mechanism of PSY1R-mediated AHA2 phosphorylation has previously been studied in detail, little is known about how PSY1R binds PSY1 peptide ligand and how the intracellular PSY1R kinase domain...

  5. Inhibition of Growth and Gene Expression by PNA-peptide Conjugates in Streptococcus pyogenes

    Directory of Open Access Journals (Sweden)

    Nadja Patenge

    2013-01-01

    Full Text Available While Streptococcus pyogenes is consistently susceptible toward penicillin, therapeutic failure of penicillin treatment has been reported repeatedly and a considerable number of patients exhibit allergic reactions to this substance. At the same time, streptococcal resistance to alternative antibiotics, e.g., macrolides, has increased. Taken together, these facts demand the development of novel therapeutic strategies. In this study, S. pyogenes growth was inhibited by application of peptide-conjugated antisense-peptide nucleic acids (PNAs specific for the essential gyrase A gene (gyrA. Thereby, HIV-1 Tat peptide-coupled PNAs were more efficient inhibitors of streptococcal growth as compared with (KFF3K-coupled PNAs. Peptide-anti-gyrA PNAs decreased the abundance of gyrA transcripts in S. pyogenes. Growth inhibition by antisense interference was enhanced by combination of peptide-coupled PNAs with protein-level inhibitors. Antimicrobial synergy could be detected with levofloxacin and novobiocin, targeting the gyrase enzyme, and with spectinomycin, impeding ribosomal function. The prospective application of carrier peptide-coupled antisense PNAs in S. pyogenes covers the use as an antimicrobial agent and the employment as a knock-down strategy for the investigation of virulence factor function.

  6. Structurally Ordered Nanowire Formation from Co-Assembly of DNA Origami and Collagen-Mimetic Peptides

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Tao [Department; Meyer, Travis A. [Wallace; Modlin, Charles [Department; Zuo, Xiaobing [X-ray; Conticello, Vincent P. [Department; Ke, Yonggang [Wallace

    2017-10-02

    We describe the co-assembly of two different building units: collagen-mimetic peptides and DNA origami. Two peptides CP++ and sCP(++) are designed with a sequence comprising a central block (Pro-Hyp-Gly) and two positively charged domains (Pro-Arg-Gly) at both N- and C-termini. Co-assembly of peptides and DNA origami two-layer (TL) nanosheets affords the formation of one-dimensional nanowires with repeating periodicity of similar to 10 nm. Structural analyses suggest a face-to-face stacking of DNA nanosheets with peptides aligned perpendicularly to the sheet surfaces. We demonstrate the potential of selective peptide-DNA association between face-to-face and edge-to-edge packing by tailoring the size of DNA nanostructures. This study presents an attractive strategy to create hybrid biomolecular assemblies from peptide and DNA-based building blocks that takes advantage of the intrinsic chemical and physical properties of the respective components to encode structural and, potentially, functional complexity within readily accessible biomimetic materials.

  7. Production and characterization of peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar

    2012-01-01

    Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies...... are powerful tools in experimental biology and are easily produced to any peptide of choice. A widely used approach for production of peptide antibodies is to immunize animals with a synthetic peptide coupled to a carrier protein. Very important is the selection of the synthetic peptide, where factors...... such as structure, accessibility and amino acid composition are crucial. Since small peptides tend not to be immunogenic, it may be necessary to conjugate them to carrier proteins in order to enhance immune presentation. Several strategies for conjugation of peptide-carriers applied for immunization exist...

  8. The intracellular pharmacokinetics of terminally capped peptides.

    NARCIS (Netherlands)

    Ruttekolk, I.R.R.; Witsenburg, J.J.; Glauner, H.B.; Bovee-Geurts, P.H.M.; Ferro, E.S.; Verdurmen, W.P.R.; Brock, R.E.

    2012-01-01

    With significant progress in delivery technologies, peptides and peptidomimetics are receiving increasing attention as potential therapeutics also for intracellular applications. However, analyses of the intracellular behavior of peptides are a challenge; therefore, knowledge on the intracellular

  9. Strategic approaches to optimizing peptide ADME properties.

    Science.gov (United States)

    Di, Li

    2015-01-01

    Development of peptide drugs is challenging but also quite rewarding. Five blockbuster peptide drugs are currently on the market, and six new peptides received first marketing approval as new molecular entities in 2012. Although peptides only represent 2% of the drug market, the market is growing twice as quickly and might soon occupy a larger niche. Natural peptides typically have poor absorption, distribution, metabolism, and excretion (ADME) properties with rapid clearance, short half-life, low permeability, and sometimes low solubility. Strategies have been developed to improve peptide drugability through enhancing permeability, reducing proteolysis and renal clearance, and prolonging half-life. In vivo, in vitro, and in silico tools are available to evaluate ADME properties of peptides, and structural modification strategies are in place to improve peptide developability.

  10. Histidine-Containing Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2000-01-01

    Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics.......Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics....

  11. Tumor Associated Antigenic Peptides in Prostate Cancer

    National Research Council Canada - National Science Library

    Tiwari, Raj

    2001-01-01

    .... Since this tumor rejection property was specifically mediated by tumor denved and not non-tumor derived gp96-peptide complexes, and that gp96 preparations stripped of its peptides are non-immunogenic...

  12. Peptides: Production, bioactivity, functionality, and applications

    DEFF Research Database (Denmark)

    Hajfathalian, Mona; Ghelichi, Sakhi; García Moreno, Pedro Jesús

    2017-01-01

    Production of peptides with various effects from proteins of different sources continues to receive academic attention. Researchers of different disciplines are putting increasing efforts to produce bioactive and functional peptides from different sources such as plants, animals, and food industry...

  13. Development and use of engineered peptide deformylase in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia

    2012-01-01

    Deze thesis beschrijft het onderzoek naar potentieel van het gebruik van het peptide deformylase (PDF) in chemo enzymatische peptide synthese. PDF is geschikt voor selective N terminale deformylatie van bepaalde N-formyl-peptides zonder gelijktijdige hydrolyse van de peptide binding. Door de

  14. Peptides, polypeptides and peptide-polymer hybrids as nucleic acid carriers.

    Science.gov (United States)

    Ahmed, Marya

    2017-10-24

    Cell penetrating peptides (CPPs), and protein transduction domains (PTDs) of viruses and other natural proteins serve as a template for the development of efficient peptide based gene delivery vectors. PTDs are sequences of acidic or basic amphipathic amino acids, with superior membrane trespassing efficacies. Gene delivery vectors derived from these natural, cationic and cationic amphipathic peptides, however, offer little flexibility in tailoring the physicochemical properties of single chain peptide based systems. Owing to significant advances in the field of peptide chemistry, synthetic mimics of natural peptides are often prepared and have been evaluated for their gene expression, as a function of amino acid functionalities, architecture and net cationic content of peptide chains. Moreover, chimeric single polypeptide chains are prepared by a combination of multiple small natural or synthetic peptides, which imparts distinct physiological properties to peptide based gene delivery therapeutics. In order to obtain multivalency and improve the gene delivery efficacies of low molecular weight cationic peptides, bioactive peptides are often incorporated into a polymeric architecture to obtain novel 'polymer-peptide hybrids' with improved gene delivery efficacies. Peptide modified polymers prepared by physical or chemical modifications exhibit enhanced endosomal escape, stimuli responsive degradation and targeting efficacies, as a function of physicochemical and biological activities of peptides attached onto a polymeric scaffold. The focus of this review is to provide comprehensive and step-wise progress in major natural and synthetic peptides, chimeric polypeptides, and peptide-polymer hybrids for nucleic acid delivery applications.

  15. STM studies of synthetic peptide monolayers

    Science.gov (United States)

    Bergeron, David J.; Clauss, Wilfried; Pilloud, Denis L.; Leslie Dutton, P.; Johnson, Alan T.

    1998-08-01

    We have used scanning probe microscopy to investigate self-assembled monolayers of chemically synthesized peptides. We find that the peptides form a dense uniform monolayer, above which is found a sparse additional layer. Using scanning tunneling microscopy, submolecular resolution can be obtained, revealing the alpha helices which constitute the peptide. The nature of the images is not significantly affected by the incorporation of redox cofactors (hemes) in the peptides.

  16. Antimicrobial activities of heparin-binding peptides.

    OpenAIRE

    Andersson, Emma; Rydengård, Victoria; Sonesson, Andreas; Mörgelin, Matthias; Björck, Lars; Schmidtchen, Artur

    2004-01-01

    Antimicrobial peptides are effector molecules of the innate immune system. We recently showed that the human antimicrobial peptides alpha-defensin and LL-37 bind to glycosaminoglycans (heparin and dermatan sulphate). Here we demonstrate the obverse, i.e. structural motifs associated with heparin affinity (cationicity, amphipaticity, and consensus regions) may confer antimicrobial properties to a given peptide. Thus, heparin-binding peptides derived from laminin isoforms, von Willebrand factor...

  17. DNA triplet repeat expansion and mismatch repair.

    Science.gov (United States)

    Iyer, Ravi R; Pluciennik, Anna; Napierala, Marek; Wells, Robert D

    2015-01-01

    DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic stability through rectification of DNA replication errors and attenuation of chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair has been implicated as a cause of triplet repeat expansions that cause neurological diseases such as Huntington disease and myotonic dystrophy. This mutagenic process requires the mismatch recognition factor MutSβ and the MutLα (and/or possibly MutLγ) endonuclease, and is thought to be triggered by the transient formation of unusual DNA structures within the expanded triplet repeat element. This review summarizes the current knowledge of DNA mismatch repair involvement in triplet repeat expansion, which encompasses in vitro biochemical findings, cellular studies, and various in vivo transgenic animal model experiments. We present current mechanistic hypotheses regarding mismatch repair protein function in mediating triplet repeat expansions and discuss potential therapeutic approaches targeting the mismatch repair pathway.

  18. Childhood experiences and repeated suicidal behavior

    DEFF Research Database (Denmark)

    Krarup, Gertrud; Nielsen, Bent; Rask, P

    1991-01-01

    The aim of this study was to elucidate the influence of various events in childhood on suicidal behavior in adult age. For this purpose, 99 patients admitted to the Department of Psychiatry of Odense University Hospital after making a suicide attempt were followed for 5 years, to register repeate......: the suicidal act is perceived--and learned--as way to solve problems.......The aim of this study was to elucidate the influence of various events in childhood on suicidal behavior in adult age. For this purpose, 99 patients admitted to the Department of Psychiatry of Odense University Hospital after making a suicide attempt were followed for 5 years, to register repeated......, and the first-evers on average were past the age of 40. Somewhat unexpectedly, significantly more repeaters than first-evers had grown up with both their parents. However, the results also showed that significantly more repeaters than first-evers had had an unhappy childhood. This indicates...

  19. Robust Repeated Auctions under Heterogeneous Buyer Behavior

    OpenAIRE

    Agrawal, Shipra; Daskalakis, Constantinos; Mirrokni, Vahab; Sivan, Balasubramanian

    2018-01-01

    We study revenue optimization in a repeated auction between a single seller and a single buyer. Traditionally, the design of repeated auctions requires strong modeling assumptions about the bidder behavior, such as it being myopic, infinite lookahead, or some specific form of learning behavior. Is it possible to design mechanisms which are simultaneously optimal against a multitude of possible buyer behaviors? We answer this question by designing a simple state-based mechanism that is simulta...

  20. One Hundred Years of Peptide Chemistry

    Indian Academy of Sciences (India)

    ber of residues are often denoted as peptides. The chemical synthesis of peptides, as envisaged by Fischer, involves ... known as genetically encoded as building blocks of peptides and proteins. Almost all of .... inhibit final stages of the enzymatic construction of the bacterial peptidoglycan cell wall component, a network of.

  1. Toxins and antimicrobial peptides: interactions with membranes

    Science.gov (United States)

    Schlamadinger, Diana E.; Gable, Jonathan E.; Kim, Judy E.

    2009-08-01

    The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of <200-nm bilayer vesicles composed of anionic and neutral lipids as well as cholesterol. Vesicle disruption, or peptide potency, was monitored with a sensitive fluorescence leakage assay. Detailed molecular information on peptidemembrane interactions and peptide structure was further gained through vibrational spectroscopy combined with circular dichroism. Finally, steady-state fluorescence experiments yielded insight into the local environment of native or engineered tryptophan residues in melittin and human cathelicidin embedded in bilayer vesicles. Collectively, our results provide clues to the functional structures of the engineered and toxic peptides and may impact the design of synthetic antibiotic peptides that can be used against the growing number of antibiotic-resistant pathogens.

  2. Ribosome evolution: Emergence of peptide synthesis machinery

    Indian Academy of Sciences (India)

    allows the histidine to position close to the PTC during the reaction, it may contribute to improving peptide bond formation. Thus, it is important to analyse biomolecular interactions in terms of the dynamic nature of the structure. 3. Origin of peptide bond formation and the RNA world. Minihelix-based peptide bond formation ...

  3. Double-Stranded Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2001-01-01

    A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  4. Synthetic Procedures for Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  5. Glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Deacon, C F; Holst, Jens Juul; Carr, R D

    1999-01-01

    Type 2 diabetes mellitus is a metabolic disease resulting in raised blood sugar which, if not satisfactorily controlled, can cause severe and often debilitating complications. Unfortunately, for many patients, the existing therapies do not give adequate control. Glucagon-like peptide-1 (GLP-1...

  6. Peptide Receptor Radionuclide Therapy & Oncology

    NARCIS (Netherlands)

    H. Bergsma (Hendrik)

    2017-01-01

    markdownabstractNeuroendocrine tumors (NETs) are rare neoplasms with differences in clinical presentation, course and prognosis. Most of the NETs express the somatostatine receptor, which can be utilized for imaging and therapy. Radiolabeled somatostatin analogs can be used for peptide receptor

  7. Glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Deacon, C F; Holst, Jens Juul; Carr, R D

    1999-01-01

    Type 2 diabetes mellitus is a metabolic disease resulting in raised blood sugar which, if not satisfactorily controlled, can cause severe and often debilitating complications. Unfortunately, for many patients, the existing therapies do not give adequate control. Glucagon-like peptide-1 (GLP-1...... advantages offered by GLP-1 and give the hope of providing effective glycemic control without the risk of overt hypoglycemia....

  8. Synthetic peptides for diagnostic use

    NARCIS (Netherlands)

    Meloen, R.H.; Langedijk, J.P.M.; Langeveld, J.P.M.

    1997-01-01

    Synthetic peptides representing relevant B-cell epitopes are, potentially, ideal antigens to be used in diagnostic assays because of their superior properties with respect to quality control as compared to those of biologically derived molecules and the much higher specificity that sometimes can be

  9. Next generation natriuretic peptide measurement

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Goetze, Jens P

    2012-01-01

    in the molecular heterogeneity could in itself contain valuable information of clinical status, and the time seems right for industry and dedicated researchers in the field to get together and discuss the next generation natriuretic peptide measurement. In such an environment, new strategies can be developed...

  10. Atrial natriuretic peptides in plasma

    DEFF Research Database (Denmark)

    Goetze, Jens P; Holst Hansen, Lasse; Terzic, Dijana

    2015-01-01

    derivatizations. In this mini-review, we summarize measurement of the principal cardiac hormone, e.g. atrial natriuretic peptide (ANP) and its precursor fragments. We also highlight some of the analytical pitfalls and problems and the concurrent clinical "proof of concept". We conclude that biochemical research...

  11. Insect Peptides - Perspectives in Human Diseases Treatment.

    Science.gov (United States)

    Chowanski, Szymon; Adamski, Zbigniew; Lubawy, Jan; Marciniak, Pawel; Pacholska-Bogalska, Joanna; Slocinska, Malgorzata; Spochacz, Marta; Szymczak, Monika; Urbanski, Arkadiusz; Walkowiak-Nowicka, Karolina; Rosinski, Grzegorz

    2017-01-01

    Insects are the largest and the most widely distributed group of animals in the world. Their diversity is a source of incredible variety of different mechanisms of life processes regulation. There are many agents that regulate immunology, reproduction, growth and development or metabolism. Hence, it seems that insects may be a source of numerous substances useful in human diseases treatment. Especially important in the regulation of insect physiology are peptides, like neuropeptides, peptide hormones or antimicrobial peptides. There are two main aspects where they can be helpful, 1) Peptides isolated from insects may become potential drugs in therapy of different diseases, 2) A lot of insect peptide hormones show structural or functional homology to mammalian peptide hormones and the comparative studies may give a new look on human disorders. In our review we focused on three group of insect derived peptides: 1) immune-active peptides, 2) peptide hormones and 3) peptides present in venoms. In our review we try to show the considerable potential of insect peptides in searching for new solutions for mammalian diseases treatment. We summarise the knowledge about properties of insect peptides against different virulent agents, anti-inflammatory or anti-nociceptive properties as well as compare insect and mammalian/vertebrate peptide endocrine system to indicate usefulness of knowledge about insect peptide hormones in drug design. The field of possible using of insect delivered peptide to therapy of various human diseases is still not sufficiently explored. Undoubtedly, more attention should be paid to insects due to searching new drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Peptide Modified ZnO Nanoparticles as Gas Sensors Array for Volatile Organic Compounds (VOCs

    Directory of Open Access Journals (Sweden)

    Marcello Mascini

    2018-04-01

    Full Text Available In this work a peptide based gas sensor array based of ZnO nanoparticles (ZnONPs has been realized. Four different pentapeptides molecularly modeled for alcohols and esters having cysteine as a common spacer have been immobilized onto ZnONPs. ZnONPs have been morphologically and spectroscopically characterized. Modified nanoparticles have been then deposited onto quartz crystal microbalances (QCMs and used as gas sensors with nitrogen as carrier gas. Analysis of the pure compounds modeled demonstrated a nice fitting of modeling with real data. The peptide based ZnONPs had very low sensitivity to water, compared to previously studied AuNPs peptide based gas sensors allowing the use of the array on samples with high water content. Real samples of fruit juices have been assayed; stability of the signal, good repeatability, and discrimination ability of the array was achieved.

  13. Preparation of polypeptides comprising multiple TAA peptides.

    Science.gov (United States)

    Ni, Bing; Jia, Zhengcai; Wu, Yuzhang

    2014-01-01

    Polypeptides consisting of multiple tumor-associated antigen epitopes (multiepitope peptides) are commonly used as therapeutic peptide cancer vaccines in experimental studies and clinical trials. These methods include polypeptides composed of multiple major histocompatibility complex (MHC) class I-restricted cytotoxic T cell (CTL) epitopes and those containing multiple CTL epitopes and one T helper (Th) epitope. This chapter describes a complete set of methods for preparing multiepitope peptides and branched multiple antigen peptides (MAPs), including sequence design, peptide synthesis, purification, preservation, and the preparation of polypeptide solutions.

  14. Automated genotyping of dinucleotide repeat markers

    Energy Technology Data Exchange (ETDEWEB)

    Perlin, M.W.; Hoffman, E.P. [Carnegie Mellon Univ., Pittsburgh, PA (United States)]|[Univ. of Pittsburgh, PA (United States)

    1994-09-01

    The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

  15. Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray.

    Directory of Open Access Journals (Sweden)

    Madlen Loebel

    Full Text Available Epstein-Barr-Virus (EBV plays an important role as trigger or cofactor for various autoimmune diseases. In a subset of patients with Chronic Fatigue Syndrome (CFS disease starts with infectious mononucleosis as late primary EBV-infection, whereby altered levels of EBV-specific antibodies can be observed in another subset of patients.We performed a comprehensive mapping of the IgG response against EBV comparing 50 healthy controls with 92 CFS patients using a microarray platform. Patients with multiple sclerosis (MS, systemic lupus erythematosus (SLE and cancer-related fatigue served as controls. 3054 overlapping peptides were synthesised as 15-mers from 14 different EBV proteins. Array data was validated by ELISA for selected peptides. Prevalence of EBV serotypes was determined by qPCR from throat washing samples.EBV type 1 infections were found in patients and controls. EBV seroarray profiles between healthy controls and CFS were less divergent than that observed for MS or SLE. We found significantly enhanced IgG responses to several EBNA-6 peptides containing a repeat sequence in CFS patients compared to controls. EBNA-6 peptide IgG responses correlated well with EBNA-6 protein responses. The EBNA-6 repeat region showed sequence homologies to various human proteins.Patients with CFS had a quite similar EBV IgG antibody response pattern as healthy controls. Enhanced IgG reactivity against an EBNA-6 repeat sequence and against EBNA-6 protein is found in CFS patients. Homologous sequences of various human proteins with this EBNA-6 repeat sequence might be potential targets for antigenic mimicry.

  16. Selection of possible signature peptides for the detection of bovine lactoferrin in infant formulas by LC-MS/MS.

    Directory of Open Access Journals (Sweden)

    Mingmei Yuan

    Full Text Available An LC-MS/MS assay based on a signature peptide was developed and fully validated for the quantitation of bovine lactoferrin in infant formulas. Three unreported signature peptides were derived and identified from the tryptic peptides of bovine lactoferrin. The peptide ETTVFENLPEK was used for quantification based on assay performance. The blank matrix camel milk powder and bovine lactoferrin protein standards were mixed and spiked with stable isotope-labeled internal standard to establish a calibration curve. The established method was extensively validated by determining the linearity (R2 > 0.999, sensitivity (limit of quantitation, 0.16 mg/100 g, recovery (83.1-91.6%, precision (RSD < 5.4% and repeatability (RSD < 7.7%. To validate the applicability of the method, four different brands of infant formulas in China were analysed. The acquired contents of bovine lactoferrin were 52.60-150.56 mg/100 g.

  17. Computer-Aided Design of Antimicrobial Peptides

    DEFF Research Database (Denmark)

    Fjell, Christopher D.; Hancock, Robert E.W.; Jenssen, Håvard

    2010-01-01

    An increasing number of reported cases of drug resistant Staphylococcus aureus and Pseudomonas aeruginosa, demonstrate the urgent need for new therapeutics that are effective against such and other multi-drug resistant bacteria. Antimicrobial peptides have for two decades now been looked upon...... as interesting leads for development of new therapeutics combating these drug resistant microbes. High-throughput screening of peptide libraries have generated large amounts of information on peptide activities. However, scientists still struggle with explaining the specific peptide motifs resulting...... in antimicrobial activity. Consequently, the majority of peptides put into clinical trials have failed at some point, underlining the importance of a thorough peptide optimization. An important tool in peptide design and optimization is quantitative structure-activity relationship (QSAR) analysis, correlating...

  18. Natural and synthetic peptides with antifungal activity.

    Science.gov (United States)

    Ciociola, Tecla; Giovati, Laura; Conti, Stefania; Magliani, Walter; Santinoli, Claudia; Polonelli, Luciano

    2016-08-01

    In recent years, the increase of invasive fungal infections and the emergence of antifungal resistance stressed the need for new antifungal drugs. Peptides have shown to be good candidates for the development of alternative antimicrobial agents through high-throughput screening, and subsequent optimization according to a rational approach. This review presents a brief overview on antifungal natural peptides of different sources (animals, plants, micro-organisms), peptide fragments derived by proteolytic cleavage of precursor physiological proteins (cryptides), synthetic unnatural peptides and peptide derivatives. Antifungal peptides are schematically reported based on their structure, antifungal spectrum and reported effects. Natural or synthetic peptides and their modified derivatives may represent the basis for new compounds active against fungal infections.

  19. Repeat aware evaluation of scaffolding tools.

    Science.gov (United States)

    Mandric, Igor; Knyazev, Sergey; Zelikovsky, Alex

    2018-03-14

    Genomic sequences are assembled into a variable, but large number of contigs that should be scaffolded (ordered and oriented) for facilitating comparative or functional analysis. Finding scaffolding is computationally challenging due to misassemblies, inconsistent coverage across the genome, and long repeats. An accurate assessment of scaffolding tools should take into account multiple locations of the same contig on the reference scaffolding rather than matching a repeat to a single best location. This makes mapping of inferred scaffoldings onto the reference a computationally challenging problem. This paper formulates the repeat-aware scaffolding evaluation problem which is to find a mapping of the inferred scaffolding onto the reference maximizing number of correct links and proposes a scalable algorithm capable of handling large whole-genome datasets. Our novel scaffolding validation framework has been applied to assess the most of state-of-the-art scaffolding tools on the representative subset of GAGE datasets and some novel simulated datasets. The source code of this evaluation framework is available at https://github.com/mandricigor/repeat-aware. The documentation is hosted at https://mandricigor.github.io/repeat-aware. imandric1@cs.gsu.edu.

  20. Role of memory errors in quantum repeaters

    International Nuclear Information System (INIS)

    Hartmann, L.; Kraus, B.; Briegel, H.-J.; Duer, W.

    2007-01-01

    We investigate the influence of memory errors in the quantum repeater scheme for long-range quantum communication. We show that the communication distance is limited in standard operation mode due to memory errors resulting from unavoidable waiting times for classical signals. We show how to overcome these limitations by (i) improving local memory and (ii) introducing two operational modes of the quantum repeater. In both operational modes, the repeater is run blindly, i.e., without waiting for classical signals to arrive. In the first scheme, entanglement purification protocols based on one-way classical communication are used allowing to communicate over arbitrary distances. However, the error thresholds for noise in local control operations are very stringent. The second scheme makes use of entanglement purification protocols with two-way classical communication and inherits the favorable error thresholds of the repeater run in standard mode. One can increase the possible communication distance by an order of magnitude with reasonable overhead in physical resources. We outline the architecture of a quantum repeater that can possibly ensure intercontinental quantum communication

  1. Children's eyewitness memory for a repeated event.

    Science.gov (United States)

    McNichol, S; Shute, R; Tucker, A

    1999-11-01

    This study examined a significant issue for chronic sexual abuse investigations: Children's eyewitness testimony about repeated events. The few previous studies focused on preschoolers and none used the present methodology of presenting repeated events differing slightly in their details, as would happen in chronic abuse. One group of 6- to 7-year-olds played individually with an experimenter on one occasion; the other group experienced three such events, with some details remaining the same and others changing. In a phased interview, children were questioned about the initial event. For details which stayed the same, the children who experienced three events had more accurate memories. They had poorer memories than the single-event group for details which were changed in the later events; however, this was due to interference errors, with errors of omission and commission being lower than in the single-event group. Children conveyed clearly that inappropriate touching did not occur. Children who experience repeated events have increased recall for repeated details but confuse the timing of details which change across events. The findings support previous suggestions that (a) it is unrealistic to expect children to be able to report repeated events without some confusion about timing of details and (b) children are resistant to misleading questions about abuse.

  2. Risk factors for repeat abortion in Nepal.

    Science.gov (United States)

    Thapa, Shyam; Neupane, Shailes

    2013-01-01

    To examine the incidence of and risk factors for repeat abortion in Nepal. Data were analyzed from a survey of 1172 women who had surgical abortions between December 2009 and March 2010 in 2 clinics in Kathmandu, Nepal. Bivariate and multivariate logistic regressions were performed to estimate odds ratios for the risk factors. Among the respondents, 32.3% (95% confidence interval, 29.6-34.9) had repeat abortions. This incidence rose sharply with age and parity, and was higher among those with no intention of having a future child, those attaining primary or secondary level education, and those attending the non-governmental sector clinic. Women with repeat abortion were similar to those with 1 abortion in terms of contraceptive practice. Among women not using contraceptives at the time of the unintended pregnancy, the 3 most commonly cited reasons were ill health, non-compliance with the method intended for use, and dislike of the method. Women with repeat abortion showed a pattern of contraceptive acceptance immediately after the procedure similar to that of women who had 1 abortion. Repeat abortion is emerging as a major public health issue in Nepal, with implications for counseling and provision of abortion, and for family planning services. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Degradation and antioxidant activities of peptides and zinc-peptide complexes during in vitro gastrointestinal digestion.

    Science.gov (United States)

    Wang, Chan; Li, Bo; Wang, Bo; Xie, Ningning

    2015-04-15

    The degradation characteristics of three peptides (Ser-Met, Asn-Cys-Ser, and glutathione) and their zinc-peptide complexes were studied using a two-stage in vitro digestion model. Enzyme-resistant peptides and zinc-peptide complexes, antioxidant activities, and free amino acids released by digestive enzymes, were measured in this study. The results revealed that the three peptides and their zinc-peptide complexes were resistant to pepsin but not to pancreatin. Pancreatin can partly hydrolyse both peptides and zinc-peptide complexes, but more than half of them remaining in their original form after gastrointestinal digestion. The coordination of zinc improved the enzymatic resistance of the peptide due to lower solubility of complexes and affected the hydrolytic site of pepsin and pancreatin. Zinc-Asn-Cys-Ser, which is highly resistant to enzymatic hydrolysis and maintains Zn in a soluble form, may have potential to improve Zn bioavailability. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Analysis of peptide uptake and location of root hair-promoting peptide accumulation in plant roots.

    Science.gov (United States)

    Matsumiya, Yoshiki; Taniguchi, Rikiya; Kubo, Motoki

    2012-03-01

    Peptide uptake by plant roots from degraded soybean-meal products was analyzed in Brassica rapa and Solanum lycopersicum. B. rapa absorbed about 40% of the initial water volume, whereas peptide concentration was decreased by 75% after 24 h. Analysis by reversed-phase HPLC showed that number of peptides was absorbed by the roots during soaking in degraded soybean-meal products for 24 h. Carboxyfluorescein-labeled root hair-promoting peptide was synthesized, and its localization, movement, and accumulation in roots were investigated. The peptide appeared to be absorbed by root hairs and then moved to trichoblasts. Furthermore, the peptide was moved from trichoblasts to atrichoblasts after 24 h. The peptide was accumulated in epidermal cells, suggesting that the peptide may have a function in both trichoblasts and atrichoblasts. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

  5. Scale-invariance in soft gamma repeaters

    Science.gov (United States)

    Chang, Zhe; Lin, Hai-Nan; Sang, Yu; Wang, Ping

    2017-06-01

    The statistical properties of the soft gamma repeater SGR J1550-5418 are investigated carefully. We find that the cumulative distributions of fluence, peak flux and duration can be well fitted by a bent power law, while the cumulative distribution of waiting time follows a simple power law. In particular, the probability density functions of fluctuations of fluence, peak flux, and duration have a sharp peak and fat tails, which can be well fitted by a q-Gaussian function. The q values keep approximately steady for different scale intervals, indicating a scale-invariant structure of soft gamma repeaters. Those results support that the origin of soft gamma repeaters is crustquakes of neutron stars with extremely strong magnetic fields. Supported by National Natural Science Foundation of China (11375203, 11675182, 11690022, 11603005), and Fundamental Research Funds for Central Universities (106112016CDJCR301206)

  6. PolyQ repeat expansions in ATXN2 associated with ALS are CAA interrupted repeats.

    Directory of Open Access Journals (Sweden)

    Zhenming Yu

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ repeats of 27-33 in ATAXIN-2 (ATXN2, encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥ 34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1-3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT, while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC. Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2.

  7. Peptide Antibiotics for ESKAPE Pathogens

    DEFF Research Database (Denmark)

    Thomsen, Thomas Thyge

    Multi-drug resistance to antibiotics represents a global health challenge that results in increased morbidity and mortality rates. The annual death-toll is >700.000 people world-wide, rising to ~10 million by 2050. New antibiotics are lacking, and few are under development as return on investment...... is considered poor compared to medicines for lifestyle diseases. According to the WHO we could be moving towards a post-antibiotic era in which previously treatable infections become fatal. Of special importance are multidrug resistant bacteria from the ESKAPE group (Enterococcus faecium, Staphylococcus aureus...... and toxicity by utilizing of the fruit fly Drosophila melanogaster as a whole animal model. This was carried out by testing of antimicrobial peptides targeting Gram-positive bacteria exemplified by the important human pathogen methicillin resistant S. aureus (MRSA). The peptide BP214 was developed from...

  8. A neuroanatomical correlate of sensorimotor recovery in response to repeated vaginocervical stimulation in rats.

    Directory of Open Access Journals (Sweden)

    Barry R Komisaruk

    2012-04-01

    Full Text Available Gentle probing against the cervix via the vagina (VCS increases tail flick latency (TFL to radiant heat; greater force totally abolishes the tail flick response and other withdrawal responses. This effect occurs in spinal cord-transected rats and in intact rats. On the basis of our earlier finding that vaginocervical stimulation (VCS releases vasoactive intestinal peptide (VIP into the spinal cord, and others’ reports of neurotrophic effects of VIP in vitro, we hypothesized that repeated VCS would stimulate sprouting and sensorimotor function of terminals of genital nerve primary afferents in the sacral spinal cord. To test this hypothesis, in the present study, we denervated the genital tract only unilaterally, which significantly reduced the TFL-elevating effect of VCS. Then we applied repeated daily VCS for one week and compared the subsequent effectiveness of acute VCS in elevating TFL. The rats that received the repeated daily VCS showed a significantly greater elevation in TFL in response to acute VCS than control rats that did not receive the repeated stimulation. Then, to test whether daily repeated VCS stimulates sprouting of genital primary afferents in such unilaterally genital tract-denervated rats, we transected the contralateral remaining intact pelvic nerve, applied horseradish peroxidase (HRP to its proximal cut end for 1-2h, and 2-3d later counted HRP particles in its terminal zone (S1 in the spinal cord. There were significantly more HRP particles in the rats that received the daily repeated VCS than in the control rats. In the context of these findings, we conclude that vaginocervical stimulation in rats can produce a functional sensorimotor recovery via a neurotrophic effect on compromised primary afferents in the spinal cord. Based on our previous research, we speculate that a similar functional sprouting antinociceptive process could occur supraspinally, after spinal cord injury, via an alternative vaginocervical sensory

  9. Safety of Repeated Yttrium-90 Radioembolization

    International Nuclear Information System (INIS)

    Lam, Marnix G. E. H.; Louie, John D.; Iagaru, Andrei H.; Goris, Michael L.; Sze, Daniel Y.

    2013-01-01

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver’s cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51–71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction

  10. The repeatability of automated and clinician refraction.

    Science.gov (United States)

    Bullimore, M A; Fusaro, R E; Adams, C W

    1998-08-01

    Auto-refractors are used as a starting point for clinicians' refractions and in studies of refractive error. We investigated the repeatability of the Hoya AR-570 and clinician refraction. Eighty-six subjects, aged 11 to 60 years, were recruited by mailing inquiries to 500 randomly selected patients who had received recent examinations at the University of California Optometric Eye Center. Contact lens wearers, patients with best corrected visual acuity worse than 20/30 in either eye, and patients with a history of diabetes were excluded. Each subject was examined by two clinicians during one visit. The first clinician obtained five auto-refractor readings for each eye (which were later averaged), performed a balanced subjective refraction (with spherical masking lenses in the phoropter), and repeated the automated refractor measurements. This protocol was then repeated by the second clinician. Clinicians were randomized with regard to testing order and masked to automated refractor results, each other's refractions, and previous spectacle prescriptions. To quantify repeatability, we used mixed model analyses of variance to estimate the appropriate variance components while accounting for the correlation among, for example, repeated measurements of the same eye. Astigmatic data were analyzed by converting into Fourier form: two cross-cylinders at axis 0 degrees (J0) and axis 45 degrees (J45). For mean spherical equivalent, the average difference between five averaged automated refractor readings, taken by two different optometrists, was +0.02 D (95% limits of agreement = -0.36 to +0.40 D). The average difference between the two optometrists' subjective refractions was -0.12 D (95% limits of agreement = -0.90 to +0.65 D). The 95% limits of agreement for the automated refractor were about half those of the clinician for both astigmatic terms (J0 and J45) and for all comparisons. Automated refraction is more repeatable than subjective refraction and therefore more

  11. Peptide-targeted polymer cancerostatics

    Czech Academy of Sciences Publication Activity Database

    Böhmová, Eliška; Pola, Robert

    2016-01-01

    Roč. 65, Suppl. 2 (2016), S153-S164 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : HPMA copolymers * tumor targeting * peptides Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S153.pdf

  12. Biopharmaceuticals: From peptide to drug

    Science.gov (United States)

    Hannappel, Margarete

    2017-08-01

    Biologics are therapeutic proteins or peptides that are produced by means of biological processes within living organisms and cells. They are highly specific molecules and play a crucial role as therapeutics for the treatment of severe and chronic diseases (e.g. cancer, rheumatoid arthritis, diabetes, autoimmune disorders). The development of new biologics and biologics-based drugs gains more and more importance in the fight against various diseases. A short overview on biotherapeutical drug development is given. Cone snails are a large group of poisonous, predatory sea snails with more than 700 species. They use a very powerful venom which rapidly inactivates and paralyzes their prey. Most bioactive venom components are small peptides (conotoxins, conopeptides) which are precisely directed towards a specific target (e.g. ion channel, receptors). Due to their small size, their precision and speed of action, naturally occurring cone snail venom peptides represent an attractive source for the identification and design of novel biological drug entities. The Jagna cone snail project is an encouraging initiative to map the ecological variety of cone snails around the island of Bohol (Philippines) and to conserve the biological information for potential future application.

  13. Coffee, hunger, and peptide YY.

    Science.gov (United States)

    Greenberg, James A; Geliebter, Allan

    2012-06-01

    There is evidence from several empirical studies suggesting that coffee may help people control body weight. Our objective was to assess the effects of caffeine, caffeinated coffee, and decaffeinated coffee, both alone and in combination with 75 g of glucose, on perceived hunger and satiety and related peptides. We conducted a placebo-controlled single-blinded randomized 4-way crossover trial. Eleven healthy male volunteers (mean age, 23.5 ± 5.7 years; mean BMI, 23.6 ± 4.2 kg/m(2)) ingested 1 of 3 test beverages (caffeine in water, caffeinated coffee, or decaffeinated coffee) or placebo (water), and 60 minutes later they ingested the glucose. Eight times during each laboratory visit, hunger and satiety were assessed by visual analog scales, and blood samples were drawn to measure 3 endogenous peptides associated with hunger and satiety: ghrelin, peptide YY (PYY), and leptin. Compared to placebo, decaffeinated coffee yielded significantly lower hunger during the whole 180-minute study period and higher plasma PYY for the first 90 minutes (p hunger or PYY. Caffeinated coffee showed a pattern between that of decaffeinated coffee and caffeine in water. These findings suggest that one or more noncaffeine ingredients in coffee may have the potential to decrease body weight. Glucose ingestion did not change the effects of the beverages. Our randomized human trial showed that decaffeinated coffee can acutely decrease hunger and increase the satiety hormone PYY.

  14. Antimicrobial Peptides: Versatile Biological Properties

    Directory of Open Access Journals (Sweden)

    Muthuirulan Pushpanathan

    2013-01-01

    Full Text Available Antimicrobial peptides are diverse group of biologically active molecules with multidimensional properties. In recent past, a wide variety of AMPs with diverse structures have been reported from different sources such as plants, animals, mammals, and microorganisms. The presence of unusual amino acids and structural motifs in AMPs confers unique structural properties to the peptide that attribute for their specific mode of action. The ability of these active AMPs to act as multifunctional effector molecules such as signalling molecule, immune modulators, mitogen, antitumor, and contraceptive agent makes it an interesting candidate to study every aspect of their structural and biological properties for prophylactic and therapeutic applications. In addition, easy cloning and recombinant expression of AMPs in heterologous plant host systems provided a pipeline for production of disease resistant transgenic plants. Besides these properties, AMPs were also used as drug delivery vectors to deliver cell impermeable drugs to cell interior. The present review focuses on the diversity and broad spectrum antimicrobial activity of AMPs along with its multidimensional properties that could be exploited for the application of these bioactive peptides as a potential and promising drug candidate in pharmaceutical industries.

  15. Chemical methods for peptide and protein production.

    Science.gov (United States)

    Chandrudu, Saranya; Simerska, Pavla; Toth, Istvan

    2013-04-12

    Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported α-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

  16. Prediction of twin-arginine signal peptides

    Directory of Open Access Journals (Sweden)

    Widdick David

    2005-07-01

    Full Text Available Abstract Background Proteins carrying twin-arginine (Tat signal peptides are exported into the periplasmic compartment or extracellular environment independently of the classical Sec-dependent translocation pathway. To complement other methods for classical signal peptide prediction we here present a publicly available method, TatP, for prediction of bacterial Tat signal peptides. Results We have retrieved sequence data for Tat substrates in order to train a computational method for discrimination of Sec and Tat signal peptides. The TatP method is able to positively classify 91% of 35 known Tat signal peptides and 84% of the annotated cleavage sites of these Tat signal peptides were correctly predicted. This method generates far less false positive predictions on various datasets than using simple pattern matching. Moreover, on the same datasets TatP generates less false positive predictions than a complementary rule based prediction method. Conclusion The method developed here is able to discriminate Tat signal peptides from cytoplasmic proteins carrying a similar motif, as well as from Sec signal peptides, with high accuracy. The method allows filtering of input sequences based on Perl syntax regular expressions, whereas hydrophobicity discrimination of Tat- and Sec-signal peptides is carried out by an artificial neural network. A potential cleavage site of the predicted Tat signal peptide is also reported. The TatP prediction server is available as a public web server at http://www.cbs.dtu.dk/services/TatP/.

  17. Chemical Methods for Peptide and Protein Production

    Directory of Open Access Journals (Sweden)

    Istvan Toth

    2013-04-01

    Full Text Available Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported a-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

  18. Natriuretic Peptides: Biochemistry, Physiology, Clinical Implication

    Directory of Open Access Journals (Sweden)

    I. A. Kozlova

    2009-01-01

    Full Text Available In the past years, the interest of theorists and clinicians has steadily increased in the myocardially secreted hormones – natriuretic peptides. At the Congress of the European Society of Anesthesiology (Munich, 2007, B-type natriuretic peptides were included into the list of the parameters of perioperative laboratory monitoring that is expedient in the practice of anesthetists and resuscitation specialists. The literature review shows the history of discovery and identification of different types of natriuretic peptides and considers the matters of their biochemistry. It also details information on the synthesis, secretion, and clearance of these peptides, as well as their receptor apparatus in various organs and tissues. The physiology of the regulatory system is described, as applied to the cardiovascular, excretory, central nervous systems, and the neuroendocrine one. Special attention is given to the current publications on the control of B-type natriuretic peptides as biomarkers of cardiac dysfunction. The diagnostic and prognostic values of peptides are analyzed in chronic circulatory insufficiency, coronary heart disease, and other car-diological and non-cardiological diseases. The prognostic value of elevated B-type natriuretic peptide levels in cardiac surgery is separately considered. It is concluded that the changes in the level of B-type natriuretic peptides in different clinical situations are the subject of numerous researches mainly made in foreign countries. The bulk of these researches are devoted to the study of peptides in cardiology and other areas of therapy. Studies on the use of peptides in reanimatology are relatively few and their results are rather discordant. The foregoing opens up wide prospects for studying the use of B-type natriuretic peptides in Russian intensive care and anesthesiology. Key words: natriuretic peptides, brain nautriuretic peptides, NT-proBNP.

  19. Inhibition of Henipavirus fusion and infection by heptad-derived peptides of the Nipah virus fusion glycoprotein

    Science.gov (United States)

    Bossart, Katharine N; Mungall, Bruce A; Crameri, Gary; Wang, Lin-Fa; Eaton, Bryan T; Broder, Christopher C

    2005-01-01

    Background The recent emergence of four new members of the paramyxovirus family has heightened the awareness of and re-energized research on new and emerging diseases. In particular, the high mortality and person to person transmission associated with the most recent Nipah virus outbreaks, as well as the very recent re-emergence of Hendra virus, has confirmed the importance of developing effective therapeutic interventions. We have previously shown that peptides corresponding to the C-terminal heptad repeat (HR-2) of the fusion envelope glycoprotein of Hendra virus and Nipah virus were potent inhibitors of both Hendra virus and Nipah virus-mediated membrane fusion using recombinant expression systems. In the current study, we have developed shorter, second generation HR-2 peptides which include a capped peptide via amidation and acetylation and two poly(ethylene glycol)-linked (PEGylated) peptides, one with the PEG moity at the C-terminus and the other at the N-terminus. Here, we have evaluated these peptides as well as the corresponding scrambled peptide controls in Nipah virus and Hendra virus-mediated membrane fusion and against infection by live virus in vitro. Results Unlike their predecessors, the second generation HR-2 peptides exhibited high solubility and improved synthesis yields. Importantly, both Nipah virus and Hendra virus-mediated fusion as well as live virus infection were potently inhibited by both capped and PEGylated peptides with IC50 concentrations similar to the original HR-2 peptides, whereas the scrambled modified peptides had no inhibitory effect. These data also indicate that these chemical modifications did not alter the functional properties of the peptides as inhibitors. Conclusion Nipah virus and Hendra virus infection in vitro can be potently blocked by specific HR-2 peptides. The improved synthesis and solubility characteristics of the second generation HR-2 peptides will facilitate peptide synthesis for pre-clinical trial

  20. Inhibition of Henipavirus fusion and infection by heptad-derived peptides of the Nipah virus fusion glycoprotein

    Directory of Open Access Journals (Sweden)

    Eaton Bryan T

    2005-07-01

    Full Text Available Abstract Background The recent emergence of four new members of the paramyxovirus family has heightened the awareness of and re-energized research on new and emerging diseases. In particular, the high mortality and person to person transmission associated with the most recent Nipah virus outbreaks, as well as the very recent re-emergence of Hendra virus, has confirmed the importance of developing effective therapeutic interventions. We have previously shown that peptides corresponding to the C-terminal heptad repeat (HR-2 of the fusion envelope glycoprotein of Hendra virus and Nipah virus were potent inhibitors of both Hendra virus and Nipah virus-mediated membrane fusion using recombinant expression systems. In the current study, we have developed shorter, second generation HR-2 peptides which include a capped peptide via amidation and acetylation and two poly(ethylene glycol-linked (PEGylated peptides, one with the PEG moity at the C-terminus and the other at the N-terminus. Here, we have evaluated these peptides as well as the corresponding scrambled peptide controls in Nipah virus and Hendra virus-mediated membrane fusion and against infection by live virus in vitro. Results Unlike their predecessors, the second generation HR-2 peptides exhibited high solubility and improved synthesis yields. Importantly, both Nipah virus and Hendra virus-mediated fusion as well as live virus infection were potently inhibited by both capped and PEGylated peptides with IC50 concentrations similar to the original HR-2 peptides, whereas the scrambled modified peptides had no inhibitory effect. These data also indicate that these chemical modifications did not alter the functional properties of the peptides as inhibitors. Conclusion Nipah virus and Hendra virus infection in vitro can be potently blocked by specific HR-2 peptides. The improved synthesis and solubility characteristics of the second generation HR-2 peptides will facilitate peptide synthesis for pre

  1. Human Antimicrobial Peptides and Proteins

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2014-05-01

    Full Text Available As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32 can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized

  2. Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides.

    Science.gov (United States)

    Mathieu, Cyrille; Augusto, Marcelo T; Niewiesk, Stefan; Horvat, Branka; Palermo, Laura M; Sanna, Giuseppina; Madeddu, Silvia; Huey, Devra; Castanho, Miguel A R B; Porotto, Matteo; Santos, Nuno C; Moscona, Anne

    2017-03-08

    Human paramyxoviruses include global causes of lower respiratory disease like the parainfluenza viruses, as well as agents of lethal encephalitis like Nipah virus. Infection is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. Paramyxovirus viral fusion proteins (F) insert into the target cell membrane, and form a transient intermediate that pulls the viral and cell membranes together as two heptad-repeat regions refold to form a six-helix bundle structure that can be specifically targeted by fusion-inhibitory peptides. Antiviral potency can be improved by sequence modification and lipid conjugation, and by adding linkers between the protein and lipid components. We exploit the uniquely broad spectrum antiviral activity of a parainfluenza F-derived peptide sequence that inhibits both parainfluenza and Nipah viruses, to investigate the influence of peptide orientation and intervening linker length on the peptides' interaction with transitional states of F, solubility, membrane insertion kinetics, and protease sensitivity. We assessed the impact of these features on biodistribution and antiviral efficacy in vitro and in vivo. The engineering approach based on biophysical parameters resulted in a peptide that is a highly effective inhibitor of both paramyxoviruses and a set of criteria to be used for engineering broad spectrum antivirals for emerging paramyxoviruses.

  3. Repeating and non-repeating fast radio bursts from binary neutron star mergers

    Science.gov (United States)

    Yamasaki, Shotaro; Totani, Tomonori; Kiuchi, Kenta

    2018-04-01

    Most fast radio bursts (FRB) do not show evidence of repetition, and such non-repeating FRBs may be produced at the time of a merger of binary neutron stars (BNS), provided that the BNS merger rate is close to the high end of the currently possible range. However, the merger environment is polluted by dynamical ejecta, which may prohibit the radio signal from propagating. We examine this by using a general-relativistic simulation of a BNS merger, and show that the ejecta appears about 1 ms after the rotation speed of the merged star becomes the maximum. Therefore there is a time window in which an FRB signal can reach outside, and the short duration of non-repeating FRBs can be explained by screening after ejecta formation. A fraction of BNS mergers may leave a rapidly rotating and stable neutron star, and such objects may be the origin of repeating FRBs like FRB 121102. We show that a merger remnant would appear as a repeating FRB on a time scale of ˜1-10 yr, and expected properties are consistent with the observations of FRB 121102. We construct an FRB rate evolution model that includes these two populations of repeating and non-repeating FRBs from BNS mergers, and show that the detection rate of repeating FRBs relative to non-repeating ones rapidly increases with improving search sensitivity. This may explain why only the repeating FRB 121102 was discovered by the most sensitive FRB search with Arecibo. Several predictions are made, including the appearance of a repeating FRB 1-10 yr after a BNS merger that is localized by gravitational waves and subsequent electromagnetic radiation.

  4. Repeatability And Validity Of IUATLD Respiratory Questionnaire ...

    African Journals Online (AJOL)

    Subjects: Two hundred and forty seven adults and children who previously reported wheeze in the past year, and 174 who did not. ... Conclusion: Our findings suggest that self-reported wheeze and asthma have good short-term repeatability, but do not closely reflect exercise-induced bronchospasm or bronchodilator ...

  5. On Solving Intransitivities in Repeated Pairwise Choices

    NARCIS (Netherlands)

    A. Maas (Arne); Th.G.G. Bezembinder (Thom); P.P. Wakker (Peter)

    1995-01-01

    textabstractAn operational method is presented for deriving a linear ranking of alternatives from repeated paired comparisons of the alternatives. Intransitivities in the observed preferences are cleared away by the introduction of decision errors of varying importance. An observed preference

  6. Y Se Repite = And It Repeats Itself

    Science.gov (United States)

    Katzew, Adriana

    2010-01-01

    In this article, the author discusses Y Se Repite [And It Repeats Itself], a project she conceptualized due to the growing number of Latino/a Mexican migrant workers in dairy farms in the state of Vermont. In 2006, approximately 2,000 Latinos/as--most of them undocumented Mexican migrant workers--worked throughout the state's dairy farms, yet…

  7. Mixed models for repeated count data.

    NARCIS (Netherlands)

    Duijn, Maria Aukje Julianne van

    1993-01-01

    Discrete data resulting from repeated counts are often collected in various fields of scientific research. They may come from experiments where, in various conditions or tasks, the number of certain happenings (e.g. a right or wrong answer) are counted. When the data are balanced (i.e., every

  8. FRB 121102: A Starquake-induced Repeater?

    Science.gov (United States)

    Wang, Weiyang; Luo, Rui; Yue, Han; Chen, Xuelei; Lee, Kejia; Xu, Renxin

    2018-01-01

    Since its initial discovery, the fast radio burst (FRB) FRB 121102 has been found to be repeating with millisecond-duration pulses. Very recently, 14 new bursts were detected by the Green Bank Telescope during its continuous monitoring observations. In this paper, we show that the burst energy distribution has a power-law form which is very similar to the Gutenberg–Richter law of earthquakes. In addition, the distribution of burst waiting time can be described as a Poissonian or Gaussian distribution, which is consistent with earthquakes, while the aftershock sequence exhibits some local correlations. These findings suggest that the repeating FRB pulses may originate from the starquakes of a pulsar. Noting that the soft gamma-ray repeaters (SGRs) also exhibit such distributions, the FRB could be powered by some starquake mechanisms associated with the SGRs, including the crustal activity of a magnetar or solidification-induced stress of a newborn strangeon star. These conjectures could be tested with more repeating samples.

  9. Simple sequence repeats in mycobacterial genomes

    Indian Academy of Sciences (India)

    Prakash

    2006-12-18

    Dec 18, 2006 ... of many pathogenic bacteria have been shown to contain these repetitive ... of many repeats in E. coli ORFs related to physiological adaptations, DNA repair ..... Graph showing ratios of observed and expected (after 1000 times randomizations) numbers of microsatellites from E. coli K12,. H. pylori (J99 and ...

  10. Preventing Repeat Teen Births PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-04-02

    This 60 second public service announcement is based on the April 2013 CDC Vital Signs report, which discusses repeat teen births and ways teens, parents and guardians, health care providers, and communities can help prevent them.  Created: 4/2/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/2/2013.

  11. Repeatability And Validity Of IUATLD Respiratory Questionnaire ...

    African Journals Online (AJOL)

    Interventions: Administered IUATLD bronchial symptoms questionnaire; standardised free-running exercise test or (for those with airflow obstruction) assessment of bronchodilator response to inhaled salbutamol. Results: Kappa values for four-week repeatability for the wheeze and asthma questions were 0.61 (95% CI 0.52 ...

  12. Multivariate linear models and repeated measurements revisited

    DEFF Research Database (Denmark)

    Dalgaard, Peter

    2009-01-01

    Methods for generalized analysis of variance based on multivariate normal theory have been known for many years. In a repeated measurements context, it is most often of interest to consider transformed responses, typically within-subject contrasts or averages. Efficiency considerations leads to s...

  13. Multivariate linear models and repeated measurements revisited

    DEFF Research Database (Denmark)

    Dalgaard, Peter

    2009-01-01

    Methods for generalized analysis of variance based on multivariate normal theory have been known for many years. In a repeated measurements context, it is most often of interest to consider transformed responses, typically within-subject contrasts or averages. Efficiency considerations leads to s...... method involving differences between orthogonal projections onto subspaces generated by within-subject models....

  14. On balanced minimal repeated measurements designs

    Directory of Open Access Journals (Sweden)

    Shakeel Ahmad Mir

    2014-10-01

    Full Text Available Repeated Measurements designs are concerned with scientific experiments in which each experimental unit is assigned more than once to a treatment either different or identical. This class of designs has the property that the unbiased estimators for elementary contrasts among direct and residual effects are obtainable. Afsarinejad (1983 provided a method of constructing balanced Minimal Repeated Measurements designs p < t , when t is an odd or prime power, one or more than one treatment may occur more than once in some sequences and  designs so constructed no longer remain uniform in periods. In this paper an attempt has been made to provide a new method to overcome this drawback. Specifically, two cases have been considered                RM[t,n=t(t-t/(p-1,p], λ2=1 for balanced minimal repeated measurements designs and  RM[t,n=2t(t-t/(p-1,p], λ2=2 for balanced  repeated measurements designs. In addition , a method has been provided for constructing              extra-balanced minimal designs for special case RM[t,n=t2/(p-1,p], λ2=1.

  15. Potent peptidic fusion inhibitors of influenza virus

    Energy Technology Data Exchange (ETDEWEB)

    Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B. G.; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J.; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H. E.; Goudsmit, Jaap; van Dongen, Maria J. P.; Wilson, Ian A.

    2017-09-28

    Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

  16. Designing anticancer peptides by constructive machine learning.

    Science.gov (United States)

    Grisoni, Francesca; Neuhaus, Claudia; Gabernet, Gisela; Müller, Alex; Hiss, Jan; Schneider, Gisbert

    2018-04-21

    Constructive machine learning enables the automated generation of novel chemical structures without the need for explicit molecular design rules. This study presents the experimental application of such a generative model to design membranolytic anticancer peptides (ACPs) de novo. A recurrent neural network with long short-term memory cells was trained on alpha-helical cationic amphipathic peptide sequences and then fine-tuned with 26 known ACPs. This optimized model was used to generate unique and novel amino acid sequences. Twelve of the peptides were synthesized and tested for their activity on MCF7 human breast adenocarcinoma cells and selectivity against human erythrocytes. Ten of these peptides were active against cancer cells. Six of the active peptides killed MCF7 cancer cells without affecting human erythrocytes with at least threefold selectivity. These results advocate constructive machine learning for the automated design of peptides with desired biological activities. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Prediction of twin-arginine signal peptides

    DEFF Research Database (Denmark)

    Bendtsen, Jannick Dyrløv; Nielsen, Henrik; Widdick, D.

    2005-01-01

    a publicly available method, TatP, for prediction of bacterial Tat signal peptides. Results: We have retrieved sequence data for Tat substrates in order to train a computational method for discrimination of Sec and Tat signal peptides. The TatP method is able to positively classify 91% of 35 known Tat signal...... peptides and 84% of the annotated cleavage sites of these Tat signal peptides were correctly predicted. This method generates far less false positive predictions on various datasets than using simple pattern matching. Moreover, on the same datasets TatP generates less false positive predictions than...... expressions, whereas hydrophobicity discrimination of Tat- and Sec- signal peptides is carried out by an artificial neural network. A potential cleavage site of the predicted Tat signal peptide is also reported. The TatP prediction server is available as a public web server at http://www.cbs.dtu.dk/services/TatP/....

  18. Use of Galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2016-03-01

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  19. Use of Galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2017-03-21

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  20. Use of galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2018-04-03

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  1. Production of peptide antisera specific for mouse and rat proinsulin C-peptide 2

    DEFF Research Database (Denmark)

    Blume, N; Madsen, O D; Kofod, Hans

    1990-01-01

    Mice and rats have two functional non-allelic insulin genes. By using a synthetic peptide representing a common sequence in mouse and rat C-peptide 2 as antigen, we have produced rabbit antisera specific for an epitope which is not present in mouse or rat C-peptide 1. Long-term immunization did...... not seem to increase the end point titre as tested in direct ELISA. The specificity of the antiserum was determined by competitive ELISA and histochemistry on pancreas sections. Only the synthetic C-peptide 2, but not the homologous synthetic C-peptide 1 from mouse and rat competed efficiently in ELISA...... for antibody binding to the immunizing antigen. Antisera to C-peptide 2, stained islet beta-cells on mouse and rat, but not monkey pancreas sections in immunocytochemical analysis. Preabsorption to the synthetic C-peptide 2, but not the synthetic mouse and rat C-peptide 1 abolished staining. In conclusion we...

  2. Synthetic peptide vaccines: palmitoylation of peptide antigens by a thioester bond increases immunogenicity

    DEFF Research Database (Denmark)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Tesser, G.I.

    1997-01-01

    Synthetic peptides have frequently been used to immunize animals. However, peptides less than about 20 to 30 amino acids long are poor immunogens. In general, to increase its immunogenicity, the presentation of the peptide should be improved, and molecular weight needs to be increased. Many...... attempts have been made to couple peptide immunogens to different carrier proteins [e.g. keyhole limper haemocyanin (KLH) or ovalbumin]. This leads to very complex structures, however. We used a controlled conjugation of a peptide to a single long-chain fatty acid like palmitic acid by a thioester...... or an amide bond. It was found that these S-palmitoylated peptides were much more immunogenic than N-palmitoylated peptides and at least similar to KLH-conjugated peptides with respect to appearance and magnitude of induced antibodies (canine parvovirus) or immunocastration effect (gonadotropin...

  3. An Evaluation of Peptide-Bond Isosteres

    OpenAIRE

    Choudhary, Amit; Raines, Ronald T.

    2011-01-01

    Peptide-bond isosteres can enable a deep interrogation of the structure and function of a peptide or protein by amplifying or attenuating particular chemical properties. In this minireview, the electronic, structural, and conformational attributes of four such isosteres—thioamides, esters, alkenes, and fluoroalkenes—are examined in detail. In particular, the ability of these isosteres to partake in noncovalent interactions is compared with that of the peptide bond. The consequential perturbat...

  4. Inhibition of breast cancer cell proliferation in repeated and non-repeated treatment with zoledronic acid

    Directory of Open Access Journals (Sweden)

    Ibrahim Toni

    2012-11-01

    Full Text Available Abstract Background Zoledronic acid is used to treat bone metastases and has been shown to reduce skeletal-related events and exert antitumor activity. The present in vitro study investigates the mechanism of action of Zoledronic Acid on breast cancer cell lines with different hormonal and HER2 patterns. Furthermore, we investigated the efficacy of repeated versus non-repeated treatments. Methods The study was performed on 4 breast cancer cell lines (BRC-230, SkBr3, MCF-7 and MDA-MB-231. Non-repeated treatment (single exposure of 168 hrs’ duration with zoledronic acid was compared with repeated treatment (separate exposures, each of 48 hrs’ duration, for a total of 168 hrs at different dosages. A dose–response profile was generated using sulforhodamine B assay. Apoptosis was evaluated by TUNEL assay and biomolecular characteristics were analyzed by western blot. Results Zoledronic acid produced a dose-dependent inhibition of proliferation in all cell lines. Anti-proliferative activity was enhanced with the repeated treatment, proving to be statistically significant in the triple-negative lines. In these lines repeated treatment showed a cytocidal effect, with apoptotic cell death caused by caspase 3, 8 and 9 activation and decreased RAS and pMAPK expression. Apoptosis was not observed in estrogen receptor-positive line: p21 overexpression suggested a slowing down of cell cycle. A decrease in RAS and pMAPK expression was seen in HER2-overexpressing line after treatment. Conclusions The study suggests that zoledronic acid has an antitumor activity in breast cancer cell lines. Its mechanism of action involves the decrease of RAS and RHO, as in osteoclasts. Repeated treatment enhances antitumor activity compared to non-repeated treatment. Repeated treatment has a killing effect on triple-negative lines due to apoptosis activation. Further research is warranted especially in the treatment of triple-negative breast cancer.

  5. Restriction of anti-peptide antibody specificity by enzyme-modified Sepharose-peptide immunoadsorbents.

    Science.gov (United States)

    Trinca, M L; Muratti, E; Camera, M; Chersi, A

    1988-06-01

    Sepharose-peptide immunoadsorbents, employed for the isolation of specific antibodies from the sera of rabbits immunized with carrier protein-peptide conjugates, were digested with suitable proteolytic enzymes, in order to obtain the splitting of a part of the peptide bound to the gel. This new modified immunoadsorbent can be advantageously used for the isolation of antibody subsets, that do not cross-react with related peptides exhibiting high sequence homology with the immunogens.

  6. Novel peptide-based protease inhibitors

    DEFF Research Database (Denmark)

    Roodbeen, Renée

    This thesis describes the design and synthesis of peptide-based serine protease inhibitors. The targeted protease, urokinase-type plasminogen activator (uPA) activates plasminogen, which plays a major role in cancer metastasis. The peptide upain-2 (S 1 ,S 12-cyclo-AcCSWRGLENHAAC-NH2) is a highly...... of novel peptide-based protease inhibitors, efforts were made towards improved methods for peptide synthesis. The coupling of Fmoc-amino acids onto N-methylated peptidyl resins was investigated. These couplings can be low yielding and the effect of the use of microwave heating combined with the coupling...

  7. TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst

    Science.gov (United States)

    Hermann, Clemens; van Hateren, Andy; Trautwein, Nico; Neerincx, Andreas; Duriez, Patrick J; Stevanović, Stefan; Trowsdale, John; Deane, Janet E; Elliott, Tim; Boyle, Louise H

    2015-01-01

    Our understanding of the antigen presentation pathway has recently been enhanced with the identification that the tapasin-related protein TAPBPR is a second major histocompatibility complex (MHC) class I-specific chaperone. We sought to determine whether, like tapasin, TAPBPR can also influence MHC class I peptide selection by functioning as a peptide exchange catalyst. We show that TAPBPR can catalyse the dissociation of peptides from peptide-MHC I complexes, enhance the loading of peptide-receptive MHC I molecules, and discriminate between peptides based on affinity in vitro. In cells, the depletion of TAPBPR increased the diversity of peptides presented on MHC I molecules, suggesting that TAPBPR is involved in restricting peptide presentation. Our results suggest TAPBPR binds to MHC I in a peptide-receptive state and, like tapasin, works to enhance peptide optimisation. It is now clear there are two MHC class I specific peptide editors, tapasin and TAPBPR, intimately involved in controlling peptide presentation to the immune system. DOI: http://dx.doi.org/10.7554/eLife.09617.001 PMID:26439010

  8. TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst.

    Science.gov (United States)

    Hermann, Clemens; van Hateren, Andy; Trautwein, Nico; Neerincx, Andreas; Duriez, Patrick J; Stevanović, Stefan; Trowsdale, John; Deane, Janet E; Elliott, Tim; Boyle, Louise H

    2015-10-06

    Our understanding of the antigen presentation pathway has recently been enhanced with the identification that the tapasin-related protein TAPBPR is a second major histocompatibility complex (MHC) class I-specific chaperone. We sought to determine whether, like tapasin, TAPBPR can also influence MHC class I peptide selection by functioning as a peptide exchange catalyst. We show that TAPBPR can catalyse the dissociation of peptides from peptide-MHC I complexes, enhance the loading of peptide-receptive MHC I molecules, and discriminate between peptides based on affinity in vitro. In cells, the depletion of TAPBPR increased the diversity of peptides presented on MHC I molecules, suggesting that TAPBPR is involved in restricting peptide presentation. Our results suggest TAPBPR binds to MHC I in a peptide-receptive state and, like tapasin, works to enhance peptide optimisation. It is now clear there are two MHC class I specific peptide editors, tapasin and TAPBPR, intimately involved in controlling peptide presentation to the immune system.

  9. Connecting peptide (c-peptide) and the duration of diabetes mellitus ...

    African Journals Online (AJOL)

    Objective: C-peptide is derived from proinsulin and it is secreted in equimolar concentration with insulin. Plasma C-peptide is more stable than insulin and it provides an indirect measure of insulin secretory reserve and beta cell function. To determine relationship between C-peptide and duration of diabetes mellitus, age, ...

  10. Synthetic peptide vaccines: palmitoylation of peptide antigens by an thioester bond increases immunogenicity

    NARCIS (Netherlands)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Tesser, G.I.; Dalsgaard, K.; Langeveld, J.P.M.; Boshuizen, R.S.; Meloen, R.H.

    1997-01-01

    Synthetic peptides have frequently been used to immunize animals. However, peptides less than about 20 to 30 amino acids long are poor immunogens. In general, to increase its immunogenicity, the presentation of the peptide should be improved, and molecular weight needs to be increased. Many attempts

  11. Obviation of hydrogen fluoride in Boc chemistry solid phase peptide synthesis of peptide-αthioesters.

    Science.gov (United States)

    Gates, Zachary P; Dhayalan, Balamurugan; Kent, Stephen B H

    2016-11-29

    Under suitable conditions, trifluoromethanesulfonic acid performs comparably to hydrogen fluoride for the on-resin global deprotection of peptides prepared by Boc chemistry solid phase peptide synthesis (SPPS). Obviation of hydrogen fluoride in Boc chemistry SPPS enables the straightforward synthesis of peptide- α thioesters for use in native chemical ligation.

  12. Atrial natriuretic peptides in plasma

    DEFF Research Database (Denmark)

    Goetze, Jens Peter; Hansen, Lasse H; Terzic, Dijana

    2014-01-01

    Measurement of cardiac natriuretic peptides in plasma has gained a diagnostic role in the assessment of heart failure. Plasma measurement is though hampered by the marked instability of the hormones, which has led to the development of analyses that target N-terminal fragments from the prohormone....... These fragments are stable in plasma and represent surrogate markers of the actual natriuretic hormone. Post-translational processing of the precursors, however, is revealing itself to be a complex event with new information still being reported on proteolysis, covalent modifications, and amino acid...

  13. Biodiscovery of Aluminum Binding Peptides

    Science.gov (United States)

    2013-08-01

    et al., "Biomimetic synthesis and patterning of silver nanoparticles," Nat. Mater. 1(3), 169-172 (2002). [5] Van Dorst, B., et al., "Phage display...Biotechnol. 68(4), 505-509 (2005). [10] Lee, Y. J., et al., "Fabricating genetically engineered high-power lithium-ion batteries using multiple virus genes...34Sequestration of zinc oxide by fimbrial designer chelators," Appl. Environ. Microbiol. 66(1), 10-14 (2000). [26] Hnilova, M., et al., "Peptide-directed co

  14. Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics.

    Science.gov (United States)

    Gupta, Kajal; Singh, Sameer; van Hoek, Monique L

    2015-08-24

    Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP). Two synthetic 11-residue peptides (ATRA-1A and ATRA-2) containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4). We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost), making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP) (EC50 = 0.05 μg/mL). High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC) assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed synergism

  15. Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics

    Directory of Open Access Journals (Sweden)

    Kajal Gupta

    2015-08-01

    Full Text Available Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP. Two synthetic 11-residue peptides (ATRA-1A and ATRA-2 containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4. We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost, making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP (EC50 = 0.05 μg/mL. High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed

  16. Structural Basis of Rap Phosphatase Inhibition by Phr Peptides

    Science.gov (United States)

    Gallego del Sol, Francisca; Marina, Alberto

    2013-01-01

    Two-component systems, composed of a sensor histidine kinase and an effector response regulator (RR), are the main signal transduction devices in bacteria. In Bacillus, the Rap protein family modulates complex signaling processes mediated by two-component systems, such as competence, sporulation, or biofilm formation, by inhibiting the RR components involved in these pathways. Despite the high degree of sequence homology, Rap proteins exert their activity by two completely different mechanisms of action: inducing RR dephosphorylation or blocking RR binding to its target promoter. However the regulatory mechanism involving Rap proteins is even more complex since Rap activity is antagonized by specific signaling peptides (Phr) through a mechanism that remains unknown at the molecular level. Using X-ray analyses, we determined the structure of RapF, the anti-activator of competence RR ComA, alone and in complex with its regulatory peptide PhrF. The structural and functional data presented herein reveal that peptide PhrF blocks the RapF-ComA interaction through an allosteric mechanism. PhrF accommodates in the C-terminal tetratricopeptide repeat domain of RapF by inducing its constriction, a conformational change propagated by a pronounced rotation to the N-terminal ComA-binding domain. This movement partially disrupts the ComA binding site by triggering the ComA disassociation, whose interaction with RapF is also sterically impaired in the PhrF-induced conformation of RapF. Sequence analyses of the Rap proteins, guided by the RapF-PhrF structure, unveil the molecular basis of Phr recognition and discrimination, allowing us to relax the Phr specificity of RapF by a single residue change. PMID:23526880

  17. Familial transmission of the FMR1 CGG repeat.

    OpenAIRE

    Nolin, S. L.; Lewis, F. A.; Ye, L. L.; Houck, G. E.; Glicksman, A. E.; Limprasert, P.; Li, S. Y.; Zhong, N.; Ashley, A. E.; Feingold, E.; Sherman, S. L.; Brown, W. T.

    1996-01-01

    To better define the nature of FMR1 CGG-repeat expansions, changes in allele sizes for 191 families with fragile X and for 33 families with gray-zone repeats (40-60) were analyzed. Expansion of the fragile X chromosome to the full mutation was seen in 13.4% of offspring from premutation mothers with 56-59 repeats, 20.6% of those with 60-69 repeats, 57.8% of those with 70-79 repeats, 72.9% of those with 80-89 repeats, and 97.3% of those with 90-199 repeats. For premutation fathers, the majorit...

  18. Nonparametric additive regression for repeatedly measured data

    KAUST Repository

    Carroll, R. J.

    2009-05-20

    We develop an easily computed smooth backfitting algorithm for additive model fitting in repeated measures problems. Our methodology easily copes with various settings, such as when some covariates are the same over repeated response measurements. We allow for a working covariance matrix for the regression errors, showing that our method is most efficient when the correct covariance matrix is used. The component functions achieve the known asymptotic variance lower bound for the scalar argument case. Smooth backfitting also leads directly to design-independent biases in the local linear case. Simulations show our estimator has smaller variance than the usual kernel estimator. This is also illustrated by an example from nutritional epidemiology. © 2009 Biometrika Trust.

  19. Overcoming fixation with repeated memory suppression.

    Science.gov (United States)

    Angello, Genna; Storm, Benjamin C; Smith, Steven M

    2015-01-01

    Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.

  20. Toxicological characteristics of petroleum products repeated exposure

    Directory of Open Access Journals (Sweden)

    V.M. Rubin

    2015-03-01

    Full Text Available Abstract. The ability of petroleum products to initiate cumulative effects was assessed in experimental intragastric admission to male albino rats for one month. The analysis of skin-resorptive effects was performed using "test-tube" method on the skin of rats’ tails. It has been established that petroleum products can penetrate the intact skin and, with repeated admission, cause a general toxic effect. There were reductions bodyweights, the negative effect on the function of the kidneys and liver, changes of hematological parameters, as well as activation of the antioksidatnoy system. Repeated intragastric administration does not lead to the death of the animals testifying to the lack of accumulation capacity for petroleum products at the level of functional mortal effects, the cumulation coefficient being > 5.1. Negative impact on urinary function and hepatobiliary system, changes in hematological parameters and activation of the «lipid peroxidation – antioksidant defense» were observed.

  1. Effect of a Fusion Peptide by Covalent Conjugation of a Mitochondrial Cell-Penetrating Peptide and a Glutathione Analog Peptide

    Directory of Open Access Journals (Sweden)

    Carmine Pasquale Cerrato

    2017-06-01

    Full Text Available Previously, we designed and synthesized a library of mitochondrial antioxidative cell-penetrating peptides (mtCPPs superior to the parent peptide, SS31, to protect mitochondria from oxidative damage. A library of antioxidative glutathione analogs called glutathione peptides (UPFs, exceptional in hydroxyl radical elimination compared with glutathione, were also designed and synthesized. Here, a follow-up study is described, investigating the effects of the most promising members from both libraries on reactive oxidative species scavenging ability. None of the peptides influenced cell viability at the concentrations used. Fluorescence microscopy studies showed that the fluorescein-mtCPP1-UPF25 (mtgCPP internalized into cells, and spectrofluorometric analysis determined the presence and extent of peptide into different cell compartments. mtgCPP has superior antioxidative activity compared with mtCPP1 and UPF25 against H2O2 insult, preventing ROS formation by 2- and 3-fold, respectively. Moreover, we neither observed effects on mitochondrial membrane potential nor production of ATP. These data indicate that mtgCPP is targeting mitochondria, protecting them from oxidative damage, while also being present in the cytosol. Our hypothesis is based on a synergistic effect resulting from the fused peptide. The mitochondrial peptide segment is targeting mitochondria, whereas the glutathione analog peptide segment is active in the cytosol, resulting in increased scavenging ability.

  2. Identification and chromosomal localization of repeat sequences ...

    Indian Academy of Sciences (India)

    Unknown

    generate linkage maps of human and cattle as well as for other mammalian ... through BAC end sequencing and identification in silico. (Larkin et al. ... LINEs. 2,344. 653,391 bp. 19.80. LTR elements. 500. 124,761 bp. 3.78. DNA elements. 267. 46,569 bp. 1.14. Total interspersed repeats. 1,105,666 bp. 33.51. Small RNA. 26.

  3. Repeatability and Workability Evaluation of SIGMOD 2011

    DEFF Research Database (Denmark)

    2011-01-01

    SIGMOD has offered, since 2008, to verify the experiments published in the papers accepted at the conference. This year, we have been in charge of reproducing the experiments provided by the authors (repeatability), and exploring changes to experiment parameters (workability). In this paper, we a...... find that most experiments are distributed as Linux packages accompanied by instructions on how to setup and run the experiments. We are still far from the vision of executable papers...

  4. Developing Aural Comprehension Skills through Repeated Listening

    OpenAIRE

    Brown, R. A.

    2006-01-01

    Listening in a foreign language is difficult. Previous research has identified a number of strategies that can result in increased comprehension. One such is simply listening to a given text more than one time. The present article describes the psychological and linguistic background to this issue, describes a small scale empirical study which provides support for the view that repeated listening increases some important aspects of comprehension and motivation, and suggests a number of techni...

  5. Repeated extraction of DNA from FTA cards

    DEFF Research Database (Denmark)

    Stangegaard, Michael; Ferrero, Laura; Børsting, Claus

    2011-01-01

    Extraction of DNA using magnetic bead based techniques on automated DNA extraction instruments provides a fast, reliable and reproducible method for DNA extraction from various matrices. However, the yield of extracted DNA from FTA-cards is typically low. Here, we demonstrate that it is possible...... to repeatedly extract DNA from the processed FTA-disk. The method increases the yield from the nanogram range to the microgram range....

  6. Electrochemical detection of DNA triplet repeat expansion

    Czech Academy of Sciences Publication Activity Database

    Fojta, Miroslav; Havran, Luděk; Vojtíšková, Marie; Paleček, Emil

    2004-01-01

    Roč. 126, č. 21 (2004), s. 6532-6533 ISSN 0002-7863 R&D Projects: GA AV ČR IAA4004402; GA AV ČR IBS5004355; GA AV ČR KJB4004302; GA AV ČR KSK4055109 Institutional research plan: CEZ:AV0Z5004920 Keywords : DNA triplet repeat expansion * PCR amplification * neurodegenerative diseases Subject RIV: BO - Biophysics Impact factor: 6.903, year: 2004

  7. Security of Quantum Repeater Network Operation

    Science.gov (United States)

    2016-10-03

    taxonomies for RFID tags, because both RFID tags and quantum links and nodes are sensitive to their local environment, and attacks at the physical level...vulnerable to being hacked . Thus, operation of the quantum repeater network is vulnerable to undetectable disruption of the network operation. This...Jogenfors, J., Elhassan, A. M., Ahrens, J., Bourennane, M., & Larsson, J. (2015). Hacking the Bell test using classical light in energy-time

  8. peptide

    Indian Academy of Sciences (India)

    Prakash

    The effects on memory formation and cognitive abilities due to injection of amyloid fragments into the brain have been very inconsistent until now. It has been ... determining the molecular basis of the recognition and assembly processes fostering amyloid-fibril formation is a very complicated task. Moreover, the synthesis of ...

  9. Multiplexing schemes for quantum repeater networks

    Science.gov (United States)

    Aparicio, Luciano; Van Meter, Rodney

    2011-08-01

    When built, quantum repeaters will allow the distribution of entangled quantum states across large distances, playing a vital part in many proposed quantum technologies. Enabling multiple users to connect through the same network will be key to their real-world deployment. Previous work on repeater technologies has focussed only on simple entanglment production, without considering the issues of resource scarcity and competition that necessarily arise in a network setting. In this paper we simulated a thirteen-node network with up to five flows sharing different parts of the network, measuring the total throughput and fairness for each case. Our results suggest that the Internet-like approach of statistical multiplexing use of a congested link gives the highest aggregate throughput. Time division multiplexing and buffer space multiplexing were slightly less effective, but all three schemes allow the sum of multiple flows to substantially exceed that of any one flow, improving over circuit switching by taking advantage of resources that are forced to remain idle in circuit switching. All three schemes proved to have excellent fairness. The high performance, fairness and simplicity of implementation support a recommendation of statistical multiplexing for shared quantum repeater networks.

  10. A Unified Model for Repeating and Non-repeating Fast Radio Bursts

    Energy Technology Data Exchange (ETDEWEB)

    Bagchi, Manjari, E-mail: manjari@imsc.res.in [The Institute of Mathematical Sciences (IMSc-HBNI), 4th Cross Road, CIT Campus, Taramani, Chennai 600113 (India)

    2017-04-01

    The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

  11. Synthetic mimics of antimicrobial peptides.

    Science.gov (United States)

    Som, Abhigyan; Vemparala, Satyavani; Ivanov, Ivaylo; Tew, Gregory N

    2008-01-01

    Infectious diseases and antibiotic resistance are now considered the most imperative global healthcare problem. In the search for new treatments, host defense, or antimicrobial, peptides have attracted considerable attention due to their various unique properties; however, attempts to develop in vivo therapies have been severely limited. Efforts to develop synthetic mimics of antimicrobial peptides (SMAMPs) have increased significantly in the last decade, and this review will focus primarily on the structural evolution of SMAMPs and their membrane activity. This review will attempt to make a bridge between the design of SMAMPs and the fundamentals of SMAMP-membrane interactions. In discussions regarding the membrane interaction of SMAMPs, close attention will be paid to the lipid composition of the bilayer. Despite many years of study, the exact conformational aspects responsible for the high selectivity of these AMPs and SMAMPs toward bacterial cells over mammalian cells are still not fully understood. The ability to design SMAMPs that are potently antimicrobial, yet nontoxic to mammalian cells has been demonstrated with a variety of molecular scaffolds. Initial animal studies show very good tissue distribution along with more than a 4-log reduction in bacterial counts. The results on SMAMPs are not only extremely promising for novel antibiotics, but also provide an optimistic picture for the greater challenge of general proteomimetics.

  12. Peptide amphiphile self-assembly

    Science.gov (United States)

    Iscen, Aysenur; Schatz, George C.

    2017-08-01

    Self-assembly is a process whereby molecules organize into structures with hierarchical order and complexity, often leading to functional materials. Biomolecules such as peptides, lipids and DNA are frequently involved in self-assembly, and this leads to materials of interest for a wide variety of applications in biomedicine, photonics, electronics, mechanics, etc. The diversity of structures and functions that can be produced provides motivation for developing theoretical models that can be used for a molecular-level description of these materials. Here we overview recently developed computational methods for modeling the self-assembly of peptide amphiphiles (PA) into supramolecular structures that form cylindrical nanoscale fibers using molecular-dynamics simulations. Both all-atom and coarse-grained force field methods are described, and we emphasize how these calculations contribute insight into fiber structure, including the importance of β-sheet formation. We show that the temperature at which self-assembly takes place affects the conformations of PA chains, resulting in cylindrical nanofibers with higher β-sheet content as temperature increases. We also present a new high-density PA model that shows long network formation of β-sheets along the long axis of the fiber, a result that correlates with some experiments. The β-sheet network is mostly helical in nature which helps to maintain strong interactions between the PAs both radially and longitudinally. Contribution to Focus Issue Self-assemblies of Inorganic and Organic Nanomaterials edited by Marie-Paule Pileni.

  13. High specific selectivity and Membrane-Active Mechanism of the synthetic centrosymmetric α-helical peptides with Gly-Gly pairs.

    Science.gov (United States)

    Wang, Jiajun; Chou, Shuli; Xu, Lin; Zhu, Xin; Dong, Na; Shan, Anshan; Chen, Zhihui

    2015-11-04

    We used a template-assisted approach to develop synthetic antimicrobial peptides, which differ from naturally occurring antimicrobial peptides that can compromise host natural defenses. Previous researches have demonstrated that symmetrical distribution patterns of amino acids contribute to the antimicrobial activity of natural peptides. However, there is little research describing such design ideas for synthetic α-helical peptides. Therefore, here, we established a centrosymmetric α-helical sequence template (y + hhh + y)n (h, hydrophobic amino acid; +, cationic amino acid; y, Gly or hydrophobic amino acid), which contributed to amphipathicity, and a series of centrosymmetric peptides was designed with pairs of small amino acids (Ala and Gly), which were utilized to modulate the biological activity. The centrosymmetric peptides with 3 repeat units exhibited strong antimicrobial activity; in particular, the Gly-rich centrosymmetric peptide GG3 showed stronger selectivity for gram-negative bacteria without hemolysis. Furthermore, beyond our expectation, fluorescence spectroscopy and electron microscopy analyses indicated that the GG3, which possessed poor α-helix conformation, dramatically exhibited marked membrane destruction via inducing bacterial membrane permeabilization, pore formation and disruption, even bound DNA to further exert antimicrobial activity. Collectively, the Gly-rich centrosymmetric peptide GG3 was an ideal candidate for commercialization as a clinical therapeutic to treat gram-negative bacterial infections.

  14. Protein identification by peptide mass fingerprinting

    DEFF Research Database (Denmark)

    Hjernø, Karin

    2007-01-01

      Peptide mass fingerprinting is an effective way of identifying, e.g., gel-separated proteins, by matching experimentally obtained peptide mass data against large databases. However, several factors are known to influence the quality of the resulting matches, such as proteins contaminating...

  15. One Hundred Years of Peptide Chemistry*

    Indian Academy of Sciences (India)

    spinal cord. These brain morphins have been well studied which is known to allow analgesia to be separated from the development of addiction and dependence. Peptide Leukotrienes: The peptide leukotrienes cause contrac- tion of the bronchial smooth muscle and probably play an impor- tant role as mediators in allergic ...

  16. Peptide Mass Fingerprinting of Egg White Proteins

    Science.gov (United States)

    Alty, Lisa T.; LaRiviere, Frederick J.

    2016-01-01

    Use of advanced mass spectrometry techniques in the undergraduate setting has burgeoned in the past decade. However, relatively few undergraduate experiments examine the proteomics tools of protein digestion, peptide accurate mass determination, and database searching, also known as peptide mass fingerprinting. In this experiment, biochemistry…

  17. To protect peptide pharmaceuticals against peptidases

    NARCIS (Netherlands)

    Rink, R.; Arkema-Meter, A.; Baudoin, I.; Post, E.; Kuipers, A.; Nelemans, S. A.; Akanbi, M. Haas Jimoh; Moll, G. N.

    2010-01-01

    Introduction: The major hurdle in the application and delivery of peptide pharmaceuticals is their rapid in vivo breakdown. Methods: We here combined two approaches to stabilize peptide pharmaceuticals, introduction of D-amino acids and cyclization, by applying an innovative enzymatic method. This

  18. Soybean peptide: optimal preparatory conditions, chemical and ...

    African Journals Online (AJOL)

    The peptide fractionation, molecular weight determination of the resolved bands, coupled with amino acid profiles, all supported the similarity of peptide H8 to MSBP. The sample H8 was prepared from protein isolate from dehulled, defatted soybean (DHSB) at the temperature setting of 42.5 o C and pH of 2.0 (pepsin), 7.5 ...

  19. Protein Inference Using Peptide Quantification Patterns

    NARCIS (Netherlands)

    Lukasse, P.N.J.; America, A.H.P.

    2014-01-01

    Determining the list of proteins present in a sample, based on the list of identified peptides, is a crucial step in the untargeted proteomics LC-MS/MS data-processing pipeline. This step, commonly referred to as protein inference, turns out to be a very challenging problem because many peptide

  20. Highly Stable Trypsin-Aggregate Coatings on Polymer Nanofibers for Repeated Protein Digestion

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byoung Chan; Lopez-Ferrer, Daniel; Lee, Sang-mok; Ahn, Hye-kyung; Nair, Sujith; Kim, Seong H.; Kim, Beom S.; Petritis, Konstantinos; Camp, David G.; Grate, Jay W.; Smith, Richard D.; Koo, Yoon-mo; Gu, Man Bock; Kim, Jungbae

    2009-04-01

    A stable and robust trypsin-based biocatalytic system was developed and demonstrated for proteomic applications. The system utilizes polymer nanofibers coated with trypsin aggregates for immobilized protease digestions. After covalently attaching an initial layer of trypsin to the polymer nanofibers, highly concentrated trypsin molecules are crosslinked to the layered trypsin by way of a glutaraldehyde treatment. This new process produced a 300-fold increase in trypsin activity compared with a conventional method for covalent trypsin immobilization and proved to be robust in that it still maintained a high level of activity after a year of repeated recycling. This highly stable form of immobilized trypsin was also resistant to autolysis, enabling repeated digestions of bovine serum albumin over 40 days and successful peptide identification by LC-MS/MS. Finally, the immobilized trypsin was resistant to proteolysis when exposed to other enzymes (i.e. chymotrypsin), which makes it suitable for use in “real-world” proteomic applications. Overall, the biocatalytic nanofibers with enzyme aggregate coatings proved to be an effective approach for repeated and automated protein digestion in proteomic analyses.

  1. Peptide ligands for targeting the extracellular domain of EGFR: Comparison between linear and cyclic peptides.

    Science.gov (United States)

    Williams, Tyrslai M; Sable, Rushikesh; Singh, Sitanshu; Vicente, Maria Graca H; Jois, Seetharama D

    2018-02-01

    Colorectal cancer (CRC) is the third most common solid internal malignancy among cancers. Early detection of cancer is key to increasing the survival rate of colorectal cancer patients. Overexpression of the EGFR protein is associated with CRC. We have designed a series of peptides that are highly specific for the extracellular domain of EGFR, based on our earlier studies on linear peptides. The previously reported linear peptide LARLLT, known to bind to EGFR, was modified with the goals of increasing its stability and its specificity toward EGFR. Peptide modifications, including D-amino acid substitution, cyclization, and chain reversal, were investigated. In addition, to facilitate labeling of the peptide with a fluorescent dye, an additional lysine residue was introduced onto the linear (KLARLLT) and cyclic peptides cyclo(KLARLLT) (Cyclo.L1). The lysine residue was also converted into an azide group in both a linear and reversed cyclic peptide sequences cyclo(K(N3)larllt) (Cyclo.L1.1) to allow for subsequent "click" conjugation. The cyclic peptides showed enhanced binding to EGFR by SPR. NMR and molecular modeling studies suggest that the peptides acquire a β-turn structure in solution. In vitro stability studies in human serum show that the cyclic peptide is more stable than the linear peptide. © 2017 John Wiley & Sons A/S.

  2. Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions

    DEFF Research Database (Denmark)

    Høgstedt, Ulrich B; Schwach, Grégoire; van de Weert, Marco

    2016-01-01

    solutions increased with concentration. Our results indicate that a viscosity difference between run buffer and sample in Taylor Dispersion Analysis may result in overestimation of the measured diffusion coefficient. Thus, Taylor Dispersion Analysis provides a practical, but as yet primarily qualitative....... In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited...... for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions...

  3. Antioxidant activity of yoghurt peptides: Part 2 – Characterisationof peptide fractions

    DEFF Research Database (Denmark)

    Farvin, Sabeena; Baron, Caroline; Nielsen, Nina Skall

    2010-01-01

    The aim of the present study was to elucidate previous findings showing that peptide fractions isolated from yoghurt had antioxidant effects. Therefore, peptides and free amino acids released during fermentation of milk were characterised. Yoghurt samples were stripped from sugars and lactic acid...... the peptides identified contained at least one proline residue. Some of the identified peptides included the hydrophobic amino acid residues Val or Leu at the N-terminus and Pro, His or Tyr in the amino acid sequence, which is characteristic of antioxidant peptides. In addition, the yoghurt contained...... a considerable amount of free amino acids such as His, Tyr, Thr and Lys, which have been reported to have antioxidant properties. Thus, our findings confirm that the antioxidant effects of the peptide fractions from yoghurt are due to the presence of certain peptides and free amino acids with recognised...

  4. Cell-penetrating peptides - Methods and protocols

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2011-09-01

    Full Text Available Among the present day scientific frontiers, the researches on the cell-penetrating peptides has a special place since the scientific community has not yet reached a consensus even in the terminology on what we are referring to when we speak about cell-penetrating peptides studies. Thus, Prof. Ulo Langel (Dept. of Neurochemistry, Stockolm University, Stockolm, Sweden rightly explain in a necessary preface that there are in use so many definition for the same things: protein transduction domain (PTDs, Trojan peptides, model amphipathic peptides (MAPs, membrane translocating sequences (MTS that the best way to refer to all of these molecules is to call all of them cell-penetrating peptides, CPPs. Thus, there is a need for an accepted definition of CPPs.....

  5. Interpreting peptide mass spectra by VEMS

    DEFF Research Database (Denmark)

    Mathiesen, Rune; Lundsgaard, M.; Welinder, Karen G.

    2003-01-01

    the calculated and the experimental mass spectrum of the called peptide. The program package includes four accessory programs. VEMStrans creates protein databases in FASTA format from EST or cDNA sequence files. VEMSdata creates a virtual peptide database from FASTA files. VEMSdist displays the distribution......Most existing Mass Spectra (MS) analysis programs are automatic and provide limited opportunity for editing during the interpretation. Furthermore, they rely entirely on publicly available databases for interpretation. VEMS (Virtual Expert Mass Spectrometrist) is a program for interactive analysis...... of peptide MS/MS spectra imported in text file format. Peaks are annotated, the monoisotopic peaks retained, and the b-and y-ion series identified in an interactive manner. The called peptide sequence is searched against a local protein database for sequence identity and peptide mass. The report compares...

  6. Molecular Engineering Solutions for Therapeutic Peptide Delivery.

    Energy Technology Data Exchange (ETDEWEB)

    Acar, Handan; Ting, Jeffrey M.; Srivastava, Samanvaya; LaBelle, James L.; Tirrell, Matthew V.

    2017-11-07

    Proteins and their interactions in and out of cells must be well-orchestrated for the healthy functioning and regulation of the body. Even the slightest disharmony can cause diseases. Therapeutic peptides are short amino acid sequences (generally considered <50 amino acids) that can naturally mimic the binding interfaces between proteins and thus, influence protein-protein interactions. Because of their fidelity of binding, peptides are a promising next generation of personalized medicines to reinstate biological harmony. Peptides as a group are highly selective, relatively safe, and biocompatible. However, they are also vulnerable to many in vivo pharmacologic barriers limiting their clinical translation. Current advances in molecular, chemical, and nanoparticle engineering are helping to overcome these previously insurmountable obstacles and improve the future of peptides as active and highly selective therapeutics. In this review, we focus on self-assembled vehicles as nanoparticles to carry and protect therapeutic peptides through this journey, and deliver them to the desired tissue.

  7. The human endolymphatic sac expresses natriuretic peptides

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas

    2017-01-01

    OBJECTIVES/HYPOTHESIS: The function of the human endolymphatic sac (ES) has been enigmatic for decades. Hypotheses include controlling endolymphatic fluid homeostasis and inner ear immunological defense. Additionally, several studies indicate a possible endocrine capacity and a yet undefined role......: Several natriuretic peptides were found expressed significantly in the ES, including uroguanylin and brain natriuretic peptide, but also peptides regulating vascular tone, including adrenomedullin 2. In addition, both neurophysin and oxytocin (OXT) were found significantly expressed. All peptides were...... vasopressin receptors and aquaporin-2 channels in the inner ear via OXT expression. We hypothesize that the ES is likely to regulate inner ear endolymphatic homeostasis, possibly through secretion of several peptides, but it may also influence systemic and/or intracranial blood pressure through direct...

  8. Intracellular Signalling by C-Peptide

    Directory of Open Access Journals (Sweden)

    Claire E. Hills

    2008-01-01

    Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

  9. Preparation and utilization of fluorescent synthetic peptides.

    Science.gov (United States)

    Chersi, A; Sezzi, M L; Romano, T F; Evangelista, M; Nista, A

    1990-06-20

    In this study, several methods for controlled labelling of synthetic peptides by the use of fluorescent compounds (fluorescein isothiocyanate and dimethylaminonaphthalene sulfonyl chloride) were investigated. The first reagent yielded monofluoresceinated, active compounds only when the peptides lacked lysine residues. Monolabelling of peptides in solution with dimethylaminonaphthalenesulphonyl chloride was hindered by the broad reactivity of the reagent, but was achieved by reacting the fluorochrome on protected resin-bound peptides in solid-phase synthesis. The remarkable stability of the linkage allowed the cleavage of the peptide from the resin and deprotection of side-chain functions without hydrolysis of the labelled group. The binding of antipeptide antibodies to the labelled fragments was then estimated using different techniques.

  10. Accessing Specific Peptide Recognition by Combinatorial Chemistry

    DEFF Research Database (Denmark)

    Li, Ming

    in recognition, a hook peptide library was built as sequence blocks containing two L-prolines, facilitating peptide back-bones to organize into a bend “hook” shape. Selection of pairs recognizing each other by entanglement with the conformational shape as a fundamental mechanism of molecular recognition...... was studied with this hook peptide library via the beadbead adhesion screening approach. The recognition pairs interlocked and formed a complex. (chapter 8) During accessing peptide molecular recognition by combinatorial chemistry, we faced several problems, which were solved by a range of analytical...... separation of is developed and used to select the best hits from the “hook” peptide library. The association strength of complex was also evaluated by MS-MS analysis. (chapter 8) a microchannel flow device was designed and utilized to measure binding constants on a single bead. (chapter 5) An important...

  11. Radiolabeled peptides: experimental and clinical applications

    International Nuclear Information System (INIS)

    Thakur, M.L.; Pallela, V.R.

    1998-01-01

    Radiolabeled receptor specific biomolecules hold unlimited potential in nuclear medicine. During the past few years much attention has been drawn to the development radiolabeled peptides for a variety of diagnostic applications, as well as for therapy of malignant tumors. Although only one peptide, In-111-DTPA-(D)-Phe 1 -octreotide, is available commercially for oncologic imaging, many more have been examined in humans with hematological disorders, and the early results appear to be promising. Impetus generated by these results have prompted investigators to label peptides with such radionuclides as Tc-99m, I-123, F-18, Cu-64, and Y-90. This review is intended to highlight the qualities of peptides, summarize the clinical results, and address some important issues associated with radiolabeling of highly potent peptides. While doing so, various methods of radiolabeling have been described, and their strengths and weaknesses have also been discussed. (author)

  12. Chemical reactions directed Peptide self-assembly.

    Science.gov (United States)

    Rasale, Dnyaneshwar B; Das, Apurba K

    2015-05-13

    Fabrication of self-assembled nanostructures is one of the important aspects in nanoscience and nanotechnology. The study of self-assembled soft materials remains an area of interest due to their potential applications in biomedicine. The versatile properties of soft materials can be tuned using a bottom up approach of small molecules. Peptide based self-assembly has significant impact in biology because of its unique features such as biocompatibility, straight peptide chain and the presence of different side chain functionality. These unique features explore peptides in various self-assembly process. In this review, we briefly introduce chemical reaction-mediated peptide self-assembly. Herein, we have emphasised enzymes, native chemical ligation and photochemical reactions in the exploration of peptide self-assembly.

  13. Harnessing supramolecular peptide nanotechnology in biomedical applications.

    Science.gov (United States)

    Chan, Kiat Hwa; Lee, Wei Hao; Zhuo, Shuangmu; Ni, Ming

    2017-01-01

    The harnessing of peptides in biomedical applications is a recent hot topic. This arises mainly from the general biocompatibility of peptides, as well as from the ease of tunability of peptide structure to engineer desired properties. The ease of progression from laboratory testing to clinical trials is evident from the plethora of examples available. In this review, we compare and contrast how three distinct self-assembled peptide nanostructures possess different functions. We have 1) nanofibrils in biomaterials that can interact with cells, 2) nanoparticles that can traverse the bloodstream to deliver its payload and also be bioimaged, and 3) nanotubes that can serve as cross-membrane conduits and as a template for nanowire formation. Through this review, we aim to illustrate how various peptides, in their various self-assembled nanostructures, possess great promise in a wide range of biomedical applications and what more can be expected.

  14. Chemical Reactions Directed Peptide Self-Assembly

    Directory of Open Access Journals (Sweden)

    Dnyaneshwar B. Rasale

    2015-05-01

    Full Text Available Fabrication of self-assembled nanostructures is one of the important aspects in nanoscience and nanotechnology. The study of self-assembled soft materials remains an area of interest due to their potential applications in biomedicine. The versatile properties of soft materials can be tuned using a bottom up approach of small molecules. Peptide based self-assembly has significant impact in biology because of its unique features such as biocompatibility, straight peptide chain and the presence of different side chain functionality. These unique features explore peptides in various self-assembly process. In this review, we briefly introduce chemical reaction-mediated peptide self-assembly. Herein, we have emphasised enzymes, native chemical ligation and photochemical reactions in the exploration of peptide self-assembly.

  15. Influence of a heptad repeat stutter on the pH-dependent conformational behavior of the central coiled-coil from influenza hemagglutinin HA2.

    Science.gov (United States)

    Higgins, Chelsea D; Malashkevich, Vladimir N; Almo, Steven C; Lai, Jonathan R

    2014-09-01

    The coiled-coil is one of the most common protein structural motifs. Amino acid sequences of regions that participate in coiled-coils contain a heptad repeat in which every third then forth residue is occupied by a hydrophobic residue. Here we examine the consequences of a "stutter," a deviation of the idealized heptad repeat that is found in the central coiled-coil of influenza hemagluttinin HA2. Characterization of a peptide containing the native stutter-containing HA2 sequence, as well as several variants in which the stutter was engineered out to restore an idealized heptad repeat pattern, revealed that the stutter is important for allowing coiled-coil formation in the WT HA2 at both neutral and low pH (7.1 and 4.5). By contrast, all variants that contained idealized heptad repeats exhibited marked pH-dependent coiled-coil formation with structures forming much more stably at low pH. A crystal structure of one variant containing an idealized heptad repeat, and comparison to the WT HA2 structure, suggest that the stutter distorts the optimal interhelical core packing arrangement, resulting in unwinding of the coiled-coil superhelix. Interactions between acidic side chains, in particular E69 and E74 (present in all peptides studied), are suggested to play a role in mediating these pH-dependent conformational effects. This conclusion is partially supported by studies on HA2 variant peptides in which these positions were altered to aspartic acid. These results provide new insight into the structural role of the heptad repeat stutter in HA2. © 2014 Wiley Periodicals, Inc.

  16. Synthetic peptide inhibitors of DNA replication in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Løbner-Olesen, Anders; Kjelstrup, Susanne

    F counterselection was developed to directly select for compounds able to disrupt selected interactions. We have subsequently constructed a cyclic peptide library for intracellular synthesis of cyclic peptides using known technology. Several cyclic peptides were able to interfere with oligomerization of Dna......N (), DnaB and DnaX (). Three peptides identified as inhibitors of DnaN have been purified. Two of these peptides inhibited growth as well as DNA replication in S. aureus. The minimal inhibitory concentration (MIC) of the peptides was approximately 50 g/ml. Overexpression of DnaN reduced the inhibitory...... effect of the peptides confirming the target of the peptides....

  17. Electrochemistry of Alzheimer disease amyloid beta peptides.

    Science.gov (United States)

    Chiorcea-Paquim, Ana-Maria; Enache, Teodor Adrian; Oliveira-Brett, Ana Maria

    2018-02-13

    Alzheimer's disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting the highest neurotoxicity. This review discusses the recent advances on the Aβ peptides electrochemical characterisation. The Aβ peptides oxidation at a glassy carbon electrode occurs in one or two steps, depending on the amino acid sequence, length and content. The first electron transfer reaction corresponds to the tyrosine Tyr10 amino acid residue oxidation, and the second to all three histidine (His6, His13 and His14) and one methionine (Met35) amino acid residues. The Aβ peptides aggregation and amyloid fibril formation is electrochemically detected via the electroactive amino acids oxidation peak currents decrease that occurs in a time dependent manner. The Aβ peptides redox behaviour is correlated with changes in the adsorption morphology from initially random coiled structures, corresponding to the Aβ peptide monomers in random coil or in α-helix conformations, to aggregates and protofibrils and two types of fibrils, corresponding to the Aβ peptides in a β-sheet configuration, observed by atomic force microscopy. Electrochemical studies of Aβ peptides aggregation, mediated by the interaction with metal ions, in particular zinc, copper, and iron, and different methodologies concerning the detection of Aβ peptide biomarkers of AD in biological fluids, using electrochemical biosensors, are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Consequences of non-uniformity in the stoichiometry of component fractions within one and two loops models of alpha-helical peptides

    Science.gov (United States)

    Atoms in biomolecular structures like alpha helices contain an array of distances and angles which include abundant multiple patterns of redundancies. Thus all peptides backbones contain the three atom sequence N-C*C, whereas the repeating set of a four atom sequences (N-C*C-N, C*-C-N-C*, and C-N-C...

  19. Mechanical processes with repeated attenuated impacts

    CERN Document Server

    Nagaev, R F

    1999-01-01

    This book is devoted to considering in the general case - using typical concrete examples - the motion of machines and mechanisms of impact and vibro-impact action accompanied by a peculiar phenomenon called "impact collapse". This phenomenon is that after the initial collision, a sequence of repeated gradually quickening collisions of decreasing-to-zero intensity occurs, with the final establishment of protracted contact between the interacting bodies. The initiation conditions of the impact collapse are determined and calculation techniques for the quantitative characteristics of the corresp

  20. Repeatability and validity of Zywave aberrometer measurements.

    Science.gov (United States)

    Hament, Willem J; Nabar, Vaisjaly A; Nuijts, Rudy M M A

    2002-12-01

    To study the repeatability of Zywave aberrometer (Bausch & Lomb) measurements and compare the measurements with those of subjective refraction and noncycloplegic and cycloplegic autorefractions in a clinical setting. Department of Ophthalmology, University Hospital Maastricht, Maastricht, The Netherlands. Subjective manifest refraction, noncycloplegic autorefraction, cycloplegic autorefraction, and Zywave aberrometer measurements were performed in 20 eyes of 20 myopic patients. Three consecutive Zywave measurements were performed with and without dilation of the pupil. The mean difference and 95% limits of agreement among the measurement methods were determined for dilated and 3.5 mm pupils. The repeatability coefficient of the Zywave aberrometer measurements was determined. The mean differences in spherical equivalent (SE), sphere, and cylinder between subjective refraction and Zywave predicted phoropter refraction (PPR) with a dilated pupil were -1.10 diopters (D) +/- 0.46 (SD) (P <.001), -1.08 +/- 0.44 D (P <.001), and -0.02 +/- 0.37 D (P =.87), respectively (paired Student t test). After the data were converted to a 3.5 mm pupil, the mean differences were -0.55 +/- 0.48 D (P <.001), -0.50 +/- 0.49 D (P <.001), and -0.16 +/- 0.50 D (P =.15), respectively. The mean difference in SE between autorefraction and cycloplegic autorefraction versus subjective refraction was +0.18 +/- 0.71 D (P =.27) and +0.35 +/- 0.62 D (P =.02), respectively. The mean difference in SE between cycloplegic autorefraction and Zywave PPR with a dilated pupil was -1.44 +/- 0.79 D (P <.001). The repeatability coefficient of Zywave PPR was +/-0.25 D for SE, +/-0.29 D for sphere, and +/-0.29 D for cylinder. Subjective refraction measurements are slightly more myopic than cycloplegic autorefraction measurements. With a dilated pupil, the Zywave measurements were significantly more myopic than subjective refractions and even more myopic than cycloplegic autorefractions. Zywave measurements and

  1. Childhood experiences and repeated suicidal behavior

    DEFF Research Database (Denmark)

    Krarup, Gertrud; Nielsen, Bent; Rask, P

    1991-01-01

    . It is commonly agreed that the experience in childhood of suicidal behavior among family members or other persons in the close environment is of importance in future suicidal risk. The results of this study indicate that the predictive value of this factor mainly applies to attempts with no fatal outcome...... that the psychological climate of the home may be more important than the rupture of early home life. It is noteworthy that the group of repeaters, as against the first-evers, could be characterized by personality disorders and abuse, especially of alcohol: disorders known to be precipitated by a discordant childhood...

  2. Adaptation and complexity in repeated games

    DEFF Research Database (Denmark)

    Maenner, Eliot Alexander

    2008-01-01

    The paper presents a learning model for two-player infinitely repeated games. In an inference step players construct minimally complex inferences of strategies based on observed play, and in an adaptation step players choose minimally complex best responses to an inference. When players randomly...... select an inference from a probability distribution with full support the set of steady states is a subset of the set of Nash equilibria in which only stage game Nash equilibria are played. When players make ‘cautious' inferences the set of steady states is the subset of self-confirming equilibria...

  3. Costly renegotiation in repeated Bertand games

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland

    2010-01-01

    This paper extends the concept of weak renegotiation-proof equilibrium (WRP) to allow for costly renegotiation and shows that even small renegotiation costs can have dramatic effects on the set of equilibria. More specifically, the paper analyzes the infinitely repeated Bertrand game. It is shown...... to the unique pure strategy WRP equilibrium without renegotiation costs, which implies marginal-cost pricing in every period. Moreover, in comparison to the findings of McCutcheon (1997), who states that renegotiation costs have to be substantial to facilitate collusion, this result points to a quite different...

  4. Repeated events and total time on test

    DEFF Research Database (Denmark)

    Kvist, Kajsa; Andersen, Per Kragh; Angst, Jules

    2008-01-01

    We adopt the total time on test procedure to investigate monotone time trends in the intensity in a repeated event setting. The correct model is assumed to be a proportional hazards model, with a random effect to account for dependence within subjects. The method offers a simple routine for testing...... relevant hypotheses for recurrent event processes, without making distributional assumptions about the frailty. Such assumptions may severely affect conclusions concerning regression coefficients and cause bias in the estimated heterogeneity. The method is illustrated by re-analyzing Danish registry data...

  5. Antimicrobial peptides interact with peptidoglycan

    Science.gov (United States)

    Neelay, Om P.; Peterson, Christian A.; Snavely, Mary E.; Brown, Taylor C.; TecleMariam, Ariam F.; Campbell, Jennifer A.; Blake, Allison M.; Schneider, Sydney C.; Cremeens, Matthew E.

    2017-10-01

    Traditional therapeutics are losing effectiveness as bacterial resistance increases, and antimicrobial peptides (AMPs) can serve as an alternative source for antimicrobial agents. Their mode of action is commonly hypothesized to involve pore formation in the lipid membrane, thereby leading to cell death. However, bacterial cell walls are much more complex than just the lipid membrane. A large portion of the wall is comprised of peptidoglycan, yet we did not find any report of AMP-peptidoglycan interactions. Consequently, this work evaluated AMP-peptidoglycan and AMP-phospholipid (multilamellar vesicles) interactions through tryptophan fluorescence. Given that peptidoglycan is insoluble and vesicles are large particles, we took advantage of the unique properties of Trp-fluorescence to use one technique for two very different systems. Interestingly, melittin and cecropin A interacted with peptidoglycan to a degree similar to vancomycin, a positive control. Whether these AMP-peptidoglycan interactions relate to a killing mode of action requires further study.

  6. Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides

    International Nuclear Information System (INIS)

    Vegt, Erik; Eek, Annemarie; Oyen, Wim J.G.; Gotthardt, Martin; Boerman, Otto C.; Jong, Marion de

    2010-01-01

    In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of radiolabelled peptides, such as positively charged amino acids, Gelofusine, or trypsinised albumin. The aim of this study was to identify more specific and potent inhibitors of the kidney reabsorption of radiolabelled peptides, based on albumin. Albumin was fragmented using cyanogen bromide and six albumin-derived peptides with different numbers of electric charges were selected and synthesised. The effect of albumin fragments (FRALB-C) and selected albumin-derived peptides on the internalisation of 111 In-albumin, 111 In-minigastrin, 111 In-exendin and 111 In-octreotide by megalin-expressing cells was assessed. In rats, the effect of Gelofusine and albumin-derived peptides on the renal uptake and biodistribution of 111 In-minigastrin, 111 In-exendin and 111 In-octreotide was determined. FRALB-C significantly reduced the uptake of all radiolabelled peptides in vitro. The albumin-derived peptides showed different potencies in reducing the uptake of 111 In-albumin, 111 In-exendin and 111 In-minigastrin in vitro. The most efficient albumin-derived peptide (peptide 6), was selected for in vivo testing. In rats, 5 mg of peptide 6 very efficiently inhibited the renal uptake of 111 In-minigastrin, by 88%. Uptake of 111 In-exendin and 111 In-octreotide was reduced by 26 and 33%, respectively. The albumin-derived peptide 6 efficiently inhibited the renal reabsorption of 111 In-minigastrin, 111 In-exendin and 111 In-octreotide and is a promising candidate for kidney protection in PRRT. (orig.)

  7. Cationic amphipathic peptides accumulate sialylated proteins and lipids in the plasma membrane of eukaryotic host cells.

    Science.gov (United States)

    Weghuber, Julian; Aichinger, Michael C; Brameshuber, Mario; Wieser, Stefan; Ruprecht, Verena; Plochberger, Birgit; Madl, Josef; Horner, Andreas; Reipert, Siegfried; Lohner, Karl; Henics, Tamás; Schütz, Gerhard J

    2011-10-01

    Cationic antimicrobial peptides (CAMPs) selectively target bacterial membranes by electrostatic interactions with negatively charged lipids. It turned out that for inhibition of microbial growth a high CAMP membrane concentration is required, which can be realized by the incorporation of hydrophobic groups within the peptide. Increasing hydrophobicity, however, reduces the CAMP selectivity for bacterial over eukaryotic host membranes, thereby causing the risk of detrimental side-effects. In this study we addressed how cationic amphipathic peptides-in particular a CAMP with Lysine-Leucine-Lysine repeats (termed KLK)-affect the localization and dynamics of molecules in eukaryotic membranes. We found KLK to selectively inhibit the endocytosis of a subgroup of membrane proteins and lipids by electrostatically interacting with negatively charged sialic acid moieties. Ultrastructural characterization revealed the formation of membrane invaginations representing fission or fusion intermediates, in which the sialylated proteins and lipids were immobilized. Experiments on structurally different cationic amphipathic peptides (KLK, 6-MO-LF11-322 and NK14-2) indicated a cooperation of electrostatic and hydrophobic forces that selectively arrest sialylated membrane constituents. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. A 31-residue peptide induces aggregation of tau's microtubule-binding region in cells

    Science.gov (United States)

    Stöhr, Jan; Wu, Haifan; Nick, Mimi; Wu, Yibing; Bhate, Manasi; Condello, Carlo; Johnson, Noah; Rodgers, Jeffrey; Lemmin, Thomas; Acharya, Srabasti; Becker, Julia; Robinson, Kathleen; Kelly, Mark J. S.; Gai, Feng; Stubbs, Gerald; Prusiner, Stanley B.; Degrado, William F.

    2017-09-01

    The self-propagation of misfolded conformations of tau underlies neurodegenerative diseases, including Alzheimer's. There is considerable interest in discovering the minimal sequence and active conformational nucleus that defines this self-propagating event. The microtubule-binding region, spanning residues 244-372, reproduces much of the aggregation behaviour of tau in cells and animal models. Further dissection of the amyloid-forming region to a hexapeptide from the third microtubule-binding repeat resulted in a peptide that rapidly forms fibrils in vitro. We show that this peptide lacks the ability to seed aggregation of tau244-372 in cells. However, as the hexapeptide is gradually extended to 31 residues, the peptides aggregate more slowly and gain potent activity to induce aggregation of tau244-372 in cells. X-ray fibre diffraction, hydrogen-deuterium exchange and solid-state NMR studies map the beta-forming region to a 25-residue sequence. Thus, the nucleus for self-propagating aggregation of tau244-372 in cells is packaged in a remarkably small peptide.

  9. Heteropoly acids triggered self-assembly of cationic peptides into photo- and electro-chromic gels.

    Science.gov (United States)

    Li, Jingfang; Xu, Jing; Li, Xiaodong; Gao, Wenmei; Wang, Liyan; Wu, Lixin; Lee, Myongsoo; Li, Wen

    2016-07-07

    A series of cationic peptides with alternating lysines and hydrophobic residues were designed and synthesized. These kinds of short peptides with protonated lysines can complex with anionic heteropoly acids (HPAs) to form a stable gel in water/ethanol mixed solution. Circular dichroism spectroscopy showed that the short peptides adopted a mixed conformation (β-sheet and random-coil) within the gel matrix. Scanning and transmission electron microscopy revealed that the heteropoly acids, acting as nanosized cross-linkers, first initiated the self-assembly of the cationic peptides into spherical nanostructures. Then these nanospheres accumulated with each other through hydrogen bonds and hydrophobic interactions to form large sheet-like assemblies, which further interconnected with each other forming continuous 3D network structures. Fourier-transform infrared spectroscopy showed that the structural integrity of the HPAs was maintained during the gelation process. The resultant hybrid gels showed reversible photo- and elecrtro-chromic properties. X-ray photoelectron spectroscopy revealed that the hybrid gels, capable of persistent and reversible changes of their colour, are attributed to the intervalence charge-transfer transition of the HPAs. Reversible information writing and erasing were demonstrated through a repeated photo-lithograph or electric stimuli without significant loss of the gel performance.

  10. Gene Therapy Vectors with Enhanced Transfection Based on Hydrogels Modified with Affinity Peptides

    Science.gov (United States)

    Shepard, Jaclyn A.; Wesson, Paul J.; Wang, Christine E.; Stevans, Alyson C.; Holland, Samantha J.; Shikanov, Ariella; Grzybowski, Bartosz A.; Shea, Lonnie D.

    2011-01-01

    Regenerative strategies for damaged tissue aim to present biochemical cues that recruit and direct progenitor cell migration and differentiation. Hydrogels capable of localized gene delivery are being developed to provide a support for tissue growth, and as a versatile method to induce the expression of inductive proteins; however, the duration, level, and localization of expression isoften insufficient for regeneration. We thus investigated the modification of hydrogels with affinity peptides to enhance vector retention and increase transfection within the matrix. PEG hydrogels were modified with lysine-based repeats (K4, K8), which retained approximately 25% more vector than control peptides. Transfection increased 5- to 15-fold with K8 and K4 respectively, over the RDG control peptide. K8- and K4-modified hydrogels bound similar quantities of vector, yet the vector dissociation rate was reduced for K8, suggesting excessive binding that limited transfection. These hydrogels were subsequently applied to an in vitro co-culture model to induce NGF expression and promote neurite outgrowth. K4-modified hydrogels promoted maximal neurite outgrowth, likely due to retention of both the vector and the NGF. Thus, hydrogels modified with affinity peptides enhanced vector retention and increased gene delivery, and these hydrogels may provide a versatile scaffold for numerous regenerative medicine applications. PMID:21514659

  11. Chromosome-specific DNA Repeat Probes

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.

    2006-03-16

    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  12. Repeated proton beam therapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hashimoto, Takayuki; Tokuuye, Koichi; Fukumitsu, Nobuyoshi; Igaki, Hiroshi; Hata, Masaharu; Kagei, Kenji; Sugahara, Shinji; Ohara, Kiyoshi; Matsuzaki, Yasushi; Akine, Yasuyuki

    2006-01-01

    Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A

  13. Aggregating quantum repeaters for the quantum internet

    Science.gov (United States)

    Azuma, Koji; Kato, Go

    2017-09-01

    The quantum internet holds promise for accomplishing quantum teleportation and unconditionally secure communication freely between arbitrary clients all over the globe, as well as the simulation of quantum many-body systems. For such a quantum internet protocol, a general fundamental upper bound on the obtainable entanglement or secret key has been derived [K. Azuma, A. Mizutani, and H.-K. Lo, Nat. Commun. 7, 13523 (2016), 10.1038/ncomms13523]. Here we consider its converse problem. In particular, we present a universal protocol constructible from any given quantum network, which is based on running quantum repeater schemes in parallel over the network. For arbitrary lossy optical channel networks, our protocol has no scaling gap with the upper bound, even based on existing quantum repeater schemes. In an asymptotic limit, our protocol works as an optimal entanglement or secret-key distribution over any quantum network composed of practical channels such as erasure channels, dephasing channels, bosonic quantum amplifier channels, and lossy optical channels.

  14. Repeatability of subjective and objective refraction.

    Science.gov (United States)

    Rosenfield, M; Chiu, N N

    1995-08-01

    Although several studies have examined the repeatability of objective refraction, data concerning the repeatability of subjective refraction under masked conditions, i.e., where the examiner is unaware of the refractive results, are limited. Accordingly, the present study compared the variability of both subjective and objective refractive techniques. Refractive error was measured in 12 subjects on 5 separate occasions. Conventional subjective procedures were used, with the exception that the sphere power scale on the phoropter was covered so that the examiner was unaware of the final result. Objective measurements were obtained using a Canon Autoref R-1 infrared autorefractor. The standard deviation (SD) of the five examinations was calculated for each individual and the mean values for the population sample determined. The mean SD's for the subjective and objective techniques were +/- 0.14 and +/- 0.18 D, indicating 95% confidence limits of +/- 0.27 and +/- 0.35 D, respectively. It is concluded that with either assessment technique, a change in refractive error of at least +/- 0.50 D should be adopted as the minimum significant shift in refractive status.

  15. Repeatable assessment protocol for electromagnetic trackers

    Science.gov (United States)

    Haidegger, Tamas; Sirokai, Beáta; Fenyvesi, Gábor; Kovács, Levente; Benyó, Balázs; Benyó, Zoltán

    2012-02-01

    In the past decades, many new trends appeared in interventional medicine. One of the most groundbreaking ones is Image-Guided Surgery (IGS). The main benefit of IGS procedures is the reduction of the patient's pain and collateral damage through improved accuracy and targeting. Electromagnetic Tracking (EMT) has been introduced to medical applications as an effective tool for navigation. However, magnetic fields can be severely distorted by ferromagnetic materials and electronic equipment, which is a major barrier towards their wider application. The focus of the study is to determine and compensate the inherent errors of the different types of EMTs, in order to improve their accuracy. Our aim is to develop a standardized, simple and repeatable assessment protocol; to determine tracking errors with sub-millimeter accuracy, hence increasing the measurement precision and reliability. For initial experiments, the NDI Aurora and the Ascension medSAFE systems were used in a standard laboratory environment. We aim to advance to the state-of-the art by describing and disseminating an easily reproducible calibration method, publishing the CAD files of the accuracy phantom and the source of the evaluation data. This should allow the wider spread of the technique, and eventually lead to the repeatable and comparable assessment of EMT systems.

  16. TERRA: telomeric repeat-containing RNA.

    Science.gov (United States)

    Luke, Brian; Lingner, Joachim

    2009-09-02

    Telomeres, the physical ends of eukaryotic chromosomes, consist of tandem arrays of short DNA repeats and a large set of specialized proteins. A recent analysis has identified telomeric repeat-containing RNA (TERRA), a large non-coding RNA in animals and fungi, which forms an integral component of telomeric heterochromatin. TERRA transcription occurs at most or all chromosome ends and it is regulated by RNA surveillance factors and in response to changes in telomere length. TERRA functions that are emerging suggest important roles in the regulation of telomerase and in orchestrating chromatin remodelling throughout development and cellular differentiation. The accumulation of TERRA at telomeres can also interfere with telomere replication, leading to a sudden loss of telomere tracts. Such a phenotype can be observed upon impairment of the RNA surveillance machinery or in cells from ICF (Immunodeficiency, Centromeric region instability, Facial anomalies) patients, in which TERRA is upregulated because of DNA methylation defects in the subtelomeric region. Thus, TERRA may mediate several crucial functions at the telomeres, a region of the genome that had been considered to be transcriptionally silent.

  17. Extending Teach and Repeat to Pivoting Wheelchairs

    Directory of Open Access Journals (Sweden)

    Guillermo Del Castillo

    2003-02-01

    Full Text Available The paper extends the teach-and-repeat paradigm that has been successful for the control of holonomic robots to nonholonomic wheelchairs which may undergo pivoting action over the course of their taught movement. Due to the nonholonomic nature of the vehicle kinematics, estimation is required -- in the example given herein, based upon video detection of wall-mounted cues -- both in the teaching and the tracking events. In order to accommodate motion that approaches pivoting action as well as motion that approaches straight-line action, the estimation equations of the Extended Kalman Filter and the control equations are formulated using two different definitions of a nontemporal independent variable. The paper motivates the need for pivoting action in real-life settings by reporting extensively on the abilities and limitations of estimation-based teach-and-repeat action where pivoting and near-pivoting action is disallowed. Following formulation of the equations in the near-pivot mode, the paper reports upon experiments where taught trajectories which entail a seamless mix of near-straight and near-pivot action are tracked.

  18. Designing Antibacterial Peptides with Enhanced Killing Kinetics

    Directory of Open Access Journals (Sweden)

    Faiza H. Waghu

    2018-02-01

    Full Text Available Antimicrobial peptides (AMPs are gaining attention as substitutes for antibiotics in order to combat the risk posed by multi-drug resistant pathogens. Several research groups are engaged in design of potent anti-infective agents using natural AMPs as templates. In this study, a library of peptides with high sequence similarity to Myeloid Antimicrobial Peptide (MAP family were screened using popular online prediction algorithms. These peptide variants were designed in a manner to retain the conserved residues within the MAP family. The prediction algorithms were found to effectively classify peptides based on their antimicrobial nature. In order to improve the activity of the identified peptides, molecular dynamics (MD simulations, using bilayer and micellar systems could be used to design and predict effect of residue substitution on membranes of microbial and mammalian cells. The inference from MD simulation studies well corroborated with the wet-lab observations indicating that MD-guided rational design could lead to discovery of potent AMPs. The effect of the residue substitution on membrane activity was studied in greater detail using killing kinetic analysis. Killing kinetics studies on Gram-positive, negative and human erythrocytes indicated that a single residue change has a drastic effect on the potency of AMPs. An interesting outcome was a switch from monophasic to biphasic death rate constant of Staphylococcus aureus due to a single residue mutation in the peptide.

  19. Synthetic multivalent antifungal peptides effective against fungi.

    Directory of Open Access Journals (Sweden)

    Rajamani Lakshminarayanan

    Full Text Available Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010 which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. B4010 displayed better antifungal properties than natamycin and amphotericin B. The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg or intravenous (100 mg/kg routes. S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides.

  20. Bioactive Peptides: Applications and Relevance for Cosmeceuticals

    Directory of Open Access Journals (Sweden)

    Tamyres Nassa Lima

    2018-03-01

    Full Text Available Peptides found in skin can act by different mechanisms of action, being able to function as epidermal or nervous growth factors or even as neurotransmitters. Due to the vast functionality of these compounds, there is growing research on bioactive peptides aimed at investigating their uses in products developed for stimulating collagen and elastin synthesis and improving skin healing. Thus, a literature search on applications of the most common bioactive peptides used in cosmeceuticals was carried out. There is a lack of proper reviews concerning this topic in scientific literature. Nine peptides with specific actions on body and facial dysfunctions were described. It could be noted while searching scientific literature that studies aimed at investigating peptides which prevent aging of the skin are overrepresented. This makes searching for peptides designed for treating other skin dysfunctions more difficult. The use of biomimetic peptides in cosmetic formulations aimed at attenuating or preventing different types of skin dysfunctions is a topic where information is still lackluster. Even though research on these compounds is relatively common, there is still a need for more studies concerning their practical uses so their mechanisms of action can be fully elucidated, as they tend to be quite complex.

  1. Safety of multiple repeated cycles of 177Lu-octreotate in patients with recurrent neuroendocrine tumour

    International Nuclear Information System (INIS)

    Yordanova, Anna; Essler, Markus; Ahmadzadehfar, Hojjat; Mayer, Karin; Brossart, Peter; Gonzalez-Carmona, Maria A.; Strassburg, Christian P.

    2017-01-01

    Peptide receptor radionuclide therapy (PRRT) is an effective therapy in patients with a somatostatin receptor-positive neuroendocrine tumour (NET). Still unclear is how many cycles of 177 Lu-octreotate can be repeated while maintaining an acceptable toxicity profile. The purpose of this study was to assess the safety of repeated PRRT in patients with recurrent NET. We retrospectively evaluated data from 15 patients treated with repeated PRRT between 2004 and 2015. The median administered activity was 63.8 GBq (range 52-96.6 GBq) in a median of 9 cycles (range 8-13 cycles). Nonhaematological and haematological toxicities were assessed from clinical reports and laboratory data. The rates of adverse events in three therapy groups were compared: during cycles 1 to 4, cycles 5 to 8, and cycles 9 to 13. Baseline laboratory assessments were also compared with data obtained at the end of treatment. The overall survival in the study patients was compared with survival data in patients who received only a baseline PRRT of three or four cycles. We observed no life-threatening adverse events (CTC-4) during 177 Lu-octreotate treatment. Reversible haematological toxicity (CTC-3) occurred in two patients (13%). No CTC-3/4 nephrotoxicity was recorded. More CTC-3 adverse events were recorded in the first therapy group than in the other two groups. Furthermore, there were no significant changes in the mean values of thrombocytes, leucocytes and serum creatinine before and after therapy. However, the mean haemoglobin levels fell from 14 g/dL to 11 g/dL. Finally, compared with those patients who received three or four cycles, there was a survival benefit in patients treated with repeated PRRT (censored overall survival 85.6 vs. 69.7 months, p < 0.001). Therapy with eight or more cycles of 177 Lu-octreotate was well tolerated and led to a survival benefit in patients with recurrent NET. (orig.)

  2. Floral organ abscission peptide IDA and its HAE/HSL2 receptors control cell separation during lateral root emergence

    OpenAIRE

    Kumpf, Robert P.; Shi, Chun-Lin; Larrieu, Antoine; Stø, Ida Myhrer; Butenko, Melinka A.; Péret, Benjamin; Riiser, Even Sannes; Bennett, Malcolm J.; Aalen, Reidunn B.

    2013-01-01

    Throughout their life cycle, plants produce new organs, such as leaves, flowers, and lateral roots. Organs that have served their purpose may be shed after breakdown of primary cell walls between adjacent cell files at the site of detachment. In Arabidopsis, floral organs abscise after pollination, and this cell separation event is controlled by the peptide INFLORESCENCE DEFICIENT IN ABSCISSION (IDA), which signals through the leucine-rich repeat receptor-like kinases HAESA (HAE) and HAESA-LI...

  3. Fourier transform infrared spectroscopy of peptides.

    Science.gov (United States)

    Bakshi, Kunal; Liyanage, Mangala R; Volkin, David B; Middaugh, C Russell

    2014-01-01

    Fourier transform infrared (FTIR) spectroscopy provides data that are widely used for secondary structure characterization of peptides. A wide array of available sampling methods permits structural analysis of peptides in diverse environments such as aqueous solution (including optically turbid media), powders, detergent micelles, and lipid bilayers. In some cases, side chain vibrations can also be resolved and used for tertiary structure and chemical analysis. Data from several low-resolution spectroscopic techniques, including FTIR, can be combined to generate an empirical phase diagram, an overall picture of peptide structure as a function of environmental conditions that can aid in the global interpretation of large amounts of spectroscopic data.

  4. Cysteine-containing peptides having antioxidant properties

    Science.gov (United States)

    Bielicki, John K [Castro Valley, CA

    2008-10-21

    Cysteine containing amphipathic alpha helices of the exchangeable apolipoproteins, as exemplified by apolipoprotein (apo) A-I.sub.Milano (R173C) and apoA-I.sub.Paris, (R151C) were found to exhibit potent antioxidant activity on phospholipid surfaces. The addition of a free thiol, at the hydrophobic/hydrophilic interface of an amphipathic alpha helix of synthetic peptides that mimic HDL-related proteins, imparts a unique antioxidant activity to these peptides which inhibits lipid peroxidation and protects phospholipids from water-soluble free radical initiators. These peptides can be used as therapeutic agents to combat cardiovascular disease, ischemia, bone disease and other inflammatory related diseases.

  5. SICLOPPS cyclic peptide libraries in drug discovery.

    Science.gov (United States)

    Tavassoli, Ali

    2017-06-01

    Cyclic peptide libraries have demonstrated significant potential when employed against challenging targets such as protein-protein interactions. While a variety of methods for library generation exist, genetically encoded libraries hold several advantages over their chemically synthesized counterparts; they are more readily accessible and allow straightforward hit deconvolution. One method for the intracellular generation of such libraries is split-intein circular ligation of peptides and proteins (SICLOPPS). Here we detail and discuss the deployment of SICLOPPS libraries for the identification of cyclic peptide inhibitors of a variety of targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The absolute number of repeat operations for complex intra ...

    African Journals Online (AJOL)

    abdominal sepsis, questions about futility of treatment frequently arise. This study focuses specifically on patients who required two or more repeat laparotomies and describes the spectrum of disease necessitating multiple repeat laparotomies ...

  7. Methods for analysing cardiovascular studies with repeated measures

    NARCIS (Netherlands)

    Cleophas, T. J.; Zwinderman, A. H.; van Ouwerkerk, B. M.

    2009-01-01

    Background. Repeated measurements in a single subject are generally more similar than unrepeated measurements in different subjects. Unrepeated analyses of repeated data cause underestimation of the treatment effects. Objective. To review methods adequate for the analysis of cardiovascular studies

  8. Simultaneous determination of heat stable peptides for eight animal and plant species in meat products using UPLC-MS/MS method.

    Science.gov (United States)

    Li, Yingying; Zhang, Yingying; Li, Huichen; Zhao, Wentao; Guo, Wenping; Wang, Shouwei

    2018-04-15

    Food adulteration and fraud is driven by economic interests; it is thus necessary to establish a high-through method that allows quantitative identification of familiar animal and plant proteins for global use. In this study, a sensitive mass spectrometric approach for the detection of eight species, including pork, beef, lamb, chicken, duck, soy, peanut, and pea, is presented and the heat stability and specificity of screened peptides are verified. To improve screening efficiency of specific peptides, several key data searching parameters, including peptides, sequence lengths, sequence coverage, and unique peptides, are investigated. Using this approach, it is possible to detect a 0.5% contamination of any of the eight species. The method is proven to have high sensitivity, specificity, repeatability, and a low quantitative detection limit with respect to adulteration of diverse types of meat products. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Isolation of an antifreeze peptide from the Antarctic sponge Homaxinella balfourensis.

    Science.gov (United States)

    Wilkins, S P; Blum, A J; Burkepile, D E; Rutland, T J; Wierzbicki, A; Kelly, M; Hamann, M T

    2002-12-01

    Polar plants and animals survive in subzero waters (-2 degrees C) and many of these marine organisms produce antifreeze proteins (AFPs) to better adapt themselves to these conditions. AFPs prevent the growth of ice crystals which disrupt cellular membranes and destroy cells by inhibiting crystallization of water within the organism. The hydrophilic extract of an Antarctic sponge Homaxinella balfourensis exhibited a non-colligative freezing point depression effect on the crystal morphology of water. The extract was purified by repeated reverse phase high-pressure liquid chromatography, then assayed and shown to contain several AFPs. The major peptide was isolated, analyzed using matrix-assisted laser desorption ionization mass spectrometry and the partial structure of the peptide identified through amino acid sequencing. AFPs have potential applications in agriculture, medicine and the food industry.

  10. The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

    Science.gov (United States)

    Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J.; Telenti, Amalio; de Bakker, Paul I.W.; Walker, Bruce D.; Jia, Xiaoming; McLaren, Paul J.; Ripke, Stephan; Brumme, Chanson J.; Pulit, Sara L.; Telenti, Amalio; Carrington, Mary; Kadie, Carl M.; Carlson, Jonathan M.; Heckerman, David; de Bakker, Paul I.W.; Pereyra, Florencia; de Bakker, Paul I.W.; Graham, Robert R.; Plenge, Robert M.; Deeks, Steven G.; Walker, Bruce D.; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M.; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P.; Guiducci, Candace; Gupta, Namrata; Carrington, Mary; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Pereyra, Florencia; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L.; Lemay, Paul; O’Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L.; Vine, Seanna; Addo, Marylyn M.; Allen, Todd M.; Altfeld, Marcus; Henn, Matthew R.; Le Gall, Sylvie; Streeck, Hendrik; Walker, Bruce D.; Haas, David W.; Kuritzkes, Daniel R.; Robbins, Gregory K.; Shafer, Robert W.; Gulick, Roy M.; Shikuma, Cecilia M.; Haubrich, Richard; Riddler, Sharon; Sax, Paul E.; Daar, Eric S.; Ribaudo, Heather J.; Agan, Brian; Agarwal, Shanu; Ahern, Richard L.; Allen, Brady L.; Altidor, Sherly; Altschuler, Eric L.; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J.; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C.; Benson, Anne M.; Berger, Judith; Bernard, Nicole F.; Bernard, Annette M.; Birch, Christopher; Bodner, Stanley J.; Bolan, Robert K.; Boudreaux, Emilie T.; Bradley, Meg; Braun, James F.; Brndjar, Jon E.; Brown, Stephen J.; Brown, Katherine; Brown, Sheldon T.; Burack, Jedidiah; Bush, Larry M.; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H.; Carmichael, J. Kevin; Casey, Kathleen K.; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T.; Chez, Nancy; Chirch, Lisa M.; Cimoch, Paul J.; Cohen, Daniel; Cohn, Lillian E.; Conway, Brian; Cooper, David A.; Cornelson, Brian; Cox, David T.; Cristofano, Michael V.; Cuchural, George; Czartoski, Julie L.; Dahman, Joseph M.; Daly, Jennifer S.; Davis, Benjamin T.; Davis, Kristine; Davod, Sheila M.; Deeks, Steven G.; DeJesus, Edwin; Dietz, Craig A.; Dunham, Eleanor; Dunn, Michael E.; Ellerin, Todd B.; Eron, Joseph J.; Fangman, John J.W.; Farel, Claire E.; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A.; French, Neel K.; Fuchs, Jonathan D.; Fuller, Jon D.; Gaberman, Jonna; Gallant, Joel E.; Gandhi, Rajesh T.; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C.; Gaultier, Cyril R.; Gebre, Wondwoosen; Gilman, Frank D.; Gilson, Ian; Goepfert, Paul A.; Gottlieb, Michael S.; Goulston, Claudia; Groger, Richard K.; Gurley, T. Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W. David; Harrigan, P. Richard; Hawkins, Trevor N.; Heath, Sonya; Hecht, Frederick M.; Henry, W. Keith; Hladek, Melissa; Hoffman, Robert P.; Horton, James M.; Hsu, Ricky K.; Huhn, Gregory D.; Hunt, Peter; Hupert, Mark J.; Illeman, Mark L.; Jaeger, Hans; Jellinger, Robert M.; John, Mina; Johnson, Jennifer A.; Johnson, Kristin L.; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C.; Kauffman, Carol A.; Khanlou, Homayoon; Killian, Robert K.; Kim, Arthur Y.; Kim, David D.; Kinder, Clifford A.; Kirchner, Jeffrey T.; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P. Todd; Kurisu, Wayne; Kwon, Douglas S.; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M.; Lee, David M.; Lee, Jean M.L.; Lee, Marah J.; Lee, Edward T.Y.; Lemoine, Janice; Levy, Jay A.; Llibre, Josep M.; Liguori, Michael A.; Little, Susan J.; Liu, Anne Y.; Lopez, Alvaro J.; Loutfy, Mono R.; Loy, Dawn; Mohammed, Debbie Y.; Man, Alan; Mansour, Michael K.; Marconi, Vincent C.; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N.; Martin, Harold L.; Mayer, Kenneth Hugh; McElrath, M. Juliana; McGhee, Theresa A.; McGovern, Barbara H.; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X.; Menezes, Prema; Mesa, Greg; Metroka, Craig E.; Meyer-Olson, Dirk; Miller, Andy O.; Montgomery, Kate; Mounzer, Karam C.; Nagami, Ellen H.; Nagin, Iris; Nahass, Ronald G.; Nelson, Margret O.; Nielsen, Craig; Norene, David L.; O’Connor, David H.; Ojikutu, Bisola O.; Okulicz, Jason; Oladehin, Olakunle O.; Oldfield, Edward C.; Olender, Susan A.; Ostrowski, Mario; Owen, William F.; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M.; Perlmutter, Aaron M.; Pierce, Michael N.; Pincus, Jonathan M.; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C.; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J.; Rhame, Frank S.; Richards, Constance Shamuyarira; Richman, Douglas D.; Robbins, Gregory K.; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C.; Rosenberg, Eric S.; Rosenthal, Daniel; Ross, Polly E.; Rubin, David S.; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R.; Sanchez, William C.; Sanjana, Veeraf M.; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M.; Shalit, Peter; Shay, William; Shirvani, Vivian N.; Silebi, Vanessa I.; Sizemore, James M.; Skolnik, Paul R.; Sokol-Anderson, Marcia; Sosman, James M.; Stabile, Paul; Stapleton, Jack T.; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F. Lisa; Stone, Valerie E.; Stone, David R.; Tambussi, Giuseppe; Taplitz, Randy A.; Tedaldi, Ellen M.; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A.; Trinh, Phuong D.; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J.; Vecino, Isabel; Vega, Vilma M.; Veikley, Wenoah; Wade, Barbara H.; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J.; Warner, Daniel A.; Weber, Robert D.; Webster, Duncan; Weis, Steve; Wheeler, David A.; White, David J.; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G.; Wout, Angelique van’t; Wright, David P.; Yang, Otto O.; Yurdin, David L.; Zabukovic, Brandon W.; Zachary, Kimon C.; Zeeman, Beth; Zhao, Meng

    2011-01-01

    Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection. PMID:21051598

  11. SUMO mediating fusion expression of antimicrobial peptide CM4 from two joined genes in Escherichia coli.

    Science.gov (United States)

    Li, Jian Feng; Zhang, Jie; Zhang, Zhen; Kang, Chun Tao; Zhang, Shuang Quan

    2011-01-01

    Antibacterial peptide CM4 (ABP-CM4) is a small cationic peptide with broad-spectrum activities against bacteria, fungi, and tumor cells, which may possibly be used as an antimicrobial agent. To improve the expression level of CM4 in Escherichia coli, two tandem repeats of CM4 genes were cloned into the vector pSUMO to construct an expression vector pSUMO-2CM4. The fusion protein SUMO-2CM4, purified by Ni(2+)-chelating chromatography, was cleaved by hydroxylamine hydrochloride to release recombinant CM4. After the cleaved sample was re-applied to a Ni-IDA column, finally, about 48 mg recombinant CM4 was obtained from 1 L bacterial culture with no less than 96% purity, which was the highest yield of CM4 reported so far.

  12. Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Verardi, Raffaello; Kim, Jin-Sik; Ghirlando, Rodolfo; Banerjee, Anirban

    2017-09-01

    DHHC enzymes catalyze palmitoylation, a major post-translational modification that regulates a number of key cellular processes. There are up to 24 DHHCs in mammals and hundreds of substrate proteins that get palmitoylated. However, how DHHC enzymes engage with their substrates is still poorly understood. There is currently no structural information about the interaction between any DHHC enzyme and protein substrates. In this study we have investigated the structural and thermodynamic bases of interaction between the ankyrin repeat domain of human DHHC17 (ANK17) and Snap25b. We solved a high-resolution crystal structure of the complex between ANK17 and a peptide fragment of Snap25b. Through structure-guided mutagenesis, we discovered key residues in DHHC17 that are critically important for interaction with Snap25b. We further extended our finding by showing that the same residues are also crucial for the interaction of DHHC17 with Huntingtin, one of its most physiologically relevant substrates.

  13. Non-Radioactive Detection of Trinucleotide Repeat Size Variability

    OpenAIRE

    Tomé, Stéphanie; Nicole, Annie; Gomes-Pereira, Mario; Gourdon, Genevieve

    2014-01-01

    Many human diseases are associated with the abnormal expansion of unstable trinucleotide repeat sequences. The mechanisms of trinucleotide repeat size mutation have not been fully dissected, and their understanding must be grounded on the detailed analysis of repeat size distributions in human tissues and animal models. Small-pool PCR (SP-PCR) is a robust, highly sensitive and efficient PCR-based approach to assess the levels of repeat size variation, providing both quantitative and qualitati...

  14. Peptide-MHC class I stability is a stronger predictor of CTL immunogenicity than peptide affinity

    DEFF Research Database (Denmark)

    Harndahl, Mikkel Nors; Rasmussen, Michael; Nielsen, Morten

    2012-01-01

    of antigen processing and presentation in defining cytotoxic T lymphocyte (CTL) immunogenicity Assarsson et al., 2007. Using an affinity-balanced approach, we demonstrated that immunogenic peptides tend to be more stably bound to MHC-I molecules compared with non-immunogenic peptides. We also developed......Peptide-MHC class I stability is a stronger predictor of CTL immunogenicity than peptide affinity Mikkel Harndahla, Michael Rasmussena, Morten Nielsenb, Soren Buusa,∗ a Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, Denmark b Center for Biological...... Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Denmark Efficient presentation of peptide-MHC class I (pMHC-I) complexes to immune T cells should benefit from a stable peptide- MHC-I interaction. However, it has been difficult to distinguish stability from other...

  15. Novel expressed sequence tag- simple sequence repeats (EST ...

    African Journals Online (AJOL)

    Using different bioinformatic criteria, the SUCEST database was used to mine for simple sequence repeat (SSR) markers. Among 42,189 clusters, 1,425 expressed sequence tag- simple sequence repeats (EST-SSRs) were identified in silico. Trinucleotide repeats were the most abundant SSRs detected. Of 212 primer pairs ...

  16. Multimerized HIV-gp41-derived peptides as fusion inhibitors and vaccines.

    Science.gov (United States)

    Nomura, Wataru; Mizuguchi, Takaaki; Tamamura, Hirokazu

    2016-11-04

    To date, several antigens based on the amino-terminal leucine/isoleucine heptad repeat (NHR) region of an HIV-1 envelope protein gp41 and fusion inhibitors based on the carboxy-terminal leucine/isoleucine heptad repeat (CHR) region of gp41 have been reported. We have developed a synthetic antigen targeting the membrane-fusion mechanism of HIV-1. This uses a template designed with C3-symmetric linkers and mimics the trimeric form of the NHR-derived peptide N36. The antiserum obtained by immunization of the N36 trimeric antigen binds preferentially to the N36 trimer and blocks HIV-1 infection effectively, compared with the antiserum obtained by immunization of the N36 monomer. Using another template designed with different C3-symmetric linkers, we have also developed a synthetic peptide mimicking the trimeric form of the CHR-derived peptide C34, with ∼100 times the inhibitory activity against the HIV-1 fusion mechanism than that of the monomer C34 peptide. A dimeric derivative of C34 has potent inhibitory activity at almost the same levels as this C34 trimer mimic, suggesting that presence of a dimeric form of C34 is structurally critical for fusion inhibitors. As examples of rising mid-size drugs, this review describes an effective strategy for the design of HIV vaccines and fusion inhibitors based on a relationship with the native structure of proteins involved in HIV fusion mechanisms. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 622-628, 2016. © 2015 Wiley Periodicals, Inc.

  17. Constitutive expression of transgenes encoding derivatives of the synthetic antimicrobial peptide BP100: impact on rice host plant fitness.

    Science.gov (United States)

    Nadal, Anna; Montero, Maria; Company, Nuri; Badosa, Esther; Messeguer, Joaquima; Montesinos, Laura; Montesinos, Emilio; Pla, Maria

    2012-09-04

    The Biopeptide BP100 is a synthetic and strongly cationic α-helical undecapeptide with high, specific antibacterial activity against economically important plant-pathogenic bacteria, and very low toxicity. It was selected from a library of synthetic peptides, along with other peptides with activities against relevant bacterial and fungal species. Expression of the BP100 series of peptides in plants is of major interest to establish disease-resistant plants and facilitate molecular farming. Specific challenges were the small length, peptide degradation by plant proteases and toxicity to the host plant. Here we approached the expression of the BP100 peptide series in plants using BP100 as a proof-of-concept. Our design considered up to three tandemly arranged BP100 units and peptide accumulation in the endoplasmic reticulum (ER), analyzing five BP100 derivatives. The ER retention sequence did not reduce the antimicrobial activity of chemically synthesized BP100 derivatives, making this strategy possible. Transformation with sequences encoding BP100 derivatives (bp100der) was over ten-fold less efficient than that of the hygromycin phosphotransferase (hptII) transgene. The BP100 direct tandems did not show higher antimicrobial activity than BP100, and genetically modified (GM) plants constitutively expressing them were not viable. In contrast, inverted repeats of BP100, whether or not elongated with a portion of a natural antimicrobial peptide (AMP), had higher antimicrobial activity, and fertile GM rice lines constitutively expressing bp100der were produced. These GM lines had increased resistance to the pathogens Dickeya chrysanthemi and Fusarium verticillioides, and tolerance to oxidative stress, with agronomic performance comparable to untransformed lines. Constitutive expression of transgenes encoding short cationic α-helical synthetic peptides can have a strong negative impact on rice fitness. However, GM plants expressing, for example, BP100 based on inverted

  18. Constitutive expression of transgenes encoding derivatives of the synthetic antimicrobial peptide BP100: impact on rice host plant fitness

    Directory of Open Access Journals (Sweden)

    Nadal Anna

    2012-09-01

    Full Text Available Abstract Background The Biopeptide BP100 is a synthetic and strongly cationic α-helical undecapeptide with high, specific antibacterial activity against economically important plant-pathogenic bacteria, and very low toxicity. It was selected from a library of synthetic peptides, along with other peptides with activities against relevant bacterial and fungal species. Expression of the BP100 series of peptides in plants is of major interest to establish disease-resistant plants and facilitate molecular farming. Specific challenges were the small length, peptide degradation by plant proteases and toxicity to the host plant. Here we approached the expression of the BP100 peptide series in plants using BP100 as a proof-of-concept. Results Our design considered up to three tandemly arranged BP100 units and peptide accumulation in the endoplasmic reticulum (ER, analyzing five BP100 derivatives. The ER retention sequence did not reduce the antimicrobial activity of chemically synthesized BP100 derivatives, making this strategy possible. Transformation with sequences encoding BP100 derivatives (bp100der was over ten-fold less efficient than that of the hygromycin phosphotransferase (hptII transgene. The BP100 direct tandems did not show higher antimicrobial activity than BP100, and genetically modified (GM plants constitutively expressing them were not viable. In contrast, inverted repeats of BP100, whether or not elongated with a portion of a natural antimicrobial peptide (AMP, had higher antimicrobial activity, and fertile GM rice lines constitutively expressing bp100der were produced. These GM lines had increased resistance to the pathogens Dickeya chrysanthemi and Fusarium verticillioides, and tolerance to oxidative stress, with agronomic performance comparable to untransformed lines. Conclusions Constitutive expression of transgenes encoding short cationic α-helical synthetic peptides can have a strong negative impact on rice fitness. However, GM

  19. A genomic view of short tandem repeats.

    Science.gov (United States)

    Gymrek, Melissa

    2017-06-01

    Short tandem repeats (STRs) are some of the fastest mutating loci in the genome. Tools for accurately profiling STRs from high-throughput sequencing data have enabled genome-wide interrogation of more than a million STRs across hundreds of individuals. These catalogs have revealed that STRs are highly multiallelic and may contribute more de novo mutations than any other variant class. Recent studies have leveraged these catalogs to show that STRs play a widespread role in regulating gene expression and other molecular phenotypes. These analyses suggest that STRs are an underappreciated but rich reservoir of variation that likely make significant contributions to Mendelian diseases, complex traits, and cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Quantum repeaters using continuous-variable teleportation

    Science.gov (United States)

    Dias, Josephine; Ralph, T. C.

    2017-02-01

    Quantum optical states are fragile and can become corrupted when passed through a lossy communication channel. Unlike for classical signals, optical amplifiers cannot be used to recover quantum signals. Quantum repeaters have been proposed as a way of reducing errors and hence increasing the range of quantum communications. Current protocols target specific discrete encodings, for example quantum bits encoded on the polarization of single photons. We introduce a more general approach that can reduce the effect of loss on any quantum optical encoding, including those based on continuous variables such as the field amplitudes. We show that in principle the protocol incurs a resource cost that scales polynomially with distance. We analyze the simplest implementation and find that while its range is limited it can still achieve useful improvements in the distance over which quantum entanglement of field amplitudes can be distributed.

  1. Substrate Capture Assay Using Inactive Oligopeptidases to Identify Novel Peptides.

    Science.gov (United States)

    Rioli, Vanessa; Ferro, Emer S

    2018-01-01

    Researchers are always searching for novel biologically active molecules including peptides. With the improvement of equipment for electrospray mass spectrometry, it is now possible to identify hundreds of novel peptides in a single run. However, after identifying the peptide sequences it is expensive to synthesize all the peptides to perform biological activity assays. Here, we describe a substrate capture assay that uses inactive oligopeptidases to identify putative biologically active peptides in complexes peptide mixtures. This methodology can use any crude extracts of biological tissues or cells, with the advantage to introduce a filter (i.e., binding to an inactive oligopeptidase) as a prior step in screening to bioactive peptides.

  2. THE EFFECTS OF ACHETA DIURETIC PEPTIDE ON ISOLATED MALPIGHIAN TUBULES FROM THE HOUSE CRICKET ACHETA DOMESTICUS

    Science.gov (United States)

    Coast; Kay

    1994-02-01

    Acheta diuretic peptide (Acheta-DP) is a corticotropin-releasing factor (CRF)-related peptide found in head extracts of the house cricket Acheta domesticus. The peptide causes a dose-dependent increase in fluid secretion by cricket Malpighian tubules isolated in vitro, and the apparent EC50 is 1.3 nmol l-1, which is within the physiological range for a peptide hormone. The CRF antagonist alpha-helical CRF(9-41) blocks the action of Acheta-DP in a dose-dependent manner, and the IC50 is estimated to be in the micromolar range. Addition of Acheta-DP to isolated Malpighian tubules is followed by a rapid and marked increase in the level of intracellular cyclic AMP. This precedes any change in voltage or fluid secretion, which strongly suggests that cyclic AMP is the intracellular mediator of Acheta-DP activity. Consistent with this, diuretic activity is potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, and there is a close relationship between the dose­response curves for cyclic AMP production and for fluid secretion. However, exogenous 8-bromo-cyclic AMP does not mimic all the effects of Acheta-DP, and the peptide may have a dual action on isolated tubules. Fluid secretion by tubules dosed repeatedly with Acheta-DP returns to near basal levels after 3­5 h. This cannot be explained by degradation of the peptide, but might be due in part to oxygen and/or metabolite deficiency. However, tubules that are refractory to Acheta-DP can be stimulated by forskolin, 8-bromo-cyclic AMP and extracts of corpora cardiaca, which is indicative of a homologous desensitization of membrane receptors for the diuretic peptide. Differences in the rate of secretion by morphologically distinct regions of cricket Malpighian tubules have been assessed. In unstimulated tubules, the rate of secretion per unit length by the short distal segment is about twice that of the main tubule. However, diuretic peptides (Acheta-DP and achetakinin-I) have little effect on distal

  3. Evolution of Antimicrobial Peptides to Self-Assembled Peptides for Biomaterial Applications

    Directory of Open Access Journals (Sweden)

    Alice P. McCloskey

    2014-10-01

    Full Text Available Biomaterial-related infections are a persistent burden on patient health, recovery, mortality and healthcare budgets. Self-assembled antimicrobial peptides have evolved from the area of antimicrobial peptides. Peptides serve as important weapons in nature, and increasingly medicine, for combating microbial infection and biofilms. Self-assembled peptides harness a “bottom-up” approach, whereby the primary peptide sequence may be modified with natural and unnatural amino acids to produce an inherently antimicrobial hydrogel. Gelation may be tailored to occur in the presence of physiological and infective indicators (e.g. pH, enzymes and therefore allow local, targeted antimicrobial therapy at the site of infection. Peptides demonstrate inherent biocompatibility, antimicrobial activity, biodegradability and numerous functional groups. They are therefore prime candidates for the production of polymeric molecules that have the potential to be conjugated to biomaterials with precision. Non-native chemistries and functional groups are easily incorporated into the peptide backbone allowing peptide hydrogels to be tailored to specific functional requirements. This article reviews an area of increasing interest, namely self-assembled peptides and their potential therapeutic applications as innovative hydrogels and biomaterials in the prevention of biofilm-related infection.

  4. Peptide binding specificity of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Sandhu, N.; Duus, K.; Jorgensen, C.S.

    2007-01-01

    Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length and composit...

  5. Biologically Active and Antimicrobial Peptides from Plants

    Directory of Open Access Journals (Sweden)

    Carlos E. Salas

    2015-01-01

    Full Text Available Bioactive peptides are part of an innate response elicited by most living forms. In plants, they are produced ubiquitously in roots, seeds, flowers, stems, and leaves, highlighting their physiological importance. While most of the bioactive peptides produced in plants possess microbicide properties, there is evidence that they are also involved in cellular signaling. Structurally, there is an overall similarity when comparing them with those derived from animal or insect sources. The biological action of bioactive peptides initiates with the binding to the target membrane followed in most cases by membrane permeabilization and rupture. Here we present an overview of what is currently known about bioactive peptides from plants, focusing on their antimicrobial activity and their role in the plant signaling network and offering perspectives on their potential application.

  6. Bioactive Proteins and Peptides from Soybeans.

    Science.gov (United States)

    Agyei, Dominic

    2015-01-01

    Dietary proteins from soybeans have been shown to offer health benefits in vivo and/or in vitro either as intact proteins or in partially digested forms also called bioactive peptides. Upon oral administration and absorption, soy-derived bioactive peptides may induce several physiological responses such as antioxidative, antimicrobial, antihypertensive, anticancer and immunomodulatory effects. There has therefore been a mounting research interest in the therapeutic potential of soy protein hydrolysates and their subsequent incorporation in functional foods and 'Food for Specified Health Uses' (FOSHU) related products where their biological activities may assist in the promotion of good health or in the control and prevention of diseases. This mini review discusses relevant patents and gives an overview on bioactive proteins and peptides obtainable from soybeans. Processes for the production and formulation of these peptides are given, together with specific examples of their therapeutic potential and possible areas of application.

  7. Di peptides of the Zeyhera digitalis roots

    International Nuclear Information System (INIS)

    Ferreira, Dalva Trevisan; Silva, Rosely Barbosa da

    1991-01-01

    Systematic investigation using 1 H NMR have been done on the Zeyhera digitalis roots for isolation, purification, and identification of substances with biological or medical potential activities , such as di peptides compounds

  8. Flourescent Peptide-Stabilized Silver-Nanoclusters

    DEFF Research Database (Denmark)

    Gregersen, Simon

    throughput dramatically with regards to discovery of novel ligands. Our approach employs Fmoc solid-phase peptide synthesis on a PEGA resin which allows for on-resin screening of peptide ligands which, in turn, removes the tedious and labor-intensive work-up of synthesized peptides. The method allows for on......Fluorescent probes are widely used in the fields of imaging, detection, and diagnostics, and in order to achieve methodical progress, the search for new tools is an on-going quest. Within the last few decades, few-atom noble metal nanoclusters (NCs) have gathered increasing attention due....../reorganization of the peptide to facilitate NC formation. Following an initial chelation involving the thiol-functionality of cysteine side-chains, the coordination of silver into a defined NC is expected to be the driving force of the folding process. This work also illustrates the shortcomings of MALDI-TOF mass spectrometry...

  9. Advances in synthetic peptides reagent discovery

    Science.gov (United States)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Stratis-Cullum, Dimitra N.

    2013-05-01

    Bacterial display technology offers a number of advantages over competing display technologies (e.g, phage) for the rapid discovery and development of peptides with interaction targeted to materials ranging from biological hazards through inorganic metals. We have previously shown that discovery of synthetic peptide reagents utilizing bacterial display technology is relatively simple and rapid to make laboratory automation possible. This included extensive study of the protective antigen system of Bacillus anthracis, including development of discovery, characterization, and computational biology capabilities for in-silico optimization. Although the benefits towards CBD goals are evident, the impact is far-reaching due to our ability to understand and harness peptide interactions that are ultimately extendable to the hybrid biomaterials of the future. In this paper, we describe advances in peptide discovery including, new target systems (e.g. non-biological materials), advanced library development and clone analysis including integrated reporting.

  10. Charge Transport Phenomena in Peptide Molecular Junctions

    Directory of Open Access Journals (Sweden)

    Alessandra Luchini

    2008-01-01

    Full Text Available Inelastic electron tunneling spectroscopy (IETS is a valuable in situ spectroscopic analysis technique that provides a direct portrait of the electron transport properties of a molecular species. In the past, IETS has been applied to small molecules. Using self-assembled nanoelectronic junctions, IETS was performed for the first time on a large polypeptide protein peptide in the phosphorylated and native form, yielding interpretable spectra. A reproducible 10-fold shift of the I/V characteristics of the peptide was observed upon phosphorylation. Phosphorylation can be utilized as a site-specific modification to alter peptide structure and thereby influence electron transport in peptide molecular junctions. It is envisioned that kinases and phosphatases may be used to create tunable systems for molecular electronics applications, such as biosensors and memory devices.

  11. The preparation and characterization of peptide's lung cancer imaging agent

    International Nuclear Information System (INIS)

    Liu Jianfeng; Chu Liping; Wang Yan; Wang Yueying; Liu Jinjian; Wu Hongying

    2010-01-01

    Objective: To screen in vivo lung cancer specific binding seven peptides by T7 phage display peptide library, so as to prepare peptide's lung cancer early diagnostic agent. Methods: Use phage display in vivo technology, the 7-peptide phage that binding the lung cancer specifically was obtained, then the DNA sequence was measured and the seven peptide was synthesized. After labeled by 125 I, the seven peptide was injected into mice via vein and the distribution was observed. Results: One peptide was obtained by four rounds screening, and the peptide can bind lung cancer tissue specifically. Two hours after injection get the best imaging of lung cancer, metabolism of peptide in mice is fast, the distribution in vivo is decrease six hours and almost disappear 20 hours after injection. Conclusion: The peptide can image and diagnose lung cancer better. (authors)

  12. Anisotropic Membrane Curvature Sensing by Amphipathic Peptides

    OpenAIRE

    Gómez-Llobregat, Jordi; Elías-Wolff, Federico; Lindén, Martin

    2016-01-01

    Many proteins and peptides have an intrinsic capacity to sense and induce membrane curvature, and play crucial roles for organizing and remodelling cell membranes. However, the molecular driving forces behind these processes are not well understood. Here, we describe a new approach to study curvature sensing, by simulating the direction-dependent interactions of single molecules with a buckled lipid bilayer. We analyse three amphipathic antimicrobial peptides, a class of membrane-associated m...

  13. 14C-labeling of synthetic peptides

    International Nuclear Information System (INIS)

    Chersi, A.; Trinca, M.L.; Camera, M.

    1988-01-01

    Two methods are described for the labelling of synthetic peptides using iodo[ 14 C]acetic acid. The first procedure may be employed when the synthetic fragment contains a cysteine with a free sulfhydryl group. Alternatively, a commercial amino-protected cysteine may be carboxymethylated using radioactive iodoacetic acid. This derivative can be added to the growing peptide chain in the manual or automatic solid-phase synthesis of the fragment. 9 refs.; 1 figure; 1 table

  14. 14C-labeling of synthetic peptides.

    Science.gov (United States)

    Chersi, A; Trinca, M L; Camera, M

    1988-06-13

    Two methods are described for the labeling of synthetic peptides using iodo[14C]acetic acid. The first procedure may be employed when the synthetic fragment contains a cysteine with a free sulfhydryl group. Alternatively, a commercial amino-protected cysteine may be carboxymethylated using radioactive iodoacetic acid. This derivative can be added to the growing peptide chain in the manual or automatic solid-phase synthesis of the fragment.

  15. Antimicrobial Peptides with Differential Bacterial Binding Characteristics

    Science.gov (United States)

    2013-03-01

    wherein each residue in the sequence is systematically replaced with alanine to produce a set of well-defined mutations, and 3) sequence generation...peptide sequences with differential binding behavior toward select microorganisms .  viii    Acknowledgements The authors would like to thank Mr. Steven...A., Sandri, L., & Giangaspero, A. (2000). Amphipathic, α-Helical Antimicrobial Peptides. Biopolymers , 55, 4-30.  2 Epand, R. M., & Vogel, H. J. (1999

  16. Glucagon-like peptide-1 (GLP-1)

    DEFF Research Database (Denmark)

    Skov, Jeppe; Dejgaard, Anders; Frøkiær, Jørgen

    2013-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone with multiple actions in addition to control of glucose homeostasis. GLP-1 is known to cause natriuresis in humans, but the effects on basic renal physiology are still partly unknown.......Glucagon-like peptide-1 (GLP-1) is an incretin hormone with multiple actions in addition to control of glucose homeostasis. GLP-1 is known to cause natriuresis in humans, but the effects on basic renal physiology are still partly unknown....

  17. Liquid-phase synthesis of bridged peptides using olefin metathesis of a protected peptide with a long aliphatic chain anchor.

    Science.gov (United States)

    Aihara, Keisuke; Komiya, Chiaki; Shigenaga, Akira; Inokuma, Tsubasa; Takahashi, Daisuke; Otaka, Akira

    2015-02-06

    Bridged peptides including stapled peptides are attractive tools for regulating protein-protein interactions (PPIs). An effective synthetic methodology in a heterogeneous system for the preparation of these peptides using olefin metathesis and hydrogenation of protected peptides with a long aliphatic chain anchor is reported.

  18. HLA-F: A New Kid Licensed for Peptide Presentation.

    Science.gov (United States)

    Sim, Malcolm J W; Sun, Peter D

    2017-06-20

    HLA-F, a non-classical MHC molecule, is not known to present peptides. Dulberger et al. (2017) show that HLA-F contains a distinct peptide-binding groove and can present a diverse array of peptides. LIR1, however, recognized HLA-F away from bound peptide, leaving open whether peptide-HLA-F-specific T and NK receptors exist. Published by Elsevier Inc.

  19. Stereo-separations of Peptides by Capillary Electrophoresis and Chromatography

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Afzal Hussain, Iqbal Hussain, Mohamed F. Al-Ajmi & Imran Ali ### Abstract Small peptides (di-, tri-, tetra- penta- hexa etc. and peptides) control many chemical and biological processes. The biological importance of stereomers of peptides is of great value. The stereo-separations of peptides are gaining importance in biological and medicinal sciences and pharmaceutical industries. There is a great need of experimental protocols of stereo-separations of peptides. The various c...

  20. New tachykinin peptides and nociception

    Directory of Open Access Journals (Sweden)

    Toshikazu Nishimori

    2013-02-01

    Full Text Available Hemokinin-1 (HK-1 and endokinins are peptides predicted from a new mammalian tachykinin gene, TAC4. The amino acid sequences derived from rat/mouse HK-1 and human HK-1 are not identical; however, the effects induced by intracerebroventricular or intrathecal administration of HK-1 are attenuated by treatment with antagonists of neurokinin 1 (NK1 receptor, substance P (SP receptor, indicating that HK-1 is an agonist of the NK1 receptor. On the other hand, a growing body of evidence indicates that pharmacological characteristics of HK-1 and SP are always not identical, suggesting that the HK-1-preferred receptor may be involved in the effects of HK-1. Endokinins are derived from human TAC4 and consist of four endokinins, endokinin A (EKA, endokinin B (EKB, endokinin C (EKC and endokinin D (EKD. Effects induced by intrathecal administration of EKA/B (the common C-terminal decapeptide in EKA and EKB and SP were very similar, while the effects of SP and EKA/B were inhibited by EKC/D (the common C-terminal duodecapeptide in EKC and EKD. This inhibitory effect of EKC/D was derived from leucine at the carboxyl-terminus. These findings suggest that HK-1 and EKA/B have an agonistic effect, while EKC/D has an antagonistic effect on the NK1 receptor in nociceptive processing.

  1. Synthetic peptide antagonists of glucagon

    International Nuclear Information System (INIS)

    Unson, C.G.; Andreu, D.; Gurzenda, E.M.; Merrifield, R.B.

    1987-01-01

    Several glucagon analogs were synthesized in an effort to find derivatives that would bind with high affinity to the glucagon receptor of rat liver membranes but would not activate membrane-bound adenylate cyclase and, therefore, would serve as antagonists of the hormone. Measurements on a series of glucagon/secretin hybrids indicated that replacement of Asp 9 in glucagon by Glu 9 , found in secretin, was the important sequence difference in the N terminus of the two hormones. Further deletion of His 1 and introduction of a C-terminal amide resulted in des-His 1 -[Glu 9 ]glucagon amide, which had a 40% binding affinity relative to that of native glucagon but caused no detectable adenylate cyclase activation in the rat liver membrane. This antagonist completely inhibited the effect of a concentration of glucagon that alone gave a full agonist response. It had an inhibition index of 12. The pA 2 was 7.2. An attempt was made to relate conformation with receptor binding. The peptides were synthesized by solid-phase methods and purified to homogeneity by reverse-phase high-performance liquid chromatography on C 18 -silica columns

  2. Membrane manufacture for peptide separations

    KAUST Repository

    Kim, Dooli

    2016-06-07

    Nanostructured polymeric membranes are key tools in biomedical applications such as hemodialysis, protein separations, in the food industry, and drinking water supply from seawater. Despite of the success in different separation processes, membrane manufacture itself is at risk, since the most used solvents are about to be banned in many countries due to environmental and health issues. We propose for the first time the preparation of polyethersulfone membranes based on dissolution in the ionic liquid 1-ethyl-3-methylimidazolium dimethylphosphate ([EMIM]DEP). We obtained a series of membranes tailored for separation of solutes with molecular weight of 30, 5, 1.3, and 1.25 kg mol-1 with respective water permeances of 140, 65, 30 and 20 Lm-2h-1bar-1. We demonstrate their superior efficiency in the separation of complex mixtures of peptides with molecular weights in the range of 800 to 3500 gmol-1. Furthermore, the thermodynamics and kinetics of phase separation leading to the pore formation in the membranes were investigated. The rheology of the solutions and the morphology of the prepared membranes were examed and compared to those of polyethersulfone in organic solvents currently used for membrane manufacture.

  3. In situ detection of tandem DNA repeat length

    Energy Technology Data Exchange (ETDEWEB)

    Yaar, R.; Szafranski, P.; Cantor, C.R.; Smith, C.L. [Boston Univ., MA (United States)

    1996-11-01

    A simple method for scoring short tandem DNA repeats is presented. An oligonucleotide target, containing tandem repeats embedded in a unique sequence, was hybridized to a set of complementary probes, containing tandem repeats of known lengths. Single-stranded loop structures formed on duplexes containing a mismatched (different) number of tandem repeats. No loop structure formed on duplexes containing a matched (identical) number of tandem repeats. The matched and mismatched loop structures were enzymatically distinguished and differentially labeled by treatment with S1 nuclease and the Klenow fragment of DNA polymerase. 7 refs., 4 figs.

  4. Parallel synthesis and screening of peptide conjugates.

    Science.gov (United States)

    Dirksen, Anouk; Madsen, Mark; Dello Iacono, Giuseppe; Matin, Marla J; Bacica, Michael; Stanković, Nebojša; Callans, Sherri; Bhat, Abhijit

    2014-06-18

    Peptide conjugates represent an emerging class of therapeutics. However, in contrast to that of small molecules and peptides, the discovery and optimization of peptide conjugates is low in throughput, resource intensive, time-consuming, and based on educated decisions rather than screening. A strategy for the parallel synthesis and screening of peptide conjugates is presented that (1) reduces variability in the conjugation steps; (2) provides a new method to rapidly and quantitatively measure conversion in crude conjugation mixtures; (3) introduces a purification step using an immobilized chemical scavenger that does not rely on protein-specific binding; and (4) is supported by robust analytical methods to characterize the large number of end products. Copper-free click chemistry is used as the chemoselective ligation method for conjugation and purification. The productivity in the generation and screening of peptide conjugates is significantly improved by applying this strategy as is demonstrated by the optimization of the anti-Angiopoietin-2 (Ang2) CovX-body, CVX-060, a peptide-antibody scaffold conjugate that has advanced in clinical trials for oncology indications.

  5. Peptide Toxins in Solitary Wasp Venoms

    Directory of Open Access Journals (Sweden)

    Katsuhiro Konno

    2016-04-01

    Full Text Available Solitary wasps paralyze insects or spiders with stinging venom and feed the paralyzed preys to their larva. Accordingly, the venoms should contain a variety of constituents acting on nervous systems. However, only a few solitary wasp venoms have been chemically studied despite thousands of species inhabiting the planet. We have surveyed bioactive substances in solitary wasp venoms found in Japan and discovered a variety of novel bioactive peptides. Pompilidotoxins (PMTXs, in the venoms of the pompilid wasps Anoplius samariensis and Batozonellus maculifrons, are small peptides consisting of 13 amino acids without a disulfide bond. PMTXs slowed Na+ channel inactivation, in particular against neuronal type Na+ channels, and were rather selective to the Nav1.6 channel. Mastoparan-like cytolytic and antimicrobial peptides are the major components of eumenine wasp venoms. They are rich in hydrophobic and basic amino acids, adopting a α-helical secondary structure, and showing mast cell degranulating, antimicrobial and hemolytic activities. The venom of the spider wasp Cyphononyx fulvognathus contained four bradykinin-related peptides. They are hyperalgesic and, dependent on the structure, differently associated with B1 or B2 receptors. Further survey led to the isolation of leucomyosuppressin-like FMRFamide peptides from the venoms of the digger wasps Sphex argentatus and Isodontia harmandi. These results of peptide toxins in solitary wasp venoms from our studies are summarized.

  6. Comprehensive computational design of ordered peptide macrocycles

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram K.; Shortridge, Matthew D.; Craven, Timothy W.; Pardo-Avila, Fatima; Rettie, Stephan A.; Kim, David E.; Silva, Daniel A.; Ibrahim, Yehia M.; Webb, Ian K.; Cort, John R.; Adkins, Joshua N.; Varani, Gabriele; Baker, David

    2017-12-14

    Mixed chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to-date, but there is currently no way to systematically search through the structural space spanned by such compounds for new drug candidates. Natural proteins do not provide a useful guide: peptide macrocycles lack regular secondary structures and hydrophobic cores and have different backbone torsional constraints. Hence the development of new peptide macrocycles has been approached by modifying natural products or using library selection methods; the former is limited by the small number of known structures, and the latter by the limited size and diversity accessible through library-based methods. To overcome these limitations, here we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L and D amino acids. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. We synthesize and characterize by NMR twelve 7-10 residue macrocycles, 9 of which have structures very close to the design models in solution. NMR structures of three 11-14 residue bicyclic designs are also very close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide based macrocycles unparalleled for other molecular systems, and vastly increase the available starting scaffolds for both rational drug design and library selection methods.

  7. SPdb – a signal peptide database

    Directory of Open Access Journals (Sweden)

    Tan Tin

    2005-10-01

    Full Text Available Abstract Background The signal peptide plays an important role in protein targeting and protein translocation in both prokaryotic and eukaryotic cells. This transient, short peptide sequence functions like a postal address on an envelope by targeting proteins for secretion or for transfer to specific organelles for further processing. Understanding how signal peptides function is crucial in predicting where proteins are translocated. To support this understanding, we present SPdb signal peptide database http://proline.bic.nus.edu.sg/spdb, a repository of experimentally determined and computationally predicted signal peptides. Results SPdb integrates information from two sources (a Swiss-Prot protein sequence database which is now part of UniProt and (b EMBL nucleotide sequence database. The database update is semi-automated with human checking and verification of the data to ensure the correctness of the data stored. The latest release SPdb release 3.2 contains 18,146 entries of which 2,584 entries are experimentally verified signal sequences; the remaining 15,562 entries are either signal sequences that fail to meet our filtering criteria or entries that contain unverified signal sequences. Conclusion SPdb is a manually curated database constructed to support the understanding and analysis of signal peptides. SPdb tracks the major updates of the two underlying primary databases thereby ensuring that its information remains up-to-date.

  8. Peptides as Therapeutic Agents for Dengue Virus

    Science.gov (United States)

    Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

    2017-01-01

    Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients. PMID:29200948

  9. Peptides as Therapeutic Agents for Dengue Virus.

    Science.gov (United States)

    Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

    2017-01-01

    Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.

  10. Harnessing supramolecular peptide nanotechnology in biomedical applications

    Directory of Open Access Journals (Sweden)

    Chan KH

    2017-02-01

    Full Text Available Kiat Hwa Chan,1 Wei Hao Lee,2 Shuangmu Zhuo,3 Ming Ni3 1Division of Science, Yale-NUS College, Singapore; 2Department of Chemistry, Krieger School of Arts & Sciences, Johns Hopkins University, Baltimore, MD, USA; 3Fujian Provincial Key Laboratory for Photonics Technology, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou, People’s Republic of China Abstract: The harnessing of peptides in biomedical applications is a recent hot topic. This arises mainly from the general biocompatibility of peptides, as well as from the ease of tunability of peptide structure to engineer desired properties. The ease of progression from laboratory testing to clinical trials is evident from the plethora of examples available. In this review, we compare and contrast how three distinct self-assembled peptide nanostructures possess different functions. We have 1 nanofibrils in biomaterials that can interact with cells, 2 nanoparticles that can traverse the bloodstream to deliver its payload and also be bioimaged, and 3 nanotubes that can serve as cross-membrane conduits and as a template for nanowire formation. Through this review, we aim to illustrate how various peptides, in their various self-assembled nanostructures, possess great promise in a wide range of biomedical applications and what more can be expected. Keywords: peptides, self-assembly, nanotechnology

  11. Peptides with Dual Antimicrobial and Anticancer Activities

    Science.gov (United States)

    Felício, Mário R.; Silva, Osmar N.; Gonçalves, Sônia; Santos, Nuno C.; Franco, Octávio L.

    2017-02-01

    In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting towards intracellular targets, which increases their success comparatively to specific one-target drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials.

  12. III. Organometallic and Bioorganometallic Chemistry - Ferrocene Peptides

    Directory of Open Access Journals (Sweden)

    Kovačević, M.

    2012-02-01

    Full Text Available This paper is devoted to the bioconjugates of ferrocene with naturally occuring amino acids/peptides - mostly dealing with authors' results accompanied, to a lesser degree, by the relevant literature data. Chapter 2 deals with natural peptides and peptidomimetics, mainly focusing on α-helix and β pleated sheet (as the most important elements of peptide secondary and tertiary structure, and artificial β-sheets nucleated by non-amino acid turn inducers. Chapter 3 describes peptides generated from ferrocenecarboxylic acid and ferroceneamine, as well as with the bioconjugates of heteroannulary substituted ferrocene-1,1'-dicarboxylic acid (Fcd and ferrocene-1,1'-diamine (Fcda. Chapter 4 elaborates authors' papers about peptides based on 1'-aminoferrocene-1-carboxylic acid (Fca. Chapter 5 is devoted to the new monosubstituted Fcd and Fcda conjugates with amino acids, while Chapter 6 describes our publications in the field of very topical peptidomimetics - ferrocene ureidopeptides and β peptides. Conformational analysis of the newly prepared ferrocene bioconjugates in solution and solid state was performed by means of spectroscopic methods (CD, IR, 1D- NMR, 2D-NMR, v. r. NMR, and temperature and concentration dependent NMR and DFT calculations.

  13. Repeat Rapid Response Events in Children: Characteristics and Outcomes.

    Science.gov (United States)

    Meulmester, Kristen M; Jaimon, Nancy; Bavare, Aarti C

    2018-04-01

    We describe the characteristics and outcomes of pediatric repeat rapid response events within a single hospitalization. We hypothesized that triggers for repeat rapid response and initial rapid response events are similar, and repeat rapid response events are associated with high prevalence of medical complexity and worse outcomes. A 3-year retrospective study. High-volume tertiary academic pediatric hospital. All rapid response events were reviewed to identify repeat rapid response events. None. Patient demographics, rapid response triggers, primary clinical diagnoses, illness acuity scores, medical interventions, transfers to ICU, occurrence of critical deterioration, and mortality were reviewed. We reviewed 146 patients with 309 rapid response events (146 initial rapid response and 163 repeat rapid response: 36% 7 d after initial rapid response). Median age was 3 years, and 60% were males. Eighty-five percentage of repeat rapid response occurred in medical complexity patients. The triggers for 71% of all repeat rapid response matched with those of initial rapid response. Transfer to ICU occurred in 69 (47%) of initial rapid response and 124 (76%) of repeat rapid response (p events correlated. Transfer to ICU was more likely after repeat rapid response and among repeat rapid response, events with ICU readmissions had a longer length of ICU and hospital stay. Mortality for the repeat rapid response cohort was higher than that for overall rapid responses in our center and per published reports from other centers.

  14. Determination of bovine lactoferrin in dairy products by ultra-high performance liquid chromatography–tandem mass spectrometry based on tryptic signature peptides employing an isotope-labeled winged peptide as internal standard

    International Nuclear Information System (INIS)

    Zhang, Jingshun; Lai, Shiyun; Cai, Zengxuan; Chen, Qi; Huang, Baifen; Ren, Yiping

    2014-01-01

    Highlights: • A UHPLC–MS/MS method for quantification of bovine lactoferrin was developed. • Tryptic fragment LRPVAAEIYGTK was chosen as signature peptide of bovine lactoferrin. • A winged peptide containing isotopically-labeled signature peptide was designed as internal standard. • The method for determining lactoferrin does not discriminate between the different forms of lactoferrin. • Meet the growing demand to quantify bovine lactoferrin in different dairy products. - Abstract: A new and sensitive determination method was developed for bovine lactoferrin in dairy products including infant formulas based on the signature peptide by ultra high-performance liquid chromatography and triple-quadrupole tandem mass spectrometry under the multiple reaction monitoring mode. The simple pretreatment procedures included the addition of a winged peptide containing the isotope-labeled signature peptide as internal standard, followed by an enzymatic digestion with trypsin. The signature peptide was chosen and identified from the tryptic hydrolyzates of bovine lactoferrin by ultra high-performance liquid chromatography and quadrupole-time-of-flight tandem mass spectrometry based on sequence database search. Analytes were separated on an ACQUITY UPLC BEH 300 C18 column and monitored by MS/MS in seven minutes. Quantitative result bias due to matrix effect and tryptic efficiency was corrected through the use of synthetic isotope-labeled standards. The limit of detection and limit of quantification were 0.3 mg/100 g and 1.0 mg/100 g, respectively. Bovine lactoferrin within the concentration range of 10–1000 nmol L −1 showed a strong linear relationship with a linear correlation coefficient (r) of >0.998. The intra- and inter-day precision of the method were RSD < 6.5% and RSD < 7.1%, respectively. Excellent repeatability (RSD < 6.4%) substantially supported the application of this method for the determination of bovine lactoferrin in dairy samples. The present

  15. Determination of bovine lactoferrin in dairy products by ultra-high performance liquid chromatography–tandem mass spectrometry based on tryptic signature peptides employing an isotope-labeled winged peptide as internal standard

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jingshun [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051 (China); Lai, Shiyun [Beingmate Research Institute, Beingmate Baby and Child Food Co., Ltd., Hangzhou 310007 (China); Cai, Zengxuan [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051 (China); Chen, Qi [Beingmate Research Institute, Beingmate Baby and Child Food Co., Ltd., Hangzhou 310007 (China); Huang, Baifen [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051 (China); Ren, Yiping, E-mail: renyiping@263.net [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051 (China)

    2014-06-01

    Highlights: • A UHPLC–MS/MS method for quantification of bovine lactoferrin was developed. • Tryptic fragment LRPVAAEIYGTK was chosen as signature peptide of bovine lactoferrin. • A winged peptide containing isotopically-labeled signature peptide was designed as internal standard. • The method for determining lactoferrin does not discriminate between the different forms of lactoferrin. • Meet the growing demand to quantify bovine lactoferrin in different dairy products. Abstract: A new and sensitive determination method was developed for bovine lactoferrin in dairy products including infant formulas based on the signature peptide by ultra high-performance liquid chromatography and triple-quadrupole tandem mass spectrometry under the multiple reaction monitoring mode. The simple pretreatment procedures included the addition of a winged peptide containing the isotope-labeled signature peptide as internal standard, followed by an enzymatic digestion with trypsin. The signature peptide was chosen and identified from the tryptic hydrolyzates of bovine lactoferrin by ultra high-performance liquid chromatography and quadrupole-time-of-flight tandem mass spectrometry based on sequence database search. Analytes were separated on an ACQUITY UPLC BEH 300 C18 column and monitored by MS/MS in seven minutes. Quantitative result bias due to matrix effect and tryptic efficiency was corrected through the use of synthetic isotope-labeled standards. The limit of detection and limit of quantification were 0.3 mg/100 g and 1.0 mg/100 g, respectively. Bovine lactoferrin within the concentration range of 10–1000 nmol L⁻¹ showed a strong linear relationship with a linear correlation coefficient (r) of >0.998. The intra- and inter-day precision of the method were RSD < 6.5% and RSD < 7.1%, respectively. Excellent repeatability (RSD < 6.4%) substantially supported the application of this method for the determination of bovine lactoferrin in dairy samples. The present method

  16. Peptide imprinted receptors for the determination of the small cell lung cancer associated biomarker progastrin releasing peptide

    DEFF Research Database (Denmark)

    Qader, A. A.; Urraca, J.; Torsetnes, S. B.

    2014-01-01

    Peptide imprinted polymers were developed for detection of progastrin releasing peptide (ProGRP); a low abundant blood based biomarker for small cell lung cancer. The polymers targeted the proteotypic nona-peptide sequence NLLGLIEAK and were used for selective enrichment of the proteotypic peptide...... investigated and optimized. Ultimately, a solid phase extraction method was developed for highly selective enrichment of the target peptide from tryptic digests. (C) 2014 Elsevier B.V. All rights reserved....

  17. Antimicrobial peptide, hdMolluscidin, purified from the gill of the abalone, Haliotis discus.

    Science.gov (United States)

    Seo, Jung-Kil; Go, Hye-Jin; Kim, Chan-Hee; Nam, Bo-Hye; Park, Nam Gyu

    2016-05-01

    A 4.7 kDa antimicrobial peptide was purified from the acidified gill extract of the Abalone, Haliotis discus, by cation-exchange and C18 reversed-phase high performance liquid chromatography (HPLC). Comparison of the amino acid sequences and molecular weight of this peptide with those of other known antimicrobial peptides revealed that this antimicrobial peptide have high sequence homology with that of cgMolluscidin and was designated hdMolluscidin. hdMolluscidin is composed of 46 amino acid residues containing several dibasic residue repeats like KK or K-R. hdMolluscidin showed potent antimicrobial activity against both Gram-positive bacteria including Bacillus subtilis and Staphylococcus aureus (minimal effective concentrations [MECs]; 0.8-19.0 μg/mL) and Gram-negative bacteria including Aeromonas hydrophila, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Shigella flexneri, and Vibrio parahemolyticus ([MECs]; 1.0-4.0 μg/mL) without hemolytic activity. However, hdMolluscidin did not show any significant activity against Candida albicans. The secondary structural prediction suggested that hdMolluscidin might not form an ordered or an amphipathic structure. hdMolluscidin did not show membrane permeabilization or leakage ability. The full-length hdMolluscidin cDNA contained 566-bp, including a 5'-untranslated region (UTR) of 63-bp, a 3'-UTR of 359-bp, and an open reading frame of 144-bp encoding 47 amino acids (containing Met). cDNA study of hdMolluscidin suggests that it is expressed as a mature peptide. Our results indicate that hdMolluscidin could relate to the innate immune defenses in abalone and it may not act directly on bacterial membrane. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Interaction of antimicrobial peptides with lipid membranes

    International Nuclear Information System (INIS)

    Hanulova, Maria

    2008-12-01

    This study aims to investigate the difference in the interaction of antimicrobial peptides with two classes of zwitterionic peptides, phosphatidylethanolamines (PE) and phosphatidylcholines (PC). Further experiments were performed on model membranes prepared from specific bacterial lipids, lipopolysaccharides (LPS) isolated from Salmonella minnesota. The structure of the lipid-peptide aqueous dispersions was studied by small-and wide-angle X-ray diffraction during heating and cooling from 5 to 85 C. The lipids and peptides were mixed at lipid-to-peptide ratios 10-10000 (POPE and POPC) or 2-50 (LPS). All experiments were performed at synchrotron soft condensed matter beamline A2 in Hasylab at Desy in Hamburg, Germany. The phases were identified and the lattice parameters were calculated. Alamethicin and melittin interact in similar ways with the lipids. Pure POPC forms only lamellar phases. POPE forms lamellar phases at low temperatures that upon heating transform into a highly curved inverse hexagonal phase. Insertion of the peptide induced inverse bicontinuous cubic phases which are an ideal compromise between the curvature stress and the packing frustration. Melittin usually induced a mixture of two cubic phases, Im3m and Pn3m, with a ratio of lattice parameters close to 1.279, related to the underlying minimal surfaces. They formed during the lamellar to hexagonal phase transition and persisted during cooling till the onset of the gel phase. The phases formed at different lipid-to-peptide ratios had very similar lattice parameters. Epitaxial relationships existed between coexisting cubic phases and hexagonal or lamellar phases due to confinement of all phases to an onion vesicle, a vesicle with several layers consisting of different lipid phases. Alamethicin induced the same cubic phases, although their formation and lattice parameters were dependent on the peptide concentration. The cubic phases formed during heating from the lamellar phase and their onset

  19. Interaction of antimicrobial peptides with lipid membranes

    Energy Technology Data Exchange (ETDEWEB)

    Hanulova, Maria

    2008-12-15

    This study aims to investigate the difference in the interaction of antimicrobial peptides with two classes of zwitterionic peptides, phosphatidylethanolamines (PE) and phosphatidylcholines (PC). Further experiments were performed on model membranes prepared from specific bacterial lipids, lipopolysaccharides (LPS) isolated from Salmonella minnesota. The structure of the lipid-peptide aqueous dispersions was studied by small-and wide-angle X-ray diffraction during heating and cooling from 5 to 85 C. The lipids and peptides were mixed at lipid-to-peptide ratios 10-10000 (POPE and POPC) or 2-50 (LPS). All experiments were performed at synchrotron soft condensed matter beamline A2 in Hasylab at Desy in Hamburg, Germany. The phases were identified and the lattice parameters were calculated. Alamethicin and melittin interact in similar ways with the lipids. Pure POPC forms only lamellar phases. POPE forms lamellar phases at low temperatures that upon heating transform into a highly curved inverse hexagonal phase. Insertion of the peptide induced inverse bicontinuous cubic phases which are an ideal compromise between the curvature stress and the packing frustration. Melittin usually induced a mixture of two cubic phases, Im3m and Pn3m, with a ratio of lattice parameters close to 1.279, related to the underlying minimal surfaces. They formed during the lamellar to hexagonal phase transition and persisted during cooling till the onset of the gel phase. The phases formed at different lipid-to-peptide ratios had very similar lattice parameters. Epitaxial relationships existed between coexisting cubic phases and hexagonal or lamellar phases due to confinement of all phases to an onion vesicle, a vesicle with several layers consisting of different lipid phases. Alamethicin induced the same cubic phases, although their formation and lattice parameters were dependent on the peptide concentration. The cubic phases formed during heating from the lamellar phase and their onset

  20. Peptide dot immunoassay and immunoblotting: electroblotting from aluminum thin-layer chromatography plates and isoelectric focusing gels to activated nitrocellulose

    DEFF Research Database (Denmark)

    Bjerrum, O.J.; Holm, A.; Lauritzen, Edgar

    1993-01-01

    Peptide dot immunoassay, electroblotting, activated nitrocellulose, dot blot, membranes, peptides and proteins......Peptide dot immunoassay, electroblotting, activated nitrocellulose, dot blot, membranes, peptides and proteins...

  1. Peptide-membrane interactions of arginine-tryptophan peptides probed using quartz crystal microbalance with dissipation monitoring.

    KAUST Repository

    Rydberg, Hanna A

    2014-04-18

    Membrane-active peptides include peptides that can cross cellular membranes and deliver macromolecular cargo as well as peptides that inhibit bacterial growth. Some of these peptides can act as both transporters and antibacterial agents. It is desirable to combine the knowledge from these two different fields of membrane-active peptides into design of new peptides with tailored actions, as transporters of cargo or as antibacterial substances, targeting specific membranes. We have previously shown that the position of the amino acid tryptophan in the peptide sequence of three arginine-tryptophan peptides affects their uptake and intracellular localization in live mammalian cells, as well as their ability to inhibit bacterial growth. Here, we use quartz crystal microbalance with dissipation monitoring to assess the induced changes caused by binding of the three peptides to supported model membranes composed of POPC, POPC/POPG, POPC/POPG/cholesterol or POPC/lactosyl PE. Our results indicate that the tryptophan position in the peptide sequence affects the way these peptides interact with the different model membranes and that the presence of cholesterol in particular seems to affect the membrane interaction of the peptide with an even distribution of tryptophans in the peptide sequence. These results give mechanistic insight into the function of these peptides and may aid in the design of membrane-active peptides with specified cellular targets and actions.

  2. Tandem repeat structure of rhamnose-binding lectin from catfish (Silurus asotus) eggs.

    Science.gov (United States)

    Hosono, M; Ishikawa, K; Mineki, R; Murayama, K; Numata, C; Ogawa, Y; Takayanagi, Y; Nitta, K

    1999-11-16

    The primary structure of catfish (Silurus asotus) egg lectin (SAL) was determined. SAL cDNA contained 1448-bp nucleotides and 308 amino acid residues, deduced from open reading frame. The SAL mature protein composed of 285-amino acid residues was followed by a predicted signal sequence having 23 residues. The mRNA of SAL was found to be expressed in eggs, but not in liver. SAL is composed of three tandem repeat domain structures divided into exactly 95 amino acid residues each, and all cysteine positions of each domain were completely conserved. Sequence homologies between the three domains, termed D1 (1-95), D2 (96-190) and D3 (191-285), were as follows; D1-D2, 28%; D2-D3, 33%; D1-D3, 43%. Two conserved peptide motifs, -(AN)YGR(TD)S(T)XCS(TGR)P- and -DPCX(G)T(Y)KY(L)-, appear to exist at the N- and C-terminal regions of each domain, respectively. The kinetic parameters of SAL obtained by measuring surface plasmon resonance were as follows: K(a) (M(-1)) for neohesperidosyl-BSA, 7. 1 x 10(6); for melibiosyl-BSA, 4.9 x 10(6); and for lactosyl-BSA, 5. 2 x 10(5). These results show that RBLs including SAL comprise a family of alpha-galactosyl binding lectins having characteristic tandem repeat domain structures.

  3. The non-peptidic part determines the internalization mechanism and intracellular trafficking of peptide amphiphiles.

    Science.gov (United States)

    Missirlis, Dimitris; Teesalu, Tambet; Black, Matthew; Tirrell, Matthew

    2013-01-01

    Peptide amphiphiles (PAs) are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol) to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.

  4. The non-peptidic part determines the internalization mechanism and intracellular trafficking of peptide amphiphiles.

    Directory of Open Access Journals (Sweden)

    Dimitris Missirlis

    Full Text Available BACKGROUND: Peptide amphiphiles (PAs are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. METHODOLOGY/PRINCIPAL FINDINGS: PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. CONCLUSIONS/SIGNIFICANCE: Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.

  5. Peptide and Peptide-Dependent Motions in MHC Proteins: Immunological Implications and Biophysical Underpinnings.

    Science.gov (United States)

    Ayres, Cory M; Corcelli, Steven A; Baker, Brian M

    2017-01-01

    Structural biology of peptides presented by class I and class II MHC proteins has transformed immunology, impacting our understanding of fundamental immune mechanisms and allowing researchers to rationalize immunogenicity and design novel vaccines. However, proteins are not static structures as often inferred from crystallographic structures. Their components move and breathe individually and collectively over a range of timescales. Peptides bound within MHC peptide-binding grooves are no exception and their motions have been shown to impact recognition by T cell and other receptors in ways that influence function. Furthermore, peptides tune the motions of MHC proteins themselves, which impacts recognition of peptide/MHC complexes by other proteins. Here, we review the motional properties of peptides in MHC binding grooves and discuss how peptide properties can influence MHC motions. We briefly review theoretical concepts about protein motion and highlight key data that illustrate immunological consequences. We focus primarily on class I systems due to greater availability of data, but segue into class II systems as the concepts and consequences overlap. We suggest that characterization of the dynamic "energy landscapes" of peptide/MHC complexes and the resulting functional consequences is one of the next frontiers in structural immunology.

  6. Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides.

    NARCIS (Netherlands)

    Vegt, E.; Eek, A.; Oyen, W.J.G.; Jong, M. de; Gotthardt, M.; Boerman, O.C.

    2010-01-01

    PURPOSE: In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of

  7. Role of Cell-Penetrating Peptides in Intracellular Delivery of Peptide Nucleic Acids Targeting Hepadnaviral Replication

    DEFF Research Database (Denmark)

    Ndeboko, Benedicte; Ramamurthy, Narayan; Lemamy, Guy Joseph

    2017-01-01

    Peptide nucleic acids (PNAs) are potentially attractive antisense agents against hepatitis B virus (HBV), although poor cellular uptake limits their therapeutic application. In the duck HBV (DHBV) model, we evaluated different cell-penetrating peptides (CPPs) for delivery to hepatocytes of a PNA...

  8. Peptide and Peptide-Dependent Motions in MHC Proteins: Immunological Implications and Biophysical Underpinnings

    Directory of Open Access Journals (Sweden)

    Cory M. Ayres

    2017-08-01

    Full Text Available Structural biology of peptides presented by class I and class II MHC proteins has transformed immunology, impacting our understanding of fundamental immune mechanisms and allowing researchers to rationalize immunogenicity and design novel vaccines. However, proteins are not static structures as often inferred from crystallographic structures. Their components move and breathe individually and collectively over a range of timescales. Peptides bound within MHC peptide-binding grooves are no exception and their motions have been shown to impact recognition by T cell and other receptors in ways that influence function. Furthermore, peptides tune the motions of MHC proteins themselves, which impacts recognition of peptide/MHC complexes by other proteins. Here, we review the motional properties of peptides in MHC binding grooves and discuss how peptide properties can influence MHC motions. We briefly review theoretical concepts about protein motion and highlight key data that illustrate immunological consequences. We focus primarily on class I systems due to greater availability of data, but segue into class II systems as the concepts and consequences overlap. We suggest that characterization of the dynamic “energy landscapes” of peptide/MHC complexes and the resulting functional consequences is one of the next frontiers in structural immunology.

  9. Peptide-MHC class I stability is a stronger predictor of CTL immunogenicity than peptide affinity

    DEFF Research Database (Denmark)

    Harndahl, Mikkel Nors; Rasmussen, Michael; Nielsen, Morten

    2012-01-01

    Peptide-MHC class I stability is a stronger predictor of CTL immunogenicity than peptide affinity Mikkel Harndahla, Michael Rasmussena, Morten Nielsenb, Soren Buusa,∗ a Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, Denmark b Center for Biological Seq...... al., 2007. J. Immunol. 178, 7890–7901. doi:10.1016/j.molimm.2012.02.025...

  10. THE USE OF DEDICATED PEPTIDE LIBRARIES PERMITS THE DISCOVERY OF HIGH-AFFINITY BINDING PEPTIDES

    NARCIS (Netherlands)

    DEKOSTER, HS; AMONS, R; BENCKHUIJSEN, WE; FEIJLBRIEF, M; SCHELLEKENS, GA; DRIJFHOUT, JW

    1995-01-01

    The motif for peptide binding to monoclonal antibody mAb A16, which is known to be directed against glycoprotein D of Herpes simplex virus type 1, was determined using two dedicated peptide libraries. As a starting point for this study we used an A-16 binding lead sequence, which had previously been

  11. Urodilatin. A renal natriuretic peptide

    International Nuclear Information System (INIS)

    Carstens, Jan

    1998-01-01

    Development and validation of a radioimmunoassay for endogenous URO in urine and synthetic URO in plasma is described. The first obstacle to overcome was to produce an antibody specific for URO. A polyclonal URO antibody with a cross-reactivity with the structural highly homologous atrial natriuretic peptide (ANP) was developed by immunization of rabbits with the whole URO(95-126). Purification of the polyclonal URO antiserum with CNBr-activated Sepharose affinity chromatography was a simple way of producing a URO-specific antibody without cross-reactivity with ANP analogues. A reliable 125 I-labelled URO tracer was made with the Iodo-Gen method. Prior to the assay, the urine samples were prepared by ethanol with a recovery of unlabelled URO between 80 - 100% and the plasma samples were Sep-Pak C 18 extracted with a recovery of about 50%. The radioimmunoassay is performed in 3 days, using polyethylene glycol for separation. The sensitivity of the assay was improved by sample preparation and concentration, reducing the amount of tracer and late addition, reducing the amount of antibody and increasing the incubation time and lowering the temperature of incubation. The infusion rate of 20 ng URO kg -1 min -1 was most potential and well tolerated in healthy subjects. The short-term natriuretic and diuretic effects were closely associated with a significant diminished sodium reabsorption in the distal nephron. Further studies are needed to exploit the therapeutical potential of URO, for example in patients with sodium-water retaining disorders. The therapeutical dose range will probably be narrow due to the blood pressure lowering effect of URO with infusion rates higher than 20-30 ng kg -1 min -1 . (EHS)

  12. Studies on Section XI ultrasonic repeatability

    International Nuclear Information System (INIS)

    Jamison, T.D.; McDearman, W.R.

    1981-05-01

    A block representative of a nuclear component has been welded containing intentional defects. Acoustic emission data taken during the welding correlate well with ultrasonic data. Repetitive ultrasonic examinations have been performed by skilled operators using a procedure based on that desribed in ASME Section XI. These examinations were performed by different examination teams using different ultrasonic equipment in such a manner that the effects on the repeatability of the ultrasonic test method caused by the operator and by the use of different equipment could be estimated. It was tentatively concluded that when considering a large number of inspections: (1) there is no significant difference in indication sizing between operators, and (2) there is a significant difference in amplitude and defect sizing when instruments having different, Code acceptable operating characteristics are used. It was determined that the Section XI sizing parameters follow a bivariate normal distribution. Data derived from ultrasonically and physically sizing indications in nuclear components during farication show that the Section XI technique tends to overestimate the size of the reflectors

  13. A Repeated Signal Difference for Recognising Patterns

    Directory of Open Access Journals (Sweden)

    Kieran Greer

    2016-08-01

    Full Text Available This paper describes a new mechanism that might help with defining pattern sequences, by the fact that it can produce an upper bound on the ensemble value that can persistently oscillate with the actual values produced from each pattern. With every firing event, a node also receives an on/off feedback switch. If the node fires then it sends a feedback result depending on the input signal strength. If the input signal is positive or larger, it can store an ‘on’ switch feedback for the next iteration. If the signal is negative or smaller it can store an ‘off’ switch feedback for the next iteration. If the node does not fire, then it does not affect the current feedback situation and receives the switch command produced by the last active pattern event for the same neuron. The upper bound therefore also represents the largest or most enclosing pattern set and the lower value is for the actual set of firing patterns. If the pattern sequence repeats, it will oscillate between the two values, allowing them to be recognised and measured more easily, over time. Tests show that changing the sequence ordering produces different value sets, which can also be measured.

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

    Science.gov (United States)

    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

  15. The effect of repeated testing vs repeated practice on skills learning in undergraduate dental education.

    Science.gov (United States)

    Sennhenn-Kirchner, S; Goerlich, Y; Kirchner, B; Notbohm, M; Schiekirka, S; Simmenroth, A; Raupach, T

    2018-02-01

    Recent studies in undergraduate medical education have demonstrated the advantage of repeated testing over repeated practice with regard to knowledge and skills retention. The aim of this study was to investigate whether this "testing effect" also applies to skills retention in undergraduate dental education. In this prospective, randomised controlled trial, fourth-year dental students at Göttingen University Medical Centre participated in a training session on surgical suturing in winter term 2014/2015. Following this, they were either assigned to two sessions of additional skills training (group A) or two sessions of skills assessment with feedback (group B). These sessions were spaced over a period of 4 weeks. Skills retention was assessed in a summative objective structured clinical examination (OSCE) at the end of term, that is 6 months after the initial teaching session. A total of 32 students completed the study. With regard to suturing, OSCE performance was significantly better in group B than group A (81.9±13.1% vs 63.0±15.4%; P=0.001; Cohen's d=1.33). There was no significant OSCE performance difference in the two groups with regard to other learning objectives that were addressed in the end-of-term examination. Thus, the group difference was specific to suturing skills. This is the first study to demonstrate that in dental education, repeated testing produces more favourable skills retention than repeated practice. Test-enhanced learning might be a viable concept for skills retention in undergraduate dentistry education. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Radionuclide therapy with peptides: bench to bedside

    International Nuclear Information System (INIS)

    Das, Tapas

    2016-01-01

    Peptides, which are short chains of amino acids linked by the peptide (amide) bond, play an important role in the management of various types of ailments. Recently, use of radiolabeled peptides has emerged as one of the prime treatment modality for combating against a variety of cancers. At present, 'Peptide Receptor Radionuclide Therapy' (PRRNT) employing 177 Lu-DOTA-TATE (lutetium-177 labeled DOTA coupled Tyr 3 -Octrotate) is considered as the only viable treatment modality for the patients suffering from inoperable and disseminated neuroendocrine cancers over expressing somatostatin receptors. In the last couple of years, clinical evaluations carried outwith 177 Lu-PSMA-617 (PSMA: Prostate Specific Membrane Antigen) have shown encouraging results in targeted radionuclide therapy of patients suffering from prostate cancer. These agents are available from a limited number of foreign suppliers; but are prohibitively expensive, which makes these agents almost unaffordable to most of the Indian patients. Therefore, it was necessary to develop methodologies to formulate these radiotherapeutic agents indigenously in our country. However, the challenges to prepare radiolabeled peptides in clinical-scale are manifold as these agents are required to be prepared with high specific activity using the 177 Lu, produced in our medium flux research reactor, for obtaining the desired therapeutic efficacy. In the past few years, methodologies for the formulation of clinical-scale 177 Lu-labelled peptides, suitable for human administration, have been developed in our facility and successfully translated to nuclear medicine centers of India, where these agents are regularly used for providing the radiotherapeutic treatment to the cancer patients.The presentation will describe our effort in successfully translating these agents from laboratory to nuclear medicine clinics and cover the aspects related to the development, demonstration and deployment of the radiolabeled

  17. Antimicrobial peptides design by evolutionary multiobjective optimization.

    Directory of Open Access Journals (Sweden)

    Giuseppe Maccari

    Full Text Available Antimicrobial peptides (AMPs are an abundant and wide class of molecules produced by many tissues and cell types in a variety of mammals, plant and animal species. Linear alpha-helical antimicrobial peptides are among the most widespread membrane-disruptive AMPs in nature, representing a particularly successful structural arrangement in innate defense. Recently, AMPs have received increasing attention as potential therapeutic agents, owing to their broad activity spectrum and their reduced tendency to induce resistance. The introduction of non-natural amino acids will be a key requisite in order to contrast host resistance and increase compound's life. In this work, the possibility to design novel AMP sequences with non-natural amino acids was achieved through a flexible computational approach, based on chemophysical profiles of peptide sequences. Quantitative structure-activity relationship (QSAR descriptors were employed to code each peptide and train two statistical models in order to account for structural and functional properties of alpha-helical amphipathic AMPs. These models were then used as fitness functions for a multi-objective evolutional algorithm, together with a set of constraints for the design of a series of candidate AMPs. Two ab-initio natural peptides were synthesized and experimentally validated for antimicrobial activity, together with a series of control peptides. Furthermore, a well-known Cecropin-Mellitin alpha helical antimicrobial hybrid (CM18 was optimized by shortening its amino acid sequence while maintaining its activity and a peptide with non-natural amino acids was designed and tested, demonstrating the higher activity achievable with artificial residues.

  18. Peptide receptor radionuclide therapy: an overview.

    Science.gov (United States)

    Dash, Ashutosh; Chakraborty, Sudipta; Pillai, Maroor Raghavan Ambikalmajan; Knapp, Furn F Russ

    2015-03-01

    Peptide receptor radionuclide therapy (PRRT) is a site-directed targeted therapeutic strategy that specifically uses radiolabeled peptides as biological targeting vectors designed to deliver cytotoxic levels of radiation dose to cancer cells, which overexpress specific receptors. Interest in PRRT has steadily grown because of the advantages of targeting cellular receptors in vivo with high sensitivity as well as specificity and treatment at the molecular level. Recent advances in molecular biology have not only stimulated advances in PRRT in a sustainable manner but have also pushed the field significantly forward to several unexplored possibilities. Recent decades have witnessed unprecedented endeavors for developing radiolabeled receptor-binding somatostatin analogs for the treatment of neuroendocrine tumors, which have played an important role in the evolution of PRRT and paved the way for the development of other receptor-targeting peptides. Several peptides targeting a variety of receptors have been identified, demonstrating their potential to catalyze breakthroughs in PRRT. In this review, the authors discuss several of these peptides and their analogs with regard to their applications and potential in radionuclide therapy. The advancement in the availability of combinatorial peptide libraries for peptide designing and screening provides the capability of regulating immunogenicity and chemical manipulability. Moreover, the availability of a wide range of bifunctional chelating agents opens up the scope of convenient radiolabeling. For these reasons, it would be possible to envision a future where the scope of PRRT can be tailored for patient-specific application. While PRRT lies at the interface between many disciplines, this technology is inextricably linked to the availability of the therapeutic radionuclides of required quality and activity levels and hence their production is also reviewed.

  19. ATXN2 trinucleotide repeat length correlates with risk of ALS.

    Science.gov (United States)

    Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar

    2017-03-01

    We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10 -18 ), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R 2  = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. New dendrimer - Peptide host - Guest complexes: Towards dendrimers as peptide carriers

    DEFF Research Database (Denmark)

    Boas, Ulrik; Sontjens, S.H.M.; Jensen, Knud Jørgen

    2002-01-01

    Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions...... between the dendrimer outer shell tertiary amines and the C-terminal carboxylic acid of the peptide, and also through host-urea to peptide-amide hydrogen bonding. The hydrogen-bonding nature of the peptide dendrimer interactions was further confirmed by using Fourier transform IR spectroscopy, for which...... on the dendrimer host. The influence of side-chain motif on interactions with the host is analyzed by using seven different N-Boc-protected tripeptides as guests for the dendrimer, Downfield shifts of up to 1.3 ppm were observed for the guest amide NH-proton signals. These shifts decrease with increasing...

  1. Acetone-Linked Peptides: A Convergent Approach for Peptide Macrocyclization and Labeling.

    Science.gov (United States)

    Assem, Naila; Ferreira, David J; Wolan, Dennis W; Dawson, Philip E

    2015-07-20

    Macrocyclization is a broadly applied approach for overcoming the intrinsically disordered nature of linear peptides. Herein, it is shown that dichloroacetone (DCA) enhances helical secondary structures when introduced between peptide nucleophiles, such as thiols, to yield an acetone-linked bridge (ACE). Aside from stabilizing helical structures, the ketone moiety embedded in the linker can be modified with diverse molecular tags by oxime ligation. Insights into the structure of the tether were obtained through co-crystallization of a constrained S-peptide in complex with RNAse S. The scope of the acetone-linked peptides was further explored through the generation of N-terminus to side chain macrocycles and a new approach for generating fused macrocycles (bicycles). Together, these studies suggest that acetone linking is generally applicable to peptide macrocycles with a specific utility in the synthesis of stabilized helices that incorporate functional tags. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Novel Zn2+-chelating peptides selected from a fimbria-displayed random peptide library

    DEFF Research Database (Denmark)

    Kjærgaard, Kristian; Schembri, Mark; Klemm, Per

    2001-01-01

    The display of peptide sequences on the surface of bacteria is a technology that offers exciting applications in biotechnology and medical research. Type 1 fimbriae are surface organelles of Escherichia coli which mediate D-mannose-sensitive binding to different host surfaces by virtue of the Fim......H adhesin. FimH is a component of the fimbrial organelle that can accommodate and display a diverse range of peptide sequences on the E. coli cell surface. In this study we have constructed a random peptide library in FimH. The library, consisting of similar to 40 million individual clones, was screened...... that completely novel Zn2+-binding peptide sequences had been isolated. By changing the protein scaffold system, we demonstrated that the Zn2+-binding seems to be uniquely mediated by the peptide insert and to be independent of the sequence of the carrier protein. These findings might be applied in the design...

  3. Urinary Peptide Levels in Patients with Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Mungli Prakash

    2010-10-01

    Full Text Available Introduction: Peptide levels in urine are found to be decreased in renal failure. In the current study urinary peptide levels were determined in chronic renal failure (CRF patients. Method: 86 CRF patients and 80 healthy controls were selected for the study. Urinary proteins and peptide levels were determined by spectrophotometer based Lowry and Bradford methods. Urinary creatinine levels were determined by clinical chemistry analyzer. Results: There was significant decrease in urinary peptide levels in CRF patients and Urinary % peptides were significantly decreased in CRF patients as compared to healthy controls. Urinary % peptides correlated negatively with proteinuria. Conclusion: we have found decrease in urinary peptides and % urinary peptides in CRF patients and possibly measurement of % urinary peptides may possibly serve as better indicator in early detection of impairment in renal function.

  4. Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

    Directory of Open Access Journals (Sweden)

    Heike L Rittner

    2009-04-01

    Full Text Available In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR and/or toll like receptor (TLR agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively. Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, beta-endorphin antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim

  5. Evaluation of the amyloid beta-GFP fusion protein as a model of amyloid beta peptides-mediated aggregation: A study of DNAJB6 chaperone

    Directory of Open Access Journals (Sweden)

    Rasha Mohamed Hussein

    2015-07-01

    Full Text Available Alzheimer’s disease is a progressive neurodegenerative disease characterized by the accumulation and aggregation of extracellular amyloid β (Aβ peptides and intracellular aggregation of hyper-phosphorylated tau protein. Recent evidence indicates that accumulation and aggregation of intracellular amyloid β peptides may also play a role in disease pathogenesis. This would suggest that intracellular Heat Shock Proteins (HSP that maintain cellular protein homeostasis might be candidates for disease amelioration. We recently found that DNAJB6, a member of DNAJ family of heat shock proteins, effectively prevented the aggregation of short aggregation-prone peptides containing large poly glutamines (associated with CAG repeat diseases both in vitro and in cells. Moreover, recent in vitro data showed that DNAJB6 can delay the aggregation of Aβ42 peptides. In this study, we investigated the ability of DNAJB6 to prevent the aggregation of extracellular and intracellular Aβ peptides using transfection of HEK293 cells with Aβ-GFP fusion construct and performing western blotting and immunofluorescence techniques. We found that DNAJB6 indeed suppresses Aβ-GFP aggregation, but not seeded aggregation initiated by extracellular Aβ peptides. Unexpectedly and unlike what we found for peptide-mediated aggregation, DNAJB6 required interaction with HSP70 to prevent the aggregation of the Aβ-GFP fusion protein and its J-domain was crucial for its anti-aggregation effect. In addition, other DNAJ proteins as well as HSPA1a overexpression also suppressed Aβ-GFP aggregation efficiently. Our findings suggest that Aβ aggregation differs from poly Q peptide induced aggregation in terms of chaperone handling and sheds doubt on the usage of Aβ-GFP fusion construct for studying Aβ peptide aggregation in cells.

  6. Peptide inhibition of human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2011-02-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100

  7. Repeated injections of orexin-A developed behavioral tolerance to its analgesic effects in rats

    Directory of Open Access Journals (Sweden)

    Elmira Ghasemi

    2015-12-01

    Full Text Available Objective(s:Reduction of pharmacological effectiveness or tolerance appears following repeated administration of many analgesic drugs. We investigated tolerance to anti-nociceptive effects of orexin-A, an endogenous potent analgesic peptide using the hot-plate test.Materials and Methods:Orexin-A was microinjected ICV (intracerebroventricular with an interval of 12 hr for 7 continuous days and its anti-nociceptive responses were measured on days 1, 4 and 7 using the hot-plate test following the first day of administration. Orexin-A was used at a dose of 100 pmol to induce analgesic effects. Results:ICV administration of orexin-A produced an effective anti-nociception on the first day of experiment as measured by hot-plate 5, 15, and 30 min after the injection, in comparison with both baselines (hot-plate test one day before the beginning of orexin-A administration and control, saline-administrated group. However, repeated administration of orexin-A on the following days revealed a significant reduction in this analgesic effect during day 4 to day 7. However, to rule out any associative tolerance resulting from learning related to experimental procedures and/or environmental cues, a single injection of orexin-A was administrated to animals of control group (which were receiving saline during 7 days of experiments and the analgesic effect was observed. Conclusion:These results, for the first time, indicated the appearance of tolerance to anti-nociceptive effects of orexin-A, following repeated administrations of this agent.

  8. Peptide assembly for nanoscale control of materials

    Science.gov (United States)

    Pochan, Darrin

    2011-03-01

    Self-assembly of molecules is an attractive materials construction strategy due to its simplicity in application. By considering peptidic, charged synthetic molecules in the bottom-up materials self-assembly design process, one can take advantage of inherently biomolecular attributes; intramolecular folding events, secondary structure, and electrostatic interactions; in addition to more traditional self-assembling molecular attributes such as amphiphilicty, to define hierarchical material structure and consequent properties. Design strategies for materials self-assembly based on small (less than 24 amino acids) beta-hairpin peptides will be discussed. Self-assembly of the peptides is predicated on an intramolecular folding event caused by desired solution properties. Importantly, kinetics of self-assembly can be tuned in order to control gelation time. The final gel behaves as a shear thinning, but immediately rehealing, solid that is potentially useful for cell injection therapies. The morphological, and viscoelastic properties of these peptide hydrogels will be discussed. In addition, slight changes in peptide primary sequence can have drastic effects on the self-assembled morphology. Additional sequences will be discussed that do not form hydrogels but rather form nanoscale templates for inorganic material assembly.

  9. Glucagon-Like Peptide-1 Gene Therapy

    Directory of Open Access Journals (Sweden)

    Anne M. Rowzee

    2011-01-01

    Full Text Available Glucagon-like peptide 1 (GLP-1 is a small peptide component of the prohormone, proglucagon, that is produced in the gut. Exendin-4, a GLP-1 receptor agonist originally isolated from the saliva of H. suspectum or Gila monster, is a peptide that shares sequence and functional homology with GLP-1. Both peptides have been demonstrated to stimulate insulin secretion, inhibit glucagon secretion, promote satiety and slow gastric emptying. As such, GLP-1 and Exendin-4 have become attractive pharmaceutical targets as an adjunctive therapy for individuals with type II diabetes mellitus, with several products currently available clinically. Herein we summarize the cell biology leading to GLP-1 production and secretion from intestinal L-cells and the endocrine functions of this peptide and Exendin-4 in humans. Additionally, gene therapeutic applications of GLP-1 and Exendin-4 are discussed with a focus on recent work using the salivary gland as a gene therapy target organ for the treatment of diabetes mellitus.

  10. Peptide synthesis in early earth hydrothermal systems

    Science.gov (United States)

    Lemke, K.H.; Rosenbauer, R.J.; Bird, D.K.

    2009-01-01

    We report here results from experiments and thermodynamic calculations that demonstrate a rapid, temperature-enhanced synthesis of oligopeptides from the condensation of aqueous glycine. Experiments were conducted in custom-made hydrothermal reactors, and organic compounds were characterized with ultraviolet-visible procedures. A comparison of peptide yields at 260??C with those obtained at more moderate temperatures (160??C) gives evidence of a significant (13 kJ ?? mol-1) exergonic shift. In contrast to previous hydrothermal studies, we demonstrate that peptide synthesis is favored in hydrothermal fluids and that rates of peptide hydrolysis are controlled by the stability of the parent amino acid, with a critical dependence on reactor surface composition. From our study, we predict that rapid recycling of product peptides from cool into near-supercritical fluids in mid-ocean ridge hydrothermal systems will enhance peptide chain elongation. It is anticipated that the abundant hydrothermal systems on early Earth could have provided a substantial source of biomolecules required for the origin of life. Astrobiology 9, 141-146. ?? 2009 Mary Ann Liebert, Inc. 2009.

  11. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    Energy Technology Data Exchange (ETDEWEB)

    San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P.R.O. (Harvard-Med); (IIT); (NCSU); (UPENN); (Manchester); (Orthovita)

    2011-09-16

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  12. Dinosaur peptides suggest mechanisms of protein survival.

    Directory of Open Access Journals (Sweden)

    James D San Antonio

    Full Text Available Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  13. Comprehensive computational design of ordered peptide macrocycles

    Science.gov (United States)

    Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram Khipple; Shortridge, Matthew D.; Craven, Timothy W.; Pardo-Avila, Fátima; Rettie, Stephen A.; Kim, David E.; Silva, Daniel-Adriano; Ibrahim, Yehia M.; Webb, Ian K.; Cort, John R.; Adkins, Joshua N.; Varani, Gabriele; Baker, David

    2018-01-01

    Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with L-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L- and D-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods. PMID:29242347

  14. Folding very short peptides using molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Bosco K Ho

    2006-04-01

    Full Text Available Peptides often have conformational preferences. We simulated 133 peptide 8-mer fragments from six different proteins, sampled by replica-exchange molecular dynamics using Amber7 with a GB/SA (generalized-Born/solvent-accessible electrostatic approximation to water implicit solvent. We found that 85 of the peptides have no preferred structure, while 48 of them converge to a preferred structure. In 85% of the converged cases (41 peptides, the structures found by the simulations bear some resemblance to their native structures, based on a coarse-grained backbone description. In particular, all seven of the beta hairpins in the native structures contain a fragment in the turn that is highly structured. In the eight cases where the bioinformatics-based I-sites library picks out native-like structures, the present simulations are largely in agreement. Such physics-based modeling may be useful for identifying early nuclei in folding kinetics and for assisting in protein-structure prediction methods that utilize the assembly of peptide fragments.

  15. Guanylin peptides: cyclic GMP signaling mechanisms

    Directory of Open Access Journals (Sweden)

    Forte L.R.

    1999-01-01

    Full Text Available Guanylate cyclases (GC serve in two different signaling pathways involving cytosolic and membrane enzymes. Membrane GCs are receptors for guanylin and atriopeptin peptides, two families of cGMP-regulating peptides. Three subclasses of guanylin peptides contain one intramolecular disulfide (lymphoguanylin, two disulfides (guanylin and uroguanylin and three disulfides (E. coli stable toxin, ST. The peptides activate membrane receptor-GCs and regulate intestinal Cl- and HCO3- secretion via cGMP in target enterocytes. Uroguanylin and ST also elicit diuretic and natriuretic responses in the kidney. GC-C is an intestinal receptor-GC for guanylin and uroguanylin, but GC-C may not be involved in renal cGMP pathways. A novel receptor-GC expressed in the opossum kidney (OK-GC has been identified by molecular cloning. OK-GC cDNAs encode receptor-GCs in renal tubules that are activated by guanylins. Lymphoguanylin is highly expressed in the kidney and heart where it may influence cGMP pathways. Guanylin and uroguanylin are highly expressed in intestinal mucosa to regulate intestinal salt and water transport via paracrine actions on GC-C. Uroguanylin and guanylin are also secreted from intestinal mucosa into plasma where uroguanylin serves as an intestinal natriuretic hormone to influence body Na+ homeostasis by endocrine mechanisms. Thus, guanylin peptides control salt and water transport in the kidney and intestine mediated by cGMP via membrane receptors with intrinsic guanylate cyclase activity.

  16. Repeated pulsed x-ray emission equipment

    International Nuclear Information System (INIS)

    Terauchi, Hikaru; Iida, Satoshi

    1982-01-01

    X-ray diffraction technique has been applied to determine the spatial positions of atoms which compose a material, and it is needless to say that the technique is a fundamental means regardless of the fields of research. However, the application of X-ray diffraction to the research on physical properties has been so far limited to know the spatial positions of atoms or molecules under thermal equilibrium condition. The addition of time element to the conventional technique, that is, the analysis of material structure including the time-varying processes under non-equilibrium conditions, is considered to approach the elucidation of the essence of materials. The authors call this dynamic structural analysis. The authors have planned to analyze X-ray diffraction intensity which has the resolution of about 10 -8 s in the real time which is conjugate with energy. However, present pulsed X-ray sources are not suitable for diffraction experiment because the pulse width is too long or X-ray wavelength is too short. Accordingly, the authors have made for trial a pulsed X-ray source for diffraction experiment. Its specifications are: diode voltage (X-ray tube voltage) from 200 to 300 kV, diode current from 2 to 5 kA, pulse width of about 30ns, maximum repetition frequency 10 pps, and X-ray focus size of 2 mm diameter. One of the features of this source is the repeated generation of pulsed X-ray. This is the first trial in the world, and is indispensable to the dynamic structural analysis described above. The quality of the emitted X-ray is also written. (Wakatsuki, Y.)

  17. Repeated speech errors: evidence for learning.

    Science.gov (United States)

    Humphreys, Karin R; Menzies, Heather; Lake, Johanna K

    2010-11-01

    Three experiments elicited phonological speech errors using the SLIP procedure to investigate whether there is a tendency for speech errors on specific words to reoccur, and whether this effect can be attributed to implicit learning of an incorrect mapping from lemma to phonology for that word. In Experiment 1, when speakers made a phonological speech error in the study phase of the experiment (e.g. saying "beg pet" in place of "peg bet") they were over four times as likely to make an error on that same item several minutes later at test. A pseudo-error condition demonstrated that the effect is not simply due to a propensity for speakers to repeat phonological forms, regardless of whether or not they have been made in error. That is, saying "beg pet" correctly at study did not induce speakers to say "beg pet" in error instead of "peg bet" at test. Instead, the effect appeared to be due to learning of the error pathway. Experiment 2 replicated this finding, but also showed that after 48 h, errors made at study were no longer more likely to reoccur. As well as providing constraints on the longevity of the effect, this provides strong evidence that the error reoccurrences observed are not due to item-specific difficulty that leads individual speakers to make habitual mistakes on certain items. Experiment 3 showed that the diminishment of the effect 48 h later is not due to specific extra practice at the task. We discuss how these results fit in with a larger view of language as a dynamic system that is constantly adapting in response to experience. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Isolation of human simple repeat loci by hybridization selection.

    Science.gov (United States)

    Armour, J A; Neumann, R; Gobert, S; Jeffreys, A J

    1994-04-01

    We have isolated short tandem repeat arrays from the human genome, using a rapid method involving filter hybridization to enrich for tri- or tetranucleotide tandem repeats. About 30% of clones from the enriched library cross-hybridize with probes containing trimeric or tetrameric tandem arrays, facilitating the rapid isolation of large numbers of clones. In an initial analysis of 54 clones, 46 different tandem arrays were identified. Analysis of these tandem repeat loci by PCR showed that 24 were polymorphic in length; substantially higher levels of polymorphism were displayed by the tetrameric repeat loci isolated than by the trimeric repeats. Primary mapping of these loci by linkage analysis showed that they derive from 17 chromosomes, including the X chromosome. We anticipate the use of this strategy for the efficient isolation of tandem repeats from other sources of genomic DNA, including DNA from flow-sorted chromosomes, and from other species.

  19. Detergent-like actions of linear amphipathic cationic antimicrobial peptides.

    Science.gov (United States)

    Bechinger, Burkhard; Lohner, Karl

    2006-09-01

    Antimicrobial peptides have raised much interest as pathogens become resistant against conventional antibiotics. We review biophysical studies that have been performed to better understand the interactions of linear amphipathic cationic peptides such as magainins, cecropins, dermaseptin, delta-lysin or melittin. The amphipathic character of these peptides and their interactions with membranes resemble the properties of detergent molecules and analogies between membrane-active peptide and detergents are presented. Several models have been suggested to explain the pore-forming, membrane-lytic and antibiotic activities of these peptides. Here we suggest that these might be 'special cases' within complicated phase diagrams describing the morphological plasticity of peptide/lipid supramolecular assemblies.

  20. Insulin and C-peptide in human brain neurons (insulin/C-peptide/brain peptides/immunohistochemistry/radioimmunoassay)

    International Nuclear Information System (INIS)

    Dorn, A.; Bernstein, H.G.; Rinne, A.; Hahn, H.J.; Ziegler, M.

    1983-01-01

    The regional distribution and cellular localization of insulin and C-peptide immunoreactivities were studied in human cadaver brains using the indirect immunofluorescence method, the peroxidase-antiperoxidase technique, and radioimmunoassay. Products of the immune reactions to both polypeptides were observed in most nerve cells in all areas of the brain examined. Immunostaining was mainly restricted to the cell soma and proximal dendrites. Radioimmunoassay revealed that human brain contains insulin and C-peptide in concentrations much higher than the blood, the highest being in the hypothalamus. These findings support the hypothesis that the 'brain insulin' is - at least in part - produced in the CNS. (author)

  1. An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting*

    OpenAIRE

    Saffert, Paul; Adamla, Frauke; Schieweck, Rico; Atkins, John F.; Ignatova, Zoya

    2016-01-01

    Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the −1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded re...

  2. Practical quantum repeaters with parametric down-conversion sources

    Science.gov (United States)

    Krovi, Hari; Guha, Saikat; Dutton, Zachary; Slater, Joshua A.; Simon, Christoph; Tittel, Wolfgang

    2016-03-01

    Conventional wisdom suggests that realistic quantum repeaters will require quasi-deterministic sources of entangled photon pairs. In contrast, we here study a quantum repeater architecture that uses simple parametric down-conversion sources, as well as frequency-multiplexed multimode quantum memories and photon-number-resolving detectors. We show that this approach can significantly extend quantum communication distances compared to direct transmission. This shows that important trade-offs are possible between the different components of quantum repeater architectures.

  3. Assembly of Repeat Content Using Next Generation Sequencing Data

    Energy Technology Data Exchange (ETDEWEB)

    labutti, Kurt; Kuo, Alan; Grigoriev, Igor; Copeland, Alex

    2014-03-17

    Repetitive organisms pose a challenge for short read assembly, and typically only unique regions and repeat regions shorter than the read length, can be accurately assembled. Recently, we have been investigating the use of Pacific Biosciences reads for de novo fungal assembly. We will present an assessment of the quality and degree of repeat reconstruction possible in a fungal genome using long read technology. We will also compare differences in assembly of repeat content using short read and long read technology.

  4. Coexistence of 3G repeaters with LTE base stations.

    Science.gov (United States)

    Yeo, Woon-Young; Lee, Sang-Min; Hwang, Gyung-Ho; Kim, Jae-Hoon

    2013-01-01

    Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters.

  5. Misleading Children: Causal Attributions of Inconsistency under Repeated Questioning.

    Science.gov (United States)

    Siegal, Michael; And Others

    1988-01-01

    Four studies investigated whether inconsistency of children aged four to six on developmental tasks may reflect a misinterpretation of the experimenter's intent in communication under repeated questioning. (SKC)

  6. R-loops: targets for nuclease cleavage and repeat instability.

    Science.gov (United States)

    Freudenreich, Catherine H

    2018-01-11

    R-loops form when transcribed RNA remains bound to its DNA template to form a stable RNA:DNA hybrid. Stable R-loops form when the RNA is purine-rich, and are further stabilized by DNA secondary structures on the non-template strand. Interestingly, many expandable and disease-causing repeat sequences form stable R-loops, and R-loops can contribute to repeat instability. Repeat expansions are responsible for multiple neurodegenerative diseases, including Huntington's disease, myotonic dystrophy, and several types of ataxias. Recently, it was found that R-loops at an expanded CAG/CTG repeat tract cause DNA breaks as well as repeat instability (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Two factors were identified as causing R-loop-dependent breaks at CAG/CTG tracts: deamination of cytosines and the MutLγ (Mlh1-Mlh3) endonuclease, defining two new mechanisms for how R-loops can generate DNA breaks (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Following R-loop-dependent nicking, base excision repair resulted in repeat instability. These results have implications for human repeat expansion diseases and provide a paradigm for how RNA:DNA hybrids can cause genome instability at structure-forming DNA sequences. This perspective summarizes mechanisms of R-loop-induced fragility at G-rich repeats and new links between DNA breaks and repeat instability.

  7. Anisotropic Membrane Curvature Sensing by Amphipathic Peptides.

    Science.gov (United States)

    Gómez-Llobregat, Jordi; Elías-Wolff, Federico; Lindén, Martin

    2016-01-05

    Many proteins and peptides have an intrinsic capacity to sense and induce membrane curvature, and play crucial roles for organizing and remodeling cell membranes. However, the molecular driving forces behind these processes are not well understood. Here, we describe an approach to study curvature sensing by simulating the interactions of single molecules with a buckled lipid bilayer. We analyze three amphipathic antimicrobial peptides, a class of membrane-associated molecules that specifically target and destabilize bacterial membranes, and find qualitatively different sensing characteristics that would be difficult to resolve with other methods. Our findings provide evidence for direction-dependent curvature sensing mechanisms in amphipathic peptides and challenge existing theories of hydrophobic insertion. The buckling approach is generally applicable to a wide range of curvature-sensing molecules, and our results provide strong motivation to develop new experimental methods to track position and orientation of membrane proteins. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  8. Antimicrobial Peptides: Multifunctional Drugs for Different Applications

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht

    2012-02-01

    Full Text Available Antimicrobial peptides (APs are an important part of the innate immune system in epithelial and non-epithelial surfaces. So far, many different antimicrobial peptides from various families have been discovered in non-vertebrates and vertebrates. They are characterized by antibiotic, antifungal and antiviral activities against a variety of microorganisms. In addition to their role as endogenous antimicrobials, APs participate in multiple aspects of immunity. They are involved in septic and non-septic inflammation, wound repair, angiogenesis, regulation of the adaptive immune system and in maintaining homeostasis. Due to those characteristics AP could play an important role in many practical applications. Limited therapeutic efficiency of current antimicrobial agents and the emerging resistance of pathogens require alternate antimicrobial drugs. The purpose of this review is to highlight recent literature on functions and mechanisms of APs. It also shows their current practical applications as peptide therapeutics and bioactive polymers and discusses the possibilities of future clinical developments.

  9. Peptide Based Radiopharmaceuticals: Specific Construct Approach

    Energy Technology Data Exchange (ETDEWEB)

    Som, P; Rhodes, B A; Sharma, S S

    1997-10-21

    The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with 99mTc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures). In this approach, the biological function domain and the 99mTc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step 99mTc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 µM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays

  10. Peptide catalysed prebiotic polymerization of RNA

    DEFF Research Database (Denmark)

    Wieczorek, Rafal; Luisi, Pier Luigi; Monnard, Pierre-Alain

    A short peptide composed of only two amino acid residues, serine and histidine, is here reported to enable oligomerization of RNA monomers. SerHis dipeptide was previously reported to catalyse formation of peptide bonds (Gorlero et al. 2009) as well as possessing broad hydrolytic activities...... – in such environment hydrolysis is thermodynamically favoured over condensation. However, the thermodynamic equilibrium towards condensation can be shifted even in this environment. In this poster we describe a prebiotically plausible system in which the SerHis dipeptide acts as catalyst for the formation of RNA...... these conditions, most of the water is in the form of ice crystals and the other reactants are upconcentrated in the remaining liquid micro-inclusions, hence creating an environment with low water activity in which condensation reactions can occur. The ability of simple peptides to catalyse RNA synthesis could...

  11. Radiolabelled RGD peptides for imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gaertner, F.C.; Schwaiger, M.; Beer, A.J. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kessler, H. [Technische Universitaet Muenchen, Institute for Advanced Study and Center of Integrated Protein Science, Department of Chemistry, Garching (Germany); King Abdulaziz University, Chemistry Department, Faculty of Science, Jeddah (Saudi Arabia); Wester, H.-J. [Institute for Pharmaceutical Radiochemistry, Garching (Germany)

    2012-02-15

    Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting, e.g. for response assessment of such targeted antiangiogenic therapies. One promising approach of angiogenesis imaging is imaging of specific molecular markers of the angiogenic cascade like the integrin {alpha}{sub v}{beta}{sub 3}. For molecular imaging of integrin expression, the use of radiolabelled peptides is still the only approach that has been successfully translated into the clinic. In this review we will summarize the current data on imaging of {alpha}{sub v}{beta}{sub 3} expression using radiolabelled RGD peptides with a focus on tracers already in clinical use. A perspective will be presented on the future clinical use of radiolabelled RGD peptides including an outlook on potential applications for radionuclide therapy. (orig.)

  12. Natriuretic peptides in common valvular heart disease.

    Science.gov (United States)

    Steadman, Christopher D; Ray, Simon; Ng, Leong L; McCann, Gerry P

    2010-05-11

    Valvular heart disease, particularly aortic stenosis and mitral regurgitation, accounts for a large proportion of cardiology practice, and their prevalence is predicted to increase. Management of the asymptomatic patient remains controversial. Biomarkers have been shown to have utility in the management of cardiovascular disease such as heart failure and acute coronary syndromes. In this state-of-the-art review, we examine the current evidence relating to natriuretic peptides as potential biomarkers in aortic stenosis and mitral regurgitation. The natriuretic peptides correlate with measures of disease severity and symptomatic status and also can be used to predict outcome. This review shows that natriuretic peptides have much promise as biomarkers in common valvular heart disease, but the impact of their measurement on clinical practice and outcomes needs to be further assessed in prospective studies before routine clinical use becomes a reality. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. Kinetics of Peptide Folding in Lipid Membranes

    Science.gov (United States)

    Oh, Kwang-Im; Smith-Dupont, Kathryn B.; Markiewicz, Beatrice N.; Gai, Feng

    2015-01-01

    Despite our extensive understanding of water-soluble protein folding kinetics, much less is known about the folding dynamics and mechanisms of membrane proteins. However, recent studies have shown that for relatively simple systems, such as peptides that form a transmembrane α-helix, helical dimer, or helix-turn-helix, it is possible to assess the kinetics of several important steps, including peptide binding to the membrane from aqueous solution, peptide folding on the membrane surface, helix insertion into the membrane, and helix-helix association inside the membrane. Herein, we provide a brief review of these studies and also suggest new initiation and probing methods that could lead to improved temporal and structural resolution in future experiments. PMID:25808575

  14. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

    2016-01-01

    meningitis patients, CSF antibodies are focussed to only one single glycoform peptide of a major viral glycoprotein. Thus, dependent on the viral disease, the serological response may be variable or constant with respect to the number of targeted peptide glycoforms. Mapping of these epitopes relies......Viral envelope glycoproteins are major targets for antibodies that bind to and inactivate viral particles. The capacity of a viral vaccine to induce virus-neutralizing antibodies is often used as a marker for vaccine efficacy. Yet the number of known neutralization target epitopes is restricted...... owing to various viral escape mechanisms. We expand the range of possible viral glycoprotein targets, by presenting a previously unknown type of viral glycoprotein epitope based on a short peptide stretch modified with small O-linked glycans. Besides being immunologically active, these epitopes have...

  15. Design and Application of Antimicrobial Peptide Conjugates

    Directory of Open Access Journals (Sweden)

    Andre Reinhardt

    2016-05-01

    Full Text Available Antimicrobial peptides (AMPs are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry.

  16. Cell-Type Specific Penetrating Peptides: Therapeutic Promises and Challenges

    Directory of Open Access Journals (Sweden)

    Maliha Zahid

    2015-07-01

    Full Text Available Cell penetrating peptides (CPP, also known as protein transduction domains (PTD, are small peptides able to carry peptides, proteins, nucleic acid, and nanoparticles, including viral particles, across the cellular membranes into cells, resulting in internalization of the intact cargo. In general, CPPs can be broadly classified into tissue-specific and non-tissue specific peptides, with the latter further sub-divided into three types: (1 cationic peptides of 6–12 amino acids in length comprised predominantly of arginine, lysine and/or ornithine residues; (2 hydrophobic peptides such as leader sequences of secreted growth factors or cytokines; and (3 amphipathic peptides obtained by linking hydrophobic peptides to nuclear localizing signals. Tissue-specific peptides are usually identified by screening of large peptide phage display libraries. These transduction peptides have the potential for a myriad of diagnostic as well as therapeutic applications, ranging from delivery of fluorescent or radioactive compounds for imaging, to delivery of peptides and proteins of therapeutic potential, and improving uptake of DNA, RNA, siRNA and even viral particles. Here we review the potential applications as well as hurdles to the tremendous potential of these CPPs, in particular the cell-type specific peptides.

  17. Hydroxyapatite Growth Inhibition Effect of Pellicle Statherin Peptides.

    Science.gov (United States)

    Xiao, Y; Karttunen, M; Jalkanen, J; Mussi, M C M; Liao, Y; Grohe, B; Lagugné-Labarthet, F; Siqueira, W L

    2015-08-01

    In our recent studies, we have shown that in vivo-acquired enamel pellicle is a sophisticated biological structure containing a significant portion of naturally occurring salivary peptides. From a functional aspect, the identification of peptides in the acquired enamel pellicle is of interest because many salivary proteins exhibit functional domains that maintain the activities of the native protein. Among the in vivo-acquired enamel pellicle peptides that have been newly identified, 5 peptides are derived from statherin. Here, we assessed the ability of these statherin pellicle peptides to inhibit hydroxyapatite crystal growth. In addition, atomistic molecular dynamics (MD) simulations were performed to better understand the underlying physical mechanisms of hydroxyapatite growth inhibition. A microplate colorimetric assay was used to quantify hydroxyapatite growth. Statherin protein, 5 statherin-derived peptides, and a peptide lacking phosphate at residues 2 and 3 were analyzed. Statherin peptide phosphorylated on residues 2 and 3 indicated a significant inhibitory effect when compared with the 5 other peptides (P hydroxyapatite for phosphopeptides, whereas unphosphorylated peptides interacted weakly with the hydroxyapatite. Our data suggest that the presence of a covalently linked phosphate group (at residues 2 and 3) in statherin peptides modulates the effect of hydroxyapatite growth inhibition. This study provides a mechanism to account for the composition and function of acquired enamel pellicle statherin peptides that will contribute as a base for the development of biologically stable and functional synthetic peptides for therapeutic use against dental caries and/or periodontal disease. © International & American Associations for Dental Research 2015.

  18. Synthetic peptides derived from the sequence of a lasso peptide microcin J25 show antibacterial activity.

    Science.gov (United States)

    Soudy, Rania; Wang, Liru; Kaur, Kamaljit

    2012-03-01

    Microcin J25 (MccJ25) is a plasmid-encoded, ribosomally synthesized antibacterial peptide with a unique lasso structure. The lasso structure, produced with the aid of two processing enzymes, provides exceptional stability to MccJ25. We report the synthesis of six peptides (1-6), derived from the MccJ25 sequence, that are designed to form folded conformation by disulfide bond formation and electrostatic or hydrophobic interactions. Two peptides (1 and 6) display good activity against Salmonella newport, and are the first synthetic derivatives of MccJ25 that are bactericidal. Peptide 1 displays potent activity against several Salmonella strains including two MccJ25 resistant strains. The solution conformation and the stability studies of the active peptides suggest that they do not fold into a lasso conformation and peptide 1 displays antimicrobial activity by inhibition of target cell respiration. Like MccJ25, the synthetic MccJ25 derivatives display minimal toxicity to mammalian cells suggesting that these peptides act specifically on bacterial cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Peptide-Targeted Radionuclide Therapy for Melanoma

    Science.gov (United States)

    Miao, Yubin; Quinn, Thomas P.

    2011-01-01

    Melanocortin-1 receptor (MC1-R) and melanin are two attractive melanoma-specific targets for peptide-targeted radionuclide therapy for melanoma. Radiolabeled peptides targeting MC1-R/melanin can selectively and specifically target cytotoxic radiation generated from therapeutic radionuclides to melanoma cells for cell killing, while sparing the normal tissues and organs. This review highlights the recent advances of peptide-targeted radionuclide therapy of melanoma targeting MC1R and melanin. The promising therapeutic efficacies of 188Re-(Arg11)CCMSH (188Re-[Cys3,4,10, d-Phe7, Arg11]-α-MSH3-13), 177Lu- and 212Pb-labeled DOTA-Re(Arg11)CCMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[ReO-(Cys3,4,10, d-Phe7, Arg11)]-α-MSH3-13) and 188Re-HYNIC-4B4 (188Re-hydrazinonicotinamide-Tyr-Glu-Arg-Lys-Phe-Trp-His-Gly-Arg-His) in preclinical melanoma-bearing models demonstrate an optimistic outlook for peptide-targeted radionuclide therapy for melanoma. Peptide-targeted radionuclide therapy for melanoma will likely contribute in an adjuvant setting, once the primary tumor has been surgically removed, to treat metastatic deposits and for treatment of end-stage disease. The lack of effective treatments for metastatic melanoma and end stage disease underscores the necessity to develop and implement new treatment strategies, such as peptide-targeted radionuclide therapy. PMID:18387816

  20. Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides.

    Science.gov (United States)

    López-García, Belén; Harries, Eleonora; Carmona, Lourdes; Campos-Soriano, Lidia; López, José Javier; Manzanares, Paloma; Gandía, Mónica; Coca, María; Marcos, Jose F

    2015-10-01

    There are short cationic and tryptophan-rich antifungal peptides such as the hexapeptide PAF26 (RKKWFW) that have selective toxicity and cell penetration properties against fungal cells. This study demonstrates that concatemeric peptides with tandem repeats of the heptapeptide PAF54 (which is an elongated PAF26 sequence) show increased fungistatic and bacteriostatic activities while maintaining the absence of hemolytic activity of the monomer. The increase in antimicrobial activity of the double-repeated PAF sequences (diPAFs), compared to the nonrepeated PAF, was higher (4-8-fold) than that seen for the triple-repeated sequences (triPAFs) versus the diPAFs (2-fold). However, concatemerization diminished the fungicidal activity against quiescent spores of the filamentous fungus Penicillium digitatum. Peptide solubility and sensitivity to proteolytic degradation were affected by the design of the concatemers: incorporation of the AGPA sequence hinge to separate PAF54 repeats increased solubility while the C-terminal addition of the KDEL sequence decreased in vitro stability. These results led to the design of the triPAF sequence PAF102 of 30 amino acid residues, with increased antimicrobial activity and minimal inhibitory concentration (MIC) value of 1-5 μM depending on the fungus. Further characterization of the mode-of-action of PAF102 demonstrated that it colocalizes first with the fungal cell wall, it is thereafter internalized in an energy dependent manner into hyphal cells of the filamentous fungus Fusarium proliferatum, and finally kills hyphal cells intracellularly. Therefore, PAF102 showed mechanistic properties against fungi similar to the parental PAF26. These observations are of high interest in the future development of PAF-based antimicrobial molecules optimized for their production in biofactories.

  1. Cardiorespiratory Coordination in Repeated Maximal Exercise

    Directory of Open Access Journals (Sweden)

    Sergi Garcia-Retortillo

    2017-06-01

    Full Text Available Increases in cardiorespiratory coordination (CRC after training with no differences in performance and physiological variables have recently been reported using a principal component analysis approach. However, no research has yet evaluated the short-term effects of exercise on CRC. The aim of this study was to delineate the behavior of CRC under different physiological initial conditions produced by repeated maximal exercises. Fifteen participants performed 2 consecutive graded and maximal cycling tests. Test 1 was performed without any previous exercise, and Test 2 6 min after Test 1. Both tests started at 0 W and the workload was increased by 25 W/min in males and 20 W/min in females, until they were not able to maintain the prescribed cycling frequency of 70 rpm for more than 5 consecutive seconds. A principal component (PC analysis of selected cardiovascular and cardiorespiratory variables (expired fraction of O2, expired fraction of CO2, ventilation, systolic blood pressure, diastolic blood pressure, and heart rate was performed to evaluate the CRC defined by the number of PCs in both tests. In order to quantify the degree of coordination, the information entropy was calculated and the eigenvalues of the first PC (PC1 were compared between tests. Although no significant differences were found between the tests with respect to the performed maximal workload (Wmax, maximal oxygen consumption (VO2 max, or ventilatory threshold (VT, an increase in the number of PCs and/or a decrease of eigenvalues of PC1 (t = 2.95; p = 0.01; d = 1.08 was found in Test 2 compared to Test 1. Moreover, entropy was significantly higher (Z = 2.33; p = 0.02; d = 1.43 in the last test. In conclusion, despite the fact that no significant differences were observed in the conventionally explored maximal performance and physiological variables (Wmax, VO2 max, and VT between tests, a reduction of CRC was observed in Test 2. These results emphasize the interest of CRC

  2. Antimicrobial Peptides, Infections and the Skin Barrier

    DEFF Research Database (Denmark)

    Clausen, Maja Lisa; Agner, Tove

    2016-01-01

    immune responses. AMPs play an essential part in maintaining an optimal and functional skin barrier - not only by direct killing of pathogens, but also by balancing immune responses and interfering in wound healing, cell differentiation, reepithelialization and their synergistic interplay with the skin......The skin serves as a strong barrier protecting us from invading pathogens and harmful organisms. An important part of this barrier comes from antimicrobial peptides (AMPs), which are small peptides expressed abundantly in the skin. AMPs are produced in the deeper layers of the epidermis...

  3. Peptoid-Peptide hybrid backbone architectures

    DEFF Research Database (Denmark)

    Olsen, Christian Adam

    2010-01-01

    Peptidomimetic oligomers and foldamers have received considerable attention for over a decade, with beta-peptides and the so-called peptoids (N-alkylglycine oligomers) representing prominent examples of such architectures. Lately, hybrid or mixed backbones consisting of both alpha- and beta......-amino acids (alpha/beta-peptides) have been investigated in some detail as well. The present Minireview is a survey of the literature concerning hybrid structures of alpha-amino acids and peptoids, including beta-peptoids (N-alkyl-beta-alanine oligomers), and is intended to give an overview of this area...

  4. Antimicrobial peptides in innate immune responses

    DEFF Research Database (Denmark)

    Sorensen, O.E.; Borregaard, N.; Cole, A.M.

    2008-01-01

    Antimicrobial peptides (AMPs) are ancient effector molecules in the innate immune response of eukaryotes. These peptides are important for the antimicrobial efficacy of phagocytes and for the innate immune response mounted by epithelia of humans and other mammals. AMPs are generated either by de...... novo synthesis or by proteolytic cleavage from antimicrobially inactive proproteins. Studies of human diseases and animal studies have given important clues to the in vivo role of AMPs. It is now evident that dysregulation of the generation of AMPs in innate immune responses plays a role in certain...

  5. Radioimmunoassay for C-peptide and proinsulin

    International Nuclear Information System (INIS)

    Heding, L.G.

    1977-01-01

    Proinsulin, the biosynthetic precursor of insulin, was discovered by Steiner et al. (1967) and shown to be converted to insulin and C-peptide in the β-cell. The first part of this paper deals with aspects of the radioimmunoassay for C-peptide with special emphasis on the development and the sources of errors encountered in our laboratory (Heding, 1975; Naithani et al., 1975). The second part deals with the many problems involved in the determination of human proinsulin and describes a direct and specific radioimmunoassay developed for measuring proinsulin in serum with a detection limit of less than 0.01 pmol/ml. (Auth.)

  6. Effect of abomasal glucose infusion on plasma concentrations of gut peptides in periparturient dairy cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Relling, A E; Reynolds, C K

    2010-01-01

    Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic plasma concentrations of gut peptides. The experimental design was a randomi......Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic plasma concentrations of gut peptides. The experimental design...... was a randomized block design with repeated measurements. Cows were assigned to one of 2 treatments: control or infusion of 1,500 g of glucose/d into the abomasum from the day of parturition to 29 d in milk. Cows were sampled 12 ± 6 d prepartum and at 4, 15, and 29 d in milk. Concentrations of glucose......-dependent insulinotropic polypeptide, glucagon-like peptide 1(7-36) amide, and oxyntomodulin were measured in pooled samples within cow and sampling day, whereas active ghrelin was measured in samples obtained 30 min before and after feeding at 0800 h. Postpartum, dry matter intake increased at a lower rate with infusion...

  7. SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis

    Directory of Open Access Journals (Sweden)

    Chang He

    2016-01-01

    Full Text Available Uveitis is a potentially sight-threatening disease characterized by repeated cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates the differentiation of pathogenic Th1 and Th17 cells that mediate uveitis. A SOCS1 mimetic peptide (SOCS1-KIR that inhibits JAK2/STAT1 pathways has recently been shown to suppress experimental autoimmune uveitis (EAU. However, it is not clear whether SOCS1-KIR ameliorated uveitis by targeting JAK/STAT pathways of pathogenic lymphocytes or via inhibition of macrophages and antigen-presenting cells that also enter the retina during EAU. To further investigate mechanisms that mediate SOCS1-KIR effects and evaluate the efficacy of SOCS1-KIR as an investigational drug for chronic uveitis, we induced EAU in rats by adoptive transfer of uveitogenic T-cells and monitored disease progression and severity by slit-lamp microscopy, histology, and optical coherence tomography. Topical administration of SOCS1-KIR ameliorated acute and chronic posterior uveitis by inhibiting Th17 cells and the recruitment of inflammatory cells into retina while promoting expansion of IL-10-producing Tregs. We further show that SOCS1-KIR conferred protection of resident retinal cells that play critical role in vision from cytotoxic effects of inflammatory cytokines by downregulating proapoptotic genes. Thus, SOCS1-KIR suppresses uveitis and confers neuroprotective effects and might be exploited as a noninvasive treatment for chronic uveitis.

  8. Plant elicitor peptides promote plant defences against nematodes in soybean.

    Science.gov (United States)

    Lee, Min Woo; Huffaker, Alisa; Crippen, Devany; Robbins, Robert T; Goggin, Fiona L

    2018-04-01

    Plant elicitor peptides (Peps) are widely distributed among angiosperms, and have been shown to amplify immune responses in multiple plant families. Here, we characterize three Peps from soybean (Glycine max) and describe their effects on plant defences against two damaging agricultural pests, the root-knot nematode (Meloidogyne incognita) and the soybean cyst nematode (Heterodera glycines). Seed treatments with exogenous GmPep1, GmPep2 or GmPep3 significantly reduced the reproduction of both nematodes. Pep treatment also protected plants from the inhibitory effects of root-knot nematodes on above-ground growth, and up-regulated basal expression levels of nematode-responsive defence genes. GmPep1 induced the expression of its propeptide precursor (GmPROPEP1), a nucleotide-binding site leucine-rich repeat protein (NBS-LRR), a pectin methylesterase inhibitor (PMEI), Respiratory Burst Oxidase Protein D (RBOHD) and the accumulation of reactive oxygen species (ROS) in leaves. In addition, GmPep2 and GmPep3 seed treatments up-regulated RBOHD expression and ROS accumulation in roots and leaves. These results suggest that GmPeps activate plant defences through systemic transcriptional reprogramming and ROS signalling, and that Pep seed treatments represent a potential strategy for nematode management. © 2017 BSPP AND JOHN WILEY & SONS LTD.

  9. Repeatability study of replicate crash tests: A signal analysis approach.

    Science.gov (United States)

    Seppi, Jeremy; Toczyski, Jacek; Crandall, Jeff R; Kerrigan, Jason

    2017-10-03

    To provide an objective basis on which to evaluate the repeatability of vehicle crash test methods, a recently developed signal analysis method was used to evaluate correlation of sensor time history data between replicate vehicle crash tests. The goal of this study was to evaluate the repeatability of rollover crash tests performed with the Dynamic Rollover Test System (DRoTS) relative to other vehicle crash test methods. Test data from DRoTS tests, deceleration rollover sled (DRS) tests, frontal crash tests, frontal offset crash tests, small overlap crash tests, small overlap impact (SOI) crash tests, and oblique crash tests were obtained from the literature and publicly available databases (the NHTSA vehicle database and the Insurance Institute for Highway Safety TechData) to examine crash test repeatability. Signal analysis of the DRoTS tests showed that force and deformation time histories had good to excellent repeatability, whereas vehicle kinematics showed only fair repeatability due to the vehicle mounting method for one pair of tests and slightly dissimilar mass properties (2.2%) in a second pair of tests. Relative to the DRS, the DRoTS tests showed very similar or higher levels of repeatability in nearly all vehicle kinematic data signals with the exception of global X' (road direction of travel) velocity and displacement due to the functionality of the DRoTS fixture. Based on the average overall scoring metric of the dominant acceleration, DRoTS was found to be as repeatable as all other crash tests analyzed. Vertical force measures showed good repeatability and were on par with frontal crash barrier forces. Dynamic deformation measures showed good to excellent repeatability as opposed to poor repeatability seen in SOI and oblique deformation measures. Using the signal analysis method as outlined in this article, the DRoTS was shown to have the same or better repeatability of crash test methods used in government regulatory and consumer evaluation test

  10. Antimicrobial activity of human islet amyloid polypeptides: an insight into amyloid peptides' connection with antimicrobial peptides.

    Science.gov (United States)

    Wang, Lan; Liu, Qian; Chen, Jin-Chun; Cui, Yi-Xian; Zhou, Bing; Chen, Yong-Xiang; Zhao, Yu-Fen; Li, Yan-Mei

    2012-07-01

    Human islet amyloid polypeptide (hIAPP) shows an antimicrobial activity towards two types of clinically relevant bacteria. The potency of hIAPP varies with its aggregation states. Circular dichroism was employed to determine the interaction between hIAPP and bacteria lipid membrane mimic. The antimicrobial activity of each aggregate species is associated with their ability to induce membrane disruption. Our findings provide new evidence revealing the antimicrobial activity of amyloid peptide, which suggest a possible connection between amyloid peptides and antimicrobial peptides.

  11. Local helix content and RNA-binding activity of the N-terminal leucine-repeat region of hepatitis delta antigen

    Energy Technology Data Exchange (ETDEWEB)

    Cheng Jyawei; Lin Ijin; Lou Yuanchou; Pai Mingtao [National Tsing Hua University, Department of Life Science (China); Wu Hueynan [Academia Sinica, Institute of Molecular Biology (China)

    1998-07-15

    Hepatitis delta virus (HDV) is a satellite virus of the hepatitis B virus (HBV) which provides the surface antigen for the viral coat. Our results show that the N-terminal leucine-repeat region of hepatitis delta antigen (HDAg), encompassing residues 24-50, binds to the autolytic domain of HDV genomic RNA and attenuates its autolytic activity. The solution conformation of a synthetic peptide corresponding to residues 24-50 of HDAg as determined by two-dimensional {sup 1}H NMR and circular dichroism techniques is found to be an {alpha}-helix. The local helix content of this peptide was analyzed by NOEs and coupling constants. Mutagenesis studies indicate that Lys{sup 38}, Lys{sup 39}, and Lys{sup 40} within this {alpha}-helical peptide may be directly involved in RNA binding. A structural knowledge of the N-terminal leucine-repeat region of HDAg thus provides a molecular basis for understanding its role in the interaction with RNA.

  12. Bombesin and Neurotensin Receptor Targeting Using Radiolabeled Peptide Analogs

    NARCIS (Netherlands)

    M. de Visser (Monique)

    2007-01-01

    textabstractSomatostatin receptor-targeting peptides are widely used for imaging and therapy of neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor patients with radiolabeled somatostatin analogs has resulted in symptomatic improvement, prolonged survival and

  13. Effect of Fatty Acid Conjugation on Antimicrobial Peptide Activity

    National Research Council Canada - National Science Library

    Chu-Kung, Alexander F; Bozzelli, Kristen N; Nguyen, Rose; Tirrell, Matthew V

    2004-01-01

    .... In the presence of bacteria-mimicking phospholipid vesicles fatty acid conjugates of the amphipathic peptide, AKK, show a larger change in helical structure than either of the unmodified peptides...

  14. [Screening of three novel antimicrobial peptides with antifungal pathogens].

    Science.gov (United States)

    Lan, Jinping; Li, Liyun; Wang, Yang; Wang, Xianyun; Liu, Lijuan; Liu, Gouzhen; Cheng, Xiongying

    2011-12-01

    In order to discover novel antimicrobial peptides against important crop pathogens, we designed and screened a high capacity random peptide library and isolated a number of clones expressing peptides with antifungal activity. We selected 96 peptides from the library and synthesized their sequence, which were used to assay their activity against crop fungal pathogens. Using agar diffusion assay, these peptides were assayed for their activity against pathogens that cause cotton Fusarium wilt (Fusarium f. sp, vasinfecum), cotton red rot (Fusarium moniliforme), wheat spot blotch (Bipolaris sorokiniana) and potato early blight (Alternaria solani). The three random peptides, A6, D4 and F10, showed the strongest activity against the above four crop fungal pathogens. Through Blastp analysis, we did not find they have homologous sequences with known antimicrobial peptides. The novel antimicrobial peptides will provide gene resources for preventing important crop pathogens.

  15. Evaluation of MAP-specific peptides following vaccination of goats

    DEFF Research Database (Denmark)

    Lybeck, Kari; Sjurseth, Siri K.; Melvang, Heidi Mikkelsen

    01 adjuvant/CAF04 for boosting). Four MAP-infected goats were also vaccinated. In a second vaccination trail, groups of 8 healthy goat kids were vaccinated with genome-based peptides, selected peptides or selected peptides linked together in a recombinant protein (20 µg/peptide or 50 µg protein......Our aim is to develop a subunit MAP vaccine not interfering with the diagnosis of paratuberculosis or bovine tuberculosis. This study’s objective was to evaluate MAP-specific peptides defined by in silico analysis. Peptides were picked by 1) comparing MAP genomes to that of other mycobacterium...... species or 2) selected based on “experience”. Peptides predicted to bind bovine MHC II by in silico analysis were included in further studies, resulting in two panels 1) genome-based and 2) selected. Initially, two groups of 15 healthy goats were vaccinated with one of the two panels (50 µg/peptide in CAF...

  16. Microwave heating in peptide side chain modification via cysteine alkylation.

    Science.gov (United States)

    Calce, Enrica; De Luca, Stefania

    2016-09-01

    Microwave irradiation has been successfully applied to a selective synthetic procedure for introducing molecular substituents on peptides, providing a noticeable reduction of the reaction time and also an increased crude peptide purity for some compounds.

  17. Helical synthetic peptides that stimulate cellular cholesterol efflux

    Science.gov (United States)

    Bielicki, John K.; Natarajan, Pradeep

    2010-04-06

    The present invention provides peptides comprising at least one amphipathic alpha helix and having an cholesterol mediating activity and a ABCA stabilization activity. The invention further provides methods of using such peptides.

  18. Screening And Optimizing Antimicrobial Peptides By Using SPOT-Synthesis

    Science.gov (United States)

    López-Pérez, Paula M.; Grimsey, Elizabeth; Bourne, Luc; Mikut, Ralf; Hilpert, Kai

    2017-04-01

    Peptide arrays on cellulose are a powerful tool to investigate peptide interactions with a number of different molecules, for examples antibodies, receptors or enzymes. Such peptide arrays can also be used to study interactions with whole cells. In this review, we focus on the interaction of small antimicrobial peptides with bacteria. Antimicrobial peptides (AMPs) can kill multidrug-resistant (MDR) human pathogenic bacteria and therefore could be next generation antibiotics targeting MDR bacteria. We describe the screen and the result of different optimization strategies of peptides cleaved from the membrane. In addition, screening of antibacterial activity of peptides that are tethered to the surface is discussed. Surface-active peptides can be used to protect surfaces from bacterial infections, for example implants.

  19. Witness recall across repeated interviews in a case of repeated abuse.

    Science.gov (United States)

    Brubacher, Sonja P; La Rooy, David

    2014-02-01

    In this illustrative case study we examine the three forensic interviews of a girl who experienced repeated sexual abuse from ages 7 to 11. She disclosed the abuse after watching a serialized television show that contained a storyline similar to her own experience. This triggered an investigation that ended in successful prosecution of the offender. Because this case involved abuse that was repeated on a weekly basis for 4 years we thus investigated the degree to which the child's narrative reflected specific episodes or generic accounts, and both the interviewer's and child's attempts to elicit and provide, respectively, specific details across the 3 interviews collected in a 1 month period. Across the 3 interviews, the child's account was largely generic, yet on a number of occasions she provided details specific to individual incidents (episodic leads) that could have been probed further. As predicted: earlier interviews were characterized more by episodic than generic prompts and the reverse was true for the third interview; the child often responded using the same style of language (episodic or generic) as the interviewer; and open questions yielded narrative information. We discuss the importance of adopting children's words to specify occurrences, and the potential benefits of permitting generic recall in investigative interviews on children's ability to provide episodic leads. Despite the fact that the testimony was characterized by generic information about what usually happened, rather than specific episodic details about individual occurrences, this case resulted in successful prosecution. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Constraining cyclic peptides to mimic protein structure motifs

    DEFF Research Database (Denmark)

    Hill, Timothy A.; Shepherd, Nicholas E.; Diness, Frederik

    2014-01-01

    Many proteins exert their biological activities through small exposed surface regions called epitopes that are folded peptides of well-defined three-dimensional structures. Short synthetic peptide sequences corresponding to these bioactive protein surfaces do not form thermodynamically stable...... and proteins, and identifies some additional restraints incorporated into natural product cyclic peptides and synthetic macrocyclic pepti-domimetics that refine peptide structure and confer biological properties....

  1. B-type natriuretic peptide secretion following scuba diving

    DEFF Research Database (Denmark)

    Passino, Claudio; Franzino, Enrico; Giannoni, Alberto

    2011-01-01

    To examine the neurohormonal effects of a scuba dive, focusing on the acute changes in the plasma concentrations of the different peptide fragments from the B-type natriuretic peptide (BNP) precursor.......To examine the neurohormonal effects of a scuba dive, focusing on the acute changes in the plasma concentrations of the different peptide fragments from the B-type natriuretic peptide (BNP) precursor....

  2. Peptide fibrils with altered stability, activity, and cell selectivity

    OpenAIRE

    Chen, Long; Liang, Jun F.

    2013-01-01

    Peptides have some unique and superior features compared to proteins. However, the use of peptides as therapeutics is hampered by their low stability and cell selectivity. In this study, a new lytic peptide (CL-1, FLGALFRALSRLL) was constructed. Under the physiological condition, peptide CL-1 self-assembled into dynamically stable aggregates with fibrils-like structures. Aggregated CL-1 demonstrated dramatically altered activity and stability in comparison with single molecule CL-1 and other ...

  3. Huntingtin gene repeat size variations affect risk of lifetime depression

    NARCIS (Netherlands)

    Gardiner, Sarah L.; van Belzen, Martine J.; Boogaard, Merel W.; van Roon-Mom, Willeke M. C.; Rozing, Maarten P.; van Hemert, Albert M.; Smit, Johannes H.; Beekman, Aartjan T. F.; van Grootheest, Gerard; Schoevers, Robert A.; Voshaar, Richard C. Oude; Roos, Raymund A. C.; Comijs, Hannie C.; Penninx, Brenda W. J. H.; van der Mast, Roos C.; Aziz, N. Ahmad

    2017-01-01

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect

  4. Triplet repeat DNA structures and human genetic disease: dynamic ...

    Indian Academy of Sciences (India)

    Unknown

    alternative to double-stranded DNA (table 2). These include single-stranded hairpins, triplex and quadruplex. DNA, and slipped-strand DNA. Studies have also con- firmed that the formation of alternative structures occurs in trinucleotide repeat sequences. Linear DNA molecules containing triplet repeats have unusual ...

  5. CTG trinucleotide repeat "big jumps": large expansions, small mice.

    Directory of Open Access Journals (Sweden)

    Mário Gomes-Pereira

    2007-04-01

    Full Text Available Trinucleotide repeat expansions are the genetic cause of numerous human diseases, including fragile X mental retardation, Huntington disease, and myotonic dystrophy type 1. Disease severity and age of onset are critically linked to expansion size. Previous mouse models of repeat instability have not recreated large intergenerational expansions ("big jumps", observed when the repeat is transmitted from one generation to the next, and have never attained the very large tract lengths possible in humans. Here, we describe dramatic intergenerational CTG*CAG repeat expansions of several hundred repeats in a transgenic mouse model of myotonic dystrophy type 1, resulting in increasingly severe phenotypic and molecular abnormalities. Homozygous mice carrying over 700 trinucleotide repeats on both alleles display severely reduced body size and splicing abnormalities, notably in the central nervous system. Our findings demonstrate that large intergenerational trinucleotide repeat expansions can be recreated in mice, and endorse the use of transgenic mouse models to refine our understanding of triplet repeat expansion and the resulting pathogenesis.

  6. Towards accurate de novo assembly for genomes with repeats

    NARCIS (Netherlands)

    Bucur, Doina

    2017-01-01

    De novo genome assemblers designed for short k-mer length or using short raw reads are unlikely to recover complex features of the underlying genome, such as repeats hundreds of bases long. We implement a stochastic machine-learning method which obtains accurate assemblies with repeats and

  7. REPEAT BURGLARY VICTIMIZATION : RESULTS OF EMPIRICAL RESEARCH by

    NARCIS (Netherlands)

    Kleemans, E R

    2001-01-01

    This paper explores some theoretical notions about repeat burglary inctimization, and reports findings from research into repeat victimization of residential burglary in the city of Bnschede, the Nether- lands, using police records over a period of six years. The study shows that there is a highly

  8. Secret key rates for an encoded quantum repeater

    Science.gov (United States)

    Bratzik, Sylvia; Kampermann, Hermann; Bruß, Dagmar

    2014-03-01

    We investigate secret key rates for the quantum repeater using encoding [L. Jiang et al., Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325] and compare them to the standard repeater scheme by Briegel, Dür, Cirac, and Zoller. The former scheme has the advantage of a minimal consumption of classical communication. We analyze the trade-off in the secret key rate between the communication time and the required resources. For this purpose we introduce an error model for the repeater using encoding which allows for input Bell states with a fidelity smaller than one, in contrast to the model given by L. Jiang et al. [Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325]. We show that one can correct additional errors in the encoded connection procedure of this repeater and develop a suitable decoding algorithm. Furthermore, we derive the rate of producing entangled pairs for the quantum repeater using encoding and give the minimal parameter values (gate quality and initial fidelity) for establishing a nonzero secret key. We find that the generic quantum repeater is optimal regarding the secret key rate per memory per second and show that the encoded quantum repeater using the simple three-qubit repetition code can even have an advantage with respect to the resources compared to other recent quantum repeater schemes with encoding.

  9. a cause of repeated myocardial infarction and symptomatic 'torsade ...

    African Journals Online (AJOL)

    Repeated serial enzyme estimations and resting ECGs were all within normal limits. 'Ventricular ectopic activity also appeared to have regressed. Submaximal treadmill stress testing was repeated but this failed to show any ischaemia or provoke ventricular arrhythmias. A thallium-20I exercise test was then performed,.

  10. Huntingtin gene repeat size variations affect risk of lifetime depression

    DEFF Research Database (Denmark)

    Gardiner, Sarah L.; van Belzen, Martine J.; Boogaard, Merel W.

    2017-01-01

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect...

  11. Trinucleotide repeat microsatellite markers for Black Poplar (Populus nigra L.)

    NARCIS (Netherlands)

    Smulders, M.J.M.; Schoot, van der J.; Arens, P.; Vosman, B.

    2001-01-01

    Using an enrichment procedure, we have cloned microsatellite repeats from black poplar (Populus nigra L.) and developed primers for microsatellite marker analysis. Ten primer pairs, mostly for trinucleotide repeats, produced polymorphic fragments in P. nigra. Some of them also showed amplification

  12. Large cryptic internal sequence repeats in protein structures from ...

    Indian Academy of Sciences (India)

    Prakash

    Like similar repeats, Proline and Histidine had a low propensity. This may be because Histidine is involved in the active site and is highly conserved, while Proline has a specific function in the three-dimensional structure of the protein. Figure 4. The propensity of different amino acids to form different types of repeats is ...

  13. Development of Repeated Sprint Ability in Talented Youth Basketball Players

    NARCIS (Netherlands)

    te Wierike, Sanne C. M.; de Jong, Mark C.; Tromp, Eveline J. Y.; Vuijk, Pieter J.; Lemmink, Koen A. P. M.; Malina, Robert M.; Elferink-Gemser, Marije T.; Visscher, Chris

    te Wierike, SCM, de Jong, MC, Tromp, EJY, Vuijk, PJ, Lemmink, KAPM, Malina, RM, Elferink-Gemser, MT, and Visscher, C. Development of repeated sprint ability in talented youth basketball players. J Strength Cond Res 28(4): 928-934, 2014-Factors affecting repeated sprint ability (RSA) were evaluated

  14. Ocular surface sensitivity repeatability with Cochet-Bonnet esthesiometer.

    Science.gov (United States)

    Chao, Cecilia; Stapleton, Fiona; Badarudin, Ezailina; Golebiowski, Blanka

    2015-02-01

    To determine the repeatability of ocular surface threshold measurements using the Cochet-Bonnet esthesiometer on the same day and 3 months apart. Two separate studies were conducted to determine the repeatability of ocular surface threshold measurements made on the same day (n = 20 subjects) and 3 months apart (n = 29 subjects). The Cochet-Bonnet esthesiometer was used to measure corneal and inferior conjunctival thresholds using the ascending method of limits. The pressure exerted by the Cochet-Bonnet esthesiometer was determined using an analytical balance, for both the 0.08- and 0.12-mm-diameter filaments. This calibration was then used to convert filament length measurements to pressure. Repeatability was determined using a Bland and Altman analysis. The pressure exerted at each filament length differed between the two filament diameters. The measured pressure also differed from values provided by the manufacturer. Repeatability of threshold measurements at the central cornea was shown to be good, with better repeatability for same-day measurements (coefficient of repeatability [CoR] = ±0.23 g/mm²) than for those 3 months apart (CoR = ±0.52 g/mm²). Threshold measurements at the inferior conjunctiva, in contrast, were poorly repeatable (CoR = ±12.78 g/mm²). Cochet-Bonnet esthesiometry is repeatable when performed on the central cornea on the same day and 3 months apart, but this instrument is not recommended for conjunctival threshold measurements.

  15. Repeated annual influenza vaccination and vaccine effectiveness: review of evidence.

    Science.gov (United States)

    Belongia, Edward A; Skowronski, Danuta M; McLean, Huong Q; Chambers, Catharine; Sundaram, Maria E; De Serres, Gaston

    2017-07-01

    Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain. Areas covered: A meta-analysis of vaccine effectiveness studies from 2010-11 through 2014-15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014-15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2. Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations.

  16. Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus

    Science.gov (United States)

    2011-01-01

    Background Chronic, infected wounds typically contain multiple genera of bacteria, including Staphylococcus aureus, many of which are strong biofilm formers. Bacterial biofilms are thought to be a direct impediment to wound healing. New therapies that focus on a biofilm approach may improve the recovery and healing rate for infected wounds. In this study, cathelicidins and related short, synthetic peptides were tested for their anti-microbial effectiveness as well as their ability to inhibit the ability of S. aureus to form biofilms. Results The helical human cathelicidin LL-37 was tested against S. aureus, and was found to exhibit effective anti-microbial, anti-attachment as well as anti-biofilm activity at concentrations in the low μg/ml range. The effect of peptide chirality and associated protease-resistance was explored through the use of an all-D amino acid peptide, D-LL-37, and in turn compared to scrambled LL-37. Helical cathelicidins have been identified in other animals such as the Chinese cobra, Naja atra (NA-CATH). We previously identified an 11-residue imperfectly repeated pattern (ATRA motif) within the sequence of NA-CATH. A series of short peptides (ATRA-1, -2, -1A), as well as a synthetic peptide, NA-CATH:ATRA1-ATRA1, were designed to explore the significance of the conserved residues within the ATRA motif for anti-microbial activity. The CD spectrum of NA-CATH and NA-CATH:ATRA1-ATRA1 revealed the structural properties of these peptides and suggested that helicity may factor into their anti-microbial and anti-biofilm activities. Conclusions The NA-CATH:ATRA1-ATRA1 peptide inhibits the production of biofilm by S. aureus in the presence of salt, exhibiting anti-biofilm activity at lower peptide concentrations than NA-CATH, LL-37 and D-LL-37; and demonstrates low cytoxicity against host cells but does not affect bacterial attachment. The peptides utilized in this anti-biofilm approach may provide templates for a new group of anti-microbials and

  17. Natural conception: repeated predictions over time.

    Science.gov (United States)

    van Eekelen, R; Scholten, I; Tjon-Kon-Fat, R I; van der Steeg, J W; Steures, P; Hompes, P; van Wely, M; van der Veen, F; Mol, B W; Eijkemans, M J; Te Velde, E R; van Geloven, N

    2017-02-01

    How can we predict chances of natural conception at various time points in couples diagnosed with unexplained subfertility? We developed a dynamic prediction model that can make repeated predictions over time for couples with unexplained subfertility that underwent a fertility workup at a fertility clinic. The most frequently used prediction model for natural conception (the 'Hunault model') estimates the probability of natural conception only once per couple, that is, after completion of the fertility workup. This model cannot be used for a second or third time for couples who wish to know their renewed chances after a certain period of expectant management. A prospective cohort studying the long-term follow-up of subfertile couples included in 38 centres in the Netherlands between January 2002 and February 2004. Couples with bilateral tubal occlusion, anovulation or a total motile sperm count conception, leading to an ongoing pregnancy. Follow-up time was censored at the start of treatment or at the last date of contact. In developing the new dynamic prediction model, we used the same predictors as the Hunault model, i.e. female age, duration of subfertility, female subfertility being primary or secondary, sperm motility and referral status. The performance of the model was evaluated in terms of calibration and discrimination. Additionally, we assessed the utility of the model in terms of the variability of the calculated predictions. Of the 4999 couples in the cohort, 1053 (21%) women reached a natural conception leading to an ongoing pregnancy within a mean follow-up of 8 months (5th and 95th percentile: 1-21). Our newly developed dynamic prediction model estimated the median probability of conceiving in the first year after the completion of the fertility workup at 27%. For couples not yet pregnant after half a year, after one year and after one and a half years of expectant management, the median probability of conceiving over the next year was estimated at

  18. Consistency of Repeated Naming in Aphasia

    Directory of Open Access Journals (Sweden)

    Elizabeth E. Galletta

    2015-09-01

    Full Text Available Background People with mild aphasia and healthy elderly often exhibit similar impairments on language tests of word retrieval. However, variable practice effects in object naming by three individuals with aphasia compared to young and elderly adults have been reported (Wingfield et al. 2006. Wingfield et al. (2006 found that naming of the same pictures of objects over five trials demonstrated decreasing response latencies over repeated trials for both older and younger adults, but not for individuals with aphasia. In fact, among their three participants with aphasia, response latencies in the consecutive trials differed considerably. The authors suggested that different underlying processes may be involved in word retrieval for people with aphasia compared to adults without brain injuries. In our study we aimed to further consider the effect of practice on both object and action naming in individuals with mild aphasia. Method One woman with anomic aphasia (age 38 years; WAB Aphasia Quotient = 88 and one healthy woman (age 25 years participated. Both were native English speakers and reported 18 years of formal education. Participants were tested individually, with a set of 27 object pictures and a set of 27 action pictures presented one at a time on a computer screen. The participants were instructed to name each picture as quickly as possible as soon as each picture appeared on the screen. There were 10 trials of each set of pictures, with different random orders for each trial. The order of presentation of the object and action picture sets alternated across participants. Naming responses were recorded to computer sound files for later measurements of response latencies. A brief tone was presented simultaneous with the picture onset, allowing later measurement of response latencies from the onset of picture presentation to the onset of the participant’s correct response. Results Our findings resembled those reported in Wingfield et al. (2006

  19. Genome-Wide Sensitivity Analysis of the Microsymbiont Sinorhizobium meliloti to Symbiotically Important, Defensin-Like Host Peptides

    Directory of Open Access Journals (Sweden)

    Markus F. F. Arnold

    2017-08-01

    Full Text Available The model legume species Medicago truncatula expresses more than 700 nodule-specific cysteine-rich (NCR signaling peptides that mediate the differentiation of Sinorhizobium meliloti bacteria into nitrogen-fixing bacteroids. NCR peptides are essential for a successful symbiosis in legume plants of the inverted-repeat-lacking clade (IRLC and show similarity to mammalian defensins. In addition to signaling functions, many NCR peptides exhibit antimicrobial activity in vitro and in vivo. Bacterial resistance to these antimicrobial activities is likely to be important for symbiosis. However, the mechanisms used by S. meliloti to resist antimicrobial activity of plant peptides are poorly understood. To address this, we applied a global genetic approach using transposon mutagenesis followed by high-throughput sequencing (Tn-seq to identify S. meliloti genes and pathways that increase or decrease bacterial competitiveness during exposure to the well-studied cationic NCR247 peptide and also to the unrelated model antimicrobial peptide polymyxin B. We identified 78 genes and several diverse pathways whose interruption alters S. meliloti resistance to NCR247. These genes encode the following: (i cell envelope polysaccharide biosynthesis and modification proteins, (ii inner and outer membrane proteins, (iii peptidoglycan (PG effector proteins, and (iv non-membrane-associated factors such as transcriptional regulators and ribosome-associated factors. We describe a previously uncharacterized yet highly conserved peptidase, which protects S. meliloti from NCR247 and increases competitiveness during symbiosis. Additionally, we highlight a considerable number of uncharacterized genes that provide the basis for future studies to investigate the molecular basis of symbiotic development as well as chronic pathogenic interactions.

  20. Repeat profile analysis in an x-ray department

    International Nuclear Information System (INIS)

    Bassey, C.E.; Ojo, O.O.; Akpabio, I.

    1991-01-01

    The repeat profile of an x-ray department in a developing country was analysed monthly between July 1989 and June 1990. Results showed an average repeat rate of 3.7% for the period of study. The main causes of film repetition were: equipment fault, 33.9%; radiographer's fault, 27.4%; film fault, 19.3%; processing fault, 10.8% and patient's fault, 8.6%. The average repeat rate in the first 6 months of study reduced by 50% in the last 6 months. This was due to the effectiveness of implementation of corrective actions. The overall repeat rate was found to correlate well with both the equipment fault and radiographer's fault with correlation coefficients, r, of 0.94 and 0.91, respectively. It is expected that a further reduction in the repeat rate will be obtained after the introduction of quality assurance programmes. (author)