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Sample records for materialy pouzite pro

  1. ProMat

    SciTech Connect

    2008-06-12

    ProMAT is a software tool for statistically analyzing data from enzyme-linked immunosorbent assay microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code

  2. Fibrinopeptide A binds Gly-Pro-Arg-Pro.

    PubMed Central

    Root-Bernstein, R S; Westall, F C

    1984-01-01

    The tetrapeptide Gly-Pro-Arg-Pro inhibits fibrinogen aggregation, probably by binding to the same sites used during initiation of fibrin formation. The Gly-Pro-Arg-Pro binding sites have not yet been identified. However, their possible sequence and locations have been predicted on the basis of the amino acid pairing hypothesis. One of these predicted sites is on fibrinopeptide A. We report here that nuclear magnetic resonance studies indicate that Gly-Pro-Arg-Pro binds to fibrinopeptide A with a binding constant, K, of ca. 10(4) per mol. We also report results of 19 related peptide combinations used as controls. PMID:6589598

  3. TOXIRAE PRO PID

    EPA Science Inventory

    The ToxiRAE Pro PID measures total volatile organic compounds (VOCs) using a photoionization detector (PID). This sensor can be programmed to measure concentrations of a specified compound automatically and has a real time reading of VOC concentrations in parts per million (ppm) ...

  4. Pro-Active Behavior Management.

    ERIC Educational Resources Information Center

    McCormack, James E., Jr.

    The paper outlines the basic tactics in pro-active behavior management, a behavior modification approach for use with severely handicapped students which reorders the staff/student relationship by focusing on positive interaction. Pro-active behavior management is noted to involve interruption of established behavior chains, environmental…

  5. Tempus Pro Patient Monitoring System

    DTIC Science & Technology

    2015-04-03

    AFRL-SA-WP-TR-2015-0006 Tempus Pro Patient Monitoring System Nigel D. Pritchard 3 April 2015 Final Report... System 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Nigel D. Pritchard 5e. TASK NUMBER...subsequent demonstration of the Tempus Pro patient monitoring system to include the AF3899L critical care patient movement record. 15. SUBJECT TERMS

  6. [Pro Familia statistics for 1974].

    PubMed

    1975-09-01

    Statistics for 1974 for the West German family planning organization Pro Familia are reported. 56 offices are now operating, and 23,726 clients were seen. Men were seen more frequently than previously. 10,000 telephone calls were also handled. 16-25 year olds were increasingly represented in the clientele, as were unmarried persons of all ages. 1,242 patients were referred to physicians or clinics for clinical diagnosis.

  7. ["Pro Ana": Psychodynamic References for Anorexia Nervosa].

    PubMed

    Siefert, Linda

    2017-02-01

    "Pro Ana": Psychodynamic References for Anorexia Nervosa The internet-based phenomenon "Pro Ana" refers to the eating disorder anorexia nervosa in a positive way. To understand what the phenomenon "Pro Ana" represents, the websites are used as a starting point of the current analysis. Based on these results, similarities and differences between "Pro Ana" and the eating disorder anorexia nervosa are discussed. Furthermore psychodynamic references for anorexia nervosa are derived and finally their importance for treatment motivation will be considered.

  8. Corner Office: ProQuest's Marty Kahn

    ERIC Educational Resources Information Center

    Fialkoff, Francine; Oder, Norman

    2009-01-01

    In a scant three years at ProQuest, Marty Kahn, CEO, has moved a company coming out of a financial morass back onto solid ground. He came on board after the purchase of ProQuest Information and Learning by the (mostly) privately owned Cambridge Information Group in late 2006 and the merger of ProQuest and CSA to form ProQuest CSA. (It's now just…

  9. BNP and NT-proBNP Test

    MedlinePlus

    ... Peptides Formal name: B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide Related tests: Cardiac ... for B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) is ...

  10. Rat pro-opiomelanocortin contains sulfate

    SciTech Connect

    Hoshina, H.; Hortin, G.; Boime, I.

    1982-07-02

    Intermediate lobes isolated from rat pituitary glands incorporated (/sup 35/S)sulfate into pro-opiomelanocortin and other adrenocorticotropic hormone-containing peptides. Incubation of intermediate lobes in medium containing the arginine analog canavanine inhibited the cleavage of pro-opiomelanocortin into smaller products. Pro-opiomelanocortin that accumulated in the presence of canavanine was also sulfated.

  11. ProMAT: protein microarray analysis tool

    SciTech Connect

    White, Amanda M.; Daly, Don S.; Varnum, Susan M.; Anderson, Kevin K.; Bollinger, Nikki; Zangar, Richard C.

    2006-04-04

    Summary: ProMAT is a software tool for statistically analyzing data from ELISA microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code. Availability: ProMAT is available at http://www.pnl.gov/statistics/ProMAT. ProMAT requires Java version 1.5.0 and R version 1.9.1 (or more recent versions) which are distributed with the tool.

  12. proPSA — EDRN Public Portal

    Cancer.gov

    ProPSA (-2), or [-2]proPSA, is a PSA isoform which has a leader peptide (-2) amino acids at its N terminal region and does not interact with ACT or alpha-2-macroglobulin or spermidine and therefore is detected as a separate isoform. ProPSA is produced primarily in the peripheral zone of the prostate gland and therefore is very useful in distinguishing between prostate cancer patients with PSA range of 2-10, from those who have BPH. Percent proPSA is the ratio of proPSA to free PSA. In July 2012 the FDA approved an assay measuring levels of [-2]proPSA for monitoring and diagnostic purposes.

  13. Clinton administration shows pro-gas bias

    SciTech Connect

    Patrick, L.

    1993-02-01

    President Bill Clinton's cabinet appointments signify a strong shift to more pro-environmental, proconservation energy policies. Clinton signaled a pro-consumer, pro-conservation tilt for the Energy Department with the nomination of Hazel O'Leary, an executive vice president of Northern States Power Co., Minneapolis, to be Secretary of Energy. O'Leary will be responsible for implementing the new National Energy Policy Act, which must resolve a number of energy efficiency and conservation issues.

  14. AnswerPro: Designing to Motivate Interaction

    ERIC Educational Resources Information Center

    AlSugair, Balsam; Hopkins, Gail; FitzGerald, Elizabeth; Brailsford, Tim

    2014-01-01

    This paper describes the design and initial testing of AnswerPro, a mobile academic peer support system for school pupils aged 11-16 years. AnswerPro is a mobile optimised web application that enables pupils to seek support with school work from knowledgeable peers on various subjects. This paper presents research findings from the project, and in…

  15. Integrated Programs and Pro-Environmental Behaviour

    ERIC Educational Resources Information Center

    Smith, Tiffany

    2008-01-01

    Research suggested that "nature experience as an education method played a role in developing environmental value and attitudes, and was influential in pro-environmental behaviour." Few of these studies however, assessed the long-term influences of outdoor education experiences on participants' pro-environmental behaviour. The Outward…

  16. Pro-Anorexia and Pro-Recovery Photo Sharing: A Tale of Two Warring Tribes

    PubMed Central

    Yom-Tov, Elad; Weber, Ingmar; Crain, Steven P

    2012-01-01

    Background There is widespread use of the Internet to promote anorexia as a lifestyle choice. Pro-anorexia content can be harmful for people affected or at risk of having anorexia. That movement is actively engaged in sharing photos on social networks such as Flickr. Objective To study the characteristics of the online communities engaged in disseminating content that encourages eating disorders (known as “pro-anorexia”) and to investigate if the posting of such content is discouraged by the posting of recovery-oriented content. Methods The extraction of pro-anorexia and pro-recovery photographs from the photo sharing site Flickr pertaining to 242,710 photos from 491 users and analyzing four separate social networks therein. Results Pro-anorexia and pro-recovery communities interact to a much higher degree among themselves than what is expected from the distribution of contacts (only 59-72% of contacts but 74-83% of comments are made to members inside the community). Pro-recovery users employ similar words to those used by pro-anorexia users to describe their photographs, possibly in order to ensure that their content appears when pro-anorexia users search for images. Pro-anorexia users who are exposed to comments from the opposite camp are less likely to cease posting pro-anorexia photographs than those who do not receive such comments (46% versus 61%), and if they cease, they do so approximately three months later. Our observations show two highly active communities, where most interaction is within each community. However, the pro-recovery community takes steps to ensure that their content is visible to the pro-anorexia community, both by using textual descriptions of their photographs that are similar to those used by the pro-anorexia group and by commenting to pro-anorexia content. The latter activity is, however, counterproductive, as it entrenches pro-anorexia users in their stance. Conclusions Our results highlight the nature of pro-anorexia and pro

  17. Manduca sexta proprophenoloxidase activating proteinase-3 (PAP3) stimulates melanization by activating proPAP3, proSPHs, and proPOs

    PubMed Central

    Wang, Yang; Lu, Zhiqiang; Jiang, Haobo

    2014-01-01

    Melanization participates in various insect physiological processes including antimicrobial immune responses. Phenoloxidase (PO), a critical component of the enzyme system catalyzing melanin formation, is produced as an inactive precursor prophenoloxidase (proPO) and becomes active via specific proteolytic cleavage by proPO activating proteinase (PAP). In Manduca sexta, three PAPs can activate proPOs in the presence of two serine proteinase homologs (SPH1 and SPH2). While the hemolymph proteinases (HPs) that generate the active PAPs are known, it is unclear how the proSPHs (especially proSPH1) are activated. In this study, we isolated from plasma of bar-stage M. sexta larvae an Ile-Glu-Ala-Arg-p-nitroanilide hydrolyzing enzyme that cleaved the proSPHs. This proteinase, PAP3, generated active SPH1 and SPH2, which function as cofactors for PAP3 in proPO activation. Cleavage of the purified recombinant proSPHs by PAP3 yielded 38 kDa bands similar in mobility to the SPHs formed in vivo. Surprisingly, PAP3 also can activate proPAP3 to stimulate melanization in a direct positive feedback loop. The enhanced proPO activation concurred with the cleavage activation of proHP6, proHP8, proPAP1, proPAP3, proSPH1, proSPH2, proPOs, but not proHP14 or proHP21. These results indicate that PAP3, like PAP1, is a key factor of the self-reinforcing mechanism in the proPO activation system, which is linked to other immune responses in M. sexta. PMID:24768974

  18. Technology evaluation: PRO-542, Progenics Pharmaceuticals inc.

    PubMed

    Mukhtar, M; Parveen, Z; Pomerantz, R J

    2000-12-01

    Progenics's rCD4-IgG2 (PRO-542) is a recombinant fusion protein, which has been developed using the company's Universal Antiviral Binding (UnAB) technology, and is in phase I/II clinical trials for the treatment of human immunodeficiency virus type I (HIV-1) infection [273391]. At the beginning of 1997, Progenics received a Phase II Small Business Innovation Research Program (SBIR) grant from the National Institute of Allergy and Infectious diseases (NIAID) to fund the development of PRO-542 [236048]. A further grant of $2.7 million was awarded in August 1998 for the clinical evaluation of PRO-542 and other anti-HIV therapies [294200]. Progenics is collaborating with the Aaron Diamond AIDS Research Center (ADARC) in New York and the Center for Disease Control and Prevention in Atlanta [178410]. In February 2000, Progenics and Genzyme Transgenics Corp signed an agreement to continue the development of a transgenic source of PRO-542. Genzyme will develop transgenic goats that produce PRO-542 in their milk in exchange for undisclosed fees and milestone payments. Genzyme will supply PRO-542 to Progenics for clinical trials with a possibility for eventual commercial supply [357291]. Following on from this, in October 2000, Progenics received an SBIR grant to fund a two-year project with Genzyme Transgenics into the development of cost-effective methods for the manufacture of PRO-542, by optimization of the production of the drug in the milk of transgenic dairy animals [385982]. In August 2000, Punk, Ziegel & Company predicted that Progenics Pharmaceuticals will become sustainably profitable in 2003 following the launch of PRO-542 and GMK (Progenics Pharmaceuticals) in 2002 [390063].

  19. Induction of systemic disease resistance in Nicotiana benthamiana by the cyclodipeptides cyclo (l-Pro-l-Pro) and cyclo (d-Pro-d-Pro).

    PubMed

    Wu, Liming; Wu, Huijun; Chen, Lina; Zhang, Hongyue; Gao, Xuewen

    2017-01-01

    Cyclodipeptides, formed from two amino acids by cyclodehydration, are produced naturally by many organisms, and are known to possess a large number of biological activities. In this study, we found that cyclo (l-Pro-l-Pro) and cyclo (d-Pro-d-Pro) (where Pro is proline) could induce defence responses and systemic resistance in Nicotiana benthamiana. Treatment with the two cyclodipeptides led to a reduction in disease severity by Phytophthora nicotianae and Tobacco mosaic virus (TMV) infections compared with controls. Both cyclopeptides triggered stomatal closure, induced reactive oxygen species production and stimulated cytosolic calcium ion and nitric oxide production in guard cells. In addition, the application of cyclodipeptides significantly up-regulated the expression of the plant defence gene PR-1a and the PR-1a protein, and increased cellular salicylic acid (SA) levels. These results suggest that the SA-dependent defence pathway is involved in cyclodipeptide-mediated pathogen resistance in N. benthamiana. We report the systemic resistance induced by cyclodipeptides, which sheds light on the potential of cyclodipeptides for the control of plant diseases.

  20. Pro-Am Collaboration and the AAVSO

    NASA Astrophysics Data System (ADS)

    Henden, A.

    2006-04-01

    Professionals need to be aware that there is a valuable resource available and waiting to be used -- the amateur astronomy community. We give some examples of how pro-am collaborations have worked in the past, indicate the advantages and disadvantages of such collaborations, and suggest methods by which a professional can find and work effectively with amateur astronomers.

  1. Pocahontas: Problematizing the Pro-Social.

    ERIC Educational Resources Information Center

    Aidman, Amy; Reese, Debbie

    The Disney film "Pocahontas" appears to be an attempt to respond to growing cultural diversity, calls for multiculturalism, and strong female role models in the United States. This paper provides an analysis of the film, examining how Disney's claims to the creation of positive, pro-social representations of women and Native Americans in…

  2. A Pro-Family Income Tax.

    ERIC Educational Resources Information Center

    Carlson, Allan

    1989-01-01

    Discusses the Tax Reform Act of 1986, which doubled the personal exemption, increased the eligibility ceiling for the Earned Income Tax Credit, and reduced marginal income-tax rates. Compares the Act with the Acts of 1948 and 1969. Outlines criteria for a pro-family income tax policy. (BJV)

  3. Crystal structure of the collagen triple helix model [(Pro-Pro-Gly)(10)](3).

    PubMed

    Berisio, Rita; Vitagliano, Luigi; Mazzarella, Lelio; Zagari, Adriana

    2002-02-01

    The first report of the full-length structure of the collagen-like polypeptide [(Pro-Pro-Gly)(10)](3) is given. This structure was obtained from crystals grown in a microgravity environment, which diffracted up to 1.3 A, using synchrotron radiation. The final model, which was refined to an R(factor) of 0.18, is the highest-resolution description of a collagen triple helix reported to date. This structure provides clues regarding a series of aspects related to collagen triple helix structure and assembly. The strict dependence of proline puckering on the position inside the Pro-Pro-Gly triplets and the correlation between backbone and side chain dihedral angles support the propensity-based mechanism of triple helix stabilization/destabilization induced by hydroxyproline. Furthermore, the analysis of [(Pro-Pro-Gly)(10)](3) packing, which is governed by electrostatic interactions, suggests that charges may act as locking features in the axial organization of triple helices in the collagen fibrils.

  4. The pro-oxidant activity of aluminum.

    PubMed

    Exley, Christopher

    2004-02-01

    Aluminum, a non-redox-active metal is, nevertheless, a pro-oxidant both in in vitro preparations and in vivo. It facilitates both superoxide- and iron-driven biological oxidation by mechanisms that remain to be resolved. More than 10 years ago Fridovich and colleagues suggested that the facilitation of superoxide-driven biological oxidation by aluminum was due to an interaction between the metal and the superoxide radical anion (Free Radic. Biol. Med. 13: 79-81; 1992). This thesis has been examined herein and it is concluded that much, if not all, of the pro-oxidant activity of aluminum might be explained by the formation of an aluminum superoxide semireduced radical ion.

  5. [Radiation Anticarcinogenesis by Thiazolidine Pro-drug

    NASA Technical Reports Server (NTRS)

    Warters, Raymond L.; Roberts, Jeanette C.; Fain, Heidi

    1999-01-01

    The original goal of this work was to determine the capacity of selected aminothiols to modulate radiation induced cytotoxicity, mutagenesis and carcinogenesis in a human mammary epithelial cell line. The conclusions from this work are that WR-1065 is the "gold standard" for protection against radiation induced cytotoxicity, mutagenesis and carcinogenesis. While a potent radiation protector, WR-1065 is cytotoxic in vitro and in vivo. Our rationale for a study of the thiazolidine pro-drugs was that these compounds are neither toxic in vitro or in vivo. The results obtained during this funding period indicate that the thiazolidine pro-drugs are as potent as WR-1065 as protectors against radiation induced mutation induction, and thus presumably against radiation induced carcinogenesis. Our results indicate that the thiazolidine prodrugs are excellent candidates to test as non-toxic anticarcinogens for protecting astronauts from cancer induction during space travel.

  6. Cryogenic system for BERLinPro

    SciTech Connect

    Anders, W.; Hellwig, A.; Knobloch, J.; Pflückhahn, D.; Rotterdam, S.

    2014-01-29

    In 2010 Helmholtz-Zentrum Berlin (HZB) received funding to design and build the Berlin Energy Recovery Linac Project BERLinPro. The goal of this compact Energy recovery linac (ERL) is to develop the accelerator physics and technology required to generate and accelerate a 100-mA, 1-mm mrad emittance electron beam. The BERLinPro know-how can then be transferred to various ERL-based applications. All accelerating RF cavities including the electron source are based on superconducting technology operated at 1.8 K. A Linde L700 helium liquefier is supplying 4.5 K helium. The subatmospheric pressure of 16 mbar of the helium bath of the cavities will be achieved by pumping with a set of cold compressors and warm vacuum pumps. While the L700 is already in operating, the 1.8 K system and the helium transfer system are in design phase.

  7. The PRO nurse: advocate for quality care.

    PubMed

    Carroll, M; Maichele, J

    1993-01-01

    Since the inception of the Social Security Amendments of 1983, nurses have assumed expanded roles in ensuring the monitoring of the quality of care received by Medicare beneficiaries. This unique area of nursing practice offers new challenges and employment opportunities for the nurse as a patient advocate. Nurses who are interested in this role may contact state PRO directors or watch for specific recruitment advertisements in nursing magazines.

  8. ProFit: Bayesian galaxy fitting tool

    NASA Astrophysics Data System (ADS)

    Robotham, A. S. G.; Taranu, D.; Tobar, R.

    2016-12-01

    ProFit is a Bayesian galaxy fitting tool that uses the fast C++ image generation library libprofit (ascl:1612.003) and a flexible R interface to a large number of likelihood samplers. It offers a fully featured Bayesian interface to galaxy model fitting (also called profiling), using mostly the same standard inputs as other popular codes (e.g. GALFIT ascl:1104.010), but it is also able to use complex priors and a number of likelihoods.

  9. Some problems with pro-competition reforms.

    PubMed

    Agich, G J; Begley, C E

    1985-01-01

    As the search for effective cost-containment policies continues, health care reform along pro-competition lines has gained considerable backing in the United States. By offering market competition to achieve allocational efficiency and vouchers and tax credits to achieve distributional equity, pro-competition reforms appear to satisfy what many believed were incommensurable goals. A critical review of this strategy reveals two practical difficulties, however. The first concerns the ambiguity arising from the proposals' reliance on the concept of equal access to some basic level of health care as its distributional objective and the second concerns the ethical dilemma arising from the proposals' reliance on physicians as rationers of health care. In considering the distributional goal of guaranteeing access to a basic minimum of health care, we argue that, despite its theoretical attractiveness, there exists no acceptable way of determining or justifying its content, and without a clear definition of the basic minimum there is no guarantee that any equity objective will be achieved under the pro-competition strategy. With regard to the use of physicians and other providers as society's gatekeepers, we point out that this role is in direct conflict with traditional responsibilities that patients expect providers to assume. Requiring doctors to ration services in response to market incentives may further erode the trust relationship between physicians and patients, and clearly puts the more seriously ill at a disadvantage.

  10. Calibrating the Prominence Magnetometer (ProMag)

    NASA Astrophysics Data System (ADS)

    Fox, Lewis; Casini, R.

    2013-07-01

    The Prominence Magnetometer (ProMag) is a dual-channel, dual-beam, slit-scanning, full Stokes spectro-polarimeter designed by the High Altitude Observatory at the National Center for Atmospheric Research (HAO/NCAR) for the study of the magnetism of solar prominences and filaments. It was deployed in August 2009 at the 40 cm coronagraph of the Evans Solar Facility (ESF) of the National Solar Observatory on Sacramento Peak (NSO/SP). In its standard mode of operation it acquires spectro-polarimetric maps of solar targets simultaneously in the two chromospheric lines of He I at 587.6 nm and 1083.0 nm. Since August 2011 ProMag has operated in “patrol mode” with a dedicated observer. We aim to routinely measure the vector magnetic field in prominences. The electro-optic modulator and polarization analyzer are integrated into a single mechanical unit located at the coude feed of the telescope. This location was necessary for proper co-alignment of the dual beams, but complicates the precise polarimeter calibration necessary to achieve the sensitivity required for prominence measurements (< 10^-3). At this sensitivity, small variations in optical alignment can become significant. We present a calibration method for ProMag, using a polarizer and retarder at coronagraph prime focus. Calibrations are recorded before and after observations. We discuss the success of this method and its limitations.

  11. ProUCL version 4.00.04 Documentation Downloads

    EPA Pesticide Factsheets

    ProUCL Version 4.00.04 is an upgrade of ProUCL Version 4.0 (EPA, 2007). ProUCL 4.00.02 contains statistical methods to address various environmental issues for both full data sets without nondetects and for data sets with NDs (also known as left-censored d

  12. c[D-pro-Pro-D-pro-N-methyl-Ala] adopts a rigid conformation that serves as a scaffold to mimic reverse-turns.

    PubMed

    Arbor, Sage; Kao, Jeff; Wu, Yun; Marshall, Garland R

    2008-01-01

    Naturally occurring cyclic tetrapeptides (CTPs) such as tentoxin (Halloin et al., Plant Physiol 1970, 45, 310-314; Saad, Phytopathology 1970, 60, 415-418), ampicidin (Darkin-Rattray, Proc Natl Acad Sci USA 1996, 93, 13143-13147), HC-toxin (Walton, Proc Natl Acad Sci USA 1987, 84, 8444-8447), and trapoxin (Yoshida and Sugita, Jpn J Cancer Res 1992, 83, 324-328; Itazaki et al., J Antibiot (Tokyo) 1990, 43, 1524-1532) have a wide range of biological activity and potential use ranging from herbicides (Walton, Proc Natl Acad Sci USA 1987, 84, 8444-8447; Judson, J Agric Food Chem 1987, 35, 451-456) to therapeutics (Loiseau, Biopolymers 2003, 69, 363-385) for malaria (Darkin-Rattray, Proc Natl Acad Sci USA 1996, 93, 13143-13147) and cancer (Yoshida and Sugita, Jpn J Cancer Res 1992, 83, 324-328). To elucidate scaffolds that have few low-energy conformations and could serve as semirigid reverse-turn mimetics, the flexibility of CTPs was determined computationally. Four analogs of cyclic tetraproline c[Pro-pro-Pro-pro] with alternating L- and D-prolines, namely c[pro-Pro-pro-NMe-Ala], c[pip-Pro-pip-Pro], c[pro-Pip-pro-Pro], and c[Ala-Pro-pip-Pro] were synthesized and characterized by NOESY NMR. Both molecular mechanics and Density Functional Theory quantum calculations found these head-to-tail CTPs to be constrained to one or two relatively stable conformations. NMR structures, while not always yielding the same lowest energy conformation as expected by in silico predictions, confirmed only one or two highly populated solution conformations for all four peptides examined. c[pro-Pro-pro-NMe-Ala] was shown to have a single all trans-amide bond conformation from both in silico predictions and NMR characterization, and to be a reverse-turn mimetic by overlapping four Calpha-Cbeta bonds with those for approximately 6.5% (Tran, J Comput Aided Mol Des 2005, 19, 551-566) of reverse-turns in the Protein Data Bank PDB with a RMSD of 0.57 A.

  13. Perl Embedded in PTC's Pro/ENGINEER, Version 1

    SciTech Connect

    2003-12-22

    Pro-PERL (AKA Pro/PERL) is a Perl extension to the PTC Pro/TOOLKIT API to the PTC Pro/ENGINEER CAD application including an embedded interpreter. It can be used to automate and customize Pro/ENGINEER, create Vendor Neutral Archive (VNA) format files and re-create CAD models from the VNA files. This has applications in sanitizing classified CAD models created in a classified environment for transfer to an open environment, creating template models for modification to finished models by non-expert users, and transfer of design intent data to other modeling technologies.

  14. BDNF pro-peptide regulates dendritic spines via caspase-3

    PubMed Central

    Guo, J; Ji, Y; Ding, Y; Jiang, W; Sun, Y; Lu, B; Nagappan, G

    2016-01-01

    The precursor of brain-derived neurotrophic factor (BDNF) (proBDNF) is enzymatically cleaved, by either intracellular (furin/PC1) or extracellular proteases (tPA/plasmin/MMP), to generate mature BDNF (mBDNF) and its pro-peptide (BDNF pro-peptide). Little is known about the function of BDNF pro-peptide. We have developed an antibody that specifically detects cleaved BDNF pro-peptide, but not proBDNF or mBDNF. Neuronal depolarization elicited a marked increase in extracellular BDNF pro-peptide, suggesting activity-dependent regulation of its extracellular levels. Exposure of BDNF pro-peptide to mature hippocampal neurons in culture dramatically reduced dendritic spine density. This effect was mediated by caspase-3, as revealed by studies with pharmacological inhibitors and genetic knockdown. BDNF pro-peptide also increased the number of ‘elongated' mitochondria and cytosolic cytochrome c, suggesting the involvement of mitochondrial-caspase-3 pathway. These results, along with BDNF pro-peptide effects recently reported on growth cones and long-term depression (LTD), suggest that BDNF pro-peptide is a negative regulator of neuronal structure and function. PMID:27310873

  15. Photoelectron spectrum of PrO-

    NASA Astrophysics Data System (ADS)

    Kafader, Jared O.; Ray, Manisha; Jarrold, Caroline Chick

    2015-08-01

    The photoelectron (PE) spectrum of PrO- exhibits a short 835 ± 20 cm-1 vibrational progression of doublets (210 ± 30 cm-1 splitting) assigned to transitions from the 4f2 [3H4] σ6s2 Ω = 4 anion ground state to the 4f2 [3H4] σ6s Ω = 3.5 and 4.5 neutral states. This assignment is analogous to that of the recently reported PE spectrum of CeO-, though the 82 cm-1 splitting between the 4f [2F2.5] σ6s Ω = 2 and Ω = 3 CeO neutral states could not be resolved [Ray et al., J. Chem. Phys. 142, 064305 (2015)]. The origin of the transition to the Ω = 3.5 neutral ground state is 0.96 ± 0.01 eV, which is the adiabatic electron affinity of PrO. Density functional theory calculations on the anion and neutral molecules support the assignment. The appearance of multiple, irregularly spaced and low-intensity features observed ca. 1 eV above the ground state cannot be reconciled with low-lying electronic states of PrO that are accessible via one-electron detachment. However, neutral states correlated with the 4f2 [3H4] 5d superconfiguration are predicted to be approximately 1 eV above the 4f2 [3H4] σ6s Ω = 3.5 neutral ground state, leading to the assignment of these features to shake-up transitions to the excited neutral states. Based on tentative hot band transition assignments, the term energy of the previously unobserved 4f2 [3H4] σ6s Ω = 2.5 neutral state is determined to be 1840 ± 110 cm-1.

  16. Adiponectinemia controls pro-angiogenic cell therapy.

    PubMed

    Eren, Philippe; Camus, Stéphane; Matrone, Gianfranco; Ebrahimian, Téni G; François, Delphine; Tedgui, Alain; Sébastien Silvestre, Jean; Blanc-Brude, Olivier P

    2009-11-01

    Angiogenic cell therapy with the transplantation of endothelial progenitor cells (EPC) or bone marrow mononuclear cells (BM-MNC) receives considerable attention as an approach to revascularize ischemic tissues. Adiponectin is a circulating hormone produced by the apM1 gene in adipocytes. Adiponectin modulates lipid metabolism and obesity, and it was recently found to promote physiological angiogenesis in response to ischemia. Patients with multiple cardiovascular disease risk factors or myocardial infarction may benefit from progenitor cell therapy, but they display depressed adiponectinemia. We hypothesized that adiponectin stimulation of transplanted cells is critical for their pro-angiogenic function. We aimed to establish whether adiponectinemia in the cell donor or in the cell recipient determines the success of pro-angiogenic cell therapy. In vitro, we found that conditioned media derived from wild-type adipocytes (adipo-CM) or purified adiponectin strongly enhanced BM-MNC survival and proliferation and stimulated EPC differentiation, whereas adipo-CM from apM1-/- adipocytes was one-half less effective. On the other hand, wild-type and apM1-/- BM-MNC displayed similar resistance to apoptosis and proliferation rates. In vivo, wild-type, and apM1-/- BM-MNC induced similar angiogenic reactions in wild-type ischemic hindlimbs. In contrast, wild-type BM-MNC had much diminished effects in apM1-/- ischemic hindlimbs. We concluded that adiponectin enhances BM-MNC survival and proliferation, and adiponectinemia in the cell therapy recipient is essential for the pro-angiogenic benefits of cell therapy. These observations imply that progenitor cell transplantation might only induce angiogenesis in patients with high adiponectinemia.

  17. Educational Opportunities in Pro-Am Collaboration

    NASA Astrophysics Data System (ADS)

    Fienberg, R. T.; Stencel, R. E.

    2006-08-01

    While many backyard stargazers take up the hobby just for fun, many others are attracted to it because of their keen interest in learning more about the universe. The best way to learn science is to do science. Happily, the technology available to today's amateur astronomers — including computer-controlled telescopes, CCD cameras, powerful astronomical software, and the Internet — gives them the potential to make real contributions to scientific research and to help support local educational objectives. Meanwhile, professional astronomers are losing access to small telescopes as funding is shifted to larger projects, including survey programs that will soon discover countless interesting objects needing follow-up observations. Clearly the field is ripe with opportunities for amateurs, professionals, and educators to collaborate. Amateurs will benefit from mentoring by expert professionals, pros will benefit from observations and data processing by increasingly knowledgeable amateurs, and educators will benefit from a larger pool of skilled talent to help them carry out astronomy-education initiatives. We will look at some successful pro-am collaborations that have already borne fruit and examine areas where the need and/or potential for new partnerships is especially large. In keeping with the theme of this special session, we will focus on how pro-am collaborations in astronomy can contribute to science education both inside and outside the classroom, not only for students of school age but also for adults who may not have enjoyed particularly good science education when they were younger. Because nighttime observations with sophisticated equipment are not always possible in formal educational settings, we will also mention other types of pro-am partnerships, including those involving remote observing, data mining, and/or distributed computing.

  18. The utility of Pro Forma Income Statements.

    PubMed

    Reiboldt, Max; Reiboldt, John

    2002-01-01

    Recent headlines surrounding the financial demise of the nation's seventh largest company, Enron, and its subsequent entanglements with its accounting and consulting firm, Arthur Andersen, have placed a cloud of suspicion upon many reasonable business practices that otherwise are considered standard procedure. The proforma income statement is one of those practices. An oft-used tool in financial management, pro formas play a useful role for projecting financial performance based on predictable forecasts or assumptions. Regardless of the current scrutiny, there is still a valid use for accurately prepared statements.

  19. Communicating stigma: the pro-ana paradox.

    PubMed

    Yeshua-Katz, Daphna; Martins, Nicole

    2013-01-01

    This study explores the personal experience of pro-ana bloggers, members of an online community for people with eating disorders. Using Erving Goffman's work on stigma, this study explores the motivations, benefits, and drawbacks of blogging about a stigmatized mental illness, as taken from the bloggers' own perceptive. We conducted 33 interviews with bloggers from seven different countries via phone, Skype, and e-mail. Participants were motivated to blog because they found social support, a way to cope with a stigmatized illness, and means of self-expression. Participants described blogging as a cathartic experience and perceived the social support they received from other members of the pro-ana community as a benefit. The fear that the eating disorder will be revealed if the blog is exposed and the concern that the blog encourages disordered eating were the perceived negative consequences of maintaining such a blog. Thus, blogging about anorexia serves to both alleviate and trigger anxiety about living with this stigmatized illness. Recommendations for future research are made.

  20. Pro-neurotrophins, sortilin, and nociception

    PubMed Central

    Lewin, Gary R; Nykjaer, Anders

    2014-01-01

    Nerve growth factor (NGF) signaling is important in the development and functional maintenance of nociceptors, but it also plays a central role in initiating and sustaining heat and mechanical hyperalgesia following inflammation. NGF signaling in pain has traditionally been thought of as primarily engaging the classic high-affinity receptor tyrosine kinase receptor TrkA to initiate sensitization events. However, the discovery that secreted proforms of nerve NGF have biological functions distinct from the processed mature factors raised the possibility that these proneurotrophins (proNTs) may have distinct function in painful conditions. ProNTs engage a novel receptor system that is distinct from that of mature neurotrophins, consisting of sortilin, a type I membrane protein belonging to the VPS10p family, and its co-receptor, the classic low-affinity neurotrophin receptor p75NTR. Here, we review how this new receptor system may itself function with or independently of the classic TrkA system in regulating inflammatory or neuropathic pain. PMID:24494677

  1. Autophagy and the (Pro)renin Receptor.

    PubMed

    Binger, Katrina J; Muller, Dominik N

    2013-10-21

    The (pro)renin receptor (PRR) is a newly reported member of the renin-angiotensin system (RAS); a hormonal cascade responsible for regulating blood pressure. Originally, identification of PRR was heralded as the next drug target of the RAS, of which such therapies would have increased benefits against target-organ damage and hypertension. However, in the years since its discovery, several conditional knockout mouse models of PRR have demonstrated an essential role for this receptor unrelated to the RAS and blood pressure. Specific deletion of PRR in podocytes or cardiomyocytes resulted in the rapid onset of organ failure and subsequently animal mortality after only a matter of weeks. In both cell types, loss of PRR resulted in the intracellular accumulation of autophagosomes and misfolded proteins, indicating a disturbance in autophagy. In light of the fact that the majority of PRR is located intracellularly, this molecular function appears to be more relevant than its ability to bind to high, non-physiological concentrations of (pro)renin. This review will focus on the role of PRR in autophagy and its importance in maintaining cellular homeostasis. Understanding the link between PRR, autophagy and how its loss results in cell death will be essential for deciphering its role in physiology and pathology.

  2. ProSAT+: visualizing sequence annotations on 3D structure.

    PubMed

    Stank, Antonia; Richter, Stefan; Wade, Rebecca C

    2016-08-01

    PRO: tein S: tructure A: nnotation T: ool-plus (ProSAT(+)) is a new web server for mapping protein sequence annotations onto a protein structure and visualizing them simultaneously with the structure. ProSAT(+) incorporates many of the features of the preceding ProSAT and ProSAT2 tools but also provides new options for the visualization and sharing of protein annotations. Data are extracted from the UniProt KnowledgeBase, the RCSB PDB and the PDBe SIFTS resource, and visualization is performed using JSmol. User-defined sequence annotations can be added directly to the URL, thus enabling visualization and easy data sharing. ProSAT(+) is available at http://prosat.h-its.org.

  3. French Pro/Am collaborations in exoplanet

    NASA Astrophysics Data System (ADS)

    Santerne, A.; Moutou, C.; Vanhuysse, M.; Bouchy, F.; Buil, C.; Cochard, F.; Thizy, O.; Martinez, P.; Desnoux, V.; Pujol, M.; Colas, F.

    2011-10-01

    Amateur astronomers have access to huge telescope time and can reach photometric precision up to a few mmag as well as radial velocity precision up to ˜ 50m.s-1 on brightest stars. We will first present some results of french amateur astronomers in transit photometry and radial velocity and then, we will present an over-view of all the collaborations which can be done between professional and amateur astronomers in the competitive exoplanet domain, and especially the current collaboration between french Pro & Am astronomers which was used in publication in A&A. Finally, we will present a new internet wiki page which goal is to develop such collaboration in different countries.

  4. Pro-Anorexia and Anti-Pro-Anorexia Videos on YouTube: Sentiment Analysis of User Responses

    PubMed Central

    Garcia, David; Sirola, Anu; Näsi, Matti; Kaakinen, Markus; Keipi, Teo; Räsänen, Pekka

    2015-01-01

    Background Pro-anorexia communities exist online and encourage harmful weight loss and weight control practices, often through emotional content that enforces social ties within these communities. User-generated responses to videos that directly oppose pro-anorexia communities have not yet been researched in depth. Objective The aim was to study emotional reactions to pro-anorexia and anti-pro-anorexia online content on YouTube using sentiment analysis. Methods Using the 50 most popular YouTube pro-anorexia and anti-pro-anorexia user channels as a starting point, we gathered data on users, their videos, and their commentators. A total of 395 anorexia videos and 12,161 comments were analyzed using positive and negative sentiments and ratings submitted by the viewers of the videos. The emotional information was automatically extracted with an automatic sentiment detection tool whose reliability was tested with human coders. Ordinary least squares regression models were used to estimate the strength of sentiments. The models controlled for the number of video views and comments, number of months the video had been on YouTube, duration of the video, uploader’s activity as a video commentator, and uploader’s physical location by country. Results The 395 videos had more than 6 million views and comments by almost 8000 users. Anti-pro-anorexia video comments expressed more positive sentiments on a scale of 1 to 5 (adjusted prediction [AP] 2.15, 95% CI 2.11-2.19) than did those of pro-anorexia videos (AP 2.02, 95% CI 1.98-2.06). Anti-pro-anorexia videos also received more likes (AP 181.02, 95% CI 155.19-206.85) than pro-anorexia videos (AP 31.22, 95% CI 31.22-37.81). Negative sentiments and video dislikes were equally distributed in responses to both pro-anorexia and anti-pro-anorexia videos. Conclusions Despite pro-anorexia content being widespread on YouTube, videos promoting help for anorexia and opposing the pro-anorexia community were more popular, gaining more

  5. Antithrombotic Protective Effects of Arg-Pro-Gly-Pro Peptide during Emotional Stress Provoked by Forced Swimming Test in Rats.

    PubMed

    Grigor'eva, M E; Lyapina, L A

    2017-01-01

    Blood coagulation was enhanced and all factors (total, enzyme, and non-enzyme) of the fibrinolytic system were suppressed in rats in 60 min after forced swimming test. Argininecontaining tetrapeptide glyproline Arg-Pro-Gly-Pro administered prior to this test activated fibrinolysis and prevented hypercoagulation. Administration of this peptide in 5 min after swimming test also enhanced anticoagulant, fibrinolytic, and antithrombotic activity of the blood. Therefore, glyproline Arg-Pro-Gly-Pro exerted both preventive and curative effects on the hemostasis system and prevented enhancement of blood coagulation provoked by emotional stress modeled by forced swimming test.

  6. Two states of the triple helix in the thermal transition of the collagen model peptide (Pro-Pro-Gly)10.

    PubMed

    Kai, T; Uchiyama, S; Nishi, Y; Kobayashi, Y; Tomiyama, T

    2004-08-01

    The collagen model peptide (Pro-Pro-Gly)10 is known to fold into a triple helix in solution. So far, the triple helix has been considered to exist as a single state. However, our previous study of (Pro-Pro-Gly)10 in solution has indicated the presence of two different states of the triple helix, a lower (HL) and a higher temperature state (HH). In the present study, these triple-helical states were investigated in more detail by NMR. Complete stereospecific assignments of the methylene protons of the proline residues were accomplished by the use of NOESY and TOCSY spectra. The temperature dependence of the 1H chemical shifts showed that the HL-to-HH thermal transition can be attributed to a conformational change of the first proline (Pro1) residues of the (Pro-Pro-Gly) triplets. Since TOCSY spectra with a 10 ms mixing-time confirmed a down puckering of these Pro residues in the HL state, but interconverting down and up puckerings in the HH state, the HL-to-HH thermal transition corresponds to conformational changes of the pyrrolidine rings of the Pro1 residues from an uniform down puckering to a more flexible state. The results confirm that thermal unfolding of the triple helix proceeds through the intermediate HH state.

  7. High-resolution structures of collagen-like peptides [(Pro-Pro-Gly)4-Xaa-Yaa-Gly-(Pro-Pro-Gly)4]: implications for triple-helix hydration and Hyp(X) puckering.

    PubMed

    Okuyama, Kenji; Hongo, Chizuru; Wu, Guanghan; Mizuno, Kazunori; Noguchi, Keiichi; Ebisuzaki, Shutoku; Tanaka, Yuji; Nishino, Norikazu; Bächinger, Hans Peter

    2009-05-01

    Structures of (Pro-Pro-Gly)4-Xaa-Yaa-Gly-(Pro-Pro-Gly)4 (ppg9-XYG) where (Xaa, Yaa)=(Pro, Hyp), (Hyp, Pro) or (Hyp, Hyp) were analyzed at high resolution using synchrotron radiation. Molecular and crystal structures of these peptides are very similar to those of the (Pro-Pro-Gly)9 peptide. The results obtained in this study, together with those obtained from related compounds, indicated the puckering propensity of the Hyp in the X position: (1) Hyp(X) residues involved in the Hyp(X):Pro(Y) stacking pairs prefer the down-puckering conformation, as in ppg9-OPG, and ppg9-OOG; (2) Hyp(X) residues involved in the Hyp(X):Hyp(Y) stacking pairs prefer the up-puckering conformation if there is no specific reason to adopt the down-puckering conformation. Water molecules in these peptide crystals are classified into two groups, the 1st and 2nd hydration waters. Water molecules in the 1st hydration group have direct hydrogen bonds with peptide oxygen atoms, whereas those in the 2nd hydration group do not. Compared with globular proteins, the number of water molecules in the 2nd hydration shell of the ppg9-XYG peptides is very large, likely due to the unique rod-like molecular structure of collagen model peptides. In the collagen helix, the amino acid residues in the X and Y positions must protrude outside of the triple helix, which forces even the hydrophobic side chains, such as Pro, to be exposed to the surrounding water molecules. Therefore, most of the waters in the 2nd hydration shell are covering hydrophobic Pro side chains by forming clathrate structures.

  8. Pro-ELT; A Teacher Training Blended Approach

    ERIC Educational Resources Information Center

    Eshtehardi, Reza

    2014-01-01

    Pro-ELT is a blended teacher training course. The aim of Pro-ELT is to strengthen English teaching and learning through a blended training approach that includes; quality face to face delivery, supported distance learning and integrated proficiency and methodology training. It delivers quality language teaching and teacher development courses to…

  9. 31 CFR 50.92 - Determination of pro rata share.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INSURANCE PROGRAM Cap on Annual Liability § 50.92 Determination of pro rata share. (a) Pro rata loss... amount that would otherwise be paid by the insurer under the terms and conditions of an insurance policy providing property and casualty insurance under the Program if there were no cap on annual liability...

  10. The PRO Instructional Strategy in the Construction of Scientific Explanations

    ERIC Educational Resources Information Center

    Tang, Kok-Sing

    2015-01-01

    This article presents an instructional strategy called Premise-Reasoning-Outcome (PRO) designed to support students in the construction of scientific explanations. Informed by the philosophy of science and linguistic studies of science, the PRO strategy involves identifying three components of a scientific explanation: (i) premise--an accepted…

  11. Peanuts & Crackerjacks: Economics of Pro Team Sports. Teacher's Guide.

    ERIC Educational Resources Information Center

    Federal Reserve Bank of Boston, MA.

    This teacher's guide presents instructional materials which examine issues in professional sports for students in high school economics and social studies classes. The issues include how the pro sports market evolved; how leagues gained market power; why athletes earn as much as they do; what are the sources of pro sports revenues; why tickets…

  12. Ethical Dilemmas of Providing Pro Bono Art Therapy

    ERIC Educational Resources Information Center

    Moon, Bruce L.

    2011-01-01

    This viewpoint addresses ethical questions regarding the provision of art therapy as a pro bono service, a term from Latin roots that mean "for the public good." Approaches to ethical reasoning are discussed using the case of pro bono art therapy in a residential treatment program for adolescents.

  13. Pro-Market Educational Governance: Is Argentina a Black Swan?

    ERIC Educational Resources Information Center

    Beech, Jason; Barrenechea, Ignacio

    2011-01-01

    In this article we explore ways in which pro-market discourses have been interpreted in policy initiatives in Argentina since the 1970s. Our argument is that even though pro-market discourses have guided reforms in many aspects of public policies in Argentina, the arena of education has overall been resistant to taking them up. The first part of…

  14. German cockroach frass proteases cleave pro-matrix metalloproteinase-9.

    PubMed

    Hughes, Valerie S; Page, Kristen

    2007-01-01

    Matrix metalloproteinase (MMP)-9, secreted as pro-MMP-9, is cleaved by serine proteases at the N-terminus to generate active MMP-9. Pro-MMP-9 has been found in the bronchoalveolar lavage fluid of patients with asthma. Because many inhaled aeroallergens contain active proteases, the authors sought to determine whether German cockroach (GC) fecal remnants (frass) and house dust mite (HDM) were able to cleave pro-MMP-9. Treatment of recombinant human (rh) pro-MMP-9 with GC frass resulted in a dose- and time-dependent cleavage. This was abrogated by pretreating frass with an inhibitor of serine, but not cysteine protease activity. GC frass also induced cleavage of pro-MMP-9 from primary human neutrophils dependent on the active serine proteases in GC frass. HDM was less potent at cleaving pro-MMP-9. Alpha1-antitrypsin (A1AT), a naturally occurring protease inhibitor, attenuated GC frass-induced cleavage of pro-MMP-9. A1AT partially inactivated the serine protease activity in GC frass, while GC frass cleaved A1AT in a dose- and time-dependent manner. These data suggest that GC frass-derived serine proteases could regulate the activity of MMP-9 and that A1AT may play an important role in modulating GC frass activity in vivo. These data suggest a mechanism by which inhalation of GC frass could regulate airway remodeling through the activation of pro-MMP-9.

  15. 31 CFR 50.92 - Determination of pro rata share.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... INSURANCE PROGRAM Cap on Annual Liability § 50.92 Determination of pro rata share. (a) Pro rata loss... amount that would otherwise be paid by the insurer under the terms and conditions of an insurance policy providing property and casualty insurance under the Program if there were no cap on annual liability...

  16. 31 CFR 50.92 - Determination of pro rata share.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... INSURANCE PROGRAM Cap on Annual Liability § 50.92 Determination of pro rata share. (a) Pro rata loss... amount that would otherwise be paid by the insurer under the terms and conditions of an insurance policy providing property and casualty insurance under the Program if there were no cap on annual liability...

  17. 31 CFR 50.92 - Determination of pro rata share.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... INSURANCE PROGRAM Cap on Annual Liability § 50.92 Determination of pro rata share. (a) Pro rata loss... amount that would otherwise be paid by the insurer under the terms and conditions of an insurance policy providing property and casualty insurance under the Program if there were no cap on annual liability...

  18. 31 CFR 50.92 - Determination of pro rata share.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... INSURANCE PROGRAM Cap on Annual Liability § 50.92 Determination of pro rata share. (a) Pro rata loss... amount that would otherwise be paid by the insurer under the terms and conditions of an insurance policy providing property and casualty insurance under the Program if there were no cap on annual liability...

  19. Pro-Cite: A Tool for Creating and Updating Bibliographies.

    ERIC Educational Resources Information Center

    Aluri, Rao; Bosch, Steve

    1987-01-01

    Describes the Pro-Cite database management system and its uses in searching RLIN, OCLC, DIALOG, BRS, etc.; downloading results on a floppy or hard disk; converting downloaded records into Pro-Cite databases; and editing, selecting, indexing, and printing out the selected records in a variety of bibliographic styles. (DMM)

  20. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  1. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  2. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  3. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  4. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  5. Intracerebroventricular infusion of the (Pro)renin receptor antagonist PRO20 attenuates deoxycorticosterone acetate-salt-induced hypertension.

    PubMed

    Li, Wencheng; Sullivan, Michelle N; Zhang, Sheng; Worker, Caleb J; Xiong, Zhenggang; Speth, Robert C; Feng, Yumei

    2015-02-01

    We previously reported that binding of prorenin to the (pro)renin receptor (PRR) plays a major role in brain angiotensin II formation and the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Here, we designed and developed an antagonistic peptide, PRO20, to block prorenin binding to the PRR. Fluorescently labeled PRO20 bound to both mouse and human brain tissues with dissociation constants of 4.4 and 1.8 nmol/L, respectively. This binding was blocked by coincubation with prorenin and was diminished in brains of neuron-specific PRR-knockout mice, indicating specificity of PRO20 for PRR. In cultured human neuroblastoma cells, PRO20 blocked prorenin-induced calcium influx in a concentration- and AT(1) receptor-dependent manner. Intracerebroventricular infusion of PRO20 dose-dependently inhibited prorenin-induced hypertension in C57Bl6/J mice. Furthermore, acute intracerebroventricular infusion of PRO20 reduced blood pressure in both DOCA-salt and genetically hypertensive mice. Chronic intracerebroventricular infusion of PRO20 attenuated the development of hypertension and the increase in brain hypothalamic angiotensin II levels induced by DOCA-salt. In addition, chronic intracerebroventricular infusion of PRO20 improved autonomic function and spontaneous baroreflex sensitivity in mice treated with DOCA-salt. In summary, PRO20 binds to both mouse and human PRRs and decreases angiotensin II formation and hypertension induced by either prorenin or DOCA-salt. Our findings highlight the value of the novel PRR antagonist, PRO20, as a lead compound for a novel class of antihypertensive agents and as a research tool to establish the validity of brain PRR antagonism as a strategy for treating hypertension.

  6. Profiling the ‘Pro-environmental Individual’: A Personality Perspective

    PubMed Central

    Markowitz, Ezra M.; Goldberg, Lewis R.; Ashton, Michael C.; Lee, Kibeom

    2011-01-01

    There is considerable scientific interest in the psychological correlates of pro-environmental behaviors. Much research has focused on demographic and social-psychological characteristics of individuals who consistently perform such actions. Here, we report the results of two studies in which we explored relations between broad personality traits and pro-environmental actions. Using a wide variety of behavior and personality measures, we consistently found moderate positive relations between Openness to Experience and pro-environmental activities in both a community sample (Study 1: N = 778) and an undergraduate student sample (Study 2: N = 115). In Study 2 we showed that the effect of Openness on pro-environmental behaviors was fully mediated by individuals’ environmental attitudes and connection to nature. Our findings suggest that high levels of aesthetic appreciation, creativity, and inquisitiveness, but not personality traits associated with altruism, may have motivated the performance of pro-environmental actions among our respondents. Implications for intervention development are discussed. PMID:21241310

  7. Pro-Am collaborations in astronomy

    NASA Astrophysics Data System (ADS)

    Hurst, G. M.

    2004-10-01

    The text of the Presidential Address delivered at The Geological Society, Burlington House, Piccadilly, London on 2003 October 29. In this second Presidential Address, I wish to discuss the very real opportunities that exist for collaboration between professional and amateur astronomers in a wide variety of fields. As the scope of research in astronomy grows by the day and some questions are answered, we are then often faced by even greater challenges. Professional astronomers naturally adjust their goals and areas of investigation. The result is that gaps are left in which the amateur can take over the role. Alternatively where there is a considerable technical challenge, the task can be shared by professional and amateurs with frequent exchanges of results and discussion. The main areas which are worthy of debate, involve whether the amateur is suitably equipped for the task, which naturally leads us to discuss the equipment available, and the observing techniques employed. It is also worth examining which classes of object are suited to the cause of Pro-Am.

  8. Pro and contra IBR-eradication.

    PubMed

    Ackermann, Mathias; Engels, Monika

    2006-03-31

    Bovine herpesvirus type 1 (BoHV-1) is the causative agent of respiratory and genital tract infections such as infectious rhinotracheitis (IBR), infectious pustular vulvovaginitis (IPV, balanoposthitis (IBP), and abortion. Despite of a pronounced immune response, the virus is never eliminated from an infected host but establishes life-long latency and may be reactivated at intervals. Europe has a long history of fighting against BoHV-1 infections, yet, only a small number of countries has achieved IBR-eradication. Therefore, it seemed appropriate to review the reasoning pro and contra such a task. Clearly, the goal can indeed be achieved as has been demonstrated by a number of European countries. However, detection and stamping out of seemingly healthy virus carriers is inevitable in the process. Unfortunately, the use of vaccines is only of temporary and limited value. Therefore, there are numerous considerations to be put forward against such plans, including the high costs, the great risks, and the unsatisfactory quality of tools. If either control or eradication of IBR is nonetheless a goal, then better vaccines are needed as well as better companion tests. Moreover, better tools for the characterization of viral isolates are required. Collaborative actions to gather viral strains from as many countries as possible for inclusion into a newly created clustering library would be most advantageous.

  9. ProPortal: A Database for Prochlorococcus

    DOE Data Explorer

    Huang, Katherine [Chisholm lab, MIT

    Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans, and is the smallest known oxygenic phototroph. All isolates described thus far can be assigned to either a tightly clustered high-light (HL) adapted clade, or a more divergent low-light (LL) adapted group. They are closely related to, but distinct from, marine Synechococcus. The genomes of 12 strains have been sequenced and they range in size from 1.6 to 2.6 Mbp. They represent diverse lineages, spanning the rRNA diversity (97 to 99.93% similarity) of cultured representatives of this group. Our analyses of these genomes inform our understanding of how adaptation occurs in the oceans along gradients of light, nutrients, and other environmental factors, providing essential context for interpreting rapidly expanding metagenomic datasets. [Copied from http://proportal.mit.edu/project/prochlorococcus/] ProPortal allows users to browse and search genome date for not only Prochlorococcus, but Cyanophage and Synechococcus. Microarray data, environmental cell concentration data, and metagenome information are also available.

  10. Pro-angiogenic properties of orosomucoid (ORM)

    SciTech Connect

    Irmak, Ster; Oliveira-Ferrer, Leticia; Erguen, Sueleyman; Tilki, Derya

    2009-11-01

    The acute phase protein orosomucoid (ORM), also known as alpha1-acid glycoprotein (AGP), is found to be increased in infection, inflammation and cancer. Recently, we demonstrated that ORM is produced by endothelial cells and detectable in urine samples of patients with bladder cancer. However, it was not clarified yet whether ORM plays a role in new vessel formation. To this aim we performed overexpression and gene silencing for ORM in human microvascular endothelial cells (HDMECs). ORM purified from human plasma was used individually or in combination with VEGF-A in endothelial tube formation, migration and proliferation assay. The in vivo effect of ORM in angiogenesis was studied using the chicken chorionallantois membrane (CAM) with subsequent counting of blood vessels on histological sections from the stimulated areas of CAM tissue. Our data show that ORM alone enhances migration but not proliferation of HDMECs. ORM alone does not induce endothelial tubes in vitro but simultaneous application of ORM with VEGF-A increases the number and the network of VEGF-A-induced endothelial tubes. Remarkably, ORM alone induces new vessel formation in vivo using CAM assay and supports the VEGF-A-induced new vessel formation in this assay. Taken together, our results let assume that ORM has pro-angiogenic properties and supports the angiogenic effect of VEGF-A. Thus, ORM seems to be involved in the regulation of angiogenesis.

  11. The Interplay among Environmental Attitudes, Pro-Environmental Behavior, Social Identity, and Pro-Environmental Institutional Climate. A Longitudinal Study

    ERIC Educational Resources Information Center

    Prati, Gabriele; Albanesi, Cinzia; Pietrantoni, Luca

    2017-01-01

    By using a panel design in a sample of 298 undergraduate/master students at an Italian public university, the present study aimed to test longitudinally the interplay among environmental attitudes, pro-environmental behavior, social identity, and pro-environmental institutional climate. The relationships were tested with cross-lagged analysis…

  12. The Experience of Bulimic College Students Who Use "Pro-Ana/Pro-Mia" Web Sites: A Two-Phase Mixed-Method Study

    ERIC Educational Resources Information Center

    Davis, Blair J.

    2010-01-01

    Eating disorders (EDs) are a serious problem in the U.S. due to their rise in prevalence during the 20th century and high morbidity and mortality rates. A relatively new, controversial phenomenon, "pro-Ana" (pro-anorexia) and "pro-Mia" (pro-bulimia) Web sites, came to the public's attention around 2000. These sites are created by and for people…

  13. The pro-apoptotic and pro-inflammatory effects of calprotectin on human periodontal ligament cells.

    PubMed

    Zheng, Yunfei; Hou, Jianxia; Peng, Lei; Zhang, Xin; Jia, Lingfei; Wang, Xian'e; Wei, Shicheng; Meng, Huanxin

    2014-01-01

    Calprotectin, a heterodimer of S100A8 and S100A9 subunits, is associated with inflammatory disorders such as rheumatoid arthritis and cystic fibrosis. Although calprotectin levels are increased significantly in the gingival crevicular fluid (GCF) of periodontitis patients, its effects on periodontal ligament cells (PDLCs) remain largely unknown. The aim of this study was to evaluate calprotectin levels in the GCF of generalized aggressive periodontitis (AgP) patients and to investigate the effects of recombinant human calprotectin (rhS100A8/A9) and its subunits (rhS100A8 and rhS100A9) in PDLCs. Both the concentration and amount of crevicular calprotectin were significantly higher in the AgP group compared with healthy controls. In addition, the GCF calprotectin levels were correlated positively with clinical periodontal parameters including bleeding index, probing depth, and clinical attachment loss. rhS100A8/A9 promoted cell apoptosis, whereas rhS100A8 and rhS100A9 individually exerted little effect on apoptosis in PDLCs. rhS100A9 and rhS100A8/A9 increased the activation of nuclear factor-κB (NF-κB) by promoting the nuclear translocation of p65 in PDLCs, subsequently inducing expression of the pro-inflammatory cytokines IL-6, IL-8, TNFα, and COX2. Treatment with an NF-κB inhibitor partially reversed the rhS100A9- and rhS100A8/A9-induced upregulation of the pro-inflammatory cytokines. rhS100A9, and not rhS100A8, was mainly responsible for the pro-inflammatory role of calprotectin. Collectively, our results suggest that calprotectin promotes apoptosis and the inflammatory response in PDLCs via rhS100A9. These findings might help identify novel treatments for periodontitis.

  14. Pro/con a precessional geodynamo

    NASA Astrophysics Data System (ADS)

    Vanyo, J.

    2003-04-01

    The modest amount of research that exists on the ability, or lack of ability, of mantle precession to power a geodynamo developed mostly during the last half of the 1900s. Papers by Roberts and Stewartson (1965) and by Busse (1968) studied precession generally without a pro/con conclusion. Malkus in the late 1960s attempted to advance a positive role for precession through experiments and analysis. His experiments have survived criticism, but his analyses were discounted, especially by Rochester, Jacobs, Smylie, and Chong (1975) and by Loper (1975). Rochester, et al. critiqued existing analyses of precession, including those of Malkus, but did not reach a strong position either pro or con a precessional geodynamo. Loper argued emphatically that precession was not capable of powering the geodynamo. Explicit analyses that either critique or support Loper’s arguments have yet to appear in the literature. During the 1970s, Vanyo and associates studied energy dissipation during precession of satellite liquid fuels and its effect on satellite attitude stability. Engineers and scientists in every country that has launched satellites completed similar research. Some is published in the aerospace literature, more is available in company and government reports. Beginning in 1981, Vanyo and associates applied this knowledge to the very similar problem of energy dissipation and flow patterns in precessing mechanical models scaled geometrically and dynamically to the Earth’s liquid core. Energy experiments indicate massive amounts of mechanical energy are dissipated at the CMB, and flow experiments show complex motions within the boundary layer and axial flows with helicity throughout the interior. Analysis of Earth core precession also advanced, especially in several papers by Kerswell and by Tilgner in the late 1990s. Detail numerical models have yet to appear. Although progress in understanding the role of precession in Earth core motions has advanced, there remains a

  15. P5CDH affects the pathways contributing to Pro synthesis after ProDH activation by biotic and abiotic stress conditions.

    PubMed

    Rizzi, Yanina S; Monteoliva, Mariela I; Fabro, Georgina; Grosso, Carola L; Laróvere, Laura E; Alvarez, María E

    2015-01-01

    Plants facing adverse conditions usually alter proline (Pro) metabolism, generating changes that help restore the cellular homeostasis. These organisms synthesize Pro from glutamate (Glu) or ornithine (Orn) by two-step reactions that share Δ(1) pyrroline-5-carboxylate (P5C) as intermediate. In the catabolic process, Pro is converted back to Glu using a different pathway that involves Pro dehydrogenase (ProDH), P5C dehydrogenase (P5CDH), and P5C as intermediate. Little is known about the coordination of the catabolic and biosynthetic routes under stress. To address this issue, we analyzed how P5CDH affects the activation of Pro synthesis, in Arabidopsis tissues that increase ProDH activity by transient exposure to exogenous Pro, or infection with Pseudomonas syringae pv. tomato. Wild-type (Col-0) and p5cdh mutant plants subjected to these treatments were used to monitor the Pro, Glu, and Orn levels, as well as the expression of genes from Pro metabolism. Col-0 and p5cdh tissues consecutively activated ProDH and Pro biosynthetic genes under both conditions. However, they manifested a different coordination between these routes. When external Pro supply was interrupted, wild-type leaves degraded Pro to basal levels at which point Pro synthesis, mainly via Glu, became activated. Under the same condition, p5cdh leaves sustained ProDH induction without reducing the Pro content but rather increasing it, apparently by stimulating the Orn pathway. In response to pathogen infection, both genotypes showed similar trends. While Col-0 plants seemed to induce both Pro biosynthetic routes, p5cdh mutant plants may primarily activate the Orn route. Our study contributes to the functional characterization of P5CDH in biotic and abiotic stress conditions, by revealing its capacity to modulate the fate of P5C, and prevalence of Orn or Glu as Pro precursors in tissues that initially consumed Pro.

  16. P5CDH affects the pathways contributing to Pro synthesis after ProDH activation by biotic and abiotic stress conditions

    PubMed Central

    Rizzi, Yanina S.; Monteoliva, Mariela I.; Fabro, Georgina; Grosso, Carola L.; Laróvere, Laura E.; Alvarez, María E.

    2015-01-01

    Plants facing adverse conditions usually alter proline (Pro) metabolism, generating changes that help restore the cellular homeostasis. These organisms synthesize Pro from glutamate (Glu) or ornithine (Orn) by two-step reactions that share Δ1 pyrroline-5-carboxylate (P5C) as intermediate. In the catabolic process, Pro is converted back to Glu using a different pathway that involves Pro dehydrogenase (ProDH), P5C dehydrogenase (P5CDH), and P5C as intermediate. Little is known about the coordination of the catabolic and biosynthetic routes under stress. To address this issue, we analyzed how P5CDH affects the activation of Pro synthesis, in Arabidopsis tissues that increase ProDH activity by transient exposure to exogenous Pro, or infection with Pseudomonas syringae pv. tomato. Wild-type (Col-0) and p5cdh mutant plants subjected to these treatments were used to monitor the Pro, Glu, and Orn levels, as well as the expression of genes from Pro metabolism. Col-0 and p5cdh tissues consecutively activated ProDH and Pro biosynthetic genes under both conditions. However, they manifested a different coordination between these routes. When external Pro supply was interrupted, wild-type leaves degraded Pro to basal levels at which point Pro synthesis, mainly via Glu, became activated. Under the same condition, p5cdh leaves sustained ProDH induction without reducing the Pro content but rather increasing it, apparently by stimulating the Orn pathway. In response to pathogen infection, both genotypes showed similar trends. While Col-0 plants seemed to induce both Pro biosynthetic routes, p5cdh mutant plants may primarily activate the Orn route. Our study contributes to the functional characterization of P5CDH in biotic and abiotic stress conditions, by revealing its capacity to modulate the fate of P5C, and prevalence of Orn or Glu as Pro precursors in tissues that initially consumed Pro. PMID:26284090

  17. Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

    PubMed Central

    EL-SAGHIRE, HOUSSEIN; VANDEVOORDE, CHARLOT; OST, PIET; MONSIEURS, PIETER; MICHAUX, ARLETTE; DE MEERLEER, GERT; BAATOUT, SARAH; THIERENS, HUBERT

    2014-01-01

    Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18–24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation. PMID:24435511

  18. Pro-oxidative action of polyphenols as action mechanism for their pro-apoptotic activity.

    PubMed

    Lecci, Raffaella Marina; Logrieco, Antonio; Leone, Antonella

    2014-01-01

    Polyphenols, secondary metabolites widely present in plant kingdom, are known for their positive effects on human health, such as treatments of degenerative disease and cancer. Many dietary polyphenols show anti-inflammatory, immunomodulatory and antioxidant properties and they are proposed as chemopreventive agents for many skin disorders and cancer. Exposure to solar UV radiation is widely considered to cause skin cancer and a consistent carcinogenic dose derived from UVA causes several skin disorders as a consequence of free radicals generation and DNA damages. In this study, verbascoside, isoverbascoside and tyrosol were investigated for their effects on HEKa (Human Epidermal Keratinocytes adult) cell cultures challenged from UVA-rays. Non-toxic doses of each polyphenol were assayed on HEKa before, during and after the exposure to a damaging dose of UVA. Treatment with polyphenols before and after the UVA-irradiation exerted a pro-oxidant effect, while the simultaneous treatment caused a weak decrease of ROS production. The increasing of ROS levels was associated with a proapoptotic effect on HEKa, detected by AnnexinV/Propidiun Iodide, mainly evident in surviving cells treated with the polyphenols after the UVA-irradiation. The pro-apoptotic effect was confirmed by the immunodetection of significant changes in the Bax and Bcl-xL protein levels, leading to apoptotic events. The hypothesis that these polyphenols could trigger the apoptosis pathway mainly in UVA-damaged cells, via ROS increase, is here proposed as action mechanism behind their protective effect.

  19. High Serum Levels of Pro-Brain Natriuretic Peptide (pro BNP) Identify Cardioembolic Origin in Undetermined Stroke

    PubMed Central

    Rodríguez-Yáñez, Manuel; Sobrino, Tomás; Blanco, Miguel; de la Ossa, Natalia Pérez; Brea, David; Rodríguez-González, Raquel; Leira, Rogelio; Dávalos, Antonio; Castillo, José

    2009-01-01

    Background: Stroke subtype diagnosis leads to specific therapies to reduce recurrences. Because nearly one third of patients remain with unknown etiology after a complete screening workup, we aim to investigate whether molecular markers of myocardial damage were associated with cardioembolic stroke and if they were useful to reclassify strokes of undetermined etiology. Methods: We included 262 patients with first ischemic stroke within the first 12 hours. Stroke subtype was evaluated by TOAST criteria. Stroke of undetermined origin were reclassified into likely atherothrombotic or likely cardioembolic according to a predefined non-validated algorithm. Blood samples were obtained on admission to determine serum levels of molecular markers (pro-BNP, pro-ANP and CK-MB) of myocardial damage. Results: Patients with cardioembolic infarct showed higher levels of pro-BNP, pro-ANP and CK-MB. Pro-BNP > 360 pg/mL was independently associated with cardioembolic stroke (OR: 28.51, CI95%: 5.90–136.75, p < 0.0001). Stroke etiology was undetermined in 82 patients (31%); 34 were reclassified as likely cardioembolic, 22 as likely atherothrombotic, and 26 remained as undetermined. Pro-BNP > 360 pg/mL was the only factor independently associated with likely cardioembolic stroke. Conclusions: Pro-BNP levels higher than 360 pg/mL are associated with cardioembolic stroke and may be useful to reclassify undetermined strokes as of cardioembolic origin. PMID:19729800

  20. Diagnostic and prognostic role of procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM) in bacterial infections.

    PubMed

    Angeletti, Silvia; Spoto, Silvia; Fogolari, Marta; Cortigiani, Marco; Fioravanti, Marta; De Florio, Lucia; Curcio, Brunella; Cavalieri, Danilo; Costantino, Sebastiano; Dicuonzo, Giordano

    2015-09-01

    Rapid diagnosis of bacterial infections is crucial for adequate antibiotic treatment. Serum molecules such as Procalcitonin (PCT) have been used as biomarkers of infection. Recently, the mid-regional pro-Adrenomedullin (MR-proADM) has been evaluated in combination with PCT for sepsis diagnosis. The diagnostic role of PCT and MR-proADM both in sepsis and in localized infections together with their contribution to effective antibiotic therapy has been evaluated. One hundred and eighty-two patients with bacterial infection has been enrolled: PCT and MR-proADM were measured at admission (T = 0), at 12-24 h (T = 1) and in the third or fifth day of antibiotic therapy (T = 3-5). ROC curve (receiver operating characteristic) and post-test probability were calculated. MR-proADM increased with the severity of the infection. PCT resulted significantly higher in sepsis than localized infection. After antibiotic therapy, PCT significantly decreased in localized respiratory infections and in sepsis, while MR-proADM decreased significantly after antibiotic therapy only in patients with severe sepsis/septic shock. The threshold values of PCT and MR-proADM were >0.1 ng/mL and >0.8 nmol/L, respectively. The combined use of PCT and MR-proADM increased the post-test probability of the diagnosis of bacterial infections compared to PCT alone. In conclusion, PCT and MR-proADM combination improves the diagnosis of bacterial infection and contribute to prognosis and antibiotic therapy effectiveness.

  1. ProUCL version 4.1.00 Documentation Downloads

    EPA Pesticide Factsheets

    ProUCL version 4.1.00 represents a comprehensive statistical software package equipped with statistical methods and graphical tools needed to address many environmental sampling and statistical issues as described in various these guidance documents.

  2. ProUCL version 4.00.05 Documentation Downloads

    EPA Pesticide Factsheets

    ProUCL 4.00.05 serves as a companion software package for Calculating Upper Confidence Limits for Exposure Point Concentrations at Hazardous Waste Sites and Guidance for Comparing Background and Chemical Concentrations in Soil for CERCLA Sites.

  3. Poliovirus protease 3C(pro) kills cells by apoptosis.

    PubMed

    Barco, A; Feduchi, E; Carrasco, L

    2000-01-20

    The tetracycline-based Tet-Off expression system has been used to analyze the effects of poliovirus protease 3C(pro) on human cells. Stable HeLa cell clones that express this poliovirus protease under the control of an inducible, tightly regulated promoter were obtained. Tetracycline removal induces synthesis of 3C protease, followed by drastic morphological alterations and cellular death. Degradation of cellular DNA in nucleosomes and generation of apoptotic bodies are observed from the second day after 3C(pro) induction. The cleavage of poly(ADP-ribose) polymerase, an enzyme involved in DNA repair, occurs after induction of 3C(pro), indicating caspase activation by this poliovirus protease. The 3C(pro)-induced apoptosis is blocked by the caspase inhibitor z-VAD-fmk. Our findings suggest that the protease 3C is responsible for triggering apoptosis in poliovirus-infected cells by a mechanism that involves caspase activation.

  4. Recent advances in tissue (pro)renin imaging.

    PubMed

    Prokai, Agnes; Peti-Peterdi, Janos

    2010-06-01

    Due to its pivotal role in blood pressure control and renal pathologies there is renewed interest in renin and its precursor prorenin. Also, the newly discovered (pro)renin receptor is a new element of the ever broadening renin-angiotensin system (RAS). The complexity of RAS including the recently recognized collecting duct site of (pro)renin (a term denoting both renin and prorenin) synthesis requires the use of advanced research techniques such as multiphoton fluorescence microscopy. With the help of this technology we have pioneered an imaging approach to directly visualize (pro)renin content, release and tissue activity in the living kidney. The use of this technology is reviewed here and exemplified by the direct visualization of (pro)renin activity in the collecting duct. New pharmacological tools, the renin inhibitor aliskiren and the handle region peptide (decoy peptide) was used to further characterize the intra-renal, collecting duct RAS.

  5. Recent advances in tissue (pro)renin imaging

    PubMed Central

    Prokai, Agnes; Peti-Peterdi, Janos

    2010-01-01

    1. ABSTRACT Due to its pivotal role in blood pressure control and renal pathologies there is renewed interest in renin and its precursor prorenin. Also, the newly discovered (pro)renin receptor is a new element of the ever broadening renin-angiotensin system (RAS). The complexity of RAS including the recently recognized collecting duct site of (pro)renin (a term denoting both renin and prorenin) synthesis requires the use of advanced research techniques such as multiphoton fluorescence microscopy. With the help of this technology we have pioneered an imaging approach to directly visualize (pro)renin content, release and tissue activity in the living kidney. The use of this technology is reviewed here and exemplified by the direct visualization of (pro)renin activity in the collecting duct. New pharmacological tools, the renin inhibitor aliskiren and the handle region peptide (decoy peptide) was used to further characterize the intra-renal, collecting duct RAS. PMID:20515794

  6. Dogs Do Not Show Pro-social Preferences towards Humans

    PubMed Central

    Quervel-Chaumette, Mylène; Mainix, Gaëlle; Range, Friederike; Marshall-Pescini, Sarah

    2016-01-01

    Pro-social behaviors are defined as voluntary actions that benefit others. Comparative studies have mostly focused on investigating the presence of pro-sociality across species in an intraspecific context. Taken together, results on both primates and non-primate species indicate that reliance on cooperation may be at work in the selection and maintenance of pro-social sentiments. Dogs appear to be the ideal model when investigating a species’ propensity for pro-sociality in an interspecific context because it has been suggested that as a consequence of domestication, they evolved an underlying temperament encouraging greater propensity to cooperate with human partners. In a recent study, using a food delivery paradigm, dogs were shown to preferentially express pro-social choices toward familiar compared to unfamiliar conspecifics. Using the same set-up and methods in the current study, we investigated dogs’ pro-social preferences toward familiar and unfamiliar human partners. We found that dogs’ pro-social tendencies did not extend to humans and the identity of the human partners did not influence the rate of food delivery. Interestingly, dogs tested with their human partners spent more time gazing at humans, and did so for longer after food consumption had ended than dogs tested with conspecific partners in the initial study. To allow comparability between results from dogs tested with a conspecific and a human partner, the latter were asked not to communicate with dogs in any way. However, this lack of communication from the human may have been aversive to dogs, leading them to cease performing the task earlier compared to the dogs paired with familiar conspecifics in the prior study. This is in line with previous findings suggesting that human communication in such contexts highly affects dogs’ responses. Consequently, we encourage further studies to examine dogs’ pro-social behavior toward humans taking into consideration their potential responses

  7. Dogs Do Not Show Pro-social Preferences towards Humans.

    PubMed

    Quervel-Chaumette, Mylène; Mainix, Gaëlle; Range, Friederike; Marshall-Pescini, Sarah

    2016-01-01

    Pro-social behaviors are defined as voluntary actions that benefit others. Comparative studies have mostly focused on investigating the presence of pro-sociality across species in an intraspecific context. Taken together, results on both primates and non-primate species indicate that reliance on cooperation may be at work in the selection and maintenance of pro-social sentiments. Dogs appear to be the ideal model when investigating a species' propensity for pro-sociality in an interspecific context because it has been suggested that as a consequence of domestication, they evolved an underlying temperament encouraging greater propensity to cooperate with human partners. In a recent study, using a food delivery paradigm, dogs were shown to preferentially express pro-social choices toward familiar compared to unfamiliar conspecifics. Using the same set-up and methods in the current study, we investigated dogs' pro-social preferences toward familiar and unfamiliar human partners. We found that dogs' pro-social tendencies did not extend to humans and the identity of the human partners did not influence the rate of food delivery. Interestingly, dogs tested with their human partners spent more time gazing at humans, and did so for longer after food consumption had ended than dogs tested with conspecific partners in the initial study. To allow comparability between results from dogs tested with a conspecific and a human partner, the latter were asked not to communicate with dogs in any way. However, this lack of communication from the human may have been aversive to dogs, leading them to cease performing the task earlier compared to the dogs paired with familiar conspecifics in the prior study. This is in line with previous findings suggesting that human communication in such contexts highly affects dogs' responses. Consequently, we encourage further studies to examine dogs' pro-social behavior toward humans taking into consideration their potential responses both with and

  8. Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    1999-01-01

    NASA's Propulsive Small Expendable Deployer System experiment (ProSEDS) will demonstrate the use of an electrodynamic tether, basically a long, thin wire, for propulsion. An electrodynamic tether uses the same principles as electric motors in toys, appliances and computer disk drives, and generators in automobiles and power plants. When electrical current is flowing through the tether, a magnetic field is produced that pushes against the magnetic field of the Earth. For ProSEDS, the current in the tether results by virtue of the voltage generated when the tether moves through the Earth's magnetic field at more than 17,000 mph. This approach can produce drag thrust generating useable power. Since electrodynamic tethers require no propellant, they could substantially reduce the weight of the spacecraft and provide a cost-effective method of reboosting spacecraft. The initial flight of ProSEDS is scheduled to fly aboard an Air Force Delta II rocket in the summer of 2002. In orbit, ProSEDS will deploy from a Delta II second stage. It will be a 3.1-mile (5 kilometer) long, ultrathin base-wire cornected with a 6.2-mile (10 kilometer) long nonconducting tether. This photograph shows Less Johnson, a scientist at MSFC inspecting the nonconducting part of a tether as it exits a deployer similar to the one to be used in the ProSEDS experiment. The ProSEDS experiment is managed by the Space Transportation Directorate at MSFC.

  9. Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities

    PubMed Central

    Xie, Hui; Wang, Zhenxing; Zhang, Liming; Lei, Qian; Zhao, Aiqi; Wang, Hongxiang; Li, Qiubai; Cao, Yilin; Jie Zhang, Wen; Chen, Zhichao

    2017-01-01

    Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are potently pro-angiogenic both in vitro and in vivo. In the current study, we fabricated a novel EV-functionalized scaffold with enhanced pro-angiogenic and pro-bone regeneration activities by coating decalcified bone matrix (DBM) with MSC-derived EVs. EVs were harvested from rat bone marrow-derived MSCs and the pro-angiogenic potential of EVs was investigated in vitro. DBM scaffolds were then coated with EVs, and the modification was verified by scanning electron microscopy and confocal microscopy. Next, the pro-angiogenic and pro-bone regeneration activities of EV-modified scaffolds were evaluated in a subcutaneous bone formation model in nude mice. Micro-computed tomography scanning analysis showed that EV-modified scaffolds with seeded cells enhanced bone formation. Enhanced bone formation was confirmed by histological analysis. Immunohistochemical staining for CD31 proved that EV-modified scaffolds promoted vascularization in the grafts, thereby enhancing bone regeneration. This novel scaffold modification method provides a promising way to promote vascularization, which is essential for bone tissue engineering. PMID:28367979

  10. Synthesis, DNA recognition and cleavage studies of novel tetrapeptide complexes, Cu(II)/Zn(II)-Ala-Pro-Ala-Pro

    NASA Astrophysics Data System (ADS)

    Arjmand, Farukh; Jamsheera, A.; Mohapatra, D. K.

    2013-05-01

    New tetrapeptide complexes Cu(II)·Ala-Pro-Ala-Pro (1) and Zn(II)·Ala-Pro-Ala-Pro (2) were synthesized from the reaction of tetrapeptide, Ala-Pro-Ala-Pro and CuCl2/ZnCl2 and were thoroughly characterized by elemental analysis, IR,1H and 13C NMR (in case of 2), ESI-MS, UV and molar conductance measurements. The solution stability study was carried out employing UV-vis absorption titrations over a broad range of pH which suggested the stability of the complexes in solution. In vitro interaction of complexes 1 and 2 with CT-DNA was studied employing UV-vis, fluorescence, circular dichroic and viscometry studies. To throw insight into molecular binding event at the target site, UV-vis titrations of 1 and 2 with mononucleotides of interest viz.; 5'-GMP and 5'-TMP were carried out. Cleavage activity of the complexes with pBR322 plasmid DNA was evaluated by agarose gel electrophoresis and, the electrophoresis pattern demonstrated that both the complexes 1 and 2 are efficient cleavage agents. Further, the Cu(II) complex displayed efficient oxidative cleavage of supercoiled DNA while various reactive oxygen species are responsible for the cleavage in Zn(II) complex.

  11. Development of the Flight Tether for ProSEDS

    NASA Technical Reports Server (NTRS)

    Curtis, Leslie; Vaughn, Jason; Welzyn, Ken; Carroll, Joe; Brown, Norman S. (Technical Monitor)

    2002-01-01

    The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system to generate thrust in space by decreasing the orbital altitude of a Delta 11 Expendable Launch Vehicle second stage. ProSEDS will use the flight-proven Small Expendable Deployer System to deploy a newly designed and developed tether which will provide tether generated drag thrust of approx. 0.4 N. The development and production of very long tethers with specific properties for performance and survivability will be required to enable future tether missions. The ProSEDS tether design and the development process may provide some lessons learned for these future missions. The ProSEDS system requirements drove the design of the tether to have three different sections of tether each serving a specialized purpose. The tether is a total of 15 kilometers long: 10 kilometers of a non-conductive Dyneema lead tether; 5 km of CCOR conductive coated wire; and 220 meters of insulated wire with a protective Kevlar overbraid. Production and joining of long tether lengths involved many development efforts. Extensive testing of tether materials including ground deployment of the full-length ProSEDS tether was conducted to validate the tether design and performance before flight.

  12. Structure and activation of pro-activin A

    PubMed Central

    Wang, Xuelu; Fischer, Gerhard; Hyvönen, Marko

    2016-01-01

    Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein. PMID:27373274

  13. Cytosolic pro-apoptotic SPIKE induces mitochondrial apoptosis in cancer.

    PubMed

    Nikolic, Ivana; Kastratovic, Tatjana; Zelen, Ivanka; Zivanovic, Aleksandar; Arsenijevic, Slobodan; Mitrovic, Marina

    2010-04-30

    Proteins of the BCL-2 family are important regulators of apoptosis. The BCL-2 family includes three main subgroups: the anti-apoptotic group, such as BCL-2, BCL-XL, BCL-W, and MCL-1; multi-domain pro-apoptotic BAX, BAK; and pro-apoptotic "BH3-only" BIK, PUMA, NOXA, BID, BAD, and SPIKE. SPIKE, a rare pro-apoptotic protein, is highly conserved throughout the evolution, including Caenorhabditis elegans, whose expression is downregulated in certain tumors, including kidney, lung, and breast. In the literature, SPIKE was proposed to interact with BAP31 and prevent BCL-XL from binding to BAP31. Here, we utilized the Position Weight Matrix method to identify SPIKE to be a BH3-only pro-apoptotic protein mainly localized in the cytosol of all cancer cell lines tested. Overexpression of SPIKE weakly induced apoptosis in comparison to the known BH3-only pro-apoptotic protein BIK. SPIKE promoted mitochondrial cytochrome c release, the activation of caspase 3, and the caspase cleavage of caspase's downstream substrates BAP31 and p130CAS. Although the informatics analysis of SPIKE implicates this protein as a member of the BH3-only BCL-2 subfamily, its role in apoptosis remains to be elucidated.

  14. ProCure21+ should speed scheme starts.

    PubMed

    Baillie, Jonathan

    2010-11-01

    This October saw the launch of the new ProCure21+ National Framework under which, the Department of Health (DH) team behind the new scheme claims, the NHS can potentially save a further pound 200 million of public money on top of the substantial sums saved under predecessor, ProCure21, via faster, more streamlined procurement, design, planning, and construction, of publicly-funded healthcare schemes. HEJ editor Jonathan Baillie discussed, with the DH's senior responsible officer (SRO) and P21+ team leader Peter Sellars, the background to the new Framework's introduction, the success of its forerunner, and the additional benefits that ProCure21 + (which is backed by organisations incuding HM Treasury, the National Audit Office, and the Office of Government Commerce) should bring to the entire healthcare building supply chain.

  15. Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts

    PubMed Central

    Gurney, Mark; Mason, Malcolm D.; Tabi, Zsuzsanna; Clayton, Aled

    2015-01-01

    Stromal fibroblasts become altered in response to solid cancers, to exhibit myofibroblastic characteristics, with disease promoting influence. Infiltrating mesenchymal stem cells (MSC) may contribute towards these changes, but the factors secreted by cancer cells that impact MSC differentiation are poorly understood. We investigated the role of nano-metre sized vesicles (exosomes), secreted by prostate cancer cells, on the differentiation of bone-marrow MSC (BM-MSC), and the subsequent functional consequences of such changes. Purified exosomes impaired classical adipogenic differentiation, skewing differentiation towards alpha-smooth muscle actin (αSMA) positive myofibroblastic cells. A single exosomes treatment generated myofibroblasts secreting high levels of VEGF-A, HGF and matrix regulating factors (MMP-1, −3 and −13). Differentiated MSC had pro-angiogenic functions and enhanced tumour proliferation and invasivity assessed in a 3D co-culture model. Differentiation was dependent on exosomal-TGFβ, but soluble TGFβ at matched dose could not generate the same phenotype. Exosomes present in the cancer cell secretome were the principal factors driving this phenotype. Prostate cancer exosomes dominantly dictate a programme of MSC differentiation generating myofibroblasts with functional properties consistent with disease promotion. PMID:25596732

  16. Pro-A-type natriuretic peptide and pro-adrenomedullin predict progression of chronic kidney disease: the MMKD Study.

    PubMed

    Dieplinger, Benjamin; Mueller, Thomas; Kollerits, Barbara; Struck, Joachim; Ritz, Eberhard; von Eckardstein, Arnold; Haltmayer, Meinhard; Kronenberg, Florian

    2009-02-01

    A-type natriuretic peptide (ANP) and adrenomedullin (ADM) are potent hypotensive, diuretic, and natriuretic peptides involved in maintaining cardiovascular and renal homeostasis. We conducted a prospective 7-year study of 177 nondiabetic patients with primary chronic kidney disease to see if ANP and ADM plasma concentrations predict the progression of their disease, using novel sandwich immunoassays covering the midregional epitopes of the stable prohormones (MRproANP and MR-proADM). Progression of chronic kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure, which occurred in 65 patients. Analysis of the receiver operating characteristic curve for the prediction of renal endpoints showed similar areas under the curve for the glomerular filtration rate (GFR) (0.838), MR-proANP (0.810), and MRproADM (0.876), respectively, as did the Kaplan-Meier curve analyses of the patients stratified according to the median of the respective markers. In separate multiple Cox-proportional hazard regression analyses, increased plasma concentrations of both peptides were each strongly predictive of the progression of chronic kidney disease after adjustments for age, gender, GFR, proteinuria and amino-terminal pro-B-type natriuretic peptide. Our study suggests that MR-proANP and MR-proADM are useful new markers of progression of primary nondiabetic chronic kidney disease.

  17. ProGolem: A System Based on Relative Minimal Generalisation

    NASA Astrophysics Data System (ADS)

    Muggleton, Stephen; Santos, José; Tamaddoni-Nezhad, Alireza

    Over the last decade Inductive Logic Programming systems have been dominated by use of top-down refinement search techniques. In this paper we re-examine the use of bottom-up approaches to the construction of logic programs. In particular, we explore variants of Plotkin's Relative Least General Generalisation (RLGG) which are based on subsumption relative to a bottom clause. With Plotkin's RLGG, clause length grows exponentially in the number of examples. By contrast, in the Golem system, the length of ij-determinate RLGG clauses were shown to be polynomially bounded for given values of i and j. However, the determinacy restrictions made Golem inapplicable in many key application areas, including the learning of chemical properties from atom and bond descriptions. In this paper we show that with Asymmetric Relative Minimal Generalisations (or ARMGs) relative to a bottom clause, clause length is bounded by the length of the initial bottom clause. ARMGs, therefore do not need the determinacy restrictions used in Golem. An algorithm is described for constructing ARMGs and this has been implemented in an ILP system called ProGolem which combines bottom-clause construction in Progol with a Golem control strategy which uses ARMG in place of determinate RLGG. ProGolem has been evaluated on several well-known ILP datasets. It is shown that ProGolem has a similar or better predictive accuracy and learning time compared to Golem on two determinate real-world applications where Golem was originally tested. Moreover, ProGolem was also tested on several non-determinate real-world applications where Golem is inapplicable. In these applications, ProGolem and Aleph have comparable times and accuracies. The experimental results also suggest that ProGolem significantly outperforms Aleph in cases where clauses in the target theory are long and complex.

  18. ProADD: A database on Protein Aggregation Diseases

    PubMed Central

    Shobana, Ramesh; Pandaranayaka, Eswari PJ

    2014-01-01

    ProADD, a database for protein aggregation diseases, is developed to organize the data under a single platform to facilitate easy access for researchers. Diseases caused due to protein aggregation and the proteins involved in each of these diseases are integrated. The database helps in classification of proteins involved in the protein aggregation diseases based on sequence and structural analysis. Analysis of proteins can be done to mine patterns prevailing among the aggregating proteins. Availability http://bicmku.in/ProADD PMID:25097386

  19. Victimization and Exposure to Pro-Self-Harm and Pro-Suicide Websites: A Cross-National Study.

    PubMed

    Minkkinen, Jaana; Oksanen, Atte; Kaakinen, Markus; Keipi, Teo; Räsänen, Pekka

    2017-02-01

    The study of websites displaying methods of both physical self-harm and suicide has become an important aspect of deliberate self-injury and suicide research. However, little is known about contextual factors related to entering such sites. Using data from 3,567 respondents aged 15-30 in the US, UK, Germany, and Finland, we found that experiences of victimization are associated with entering pro-self-harm sites and pro-suicide sites. Also, the victimization context had relevance, as online victimization was particularly related to pro-self-harm behavior. The findings suggest a need to organize more specific online support for the victims of violence and online aggression.

  20. Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities

    PubMed Central

    Teresa Pinto, Ana; Laranjeiro Pinto, Marta; Patrícia Cardoso, Ana; Monteiro, Cátia; Teixeira Pinto, Marta; Filipe Maia, André; Castro, Patrícia; Figueira, Rita; Monteiro, Armanda; Marques, Margarida; Mareel, Marc; dos Santos, Susana Gomes; Seruca, Raquel; Adolfo Barbosa, Mário; Rocha, Sónia; José Oliveira, Maria

    2016-01-01

    In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2 Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10 Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more pro-inflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy. PMID:26735768

  1. Severe Sepsis and Septic Shock Trials (ProCESS, ARISE, ProMISe): What is Optimal Resuscitation?

    PubMed

    Osborn, Tiffany M

    2017-04-01

    Between 2014 and 2015, 3 independent, multicenter, randomized controlled trials evaluated early goal-directed therapy (EGDT) in severe sepsis and septic shock: Protocolized Care for Early Septic Shock (ProCESS) from the United States; Australasian Resuscitation in Sepsis Evaluation (ARISE), and Protocolised Management in Sepsis (ProMISe) in the United Kingdom. All 3 trials confirmed that there was no survival benefit of EGDT compared to usual resuscitation. How should we define usual care for sepsis given these study findings? Furthermore, the definition of sepsis has now been updated. This article reviews key findings of these 3 trials and discusses these important issues in sepsis management.

  2. ProOpDB: Prokaryotic Operon DataBase.

    PubMed

    Taboada, Blanca; Ciria, Ricardo; Martinez-Guerrero, Cristian E; Merino, Enrique

    2012-01-01

    The Prokaryotic Operon DataBase (ProOpDB, http://operons.ibt.unam.mx/OperonPredictor) constitutes one of the most precise and complete repositories of operon predictions now available. Using our novel and highly accurate operon identification algorithm, we have predicted the operon structures of more than 1200 prokaryotic genomes. ProOpDB offers diverse alternatives by which a set of operon predictions can be retrieved including: (i) organism name, (ii) metabolic pathways, as defined by the KEGG database, (iii) gene orthology, as defined by the COG database, (iv) conserved protein domains, as defined by the Pfam database, (v) reference gene and (vi) reference operon, among others. In order to limit the operon output to non-redundant organisms, ProOpDB offers an efficient method to select the most representative organisms based on a precompiled phylogenetic distances matrix. In addition, the ProOpDB operon predictions are used directly as the input data of our Gene Context Tool to visualize their genomic context and retrieve the sequence of their corresponding 5' regulatory regions, as well as the nucleotide or amino acid sequences of their genes.

  3. The "Creation-Science" Case and Pro Bono Publico.

    ERIC Educational Resources Information Center

    Kerr, Peggy L.

    1982-01-01

    Describes contributions and efforts of New York law firm (Skadden, Arps, Slate, Meagher, Flom) personnel in developing plaintiff's case in McLean v. Arkansas 590 (balanced treatment of creationism/evolution). Discusses aspects of "Pro Bono Publico" (unpaid public interest service) endeavors in general and those related to this law firm in…

  4. Enhancements to Demilitarization Process Maps Program (ProMap)

    DTIC Science & Technology

    2016-10-14

    Mar 16 100% 100% 3 Quarterly Technical and Business Status Report 20 Dec 15 100% 100% 4 Task 3: ProMap program update that imports MIDAS 30 Jun 16...100% 100% 5 Quarterly Technical and Business Status Report 20 Mar 16 100% 100% 6 Quarterly Technical and Business Status Report 20 Jun 16 100% 100

  5. 19 CFR 122.74 - Incomplete (pro forma) manifest.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Incomplete (pro forma) manifest. 122.74 Section 122.74 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT...; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard...

  6. 31 CFR 50.93 - Application of pro rata share.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Application of pro rata share. 50.93 Section 50.93 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE... from a subsequent act of terrorism....

  7. Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This Quick Time movie is of NASA's Propulsive Small Expendable Deployer System experiment (ProSEDS). ProSEDS will demonstrate the use of an electrodynamic tether, basically a long, thin wire, for propulsion. An electrodynamic tether uses the same principles as electric motors in toys, appliances and computer disk drives, and generators in automobiles and power plants. When electrical current is flowing through the tether, a magnetic field is produced that pushes against the magnetic field of the Earth. For ProSEDS, the current in the tether results by virtue of the voltage generated when the tether moves through the Earth's magnetic field at more than 17,000 mph. This approach can produce drag thrust generating useable power. Since electrodynamic tethers require no propellant, they could substantially reduce the weight of the spacecraft and provide a cost-effective method of reboosting spacecraft. The tether would be a 3.1-mile (5 kilometer) long, ultrathin base-wire tether connected with a 6.2-mile (10 kilometer) long nonconducting tether. The ProSEDS experiment is managed by the Space Transportation Directorate at the Marshall Space Flight Center.

  8. Inoculating against Pro-Plagiarism Justifications: Rational and Affective Strategies

    ERIC Educational Resources Information Center

    Compton, Josh; Pfau, Michael

    2008-01-01

    Student plagiarism continues to threaten academic integrity. This investigation assessed whether an inoculation message strategy could combat university plagiarism by protecting student attitudes against pro-plagiarism justification arguments. Additionally, we sought theoretical confirmation of previous findings on involvement and accessibility in…

  9. Watts Up? Pro AC Power Meter for Automated Energy Recording

    PubMed Central

    Hirst, Jason M.; Miller, Jonathan R.; Kaplan, Brent A.; Reed, Derek D.

    2013-01-01

    The purpose of the present paper is to review the Watts up? Pro AC power meter. Evaluations of the meter's reliability for measuring energy consumption by consumer electronics yielded acceptable levels of reliability. Implications and limitations for the use of this product in behavior analytic research and practice are discussed.

  10. Putting the "Pro" into TESL/TEFL Professionalism.

    ERIC Educational Resources Information Center

    Edstam, Tina

    2001-01-01

    Offers seven steps practicing English-as-a-Second-Language (ESL) teachers can take to create a strong professional identity: become an articulate ESL spokesperson, collaborate with a mainstream teacher or content-area teacher, be a learner as well as a teacher, take a pro-active stance on ESL issues, become an active member of your state TESL…

  11. Do Null Subjects (Mis-)Trigger Pro-Drop Grammars?

    ERIC Educational Resources Information Center

    Frazier, Lyn

    2015-01-01

    Native speakers of English regularly hear sentences without overt subjects. Nevertheless, they maintain a [[superscript -]pro] grammar that requires sentences to have an overt subject. It is proposed that listeners of English recognize that speakers reduce predictable material and thus attribute null subjects to this process, rather than changing…

  12. The Role of Cyclo(His-Pro) in Neurodegeneration

    PubMed Central

    Grottelli, Silvia; Ferrari, Ilaria; Pietrini, Grazia; Peirce, Matthew J.; Minelli, Alba; Bellezza, Ilaria

    2016-01-01

    Neurodegenerative diseases may have distinct genetic etiologies and pathological manifestations, yet share common cellular mechanisms underpinning neuronal damage and dysfunction. These cellular mechanisms include excitotoxicity, calcium dysregulation, oxidative damage, ER stress and neuroinflammation. Recent data have identified a dual role in these events for glial cells, such as microglia and astrocytes, which are able both to induce and to protect against damage induced by diverse stresses. Cyclo(His-Pro), a cyclic dipeptide derived from the hydrolytic removal of the amino-terminal pyroglutamic acid residue of the hypothalamic thyrotropin-releasing hormone, may be important in regulating the nature of the glial cell contribution. Cyclo(His-Pro) is ubiquitous in the central nervous system and is a key substrate of organic cation transporters, which are strongly linked to neuroprotection. The cyclic dipeptide can also cross the brain-blood-barrier and, once in the brain, can affect diverse inflammatory and stress responses by modifying the Nrf2-NF-κB signaling axis. For these reasons, cyclo(His-Pro) has striking potential for therapeutic application by both parenteral and oral administration routes and may represent an important new tool in counteracting neuroinflammation-based degenerative pathologies. In this review, we discuss the chemistry and biology of cyclo(His-Pro), how it may interact with the biological mechanisms driving neurodegenerative disease, such as amyotrophic lateral sclerosis, and thereby act to preserve or restore neuronal function. PMID:27529240

  13. PRO development: rigorous qualitative research as the crucial foundation.

    PubMed

    Lasch, Kathryn Eilene; Marquis, Patrick; Vigneux, Marc; Abetz, Linda; Arnould, Benoit; Bayliss, Martha; Crawford, Bruce; Rosa, Kathleen

    2010-10-01

    Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity.

  14. QSAR Study of Mosquito Repellents Using Codessa Pro

    DTIC Science & Technology

    2006-01-01

    SciFinder catalog.21 Using Codessa Pro in the normal manner gave the 3-descriptor model for the vapor pressure shown in Table 3 with the follow- ing...20. Stone, M. J. R. Stat. Soc. B. 1977, 38, 44. 21. SciFinder Scholar, American Chemical Society, 2003. 22. Katritzky, A. R.; Wang, Y.; Sild, S.; Tamm

  15. Affecting Community Change: Involving "Pro Bono" Professionals as Extension Volunteers

    ERIC Educational Resources Information Center

    Kelley, Diane T.; Culp, Ken, III

    2013-01-01

    "Pro bono" volunteers provide an effective means for Extension professionals to expand limited financial and human resources. Volunteers recruited from business settings can provide skills, abilities, expertise, leadership, and resources to Extension programs. Allowing professional volunteers to meet their desired leadership goals while…

  16. Virtex-II Pro SEE Test Methods and Results

    NASA Technical Reports Server (NTRS)

    Petrick, David; Powell, Wesley; Howard, James W., Jr.; LaBel, Kenneth A.

    2004-01-01

    The objective of this coarse Single Event Effect (SEE) test is to determine the suitability of the commercial Virtex-II Pro family for use in spaceflight applications. To this end, this test is primarily intended to determine any Singe Event Latchup (SEL) susceptibilities for these devices. Secondly, this test is intended to measure the level of Single Event Upset (SEU) susceptibilities and in a general sense where they occur. The coarse SEE test was performed on a commercial XC2VP7 device, a relatively small single processor version of the Virtex-II Pro. As the XC2VP7 shares the same functional block design and fabrication process with the larger Virtex-II Pro devices, the results of this test should also be applicable to the larger devices. The XC2VP7 device was tested on a commercial Virtex-II Pro development board. The testing was performed at the Cyclotron laboratories at Texas A&M and Michigan State Universities using ions of varying energy levels and fluences.

  17. Affordance, Learning Opportunities, and the Lesson Plan Pro Forma

    ERIC Educational Resources Information Center

    Anderson, Jason

    2015-01-01

    This article argues that the most commonly used lesson plan pro formas in language teacher education are inappropriately premised on an outcomes-based approach to teaching, one that is in conflict with what we know about how languages are learnt and how experienced teachers teach. It proposes an alternative, affordance-based approach to lesson…

  18. HBpF-proBDNF: A New Tool for the Analysis of Pro-Brain Derived Neurotrophic Factor Receptor Signaling and Cell Biology

    PubMed Central

    Gaub, Perrine; de Léon, Andrès; Gibon, Julien; Soubannier, Vincent; Dorval, Geneviève; Séguéla, Philippe; Barker, Philip A.

    2016-01-01

    Neurotrophins activate intracellular signaling pathways necessary for neuronal survival, growth and apoptosis. The most abundant neurotrophin in the adult brain, brain-derived neurotrophic factor (BDNF), is first synthesized as a proBDNF precursor and recent studies have demonstrated that proBDNF can be secreted and that it functions as a ligand for a receptor complex containing p75NTR and sortilin. Activation of proBDNF receptors mediates growth cone collapse, reduces synaptic activity, and facilitates developmental apoptosis of motoneurons but the precise signaling cascades have been difficult to discern. To address this, we have engineered, expressed and purified HBpF-proBDNF, an expression construct containing a 6X-HIS tag, a biotin acceptor peptide (BAP) sequence, a PreScission™ Protease cleavage site and a FLAG-tag attached to the N-terminal part of murine proBDNF. Intact HBpF-proBDNF has activities indistinguishable from its wild-type counterpart and can be used to purify proBDNF signaling complexes or to monitor proBDNF endocytosis and retrograde transport. HBpF-proBDNF will be useful for characterizing proBDNF signaling complexes and for deciphering the role of proBDNF in neuronal development, synapse function and neurodegenerative disease. PMID:26950209

  19. Polymorphism of collagen triple helix revealed by 19F NMR of model peptide [Pro-4(R)-hydroxyprolyl-Gly]3-[Pro-4(R)-fluoroprolyl-Gly]-[Pro-4(R)-hydroxyprolyl-Gly]3.

    PubMed

    Kawahara, Kazuki; Nemoto, Nobuaki; Motooka, Daisuke; Nishi, Yoshinori; Doi, Masamitsu; Uchiyama, Susumu; Nakazawa, Takashi; Nishiuchi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Kobayashi, Yuji

    2012-06-14

    We have characterized various structures of (Pro-Hyp(R)-Gly)(3)-Pro-fPro(R)-Gly-(Pro-Hyp(R)-Gly)(3) in the process of cis-trans isomerization and helix-coil transition by exploiting the sole (19)F NMR probe in 4(R)-fluoroproline (fPro(R)). Around the transition temperature (T(m)), we detected a species with a triple helical structure distinct from the ordinary one concerning the alignment of three strands. The (19)F-(19)F exchange spectroscopy showed that this misaligned and that the ordinary triple helices were interchangeable only indirectly via an extended monomer strand with all-trans peptide bonds at Pro-fPro(R), Pro-Hyp(R), and Gly-Pro in the central segment. This finding demonstrates that the helix-coil transition of collagen peptides is not described with a simple two-state model. We thus elaborated a scheme for the transition mechanism of (Pro-Hyp(R)-Gly)(n) that the most extended monomer strand can be the sole source both to the misaligned and correctly folded triple-helices. The staggered ends could help misaligned triple helices to self-assemble to higher-order structures. We have also discussed the possible relationship between the misaligned triple helix accumulating maximally at T(m) and the kinetic hysteresis associated with the helix-coil transition of collagen.

  20. Using Pro/ENGINEER`s{reg_sign} interface module

    SciTech Connect

    Schulze, J.

    1994-06-01

    When the ACCORD Process introduced Pro/ENGINEER to Sandians several years ago, a new process for design/definition was implemented. Prior to ACCORD, engineers and draftsmen worked in the 2-D mode with a program caned ANVIL{reg_sign}, which had limited capabilities. Although the transition from 2-D modeling to 3-D modeling met with some resistance, most engineers have embraced this new concept with enthusiasm They are now able to work in the 3-D mode and at increased levels of productivity with appropriate time savings never achieved before. One area that Pro/ENGINEER is noted for that this report will concentrate on, is the powerful interface module with its wide selection of transfer file configurations. This allows the engineer to create parts or assemblies and transfer them to many different second party software packages whose vendors can provide the capability for stress analysis, rapid prototypes, virtual reality environments, or many other forms of advanced manufacturing modes of communication. The ACCORD Program has at its core, the Pro/ENGINEER program from Parametric Technology Inc. Included in the ACCORD program, are several supporting programs from other vendors to make this cooperation between software packages a reality. It is possible to create parts in Pro/ENG transfer those parts to another package that has the capability to analyze the parts for deficiencies, then optimize those parts, and allow for changes to be made. Also included in this report, are other packages closely tied to Pro/ENGINEER, but not necessarily supported under the ACCORD program. Some of these packages allow you to create very impressive video productions, or allow you to meander through a virtual reality scenario. All of these new software packages will give you a new perspective on performance. This report will show how some of these interfaces work, and how you can improve your productivity if you utilize the ACCORD program as it is implemented here at Sandia.

  1. Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    Curtis, Leslie; Johnson, Les; Brown, Norman S. (Technical Monitor)

    2002-01-01

    The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system to generate thrust in space by decreasing the orbital altitude of a Delta 11 Expendable Launch Vehicle second stage. ProSEDS, which is planned on an Air Force GPS Satellite replacement mission in June 2002, will use the flight proven Small Expendable Deployer System (SEDS) to deploy a tether (5 km bare wire plus 10 km non-conducting Dyneema) from a Delta 11 second stage to achieve approx. 0.4N drag thrust. ProSEDS will utilize the tether-generated current to provide limited spacecraft power. The ProSEDS instrumentation includes Langmuir probes and Differential Ion Flux Probes, which will determine the characteristics of the ambient ionospheric plasma. Two Global Positioning System (GPS) receivers will be used (one on the Delta and one on the endmass) to help determine tether dynamics and to limit transmitter operations to occasions when the spacecraft is over selected ground stations. The flight experiment is a precursor to the more ambitious electrodynamic tether upper stage demonstration mission, which will be capable of orbit raising, lowering and inclination changes-all using electrodynamic thrust. An immediate application of ProSEDS technology is for the removal of spent satellites for orbital debris mitigation. In addition to the use of this technology to provide orbit transfer and debris mitigation it may also be an attractive option for future missions to Jupiter and any other planetary body with a magnetosphere.

  2. [BNP or NT-proBNP: "that is the question"].

    PubMed

    Lebrun, C; Neuder, Y; Pison, C; Chouri, N; Barnoud, D; Belle, L; Beaune, G

    2007-01-01

    Blood measurements of BNP and NT-proBNP, its catabolite, improve diagnosis for patients admitted to emergency departments with dyspnoea. In this paper, we have compared the BNP to the NT-proBNP for 119 dyspnoeic patients using at random clear clinical status. Among the test group of 119 patients, 57 showed coherent biological results for the 2 markers. These results confirm the final clinical diagnosis. Nine patients with congestive heart failure had abnormally low BNP and NT-proBNP rates. Six of these patients experienced long delays (longer than 48 hours and less than 72 hours) between their admission in emergency and the biological measurement of the natriuretic biomarkers. Three of the other patients could be not only flash OAP cases with a fast growth and a fast normalisation of BNP but also could have existing genetical factors. These genetical factors leading to high variability in BNP synthesis are not related to physiological or cardiac factors. 43 patients showed a mismatch between BNP and NT-proBNP. BNP appeared to be unstable in vitro. The lack of stability in whole blood or plasma samples is increased by sampling in a glass EDTA collection tube and too long delays in transferring the samples from the emergency area and the laboratory in a big hospital. Ten patients showed a mismatch with abnormally high NT-proBNP or false positive results. Among these 10 patients, 5 had renal dysfunction with a high level of creatinine concentration. It is clear that all Diagnostics Manufacturers should now propose different cut-off for natriuretic peptides tests according to the degree of patients' renal impairment.

  3. Development of Polymer Coatings for the ProSEDS Tether

    NASA Technical Reports Server (NTRS)

    Vaughn, Jason A.; Kamenetsky, Rachel R.; Finckenor, Miria; Wright, Ken

    2000-01-01

    The ProSEDS mission is designed to provide an on-orbit demonstration of the electrodynamic propulsion capabilities of tethers in space. The ProSEDS experiment will be a secondary payload on a Delta 11 unmanned, expendable booster. A 5 km conductive tether is attached to the deployer baseplate on the Delta 11 second stage and collects current from the low Earth orbit (LEO) plasma to facilitate de-orbit of the Delta II second stage. The conductive tether is attached to a 10-15 km non-conductive tether, which in turn is attached to an endmass. A bare metal tether would have the best conductivity but thermal concerns preclude this design. A conductive polymer developed by Triton Systems has been optimized for optimum conductivity and thermo-optical properties. The current design for the ProSEDS conductive tether is seven individually coated strands of 28 AWG aluminum wire, coated with 12.7 micrometers (0.5 mil) atomic oxygen-resistant conductive polymer composed of a mixture of COR and PANi, wrapped around a braided Kevlar 29 core. Extensive testing has been performed at the Marshall Space Flight Center to qualify this material for flight on ProSEDS. Atomic oxygen exposure has been performed, with solar absorptance and infrared emittance measured before and after exposure. Plasma chamber tests have been completed, as well as tether deployment tests. Also developed for the ProSEDS mission was the insulating polymer TOR-BP. Approximately 200 meters of the conductive tether closest to the Delta II second stage is insulated to prevent any electron reconnection to the tether from the plasma contactor. The insulating material is TOR-BP with a dielectric strength of TBD.

  4. Association between GPX1 Pro189Leu polymorphism and the occurrence of bladder cancer in Morocco.

    PubMed

    Hadami, K; Ameziane El Hassani, R; Ameur, A; Dakka, N; Abbar, M; Al Bouzidi, A; Attaleb, M; El Mzibri, M

    2016-12-30

    Worldwide, Bladder cancer is the most frequent male malignancy. It is the third most common male malignancy in Morocco. The risk factors for developing bladder cancer are multiples including dietary conditions, environmental exposure and oxidative stress. GPX1 gene encoding for the human cellular antioxidant enzyme glutathione peroxidase1 is a key factor in the cell detoxification process. GPX1 Pro198Leu polymorphism is associated with a decrease of enzyme activity and may contribute to bladder cancer susceptibility. The present case-control study was planned to assess the presence of GPX1 Pro198Leu polymorphism in Moroccan population to determine whether it is associated with the risk of developing bladder cancer in Moroccan patients. A total of 32 patients with bladder cancer and 40 healthy controls were enrolled. Genotyping of the GPX1 Pro198Leu polymorphism was carried out by PCR amplification and DNA sequencing. Pro198Leu polymorphism was observed in both bladder cancer patients and healthy controls. No significant association between the polymorphism and bladder cancer occurrence was found (Pro/Leu vs. Pro/Pro: p=0.425; Leu vs. Pro: p=0.435). For the analysis of Pro198Leu polymorphism and progression of bladder cancer, no association was observed neither for stages (Pro/Leu vs. Pro/Pro: p=0.500; Leu vs. Pro: p=0.500) nor grades (Pro/Leu vs. Pro/Pro: p=0.415; Leu vs. Pro: p=0.427). Our results clearly showed no significant association between Pro198Leu polymorphism and risk of bladder cancer in our population, suggesting that the effect of this polymorphism on bladder cancer development might be a result of a combination with other genetic alterations and/or non-genetic variables such as diet and lifestyle factors.

  5. Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells.

    PubMed

    Egan, Karl; Crowley, Darragh; Smyth, Paul; O'Toole, Sharon; Spillane, Cathy; Martin, Cara; Gallagher, Michael; Canney, Aoife; Norris, Lucy; Conlon, Niamh; McEvoy, Lynda; Ffrench, Brendan; Stordal, Britta; Keegan, Helen; Finn, Stephen; McEneaney, Victoria; Laios, Alex; Ducrée, Jens; Dunne, Eimear; Smith, Leila; Berndt, Michael; Sheils, Orla; Kenny, Dermot; O'Leary, John

    2011-01-01

    Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cells with the most significant adhesion to the 59M cell line. Ovarian cancer cells induced platelet activation [P-selectin expression] in a dose dependent manner, with the most significant activation seen in response to the 59M cell line. The platelet antagonists [cangrelor, MRS2179, and apyrase] inhibited 59M cell induced activation suggesting a P2Y12 and P2Y1 receptor mediated mechanism of platelet activation dependent on the release of ADP by 59M cells. A2780 and 59M cells potentiated PAR-1, PAR-4, and TxA2 receptor mediated platelet activation, but had no effect on ADP, epinephrine, or collagen induced activation. Analysis of gene expression changes in ovarian cancer cells following treatment with washed platelets or platelet releasate showed a subtle but valid upregulation of anti-apoptotic, anti-autophagy pro-angiogenic, pro-cell cycle and metabolic genes. Thus, ovarian cancer cells with different metastatic potential adhere and activate platelets differentially while both platelets and platelet releasate mediate pro-survival and pro-angiogenic signals in ovarian cancer cells.

  6. Nanomolar aluminum induces pro-inflammatory and pro-apoptotic gene expression in human brain cells in primary culture.

    PubMed

    Lukiw, Walter J; Percy, Maire E; Kruck, Theo P

    2005-09-01

    Aluminum, the most abundant neurotoxic metal in our biosphere, has been implicated in the etiology of several neurodegenerative disorders including Alzheimer's disease (AD). To further understand aluminum's influence on gene expression, we examined total messenger RNA levels in untransformed human neural cells exposed to 100 nanomolar aluminum sulfate using high density DNA microarrays that interrogate the expression of every human gene. Preliminary data indicate that of the most altered gene expression levels, 17/24 (70.8%) of aluminum-affected genes, and 7/8 (87.5%) of aluminum-induced genes exhibit expression patterns similar to those observed in AD. The seven genes found to be significantly up-regulated by aluminum encode pro-inflammatory or pro-apoptotic signaling elements, including NF-kappaB subunits, interleukin-1beta precursor, cytosolic phospholipase A2, cyclooxygenase-2, beta-amyloid precursor protein and DAXX, a regulatory protein known to induce apoptosis and repress transcription. The promoters of genes up-regulated by aluminum are enriched in binding sites for the stress-inducible transcription factors HIF-1 and NF-kappaB, suggesting a role for aluminum, HIF-1 and NF-kappaB in driving atypical, pro-inflammatory and pro-apoptotic gene expression. The effect of aluminum on specific stress-related gene expression patterns in human brain cells clearly warrant further investigation.

  7. The 2015-16 Pro-Kid Policy Agenda for California: A Guide to Pro-Kid Policymaking

    ERIC Educational Resources Information Center

    Children Now, 2015

    2015-01-01

    The 2015-16 Pro-Kid Policy Agenda for California is the only comprehensive roadmap at the state level for policymakers, stakeholders, and others who want all children--especially children of color and children from low-income families--to have the opportunity to reach their full potential. A plethora of research shows that investments in quality…

  8. Diacerein inhibits the pro-atherogenic & pro-inflammatory effects of IL-1 on human keratinocytes & endothelial cells

    PubMed Central

    Bao, Lei; Many, Benjamin; Chan, Lawrence S.

    2017-01-01

    We investigated IL-1-induced regulation of genes related to inflammation and atherogenesis in human keratinocytes and endothelial cells, and if ‘diacerein’, an oral IL-1 inhibiting drug currently approved for use in osteoarthritis, would reverse IL-1’s effects on these cells. Primary human keratinocytes and coronary artery endothelial cells were treated with either IL-1α or IL-1β, with and without diacerein. Using PCR-array, we assessed differential gene-expression regulated by IL-1 and diacerein. We identified 34 pro-atherogenic genes in endothelial cells and 68 pro-inflammatory genes in keratinocytes significantly (p<0.05) regulated at least 2-fold by IL-1, in comparison to control. Diacerein completely or partially reversed this regulation on almost all genes. Using ELISA, we confirmed diacerein’s ability to reverse IL-1-driven gene-regulation of 11 selected factors, at the protein level. The results support a novel idea that diacerein acts as an inhibitor of the pro-atherogenic and pro-inflammatory effects of IL-1. Diacerein may have therapeutic applications to diminish IL-1-induced skin inflammation in psoriasis and attenuate IL-1-induced development of atherosclerosis. Further investigation into diacerein’s effect on skin inflammation, atherogenesis and cardiovascular risk in animal models or humans is warranted. PMID:28323859

  9. Cell surface chondroitin sulfate glycosaminoglycan in melanoma: role in the activation of pro-MMP-2 (pro-gelatinase A).

    PubMed

    Iida, Joji; Wilhelmson, Krista L; Ng, Janet; Lee, Peter; Morrison, Charlotte; Tam, Eric; Overall, Christopher M; McCarthy, James B

    2007-05-01

    We previously reported that CS (chondroitin sulfate) GAG (glycosaminoglycan), expressed on MCSP (melanoma-specific CS proteoglycan), is important for regulating MT3-MMP [membrane-type 3 MMP (matrix metalloproteinase)]-mediated human melanoma invasion and gelatinolytic activity in vitro. In the present study, we sought to determine if CS can directly enhance MT3-MMP-mediated activation of pro-MMP-2. Co-immunoprecipitation studies suggest that MCSP forms a complex with MT3-MMP and MMP-2 on melanoma cell surface. When melanoma cells were treated with betaDX (p-nitro-beta-D-xylopyranoside) to inhibit coupling of CS on the core protein, both active form and proform of MMP-2 were no longer co-immunoprecipitated with either MCSP or MT3-MMP, suggesting a model in which CS directly binds to MMP-2 and presents the gelatinase to MT3-MMP to be activated. By using recombinant proteins, we determined that MT3-MMP directly activates pro-MMP-2 and that this activation requires the interaction of the C-terminal domain of pro-MMP-2 with MT3-MMP. Activation of pro-MMP-2 by suboptimal concentrations of MT3-MMP is also significantly enhanced in the presence of excess C4S (chondroitin 4-sulfate), whereas C6S (chondroitin 6-sulfate) or low-molecular-mass hyaluronan was ineffective. Affinity chromatography studies using CS isolated from aggrecan indicate that the catalytic domain of MT3-MMP and the C-terminal domain of MMP-2 directly bind to the GAG. Thus the direct binding of pro-MMP-2 with CS through the C-domain would present the catalytic domain of pro-MMP-2 to MT3-MMP, which facilitates the generation of the active form of MMP-2. These results suggest that C4S, which is expressed on tumour cell surface, can function to bind to pro-MMP-2 and facilitate its activation by MT3-MMP-expressing tumour cells to enhance invasion and metastasis.

  10. Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats.

    PubMed

    Aréchiga-Ceballos, F; Alvarez-Salas, E; Matamoros-Trejo, G; Amaya, M I; García-Luna, C; de Gortari, P

    2014-04-01

    Neuroendocrine axes adapt to nutrient availability. During fasting, the function of the hypothalamus-pituitary-thyroid axis (HPT) is reduced, whereas that of the hypothalamus-pituitary-adrenal axis (HPA) is increased. Overfeeding-induced hyperleptinemia during lactation may alter the regulatory set point of neuroendocrine axes and their adaptability to fasting in adulthood. Hyperleptinemia is developed in rodents by litter size reduction during lactation; adult rats from small litters become overweight, but their paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether peptide expression still responds to nutrient availability. PVN corticotropin-releasing factor (CRF) expression has not been evaluated in this model. We analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of reduced-litter adult rats. Offspring litters were reduced to 2-3/dam (early-overfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of animals from each group was fasted for 48 h and leptin, corticosterone, and thyroid hormones serum levels were analyzed. In brain, expressions of leptin receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN subcompartments was assayed by in situ hybridization. Early-overfed adults developed hyperphagia and excessive weight, together with decreased proTRH expression in anterior PVN, supporting the anorexigenic effects of TRH. Early-overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a further reduction. Fasting-induced stress was unable to increase corticosterone levels, contributing to reduced body weight loss in early-overfed rats. We concluded that early overfeeding impaired the adaptability of HPT and HPA axes to excess weight and fasting in adults.

  11. The increase of serum Bcl-2 concentration in moderate head injury outcome: The role of ACTH4-10Pro8-Gly9-Pro10

    PubMed Central

    Indharty, Rr Suzy

    2013-01-01

    Background: Traumatic brain injury (TBI) is one of the major causes of death and disability. Apoptosis after TBI contributes significantly to the final extent of tissue damage. The Bcl-2 family proteins are important apoptosis modulators which increased in injured neurons. Bcl-2 has shown an antiapoptotic effect in rats and mice. ACTH4-10Pro8-Gly9-Pro10 is a synthetic short fragment of ACTH devoid of hormonal effects and has neuromodulatory properties. ACTH4-10Pro8-Gly9-Pro10 has been shown to increase levels of Bcl-2 and BDNF in vitro as well as in vivo. It has been postulated that ACTH4-10Pro8-Gly9-Pro10 will result in improved clinical outcome and reduce hospital length of stay. The goal of this study is to compare the effect of standard therapy only with standard therapy and ACTH4-10Pro8-Gly9-Pro10, the increase of Bcl-2, and clinical outcome with reduction of hospital stay. Materials and Methods: Subjects of moderate head injury (MHI) with no indication of surgery were taken consecutively (n = 40) and separated into two groups: standard treatment only and standard treatment combined with ACTH4-10Pro8-Gly9-Pro10. Blood samples were taken on day 1 and day 5 from each subject for measurements of Bcl-2 concentration. Barthel Index and MMSE were measured, at discharge and hospital length of stay was noted. Results: Forty subjects have been involved in this study, three subjects died in the standard therapy group, and one subject in ACTH4-10Pro8-Gly9-Pro10 group. Bcl-2 serum level in standard therapy was 1.39 ± 0.75 ng/mL on day 1 and 1.48 ± 0.77 ng/mL on day 5. After treatment with ACTH4-10Pro8-Gly9-Pro10, Bcl-2 level was 1.39 ± 0.70 ng/mL on day 1 and 3.70 ± 1.02 ng/mL on day 5. The serum Bcl-2 concentration was significantly increased with ACTH4-10Pro8-Gly9-Pro10 therapy with shorter hospital length of stay (P < 0.05). Conclusion: ACTH4-10Pro8-Gly9-Pro10 increased serum Bcl-2 levels and reduced hospital length of stay significantly compared with standard

  12. Systematic Evaluation of the Patient-Reported Outcome (PRO) Content of Clinical Trial Protocols

    PubMed Central

    Kyte, Derek; Duffy, Helen; Fletcher, Benjamin; Gheorghe, Adrian; Mercieca-Bebber, Rebecca; King, Madeleine; Draper, Heather; Ives, Jonathan; Brundage, Michael; Blazeby, Jane; Calvert, Melanie

    2014-01-01

    Background Qualitative evidence suggests patient-reported outcome (PRO) information is frequently absent from clinical trial protocols, potentially leading to inconsistent PRO data collection and risking bias. Direct evidence regarding PRO trial protocol content is lacking. The aim of this study was to systematically evaluate the PRO-specific content of UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme trial protocols. Methods and Findings We conducted an electronic search of the NIHR HTA programme database (inception to August 2013) for protocols describing a randomised controlled trial including a primary/secondary PRO. Two investigators independently reviewed the content of each protocol, using a specially constructed PRO-specific protocol checklist, alongside the ‘Standard Protocol Items: Recommendations for Interventional Trials’ (SPIRIT) checklist. Disagreements were resolved through discussion with a third investigator. 75 trial protocols were included in the analysis. Protocols included a mean of 32/51 (63%) SPIRIT recommendations (range 16–41, SD 5.62) and 11/33 (33%) PRO-specific items (range 4–18, SD 3.56). Over half (61%) of the PRO items were incomplete. Protocols containing a primary PRO included slightly more PRO checklist items (mean 14/33 (43%)). PRO protocol content was not associated with general protocol completeness; thus, protocols judged as relatively ‘complete’ using SPIRIT were still likely to have omitted a large proportion of PRO checklist items. Conclusions The PRO components of HTA clinical trial protocols require improvement. Information on the PRO rationale/hypothesis, data collection methods, training and management was often absent. This low compliance is unsurprising; evidence shows existing PRO guidance for protocol developers remains difficult to access and lacks consistency. Study findings suggest there are a number of PRO protocol checklist items that are not fully

  13. ColorPro: PSF-corrected aperture-matched photometry

    NASA Astrophysics Data System (ADS)

    Coe, Dan; Benitez, Narciso

    2015-08-01

    ColorPro automatically obtains robust colors across images of varied PSF. To correct for the flux lost in images with poorer PSF, the "detection image" is blurred to match the PSF of these other images, allowing observation of how much flux is lost. All photometry is performed in the highest resolution frame (images being aligned given WCS information in the FITS headers), and identical apertures are used in every image. Usually isophotal apertures are used, as determined by SExtractor (ascl:1010.064). Using SExSeg (ascl:1508.006), object aperture definitions can be pre-defined and object detections from different image filters can be combined automatically into a single comprehensive "segmentation map." After producing the final photometric catalog, ColorPro can automatically run BPZ (ascl:1108.011) to obtain Bayesian Photometric Redshifts.

  14. Psychological antecedents of heterosexuals' pro-gay activism behavior.

    PubMed

    Wilkinson, Wayne W; Sagarin, Brad J

    2010-01-01

    Previous research on heterosexuals' attitudes toward gays is characterized by a focus on negative attitudes and minimal use of behavioral dependent variables. In an attempt to rectify this situation, the present study explored the psychological antecedents of heterosexuals' pro-gay activism behavior in an undergraduate sample using the theory of planned behavior (Ajzen, 1991). Findings suggest that intentions predict activism behavior (in the form of signing an online petition supporting the construction of a new lesbian, gay, and bisexual resource center on their campus). In addition, attitudes toward the possible outcomes of the behavior, attitudes toward the behavior itself, and self-identity were found to predict intentions. Directions for future research on pro-gay activism are discussed.

  15. The PACA Project : Pro-Am Collaborative Astronomy

    NASA Astrophysics Data System (ADS)

    Yanamandra-Fisher, P. A.

    2014-04-01

    The Pro-Am Collaborative Astronomy (PACA) project is the next stage of evolution of the paradigm developed for the observational campaign of C/2012 S1 or C/ISON. Four different phases of collaboration are identified, and illustrate the integration of scientific investigations with amateur astronomer community via observations, and models; and the rapid dissemination of the results via a multitude of social media for rapid global access. The success of the paradigm shift in scientific research is now implemented in other comet observing campaigns. Both communities (scientific and amateur astronomers) benefit from these collective, collaborative partnerships; while outreach is the instantaneous deliverable that provides both a framework for future data analyses and the dissemination of the results. While PACA identifies a collaborative approach to pro-am collaborations, given the volume of data generated for each campaign, new ways of rapid data analysis, mining access and storage are needed.

  16. Online Stigma Resistance in the Pro-Ana Community.

    PubMed

    Yeshua-Katz, Daphna

    2015-10-01

    Media scholars often use concepts from Goffman's dramaturgical approach to study online communities of stigmatized individuals as "backstages," spaces where members take refuge from social disapproval. In this study, I extend this view through an examination of in-depth interviews with bloggers from the "pro-ana" community, an online community for people with eating disorders. To explore how this community uses an online environment that is both anonymous and public, I fuse Goffman's ideas about identity performance and stigma with more recent theories about boundary maintenance. In-depth interviews with "pro-ana" bloggers reveal that to protect this virtual group and resist stigmas associated both with their illness and with their online presence, they construct their own norms and rules in the online realm, and discipline and eject members deemed to be out-group.

  17. Sex education training: a Pro Familia pilot project.

    PubMed

    1979-07-01

    A Pro Familia (Saarbrucken) project has established a pilot sex education project to teach youth leaders happy sexual relationships, how relationships are formed and influenced, and the physiological and biological realities surrounding those relationships. The training is intended for two groups. Personnel involved in out-of-school activities will be trained in 5-10 sessions of 2-3 hours each. The basic course highlights the participants' attitudes towards sexuality, sex education, and conflicts arising in youth work. 6 months later a further course follows in which practical experiences are exchanged. Training in the field is also provided for personnel of youth clubs, centres. Personal attitudes are discussed and a discussion group, led by Pro Familia personnel, are formed. Future workers in out-of-school activities need further training. A 2 term course at the Technical High School for social workers and extra courses in sociology, psychology, and teacher training, are being considered.

  18. Identifying Parents Who Are Amenable to Pro-Vaccination Conversations

    PubMed Central

    Brunson, Emily K.

    2015-01-01

    While health care providers are often cited as parents’ most trusted source for information and advice about vaccination, parents differ in their level of receptiveness to pro-vaccination conversations. The purpose of this research was to identify points in individual parents’ decision-making processes when parents are particularly open to receiving information and advice from their children’s health care providers. Interview data were collected from 20 mothers and 5 couples. Analysis of these data suggested 3 primary circumstances when parents were particularly open to receiving information and advice: during parents’ initial decision-making, as parents continued to assess vaccination options, and during particular circumstances that prompted parents to reconsider previously made vaccination choices. These results provide a mechanism for providers to identify parents who may be particularly receptive to pro-vaccination conversations. By prioritizing conversations with parents at one of these points, health care providers’ efforts at promoting vaccination may be more effective. PMID:27335987

  19. Cavum Septum Pellucidum in Retired American Pro-Football Players

    PubMed Central

    Hess, Christopher P.; Brus-Ramer, Marcel; Possin, Katherine L.; Cohn-Sheehy, Brendan I.; Kramer, Joel H.; Berger, Mitchel S.; Yaffe, Kristine; Miller, Bruce; Rabinovici, Gil D.

    2016-01-01

    Abstract Previous studies report that cavum septum pellucidum (CSP) is frequent among athletes with a history of repeated traumatic brain injury (TBI), such as boxers. Few studies of CSP in athletes, however, have assessed detailed features of the septum pellucidum in a case-control fashion. This is important because prevalence of CSP in the general population varies widely (2% to 85%) between studies. Further, rates of CSP among American pro-football players have not been described previously. We sought to characterize MRI features of the septum pellucidum in a series of retired pro-football players with a history of repeated concussive/subconcussive head traumas compared with controls. We retrospectively assessed retired American pro-football players presenting to our memory clinic with cognitive/behavioral symptoms in whom structural MRI was available with slice thickness ≤2 mm (n=17). Each player was matched to a memory clinic control patient with no history of TBI. Scans were interpreted by raters blinded to clinical information and TBI/football history, who measured CSP grade (0–absent, 1–equivocal, 2–mild, 3–moderate, 4–severe) and length according to a standard protocol. Sixteen of 17 (94%) players had a CSP graded ≥2 compared with 3 of 17 (18%) controls. CSP was significantly higher grade (p<0.001) and longer in players than controls (mean length±standard deviation: 10.6 mm±5.4 vs. 1.1 mm±1.3, p<0.001). Among patients presenting to a memory clinic, long high-grade CSP was more frequent in retired pro-football players compared with patients without a history of TBI. PMID:25970145

  20. Cerebral Lateralization of Pro- and Anti-Social Tendencies

    PubMed Central

    2014-01-01

    Mounting evidence suggest that the right-hemisphere (RH) has a relative advantage, over the left-hemisphere (LH), in mediating social intelligence - identifying social stimuli, understanding the intentions of other people, awareness of the dynamics in social relationships, and successful handling of social interactions. Furthermore, a review and synthesis of the literature suggest that pro-social attitudes and behaviors are associated with physiological activity in the RH, whereas unsocial and anti-social tendencies are mediated primarily by the LH. This hemispheric asymmetry is rooted in several neurobiological and functional differences between the two hemispheres. (I) Positive social interactions often require inhibiting one's immediate desires and considering the perspectives and needs of others. Given that self-control is mediated by the RH, pro-social emotions and behaviors are, therefore, inherently associated with the RH as it subserves the brain's self-restraint mechanisms. (II) The RH mediates experiences of vulnerability. It registers the relative clumsiness and motor weakness of the left limbs, and it is involved, more than the LH, in processing threats and mediating fear. Emotional states of vulnerability trigger the need for affiliation and sociality, therefore the RH has a greater role in mediating pro-social attitudes and behaviors. (III) The RH mediates a holistic mode of representing the world. Holistic perception emphasizes similarities rather than differences, takes a long-term perspective, is associated with divergent thinking and seeing other points-of-view, and it mediates a personal mode of relating to people. All these features of holistic perception facilitate a more empathetic attitude toward others and pro-social behaviors. PMID:24737936

  1. The Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    Lorenzini, Enrico C.; Cosmo, Mario L.; Curtis, Leslie (Technical Monitor)

    2003-01-01

    The summary of activity during this reporting period, most of which was covered by a no-cost extension of the grant, is as follows: 1) Participation in remote and in-situ (at MSFC EDAC facility) mission operation simulations; 2) Analysis of the decay rate of ProSEDS when starting the mission at a lower altitude; 3) Analysis of the deployment control law performance when deploying at a lower altitude.

  2. Cavum Septum Pellucidum in Retired American Pro-Football Players.

    PubMed

    Gardner, Raquel C; Hess, Christopher P; Brus-Ramer, Marcel; Possin, Katherine L; Cohn-Sheehy, Brendan I; Kramer, Joel H; Berger, Mitchel S; Yaffe, Kristine; Miller, Bruce; Rabinovici, Gil D

    2016-01-01

    Previous studies report that cavum septum pellucidum (CSP) is frequent among athletes with a history of repeated traumatic brain injury (TBI), such as boxers. Few studies of CSP in athletes, however, have assessed detailed features of the septum pellucidum in a case-control fashion. This is important because prevalence of CSP in the general population varies widely (2% to 85%) between studies. Further, rates of CSP among American pro-football players have not been described previously. We sought to characterize MRI features of the septum pellucidum in a series of retired pro-football players with a history of repeated concussive/subconcussive head traumas compared with controls. We retrospectively assessed retired American pro-football players presenting to our memory clinic with cognitive/behavioral symptoms in whom structural MRI was available with slice thickness ≤2 mm (n=17). Each player was matched to a memory clinic control patient with no history of TBI. Scans were interpreted by raters blinded to clinical information and TBI/football history, who measured CSP grade (0-absent, 1-equivocal, 2-mild, 3-moderate, 4-severe) and length according to a standard protocol. Sixteen of 17 (94%) players had a CSP graded ≥2 compared with 3 of 17 (18%) controls. CSP was significantly higher grade (p<0.001) and longer in players than controls (mean length±standard deviation: 10.6 mm±5.4 vs. 1.1 mm±1.3, p<0.001). Among patients presenting to a memory clinic, long high-grade CSP was more frequent in retired pro-football players compared with patients without a history of TBI.

  3. PRoNTo: pattern recognition for neuroimaging toolbox.

    PubMed

    Schrouff, J; Rosa, M J; Rondina, J M; Marquand, A F; Chu, C; Ashburner, J; Phillips, C; Richiardi, J; Mourão-Miranda, J

    2013-07-01

    In the past years, mass univariate statistical analyses of neuroimaging data have been complemented by the use of multivariate pattern analyses, especially based on machine learning models. While these allow an increased sensitivity for the detection of spatially distributed effects compared to univariate techniques, they lack an established and accessible software framework. The goal of this work was to build a toolbox comprising all the necessary functionalities for multivariate analyses of neuroimaging data, based on machine learning models. The "Pattern Recognition for Neuroimaging Toolbox" (PRoNTo) is open-source, cross-platform, MATLAB-based and SPM compatible, therefore being suitable for both cognitive and clinical neuroscience research. In addition, it is designed to facilitate novel contributions from developers, aiming to improve the interaction between the neuroimaging and machine learning communities. Here, we introduce PRoNTo by presenting examples of possible research questions that can be addressed with the machine learning framework implemented in PRoNTo, and cannot be easily investigated with mass univariate statistical analysis.

  4. PPARγ2Pro12Ala Polymorphism and Human Health

    PubMed Central

    He, Weimin

    2009-01-01

    The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARγ) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPARγ have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPARγ, Pro12Ala of PPARγ2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPARγ2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPARγ2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPARγ2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies. PMID:19390629

  5. Control of the Immune Response by Pro-Angiogenic Factors

    PubMed Central

    Voron, Thibault; Marcheteau, Elie; Pernot, Simon; Colussi, Orianne; Tartour, Eric; Taieb, Julien; Terme, Magali

    2014-01-01

    The progressive conversion of normal cells into cancer cells is characterized by the acquisition of eight hallmarks. Among these criteria, the capability of the cancer cell to avoid the immune destruction has been noted. Thus, tumors develop mechanisms to become invisible to the immune system, such as the induction of immunosuppressive cells, which are able to inhibit the development of an efficient immune response. Molecules produced in the tumor microenvironment are involved in the occurrence of an immunosuppressive microenvironment. Recently, it has been shown that vascular endothelial growth factor A (VEGF-A) exhibits immunosuppressive properties in addition to its pro-angiogenic activities. VEGF-A can induce the accumulation of immature dendritic cells, myeloid-derived suppressor cells, regulatory T cells, and inhibit the migration of T lymphocytes to the tumor. Other pro-angiogenic factors such as placental growth factor (PlGF) could also participate in tumor-induced immunosuppression, but only few works have been performed on this point. Here, we review the impact of pro-angiogenic factors (especially VEGF-A) on immune cells. Anti-angiogenic molecules, which target VEGF-A/VEGFR axis, have been developed in the last decades and are commonly used to treat cancer patients. These drugs have anti-angiogenic properties but can also counteract the tumor-induced immunosuppression. Based on these immunomodulatory properties, anti-angiogenic molecules could be efficiently associated with immunotherapeutic strategies in preclinical models. These combinations are currently under investigation in cancer patients. PMID:24765614

  6. BH3 mimetics activate multiple pro-autophagic pathways.

    PubMed

    Malik, S A; Orhon, I; Morselli, E; Criollo, A; Shen, S; Mariño, G; BenYounes, A; Bénit, P; Rustin, P; Maiuri, M C; Kroemer, G

    2011-09-15

    The BH3 mimetic ABT737 induces autophagy by competitively disrupting the inhibitory interaction between the BH3 domain of Beclin 1 and the anti-apoptotic proteins Bcl-2 and Bcl-X(L), thereby stimulating the Beclin 1-dependent allosteric activation of the pro-autophagic lipid kinase VPS34. Here, we examined whether ABT737 stimulates other pro-autophagic signal-transduction pathways. ABT737 caused the activating phosphorylation of AMP-dependent kinase (AMPK) and of the AMPK substrate acetyl CoA carboxylase, the activating phosphorylation of several subunits of the inhibitor of NF-κB (IκB) kinase (IKK) and the hyperphosphorylation of the IKK substrate IκB, inhibition of the activity of mammalian target of rapamycin (mTOR) and consequent dephosphorylation of the mTOR substrate S6 kinase. In addition, ABT737 treatment dephosphorylates (and hence likewise inhibits) p53, glycogen synthase kinase-3 and Akt. All these effects were shared by ABT737 and another structurally unrelated BH3 mimetic, HA14-1. Functional experiments revealed that pharmacological or genetic inhibition of IKK, Sirtuin and the p53-depleting ubiquitin ligase MDM2 prevented ABT737-induced autophagy. These results point to unexpected and pleiotropic pro-autophagic effects of BH3 mimetics involving the modulation of multiple signalling pathways.

  7. The Pro-inflammatory Effects of Glucocorticoids in the Brain

    PubMed Central

    Duque, Erica de Almeida; Munhoz, Carolina Demarchi

    2016-01-01

    Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein–protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981

  8. Anti-Inflammatory and Pro-Resolving Lipid Mediators

    PubMed Central

    Serhan, Charles N.; Yacoubian, Stephanie; Yang, Rong

    2009-01-01

    The popular view that all lipid mediators are pro-inflammatory arises largely from the finding that non-steroidal anti-inflammatory drugs block the biosynthesis of prostaglandins. The resolution of inflammation was widely held to be a passive event until recently, with the characterization of novel biochemical pathways and lipid-derived mediators that are actively turned on in resolution possessing potent anti-inflammatory and pro-resolving actions. A lipid mediator informatics approach was employed to systematically identify new families of endogenous local-acting mediators from omega-3-polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in resolving exudates in addition to the lipoxins and aspirin-triggered lipoxins generated from arachidonic acid. These new chemical mediator families were coined resolvins and protectins, given their potent bioactions. In this annual review, we present recent advances on the biosynthesis and stereospecific actions of these new pro-resolving mediators, which have also proven to be organ protective and anti-fibrotic. PMID:18233953

  9. Inhibition of murine AIDS by pro-glutathione (GSH) molecules.

    PubMed

    Fraternale, A; Paoletti, M F; Casabianca, A; Orlandi, C; Schiavano, G F; Chiarantini, L; Clayette, P; Oiry, J; Vogel, J-U; Cinatl, J; Magnani, M

    2008-02-01

    Antioxidant molecules can be used both to replenish the depletion of reduced glutathione (GSH) occurring during HIV infection, and to inhibit HIV replication. The purpose of this work was to assess the efficacy of two pro-GSH molecules able to cross the cell membrane more easily than GSH. We used an experimental animal model consisting of C57BL/6 mice infected with the LP-BM5 viral complex; the treatments were based on the intramuscular administration of I-152, a pro-drug of N-acetylcysteine and S-acetyl-beta-mercaptoethylamine, and S-acetylglutathione, an acetylated GSH derivative. The results show that I-152, at a concentration of 10.7 times lower than GSH, caused a reduction in lymph node and spleen weights of about 55% when compared to infected animals and an inhibition of about 66% in spleen and lymph node virus content. S-acetylglutathione, at half the concentration of GSH, caused a reduction in lymph node weight of about 17% and in spleen and lymph node virus content of about 70% and 30%, respectively. These results show that the administration of pro-GSH molecules may favorably substitute for the use of GSH as such.

  10. Propulsive Small Expendable Deployer System (ProSEDS) Space Demonstration

    NASA Technical Reports Server (NTRS)

    Johnson, Les; Ballance, Judy

    1998-01-01

    The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system. The flight experiment is a precursor to the more ambitious electrodynamic tether upper stage demonstration mission which will be capable of orbit raising, lowering and inclination changes-all using electrodynamic thrust. ProSEDS which is planned to fly in 2000, will use the flight proven Small Expendable C, Deployer System (SEDS) to deploy a tether (5 km bare wire plus 15 km spectra) from a Delta II upper stage to achieve approximately 0.4N drag thrust, thus deorbiting the stage. The experiment will use a predominantly 'bare' tether for current collection in lieu of endmass collector and insulated tether approach used on previous missions. ProSEDS will utilize tether-generated current to provide limited spacecraft power. In addition to the use of this technology to provide orbit transfer of payloads and upper stages from LEO to higher orbits it may also be an attractive option for future missions to Jupiter and any other planetary body with a magnetosphere.

  11. Propulsive Small Expendable Deployer System (ProSEDS) Space Experiment

    NASA Technical Reports Server (NTRS)

    Johnson, Les; Gilchrist, Brian; Estes, Robert D.; Lorenzini, Enrico; Ballance, Judy

    1998-01-01

    The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system. The flight experiment is a precursor to the more ambitious electrodynamic tether upper stage demonstration mission which will be capable of orbit raising, lowering and inclination changes-all using electrodynamic thrust. ProSEDS which is planned to fly in 2000, will use the flight proven Small Expendable Deployer System (SEDS) to deploy a tether (5km bare wire plus 15 km spectra) from a Delta II upper stage to achieve approximately 0.4N drag thrust, thus demonstrating deorbit thrust. The experiment will use a predominantly 'bare' tether for current collection in lieu of endmass collector and insulated tether approach used on previous missions. ProSEDS will utilize tether-generated current to provide limited spacecraft power. In addition to the use of this technology to provide orbit transfer of payloads and upper stages from LEO to higher orbits it may also be an attractive option for future missions to Jupiter and any other planetary body with a magnetosphere.

  12. Tenocytes, pro-inflammatory cytokines and leukocytes: a relationship?

    PubMed Central

    Al-Sadi, Onays; Schulze-Tanzil, Gundula; Kohl, Benjamin; Lohan, Anke; Lemke, Marion; Ertel, Wolfgang; John, Thilo

    2011-01-01

    Summary Leukocyte derived pro-inflammatory mediators could be involved in tendon healing and scar formation. Hence, the effect of autologous leukocytes (PBMCs, peripheral blood mononuclear cells and neutrophils) on primary rabbit Achilles tenocytes gene expression was tested in insert assisted co-cultures. Subsequently, tenocytes gene expression of extra-cellular matrix (ECM) components (type I collagen, decorin, fibronectin), the cell-ECM receptor β1-integrin, the angiogenic factor myodulin, ECM degrading matrix-metalloproteinase (MMP)1 and pro-inflammatory cytokines (interleukin [IL]-1β, tumour necrosis factor [TNFα] and IL-6) was analysed. The only significant effect of leukocytes on tenocytes ECM genes expression was a suppression of type I collagen by neutrophils combined with TNFα stimulation. The same effect could be observed analysing the β1-integrin and myodulin gene expression. However, PBMCs up-regulated significantly cytokine and MMP1 gene expression in tenocytes. These in vitro results suggest that mononuclear cells could present an exogenic stimulus for the induction of pro-inflammatory and catabolic mediators in tendon. PMID:23738251

  13. Increase in osmotolerance of Rhizobium fredii soybean isolate BD32 by the proB proA operon of Escherichia coli.

    PubMed

    Neumivakin, L V; Solovjev, V P; Sokhansanj, A; Tilba, V A; Moseiko, N A; Shachbasian, R V; Piruzian, E S

    1995-12-26

    The proB proA operons (which are blocked by the feedback inhibition of proline production) of Escherichia coli wild type or with the mutation proBosm, blocking feedback inhibition effect of proline production, were cloned in a broad host range shuttle vector pVA 12-2. The hybrid plasmids pLVA(proB+A+) and pNSA(proBosm proA), were transferred into a low level osmotolerance Rhizobium fredii strain BD32. Both types of transconjugants were characterised by increased osmotolerance in a minimal medium supplied with 0.4-0.8 M NaCl but in the case of pNSA the effect was more significant. The strain BD32/pNSA had an increased level of intracellular proline concentration. Practical application of the increase in Rhizobium resistance to the stress factors is discussed.

  14. Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses.

    PubMed

    Je, H Shawn; Yang, Feng; Ji, Yuanyuan; Nagappan, Guhan; Hempstead, Barbara L; Lu, Bai

    2012-09-25

    Formation of specific neuronal connections often involves competition between adjacent axons, leading to stabilization of the active terminal, while retraction of the less active ones. The underlying molecular mechanisms remain unknown. We show that activity-dependent conversion of pro-brain-derived neurotrophic factor (proBDNF) to mature (m)BDNF mediates synaptic competition. Stimulation of motoneurons triggers proteolytic conversion of proBDNF to mBDNF at nerve terminals. In Xenopus nerve-muscle cocultures, in which two motoneurons innervate one myocyte, proBDNF-p75(NTR) signaling promotes retraction of the less active terminal, whereas mBDNF-tyrosine-related kinase B (TrkB) p75NTR (p75 neurotrophin receptor) facilitates stabilization of the active one. Thus, proBDNF and mBDNF may serve as potential "punishment" and "reward" signals for inactive and active terminals, respectively, and activity-dependent conversion of proBDNF to mBDNF may regulate synapse elimination.

  15. ProQ3: Improved model quality assessments using Rosetta energy terms

    PubMed Central

    Uziela, Karolis; Shu, Nanjiang; Wallner, Björn; Elofsson, Arne

    2016-01-01

    Quality assessment of protein models using no other information than the structure of the model itself has been shown to be useful for structure prediction. Here, we introduce two novel methods, ProQRosFA and ProQRosCen, inspired by the state-of-art method ProQ2, but using a completely different description of a protein model. ProQ2 uses contacts and other features calculated from a model, while the new predictors are based on Rosetta energies: ProQRosFA uses the full-atom energy function that takes into account all atoms, while ProQRosCen uses the coarse-grained centroid energy function. The two new predictors also include residue conservation and terms corresponding to the agreement of a model with predicted secondary structure and surface area, as in ProQ2. We show that the performance of these predictors is on par with ProQ2 and significantly better than all other model quality assessment programs. Furthermore, we show that combining the input features from all three predictors, the resulting predictor ProQ3 performs better than any of the individual methods. ProQ3, ProQRosFA and ProQRosCen are freely available both as a webserver and stand-alone programs at http://proq3.bioinfo.se/. PMID:27698390

  16. NetPro: Methodologies and Tools for Project Based Learning in Internet.

    ERIC Educational Resources Information Center

    Markkanen, Hannu; Donzellini, Giuliano; Ponta, Domenico

    The mission of the NetPro European project is to develop project-based learning through the Internet. The NetPro project is creating tools and services to facilitate communication and collaboration between distant students, and to manage access and control of project deliverables. NetPro project teams form cross-institutional learning communities.…

  17. ProQ3: Improved model quality assessments using Rosetta energy terms.

    PubMed

    Uziela, Karolis; Shu, Nanjiang; Wallner, Björn; Elofsson, Arne

    2016-10-04

    Quality assessment of protein models using no other information than the structure of the model itself has been shown to be useful for structure prediction. Here, we introduce two novel methods, ProQRosFA and ProQRosCen, inspired by the state-of-art method ProQ2, but using a completely different description of a protein model. ProQ2 uses contacts and other features calculated from a model, while the new predictors are based on Rosetta energies: ProQRosFA uses the full-atom energy function that takes into account all atoms, while ProQRosCen uses the coarse-grained centroid energy function. The two new predictors also include residue conservation and terms corresponding to the agreement of a model with predicted secondary structure and surface area, as in ProQ2. We show that the performance of these predictors is on par with ProQ2 and significantly better than all other model quality assessment programs. Furthermore, we show that combining the input features from all three predictors, the resulting predictor ProQ3 performs better than any of the individual methods. ProQ3, ProQRosFA and ProQRosCen are freely available both as a webserver and stand-alone programs at http://proq3.bioinfo.se/.

  18. Quality of Patient-Reported Outcome (PRO) Reporting Across Cancer Randomized Controlled Trials According to the CONSORT PRO Extension: A Pooled Analysis of 557 Trials

    PubMed Central

    Efficace, Fabio; Fayers, Peter; Pusic, Andrea; Cemal, Yeliz; Yanagawa, Jane; Jacobs, Marc; la Sala, Andrea; Cafaro, Valentina; Whale, Katie; Rees, Jonathan; Blazeby, Jane

    2016-01-01

    Background The main objectives of this study were to identify the number of randomized controlled trials (RCTs) that have included a patient-reported outcome (PRO) endpoint across a wide range of cancer specialties and to evaluate completeness of PRO reporting according to the CONSORT PRO extension. Methods RCTs with a PRO endpoint, conducted across several cancer specialties and published between 2004 and 2013 were considered. Studies were evaluated based on previously defined criteria, including the CONSORT PRO extension and the Cochrane Collaboration's tool for assessing RCT Risk of Bias. Analyses were also conducted by type of PRO endpoint (primary versus secondary) and by cancer disease site. Results A total of 56,696 potentially eligible records were scrutinized and 557 RCTs with a PRO evaluation, enrolling overall 254,677 patients, were identified. PROs were most frequently used in RCTs of breast (N=123), lung (N=85) and colorectal (N=66) cancer. Overall, PROs were secondary endpoint in 421 (76%) RCTs. Four out of six CONSORT PRO items evaluated were documented in less than 50% of the RCTs. Level of reporting was higher in RCTs with PRO as a primary endpoint. Presence of a supplementary report was the only statistically significant factor associated with greater completeness of reporting for both RCTs with PRO as primary (β=0.19; P=0.001) or secondary endpoint (β=0.30; P<0.001). Conclusion Implementation of the CONSORT PRO extension is equally important across all cancer specialties. Its use can also contribute in revealing the robust PRO design of some studies, which might be obscured by poor outcome reporting. PMID:26079197

  19. Phase behavior and crystallogenesis under counter-diffusion conditions of the collagen-model peptide (Pro-Pro-Gly) 10

    NASA Astrophysics Data System (ADS)

    Vergara, Alessandro; Castagnolo, Dario; Carotenuto, Luigi; Vitagliano, Luigi; Berisio, Rita; Sorrentino, Giosué; González-Ramírez, Luis; García-Ruiz, Juan; Zagari, Adriana

    2009-01-01

    Single chains of the collagen-model polypeptide with sequence (Pro-Pro-Gly) 10, hereafter referred to as (PPG) 10, aggregate to form rod-shaped triple helices. Precipitation diagrams of (PPG) 10 as a function of pH and various molecular mass poly(ethylene glycol) concentrations have been measured. These results were used to design experiments to test the quality of (PPG) 10 crystal grown on ground (in gelled and free solutions) and in space in two different facilities, the Advanced Protein Crystallization Facility based on the free-interface diffusion technique and the Granada Crystallization Facility based on counter-diffusion technique. Experiments were monitored by optical microscopy on earth. X-ray diffraction analysis of the grown crystals reveals the benefit of the counter-diffusion technique.

  20. Association of protein S p.Pro667Pro dimorphism with plasma protein S levels in normal individuals and patients with inherited protein S deficiency.

    PubMed

    Castaman, G; Biguzzi, E; Razzari, C; Tosetto, A; Fontana, G; Asti, D; Brancaccio, V; Castori, D; Lane, D A; Faioni, E M

    2007-01-01

    A dimorphism in PROS1 gene (c.A2,001G, p.Pro667Pro) has been associated with significantly reduced levels of both free and total protein S in carriers of the GG genotype. It is not known how the GG genotype could influence PS levels in normals, whether it could influence the levels of protein S in carriers of mutations in PROS1 gene and whether this genotype acts as an isolated or additive risk factor for venous thrombosis. With this as background, we evaluated the association of p.Pro667Pro dimorphism with free and total protein S centrally measured in a panel of 119 normal controls, 222 individuals with low protein S and 137 individuals with normal PS levels belonging to 76 families with protein S deficiency enrolled in the ProSIT study. Transient expression of recombinant wild type protein S and p.Pro667Pro protein S was performed to evaluate the role of the A to G transition at position 2001 in vitro. The p.Pro667Pro polymorphism was also expressed together with a p.Glu67Ala variant to assess a possible influence on protein S levels in protein S deficient subjects. Free and total protein S levels were significantly lower in normal women. In normal women only was the GG genotype associated with significantly lower free protein S levels in comparison to AA and AG genotypes (P=0.032). No significant influence of GG genotype was observed in patients, either with known mutations or with low protein S levels. These data were confirmed by in vitro transient expression, showing no difference in secretion levels of the p.Pro667Pro variant (even in association with the p.Glu67Ala mutation), compared to the wild type protein S. The genotype in itself was neither a significant risk factor for venous thrombosis nor a risk modifier in patients with known mutations.

  1. An in vitro analysis of separation of multi-use ProTaper Universal and ProTaper Next instruments in extracted mandibular molar teeth.

    PubMed

    Ertas, Huseyin; Capar, Ismail Davut

    2015-01-01

    This study investigated the separation incidence of reused ProTaper Universal and ProTaper Next rotary instruments and identified the location of separated fragments. The root canals of extracted human mandibular molars were prepared with 10 assorted sets of ProTaper Universal and ProTaper Next instruments. After each preparation, instrument sets were autoclaved. This arrangement was repeated until an instrument fractured. The number of prepared teeth until fracture occurred was recorded for each instrument set. Teeth in which the instruments fractured were analyzed to determine the separation grade, apical relation, and coronal position. Fracture surfaces of the instruments were examined with scanning electron microscope. ProTaper Universal instruments fractured after application to a mean of 7.3 teeth, and ProTaper Next instruments after application to a mean of 5.7 teeth (p > 0.05). In the ProTaper Universal and ProTaper Next groups, F2 and X1 were the most commonly fractured instruments, respectively. Torsional and cyclic failures were evenly distributed in both the groups. The mean lengths of the fractured fragments of the instruments showed no statistically significant difference. The distance between the tip of the fractured instruments and apical constriction was similar (p > 0.05). However, the mean distance between the root canal orifice and coronal part of the fractured instrument was shorter in the ProTaper Next group (p < 0.05). The life span of ProTaper Universal and ProTaper Next instruments was the same for preparation of mandibular molar teeth. None of the instruments were fractured in the first usage.

  2. Expression, purification and functional characterization of recombinant Zucchini yellow mosaic virus HC-Pro.

    PubMed

    Fuellgrabe, Marc W; Boonrod, Kajohn; Jamous, Rana; Moser, Mirko; Shiboleth, Yoel; Krczal, Gabi; Wassenegger, Michael

    2011-01-01

    HC-Pro is a helper component-proteinase which acts as a multifunctional protein in the potyviral life cycle. Apart from its proteolytic activity, HC-Pro has the capacity to bind duplex small RNAs (sRNAs). To investigate HC-Pro-mediated sRNA binding in vitro, high amounts of purified protein are required. For this purpose, the Zucchini yellow mosaic virus (ZYMV) HC-Pro was expressed as a fusion with hexa-histidine (6xHis) or maltose-binding protein (MBP) in Escherichia coli. The expressed fusion proteins were purified by affinity chromatography. 6xHis:HC-Pro and MBP:HC-Pro were partially soluble. Electrophoretic mobility-shift assays demonstrated that only MBP:HC-Pro exhibits the sRNA binding activity. The recombinant HC-Pro bound 21 bp siRNAs as well as 19 bp and 24 bp siRNAs. A point mutation in the highly conserved FRNK box produced the HC-Pro(FINK) protein, previously shown to be associated with reduced viral symptoms and weak sRNA binding. In this study, sRNA binding of the MBP:HA-HC-Pro(FINK) was not detectable. The high yield of purified HC-Pro offers the possibility to study the biochemistry of the protein in detail.

  3. Computer-assisted design of pro-drugs for antimalarial atovaquone.

    PubMed

    Karaman, Rafik; Hallak, Hussein

    2010-10-01

    Density Functional Theory (DFT) and ab initio calculation results for the proton transfer reaction in Kirby's enzyme models 1-6 reveal that the reaction rate is largely dependent on the existence of a hydrogen bonding net in the reactants and the corresponding transition states. Further, the distance between the two reacting centers and the angle of the hydrogen bonding formed along the reaction path has profound effects on the rate. Hence, the study on the systems reported herein could provide a good basis for designing antimalarial (atovaquone) pro-drug systems that can be used to release the parent drug in a controlled manner. For example, based on the calculated log EM, the cleavage process for pro-drug 1Pro may be predicted to be about 10¹¹ times faster than that for a pro-drug 4Pro and about 10⁴ times faster than pro-drug 2Pro: rate (1Pro) > rate (2Pro > rate (4Pro). Thus, the rate by which the pro-drug releases the antimalarial drug can be determined according to the nature of the linker (Kirby's enzyme model 1-6).

  4. Flexibility of K3 and ProTaper universal instruments.

    PubMed

    Grazziotin-Soares, Renata; Barato Filho, Flares; Vanni, José Roberto; Almeida, Susimara; Oliveira, Elias Pandonor Motcy de; Barletta, Fernando Branco; Limongi, Orlando

    2011-01-01

    This study used a mechanical test to evaluate the flexibility of instruments from the K3 (conicity 0.04) and the ProTaper Universal systems when they were new and after 5 uses in simulated canals. Five sets of instruments of each system were tested: K3 (15, 20, 25, 30, 35, 40 and 45) and ProTaper Universal (S1, S2, F1, F2, F3, F4 and F5). Each set of instruments was used to prepare a simulated canal and the same set of instruments was used 5 times (50 canals). The number of each subgroup represented the number of uses: 0 (control), 1, 3 and 5 uses. Before and after each use, the instruments were submitted to a mechanical flexibility test performed in a Versat 502 universal testing machine. Interactions between the instrument and the number of uses were analyzed by ANOVA and Tukey's test at a 5% level of significance. Instruments from both systems presented lower flexibility after the third use compared to the flexibility obtained after uses 0 and 1 (p<0.05), and maintained the same flexibility after the fifth use. The flexibility of instruments from the K3 system decreased with the increase of diameter, irrespective of the number of uses. Among the instruments from the ProTaper Universal system, the shaping files presented greater flexibility than the finishing files. F2 and F3 were the least flexible instruments, and F4 and F5 presented flexibility values similar to those of F1.

  5. Context of action of Proline Dehydrogenase (ProDH) in the Hypersensitive Response of Arabidopsis

    PubMed Central

    2014-01-01

    Background Proline (Pro) dehydrogenase (ProDH) potentiates the oxidative burst and cell death of the plant Hypersensitive Response (HR) by mechanisms not yet elucidated. ProDH converts Pro into ∆1 pyrroline-5-carboxylate (P5C) and can act together with P5C dehydrogenase (P5CDH) to produce Glu, or with P5C reductase (P5CR) to regenerate Pro and thus stimulate the Pro/P5C cycle. To better understand the effects of ProDH in HR, we studied the enzyme at three stages of the defense response differing in their ROS and cell death levels. In addition, we tested if ProDH requires P5CDH to potentiate HR. Results Control and infected leaves of wild type and p5cdh plants were used to monitor ProDH activity, in vivo Pro catabolism, amino acid content, and gene expression. Wild type plants activated ProDH at all HR stages. They did not consume Pro during maximal ROS accumulation, and maintained almost basal P5C levels at all conditions. p5cdh mutants activated ProDH as wild type plants. They achieved maximum oxidative burst and cell death levels producing normal HR lesions, but evidenced premature defense activation. Conclusion ProDH activation has different effects on HR. Before the oxidative burst it leads to Pro consumption involving the action of P5CDH. During the oxidative burst, ProDH becomes functionally uncoupled to P5CDH and apparently works with P5CR. The absence of P5CDH does not reduce ROS, cell death, or pathogen resistance, indicating this enzyme is not accompanying ProDH in the potentiation of these defense responses. In contrast, p5cdh infected plants displayed increased ROS burst and earlier initiation of HR cell death. In turn, our results suggest that ProDH may sustain HR by participating in the Pro/P5C cycle, whose action on HR must be formally evaluated in a future. PMID:24410747

  6. The Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    Lorenzini, Enrico C.; Estes, Robert D.; Cosmo, Mario L.

    2001-01-01

    This is the Annual Report #2 entitled "The Propulsive Small Expendable Deployer System (ProSEDS)" prepared by the Smithsonian Astrophysical Observatory for NASA Marshall Space Flight Center. This report covers the period of activity from 1 August 2000 through 30 July 2001. The topics include: 1) Updated System Performance; 2) Mission Analysis; 3) Updated Dynamics Reference Mission; 4) Updated Deployment Control Profiles and Simulations; 5) Comparison of ED tethers and electrical thrusters; 6) Kalman filters for mission estimation; and 7) Delivery of interactive software for ED tethers.

  7. C-terminal Pro-Gly-Pro tripeptide in contrast to full-length neuropeptide semax exhibits no neuroprotective effect in experimental cerebral ischemia.

    PubMed

    Fadyukova, O E; Kadi, A; Bai, Ou; Andzhusheva, G M; Koshelev, V B

    2005-04-01

    The C-terminal fragment Pro-Gly-Pro of semax does not modulate the development of symptoms of neurological deficiency and mortality in rats with incomplete global cerebral ischemia. Hence, previously revealed neuroprotective effects of semax are mainly determined by corticotropin ACTH4-7 fragment.

  8. Making Women the Subjects of the Abortion Debate: A Class Exercise that Moves beyond "Pro-Choice" and "Pro-Life"

    ERIC Educational Resources Information Center

    Crawley, Sara L.; Willman, Rebecca K.; Clark, Leisa; Walsh, Clare

    2009-01-01

    In this article, the authors describe a classroom exercise designed to put women (and children and men) back at the center of the abortion debate, avoiding the standard rhetoric and engaging reflection on how everyone might find common political goals among the so-called pro-life and pro-choice sides. The exercise the authors offer in this article…

  9. Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience.

    PubMed

    Yang, Bangkun; Yang, Chun; Ren, Qian; Zhang, Ji-Chun; Chen, Qian-Xue; Shirayama, Yukihiko; Hashimoto, Kenji

    2016-12-01

    Using learned helplessness (LH) model of depression, we measured protein expression of brain-derived neurotrophic factor (BDNF) pro-peptide, BDNF precursors (proBDNF and preproBDNF) in the brain regions of LH (susceptible) and non-LH rats (resilience). Expression of preproBDNF, proBDNF and BDNF pro-peptide in the medial prefrontal cortex of LH rats, but not non-LH rats, was significantly higher than control rats, although expression of these proteins in the nucleus accumbens of LH rats was significantly lower than control rats. This study suggests that regional differences in conversion of BDNF precursors into BDNF and BDNF pro-peptide by proteolytic cleavage may contribute to stress resilience.

  10. Capturing Patient-Reported Outcome (PRO) Data Electronically: The Past, Present, and Promise of ePRO Measurement in Clinical Trials.

    PubMed

    Coons, Stephen Joel; Eremenco, Sonya; Lundy, J Jason; O'Donohoe, Paul; O'Gorman, Hannah; Malizia, William

    2015-08-01

    Patient-reported outcomes (PROs) are an important means of evaluating the treatment benefit of new medical products. It is recognized that PRO measures should be used when assessing concepts best known by the patient or best measured from the patient's perspective. As a result, there is growing emphasis on well defined and reliable PRO measures. In addition, advances in technology have significantly increased electronic PRO (ePRO) data collection capabilities and options in clinical trials. The movement from paper-based to ePRO data capture has enhanced the integrity and accuracy of clinical trial data and is encouraged by regulators. A primary distinction in the types of ePRO platforms is between telephone-based interactive voice response systems and screen-based systems. Handheld touchscreen-based devices have become the mainstay for remote (i.e., off-site, unsupervised) PRO data collection in clinical trials. The conventional approach is to provide study subjects with a handheld device with a device-based proprietary software program. However, an emerging alternative for clinical trials is called bring your own device (BYOD). Leveraging study subjects' own Internet-enabled mobile devices for remote PRO data collection (via a downloadable app or a Web-based data collection portal) has become possible due to the widespread use of personal smartphones and tablets. However, there are a number of scientific and operational issues that must be addressed before BYOD can be routinely considered as a practical alternative to conventional ePRO data collection methods. Nevertheless, the future for ePRO data collection is bright and the promise of BYOD opens a new chapter in its evolution.

  11. Antioxidant, pro-oxidant and cytotoxic properties of parsley.

    PubMed

    Dorman, H J Damien; Lantto, Tiina A; Raasmaja, Atso; Hiltunen, Raimo

    2011-06-01

    Parsley (Petroselinum crispum) leaves were macerated with a mixture of methanol: water: acetic acid to produce a crude extract which was then defatted with (40°-60°) petrol. Antioxidant activity of the extract was evaluated using a battery of in vitro assays, viz., iron(iii) reduction, iron(ii) chelation and free radical scavenging assays. Evaluation of the pro-oxidant activity of the extract was based upon its effects upon DNA fragmentation and protein carbonylation. Cytotoxicity and apoptotic effects of the extract were determined in non-cancerous CV1-P fibroblast and cancerous A375 melanoma cells using MTT and LDH tests and caspase 3-like activity assay. The highest concentration, 2.0 mg ml(-1), decreased the viability of both cell lines, however, the cancerous melanoma cells were slightly susceptible to the effects. The observed cytotoxicity was not due to the caspase 3 activity. In conclusion, the toxicity might be explained by the pro-oxidative activity of components within the extract against proteins and/or DNA but it is not related to caspase 3-dependent apoptosis within cells.

  12. PRoViScout: a planetary scouting rover demonstrator

    NASA Astrophysics Data System (ADS)

    Paar, Gerhard; Woods, Mark; Gimkiewicz, Christiane; Labrosse, Frédéric; Medina, Alberto; Tyler, Laurence; Barnes, David P.; Fritz, Gerald; Kapellos, Konstantinos

    2012-01-01

    Mobile systems exploring Planetary surfaces in future will require more autonomy than today. The EU FP7-SPACE Project ProViScout (2010-2012) establishes the building blocks of such autonomous exploration systems in terms of robotics vision by a decision-based combination of navigation and scientific target selection, and integrates them into a framework ready for and exposed to field demonstration. The PRoViScout on-board system consists of mission management components such as an Executive, a Mars Mission On-Board Planner and Scheduler, a Science Assessment Module, and Navigation & Vision Processing modules. The platform hardware consists of the rover with the sensors and pointing devices. We report on the major building blocks and their functions & interfaces, emphasizing on the computer vision parts such as image acquisition (using a novel zoomed 3D-Time-of-Flight & RGB camera), mapping from 3D-TOF data, panoramic image & stereo reconstruction, hazard and slope maps, visual odometry and the recognition of potential scientifically interesting targets.

  13. Pro-Tumoral Inflammatory Myeloid Cells as Emerging Therapeutic Targets

    PubMed Central

    Szebeni, Gabor J.; Vizler, Csaba; Nagy, Lajos I.; Kitajka, Klara; Puskas, Laszlo G.

    2016-01-01

    Since the observation of Virchow, it has long been known that the tumor microenvironment constitutes the soil for the infiltration of inflammatory cells and for the release of inflammatory mediators. Under certain circumstances, inflammation remains unresolved and promotes cancer development. Here, we review some of these indisputable experimental and clinical evidences of cancer related smouldering inflammation. The most common myeloid infiltrate in solid tumors is composed of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). These cells promote tumor growth by several mechanisms, including their inherent immunosuppressive activity, promotion of neoangiogenesis, mediation of epithelial-mesenchymal transition and alteration of cellular metabolism. The pro-tumoral functions of TAMs and MDSCs are further enhanced by their cross-talk offering a myriad of potential anti-cancer therapeutic targets. We highlight these main pro-tumoral mechanisms of myeloid cells and give a general overview of their phenotypical and functional diversity, offering examples of possible therapeutic targets. Pharmacological targeting of inflammatory cells and molecular mediators may result in therapies improving patient condition and prognosis. Here, we review experimental and clinical findings on cancer-related inflammation with a major focus on creating an inventory of current small molecule-based therapeutic interventions targeting cancer-related inflammatory cells: TAMs and MDSCs. PMID:27886105

  14. Pro-Resolving Molecules—New Approaches to Treat Sepsis?

    PubMed Central

    Buechler, Christa; Pohl, Rebekka; Aslanidis, Charalampos

    2017-01-01

    Inflammation is a complex response of the body to exogenous and endogenous insults. Chronic and systemic diseases are attributed to uncontrolled inflammation. Molecules involved in the initiation of inflammation are very well studied while pathways regulating its resolution are insufficiently investigated. Approaches to down-modulate mediators relevant for the onset and duration of inflammation are successful in some chronic diseases, while all of them have failed in sepsis patients. Inflammation and immune suppression characterize sepsis, indicating that anti-inflammatory strategies alone are inappropriate for its therapy. Heme oxygenase 1 is a sensitive marker for oxidative stress and is upregulated in inflammation. Carbon monoxide, which is produced by this enzyme, initiates multiple anti-inflammatory and pro-resolving activities with higher production of omega-3 fatty acid-derived lipid metabolites being one of its protective actions. Pro-resolving lipids named maresins, resolvins and protectins originate from the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid while lipoxins are derived from arachidonic acid. These endogenously produced lipids do not simply limit inflammation but actively contribute to its resolution, and thus provide an opportunity to combat chronic inflammatory diseases and eventually sepsis. PMID:28241480

  15. Do Null Subjects (mis-)Trigger Pro-drop Grammars?

    PubMed

    Frazier, Lyn

    2015-12-01

    Native speakers of English regularly hear sentences without overt subjects. Nevertheless, they maintain a [−pro] grammar that requires sentences to have an overt subject. It is proposed that listeners of English recognize that speakers reduce predictable material and thus attribute null subjects to this process, rather than changing their grammars to a [−pro] setting. Mack et al. (J Memory Lang 67(1):211-223, 2012) showed that sentences with noise covering the subject are analyzed as having null subjects more often with a first person pronoun and with a present tense--properties correlated with more predictable referents--compared to a third person pronoun and past tense. However, those results might in principle have been due to reporting null subjects for verbs that often occur with null subjects. An experiment is reported here in which comparable results are found for sentences containing nonsense verbs. Participants preferred a null subject more often for first person present tense sentences than for third person past tense sentences. The results are as expected if participants are responding to predictability, the likelihood of reduction, rather than to lexical statistics. The results are argued to be important in removing a class of mis-triggering examples from the language acquisition problem.

  16. The effects of Operation Rescue on pro-life support.

    PubMed

    Ansuini, C G; Fiddler-woite, J; Woitaszek, R S

    1994-12-01

    Operation Rescue is a militant anti-abortion group. The organization conveys its position against abortion by targeting a city in which it will mount speeches, rallies, pickets, and media barrages. Operation Rescue held activities in Greater Buffalo, New York, in 1992. The authors investigated the effect of the anti-abortion campaign upon a sample of non-activist university undergraduate students and the anti-abortion cause in general. 114 male and 195 female students of the State University of New York College at Buffalo participated. 60% were younger than age 22 years and 17% were 46 years of age or older. 87% were sexually active, but only 18% were married. 11% reported having an abortion themselves or dating someone who had. 150 subjects were surveyed each spring for three years with regard to their abortion-related attitudes and behaviors. 18% of the participants identified themselves as pro-life in 1991, 22% in 1992, and 12% in 1993, the year after the Operation Rescue campaign. 70% identified themselves as pro-choice in 1991, 60% in 1992, and 57% in 1993. The percentage of respondents reporting that they would not have an abortion themselves, but support a woman's right to free choice with regard to abortion steadily increased from 11% in 1991 to 19% in 1992 and 30% in 1993. In general, support for the anti-abortion camp increased during protest activities, but decreased overall over the long term. The campaign had a particularly negative effect upon males.

  17. idRHa+ProMod - Rail Hardening Control System

    NASA Astrophysics Data System (ADS)

    Ferro, L.

    2016-03-01

    idRHa+ProMod is the process control system developed by Primetals Technologies to foresee the thermo-mechanical evolution and micro-structural composition of rail steels subjected to slack quenching into idRHa+ Rail Hardening equipments in a simulation environment. This tool can be used both off-line or in-line, giving the user the chance to test and study the best cooling strategies or letting the automatic control system free to adjust the proper cooling recipe. Optimization criteria have been tailored in order to determine the best cooling conditions according to the metallurgical requirements imposed by the main rail standards and also taking into account the elastoplastic bending phenomena occurring during all stages of the head hardening process. The computational core of idRHa+ProMod is a thermal finite element procedure coupled with special algorithms developed to work out the main thermo-physical properties of steel, to predict the non-isothermal austenite decomposition into all the relevant phases and subsequently to evaluate the amount of latent heat of transformation released, the compound thermal expansion coefficient and the amount of plastic deformation in the material. Air mist and air blades boundary conditions have been carefully investigated by means of pilot plant tests aimed to study the jet impingement on rail surfaces and the cooling efficiency at all working conditions. Heat transfer coefficients have been further checked and adjusted directly on field during commissioning. idRHa+ is a trademark of Primetals Technologies Italy Srl

  18. Development of novel cyclic peptides as pro-apoptotic agents.

    PubMed

    Brindisi, Margherita; Maramai, Samuele; Brogi, Simone; Fanigliulo, Emanuela; Butini, Stefania; Guarino, Egeria; Casagni, Alice; Lamponi, Stefania; Bonechi, Claudia; Nathwani, Seema M; Finetti, Federica; Ragonese, Francesco; Arcidiacono, Paola; Campiglia, Pietro; Valenti, Salvatore; Novellino, Ettore; Spaccapelo, Roberta; Morbidelli, Lucia; Zisterer, Daniela M; Williams, Clive D; Donati, Alessandro; Baldari, Cosima; Campiani, Giuseppe; Ulivieri, Cristina; Gemma, Sandra

    2016-07-19

    Our recent finding that paclitaxel behaves as a peptidomimetic of the endogenous protein Nur77 inspired the design of two peptides (PEP1 and PEP2) reproducing the effects of paclitaxel on Bcl-2 and tubulin, proving the peptidomimetic nature of paclitaxel. Starting from these peptide-hits, we herein describe the synthesis and the biological investigation of linear and cyclic peptides structurally related to PEP2. While linear peptides (2a,b, 3a,b, 4, 6a-f) were found inactive in cell-based assays, biological analysis revealed a pro-apoptotic effect for most of the cyclic peptides (5a-g). Cellular permeability of 5a (and also of 2a,b) on HL60 cells was assessed through confocal microscopy analysis. Further cellular studies on a panel of leukemic cell lines (HL60, Jurkat, MEC, EBVB) and solid tumor cell lines (breast cancer MCF-7 cells, human melanoma A375 and 501Mel cells, and murine melanoma B16F1 cells) confirmed the pro-apoptotic effect of the cyclic peptides. Cell cycle analysis revealed that treatment with 5a, 5c, 5d or 5f resulted in an increase in the number of cells in the sub-G0/G1 peak. Direct interaction with tubulin (turbidimetric assay) and with microtubules (immunostaining experiments) was assessed in vitro for the most promising compounds.

  19. The Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    Lorenzini, Enrico C.

    2002-01-01

    This Annual Report covers the following main topics: 1) Updated Reference Mission. The reference ProSEDS (Propulsive Small Expendable Deployer System) mission is evaluated for an updated launch date in the Summer of 2002 and for the new 80-s current operating cycle. Simulations are run for nominal solar activity condition at the time of launch and for extreme conditions of dynamic forcing. Simulations include the dynamics of the system, the electrodynamics of the bare tether, the neutral atmosphere and the thermal response of the tether. 2) Evaluation of power delivered by the tether system. The power delivered by the tethered system during the battery charging mode is computed under the assumption of minimum solar activity for the new launch date. 3) Updated Deployment Control Profiles and Simulations. A number of new deployment profiles were derived based on the latest results of the deployment ground tests. The flight profile is then derived based on the friction characteristics obtained from the deployment tests of the F-1 tether. 4) Analysis/estimation of deployment flight data. A process was developed to estimate the deployment trajectory of the endmass with respect to the Delta and the final libration amplitude from the data of the deployer turn counters. This software was tested successfully during the ProSEDS mission simulation at MSFC (Marshall Space Flight Center) EDAC (Environments Data Analysis Center).

  20. The propeptide precursor proSAAS is involved in fetal neuropeptide processing and body weight regulation.

    PubMed

    Morgan, Daniel J; Wei, Suwen; Gomes, Ivone; Czyzyk, Traci; Mzhavia, Nino; Pan, Hui; Devi, Lakshmi A; Fricker, Lloyd D; Pintar, John E

    2010-06-01

    Mice with a targeted mutation in proSAAS have been generated to investigate whether peptides derived from this precursor could function as an inhibitor of prohormone convertase 1/3 (PC1/3) in vivo as well as to determine any alternate roles for proSAAS in nervous and endocrine tissues. Fetal mice lacking proSAAS exhibit complete, adult-like processing of prodynorphin in the prenatal brain instead of the incomplete processing seen in the brains of wild-type fetal mice where inhibitory proSAAS intermediates are transiently accumulated. This study provides evidence that proSAAS is directly involved in the prenatal regulation of neuropeptide processing in vivo. However, adult mice lacking proSAAS have normal levels of all peptides detected using a peptidomics approach, suggesting that PC1/3 activity is not affected by the absence of proSAAS in adult mice. ProSAAS knockout mice exhibit decreased locomotion and a male-specific 10-15% decrease in body weight, but maintain normal fasting blood glucose levels and are able to efficiently clear glucose from the blood in response to a glucose challenge. This work suggests that proSAAS-derived peptides can inhibit PC1/3 in embryonic brain, but in the adult brain proSAAS peptides may function as neuropeptides that regulate body weight and potentially other behaviors.

  1. Characterization of collagen model peptides containing 4-fluoroproline; (4(S)-fluoroproline-pro-gly)10 forms a triple helix, but (4(R)-fluoroproline-pro-gly)10 does not.

    PubMed

    Doi, Masamitsu; Nishi, Yoshinori; Uchiyama, Susumu; Nishiuchi, Yuji; Nakazawa, Takashi; Ohkubo, Tadayasu; Kobayashi, Yuji

    2003-08-20

    Collagen model peptide (Pro-Pro-Gly)10 has a triple helical structure and undergoes a thermal transition to a single random coil structure. The transition temperature of the analogous model peptides depends largely on amino acid substitution. Substitution of Pro by 4-hydroxyproline (Hyp) or 4-fluoroproline (fPro) has especially attracted attention because the position of substitution and chirality of the hydroxyl group or fluorine atom affect the transition temperatures. Here, we demonstrated that (4(S)-fPro-Pro-Gly)10 takes a triple helical structure, but (4(R)-fPro-Pro-Gly)10 exists in a single chain structure. This is not consistent with the case of Hyp substitution in our previous report where both (4(S)-Hyp-Pro-Gly)10 and (4(R)-Hyp-Pro-Gly)10 are in a single random coil state.

  2. PRO-2-PAM: The First Therapeutic Drug for Reactivation of Organo-Phosphate-Inhibited Central (Brain) and Peripheral Cholinesterases

    DTIC Science & Technology

    2008-12-01

    1. Synthesis and Properties of 1-Methyl- 1,6- dihydropyridine -2-carbaldoxime, a Pro-Drug of N- Methylpyridinium-2-carbaldoxime Chloride, J. Med... Synthesis of pro-2-PAM (Fig. 1). We synthesized the pro-drug, pro-2-PAM, as previously described (Bodor, 1976). However, the final step, the E1

  3. Glucose Promotes a Pro-Oxidant and Pro-Inflammatory Stromal Microenvironment Which Favors Motile Properties in Breast Tumor Cells.

    PubMed

    Kallens, Violeta; Tobar, Nicolás; Molina, Jessica; Bidegain, Arantzazú; Smith, Patricio C; Porras, Omar; Martínez, Jorge

    2017-05-01

    Chronic inflammation and metabolic reprogramming have been proposed as hallmarks of cancer development. Currently, many of the functional clues between these two phenomena are studied under the integrative view of functional stroma-epithelia interaction. It has been proposed that stromal cells, due to their abundance and avidity for glucose, are able to modify the metabolic behavior of an entire solid tumor. In the present study, using a mammary stromal cell line derived from healthy tissue subjected to long-term culture in low (5 mM) or high (25 mM) glucose, we found that the hyperglycemic condition favors the establishment of a pro-inflammatory and pro-oxidant environment characterized by the induction of the COX-2/PGE2 axis. In this condition, epithelial migration was stimulated. Moreover, we also found that stromal-derived PGE2, acting as a stimulator of IL-1 epithelial expression was one of the factors that promote the acquisition of motile properties by epithelial cells and the maintenance of a COX-2/PGE2-dependent inflammatory condition. Overall, our work provides experimental evidence that glucose stimulates a tumor inflammatory environment that, as a result of a functional cross-talk between stroma and epithelia, may be responsible for tumor progression. J. Cell. Biochem. 118: 994-1002, 2017. © 2016 Wiley Periodicals, Inc.

  4. An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques

    PubMed Central

    Fredman, Gabrielle; Hellmann, Jason; Proto, Jonathan D.; Kuriakose, George; Colas, Romain A.; Dorweiler, Bernhard; Connolly, E. Sander; Solomon, Robert; Jones, David M.; Heyer, Eric J.; Spite, Matthew; Tabas, Ira

    2016-01-01

    Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically-defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro-inflammatory leukotriene B4 (LTB4), are significantly decreased in the vulnerable regions. SPMs are also decreased in advanced plaques of fat-fed Ldlr−/− mice. Administration of RvD1 to these mice during plaque progression restores the RvD1:LTB4 ratio to that of less advanced lesions and promotes plaque stability, including decreased lesional oxidative stress and necrosis, improved lesional efferocytosis, and thicker fibrous caps. These findings provide molecular support for the concept that defective inflammation resolution contributes to the formation of clinically dangerous plaques and offer a mechanistic rationale for SPM therapy to promote plaque stability. PMID:27659679

  5. Comparison of canal transportation in simulated curved canals prepared with ProTaper Universal and ProTaper Gold systems

    PubMed Central

    Muniz, Brenda Leite; Pires, Frederico; Belladonna, Felipe Gonçalves; Neves, Aline Almeida; Souza, Erick Miranda; De-Deus, Gustavo

    2016-01-01

    Objectives The purpose of this study was to assess the ability of ProTaper Gold (PTG, Dentsply Maillefer) in maintaining the original profile of root canal anatomy. For that, ProTaper Universal (PTU, Dentsply Maillefer) was used as reference techniques for comparison. Materials and Methods Twenty simulated curved canals manufactured in clear resin blocks were randomly assigned to 2 groups (n = 10) according to the system used for canal instrumentation: PTU and PTG groups, upto F2 files (25/0.08). Color stereomicroscopic images from each block were taken exactly at the same position before and after instrumentation. All image processing and data analysis were performed with an open source program (FIJI). Evaluation of canal transportation was obtained for two independent canal regions: straight and curved levels. Student's t test was used with a cut-off for significance set at α = 5%. Results Instrumentation systems significantly influenced canal transportation (p < 0.0001). A significant interaction between instrumentation system and root canal level (p < 0.0001) was found. PTU and PTG systems produced similar canal transportation at the straight part, while PTG system resulted in lower canal transportation than PTU system at the curved part. Canal transportation was higher at the curved canal portion (p < 0.0001). Conclusions PTG system produced overall less canal transportation in the curved portion when compared to PTU system. PMID:26877984

  6. Pro-Brain-Derived Neurotrophic Factor (proBDNF)-Mediated p75NTR Activation Promotes Depolarizing Actions of GABA and Increases Susceptibility to Epileptic Seizures.

    PubMed

    Riffault, Baptiste; Kourdougli, Nazim; Dumon, Camille; Ferrand, Nadine; Buhler, Emmanuelle; Schaller, Fabienne; Chambon, Caroline; Rivera, Claudio; Gaiarsa, Jean-Luc; Porcher, Christophe

    2016-12-01

    The brain-derived neurotrophic factor (BDNF) is synthesized as a precursor, namely proBDNF, which can be processed into mature BDNF (mBDNF). Evidences suggest that proBDNF signaling through p75(NTR) may account for the emergence of neurological disorders. These findings support the view that the relative availability of mBDNF and proBDNF forms is an important mechanism underlying brain circuit formation and cognitive functions. Here we describe novel insights into the proBDNF/p75(NTR) mechanisms and function in vivo in modulating neuronal circuit and synaptic plasticity during the first postnatal weeks in rats. Our results showed that increased proBDNF/p75(NTR) signaling during development maintains a depolarizing γ-aminobutyric acid (GABA) response in a KCC2-dependent manner in mature neuronal cells. This resulted in altered excitation/inhibition balance and enhanced neuronal network activity. The enhanced proBDNF/p75(NTR) signaling ultimately led to increased seizure susceptibility that was abolished by in vivo injection of function blocking p75(NTR) antibody. Altogether, our study shed new light on how proBDNF/p75(NTR) signaling can orchestrate the GABA excitatory/inhibitory developmental sequence leading to depolarizing and excitatory actions of GABA in adulthood and subsequent epileptic disorders.

  7. ProQ3D: improved model quality assessments using deep learning.

    PubMed

    Uziela, Karolis; Menéndez Hurtado, David; Shu, Nanjiang; Wallner, Björn; Elofsson, Arne

    2017-01-03

    Protein quality assessment is a long-standing problem in bioinformatics. For more than a decade we have developed state-of-art predictors by carefully selecting and optimising inputs to a machine learning method. The correlation has increased from 0.60 in ProQ to 0.81 in ProQ2 and 0.85 in ProQ3 mainly by adding a large set of carefully tuned descriptions of a protein. Here, we show that a substantial improvement can be obtained using exactly the same inputs as in ProQ2 or ProQ3 but replacing the support vector machine by a deep neural network. This improves the Pearson correlation to 0.90 (0.85 using ProQ2 input features).

  8. Midregional pro-adrenomedullin plasma concentrations are blunted in severe preeclampsia

    PubMed Central

    Matson, Brooke C.; Corty, Robert W.; Karpinich, Natalie O.; Murtha, Amy P.; Valdar, William; Grotegut, Chad A.; Caron, Kathleen M.

    2014-01-01

    Levels of the peptide hormone adrenomedullin (AM) are elevated during normal pregnancy, but whether this differs during complications of pregnancy remains unresolved. AM can be quantified by measuring its preprohormone byproduct, midregional pro-adrenomedullin (MR-proADM). MR-pro ADM has shown prognostic value as a biomarker of heart failure, sepsis, and community-acquired pneumonia. Given the relevance of AM to pregnancy, we tested the hypothesis that MR-proADM provides a biomarker for preeclampsia. We find that MR-proADM plasma concentrations are blunted in severe preeclampsia and that MR-proADM is similarly effective as established biomarkers endoglin and placental growth factor at discriminating patients with severe preeclampsia from controls. PMID:25043691

  9. N-terminal pro b-type natriuretic peptide (NT-pro-BNP) –based score can predict in-hospital mortality in patients with heart failure

    PubMed Central

    Huang, Ya-Ting; Tseng, Yuan-Teng; Chu, Tung-Wei; Chen, John; Lai, Min-Yu; Tang, Woung-Ru; Shiao, Chih-Chung

    2016-01-01

    Serum N-terminal pro b-type natriuretic peptide (NT-pro-BNP) testing is recommended in the patients with heart failure (HF). We hypothesized that NT-pro-BNP, in combination with other clinical factors in terms of a novel NT-pro BNP-based score, may provide even better predictive power for in-hospital mortality among patients with HF. A retrospective study enrolled adult patients with hospitalization-requiring HF who fulfilled the predefined criteria during the period from January 2011 to December 2013. We proposed a novel scoring system consisting of several independent predictors including NT-pro-BNP for predicting in-hospital mortality, and then compared the prognosis-predictive power of the novel NT-pro BNP-based score with other prognosis-predictive scores. A total of 269 patients were enrolled in the current study. Factors such as “serum NT-pro-BNP level above 8100 mg/dl,” “age above 79 years,” “without taking angiotensin converting enzyme inhibitors/angiotensin receptor blocker,” “without taking beta-blocker,” “without taking loop diuretics,” “with mechanical ventilator support,” “with non-invasive ventilator support,” “with vasopressors use,” and “experience of cardio-pulmonary resuscitation” were found as independent predictors. A novel NT-pro BNP-based score composed of these risk factors was proposed with excellent predictability for in-hospital mortality. The proposed novel NT-pro BNP-based score was extremely effective in predicting in-hospital mortality in HF patients. PMID:27411951

  10. ProRaman: a program to classify Raman spectra.

    PubMed

    de Paula, Alderico Rodrigues; Silveira, Landulfo; Pacheco, Marcos Tadeu Tavares

    2009-06-01

    The program ProRaman, developed for the Matlab platform, provides an interactive and flexible graphic interface to develop efficient algorithms to classify Raman spectra into two or three different classes. A set of preprocessing algorithms to decrease the variable dimensionality and to extract the main features which improve the correct classification ratio was implemented. The implemented classification algorithms were based on the Mahalanobis distance and neural network. To verify the functionality of the developed program, 72 spectra from human artery samples, 36 of which had been histopathologically diagnosed as non-diseased and 36 as having an atherosclerotic lesion, were processed using a combination of different preprocessing and classification techniques. The best result was accomplished when the variables were selected from the Raman spectrum shift range from 1200 to 1700 cm(-1), then preprocessed using wavelets for compression and principal component analysis for feature extraction and, finally, classified by a multilayer perceptron with one hidden layer with eight neurons.

  11. Pro-oxidative, genotoxic and cytotoxic properties of uranyl ions.

    PubMed

    Garmash, S A; Smirnova, V S; Karp, O E; Usacheva, A M; Berezhnov, A V; Ivanov, V E; Chernikov, A V; Bruskov, V I; Gudkov, S V

    2014-01-01

    It is demonstrated that hydroxyl radicals and hydrogen peroxide are formed under the action of uranyl ions in aqueous solutions containing no reducing agents. In the presence of uranyl ions, formation of 8-oxoguanine in DNA and long-lived protein radicals are observed in vitro. It is shown that the pro-oxidant properties of uranyl at micromolar concentrations mostly result from the physico-chemical nature of the compound rather than its radioactive decay. Uranyl ions lead to damage in DNA and proteins causing death of HEp-2 cells by necrotic pathway. It is revealed that the uranyl ions enhance radiation-induced oxidative stress and significantly increase a death rate of mice exposed to sublethal doses of X-rays.

  12. Further evidence for direct pro-resorptive actions of FSH.

    PubMed

    Sun, Li; Zhang, Zhiyuan; Zhu, Ling-Ling; Peng, Yuanzhen; Liu, Xuan; Li, Jianhua; Agrawal, Manasi; Robinson, Lisa J; Iqbal, Jameel; Blair, Harry C; Zaidi, Mone

    2010-03-26

    We confirm that FSH stimulates osteoclast formation, function and survival to enhance bone resorption. It does so via the activation of a pertussis toxin-sensitive G(i)-coupled FSH receptor that we and others have identified on murine and human osteoclast precursors and mature osteoclasts. FSH additionally enhances the production of several osteoclastogenic cytokines, importantly TNFalpha, likely within the bone marrow microenvironment, to augment its pro-resorptive action. FSH levels in humans rise before estrogen falls, and this hormonal change coincides with the most rapid rates of bone loss. On the basis of accumulating evidence, we reaffirm that FSH contributes to the rapid peri-menopausal and early post-menopausal bone loss, which might thus be amenable to FSH blockade.

  13. Pro-oxidant and antioxidant processes in aquatic invertebrates.

    PubMed

    Canesi, Laura

    2015-03-01

    Most aquatic organisms behave as conformers with respect to environmental variables, including changes in O2 availability. Aquatic species that show tolerance to hypoxia/anoxia or hyperoxia can be excellent models for investigating physiological and biochemical adaptations that deal with changing O2 and consequent changes in metabolic rate and production of reactive oxygen species (ROS). Here, I summarize selected data on ROS production and antioxidant defenses in a model marine invertebrate, the bivalve Mytilus, under different environmental and physiological conditions. An example of other bivalves adapted to particular environments (the Antarctic Sea) is also reported. These studies contributed to the knowledge on pro-oxidant and antioxidant processes in aquatic invertebrates from comparative and environmental perspectives. A common role for metallothioneins in antioxidant protection in mammals and aquatic invertebrates is underlined in different conditions, from human disease to responses to environmental exposure to heavy metals.

  14. The nephron (pro)renin receptor: function and significance.

    PubMed

    Ramkumar, Nirupama; Kohan, Donald E

    2016-12-01

    The (pro)renin receptor (PRR) is a multifunctional protein that is part of the renin-angiotensin system and is an important accessory molecule for the vacuolar H(+)-ATPase. The PRR is widely expressed in the kidney with relatively high abundance in the distal nephron. Determining the physiological relevance of the PRR has been challenging due to early lethality in whole animal and cell-specific PRR knockout models. Recently, viable renal cell-specific PRR knockout mice have been developed; these studies suggest that PRR in the nephron can modulate renal function via angiotensin II (ANG II)-dependent and -independent cell signaling pathways. In this mini-review, we highlight new developments in nephron PRR function in health and in pathophysiological conditions.

  15. Variables related to pro-choice attitudes among undergraduates.

    PubMed

    Wright, L S; Rogers, R R

    1987-01-01

    Pro-choice attitudes among undergraduates were assessed to determine the extent of anti-abortion sentiments during President Reagan's first term in office, which was marked by his support of the anti-abortion issue as well as by increased media coverage of the right-to-life movement. Self-administered questionnaires were completed by 840 participants enrolled in introductory psychology classes at a university in central Texas during the week prior to the presidential election of 1984. Students were asked if they would approve or disapprove of abortion under four different circumstances. Results indicated that the majority of both males and females were in favor of allowing abortion under all four conditions.

  16. A Methodological Critique of the ProPublica Surgeon Scorecard

    PubMed Central

    Friedberg, Mark W.; Pronovost, Peter J.; Shahian, David M.; Safran, Dana Gelb; Bilimoria, Karl Y.; Elliott, Marc N.; Damberg, Cheryl L.; Dimick, Justin B.; Zaslavsky, Alan M.

    2016-01-01

    Abstract On July 14, 2015, ProPublica published its Surgeon Scorecard, which displays “Adjusted Complication Rates” for individual, named surgeons for eight surgical procedures performed in hospitals. Public reports of provider performance have the potential to improve the quality of health care that patients receive. A valid performance report can drive quality improvement and usefully inform patients' choices of providers. However, performance reports with poor validity and reliability are potentially damaging to all involved. This article critiques the methods underlying the Scorecard and identifies opportunities for improvement. Until these opportunities are addressed, the authors advise users of the Scorecard—most notably, patients who might be choosing their surgeons—not to consider the Scorecard a valid or reliable predictor of the health outcomes any individual surgeon is likely to provide. The authors hope that this methodological critique will contribute to the development of more-valid and more-reliable performance reports in the future. PMID:28083411

  17. A Methodological Critique of the ProPublica Surgeon Scorecard.

    PubMed

    Friedberg, Mark W; Pronovost, Peter J; Shahian, David M; Safran, Dana Gelb; Bilimoria, Karl Y; Elliott, Marc N; Damberg, Cheryl L; Dimick, Justin B; Zaslavsky, Alan M

    2016-05-09

    On July 14, 2015, ProPublica published its Surgeon Scorecard, which displays "Adjusted Complication Rates" for individual, named surgeons for eight surgical procedures performed in hospitals. Public reports of provider performance have the potential to improve the quality of health care that patients receive. A valid performance report can drive quality improvement and usefully inform patients' choices of providers. However, performance reports with poor validity and reliability are potentially damaging to all involved. This article critiques the methods underlying the Scorecard and identifies opportunities for improvement. Until these opportunities are addressed, the authors advise users of the Scorecard-most notably, patients who might be choosing their surgeons-not to consider the Scorecard a valid or reliable predictor of the health outcomes any individual surgeon is likely to provide. The authors hope that this methodological critique will contribute to the development of more-valid and more-reliable performance reports in the future.

  18. The Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    Lorenzini, Enrico C.; Cosmo, Mario L.; Estes, Robert D.; Sanmartin, Juan; Pelaez, Jesus; Ruiz, Manuel

    2003-01-01

    This Final Report covers the following main topics: 1) Brief Description of ProSEDS; 2) Mission Analysis; 3) Dynamics Reference Mission; 4) Dynamics Stability; 5) Deployment Control; 6) Updated System Performance; 7) Updated Mission Analysis; 8) Updated Dynamics Reference Mission; 9) Updated Deployment Control Profiles and Simulations; 10) Updated Reference Mission; 11) Evaluation of Power Delivered by the Tether; 12) Deployment Control Profile Ref. #78 and Simulations; 13) Kalman Filters for Mission Estimation; 14) Analysis/Estimation of Deployment Flight Data; 15) Comparison of ED Tethers and Electrical Thrusters; 16) Dynamics Analysis for Mission Starting at a Lower Altitude; 17) Deployment Performance at a Lower Altitude; 18) Satellite Orbit after a Tether Cut; 19) Deployment with Shorter Dyneema Tether Length; 20) Interactive Software for ED Tethers.

  19. Thermodynamic assessment of the Pr-O system

    SciTech Connect

    McMurray, Jake W.

    2015-12-24

    We found that the Calphad method was used to perform a thermodynamic assessment of the Pr–O system. Compound energy formalism representations were developed for the fluorite α-PrO 2–x and bixbyite σ-Pr 3 O 5 ± x solid solutions while the two-sublattice liquid model was used to describe the binary melt. The series of phases between Pr 2 O 3 and PrO 2 were taken to be stoichiometric. Moreover, the equilibrium oxygen pressure, phase equilibria, and enthalpy data were used to optimize the adjustable parameters of the models for a self-consistent representation of the thermodynamic behavior of the Pr–O system from 298 K to melting.

  20. Thermodynamic assessment of the Pr-O system

    DOE PAGES

    McMurray, Jake W.

    2015-12-24

    We found that the Calphad method was used to perform a thermodynamic assessment of the Pr–O system. Compound energy formalism representations were developed for the fluorite α-PrO 2–x and bixbyite σ-Pr 3 O 5 ± x solid solutions while the two-sublattice liquid model was used to describe the binary melt. The series of phases between Pr 2 O 3 and PrO 2 were taken to be stoichiometric. Moreover, the equilibrium oxygen pressure, phase equilibria, and enthalpy data were used to optimize the adjustable parameters of the models for a self-consistent representation of the thermodynamic behavior of the Pr–O system frommore » 298 K to melting.« less

  1. The limits to pride: A test of the pro-anorexia hypothesis.

    PubMed

    Cornelius, Talea; Blanton, Hart

    2016-01-01

    Many social psychological models propose that positive self-conceptions promote self-esteem. An extreme version of this hypothesis is advanced in "pro-anorexia" communities: identifying with anorexia, in conjunction with disordered eating, can lead to higher self-esteem. The current study empirically tested this hypothesis. Results challenge the pro-anorexia hypothesis. Although those with higher levels of pro-anorexia identification trended towards higher self-esteem with increased disordered eating, this did not overcome the strong negative main effect of pro-anorexia identification. These data suggest a more effective strategy for promoting self-esteem is to encourage rejection of disordered eating and an anorexic identity.

  2. Inhibitory properties of cysteine protease pro-peptides from barley confer resistance to spider mite feeding.

    PubMed

    Santamaria, M Estrella; Arnaiz, Ana; Diaz-Mendoza, Mercedes; Martinez, Manuel; Diaz, Isabel

    2015-01-01

    C1A plant cysteine proteases are synthesized as pre-pro-enzymes that need to be processed to become active by the pro-peptide claves off from its cognate enzyme. These pro-sequences play multifunctional roles including the capacity to specifically inhibit their own as well as other C1A protease activities from diverse origin. In this study, it is analysed the potential role of C1A pro-regions from barley as regulators of cysteine proteases in target phytophagous arthropods (coleopteran and acari). The in vitro inhibitory action of these pro-sequences, purified as recombinant proteins, is demonstrated. Moreover, transgenic Arabidopsis plants expressing different fragments of HvPap-1 barley gene containing the pro-peptide sequence were generated and the acaricide function was confirmed by bioassays conducted with the two-spotted spider mite Tetranychus urticae. Feeding trials resulted in a significant reduction of leaf damage in the transgenic lines expressing the pro-peptide in comparison to non-transformed control and strongly correlated with an increase in mite mortality. Additionally, the analysis of the expression levels of a selection of potential mite targets (proteases and protease inhibitors) revealed a mite strategy to counteract the inhibitory activity produced by the C1A barley pro-prodomain. These findings demonstrate that pro-peptides can control mite pests and could be applied as defence proteins in biotechnological systems.

  3. Inhibitory Properties of Cysteine Protease Pro-Peptides from Barley Confer Resistance to Spider Mite Feeding

    PubMed Central

    Diaz-Mendoza, Mercedes; Martinez, Manuel; Diaz, Isabel

    2015-01-01

    C1A plant cysteine proteases are synthesized as pre-pro-enzymes that need to be processed to become active by the pro-peptide claves off from its cognate enzyme. These pro-sequences play multifunctional roles including the capacity to specifically inhibit their own as well as other C1A protease activities from diverse origin. In this study, it is analysed the potential role of C1A pro-regions from barley as regulators of cysteine proteases in target phytophagous arthropods (coleopteran and acari). The in vitro inhibitory action of these pro-sequences, purified as recombinant proteins, is demonstrated. Moreover, transgenic Arabidopsis plants expressing different fragments of HvPap-1 barley gene containing the pro-peptide sequence were generated and the acaricide function was confirmed by bioassays conducted with the two-spotted spider mite Tetranychus urticae. Feeding trials resulted in a significant reduction of leaf damage in the transgenic lines expressing the pro-peptide in comparison to non-transformed control and strongly correlated with an increase in mite mortality. Additionally, the analysis of the expression levels of a selection of potential mite targets (proteases and protease inhibitors) revealed a mite strategy to counteract the inhibitory activity produced by the C1A barley pro-prodomain. These findings demonstrate that pro-peptides can control mite pests and could be applied as defence proteins in biotechnological systems. PMID:26039069

  4. Renin, (pro)renin and receptor: an update.

    PubMed

    Nguyen, Genevieve

    2011-03-01

    PRR [(pro)renin receptor] was named after its biological characteristics, namely the binding of renin and of its inactive precursor prorenin, that triggers intracellular signalling involving ERK (extracellular-signal-regulated kinase) 1/2. However the gene encoding for PRR is named ATP6ap2 (ATPase 6 accessory protein 2) because PRR was initially found as a truncated form co-purifying with V-ATPase (vacuolar H+-ATPase). There are now data showing that this interaction is not only physical, but also functional in the kidney and the heart. However, the newest and most fascinating development of PRR is its involvement in both the canonical Wnt/β-catenin and non-canonical Wnt/PCP (planar cell polarity) pathways, which are essential for adult and embryonic stem cell biology, embryonic development and disease, including cancer. In the Wnt/β-catenin pathway, it has been shown that PRR acts as an adaptor between the Wnt receptor LRP5/6 (low-density lipoprotein receptor-related protein 5/6) and Fz (frizzled) and that the proton gradient generated by the V-ATPase in endosomes is necessary for LRP5/6 phosphorylation and β-catenin activation. In the Wnt/PCP pathway, PRR binds to Fz and controls its asymetrical subcellular distribution and therefore the polarization of the cells in a plane of a tissue. These essential cellular functions of PRR are independent of renin and open new avenues on the pathophysiological role of PRR. The present review will summarize our knowledge of (pro)renin-dependent functions of PRR and will discuss the newly recognized functions of PRR related to the V-ATPase and to Wnt signalling.

  5. Pro-poor health policies in poverty reduction strategies.

    PubMed

    Laterveer, Leontien; Niessen, Louis W; Yazbeck, Abdo S

    2003-06-01

    Since 1999, the International Monetary Fund and World Bank have required low-income countries soliciting for debt relief and financial support to prepare a Poverty Reduction Strategy Paper (PRSP). The objective of this study is to arrive at a systematic assessment of the extent to which the first batch of interim PRSPs actually addresses the health of the poor and vulnerable. A literature study was used to design and test a semi-quantitative approach to assess the pro-poor focus of health policies in national documents. The approach was applied to the existing interim proposals for 23 Highly Indebted Poor Countries. Results show that a majority of proposals lack country-specific data on the distribution and composition of the burden of disease, a clear identification of health system constraints and an assessment of the impact of health services on the population. More importantly, they make little effort to analyze these issues in relation to the poor. Furthermore, only a small group explicitly includes the interests of the poor in health policy design. Attention to policies aiming at enhancing equity in public health spending is even more limited. Few papers that include expenditure proposals also show pro-poor focused health budgets. We conclude that our systematic assessment of a new international development policy instrument, PRSP, raises strong concerns about the attributed role of health in development and the limited emphasis on the poor, the supposed primary beneficiaries of this instrument. There is a need and an opportunity for the international development community to provide assistance and inputs as poor countries shift their policy thinking from an interim stage to fully developed national policies. This paper presents a menu of analytical and policy options that can be pursued.

  6. Distinguishing Isomeric Peptides: The Unimolecular Reactivity and Structures of (LeuPro)M(+) and (ProLeu)M(+) (M = Alkali Metal).

    PubMed

    Jami-Alahmadi, Yasaman; Linford, Bryan D; Fridgen, Travis D

    2016-12-29

    The unimolecular chemistries and structures of gas-phase (ProLeu)M(+) and (LeuPro)M(+) complexes when M = Li, Na, Rb, and Cs have been explored using a combination of SORI-CID, IRMPD spectroscopy, and computational methods. CID of both (LeuPro)M(+) and (ProLeu)M(+) showed identical fragmentation pathways and could not be differentiated. Two of the fragmentation routes of both peptides produced ions at the same nominal mass as (Pro)M(+) and (Leu)M(+), respectively. For the litiated peptides, experiments revealed identical IRMPD spectra for each of the m/z 122 and 138 ions coming from both peptides. Comparison with computed IR spectra identified them as the (Pro)Li(+) and (Leu)Li(+), and it is concluded that both zwitterionic and canonical forms of (Pro)Li(+) exist in the ion population from CID of both (ProLeu)Li(+) and (LeuPro)Li(+). The two isomeric peptide complexes could be distinguished using IRMPD spectroscopy in both the fingerprint and the CH/NH/OH regions. The computed IR spectra for the lowest energy structures of each charge solvated complexes are consistent with the IRMPD spectra in both regions for all metal cation complexes. Through comparison between the experimental spectra, it was determined that in lithiated and sodiated ProLeu, metal cation is bound to both carbonyl oxygens and the amine nitrogen. In contrast, the larger metal cations are bound to the two carbonyls, while the amine nitrogen is hydrogen bonded to the amide hydrogen. In the lithiated and sodiated LeuPro complexes, the metal cation is bound to the amide carbonyl and the amine nitrogen while the amine nitrogen is hydrogen bonded to the carboxylic acid carbonyl. However, there is no hydrogen bond in the rubidiated and cesiated complexes; the metal cation is bound to both carbonyl oxygens and the amine nitrogen. Details of the position of the carboxylic acid C═O stretch were especially informative in the spectroscopic confirmation of the lowest energy computed structures.

  7. Association between the p53 codon 72 Arg/Pro polymorphism and hepatocellular carcinoma risk.

    PubMed

    Lv, Long; Wang, Ping; Zhou, Xiaoqing; Sun, Beicheng

    2013-06-01

    Previous studies regarding the association of p53 codon 72 Arg/Pro polymorphism with hepatocellular carcinoma (HCC) risk have provided conflicting and inconclusive findings. Thus, a meta-analysis of all currently available publications was performed to address this issue. Eleven individual case-control studies involving a total of 2,718 cases and 3,752 controls were identified after a systematic search of the PubMed, Embase, Web of Science, and Wanfang databases. The strength of the association of p53 codon 72 Arg/Pro polymorphism with HCC risk was estimated by the pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI). Subgroup analyses stratified by ethnicity, source of controls, gender, hepatitis virus infection status, and family history of HCC were also conducted to assess the association. Overall, significantly increased risk of HCC was identified among carriers of the homozygous genotype ProPro (ORProPro vs. ArgArg=1.38 (95 % CI, 1.03-1.85), P OR=0.033; ORProPro vs. ArgArg + ArgPro =1.28 (95 % CI, 1.03-1.59), P OR=0.026). In subgroup analysis by ethnicity, the pooled results suggested that the p53 codon 72 Arg/Pro polymorphism was associated with an increased risk of HCC in Asians and Caucasians (for Asians, ORProPro vs. ArgArg + ArgPro=1.17 (95 % CI, 1.02-1.34), P OR=0.025; for Caucasians, ORProPro vs. ArgArg = 1.65 (95 % CI, 1.07-2.56), P OR=0.025; ORProPro vs. ArgArg + ArgPro=1.74 (95 % CI, 1.14-2.66), P OR=0.010). Subgroup analyses by source of controls and hepatitis virus infection status further demonstrated the significant association, whereas stratification factors involving gender and family history of HCC did not modify the association between p53 codon 72 Arg/Pro polymorphism and HCC risk. This meta-analysis suggests that the p53 codon 72 Arg/Pro polymorphism may play a critical role in the development of HCC, and gender and family history of HCC may not modulate the effect of p53 codon 72 Arg/Pro in HCC risk.

  8. Pro-nerve growth factor in the ovary and human granulosa cells

    PubMed Central

    Meinel, Sabine; Blohberger, Jan; Berg, Dieter; Berg, Ulrike; Dissen, Gregory A.; Ojeda, Sergio R.; Mayerhofer, Artur

    2016-01-01

    Background Pro-nerve growth factor must be cleaved to generate mature NGF, which was suggested to be a factor involved in ovarian physiology and pathology. Extracellular proNGF can induce cell death in many tissues. Whether extracellular proNGF exists in the ovary and may play a role in the death of follicular cells or atresia was unknown. Material and Methods Immunohistochemistry of human and Rhesus monkey ovarian sections was performed. IVF-derived follicular fluid and human granulosa cells were studied by RT-PCR, qPCR, Western blotting, ATP- and caspase-assays. Results and Conclusions Immunohistochemistry of ovarian sections identified proNGF in granulosa cells and Western blotting of human isolated granulosa cells confirmed the presence of proNGF. Ovarian granulosa cells thus produce proNGF. Recombinant human proNGF even at high concentrations did not affect the levels of ATP or the activity of caspase 3/7, indicating that in granulosa cells proNGF does not induce death. In contrast, mature NGF, which was detected previously in follicular fluid, may be a trophic molecule for granulosa cells with unexpected functions. We found that in contrast to proNGF, NGF increased the levels of the transcription factor early growth response 1 and of the enzyme choline acetyl-transferase. A mechanism for the generation of mature NGF from proNGF in the follicular fluid may be extracellular enzymatic cleavage. The enzyme MMP7 is known to cleave proNGF and was identified in follicular fluid and as a product of granulosa cells. Thus the generation of NGF in the ovarian follicle may depend on MMP7. PMID:26457789

  9. Effects of semax and its Pro-Gly-Pro fragment on calcium homeostasis of neurons and their survival under conditions of glutamate toxicity.

    PubMed

    Storozhevykh, T P; Tukhbatova, G R; Senilova, Ya E; Pinelis, V G; Andreeva, L A; Myasoyedov, N F

    2007-05-01

    Semax (100 microM) and its Pro-Gly-Pro fragment (20 and 100 microM) delayed the development of calcium dysregulation and reduction of the mitochondrial potential in cultured cerebellar granule cells under conditions of glutamate neurotoxicity. Incubation with these peptides improved neuronal survival by on average 30%. The neuroprotective effect of semax in cerebral ischemia/hypoxia can be due to improvement of mitochondrial resistance to "calcium" stress.

  10. Comparison of debris extruded apically and working time used by ProTaper Universal rotary and ProTaper retreatment system during gutta-percha removal

    PubMed Central

    UEZU, Mary Kinue Nakamune; BRITTO, Maria Leticia Borges; NABESHIMA, Cleber K.; PALLOTTA, Raul Capp

    2010-01-01

    Objective The aim of this study was to evaluate the in vitro action of ProTaper retreatment files and ProTaper Universal in the retreatment of mandibular premolars. Material and methods The amount of debris extruded apically was measured and the time to reach the working length and to complete the removal of gutta-percha was observed. Thirty teeth had their canals prepared using ProTaper Universal files and were obturated by the single cone technique. The teeth were then stored at 37ºC in a humid environment for 7 days. During the use of the rotary instruments for root canal filling removal, the apical portions of the teeth were attached to the open end of a resin tube to collect the apically extruded debris. Results ProTaper Universal files were significantly faster (p=0.0011) than the ProTaper retreatment files to perform gutta-percha removal, but no significant difference was found between the files regarding the time to reach the working length or the amount of apical extrusion. Conclusions ProTaper Universal rotary had better results for endodontic retreatment, and both techniques promote similar apical extrusion of debris. PMID:21308282

  11. Geological interpretation and analysis of surface based, spatially referenced planetary imagery data using PRoGIS 2.0 and Pro3D.

    NASA Astrophysics Data System (ADS)

    Barnes, R.; Gupta, S.; Giordano, M.; Morley, J. G.; Muller, J. P.; Tao, Y.; Sprinks, J.; Traxler, C.; Hesina, G.; Ortner, T.; Sander, K.; Nauschnegg, B.; Paar, G.; Willner, K.; Pajdla, T.

    2015-10-01

    We apply the capabilities of the geospatial environment PRoGIS 2.0 and the real time rendering viewer PRo3D to geological analysis of NASA's Mars Exploration Rover-B (MER-B Opportunity rover) and Mars Science Laboratory (MSL Curiosity rover) datasets. Short baseline and serendipitous long baseline stereo Pancam rover imagery are used to create 3D point clouds which can be combined with super-resolution images derived from Mars Reconnaissance Orbiter HiRISE orbital data, andsuper-resolution outcrop images derived from MER Pancam, as well as hand-lens scale images for geology and outcrop characterization at all scales. Data within the PRoViDE database are presented and accessed through the PRoGIS interface. Simple geological measurement tools are implemented within the PRoGIS and PRo3D web software to accurately measure the dip and strike of bedding in outcrops, create detailed stratigraphic logs for correlation between the areas investigated, and to develop realistic 3D models for the characterization of planetary surface processes. Annotation tools are being developed to aid discussion and dissemination of the observations within the planetary science community.

  12. New strategy for specific activation of recombinant microbial pro-transglutaminase by introducing an enterokinase cleavage site.

    PubMed

    Wang, Kun; Wang, Bin; Yang, Hui-Lin; Pan, Li

    2013-03-01

    Recombinant microbial transglutaminase (rMTG) is usually expressed as a soluble zymogen (pro-rMTG) in heterologous expression systems but proteolytic activation of the inactive pro-rMTG is essential. Instead of screening proteases for activating pro-rMTG, we examined an alternative method by introducing a specific cleavage site of enterokinase between the pro-peptide and mature rMTG, generating three pro-rMTG variants (Pro-mrMTG, Pro-m-rMTG and mPro-rMTG). Pro-mrMTG and Pro-m-rMTG were activated by enterokinase without degrading mature rMTG. The activation productivity of Pro-m-rMTG by enterokinase reached 92 % after 22 h activation, while the activation productivity of Pro-rMTG activated by trypsin was 47 %. MALDI-MS analysis revealed that the pro-peptide including the cleavage site was specifically removed from Pro-m-rMTG after activation. This methodology has the potential to be applied in rMTG production by incorporating highly specific cleavage sites of other proteases.

  13. Tribenuron-methyl resistance and mutation diversity of Pro197 in flixweed (Descurainia Sophia L.) accessions from China.

    PubMed

    Deng, Wei; Liu, Ming Jie; Yang, Qian; Mei, Yu; Li, Xue Feng; Zheng, Ming Qi

    2015-01-01

    Flixweed (Descurainia Sophia L.) is a problematic weed in winter wheat fields in China, which causes great loss of wheat yield. A total of 46 flixweed accessions from winter wheat-planting areas were collected and used for the survey of resistance to tribenuron-methyl and Pro197 mutation diversity. According to the "R" resistance rating system, 16 flixweed accessions have evolved resistance to tribenuron-methyl, 13 accessions have high risk of developing resistance to this herbicide and 17 accessions are susceptible. The mutation of Pro197 codon (CCT) changed proline (Pro) into leucine (Leu) (homozygous, RR), serine (Ser, RR), histidine (His, RR), threonine (Thr, RR), Pro/Leu (heterozygous, RS), Pro/Ser (RS), Pro/His, Pro/Thr (RS) and Pro/Tyr (RS). Among these amino acid changes, a Pro197-Pro/Tyr (heterozygous, RS) substitution caused by the mutation of two successive nucleotides was identified for the first time in resistant weed species. In addition, the Pro197-His and Pro197-Pro/His mutations have not been reported previously in flixweed. Finally, a CPAS marker was developed to identify flixweed plants with or without Pro197 mutation.

  14. 78 FR 57796 - Safety Zone; Pro Hydro-X Tour, Atlantic Ocean, Islamorada, FL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Pro Hydro-X Tour, Atlantic Ocean... establishing a temporary safety zone on the waters of the Atlantic Ocean, Islamorada, Florida during the Pro... jet ski races. The event will be held on the waters of the Atlantic Ocean, Islamorada,...

  15. GoPro as an Ethnographic Tool: A Wayfinding Study in an Academic Library

    ERIC Educational Resources Information Center

    Kinsley, Kirsten M.; Schoonover, Dan; Spitler, Jasmine

    2016-01-01

    In this study, researchers sought to capture students' authentic experience of finding books in the main library using a GoPro camera and the think-aloud protocol. The GoPro provided a first-person perspective and was an effective ethnographic tool for observing a student's individual experience, while also demonstrating what tools they use to…

  16. Pro-apoptotic gene regulation in the Caribbean fruit fly, Anastrepha suspensa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transcriptional activation of pro-apoptotic genes in response to cytotoxic stimuli is a conserved feature of the cell death pathway proposed for metazoans. However, understanding the extent of this conservation in insects, as well as other organisms, has been limited by the lack of known pro-apoptot...

  17. 17 CFR 240.15c1-9 - Use of pro forma balance sheets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Use of pro forma balance sheets. 240.15c1-9 Section 240.15c1-9 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... pro forma balance sheets. The term manipulative, deceptive, or other fraudulent device or...

  18. 17 CFR 240.15c1-9 - Use of pro forma balance sheets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Use of pro forma balance sheets. 240.15c1-9 Section 240.15c1-9 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... pro forma balance sheets. The term manipulative, deceptive, or other fraudulent device or...

  19. 17 CFR 240.15c1-9 - Use of pro forma balance sheets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Use of pro forma balance sheets. 240.15c1-9 Section 240.15c1-9 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... pro forma balance sheets. The term manipulative, deceptive, or other fraudulent device or...

  20. 17 CFR 240.15c1-9 - Use of pro forma balance sheets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Use of pro forma balance sheets. 240.15c1-9 Section 240.15c1-9 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... pro forma balance sheets. The term manipulative, deceptive, or other fraudulent device or...

  1. 17 CFR 240.15c1-9 - Use of pro forma balance sheets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Use of pro forma balance sheets. 240.15c1-9 Section 240.15c1-9 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... pro forma balance sheets. The term manipulative, deceptive, or other fraudulent device or...

  2. MyPro: A seamless pipeline for automated prokaryotic genome assembly and annotation

    PubMed Central

    Liao, Yu-Chieh; Lin, Hsin-Hung; Sabharwal, Amarpreet; Haase, Elaine M.; Scannapieco, Frank A.

    2016-01-01

    MyPro is a software pipeline for high-quality prokaryotic genome assembly and annotation. It was validated on 18 oral streptococcal strains to produce submission-ready, annotated draft genomes. MyPro installed as a virtual machine and supported by updated databases will enable biologists to perform quality prokaryotic genome assembly and annotation with ease. PMID:25911337

  3. MyPro: A seamless pipeline for automated prokaryotic genome assembly and annotation.

    PubMed

    Liao, Yu-Chieh; Lin, Hsin-Hung; Sabharwal, Amarpreet; Haase, Elaine M; Scannapieco, Frank A

    2015-06-01

    MyPro is a software pipeline for high-quality prokaryotic genome assembly and annotation. It was validated on 18 oral streptococcal strains to produce submission-ready, annotated draft genomes. MyPro installed as a virtual machine and supported by updated databases will enable biologists to perform quality prokaryotic genome assembly and annotation with ease.

  4. Striving for Sustainable Development in Higher Education: ProSPER.Net Members Meet in Shanghai

    ERIC Educational Resources Information Center

    Tabucanon, Mario T.; Tanaka, Aurea Christine; Aipanjiguly, Sampreethi

    2011-01-01

    To celebrate the two-year anniversary of the founding of ProSPER.Net--the Promotion of Sustainability in Postgraduate Education and Research Network--members convened on 5-9 July 2010 in Shanghai, China, at a meeting hosted by Tongji University, a founding member. ProSPER.Net is an alliance of 21 higher education institutions in the Asia-Pacific…

  5. Portrayals of Pro-Beijing Workers' Night Schools in Hong Kong from 1946 to Post-1997

    ERIC Educational Resources Information Center

    Lau, Chui Shan

    2011-01-01

    This study focuses on the transformation of pro-Beijing labour education in the socio-political context of Hong Kong. It explores the reasons that Hong Kong pro-Beijing educators initiated Workers' Night Schools for adults; the organisation of schools in many locales and the transformation of labour education that workers received in these…

  6. 77 FR 75819 - Death of Senator Daniel K. Inouye, President Pro Tempore of the Senate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-21

    ... From the Federal Register Online via the Government Publishing Office ] Vol. 77 Friday, No. 246 December 21, 2012 Part VI The President Proclamation 8919--Death of Senator Daniel K. Inouye, President Pro... ] Proclamation 8919 of December 18, 2012 Death of Senator Daniel K. Inouye, President Pro Tempore of the...

  7. Extending the Human Life Span: An Exploratory Study of Pro- and Anti-Longevity Attitudes

    ERIC Educational Resources Information Center

    Kogan, Nathan; Tucker, Jennifer; Porter, Matthew

    2011-01-01

    Successful efforts by biologists to substantially increase the life span of non-human animals has raised the possibility of extrapolation to humans, which in turn has given rise to bioethical argumentation, pro and con. The present study converts these arguments into pro- and anti-longevity items on a questionnaire and examines the structure and…

  8. P53 codon 72 Arg/Pro polymorphism and glioma risk: an updated meta-analysis.

    PubMed

    He, Fang; Xia, Yi; Liu, Huafeng; Li, Jin; Wang, Chao

    2013-10-01

    P53 codon 72 Arg/Pro is a C/G variation upstream of the p53 gene on human chromosome 17p13. Many case-control studies have investigated the association between p53 codon 72 Arg/Pro polymorphism and glioma risk but provided inconsistent findings. To better understand the pathogenesis of glioma, we performed the current meta-analysis by pooling data from all available individual studies. According to the inclusion criteria, ten independent publications with 11 case-control studies were included into this meta-analysis. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the effect of p53 codon 72 Arg/Pro variant on the development of glioma. Overall, no appreciable correlation was observed among the total studies in all gene models (ORPro allele vs. Arg allele = 1.04, 95 % CI = 0.90-1.20, P OR = 0.581; ORPro/Pro vs. Arg/Arg = 0.95, 95 % CI = 0.80-1.14, P OR = 0.614; ORPro/Arg vs. Arg/Arg = 1.01, 95 % CI = 0.79-1.29, P OR = 0.993; ORPro/Arg + Pro/Pro vs. Arg/Arg = 1.03, 95 % CI = 0.82-1.29, P OR = 0.799; ORPro/Pro vs. Arg/Arg + Pro/Arg = 1.02, 95 % CI = 0.86-1.22, P OR = 0.785). In stratified analyses by ethnicity, source of controls, and glioma subtypes, the p53 codon 72 Arg/Pro polymorphism did not alter the risk for glioma in population-based, hospital-based, astrocytoma, and oligodendroglioma studies among Caucasian. Interestingly, the Pro/Pro genotype seemed to be negatively associated with the glioma risk among patients with glioblastoma (ORPro/Pro vs. Arg/Arg = 0.68, 95 % CI = 0.48-0.95, P OR = 0.026). Our study suggests that the polymorphism of p53 codon 72 Arg/Pro may play a protective role in the development of glioblastoma. The relationship of p53 codon 72 Arg/Pro polymorphism with the susceptibility to glioma needs further estimation by more individual studies with high quality across ethnicities.

  9. Aberrant Expression of proPTPRN2 in Cancer Cells Confers Resistance to Apoptosis.

    PubMed

    Sorokin, Alexey V; Nair, Binoj C; Wei, Yongkun; Aziz, Kathryn E; Evdokimova, Valentina; Hung, Mien-Chie; Chen, Junjie

    2015-05-01

    The protein tyrosine phosphatase receptor PTPRN2 is expressed predominantly in endocrine and neuronal cells, where it functions in exocytosis. We found that its immature isoform proPTPRN2 is overexpressed in various cancers, including breast cancer. High proPTPRN2 expression was associated strongly with lymph node-positive breast cancer and poor clinical outcome. Loss of proPTPRN2 in breast cancer cells promoted apoptosis and blocked tumor formation in mice, whereas enforced expression of proPTPRN2 in nontransformed human mammary epithelial cells exerted a converse effect. Mechanistic investigations suggested that ProPTPRN2 elicited these effects through direct interaction with TRAF2, a hub scaffold protein for multiple kinase cascades, including ones that activate NF-κB. Overall, our results suggest PTPRN2 as a novel candidate biomarker and therapeutic target in breast cancer.

  10. The process for the activation of frog epidermis pro-tyrosinase.

    PubMed Central

    Peñafiel, R; Galindo, J D; Pedreño, E; Lozano, J A

    1982-01-01

    1. Purified pro-tyrosinase from epidermis of the frog Rana esculenta ridibunda can be activated in vitro by several proteinases (trypsin, alpha-chymotrypsin, Pronase) and by light. 2. Both pro-tyrosinase and tyrosinase are composed of a single type of subunit having pI 7.2 and approximate molecular weights 68000 and 62000 respectively. A peptide of low molecular weight is released as a consequence of the proteolytic activation. Pro-tyrosinase and tyrosinase have different quaternary structures, the proenzyme being a dimer of Mr approx. 115000 and the enzyme a tetramer of Mr approx. 210 000. 3. The activation process was affected by several agents (L-3,4-dihydroxyphenylalanine, urea, formamide) that prevented, partially or totally, the activation of pro-tyrosinase. 4. The activation of pro-tyrosinase seems to be the result of a cleavage of the polypeptide chain that determines changes in tertiary or quaternary structure. PMID:6814426

  11. HiC-Pro: an optimized and flexible pipeline for Hi-C data processing.

    PubMed

    Servant, Nicolas; Varoquaux, Nelle; Lajoie, Bryan R; Viara, Eric; Chen, Chong-Jian; Vert, Jean-Philippe; Heard, Edith; Dekker, Job; Barillot, Emmanuel

    2015-12-01

    HiC-Pro is an optimized and flexible pipeline for processing Hi-C data from raw reads to normalized contact maps. HiC-Pro maps reads, detects valid ligation products, performs quality controls and generates intra- and inter-chromosomal contact maps. It includes a fast implementation of the iterative correction method and is based on a memory-efficient data format for Hi-C contact maps. In addition, HiC-Pro can use phased genotype data to build allele-specific contact maps. We applied HiC-Pro to different Hi-C datasets, demonstrating its ability to easily process large data in a reasonable time. Source code and documentation are available at http://github.com/nservant/HiC-Pro .

  12. (Pro)cambium formation and proliferation: two sides of the same coin?

    PubMed

    Jouannet, Virginie; Brackmann, Klaus; Greb, Thomas

    2015-02-01

    The body of higher plants is usually pervaded by the (pro)cambium, a reticulate system of meristematic cells harboring the potential for producing vascular tissues at critical times and places. The (pro)cambium thereby provides the basis for the differential modulation of long-distance transport capacities and plant body stability. Distinct regulatory networks responsible for the initiation and proliferation of (pro)cambium cells have been identified. However, although a tight interaction between these networks can be expected, connections have been established only sporadically. Here we highlight recent discoveries of how (pro)cambium development is regulated and discuss possible interfaces between networks regulating two processes: (pro)cambium formation and cambium proliferation.

  13. InterPro in 2017—beyond protein family and domain annotations

    PubMed Central

    Finn, Robert D.; Attwood, Teresa K.; Babbitt, Patricia C.; Bateman, Alex; Bork, Peer; Bridge, Alan J.; Chang, Hsin-Yu; Dosztányi, Zsuzsanna; El-Gebali, Sara; Fraser, Matthew; Gough, Julian; Haft, David; Holliday, Gemma L.; Huang, Hongzhan; Huang, Xiaosong; Letunic, Ivica; Lopez, Rodrigo; Lu, Shennan; Marchler-Bauer, Aron; Mi, Huaiyu; Mistry, Jaina; Natale, Darren A.; Necci, Marco; Nuka, Gift; Orengo, Christine A.; Park, Youngmi; Pesseat, Sebastien; Piovesan, Damiano; Potter, Simon C.; Rawlings, Neil D.; Redaschi, Nicole; Richardson, Lorna; Rivoire, Catherine; Sangrador-Vegas, Amaia; Sigrist, Christian; Sillitoe, Ian; Smithers, Ben; Squizzato, Silvano; Sutton, Granger; Thanki, Narmada; Thomas, Paul D; Tosatto, Silvio C. E.; Wu, Cathy H.; Xenarios, Ioannis; Yeh, Lai-Su; Young, Siew-Yit; Mitchell, Alex L.

    2017-01-01

    InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder. These developments enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences. PMID:27899635

  14. Drive for muscularity and drive for thinness: the impact of pro-anorexia websites.

    PubMed

    Juarez, Lilia; Soto, Ernesto; Pritchard, Mary E

    2012-01-01

    In recent years, websites that stress the message of thinness as the ideal and only choice have surfaced on the internet. The possibility that pro-anorexia websites may reinforce restrictive eating and exercise behaviors is an area of concern. In addition, friends may be influencing one another to view these websites, further contributing to drive for thinness in women and drive for muscularity in men. Three hundred male and female undergraduate psychology students responded to questionnaires assessing: internalization of pro-anorexia website content, internalization of general media content, influence of friends to view pro-anorexia websites, peer influence, drive for muscularity, and drive for thinness. Results showed internalization of pro-anorexia website content was positively correlated with drive for thinness in women, and negatively correlated with drive for muscularity in men. Internalization of pro-anorexia website content was found to be related to both drive for thinness in women and drive for muscularity in men.

  15. Crystal structures of Boc-D- and L-Iva-L-Pro-OBzl: unturned conformation of Aib-Pro sequence unaffected by replacement of Me with Et in Aib.

    PubMed

    Kawai, M; Omori, Y; Yamamura, H; Butsugan, Y; Taga, T; Miwa, Y

    1993-08-01

    The crystal structures of the isovaline (Iva) containing dipeptides, Boc-D-Iva-L-Pro-OBzl and Boc-L-Iva-L-Pro-OBzl, were determined by x-ray diffraction. The diastereomeric peptides were shown to adopt unturned conformations closely similar to each other (phi Iva 52 degrees, psi Iva 46 degrees, phi Pro -65 degrees, and psi Pro 143 degrees for D-Iva-L-Pro sequence and phi Iva 52 degrees, psi Iva 44 degrees, phi Pro -63 degrees, and psi Pro 148 degrees for L-Iva-L-Pro sequence). The Pro ring of each peptide was in C gamma-endo conformation. The unusually large angle CIva-NPro-C delta Pro values (131 degrees in both peptides) were observed, that was due to steric repulsion between the delta-methylene of Pro and the alkyl side chain of Iva residue. These conformations were essentially the same as that of the corresponding alpha-aminoisobutyric acid (Aib)-containing peptide Boc-Aib-L-Pro-OBzl. The result has demonstrated that replacement of either one of the two methyl groups of the Aib residue in Boc-Aib-L-Pro-OBzl with an ethyl group does not cause any significant change in the unturned conformation of the dipeptide.

  16. Autocatalytic activity and substrate specificity of the pestivirus N-terminal protease N{sup pro}

    SciTech Connect

    Gottipati, Keerthi; Acholi, Sudheer; Ruggli, Nicolas; Choi, Kyung H.

    2014-03-15

    Pestivirus N{sup pro} is the first protein translated in the viral polypeptide, and cleaves itself off co-translationally generating the N-terminus of the core protein. Once released, N{sup pro} blocks the host's interferon response by inducing degradation of interferon regulatory factor-3. N{sup pro'}s intracellular autocatalytic activity and lack of trans-activity have hampered in vitro cleavage studies to establish its substrate specificity and the roles of individual residues. We constructed N{sup pro}-GFP fusion proteins that carry the authentic cleavage site and determined the autoproteolytic activities of N{sup pro} proteins containing substitutions at the predicted catalytic sites Glu22 and Cys69, at Arg100 that forms a salt bridge with Glu22, and at the cleavage site Cys168. Contrary to previous reports, we show that N{sup pro'}s catalytic activity does not involve Glu22, which may instead be involved in protein stability. Furthermore, N{sup pro} does not have specificity for Cys168 at the cleavage site even though this residue is conserved throughout the pestivirus genus. - Highlights: • N{sup pro'}s autoproteolysis is studied using N{sup pro}-GFP fusion proteins. • N-terminal 17 amino acids are dispensable without loss of protease activity. • The putative catalytic residue Glu22 is not involved in protease catalysis. • No specificity for Cys168 at the cleavage site despite evolutionary conservation. • N{sup pro} prefers small amino acids with non-branched beta carbons at the P1 position.

  17. Association of [-2]proPSA with Biopsy Reclassification During Active Surveillance for Prostate Cancer

    PubMed Central

    Tosoian, Jeffrey J.; Loeb, Stacy; Feng, Zhaoyong; Isharwal, Sumit; Landis, Patricia; Elliot, Debra J.; Veltri, Robert; Epstein, Jonathan I.; Partin, Alan W.; Carter, H. Ballentine; Trock, Bruce; Sokoll, Lori J.

    2014-01-01

    Purpose Previous studies have suggested an association between [-2]proPSA expression and prostate cancer detection. Less is known about the utility of this marker in following prostate cancer patients on active surveillance. Thus, our objective was to examine the relationship between [-2]proPSA and biopsy results in men enrolled in an active surveillance program. Materials and Methods In 167 men from our institutional active surveillance program, we used Cox proportional hazards models to examine the relationship between [-2]proPSA and annual surveillance biopsy results. The outcome of interest was biopsy reclassification (Gleason score ≥7, or >2 positive biopsy cores, or >50% involvement of any core with cancer). We also examined the association of biopsy results with total PSA, %fPSA, [-2]proPSA/%fPSA, and the Beckman Coulter Prostate Health Index [phi=([-2]proPSA/fPSA) x (tPSA)½]. Results While on active surveillance (median time from diagnosis 4.3 years), 63 (37.7%) men demonstrated biopsy reclassification based on the above criteria, including 28 (16.7%) of whom had reclassification based on Gleason score upgrading (Gleason score≥7). Baseline and longitudinal %fPSA, %[-2]proPSA, [-2]proPSA/%fPSA, and phi measurements were significantly associated with biopsy reclassification, and %[-2]proPSA and phi provided the greatest predictive accuracy for high-grade cancer. Conclusions In men on active surveillance, measures based on [-2]proPSA such as phi, appear to provide improved prediction of biopsy reclassification during follow-up. Additional validation is warranted to determine whether clinically useful thresholds can be defined, and to better characterize the role of %[-2]proPSA and phi in conjunction with other markers in monitoring patients enrolled in active surveillance. PMID:22901577

  18. ProSAR: a new methodology for combinatorial library design.

    PubMed

    Chen, Hongming; Börjesson, Ulf; Engkvist, Ola; Kogej, Thierry; Svensson, Mats A; Blomberg, Niklas; Weigelt, Dirk; Burrows, Jeremy N; Lange, Tim

    2009-03-01

    A method is introduced for performing reagent selection for chemical library design based on topological (2D) pharmacophore fingerprints. Optimal reagent selection is achieved by optimizing the Shannon entropy of the 2D pharmacophore distribution for the reagent set. The method, termed ProSAR, is therefore expected to enumerate compounds that could serve as a good starting point for deriving a structure activity relationship (SAR) in combinatorial library design. This methodology is exemplified by library design examples where the active compounds were already known. The results show that most of the pharmacophores on the substituents for the active compounds are covered by the designed library. This strategy is further expanded to include product property profiles for aqueous solubility, hERG risk assessment, etc. in the optimization process so that the reagent pharmacophore diversity and the product property profile are optimized simultaneously via a genetic algorithm. This strategy is applied to a two-dimensional library design example and compared with libraries designed by a diversity based strategy which minimizes the average ensemble Tanimoto similarity. Our results show that by using the PSAR methodology, libraries can be designed with simultaneously good pharmacophore coverage and product property profile.

  19. DNA-METAFECTENE PRO complexation: a physical chemistry study.

    PubMed

    Alatorre-Meda, Manuel; González-Pérez, Alfredo; Rodríguez, Julio R

    2010-07-21

    Complexes formed between cationic liposomes and DNA (also known as lipoplexes or genosomes) have proven, for years now, to be a suitable option for gene delivery to cells, transfection, however, some aspects regarding the liposome-DNA interaction mechanism and complex stability remain still unclear. This work aims to improve the understanding of the poorly defined mechanisms and structural conformation associated with the interaction of METAFECTENE PRO (MEP), a commercial liposomal transfection reagent, with poly-anion DNA at mass ratios around the mass ratio recommended for transfection (L/D congruent with 700). A physical chemistry characterization was conducted at a pH of 6.5 and at a temperature of 25 degrees C by means of dynamic light scattering (DLS), electrophoretic mobility (zeta-potential), transmission electron microscopy (TEM), and atomic force microscopy (AFM). Five parameters important for transfection were determined for the lipoplexes: (i) the hydrodynamic radius, R(H), (ii) the stability with time, (iii) the mass ratio of at which both moieties start to interact, (L/D)(i), (iv) the overall charge, and (v) the morphology. Results in ensemble point to a "beads on a string" conformation, with the lipoplex formation occurring well below isoneutrality from (L/D)(i) congruent with 600. The lipoplexes were found to be stable within at least seven days presenting an average R(H) of 135 nm.

  20. (Pro)renin receptor as a new drug target.

    PubMed

    Ahmed, Basma A M; Seda, Ondrej; Lavoie, Julie L

    2011-11-01

    Over the last few years, the implication of the (pro)renin receptor [(P)RR] in the pathogenesis of end-organ damage has been shown through many different studies. The (P)RR plays a dual role when stimulated by renin or prorenin as it enhances both cell surface production of angiotensin and stimulates angiotensin-independent intracellular signaling cascades. Since Ichihara's group demonstrated activation of prorenin when it was bound to antibodies targeted against a specific region in the renin prosegment, they designed a complementary decapeptide to this region called the handle region to use as a potential (P)RR blocker (PRRB). The effects of systemic administration of the PRRB on the development and progression of different renal, cardiac and ocular pathologies have been observed and have thus proposed the blocker as a potential new treatment for these afflictions. Conversely, the specificity of the PRRB has been questioned as conflicting results have been reported in the literature. A recent study has described a new high affinity binding site for renin and prorenin to the (P)RR called the hinge region. Hence, although there is great promise in the (P)RR potential as a therapeutic target, still much research is required to better identify adequate blockers.

  1. Regulation of growth hormone secretion by (pro)renin receptor.

    PubMed

    Tani, Yuji; Yamada, Shozo; Inoshita, Naoko; Hirata, Yukio; Shichiri, Masayoshi

    2015-06-03

    (Pro)renin receptor (PRR) has a single transmembrane domain that co-purifies with the vacuolar H(+)-ATPase (V-ATPase). In addition to its role in cellular acidification, V-ATPase has been implicated in membrane fusion and exocytosis via its Vo domain. Results from the present study show that PRR is expressed in pituitary adenoma cells and regulates growth hormone (GH) release via V-ATPase-induced cellular acidification. Positive PRR immunoreactivity was detected more often in surgically resected, growth hormone-producing adenomas (GHomas) than in nonfunctional pituitary adenomas. GHomas strongly expressing PRR showed excess GH secretion, as evidenced by distinctly high plasma GH and insulin-like growth factor-1 levels, as well as an elevated nadir GH in response to the oral glucose tolerance test. Suppression of PRR expression in rat GHoma-derived GH3 cells using PRR siRNA resulted in reduced GH secretion and significantly enhanced intracellular GH accumulation. GH3 treatment with bafilomycin A1, a V-ATPase inhibitor, also blocked GH release, indicating mediation via impaired cellular acidification of V-ATPase. PRR knockdown decreased Atp6l, a subunit of the Vo domain that destabilizes V-ATPase assembly, increased intracellular GH, and decreased GH release. To our knowledge, this is the first report demonstrating a pivotal role for PRR in a pituitary hormone release mechanism.

  2. Anti- and pro-tumor functions of autophagy.

    PubMed

    Morselli, Eugenia; Galluzzi, Lorenzo; Kepp, Oliver; Vicencio, José-Miguel; Criollo, Alfredo; Maiuri, Maria Chiara; Kroemer, Guido

    2009-09-01

    Autophagy constitutes one of the major responses to stress in eukaryotic cells, and is regulated by a complex network of signaling cascades. Not surprisingly, autophagy is implicated in multiple pathological processes, including infection by pathogens, inflammatory bowel disease, neurodegeneration and cancer. Both oncogenesis and tumor survival are influenced by perturbations of the molecular machinery that controls autophagy. Numerous oncoproteins, including phosphatidylinositol 3-kinase, Akt1 and anti-apoptotic members of the Bcl-2 family suppress autophagy. Conversely, several tumor suppressor proteins (e.g., Atg4c; beclin 1; Bif-1; BH3-only proteins; death-associated protein kinase 1; LKB1/STK11; PTEN; UVRAG) promote the autophagic pathway. This does not entirely apply to p53, one of the most important tumor suppressor proteins, which regulates autophagy in an ambiguous fashion, depending on its subcellular localization. Irrespective of the controversial role of p53, basal levels of autophagy appear to inhibit tumor development. On the contrary, chemotherapy- and metabolic stress-induced activation of the autophagic pathway reportedly contribute to the survival of formed tumors, thereby favoring resistance. In this context, autophagy inhibition would represent a major therapeutic target for chemosensitization. Here, we will review the current knowledge on the dual role of autophagy as an anti- and pro-tumor mechanism.

  3. BERLinPro Booster Cavity Design, Fabrication and Test Plans

    SciTech Connect

    Burrill, Andrew; Anders, W; Frahm, A.; Knobloch, Jens; Neumann, Axel; Ciovati, Gianluigi; Kneisel, Peter K.; Turlington, Larry D.

    2014-12-01

    The bERLinPro project, a 100 mA, 50 MeV superconducting RF (SRF) Energy Recovery Linac (ERL) is under construction at Helmholtz-Zentrum Berlin for the purpose of studying the technical challenges and physics of operating a high current, c.w., 1.3 GHz ERL. This machine will utilize three unique SRF cryomodules for the injector, booster and linac module respectively. The booster cryomodule will contain three 2-cell SRF cavities, based on the original design by Cornell University, and will be equipped with twin 115 kW RF power couplers in order to provide the appropriate acceleration to the high current electron beam. This paper will review the status of the fabrication of the 4 booster cavities that have been built for this project by Jefferson Laboratory and look at the challenges presented by the incorporation of fundamental power couplers capable of delivering 115 kW. The test plan for the cavities and couplers will be given along with a brief overview of the cryomodule design.

  4. Harnessing Satellite Imageries in Feature Extraction Using Google Earth Pro

    NASA Astrophysics Data System (ADS)

    Fernandez, Sim Joseph; Milano, Alan

    2016-07-01

    Climate change has been a long-time concern worldwide. Impending flooding, for one, is among its unwanted consequences. The Phil-LiDAR 1 project of the Department of Science and Technology (DOST), Republic of the Philippines, has developed an early warning system in regards to flood hazards. The project utilizes the use of remote sensing technologies in determining the lives in probable dire danger by mapping and attributing building features using LiDAR dataset and satellite imageries. A free mapping software named Google Earth Pro (GEP) is used to load these satellite imageries as base maps. Geotagging of building features has been done so far with the use of handheld Global Positioning System (GPS). Alternatively, mapping and attribution of building features using GEP saves a substantial amount of resources such as manpower, time and budget. Accuracy-wise, geotagging by GEP is dependent on either the satellite imageries or orthophotograph images of half-meter resolution obtained during LiDAR acquisition and not on the GPS of three-meter accuracy. The attributed building features are overlain to the flood hazard map of Phil-LiDAR 1 in order to determine the exposed population. The building features as obtained from satellite imageries may not only be used in flood exposure assessment but may also be used in assessing other hazards and a number of other uses. Several other features may also be extracted from the satellite imageries.

  5. Quid Pro Quo: Tobacco Companies and the Black Press

    PubMed Central

    McCandless, Phyra M.; Yerger, Valerie B.

    2012-01-01

    Objectives. We explored the relationship between tobacco companies and the Black press, which plays an important role in conveying information and opinions to Black communities. Methods. In this archival case study, we analyzed data from internal tobacco industry documents and archives of the National Newspaper Publishers Association (NNPA), the trade association of the Black press. Results. In exchange for advertising dollars and other support, the tobacco industry expected and received support from Black newspapers for tobacco industry policy positions. Beginning in the 1990s, resistance from within the Black community and reduced advertising budgets created counterpressures. The tobacco industry, however, continued to sustain NNPA support. Conclusions. The quid pro quo between tobacco companies and the Black press violated journalistic standards and represented an unequal trade. Although numerous factors explain today's tobacco-related health disparities, the Black press's service to tobacco companies is problematic because of the trust that the community placed in such media. Understanding the relationship between the tobacco industry and the NNPA provides insight into strategies that the tobacco industry may use in other communities and countries. PMID:21852652

  6. Self-interest and pro-environmental behaviour

    NASA Astrophysics Data System (ADS)

    Evans, Laurel; Maio, Gregory R.; Corner, Adam; Hodgetts, Carl J.; Ahmed, Sameera; Hahn, Ulrike

    2013-02-01

    Inspired by the principles used to market physical products, campaigns to promote pro-environmental behaviour have increasingly emphasized self-interested (for example, economic) reasons for engaging with a self-transcendent cause (that is, protecting the environment). Yet, psychological evidence about values and behaviour suggests that giving self-interested reasons, rather than self-transcending reasons, to carry out a self-transcending action should be ineffective at increasing self-transcending behaviour more generally. In other words, such a campaign may fail to cause spillover, or an increase in other, different environmental behaviours. Here we show that recycling rates are dependent on the information participants receive about a separate environmental behaviour, car-sharing (carpooling in the USA). In two experiments, we found that recycling was significantly higher than control when participants received environmental information about car-sharing, but was no different from control when they received financial information or (in experiment 2) received both financial and environmental information. Our results suggest that, congruent with value theory, positive spillover from one environmental message to another behaviour (car-sharing to recycling) may occur primarily when self-transcending reasons alone are made salient.

  7. Anionic Amino Acids near the Pro-α-defensin N Terminus Mediate Inhibition of Bactericidal Activity in Mouse Pro-cryptdin-4*S⃞

    PubMed Central

    Figueredo, Sharel M.; Weeks, Colby S.; Young, Steven K.; Ouellette, André J.

    2009-01-01

    In mouse Paneth cells, α-defensins, termed cryptdins (Crps), are activated by matrix metalloproteinase-7-mediated proteolysis of inactive precursors (pro-Crps) to bactericidal forms. The activating cleavage step at Ser43 ↓ Ile44 in mouse pro-Crp4-(20–92) removes nine acidic amino acids that collectively block the membrane-disruptive behavior of the Crp4 moiety of the proform. This inhibitory mechanism has been investigated further to identify whether specific cluster(s) of electronegative amino acids in pro-Crp4-(20–43) are responsible for blocking bactericidal activity and membrane disruption. To test whether specific cluster(s) of electronegative amino acids in pro-Crp4-(20–43) have specific positional effects that block bactericidal peptide activity and membrane disruption, acidic residues positioned at the distal (Asp20, Asp26, Glu27, and Glu28), mid (Glu32 and Glu33), and proximal (Glu37, Glu38, and Asp39) clusters in pro-Crp4-(20–92) were mutagenized, and variants were assayed for differential effects of mutagenesis on bactericidal peptide activity. Substitution of the mid and proximal Asp and Glu clusters with Gly produced additive effects with respect to the induction of both bactericidal activity and membrane permeabilization of live Escherichia coli ML35 cells. In contrast, substitution of distal Glu and Asp residues with Gly or their deletion resulted in pro-Crp4-(20–92) variants with bactericidal and membrane-disruptive activities equal to or greater than that of fully mature Crp4. These findings support the conclusion that the most distal N-terminal anionic residues of pro-Crp4-(20–92) are primarily responsible for blocking Crp4-mediated membrane disruption in the precursor. PMID:19106102

  8. Rapid Increases in proBDNF after Pilocarpine-Induced Status Epilepticus in Mice Are Associated with Reduced proBDNF Cleavage Machinery123

    PubMed Central

    Cruz Del Angel, Yasmin; Gonzalez, Marco I.; Carrel, Andrew J.; Carlsen, Jessica; Lam, Philip M.; Hempstead, Barbara L.; Russek, Shelley. J.

    2016-01-01

    Abstract Brain-derived neurotrophic factor (BDNF) levels are elevated after status epilepticus (SE), leading to activation of multiple signaling pathways, including the janus kinase/signal transducer and activator of transcription pathway that mediates a decrease in GABAA receptor α1 subunits in the hippocampus (Lund et al., 2008). While BDNF can signal via its pro or mature form, the relative contribution of these forms to signaling after SE is not fully known. In the current study, we investigate changes in proBDNF levels acutely after SE in C57BL/6J mice. In contrast to previous reports (Unsain et al., 2008; Volosin et al., 2008; VonDran et al., 2014), our studies found that levels of proBDNF in the hippocampus are markedly elevated as early as 3 h after SE onset and remain elevated for 7 d. Immunohistochemistry studies indicate that seizure-induced BDNF localizes to all hippocampal subfields, predominantly in principal neurons and also in astrocytes. Analysis of the proteolytic machinery that cleaves proBDNF to produce mature BDNF demonstrates that acutely after SE there is a decrease in tissue plasminogen activator and an increase in plasminogen activator inhibitor-1 (PAI-1), an inhibitor of extracellular and intracellular cleavage, which normalizes over the first week after SE. In vitro treatment of hippocampal slices from animals 24 h after SE with a PAI-1 inhibitor reduces proBDNF levels. These findings suggest that rapid proBDNF increases following SE are due in part to reduced cleavage, and that proBDNF may be part of the initial neurotrophin response driving intracellular signaling during the acute phase of epileptogenesis. PMID:27057559

  9. NGF and proNGF Reciprocal Interference in Immunoassays: Open Questions, Criticalities, and Ways Forward

    PubMed Central

    Malerba, Francesca; Paoletti, Francesca; Cattaneo, Antonino

    2016-01-01

    The homeostasis between mature neurotrophin NGF and its precursor proNGF is thought to be crucial in physiology and in pathological states. Therefore, the measurement of the relative amounts of NGF and proNGF could serve as a footprint for the identification of disease states, for diagnostic purposes. Since NGF is part of proNGF, their selective identification with anti-NGF antibodies is not straightforward. Currently, many immunoassays for NGF measurement are available, while the proNGF assays are few and not validated by published information. The question arises, as to whether the commercially available assays are able to distinguish between the two forms. Also, since in biological samples the two forms coexist, are the measurements of one species affected by the presence of the other? We describe experiments addressing these questions. For the first time, NGF and proNGF were measured together and tested in different immunoassays. Unexpectedly, NGF and proNGF were found to reciprocally interfere with the experimental outcome. The interference also calls into question the widely used NGF ELISA methods, applied to biological samples where NGF and proNGF coexist. Therefore, an immunoassay, able to distinguish between the two forms is needed. We propose possible ways forward, toward the development of a selective assay. In particular, the use of the well validated anti-NGF αD11 antibody in an alphaLISA assay with optimized incubation times would be a solution to avoid the interference in the measurement of a mixed sample containing NGF and proNGF. Furthermore, we explored the possibility of measuring proNGF in a biological sample. But the available commercial kit for the detection of proNGF does not allow the measurement of proNGF in mouse brain tissues. Therefore, we validated an SPR approach for the measurement of proNGF in a biological sample. Our experiments help in understanding the technical limits in the measurement of the NGF/proNGF ratio in biological

  10. Feedback on the FDA's February 2006 draft guidance on Patient Reported Outcome (PRO) measures from a developer of PRO measures.

    PubMed

    Bradley, Clare

    2006-10-09

    I believe that the FDA guidelines have already had an impact in encouraging good practice in the use of PROs. There are, however, important improvements that need to be made to the guidelines, particularly in the use of health status and quality of life terminology. It is essential to distinguish between health status and quality of life and to use both terms. Nothing is to be gained and a great deal will be lost if the term quality of life (which has been misused as an umbrella term in the past) is abandoned and replaced with the term health status. Patients want us to consider their quality of life as well as their health. To abandon the term would be to forget about their quality of life and focus only on their health. Patients are well able to tell us what quality of life means to them and to rate the impact of a condition on their quality of life if we use individualised quality of life measures and individualised condition-specific quality of life measures to allow them to do so. Although my experience with PRO measures would support many of the recommendations in the guidelines there are others that I would not fully agree with or would contradict on the basis of my own research evidence. I have provided references to that research and hope that the FDA will feel able to do the same when they finalize their guidelines.

  11. Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses

    PubMed Central

    Je, H. Shawn; Yang, Feng; Ji, Yuanyuan; Nagappan, Guhan; Hempstead, Barbara L.; Lu, Bai

    2012-01-01

    Formation of specific neuronal connections often involves competition between adjacent axons, leading to stabilization of the active terminal, while retraction of the less active ones. The underlying molecular mechanisms remain unknown. We show that activity-dependent conversion of pro–brain-derived neurotrophic factor (proBDNF) to mature (m)BDNF mediates synaptic competition. Stimulation of motoneurons triggers proteolytic conversion of proBDNF to mBDNF at nerve terminals. In Xenopus nerve–muscle cocultures, in which two motoneurons innervate one myocyte, proBDNF-p75NTR signaling promotes retraction of the less active terminal, whereas mBDNF–tyrosine-related kinase B (TrkB) p75NTR (p75 neurotrophin receptor) facilitates stabilization of the active one. Thus, proBDNF and mBDNF may serve as potential “punishment” and “reward” signals for inactive and active terminals, respectively, and activity-dependent conversion of proBDNF to mBDNF may regulate synapse elimination. PMID:23019376

  12. Higher level of NT-proCNP in cerebrospinal fluid of patients with meningitis.

    PubMed

    Tomasiuk, Ryszard; Lipowski, Dariusz; Szlufik, Stanislaw; Peplinska, Krystyna; Mikaszewska-Sokolewicz, Malgorzata

    2016-02-12

    Aminoterminal pro-C type natriuretic peptide (NT-proCNP) as an active form of CNP, has been recently proven to be a potential marker of sepsis and to be linked to inflammatory diseases. So far, there are no studies describing the level of NT-proCNP in meningitis. The purpose of this study was to evaluate the diagnostic value of NT-proCNP in cerebrospinal fluid (CSF) in patients with meningitis and to compare it with the serum level of CRP and procalcitonin (PCT) in this group of patients. The results were compared to serum levels of CRP, PCT and CSF levels of cytosis, protein and lactate. NT-proCNP levels were statistically significant between the control group and the meningitis groups (p=0.02; R=0.3). We also noted a correlation between the level of NT-proCNP in the CSF of all of the study groups (controls and meningitis patients) and the CSF levels of cytosis (p<0.5; R=0.43), protein (p<0.05; R=0.39) and lactate (p<0.05; R=0.34), and also the serum level of CRP (p<0.05; R=0.30), but not serum PCT (p>0.05; R=0.11). These results suggest that NT-proCNP could be a potential marker of meningitis, but it cannot be used to distinguish between the types of meningitis.

  13. Midregional pro-atrial natriuretic peptide and procalcitonin improve survival prediction in VAP.

    PubMed

    Boeck, L; Eggimann, P; Smyrnios, N; Pargger, H; Thakkar, N; Siegemund, M; Marsch, S; Rakic, J; Tamm, M; Stolz, D

    2011-03-01

    Ventilator-associated pneumonia (VAP) affects mortality, morbidity and cost of critical care. Reliable risk estimation might improve end-of-life decisions, resource allocation and outcome. Several scoring systems for survival prediction have been established and optimised over the last decades. Recently, new biomarkers have gained interest in the prognostic field. We assessed whether midregional pro-atrial natriuretic peptide (MR-proANP) and procalcitonin (PCT) improve the predictive value of the Simplified Acute Physiologic Score (SAPS) II and Sequential Related Organ Failure Assessment (SOFA) in VAP. Specified end-points of a prospective multinational trial including 101 patients with VAP were analysed. Death <28 days after VAP onset was the primary end-point. MR-proANP and PCT were elevated at the onset of VAP in nonsurvivors compared with survivors (p = 0.003 and p = 0.017, respectively) and their slope of decline differed significantly (p = 0.018 and p = 0.039, respectively). Patients with the highest MR-proANP quartile at VAP onset were at increased risk for death (log rank p = 0.013). In a logistic regression model, MR-proANP was identified as the best predictor of survival. Adding MR-proANP and PCT to SAPS II and SOFA improved their predictive properties (area under the curve 0.895 and 0.880). We conclude that the combination of two biomarkers, MR-proANP and PCT, improve survival prediction of clinical severity scores in VAP.

  14. Isolation and cloning of a Azospirillum lipoferum locus that complements Escherichia coli proU mutant.

    PubMed

    Tripathi, A K; Mishra, B M

    1998-05-15

    Glycine betaine relieved sodium chloride-mediated inhibition of growth in Azospirillum lipoferum ATCC 29708. 35S-methionine labelling of proteins after salinity up-shock revealed strong induction of a 30 kDa protein which cross-reacted with the anti-glycine betaine binding protein antibody from Escherichia coli. This suggested that A. lipoferum had a salinity-induced ProU-like high-affinity glycine betaine transport system. A genomic library of A. lipoferum ATCC 29708 was screened for the proU-like gene by complementation of a proU mutant of E. coli. Four recombinant cosmids, capable of restoring growth of the proU mutant on plates containing 600 mM NaCl and 1 mM glycine betaine were selected. Selected recombinant cosmids hybridized with a proU gene probe from E. coli. Complementation of E. coli proU mutant with the A. lipoferum genomic DNA was evident by the ability of proU mutant (containing selected recombinant cosmids) to grow on minimal medium supplemented with 600 mM NaCl and 1 mM glycine betaine.

  15. The InterPro protein families database: the classification resource after 15 years.

    PubMed

    Mitchell, Alex; Chang, Hsin-Yu; Daugherty, Louise; Fraser, Matthew; Hunter, Sarah; Lopez, Rodrigo; McAnulla, Craig; McMenamin, Conor; Nuka, Gift; Pesseat, Sebastien; Sangrador-Vegas, Amaia; Scheremetjew, Maxim; Rato, Claudia; Yong, Siew-Yit; Bateman, Alex; Punta, Marco; Attwood, Teresa K; Sigrist, Christian J A; Redaschi, Nicole; Rivoire, Catherine; Xenarios, Ioannis; Kahn, Daniel; Guyot, Dominique; Bork, Peer; Letunic, Ivica; Gough, Julian; Oates, Matt; Haft, Daniel; Huang, Hongzhan; Natale, Darren A; Wu, Cathy H; Orengo, Christine; Sillitoe, Ian; Mi, Huaiyu; Thomas, Paul D; Finn, Robert D

    2015-01-01

    The InterPro database (http://www.ebi.ac.uk/interpro/) is a freely available resource that can be used to classify sequences into protein families and to predict the presence of important domains and sites. Central to the InterPro database are predictive models, known as signatures, from a range of different protein family databases that have different biological focuses and use different methodological approaches to classify protein families and domains. InterPro integrates these signatures, capitalizing on the respective strengths of the individual databases, to produce a powerful protein classification resource. Here, we report on the status of InterPro as it enters its 15th year of operation, and give an overview of new developments with the database and its associated Web interfaces and software. In particular, the new domain architecture search tool is described and the process of mapping of Gene Ontology terms to InterPro is outlined. We also discuss the challenges faced by the resource given the explosive growth in sequence data in recent years. InterPro (version 48.0) contains 36,766 member database signatures integrated into 26,238 InterPro entries, an increase of over 3993 entries (5081 signatures), since 2012.

  16. Pro-region engineering for improved yeast display and secretion of brain derived neurotrophic factor.

    PubMed

    Burns, Michael L; Malott, Thomas M; Metcalf, Kevin J; Puguh, Arthya; Chan, Jonah R; Shusta, Eric V

    2016-03-01

    Brain derived neurotrophic factor (BDNF) is a promising therapeutic candidate for a variety of neurological diseases. However, it is difficult to produce as a recombinant protein. In its native mammalian context, BDNF is first produced as a pro-protein with subsequent proteolytic removal of the pro-region to yield mature BDNF protein. Therefore, in an attempt to improve yeast as a host for heterologous BDNF production, the BDNF pro-region was first evaluated for its effects on BDNF surface display and secretion. Addition of the wild-type pro-region to yeast BDNF production constructs improved BDNF folding both as a surface-displayed and secreted protein in terms of binding its natural receptors TrkB and p75, but titers remained low. Looking to further enhance the chaperone-like functions provided by the pro-region, two rounds of directed evolution were performed, yielding mutated pro-regions that further improved the display and secretion properties of BDNF. Subsequent optimization of the protease recognition site was used to control whether the produced protein was in pro- or mature BDNF forms. Taken together, we have demonstrated an effective strategy for improving BDNF compatibility with yeast protein engineering and secretion platforms.

  17. Oxidation pathways underlying the pro-oxidant effects of apigenin.

    PubMed

    Andueza, Aitor; García-Garzón, Antonia; Ruiz de Galarreta, Marina; Ansorena, Eduardo; Iraburu, María J; López-Zabalza, María J; Martínez-Irujo, Juan J

    2015-10-01

    Apigenin, a natural flavone, is emerging as a promising compound for the treatment of several diseases. One of the hallmarks of apigenin is the generation of intracellular reactive oxygen species (ROS), as judged by the oxidation of reduced dichlorofluorescein derivatives seen in many cell types. This study aimed to reveal some mechanisms by which apigenin can be oxidized and how apigenin-derived radicals affect the oxidation of 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein (H(2)DCF), a probe usually employed to detect intracellular ROS. Apigenin induced a rapid oxidation of H(2)DCF in two different immortalized cell lines derived from rat and human hepatic stellate cells. However, apigenin did not generate ROS in these cells, as judged by dihydroethidium oxidation and extracellular hydrogen peroxide production. In cell-free experiments we found that oxidation of apigenin leads to the generation of a phenoxyl radical, which directly oxidizes H(2)DCF with catalytic amounts of hydrogen peroxide. The net balance of the reaction was the oxidation of the probe by molecular oxygen due to redox cycling of apigenin. This flavonoid was also able to deplete NADH and glutathione by a similar mechanism. Interestingly, H(2)DCF oxidation was significantly accelerated by apigenin in the presence of horseradish peroxidase and xanthine oxidase, but not with other enzymes showing peroxidase-like activity, such as cytochrome c or catalase. We conclude that in cells treated with apigenin oxidation of reduced dichlorofluorescein derivatives does not measure intracellular ROS and that pro- and antioxidant effects of flavonoids deduced from these experiments are inconclusive and must be confirmed by other techniques.

  18. Biosynthesis of amidated joining peptide from pro-adrenocorticotropin-endorphin

    SciTech Connect

    Cullen, E.I.; Mains, R.E. )

    1987-09-01

    Joining peptide is the major alpha-amidated product of pro-ACTH/endorphin (PAE) in AtT-20 corticotropic tumor cells. To study intracellular joining peptide synthesis, affinity purified antibodies directed against gamma-MSH, joining peptide, and ACTH were used to immunoprecipitate extracts from biosynthetically labeled AtT-20 cells. Immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by tryptic peptide mapping on HPLC. In steady labeling experiments, radioactivity in amidated joining peptide (JP) increased roughly linearly with time, in the manner of a final product, whereas radioactivity associated with PAE (1-94)NH2 reached a constant value after 2-4 h, indicating that PAE(1-94)NH2 is an intermediate in the biosynthesis of JP. Radioactivity appeared in ACTH(1-39) well before JP, consistent with a cleavage order in which ACTH is cleaved from PAE(1-95) before JP sequences are cleaved from PAE(1-74). This conclusion was supported by tryptic peptide analyses of immunoprecipitates, which indicated that less than 5% of JP-related material is cleaved from PAE(1-74) before being cleaved from ACTH-related sequences. After a pulse label, radioactivity in PAE(1-94)NH2 reached a peak value after 1 h of chase and declined with a half-life of less than 1 h. Amidated JP increased to a constant level after 2 h of chase. Enough radiolabeled PAE(1-94)NH2 was detected to account for about half of the radioactivity found in amidated JP, indicating that about half of JP-related material is first cleaved from PAE(1-95) before being amidated. This result was corroborated using HPLC purification to determine both amidated and glycine-extended forms of JP.

  19. Macrophage Pro-Resolving Mediators—the When and Where

    PubMed Central

    DALLI, JESMOND; SERHAN, CHARLES

    2016-01-01

    Macrophages and neutrophils orchestrate acute inflammation and host defense as well as the resolution phase and return to homeostasis. In this article, we review the contribution of macrophages to local lipid mediator (LM) levels and the regulation of macrophage LM profiles by neutrophils and neutrophil-derived microparticles. We carried out LM metabololipidomics profiling distinct phagocytes: neutrophils (PMN), apoptotic PMN, and macrophages. Efferocytosis increased specialized proresolving mediator (SPM) biosynthesis, including Resolvin D1 (RvD1), RvD2, and RvE2, which were further elevated by PMN microparticles. Using deuterium-labeled precursors (d8-arachidonic acid, d5-eicosapentaenoic acid, and d5-docosahexaenoic acid), apoptotic PMN and microparticles contributed to SPM biosynthesis during efferocytosis. Assessment of macrophage LM profiles in M2 macrophages demonstrated higher SPM levels in this macrophage subset, including maresin 1 (MaR1), and lower amounts of leukotriene B4 and prostaglandins than M1. Apoptotic PMN uptake by both macrophage subtypes led to modulation of their LM profiles. Leukotriene B4 was down-regulated in M2 whereas SPM including lipoxin A4 were increased. Conversely, uptake of apoptotic PMN by M2 macrophages reduced (~ 25%) overall LM. MaR1 displays potent tissue regenerative and anti-nociceptive actions in addition to its pro-resolving and anti-inflammatory actions. In addition the MaR1 biosynthetic intermediate 13S,14S-epoxy-Maresin is also bioactive, inhibiting LTB4 biosynthesis and switching macrophage phenotypes from M1 to M2. Together, these results establish LM signature profiles of human phagocytes and related subpopulations. They demonstrate microparticle regulation of specific macrophage endogenous LM during defined stages of acute inflammation and their dynamic changes in human primary phagocytes. PMID:27337457

  20. ICPEAC XX: A Retro- and Pro-Spective Analysis

    SciTech Connect

    Datz, S.

    1997-12-31

    There is something magical about ``round birthdays.`` They make one stop and think about where he is, how he got there, and where he is going. The same is apparently true of conferences, especially those like ICPEAC which represent the periodic coming together of a broad range of scientists in a reasonably well-defined discipline. This Vienna conference is the 20th in the ICPEAC series, and a retro- and pro-spective analysis seems appropriate. At the first ICPEAC in New York (1958), there were about 50 participants. In Vienna (1997), there were more than 800 participants. How do we account for this growth? ICPEAC is one of the most democratic conferences of its size. For example, input from a general committee of 50 representing the many geographic and sub- disciplinary areas gives continuous refreshment of ideas for the invited program. And, as in any democracy, there is a constant state of turmoil and self doubt. After all, atomic collisions is a ``mature`` field, and was a ``mature`` field at the time of the first ICPEAC in 1958, 50 what can one expect in new developments? This self doubt is best expressed in the comment of Ben Bederson (the ``Father of ICPEAC``) following the second in Boulder, Colorado, in 1961: ``This conference is the second in a series of informal meetings organized by a group of workers in the general field of electronic and atomic collisions. The first such meeting was held at New York University in 1958, and we will probably continue to meet at irregular intervals in the future....`` As part of my ``keynote`` talk at the New York ICPEAC XVI in 1989, I gave a brief history of the conference which we can build on to round things off for our twentieth.

  1. Idebenone and Neuroprotection: Antioxidant, Pro-oxidant, or Electron Carrier?

    PubMed Central

    Jaber, Sausan; Polster, Brian M.

    2015-01-01

    Ubiquinone, commonly called coenzyme Q10 (CoQ), is a lipophilic electron carrier and endogenous antioxidant found in all cellular membranes. In the mitochondrial inner membrane it transfers electrons to complex III of the electron transport chain. The short chain CoQ analogue idebenone is in clinical trials for a number of diseases that exhibit a mitochondrial etiology. Nevertheless, evidence that idebenone ameliorates neurological symptoms in human disease is inconsistent. Although championed as an antioxidant, idebenone can also act as a pro-oxidant by forming an unstable semiquinone at complex I. The antioxidant function of idebenone is critically dependent on two-electron reduction to idebenol without the creation of unstable intermediates. Recently, cytoplasmic NAD(P)H:quinone oxidoreductase 1 (NQO1) was identified as a major enzyme catalyzing idebenone reduction. While reduction allows idebenone to act as an antioxidant, evidence also suggests that NQO1 enables idebenone to shuttle reducing equivalents from cytoplasmic NAD(P)H to mitochondrial complex III, bypassing any upstream damage to the electron transport chain. In this mini-review we discuss how idebenone can influence mitochondrial function within the context of cytoprotection. Importantly, in the brain NQO1 is expressed primarily by glia rather than neurons. As NQO1 is an inducible enzyme regulated by oxidative stress and the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway, optimizing NQO1 expression in appropriate cell types within a specific disease context may be key to delivering on idebenone's therapeutic potential. PMID:25262284

  2. Development of Composite Indices to Measure the Adoption of Pro-Environmental Behaviours across Canadian Provinces

    PubMed Central

    Canuel, Magalie; Abdous, Belkacem; Bélanger, Diane; Gosselin, Pierre

    2014-01-01

    Objective The adoption of pro-environmental behaviours reduces anthropogenic environmental impacts and subsequent human health effects. This study developed composite indices measuring adoption of pro-environmental behaviours at the household level in Canada. Methods The 2007 Households and the Environment Survey conducted by Statistics Canada collected data on Canadian environmental behaviours at households' level. A subset of 55 retained questions from this survey was analyzed by Multiple Correspondence Analysis (MCA) to develop the index. Weights attributed by MCA were used to compute scores for each Canadian province as well as for socio-demographic strata. Scores were classified into four categories reflecting different levels of adoption of pro-environmental behaviours. Results Two indices were finally created: one based on 23 questions related to behaviours done inside the dwelling and a second based on 16 questions measuring behaviours done outside of the dwelling. British Columbia, Quebec, Prince-Edward-Island and Nova-Scotia appeared in one of the two top categories of adoption of pro-environmental behaviours for both indices. Alberta, Saskatchewan, Manitoba and Newfoundland-and-Labrador were classified in one of the two last categories of pro-environmental behaviours adoption for both indices. Households with a higher income, educational attainment, or greater number of persons adopted more indoor pro-environmental behaviours, while on the outdoor index, they adopted fewer such behaviours. Households with low-income fared better on the adoption of outdoors pro-environmental behaviours. Conclusion MCA was successfully applied in creating Indoor and Outdoor composite Indices of pro-environmental behaviours. The Indices cover a good range of environmental themes and the analysis could be applied to similar surveys worldwide (as baseline weights) enabling temporal trend comparison for recurring themes. Much more than voluntary measures, the study shows that

  3. Modulation of the Activities of Neuronal Ion Channels by Fatty Acid-Derived Pro-Resolvents

    PubMed Central

    Choi, Geunyeol; Hwang, Sun Wook

    2016-01-01

    Progress of inflammation depends on the balance between two biological mechanisms: pro-inflammatory and pro-resolving processes. Many extracellular and intracellular molecular components including cytokines, growth factors, steroids, neurotransmitters, and lipidergic mediators and their receptors contribute to the two processes, generated from cellular participants during inflammation. Fatty acid-derived mediators are crucial in directing the inflammatory phase and orchestrating heterogeneous reactions of participants such as inflamed cells, innate immune cells, vascular components, innervating neurons, etc. As well as activating specific types of receptor molecules, lipidergic mediators can actively control the functions of various ion channels via direct binding and/or signal transduction, thereby altering cellular functions. Lipid mediators can be divided into two classes based on which of the two processes they promote: pro-inflammatory, which includes prostaglandins and leukotrienes, and pro-resolving, which includes lipoxins, resolvins, and maresins. The research on the modulations of neuronal ion channels regarding the actions of the pro-inflammatory class has begun relatively earlier while the focus is currently expanding to cover the ion channel interaction with pro-resolvents. As a result, knowledge of inhibitory mechanisms by the pro-resolvents, historically seldom found for other known endogenous modulators or pro-inflammatory mediators, is accumulating particularly upon sensory neuronal cation channels. Diverse mechanistic explanations at molecular levels are being proposed and refined. Here we overviewed the interactions of lipidergic pro-resolvents with neuronal ion channels and outcomes from the interactions, focusing on transient receptor potential (TRP) ion channels. We also discuss unanswered hypotheses and perspectives regarding their interactions. PMID:27877134

  4. Rapid Activation of Bone Morphogenic Protein 9 by Receptor-mediated Displacement of Pro-domains*

    PubMed Central

    Kienast, Yvonne; Jucknischke, Ute; Scheiblich, Stefan; Thier, Martina; de Wouters, Mariana; Haas, Alexander; Lehmann, Christian; Brand, Verena; Bernicke, Dirk; Honold, Konrad; Lorenz, Stefan

    2016-01-01

    By non-covalent association after proteolytic cleavage, the pro-domains modulate the activities of the mature growth factor domains across the transforming growth factor-β family. In the case of bone morphogenic protein 9 (BMP9), however, the pro-domains do not inhibit the bioactivity of the growth factor, and the BMP9·pro-domain complexes have equivalent biological activities as the BMP9 mature ligand dimers. By using real-time surface plasmon resonance, we could demonstrate that either binding of pro-domain-complexed BMP9 to type I receptor activin receptor-like kinase 1 (ALK1), type II receptors, co-receptor endoglin, or to mature BMP9 domain targeting antibodies leads to immediate and complete displacement of the pro-domains from the complex. Vice versa, pro-domain binding by an anti-pro-domain antibody results in release of the mature BMP9 growth factor. Based on these findings, we adjusted ELISA assays to measure the protein levels of different BMP9 variants. Although mature BMP9 and inactive precursor BMP9 protein were directly detectable by ELISA, BMP9·pro-domain complex could only be measured indirectly as dissociated fragments due to displacement of mature growth factor and pro-domains after antibody binding. Our studies provide a model in which BMP9 can be readily activated upon getting into contact with its receptors. This increases the understanding of the underlying biology of BMP9 activation and also provides guidance for ELISA development for the detection of circulating BMP9 variants. PMID:26677222

  5. ProSEDS Telemetry System Utilization of GPS Position Data for Transmitter Cycling

    NASA Technical Reports Server (NTRS)

    Kennedy, Paul; Sims, Herb

    2000-01-01

    NASA Marshall Space Flight Center will launch the Propulsive Small Expendable Deployer System (ProSEDS) space experiment in late 2000. ProSEDS will demonstrate the use of an electrodynamic tether propulsion system and will utilize a conducting wire tether to generate limited spacecraft power. This paper will provide an overview of the ProSEDS mission and will discuss the design, development and test of the spacecraft telemetry system which utilizes a custom designed GPS subsystem to determine spacecraft position relative to ground station location and to control transmitter on/off cycling based on spacecraft state vector and ground station visibility.

  6. ProBNP1-108 Processing and Degradation in Human Heart Failure

    PubMed Central

    Huntley, Brenda K.; Sandberg, Sharon M.; Heublein, Denise M.; Sangaralingham, S. Jeson; Burnett, John C.; Ichiki, Tomoko

    2014-01-01

    Background We have reported that proBNP1-108 circulates and is processed to mature BNP1-32 in human blood. Building on these findings, we sought to determine whether proBNP1-108 processed forms in normal circulation are biologically active and stimulate cGMP, and whether proBNP1-108 processing and activity are altered in human heart failure (HF) compared to normal. Since BNP1-32 is deficient while proBNP1-108 is abundant in HF, we hypothesize that proBNP1-108 processing and degradation are impaired in HF patients ex vivo. Methods and Results We measured circulating molecular forms including BNP1-32, proBNP1-108, and NT-proBNP and all were significantly higher in HF patients compared to normals. Fresh serum samples from normals or HF patients were incubated with or without exogenous non-glycosylated proBNP1-108 tagged with 6 C-terminal Histidines to facilitate peptide isolation. His-tag ProBNP1-108 was efficiently processed into BNP1-32/3-32 at 5 min in normal serum, persisted for 15 min, then disappeared. Delayed processing of proBNP1-108 was observed in HF samples and the degradation pattern differed depending on LV function. The 5 min processed forms from both normal and HF serums were active and generated cGMP via GC-A receptors, however the 180 min samples were not active. The proBNP1-108 processing enzyme corin and BNP degrading enzyme DPPIV were reduced in HF versus normal, perhaps contributing to differential BNP metabolism in HF. Conclusions Exogenous proBNP1-108 is processed into active BNP1-32 and ultimately degraded in normal circulation. The processing and degradation of BNP molecular forms was altered but complete in HF which may contribute the pathophysiology of HF. PMID:25339504

  7. The use of pro-ana blogs for online social support.

    PubMed

    Tong, Stephanie Tom; Heinemann-Lafave, Daria; Jeon, Jehoon; Kolodziej-Smith, Renata; Warshay, Nathaniel

    2013-01-01

    The aim of this research was to document the content on pro-ana blogs and to uncover how the unique socio-technical features of blogs (interactivity, self-disclosure, masspersonal communication) facilitate social support among members. A final sample of 48 pro-ana blogs provided 624 individual units for coding. Results indicate that prevalent forms of social support were emotional support, esteem support, and informational support. A new category, reciprocal self-disclosure, was also revealed to be quite frequent. Blogs are spaces where social support is sought and communicated among members of the pro-ana network. Interpretation of blog communication and implications for treatment and research are discussed.

  8. 17 CFR 270.17a-5 - Pro rata distribution neither “sale” nor “purchase.”

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.17a-5 Pro rata distribution neither “sale” nor “purchase.” When a company makes a pro rata distribution in cash or in kind... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Pro rata distribution...

  9. A Prospective Open-label Pilot Study of Fluvastatin on Pro-inflammatory and Pro-thrombotic Biomarkers in Antiphospholipid Antibody Positive Patients

    PubMed Central

    Erkan, Doruk; Willis, Rohan; Murthy, Vijaya L.; Basra, Gurjot; Vega, JoAnn; Ruiz Limón, Patricia; Carrera, Ana Laura; Papalardo, Elizabeth; Martínez-Martínez, Laura Aline; González, Emilio B.; Pierangeli, Silvia S.

    2014-01-01

    Objective: To determine if pro-inflammatory and pro-thrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. Methods: Four groups of patients (age 18-65) were recruited: a) Primary Antiphospholipid Syndrome (PAPS); b) Systemic Lupus Erythematosus (SLE) with APS (SLE/APS); c) Persistent aPL positivity without SLE or APS (Primary aPL); and d) Persistent aPL positivity with SLE but no APS (SLE/aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for three months. At three months, patients stopped the study medication and they were followed for another three months. Blood samples for 12 pro-inflammatory and pro-thrombotic biomarkers were collected monthly for six months. Results: Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75%) biomarkers (interleukin [IL]-6, IL1β, vascular endothelial growth factor [VEGF], tumor necrosis factor [TNF]-□α, interferon [IFN]-α, inducible protein-10 [IP10], soluble CD40 ligand [sCD40L], soluble tissue factor [sTF], and intracellular cellular adhesion molecule [ICAM]-1) were significantly elevated. Twenty-four patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50%) biomarkers (IL1β, VEGF, TNFα, IP10, sCD40L, and sTF). Conclusion: Our prospective mechanistic study demonstrates that pro-inflammatory and pro-thrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients. PMID:23933625

  10. Thermal effects of added propanol on the helix-coil transition of (Pro-Pro-Gly) 10 in D 2O solution: An NMR study

    NASA Astrophysics Data System (ADS)

    Kai, Tsutomu; Uchiyama, Susumu; Nishi, Yoshinori; Kobayashi, Yuji; Tomiyama, Tetsuo

    2010-05-01

    The conformational transition of collagen model peptide, (Pro-Pro-Gly) 10, from the triple helical structure to the statistical coil was observed in various aqueous alcohol solutions by NMR measurements. In methanol or ethanol solution, the thermal transition temperature, Tm, of the peptide increased regularly with the concentration of alcohols. In 1- or 2-propanol, however, Tm first decreased and then increased steeply, in apparent contrast to the general trend that the addition of alcohol on aqueous solution increases the stability of ordered structure of polypeptides. This exceptional behavior of the collagen model peptide in propanols might provide a clue to investigate the mechanism of stabilization of protein conformation.

  11. Alumna World, Inc. d/b/a Home Pro Information Sheet

    EPA Pesticide Factsheets

    Alumna World, Inc. d/b/a Home Pro (the Company) is located in Joplin, Missouri. The settlement involves renovation activities conducted at residential properties constructed prior to 1978, located in Carthage and Joplin, Missouri.

  12. Role of (pro)renin receptor in cardiovascular cells from the aspect of signaling.

    PubMed

    Hitom, Hirofumi; Liu, Gang; Nishiyama, Akira

    2010-06-01

    The renin-angiotensin-aldosterone system regulates homeostasis of salt and water, vasoconstriction, and remodeling in cardiovascular and renal cells via activation of intracellular signaling pathway. Prorenin, the precursor of renin, had long been considered to be an inactive form. However, a receptor--the (pro)renin receptor--that binds to both renin and prorenin has been recently identified. Prorenin binding to (pro)renin receptors both results in angiotensinogen cleaving into angiotensin (Ang) I, and triggers activation of (pro)renin receptor-stimulated signal transduction pathways, independent of generating Ang II. In the last decade, it has been reported that the intracellular signaling pathway is activated by prorenin in cardiomyocytes, mesangial cells, podocytes, distal tubular cells, vascular endothelial cells and vascular smooth muscle cells, indicating that prorenin mediates intracellular effects in various cardiovascular and kidney cells. In this review, we summarize novel intracellular signaling systems and their downstream effects via (pro)renin receptors in cardiovascular and kidney cells.

  13. New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure

    PubMed Central

    Valenzuela-Méndez, Blanca; Rodríguez-Gutiérrez, Juan Francisco; Estella-García, Ángel; González-García, María Ángela

    2016-01-01

    Mid-regional pro-adrenomedullin (MR-proADM) has a good biomarker profile: its half-life is several hours, and its plasma concentrations can be determined in clinical practice, it is essentially irrelevant, but proportionally represents the levels and activity of adrenomedullin (ADM). ADM synthesis is widely distributed in tissues, including bone, adrenal cortex, kidney, lung, blood vessels and heart. Its fundamental biological effects include vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator. It has been described high levels in septic patients, interacting directly with the relaxation of vascular tone, triggering hypotension of these patients. It is also found high levels in other diseases such as hypertension, heart failure, respiratory failure, renal failure, cirrhosis and cancer. MR-proADM has been identified as a prognostic marker, stratifying the mortality risk in patients with sepsis in emergency department (ED) and ICU. Evolutionary MR-proADM levels and clearance marker to the 2nd–5th days of admission help to determine the poor performance and the risk of mortality in patients with severe sepsis admitted to the ICU. The MR-proADM levels are more effective than procalcitonin (PCT) and C-reactive protein (CRP) levels to determine an unfavorable outcome and the risk of mortality in patients with sepsis admitted to the ICU. It has also proved useful in patients diagnosed with organ dysfunction of infectious etiology. MR-proADM levels are independent of the germ conversely it is related to the magnitude of organ failure and therefore severity. We consider advisable incorporating the MR-proADM the panel of biomarkers necessary for the diagnosis and treatment of critically ill patients admitted to the ICU with severe sepsis. The combined PCT and MR-proADM levels could represent a valid tool in the clinical practice to timely identify patients with bacterial infections and guide the diagnosis and treatment of sepsis and septic shock. PMID

  14. Association of NT-proBNP and interleukin-17 levels with heart failure in elderly patients.

    PubMed

    Li, X F; Pan, D; Zhang, W L; Zhou, J; Liang, J J

    2016-05-13

    Pro-B-type natriuretic peptide (NT-proBNP) and interleukin-17 (IL-17) are involved in the pathophysiological processes of heart failure; however, the exact role of IL-17 is not clear. We explored the relationship between IL-17 and NT-proBNP, as a clinical parameter, in heart failure. The whole blood IL-17 and NT-proBNP levels and the readmission rates in 70 patients with chronic heart failure class III or IV according to the New York Heart Association and 35 patients with normal heart function (control group) were measured and compared. The left ventricle ejection fractions (LVEFs) and NT-proBNP and IL-17 levels in cardiac functional class III (40.38 ± 4.76%, 7780 ± 6393 pg/mL, 8.65 ± 3.05 pg/mL, respectively) and class IV (31.59 ± 4.31%, 13,704 ± 10,945, 21.10 ± 10.60 pg/mL, respectively) were higher than those in the control group (61.27 ± 5.66%, 420 ± 256 pg/mL, 3.53 ± 2.05 pg/mL, respectively). Compared to the cardiac functional class IV, class III showed significantly higher values for LVEF and NT-proBNP and IL-17 levels (P < 0.05). The readmission rates of the patients in cardiac functional class III at 3 and 6 months (15.7 and 34.4%, respectively) and cardiac functional class IV at 3 and 6 months (39.5 and 76.3%, respectively) were significantly higher than those in the control group (0 and 5.7%, respectively) (P < 0.05). The NT-proBNP and IL-17 levels increased as the heart function worsened. NT-proBNP and IL-17 may play essential roles in the process of heart failure.

  15. Semisynthesis and characterization of the first analogues of pro-neuropeptide y.

    PubMed

    von Eggelkraut-Gottanka, Regula; Machova, Zuzana; Grouzmann, Eric; Beck-Sickinger, Annette G

    2003-05-09

    Enzymatic cleavage of prohormone neuropeptide Y (proNPY) leads to mature neuropeptide Y (NPY), a widely distributed neuropeptide with multiple functions both peripherally and centrally. A single dibasic pair of amino acids, Lys38-Arg39, represents the recognition motif for a class of hormone-processing enzymes known as prohormone convertases (PCs). Two members of this PC family, PC1/3 and PC2, are involved in proNPY cleavage. The aim of this work was to establish an effective method for the generation of full-length 69-amino acid proNPY analogues for further studies of prohormone convertase interaction. We have chosen two ligation sites in order to perform the semisynthesis of proNPY analogues by expressed protein ligation (EPL). By using the intein-mediated purification system (IMPACT) with improved conditions for intein splicing, we were able to isolate proNPY 1-40 and proNPY 1-54 fragments as Cterminal thioesters. Peptides bearing Nterminal cysteine instead of the naturally occurring Ser41 and Thr55 residues, respectively, were generated by solid-phase peptide synthesis. Moreover, labels (carboxyfluorescein and biotin) were inserted into the peptide sequences. The synthesis of the [C41]proNPY 41-69 fragment, which proved to be a difficult peptide sequence, could be achieved by the incorporation of two pseudo-proline derivatives. Western blot analysis revealed that all five proNPY analogues are recognized by monoclonal antibodies directed against NPY as well as against the Cflanking peptide of NPY (CPON).

  16. A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes

    PubMed Central

    Oehmcke, Sonja; Westman, Johannes; Malmström, Johan; Mörgelin, Matthias; Olin, Anders I.; Kreikemeyer, Bernd; Herwald, Heiko

    2013-01-01

    Previous studies have shown that stimulation of whole blood or peripheral blood mononuclear cells with bacterial virulence factors results in the sequestration of pro-coagulant microvesicles (MVs). These particles explore their clotting activity via the extrinsic and intrinsic pathway of coagulation; however, their pathophysiological role in infectious diseases remains enigmatic. Here we describe that the interaction of pro-coagulant MVs with bacteria of the species Streptococcus pyogenes is part of the early immune response to the invading pathogen. As shown by negative staining electron microscopy and clotting assays, pro-coagulant MVs bind in the presence of plasma to the bacterial surface. Fibrinogen was identified as a linker that, through binding to the M1 protein of S. pyogenes, allows the opsonization of the bacteria by MVs. Surface plasmon resonance analysis revealed a strong interaction between pro-coagulant MVs and fibrinogen with a KD value in the nanomolar range. When performing a mass-spectrometry-based strategy to determine the protein quantity, a significant up-regulation of the fibrinogen-binding integrins CD18 and CD11b on pro-coagulant MVs was recorded. Finally we show that plasma clots induced by pro-coagulant MVs are able to prevent bacterial dissemination and possess antimicrobial activity. These findings were confirmed by in vivo experiments, as local treatment with pro-coagulant MVs dampens bacterial spreading to other organs and improved survival in an invasive streptococcal mouse model of infection. Taken together, our data implicate that pro-coagulant MVs play an important role in the early response of the innate immune system in infectious diseases. PMID:23935504

  17. Pro-Nets versus No-Nets: Differences in Urban Older Adults' Predilections for Internet Use

    ERIC Educational Resources Information Center

    Cresci, M. Kay; Yarandi, Hossein N.; Morrell, Roger W.

    2010-01-01

    Enthusiasm for information technology (IT) is growing among older adults. Many older adults enjoy IT and the Internet (Pro-Nets), but others have no desire to use it (No-Nets). This study found that Pro-Nets and No-Nets were different on a number of variables that might predict IT use. No-Nets were older, had less education and income, were…

  18. Affinity purification of HC-Pro of potyviruses with Ni2+-NTA resin.

    PubMed

    Kadouri, D; Peng, Y; Wang, Y; Singer, S; Huet, H; Raccah, B; Gal-On, A

    1998-12-01

    The HC-Pro of zucchini yellow mosiac virus (ZYMV) was found to bind to Ni2+-NTA resin with or without His-tagging. The binding stringency was similar to that observed in proteins with a zinc finger motif like the HC-Pro. Using this characteristic we developed an efficient and rapid method (2-3 h) for purification of the HC-Pro of several potyviruses. A dominant protein of about 150 kDa was extracted and identified as the HC-Pro of ZYMV by means of immunoblotting. About 150 microg of HC-Pro were partially purified from the soluble fraction of 1 g of leaves. High titers of HC-Pro protein were obtained from plants infected with four potyviruses [ZYMV, watermelon mosaic virus II (WMVII), papaya ringspot virus (PRSV) and turnip mosaic virus (TuMV)]. The HC-Pros of potato virus Y (PVY) and tobacco vein mottling virus (TVMV) did not bind to the Ni2+-NTA resin. The ZYMV-HC-Pro purified by the Ni2+-NTA resin could bind in vitro to ZYMV virions blotted onto a membrane. All the HC-Pros which had been successfully purified by the Ni2+-NTA resin were bound in vitro to membrane-blotted ZYMV coat protein. However, only the HC-Pros of ZYMV and WMVII were able to mediate aphid transmission of purified ZYMV virions. The purification procedure described herein is efficient and convenient, and enables HC-Pro for a number of potyviruses to be obtained in larger amounts and at higher purity than possible by means of most existing methods, based on ultracentrifugation.

  19. Japan turns pro-life: recent change in reproductive health policy and challenges by new technologies

    PubMed Central

    Okamoto, Etsuji

    2014-01-01

    Japan, known as a pro-choice country in terms of abortion, is currently facing the increase of “selective abortions” thanks to new prenatal screening. Efforts to restrict proliferation of new technology has not been successful and it is likely that Japan will turn pro-life by strictly enforcing the Maternity Protection Act (MPA), which prohibits abortions due to “fetal cause”. PMID:24639978

  20. DAPAR & ProStaR: software to perform statistical analyses in quantitative discovery proteomics.

    PubMed

    Wieczorek, Samuel; Combes, Florence; Lazar, Cosmin; Giai Gianetto, Quentin; Gatto, Laurent; Dorffer, Alexia; Hesse, Anne-Marie; Couté, Yohann; Ferro, Myriam; Bruley, Christophe; Burger, Thomas

    2017-01-01

    DAPAR and ProStaR are software tools to perform the statistical analysis of label-free XIC-based quantitative discovery proteomics experiments. DAPAR contains procedures to filter, normalize, impute missing value, aggregate peptide intensities, perform null hypothesis significance tests and select the most likely differentially abundant proteins with a corresponding false discovery rate. ProStaR is a graphical user interface that allows friendly access to the DAPAR functionalities through a web browser.

  1. Accumulation of pro-apolipoprotein A-II in mouse senile amyloid fibrils.

    PubMed Central

    Higuchi, K; Kogishi, K; Wang, J; Xia, C; Chiba, T; Matsushita, T; Hosokawa, M

    1997-01-01

    Apolipoprotein A-II (apoA-II), the major apoprotein of serum high-density lipoprotein, is deposited as amyloid fibrils (AApoAII) in murine senile amyloidosis. We have identified and purified a more basic amyloid protein from old-mouse liver. N-terminal sequencing of the protein revealed that the pro-segment of five amino acid residues (Ala-Leu-Val-Lys-Arg) extended from the N-terminal glutamine residue of mature apoA-II protein. MS analysis revealed the deposit of intact pro-apoA-II protein (molecular mass 9319 Da). Antiserum was prepared for staining of the AApoAII amyloid deposition. The relative abundance of pro-apoA-II to mature apoA-II in the amyloid-fibril fraction isolated from livers of mice with severe amyloidosis was 14.1%. The similar abundance of pro-apoA-II in the amyloid fibril fraction from the spleen (16.3%) suggested that deposited pro-apoA-II originated from the blood. The concentration of pro-apoA-II was much lower in the serum (1.5% of mature apoA-II) than in the amyloid-fibril fraction. There was no difference in the content of pro-apoA-II between the amyloidogenetic R1.P1-Apoa2c and amyloid-resistant SAMR1 strains at the age of 3 months. The abundance of pro-apoA-II in the amyloid-fibril fraction compared with the serum suggested that it plays a key role in the initialization of mouse senile amyloidosis. PMID:9271085

  2. ProBDNF inhibits collective migration and chemotaxis of rat Schwann cells.

    PubMed

    Ding, You-Quan; Li, Xuan-Yang; Xia, Guan-Nan; Ren, Hong-Yi; Zhou, Xin-Fu; Su, Bing-Yin; Qi, Jian-Guo

    2016-10-01

    Schwann cell migration, including collective migration and chemotaxis, is essential for the formation of coordinate interactions between Schwann cells and axons during peripheral nerve development and regeneration. Moreover, limited migration of Schwann cells imposed a serious obstacle on Schwann cell-astrocytes intermingling and spinal cord repair after Schwann cell transplantation into injured spinal cords. Recent studies have shown that mature brain-derived neurotrophic factor, a member of the neurotrophin family, inhibits Schwann cell migration. The precursor form of brain-derived neurotrophic factor, proBDNF, was expressed in the developing or degenerating peripheral nerves and the injured spinal cords. Since "the yin and yang of neurotrophin action" has been established as a common sense, proBDNF would be expected to promote Schwann cell migration. However, we found, in the present study, that exogenous proBDNF also inhibited in vitro collective migration and chemotaxis of RSC 96 cells, a spontaneously immortalized rat Schwann cell line. Moreover, proBDNF suppressed adhesion and spreading of those cells. At molecular level, proBDNF inhibits F-actin polymerization and focal adhesion dynamics in cultured RSC 96 cells. Therefore, our results suggested a special case against the classical opinion of "the yin and yang of neurotrophin action" and implied that proBDNF might modulate peripheral nerve development or regeneration and spinal cord repair through perturbing native or transplanted Schwann cell migration.

  3. Comparison of guided insertion of the LMA ProSeal vs the i-gel.

    PubMed

    Gasteiger, L; Brimacombe, J; Perkhofer, D; Kaufmann, M; Keller, C

    2010-09-01

    In a randomised, non-crossover study, we tested the hypothesis that the ease of insertion using a duodenal tube guided insertion technique and the oropharyngeal leak pressure differ between the LMA ProSeal and the i-gel in non-paralysed, anesthetised female subjects. One hundred and fifty-two females aged 19-70 years were studied. Insertion success rate, insertion time and oropharyngeal leak pressure were measured. First attempt and overall insertion success were similar (LMA ProSeal, 75/76 (99%) and 76/76 (100%); i-gel 73/75 (97%) and 75 (100%), respectively). Mean (SD) insertion times were similar (LMA ProSeal, 40 (16) s; i-gel 43 (21) s). Mean oropharyngeal leak pressure was 7 cmH(2) O higher with the LMA ProSeal (p < 0.0001). Insertion of the LMA ProSeal and i-gel is similarly easy using a duodenal tube guided technique, but the LMA ProSeal forms a more effective seal for ventilation.

  4. Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males.

    PubMed

    Skov, Jeppe; Holst, Jens Juul; Gøtze, Jens Peter; Frøkiær, Jørgen; Christiansen, Jens Sandahl

    2014-01-01

    The antihypertensive actions of glucagon-like peptide-1 (GLP1) receptor agonists have been linked to the release of atrial natriuretic peptide (ANP) in mice. Whether a GLP1-ANP axis exists in humans is unknown. In this study, we examined 12 healthy young males in a randomized, controlled, double-blinded, single-day, cross-over study to evaluate the effects of a 2-h native GLP1 infusion. Plasma proANP concentrations were measured by an automated mid-region-directed proANP immunoassay and N-terminal pro B-type natriuretic peptide (BNP) on Roche Modular E170. Urine was collected for measurements of sodium excretion. Although GLP1 infusion increased the urinary sodium excretion markedly, there were no significant changes in either proANP or proBNP concentrations. When GLP1 infusion was stopped, sodium excretion declined rapidly. As proANP concentration reflects ANP secretion, our data could not confirm the existence of a GLP1-ANP axis in humans. Especially, the natriuretic effects of GLP1 seem unlikely to be mediated exclusively via ANP.

  5. Protein Ontology (PRO): enhancing and scaling up the representation of protein entities

    PubMed Central

    Natale, Darren A.; Arighi, Cecilia N.; Blake, Judith A.; Bona, Jonathan; Chen, Chuming; Chen, Sheng-Chih; Christie, Karen R.; Cowart, Julie; D'Eustachio, Peter; Diehl, Alexander D.; Drabkin, Harold J.; Duncan, William D.; Huang, Hongzhan; Ren, Jia; Ross, Karen; Ruttenberg, Alan; Shamovsky, Veronica; Smith, Barry; Wang, Qinghua; Zhang, Jian; El-Sayed, Abdelrahman; Wu, Cathy H.

    2017-01-01

    The Protein Ontology (PRO; http://purl.obolibrary.org/obo/pr) formally defines and describes taxon-specific and taxon-neutral protein-related entities in three major areas: proteins related by evolution; proteins produced from a given gene; and protein-containing complexes. PRO thus serves as a tool for referencing protein entities at any level of specificity. To enhance this ability, and to facilitate the comparison of such entities described in different resources, we developed a standardized representation of proteoforms using UniProtKB as a sequence reference and PSI-MOD as a post-translational modification reference. We illustrate its use in facilitating an alignment between PRO and Reactome protein entities. We also address issues of scalability, describing our first steps into the use of text mining to identify protein-related entities, the large-scale import of proteoform information from expert curated resources, and our ability to dynamically generate PRO terms. Web views for individual terms are now more informative about closely-related terms, including for example an interactive multiple sequence alignment. Finally, we describe recent improvement in semantic utility, with PRO now represented in OWL and as a SPARQL endpoint. These developments will further support the anticipated growth of PRO and facilitate discoverability of and allow aggregation of data relating to protein entities. PMID:27899649

  6. Artist's Concept of Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Pictured is an artist's concept of NASA's Propulsive Small Expendable Deployer System experiment (ProSEDS). ProSEDS will demonstrate the use of an electrodynamic tether, basically a long, thin wire, for propulsion. An electrodynamic tether uses the same principles as electric motors in toys, appliances and computer disk drives, and generators in automobiles and power plants. When electrical current is flowing through the tether, a magnetic field is produced that pushes against the magnetic field of the Earth. For ProSEDS, the current in the tether results by virtue of the voltage generated when the tether moves through the Earth's magnetic field at more than 17,000 mph. This approach can produce drag thrust generating useable power. Since electrodynamic tethers require no propellant, they could substantially reduce the weight of the spacecraft and provide a cost-effective method of reboosting spacecraft. The initial flight of ProSEDS is scheduled to fly aboard an Air Force Delta II rocket in summer of 2002. In orbit, ProSEDS will deploy from a Delta II second stage. It will be a 3.1-mile (5 kilometer) long, ultrathin base-wire tether cornected with a 6.2-mile (10 kilometer) long nonconducting tether. The ProSEDS experiment is managed by the Space Transportation Directorate at the Marshall Space Flight Center.

  7. Managing Stigma: Disclosure-Response Communication Patterns in Pro-Anorexic Websites.

    PubMed

    Chang, Pamara F; Bazarova, Natalya N

    2016-01-01

    Pro-anorexic websites are a popular online venue for individuals with anorexia, but recent research suggests that they play a role of "online negative enabling support groups" because they can undermine recovery and encourage negative behaviors by validating pro-anorexic views. By analyzing 22,811 messages from 5,590 conversations from the Pro-Ana Nation online discussion board forum, this study examines communicative mechanisms of online negative enabling support through language analysis of disclosure-response sequences, changes in the language of the initial discloser within an interaction exchange, and the role of responses in eliciting those changes. The findings show that initiating disclosures containing stigma-related emotion words, anorexia-specific content, and sociorelational content are typically met with negatively valenced responses from other members of the pro-anorexic community. Moreover, although the act of revealing stigmatized information has some cathartic effects, disclosers use more, not fewer, stigma-related emotion words when they receive negatively valenced responses. These results provide insight into communicative dynamics and effects of online negative enabling support through validation of the pro-anorexic identity and the dangerous cycle of stigma escalation in disclosure-response exchanges on pro-anorexic online communities.

  8. Attenuation of classical swine fever virus by deletion of the viral N(pro) gene.

    PubMed

    Mayer, Daniel; Hofmann, Martin A; Tratschin, Jon Duri

    2004-01-02

    We have reported earlier that replacement of the N(pro) gene of classical swine fever virus (CSFV) by the murine ubiquitin gene only slightly affects the characteristics of virus replication in the porcine kidney cell line SK-6 [J. Virol. 72 (1998) 7681]. Here, for the moderately virulent CSFV strain Alfort/187 as well as for the highly virulent strain Eystrup we show that the respective N(pro)-deleted viruses are attenuated. Vaccination of pigs with either of the two deletion mutants resulted in the induction of a strong antibody response. Animals were protected against challenge with a lethal dose of highly virulent CSFV indicating that N(pro) deletion mutants are excellent candidates for a modified live virus vaccine. A chimeric virus obtained by replacement of the N(pro) gene in the Eystrup virus by the corresponding sequence of the avirulent CSFV vaccine strain Riems resulted in a virus that was highly virulent. This indicates that the virulence of CSFV correlates with the presence of N(pro) and also suggests that N(pro) is not responsible for the varying virulence observed between individual strains of CSFV.

  9. Structural Analysis of Tobacco Etch Potyvirus HC-Pro Oligomers Involved in Aphid Transmission†

    PubMed Central

    Ruiz-Ferrer, Virginia; Boskovic, Jasminka; Alfonso, Carlos; Rivas, Germán; Llorca, Oscar; López-Abella, Dionisio; López-Moya, Juan José

    2005-01-01

    Oligomeric forms of the HC-Pro protein of the tobacco etch potyvirus (TEV) have been analyzed by analytical ultracentrifugation and single-particle electron microscopy combined with three-dimensional (3D) reconstruction. Highly purified HC-Pro protein was obtained from plants infected with TEV by using a modified version of the virus that incorporates a histidine tag at the HC-Pro N terminus (hisHC-Pro). The purified protein retained a high biological activity in solution when tested for aphid transmission. Sedimentation equilibrium showed that the hisHC-Pro preparations were heterogenous in size. Sedimentation velocity confirmed the previous observation and revealed that the active protein solution contained several sedimenting species compatible with dimers, tetramers, hexamers, and octamers of the protein. Electron microscopy fields of purified protein showed particles of different sizes and shapes. The reconstructed 3D structures suggested that the observed particles could correspond to dimeric, tetrameric, and hexameric forms of the protein. A model of the interactions required for oligomerization of the HC-Pro of potyviruses is proposed. PMID:15731269

  10. Enhancing endorsement of scientific inquiry increases support for pro-environment policies

    PubMed Central

    Palmer, Matthew A.; Sauer, James D.

    2016-01-01

    Pro-environment policies require public support and engagement, but in countries such as the USA, public support for pro-environment policies remains low. Increasing public scientific literacy is unlikely to solve this, because increased scientific literacy does not guarantee increased acceptance of critical environmental issues (e.g. that climate change is occurring). We distinguish between scientific literacy (basic scientific knowledge) and endorsement of scientific inquiry (perceiving science as a valuable way of accumulating knowledge), and examine the relationship between people's endorsement of scientific inquiry and their support for pro-environment policy. Analysis of a large, publicly available dataset shows that support for pro-environment policies is more strongly related to endorsement of scientific inquiry than to scientific literacy among adolescents. An experiment demonstrates that a brief intervention can increase support for pro-environment policies via increased endorsement of scientific inquiry among adults. Public education about the merits of scientific inquiry may facilitate increased support for pro-environment policies. PMID:27703700

  11. Documenting the rationale and psychometric characteristics of patient reported outcomes for labeling and promotional claims: the PRO Evidence Dossier.

    PubMed

    Revicki, Dennis A; Gnanasakthy, Ari; Weinfurt, Kevin

    2007-05-01

    The Food and Drug Administration (FDA) and European Medicines Agency (EMEA) are willing to consider including information on patient reported outcomes (PROs) in product labeling and advertising. Pharmaceutical industry researchers must provide sufficient evidence supporting PRO benefit before an approval may be granted. This report describes the purpose and content of a PRO Evidence Dossier, which consists of important information supporting PRO claims. The dossier should be completed by pharmaceutical industry or other researchers to document the planning of the PRO assessment strategy, psychometric evidence, desired target labeling statements, and the clinical trial evidence of PRO benefits. The systematic reporting and documentation of information on the rationale for including PROs, rationale for the selection of specific PRO instruments, evidence on the psychometric qualities of the PRO measures, and guidelines for interpreting PRO findings will facilitate achieving a PRO labeling or promotional claim. Combining all the relevant information into a single document will facilitate the review and evaluation process for clinical and regulatory reviewers. The PRO Evidence Dossier may also be helpful to industry and academic researchers in identifying further information that will need to be developed to support the clinical development program and the PRO endpoints.

  12. Activation of a synapse weakening pathway by human Val66 but not Met66 pro-brain-derived neurotrophic factor (proBDNF)

    PubMed Central

    Kailainathan, Sumangali; Piers, Thomas M.; Yi, Jee Hyun; Choi, Seongmin; Fahey, Mark S.; Borger, Eva; Gunn-Moore, Frank J.; O’Neill, Laurie; Lever, Michael; Whitcomb, Daniel J.; Cho, Kwangwook; Allen, Shelley J.

    2016-01-01

    This study describes a fundamental functional difference between the two main polymorphisms of the pro-form of brain-derived neurotrophic factor (proBDNF), providing an explanation as to why these forms have such different age-related neurological outcomes. Healthy young carriers of the Met66 form (present in ∼30% Caucasians) have reduced hippocampal volume and impaired hippocampal-dependent memory function, yet the same polymorphic population shows enhanced cognitive recovery after traumatic brain injury, delayed cognitive dysfunction during aging, and lower risk of late-onset Alzheimer’s disease (AD) compared to those with the more common Val66 polymorphism. To examine the differences between the protein polymorphisms in structure, kinetics of binding to proBDNF receptors and in vitro function, we generated purified cleavage-resistant human variants. Intriguingly, we found no statistical differences in those characteristics. As anticipated, exogenous application of proBDNF Val66 to rat hippocampal slices dysregulated synaptic plasticity, inhibiting long-term potentiation (LTP) and facilitating long-term depression (LTD). We subsequently observed that this occurred via the glycogen synthase kinase 3β (GSK3β) activation pathway. However, surprisingly, we found that Met66 had no such effects on either LTP or LTD. These novel findings suggest that, unlike Val66, the Met66 variant does not facilitate synapse weakening signaling, perhaps accounting for its protective effects with aging. PMID:26687096

  13. The citrus flavone nobiletin reduces pro-inflammatory and pro-labour mediators in fetal membranes and myometrium: implications for preterm birth.

    PubMed

    Morwood, Carrington J; Lappas, Martha

    2014-01-01

    Spontaneous preterm birth is the leading cause of infant death and of neurological disabilities in survivors. A significant proportion of spontaneous preterm births are associated with infection. Infection activates inflammation which induces a cascade of events that leads to myometrial contractions and rupture of fetal membranes. In non-gestational tissues, the citrus flavone nobiletin has been shown to exert potent anti-inflammatory properties. Thus, in this study, we sought to determine the effect of nobiletin on pro-inflammatory mediators in human fetal membranes and myometrium. Human fetal membranes and myometrium were treated with bacterial endotoxin lipopolysaccharide (LPS) in the absence or presence of nobiletin. In addition, the effect of nobiletin in fetal membranes taken from spontaneous preterm deliveries with and without infection (i.e. histological chorioamnionitis) was also examined. In human fetal membranes and myometrium, nobiletin significantly decreased LPS-stimulated expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) and MMP-9 expression and pro-MMP-9 secretion. Additionally, nobiletin significantly decreased COX-2 expression and subsequent prostaglandin (PG) E2 production. Notably, nobiletin was also able to reduce the expression and production of pro-inflammatory cytokines and MMP-9 in fetal membranes taken from women after spontaneous preterm birth. In conclusion, our study demonstrates that nobiletin can reduce infection-induced pro-inflammatory mediators in human fetal membranes and myometrium. These in vitro studies further support the increasing volume and quality of evidence that high fruit and vegetable intake in pregnancy is associated with a decreased risk of adverse pregnancy outcomes.

  14. Synthesis of poly(Pro-Hyp-Gly)(n) by direct poly-condensation of (Pro-Hyp-Gly)(n), where n=1, 5, and 10, and stability of the triple-helical structure.

    PubMed

    Kishimoto, Takahiro; Morihara, Yasushi; Osanai, Michinori; Ogata, Shin-Ichi; Kamitakahara, Masanobu; Ohtsuki, Chikara; Tanihara, Masao

    2005-10-15

    Pro-Hyp-Gly is a characteristic amino acid sequence found in fibrous collagens, and (Pro-Hyp-Gly)(10), which has been widely used as a collagen-model peptide, forms a stable triple-helical structure. Here, we synthesized polypeptides consisting of the Pro-Hyp-Gly sequence by direct poly-condensation of (Pro-Hyp-Gly)(n), where n=1, 5, and 10, using 1-hydroxybenzotriazole and 1-ethyl-3-(3-dimethyl-aminopropyl)-carbodiimide hydrochloride in both phosphate buffer (pH=7.4) and dimethylsulfoxide (DMSO) solutions for 48 h at 20 degrees C. The reaction of (Pro-Hyp-Gly)(5) and (Pro-Hyp-Gly)(10) in DMSO successfully gave polypeptides with molecular weights over 10,000, whereas low molecular weight products were obtained by reaction in phosphate buffer (pH=7.4). In contrast, Pro-Hyp-Gly at a concentration of 50 mg/mL in phosphate buffer (pH=7.4) gave polypeptides with molecular weights over 10,000. The Fourier transform infrared (FTIR) and (1)H nuclear magnetic resonance (NMR) spectra of poly(Pro-Hyp-Gly)(10) revealed that the polymerization of (Pro-Hyp-Gly)(10) described in this report had no side reactions. Each polypeptide obtained shows a collagen-like triple-helical structure, and the triple-helical structures of poly(Pro-Hyp-Gly) and poly(Pro-Hyp-Gly)(10) were stable up to T=80 degrees C, which suggests that the high molecular weight promotes stability of the triple-helical structure, in addition to the high Hyp content. Furthermore, transmission electron microscopy (TEM) observations show that poly(Pro-Hyp-Gly)(10) aggregates to form nanofiber-like structures about 10 nm in width, which suggests that a Pro-Hyp-Gly repeating sequence contains enough information for triple-helix formation, and for subsequent nanofiber-like structure formation.

  15. The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment.

    PubMed Central

    Bode, W; Mayr, I; Baumann, U; Huber, R; Stone, S R; Hofsteenge, J

    1989-01-01

    A stoichiometric complex formed between human alpha-thrombin and D-Phe-Pro-Arg chloromethylketone was crystallized in an orthorhombic crystal form. Orientation and position of a starting model derived from homologous modelling were determined by Patterson search methods. The thrombin model was completed in a cyclic modelling-crystallographic refinement procedure to a final R-value of 0.171 for X-ray data to 1.92 A. The structure is in full agreement with published cDNA sequence data. The A-chain, ordered only in its central part, is positioned along the molecular surface opposite to the active site. The B-chain exhibits the characteristic polypeptide fold of trypsin-like proteinases. Several extended insertions form, however, large protuberances; most important for interaction with macromolecular substrates is the characteristic thrombin loop around Tyr60A-Pro60B-Pro60C-Trp60D (chymotrypsinogen numbering) and the enlarged loop around the unique Trp148. The former considerably restricts the active site cleft and seems likely to be responsible for poor binding of most natural proteinase inhibitors to thrombin. The exceptional specificity of D-Phe-Pro-Arg chloromethylketone can be explained by a hydrophobic cage formed by Ile174, Trp215, Leu99, His57, Tyr60A and Trp60D. The narrow active site cleft, with a more polar base and hydrophobic rims, extends towards the arginine-rich surface of loop Lys70-Glu80 that probably represents part of the anionic binding region for hirudin and fibrinogen. Images PMID:2583108

  16. PRO-GRADE: GIS toolkits for ground water recharge and discharge estimation.

    PubMed

    Lin, Yu-Feng; Wang, Jihua; Valocchi, Albert J

    2009-01-01

    PRO-GRADE is an ESRI ArcGIS 9.2 plug-in package that consists of two separate toolkits: (1) the pattern recognition organizer for geographic information system (PRO-GIS) and (2) the ground water recharge and discharge estimator for GIS (GRADE-GIS). PRO-GIS is a collection of several existing image-processing algorithms into one user interface to offer the flexibility to extract spatial patterns according to the user's needs. GRADE-GIS is a ground water recharge and discharge estimation interface using a mass balance method that requires only hydraulic conductivity, water table, and bedrock elevation data for simulating two-dimensional steady-state unconfined aquifers. PRO-GRADE was developed to assist ongoing assessments of the water resources in Illinois and Wisconsin, and is being used to assist several ground water resource studies in several locations in the United States. The advantage of using PRO-GRADE is to enable fast production of initial recharge and discharge maps that can be further enhanced by using a follow-up ground water flow model with parameter estimation codes. PRO-GRADE leverages ArcGIS to provide a computer-assisted framework to support expert judgment in order to efficiently select alternative recharge and discharge maps that can be used as (1) guidelines for field study planning and decision making; (2) initial conditions for numerical simulation; and (3) screening for alternative model selection and prediction/parameter uncertainty evaluation. In addition, PRO-GRADE allows for more easy and rapid correlation of those maps with other hydrologically relevant geospatial data.

  17. Quantifying the Persistence of Pro-Smoking Media Effects on College Students’ Smoking Risk

    PubMed Central

    Setodji, Claude M.; Martino, Steven C.; Scharf, Deborah M.; Shadel, William G.

    2013-01-01

    Purpose To quantify the persistence of pro-smoking media exposure effects on college students’ intentions to smoke and smoking refusal self-efficacy. Method A total of 134 college students (ages 18–24) were enrolled in an ecological momentary assessment study in which they carried handheld data collection devices for three weeks and reported their exposures to pro-smoking media as they occurred in the real world. Smoking intentions and smoking refusal self-efficacy were assessed after each exposure to pro-smoking media and at random prompts during each day of the three-week assessment period. A generalized additive model was used to determine how long the effect of an exposure to pro-smoking media persisted. Results The effect of pro-smoking media exposures persisted for 7 days. After exposure, smoking intentions immediately increased (0.56; 95% confidence interval [CI]: [0.26, 0.87]) and then steadily decreased (−0.12; 95% CI: [−0.19, −0.05]) each day for 7 days, while smoking refusal self-efficacy immediately decreased (−0.42; 95% CI: [−0.75, −0.10]) and then steadily increased (0.09; 95% CI: [0.02, 0.16]) each day for 7 days. Daily changes occurring after 7 days were not statistically significant, suggesting that smoking intentions and refusal self-efficacy had stabilized and were no longer affected by pro-smoking media exposure. Conclusions Exposures to pro-smoking media may have strong implications for emerging young adults smoking risk as the impact of an individual exposure appears to persist for at least a week. PMID:24268361

  18. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    SciTech Connect

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  19. Effects of poliovirus 2A(pro) on vaccinia virus gene expression.

    PubMed

    Feduchi, E; Aldabe, R; Novoa, I; Carrasco, L

    1995-12-15

    The effects of transient expression of poliovirus 2A(pro) on p220 cleavage in COS cells have been analyzed. When 2A(pro) was cloned in plasmid pTM1 and transiently expressed in COS cells, efficient cleavage of p220 occurred after infection of these cells with a recombinant vaccinia virus bearing phage T7 RNA polymerase. High numbers of COS cells were transfected with pTM1-2A, as judged by p220 cleavage, thereby allowing an analysis of the effects of poliovirus 2A(pro) on vaccinia virus gene expression. A 40-50% cleavage of p220 by transfected poliovirus 2A(pro) was observed ten hours post infection and cleavage was almost complete (80-90%) 20-25 hours post infection with vaccinia virus. Profound inhibition of vaccinia virus protein synthesis was detectable ten hours post infection and was maximal 20-25 hours post infection. This inhibition resulted from neither a blockade of transcription of vaccinia virus nor a lack of translatability of the mRNAs present in cells that synthesize poliovirus 2A(pro). Addition of ara-C inhibited the replication of vaccinia virus and allowed the continued synthesis of cellular proteins. Under these conditions, 2A(pro) is expressed and blocks cellular translation. Finally, p220 cleavage by 2A(pro) did not inhibit the translation of a mRNA encoding poliovirus protein 2C, as directed by the 5' leader sequences of encephalomiocarditis virus. Therefore, these findings show a correlation between p220 cleavage and inhibition of translation from newly made mRNAs. Our results are discussed in the light of present knowledge of p220 function, and new approaches are considered that might provide further insights into the function(s) of initiation factor eIF-4F.

  20. Patient-Reported Outcome (PRO) Assessment in Clinical Trials: A Systematic Review of Guidance for Trial Protocol Writers

    PubMed Central

    Calvert, Melanie; Kyte, Derek; Duffy, Helen; Gheorghe, Adrian; Mercieca-Bebber, Rebecca; Ives, Jonathan; Draper, Heather; Brundage, Michael; Blazeby, Jane; King, Madeleine

    2014-01-01

    Background Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers. Methods and Findings We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency. Conclusions PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information

  1. Plasma NT-proBNP and white matter hyperintensities in type 2 diabetic patients

    PubMed Central

    2012-01-01

    Abstract Elevated plasma N-terminal (NT)-proBNP from the heart as well as white matter hyperintensities (WMH) in the brain predict cardiovascular (CV) mortality in the general population. The cause of poor prognosis associated with elevated P-NT-proBNP is not known but WMH precede strokes in high risk populations. We assessed the association between P-NT-proBNP and WMH or brain atrophy measured with magnetic resonance imaging (MRI) in type 2 diabetic patients, and age-matched controls. Methods and results We measured P-NT-proBNP(ng/l) in 20 diabetic patients without prior stroke but with(n = 10) or without(n = 10) asymptomatic coronary artery disease(CAD) in order to include patients with a wide-ranging CV risk profile. All patients and 26 controls had a 3D MRI and brain volumes(ml) with WMH and brain parenchymal fraction(BPF), an indicator of brain atrophy, were determined. P-NT-proBNP was associated with WMH in linear regression analysis adjusted for CV risk factors(r = 0.94, p = 0.001) and with BPF in univariate analysis(r = 0.57, p = 0.009). Patients divided into groups of increased P-NT-proBNP levels were paralleled with increased WMH volumes(geometric mean[SD];(2.86[5.11] ml and 0.76[2.49] ml compared to patients with low P-NT-proBNP 0.20[2.28] ml, p = 0.003)) and also when adjusted for age, sex and presence of CAD(p = 0.017). The association was strengthened by CV risk factors and we did not find a common heart or brain specific driver of both P-NT-proBNP and WMH. Patients and particular patients with CAD had higher WMH, however no longer after adjustment for age and sex. Conclusion P-NT-proBNP was associated with WMH in type 2 diabetic patients, suggesting a linkage between heart and brain disease. PMID:23033840

  2. Validation of the VERITAS-Pro treatment adherence scale in a Spanish sample population with hemophilia

    PubMed Central

    Cuesta-Barriuso, Rubén; Torres-Ortuño, Ana; Galindo-Piñana, Pilar; Nieto-Munuera, Joaquín; Duncan, Natalie; López-Pina, José Antonio

    2017-01-01

    Purpose We aimed to conduct a validation in Spanish of the Validated Hemophilia Regimen Treatment Adherence Scale – Prophylaxis (VERITAS-Pro) questionnaire for use in patients with hemophilia under prophylactic treatment. Patients and methods The VERITAS-Pro scale was adapted through a process of back translation from English to Spanish. A bilingual native Spanish translator translated the scale from English to Spanish. Subsequently, a bilingual native English translator translated the scale from Spanish to English. The disagreements were resolved by agreement between the research team and translators. Seventy-three patients with hemophilia, aged 13–62 years, were enrolled in the study. The scale was applied twice (2 months apart) to evaluate the test–retest reliability. Results Internal consistency reliability was lower on the Spanish VERITAS-Pro than on the English version. Test–retest reliability was high, ranging from 0.83 to 0.92. No significant differences (P>0.05) were found between test and retest scores in subscales of VERITAS-Pro. In general, Spanish patients showed higher rates of nonadherence than American patients in all subscales. Conclusion The Spanish version of the VERITAS-Pro has high levels of consistency and empirical validity. This scale can be administered to assess the degree of adherence of prophylactic treatment in patients with hemophilia.

  3. Rapid diagnosis of MDR and XDR tuberculosis with the MeltPro TB assay in China.

    PubMed

    Pang, Yu; Dong, Haiyan; Tan, Yaoju; Deng, Yunfeng; Cai, Xingshan; Jing, Hui; Xia, Hui; Li, Qiang; Ou, Xichao; Su, Biyi; Li, Xuezheng; Zhang, Zhiying; Li, Junchen; Zhang, Jiankang; Huan, Shitong; Zhao, Yanlin

    2016-05-06

    New diagnostic methods have provided a promising solution for rapid and reliable detection of drug-resistant TB strains. The aim of this study was to evaluate the performance of the MeltPro TB assay in identifying multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) patients from sputum samples. The MeltPro TB assay was evaluated using sputum samples from 2057 smear-positive TB patients. Phenotypic Mycobacterial Growth Indicator Tube (MGIT) 960 drug susceptibility testing served as a reference standard. The sensitivity of the MeltPro TB assay was 94.2% for detecting resistance to rifampicin and 84.9% for detecting resistance to isoniazid. For second-line drugs, the assay showed a sensitivity of 83.3% for ofloxacin resistance, 75.0% for amikacin resistance, and 63.5% for kanamycin resistance. However, there was a significant difference for detecting kanamycin resistance between the two pilot sites in sensitivity, which was 53.2% in Guangdong and 81.5% in Shandong (P = 0.015). Overall, the MeltPro TB assay demonstrated good performance for the detection of MDR- and XDR-TB, with a sensitivity of 86.7% and 71.4%, respectively. The MeltPro TB assay is an excellent alternative for the detection of MDR- and XDR-TB cases in China, with high accuracy, short testing turn-around time, and low unit price compared with other tests.

  4. Total Phenolics, Total Anthocyanins, Antioxidant and Pro-oxidant Activity of Some Red Fruits Teas.

    PubMed

    Moldovan, Bianca; Hosu, Anamaria; David, Luminita; Cimpoiu, Claudia

    2016-01-01

    Fruits represent one of the main dietary sources of bioactive compounds. Due to their remarkable health benefits, many functional foods of fruit origin, including fruit teas, are present on the market and there is an increased interest regarding the investigation of their nutritional parameters and quality. The aims of our study were: 1) to determine the total phenolic content (TPC), total anthocyanins content (TAC), antioxidant activity (AA), the scavenging capacity (IC50), the pro-oxidant activity (Pro-ox) and Pro-Antidex of 12 commercially available red fruit teas, 2) to classify the analysed teas and 3) to evaluate the similarities between samples. The TPC was between 12.5 and 29.3 mg gallic acid equivalents (GAE)/g tea, the TAC varied between 2.6 and 5.6 mg cyanidin-3-glucoside (Cy-3-glu)/g tea and AA was in the range of 10.9-19.1 mg ascorbic acid equivalents (AAE)/g tea. The Pro-ox activity varied between 3.9 and 10.0 mg/mL tea extract and Pro-Antidex was between 3.3 and 7.3.

  5. Stoichiometry and heterogeneity of the pro-region chain in tetrameric human cathepsin C.

    PubMed

    Cigić, B; Krizaj, I; Kralj, B; Turk, V; Pain, R H

    1998-01-15

    The subunit structure and composition of mature human cathepsin C, an oligomeric cysteine proteinase, has been characterised in detail. The heavy chain, light chain and pro-region peptides are shown to be held together solely by non-covalent interactions, and to be present in equimolar ratio, suggesting an important structural role for the residual pro-region chain which is strongly bound to the enzyme. The mass of the light chain, as determined by mass spectrometry, combined with its N-terminal sequence, determines the position of cleavage from the heavy chain. Amino-acid sequencing has led to definition of the 13.5 kDa N-terminal part of the pro-region which remains in the mature enzyme, the C-terminal moiety of 10 kDa being cleaved out and lost from the pro-peptide on activation. The residual pro-region is heterogeneous, a proportion being intact and the remainder being cleaved at alternative positions 58 or 61, yielding two smaller peptides joined by disulphide bond. The proportion of cleaved form was found to vary with tissue and enzyme preparation but did not affect enzyme activity. The molecular masses of the constituent chains after deglycosylation lead to a protein mass of 158 kDa. All four potential glycosylation sites are glycosylated.

  6. Pro-socially shareable entertainment television programmes: a programming alternative in developing countries?

    PubMed

    Singhal, A; Svenkerud, P J

    1994-12-01

    Over the period 1975-82, the Mexican television network created and aired seven entertainment soap operas promoting educational-development themes like adult literacy, smaller family size norms, and an higher social status for women. These emissions earned high ratings in Mexico and in other Latin American countries where they were subsequently broadcast. Evidence suggests that many of the social objectives of the soaps were met. In light of such success, the authors investigated the potential of pro-socially shareable entertainment television programs in developing countries. These programs use entertaining media formats to carry pro-social messages to a wide, yet culturally-proximate audience group. Entertainment television genres such as melodramatic soap operas offer certain advantages for carrying pro-socially shareable messages to audiences. The possibility of using other television genres and media channels, however, also needs to be seriously considered. Pro-socially shareable entertainment programs do have their limitations and problems, with a certain degree of message dilution invariably accompanying the quest for shareability. Targeting specific problems in specific audience groups is difficult and the identity of a relatively small homogeneous group can be threatened in a larger culturally proximate group. The value-laden nature of pro-social content can also be problematic.

  7. SAS-Pro: simultaneous residue assignment and structure superposition for protein structure alignment.

    PubMed

    Shah, Shweta B; Sahinidis, Nikolaos V

    2012-01-01

    Protein structure alignment is the problem of determining an assignment between the amino-acid residues of two given proteins in a way that maximizes a measure of similarity between the two superimposed protein structures. By identifying geometric similarities, structure alignment algorithms provide critical insights into protein functional similarities. Existing structure alignment tools adopt a two-stage approach to structure alignment by decoupling and iterating between the assignment evaluation and structure superposition problems. We introduce a novel approach, SAS-Pro, which addresses the assignment evaluation and structure superposition simultaneously by formulating the alignment problem as a single bilevel optimization problem. The new formulation does not require the sequentiality constraints, thus generalizing the scope of the alignment methodology to include non-sequential protein alignments. We employ derivative-free optimization methodologies for searching for the global optimum of the highly nonlinear and non-differentiable RMSD function encountered in the proposed model. Alignments obtained with SAS-Pro have better RMSD values and larger lengths than those obtained from other alignment tools. For non-sequential alignment problems, SAS-Pro leads to alignments with high degree of similarity with known reference alignments. The source code of SAS-Pro is available for download at http://eudoxus.cheme.cmu.edu/saspro/SAS-Pro.html.

  8. Fragments of pro-peptide activate mature penicillin amidase of Alcaligenes faecalis.

    PubMed

    Kasche, Volker; Galunsky, Boris; Ignatova, Zoya

    2003-12-01

    Penicillin amidase from Alcaligenes faecalis is a recently identified N-terminal nucleophile hydrolase, which possesses the highest specificity constant (kcat/Km) for the hydrolysis of benzylpenicillin compared with penicillin amidases from other sources. Similar to the Escherichia coli penicillin amidase, the A. faecalis penicillin amidase is maturated in vivo from an inactive precursor into the catalytically active enzyme, containing one tightly bound Ca2+ ion, via a complex post-translational autocatalytic processing with a multi-step excision of a small internal pro-peptide. The function of the pro-region is so far unknown. In vitro addition of chemically synthesized fragments of the pro-peptide to purified mature A. faecalis penicillin amidase increased its specific activity up to 2.3-fold. Mutations were used to block various steps in the proteolytic processing of the pro-peptide to obtain stable mutants with covalently attached fragments of the pro-region to their A-chains. These extensions of the A-chain raised the activity up to 2.3-fold and increased the specificity constants for benzylpenicillin hydrolysis mainly by an increase of the turnover number (kcat).

  9. An uncleavable form of pro-scatter factor suppresses tumor growth and dissemination in mice.

    PubMed

    Mazzone, Massimiliano; Basilico, Cristina; Cavassa, Silvia; Pennacchietti, Selma; Risio, Mauro; Naldini, Luigi; Comoglio, Paolo M; Michieli, Paolo

    2004-11-01

    Scatter factor (SF), also known as hepatocyte growth factor, is ubiquitously present in the extracellular matrix of tissues in the form of an inactive precursor (pro-SF). In order to acquire biological activity, pro-SF must be cleaved by specific proteases present on the cell surface. The mature form of SF controls invasive cues in both physiological and pathological processes through activation of its receptor, the Met tyrosine kinase. By substituting a single amino acid in the proteolytic site, we engineered an unprocessable form of pro-SF (uncleavable SF). Using lentivirus vector technology, we achieved local or systemic delivery of uncleavable SF in mice. We provide evidence that (a) uncleavable SF inhibits both protease-mediated pro-SF conversion and active SF-induced Met activation; (b) local expression of uncleavable SF in tumors suppresses tumor growth, impairs tumor angiogenesis, and prevents metastatic dissemination; and (c) systemic expression of uncleavable SF dramatically inhibits the growth of transplanted tumors and abolishes the formation of spontaneous metastases without perturbing vital physiological functions. These data show that proteolytic activation of pro-SF is a limiting step in tumor progression, thus suggesting a new strategy for the treatment or prevention of the malignant conversion of neoplastic lesions.

  10. Complexes of mutants of Escherichia coli aminopeptidase P and the tripeptide substrate ValProLeu

    SciTech Connect

    Graham, Stephen C.; Guss, J. Mitchell

    2008-09-17

    Aminopeptidase P (APPro) is a manganese-containing enzyme that catalyses the hydrolysis of the N-terminal residue of a polypeptide if the second residue is proline. Structures of APPro mutants with reduced or negligible activity have been determined in complex with the tripeptide substrate ValProLeu. In the complex of Glu383Ala APPro with ValProLeu one of the two metal sites is only partly occupied, indicating an essential role for Glu383 in metal binding in the presence of substrate. His361Ala APPro clearly possesses residual activity as the ValProLeu substrate has been cleaved in the crystals; difference electron density consistent with bound ProLeu dipeptide and a disordered Val amino acid is present at the active site. Contrary to previous suggestions, the His243Ala mutant is capable of binding substrate. The structure of the His243Ala APPro complex with ValProLeu shows that the peptide interacts with one of the active-site metal atoms via its terminal amino group. The implications of these complexes for the roles of the respective residues in APPro catalysis are discussed.

  11. ProMMP-2: TIMP-1 complexes identified in plasma of healthy individuals.

    PubMed

    Zucker, Stanley; Schmidt, Cathleen E; Dufour, Antoine; Kaplan, Robert C; Park, Hyun I; Jiang, Weiping

    2009-01-01

    Activation of MMPs in tissues is an important component of tissue injury. Based on earlier reports that (latent) proMMP-2 is incapable of forming a complex with TIMP-1, we reasoned that the identification of MMP-2:TIMP-1 complexes in blood might serve as a surrogate marker ("smoking gun") of MMP-2 activation in tissues. Using specific antibodies, we developed a sensitive and specific assay to detect MMP-2:TIMP-1 complexes. We were perplexed to find that approximate 40% of plasma specimens from healthy individuals had detectable levels of the MMP-2:TIMP-1 complexes. Employing recombinant TIMP-1 bound Sepharose beads and Western blots, we demonstrated binding between recombinant proMMP-2 and TIMP-1 proteins. Recombinant MMP-2 lacking the catalytic domain also bound to TIMP-1 coated beads. These data are consistent with TIMP-1 binding to the hemopexin or hinge domain of proMMP-2. The explanation for the presence of plasma proMMP-2:TIMP-1 complexes in selected healthy individuals remains to be determined. In contrast to our immunoassay and bead-binding experiments, proMMP-2 failed to bind to immobilized TIMP-1 employing surface plasmon resonance technology. Additional studies are needed to clarify these contrasting results.

  12. Does Pro12Ala Polymorphism Enhance the Physiological Role of PPARγ2?

    PubMed Central

    Pereira, A. C.; Oliveira, R.; Castro, A. C.; Fernandes, R.

    2013-01-01

    Obesity and type 2 diabetes mellitus (T2D) are two major public health problems that have motivated the scientific community to investigate the high contribution of genetic factors to these disorders. The peroxisome proliferator activated by gamma 2 (PPARγ2) plays an important role in the lipid metabolism. Since PPARγ2 is expressed mainly in adipose tissue, a moderate reduction of its activity influences the sensitivity to insulin, diabetes, and other metabolic parameters. The present study aims to contribute to the elucidation of the impact of the Pro12Ala polymorphism associated with T2D and obesity through a meta-analysis study of the literature that included approximately 11500 individuals, from which 3870 were obese and 7625 were diabetic. Statistical evidence supports protective effect in T2D of polymorphism Pro12Ala of PPARγ2 (OR = 0.702 with 95% CI: 0.622; 0.791, P < 0.01). Conversely the same polymorphism Pro12Ala of PPARγ2 seems to favor obesity since 1.196 more chance than nonobese was found (OR = 1.196 with 95% CI: 1.009; 1.417, P < 0.004). Our results suggest that Pro12Ala polymorphism enhances both adipogenic and antidiabetogenic physiological role of PPARγ. Does Pro12Ala polymorphism represent an evolutionary step towards the stabilization of the molecular function of PPARγ transcription factor signaling pathway? PMID:23983677

  13. Depot-Based Delivery Systems for Pro-Angiogenic Peptides: A Review

    PubMed Central

    Van Hove, Amy H.; Benoit, Danielle S. W.

    2015-01-01

    Insufficient vascularization currently limits the size and complexity for all tissue engineering approaches. Additionally, increasing or re-initiating blood flow is the first step toward restoration of ischemic tissue homeostasis. However, no FDA-approved pro-angiogenic treatments exist, despite the many pre-clinical approaches that have been developed. The relatively small size of peptides gives advantages over protein-based treatments, specifically with respect to synthesis and stability. While many pro-angiogenic peptides have been identified and shown promising results in vitro and in vivo, the majority of biomaterials developed for pro-angiogenic drug delivery focus on protein delivery. This narrow focus limits pro-angiogenic therapeutics as peptides, similar to proteins, suffer from poor pharmacokinetics in vivo, necessitating the development of controlled release systems. This review discusses pro-angiogenic peptides and the biomaterials delivery systems that have been developed, or that could easily be adapted for peptide delivery, with a particular focus on depot-based delivery systems. PMID:26236708

  14. Pro-oxidant effects of phenothiazine and phenoxazine on erythrocytes in the presence of peroxyl radical.

    PubMed

    Li, Guo-Xiang; Tang, You-Zhi; Liu, Zai-Qun

    2009-01-01

    Phenothiazine (PtzNH) and phenoxazine (PozNH) can protect human erythrocytes against hemolysis induced by 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), a peroxyl radical supplier. However, an antioxidant may be a pro-oxidant to accelerate the oxidation in the presence of radicals. The aim of this work is to assess whether PtzNH and PozNH have the potential to be pro-oxidants in AAPH-induced hemolysis of human erythrocytes. It has been found that high concentrations of PtzNH and PozNH employed were able to initiate hemolysis even in the absence of AAPH. In the presence of AAPH, the period of PtzNH and PozNH to lag hemolysis (t(lag)) decreased with the increase in the concentrations of PtzNH and PozNH, implicating that high concentration of PtzNH and PozNH accelerated hemolysis. So, PtzNH and PozNH played pro-oxidants' role in this case. Furthermore, high concentrations of AAPH employed made the pro-oxidant effect of PtzNH more remarkable. On the contrary, PozNH played a pro-oxidant role if only low concentration of AAPH was employed.

  15. NIa-pro of Papaya ringspot virus interacts with papaya methionine sulfoxide reductase B1.

    PubMed

    Gao, Le; Shen, Wentao; Yan, Pu; Tuo, Decai; Li, Xiaoying; Zhou, Peng

    2012-12-05

    A chloroplast-localized papaya methionine sulfoxide reductase B1 (PaMsrB1) interacting with Papaya ringspot virus (PRSV) NIa-Pro was identified using a Sos recruitment two-hybrid system (SRS). SRS analysis of several deletion mutants of PRSV NIa-Pro and PaMsrB1 demonstrated that the C-terminal (residues 133-239) fragment of PRSV NIa-Pro and residues 112-175 of PaMsrB1 were necessary for this interaction between PRSV NIa-Pro and PaMsrB1. MsrB1 can repair Met-oxidized proteins damaged by reactive oxygen species (ROS). We confirmed that PRSV infection leads to ROS accumulation and a slight upregulation of level PaMsrB1 mRNA in papaya. This interaction between PaMsrB1 with PRSV NIa-Pro may disturb the import of PaMsrB1 into the chloroplasts. These results suggest that this specific interaction could interfere with PaMsrB1 into the chloroplasts to scavenge ROS caused by PRSV infection. This may be a novel mechanism of PRSV towards the host defense.

  16. Effects of pre- and pro-sequence of thaumatin on the secretion by Pichia pastoris.

    PubMed

    Ide, Nobuyuki; Masuda, Tetsuya; Kitabatake, Naofumi

    2007-11-23

    Thaumatin is a 22-kDa sweet-tasting protein containing eight disulfide bonds. When thaumatin is expressed in Pichia pastoris using the thaumatin cDNA fused with both the alpha-factor signal sequence and the Kex2 protease cleavage site from Saccharomyces cerevisiae, the N-terminal sequence of the secreted thaumatin molecule is not processed correctly. To examine the role of the thaumatin cDNA-encoded N-terminal pre-sequence and C-terminal pro-sequence on the processing of thaumatin and efficiency of thaumatin production in P. pastoris, four expression plasmids with different pre-sequence and pro-sequence were constructed and transformed into P. pastoris. The transformants containing pre-thaumatin gene that has the native plant signal, secreted thaumatin molecules in the medium. The N-terminal amino acid sequence of the secreted thaumatin molecule was processed correctly. The production yield of thaumatin was not affected by the C-terminal pro-sequence, and the pro-sequence was not processed in P. pastoris, indicating that pro-sequence is not necessary for thaumatin synthesis.

  17. Detection of endogenous and food-derived collagen dipeptide prolylhydroxyproline (Pro-Hyp) in allergic contact dermatitis-affected mouse ear.

    PubMed

    Kusubata, Masashi; Koyama, Yoh-Ichi; Tometsuka, Chisa; Shigemura, Yasutaka; Sato, Kenji

    2015-01-01

    Generation of collagen dipeptides and deposition of orally administered prolylhydroxyproline (Pro-Hyp) in local inflammatory sites were examined in mice with hapten (2,4-dinitrofluorobenzene)-induced dermatitis in the ear. Pro-Hyp content in the hapten-treated ear was significantly higher in the chronic phase of contact dermatitis than the vehicle control. In contrast, hydroxyprolylglycine contents remained at lower levels in all cases compared to Pro-Hyp. Four hours after the ingestion of [(13)C5,(15)N]Pro and [(13)C5,(15)N]Pro-Hyp, labeled-Pro-Hyp and Pro, respectively, appeared only in the ear with dermatitis. Thus, Pro-Hyp is generated and degraded as part of the rapid synthesis and degradation of collagen in the ear with dermatitis. In addition to the endogenously generated Pro-Hyp, the orally administered Pro-Hyp was deposited in the ears.

  18. Shaping ability of ProTaper NEXT, ProTaper Universal and iRace files in simulated S-shaped canals.

    PubMed

    Hiran-us, Sirawut; Pimkhaokham, Somsinee; Sawasdichai, Jirapat; Ebihara, Arata; Suda, Hideaki

    2016-04-01

    The aim of this study was to determine the shaping ability of three nickel-titanium endodontic file systems by comparing three parameters: canal deviation, apical foramen position and instrumentation time. A glide path was established in 30 simulated S-shaped canal blocks that were randomly assigned into three groups (n = 10): ProTaper Universal, ProTaper NEXT and iRace. Each group was instrumented per its manufacturer's directions. Pre- and postoperative images were superimposed to determine any canal deviation or change in apical foramen position. The instrumentation times were recorded. The iRace system resulted in the least mean canal deviation. The apical foramen position was least shifted by the iRace system. The iRace system also required the least instrumentation time. The iRace system demonstrated the most favourable shaping ability in all three parameters.

  19. Suppression of pro-inflammatory and pro-survival biomarkers in oral cancer patients consuming a black raspberry phytochemical-rich troche

    PubMed Central

    Knobloch, Thomas J.; Uhrig, Lana K.; Pearl, Dennis K.; Casto, Bruce C.; Warner, Blake M.; Clinton, Steven K.; Sardo-Molmenti, Christine L.; Ferguson, Jeanette M.; Daly, Brett T.; Riedl, Kenneth; Schwartz, Steven J.; Vodovotz, Yael; Buchta, Anthony J.; Schuller, David E.; Ozer, Enver; Agrawal, Amit; Weghorst, Christopher M.

    2016-01-01

    Black raspberries (BRBs) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food-based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce pro-inflammatory and anti-apoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCCs) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and non-involved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of pro-survival genes (AURKA, BIRC5, EGFR) and pro-inflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated Grade 3–4 toxicities or adverse events and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark anti-apoptotic and pro-inflammatory molecular biomarkers were over-expressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. Since these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention. PMID:26701664

  20. Gonadal Identity in the Absence of Pro-Testis Factor SOX9 and Pro-Ovary Factor Beta-Catenin in Mice1

    PubMed Central

    Nicol, Barbara; Yao, Humphrey H.-C.

    2015-01-01

    Sex-reversal cases in humans and genetic models in mice have revealed that the fate of the bipotential gonad hinges upon the balance between pro-testis SOX9 and pro-ovary beta-catenin pathways. Our central query was: if SOX9 and beta-catenin define the gonad's identity, then what do the gonads become when both factors are absent? To answer this question, we developed mouse models that lack either Sox9, beta-catenin, or both in the somatic cells of the fetal gonads and examined the morphological outcomes and transcriptome profiles. In the absence of Sox9 and beta-catenin, both XX and XY gonads progressively lean toward the testis fate, indicating that expression of certain pro-testis genes requires the repression of the beta-catenin pathway, rather than a direct activation by SOX9. We also observed that XY double knockout gonads were more masculinized than their XX counterpart. To identify the genes responsible for the initial events of masculinization and to determine how the genetic context (XX vs. XY) affects this process, we compared the transcriptomes of Sox9/beta-catenin mutant gonads and found that early molecular changes underlying the XY-specific masculinization involve the expression of Sry and 21 SRY direct target genes, such as Sox8 and Cyp26b1. These results imply that when both Sox9 and beta-catenin are absent, Sry is capable of activating other pro-testis genes and drive testis differentiation. Our findings not only provide insight into the mechanism of sex determination, but also identify candidate genes that are potentially involved in disorders of sex development. PMID:26108792

  1. Influence of the body mass and visceral adiposity on glucose metabolism in obese women with Pro12Pro genotype in PPARgamma2 gene.

    PubMed

    Kaippert, Vanessa Chaia; Uehara, Sofia Kimi; D'Andrea, Carla Lima; Nogueira, Juliana; do Lago, Márcia Fófano; Cunha Oliveira dos Santos Lopes, Marcelly; Oliveira, Edna Maria Morais; Rosado, Eliane Lopes

    2013-01-01

    Introducción: El metabolismo de la glucosa puede estar alterado en la obesidad y el genotipo del gene PPAR 2 puede influir en este variable. Objetivo: Evaluar la influencia de la masa corporal (MC) y de la adiposidad visceral (AV) en el metabolismo de la glucosa en mujeres con obesidad de grado 3 con el genotipo Pro12Pro. Métodos: Se seleccionaron 25 mujeres con obesidad de grado 3. Se formaron grupos de acuerdo con el índice de masa corporal (IMC) [G1: 40-45 kg/m2 (n = 17), G2: > 45 kg/m2 (n = 8)]. Fueron hechas evaluaciones antropométricas, de la glucemia y de la insulinemia (en ayunas, 60 y 120 minutos después de la comida rica en ácidos grasos poliinsaturados). La resistencia a la insulina (RI) y sensibilidad a la insulina (SI) fueron evaluados por el HOMA-IR y QUICKI, respectivamente. Resultados: G2 tuvieron mayor índice de masa corporal y circunferencia de la cintura, en comparación con G1, peor glucemia en ayunas, baja SI y alta RI. La glucosa postprandial fue normal, pero hubo un pico de insulina más alto una hora después de la comida en G2. Conclusión: El aumento de la MC y de la AV se asociaron con peor metabolismo de la glucosa lo que sugiere diferencias metabólicas entre obesos de grado 3 con el genotipo Pro12Pro.

  2. Exposure to 900 MHz electromagnetic field induces an unbalance between pro-apoptotic and pro-survival signals in T-lymphoblastoid leukemia CCRF-CEM cells.

    PubMed

    Marinelli, F; La Sala, D; Cicciotti, G; Cattini, L; Trimarchi, C; Putti, S; Zamparelli, A; Giuliani, L; Tomassetti, G; Cinti, Caterina

    2004-02-01

    It has been recently established that low-frequency electromagnetic field (EMFs) exposure induces biological changes and could be associated with increased incidence of cancer, while the issue remains unresolved as to whether high-frequency EMFs can have hazardous effect on health. Epidemiological studies on association between childhood cancers, particularly leukemia and brain cancer, and exposure to low- and high-frequency EMF suggested an etiological role of EMFs in inducing adverse health effects. To investigate whether exposure to high-frequency EMFs could affect in vitro cell survival, we cultured acute T-lymphoblastoid leukemia cells (CCRF-CEM) in the presence of unmodulated 900 MHz EMF, generated by a transverse electromagnetic (TEM) cell, at various exposure times. We evaluated the effects of high-frequency EMF on cell growth rate and apoptosis induction, by cell viability (MTT) test, FACS analysis and DNA ladder, and we investigated pro-apoptotic and pro-survival signaling pathways possibly involved as a function of exposure time by Western blot analysis. At short exposure times (2-12 h), unmodulated 900 MHz EMF induced DNA breaks and early activation of both p53-dependent and -independent apoptotic pathways while longer continuous exposure (24-48 h) determined silencing of pro-apoptotic signals and activation of genes involved in both intracellular (Bcl-2) and extracellular (Ras and Akt1) pro-survival signaling. Overall our results indicate that exposure to 900 MHz continuous wave, after inducing an early self-defense response triggered by DNA damage, could confer to the survivor CCRF-CEM cells a further advantage to survive and proliferate.

  3. Gonadal Identity in the Absence of Pro-Testis Factor SOX9 and Pro-Ovary Factor Beta-Catenin in Mice.

    PubMed

    Nicol, Barbara; Yao, Humphrey H-C

    2015-08-01

    Sex-reversal cases in humans and genetic models in mice have revealed that the fate of the bipotential gonad hinges upon the balance between pro-testis SOX9 and pro-ovary beta-catenin pathways. Our central query was: if SOX9 and beta-catenin define the gonad's identity, then what do the gonads become when both factors are absent? To answer this question, we developed mouse models that lack either Sox9, beta-catenin, or both in the somatic cells of the fetal gonads and examined the morphological outcomes and transcriptome profiles. In the absence of Sox9 and beta-catenin, both XX and XY gonads progressively lean toward the testis fate, indicating that expression of certain pro-testis genes requires the repression of the beta-catenin pathway, rather than a direct activation by SOX9. We also observed that XY double knockout gonads were more masculinized than their XX counterpart. To identify the genes responsible for the initial events of masculinization and to determine how the genetic context (XX vs. XY) affects this process, we compared the transcriptomes of Sox9/beta-catenin mutant gonads and found that early molecular changes underlying the XY-specific masculinization involve the expression of Sry and 21 SRY direct target genes, such as Sox8 and Cyp26b1. These results imply that when both Sox9 and beta-catenin are absent, Sry is capable of activating other pro-testis genes and drive testis differentiation. Our findings not only provide insight into the mechanism of sex determination, but also identify candidate genes that are potentially involved in disorders of sex development.

  4. An injury prevention strategy for teen restaurant workers. Washington State's ProSafety project.

    PubMed

    Ward, Julie A; de Castro, A B; Tsai, Jenny Hsin-Chun; Linker, Darren; Hildahl, Lyle; Miller, Mary E

    2010-02-01

    High levels of youth employment, workplace hazards, and characteristics unique to adolescents contribute to a relatively high incidence of injuries among teens in the restaurant industry. This article discusses the ProSafety model of injury prevention among teen restaurant workers. Through integration with an existing career and technical education program, the ProSafety project seeks to prevent occupational injuries among the teen worker population through classroom safety education and internship skills reinforcement. ProSafety is the product of an innovative collaboration with occupational health nurses, business professionals, educators, and government. Its approach is derived from Social Cognitive Theory, is consistent with key values and strategies of occupational health nurses, and provides lessons for practitioners seeking to reduce occupational injuries in food service or among other populations of adolescent workers.

  5. Pro-Nuclear Environmentalism: Should We Learn to Stop Worrying and Love Nuclear Energy?

    PubMed

    van Munster, Rens; Sylvest, Casper

    2015-10-01

    In light of repeated failures to reach political agreement on effective policies to combat climate change, pro-nuclear environmentalists have set out to reverse the traditionally anti-nuclear inclinations of environmentalists. This essay examines the ideological commitments and assumptions of pro-nuclear environmentalism by performing a critical, historical analysis of the nuclear-environment nexus through the prism of documentary film. We focus on the work and career of documentary filmmaker Rob Stone, whose most recent production, Pandora's Promise (PP) (2013), has emerged as a central statement of this creed. PP actively forges a new political imaginary that replaces the apocalyptic image of nuclear fallout with that of catastrophic climate change. In terms of its rhetorical and visual strategies, however, PP also reveals that pro-nuclear environmentalist arguments have a long lineage. A close study of such continuities reveals a number of political implications that call for reflection as well as caution.

  6. Pain management improves care and revenue: an interview with ProCare Systems.

    PubMed

    Davis, F N; Walsh, C

    2000-01-01

    As provider and managed care organizations continue to look for better ways to control costs and improve patient outcomes, disease management programs are getting an increasing share of their attention. One often-over-looked area with significant potential to improve outcomes, reduce costs, and enhance revenues is pain management. It has been estimated that at least 40 percent of senior citizens suffer from chronic pain, and as the population ages, the number of chronic pain sufferers will only increase. Pain management companies have been forming to meet the current and future demand for comprehensive pain management programs. One such company is ProCare Systems, a single-specialty physician practice management company based in Grand Rapids, Michigan. HFM spoke with Fred N. Davis, MD, president and cofounder of ProCare Systems, and Cyndy Walsh, ProCare System's CEO, about pain management programs and the patient care and financial impact they can effect.

  7. Radioimmunoassay of Pro-. gamma. -melanotropin, the amino-terminal fragment of proopiolipomelanocortin. [Swine

    SciTech Connect

    Ekman, R.; Hakanson, R.; Larsson, I.; Sundler, F.; Thorell, J.I.

    1982-08-01

    A RIA has been developed for natural porcine pro-..gamma..-MSH, the 103-amino acid peptide that represents the amino-terminal part of proopiolipomelanocortin. Rabbits were immunized with the purified peptide polymerized with glutaraldehyde. The antiserum is directed against the amino-terminial end of the antigen and does not cross-react with corticotropin, ..beta..-lipotropin, ..beta..-endorphin, ..gamma../sub 3/MSH, or ..gamma../sub 2/MSH. The minimum detectable concentration is 0.15 ng/ml standard pro-..gamma..MSH (15 pg/tube). Pro-..gamma..MSH-like immunoreactivity was detected in plasma and extracts of the hypothalamus and pituitary of pigs. Gel chromatography of these extracts revealed at least three immunoreactive peaks in the anterior and neurointermediate lobes of the pituitary, wheras two immunoreactive peaks were found in extracts of the hypothalalmus. (Endocrinology 111:578,1982)

  8. The enhanced Software Life Cyle Support Environment (ProSLCSE): Automation for enterprise and process modeling

    NASA Technical Reports Server (NTRS)

    Milligan, James R.; Dutton, James E.

    1993-01-01

    In this paper, we have introduced a comprehensive method for enterprise modeling that addresses the three important aspects of how an organization goes about its business. FirstEP includes infrastructure modeling, information modeling, and process modeling notations that are intended to be easy to learn and use. The notations stress the use of straightforward visual languages that are intuitive, syntactically simple, and semantically rich. ProSLCSE will be developed with automated tools and services to facilitate enterprise modeling and process enactment. In the spirit of FirstEP, ProSLCSE tools will also be seductively easy to use. Achieving fully managed, optimized software development and support processes will be long and arduous for most software organizations, and many serious problems will have to be solved along the way. ProSLCSE will provide the ability to document, communicate, and modify existing processes, which is the necessary first step.

  9. The Role of Social Influences on Pro-Environment Behaviors in the San Diego Region.

    PubMed

    Estrada, Mica; Schultz, P Wesley; Silva-Send, Nilmini; Boudrias, Michel A

    2017-03-06

    From a social psychological perspective, addressing the threats of climate change involves not only education, which imparts objective facts upon a passive individual, but also a socializing process. The Tripartite Integration Model of Social Influence (TIMSI) provides a theoretical framework that connects acquiring climate change knowledge with integration into a community, which results in greater engagement in climate friendly behaviors. Survey data were collected from 1000 residents in San Diego County. Measures included (a) knowledge about climate change; (b) self-efficacy, what pro-environmental actions they felt they could do; (c) identity, to what extent they identified as part of a community that is concerned about climate change; (d) values, endorsement of values of the community that is concerned about climate change; and (e) pro-environmental behavior, engagement in conservation behaviors. Results indicated that self-efficacy and values mediated the relationship between knowledge and pro-environmental behavior.

  10. Propulsion Diagnostic Method Evaluation Strategy (ProDiMES) User's Guide

    NASA Technical Reports Server (NTRS)

    Simon, Donald L.

    2010-01-01

    This report is a User's Guide for the Propulsion Diagnostic Method Evaluation Strategy (ProDiMES). ProDiMES is a standard benchmarking problem and a set of evaluation metrics to enable the comparison of candidate aircraft engine gas path diagnostic methods. This Matlab (The Mathworks, Inc.) based software tool enables users to independently develop and evaluate diagnostic methods. Additionally, a set of blind test case data is also distributed as part of the software. This will enable the side-by-side comparison of diagnostic approaches developed by multiple users. The Users Guide describes the various components of ProDiMES, and provides instructions for the installation and operation of the tool.

  11. The Resolution Code of Acute Inflammation: Novel Pro-Resolving Lipid Mediators in Resolution

    PubMed Central

    Serhan, Charles N.; Chiang, Nan; Dalli, Jesmond

    2015-01-01

    Studies into the mechanisms in resolution of self-limited inflammation and acute reperfusion injury have uncovered a new genus of pro-resolving lipid mediators coined specialized pro-resolving mediators (SPM) including lipoxins, resolvins, protectins and maresins that are each temporally produced by resolving-exudates with distinct actions for return to homeostasis. SPM evoke potent anti-inflammatory and novel pro-resolving mechanisms as well as enhance microbial clearance. While born in inflammation-resolution, SPM are conserved structures with functions discovered in microbial defense, pain, organ protection and tissue regeneration, wound healing, cancer, reproduction, and neurobiology-cognition. This review covers these SPM mechanisms and other new omega-3 PUFA pathways that open their path for functions in resolution physiology. PMID:25857211

  12. NT-proBNP in Children With Left to Right Shunt and Dilated Cardiomyopathy

    PubMed Central

    Koura, Hala Mahmoud; Abdalla, Neamat M.; Hamed Ibrahim, Mona; Abo Hashish, Maha M. A.; Zaki, Sherif Mohamed

    2016-01-01

    Background B-type natriuretic peptide (BNP) levels are elevated in children with congenital heart disease involving a left-to-right shunt (LRS) and are also raised in dilated cardiomyopathy (DCM). As far as we know, there are few reports in the literature comparing the change of the NT-proBNP in LRS and DCM especially in the pediatric age group. Objectives The aim of the study was to compare the changes of the NT-proBNP in pediatric patients with LRS and DCM. Correlation between the levels of NT-proBNP and the echocardiographic parameters in both groups was determined. Patients and Methods A total of 30 children (13 males and 17 females) participated in the study. There were 11/30 (36.7%) DCM and 19/30 (63.3%) LRS. The control group consisted of 44 healthy infants and children. Manifestations of heart failure (decompensation) were recorded. The NT-pro BNP levels were measured. The following Echo parameters were assessed: systolic function (ejection fraction and fraction shortening), pulmonary to systemic flow (Qp/Qs) in LRS, pulmonary flow and pulmonary artery pressure (SPAP) and LV diastolic function (E-wave, A-wave, E/A ratio and deceleration time). Results Clinically 17/30 (56.7%) (11 of the LRS and 5 of the DCM) were decompensated. Significant shunt was present in 15/19 (78.9%) in LRS. Systolic dysfunction was presented in 5/30 (16.7%) cases (4 patients were DCM and one case was LRS). Two types of diastolic dysfunction, impaired relaxation in 5/22 (22.7%) patients and restrictive-like filling pattern in 5/16 (31.2 %) were observed. The NT-Pro BNP level was significantly elevated 11 and 16 times in the LRS and DCM groups respectively. Negative significant correlations were observed between the levels of NT-ProBNP and the following echo variables; EDD, LAD, E wave and E/A ratio in the LRS patients. Positive significant correlations were observed between the levels of NT-ProBNP and the following echo variables; PAP and QP/QS in the LRS. Both the PAP and QP/QS were

  13. In vitro cellular responses to silicon carbide particles manufactured through the Acheson process: impact of physico-chemical features on pro-inflammatory and pro-oxidative effects.

    PubMed

    Boudard, Delphine; Forest, Valérie; Pourchez, Jérémie; Boumahdi, Najih; Tomatis, Maura; Fubini, Bice; Guilhot, Bernard; Cottier, Michèle; Grosseau, Philippe

    2014-08-01

    Silicon carbide (SiC) an industrial-scale product manufactured through the Acheson process, is largely employed in various applications. Its toxicity has been poorly investigated. Our study aims at characterizing the physico-chemical features and the in vitro impact on biological activity of five manufactured SiC powders: two coarse powders (SiC C1/C2), two fine powders (SiC F1/F2) and a powder rich in iron impurities (SiC I). RAW 264.7 macrophages were exposed to the different SiC particles and the cellular responses were evaluated. Contrary to what happens with silica, no SiC cytotoxicity was observed but pro-oxidative and pro-inflammatory responses of variable intensity were evidenced. Oxidative stress (H₂O₂ production) appeared related to SiC particle size, while iron level regulated pro-inflammatory response (TNFα production). To investigate the impact of surface reactivity on the biological responses, coarse SiC C1 and fine SiC F1 powders were submitted to different thermal treatments (650-1400 °C) in order to alter the oxidation state of the particle surface. At 1400 °C a decrease in TNFα production and an increase in HO·, COO(·-) radicals production were observed in correlation with the formation of a surface layer of crystalline silica. Finally, a strong correlation was observed between surface oxidation state and in vitro toxicity.

  14. Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients.

    PubMed

    Bocchia, Monica; Galimberti, Sara; Aprile, Lara; Sicuranza, Anna; Gozzini, Antonella; Santilli, Francesca; Abruzzese, Elisabetta; Baratè, Claudia; Scappini, Barbara; Fontanelli, Giulia; Trawinska, Monika Malgorzata; Defina, Marzia; Gozzetti, Alessandro; Bosi, Alberto; Petrini, Mario; Puccetti, Luca

    2016-11-01

    Several reports described an increased risk of cardiovascular (CV) events, mainly atherothrombotic, in Chronic Myeloid Leukemia (CML) patients receiving nilotinib. However, the underlying mechanism remains elusive. The objective of the current cross-sectional retrospective study is to address a potential correlation between Tyrosine Kinase Inhibitors (TKIs) treatment and CV events. One hundred and 10 chronic phase CML patients in complete cytogenetic response during nilotinib or imatinib, were screened for CV events and evaluated for: traditional CV risk factors, pro/anti-inflammatory biochemical parameters and detrimental ORL1 gene polymorphisms (encoding for altered oxidized LDL receptor-1). Multivariate analysis of the whole cohort showed that the cluster of co-existing nilotinib treatment, dyslipidaemia and G allele of LOX-1 polymorphism was the only significant finding associated with CV events. Furthermore, multivariate analysis according to TKI treatment confirmed IVS4-14 G/G LOX-1 polymorphism as the strongest predictive factor for a higher incidence of CV events in nilotinib patients. Biochemical assessment showed an unbalanced pro-inflammatory cytokines network in nilotinib vs imatinib patients. Surprisingly, pre-existing traditional CV risk factors were not always predictive of CV events. We believe that in nilotinib patients an induced "inflammatory/oxidative status", together with a genetic pro-atherothrombotic predisposition, may favour the increased incidence of CV events. Prospective studies focused on this issue are ongoing.

  15. Harmonizing international trials of early goal-directed resuscitation for severe sepsis and septic shock: methodology of ProCESS, ARISE, and ProMISe

    PubMed Central

    2013-01-01

    Purpose To describe and compare the design of three independent but collaborating multicenter trials of early goal-directed resuscitation for severe sepsis and septic shock. Methods We reviewed the three current trials, one each in the USA (ProCESS: protocolized care for early septic shock), Australasia (ARISE: Australasian resuscitation in sepsis evaluation), and the UK (ProMISe: protocolised management in sepsis). We used the 2010 CONSORT (consolidated standards of reporting trials) statement and the 2008 CONSORT extension for trials assessing non-pharmacologic treatments to describe and compare the underlying rationale, commonalities, and differences. Results All three trials conform to CONSORT guidelines, address the same fundamental questions, and share key design elements. Each trial is a patient-level, equal-randomized, parallel-group superiority trial that seeks to enroll emergency department patients with inclusion criteria that are consistent with the original early goal-directed therapy (EGDT) trial (suspected or confirmed infection, two or more systemic inflammatory response syndrome criteria, and refractory hypotension or elevated lactate), is powered to detect a 6–8 % absolute mortality reduction (hospital or 90-day), and uses trained teams to deliver EGDT. Design differences appear to primarily be driven by between-country variation in health care context. The main difference between the trials is the inclusion of a third, alternative resuscitation strategy arm in ProCESS. Conclusions Harmonization of study design and methods between severe sepsis trials is feasible and may facilitate pooling of data on completion of the trials. PMID:23958738

  16. Utilizing Pro-bono Commercial Assets for Marine Mammal Surveys in High Naval Activity Area in Hawaiian Waters

    DTIC Science & Technology

    2013-11-12

    3. DATES COVERED (From - To) 01/01/12-06/30/13 4. TITLE AND SUBTITLE Utilizing Pro- bono Commercial Assets for Marine Mammal Surveys In High Naval...and use our acoustic instruments to collect data, on a pro- bono basis. The goal was to establish a robust database of information that currently...for public release; distribution is unlimited Utilizing Pro- bono Commercial Assets for Marine Mammal Surveys In High Naval Activity Area in Hawaiian

  17. Trigger factor: a soluble protein that folds pro-OmpA into a membrane-assembly-competent form

    SciTech Connect

    Crooke, E.; Wickner, W.

    1987-08-01

    Pro-OmpA that is synthesized in vitro can assemble into bacterial inner membrane vesicles in the presence of ATP and NADH. The authors have purified pro-OmpA to determine which additional soluble proteins are necessary for its membrane assembly. (/sup 35/S)Pro-OmpA was bound to Sepharose-linked antibody to OmpA, then eluted with 8 M urea and chromatographed on an anion-exchange resin in 8 M urea. This pro-OmpA is purified 2000-fold and is radiochemically pure. After dialysis, it is soluble but incompetent for membrane assembly. Addition of an Escherichia coli cytoplasmic fraction (S100) to the assembly reaction does not allow translocation. However, when S100 is added to pro-OmpA prior to dialysis, full assembly competence is restored, suggesting that a soluble factor, termed trigger factor, triggers the folding of pro-OmpA into an assembly-competent form as the urea is removed. They noted that, prior to the last purification step, the immunoaffinity-purified pro-OmpA was partially competent for membrane assembly without addition of trigger factor. To test whether trigger factor had bound to the antibody column by means of its association with pro-OmpA, the crude pro-OmpA was acid-denatured prior to immunoadsorption. In this experiment, the trigger factor did not bind to the anti-OmpA column, and S100 was required for renaturation of this (/sup 35/S)pro-OmpA. As suggested by this experiment, the crude (/sup 35/S)pro-OmpA was in complex with other proteins. Sedimentation velocity studies showed that the trigger factor has an apparent molecular weight of approx. = 60,000. They propose that it is required for translocation-competent folding of pro-OmpA and other precursor proteins.

  18. PPARgamma Pro12Ala polymorphism in HIV-1-infected patients with HAART-related lipodystrophy.

    PubMed

    Saumoy, Maria; Veloso, Sergi; Alonso-Villaverde, Carlos; Domingo, Pere; Chacón, Matilde R; Miranda, Merce; Aragonès, Gerard; Gutiérrez, Maria Mar; Viladés, Consuelo; Peraire, Joaquim; Sirvent, Joan-Josep; López-Dupla, Miguel; Aguilar, Carmen; Richart, Cristóbal; Vidal, Francesc

    2009-09-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in obesity and in some components of the metabolic syndrome in unselected population. To determine whether PPARgamma genetic variants are associated with the risk of developing lipodystrophy and its associated metabolic disturbances in HIV-1-infected patients treated with HAART and to assess PPARgamma mRNA expression in subcutaneous adipose tissue (SAT). The study group comprised 278 patients infected with HIV-1 and treated with antiretroviral drugs (139 with lipodystrophy and 139 without) and 105 uninfected controls (UC). The PPARgamma Pro12Ala (C%>G) single nucleotide polymorphism (SNP) was assessed using PCR-RFLPs on white cell DNA. PPARgamma mRNA expression in SAT was assessed in 38 patients (25 with lipodystrophy and 13 without) and in 21 UC by real-time PCR. Statistical analysis was based on Student's T tests, Chi(2) tests, Spearman's correlations tests and logistic regression tests. PPARgamma Pro12Ala genotype distribution and allele frequencies were non-significantly different between both HIV-1-infected categories, lipodystrophy vs non-lipodystrophy (p=0.9 and p=0.87, respectively). Lipodystrophic patients harbouring the rare X/Ala genotype (Ala/Ala plus Pro/Ala) had significantly greater plasma total and LDL cholesterol levels compared with carriers of the common Pro/Pro genotype (p=0.029 and p=0.016, respectively) at univariate analyses. At multivariate analyses these associations were no longer significant. There was a near-significant decreased SAT PPARgamma mRNA expression in patients with lipodystrophy compared to UC (p=0.054). PPARgamma Pro12Ala SNP has no effect on the risk of developing lipodystrophy in HIV-1-infected patients treated with HAART. PPARgamma mRNA SAT expression appears decreased in lipodystrophy.

  19. Sharing knowledge of Planetary Datasets through the Web-Based PRoGIS

    NASA Astrophysics Data System (ADS)

    Giordano, M. G.; Morley, J. M.; Muller, J. P. M.; Barnes, R. B.; Tao, Y. T.

    2015-10-01

    The large amount of raw and derived data available from various planetary surface missions (e.g. Mars and Moon in our case) has been integrated withco-registered and geocoded orbital image data to provide rover traverses and camera site locations in universal global co-ordinates [1]. This then allows an integrated GIS to use these geocoded products for scientific applications: we aim to create a web interface, PRoGIS, with minimal controls focusing on the usability and visualisation of the data, to allow planetary geologists to share annotated surface observations. These observations in a common context are shared between different tools and software (PRoGIS, Pro3D, 3D point cloud viewer). Our aim is to use only Open Source components that integrate Open Web Services for planetary data to make available an universal platform with a WebGIS interface, as well as a 3D point cloud and a Panorama viewer to explore derived data. On top of these tools we are building capabilities to make and share annotations amongst users. We use Python and Django for the server-side framework and Open Layers 3 for the WebGIS client. For good performance previewing 3D data (point clouds, pictures on the surface and panoramas) we employ ThreeJS, a WebGL Javascript library. Additionally, user and group controls allow scientists to store and share their observations. PRoGIS not only displays data but also launches sophisticated 3D vision reprocessing (PRoVIP) and an immersive 3D analysis environment (PRo3D).

  20. Pupil size reveals preparatory processes in the generation of pro-saccades and anti-saccades.

    PubMed

    Wang, Chin-An; Brien, Donald C; Munoz, Douglas P

    2015-04-01

    The ability to generate flexible behaviors to accommodate changing goals in response to identical sensory stimuli is a signature that is inherited in humans and higher-level animals. In the oculomotor system, this function has often been examined with the anti-saccade task, in which subjects are instructed, prior to stimulus appearance, to either automatically look at the peripheral stimulus (pro-saccade) or to suppress the automatic response and voluntarily look in the opposite direction from the stimulus (anti-saccade). Distinct neural preparatory activity between the pro-saccade and anti-saccade conditions has been well documented, particularly in the superior colliculus (SC) and the frontal eye field (FEF), and this has shown higher inhibition-related fixation activity in preparation for anti-saccades than in preparation for pro-saccades. Moreover, the level of preparatory activity related to motor preparation is negatively correlated with reaction times. We hypothesised that preparatory signals may be reflected in pupil size through a link between the SC and the pupil control circuitry. Here, we examined human pupil dynamics during saccade preparation prior to the execution of pro-saccades and anti-saccades. Pupil size was larger in preparation for correct anti-saccades than in preparation for correct pro-saccades and erroneous pro-saccades made in the anti-saccade condition. Furthermore, larger pupil dilation prior to stimulus appearance accompanied saccades with faster reaction times, with a trial-by-trial correlation between dilation size and anti-saccade reaction times. Overall, our results demonstrate that pupil size is modulated by saccade preparation, and neural activity in the SC, together with the FEF, supports these findings, providing unique insights into the neural substrate coordinating cognitive processing and pupil diameter.

  1. Root and shoot parts of strawberry: factories for production of functional human pro-insulin.

    PubMed

    Tavizi, Ashkan; Javaran, Mokhtar Jalali; Moieni, Ahmad; Mohammadi-Dehcheshmeh, Manijeh; Mohebodini, Mehdi; Ebrahimie, Esmaeil

    2015-05-01

    Diabetes, a disease caused by excessive blood sugar, is caused by the lack of insulin. For commercial production, insulin is made in bacteria or yeast by protein recombinant technology. The focus of this research is evaluating another resource and producing of recombinant insulin protein in as strawberry as this plant has high potential in production of pharmaceutical proteins. Strawberry is a suitable bioreactor for production of recombinant proteins especially edible vaccines. In this research, human pro-insulin gene was cloned in pCAMBIA1304 vector under CaMV35S promoter and NOS terminator. Agrobacterium tumefaciens LBA4404, AGL1, EHA105, EHA101, C58, C58 (pGV2260) and C58 (pGV3101) strains were used for transformation of pro-insulin gene into strawberry cv. Camarosa, Selva, Sarian Hybrid, Pajaro, Paros, Gaviota, Alpine. Additionally, Agrobacterium rhizogenes K599, R1000, A4 and MSU440 strains were utilized for gene transformation into hairy roots. PCR analysis indicated the presence of transformed human pro-insulin gene in the strawberry and hairy roots. Also, its transcription was confirmed using RT-PCR. Furthermore, the analysis of plants, fruits and hairy roots at the level of proteins using dot blot, ELISA, SDS-PAGE and ECL tests re-confirmed the expression of this protein in the transgenic plants as well as hairy roots. Protein purification of human pro-insulin from transgenic tissues was performed using affinity chromatography. Finally, the bioassay of recombinant pro-insulin was performed. The analysis of second generations of transgenic plants (T1) at DNA and protein levels was also performed as a complementary experiment. This study opens a new avenue in molecular farming of human pro-insulin through its mass production in roots and shoots of strawberry.

  2. Finding correct protein–protein docking models using ProQDock

    PubMed Central

    Basu, Sankar; Wallner, Björn

    2016-01-01

    Motivation: Protein–protein interactions are a key in virtually all biological processes. For a detailed understanding of the biological processes, the structure of the protein complex is essential. Given the current experimental techniques for structure determination, the vast majority of all protein complexes will never be solved by experimental techniques. In lack of experimental data, computational docking methods can be used to predict the structure of the protein complex. A common strategy is to generate many alternative docking solutions (atomic models) and then use a scoring function to select the best. The success of the computational docking technique is, to a large degree, dependent on the ability of the scoring function to accurately rank and score the many alternative docking models. Results: Here, we present ProQDock, a scoring function that predicts the absolute quality of docking model measured by a novel protein docking quality score (DockQ). ProQDock uses support vector machines trained to predict the quality of protein docking models using features that can be calculated from the docking model itself. By combining different types of features describing both the protein–protein interface and the overall physical chemistry, it was possible to improve the correlation with DockQ from 0.25 for the best individual feature (electrostatic complementarity) to 0.49 for the final version of ProQDock. ProQDock performed better than the state-of-the-art methods ZRANK and ZRANK2 in terms of correlations, ranking and finding correct models on an independent test set. Finally, we also demonstrate that it is possible to combine ProQDock with ZRANK and ZRANK2 to improve performance even further. Availability and implementation: http://bioinfo.ifm.liu.se/ProQDock Contact: bjornw@ifm.liu.se Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307625

  3. Peptide ligands for pro-survival protein Bfl-1 from computationally guided library screening

    PubMed Central

    Dutta, Sanjib; Chen, T. Scott; Keating, Amy E.

    2013-01-01

    Pro-survival members of the Bcl-2 protein family inhibit cell death by binding short helical BH3 motifs in pro-apoptotic proteins. Mammalian pro-survival proteins Bcl-xL, Bcl-2, Bcl-w, Mcl-1 and Bfl-1 bind with varying affinities and specificities to native BH3 motifs, engineered peptides and small molecules. Biophysical studies have determined interaction patterns for these proteins, particularly for the most-studied family members Bcl-xL and Mcl-1. Bfl-1 is a pro-survival protein implicated in preventing apoptosis in leukemia, lymphoma and melanoma. Although Bfl-1 is a promising therapeutic target, relatively little is known about its binding preferences. We explored the binding of Bfl-1 to BH3-like peptides by screening a peptide library that was designed to sample a high degree of relevant sequence diversity. Screening using yeast-surface display led to several novel high-affinity Bfl-1 binders and to thousands of putative binders identified through deep sequencing. Further screening for specificity led to identification of a peptide that bound to Bfl-1 with Kd < 1 nM and very slow dissociation from Bfl-1 compared to other pro-survival Bcl-2 family members. A point mutation in this sequence gave a peptide with ~50 nM affinity for Bfl-1 that was selective for Bfl-1 in equilibrium binding assays. Analysis of engineered Bfl-1 binders deepens our understanding of how the binding profiles of pro-survival proteins differ, and may guide the development of targeted Bfl-1 inhibitors. PMID:23363053

  4. Total plasma proANP increases with atrial dilatation in horses.

    PubMed

    Van Der Vekens, N; Hunter, I; Timm, A; Decloedt, A; De Clercq, D; Deprez, P; Goetze, J P; van Loon, G

    2015-12-19

    Equine atrial natriuretic peptide (ANP) plasma concentrations are correlated with left atrial size. However, species-specific assays are lacking and the results from human assays are poorly reproducible. A new methodology called processing independent analysis (PIA) that measures the total proANP product in plasma has proven to be successful in human medicine, but has never been used in horses. The aims were to establish an equine proANP reference interval by measurement of the total proANP product using PIA and to examine the proANP concentrations in horses with atrial dilatation. Sample stability was studied by comparison of storage at -80°C and -20°C. Plasma samples were obtained from 23 healthy horses, 12 horses with moderate or severe valvular regurgitation without atrial dilatation and 42 horses with valvular regurgitation and atrial dilatation. The proANP concentration was significantly (P<0.001) higher in horses with atrial dilatation (761.4 (442.1-1859.1) pmol/l) than in healthy horses (491.6 (429.5-765.9) pmol/l; P<0.001) or horses with cardiac disease but without atrial dilatation (544.4 (457.0-677.6) pmol/l). A cut-off value (573.8 pmol/l) for detection of atrial dilatation was calculated. Sample storage at -80°C did not differ from sample storage at -20°C. The measurement of total proANP in plasma detects atrial dilatation in horses and may be useful for clinical evaluation in equine medicine.

  5. Peptide ligands for pro-survival protein Bfl-1 from computationally guided library screening.

    PubMed

    Dutta, Sanjib; Chen, T Scott; Keating, Amy E

    2013-04-19

    Pro-survival members of the Bcl-2 protein family inhibit cell death by binding short helical BH3 motifs in pro-apoptotic proteins. Mammalian pro-survival proteins Bcl-x(L), Bcl-2, Bcl-w, Mcl-1, and Bfl-1 bind with varying affinities and specificities to native BH3 motifs, engineered peptides, and small molecules. Biophysical studies have determined interaction patterns for these proteins, particularly for the most-studied family members Bcl-x(L) and Mcl-1. Bfl-1 is a pro-survival protein implicated in preventing apoptosis in leukemia, lymphoma, and melanoma. Although Bfl-1 is a promising therapeutic target, relatively little is known about its binding preferences. We explored the binding of Bfl-1 to BH3-like peptides by screening a peptide library that was designed to sample a high degree of relevant sequence diversity. Screening using yeast-surface display led to several novel high-affinity Bfl-1 binders and to thousands of putative binders identified through deep sequencing. Further screening for specificity led to identification of a peptide that bound to Bfl-1 with K(d) < 1 nM and very slow dissociation from Bfl-1 compared to other pro-survival Bcl-2 family members. A point mutation in this sequence gave a peptide with ~50 nM affinity for Bfl-1 that was selective for Bfl-1 in equilibrium binding assays. Analysis of engineered Bfl-1 binders deepens our understanding of how the binding profiles of pro-survival proteins differ and may guide the development of targeted Bfl-1 inhibitors.

  6. Disruption of disulfide bond formation alters the trafficking of prothyrotropin releasing hormone (proTRH)-derived peptides.

    PubMed

    Mulcahy, Lawrence R; Barker, Alison J; Nillni, Eduardo A

    2006-01-15

    Rat prothyrotropin releasing hormone (proTRH) is processed in the regulated secretory pathway (RSP) of neuroendocrine cells yielding five TRH peptides and several non-TRH peptides. It is not understood how these peptides are targeted to the RSP. We show here that a disulfide bond in the carboxy-terminus of proTRH plays an important role in the trafficking of this prohormone. Recombinant proTRH was observed to migrate faster on a native gel when treated with dithiothreitol (DTT) suggesting the presence of a disulfide bond. In vitro disulfide bond formation was prevented either by DTT treatment or by mutating cysteines 213 and 219 to glycines. In both cases the peptides derived from these mutants exhibited increased constitutive release and processing defects when expressed in AtT20 cells, a neuroendocrine cell line used in our prior studies on proTRH processing. Immunocytochemistry revealed that wild-type proTRH and mutant proTRH localized in a punctate pattern typical of proteins sorted to the regulated secretory pathway. These data suggest that the proposed disulfide bond of proTRH is involved in sorting of proTRH-derived peptides and in their retention within maturing secretory granules. This is the first evidence of structural motifs being important for the sorting of proTRH.

  7. No significant association between p53 codon 72 Arg/Pro polymorphism and risk of oral cancer.

    PubMed

    Jiang, Ning; Pan, Jie; Wang, Lei; Duan, Yin-Zhong

    2013-02-01

    The genetic polymorphism of p53 codon 72 Arg/Pro has been implicated in oral cancer risk, but the results of previous studies remain controversial and ambiguous. To estimate the effect of the p53 codon 72 Arg/Pro polymorphism on the risk of oral cancer, a meta-analysis was performed. Based on a comprehensive search in PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases, we identified all available publications assessing the association between p53 codon 72 Arg/Pro polymorphism and oral cancer risk. The pooled odds ratio (OR) with its corresponding 95 % confidence interval (CI) was calculated to assess the association. Subgroup analyses by ethnicity and study quality were performed to further identify the correlation. Totally, 17 studies with 2,975 cases and 3,413 controls were included into this meta-analysis. There was no statistically significant association between the p53 codon 72 Arg/Pro polymorphism and oral cancer risk in all genetic contrast models (OR(Pro allele vs. Arg allele) = 1.05, 95 % CI 0.94-1.18, P(OR) = 0.379; OR(Pro/Pro vs. Arg/Arg) = 1.11, 95 % CI 0.89-1.40, P(OR) = 0.356; OR(Pro/Arg vs. Arg/Arg) = 1.10, 95 % CI 0.93-1.30, P(OR) = 0.256; OR(Pro/Arg + Pro/Pro vs. Arg/Arg) = 1.10, 95 % CI 0.93-1.31, P(OR) = 0.263; and OR(Pro/Pro vs. Arg/Arg + Pro/Arg) = 1.03, 95 % CI 0.90-1.18, P(OR) = 0.647). In the subgroup analysis of high-quality studies, we failed to find the susceptibility of p53 codon 72 Arg/Pro polymorphism to oral cancer. Moreover, the results were similar among Asians, Caucasians, and mixed populations when stratifying by ethnicity. Sensitivity analysis further confirmed the stability of the results. The present meta-analysis of currently available data shows no association between the p53 codon 72 Arg/Pro polymorphism and oral cancer risk.

  8. Pro-eating disorder search patterns: the possible influence of celebrity eating disorder stories in the media.

    PubMed

    Lewis, Stephen P; Klauninger, Laura; Marcincinova, Ivana

    2016-01-01

    Pro eating disorder websites often contain celebrity-focused content (e.g., images) used as thinspiration to engage in unhealthy eating disorder behaviours. The current study was conducted to examine whether news media stories covering eating disorder disclosures of celebrities corresponded with increases in Internet searches for pro eating disorder material. Results indicated that search volumes for pro eating disorder terms spiked in the month immediately following such news coverage but only for particularly high-profile celebrities. Hence, there may be utility in providing recovery-oriented resources within the search results for pro-eating disorder Internet searches and within news stories of this nature.

  9. 1DTempPro: analyzing temperature profiles for groundwater/surface-water exchange

    USGS Publications Warehouse

    Voytek, Emily B.; Drenkelfuss, Anja; Day-Lewis, Frederick D.; Healy, Richard; Lane, Jr., John W.; Werkema, Dale

    2014-01-01

    A new computer program, 1DTempPro, is presented for the analysis of vertical one-dimensional (1D) temperature profiles under saturated flow conditions. 1DTempPro is a graphical user interface to the U.S. Geological Survey code Variably Saturated 2-Dimensional Heat Transport (VS2DH), which numerically solves the flow and heat-transport equations. Pre- and postprocessor features allow the user to calibrate VS2DH models to estimate vertical groundwater/surface-water exchange and also hydraulic conductivity for cases where hydraulic head is known.

  10. Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertases.

    PubMed Central

    Seidah, N G; Benjannet, S; Pareek, S; Savaria, D; Hamelin, J; Goulet, B; Laliberte, J; Lazure, C; Chrétien, M; Murphy, R A

    1996-01-01

    In order to define the enzymes responsible for the maturation of the precursor of nerve growth factor (proNGF), its biosynthesis and intracellular processing by the pro-protein convertases furin, PC1, PC2, PACE4, PC5 and the PC5 isoform PC5/6-B were analysed using the vaccinia virus expression system in cells containing a regulated and/or a constitutive secretory pathway. Results demonstrate that in both cell types furin, and to a lesser extent PACE4 and PC5/6-B, are the best candidate proNGF convertases. Furthermore, two processed NGF forms of 16.5 and 13.5 kDa were evident in constitutively secreting cell lines such as LoVo and BSC40 cells, whereas only the 13.5 kDa form was observed in AtT20 cells, which contain secretory granules. Both forms display the same N-terminal sequence as mature NGF, and were also produced following site-directed mutagenesis of the C-terminal Arg-Arg sequence of NGF into Ala-Ala, suggesting that the difference between them is not at the C-terminus. Co-expression of proNGF with furin and either chromogranin B or secretogranin II (but not chromogranin A) in BSC40 cells eliminated the 16.5 kDa form. Data also show that N-glycosylation of the pro-segment of proNGF and trimming of the oligosaccharide chains are necessary for the exit of this precursor from the endoplasmic reticulum and its eventual processing and secretion. Sulphate labelling experiments demonstrated that proNGF is processed into mature NGF following the arrival of the precursor in the trans-Golgi network. This comparative study shows that the three candidate mammalian subtilisin/kexin-like convertases identified process proNGF into NGF and that the nature of the final processed products is dependent on the intracellular environment. PMID:8615794

  11. Pro-inflammatory cytokines: Useful markers for the diagnosis of canine mammary tumours?

    PubMed

    Andaluz, Ana; Yeste, Marc; Rodríguez-Gil, Joan E; Rigau, Teresa; García, Félix; Rivera del Álamo, Maria Montserrat

    2016-04-01

    The aim of the present study was to analyse the expression of 60 pro-inflammatory cytokines as possible markers of malignancy in canine mammary tumours using a human cytokine antibody array. The cytokines were grouped into two different categories: (1) cytokines in which expression indicated the presence of a mammary tumour and (2) cytokines in which expression differentiated between simple mammary adenoma, tubulopapillary carcinoma or complex carcinoma. These data suggest that specific pro-inflammatory cytokines could be useful as tools for the diagnosis of canine mammary tumours.

  12. Chemotherapy pro-drug activation by biocatalytic virus-like nanoparticles containing cytochrome P450.

    PubMed

    Sánchez-Sánchez, Lorena; Cadena-Nava, Rubén D; Palomares, Laura A; Ruiz-Garcia, Jaime; Koay, Melissa S T; Cornelissen, Jeroen J M T; Vazquez-Duhalt, Rafael

    2014-06-10

    This work shows, for the first time, the encapsulation of a highly relevant protein in the biomedical field into virus-like particles (VLPs). A bacterial CYP variant was effectively encapsulated in VLPs constituted of coat protein from cowpea chlorotic mottle virus (CCMV). The catalytic VLPs are able to transform the chemotherapeutic pro-drug, tamoxifen, and the emerging pro-drug resveratrol. The chemical nature of the products was identified, confirming similar active products than those obtained with human CYP. The enzymatic VLPs remain stable after the catalytic reaction. The potential use of these biocatalytic nanoparticles as targeted CYP carriers for the activation of chemotherapy drugs is discussed.

  13. ProPhenol-Catalyzed Asymmetric Additions by Spontaneously Assembled Dinuclear Main Group Metal Complexes

    PubMed Central

    2016-01-01

    Conspectus The development of catalytic enantioselective transformations has been the focus of many research groups over the past half century and is of paramount importance to the pharmaceutical and agrochemical industries. Since the award of the Nobel Prize in 2001, the field of enantioselective transition metal catalysis has soared to new heights, with the development of more efficient catalysts and new catalytic transformations at increasing frequency. Furthermore, catalytic reactions that allow higher levels of redox- and step-economy are being developed. Thus, alternatives to asymmetric alkene dihydroxylation and the enantioselective reduction of α,β-unsaturated ketones can invoke more strategic C–C bond forming reactions, such as asymmetric aldol reactions of an aldehyde with α-hydroxyketone donors or enantioselective alkynylation of an aldehyde, respectively. To facilitate catalytic enantioselective addition reactions, including the aforementioned aldol and alkynylation reactions, our lab has developed the ProPhenol ligand. In this Account, we describe the development and application of the ProPhenol ligand for asymmetric additions of both carbon- and heteroatom-based nucleophiles to various electrophiles. The ProPhenol ligand spontaneously forms chiral dinuclear metal complexes when treated with an alkyl metal reagent, such as Et2Zn or Bu2Mg. The resulting complex contains both a Lewis acidic site to activate an electrophile and a Brønsted basic site to deprotonate a pronucleophile. Initially, our research focused on the use of Zn-ProPhenol complexes to facilitate the direct aldol reaction. Fine tuning of the reaction through ligand modification and the use of additives enabled the direct aldol reaction to proceed in high yields and stereoselectivities with a broad range of donor substrates, including acetophenones, methyl ynones, methyl vinyl ketone, acetone, α-hydroxy carbonyl compounds, and glycine Schiff bases. Additionally, an analogous

  14. Pro-eating disorder communities on social networking sites: a content analysis.

    PubMed

    Juarascio, Adrienne S; Shoaib, Amber; Timko, C Alix

    2010-01-01

    The purpose of this study was to assess the number of pro-ana groups on social networking sites and to analyze their content. A general inductive approach was used to analyze the content. Two main themes emerged from the content analysis: social support and eating disorder specific content. Themes were similar across all groups; however, a linguistic analysis indicated differences between groups on the two different networking sites. There was an absence of content typically found on Internet sites. Pro-ana groups on social networking sites are focused on social interactions, and lack eating disorder specific content found on Internet sites.

  15. A second proPO present in white shrimp Litopenaeus vannamei and expression of the proPOs during a Vibrio alginolyticus injection, molt stage, and oral sodium alginate ingestion.

    PubMed

    Yeh, Maw-Sheng; Lai, Ching-Yi; Liu, Chun-Hung; Kuo, Ching-Ming; Cheng, Winton

    2009-01-01

    Prophenoloxidase (proPO) is a melanin-synthesising enzyme that plays important roles in immune responses by crustaceans. Previously, we cloned and characterized proPO-I from white shrimp, Litopenaeus vannamei. In the present study, a novel prophenoloxidase-II (proPO-II) cDNA was also cloned from haemocytes of L. vannamei using oligonucleotide primers and reverse-transcriptase polymerase chain reaction (RT-PCR). Both 3'- and 5'-regions were isolated by the rapid amplification of complementary (c)DNA end (RACE) method. The 2504-bp cDNA contained an open reading frame (ORF) of 2073 bp, an 84-bp 5'-untranslated region, and a 347-bp 3'-untranslated region containing the poly A tail. The molecular mass of the deduced amino acid sequence (691 amino acids) was 78.8 kDa with an estimated pI of 6.07. It contains two putative tyrosinase copper-binding motifs and a conserved C-terminal region common to all known proPOs. Comparisons of the amino acid sequences showed that white shrimp proPO-II is more closely related to the proPO of other penaeids than to that of crayfish, lobsters, crab, or a freshwater prawn, and is the ancestor type of known penaeid proPOs. proPO-I and proPO-II messenger (m)RNAs of shrimp were located on different loci, and were constitutively expressed mainly in haemocytes. The transcriptional regulation of these two proPOs in shrimp at different molt stages, those administered dietary sodium alginate, and those challenged with Vibrio alginolyticus were surveyed. The results showed that the proPOs may be directly involved in the acute-phase immune defence, and proPO-II may contribute earlier to immune defence in shrimp injected with V. alginolyticus, and it may be regulated by ecdysone. However, a similar effect was found by stimulating proPO-I and proPO-II mRNA expression in shrimp fed a sodium alginate-containing diet. Results of this study provide a basis for developing a comprehensive understanding of expression/function relationships of individual pro

  16. Structure and function of transmembrane segment XII in osmosensor and osmoprotectant transporter ProP of Escherichia coli.

    PubMed

    Liu, Feng; Culham, Doreen E; Vernikovska, Yaroslava I; Keates, Robert A B; Boggs, Joan M; Wood, Janet M

    2007-05-15

    Escherichia coli transporter ProP acts as both an osmosensor and an osmoregulator. As medium osmolality rises, ProP is activated and mediates H+-coupled uptake of osmolytes like proline. A homology model of ProP with 12-transmembrane (TM) helices and cytoplasmic termini was created, and the protein's topology was substantiated experimentally. Residues 468-497, at the end of the C-terminal domain and linked to TM XII, form an intermolecular, homodimeric alpha-helical coiled-coil that tunes the transporter's response to osmolality. We aim to further define the structure and function of ProP residues Q415-E440, predicted to include TM XII. Each residue was replaced with cysteine (Cys) in a histidine-tagged, Cys-less ProP variant (ProP*). Cys at positions 415-418 and 438-440 were most reactive with Oregon Green Maleimide (OGM), suggesting that residues 419 through 437 are in the membrane. Except for V429-I433, reactivity of those Cys varied with helical periodicity. Cys predicted to face the interior of ProP were more reactive than Cys predicted to face the lipid. The former may be exposed to hydrated polar residues in the protein interior, particularly on the periplasmic side. Intermolecular cross-links formed when ProP* variants with Cys at positions 419, 420, 422, and 439 were treated with DTME. Thus TM XII can participate, along its entire length, in the dimer interface of ProP. Cys substitution E440C rendered ProP* inactive. All other variants retained more than 30% of the proline uptake activity of ProP* at high osmolality. Most variants with Cys substitutions in the periplasmic half of TM XII activated at lower osmolalities than ProP*. Variants with Cys substitutions on one face of the cytoplasmic half of TM XII required a higher osmolality to activate. They included elements of a GXXXG motif that are predicted to form the interface of TM XII with TM VII. These studies define the position of ProP TM XII within the membrane, further support the predicted

  17. Salinity-dependent impacts of ProQ, Prc, and Spr deficiencies on Escherichia coli cell structure.

    PubMed

    Kerr, Craig H; Culham, Doreen E; Marom, David; Wood, Janet M

    2014-03-01

    ProQ is a cytoplasmic protein with RNA chaperone activities that reside in FinO- and Hfq-like domains. Lesions at proQ decrease the level of the osmoregulatory glycine betaine transporter ProP. Lesions at proQ eliminated ProQ and Prc, the periplasmic protease encoded by the downstream gene prc. They dramatically slowed the growth of Escherichia coli populations and altered the morphologies of E. coli cells in high-salinity medium. ProQ and Prc deficiencies were associated with different phenotypes. ProQ-deficient bacteria were elongated unless glycine betaine was provided. High-salinity cultures of Prc-deficient bacteria included spherical cells with an enlarged periplasm and an eccentric nucleoid. The nucleoid-containing compartment was bounded by the cytoplasmic membrane and peptidoglycan. This phenotype was not evident in bacteria cultivated at low or moderate salinity, nor was it associated with murein lipoprotein (Lpp) deficiency, and it differed from those elicited by the MreB inhibitor A-22 or the FtsI inhibitor aztreonam at low or high salinity. It was suppressed by deletion of spr, which encodes one of three murein hydrolases that are redundantly essential for enlargement of the murein sacculus. Prc deficiency may alter bacterial morphology by impairing control of Spr activity at high salinity. ProQ and Prc deficiencies lowered the ProP activity of bacteria cultivated at moderate salinity by approximately 70% and 30%, respectively, but did not affect other osmoregulatory functions. The effects of ProQ and Prc deficiencies on ProP activity are indirect, reflecting their roles in the maintenance of cell structure.

  18. Overexpression of tnaC of Escherichia coli Inhibits Growth by Depleting tRNA2Pro Availability

    PubMed Central

    Gong, Ming; Gong, Feng; Yanofsky, Charles

    2006-01-01

    Transcription of the tryptophanase (tna) operon of Escherichia coli is regulated by catabolite repression and tryptophan-induced transcription antitermination. Induction results from ribosome stalling after translation of tnaC, the coding region for a 24-residue leader peptide. The last sense codon of tnaC, proline codon 24 (CCU), is translated by tRNA2Pro. We analyzed the consequences of overexpression of tnaC from a multicopy plasmid and observed that under inducing conditions more than 60% of the tRNA2Pro in the cell was sequestered in ribosomes as TnaC-tRNA2Pro. The half-life of this TnaC-tRNA2Pro was shown to be 10 to 15 min under these conditions. Plasmid-mediated overexpression of tnaC, under inducing conditions, reduced cell growth rate appreciably. Increasing the tRNA2Pro level relieved this growth inhibition, suggesting that depletion of this tRNA was primarily responsible for the growth rate reduction. Growth inhibition was not relieved by overexpression of tRNA1Pro, a tRNAPro that translates CCG, but not CCU. Replacing the Pro24CCU codon of tnaC by Pro24CCG, a Pro codon translated by tRNA1Pro, also led to growth rate reduction, and this reduction was relieved by overexpression of tRNA1Pro. These findings establish that the growth inhibition caused by tnaC overexpression during induction by tryptophan is primarily a consequence of tRNAPro depletion, resulting from TnaC-tRNAPro retention within stalled, translating ribosomes. PMID:16484200

  19. Visual setup of logical models of signaling and regulatory networks with ProMoT

    PubMed Central

    Saez-Rodriguez, Julio; Mirschel, Sebastian; Hemenway, Rebecca; Klamt, Steffen; Gilles, Ernst Dieter; Ginkel, Martin

    2006-01-01

    Background The analysis of biochemical networks using a logical (Boolean) description is an important approach in Systems Biology. Recently, new methods have been proposed to analyze large signaling and regulatory networks using this formalism. Even though there is a large number of tools to set up models describing biological networks using a biochemical (kinetic) formalism, however, they do not support logical models. Results Herein we present a flexible framework for setting up large logical models in a visual manner with the software tool ProMoT. An easily extendible library, ProMoT's inherent modularity and object-oriented concept as well as adaptive visualization techniques provide a versatile environment. Both the graphical and the textual description of the logical model can be exported to different formats. Conclusion New features of ProMoT facilitate an efficient set-up of large Boolean models of biochemical interaction networks. The modeling environment is flexible; it can easily be adapted to specific requirements, and new extensions can be introduced. ProMoT is freely available from . PMID:17109765

  20. PRO*CAST: Providing Timely Information to Monitor Progress Toward University Goals.

    ERIC Educational Resources Information Center

    Jackson, Tad; And Others

    1995-01-01

    In the University of Massachusetts' multicampus system, an integrated suite of technologies called PRO*CAST provides administrators, planners, and policymakers with access to timely, accurate information to support decision making and monitor progress toward established goals. The system is structured as an information warehouse with executive…

  1. Creating Well-Being: Increased Creativity and proNGF Decrease following Quadrato Motor Training

    PubMed Central

    Venditti, Sabrina; Verdone, Loredana; Pesce, Caterina; Tocci, Nicoletta; Caserta, Micaela; Ben-Soussan, Tal Dotan

    2015-01-01

    Mind-body practices (MBP) are known to induce electrophysiological and morphological changes, whereas reports related to changes of neurotrophins are surprisingly scarce. Consequently, in the current paper, we focused on the Quadrato motor training (QMT), a newly developed whole-body movement-based MBP, which has been reported to enhance creativity. Here we report the effects of 4 weeks of daily QMT on creativity and proNGF level in two interrelated studies. In Study A, we examined the effects of QMT compared with a walking training (WT) in healthy adults, utilizing the alternate uses task. In contrast with the WT, QMT resulted in increased creativity. In addition, the change in creativity negatively correlated with the change in proNGF levels. In Study B, we examined QMT effects on creativity and additional metacognitive functions in children, using a nonintervention group as control. Similar to Study A, following QMT, we found a negative correlation of proNGF with creativity, as well as working memory updating and planning ability. Together, the current results point to the relationship between increased creativity and decreased proNGF following MBP. Thus, the current research emphasizes the importance of widening the scope of examination of “MBP in motion” in relation to metacognition and well-being. PMID:26137470

  2. Religious Pro-Sociality? Experimental Evidence from a Sample of 766 Spaniards

    PubMed Central

    Brañas-Garza, Pablo; Espín, Antonio M.; Neuman, Shoshana

    2014-01-01

    This study explores the relationship between several personal religion-related variables and social behaviour, using three paradigmatic economic games: the dictator (DG), ultimatum (UG), and trust (TG) games. A large carefully designed sample of the urban adult population in Granada (Spain) is employed (N = 766). From participants' decisions in these games we obtain measures of altruism, bargaining behaviour and sense of fairness/equality, trust, and positive reciprocity. Three dimensions of religiosity are examined: (i) religious denomination; (ii) intensity of religiosity, measured by active participation at church services; and (iii) conversion out into a different denomination than the one raised in. The major results are: (i) individuals with “no religion” made decisions closer to rational selfish behaviour in the DG and the UG compared to those who affiliate with a “standard” religious denomination; (ii) among Catholics, intensity of religiosity is the key variable that affects social behaviour insofar as religiously-active individuals are generally more pro-social than non-active ones; and (iii) the religion raised in seems to have no effect on pro-sociality, beyond the effect of the current measures of religiosity. Importantly, behaviour in the TG is not predicted by any of the religion-related variables we analyse. While the results partially support the notion of religious pro-sociality, on the other hand, they also highlight the importance of closely examining the multidimensional nature of both religiosity and pro-social behaviour. PMID:25115938

  3. Pro-B-cell-specific transcription and proapoptotic function of protein kinase Ceta.

    PubMed

    Morrow, T A; Muljo, S A; Zhang, J; Hardwick, J M; Schlissel, M S

    1999-08-01

    Using a subtractive cloning scheme on cDNA prepared from primary pro-B and pre-B cells, we identified several genes whose products regulate apoptosis. We further characterized one of these genes, encoding protein kinase Ceta (PKCeta). PKCeta transcripts were readily detected in pro-B cells but were absent in pre-B cells. Although both a full-length and a truncated form of PKCeta were detectable in bone marrow pro-B cells, transition to the pre-B-cell stage was associated with increased relative levels of truncated PKCeta. We found that PKCeta is proteolyzed in apoptotic lymphocytes, generating a kinase-active fragment identical to the truncated form which is capable of inducing apoptosis when expressed in a pro-B cell line. Caspase-3 can generate an identical PKCeta cleavage product in vitro, and caspase inhibitors prevent the generation of this product during apoptosis in transfected cell lines. Inducible overexpression of either the full-length or truncated form of PKCeta results in cell cycle arrest at the G(1)/S transition. These results suggest that the expression and proteolytic activation of PKCeta play an important role in the regulation of cell division and cell death during early B-cell development.

  4. 47 CFR 27.1237 - Pro rata allocation of transition costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Proponent-driven transitions. BRS licensees and lessees, entities that lease EBS spectrum for a commercial... equals the pro rata share; (2) L equals the amount of spectrum used by a BRS licensee or lessee or... agreement with an EBS or BRS licensee; (3) T equals the total amount of spectrum licensed or leased...

  5. 47 CFR 27.1237 - Pro rata allocation of transition costs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Proponent-driven transitions. BRS licensees and lessees, entities that lease EBS spectrum for a commercial... equals the pro rata share; (2) L equals the amount of spectrum used by a BRS licensee or lessee or... agreement with an EBS or BRS licensee; (3) T equals the total amount of spectrum licensed or leased...

  6. 47 CFR 27.1237 - Pro rata allocation of transition costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Proponent-driven transitions. BRS licensees and lessees, entities that lease EBS spectrum for a commercial... equals the pro rata share; (2) L equals the amount of spectrum used by a BRS licensee or lessee or... agreement with an EBS or BRS licensee; (3) T equals the total amount of spectrum licensed or leased...

  7. 47 CFR 27.1237 - Pro rata allocation of transition costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Proponent-driven transitions. BRS licensees and lessees, entities that lease EBS spectrum for a commercial... equals the pro rata share; (2) L equals the amount of spectrum used by a BRS licensee or lessee or... agreement with an EBS or BRS licensee; (3) T equals the total amount of spectrum licensed or leased...

  8. Religious pro-sociality? Experimental evidence from a sample of 766 Spaniards.

    PubMed

    Brañas-Garza, Pablo; Espín, Antonio M; Neuman, Shoshana

    2014-01-01

    This study explores the relationship between several personal religion-related variables and social behaviour, using three paradigmatic economic games: the dictator (DG), ultimatum (UG), and trust (TG) games. A large carefully designed sample of the urban adult population in Granada (Spain) is employed (N = 766). From participants' decisions in these games we obtain measures of altruism, bargaining behaviour and sense of fairness/equality, trust, and positive reciprocity. Three dimensions of religiosity are examined: (i) religious denomination; (ii) intensity of religiosity, measured by active participation at church services; and (iii) conversion out into a different denomination than the one raised in. The major results are: (i) individuals with "no religion" made decisions closer to rational selfish behaviour in the DG and the UG compared to those who affiliate with a "standard" religious denomination; (ii) among Catholics, intensity of religiosity is the key variable that affects social behaviour insofar as religiously-active individuals are generally more pro-social than non-active ones; and (iii) the religion raised in seems to have no effect on pro-sociality, beyond the effect of the current measures of religiosity. Importantly, behaviour in the TG is not predicted by any of the religion-related variables we analyse. While the results partially support the notion of religious pro-sociality, on the other hand, they also highlight the importance of closely examining the multidimensional nature of both religiosity and pro-social behaviour.

  9. Effects of aging on switching the response direction of pro- and antisaccades.

    PubMed

    Olk, Bettina; Jin, Yu

    2011-01-01

    The present study investigated effects of task switching between pro- and antisaccades and switching the direction of these saccades (response switching) on performance of younger and older adults. Participants performed single-task blocks, in which only pro- or only antisaccades had to be made as well as mixed-task blocks, in which pro- and antisaccades were required. Analysis of specific task switch effects in the mixed-task blocks showed switch costs for error rates for prosaccades for both groups, suggesting that antisaccade task rules persisted and affected the following prosaccade. The comparison between single- and mixed-task blocks showed that mixing costs were either equal or smaller for older than younger participants, indicating that the older participants were well able to keep task sets in working memory. The most prominent age difference that was observed for response switching was that for the older but not younger group task switching and response switching interacted, resulting in less errors when two consecutive antisaccades were made in the same direction. This finding is best explained with a facilitation of these consecutive antisaccades. The present study clearly demonstrated the impact of response switching and a difference between age groups, underlining the importance of considering this factor when investigating pro- and antisaccades, especially antisaccades, and when investigating task switching and aging.

  10. For robust big data analyses: a collection of 150 important pro-metastatic genes.

    PubMed

    Mei, Yan; Yang, Jun-Ping; Qian, Chao-Nan

    2017-01-21

    Metastasis is the greatest contributor to cancer-related death. In the era of precision medicine, it is essential to predict and to prevent the spread of cancer cells to significantly improve patient survival. Thanks to the application of a variety of high-throughput technologies, accumulating big data enables researchers and clinicians to identify aggressive tumors as well as patients with a high risk of cancer metastasis. However, there have been few large-scale gene collection studies to enable metastasis-related analyses. In the last several years, emerging efforts have identified pro-metastatic genes in a variety of cancers, providing us the ability to generate a pro-metastatic gene cluster for big data analyses. We carefully selected 285 genes with in vivo evidence of promoting metastasis reported in the literature. These genes have been investigated in different tumor types. We used two datasets downloaded from The Cancer Genome Atlas database, specifically, datasets of clear cell renal cell carcinoma and hepatocellular carcinoma, for validation tests, and excluded any genes for which elevated expression level correlated with longer overall survival in any of the datasets. Ultimately, 150 pro-metastatic genes remained in our analyses. We believe this collection of pro-metastatic genes will be helpful for big data analyses, and eventually will accelerate anti-metastasis research and clinical intervention.

  11. PRO-COAGULANT CARDIAC GENE EXPRESSION IN RESPONSE TO PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    PRO-COAGULANT CARDIAC GENE EXPRESSION IN RESPONSE TO PULMONARY ZINC EXPOSURE
    PS Gilmour, MC Schladweiler, AD Ledbetter, and UP Kodavanti, CEMALB, UNC, Chapel Hill, NC, and US-EPA, DURHAM, NC.

    Zinc is one of the major transition metal components of ambient and combustio...

  12. Video Recording With a GoPro in Hand and Upper Extremity Surgery.

    PubMed

    Vara, Alexander D; Wu, John; Shin, Alexander Y; Sobol, Gregory; Wiater, Brett

    2016-10-01

    Video recordings of surgical procedures are an excellent tool for presentations, analyzing self-performance, illustrating publications, and educating surgeons and patients. Recording the surgeon's perspective with high-resolution video in the operating room or clinic has become readily available and advances in software improve the ease of editing these videos. A GoPro HERO 4 Silver or Black was mounted on a head strap and worn over the surgical scrub cap, above the loupes of the operating surgeon. Five live surgical cases were recorded with the camera. The videos were uploaded to a computer and subsequently edited with iMovie or the GoPro software. The optimal settings for both the Silver and Black editions, when operating room lights are used, were determined to be a narrow view, 1080p, 60 frames per second (fps), spot meter on, protune on with auto white balance, exposure compensation at -0.5, and without a polarizing lens. When the operating room lights were not used, it was determined that the standard settings for a GoPro camera were ideal for positioning and editing (4K, 15 frames per second, spot meter and protune off). The GoPro HERO 4 provides high-quality, the surgeon perspective, and a cost-effective video recording of upper extremity surgical procedures. Challenges include finding the optimal settings for each surgical procedure and the length of recording due to battery life limitations.

  13. HRP and prorenin: focus on the (pro)renin receptor and vacuolar H+-ATPase.

    PubMed

    Lu, Xifeng; Danser, Alexander H J; Meima, Marcel E

    2011-06-01

    The function of prorenin, the precursor of renin, remained unknown until the discovery of the (pro)renin receptor ((P)RR). (Pro)renin binding to this receptor allows angiotensin generation and induces signaling. Thus, (P)RR blockade will exert effects beyond angiotensin suppression. Recently, the (P)RR has been identified as an accessory protein of the vacuolar-type H+-ATPase, with important roles in Wnt signaling. In addition, transgenic animals overexpressing prorenin display the consequences of angiotensin generation, whereas transgenic animals overexpressing the (P)RR display an angiotensin-independent phenotype. Finally, both beneficial and deleterious effects have been described following treatment with the (P)RR antagonist 'handle region peptide' (HRP), while a (P)RR knockout in cardiomyocytes is lethal. This review highlights the latest findings in the (P)RR area, focusing on cardiovascular and renal pathology. It critically addresses the possibility that (pro)renin acts as an agonist of this receptor in vivo, and discusses the efficacy of HRP. Conclusions are that convincing evidence for (pro)renin-(P)RR interaction in vivo is currently lacking and, thus, that the concept of HRP exerting beneficial effects by blocking such interaction remains to be proven.

  14. Structure of the Escherichia coli ProQ RNA chaperone protein.

    PubMed

    Gonzalez, Grecia; Hardwick, Steven; Maslen, Sarah L; Skehel, J Mark; Holmqvist, Erik; Vogel, Jörg; Bateman, Alex; Luisi, Ben; Broadhurst, R William

    2017-02-13

    The protein ProQ has recently been identified as a global RNA chaperone in Salmonella, and a similar role is anticipated for its numerous homologues in divergent bacterial species. We report the solution structure of Escherichia coli ProQ, revealing an N-terminal FinO-like domain, a C-terminal domain that unexpectedly has a Tudor-domain fold commonly found in eukaryotes, and an elongated bridging intra-domain linker that is flexible but nonetheless incompressible. Structure based sequence analysis suggests that the Tudor domain was acquired through horizontal gene transfer and gene fusion to the ancestral FinO-like domain. Through a combination of biochemical and biophysical approaches, we have mapped putative RNA binding surfaces on all three domains of ProQ and modelled the protein's conformation in the apo and RNA-bound forms. Taken together, these data suggest how the FinO, Tudor and linker domains of ProQ cooperate to recognise complex RNA structures and serve to promote RNA-mediated regulation.

  15. Pro-sustainability choices and child deaths averted: from project experience to investment strategy.

    PubMed

    Sarriot, Eric G; Swedberg, Eric A; Ricca, James G

    2011-05-01

    The pursuit of the Millennium Development Goals and advancing the 'global health agenda' demand the achievement of health impact at scale through efficient investments. We have previously offered that sustainability-a necessary condition for successful expansion of programmes-can be addressed in practical terms. Based on benchmarks from actual child survival projects, we assess the expected impact of translating pro-sustainability choices into investment strategies. We review the experience of Save the Children US in Guinea in terms of investment, approach to sustainability and impact. It offers three benchmarks for impact: Entry project (21 lives saved of children under age five per US$100 000), Expansion project (37 LS/US$100k), and Continuation project (100 LS/US$100k). Extrapolating this experience, we model the impact of a traditional investment scenario against a pro-sustainability scenario and compare the deaths averted per dollar spent over five project cycles. The impact per dollar spent on a pro-sustainability strategy is 3.4 times that of a traditional one over the long run (range from 2.2 to 5.7 times in a sensitivity analysis). This large efficiency differential between two investment approaches offers a testable hypothesis for large-scale/long-term studies. The 'bang for the buck' of health programmes could be greatly increased by following a pro-sustainability investment strategy.

  16. DL-PRO: A Novel Deep Learning Method for Protein Model Quality Assessment.

    PubMed

    Nguyen, Son P; Shang, Yi; Xu, Dong

    2014-07-01

    Computational protein structure prediction is very important for many applications in bioinformatics. In the process of predicting protein structures, it is essential to accurately assess the quality of generated models. Although many single-model quality assessment (QA) methods have been developed, their accuracy is not high enough for most real applications. In this paper, a new approach based on C-α atoms distance matrix and machine learning methods is proposed for single-model QA and the identification of native-like models. Different from existing energy/scoring functions and consensus approaches, this new approach is purely geometry based. Furthermore, a novel algorithm based on deep learning techniques, called DL-Pro, is proposed. For a protein model, DL-Pro uses its distance matrix that contains pairwise distances between two residues' C-α atoms in the model, which sometimes is also called contact map, as an orientation-independent representation. From training examples of distance matrices corresponding to good and bad models, DL-Pro learns a stacked autoencoder network as a classifier. In experiments on selected targets from the Critical Assessment of Structure Prediction (CASP) competition, DL-Pro obtained promising results, outperforming state-of-the-art energy/scoring functions, including OPUS-CA, DOPE, DFIRE, and RW.

  17. Reconciling Faith and Fact: Pro-life Women Discuss Media, Science and the Abortion Debate.

    ERIC Educational Resources Information Center

    Press, Andrea L.; Cole, Elizabeth R.

    1995-01-01

    Finds that pro-life women actively searched for authorities and authoritative information that were not "corrupted" by the values of secular society. Finds that, paradoxically, they drew on secular forms of argument, claiming scientific authenticity for their own sources, and that their selective viewing habits resulted in the…

  18. 24 CFR 203.268 - Pro rata payment of periodic MIP.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Pro rata payment of periodic MIP. 203.268 Section 203.268 Housing and Urban Development Regulations Relating to Housing and...

  19. 24 CFR 203.319 - Pro rata payment of premiums and charges.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Pro rata payment of premiums and charges. 203.319 Section 203.319 Housing and Urban Development Regulations Relating to Housing and...

  20. 24 CFR 203.319 - Pro rata payment of premiums and charges.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Pro rata payment of premiums and charges. 203.319 Section 203.319 Housing and Urban Development Regulations Relating to Housing and...

  1. 24 CFR 203.268 - Pro rata payment of periodic MIP.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Pro rata payment of periodic MIP. 203.268 Section 203.268 Housing and Urban Development Regulations Relating to Housing and...

  2. 24 CFR 203.319 - Pro rata payment of premiums and charges.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Pro rata payment of premiums and charges. 203.319 Section 203.319 Housing and Urban Development Regulations Relating to Housing and...

  3. 24 CFR 203.268 - Pro rata payment of periodic MIP.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Pro rata payment of periodic MIP. 203.268 Section 203.268 Housing and Urban Development Regulations Relating to Housing and...

  4. 24 CFR 203.319 - Pro rata payment of premiums and charges.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Pro rata payment of premiums and charges. 203.319 Section 203.319 Housing and Urban Development Regulations Relating to Housing and...

  5. 24 CFR 203.268 - Pro rata payment of periodic MIP.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Pro rata payment of periodic MIP. 203.268 Section 203.268 Housing and Urban Development Regulations Relating to Housing and...

  6. 24 CFR 203.268 - Pro rata payment of periodic MIP.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Pro rata payment of periodic MIP. 203.268 Section 203.268 Housing and Urban Development Regulations Relating to Housing and...

  7. 24 CFR 203.319 - Pro rata payment of premiums and charges.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Pro rata payment of premiums and charges. 203.319 Section 203.319 Housing and Urban Development Regulations Relating to Housing and...

  8. Rap2b, a novel p53 target, regulates p53-mediated pro-survival function

    PubMed Central

    Zhang, Xinyue; He, Yunlong; Lee, Kyoung-Hwa; Dubois, Wendy; Li, Ziqing; Wu, Xiaolin; Kovalchuk, Alexander; Zhang, Weimin; Huang, Jing

    2013-01-01

    The tumor suppressor p53 is a critical regulator of apoptosis and cell cycle arrest/pro-survival. Upon DNA damage, p53 evokes both cell cycle arrest/pro-survival and apoptosis transcriptional programs. The ultimate cellular outcome depends on the balance of these two programs. However, the p53 downstream targets that mediate this cell fate decision remain to be identified. Using an integrative genomic approach, we identify Rap2b as a conserved p53-activated gene that counters p53-mediated apoptosis after DNA damage. Upon DNA damage, p53 directly binds to the promoter of Rap2b and activates its transcription. The reduction of Rap2b levels by small interference RNA sensitizes cells to DNA damage-induced apoptosis in a p53-dependent manner. Consistent with its pro-survival function, analysis of cancer genomic data reveals that Rap2b is overexpressed in many types of tumors. Anchorage-independent growth assays show that Rap2b has only weak transformation activity, suggesting that it is not an oncogene by itself. Together, our results identify Rap2b as a new player in the pro-survival program conducted by p53 and raise the possibility that targeting Rap2b could sensitize tumor cells to apoptosis in response to DNA damage. PMID:23535297

  9. Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells

    SciTech Connect

    Del Regno, Marisanta; Adesso, Simona; Popolo, Ada; Quaroni, Andrea; Autore, Giuseppina; Severino, Lorella; Marzocco, Stefania

    2015-06-01

    Mycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern. - Highlights: • Nivalenol induces oxidative stress in intestinal epithelial cells (IECs). • Nivalenol increases deoxynivalenol pro-oxidant effects in IECs. • Nivalenol and deoxynivalenol trigger antioxidant response IECs. • These results indicate the importance of mycotoxins co-contamination.

  10. 24 CFR 220.806 - Pro rata refund of insurance premium.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... AUTHORITIES MORTGAGE INSURANCE AND INSURED IMPROVEMENT LOANS FOR URBAN RENEWAL AND CONCENTRATED DEVELOPMENT... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Pro rata refund of insurance premium. 220.806 Section 220.806 Housing and Urban Development Regulations Relating to Housing and...

  11. 24 CFR 220.806 - Pro rata refund of insurance premium.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... AUTHORITIES MORTGAGE INSURANCE AND INSURED IMPROVEMENT LOANS FOR URBAN RENEWAL AND CONCENTRATED DEVELOPMENT... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Pro rata refund of insurance premium. 220.806 Section 220.806 Housing and Urban Development Regulations Relating to Housing and...

  12. 24 CFR 220.806 - Pro rata refund of insurance premium.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... AUTHORITIES MORTGAGE INSURANCE AND INSURED IMPROVEMENT LOANS FOR URBAN RENEWAL AND CONCENTRATED DEVELOPMENT... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Pro rata refund of insurance premium. 220.806 Section 220.806 Housing and Urban Development Regulations Relating to Housing and...

  13. 24 CFR 220.806 - Pro rata refund of insurance premium.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... AUTHORITIES MORTGAGE INSURANCE AND INSURED IMPROVEMENT LOANS FOR URBAN RENEWAL AND CONCENTRATED DEVELOPMENT... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Pro rata refund of insurance premium. 220.806 Section 220.806 Housing and Urban Development Regulations Relating to Housing and...

  14. Imagination, Hope and the Positive Face of Feminism: Pro/Feminist Pedagogy in "Post" Feminist Times?

    ERIC Educational Resources Information Center

    Lambert, Cath; Parker, Andrew

    2006-01-01

    This article presents an analysis of the way in which a group of students at one UK university mobilised their interest in and commitment to pro/feminist values and ideals through the establishment of a student society geared towards combating anti-sexism. Placing the students at the centre of the discussion, the article describes the various…

  15. Urolithins display both antioxidant and pro-oxidant activities depending on assay system and conditions.

    PubMed

    Kallio, Tuija; Kallio, Johanna; Jaakkola, Mari; Mäki, Marianne; Kilpeläinen, Pekka; Virtanen, Vesa

    2013-11-13

    The biological effects of polyphenolic ellagitannins are mediated by their intestinal metabolites, urolithins. This study investigated redox properties of urolithins A and B using ORAC assay, three cell-based assays, copper-initiated pro-oxidant activity (CIPA) assay, and cyclic voltammetry. Urolithins were strong antioxidants in the ORAC assay, but mostly pro-oxidants in cell-based assays, although urolithin A was an antioxidant in cell culture medium. Parent compound ellagic acid was a strong extracellular antioxidant, but showed no response in the intracellular assay. The CIPA assay confirmed the pro-oxidant activity of ellagitannin metabolites. In the cell proliferation assay, urolithins but not ellagic acid decreased growth and metabolism of HepG2 liver cells. In cyclic voltammetry, the oxidation of urolithin A was partly reversible, but that of urolithin B was irreversible. These results illustrate how strongly measured redox properties depend on the employed assay system and conditions and emphasize the importance of studying pro-oxidant and antioxidant activities in parallel.

  16. Pro-Am Cooperation for the Reporting of Unusual Observations in the Atmosphere

    NASA Astrophysics Data System (ADS)

    Ailleris, P.

    2011-10-01

    During this presentation, we will provide an overview of the project, highlighting the latest results, infrastructure and outreach activities. We will stress the current status of the Pro-Am cooperation; explore possible future plans for strengthening the visibility and relevance of the project, while requesting feedback from the community of planetary scientists.

  17. 17 CFR 240.16a-9 - Stock splits, stock dividends, and pro rata rights.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Stock splits, stock dividends... Government Securities Dealers § 240.16a-9 Stock splits, stock dividends, and pro rata rights. The following... held as a result of a stock split or stock dividend applying equally to all securities of a...

  18. 17 CFR 240.16a-9 - Stock splits, stock dividends, and pro rata rights.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Stock splits, stock dividends... Government Securities Dealers § 240.16a-9 Stock splits, stock dividends, and pro rata rights. The following... held as a result of a stock split or stock dividend applying equally to all securities of a...

  19. 17 CFR 240.16a-9 - Stock splits, stock dividends, and pro rata rights.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Stock splits, stock dividends... Government Securities Dealers § 240.16a-9 Stock splits, stock dividends, and pro rata rights. The following... held as a result of a stock split or stock dividend applying equally to all securities of a...

  20. 17 CFR 240.16a-9 - Stock splits, stock dividends, and pro rata rights.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Stock splits, stock dividends... Government Securities Dealers § 240.16a-9 Stock splits, stock dividends, and pro rata rights. The following... held as a result of a stock split or stock dividend applying equally to all securities of a...

  1. 17 CFR 240.16a-9 - Stock splits, stock dividends, and pro rata rights.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Stock splits, stock dividends... Government Securities Dealers § 240.16a-9 Stock splits, stock dividends, and pro rata rights. The following... held as a result of a stock split or stock dividend applying equally to all securities of a...

  2. Naloxone pro-drug rescues morphine induced respiratory depression in Sprague-Dawley rats.

    PubMed

    Wallisch, Michael; El Rody, Nehad M; Huang, Baohua; Koop, Dennis R; Baker, James R; Olsen, George D

    2012-01-15

    Respiratory depression is the main obstacle for the safe administration of morphine for acute pain after injury. Due to this complication, new delivery methods are needed to insure that safe and effective doses of opioid analgesics are administered during emergencies. A depot formulation containing a naloxone pro-drug was designed to release the antidote when morphine causes dangerous hypoxic conditions in the blood. The aim of this work was to test the naloxone release in vivo in response to a severe overdose of morphine in the Sprague-Dawley rat model. Non-invasive two-chamber plethysmography was used to monitor and record respiration and to test the capability of the naloxone pro-drug to respond to and rescue morphine-induced respiratory depression in the animal. We show that the pro-drug formulation can both prevent and reverse severe morphine induced respiratory depression. The animal model demonstrates that co-administration of the naloxone pro-drug reliably antagonizes profound respiratory depressive effects of morphine.

  3. HAP-PRO USER'S MANUAL (FOR USE WITH VERSION 1.0)

    EPA Science Inventory

    The primary purpose of the Hazardous Air Pollutant Program (HAP-PRO) is to assist permit engineers in reviewing applications for control of air toxics by calculating the capital and annual costs for 6 volatile organic compound (VOC) and 3 different particulate control devices, i...

  4. The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention.

    PubMed

    Lambert, Joshua D; Elias, Ryan J

    2010-09-01

    Green tea (Camellia sinensis) is rich in catechins, of which (-)-epigallocatechin-3-gallate (EGCG) is the most abundant. Studies in animal models of carcinogenesis have shown that green tea and EGCG can inhibit tumorigenesis during the initiation, promotion and progression stages. Many potential mechanisms have been proposed including both antioxidant and pro-oxidant effects, but questions remain regarding the relevance of these mechanisms to cancer prevention. In the present review, we will discuss the redox chemistry of the tea catechins and the current literature on the antioxidant and pro-oxidative effects of the green tea polyphenols as they relate to cancer prevention. We report that although the catechins are chemical antioxidants which can quench free radical species and chelate transition metals, there is evidence that some of the effects of these compounds may be related to induction of oxidative stress. Such pro-oxidant effects appear to be responsible for the induction of apoptosis in tumor cells. These pro-oxidant effects may also induce endogenous antioxidant systems in normal tissues that offer protection against carcinogenic insult. This review is meant point out understudied areas and stimulate research on the topic with the hope that insights into the mechanisms of cancer preventive activity of tea polyphenols will result.

  5. CanProVar 2.0: An Updated Database of Human Cancer Proteome Variation.

    PubMed

    Zhang, Menghuan; Wang, Bo; Xu, Jia; Wang, Xiaojing; Xie, Lu; Zhang, Bing; Li, Yixue; Li, Jing

    2017-02-03

    Identification and annotation of the mutations involved in oncogenesis and tumor progression are crucial for both cancer biology and clinical applications. Previously, we developed a public resource CanProVar, a human cancer proteome variation database for storing and querying single amino acid alterations in the human cancers. Since the publication of CanProVar, extensive cancer genomics efforts have revealed the enormous genomic complexity of various types of human cancers. Thus, there is an overwhelming need for comprehensive annotation of the genomic alterations at the protein level and making such knowledge easily accessible. Here, we describe CanProVar 2.0, a significantly expanded version of CanProVar, in which the amount of cancer-related variations and noncancer specific variations was increased by about 10-fold as compared to the previous version. To facilitate the interpretation of the variations, we added to the database functional data on potential impact of the cancer-related variations on 3D protein interaction and on the differential expression of the variant-bearing proteins between cancer and normal samples. The web interface allows for flexible queries based on gene or protein IDs, cancer types, chromosome locations, or pathways. An integrated protein sequence database containing variations that can be directly used for proteomics database searching can be downloaded.

  6. Questions and Answers on Gift Substantiation and Quid Pro Quo Disclosure Statement Requirements for Private Schools.

    ERIC Educational Resources Information Center

    United States Catholic Conference, Washington, DC.

    This publication is a guide to recent tax law changes affecting requirements about acknowledging gifts to education institutions and about quid pro quo disclosure. The Omnibus Budget Reconciliation Act of 1993 states that donors may not deduct cash or noncash contributions of $250 or more to a private school or other charitable organization unless…

  7. Personal and social factors that influence pro-environmental concern and behaviour: a review.

    PubMed

    Gifford, Robert; Nilsson, Andreas

    2014-06-01

    We review the personal and social influences on pro-environmental concern and behaviour, with an emphasis on recent research. The number of these influences suggests that understanding pro-environmental concern and behaviour is far more complex than previously thought. The influences are grouped into 18 personal and social factors. The personal factors include childhood experience, knowledge and education, personality and self-construal, sense of control, values, political and world views, goals, felt responsibility, cognitive biases, place attachment, age, gender and chosen activities. The social factors include religion, urban-rural differences, norms, social class, proximity to problematic environmental sites and cultural and ethnic variations We also recognize that pro-environmental behaviour often is undertaken based on none of the above influences, but because individuals have non-environmental goals such as to save money or to improve their health. Finally, environmental outcomes that are a result of these influences undoubtedly are determined by combinations of the 18 categories. Therefore, a primary goal of researchers now should be to learn more about how these many influences moderate and mediate one another to determine pro-environmental behaviour.

  8. Low Cost Private Schooling in India: Is It Pro Poor and Equitable?

    ERIC Educational Resources Information Center

    Harma, Joanna

    2011-01-01

    India has seen an explosion in low-fee private (LFP) schooling aimed at the poorer strata of society, and this once-urban phenomenon has spread in the last decade to rural areas, with implications for equity due to the level of direct costs involved. This study explores whether or not LFP schooling in rural India is pro-poor and equitable, and…

  9. 24 CFR 220.806 - Pro rata refund of insurance premium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AUTHORITIES MORTGAGE INSURANCE AND INSURED IMPROVEMENT LOANS FOR URBAN RENEWAL AND CONCENTRATED DEVELOPMENT... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Pro rata refund of insurance premium. 220.806 Section 220.806 Housing and Urban Development Regulations Relating to Housing and...

  10. Pro-Social Behaviour and Behaviour Problems Independently Predict Maternal Stress

    ERIC Educational Resources Information Center

    Beck, Alexandra; Hastings, Richard; Daley, Dave; Stevenson, Jim

    2004-01-01

    Parents of children with intellectual and developmental disabilities generally report more stress than other parents. Child behavioural features, and specifically their behaviour problems, have been shown to account for some of the variation in parents' experience of stress. However, there has been no exploration of whether the child's pro-social…

  11. Sampling of adult mosquito vectors with Mosquito Magnet Pro in Panaji, Goa, India.

    PubMed

    Korgaonkar, Nandini S; Kumar, Ashwani; Yadav, Rajpal S; Kabadi, Dipak; Dash, Aditya P

    2008-12-01

    For mosquito vector population monitoring, a new commercial trap, Mosquito Magnet Pro (MM-PRO), was tested for its usefulness in Goa, India. Anopheles stephensi was tested for the presence of Plasmodium sporozoite infection in the salivary glands. Using the MM-PRO 24 h a day for 34 days, 2,329 mosquitoes belonging to 16 species were collected. These included 6 species each of the genera Anopheles and Culex, 2 species of Aedes, and 1 each of Mansonia and Armigeres. Most (91%) of the mosquitoes caught were females. Among these the number and percentage of each species were Anopheles stephensi 59 (2.78%), Culex quinquefasciatus 1013 (47.78%), Culex vishnui 551 (26.0%), Mansonia uniformis 216 (10.19%), and Aedes albopictus 1 (0.04%). Of the 54 An. stephensi females tested for the presence of circumsporozoite protein (CSP) by an ELISA technique, 1 was found to be Plasmodium falciparum CSP positive. The MM-PRO device was found useful for mosquito population sampling in the urban setting of Goa.

  12. Data Independent Acquisition analysis in ProHits 4.0.

    PubMed

    Liu, Guomin; Knight, James D R; Zhang, Jian Ping; Tsou, Chih-Chiang; Wang, Jian; Lambert, Jean-Philippe; Larsen, Brett; Tyers, Mike; Raught, Brian; Bandeira, Nuno; Nesvizhskii, Alexey I; Choi, Hyungwon; Gingras, Anne-Claude

    2016-10-21

    Affinity purification coupled with mass spectrometry (AP-MS) is a powerful technique for the identification and quantification of physical interactions. AP-MS requires careful experimental design, appropriate control selection and quantitative workflows to successfully identify bona fide interactors amongst a large background of contaminants. We previously introduced ProHits, a Laboratory Information Management System for interaction proteomics, which tracks all samples in a mass spectrometry facility, initiates database searches and provides visualization tools for spectral counting-based AP-MS approaches. More recently, we implemented Significance Analysis of INTeractome (SAINT) within ProHits to provide scoring of interactions based on spectral counts. Here, we provide an update to ProHits to support Data Independent Acquisition (DIA) with identification software (DIA-Umpire and MSPLIT-DIA), quantification tools (through DIA-Umpire, or externally via targeted extraction), and assessment of quantitative enrichment (through mapDIA) and scoring of interactions (through SAINT-intensity). With additional improvements, notably support of the iProphet pipeline, facilitated deposition into ProteomeXchange repositories and enhanced export and viewing functions, ProHits 4.0 offers a comprehensive suite of tools to facilitate affinity proteomics studies.

  13. [Minus]Plastic: Influencing Pro-Environmental Attitudes among Singaporean Youth

    ERIC Educational Resources Information Center

    Chib, Arul; Chiew, Han Joo; Kumar, Chitraveni; Choon, Lim Geok; Ale, Komathi

    2009-01-01

    Plastics have much to offer as a modern convenience, but lack of responsible plastic waste management habits can lead to potentially harmful environmental effects. Past environmental initiatives revealed a lack of understanding about youth attitudes towards pro-environmental issues. [minus]plastic, an online public environmental promotional…

  14. Going "Above and Beyond": Are Those High in Autistic Traits Less Pro-Social?

    ERIC Educational Resources Information Center

    Jameel, Leila; Vyas, Karishma; Bellesi, Giulia; Roberts, Victoria; Channon, Shelley

    2014-01-01

    Few studies have explored how the cognitive differences associated with autistic spectrum disorder translate into everyday social behaviour. This study investigated pro-social behaviour in students scoring high and low on the autism-spectrum quotient (AQ), using a novel scenario task: "Above and Beyond." Each scenario involved an…

  15. Pro-Social Behavior Amongst Students of Tertiary Institutions: An Explorative and a Quantitative Approach

    ERIC Educational Resources Information Center

    Quain, Samuel; Yidana, Xiaaba Dantallah; Ambotumah, Bernard Baba; Mensah-Livivnstone, Ike Joe Nii Annang

    2016-01-01

    The purpose of this paper was to explore antecedents of pro-social behavior amongst university students, using a private university as a case study. Following an explorative research, the study was guided by some theories relating to the phenomenon, focusing on gender and location factors. A quantitative approach was used in the follow up to the…

  16. Pro-apoptotic cell death genes, hid and reaper, from the tephritid pest species, Anastrepha suspensa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pro-apoptotic proteins from the reaper, hid, grim (RHG) family are primary regulators of programmed cell death in Drosophila due to their antagonistic effect on inhibitor of apoptosis (IAP) proteins, thereby releasing IAP inhibition of caspases that effect apoptosis. Using a degenerate PCR approach ...

  17. N(pro) fusion technology: On-column complementation to improve efficiency in biopharmaceutical production.

    PubMed

    Schindler, S; Missbichler, B; Walther, C; Sponring, M; Cserjan-Puschmann, M; Auer, B; Schneider, R; Dürauer, A

    2016-04-01

    N(pro) fusion technology, a highly efficient system for overexpression of proteins and peptides in Escherichia coli, was further developed by splitting the autoprotease N(pro) into two fragments to generate a functional complementation system. The size of the expression tag is thus reduced from 168 to 58 amino acids, so by 66%. Upon complementation of the fragments auto-proteolytic activity is restored. This process has been shown for three model proteins of different size, a short 16 aa-peptide, MCP-1, and lysozyme. Moreover, the complementation was still functional after immobilization of the N-terminal fragment to a solid support which enables recycling of the immobilized fragment. This strategy enhances overall productivity of N(pro) Fusion Technology and thus allows more efficient production of recombinant proteins with reduced costs and in higher yields. Overall, the N(pro) complementation system has, depending on the size of the target molecule, potential to increase the productivity up to 4 fold for batch refolding and even more for on-column refolding strategies by the proven possibility of regeneration of the immobilized fragment.

  18. The Sensorial Effect: Dynamics of Emotion in Pro-Environmental Behavior

    ERIC Educational Resources Information Center

    Hipolito, Joana

    2011-01-01

    In this article, sensorial effects are introduced as emotional stimuli for shaping environmentally significant behaviors. This research provides a link between sensorial effect as ubiquitous environmental behavior feedback and the effect of sensorial stimuli on emotions that trigger individuals' pro-environment behavior. A case study of using…

  19. Think Leader, Think White? Capturing and Weakening an Implicit Pro-White Leadership Bias

    PubMed Central

    Gündemir, Seval; Homan, Astrid C.; de Dreu, Carsten K. W.; van Vugt, Mark

    2014-01-01

    Across four studies, we found evidence for an implicit pro-White leadership bias that helps explain the underrepresentation of ethnic minorities in leadership positions. Both White-majority and ethnic minority participants reacted significantly faster when ethnically White names and leadership roles (e.g., manager; Study 1) or leadership traits (e.g., decisiveness; Study 2 & 3) were paired in an Implicit Association Test (IAT) rather than when ethnic minority names and leadership traits were paired. Moreover, the implicit pro-White leadership bias showed discriminant validity with the conventional implicit bias measures (Study 3). Importantly, results showed that the pro-White leadership bias can be weakened when situational cues increase the salience of a dual identity (Study 4). This, in turn, can diminish the explicit pro-White bias in promotion related decision making processes (Study 4). This research offers a new tool to measure the implicit psychological processes underlying the underrepresentation of ethnic minorities in leadership positions and proposes interventions to weaken such biases. PMID:24416181

  20. Self-respect and pro-relationship behavior in marital relationships.

    PubMed

    Kumashiro, Madoka; Finkel, Eli J; Rusbult, Caryl E

    2002-12-01

    This work advances an interdependence theoretic analysis of the role of self-respect in ongoing close relationships. Self-respect is defined as the tendency to perceive the self as a principled person who is worthy of honor and high regard and is argued to rest on moral integrity. Consistent with predictions, results from a study of marital relationships revealed that individual self-respect is positively associated with both the individual's and the partner's pro-relationship behavior (accommodation, forgiveness, conciliation). Mediation analyses revealed that self-respect not only exhibits direct associations with each person's behavior, but also exhibits indirect associations with each person's behavior, via the impact of each person's actions on reciprocal pro-relationship behavior from the partner. Mediation was more reliably observed for the association of self-respect with partner behavior than for the association with individual behavior. Both individual pro-relationship behavior and partner pro-relationship behavior are positively associated with couple well-being, which in turn is positively associated with personal well-being (life satisfaction, physical health, psychological adjustment). These associations were evident in both within-participant and across-partner analyses and for both self-report and interaction-based measures of behavior. Self-respect reliably accounts for unique variance beyond variance attributable to self-esteem.

  1. 26 CFR 1.355-4 - Non pro rata distributions, etc.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) INCOME TAXES Effects on Shareholders and Security Holders § 1.355-4 Non pro rata distributions... transaction is merely an exchange between shareholders or security holders of stock or securities in one corporation for stock or securities in another corporation. For example, if two individuals, A and B, each...

  2. 26 CFR 1.355-4 - Non pro rata distributions, etc.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) INCOME TAXES (CONTINUED) Effects on Shareholders and Security Holders § 1.355-4 Non pro rata... substance of a transaction is merely an exchange between shareholders or security holders of stock or securities in one corporation for stock or securities in another corporation. For example, if two...

  3. 26 CFR 1.355-4 - Non pro rata distributions, etc.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) INCOME TAXES (CONTINUED) Effects on Shareholders and Security Holders § 1.355-4 Non pro rata... substance of a transaction is merely an exchange between shareholders or security holders of stock or securities in one corporation for stock or securities in another corporation. For example, if two...

  4. 26 CFR 1.355-4 - Non pro rata distributions, etc.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) INCOME TAXES Effects on Shareholders and Security Holders § 1.355-4 Non pro rata distributions... transaction is merely an exchange between shareholders or security holders of stock or securities in one corporation for stock or securities in another corporation. For example, if two individuals, A and B, each...

  5. 26 CFR 1.355-4 - Non pro rata distributions, etc.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) INCOME TAXES (Continued) Effects on Shareholders and Security Holders § 1.355-4 Non pro rata... substance of a transaction is merely an exchange between shareholders or security holders of stock or securities in one corporation for stock or securities in another corporation. For example, if two...

  6. Promoting Pro-Environmental Printing Behavior: The Role of ICT Barriers and Sustainable Values

    ERIC Educational Resources Information Center

    Suleri, Javed; Cavagnaro, Elena

    2016-01-01

    This study aims to explore how to reduce printing at elementary schools through strengthening both the effective use of ICT and pro-environmental values. Literature review is presented in themes--ICT barriers (fears, knowledge, skills and time), demographic, printing behavior and sustainable values (egoistic, hedonic, prosocial & biospheric).…

  7. A Pro Bono Relationship Works: But an Agreement, Patience, and Understanding Help.

    ERIC Educational Resources Information Center

    Girouard, Nancy

    1984-01-01

    The world's largest public relations firm brought Humphrey Institute into contact with skilled special events professionals, fund raisers, and promotional strategists, and they didn't have to pay for their services. As pro bono consultants, the firm and the institute have learned to respect each other's needs and different agendas. (MLW)

  8. The CONSORT Patient-Reported Outcome (PRO) extension: implications for clinical trials and practice

    PubMed Central

    2013-01-01

    To inform clinical guidelines and patient care we need high quality evidence on the relative benefits and harms of intervention. Patient reported outcome (PRO) data from clinical trials can “empower patients to make decisions based on their values” and “level the playing field between physician and patient”. While clinicians have a good understanding of the concept of health-related quality of life and other PROs, evidence suggests that many do not feel comfortable in using the data from trials to inform discussions with patients and clinical practice. This may in part reflect concerns over the integrity of the data and difficulties in interpreting the results arising from poor reporting. The new CONSORT PRO extension aims to improve the reporting of PROs in trials to facilitate the use of results to inform clinical practice and health policy. While the CONSORT PRO extension is an important first step in the process, we need broader engagement with the guidance to facilitate optimal reporting and maximize use of PRO data in a clinical setting. Endorsement by journal editors, authors and peer reviewers are crucial steps. Improved design, implementation and transparent reporting of PROs in clinical trials are necessary to provide high quality evidence to inform evidence synthesis and clinical practice guidelines. PMID:24168680

  9. "We Don't Know Enough": Environmental Education and Pro-Environmental Behaviour Perceptions

    ERIC Educational Resources Information Center

    Ajaps, Sandra; McLellan, Ros

    2015-01-01

    This study sought to understand environmental knowledge and attitudes among young people to explain the relationship between environmental education (EE) and reported pro-environmental behaviours (PEB). A mixed-methods design was employed: 88 university students in the UK and Nigeria were surveyed and 6 were subsequently interviewed. The findings…

  10. Molecular and cellular characterization of the tomato pollen profilin, LePro1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Profilin is an actin-binding protein involved in the dynamic turnover and restructuring of the actin cytoskeleton in all eukaryotic cells. We previously cloned a profilin gene, designated as LePro1 from tomato pollen. To investigate its biological role, in the present study, We investigated the tem...

  11. Promoting Pro-Environmental Behaviour: Collection of Used Batteries by Secondary School Pupils

    ERIC Educational Resources Information Center

    Rioux, Liliane

    2011-01-01

    This research is based on Kollmuss and Agyeman's mode, and aims to determine if the prerequisites for pro-environmental behaviour, such as the collection of used batteries at school, are ethical, cognitive and environmental. A questionnaire/opinionnaire was given to 102, 14-17-year-olds to gather data on: (1) their current recycling habits, (2)…

  12. Teacher Mobility and Financial Incentives: A Descriptive Analysis of Denver's ProComp

    ERIC Educational Resources Information Center

    Fulbeck, Eleanor S.

    2014-01-01

    Extensive teacher mobility can undermine policy efforts to develop a high-quality workforce. In response, policymakers have increasingly championed financial incentives to retain teachers. In 2006, the Denver Public Schools adopted an alternative teacher compensation reform, the Professional Compensation System for Teachers ("ProComp").…

  13. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors.

    PubMed

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-08-02

    Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  14. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mice lacking 5-HT 2C receptors displayed hepatic insulin resistance, a phenotype normalized by re-expression of 5-HT2CRs only in pro-opiomelanocortin (POMC) neurons. 5-HT2CR deficiency also abolished the anti-diabetic effects of meta-chlorophenylpiperazine (a 5-HT2CR agonist); these effects were re...

  15. Preschool Children's Understanding of Pro-Environmental Behaviours: Is It Too Hard for Them?

    ERIC Educational Resources Information Center

    Kos, Marjanca; Jerman, Janez; Anžlovar, Urška; Torkar, Gregor

    2016-01-01

    Early childhood is a period of life in which lifelong attitudes, values and patterns of behaviour regarding nature are shaped. Environmental education is becoming a growing area of interest in early childhood education. The aim of the research study was to identify children's understanding of why and how their pro-environmental behaviours…

  16. Creating Well-Being: Increased Creativity and proNGF Decrease following Quadrato Motor Training.

    PubMed

    Venditti, Sabrina; Verdone, Loredana; Pesce, Caterina; Tocci, Nicoletta; Caserta, Micaela; Ben-Soussan, Tal Dotan

    2015-01-01

    Mind-body practices (MBP) are known to induce electrophysiological and morphological changes, whereas reports related to changes of neurotrophins are surprisingly scarce. Consequently, in the current paper, we focused on the Quadrato motor training (QMT), a newly developed whole-body movement-based MBP, which has been reported to enhance creativity. Here we report the effects of 4 weeks of daily QMT on creativity and proNGF level in two interrelated studies. In Study A, we examined the effects of QMT compared with a walking training (WT) in healthy adults, utilizing the alternate uses task. In contrast with the WT, QMT resulted in increased creativity. In addition, the change in creativity negatively correlated with the change in proNGF levels. In Study B, we examined QMT effects on creativity and additional metacognitive functions in children, using a nonintervention group as control. Similar to Study A, following QMT, we found a negative correlation of proNGF with creativity, as well as working memory updating and planning ability. Together, the current results point to the relationship between increased creativity and decreased proNGF following MBP. Thus, the current research emphasizes the importance of widening the scope of examination of "MBP in motion" in relation to metacognition and well-being.

  17. University Students' Subjective Knowledge of Green Computing and Pro-Environmental Behavior

    ERIC Educational Resources Information Center

    Ahmad, Tunku Badariah Tunku; Nordin, Mohamad Sahari

    2014-01-01

    This cross-sectional survey examined the structure of university students' subjective knowledge of green computing--hypothesized to be a multidimensional construct with three important dimensions--and its association with pro-environmental behavior (PEB). Using a previously validated green computing questionnaire, data were collected from 842…

  18. Legal Bans on Pro-Suicide Web Sites: An Early Retrospective from Australia

    ERIC Educational Resources Information Center

    Pirkis, Jane; Neal, Luke; Dare, Andrew; Blood, R. Warwick; Studdert, David

    2009-01-01

    There are worldwide concerns that pro-suicide web sites may trigger suicidal behaviors among vulnerable individuals. In 2006, Australia became the first country to criminalize such sites, sparking heated debate. Concerns were expressed that the law casts the criminal net too widely; inappropriately interferes with the autonomy of those who wish to…

  19. Amino-terminal pro-brain natriuretic peptide in children with latent rheumatic heart disease

    PubMed Central

    Zachariah, Justin P; Aliku, Twalib; Scheel, Amy; Hasan, Babar S; Lwabi, Peter; Sable, Craig; Beaton, Andrea Z

    2016-01-01

    Background: Rheumatic heart disease (RHD) is a global cause of early heart failure. Early RHD is characterized by valvar regurgitation, leading to ventricular distention and possible elaboration of amino-terminal pro-brain natriuretic peptide (NT-proBNP). We investigated the ability of NT-proBNP to distinguish cases of latent RHD detected by echocardiographic screening from the controls. Materials and Methods: Ugandan children (N = 44, 36% males, mean age: 12 ± 2 years) with latent RHD (cases) and siblings (controls) by echocardiography were enrolled. Cases and controls were matched for age and sex, and they had normal hemoglobin (mean: 12.8 mg/dL). Children with congenital heart disease, pregnancy, left ventricular dilation or ejection fraction (EF) below 55%, or other acute or known chronic health conditions were excluded. RHD cases were defined by the World Heart Federation (WHF) 2012 consensus guideline criteria as definite. Controls had no echocardiography (echo) evidence for RHD. At the time of echo, venous blood samples were drawn and stored as serum. NT-proBNP levels were measured using sandwich immunoassay. Paired t-tests were used to compare NT-proBNP concentrations including sex-specific analyses. Results: The mean NT-proBNP concentration in the cases was 105.74 ± 67.21 pg/mL while in the controls, it was 86.63 ± 55.77 pg/mL. The cases did not differ from the controls (P = 0.3). In sex-specific analyses, male cases differed significantly from the controls (158.78 ± 68.82 versus 76 ± 42.43, P = 0.008). Female cases did not differ from the controls (75.44 ± 45.03 versus 92.30 ± 62.35 respectively, P = 0.4). Conclusion: Serum NT-proBNP did not distinguish between latent RHD cases and the controls. Sex and within-family exposures may confound this result. More investigation into biomarker-based RHD detection is warranted. PMID:27212845

  20. The killing of neurons by beta-amyloid peptides, prions, and pro-inflammatory cytokines.

    PubMed

    Chiarini, Anna; Dal Pra, Ilaria; Whitfield, James F; Armato, Ubaldo

    2006-01-01

    Reportedly, beta-amyloid peptides (Abeta40 and Abeta42) induce the neurodegenerative changes of Alzheimer's disease (AD) both directly by interacting with components of the cell surface to trigger apoptogenic signaling and indirectly by activating astrocytes and microglia to produce excess amounts of inflammatory cytokines. A possible cell surface target for Abetas is the p75 neurotrophin receptor (p75(NTR)). By using SK-N-BE neuroblastoma cells without neurotrophin receptors or engineered to express the full-length p75(NTR) or various parts of it, we have proven that p75(NTR) does mediate the Abeta-induced cell killing via its intracellular death domain (DD). This signaling via the DD activates caspase-8, which then activates caspase-3 and apoptogenesis. We also found a strong cytocidal interaction of direct p75(NTR)-mediated and indirect pro-inflammatory cytokine-mediated neuronal damage induced by Abeta. In fact, pro-inflammatory cytokines such as TNF-alpha and IL-1beta from Abeta-activated microglia potentiated the neurotoxic action of Aalpha mediated by p75(NTR) signaling. The pro-inflammatory cytokines probably amplify neuronal damage and killing by causing astrocytes to flood their associated neurons with NO and its lethal oxidizing ONOO- derivative. Indeed, we have found that a combination of three major pro-inflammatory cytokines, IL-1beta+IFN-gamma+TNF-alpha, causes normal adult human astrocytes (NAHA) to express nitric oxide synthase-2 (NOS-2) and make dangerously large amounts of NO via mitogen-activated protein kinases (MAPKs). Soluble Abeta40, the major amyloid precursor protein cleavage product, by itself stimulates astrocytes to express NOS-2 and make NO, possibly by activating p75(NTR) receptors, which they share with neurons, and can considerably amplify NOS-2 expression by the pro-inflammatory cytokine trio. These observations have uncovered a deadly synergistic interaction of Abeta peptides with pro-inflammatory cytokines in the neuron

  1. Comparison of the Lactate Pro and Analox GM7 blood lactate analysers.

    PubMed

    van Someren, K A; Howatson, G; Nunan, D; Thatcher, R; Shave, R

    2005-10-01

    The purpose of this study was firstly, to determine the level of agreement between the Lactate Pro and Analox GM7 for the measurement of blood lactate, and secondly, to examine whether these analysers may be used interchangeably to identify lactate parameters routinely used in the physiological assessment of athletes. Twenty well-trained male cyclists performed an incremental cycle ergometry test; duplicate blood samples were taken simultaneously throughout the test for lactate determination using the two analysers. Power output and heart rate at LT, LT1, 2 mmol.L-1, and 4 mmol.L-1 were calculated from the lactate values obtained from the two analysers. There was a strong linear relationship between the two analysers (Lactate Pro=1.4541xAnalox GM7-0.1287; R2=0.969, p<0.001; SEE=0.704) though the Lactate Pro overestimated blood lactate when compared to the Analox GM7; 95% ratio limits of agreement (Lactate Pro/Analox GM7) were 1.40x//1.35. Differences were found between analysers for power output and heart rate at LT1 (p<0.01), 2 mmol.L-1 (p<0.001), and 4 mmol.L-1 (p<0.001); no differences were found between analysers for power output or heart rate at LT. In conclusion, the average difference in blood lactate concentration measured by the Lactate Pro and the Analox GM7 was 40%, with 95% of measures differing by between 4% and 89%. This poor level of agreement and the significant differences between the two analysers in power output and heart rate associated with a number of lactate parameters indicate that these analysers should not be used interchangeably.

  2. Estradiol inhibits vascular endothelial cells pro-inflammatory activation induced by C-reactive protein.

    PubMed

    Cossette, Émilie; Cloutier, Isabelle; Tardif, Kim; DonPierre, Geneviève; Tanguay, Jean-François

    2013-01-01

    In addition of being an important inflammatory biomarker and a risk factor for cardiovascular disease, much evidence indicates that the C-reactive protein (CRP) contributes to the atherosclerosis development process. This plasmatic protein synthesized by hepatocytes in response to inflammation and tissue injury induces pro-inflammatory molecules' expression by endothelial cells (ECs). Previous studies showed that the 17β-estradiol (E2) has beneficial effects on vascular cells by reducing in vitro pro-inflammatory molecules expressions in EC. Therefore, we hypothesize that E2 blocks or reduces CRP-mediated inflammatory responses by modulating endogenous production of CRP in EC and/or activation mechanisms. Using human aortic ECs (HAECs), we first evaluated CRP production by vascular EC and second demonstrated its self-induction. Indeed, recombinant human CRP stimulation induces a fivefold increase of CRP expression. A 1-h pre-treatment of E2 at a physiologic dose (10(-9 )M) leads to an important decrease of CRP production suggesting a partial blockage of its amplification loop mechanism. Furthermore, in HAEC, E2 reduces the secretion of the most potent agonist of CRP induction, the IL-6, by 21 %. E2 pre-treatment also decreased the expression of pro-inflammatory molecules IL-8, VCAM-1, and ICAM-1 induced by CRP and involved in leukocytes recruitment. In addition, we demonstrated that E2 could restore vascular endothelial growth factor-mediated EC migration response impaired by CRP suggesting another pro-angiogenic property of this hormone. These findings suggest that E2 can interfere with CRP pro-inflammatory effects via activation signals using its rapid, non-genomic pathway that may provide a new mechanism to improve vascular repair.

  3. The Effect of Icing with the Pro-Stim Edema Management System on Cutaneous Cooling

    PubMed Central

    Holcomb, William R.; Mangus, Brent C.; Tandy, Richard

    1996-01-01

    The simultaneous administration of ice, compression, and electrical stimulation is a technique sometimes used to control the magnitude and duration of edema. The Pro-Stim Edema Management System (TKO, Inc, Alameda, CA) was developed to make this simultaneous treatment both simplistic and more effective. The system is designed to be more effective because the stimulating electrodes are incorporated into the fabric of the ice pack thus providing little insulation to cold. The purpose of our study was to test the effectiveness of icing with Pro-Stim on cutaneous cooling by comparing it to ice bag application with conventional stimulator electrodes. Twelve subjects received the ice portion of the two experimental conditions for 30 minutes. Cutaneous temperatures were monitored at two sites: one under the electrode and one away from the electrode (centered between the stimulating electrodes). Temperatures were recorded via surface probes interfaced to digital thermometers each minute for 5 minutes before and after icing and during the 30 minutes of ice application. Temperature data were analyzed with three-way factorial analysis of variance with repeated measures. The administration of ice decreased the temperature for all conditions. However, the temperature under the electrode with Pro-Stim was significantly lower during the treatment period than the temperature under the electrode with the conventional system. Thus, Pro-Stim provides more cooling of the entire treatment area. Further research should include an investigation of the effect of the Pro-Stim Edema Management System on cooling while using electrical stimulation. ImagesFig 1.Fig 2. PMID:16558385

  4. Chitosan drives anti-inflammatory macrophage polarisation and pro-inflammatory dendritic cell stimulation.

    PubMed

    Oliveira, Marta I; Santos, Susana G; Oliveira, Maria J; Torres, Ana L; Barbosa, Mário A

    2012-07-24

    Macrophages and dendritic cells (DC) share the same precursor and play key roles in immunity. Modulation of their behaviour to achieve an optimal host response towards an implanted device is still a challenge. Here we compare the differentiation process and polarisation of these related cell populations and show that they exhibit different responses to chitosan (Ch), with human monocyte-derived macrophages polarising towards an anti-inflammatory phenotype while their DC counterparts display pro-inflammatory features. Macrophages and DC, whose interactions with biomaterials are frequently analysed using fully differentiated cells, were cultured directly on Ch films, rather than exposed to the polymer after complete differentiation. Ch was the sole stimulating factor and activated both macrophages and DC, without leading to significant T cell proliferation. After 10 d on Ch, macrophages significantly down-regulated expression of pro-inflammatory markers, CD86 and MHCII. Production of pro-inflammatory cytokines, particularly TNF-α, decreased with time for cells cultured on Ch, while anti-inflammatory IL-10 and TGF-β1, significantly increased. Altogether, these results suggest an M2c polarisation. Also, macrophage matrix metalloproteinase activity was augmented and cell motility was stimulated by Ch. Conversely, DC significantly enhanced CD86 expression, reduced IL-10 secretion and increased TNF-α and IL-1β levels. Our findings indicate that cells with a common precursor may display different responses, when challenged by the same biomaterial. Moreover, they help to further comprehend macrophage/DC interactions with Ch and the balance between pro- and anti-inflammatory signals associated with implant biomaterials. We propose that an overall pro-inflammatory reaction may hide the expression of anti-inflammatory cytokines, likely relevant for tissue repair/regeneration.

  5. Preferential expansion of pro-inflammatory Tregs in human non-small cell lung cancer

    PubMed Central

    Phillips, Joseph D.; Blatner, Nichole R.; Haghi, Leila; DeCamp, Malcolm M.; Meyerson, Shari L.; Heiferman, Michael J.; Heiferman, Jeffrey R.; Gounari, Fotini; Bentrem, David J.; Khazaie, Khashayarsha

    2016-01-01

    Objectives Lung cancer is the leading cause of cancer-related death in the USA. Regulatory T cells (Tregs) normally function to temper immune responses and decrease inflammation. Previous research has demonstrated different subsets of Tregs with contrasting anti- or pro-inflammatory properties. This study aimed to determine Treg subset distributions and characteristics present in non-small cell lung cancer (NSCLC) patients. Methods Peripheral blood was collected from healthy controls (HC) and NSCLC patients preceding surgical resection, and mononuclear cells were isolated, stained, and analyzed by flow cytometry. Tregs were defined by expression of CD4 and CD25 and classified into CD45RA+Foxp3int (naïve, Fr. I) or CD45RA−Foxp3hi (activated Fr. II). Activated conventional T cells were CD4+CD45RA−Foxp3int (Fr. III). Results Samples from 23 HC and 26 NSCLC patients were collected. Tregs isolated from patients with NSCLC were found to have enhanced suppressive function on naive T cells. Cancer patients had significantly increased frequencies of activated Tregs (fraction II: FrII), 17.5 versus 3.2 % (P < 0.001). FrII Tregs demonstrated increased RORγt and IL17 expression and decreased IL10 expression compared to Tregs from HC, indicating pro-inflammatory characteristics. Conclusions This study demonstrates that a novel subset of Tregs with pro-inflammatory characteristics preferentially expand in NSCLC patients. This Treg subset appears identical to previously reported pro-inflammatory Tregs in human colon cancer patients and in mouse models of polyposis. We expect the pro-inflammatory Tregs in lung cancer to contribute to the immune pathogenesis of disease and propose that targeting this Treg subset may have protective benefits in NSCLC. PMID:26047578

  6. Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity.

    PubMed

    Hucke, Stephanie; Eschborn, Melanie; Liebmann, Marie; Herold, Martin; Freise, Nicole; Engbers, Annika; Ehling, Petra; Meuth, Sven G; Roth, Johannes; Kuhlmann, Tanja; Wiendl, Heinz; Klotz, Luisa

    2016-02-01

    The increasing incidence in Multiple Sclerosis (MS) during the last decades in industrialized countries might be linked to a change in dietary habits. Nowadays, enhanced salt content is an important characteristic of Western diet and increased dietary salt (NaCl) intake promotes pathogenic T cell responses contributing to central nervous system (CNS) autoimmunity. Given the importance of macrophage responses for CNS disease propagation, we addressed the influence of salt consumption on macrophage responses in CNS autoimmunity. We observed that EAE-diseased mice receiving a NaCl-high diet showed strongly enhanced macrophage infiltration and activation within the CNS accompanied by disease aggravation during the effector phase of EAE. NaCl treatment of macrophages elicited a strong pro-inflammatory phenotype characterized by enhanced pro-inflammatory cytokine production, increased expression of immune-stimulatory molecules, and an antigen-independent boost of T cell proliferation. This NaCl-induced pro-inflammatory macrophage phenotype was accompanied by increased activation of NF-kB and MAPK signaling pathways. The pathogenic relevance of NaCl-conditioned macrophages is illustrated by the finding that transfer into EAE-diseased animals resulted in significant disease aggravation compared to untreated macrophages. Importantly, also in human monocytes, NaCl promoted a pro-inflammatory phenotype that enhanced human T cell proliferation. Taken together, high dietary salt intake promotes pro-inflammatory macrophages that aggravate CNS autoimmunity. Together with other studies, these results underline the need to further determine the relevance of increased dietary salt intake for MS disease severity.

  7. An Engineered Bivalent Neuregulin Protects Against Doxorubicin-Induced Cardiotoxicity with Reduced Pro-Neoplastic Potential

    PubMed Central

    Jay, Steven M.; Murthy, Ashwin C.; Hawkins, Jessica F.; Wortzel, Joshua R.; Steinhauser, Matthew L.; Alvarez, Luis M.; Gannon, Joseph; Macrae, Calum A.; Griffith, Linda G.; Lee, Richard T.

    2013-01-01

    Background Doxorubicin (DOXO) is an effective anthracycline chemotherapeutic, but its use is limited by cumulative dose-dependent cardiotoxicity. Neuregulin-1β (NRG1B) is an ErbB receptor family ligand that is effective against DOXO-induced cardiomyopathy in experimental models but is also pro-neoplastic. We previously showed that an engineered bivalent neuregulin-1β (NN) has reduced pro-neoplastic potential compared to the epidermal growth factor (EGF)-like domain of NRG1B (NRG), an effect mediated by receptor biasing towards ErbB3 homotypic interactions uncommonly formed by native NRG1B. Here, we hypothesized that a newly formulated, covalent NN would be cardioprotective with reduced pro-neoplastic effects compared to NRG. Methods and Results NN was expressed as a maltose-binding protein fusion in E. coli. As established previously, NN stimulated anti-neoplastic or cytostatic signaling and phenotype in cancer cells, whereas NRG stimulated pro-neoplastic signaling and phenotype. In neonatal rat cardiomyocytes (NRCM), NN and NRG induced similar downstream signaling. NN, like NRG, attenuated the double-stranded DNA breaks associated with DOXO exposure in NRCM and human cardiomyocytes derived from induced pluripotent stem cells. NN treatment significantly attenuated DOXO-induced decrease in fractional shortening as measured by blinded echocardiography in mice in a chronic cardiomyopathy model (57.7% ± 0.6% vs. 50.9% ± 2.6%, P=0.004), whereas native NRG had no significant effect (49.4% ± 3.7% vs. 50.9% ± 2.6%, P=0.813). Conclusions NN is a cardioprotective agent that promotes cardiomyocyte survival and improves cardiac function in DOXO-induced cardiotoxicity. Given the reduced pro-neoplastic potential of NN versus NRG, NN has translational potential for cardioprotection in cancer patients receiving anthracyclines. PMID:23757312

  8. Utilising a Blended Ethnographic Approach to Explore the Online and Offline Lives of Pro-Ana Community Members

    ERIC Educational Resources Information Center

    Dyke, Sarah

    2013-01-01

    The article critically interrogates contemporary discourses and practices around "anorexia nervosa" through an ethnographic study that moves between two sites: an online pro-anorexia (pro-ana) community, and a Local Authority-funded eating disorder prevention project located in schools and youth centres in the north of England. The…

  9. Effect of sodium butyrate on pro-matrix metalloproteinase-9 and -2 differential secretion in pediatric tumors and cell lines.

    PubMed

    Rodríguez-Salvador, J; Armas-Pineda, C; Perezpeña-Diazconti, M; Chico-Ponce de León, F; Sosa-Sáinz, G; Lezama, P; Recillas-Targa, F; Arenas-Huertero, F

    2005-09-01

    Matrix metalloproteinases (MMPs) are enzymes responsible for extracellular matrix degradation and contribute to local and distant cell invasion during cancer progression or metastasis. The effects of chromatin structure on gene expression and the use of histone deacetylase inhibitors such as sodium butyrate (NaBu) may directly influence pro-MMPs secretion. In the present study, we evaluated the effect of NaBu on pro-MMP-9 and pro-MMP-2 secretion in human Jurkat and HT1080 cells, and in 36 pediatric solid tumors. Cell lines and samples were exposed to 8 mM of NaBu and proteinase activity was evaluated in the supernatant by gelatin zymograms. Our results showed, for Jurkat cells treated with NaBu, increases of 2-fold and 1.5-fold in pro-MMP-9 and pro-MMP-2 secretion, respectively. A 50% decrease in pro-MMP-9 secretion due to NaBu was observed in HT1080 cells. NaBu induced a 0.62 reduction in levels of pro-MMP-9 secretion in untreated tumors. For cell lines and some NaBu-treated tumors we found histone H4 hyperacetylation. We conclude that pro-MMPs gene expression and their secretion can be epigenetically mis-regulated in tumoral processes.

  10. Molecular cloning of insect pro-phenol oxidase: a copper-containing protein homologous to arthropod hemocyanin.

    PubMed Central

    Kawabata, T; Yasuhara, Y; Ochiai, M; Matsuura, S; Ashida, M

    1995-01-01

    Pro-phenol oxidase [pro-PO; zymogen of phenol oxidase (monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1)] is present in the hemolymph plasma of the silkworm Bombyx mori. Pro-PO is a heterodimeric protein synthesized by hemocytes. A specific serine proteinase activates both subunits through a limited proteolysis. The amino acid sequences of both subunits were deduced from their respective cDNAs; amino acid sequence homology between the subunits was 51%. The deduced amino acid sequences revealed domains highly homologous to the copper-binding site sequences (copper-binding sites A and B) of arthropod hemocyanins. The overall sequence homology between silkworm pro-PO and arthropod hemocyanins ranged from 29 to 39%. Phenol oxidases from prokaryotes, fungi, and vertebrates have sequences homologous to only the copper-binding site B of arthropod hemocyanins. Thus, silkworm pro-PO DNA described here appears distinctive and more closely related to arthropod hemocyanins. The pro-PO-activating serine proteinase was shown to hydrolyze peptide bonds at the carboxyl side of arginine in the sequence-Asn-49-Arg-50-Phe-51-Gly-52- of both subunits. Amino groups of N termini of both subunits were indicated to be N-acetylated. The cDNAs of both pro-PO subunits lacked signal peptide sequences. This result supports our contention that mature pro-PO accumulates in the cytoplasm of hemocytes and is released by cell rupture, as for arthropod hemocyanins. PMID:7644494

  11. 3 CFR 8919 - Proclamation 8919 of December 18, 2012. Death of Senator Daniel K. Inouye, President Pro Tempore...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 3 The President 1 2013-01-01 2013-01-01 false Proclamation 8919 of December 18, 2012. Death of Senator Daniel K. Inouye, President Pro Tempore of the Senate 8919 Proclamation 8919 Presidential... of respect for the memory and longstanding service of Senator Daniel K. Inouye, President pro...

  12. 77 FR 16890 - In the Matter of ProElite, Inc. and Universal Guardian Holdings, Inc.: Order of Suspension of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-22

    ... From the Federal Register Online via the Government Publishing Office ] SECURITIES AND EXCHANGE COMMISSION In the Matter of ProElite, Inc. and Universal Guardian Holdings, Inc.: Order of Suspension of... current and accurate information concerning the securities of ProElite, Inc. because it has not filed...

  13. Models that Teach about the Computer: AppleWorks and ProDOS, the Computer's Memory and Disk Storage.

    ERIC Educational Resources Information Center

    Niess, Margaret L.

    1989-01-01

    This final article in a series on creating models for teaching about computer memory and disk storage and retrieval focuses on AppleWorks software and the Professional Disk Operating System (ProDOS). Instructions for creating a paper model of the AppleWorks menu system and the ProDOS disk file are given. (LRW)

  14. A C69-family cysteine dipeptidase from Lactobacillus farciminis JCM1097 possesses strong Gly-Pro hydrolytic activity.

    PubMed

    Sakamoto, Takuma; Otokawa, Takuya; Kono, Ryosuke; Shigeri, Yasushi; Watanabe, Kunihiko

    2013-11-01

    Dipeptide Gly-Pro, a hard-to-degrade and collagenous peptide, is thought to be hydrolysed by prolidases that can work on various X-Pro dipeptides. Here, we found an entirely different type of dipeptidase from Lactobacillus farciminis JCM1097 that cleaves Gly-Pro far more efficiently and with higher specificity than prolidases, and then investigated its properties by use of a recombinant enzyme. Although L. farciminis dipeptidase was expressed in the form of an inclusion body in Escherichia coli at 37 °C, it was smoothly over-expressed in a soluble form at a lower temperature. The maximal Gly-Pro hydrolytic activity was attained in E. coli at 30 °C. In contrast to prolidases that are metallopeptidases showing the modest or marginal activity toward Gly-Pro, this L. farciminis dipeptidase belongs to the cysteine peptidase family C69. Lactobacillus farciminis dipeptidase occurs in cytoplasm and utilizes the side chain of an amino-terminal cysteine residue to perform the nucleophilic attack on the target amide bond between Gly-Pro after processing eight amino acid residues at the N-terminus. Furthermore, L. farciminis dipeptidase is potent enough to synthesize Gly-Pro from Gly and Pro by a reverse reaction. These novel properties could be revealed by virtue of the success in preparing recombinant enzymes in higher yield and in a stable form.

  15. The integrated project NF-PRO: recent advances in European research on the near-field system

    SciTech Connect

    Sneyers, Alain; Grambow, Bernd; Aranyossy, Jean-Francois; Johnson, Lawrence

    2007-07-01

    The Integrated Project NF-PRO (Sixth Framework Programme by the European Commission) investigates key-processes in the near-field of a geological repository for the disposal of high-level vitrified waste and spent fuel. The paper discusses the project scope and content and gives a summary overview of advances made by NF-PRO. (authors)

  16. Pro-adrenomedullin usefulness in the management of children with community-acquired pneumonia, a preliminar prospective observational study

    PubMed Central

    2012-01-01

    Background In adult population with community acquired pneumonia high levels of pro-adrenomedullin (pro-ADM) have been shown to be predictors of worse prognosis. The role of this biomarker in pediatric patients had not been analyzed to date. The objective of this study is to know the levels of pro-ADM in children with community acquired pneumonia (CAP) and analyze the relation between these levels and the patients’ prognosis. Findings Prospective observational study including patients attended in the emergency service (January to October 2009) admitted to hospital with CAP and no complications at admission. The values for pro-ADM were analyzed in relation to: need for oxygen therapy, duration of oxygen therapy, fever and antibiotic therapy, complications, admission to the intensive care unit, and length of hospital stay. Fifty patients were included. Ten presented complications (7 pleural effusion). The median level of pro-ADM was 1.0065 nmol/L (range 0.3715 to 7.2840 nmol/L). The patients presenting complications had higher levels of pro-ADM (2.3190 vs. 1.1758 nmol/L, p = 0.013). Specifically, the presence of pleural effusion was associated with higher levels of pro-ADM (2.9440 vs. 1.1373 nmol/L, p < 0.001). Conclusions In our sample of patients admitted to hospital with CAP, pro-ADM levels are related to the development of complications during hospitalization. PMID:22818355

  17. Strategic Pay Reform: A Student Outcomes-Based Evaluation of Denver's ProComp Teacher Pay Initiative

    ERIC Educational Resources Information Center

    Goldhaber, Dan; Walch, Joe

    2012-01-01

    Denver Public Schools utilizes one of the nation's highest profile alternative teacher compensation systems, and a key element of Denver's Professional Compensation System for Teachers (ProComp) is pay for performance. This study analyzes the student achievement implications of ProComp utilizing matched student- and teacher-level data from 2003 to…

  18. The relationship between relative solvent accessible surface area (rASA) and irregular structures in protean segments (ProSs)

    PubMed Central

    Shaji, Divya

    2016-01-01

    Intrinsically Disordered Proteins (IDPs) lack a stable, three-dimensional structure under physiological conditions, yet they exhibit numerous biological activities. Protean segments (ProSs) are the functional regions of intrinsically disordered proteins that undergo disorder-to-order transitions upon binding to their partners. Example ProSs collected from the intrinsically disordered proteins with extensive annotations and literature (IDEAL) database. The interface of protean segments (ProSs) is classified into core, rim, and support, and analyzed their secondary structure elements (SSEs) based on the relative accessible surface area (rASA). The amino acid compositions and the relative solvent accessible surface areas (rASAs) of ProS secondary structural elements (SSEs) at the interface, core and rim were compared to those of heterodimers. The average number of contacts of alpha helices and irregular residues was calculated for each ProS and heterodimer. Furthermore, the ProSs were classified into high and low efficient based on their average number of contacts at the interface. The results indicate that the irregular structures of ProSs and heterodimers are significantly different. The rASA of irregular structures in the monomeric state (rASAm) is large, leads to the formation of larger ΔrASA and many contacts in ProSs. PMID:28250616

  19. Endomorphin synthesis in rat brain from intracerebroventricularly injected [3H]-Tyr-Pro: a possible biosynthetic route for endomorphins.

    PubMed

    Rónai, András Z; Szemenyei, Erzsébet; Kató, Erzsébet; Kocsis, László; Orosz, György; Al-Khrasani, Mahmoud; Tóth, Géza

    2006-03-15

    In spite of concentrated efforts, the biosynthetic route of mu-opioid receptor agonist brain tetrapeptide endomorphins (Tyr-Pro-Trp-Phe-NH2 and Tyr-Pro-Phe-Phe-NH2), discovered in 1997, is still obscure. We report presently that 30 min after intracerebroventricular injection of 20 or 200 microCi [3H]Tyr-Pro (49.9 Ci mmol(-1)) the incorporated radioactivity was found in endomorphin-related tetra- and tripeptides in rat brain extracts. As detected by the combination of HPLC with radiodetection, a peak corresponding to endomorphin-2-OH could be identified in two of four extracts of "20 microCi" series. Radioactive peaks in position of Tyr, Tyr-Pro, Tyr-Pro-Phe or Tyr-Pro-Trp appeared regularly in both series and also in the "tetrapeptide cluster" constituted by endomorphins and their free carboxylic forms. In one of the four extracts in the "200 microCi" series a robust active peak in the position of endomorphin 2 could be detected. Intracerebroventricularly injected 100 nmol, but not 10 or 1000 nmol cold Tyr-Pro (devoid of opioid activity in vitro), caused a naloxone-reversible prolongation of tail-flick latency in rats, peaking between 15 and 30 min. We suggest that Tyr-Pro may serve as a biosynthetic precursor to endomorphin synthesis.

  20. Children's Perceived Reality of Television and the Effects of Pro- and Anti-Social TV Content on Social Behavior.

    ERIC Educational Resources Information Center

    Reeves, Byron

    Interviews were conducted with 721 students in fourth, sixth, and eighth grades to study whether children's perceived reality of television would affect the relationship between pro-social and anti-social television content and pro-social and anti-social behavior. Social behavior variables, a perceived reality index, and television exposure…

  1. LPS-induced TNF-α factor mediates pro-inflammatory and pro-fibrogenic pattern in non-alcoholic fatty liver disease.

    PubMed

    Ceccarelli, Sara; Panera, Nadia; Mina, Marco; Gnani, Daniela; De Stefanis, Cristiano; Crudele, Annalisa; Rychlicki, Chiara; Petrini, Stefania; Bruscalupi, Giovannella; Agostinelli, Laura; Stronati, Laura; Cucchiara, Salvatore; Musso, Giovanni; Furlanello, Cesare; Svegliati-Baroni, Gianluca; Nobili, Valerio; Alisi, Anna

    2015-12-08

    Lipopolysaccharide (LPS) is currently considered one of the major players in non-alcoholic fatty liver disease (NAFLD) pathogenesis and progression. Here, we aim to investigate the possible role of LPS-induced TNF-α factor (LITAF) in inducing a pro-inflammatory and pro-fibrogenic phenotype of non-alcoholic steatohepatitis (NASH).We found that children with NAFLD displayed, in different liver-resident cells, an increased expression of LITAF which correlated with histological traits of hepatic inflammation and fibrosis. Total and nuclear LITAF expression increased in mouse and human hepatic stellate cells (HSCs). Moreover, LPS induced LITAF-dependent transcription of IL-1β, IL-6 and TNF-α in the clonal myofibroblastic HSC LX-2 cell line, and this effect was hampered by LITAF silencing. We showed, for the first time in HSCs, that LITAF recruitment to these cytokine promoters is LPS dependent. However, preventing LITAF nuclear translocation by p38MAPK inhibitor, the expression of IL-6 and TNF-α was significantly reduced with the aid of p65NF-ĸB, while IL-1β transcription exclusively required LITAF expression/activity. Finally, IL-1β levels in plasma mirrored those in the liver and correlated with LPS levels and LITAF-positive HSCs in children with NASH.In conclusion, a more severe histological profile in paediatric NAFLD is associated with LITAF over-expression in HSCs, which in turn correlates with hepatic and circulating IL-1β levels outlining a panel of potential biomarkers of NASH-related liver damage. The in vitro study highlights the role of LITAF as a key regulator of the LPS-induced pro-inflammatory pattern in HSCs and suggests p38MAPK inhibitors as a possible therapeutic approach against hepatic inflammation in NASH.

  2. Pro-Inflammatory and Pro-Fibrogenic Effects of Ionic and Particulate Arsenide and Indium-Containing Semiconductor Materials in the Murine Lung.

    PubMed

    Jiang, Wen; Wang, Xiang; Osborne, Olivia J; Du, Yingjie; Chang, Chong Hyun; Liao, Yu-Pei; Sun, Bingbing; Jiang, Jinhong; Ji, Zhaoxia; Li, Ruibin; Liu, Xiangsheng; Lu, Jianqin; Lin, Sijie; Meng, Huan; Xia, Tian; Nel, André E

    2017-02-28

    We have recently shown that the toxicological potential of GaAs and InAs particulates in cells is size- and dissolution-dependent, tending to be more pronounced for nano- vs micron-sized particles. Whether the size-dependent dissolution and shedding of ionic III-V materials also apply to pulmonary exposure is unclear. While it has been demonstrated that micron-sized III-V particles, such as GaAs and InAs, are capable of inducing hazardous pulmonary effects in an occupational setting as well as in animal studies, the effect of submicron particles (e.g., the removal of asperities during processing of semiconductor wafers) is unclear. We used cytokine profiling to compare the pro-inflammatory effects of micron- and nanoscale GaAs and InAs particulates in cells as well as the murine lung 40 h and 21 days after oropharyngeal aspiration. Use of cytokine array technology in macrophage and epithelial cell cultures demonstrated a proportionally higher increase in the levels of matrix metalloproteinase inducer (EMMPRIN), macrophage migration inhibitory factor (MIF), and interleukin 1β (IL-1β) by nanosized (n) GaAs and n-InAs as well as As(III). n-GaAs and n-InAs also triggered higher neutrophil counts in the bronchoalveolar lavage fluid (BALF) of mice than micronscale particles 40 h post-aspiration, along with increased production of EMMPRIN and MIF. In contrast, in animals sacrificed 21 days after exposure, only n-InAs induced fibrotic lung changes as determined by increased lung collagen as well as increased levels of TGF-β1 and PDGF-AA in the BALF. A similar trend was seen for EMMPRIN and matrix metallopeptidase (MMP-9) levels in the BALF. Nano- and micron-GaAs had negligible subacute effects. Importantly, the difference between the 40 h and 21 days data appears to be biopersistence of n-InAs, as demonstrated by ICP-OES analysis of lung tissue. Interestingly, an ionic form of In, InCl3, also showed pro-fibrogenic effects due to the formation of insoluble In(OH)3

  3. The triple helical structure and stability of collagen model peptide with 4(S)-hydroxyprolyl-Pro-Gly units.

    PubMed

    Motooka, Daisuke; Kawahara, Kazuki; Nakamura, Shota; Doi, Masamitsu; Nishi, Yoshinori; Nishiuchi, Yuji; Kang, Young Kee; Nakazawa, Takashi; Uchiyama, Susumu; Yoshida, Takuya; Ohkubo, Tadayasu; Kobayashi, Yuji

    2012-01-01

    Extensive studies on the structure of collagen have revealed that the hydroxylation of Pro residues in a variety of model peptides with the typical (X-Y-Gly)(n) repeats (X and Y: Pro and its analogues) represents one of the major factors influencing the stability of triple helices. While(2S,4R)-hydroxyproline (Hyp) at the position Y stabilizes the triple helix, (2S,4S)-hydroxyproline (hyp) at the X-position destabilizes the helix as demonstrated that the triple helix of (hyp-Pro-Gly)(15) is less stable than that of (Pro-Pro-Gly)(15) and that a shorter peptide (hyp-Pro-Gly)(10) does not form the helix. To clarify the role of the hydroxyl group of Pro residues to play in the stabilization mechanism of the collagen triple helix, we synthesized and crystallized a model peptide (Pro-Hyp-Gly)(4) -(hyp-Pro-Gly)(2) -(Pro-Hyp-Gly)(4) and analyzed its structure by X-ray crystallography and CD spectroscopy. In the crystal, the main-chain of this peptide forms a typical collagen like triple helix. The majority of hyp residues take down pucker with exceptionally shallow angles probably to relieve steric hindrance, but the remainders protrude the hydroxyl group toward solvent with the less favorable up pucker to fit in a triple helix. There is no indication of the existence of an intra-molecular hydrogen bond between the hydroxyl moiety and the carbonyl oxygen of hyp supposed to destabilize the triple helix. We also compared the conformational energies of up and down packers of the pyrrolidine ring in Ac-hyp-NMe(2) by quantum mechanical calculations.

  4. Swapping of pro-sequences between keratinases of Bacillus licheniformis and Bacillus pumilus: altered substrate specificity and thermostability.

    PubMed

    Rajput, Rinky; Tiwary, Ekta; Sharma, Richa; Gupta, Rani

    2012-08-10

    Pro-sequences were swapped in cis between keratinases from Bacillus licheniformis (Ker BL) and Bacillus pumilus (Ker BP) to construct Ker ProBP-BL and Ker ProBL-BP, respectively. Expression of these keratinases was carried out constitutively by E. coli HB101-pEZZ18 system. They were characterized with respect to their parent enzymes, Ker BL and Ker BP, respectively. Ker ProBP-BL became more thermostable with a t(1/2) of 45 min at 80°C contrary to Ker BL which was not stable beyond 60°C. Similarly, the activity of Ker ProBP-BL on keratin and casein substrate, i.e. K:C ratio increased to 1.2 in comparison to 0.1 for Ker BL. Hydrolysis of insulin B-chain revealed that the cleavage sites increased to six from four in case of Ker ProBP-BL in comparison to Ker BL. However, cleavage sites decreased from seven to four in case of Ker ProBL-BP in comparison to the parent keratinase, Ker BP. Likewise, Ker ProBL-BP revealed altered pH and temperature kinetics with optima at pH 10 and 60°C in comparison to Ker BP which had optima at pH 9 and 70°C. It also cleaved soluble substrates with better efficiency in comparison to Ker BP with K:C ratio of 1.6. Pro-sequence mediated conformational changes were also observed in trans and were almost similar to the features acquired by the chimeras constructed in cis by swapping the pro-sequence region.

  5. Design, implementation and reporting strategies to reduce the instance and impact of missing patient-reported outcome (PRO) data: a systematic review

    PubMed Central

    Mercieca-Bebber, Rebecca; Palmer, Michael J; Brundage, Michael; Stockler, Martin R; King, Madeleine T

    2016-01-01

    Objectives Patient-reported outcomes (PROs) provide important information about the impact of treatment from the patients' perspective. However, missing PRO data may compromise the interpretability and value of the findings. We aimed to report: (1) a non-technical summary of problems caused by missing PRO data; and (2) a systematic review by collating strategies to: (A) minimise rates of missing PRO data, and (B) facilitate transparent interpretation and reporting of missing PRO data in clinical research. Our systematic review does not address statistical handling of missing PRO data. Data sources MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases (inception to 31 March 2015), and citing articles and reference lists from relevant sources. Eligibility criteria English articles providing recommendations for reducing missing PRO data rates, or strategies to facilitate transparent interpretation and reporting of missing PRO data were included. Methods 2 reviewers independently screened articles against eligibility criteria. Discrepancies were resolved with the research team. Recommendations were extracted and coded according to framework synthesis. Results 117 sources (55% discussion papers, 26% original research) met the eligibility criteria. Design and methodological strategies for reducing rates of missing PRO data included: incorporating PRO-specific information into the protocol; carefully designing PRO assessment schedules and defining termination rules; minimising patient burden; appointing a PRO coordinator; PRO-specific training for staff; ensuring PRO studies are adequately resourced; and continuous quality assurance. Strategies for transparent interpretation and reporting of missing PRO data include utilising auxiliary data to inform analysis; transparently reporting baseline PRO scores, rates and reasons for missing data; and methods for handling missing PRO data. Conclusions The instance of missing PRO data and its

  6. Steroidal Saponin Diosgenin from Dioscorea bulbifera Protects Cardiac Cells from Hypoxia-reoxygenation Injury Through Modulation of Pro-survival and Pro-death Molecules

    PubMed Central

    Jayachandran, Karuppiah Shanmugasundarapandian; Vasanthi, A. Hannah Rachel; Gurusamy, Narasimman

    2016-01-01

    Background: Diosgenin, a steroidal saponin from plants, exhibits many biological potentials. Herein, the cardioprotective role of diosgenin is studied. Materials and Methods: The effect of diosgenin, isolated from Dioscorea bulbifera, was studied on hypoxia-reoxygenation (HR) in H9c2 cardiomyoblast cells. The amount of diosgenin in the plant extract was analyzed by high-performance thin layer chromatography using a solvent system comprising of chloroform:methanol:acetic acid:formic acid (13:4.5:1.5:1). Cardioprotection was checked by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Further, the release of lactate dehydrogenase, an enzyme released during cell death was checked. The proteins responsible for cell death (Bax) and cell survival (Bcl-2, hemeoxygenase-1 and Akt) were analyzed using Western blot to check the cardioprotective role of diosgenin. Conclusion: Supplementation of diosgenin mitigates HR injury, thereby exhibiting cardioprotective potential. SUMMARY The cardioprotective effect of Diosgenin was evidenced from the improved cell survival after hypoxia-reoxygenation injury demonstrated through MTT cell survival assay.The release of lactate dehydrogenase, an enzyme released during cell death was decreased by Diosgenin.Diosgenin upregulated the pro-survival molecules like B-cell lymphoma 2 (Bcl-2), heme oxygenase-1 and the phosphorylation of ATK (at serine 473); and at the same time pro-.death molecules like Bax was downregulated.Thus, Diosgenin as a plant based steroidal saponin is confirmed to mitigate ischemic reperfusion injury. Figure PMID:27041852

  7. Potent pro-inflammatory and pro-fibrotic molecules, osteopontin and galectin-3, are not major disease modulators of laminin α2 chain-deficient muscular dystrophy

    PubMed Central

    Gawlik, Kinga I.; Holmberg, Johan; Svensson, Martina; Einerborg, Mikaela; Oliveira, Bernardo M. S.; Deierborg, Tomas; Durbeej, Madeleine

    2017-01-01

    A large number of human diseases are caused by chronic tissue injury with fibrosis potentially leading to organ failure. There is a need for more effective anti-fibrotic therapies. Congenital muscular dystrophy type 1A (MDC1A) is a devastating form of muscular dystrophy caused by laminin α2 chain-deficiency. It is characterized with early inflammation and build-up of fibrotic lesions, both in patients and MDC1A mouse models (e.g. dy3K/dy3K). Despite the enormous impact of inflammation on tissue remodelling in disease, the inflammatory response in MDC1A has been poorly described. Consequently, a comprehensive understanding of secondary mechanisms (impaired regeneration, enhanced fibrosis) leading to deterioration of muscle phenotype in MDC1A is missing. We have monitored inflammatory processes in dy3K/dy3K muscle and created mice deficient in laminin α2 chain and osteopontin or galectin-3, two pro-inflammatory and pro-fibrotic molecules drastically increased in dystrophic muscle. Surprisingly, deletion of osteopontin worsened the phenotype of dy3K/dy3K mice and loss of galectin-3 did not reduce muscle pathology. Our results indicate that osteopontin could even be a beneficial immunomodulator in MDC1A. This knowledge is essential for the design of future therapeutic interventions for muscular dystrophies that aim at targeting inflammation, especially that osteopontin inhibition has been suggested for Duchenne muscular dystrophy therapy. PMID:28281577

  8. Topical simvastatin improves the pro-angiogenic and pro-osteogenic properties of bioglass putty in the rat calvaria critical-size model.

    PubMed

    Allon, Irit; Anavi, Yakir; Allon, Dror Michael

    2012-03-12

    Abstract Objective: To describe the effect of bioactive glass putty with and without topical simvastatin on new bone formation in critical-sized defects of rat calvaria. Study design: A calvarial bone defect was created in 20 male Wistar rats and filled with bioactive glass alone (n=10) or combined with simvastatin (n=10). After 4 weeks, the defects were histomorphometrically evaluated for volume fraction (Vv) of woven bone, vessel density, bioglass quantity, and inflammation. Results: Compared to the bioglass-only group, rats treated with simvastatin had greater Vv of blood vessels (3.3%+0.7 vs 1.6%+0.1, P=0.0002) and new bone (2.3%+0.2 vs 1.8%+2.5, P=0.003). The Vv of the bioglass remnants in the bioglass-only group was higher than in the group treated with simvastatin (2.4% +0.08 vs 1.7%+0.3, P<0.0004). Chronic inflammation was noted in one rat from each group. Conclusion: Topical simvastatin seems to improve the pro-angiogenic and pro-osteogenic properties of bioglass putty in rat calvaria critical-size defects without significant inflammation.

  9. Topical simvastatin improves the pro-angiogenic and pro-osteogenic properties of bioglass putty in the rat calvaria critical-size model.

    PubMed

    Allon, Irit; Anavi, Yakir; Allon, Dror M

    2014-06-01

    Objective was to describe the effect of bioactive glass putty with and without topical simvastatin on new bone formation in critical-sized defects of rat calvaria. A calvarial bone defect was created in 20 male Wistar rats and filled with bioactive glass alone (n = 10) or combined with simvastatin (n = 10). After 4 weeks, the defects were histomorphometrically evaluated for volume fraction (Vv) of woven bone, vessel density, bioglass quantity, and inflammation. Compared to the bioglass-only group, rats treated with simvastatin had greater Vv of blood vessels (3.3% ± 0.7 vs 1.6% ± 0.1, P = .0002) and new bone (2.3% ± 0.2 vs 1.8% ± 2.5, P = .003). The Vv of the bioglass remnants in the bioglass-only group was higher than in the group treated with simvastatin (2.4% ± 0.08 vs 1.7% ± 0.3, P < .0004). Chronic inflammation was noted in 1 rat from each group. Topical simvastatin seems to improve the pro-angiogenic and pro-osteogenic properties of bioglass putty in rat calvaria critical-size defects without significant inflammation.

  10. Potent pro-inflammatory and pro-fibrotic molecules, osteopontin and galectin-3, are not major disease modulators of laminin α2 chain-deficient muscular dystrophy.

    PubMed

    Gawlik, Kinga I; Holmberg, Johan; Svensson, Martina; Einerborg, Mikaela; Oliveira, Bernardo M S; Deierborg, Tomas; Durbeej, Madeleine

    2017-03-10

    A large number of human diseases are caused by chronic tissue injury with fibrosis potentially leading to organ failure. There is a need for more effective anti-fibrotic therapies. Congenital muscular dystrophy type 1A (MDC1A) is a devastating form of muscular dystrophy caused by laminin α2 chain-deficiency. It is characterized with early inflammation and build-up of fibrotic lesions, both in patients and MDC1A mouse models (e.g. dy(3K)/dy(3K)). Despite the enormous impact of inflammation on tissue remodelling in disease, the inflammatory response in MDC1A has been poorly described. Consequently, a comprehensive understanding of secondary mechanisms (impaired regeneration, enhanced fibrosis) leading to deterioration of muscle phenotype in MDC1A is missing. We have monitored inflammatory processes in dy(3K)/dy(3K) muscle and created mice deficient in laminin α2 chain and osteopontin or galectin-3, two pro-inflammatory and pro-fibrotic molecules drastically increased in dystrophic muscle. Surprisingly, deletion of osteopontin worsened the phenotype of dy(3K)/dy(3K) mice and loss of galectin-3 did not reduce muscle pathology. Our results indicate that osteopontin could even be a beneficial immunomodulator in MDC1A. This knowledge is essential for the design of future therapeutic interventions for muscular dystrophies that aim at targeting inflammation, especially that osteopontin inhibition has been suggested for Duchenne muscular dystrophy therapy.

  11. HEAT.PRO - THERMAL IMBALANCE FORCE SIMULATION AND ANALYSIS USING PDE2D

    NASA Technical Reports Server (NTRS)

    Vigue, Y.

    1994-01-01

    HEAT.PRO calculates the thermal imbalance force resulting from satellite surface heating. The heated body of a satellite re-radiates energy at a rate that is proportional to its temperature, losing the energy in the form of photons. By conservation of momentum, this momentum flux out of the body creates a reaction force against the radiation surface, and the net thermal force can be observed as a small perturbation that affects long term orbital behavior of the satellite. HEAT.PRO calculates this thermal imbalance force and then determines its effects on satellite orbits, especially where the Earth's shadowing of an orbiting satellite causes periodic changes in the spacecraft's thermal environment. HEAT.PRO implements a finite element method routine called PDE2D which incorporates material properties to determine the solar panel surface temperatures. The nodal temperatures are computed at specified time steps and are used to determine the magnitude and direction of the thermal force on the spacecraft. These calculations are based on the solar panel orientation and satellite's position with respect to the earth and sun. It is necessary to have accurate, current knowledge of surface emissivity, thermal conductivity, heat capacity, and material density. These parameters, which may change due to degradation of materials in the environment of space, influence the nodal temperatures that are computed and thus the thermal force calculations. HEAT.PRO was written in FORTRAN 77 for Cray series computers running UNICOS. The source code contains directives for and is used as input to the required partial differential equation solver, PDE2D. HEAT.PRO is available on a 9-track 1600 BPI magnetic tape in UNIX tar format (standard distribution medium) or a .25 inch streaming magnetic tape cartridge in UNIX tar format. An electronic copy of the documentation in Macintosh Microsoft Word format is included on the distribution tape. HEAT.PRO was developed in 1991. Cray and UNICOS are

  12. GlutenTox® Pro Test for the Detection of Gluten in Select Foods and Surfaces.

    PubMed

    Síglez, Miguel A; Nocea, Bárbara; del Mar Pérez, María; Ma García, Eva; León, Laura; Galera, Carlos

    2015-01-01

    The GlutenTox® Pro Test is an immunochromatographic test for the detection of gluten in foods and on surfaces with varying compositions and levels of processing, from raw foods/ingredients to final product testing. The Method Developer evaluation for the validation of the GlutenTox Pro Test Kit (Biomedal Diagnostics, Sevilla, Spain) for the detection of gluten in foods and on surfaces was conducted at Biomedal, S. L., Camas, Sevilla, Spain. The GlutenTox Pro test method was evaluated by testing the following: cross-reactivity, interference, specificity and sensitivity, robustness, stability, lot-to-lot variation, food matrix, and environmental surface. To evaluate the performance of the GlutenToxPro test for the detection of gluten, 10 matrixes were selected: rice flour, bread/biscuit, rolled oat, pâté, and yogurt (and a second bread matrix for incurred sampled testing) for the food matrix study and food-grade painted wood, plastic, rubber, sealed ceramic, and stainless steel for the environmental surface matrix study. For the food matrix study, 30 replicates were evaluated at six spiked levels of gluten (0, 3, 8, 15, 25, and 45 ppm) against four detection thresholds (5, 10, 20, and 40 ppm) for each food matrix. Additionally, 10 replicates were evaluated at a concentration of 10,000 ppm using all four detection thresholds only for rice flour matrix. Three replicates of each concentration level of gluten were analyzed using paired samples by the AOAC OMA 2012.01 reference method for each food matrix. For the environmental surface study, 30 replicates were evaluated at a low spike level of gluten (16 ng/16 cm2), five replicates at a high spike level of gluten (400 ng/16 cm2), and five replicates at an unspiked control level (0 ng/16 cm2) for each surface matrix. Upon completion of testing, the probability of detection values and confidence intervals were calculated and plotted versus the concentration level as determined by the reference method when applicable. An

  13. Pro-development soap operas: a novel approach to development communication.

    PubMed

    Brown, W J; Singhal, A; Rogers, E M

    1989-01-01

    Soap operas have their roots in 18th century English romance novels. These evolved into serialized radio dramas. In their current form, they were developed primarily to attract large audiences in order to sell consumer products. Hence the name soap which refers to the soap manufacturers who commonly advertise on such programs. In the world of soap operas there are 2 kinds. Those that function primarily to entertain and sell consumer products, and those that primarily entertain, but infuse positive social messages. The former are found everywhere, but are the only kind in America. The latter are found exclusively in developing countries. American soap operas have conveyed pro-social messages in the past, but they differ fundamentally from pro-development soap operas in their theoretical foundations. American soap operas are created by people who want to sell consumer goods. Development soap operas are created by people who want to convey pro-social messages that will aid their country's development. Both must be popular in order to be successful, but the former lack moral coherency, are unrealistic, erode values, and are created through a process of a theoretical development; while the latter have moral coherency, are realistic, promote values, and are created through a process of theoretical development. The 1st pro-development soap opera was Ven Conmigo (Come With Me) and was produced in Mexico between 1975-76. Its primary purpose was to increase adult literacy. During the year it ran, applicants at adult literacy centers rose by 600,000 or 63% compared to 7% the year before, and 2% the year after. The 2nd pro-development soap opera was Acompaname (Accompany Me) and it primary purpose was to promote family planning. It ran from 1977-78 and during that time the number of family planning adopters rose by 560,000 and contraceptive sale sin Mexico rose sharply. The question of what are pro-social messages and who should control them must be answered by each country in

  14. Utility of Procalcitonin (PCT) and Mid regional pro-Adrenomedullin (MR-proADM) in risk stratification of critically ill febrile patients in Emergency Department (ED). A comparison with APACHE II score

    PubMed Central

    2012-01-01

    Background The aim of our study was to evaluate the prognostic value of MR-proADM and PCT levels in febrile patients in the ED in comparison with a disease severity index score, the APACHE II score. We also evaluated the ability of MR-proADM and PCT to predict hospitalization. Methods This was an observational, multicentric study. We enrolled 128 patients referred to the ED with high fever and a suspicion of severe infection such as sepsis, lower respiratory tract infections, urinary tract infections, gastrointestinal infections, soft tissue infections, central nervous system infections, or osteomyelitis. The APACHE II score was calculated for each patient. Results MR-proADM median values in controls were 0.5 nmol/l as compared with 0.85 nmol/l in patients (P < 0.0001), while PCT values in controls were 0.06 ng/ml versus 0.56 ng/ml in patients (P < 0.0001). In all patients there was a statistically significant stepwise increase in MR-proADM levels in accordance with PCT values (P < 0.0001). MR-proADM and PCT levels were significantly increased in accordance with the Apache II quartiles (P < 0.0001 and P = 0.0012 respectively). In the respiratory infections, urinary infections, and sepsis-septic shock groups we found a correlation between the Apache II and MR-proADM respectively and MR-proADM and PCT respectively. We evaluated the ability of MR-proADM and PCT to predict hospitalization in patients admitted to our emergency departments complaining of fever. MR-proADM alone had an AUC of 0.694, while PCT alone had an AUC of 0.763. The combined use of PCT and MR-proADM instead showed an AUC of 0.79. Conclusions The present study highlights the way in which MR-proADM and PCT may be helpful to the febrile patient’s care in the ED. Our data support the prognostic role of MR-proADM and PCT in that setting, as demonstrated by the correlation with the APACHE II score. The combined use of the two biomarkers can predict a subsequent

  15. Shaping ability of three ProFile rotary instrumentation techniques in simulated resin root canals.

    PubMed

    Kum, K Y; Spängberg, L; Cha, B Y; Il-Young, J; Msd; Seung-Jong, L; Chan-Young, L

    2000-12-01

    The aim of this study was to compare the shaping ability of three ProFile rotary instrumentation techniques and a conventional step-back method in simulated root canals. Prevalence of canal aberrations, change in working length, and preparation time were measured. A total of 48 composite images were made from pre- and postcanal scanned images using Corel Photopaint 8.0 and then the amount of coronal substance the instruments removed was also calculated two-dimensionally on digitized images with the Brain C software to compare the enlarging efficiency. There were no significant differences between the three rotary groups in preparation time, change in working length, and the incidence of aberrations (p > 0.05). The amount of coronal substance the instruments removed in the ProFile .04 taper group was significantly smaller than the other three groups (p < 0.05).

  16. Pro-apoptotic NOXA is implicated in atmospheric-pressure plasma-induced melanoma cell death

    NASA Astrophysics Data System (ADS)

    Ishaq, M.; Bazaka, K.; Ostrikov, K.

    2015-11-01

    Atmospheric-pressure plasma (APP) has been successfully used to treat several types of cancers in vivo and in vitro, with the effect being primarily attributed to the generation of reactive oxygen species (ROS). However, the mechanisms by which APP induces apoptosis in cancer cells require further elucidation. In this study, the effects of APP on the expression of 500 genes in melanoma Mel007 cancer cells were examined. Pro-apoptotic phorbol-12-myristate-13-acetate-induced protein (PMAIP1), also known as NOXA, was highly expressed as a result of APP treatment in a dose-dependent manner. Blocking of ROS using scavenger NAC or silencing of NOXA gene by RNA interference inhibited the APP-induced NOXA genes upregulation and impaired caspases 3/7 mediated apoptosis, confirming the important role plasma-generated ROS species and pro-apoptotic NOXA play in APP-induced cancer cell death.

  17. A pro-chelator triggered by hydrogen peroxide inhibits iron-promoted hydroxyl radical formation.

    PubMed

    Charkoudian, Louise K; Pham, David M; Franz, Katherine J

    2006-09-27

    The synthesis and structural characterization of a new pro-chelating agent, isonicotinic acid [2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzylidene]-hydrazide (BSIH), are presented. BSIH only weakly interacts with iron unless hydrogen peroxide (H2O2) is present to remove the boronic ester protecting group to reveal a phenol that is a key metal-binding group of tridentate salicylaldehyde isonicotinoyl hydrazone (SIH). BSIH prevents deoxyribose degradation caused by hydroxyl radicals that are generated from H2O2 and redox-active iron by sequestering Fe3+ and preventing iron-promoted hydroxyl radical formation. The rate-determining step for iron sequestration is conversion of BSIH to SIH, followed by rapid Fe3+ complexation. The pro-chelate approach of BSIH represents a promising strategy for chelating a specific pool of detrimental metal ions without disturbing healthy metal ion distribution.

  18. Chemiluminescent assay of enzymes using proenhancers and pro-anti-enhancers.

    PubMed

    Kricka, L J; Schmerfeld-Pruss, D; Edwards, B

    1991-01-01

    Enhanced chemiluminescent assays for hydrolase enzymes have been developed using proenhancer and pro-anti-enhancer substrates. Alkaline phosphatase is measured using disodium para-iodophenyl phosphate (proenhancer) which is converted to para-iodophenol and this in turn enhances the light emission from the horseradish peroxidase catalysed chemiluminescent oxidation of luminol by peroxide. An alternative strategy uses para-nitrophenyl phosphate which is converted by alkaline phosphatase to para-nitrophenol which inhibits the enhanced chemiluminescent reaction. The detection limit for the enzyme using the proenhancer and pro-anti-enhancer assays was 100 attomoles and 1 picomole, respectively. The proenhancer strategy was effective in assays for beta-D-galactosidase, beta-D-glucosidase and aryl sulfatase. A limited comparison of the proenhancer and a conventional colorimetric assay for an alkaline phosphatase label in an enzyme immunoassay for alpha-fetoprotein showed good agreement.

  19. Pro-oxidant activity of dietary chemopreventive agents: an under-appreciated anti-cancer property.

    PubMed

    Azmi, Asfar S; Sarkar, Fazlul H; Hadi, S M

    2013-01-01

    " Let food be thy medicine and medicine be thy food" was quoted by Hippocrates more than two thousand years ago and since ancient times the health benefits of different natural agents have been exploited. In modern research, the disease preventive benefits of many such natural agents, particularly dietary compounds and their derivatives, has been attributed to their well recognized activity as the regulators of redox state of the cell. Nevertheless, most of these studies have focused on their antioxidant activity. A large body of evidence indicates that a major fraction of these agents can elicit pro-oxidant (radical generating) behavior which has been linked to their anti-cancer effects. This editorial provides an overview of the under-appreciated pro-oxidant activity of natural products, with a special focus on their ability to generate reactive oxygen species in the presence of transition metal ions, and discusses their possible use as cancer chemotherapeutic agents.

  20. Pro-Amateur Observatories as a Significant Resource for Professional Astronomers - Taurus Hill Observatory

    NASA Astrophysics Data System (ADS)

    Haukka, H.; Hentunen, V.-P.; Nissinen, M.; Salmi, T.; Aartolahti, H.; Juutilainen, J.; Vilokki, H.

    2013-09-01

    Taurus Hill Observatory (THO), observatory code A95, is an amateur observatory located in Varkaus, Finland. The observatory is maintained by the local astronomical association of Warkauden Kassiopeia [8]. THO research team has observed and measured various stellar objects and phenomena. Observatory has mainly focuse d on asteroid [1] and exoplanet light curve measurements, observing the gamma rays burst, supernova discoveries and monitoring [2]. We also do long term monitoring projects [3]. THO research team has presented its research work on previous EPSC meetings ([4], [5],[6], [7]) and got very supportive reactions from the European planetary science community. The results and publications that pro-amateur based observatories, like THO, have contributed, clearly demonstrates that pro-amateurs area significant resource for the professional astronomers now and even more in the future.

  1. Surface Chirality of Gly-Pro Dipeptide Adsorbed on a Cu(110) Surface.

    PubMed

    Cruguel, Hervé; Méthivier, Christophe; Pradier, Claire-Marie; Humblot, Vincent

    2015-07-01

    The adsorption of chiral Gly-Pro dipeptide on Cu(110) has been characterized by combining in situ polarization modulation infrared reflection absorption spectroscopy (PM-RAIRS) and X-ray photoelectron spectroscopy (XPS). The chemical state of the dipeptide, and its anchoring points and adsorption geometry, were determined at various coverage values. Gly-Pro molecules are present on Cu(110) in their anionic form (NH2 /COO(-)) and adsorb under a 3-point binding via both oxygen atoms of the carboxylate group and via the nitrogen atom of the amine group. Low-energy electron diffraction (LEED) and scanning tunneling microscopy (STM) have shown the presence of an extended 2D chiral array, sustained via intermolecular H-bonds interactions. Furthermore, due to the particular shape of the molecule, only one homochiral domain is formed, creating thus a truly chiral surface.

  2. How forgiveness promotes offender pro-relational intentions: The mediating role of offender gratitude.

    PubMed

    Mooney, Louise; Strelan, Peter; McKee, Ian

    2016-03-01

    Although relationship restoration is an important outcome of forgiveness, little is known about how forgiveness facilitates such an outcome. In addition, in forgiveness research, little attention is paid to the perspective of the offender. We address these two shortcomings simultaneously, testing the idea that forgiveness promotes offender gratitude, which in turn encourages offender pro-relational intentions. Across three experimental studies, participants were induced to believe they had transgressed; recalled a time when they had transgressed; and imagined transgressing. In studies 1 and 2, forgiveness was manipulated; in Study 3, victim motivation for forgiving was manipulated. State gratitude--in comparison with guilt, indebtedness, and positive affect--was consistently found to play the primary mediating role between forgiveness and pro-relational intentions.

  3. Contextualising and Analysing Planetary Rover Image Products through the Web-Based PRoGIS

    NASA Astrophysics Data System (ADS)

    Morley, Jeremy; Sprinks, James; Muller, Jan-Peter; Tao, Yu; Paar, Gerhard; Huber, Ben; Bauer, Arnold; Willner, Konrad; Traxler, Christoph; Garov, Andrey; Karachevtseva, Irina

    2014-05-01

    The international planetary science community has launched, landed and operated dozens of human and robotic missions to the planets and the Moon. They have collected various surface imagery that has only been partially utilized for further scientific purposes. The FP7 project PRoViDE (Planetary Robotics Vision Data Exploitation) is assembling a major portion of the imaging data gathered so far from planetary surface missions into a unique database, bringing them into a spatial context and providing access to a complete set of 3D vision products. Processing is complemented by a multi-resolution visualization engine that combines various levels of detail for a seamless and immersive real-time access to dynamically rendered 3D scenes. PRoViDE aims to (1) complete relevant 3D vision processing of planetary surface missions, such as Surveyor, Viking, Pathfinder, MER, MSL, Phoenix, Huygens, and Lunar ground-level imagery from Apollo, Russian Lunokhod and selected Luna missions, (2) provide highest resolution & accuracy remote sensing (orbital) vision data processing results for these sites to embed the robotic imagery and its products into spatial planetary context, (3) collect 3D Vision processing and remote sensing products within a single coherent spatial data base, (4) realise seamless fusion between orbital and ground vision data, (5) demonstrate the potential of planetary surface vision data by maximising image quality visualisation in 3D publishing platform, (6) collect and formulate use cases for novel scientific application scenarios exploiting the newly introduced spatial relationships and presentation, (7) demonstrate the concepts for MSL, (9) realize on-line dissemination of key data & its presentation by a web-based GIS and rendering tool named PRoGIS (Planetary Robotics GIS). PRoGIS is designed to give access to rover image archives in geographical context, using projected image view cones, obtained from existing meta-data and updated according to

  4. ProSight Lite: graphical software to analyze top-down mass spectrometry data.

    PubMed

    Fellers, Ryan T; Greer, Joseph B; Early, Bryan P; Yu, Xiang; LeDuc, Richard D; Kelleher, Neil L; Thomas, Paul M

    2015-04-01

    Many top-down proteomics experiments focus on identifying and localizing PTMs and other potential sources of “mass shift” on a known protein sequence. A simple application to match ion masses and facilitate the iterative hypothesis testing of PTM presence and location would assist with the data analysis in these experiments. ProSight Lite is a free software tool for matching a single candidate sequence against a set of mass spectrometric observations. Fixed or variable modifications, including both PTMs and a select number of glycosylations, can be applied to the amino acid sequence. The application reports multiple scores and a matching fragment list. Fragmentation maps can be exported for publication in either portable network graphic (PNG) or scalable vector graphic (SVG) format. ProSight Lite can be freely downloaded from http://prosightlite.northwestern.edu, installs and updates from the web, and requires Windows 7 or a higher version.

  5. Basic mechanisms of longevity: A case study of Drosophila pro-longevity genes.

    PubMed

    Proshkina, Ekaterina N; Shaposhnikov, Mikhail V; Sadritdinova, Asiya F; Kudryavtseva, Anna V; Moskalev, Alexey A

    2015-11-01

    Drosophila is one of the most convenient model organisms in the genetics of aging and longevity. Unlike the nematodes, which allow for the detection of new pro-aging genes by knockout and RNAi-mediated knock-down, Drosophila also provides an opportunity to find new pro-longevity genes by driver-induced overexpression. Similar studies on other models are extremely rare. In this review, we focused on genes whose overexpression prolongs the life of fruit flies. The majority of longevity-associated genes regulates metabolism and stress resistance, and belongs to the IGF-1R, PI3K, PKB, AMPK and TOR metabolic regulation cluster and the FOXO, HDAC, p53 stress response cluster.

  6. Interaction of antibodies to synthetic peptides of proNGF with in vitro synthesized NGF precursors.

    PubMed

    Dicou, E

    1989-09-25

    Sera raised against three synthetic peptides that reproduce sequences of the pro-nerve growth factor (proNGF) protein were tested in immunoprecipitation experiments using in vitro translation products of SP6-directed NGF mRNA in a rabbit reticulocyte lysate. The interaction of these antibodies with bacterially synthesized chimeric preproNGF was also examined. Digestion of the translation products by the gamma-subunit generated the 22 and 18 kDa intermediates. A predominant 13 kDa intermediate was obtained after digestion of translation products in wheat germ extract. This is shown to be the N-terminal peptide by immunoprecipitation with an anti-peptide serum. These antibodies may be used to detect NGF precursor cleavage products in vivo.

  7. Follistatin-like protein 1 suppressed pro-inflammatory cytokines expression during neuroinflammation induced by lipopolysaccharide.

    PubMed

    Cheng, Kai-Yuan; Liu, Yi; Han, Ying-Guang; Li, Jing-Kun; Jia, Jia-Lin; Chen, Bin; Yao, Zhi-Xiao; Nie, Lin; Cheng, Lei

    2017-04-01

    Follistain-like protein 1 (FSTL1), has been recently demonstrated to be involved in the embryo development of nervous system and glioblastoma. However, the role of FSTL1 in neuroinflammation remains unexplored. In this study, the expression of FSTL1 in astrocytes was verified and its role was studied in neuroinflammation induced by in vivo intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) or LPS treatment to astrocytes in vitro. FSTL1 was significantly induced after ICV LPS injection or LPS treatment. FSTL1 suppressed upregulation of pro-inflammatory cytokines in astrocytes after LPS treatment. Moreover, FSTL1 downregulated expression of pro-inflammatory cytokines through suppressing MAPK/p-ERK1/2 pathway in astrocytes. Our results suggest that FSTL1 may play an anti-inflammatory role in neuroinflammation mediated by astrocytes.

  8. Caveolins: targeting pro-survival signaling in the heart and brain

    PubMed Central

    Stary, Creed M.; Tsutsumi, Yasuo M.; Patel, Piyush M.; Head, Brian P.; Patel, Hemal H.; Roth, David M.

    2012-01-01

    The present review discusses intracellular signaling moieties specific to membrane lipid rafts (MLRs) and the scaffolding proteins caveolin and introduces current data promoting their potential role in the treatment of pathologies of the heart and brain. MLRs are discreet microdomains of the plasma membrane enriched in gylcosphingolipids and cholesterol that concentrate and localize signaling molecules. Caveolin proteins are necessary for the formation of MLRs, and are responsible for coordinating signaling events by scaffolding and enriching numerous signaling moieties in close proximity. Specifically in the heart and brain, caveolins are necessary for the cytoprotective phenomenon termed ischemic and anesthetic preconditioning. Targeted overexpression of caveolin in the heart and brain leads to induction of multiple pro-survival and pro-growth signaling pathways; thus, caveolins represent a potential novel therapeutic target for cardiac and neurological pathologies. PMID:23060817

  9. BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain neurons

    PubMed Central

    Dieni, Sandra; Matsumoto, Tomoya; Dekkers, Martijn; Rauskolb, Stefanie; Ionescu, Mihai S.; Deogracias, Ruben; Gundelfinger, Eckart D.; Kojima, Masami; Nestel, Sigrun; Frotscher, Michael

    2012-01-01

    Although brain-derived neurotrophic factor (BDNF) regulates numerous and complex biological processes including memory retention, its extremely low levels in the mature central nervous system have greatly complicated attempts to reliably localize it. Using rigorous specificity controls, we found that antibodies reacting either with BDNF or its pro-peptide both stained large dense core vesicles in excitatory presynaptic terminals of the adult mouse hippocampus. Both moieties were ∼10-fold more abundant than pro-BDNF. The lack of postsynaptic localization was confirmed in Bassoon mutants, a seizure-prone mouse line exhibiting markedly elevated levels of BDNF. These findings challenge previous conclusions based on work with cultured neurons, which suggested activity-dependent dendritic synthesis and release of BDNF. They instead provide an ultrastructural basis for an anterograde mode of action of BDNF, contrasting with the long-established retrograde model derived from experiments with nerve growth factor in the peripheral nervous system. PMID:22412021

  10. Cyclo(His-Pro) promotes cytoprotection by activating Nrf2-mediated up-regulation of antioxidant defence

    PubMed Central

    Minelli, Alba; Conte, Carmela; Grottelli, Silvia; Bellezza, Maria; Cacciatore, Ivana; Bolaños, Juan P

    2009-01-01

    Hystidyl-proline [cyclo(His-Pro)] is an endogenous cyclic dipeptide produced by the cleavage of thyrotropin releasing hormone. Previous studies have shown that cyclo(His-Pro) protects against oxidative stress, although the underlying mechanism has remained elusive. Here, we addressed this issue and found that cyclo(His-Pro) triggered nuclear accumulation of NF-E2-related factor-2 (Nrf2), a transcription factor that up-regulates antioxidant-/electrophile-responsive element (ARE-EpRE)-related genes, in PC12 cells. Cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion caused by glutamate, rotenone, paraquat and β-amyloid treatment. Moreover, real-time PCR analyses revealed that cyclo(His-Pro) induced the expression of a number of ARE-related genes and protected cells against hydrogen peroxide-mediated apoptotic death. Furthermore, these effects were abolished by RNA interference-mediated Nrf2 knockdown. Finally, pharmacological inhibition of p-38 MAPK partially prevented both cyclo(His-Pro)-mediated Nrf2 activation and cellular protection. These results suggest that the signalling mechanism responsible for the cytoprotective actions of cyclo(His-Pro) would involve p-38 MAPK activation leading to Nrf2-mediated up-regulation of antioxidant cellular defence. PMID:18373731

  11. "I am a waste of breath, of space, of time": metaphors of self in a pro-anorexia group.

    PubMed

    Bates, Carolina Figueras

    2015-02-01

    According to recent research on eating disorders, heavy users of pro-anorexia (pro-ana) sites show higher levels of disordered eating and more severe impairment of quality of life than non-heavy users. A better understanding of how pro-ana members self-present in the virtual world could shed some light on these offline behaviors. Through discourse analysis, I examined the metaphors the members of a pro-ana group invoked in their personal profiles on a popular social networking site, to talk about the self. I applied the Metaphor Identification Procedure to 757 text profiles. I identified four key metaphorical constructions in pro-ana members' self-descriptions: self as space, self as weight, perfecting the self, and the social self. These four main metaphors represented discourse strategies, both to create a collective pro-ana identity and to enact an individual identity as pro-ana. In this article, I discuss the implications of these findings for the treatment of eating disorders.

  12. Brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) in genetically defined fear-induced aggression.

    PubMed

    Ilchibaeva, Tatiana V; Kondaurova, Elena M; Tsybko, Anton S; Kozhemyakina, Rimma V; Popova, Nina K; Naumenko, Vladimir S

    2015-09-01

    The brain-derived neurotrophic factor (BDNF), its precursor (proBDNF) and BDNF mRNA levels were studied in the brain of wild rats selectively bred for more than 70 generations for either high level or for the lack of affective aggressiveness towards man. Significant increase of BDNF mRNA level in the frontal cortex and increase of BDNF level in the hippocampus of aggressive rats was revealed. In the midbrain and hippocampus of aggressive rats proBDNF level was increased, whereas BDNF/proBDNF ratio was reduced suggesting the prevalence and increased influence of proBDNF in highly aggressive rats. In the frontal cortex, proBDNF level in aggressive rats was decreased. Thus, considerable structure-specific differences in BDNF and proBDNF levels as well as in BDNF gene expression between highly aggressive and nonaggressive rats were shown. The data suggested the implication of BDNF and its precursor proBDNF in the mechanism of aggressiveness and in the creation of either aggressive or nonaggressive phenotype.

  13. Early down-regulation of PKCδ as a pro-survival mechanism in Huntington's disease.

    PubMed

    Rué, Laura; Alcalá-Vida, Rafael; López-Soop, Graciela; Creus-Muncunill, Jordi; Alberch, Jordi; Pérez-Navarro, Esther

    2014-03-01

    A balance between cell survival and apoptosis is crucial to avoid neurodegeneration. Here, we analyzed whether the pro-apoptotic protein PKCδ, and the pro-survival PKCα and βII, were dysregulated in the brain of R6/1 mouse model of Huntington's disease (HD). Protein levels of the three PKCs examined were reduced in all the brain regions analyzed being PKCδ the most affected isoform. Interestingly, PKCδ protein levels were also decreased in the striatum and cortex of R6/2 and Hdh(Q111/Q111) mice, and in the putamen of HD patients. Nuclear PKCδ induces apoptosis, but we detected reduced PKCδ in both cytoplasmic and nuclear enriched fractions from R6/1 mouse striatum, cortex and hippocampus. In addition, we show that phosphorylation and ubiquitination of PKCδ are increased in 30-week-old R6/1 mouse brain. All together these results suggest a pro-survival role of reduced PKCδ levels in response to mutant huntingtin-induced toxicity. In fact, we show that over-expression of PKCδ increases mutant huntingtin-induced cell death in vitro, whereas over-expression of a PKCδ dominant negative form or silencing of endogenous PKCδ partially blocks mutant huntingtin-induced cell death. Finally, we show that the analysis of lamin B protein levels could be a good marker of PKCδ activity, but it is not involved in PKCδ-mediated cell death in mutant huntingtin-expressing cells. In conclusion, our results suggest that neurons increase the degradation of PKCδ as a compensatory pro-survival mechanism in response to mutant huntingtin-induced toxicity that can help to understand why cell death appears late in the disease.

  14. Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

    SciTech Connect

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana; Klegeris, Andis; Little, Jonathan P.

    2014-03-28

    Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.

  15. Pro-survival function of MEF2 in cardiomyocytes is enhanced by β-blockers

    PubMed Central

    Hashemi, S; Salma, J; Wales, S; McDermott, JC

    2015-01-01

    β1-Adrenergic receptor (β1-AR) stimulation increases apoptosis in cardiomyocytes through activation of cAMP/protein kinase A (PKA) signaling. The myocyte enhancer factor 2 (MEF2) proteins function as important regulators of myocardial gene expression. Previously, we reported that PKA signaling directly represses MEF2 activity. We determined whether (a) MEF2 has a pro-survival function in cardiomyocytes, and (b) whether β-adrenergic/PKA signaling modulates MEF2 function in cardiomyocytes. Initially, we observed that siRNA-mediated gene silencing of MEF2 induces cardiomyocyte apoptosis as indicated by flow cytometry. β1-AR activation by isoproterenol represses MEF2 activity and promotes apoptosis in cultured neonatal cardiomyocytes. Importantly, β1-AR mediated apoptosis was abrogated in cardiomyocytes expressing a PKA-resistant form of MEF2D (S121/190A). We also observed that a β1-blocker, Atenolol, antagonizes isoproterenol-induced apoptosis while concomitantly enhancing MEF2 transcriptional activity. β-AR stimulation modulated MEF2 cellular localization in cardiomyocytes and this effect was reversed by β-blocker treatment. Furthermore, Kruppel-like factor 6, a MEF2 target gene in the heart, functions as a downstream pro-survival factor in cardiomyocytes. Collectively, these data indicate that (a) MEF2 has an important pro-survival role in cardiomyocytes, and (b) β-adrenergic signaling antagonizes the pro-survival function of MEF2 in cardiomyocytes and β-blockers promote it. These observations have important clinical implications that may contribute to novel strategies for preventing cardiomyocyte apoptosis associated with heart pathology. PMID:27551452

  16. An Analysis of Mimosa pudica Leaves Movement by Using LoggerPro Software

    NASA Astrophysics Data System (ADS)

    Sugito; Susilo; Handayani, L.; Marwoto, P.

    2016-08-01

    The unique phenomena of Mimosa pudica are the closing and opening movements of its leaves when they got a stimulus. By using certain software, these movements can be drawn into graphic that can be analysed. The LoggerPro provides facilities needed to analyse recorded videos of the plant's reaction to stimulus. Then, through the resulted graph, analysis of some variables can be carried out. The result showed that the plant's movement fits an equation of y = mx + c.

  17. Stage for texture measurements above room temperature in a Philips X'Pert Pro MPD diffractometer

    SciTech Connect

    Sobrero, Cesar E.; Castellani, Daniel; Bolmaro, Raul E.; Malarria, Jorge A.

    2009-11-15

    A special stage for texture measurements above room temperature was designed with the proper size and weight to be fitted onto the Eulerean cradle of the Philips X'Pert Pro MPD diffractometer. With such device, flat samples of 2x2 cm{sup 2} area can be analyzed at a nearly constant temperature with variations below {+-}4 deg. C in the range between ambient temperature and 200 deg. C.

  18. 1DTempPro V2: new features for inferring groundwater/surface-water exchange

    USGS Publications Warehouse

    Koch, Franklin W.; Voytek, Emily B.; Day-Lewis, Frederick D.; Healy, Richard W.; Briggs, Martin; Lane, Jr., John W.; Werkema, Dale

    2016-01-01

    A new version of the computer program 1DTempPro extends the original code to include new capabilities for (1) automated parameter estimation, (2) layer heterogeneity, and (3) time-varying specific discharge. The code serves as an interface to the U.S. Geological Survey model VS2DH and supports analysis of vertical one-dimensional temperature profiles under saturated flow conditions to assess groundwater/surface-water exchange and estimate hydraulic conductivity for cases where hydraulic head is known.

  19. Pro-inflammatory effects of hydrogen sulphide on substance P in caerulein-induced acute pancreatitis.

    PubMed

    Bhatia, Madhav; Sidhapuriwala, Jenab N; Ng, Siaw Wei; Tamizhselvi, Ramasamy; Moochhala, Shabbir M

    2008-04-01

    Hydrogen sulphide (H(2)S), a novel gasotransmitter, has been recognized to play an important role in inflammation. Cystathionine-gamma-lyase (CSE) is a major H(2)S synthesizing enzyme in the cardiovascular system and DL-propargylglycine (PAG) is an irreversible inhibitor of CSE. Substance P (SP), a product of preprotachykinin-A (PPT-A) gene, is a well-known pro-inflammatory mediator which acts principally through the neurokinin-1 receptor (NK-1R). We have shown an association between H(2)S and SP in pulmonary inflammation as well as a pro-inflammatory role of H(2)S and SP in acute pancreatitis. The present study was aimed to investigate the interplay between pro-inflammatory effects of H(2)S and SP in a murine model of caerulein-induced acute pancreatitis. Acute pancreatitis was induced in mice by 10 hourly intraperitoneal injections of caerulein (50 (g/kg). PAG (100 mg/kg, i.p.) was administered either 1 hr before (prophylactic) or 1 hr after (therapeutic) the first caerulein injection. PAG, given prophylactically as well as therapeutically, significantly reduced plasma H(2)S levels and pancreatic H(2)S synthesizing activities as well as SP concentrations in plasma, pancreas and lung compared with caerulein-induced acute pancreatitis. Furthermore, prophylactic as well as therapeutic administration of PAG significantly reduced PPT-A mRNA expression and NK-1R mRNA expression in both pancreas and lung when compared with caerulein-induced acute pancreatitis. These results suggest that the pro-inflammatory effects of H(2)S may be mediated by SP-NK-1R pathway in acute pancreatitis.

  20. Determining Erosion Rates and Processes in the Pro-Glacial Area over a 28-Year Period

    NASA Astrophysics Data System (ADS)

    Delaney, I. A.; Huss, M.; Weidmann, Y.

    2015-12-01

    Glacially fed hydropower reservoirs in the Swiss Alps have experienced substantial increases in sedimentation recently. This sedimenation causes reduced reservoir capacity, turbine abrasion and increased need for sediment flushing, all of which reduce the efficiency and economic viability of hydropower in the region. Although the issue is largely attributed to regional glacier retreat, there is a need for greater understanding of the specific processes that contribute to the increased sedimentation. To evaluate these processes, we examine the Griesgletscher catchment, which lies in the central Swiss Alps and its runoff feeds a hydropower reservoir. The recent exposure of the glacier's fore-field (roughly 1986) due to the glacier's retreat beyond the reservoir's margin, along with its simple catchment area make it an ideal location to examine pro-glacial erosion. Here we present a time-series from 1986 to 2014 of digital elevation models (DEM) created from aerial photographs of the Griesgletscher's fore-field from each year except for 2. Comparison of DEMs from subsequent years yields erosion volumes and sediment balance over the 28 year period for the pro-glacial area. Bathymetry of the pro-glacial reservoir for select years allows us to speculate if the erosion of the recently exposed glacier fore-field is the sole source of sediment to the reservoir, or if alternative processes such as increased glacial erosion or mobilization of sub-glacial sediments could contribute. We correlate erosion amounts with runoff volumes from the Griesgletscher and changes in the the glacier's morophology and coverage. Additionally, implimentation of the Glacier Evolution Runoff Model allows us to examine the variability in the glacier's runoff on the hourly to daily scale. By examining these relationships we constrain the processes contributing to the erosion of the Griesgletscher's pro-glacial area.