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Sample records for proteolysis studies identified

  1. Peptidomics for Studying Limited Proteolysis.

    Science.gov (United States)

    Tsuchiya, Takashi; Osaki, Tsukasa; Minamino, Naoto; Sasaki, Kazuki

    2015-11-06

    Limited proteolysis is a pivotal mechanism regulating protein functions. Identifying physiologically or pathophysiologically relevant cleavage sites helps to develop molecular tools that can be used for diagnostics or therapeutics. During proteolysis of secretory and membrane proteins, part of the cleaved protein is liberated and destined to undergo degradation but should retain original cleavage sites created by proteolytic enzymes. We profiled endogenous peptides accumulated for 4 h in media conditioned by primary cultured rat cardiac fibroblasts. A total of 3916 redundant peptide sequences from 94 secretory proteins and membrane proteins served to identify limited cleavage sites, both annotated and unannotated, for signal peptide or propeptide removal, peptide hormone processing, ectodomain shedding, and regulated intramembrane proteolysis. Incorrectly predicted signal cleavage sites are found in typical proteins such as extracellular matrix proteins and the peptide hormone precursor adrenomedullin ADM. The revealed signal peptide cleavage site for ADM was experimentally verified by identifying the major molecular form of flanking proadrenomedullin N-terminal peptide. We suggest that profiling of endogenous peptides, like transcriptome sequence reads, makes sense in regular cells such as fibroblasts and that peptidomics provides insight into proteolysis-regulated protein functions.

  2. Proteolysis in hyperthermophilic microorganisms

    Directory of Open Access Journals (Sweden)

    Donald E. Ward

    2002-01-01

    Full Text Available Proteases are found in every cell, where they recognize and break down unneeded or abnormal polypeptides or peptide-based nutrients within or outside the cell. Genome sequence data can be used to compare proteolytic enzyme inventories of different organisms as they relate to physiological needs for protein modification and hydrolysis. In this review, we exploit genome sequence data to compare hyperthermophilic microorganisms from the euryarchaeotal genus Pyrococcus, the crenarchaeote Sulfolobus solfataricus, and the bacterium Thermotoga maritima. An overview of the proteases in these organisms is given based on those proteases that have been characterized and on putative proteases that have been identified from genomic sequences, but have yet to be characterized. The analysis revealed both similarities and differences in the mechanisms utilized for proteolysis by each of these hyperthermophiles and indicated how these mechanisms relate to proteolysis in less thermophilic cells and organisms.

  3. A primary study on texture modification and proteolysis of mao-tofu ...

    African Journals Online (AJOL)

    Proteolysis occurred during fermentation was evaluated by SDS-PAGE and chemical analysis. Results from Texture Profile Analysis showed that adhesiveness of mao-tofu had an increase trend while hardness, cohesiveness and springiness had a decrease trend as fermentation progressed. SEM analysis showed that the ...

  4. A SIMPLE FLUORESCENT LABELING METHOD FOR STUDIES OF PROTEIN OXIDATION, PROTEIN MODIFICATION, AND PROTEOLYSIS

    Science.gov (United States)

    Pickering, Andrew. M.; Davies, Kelvin. J. A.

    2014-01-01

    Proteins are sensitive to oxidation, and oxidized proteins are excellent substrates for degradation by proteolytic enzymes such as the Proteasome and the mitochondrial Lon protease. Protein labeling is required for studies of protein turnover. Unfortunately, most labeling techniques involve 3H or 14C methylation which is expensive, exposes researchers to radioactivity, generates large amounts of radioactive waste, and allows only single-point assays because samples require acid-precipitation. Alternative labeling methods, have largely proven unsuitable, either because the probe itself is modified by the oxidant(s) being studied, or because the alternative labeling techniques are too complex or too costly for routine use. What is needed is a simple, quick, and cheap labeling technique that uses a non-radioactive marker, that binds strongly to proteins, is resistant to oxidative modification, and emits a strong signal. We have devised a new reductive method for labeling free carboxyl groups of proteins with the small fluorophore 7-amino-4-methycoumarin (AMC). When bound to target proteins, AMC fluoresces very weakly but when AMC is released by proteinases, proteases, or peptidases, it fluoresces strongly. Thus, without acid-precipitation, the proteolysis of any target protein can be studied continuously, in multiwell plates. In direct comparisons, 3H-labeled proteins and AMC-labeled proteins exhibited essentially identical degradation patterns during incubation with trypsin, cell extracts, and purified proteasome. AMC-labeled proteins are well-suited to study increased proteolytic susceptibility following protein modification, since the AMC-protein bond is resistant to oxidizing agents such as hydrogen peroxide and peroxynitrite, and is stable over time and to extremes of pH, temperature (even boiling), freeze-thawing, mercaptoethanol, and methanol. PMID:21988844

  5. Protein trafficking and maturation regulate intramembrane proteolysis.

    Science.gov (United States)

    Morohashi, Yuichi; Tomita, Taisuke

    2013-12-01

    Intramembrane-cleaving proteases (I-CLiPs) are membrane embedded proteolytic enzymes. All substrates identified so far are also membrane proteins, involving a number of critical cellular signaling as well as human diseases. After synthesis and assembly at the endoplasmic reticulum, membrane proteins are exported to the Golgi apparatus and transported to their sites of action. A number of studies have revealed the importance of the intracellular membrane trafficking in i-CLiP-mediated intramembrane proteolysis, not only for limiting the unnecessary encounter between i-CLiPs and their substrate but also for their cleavage site preference. In this review, we will discuss recent advances in our understanding of how each i-CLiP proteolysis is regulated by intracellular vesicle trafficking. This article is part of a Special Issue entitled: Intramembrane Proteases. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Complementary methods for the identification of substrates of proteolysis.

    Science.gov (United States)

    Pham, Victoria C; Anania, Veronica G; Phung, Qui T; Lill, Jennie R

    2014-01-01

    Proteolysis describes the cleavage of proteins into smaller components, which in vivo occurs typically to either activate or impair the functionality of cellular proteins. Proteolysis can occur during cellular homeostasis or can be induced due to external stress stimuli such as heat, biological or chemical insult, and is mediated by the activity of cellular enzymes, namely, proteases. Proteolytic cleavage of proteins can influence protein activation by exposing an active site or disrupting inhibitor binding. Conversely, proteolytic cleavage of many proteins has also been shown to lead to protein degradation resulting in inactivation of the substrate. Thousands of proteolytic events are known to take place in regulated cellular processes such as apoptosis and pyroptosis, however, their individual contribution to these processes remains poorly understood. Additionally, many cellular homeostatic processes are regulated by proteolytic events, however, in some cases, few proteolytic substrates have been identified. To gain further insight into the mechanism of action of these cellular processes, and to characterize biomarkers of cell death and other pathological indications, it is imperative to utilize a complete arsenal of tools for studying proteolysis events in vivo and in vitro. In this chapter, we focus on alternative methodologies to N-terminomics for profiling substrates of proteolysis and describe an additional suite of tools including orthogonal biophysical separation techniques such as COFRADIC or GASSP, and affinity capture tools that can enrich for newly formed C-termini (C-terminomics) generated as a result of caspase-mediated proteolysis. © 2014 Elsevier Inc. All rights reserved.

  7. Continuous fast Fourier transforms cyclic voltammetry as a new approach for investigation of skim milk k-casein proteolysis, a comparative study.

    Science.gov (United States)

    Shayeh, Javad Shabani; Sefidbakht, Yahya; Siadat, Seyed Omid Ranaei; Niknam, Kaveh

    2017-10-01

    Cheese production is relied upon the action of Rennet on the casein micelles of milk. Chymosin assay methods are usually time consuming and offline. Herein, we report a new electrochemical technique for studying the proteolysis of K-casein. The interaction of rennet and its substrate was studied by fast Fourier transform continuous cyclic voltammetry (FFTCCV) based on a determination of k-casein in aqueous solution. FFTCCV technique is a very useful method for studying the enzymatic procedures. Fast response, no need of modified electrodes or complex equipment is some of FFTCCV advantages. Various concentrations of enzyme and substrate were selected and the increase in the appearance of charged species in solution as a result of the addition of rennet was studied. Data obtained using FFTCCV technique were also confirmed by turbidity analysis. The results show that rennet proteolysis activity occurs in much shorter time scales compare with its aggregation. Hence, following the appearance of charged segments as a result of proteolysis could be under consideration as a rapid and online method. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Limited proteolysis combined with isotope labeling and quantitative LC-MALDI MS for monitoring protein conformational changes: a study on calcium-binding sites of cardiac Troponin C

    International Nuclear Information System (INIS)

    McDonald, Chris; Li Liang

    2005-01-01

    Studies of protein-protein and protein-ligand interactions are important for understanding biological functions of proteins. A new technique based on the partial proteolysis of proteins combined with quantitative mass spectrometry is developed as a means of tracking structural changes after the formation of a protein-ligand complex. In this technique, a protein of interest with and without the binding of a ligand is digested with an enzyme to generate a set of peptides, followed by separation of the peptides by liquid chromatography. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) is used to identify chromatographically separated peptides, and locate their sequence alignments in the parent protein. Using an isotopically labeled protein as a sample against an unlabeled protein standard, quantitative information can be gathered. This overcomes the inherent lack of quantitative capability of MALDI MS. The utility of the technique to investigate protein-ligand interactions is demonstrated in a model system involving calcium binding to cardiac Troponin C (cTnC). Using this technique, the general location of the three calcium-binding sites of cTnC can be determined by using several different enzymes to generate overlapping peptide maps of cTnC

  9. Proteolysis in soft cheese, studied on Meshanger cheese and cheese models

    NARCIS (Netherlands)

    Noomen, A.

    1978-01-01

    Enzymes predominantly responsible for the primary degradation of protein in soft cheese and for the related changes in consistency were studied. Reconstructed Noordhollandse Meshanger cheese and preserved simulated soft cheeses of different composition were used as models in the

  10. Cooperation of two ADAMTS metalloproteases in closure of the mouse palate identifies a requirement for versican proteolysis in regulating palatal mesenchyme proliferation

    OpenAIRE

    Enomoto, Hiroyuki; Nelson, Courtney M.; Somerville, Robert P. T.; Mielke, Katrina; Dixon, Laura J.; Powell, Kimerly; Apte, Suneel S.

    2010-01-01

    We have identified a role for two evolutionarily related, secreted metalloproteases of the ADAMTS family, ADAMTS20 and ADAMTS9, in palatogenesis. Adamts20 mutations cause the mouse white-spotting mutant belted (bt), whereas Adamts9 is essential for survival beyond 7.5 days gestation (E7.5). Functional overlap of Adamts9 with Adamts20 was identified using Adamts9+/–;bt/bt mice, which have a fully penetrant cleft palate. Palate closure was delayed, although eventually completed, in both Adamts9...

  11. Estrogen receptor of primary breast cancers: evidence for intracellular proteolysis

    International Nuclear Information System (INIS)

    Maaroufi, Younes; Lacroix, Marc; Lespagnard, Laurence; Journé, Fabrice; Larsimont, Denis; Leclercq, Guy

    2000-01-01

    Iodinated oestradiol-labeled oestrogen receptor (ER) isoforms devoid of amino-terminal ABC domains represent about two-thirds of the whole receptor population detected in cytosol samples from human breast cancers. This high frequency could not be ascribed to the expression of truncated mRNAs, or to the proteolysis of the native ER peptide at the time of homogenization or assay, suggesting an intracellular proteolysis. Free amino-terminal and ligand-binding domains maintained together within oligomeric structure(s); increase of ionic strength separated them. The amino-terminal region was consistently detected in the cell nucleus by specific immunohistochemistry leading to the concept of a potential intranuclear association between ER cleavage products and/or other regulatory proteins. We previously reported that about two-thirds of [ 125 I]oestradiol-labelled cytosolic ERs from breast cancer samples eluted as low-molecular-weight isoforms (≤ 37 kDa, size-exclusion fast pressure liquid chromatography [FPLC]). These isoforms failed to adsorb strongly to hydroxylapatite at high ionic strength, a property that was ascribed to receptors devoid of amino-terminal ABC domains. In view of recent data concerning intracellular proteolysis of several transcriptional regulators, the possibility of such behaviour for ER was assessed. The clinical significance of ER measurement in breast cancer cytosols is well established; approximately 50% of ER-positive cases respond to endocrine therapy. Whether such a poor correlation is related to a high proportion of cleaved ER is a question of prime importance. Failure of routine ER assays to discriminate between full-length and cleaved receptors led us to develop an oestradiol-binding assay based on hydroxylapatite adsorption. The aims of the present study were to demonstrate that hydroxylapatite adsorption assay easily identifies cleaved cytosolic ER forms and to assess the origin of such ER forms. Breast cancer cytosols classified as

  12. Ubiquitin-mediated proteolysis in Xenopus extract.

    Science.gov (United States)

    McDowell, Gary S; Philpott, Anna

    2016-01-01

    The small protein modifier, ubiquitin, can be covalently attached to proteins in the process of ubiquitylation, resulting in a variety of functional outcomes. In particular, the most commonly-associated and well-studied fate for proteins modified with ubiquitin is their ultimate destruction: degradation by the 26S proteasome via the ubiquitin-proteasome system, or digestion in lysosomes by proteolytic enzymes. From the earliest days of ubiquitylation research, a reliable and versatile "cell-in-a-test-tube" system has been employed in the form of cytoplasmic extracts from the eggs and embryos of the frog Xenopus laevis. Biochemical studies of ubiquitin and protein degradation using this system have led to significant advances particularly in the study of ubiquitin-mediated proteolysis, while the versatility of Xenopus as a developmental model has allowed investigation of the in vivo consequences of ubiquitylation. Here we describe the use and history of Xenopus extract in the study of ubiquitin-mediated protein degradation, and highlight the versatility of this system that has been exploited to uncover mechanisms and consequences of ubiquitylation and proteolysis.

  13. Effect of protein degradation on spot Mr distribution in 2-D gels – a case study of proteolysis during development of Streptomyces coelicolor cultures

    Czech Academy of Sciences Publication Activity Database

    Vohradský, Jiří; Branny, Pavel; Li, X.-M.; Thompson, CH. J.

    2008-01-01

    Roč. 8, č. 12 (2008), s. 2371-2375 ISSN 1615-9853 R&D Projects: GA ČR GA310/07/1009 Grant - others:AT(AT) EC Integrated Project ActinoGEN, LSHM-CT-2004-005224 Institutional research plan: CEZ:AV0Z50200510 Keywords : 2-de * proteolysis * streptomyces Subject RIV: EE - Microbiology, Virology Impact factor: 4.586, year: 2008

  14. Implications of the Maillard reaction on bovine alpha-lactalbumin and its proteolysis during in vitro infant digestion.

    Science.gov (United States)

    Joubran, Yousef; Moscovici, Alice; Portmann, Reto; Lesmes, Uri

    2017-06-21

    This study investigated the functionality and digestibility of Maillard reaction products (MRPs) of alpha-lactalbumin (α-la), a major whey protein and component of infant formulas. The impact of different carbohydrates (glucose, galactose or galacto-oligosaccharides (GOS)) and heating duration was studied. SDS-PAGE, UV and color measurements monitored reaction extent, which varied between carbohydrates whereby galactose reacted more readily than glucose. Surface hydrophobicity and antioxidant capacity were found to be significantly (p Maillard conjugation, with GOS-based MRPs elevating antioxidant capacity ∼50-fold compared to α-la. In addition, the digestive proteolysis of MRPs was evaluated using an infant in vitro gastro-duodenal model. SDS-PAGE analyses of digesta revealed Maillard conjugation generally increased α-la's susceptibility to proteolysis. Interestingly, GOS-based MRPs presented an optimization challenge, since heating for 12 h delayed proteolysis, while extended heating resulted in the highest susceptibility to proteolysis. Proteomic analyses further demonstrated the differences in enzymatic cleavage patterns and helped identify bioactive peptides rendered bioaccessible during the digestion of α-la or its MRPs. Bioinformatic mining of the proteomic data using PeptideRanker also gave rise to two potentially novel bioactive peptides, FQINNKIW and GINYWLAHKALCS. Finally, antioxidant capacity of luminal contents, measured by DPPH, revealed Maillard conjugation increased the antioxidant capacity of both gastric and duodenal digesta. Overall, this work draws a link between the Maillard reaction, digestive proteolysis and the bioaccessibility of bioactive peptides and antioxidant species in the infant alimentary canal. This could help rationally process infant formulas towards improved nutritional and extra-nutritional benefits.

  15. The effect of different packaging materials on proteolysis, sensory ...

    African Journals Online (AJOL)

    In this study, tulum cheese was manufactured using raw ewe's milk and was ripened in goat's skin and plastic bags. The effect of ripening materials (skin bag or plastic) on proteolysis was investigated during 120 days of ripening. In addition, sensory scores of the cheeses were assessed at the 90th and 120th days.

  16. Sequence analysis of PROTEOLYSIS 6 from Solanum lycopersicum

    Science.gov (United States)

    Roslan, Nur Farhana; Chew, Bee Lyn; Goh, Hoe-Han; Isa, Nurulhikma Md

    2018-04-01

    The N-end rule pathway is a protein degradation pathway that relates the protein half-life with the identity of its N-terminal residues. A destabilizing N-terminal residues is created by enzymatic reaction or chemical modifications. This destabilized substrate will be recognized by PROTEOLYSIS 6 (PRT6) protein, which encodes an E3 ligase enzyme and resulted in substrate degradation by proteasome. PRT6 has been studied in Arabidopsis thaliana and barley but not yet been studied in fleshy fruit plants. Hence, this study was carried out in tomato that is known as the model for fleshy fruit plants. BLASTX analysis identified that Solyc09g010830 which encodes for a PRT6 gene in tomato based on its sequence similarity with PRT6 in A. thaliana. In silico gene expression analysis shows that PRT6 gene was highly expressed in tomato fruits breaker +5. Co-expression analysis shows that PRT6 may not only involved in abiotic stresses but also in biotic stresses. The objective is to analyze the sequence and characterize PRT6 gene in tomato.

  17. [Pharmacological mechanism analysis of oligopeptide from Pinctada fucata based on in silico proteolysis and protein interaction network].

    Science.gov (United States)

    Chen, Yan-Kun; Qiao, Lian-Sheng; Huo, Xiao-Qian; Zhang, Xu; Han, Na; Zhang, Yan-Ling

    2017-09-01

    Pinctada fucata oligopeptide is one of key pharmaceutical effective constituents of P. fucata. It is significant to analyze its pharmacological effect and mechanism. This study aims to discover the potential oligopeptides from P. fucata and analyze the mechanism of P. fucata oligopeptide based on in silico technologies and protein interaction network(PIN). First, main protein sequences of P. fucata were collected, and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then, key potential targets of P. fucata oligopeptides were obtained through pharmacophore screening. The protein-protein interaction(PPI) of targets was achieved and implemented to construct PIN and analyze the mechanism of P. fucata oligopeptides. P. fucata oligopeptide database was constructed based on in silico technologies, including 458 oligopeptides. Twelve modules were identified from PIN by a graph theoretic clustering algorithm Molecular Complex Detection(MCODE) and analyzed by Gene ontology(GO) enrichment. The results indicated that P. fucata oligopeptides have an effect in treating neurological diseases, such as Alzheimer's disease. In silico proteolysis could be used to analyze the protein sequences of traditional Chinese medicine(TCM). According to the combination of in silico proteolysis and PIN, the biological activity of oligopeptides could be interpreted rapidly based on the known TCM protein sequence. The study provides the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides. Copyright© by the Chinese Pharmaceutical Association.

  18. Allosteric regulation of rhomboid intramembrane proteolysis.

    Science.gov (United States)

    Arutyunova, Elena; Panwar, Pankaj; Skiba, Pauline M; Gale, Nicola; Mak, Michelle W; Lemieux, M Joanne

    2014-09-01

    Proteolysis within the lipid bilayer is poorly understood, in particular the regulation of substrate cleavage. Rhomboids are a family of ubiquitous intramembrane serine proteases that harbour a buried active site and are known to cleave transmembrane substrates with broad specificity. In vitro gel and Förster resonance energy transfer (FRET)-based kinetic assays were developed to analyse cleavage of the transmembrane substrate psTatA (TatA from Providencia stuartii). We demonstrate significant differences in catalytic efficiency (kcat/K0.5) values for transmembrane substrate psTatA (TatA from Providencia stuartii) cleavage for three rhomboids: AarA from P. stuartii, ecGlpG from Escherichia coli and hiGlpG from Haemophilus influenzae demonstrating that rhomboids specifically recognize this substrate. Furthermore, binding of psTatA occurs with positive cooperativity. Competitive binding studies reveal an exosite-mediated mode of substrate binding, indicating allostery plays a role in substrate catalysis. We reveal that exosite formation is dependent on the oligomeric state of rhomboids, and when dimers are dissociated, allosteric substrate activation is not observed. We present a novel mechanism for specific substrate cleavage involving several dynamic processes including positive cooperativity and homotropic allostery for this interesting class of intramembrane proteases. © 2014 The Authors.

  19. Proteolysis and consistency of Meshanger cheese

    NARCIS (Netherlands)

    Jong, de L.

    1978-01-01

    Proteolysis in Meshanger cheese, estimated by quantitative polyacrylamide gel electrophoresis is discussed. The conversion of α s1 -casein was proportional to rennet concentration in the cheese. Changes in consistency, after a maximum, were correlated to breakdown of

  20. Taking a position on intramembrane proteolysis.

    Science.gov (United States)

    Lemieux, M Joanne

    2018-03-30

    Decades of work have contributed to our in-depth mechanistic understanding of soluble proteases, but much less is known about the catalytic mechanism of intramembrane proteolysis due to inherent difficulties in both preparing and analyzing integral membrane enzymes and transmembrane substrates. New work from Naing et al. tackles this challenge by examining the catalytic parameters of an aspartyl intramembrane protease homologous to the enzyme that cleaves amyloid precursor protein, finding that both chemistry and register contribute to specificity in substrate cleavage. © 2018 Joanne Lemieux.

  1. Regulation of progranulin expression in human microglia and proteolysis of progranulin by matrix metalloproteinase-12 (MMP-12.

    Directory of Open Access Journals (Sweden)

    Hyeon-Sook Suh

    Full Text Available The essential role of progranulin (PGRN as a neurotrophic factor has been demonstrated by the discovery that haploinsufficiency due to GRN gene mutations causes frontotemporal lobar dementia. In addition to neurons, microglia in vivo express PGRN, but little is known about the regulation of PGRN expression by microglia.In the current study, we examined the regulation of expression and function of PGRN, its proteolytic enzyme macrophage elastase (MMP-12, as well as the inhibitor of PGRN proteolysis, secretory leukocyte protease inhibitor (SLPI, in human CNS cells.Cultures of primary human microglia and astrocytes were stimulated with the TLR ligands (LPS or poly IC, Th1 cytokines (IL-1/IFNγ, or Th2 cytokines (IL-4, IL-13. Results were analyzed by Q-PCR, immunoblotting or ELISA. The roles of MMP-12 and SLPI in PGRN cleavage were also examined.Unstimulated microglia produced nanogram levels of PGRN, and PGRN release from microglia was suppressed by the TLR ligands or IL-1/IFNγ, but increased by IL-4 or IL-13. Unexpectedly, while astrocytes stimulated with proinflammatory factors released large amounts of SLPI, none were detected in microglial cultures. We also identified MMP-12 as a PGRN proteolytic enzyme, and SLPI as an inhibitor of MMP-12-induced PGRN proteolysis. Experiments employing PGRN siRNA demonstrated that microglial PGRN was involved in the cytokine and chemokine production following TLR3/4 activation, with its effect on TNFα being the most conspicuous.Our study is the first detailed examination of PGRN in human microglia. Our results establish microglia as a significant source of PGRN, and MMP-12 and SLPI as modulators of PGRN proteolysis. Negative and positive regulation of microglial PGRN release by the proinflammatory/Th1 and the Th2 stimuli, respectively, suggests a fundamentally different aspect of PGRN regulation compared to other known microglial activation products. Microglial PGRN appears to function as an endogenous

  2. Conformational changes in DNA gyrase revealed by limited proteolysis

    DEFF Research Database (Denmark)

    Kampranis, S C; Maxwell, A

    1998-01-01

    We have used limited proteolysis to identify conformational changes in DNA gyrase. Gyrase exhibits a proteolytic fingerprint dominated by two fragments, one of approximately 62 kDa, deriving from the A protein, and another of approximately 25 kDa from the B protein. Quinolone binding to the enzyme......-DNA intermediate by calcium ions does not reveal any protection, suggesting that the quinolone-induced conformational change is different from an "open-gate" state of the enzyme. A quinolone-resistant mutant of gyrase fails to give the characteristic quinolone-associated proteolytic signature. The ATP...... does not prevent dimerization since incubation of the enzyme-DNA complex with both ADPNP and quinolones gives rise to a complex whose proteolytic pattern retains the characteristic signature of dimerization but has lost the quinolone-induced protection. As a result, the quinolone-gyrase complex can...

  3. New concepts in molecular imaging: non-invasive MRI spotting of proteolysis using an Overhauser effect switch.

    Directory of Open Access Journals (Sweden)

    Philippe Mellet

    Full Text Available Proteolysis, involved in many processes in living organisms, is tightly regulated in space and time under physiological conditions. However deregulation can occur with local persistent proteolytic activities, e.g. in inflammation, cystic fibrosis, tumors, or pancreatitis. Furthermore, little is known about the role of many proteases, hence there is a need of new imaging methods to visualize specifically normal or disease-related proteolysis in intact bodies.In this paper, a new concept for non invasive proteolysis imaging is proposed. Overhauser-enhanced Magnetic Resonance Imaging (OMRI at 0.2 Tesla was used to monitor the enzymatic hydrolysis of a nitroxide-labeled protein. In vitro, image intensity switched from 1 to 25 upon proteolysis due to the associated decrease in the motional correlation time of the substrate. The OMRI experimental device used in this study is consistent with protease imaging in mice at 0.2 T without significant heating. Simulations show that this enzymatic-driven OMRI signal switch can be obtained at lower frequencies suitable for larger animals or humans.The method is highly sensitive and makes possible proteolysis imaging in three dimensions with a good spatial resolution. Any protease could be targeted specifically through the use of taylor-made cleavable macromolecules. At short term OMRI of proteolysis may be applied to basic research as well as to evaluate therapeutic treatments in small animal models of experimental diseases.

  4. Immobilization of trypsin on miniature incandescent bulbs for infrared-assisted proteolysis

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Huimin; Bao, Huimin; Zhang, Luyan; Chen, Gang, E-mail: gangchen@fudan.edu.cn

    2014-10-03

    Highlights: • Trypsin was immobilized on miniature incandescent bulbs via chitosan coating. • The bulbs acted as enzymatic reactors and the generators of infrared radiation. • The bulb bioreactors were successfully employed in infrared-assisted proteolysis. • The proteolysis could accomplish within 5 min with high sequence coverages. - Abstract: A novel efficient proteolysis approach was developed based on trypsin-immobilized miniature incandescent bulbs and infrared (IR) radiation. Trypsin was covalently immobilized in the chitosan coating on the outer surface of miniature incandescent bulbs with the aid of glutaraldehyde. When an illuminated enzyme-immobilized bulb was immersed in protein solution, the emitted IR radiation could trigger and accelerate heterogeneous protein digestion. The feasibility and performance of the novel proteolysis approach were demonstrated by the digestion of hemoglobin (HEM), cytochrome c (Cyt-c), lysozyme (LYS), and ovalbumin (OVA) and the digestion time was significantly reduced to 5 min. The obtained digests were identified by MALDI-TOF-MS with the sequence coverages of 91%, 77%, 80%, and 52% for HEM, Cyt-c, LYS, and OVA (200 ng μL{sup −1} each), respectively. The suitability of the prepared bulb bioreactors to complex proteins was demonstrated by digesting human serum.

  5. Cellular signaling identifiability analysis: a case study.

    Science.gov (United States)

    Roper, Ryan T; Pia Saccomani, Maria; Vicini, Paolo

    2010-05-21

    Two primary purposes for mathematical modeling in cell biology are (1) simulation for making predictions of experimental outcomes and (2) parameter estimation for drawing inferences from experimental data about unobserved aspects of biological systems. While the former purpose has become common in the biological sciences, the latter is less common, particularly when studying cellular and subcellular phenomena such as signaling-the focus of the current study. Data are difficult to obtain at this level. Therefore, even models of only modest complexity can contain parameters for which the available data are insufficient for estimation. In the present study, we use a set of published cellular signaling models to address issues related to global parameter identifiability. That is, we address the following question: assuming known time courses for some model variables, which parameters is it theoretically impossible to estimate, even with continuous, noise-free data? Following an introduction to this problem and its relevance, we perform a full identifiability analysis on a set of cellular signaling models using DAISY (Differential Algebra for the Identifiability of SYstems). We use our analysis to bring to light important issues related to parameter identifiability in ordinary differential equation (ODE) models. We contend that this is, as of yet, an under-appreciated issue in biological modeling and, more particularly, cell biology. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  6. Proteolysis produced within biofilms of bacterial isolates from raw milk tankers.

    Science.gov (United States)

    Teh, Koon Hoong; Flint, Steve; Palmer, Jon; Andrewes, Paul; Bremer, Phil; Lindsay, Denise

    2012-06-15

    In this study, six bacterial isolates that produced thermo-resistant enzymes isolated from the internal surfaces of raw milk tankers were evaluated for their ability to produce proteolysis within either single culture biofilms or co-culture biofilms. Biofilms were formed in an in vitro model system that simulated the upper internal surface of a raw milk tanker during a typical summer's day of milk collection in New Zealand. The bacterial isolates were further evaluated for their ability to form biofilms at 25, 30 and 37°C. Mutual and competitive effects were observed in some of the co-culture biofilms, with all isolates being able to form biofilms in either single culture or co-culture at the three temperatures. The proteolysis was also evaluated in both biofilms and corresponding planktonic cultures. The proteolysis per cell decreased as the temperature of incubation (20-37°C) increased. Furthermore, mutualistic interactions in terms of proteolysis were observed when cultures were grown as co-culture biofilms. This is the first study to show that proteolytic enzymes can be produced in biofilms on the internal surfaces of raw milk tankers. This has important implications for the cleaning and the temperature control of raw milk transport tankers. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Degradation of connective tissue matrices by macrophages. III. Morphological and biochemical studies on extracellular, pericellular, and intracellular events in matrix proteolysis by macrophages in culture

    International Nuclear Information System (INIS)

    Werb, Z.; Bainton, D.F.; Jones, P.A.

    1980-01-01

    The aim of the present study was to determine the localization of macrophage-mediated degradation of matrix proteins. The sites of matrix degradation were examined ultrastructurally, and the effects of modulation of macrophage secretion, endocytosis, and activity of macrophage hydrolases on matrix degradation were monitored biochemically

  8. Functional Imaging of Proteolysis: Stromal and Inflammatory Cells Increase Tumor Proteolysis

    Directory of Open Access Journals (Sweden)

    Mansoureh Sameni

    2003-07-01

    Full Text Available The underlying basement membrane is degraded during progression of breast and colon carcinoma. Thus, we imaged degradation of a quenched fluorescent derivative of basement membrane type IV collagen (DQ-collagen IV by living human breast and colon tumor spheroids. Proteolysis of DQ-collagen IV by HCT 116 and HKh-2 human colon tumor spheroids was both intracellular and pericellular. In contrast, proteolysis of DQ-collagen IV by BT20 human breast tumor spheroids was pericellular. As stromal elements can contribute to proteolytic activities associated with tumors, we also examined degradation of DQ-collagen IV by human monocytes/macrophages and colon and breast fibroblasts. Fibroblasts themselves exhibited a modest amount of pericellular degradation. Degradation was increased 4–17-fold in cocultures of fibroblasts and tumor cells as compared to either cell type alone. Inhibitors of matrix metalloproteinases, plasmin, and the cysteine protease, cathepsin B, all reduced degradation in the cocultures. Monocytes did not degrade DQ-collagen IV; however, macrophages degraded DQ-collagen IV intracellularly. In coculture of tumor cells, fibroblasts, and macrophages, degradation of DQ-collagen IV was further increased. Imaging of living tumor and stromal cells has, thus, allowed us to establish that tumor proteolysis occurs pericellularly and intracellularly and that tumor, stromal, and inflammatory cells all contribute to degradative processes.

  9. The Vip3Ag4 Insecticidal Protoxin from Bacillus thuringiensis Adopts A Tetrameric Configuration That Is Maintained on Proteolysis

    Directory of Open Access Journals (Sweden)

    Leopoldo Palma

    2017-05-01

    Full Text Available The Vip3 proteins produced during vegetative growth by strains of the bacterium Bacillus thuringiensis show insecticidal activity against lepidopteran insects with a mechanism of action that may involve pore formation and apoptosis. These proteins are promising supplements to our arsenal of insecticidal proteins, but the molecular details of their activity are not understood. As a first step in the structural characterisation of these proteins, we have analysed their secondary structure and resolved the surface topology of a tetrameric complex of the Vip3Ag4 protein by transmission electron microscopy. Sites sensitive to proteolysis by trypsin are identified and the trypsin-cleaved protein appears to retain a similar structure as an octomeric complex comprising four copies each of the ~65 kDa and ~21 kDa products of proteolysis. This processed form of the toxin may represent the active toxin. The quality and monodispersity of the protein produced in this study make Vip3Ag4 a candidate for more detailed structural analysis using cryo-electron microscopy.

  10. Identifying Relevant Studies in Software Engineering

    DEFF Research Database (Denmark)

    Zhang, He; Ali Babar, Muhammad; Tell, Paolo

    2011-01-01

    Context: Systematic literature review (SLR) has become an important research methodology in software engineering since the introduction of evidence-based software engineering (EBSE) in 2004. One critical step in applying this methodology is to design and execute appropriate and effective search....... Objective: The main objective of the research reported in this paper is to improve the search step of undertaking SLRs in software engineering (SE) by devising and evaluating systematic and practical approaches to identifying relevant studies in SE. Method: We have systematically selected and analytically...

  11. Proteolysis targeting peptide (PROTAP) strategy for protein ubiquitination and degradation.

    Science.gov (United States)

    Zheng, Jing; Tan, Chunyan; Xue, Pengcheng; Cao, Jiakun; Liu, Feng; Tan, Ying; Jiang, Yuyang

    2016-02-19

    Ubiquitination proteasome pathway (UPP) is the most important and selective way to degrade proteins in vivo. Here, a novel proteolysis targeting peptide (PROTAP) strategy, composed of a target protein binding peptide, a linker and a ubiquitin E3 ligase recognition peptide, was designed to recruit both target protein and E3 ligase and then induce polyubiquitination and degradation of the target protein through UPP. In our study, the PROTAP strategy was proved to be a general method with high specificity using Bcl-xL protein as model target in vitro and in cells, which indicates that the strategy has great potential for in vivo application. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. The Degradome database: mammalian proteases and diseases of proteolysis.

    Science.gov (United States)

    Quesada, Víctor; Ordóñez, Gonzalo R; Sánchez, Luis M; Puente, Xose S; López-Otín, Carlos

    2009-01-01

    The degradome is defined as the complete set of proteases present in an organism. The recent availability of whole genomic sequences from multiple organisms has led us to predict the contents of the degradomes of several mammalian species. To ensure the fidelity of these predictions, our methods have included manual curation of individual sequences and, when necessary, direct cloning and sequencing experiments. The results of these studies in human, chimpanzee, mouse and rat have been incorporated into the Degradome database, which can be accessed through a web interface at http://degradome.uniovi.es. The annotations about each individual protease can be retrieved by browsing catalytic classes and families or by searching specific terms. This web site also provides detailed information about genetic diseases of proteolysis, a growing field of great importance for multiple users. Finally, the user can find additional information about protease structures, protease inhibitors, ancillary domains of proteases and differences between mammalian degradomes.

  13. Discovery of Anti-Hypertensive Oligopeptides from Adlay Based on In Silico Proteolysis and Virtual Screening

    Directory of Open Access Journals (Sweden)

    Liansheng Qiao

    2016-12-01

    Full Text Available Adlay (Coix larchryma-jobi L. was the commonly used Traditional Chinese Medicine (TCM with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopeptides from adlay were not clear. To discover the definite anti-hypertensive oligopeptides from adlay, in silico proteolysis and virtual screening were implemented to obtain potential oligopeptides, which were further identified by biochemistry assay and molecular dynamics simulation. In this paper, ten sequences of adlay prolamins were collected and in silico hydrolyzed to construct the oligopeptide library with 134 oligopeptides. This library was reverse screened by anti-hypertensive pharmacophore database, which was constructed by our research team and contained ten anti-hypertensive targets. Angiotensin-I converting enzyme (ACE was identified as the main potential target for the anti-hypertensive activity of adlay oligopeptides. Three crystal structures of ACE were utilized for docking studies and 19 oligopeptides were finally identified with potential ACE inhibitory activity. According to mapping features and evaluation indexes of pharmacophore and docking, three oligopeptides were selected for biochemistry assay. An oligopeptide sequence, NPATY (IC50 = 61.88 ± 2.77 µM, was identified as the ACE inhibitor by reverse-phase high performance liquid chromatography (RP-HPLC assay. Molecular dynamics simulation of NPATY was further utilized to analyze interactive bonds and key residues. ALA354 was identified as a key residue of ACE inhibitors. Hydrophobic effect of VAL518 and electrostatic effects of HIS383, HIS387, HIS513 and Zn2+ were also regarded as playing a key role in inhibiting ACE activities. This study provides a research strategy to explore the pharmacological mechanism of Traditional Chinese Medicine (TCM proteins based on

  14. Age-related changes in factor VII proteolysis in vivo.

    Science.gov (United States)

    Ofosu, F A; Craven, S; Dewar, L; Anvari, N; Andrew, M; Blajchman, M A

    1996-08-01

    Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

  15. Proteolysis of bovine beta-lactoglobulin during thermal treatment in subdenaturing conditions highlights some structural features of the temperature-modified protein and yields fragments with low immunoreactivity

    DEFF Research Database (Denmark)

    Iametti, S.; Rasmussen, P.; Frøkiær, Hanne

    2002-01-01

    Bovine beta-lactoglobulin was hydrolyzed with trypsin or chymotrypsin in the course of heat treatment at 55, 60 and 65 C at neutral pH. At these temperatures beta-lactoglobulin undergoes significant but reversible structural changes. In the conditions used in the present study, beta......-lactoglobulin was virtually insensitive to proteolysis by either enzyme at room temperature, but underwent extensive proteolysis when either protease was present during the heat treatment. High-temperature proteolysis occurs in a progressive manner. Mass spectrometry analysis of some large-sized breakdown intermediates...

  16. Regulatory Proteolysis in Arabidopsis-Pathogen Interactions.

    Science.gov (United States)

    Pogány, Miklós; Dankó, Tamás; Kámán-Tóth, Evelin; Schwarczinger, Ildikó; Bozsó, Zoltán

    2015-09-24

    Approximately two and a half percent of protein coding genes in Arabidopsis encode enzymes with known or putative proteolytic activity. Proteases possess not only common housekeeping functions by recycling nonfunctional proteins. By irreversibly cleaving other proteins, they regulate crucial developmental processes and control responses to environmental changes. Regulatory proteolysis is also indispensable in interactions between plants and their microbial pathogens. Proteolytic cleavage is simultaneously used both by plant cells, to recognize and inactivate invading pathogens, and by microbes, to overcome the immune system of the plant and successfully colonize host cells. In this review, we present available results on the group of proteases in the model plant Arabidopsis thaliana whose functions in microbial pathogenesis were confirmed. Pathogen-derived proteolytic factors are also discussed when they are involved in the cleavage of host metabolites. Considering the wealth of review papers available in the field of the ubiquitin-26S proteasome system results on the ubiquitin cascade are not presented. Arabidopsis and its pathogens are conferred with abundant sets of proteases. This review compiles a list of those that are apparently involved in an interaction between the plant and its pathogens, also presenting their molecular partners when available.

  17. Study Identifies New Lymphoma Treatment Target

    Science.gov (United States)

    NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

  18. Peptides Displayed as High Density Brush Polymers Resist Proteolysis and Retain Bioactivity

    Science.gov (United States)

    2015-01-01

    We describe a strategy for rendering peptides resistant to proteolysis by formulating them as high-density brush polymers. The utility of this approach is demonstrated by polymerizing well-established cell-penetrating peptides (CPPs) and showing that the resulting polymers are not only resistant to proteolysis but also maintain their ability to enter cells. The scope of this design concept is explored by studying the proteolytic resistance of brush polymers composed of peptides that are substrates for either thrombin or a metalloprotease. Finally, we demonstrate that the proteolytic susceptibility of peptide brush polymers can be tuned by adjusting the density of the polymer brush and offer in silico models to rationalize this finding. We contend that this strategy offers a plausible method of preparing peptides for in vivo use, where rapid digestion by proteases has traditionally restricted their utility. PMID:25314576

  19. Acid-Mediated Tumor Proteolysis: Contribution of Cysteine Cathepsins

    Directory of Open Access Journals (Sweden)

    Jennifer M Rothberg

    2013-10-01

    Full Text Available One of the noncellular microenvironmental factors that contribute to malignancy of solid tumors is acidic peritumoral pH. We have previously demonstrated that extracellular acidosis leads to localization of the cysteine pro-tease cathepsin B on the tumor cell membrane and its secretion. The objective of the present study was to determine if an acidic extracellular pH such as that observed in vivo (i.e., pHe 6.8 affects the activity of proteases, e.g., cathepsin B, that contribute to degradation of collagen IV by tumor cells when grown in biologically relevant three-dimensional (3D cultures. For these studies, we used 1 3D reconstituted basement membrane overlay cultures of human carcinomas, 2 live cell imaging assays to assess proteolysis, and 3 in vivo imaging of active tumor proteases. At pHe 6.8, there were increases in pericellular active cysteine cathepsins and in degradation of dye-quenched collagen IV, which was partially blocked by a cathepsin B inhibitor. Imaging probes for active cysteine cathepsins localized to tumors in vivo. The amount of bound probe decreased in tumors in bicarbonate-treated mice, a treatment previously shown to increase peritumoral pHe and reduce local invasion of the tumors. Our results are consistent with the acid-mediated invasion hypothesis and with a role for cathepsin B in promoting degradation of a basement membrane protein substrate, i.e., type IV collagen, in an acidic peritumoral environment.

  20. MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.

    Directory of Open Access Journals (Sweden)

    Mervi Toriseva

    Full Text Available Proteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The role of matrix metalloproteinase-13 (MMP-13 in granulation tissue growth was studied in subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13(-/- and wild type (WT mice. The tissue samples were harvested at time points day 7, 14 and 21 and subjected to histological analysis and gene expression profiling. Granulation tissue growth was significantly reduced (42% at day 21 in Mmp13(-/- mice. Granulation tissue in Mmp13(-/- mice showed delayed organization of myofibroblasts, increased microvascular density at day 14, and virtual absence of large vessels at day 21. Gene expression profiling identified differentially expressed genes in Mmp13(-/- mouse granulation tissue involved in biological functions including inflammatory response, angiogenesis, cellular movement, cellular growth and proliferation and proteolysis. Among genes linked to angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation tissue in Mmp13(-/- mice, and a set of genes involved in leukocyte motility including Il6 were systematically downregulated at day 14. The expression of Pdgfd was downregulated in Mmp13(-/- granulation tissue in all time points. The expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly downregulated in granulation tissue of Mmp13(-/- mice compared to WT mice. Mmp13(-/- mouse skin fibroblasts displayed altered cell morphology and impaired ability to contract collagen gel and decreased production of MMP-2. These results provide evidence for an important role for MMP-13 in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis.

  1. Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis.

    Science.gov (United States)

    Sevillano, Alejandro M; Fernández-Borges, Natalia; Younas, Neelam; Wang, Fei; R Elezgarai, Saioa; Bravo, Susana; Vázquez-Fernández, Ester; Rosa, Isaac; Eraña, Hasier; Gil, David; Veiga, Sonia; Vidal, Enric; Erickson-Beltran, Melissa L; Guitián, Esteban; Silva, Christopher J; Nonno, Romolo; Ma, Jiyan; Castilla, Joaquín; R Requena, Jesús

    2018-01-01

    Very solid evidence suggests that the core of full length PrPSc is a 4-rung β-solenoid, and that individual PrPSc subunits stack to form amyloid fibers. We recently used limited proteolysis to map the β-strands and connecting loops that make up the PrPSc solenoid. Using high resolution SDS-PAGE followed by epitope analysis, and mass spectrometry, we identified positions ~116/118, 133-134, 141, 152-153, 162, 169 and 179 (murine numbering) as Proteinase K (PK) cleavage sites in PrPSc. Such sites likely define loops and/or borders of β-strands, helping us to predict the threading of the β-solenoid. We have now extended this approach to recombinant PrPSc (recPrPSc). The term recPrPSc refers to bona fide recombinant prions prepared by PMCA, exhibiting infectivity with attack rates of ~100%. Limited proteolysis of mouse and bank vole recPrPSc species yielded N-terminally truncated PK-resistant fragments similar to those seen in brain-derived PrPSc, albeit with varying relative yields. Along with these fragments, doubly N- and C-terminally truncated fragments, in particular ~89/97-152, were detected in some recPrPSc preparations; similar fragments are characteristic of atypical strains of brain-derived PrPSc. Our results suggest a shared architecture of recPrPSc and brain PrPSc prions. The observed differences, in particular the distinct yields of specific PK-resistant fragments, are likely due to differences in threading which result in the specific biochemical characteristics of recPrPSc. Furthermore, recombinant PrPSc offers exciting opportunities for structural studies unachievable with brain-derived PrPSc.

  2. Physiological regulation of epithelial sodium channel by proteolysis

    DEFF Research Database (Denmark)

    Svenningsen, Per; Friis, Ulla G; Bistrup, Claus

    2011-01-01

    PURPOSE OF REVIEW: Activation of epithelial sodium channel (ENaC) by proteolysis appears to be relevant for day-to-day physiological regulation of channel activity in kidney and other epithelial tissues. Pathophysiogical, proteolytic activation of ENaC in kidney has been demonstrated in proteinuric...

  3. Perlecan and the Blood-Brain Barrier: Beneficial Proteolysis?

    Directory of Open Access Journals (Sweden)

    Jill eRoberts

    2012-08-01

    Full Text Available The cerebral microvasculature is important for maintaining brain homeostasis. This is achieved via the blood-brain barrier (BBB, composed of endothelial cells with specialized tight junctions, astrocytes and a basement membrane. Prominent components of the basement membrane extracellular matrix (ECM include fibronectin, laminin, collagen IV and perlecan, all of which regulate cellular processes via signal transduction through various cell membrane bound ECM receptors. Expression and proteolysis of these ECM components can be rapidly altered during pathological states of the central nervous system. In particular, proteolysis of perlecan, a heparan sulfate proteoglycan, occurs within hours following ischemia induced by experimental stroke. Proteolysis of ECM components following stroke results in the degradation of the basement membrane and further disruption of the BBB. While it is clear that such proteolysis has negative consequences for the BBB, we propose that it also may lead to generation of ECM protein fragments, including the C-terminal domain V (DV of perlecan, that potentially have a positive influence on other aspects of CNS health. Indeed, perlecan DV has been shown to be persistently generated after stroke and beneficial as a neuroprotective molecule and promoter of post-stroke brain repair. This mini-review will discuss beneficial roles of perlecan protein fragment generation within the brain during stroke.

  4. Effects of proteolysis on the adenosinetriphosphatase activities of thymus myosin

    International Nuclear Information System (INIS)

    Vu, N.D.; Wagner, P.D.

    1987-01-01

    Limited proteolysis was used to identify regions on the heavy chains of calf thymus myosin which may be involved in ATP and actin binding. Assignments of the various proteolytic fragments to different parts of the myosin heavy chain were based on solubility, gel filtration, electron microscopy, and binding of 32 P-labeled regulatory light chains. Chymotrypsin rapidly cleaved within the head of thymus myosin to give a 70,000-dalton N-terminal fragment and a 140,000-dalton C-terminal fragment. These two fragments did not dissociate under nondenaturing conditions. Cleavage within the myosin tail to give heavy meromyosin occurred more slowly. Cleavage at the site 70,000 daltons from the N-terminus of the heavy chain caused about a 30-fold decrease in the actin concentration required to achieve half-maximal stimulation of the magnesium-adenosinetriphosphatase (Mg-ATPase) activity of unphosphorylated thymus myosin. The actin-activated ATPase activity of this digested myosin was only slightly affected by light chain phosphorylation. Actin inhibited the cleavage at this site by chymotrypsin. In the presence of ATP, chymotrypsin rapidly cleaved the thymus myosin heavy chain at an additional site about 4000 daltons from the N-terminus. Cleavage at this site caused a 2-fold increase in the ethylenediaminetetraacetic acid-ATPase activity and 3-fold decreases in the Ca 2+ - and Mg-ATPase activities of thymus myosin. Thus, cleavage at the N-terminus of thymus myosin was affected by ATP, and this cleavage altered ATPase activity. Papain cleaved the thymus myosin heavy chain about 94,000 daltons from the N-terminus to give subfragment 1. Although this subfragment 1 contained intact light chains, its actin-activated ATPase activity was not affected by light chain phosphorylation

  5. Chemotherapy inhibits skeletal muscle ubiquitin-proteasome-dependent proteolysis.

    Science.gov (United States)

    Tilignac, Thomas; Temparis, Sandrine; Combaret, Lydie; Taillandier, Daniel; Pouch, Marie-Noëlle; Cervek, Matjaz; Cardenas, Diana M; Le Bricon, Thierry; Debiton, Eric; Samuels, Susan E; Madelmont, Jean-Claude; Attaix, Didier

    2002-05-15

    Chemotherapy has cachectic effects, but it is unknown whether cytostatic agents alter skeletal muscle proteolysis. We hypothesized that chemotherapy-induced alterations in protein synthesis should result in the increased incidence of abnormal proteins, which in turn should stimulate ubiquitin-proteasome-dependent proteolysis. The effects of the nitrosourea cystemustine were investigated in skeletal muscles from both healthy and colon 26 adenocarcinoma-bearing mice, an appropriate model for testing the impact of cytostatic agents. Muscle wasting was seen in both groups of mice 4 days after a single cystemustine injection, and the drug further increased the loss of muscle proteins already apparent in tumor-bearing animals. Cystemustine cured the tumor-bearing mice with 100% efficacy. Surprisingly, within 11 days of treatment, rates of muscle proteolysis progressively decreased below basal levels observed in healthy control mice and contributed to the cessation of muscle wasting. Proteasome-dependent proteolysis was inhibited by mechanisms that include reduced mRNA levels for 20S and 26S proteasome subunits, decreased protein levels of 20S proteasome subunits and the S14 non-ATPase subunit of the 26S proteasome, and impaired chymotrypsin- and trypsin-like activities of the enzyme. A combination of cisplatin and ifosfamide, two drugs that are widely used in the treatment of cancer patients, also depressed the expression of proteasomal subunits in muscles from rats bearing the MatB adenocarcinoma below basal levels. Thus, a down-regulation of ubiquitin-proteasome-dependent proteolysis is observed with various cytostatic agents and contributes to reverse the chemotherapy-induced muscle wasting.

  6. Chemical and proteolysis-derived changes during long-term storage of lactose-hydrolyzed ultrahigh-temperature (UHT) milk.

    Science.gov (United States)

    Jansson, Therese; Jensen, Hanne B; Sundekilde, Ulrik K; Clausen, Morten R; Eggers, Nina; Larsen, Lotte B; Ray, Colin; Andersen, Henrik J; Bertram, Hanne C

    2014-11-19

    Proteolytic activity in milk may release bitter-tasting peptides and generate free amino terminals that react with carbohydrates, which initiate Maillard reaction. Ultrahigh temperature (UHT) heat treatment inactivates the majority of proteolytic enzymes in milk. In lactose-hydrolyzed milk a β-galactosidase preparation is applied to the milk after heat treatment, which has proteolytic side activities that may induce quality deterioration of long-term-stored milk. In the present study proteolysis, glycation, and volatile compound formation were investigated in conventional (100% lactose), filtered (60% lactose), and lactose-hydrolyzed (<1% lactose) UHT milk using reverse phase high-pressure liquid chromatography-mass spectrometry, proton nuclear magnetic resonance, and gas chromatography-mass spectrometry. Proteolysis was observed in all milk types. However, the degree of proteolysis was significantly higher in the lactose-hydrolyzed milk compared to the conventional and filtered milk. The proteins most prone to proteolysis were β-CN and αs1-CN, which were clearly hydrolyzed after approximately 90 days of storage in the lactose-hydrolyzed milk.

  7. LSD1 demethylase and the methyl-binding protein PHF20L1 prevent SET7 methyltransferase-dependent proteolysis of the stem-cell protein SOX2.

    Science.gov (United States)

    Zhang, Chunxiao; Hoang, Nam; Leng, Feng; Saxena, Lovely; Lee, Logan; Alejo, Salvador; Qi, Dandan; Khal, Anthony; Sun, Hong; Lu, Fei; Zhang, Hui

    2018-03-09

    The pluripotency-controlling stem-cell protein SRY-box 2 (SOX2) plays a pivotal role in maintaining the self-renewal and pluripotency of embryonic stem cells and also of teratocarcinoma or embryonic carcinoma cells. SOX2 is monomethylated at lysine 119 (Lys-119) in mouse embryonic stem cells by the SET7 methyltransferase, and this methylation triggers ubiquitin-dependent SOX2 proteolysis. However, the molecular regulators and mechanisms controlling SET7-induced SOX2 proteolysis are unknown. Here, we report that in human ovarian teratocarcinoma PA-1 cells, methylation-dependent SOX2 proteolysis is dynamically regulated by the LSD1 lysine demethylase and a methyl-binding protein, PHD finger protein 20-like 1 (PHF20L1). We found that LSD1 not only removes the methyl group from monomethylated Lys-117 (equivalent to Lys-119 in mouse SOX2), but it also demethylates monomethylated Lys-42 in SOX2, a reaction that SET7 also regulated and that also triggered SOX2 proteolysis. Our studies further revealed that PHF20L1 binds both monomethylated Lys-42 and Lys-117 in SOX2 and thereby prevents SOX2 proteolysis. Down-regulation of either LSD1 or PHF20L1 promoted SOX2 proteolysis, which was prevented by SET7 inactivation in both PA-1 and mouse embryonic stem cells. Our studies also disclosed that LSD1 and PHF20L1 normally regulate the growth of pluripotent mouse embryonic stem cells and PA-1 cells by preventing methylation-dependent SOX2 proteolysis. In conclusion, our findings reveal an important mechanism by which the stability of the pluripotency-controlling stem-cell protein SOX2 is dynamically regulated by the activities of SET7, LSD1, and PHF20L1 in pluripotent stem cells. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Impact of microencapsulated peptidase (Aspergillus oryzae) on cheddar cheese proteolysis and its biologically active peptide profile.

    Science.gov (United States)

    Seneweera, Saman; Kailasapathy, Kaila

    2011-07-01

    We investigated the delivery of calcium-alginate encapsulated peptidase (Flavourzyme(®), Aspergillus oryzae) on proteolysis of Cheddar cheese. Physical and chemical characteristics such as moisture, pH and fat content were measured, and no differences were found between control and experimental cheese at day 0. SDS-PAGE analysis clearly showed that proteolysis of α and k casein was significantly accelerated after three months of maturity in the experimental cheese. A large number of low molecular weight peptides were found in the water soluble fraction of the experimental cheeses and some of these peptides were new. N-terminal amino acid sequence analysis identified these as P(1), Leu-Thu-Glu; P(3), Asp-Val-Pro-Ser-Glu) and relatively abundant stable peptides P(2), P(4), Arg-Pro-Lys-His-Pro-Ile; P(5), Arg-Pro-Lys-His-Pro-Ile-Lys and P(6). These peptides were mainly originated from αs1-CN and β-CN. Three of the identified peptides (P(1), P(2), P(3) and P(4)) are known to biologically active and P(1) and P(3) were only present in experimental cheese suggesting that experimental cheese has improved health benefits.

  9. Histopathological growth pattern, proteolysis and angiogenesis in chemonaive patients resected for multiple colorectal liver metastases

    DEFF Research Database (Denmark)

    Eefsen, Rikke Løvendahl; Van den Eynden, Gert G; Høyer-Hansen, Gunilla

    2012-01-01

    The purpose of this study was to characterise growth patterns, proteolysis, and angiogenesis in colorectal liver metastases from chemonaive patients with multiple liver metastases. Twenty-four patients were included in the study, resected for a median of 2.6 metastases. The growth pattern......-type plasminogen activator receptor (P = 0.0008). Angiogenesis was most pronounced in metastases with a pushing growth pattern in comparison to those with desmoplastic (P = 0.0007) and replacement growth pattern (P = 0.021). Although a minor fraction of the patients harboured metastases with different growth...

  10. Use of high-gradient magnetic fishing for reducing proteolysis during fermentation

    DEFF Research Database (Denmark)

    Maury, Trine Lütken; Ottow, Kim Ekelund; Brask, Jesper

    2012-01-01

    Proteolysis during fermentation may have a severe impact on the yield and quality of a secreted product. In the current study, we demonstrate the use of high-gradient magnetic fishing (HGMF) as an efficient alternative to the more conventional methods of preventing proteolytic degradation....... Bacitracin-linked magnetic affinity adsorbents were employed directly in a fermenter during Bacillus licheniformis cultivation to remove trace amounts of unwanted proteases. The constructed magnetic adsorbents had excellent, highly specific binding characteristics in the fermentation broth (K(d) = 1...

  11. Autophagic dysfunction in a lysosomal storage disorder due to impaired proteolysis.

    Science.gov (United States)

    Elrick, Matthew J; Lieberman, Andrew P

    2013-02-01

    Alterations in macroautophagy (hereafter referred to as "autophagy") are a common feature of lysosomal storage disorders, and have been hypothesized to play a major role in the pathogenesis of these diseases. We have recently reported multiple defects in autophagy contributing to the lysosomal storage disorder Niemann-Pick type C (NPC). These include increased formation of autophagosomes, slowed turnover of autophagosomes secondary to impaired lysosomal proteolysis, and delivery of stored lipids to the lysosome via autophagy. The study summarized here describes novel methods for the interrogation of individual stages of the autophagic pathway, and suggests mechanisms by which lipid storage may result in broader lysosomal dysfunction.

  12. Calpain-mediated proteolysis of tropomodulin isoforms leads to thin filament elongation in dystrophic skeletal muscle.

    Science.gov (United States)

    Gokhin, David S; Tierney, Matthew T; Sui, Zhenhua; Sacco, Alessandra; Fowler, Velia M

    2014-03-01

    Duchenne muscular dystrophy (DMD) induces sarcolemmal mechanical instability and rupture, hyperactivity of intracellular calpains, and proteolytic breakdown of muscle structural proteins. Here we identify the two sarcomeric tropomodulin (Tmod) isoforms, Tmod1 and Tmod4, as novel proteolytic targets of m-calpain, with Tmod1 exhibiting ∼10-fold greater sensitivity to calpain-mediated cleavage than Tmod4 in situ. In mdx mice, increased m-calpain levels in dystrophic soleus muscle are associated with loss of Tmod1 from the thin filament pointed ends, resulting in ∼11% increase in thin filament lengths. In mdx/mTR mice, a more severe model of DMD, Tmod1 disappears from the thin filament pointed ends in both tibialis anterior (TA) and soleus muscles, whereas Tmod4 additionally disappears from soleus muscle, resulting in thin filament length increases of ∼10 and ∼12% in TA and soleus muscles, respectively. In both mdx and mdx/mTR mice, both TA and soleus muscles exhibit normal localization of α-actinin, the nebulin M1M2M3 domain, Tmod3, and cytoplasmic γ-actin, indicating that m-calpain does not cause wholesale proteolysis of other sarcomeric and actin cytoskeletal proteins in dystrophic skeletal muscle. These results implicate Tmod proteolysis and resultant thin filament length misspecification as novel mechanisms that may contribute to DMD pathology, affecting muscles in a use- and disease severity-dependent manner.

  13. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    Science.gov (United States)

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-07-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting.

  14. Regulated Proteolysis of Arabidopsis Argonaute1

    DEFF Research Database (Denmark)

    Kausika, Swathi Pranavi

    . These are large multi domain proteins found in both eukaryotes and prokaryotes. They consist of four domains namely N, PAZ, MID and PIWI domain. The PAZ and MID domains bind small RNA 3´ and 5´ends while the PIWI domain harbors the endonucleolytic activity responsible for target RNA cleavage. This study focuses...

  15. IDGenerator: unique identifier generator for epidemiologic or clinical studies

    Directory of Open Access Journals (Sweden)

    Matthias Olden

    2016-09-01

    Full Text Available Abstract Background Creating study identifiers and assigning them to study participants is an important feature in epidemiologic studies, ensuring the consistency and privacy of the study data. The numbering system for identifiers needs to be random within certain number constraints, to carry extensions coding for organizational information, or to contain multiple layers of numbers per participant to diversify data access. Available software can generate globally-unique identifiers, but identifier-creating tools meeting the special needs of epidemiological studies are lacking. We have thus set out to develop a software program to generate IDs for epidemiological or clinical studies. Results Our software IDGenerator creates unique identifiers that not only carry a random identifier for a study participant, but also support the creation of structured IDs, where organizational information is coded into the ID directly. This may include study center (for multicenter-studies, study track (for studies with diversified study programs, or study visit (baseline, follow-up, regularly repeated visits. Our software can be used to add a check digit to the ID to minimize data entry errors. It facilitates the generation of IDs in batches and the creation of layered IDs (personal data ID, study data ID, temporary ID, external data ID to ensure a high standard of data privacy. The software is supported by a user-friendly graphic interface that enables the generation of IDs in both standard text and barcode 128B format. Conclusion Our software IDGenerator can create identifiers meeting the specific needs for epidemiologic or clinical studies to facilitate study organization and data privacy. IDGenerator is freeware under the GNU General Public License version 3; a Windows port and the source code can be downloaded at the Open Science Framework website: https://osf.io/urs2g/ .

  16. Proteolysis of Sardine (Sardina pilchardus and Anchovy (Stolephorus commersonii by Commercial Enzymes in Saline Solutions

    Directory of Open Access Journals (Sweden)

    Chau Minh Le

    2015-01-01

    Full Text Available Fish sauce production is a very long process and there is a great interest in shortening it. Among the different strategies to speed up this process, the addition of external proteases could be a solution. This study focuses on the eff ect of two commercial enzymes (Protamex and Protex 51FP on the proteolysis of two fish species traditionally converted into fish sauce: sardine and anchovy, by comparison with classical autolysis. Hydrolysis reactions were conducted with fresh fish at a temperature of 30 °C and under different saline conditions (from 0 to 30 % NaCl. Hydrolysis degree and liquefaction of the raw material were used to follow the process. As expected, the proteolysis decreased with increasing amount of salt. Regarding the fi sh species, higher rate of liquefaction and higher hydrolysis degree were obtained with anchovy. Between the two proteases, Protex 51FP gave better results with both fi sh types. This study demonstrates that the addition of commercial proteases could be helpful for the liquefaction of fi sh and cleavage of peptide bonds that occur during fi sh sauce production and thus speed up the production process.

  17. The use of in situ proteolysis in the crystallization of murine CstF-77

    International Nuclear Information System (INIS)

    Bai, Yun; Auperin, Thierry C.; Tong, Liang

    2007-01-01

    In situ proteolysis with fungal protease or subtilisin is crucial for the crystallization of murine CstF-77. The cleavage-stimulation factor (CstF) is required for the cleavage of the 3′-end of messenger RNA precursors in eukaryotes. During structure determination of the 77 kDa subunit of the murine CstF complex (CstF-77), it was serendipitously discovered that a solution infected by a fungus was crucial for the crystallization of this protein. CstF-77 was partially proteolyzed during crystallization; this was very likely to have been catalyzed by a protease secreted by the fungus. It was found that the fungal protease can be replaced by subtilisin and this in situ proteolysis protocol produced crystals of sufficient size for structural studies. After an extensive search, it was found that 55% glucose can be used as a cryoprotectant while maintaining the diffraction quality of the crystals; most other commonly used cryoprotectants were detrimental to the diffraction quality

  18. Bystander protein protects potential vaccine-targeting ligands against intestinal proteolysis.

    Science.gov (United States)

    Reuter, Fabian; Bade, Steffen; Hirst, Timothy R; Frey, Andreas

    2009-07-20

    Endowing mucosal vaccines with ligands that target antigen to mucosal lymphoid tissues may improve immunization efficacy provided that the ligands withstand the proteolytic environment of the gastro-intestinal tract until they reach their destination. Our aim was to investigate whether and how three renowned ligands - Ulex europaeus agglutinin I and the B subunits of cholera toxin and E. coli heat-labile enterotoxin - master this challenge. We assessed the digestive power of natural murine intestinal fluid (natIF) using assays for trypsin, chymotrypsin and pancreatic elastase along with a test for nonspecific proteolysis. The natIF was compared with simulated murine intestinal fluid (simIF) that resembled the trypsin, chymotrypsin and elastase activities of its natural counterpart but lacked or contained albumins as additional protease substrates. The ligands were exposed to the digestive fluids and degradation was determined. The studies revealed that (i) the three pancreatic endoproteases constitute only one third of the total protease activity of natIF and (ii) the ligands resist proteolysis in natIF and protein-enriched simIF over 3 h but (iii) are partially destroyed in simIF that lacks additional protease substrate. We assume that the proteins of natIF are preferred substrates for the intestinal proteases and thus can protect vaccine-targeting ligands from destruction.

  19. Excess alpha chains are lost from beta-thalassemic reticulocytes by proteolysis

    International Nuclear Information System (INIS)

    Testa, U.; Hinard, N.; Beuzard, Y.; Tsapis, A.; Galacteros, F.; Thomopoulos, P.; Rosa, J.

    1981-01-01

    During incubation of reticulocytes from patients with beta-thalassemia, after labeling of the hemoglobin with radioactive amino acids, the excess alpha chains are gradually lost from the cells. The aim of this study was to investigate the mechanism of this phenomenon. A system was developed in which reticulocytes from beta-thalassemia patients are labeled with [3H]leucine, washed several times in nonradioactive medium, and then incubated in the same medium containing puromycin added in order to stop further protein synthesis. The results have clearly shown that excess alpha chains are gradually degraded by proteolysis. N-ethylmaleimide or epsilon-aminocaproic acid inhibited the proteolysis of free alpha chains. The addition of either ATP or hemin did not change the rate of alpha chain degradation. The time required to degrade 50% of the pool of free alpha chains was directly dependent on the initial value of this pool. This finding suggests the absence of a significant individual variation in the ability to proteolyse free alpha chains

  20. Proteolysis inside the membrane is a rate-governed reaction not driven by substrate affinity.

    Science.gov (United States)

    Dickey, Seth W; Baker, Rosanna P; Cho, Sangwoo; Urban, Siniša

    2013-12-05

    Enzymatic cleavage of transmembrane anchors to release proteins from the membrane controls diverse signaling pathways and is implicated in more than a dozen diseases. How catalysis works within the viscous, water-excluding, two-dimensional membrane is unknown. We developed an inducible reconstitution system to interrogate rhomboid proteolysis quantitatively within the membrane in real time. Remarkably, rhomboid proteases displayed no physiological affinity for substrates (K(d) ~190 μM/0.1 mol%). Instead, ~10,000-fold differences in proteolytic efficiency with substrate mutants and diverse rhomboid proteases were reflected in k(cat) values alone. Analysis of gate-open mutant and solvent isotope effects revealed that substrate gating, not hydrolysis, is rate limiting. Ultimately, a single proteolytic event within the membrane normally takes minutes. Rhomboid intramembrane proteolysis is thus a slow, kinetically controlled reaction not driven by transmembrane protein-protein affinity. These properties are unlike those of other studied proteases or membrane proteins but are strikingly reminiscent of one subset of DNA-repair enzymes, raising important mechanistic and drug-design implications. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Role of calpain in eccentric contraction-induced proteolysis of Ca2+-regulatory proteins and force depression in rat fast-twitch skeletal muscle.

    Science.gov (United States)

    Kanzaki, Keita; Watanabe, Daiki; Kuratani, Mai; Yamada, Takashi; Matsunaga, Satoshi; Wada, Masanobu

    2017-02-01

    The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca 2+ -regulatory proteins and force production in fast-twitch skeletal muscles. Rat extensor digitorum longus muscles were exposed to 200 repeated ECC in situ and excised immediately [recovery 0 (REC0)] or 3 days [recovery 3 (REC3)] after cessation of ECC. Calpain inhibitor (CI)-treated rats were intraperitoneally injected with MDL-28170 before ECC and during REC3. Tetanic force was markedly reduced at REC0 and remained reduced at REC3. CI treatment ameliorated the ECC-induced force decline but only at REC3. No evidence was found for proteolysis of dihydropyridine receptor (DHPR), junctophilin (JP)1, JP2, ryanodine receptor (RyR), sarcoplasmic reticulum Ca 2+ -ATPase (SERCA)1a, or junctional face protein-45 at REC0. At REC3, ECC resulted in decreases in DHPR, JP1, JP2, RyR, and SERCA1a. CI treatment prevented the decreases in DHPR, JP1, and JP2, whereas it had little effect on RyR and SERCA1a. These findings suggest that DHPR, JP1, and JP2, but not RyR and SERCA1a, undergo calpain-dependent proteolysis in in vivo muscles subjected to ECC and that impaired function of DHPR and/or JP might cause prolonged force deficits with ECC. NEW & NOTEWORTHY Calpain-dependent proteolysis is one of the contributing factors to muscle damage that occurs with eccentric contraction (ECC). It is unclear, however, whether calpains account for proteolysis of Ca 2+ -regulatory proteins in in vivo muscles subjected to ECC. Here, we provide evidence that dihydropyridine receptor and junctophilin, but not ryanodine receptor and sarcoplasmic reticulum Ca 2+ -ATPase, undergo calpain-dependent proteolysis. Copyright © 2017 the American Physiological Society.

  2. Guidance for Identifying, Selecting and Evaluating Open Literature Studies

    Science.gov (United States)

    This guidance for Office of Pesticide Program staff will assist in their evaluation of open literature studies of pesticides. It also describes how we identify, select, and ensure that data we use in risk assessments is of sufficient scientific quality.

  3. Involvement of μ/m-calpain in the proteolysis and meat quality changes during postmortem storage of chicken breast muscle.

    Science.gov (United States)

    Zhao, Liang; Xing, Tong; Huang, Jichao; Qiao, Yan; Chen, Yulian; Huang, Ming

    2018-02-01

    The objective of this study was to investigate the role of calpain isotypes, especially poultry-specific μ/m-calpain in the proteolysis and meat quality changes of chicken breast muscle during postmortem storage. Calpain activity was detected by casein zymography, while the degradation of titin, desmin and Troponin-T was analyzed by sodium dodecyl sulfate - polyacrylamide gel electrophoresis and western blot. Meat quality indicators such as water holding capacity and tenderness were also studied. The correlation analysis between calpain activity, proteolysis and the changes in meat quality indicators indicated that there were strong correlations for μ-calpain during the first 12 h of storage, while such strong correlations for μ/m-calpain were only found in samples stored from 12 h to 7 days. Our study suggested that μ-calpain played a major role in meat quality changes while μ/m-calpain could also be involved but played a limited role in the proteolysis and meat quality changes during 12 h to 7 days postmortem storage of chicken breast muscle. © 2017 Japanese Society of Animal Science.

  4. Plant senescence and proteolysis: two processes with one destiny.

    Science.gov (United States)

    Diaz-Mendoza, Mercedes; Velasco-Arroyo, Blanca; Santamaria, M Estrella; González-Melendi, Pablo; Martinez, Manuel; Diaz, Isabel

    2016-01-01

    Senescence-associated proteolysis in plants is a complex and controlled process, essential for mobilization of nutrients from old or stressed tissues, mainly leaves, to growing or sink organs. Protein breakdown in senescing leaves involves many plastidial and nuclear proteases, regulators, different subcellular locations and dynamic protein traffic to ensure the complete transformation of proteins of high molecular weight into transportable and useful hydrolysed products. Protease activities are strictly regulated by specific inhibitors and through the activation of zymogens to develop their proteolytic activity at the right place and at the proper time. All these events associated with senescence have deep effects on the relocation of nutrients and as a consequence, on grain quality and crop yield. Thus, it can be considered that nutrient recycling is the common destiny of two processes, plant senescence and, proteolysis. This review article covers the most recent findings about leaf senescence features mediated by abiotic and biotic stresses as well as the participants and steps required in this physiological process, paying special attention to C1A cysteine proteases, their specific inhibitors, known as cystatins, and their potential targets, particularly the chloroplastic proteins as source for nitrogen recycling.

  5. Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via β-catenin signaling.

    Science.gov (United States)

    Stoyanova, Tanya; Goldstein, Andrew S; Cai, Houjian; Drake, Justin M; Huang, Jiaoti; Witte, Owen N

    2012-10-15

    The cell surface protein Trop2 is expressed on immature stem/progenitor-like cells and is overexpressed in many epithelial cancers. However the biological function of Trop2 in tissue maintenance and tumorigenesis remains unclear. In this study, we demonstrate that Trop2 is a regulator of self-renewal, proliferation, and transformation. Trop2 controls these processes through a mechanism of regulated intramembrane proteolysis that leads to cleavage of Trop2, creating two products: the extracellular domain and the intracellular domain. The intracellular domain of Trop2 is released from the membrane and accumulates in the nucleus. Heightened expression of the Trop2 intracellular domain promotes stem/progenitor self-renewal through signaling via β-catenin and is sufficient to initiate precursor lesions to prostate cancer in vivo. Importantly, we demonstrate that loss of β-catenin or Trop2 loss-of-function cleavage mutants abrogates Trop2-driven self-renewal and hyperplasia in the prostate. These findings suggest that heightened expression of Trop2 is selected for in epithelial cancers to enhance the stem-like properties of self-renewal and proliferation. Defining the mechanism of Trop2 function in self-renewal and transformation is essential to identify new therapeutic strategies to block Trop2 activation in cancer.

  6. MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

    Science.gov (United States)

    Lindert, Uschi; Cabral, Wayne A.; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M.; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N.; Janecke, Andreas R.; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R.; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C.; Shotelersuk, Vorasuk

    2016-01-01

    Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID:27380894

  7. Perennial peanut (Arachis glabrata Benth.) contains polyphenol oxidase (PPO) and PPO substrates that can reduce post-harvest proteolysis.

    Science.gov (United States)

    Sullivan, Michael L; Foster, Jamie L

    2013-08-15

    Studies of perennial peanut (Arachis glabrata Benth.) suggest its hay and haylage have greater levels of rumen undegraded protein (RUP) than other legume forages such as alfalfa (Medicago sativa L.). Greater RUP can result in more efficient nitrogen utilization by ruminant animals with positive economic and environmental effects. We sought to determine whether, like red clover (Trifolium pretense L.), perennial peanut contains polyphenol oxidase (PPO) and PPO substrates that might be responsible for increased RUP. Perennial peanut extracts contain immunologically detectible PPO protein and high levels of PPO activity (>100 nkatal mg(-1) protein). Addition of caffeic acid (PPO substrate) to perennial peanut extracts depleted of endogenous substrates reduced proteolysis by 90%. Addition of phenolics prepared from perennial peanut leaves to extracts of either transgenic PPO-expressing or control (non-expressing) alfalfa showed peanut phenolics could reduce proteolysis >70% in a PPO-dependent manner. Two abundant likely PPO substrates are present in perennial peanut leaves including caftaric acid. Perennial peanut contains PPO and PPO substrates that together are capable of inhibiting post-harvest proteolysis, suggesting a possible mechanism for increased RUP in this forage. Research related to optimizing the PPO system in other forage crops will likely be applicable to perennial peanut. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  8. Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α.

    LENUS (Irish Health Repository)

    Afonina, Inna S

    2011-10-21

    Granzyme B is a cytotoxic lymphocyte-derived protease that plays a central role in promoting apoptosis of virus-infected target cells, through direct proteolysis and activation of constituents of the cell death machinery. However, previous studies have also implicated granzymes A and B in the production of proinflammatory cytokines, via a mechanism that remains undefined. Here we show that IL-1α is a substrate for granzyme B and that proteolysis potently enhanced the biological activity of this cytokine in vitro as well as in vivo. Consistent with this, compared with full-length IL-1α, granzyme B-processed IL-1α exhibited more potent activity as an immunoadjuvant in vivo. Furthermore, proteolysis of IL-1α within the same region, by proteases such as calpain and elastase, was also found to enhance its biological potency. Thus, IL-1α processing by multiple immune-related proteases, including granzyme B, acts as a switch to enhance the proinflammatory properties of this cytokine.

  9. Yak milk casein as potential precursor of angiotensin I-converting enzyme inhibitory peptides based on in silico proteolysis.

    Science.gov (United States)

    Lin, Kai; Zhang, Lan-Wei; Han, Xue; Xin, Liang; Meng, Zhao-Xu; Gong, Pi-Min; Cheng, Da-You

    2018-07-15

    Yak milk casein was selected as a potential precursor of bioactive peptides based on in silico analysis. Most notable among these are the angiotensin I-converting enzyme (ACE) inhibitory peptides. First, yak milk casein has high homology with cow milk casein by homologous analysis. The potential of yak milk casein for the releasing bioactive peptides was evaluated by determining the frequency of occurrence of fragments with a given activity. Through the BIOPEP database analysis, there are many bioactive peptides in yak milk casein sequences. Then, an in silico proteolysis using single or combined enzymes to obtained ACE inhibitory peptides was investigated. Cytotoxicity analysis using the online toxic prediction tool ToxinPred revealed that all in silico proteolysis derived ACE inhibitory peptides are non-cytotoxic. Overall, the present study highlights a in silico proteolysis approach to assist the yak milk casein releasing ACE inhibitory peptides and provides a guidance for the actual hydrolysis of proteins for the production of bioactive peptides. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Laser-light backscattering response to water content and proteolysis in dry-cured ham

    DEFF Research Database (Denmark)

    Fulladosa, E.; Rubio-Celorio, M.; Skytte, Jacob Lercke

    2017-01-01

    on the acquisition conditions used. Laser backscattering was influenced by both dryness and proteolysis intensity showing an average light intensity decrease of 0.2 when decreasing water content (1% weight loss) and increasing proteolysis (equivalent to one-hour enzyme action). However, a decrease of scattering area...... was only detected when the water content was decreased (618 mm(2) per 1% weight loss). Changes on scattering of light profiles were only observed when the water content changed. Although there is a good correlation between water content and LBI parameters when analysing commercial samples, proteolysis...... of laser incidence) and to analyse the laser-light backscattering changes caused by additional hot air drying and proteolysis of dry-cured ham slices. The feasibility of the technology to determine water content and proteolysis (which is related to textural characteristics) of commercial sliced dry...

  11. VEGFR2 Trafficking, Signaling and Proteolysis is Regulated by the Ubiquitin Isopeptidase USP8.

    Science.gov (United States)

    Smith, Gina A; Fearnley, Gareth W; Abdul-Zani, Izma; Wheatcroft, Stephen B; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

    2016-01-01

    Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular function. VEGF-A binding to vascular endothelial growth factor receptor 2 (VEGFR2) stimulates endothelial signal transduction and regulates multiple cellular responses. Activated VEGFR2 undergoes ubiquitination but the enzymes that regulate this post-translational modification are unclear. In this study, the de-ubiquitinating enzyme, USP8, is shown to regulate VEGFR2 trafficking, de-ubiquitination, proteolysis and signal transduction. USP8-depleted endothelial cells displayed altered VEGFR2 ubiquitination and production of a unique VEGFR2 extracellular domain proteolytic fragment caused by VEGFR2 accumulation in the endosome-lysosome system. In addition, perturbed VEGFR2 trafficking impaired VEGF-A-stimulated signal transduction in USP8-depleted cells. Thus, regulation of VEGFR2 ubiquitination and de-ubiquitination has important consequences for the endothelial cell response and vascular physiology. © 2015 The Authors. Traffic published by John Wiley & Sons Ltd.

  12. Identifying, studying and making good use of macromolecular crystals

    Energy Technology Data Exchange (ETDEWEB)

    Calero, Guillermo [University of Pittsburgh Medical School, Pittsburgh, PA 15261 (United States); Cohen, Aina E. [SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025 (United States); Luft, Joseph R. [Hauptman–Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203 (United States); State University of New York at Buffalo, 700 Ellicott Street, Buffalo, NY 14203 (United States); Newman, Janet [CSIRO Collaborative Crystallisation Centre, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Snell, Edward H., E-mail: esnell@hwi.buffalo.edu [Hauptman–Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203 (United States); State University of New York at Buffalo, 700 Ellicott Street, Buffalo, NY 14203 (United States); University of Pittsburgh Medical School, Pittsburgh, PA 15261 (United States)

    2014-07-25

    As technology advances, the crystal volume that can be used to collect useful X-ray diffraction data decreases. The technologies available to detect and study growing crystals beyond the optical resolution limit and methods to successfully place the crystal into the X-ray beam are discussed. Structural biology has contributed tremendous knowledge to the understanding of life on the molecular scale. The Protein Data Bank, a depository of this structural knowledge, currently contains over 100 000 protein structures, with the majority stemming from X-ray crystallography. As the name might suggest, crystallography requires crystals. As detectors become more sensitive and X-ray sources more intense, the notion of a crystal is gradually changing from one large enough to embellish expensive jewellery to objects that have external dimensions of the order of the wavelength of visible light. Identifying these crystals is a prerequisite to their study. This paper discusses developments in identifying these crystals during crystallization screening and distinguishing them from other potential outcomes. The practical aspects of ensuring that once a crystal is identified it can then be positioned in the X-ray beam for data collection are also addressed.

  13. Identifying, studying and making good use of macromolecular crystals

    International Nuclear Information System (INIS)

    Calero, Guillermo; Cohen, Aina E.; Luft, Joseph R.; Newman, Janet; Snell, Edward H.

    2014-01-01

    As technology advances, the crystal volume that can be used to collect useful X-ray diffraction data decreases. The technologies available to detect and study growing crystals beyond the optical resolution limit and methods to successfully place the crystal into the X-ray beam are discussed. Structural biology has contributed tremendous knowledge to the understanding of life on the molecular scale. The Protein Data Bank, a depository of this structural knowledge, currently contains over 100 000 protein structures, with the majority stemming from X-ray crystallography. As the name might suggest, crystallography requires crystals. As detectors become more sensitive and X-ray sources more intense, the notion of a crystal is gradually changing from one large enough to embellish expensive jewellery to objects that have external dimensions of the order of the wavelength of visible light. Identifying these crystals is a prerequisite to their study. This paper discusses developments in identifying these crystals during crystallization screening and distinguishing them from other potential outcomes. The practical aspects of ensuring that once a crystal is identified it can then be positioned in the X-ray beam for data collection are also addressed

  14. Identifying Primary Spontaneous Pneumothorax from Administrative Databases: A Validation Study

    Directory of Open Access Journals (Sweden)

    Eric Frechette

    2016-01-01

    Full Text Available Introduction. Primary spontaneous pneumothorax (PSP is a disorder commonly encountered in healthy young individuals. There is no differentiation between PSP and secondary pneumothorax (SP in the current version of the International Classification of Diseases (ICD-10. This complicates the conduct of epidemiological studies on the subject. Objective. To validate the accuracy of an algorithm that identifies cases of PSP from administrative databases. Methods. The charts of 150 patients who consulted the emergency room (ER with a recorded main diagnosis of pneumothorax were reviewed to define the type of pneumothorax that occurred. The corresponding hospital administrative data collected during previous hospitalizations and ER visits were processed through the proposed algorithm. The results were compared over two different age groups. Results. There were 144 cases of pneumothorax correctly coded (96%. The results obtained from the PSP algorithm demonstrated a significantly higher sensitivity (97% versus 81%, p=0.038 and positive predictive value (87% versus 46%, p<0.001 in patients under 40 years of age than in older patients. Conclusions. The proposed algorithm is adequate to identify cases of PSP from administrative databases in the age group classically associated with the disease. This makes possible its utilization in large population-based studies.

  15. Proteolysis in model Portuguese cheeses: Effects of rennet and starter culture.

    Science.gov (United States)

    Pereira, Cláudia I; Gomes, Eliza O; Gomes, Ana M P; Malcata, F Xavier

    2008-06-01

    To shed further light onto the mechanisms of proteolysis that prevail throughout ripening of Portuguese cheeses, model cheeses were manufactured from bovine milk, following as much as possible traditional manufacture practices - using either animal or plant rennet. The individual role upon proteolysis of two (wild) strains of lactic acid bacteria - viz. Lactococcus lactis and Lactobacillus brevis, which are normally found to high viable numbers in said cheeses, was also considered, either as single or mixed cultures. Our experimental results confirmed the influence of rennet on the proteolysis extent, but not on proteolysis depth. On the other hand, the aforementioned strains clearly improved release of medium- and small-sized peptides, and contributed as well to the free amino acid pool in cheese. Copyright © 2007 Elsevier Ltd. All rights reserved.

  16. Effects of natural plant tenderizers on proteolysis and texture of dry ...

    African Journals Online (AJOL)

    , and overall acceptability. From these results, it is shown that those enzymes as a raw plant juices could be used as tenderizers in dry sausage production. Keywords: Dry sausages, wild boar meat, plant enzymes, proteolysis, texture, sensory ...

  17. A study on the re-identifiability of Dutch citizens

    OpenAIRE

    Koot, M.R.; van 't Noordende, G.; de Laat, C.; Serjantov, A.; Troncoso, C.

    2010-01-01

    This paper analyses the re-identifiability of Dutch citizens by various demographics. Our analysis is based on registry office data of 2.7 million Dutch citizens, ~16% of the total population. We provide overall statistics on re-identifiability for a range of quasi-identifiers, and present an in-depth analysis of quasi-identifiers found in two de-identified data sets. We found that 67.0% of the sampled population is unambiguously identifiable by date of birth and four-digit postal code alone,...

  18. Pre-cure freezing affects proteolysis in dry-cured hams.

    Science.gov (United States)

    Bañón, S; Cayuela, J M; Granados, M V; Garrido, M D

    1999-01-01

    Several parameters (sodium chloride, moisture, intramuscular fat, total nitrogen, non-protein nitrogen, white precipitates, free tyrosine, L* a* b* values and acceptability) related with proteolysis during the curing were compared in dry-cured hams manufactured from refrigerated and frozen/thawed raw material. Pre-cure freezing increased the proteolysis levels significantly (pcured meat, although it does not significantly affect the sensory quality of the dry-cured ham.

  19. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    OpenAIRE

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-01-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlyso...

  20. Social network analysis in identifying influential webloggers: A preliminary study

    Science.gov (United States)

    Hasmuni, Noraini; Sulaiman, Nor Intan Saniah; Zaibidi, Nerda Zura

    2014-12-01

    In recent years, second generation of internet-based services such as weblog has become an effective communication tool to publish information on the Web. Weblogs have unique characteristics that deserve users' attention. Some of webloggers have seen weblogs as appropriate medium to initiate and expand business. These webloggers or also known as direct profit-oriented webloggers (DPOWs) communicate and share knowledge with each other through social interaction. However, survivability is the main issue among DPOW. Frequent communication with influential webloggers is one of the way to keep survive as DPOW. This paper aims to understand the network structure and identify influential webloggers within the network. Proper understanding of the network structure can assist us in knowing how the information is exchanged among members and enhance survivability among DPOW. 30 DPOW were involved in this study. Degree centrality and betweenness centrality measurement in Social Network Analysis (SNA) were used to examine the strength relation and identify influential webloggers within the network. Thus, webloggers with the highest value of these measurements are considered as the most influential webloggers in the network.

  1. Identifying the educational needs of menopausal women: a feasibility study.

    Science.gov (United States)

    Trudeau, Kimberlee J; Ainscough, Jessica L; Trant, Meredith; Starker, Joan; Cousineau, Tara M

    2011-01-01

    The goal of this project was to identify the educational needs of menopausal women and test the feasibility of an online self management program based on social learning theory. The four stages included 1) a needs assessment using a) focus groups with 24 women ages 40 to 55 and b) phone interviews with eight health experts; 2) the use of concept mapping methodology for quantifying qualitative data from stage 1 to identify the core programmatic concepts; 3) development of a demonstration program; and 4) a pilot study with 35 women and 9 health experts to assess knowledge gained and program satisfaction. Results show that women desire more information about normalcy of menopause and symptom management and found the program to meet a need for menopausal education otherwise perceived as unavailable. The women significantly increased their menopausal knowledge after brief exposure (t(34) = 3.64; p = .001). This project provides support for an online health education program for menopausal women and content ideas for inclusion in women's health education curriculum. Copyright © 2011 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  2. 11S Storage globulin from pumpkin seeds: regularities of proteolysis by papain.

    Science.gov (United States)

    Rudakova, A S; Rudakov, S V; Kakhovskaya, I A; Shutov, A D

    2014-08-01

    Limited proteolysis of the α- and β-chains and deep cleavage of the αβ-subunits by the cooperative (one-by-one) mechanism was observed in the course of papain hydrolysis of cucurbitin, an 11S storage globulin from seeds of the pumpkin Cucurbita maxima. An independent analysis of the kinetics of the limited and cooperative proteolyses revealed that the reaction occurs in two successive steps. In the first step, limited proteolysis consisting of detachments of short terminal peptides from the α- and β-chains was observed. The cooperative proteolysis, which occurs as a pseudo-first order reaction, started at the second step. Therefore, the limited proteolysis at the first step plays a regulatory role, impacting the rate of deep degradation of cucurbitin molecules by the cooperative mechanism. Structural alterations of cucurbitin induced by limited proteolysis are suggested to generate its susceptibility to cooperative proteolysis. These alterations are tentatively discussed on the basis of the tertiary structure of the cucurbitin subunit pdb|2EVX in comparison with previously obtained data on features of degradation of soybean 11S globulin hydrolyzed by papain.

  3. Regulation of proteolysis in Bacillus subtilis: effects of calcium ions and energy poisons

    International Nuclear Information System (INIS)

    O'Hara, M.B.; Hageman, J.H.

    1987-01-01

    Bacillus subtilis cells carry out extensive intracellular proteolysis (k = 0.15-0.23/h) during sporulation. Protein degradation was measured in cells growing in chemically defined sporulation medium, by following the release of [ 14 C]-leucine from the cells during spore formation. Sodium arsenate, carbonyl cyanide 3-chlorophenyl hydrazone, and sodium azide strongly inhibited proteolysis without altering cell viability greatly, which suggested that bulk proteolysis in B. subtilis is energy dependent. The authors have tested the hypothesis that the energy requirement may be for pumping in Ca 2+ . When [Ca 2+ ] was -6 , rates of proteolysis in sporulating cells were reduced 4-8 times that in cells in calcium ion- sufficient medium. Further, omission of Ca 2+ from the medium prevented the increase in the activity of the major intracellular serine protease. However, the presence of energy poisons in the media at levels which inhibited proteolysis, had no detectable effect on the uptake of by cells [ 45 Ca]. The authors concluded that B. subtilis cells required both metabolic energy and calcium ions for normal proteolysis

  4. Proteolysis of truncated hemolysin A yields a stable dimerization interface

    Energy Technology Data Exchange (ETDEWEB)

    Novak, Walter R.P.; Bhattacharyya, Basudeb; Grilley, Daniel P.; Weaver, Todd M. (Wabash); (UW)

    2017-02-21

    Wild-type and variant forms of HpmA265 (truncated hemolysin A) fromProteus mirabilisreveal a right-handed, parallel β-helix capped and flanked by segments of antiparallel β-strands. The low-salt crystal structures form a dimeric structureviathe implementation of on-edge main-chain hydrogen bonds donated by residues 243–263 of adjacent monomers. Surprisingly, in the high-salt structures of two variants, Y134A and Q125A-Y134A, a new dimeric interface is formedviamain-chain hydrogen bonds donated by residues 203–215 of adjacent monomers, and a previously unobserved tetramer is formed. In addition, an eight-stranded antiparallel β-sheet is formed from the flap regions of crystallographically related monomers in the high-salt structures. This new interface is possible owing to additional proteolysis of these variants after Tyr240. The interface formed in the high-salt crystal forms of hemolysin A variants may mimic the on-edge β-strand positioning used in template-assisted hemolytic activity.

  5. Imaging Proteolysis by Living Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mansoureh Sameni

    2000-01-01

    Full Text Available Malignant progression is accompanied by degradation of extracellular matrix proteins. Here we describe a novel confocal assay in which we can observe proteolysis by living human breast cancer cells (BT20 and BT549 through the use of quenchedfluorescent protein substrates. Degradation thus was imaged, by confocal optical sectioning, as an accumulation of fluorescent products. With the BT20 cells, fluorescence was localized to pericellular focal areas that coincide with pits in the underlying matrix. In contrast, fluorescence was localized to intracellular vesicles in the BT549 cells, vesicles that also label for lysosomal markers. Neither intracellular nor pericellular fluorescence was observed in the BT549 cells in the presence of cytochalasin B, suggesting that degradation occurred intracellularly and was dependent on endocytic uptake of substrate. In the presence of a cathepsin 13-selective cysteine protease inhibitor, intracellular fluorescence was decreased ~90% and pericellular fluorescence decreased 67% to 96%, depending on the protein substrate. Matrix metallo protease inhibitors reduced pericellular fluorescence ~50%, i.e., comparably to a serine and a broad spectrum cysteine protease inhibitor. Our results suggest that: 1 a proteolytic cascade participates in pericellular digestion of matrix proteins by living human breast cancer cells, and 2 the cysteine protease cathepsin B participates in both pericellular and intracellular digestion of matrix proteins by living human breast cancer cells.

  6. Proteolysis of virulence regulator ToxR is associated with entry of Vibrio cholerae into a dormant state.

    Directory of Open Access Journals (Sweden)

    Salvador Almagro-Moreno

    2015-04-01

    Full Text Available Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio Pathogenicity Island (VPI, a horizontally acquired mobile genetic element, and functions primarily in virulence gene regulation. TcpP has been shown to undergo regulated intramembrane proteolysis (RIP in response to environmental conditions that are unfavorable for virulence gene expression. ToxR is encoded in the ancestral genome and is present in non-pathogenic strains of V. cholerae, indicating it has roles outside of the human host. In this study, we show that ToxR undergoes RIP in V. cholerae in response to nutrient limitation at alkaline pH, a condition that occurs during the stationary phase of growth. This process involves the site-2 protease RseP (YaeL, and is dependent upon the RpoE-mediated periplasmic stress response, as deletion mutants for the genes encoding these two proteins cannot proteolyze ToxR under nutrient limitation at alkaline pH. We determined that the loss of ToxR, genetically or by proteolysis, is associated with entry of V. cholerae into a dormant state in which the bacterium is normally found in the aquatic environment called viable but nonculturable (VBNC. Strains that can proteolyze ToxR, or do not encode it, lose culturability, experience a change in morphology associated with cells in VBNC, yet remain viable under nutrient limitation at alkaline pH. On the other hand, mutant strains that cannot proteolyze ToxR remain culturable and maintain the morphology of cells in an active state of growth. Overall, our findings provide a link between the proteolysis of a virulence regulator and the entry of a pathogen into an environmentally persistent state.

  7. Rapid and efficient proteolysis through laser-assisted immobilized enzyme reactors.

    Science.gov (United States)

    Zhang, Peng; Gao, Mingxia; Zhu, Shaochun; Lei, Jie; Zhang, Xiangmin

    2011-11-25

    In this report, laser radiation (808nm) for the first time was employed to enhance the efficiency of proteolysis through immobilized enzyme reactor (IMER). IMER based monolithic support was prepared in the fused-silica capillary via a simple two-step procedure including acryloylation on trypsin surface and in situ aqueous polymerization/immobilization. The feasibility and high efficiency of the laser-assisted IMER were demonstrated by the digestion of bovine serum albumin (BSA), cytochrome c (Cyt-c) and β-casein. The digestion process was achieved in 60s. The peptides were identified by MALDI-TOF-MS, yielding the sequence coverage of 33% for BSA, 73% for Cyt-c and 22% for β-casein. The comparisons between the in-solution digestion and on IMER reaction with/without laser assistance were made. To further confirm its efficiency in proteome analysis, the laser-assisted IMER was also applied to the analysis of one fraction of human serum sample through two-dimensional (2-D) separation of strong anion exchange/reversed-phase liquid chromatography (SAX/RPLC). After a database search, 49 unique peptides corresponding to 5 proteins were identified. The results showed that the laser-assisted IMER provides a promising platform for the high-throughput protein identification. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Identifying early indicators in bipolar disorder: a qualitative study.

    Science.gov (United States)

    Benti, Liliane; Manicavasagar, Vijaya; Proudfoot, Judy; Parker, Gordon

    2014-06-01

    The identification of early markers has become a focus for early intervention in bipolar disorder. Using a retrospective, qualitative methodology, the present study compares the early experiences of participants with bipolar disorder to those with unipolar depression up until their first diagnosed episode. The study focuses on differences in early home and school environments as well as putative differences in personality characteristics between the two groups. Finally we a compare and contrast prodromal symptoms in these two populations. Thirty-nine participants, 20 diagnosed with unipolar depression and 19 diagnosed with bipolar disorder, took part in the study. A semi-structured interview was developed to elicit information about participants' experiences prior to their first episode. Participants with bipolar disorder reported disruptive home environments, driven personality features, greater emotion dysregulation and adverse experiences during the school years, whereas participants with depression tended to describe more supportive home environments, and more compliant and introvert personality traits. Retrospective data collection and no corroborative evidence from other family members. No distinction was made between bipolar I and bipolar II disorder nor between melancholic and non-melancholic depression in the sample. Finally the study spanned over a 12-month period which does not allow for the possibility of diagnostic reassignment of some of the bipolar participants to the unipolar condition. These findings indicate that there may be benefits in combining both proximal and distal indicators in identifying a bipolar disorder phenotype which, in turn, may be relevant to the development of early intervention programs for young people with bipolar disorder.

  9. Parents of Youth Who Identify as Transgender: An Exploratory Study

    Science.gov (United States)

    Johnson, Danielle; Sikorski, Jonathon; Savage, Todd A.; Woitaszewski, Scott A.

    2014-01-01

    This article explores the experiences, perceptions, support systems, and coping strategies on which parents of youth who identify as transgender rely. Based on data gathered via interviews with parents of youth who identify as transgender and analyzed using the consensual qualitative research method, parental challenges and concerns about their…

  10. Nitrogen-15 studies on identifying fertilizer excess in environmental systems

    International Nuclear Information System (INIS)

    Freyer, H.D.; Aly, A.I.M.

    1975-01-01

    The feasibility of identifying fertilizer excesses in surface and ground waters on the basis of variations in the isotope ratio of nitrogen has been studied. The isotope ratio of the commonly used ammonium and nitrate fertilizers is similar to that of atmospheric nitrogen. These ratios are shifted when fertilizers are added to the soil. In the soil, fertilizer ammonium is oxidized and the nitrate formed is reduced in the heavy isotope. The fractionation factors are calculated. This artificially added nitrate becomes mixed with natural nitrate which, in general, is enriched in the heavy isotope. Only 50% (or even less) of the nitrate formed may stem from the added fertilizer. The mixing ratios are time-dependent, and different for various types and conditions of soil. In spite of this complexity, information on this isotopic process should be obtainable, if the isotope ratios of artificial and natural nitrate, respectively, are substantially different. Surface waters, in general, show no significant correlation between nitrate content and isotope ratio due to additions of sewage waters. Some data on ground waters from agricultural areas, however, where the nitrate content apparently resulted from fertilizers, gave a negative correlation of lower isotope ratios with higher nitrate contents. An inverse correlation was found in the isotope ratios of nitrate in untouched surface waters, and they even reflect the composition of the total soil nitrogen. (author)

  11. TCGA study identifies genomic features of cervical cancer

    Science.gov (United States)

    Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified novel genomic and molecular characteristics of cervical cancer that will aid in subclassification of the disease and may help target therapies that are most appropriate for each patient.

  12. A Study of Scientometric Methods to Identify Emerging Technologies

    Energy Technology Data Exchange (ETDEWEB)

    Abercrombie, Robert K [ORNL; Udoeyop, Akaninyene W [ORNL

    2011-01-01

    This work examines a scientometric model that tracks the emergence of an identified technology from initial discovery (via original scientific and conference literature), through critical discoveries (via original scientific, conference literature and patents), transitioning through Technology Readiness Levels (TRLs) and ultimately on to commercial application. During the period of innovation and technology transfer, the impact of scholarly works, patents and on-line web news sources are identified. As trends develop, currency of citations, collaboration indicators, and on-line news patterns are identified. The combinations of four distinct and separate searchable on-line networked sources (i.e., scholarly publications and citation, worldwide patents, news archives, and on-line mapping networks) are assembled to become one collective network (a dataset for analysis of relations). This established network becomes the basis from which to quickly analyze the temporal flow of activity (searchable events) for the example subject domain we investigated.

  13. Identifying nurses' rewards: a qualitative categorization study in Belgium

    Directory of Open Access Journals (Sweden)

    Du Bois Cindy

    2006-07-01

    Full Text Available Abstract Background Rewards are important in attracting, motivating and retaining the most qualified employees, and nurses are no exception to this rule. This makes the establishment of an efficient reward system for nurses a true challenge for every hospital manager. A reward does not necessarily have a financial connotation: non-financial rewards may matter too, or may even be more important. Therefore, the present study examines nurses' reward perceptions, in order to identify potential reward options. Methods To answer the research question "What do nurses consider a reward and how can these rewards be categorized?", 20 in-depth semi-structured interviews with nurses were conducted and analysed using discourse and content analyses. In addition, the respondents received a list of 34 rewards (derived from the literature and were asked to indicate the extent to which they perceived each of them to be rewarding. Results Discourse analysis revealed three major reward categories: financial, non-financial and psychological, each containing different subcategories. In general, nurses more often mentioned financial rewards spontaneously in the interview, compared to non-financial and psychological rewards. The questionnaire results did not, however, indicate a significant difference in the rewarding potential of these three categories. Both the qualitative and quantitative data revealed that a number of psychological and non-financial rewards were important for nurses in addition to their monthly pay and other remunerations. In particular, appreciation for their work by others, compliments from others, presents from others and contact with patients were highly valued. Moreover, some demographical variables influenced the reward perceptions. Younger and less experienced nurses considered promotion possibilities as more rewarding than the older and more senior ones. The latter valued job security and working for a hospital with a good reputation higher

  14. Effect of Aloe vera (Aloe barbadensis Miller) on survivability, extent of proteolysis and ACE inhibition of potential probiotic cultures in fermented milk.

    Science.gov (United States)

    Basannavar, Santosh; Pothuraju, Ramesh; Sharma, Raj Kumar

    2014-10-01

    In the present investigation, the effect of Aloe vera gel powder on angiotensin-converting enzyme (ACE) inhibitory activity, extent of proteolysis during fermentation and survival of Lactobacillus casei NCDC19 during storage of fermented milk was studied. Among the different cultures screened for ACE inhibitory activity, Lactobacillus casei NCDC 19 exhibited the highest ACE inhibition (approx. 40%) as well as extent of proteolysis (0.37, Abs₃₄₀). In the presence of Aloe vera (0.5% and 1% w/v) an increase in extent of proteolysis (0.460 ± 0.047 and 0.480 ± 0.027) and percent ACE inhibitory activity (44.32 ± 2.83 and 47.52 ± 1.83) was observed in comparison to control. Aloe vera powder addition also led to an increase in viable counts (>11 log cfu mL⁻¹) of L. casei NCDC 19 in fermented milk during storage for 7 days and the counts were maintained in sufficiently higher numbers. The study suggests Aloe vera to be a good functional ingredient which can be further explored for different health attributes. © 2014 Society of Chemical Industry.

  15. Molecular characterization of a proteolysis-resistant lipase from Bacillus pumilus SG2

    Directory of Open Access Journals (Sweden)

    R. Sangeetha

    2014-06-01

    Full Text Available Proteolysis-resistant lipases can be well exploited by industrial processes which employ both lipase and protease as biocatalysts. A proteolysis resistant lipase from Bacillus pumilus SG2 was isolated, purified and characterized earlier. The lipase was resistant to native and commercial proteases. In the present work, we have characterized the lip gene which encodes the proteolysis-resistant lipase from Bacillus pumilus SG2. The parameters and structural details of lipase were analysed. The lip gene consisted of 650 bp. The experimental molecular weight of SG2 lipase was nearly double that of its theoretical molecular weight, thus suggesting the existence of the functional lipase as a covalent dimer. The proteolytic cleavage sites of the lipase would have been made inaccessible by dimerisation, thus rendering the lipase resistant to protease.

  16. Structural Basis for Regulated Proteolysis by the α-Secretase ADAM10.

    Science.gov (United States)

    Seegar, Tom C M; Killingsworth, Lauren B; Saha, Nayanendu; Meyer, Peter A; Patra, Dhabaleswar; Zimmerman, Brandon; Janes, Peter W; Rubinstein, Eric; Nikolov, Dimitar B; Skiniotis, Georgios; Kruse, Andrew C; Blacklow, Stephen C

    2017-12-14

    Cleavage of membrane-anchored proteins by ADAM (a disintegrin and metalloproteinase) endopeptidases plays a key role in a wide variety of biological signal transduction and protein turnover processes. Among ADAM family members, ADAM10 stands out as particularly important because it is both responsible for regulated proteolysis of Notch receptors and catalyzes the non-amyloidogenic α-secretase cleavage of the Alzheimer's precursor protein (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain, which, together with biochemical and cellular studies, reveals how access to the enzyme active site is regulated. The enzyme adopts an unanticipated architecture in which the C-terminal cysteine-rich domain partially occludes the enzyme active site, preventing unfettered substrate access. Binding of a modulatory antibody to the cysteine-rich domain liberates the catalytic domain from autoinhibition, enhancing enzymatic activity toward a peptide substrate. Together, these studies reveal a mechanism for regulation of ADAM activity and offer a roadmap for its modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2016-05-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A–VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor–ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145 promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes.

  18. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis.

    Science.gov (United States)

    Fearnley, Gareth W; Smith, Gina A; Abdul-Zani, Izma; Yuldasheva, Nadira; Mughal, Nadeem A; Homer-Vanniasinkam, Shervanthi; Kearney, Mark T; Zachary, Ian C; Tomlinson, Darren C; Harrison, Michael A; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2016-05-15

    Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A-VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor-ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes. © 2016. Published by The Company of Biologists Ltd.

  19. Proteolysis of complement factors iC3b and C5 by the serine protease prostate-specific antigen in prostatic fluid and seminal plasma.

    Science.gov (United States)

    Manning, Michael L; Williams, Simon A; Jelinek, Christine A; Kostova, Maya B; Denmeade, Samuel R

    2013-03-15

    Prostate-specific Ag (PSA) is a serine protease that is expressed exclusively by normal and malignant prostate epithelial cells. The continued high-level expression of PSA by the majority of men with both high- and low-grade prostate cancer throughout the course of disease progression, even in the androgen-ablated state, suggests that PSA has a role in the pathogenesis of disease. Current experimental and clinical evidence suggests that chronic inflammation, regardless of the cause, may predispose men to prostate cancer. The responsibility of the immune system in immune surveillance and eventually tumor progression is well appreciated but not completely understood. In this study, we used a mass spectrometry-based evaluation of prostatic fluid obtained from diseased prostates after removal by radical prostatectomy to identify potential immunoregulatory proteins. This analysis revealed the presence of Igs and the complement system proteins C3, factor B, and clusterin. Verification of these findings by Western blot confirmed the high-level expression of C3 in the prostatic fluid and the presence of a previously uncharacterized C-terminal C3 cleavage product. Biochemical analysis of this C3 cleavage fragment revealed a putative PSA cleavage site after tyrosine-1348. Purified PSA was able to cleave iC3b and the related complement protein C5. These results suggest a previously uncharacterized function of PSA as an immunoregulatory protease that could help to create an environment hospitable to malignancy through proteolysis of the complement system.

  20. Enhancement of 9α-Hydroxy-4-androstene-3,17-dione Production from Soybean Phytosterols by Deficiency of a Regulated Intramembrane Proteolysis Metalloprotease in Mycobacterium neoaurum.

    Science.gov (United States)

    Xiong, Liang-Bin; Sun, Wan-Ju; Liu, Yong-Jun; Wang, Feng-Qing; Wei, Dong-Zhi

    2017-12-06

    Modification of the sterol catabolism pathway in mycobacteria may result in the accumulation of some valuable steroid pharmaceutical intermediates, such as 9α-hydroxy-4-androstene-3,17-dione (9-OHAD). In previous work, sigma factor D (SigD) was identified as a negative factor of the 9-OHAD production in Mycobacterium neoaurum. Here, the deficiency of rip1 putatively coding for a regulated intramembrane proteolysis metalloprotease (Rip1), which could cleave the negative regulator of SigD (anti-SigD), enhanced the transcription of some key genes (choM1, kshA, and hsd4A) in the sterol catabolic pathway. Furthermore, the deletion of rip1 increased the consumption of phytosterols by 37.8% after 96 h of growth in M. neoaurum. The production of 9-OHAD in the engineered M. neoaurumΔkstD1ΔkstD2ΔkstD3Δrip1 (MnΔk123Δrip1) strain was ultimately increased by 27.3% compared to that in its parental strain M. neoaurumΔkstD1ΔkstD2ΔkstD3 (MnΔk123). This study further confirms the important role of SigD-related factors in the catabolism of sterols.

  1. The cachectic mediator proteolysis inducing factor activates NF-kappaB and STAT3 in human Kupffer cells and monocytes

    NARCIS (Netherlands)

    Watchorn, T.M.; Dowidar, N.; Dejong, C.H.; Waddell, I.D.; Garden, O.J.; Ross, J.A.

    2005-01-01

    A novel proteoglycan, proteolysis inducing factor (PIF), is capable of inducing muscle proteolysis during the process of cancer cachexia, and of inducing an acute phase response in human hepatocytes. We investigated whether PIF is able to activate pro-inflammatory pathways in human Kupffer cells,

  2. Region-specific proteolysis differentially regulates type 1 inositol 1,4,5-trisphosphate receptor activity.

    Science.gov (United States)

    Wang, Liwei; Wagner, Larry E; Alzayady, Kamil J; Yule, David I

    2017-07-14

    The inositol 1,4,5 trisphosphate receptor (IP 3 R) is an intracellular Ca 2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP 3 R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP 3 R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP 3 binding despite the loss of peptide continuity. In this study, we demonstrate that region-specific receptor fragmentation modifies channel regulation. Specifically, the agonist-evoked temporal Ca 2+ release profile and protein kinase A modulation of Ca 2+ release are markedly altered. Moreover, we also demonstrate that activation of fragmented IP 3 R1 can result in a distinct functional outcome. Our work suggests that proteolysis of IP 3 R1 may represent a novel form of modulation of IP 3 R1 channel function and increases the repertoire of Ca 2+ signals achievable through this channel. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity.

    Science.gov (United States)

    Klein, Theo; Viner, Rosa I; Overall, Christopher M

    2016-10-28

    Adaptive immunity is the specialized defence mechanism in vertebrates that evolved to eliminate pathogens. Specialized lymphocytes recognize specific protein epitopes through antigen receptors to mount potent immune responses, many of which are initiated by nuclear factor-kappa B activation and gene transcription. Most, if not all, pathways in adaptive immunity are further regulated by post-translational modification (PTM) of signalling proteins, e.g. phosphorylation, citrullination, ubiquitination and proteolytic processing. The importance of PTMs is reflected by genetic or acquired defects in these pathways that lead to a dysfunctional immune response. Here we discuss the state of the art in targeted proteomics and systems biology approaches to dissect the PTM landscape specifically regarding ubiquitination and proteolysis in B- and T-cell activation. Recent advances have occurred in methods for specific enrichment and targeted quantitation. Together with improved instrument sensitivity, these advances enable the accurate analysis of often rare PTM events that are opaque to conventional proteomics approaches, now rendering in-depth analysis and pathway dissection possible. We discuss published approaches, including as a case study the profiling of the N-terminome of lymphocytes of a rare patient with a genetic defect in the paracaspase protease MALT1, a key regulator protease in antigen-driven signalling, which was manifested by elevated linear ubiquitination.This article is part of the themed issue 'Quantitative mass spectrometry'. © 2016 The Authors.

  4. Genome-wide association study identifies five new schizophrenia loci

    NARCIS (Netherlands)

    Ripke, S.; Sanders, A. R.; Kendler, K. S.; Levinson, D. F.; Sklar, P.; Holmans, P. A.; Lin, D. Y.; Duan, J.; Ophoff, R. A.; Andreassen, O. A.; Scolnick, E.; Cichon, S.; St Clair, D.; Corvin, A.; Gurling, H.; Werge, T.; Rujescu, D.; Blackwood, D. H.; Pato, C. N.; Malhotra, A. K.; Purcell, S.; Dudbridge, F.; Neale, B. M.; Rossin, L.; Visscher, P. M.; Posthuma, D.; Ruderfer, D. M.; Fanous, A.; Stefansson, H.; Steinberg, S.; Mowry, B. J.; Golimbet, V.; de Hert, M.; Jonsson, E. G.; Bitter, I.; Pietilainen, O. P.; Collier, D. A.; Tosato, S.; Agartz, I.; Albus, M.; Alexander, M.; Amdur, R. L.; Amin, F.; Bass, N.; Bergen, S. E.; Black, D. W.; Borglum, A. D.; Brown, M. A.; Bruggeman, R.; Buccola, N. G.; Byerley, W. F.; Cahn, W.; Cantor, R. M.; Carr, V. J.; Catts, S. V.; Choudhury, K.; Cloninger, C. R.; Cormican, P.; Craddock, N.; Danoy, P. A.; Datta, S.; de Haan, L.; Demontis, D.; Dikeos, D.; Djurovic, S.; Donnely, P.; Donohoe, G.; Duong, L.; Dwyer, S.; Fink-Jensen, A.; Freedman, R.; Freimer, N. B.; Friedl, M.; Georgieva, L.; Giegling, I.; Gill, M.; Glenthoj, B.; Godard, S.; Hamshere, M.; Hansen, M.; Hartmann, A. M.; Henskens, F. A.; Hougaard, D. M.; Hultman, C. M.; Ingason, A.; Jablensky, A. V.; Jakobsen, K. D.; Jay, M.; Jurgens, G.; Kahn, R. S.; Keller, M. C.; Kenis, G.; Kenny, E.; Kim, Y.; Kirov, G. K.; Konnerth, H.; Konte, B.; Krabbendam, L.; Krasucki, R.; Lasseter, V. K.; Laurent, C.; Lawrence, J.; Lencz, T.; Lerer, F. B.; Liang, K. Y.; Lichtenstein, P.; Lieberman, J. A.; Linszen, D. H.; Lonnqvist, J.; Loughland, C. M.; Maclean, A. W.; Maher, B. S.; Maier, W.; Mallet, J.; Malloy, P.; Mattheisen, M.; Mattingsdal, M.; McGhee, K. A.; McGrath, J. J.; McIntosh, A.; McLean, D. E.; McQuillin, A.; Melle, I.; Michie, P. T.; Milanova, V.; Morris, D. W.; Mors, O.; Mortensen, P. B.; Moskvina, V.; Muglia, P.; Myin-Germeys, I.; Nertney, D. A.; Nestadt, G.; Nielsen, J.; Nikolov, I.; Nordentoft, M.; Norton, N.; Nothen, M. M.; O'Dushlaine, C. T.; Olincy, A.; Olsen, L.; O'Neill, F. A.; Orntoft, T. F.; Owen, M. J.; Pantelis, C.; Papadimitriou, G.; Pato, M. T.; Peltonen, L.; Petursson, H.; Pickard, B.; Pimm, J.; Pulver, A. E.; Puri, V.; Quested, D.; Quinn, E. M.; Rasmussen, H. B.; Rethelyi, J. M.; Ribble, R.; Rietschel, M.; Riley, B. P.; Ruggeri, M.; Schall, U.; Schulze, T. G.; Schwab, S. G.; Scott, R. J.; Shi, J.; Sigurdsson, E.; Silvermann, J. M.; Spencer, C. C.; Stefansson, K.; Strange, A.; Strengman, E.; Stroup, T. S.; Suvisaari, J.; Terenius, L.; Thirumalai, S.; Thygesen, J. H.; Timm, S.; Toncheva, D.; van den Oord, E.; van Os, J.; van Winkel, R.; Veldink, J.; Walsh, D.; Wang, A. G.; Wiersma, D.; Wildenauer, D. B.; Williams, H. J.; Williams, N. M.; Wormley, B.; Zammit, S.; Sullivan, P. F.; O'Donovan, M. C.; Daly, M. J.; Gejman, P. V.

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded

  5. Identifying Threshold Concepts for Information Literacy: A Delphi Study

    Science.gov (United States)

    Townsend, Lori; Hofer, Amy R.; Hanick, Silvia Lin; Brunetti, Korey

    2016-01-01

    This study used the Delphi method to engage expert practitioners on the topic of threshold concepts--core ideas and processes in a discipline that students need to grasp in order to progress in their learning, but that are often unspoken or unrecognized by expert practitioners--for information literacy. A panel of experts considered two questions:…

  6. Identifying Threshold Concepts for Information Literacy: A Delphi Study

    Directory of Open Access Journals (Sweden)

    Lori Townsend

    2016-06-01

    Full Text Available This study used the Delphi method to engage expert practitioners on the topic of threshold concepts for information literacy. A panel of experts considered two questions. First, is the threshold concept approach useful for information literacy instruction? The panel unanimously agreed that the threshold concept approach holds potential for information literacy instruction. Second, what are the threshold concepts for information literacy instruction? The panel proposed and discussed over fifty potential threshold concepts, finally settling on six information literacy threshold concepts.

  7. Identifying Threshold Concepts for Information Literacy: A Delphi Study

    OpenAIRE

    Lori Townsend; Amy R. Hofer; Silvia Lin Hanick; Korey Brunetti

    2016-01-01

    This study used the Delphi method to engage expert practitioners on the topic of threshold concepts for information literacy. A panel of experts considered two questions. First, is the threshold concept approach useful for information literacy instruction? The panel unanimously agreed that the threshold concept approach holds potential for information literacy instruction. Second, what are the threshold concepts for information literacy instruction? The panel proposed and discussed over fift...

  8. Study on determination method of identifying irradiated chicken

    International Nuclear Information System (INIS)

    Guo Liping; Yu Xuejun; Yu Menghong; Fu Junjie; Zhang Shimin; Bao Jinsong

    2003-01-01

    The effects of gamma irradiation on the activities of aleipsis, peroxidase, perhydrol catalase and the peroxide values in chicken oil and effects of different storage time on self-oxidation of fat and lipa in irradiated chicken were studied. The results showed that the activities of aleipsis and perhydrol catalase in irradiated chicken decreased with increasing doses, and the peroxide activity and peroxide value of lipa increased with increase of doses. No significant effect of storage time on peroxide value was observed in the irradiated chicken

  9. Genome-wide association study identifies five new schizophrenia loci.

    LENUS (Irish Health Repository)

    Ripke, Stephan

    2011-10-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).

  10. Energy and calcium ion dependence of proteolysis during sporulation of Bacillus subtilis cells

    International Nuclear Information System (INIS)

    O'Hara, M.B.; Hageman, J.H.

    1990-01-01

    The authors have shown, with an optimized [ 14 C]leucine-labeling and chasing procedure, that intracellular protein degradation in sporulating cells of Bacillus subtilis 168 (trpC2) is apparently energy dependent. Sodium arsenate, sodium azide, carbonyl cyanide m-chlorophenylhydrozone, and N,N'-dicyclohexylcarbodiimide, at levels which did not induce appreciable lysis (≤ 10%) over 10-h periods of sporulation, inhibited intracellular proteolysis by 13 to 93%. Exponentially growing cells acquired arsenate resistance. In contrast to earlier reports, the authors found that chloramphenicol strongly inhibited proteolysis even when added 6 h into the sporulation process. Restricting the calcium ion concentration in the medium had no effect on rates or extent of vegetative growth, strongly inhibited sporulation, and inhibited rates of proteolysis by 60% or more. Inhibitors of energy metabolism, at the same levels which inhibited proteolysis, did not affect the rate or degree of uptake of Ca 2+ by cells. Restricting the Ca 2+ concentration in the medium reduced by threefold of the specific activity in cells of the major intracellular serine proteinase after 12 h of sporulation. finally, cells of a mutant of B. subtilis bearing an insertionally inactivated gene for the Ca 2+ -dependent intracellular proteinase-1 degraded protein in chemically defined sporulation medium at a rate indistinguishable from that of the wild-type cells for period of 8 h

  11. Characterization of linear forms of the circular enterocin AS-48 obtained by limited proteolysis

    NARCIS (Netherlands)

    Montalbán-López, Manuel; Spolaore, Barbara; Pinato, Odra; Martínez-Bueno, Manuel; Valdivia, Eva; Maqueda, Mercedes; Fontana, Angelo

    2008-01-01

    AS-48 is a 70-residue circular peptide from Enterococcus faecalis with a broad antibacterial activity. Here, we produced by limited proteolysis a protein species carrying a single nicking and fragments of 55 and 38 residues. Nicked AS-48 showed a lower helicity by far-ultraviolet circular dichroism

  12. Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis

    Directory of Open Access Journals (Sweden)

    Kanbe Katsuaki

    2008-06-01

    Full Text Available Abstract The von Willebrand Factor A (vWF A domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED, however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3. First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.

  13. Structural inferences for the native skeletal muscle sodium channel as derived from patterns of endogenous proteolysis

    International Nuclear Information System (INIS)

    Kraner, S.; Yang, J.; Barchi, R.

    1989-01-01

    The alpha subunit (Mr approximately 260,000) of the rat skeletal muscle sodium channel is sensitive to cleavage by endogenous proteases during the isolation of muscle surface membrane. Antisera against synthetic oligopeptides were used to map the resultant fragments in order to identify protease-sensitive regions of the channel's structure in its native membrane environment. Antibodies to the amino terminus labeled major fragments of Mr approximately 130,000 and 90,000 and lesser amounts of other peptides as small as Mr approximately 12,000. Antisera to epitopes within the carboxyl-terminal half of the primary sequence recognized two fragments of Mr approximately 110,000 and 78,000. Individual antisera also selectively labeled smaller polypeptides in the most extensively cleaved preparations. The immunoreactivity patterns of monoclonal antibodies previously raised against the purified channel were then surveyed. The binding sites for one group of monoclonals, including several that recognize subtype-specific epitopes in the channel structure, were localized within a 12-kDa fragment near the amino terminus. The distribution of carbohydrate along the primary structure of the channel was also assessed by quantitating 125 I-wheat germ agglutinin and 125I-concanavalin A binding to the proteolytic peptides. Most of the carbohydrate detected by these lectins was located between 22 and 90 kDa from the amino terminus of the protein. No lectin binding was detected to fragments arising from carboxyl-terminal half of the protein. These results were analyzed in terms of current models of sodium channel tertiary structure. In its normal membrane environment, the skeletal muscle sodium channel appears sensitive to cleavage by endogenous proteases in regions predicted to link the four repeat domains on the cytoplasmic side of the membrane while the repeat domains themselves are resistant to proteolysis

  14. Proteolysis of His-Phe-Arg-Trp-Pro-Gly-Pro in the blood and brain of rats in vivo.

    Science.gov (United States)

    Shevchenko, K V; Nagaev, I Yu; Babakov, V N; Andreeva, L A; Shevchenko, V P; Radilov, A S; Myasoedov, N F

    2015-01-01

    The kinetics of the content of His-Phe-Arg-Trp-Pro-Gly-Pro (ACTH (6-9)PGP) and its hydrolysis products in the blood and brain of rats in the case of intranasal administration and intravenous injection of tritiated ACTH(6-9)PGP was studied. The parameters of bioavailability of ACTH(6-9)PGP administered intranasally were higher, indicating certain prospects in the intranasal application in clinical practice. We also found that the factor that determines ACTH(6-9)PGP proteolysis in experiments both in vivo and in vitro is aminopeptidases. The main products of ACTH(6-9)PGP during its metabolism in rats are short peptides and amino acids.

  15. Protein translation, proteolysis and autophagy in human skeletal muscle atrophy after spinal cord injury.

    Science.gov (United States)

    Lundell, L S; Savikj, M; Kostovski, E; Iversen, P O; Zierath, J R; Krook, A; Chibalin, A V; Widegren, U

    2018-02-08

    Spinal cord injury-induced loss of skeletal muscle mass does not progress linearly. In humans, peak muscle loss occurs during the first 6 weeks postinjury, and gradually continues thereafter. The aim of this study was to delineate the regulatory events underlying skeletal muscle atrophy during the first year following spinal cord injury. Key translational, autophagic and proteolytic proteins were analysed by immunoblotting of human vastus lateralis muscle obtained 1, 3 and 12 months following spinal cord injury. Age-matched able-bodied control subjects were also studied. Several downstream targets of Akt signalling decreased after spinal cord injury in skeletal muscle, without changes in resting Akt Ser 473 and Akt Thr 308 phosphorylation or total Akt protein. Abundance of mTOR protein and mTOR Ser 2448 phosphorylation, as well as FOXO1 Ser 256 phosphorylation and FOXO3 protein, decreased in response to spinal cord injury, coincident with attenuated protein abundance of E3 ubiquitin ligases, MuRF1 and MAFbx. S6 protein and Ser 235/236 phosphorylation, as well as 4E-BP1 Thr 37/46 phosphorylation, increased transiently after spinal cord injury, indicating higher levels of protein translation early after injury. Protein abundance of LC3-I and LC3-II decreased 3 months postinjury as compared with 1 month postinjury, but not compared to able-bodied control subjects, indicating lower levels of autophagy. Proteins regulating proteasomal degradation were stably increased in response to spinal cord injury. Together, these data provide indirect evidence suggesting that protein translation and autophagy transiently increase, while whole proteolysis remains stably higher in skeletal muscle within the first year after spinal cord injury. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  16. Toxoplasma gondii infection shifts dendritic cells into an amoeboid rapid migration mode encompassing podosome dissolution, secretion of TIMP-1, and reduced proteolysis of extracellular matrix.

    Science.gov (United States)

    Ólafsson, Einar B; Varas-Godoy, Manuel; Barragan, Antonio

    2018-03-01

    Dendritic cells (DCs) infected by Toxoplasma gondii rapidly acquire a hypermigratory phenotype that promotes systemic parasite dissemination by a "Trojan horse" mechanism in mice. Recent paradigms of leukocyte migration have identified the amoeboid migration mode of DCs as particularly suited for rapid locomotion in extracellular matrix and tissues. Here, we have developed a microscopy-based high-throughput approach to assess motility and matrix degradation by Toxoplasma-challenged murine and human DCs. DCs challenged with T. gondii exhibited dependency on metalloproteinase activity for hypermotility and transmigration but, strikingly, also dramatically reduced pericellular proteolysis. Toxoplasma-challenged DCs up-regulated expression and secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) and their supernatants impaired matrix degradation by naïve DCs and by-stander DCs dose dependently. Gene silencing of TIMP-1 by short hairpin RNA restored matrix degradation activity in Toxoplasma-infected DCs. Additionally, dissolution of podosome structures in parasitised DCs coincided with abrogated matrix degradation. Toxoplasma lysates inhibited pericellular proteolysis in a MyD88-dependent fashion whereas abrogated proteolysis persevered in Toxoplasma-infected MyD88-deficient DCs. This indicated that both TLR/MyD88-dependent and TLR/MyD88-independent signalling pathways mediated podosome dissolution and the abrogated matrix degradation. We report that increased TIMP-1 secretion and cytoskeletal rearrangements encompassing podosome dissolution are features of Toxoplasma-induced hypermigration of DCs with an impact on matrix degradation. Jointly, the data highlight how an obligate intracellular parasite orchestrates key regulatory cellular processes consistent with non-proteolytic amoeboid migration of the vehicle cells that facilitate its dissemination. © 2017 John Wiley & Sons Ltd.

  17. Autophagic dysfunction in a lysosomal storage disorder due to impaired proteolysis

    OpenAIRE

    Elrick, Matthew J.; Lieberman, Andrew P.

    2013-01-01

    Alterations in macroautophagy (hereafter referred to as “autophagy”) are a common feature of lysosomal storage disorders, and have been hypothesized to play a major role in the pathogenesis of these diseases. We have recently reported multiple defects in autophagy contributing to the lysosomal storage disorder Niemann-Pick type C (NPC). These include increased formation of autophagosomes, slowed turnover of autophagosomes secondary to impaired lysosomal proteolysis, and delivery of stored lip...

  18. Extracellular proteolysis in structural and functional plasticity of mossy fiber synapses in hippocampus

    Directory of Open Access Journals (Sweden)

    Grzegorz eWiera

    2015-11-01

    Full Text Available Brain is continuously altered in response to experience and environmental changes. One of the underlying mechanisms is synaptic plasticity, which is manifested by modification of synapse structure and function. It is becoming clear that regulated extracellular proteolysis plays a pivotal role in the structural and functional remodeling of synapses during brain development, learning and memory formation. Clearly, plasticity mechanisms may substantially differ between projections. Mossy fiber synapses onto CA3 pyramidal cells display several unique functional features, including pronounced short-term facilitation, a presynaptically expressed LTP that is independent of NMDAR activation, and NMDA-dependent metaplasticity. Moreover, structural plasticity at mossy fiber synapses ranges from the reorganization of projection topology after hippocampus-dependent learning, through intrinsically different dynamic properties of synaptic boutons to pre- and postsynaptic structural changes accompanying LTP induction. Although concomitant functional and structural plasticity in this pathway strongly suggests a role of extracellular proteolysis, its impact only starts to be investigated in this projection. In the present report, we review the role of extracellular proteolysis in various aspects of synaptic plasticity in hippocampal mossy fiber synapses. A growing body of evidence demonstrates that among perisynaptic proteases, tPA/plasmin system, β-site amyloid precursor protein-cleaving enzyme 1 (BACE1 and metalloproteinases play a crucial role in shaping plastic changes in this projection. We discuss recent advances and emerging hypotheses on the roles of proteases in mechanisms underlying mossy fiber target specific synaptic plasticity and memory formation.

  19. Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis.

    Science.gov (United States)

    Perumal, Shiamalee; Antipova, Olga; Orgel, Joseph P R O

    2008-02-26

    We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or "collagenolysis." The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibril is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's "interaction domain," which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.

  20. A novel Meloidogyne graminicola effector, MgGPP, is secreted into host cells and undergoes glycosylation in concert with proteolysis to suppress plant defenses and promote parasitism.

    Directory of Open Access Journals (Sweden)

    Jiansong Chen

    2017-04-01

    Full Text Available Plant pathogen effectors can recruit the host post-translational machinery to mediate their post-translational modification (PTM and regulate their activity to facilitate parasitism, but few studies have focused on this phenomenon in the field of plant-parasitic nematodes. In this study, we show that the plant-parasitic nematode Meloidogyne graminicola has evolved a novel effector, MgGPP, that is exclusively expressed within the nematode subventral esophageal gland cells and up-regulated in the early parasitic stage of M. graminicola. The effector MgGPP plays a role in nematode parasitism. Transgenic rice lines expressing MgGPP become significantly more susceptible to M. graminicola infection than wild-type control plants, and conversely, in planta, the silencing of MgGPP through RNAi technology substantially increases the resistance of rice to M. graminicola. Significantly, we show that MgGPP is secreted into host plants and targeted to the ER, where the N-glycosylation and C-terminal proteolysis of MgGPP occur. C-terminal proteolysis promotes MgGPP to leave the ER, after which it is transported to the nucleus. In addition, N-glycosylation of MgGPP is required for suppressing the host response. The research data provide an intriguing example of in planta glycosylation in concert with proteolysis of a pathogen effector, which depict a novel mechanism by which parasitic nematodes could subjugate plant immunity and promote parasitism and may present a promising target for developing new strategies against nematode infections.

  1. Probing the 3-D Structure, Dynamics, and Stability of Bacterial Collagenase Collagen Binding Domain (apo- versus holo-) by Limited Proteolysis MALDI-TOF MS

    Science.gov (United States)

    Sides, Cynthia R.; Liyanage, Rohana; Lay, Jackson O.; Philominathan, Sagaya Theresa Leena; Matsushita, Osamu; Sakon, Joshua

    2012-03-01

    Pairing limited proteolysis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to probe clostridial collagenase collagen binding domain (CBD) reveals the solution dynamics and stability of the protein, as these factors are crucial to CBD effectiveness as a drug-delivery vehicle. MS analysis of proteolytic digests indicates initial cleavage sites, thereby specifying the less stable and highly accessible regions of CBD. Modulation of protein structure and stability upon metal binding is shown through MS analysis of calcium-bound and cobalt-bound CBD proteolytic digests. Previously determined X-ray crystal structures illustrate that calcium binding induces secondary structure transformation in the highly mobile N-terminal arm and increases protein stability. MS-based detection of exposed residues confirms protein flexibility, accentuates N-terminal dynamics, and demonstrates increased global protein stability exported by calcium binding. Additionally, apo- and calcium-bound CBD proteolysis sites correlate well with crystallographic B-factors, accessibility, and enzyme specificity. MS-observed cleavage sites with no clear correlations are explained either by crystal contacts of the X-ray crystal structures or by observed differences between Molecules A and B in the X-ray crystal structures. The study newly reveals the absence of the βA strand and thus the very dynamic N-terminal linker, as corroborated by the solution X-ray scattering results. Cobalt binding has a regional effect on the solution phase stability of CBD, as limited proteolysis data implies the capture of an intermediate-CBD solution structure when cobalt is bound.

  2. The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes.

    Science.gov (United States)

    Bergantin, Leandro Bueno; Figueiredo, Leonardo Bruno; Godinho, Rosely Oliveira

    2011-12-01

    The molecular regulation of skeletal muscle proteolysis and the pharmacological screening of anticatabolic drugs have been addressed by measuring tyrosine release from prepubertal rat skeletal muscles, which are thin enough to allow adequate in vitro diffusion of oxygen and substrates. However, the use of muscle at accelerated prepubertal growth has limited the analysis of adult muscle proteolysis or that associated with aging and neurodegenerative diseases. Here we established the adult rat lumbrical muscle (4/hindpaw; 8/rat) as a new in situ experimental model for dynamic measurement of skeletal muscle proteolysis. By incubating lumbrical muscles attached to their individual metatarsal bones in Tyrode solution, we showed that the muscle proteolysis rate of adult and aged rats (3-4 to 24 mo old) is 45-25% of that in prepubertal animals (1 mo old), which makes questionable the usual extrapolation of proteolysis from prepubertal to adult/senile muscles. While acute mechanical injury or 1- to 7-day denervation increased tyrosine release from adult lumbrical muscle by up to 60%, it was reduced by 20-28% after 2-h incubation with β-adrenoceptor agonists, forskolin or phosphodiesterase inhibitor IBMX. Using inhibitors of 26S-proteasome (MG132), lysosome (methylamine), or calpain (E64/leupeptin) systems, we showed that ubiquitin-proteasome is accountable for 40-50% of total lumbrical proteolysis of adult, middle-aged, and aged rats. In conclusion, the lumbrical model allows the analysis of muscle proteolysis rate from prepubertal to senile rats. By permitting eight simultaneous matched measurements per rat, the new model improves similar protocols performed in paired extensor digitorum longus (EDL) muscles from prepubertal rats, optimizing the pharmacological screening of drugs for anticatabolic purposes.

  3. The effect of different packaging materials on proteolysis, sensory ...

    African Journals Online (AJOL)

    Administrator

    2011-05-23

    May 23, 2011 ... In this study, tulum cheese was manufactured using raw ewe's milk and was ripened in goat's skin and plastic bags. The effect of ... terms of gross composition due to the porous structure of skin bag, which causes moisture loses during ripening. ... pasteurized milk and starter culture for tulum cheese.

  4. cAMP-dependent proteolysis of GATA-6 is linked to JNK-signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ushijima, Hironori [Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694 (Japan); Maeda, Masatomo, E-mail: mmaeda@iwate-med.ac.jp [Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6. Black-Right-Pointing-Pointer Effect of a JNK activator anisomycin on the proteolysis was examined. Black-Right-Pointing-Pointer Anisomycin stimulated the export of nuclear GATA-6 into the cytoplasm. Black-Right-Pointing-Pointer JNK activated the CRM1 mediated nuclear export of GATA-6. Black-Right-Pointing-Pointer JNK further stimulated slowly the degradation of GATA-6 by cytoplasmic proteasomes. -- Abstract: A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6 by proteasomes around its IC50. We further examined the effects of SP600125 on the degradation of GATA-6 in detail, since an activator of JNK (anisomycin) is available. Interestingly, anisomycin immediately stimulated the export of nuclear GATA-6 into the cytoplasm, and then the cytoplasmic content of GATA-6 decreased slowly through degradation by proteasomes. Such an effect of anisomycin was inhibited by SP600125, indicating that the observed phenomenon might be linked to the JNK signaling pathway. The inhibitory effect of SP600125 could not be ascribed to the inhibition of PKA, since phosphorylation of CREB occurred in the presence of dbcAMP and SP600125. The nuclear export of GATA-6 was inhibited by leptomycin B, suggesting that CRM1-mediated export could be activated by anisomycin. Furthermore, it seems likely that the JNK activated by anisomycin may stimulate not only the nuclear export of GATA-6 through CRM1 but also the degradation of GATA-6 by cytoplasmic proteasomes. In contrast, A-kinase might activate only the latter process through JNK.

  5. Validation of search filters for identifying pediatric studies in PubMed

    NARCIS (Netherlands)

    Leclercq, Edith; Leeflang, Mariska M. G.; van Dalen, Elvira C.; Kremer, Leontien C. M.

    2013-01-01

    To identify and validate PubMed search filters for retrieving studies including children and to develop a new pediatric search filter for PubMed. We developed 2 different datasets of studies to evaluate the performance of the identified pediatric search filters, expressed in terms of sensitivity,

  6. Physiological hypercortisolemia increases proteolysis, glutamine, and alanine production

    International Nuclear Information System (INIS)

    Darmaun, D.; Matthews, D.E.; Bier, D.M.

    1988-01-01

    Physiological elevations of plasma cortisol levels, as are encountered in stress and severe trauma, were produced in six normal subjects by infusing them with hydrocortisone for 64 h. Amino acid kinetics were measured in the postabsorptive state using three 4-h infusions of L-[1- 13 C]leucine, L-phenyl[ 2 H 5 ]phenylalanine, L-[2- 15 N]glutamine, and L-[1- 13 C]alanine tracers (1) before, (2) at 12 h, and (3) at 60 h of cortisol infusion. Before and throughout the study, the subjects ate a normal diet of adequate protein and energy intake. The cortisol infusion raised plasma cortisol levels significantly from 10 ± 1 to 32 ± 4 μg/dl, leucine flux from 83 ± 3 to 97 ± 3 μmol·kg -1 ·h -1 , and phenylalanine flux from 34 ± 1 to 39 ± 1 (SE) μmol·kg -1 ·h -1 after 12 h of cortisol infusion. These increases were maintained until the cortisol infusion was terminated. These nearly identical 15% increases in two different essential amino acid appearance rates are reflective of increased whole body protein breakdown. Glutamine flux rose by 12 h of cortisol infusion and remained elevated at the same level at 64 h. The increase in flux was primarily due to a 55% increase in glutamine de novo synthesis. Alanine flux increased with acute hypercortisolemia and increased further at 60 h of cortisol infusion, a result primarily of increased alanine de novo synthesis. Insulin, alanine, and lactate plasma levels responded similarly with significant rises between the acute and chronic periods of cortisol infusion. Thus hypercortisolemia increases both protein breakdown and the turnover of important nonessential amino acids for periods of up to 64 h

  7. Cathepsin E deficiency impairs autophagic proteolysis in macrophages.

    Directory of Open Access Journals (Sweden)

    Takayuki Tsukuba

    Full Text Available Cathepsin E is an endosomal aspartic proteinase that is predominantly expressed in immune-related cells. Recently, we showed that macrophages derived from cathepsin E-deficient (CatE(-/- mice display accumulation of lysosomal membrane proteins and abnormal membrane trafficking. In this study, we demonstrated that CatE(-/- macrophages exhibit abnormalities in autophagy, a bulk degradation system for aggregated proteins and damaged organelles. CatE(-/- macrophages showed increased accumulation of autophagy marker proteins such as LC3 and p62, and polyubiquitinated proteins. Cathepsin E deficiency also altered autophagy-related signaling pathways such as those mediated by the mammalian target of rapamycin (mTOR, Akt, and extracellular signal-related kinase (ERK. Furthermore, immunofluorescence microscopy analyses showed that LC3-positive vesicles were merged with acidic compartments in wild-type macrophages, but not in CatE(-/- macrophages, indicating inhibition of fusion of autophagosome with lysosomes in CatE(-/- cells. Delayed degradation of LC3 protein was also observed under starvation-induced conditions. Since the autophagy system is involved in the degradation of damaged mitochondria, we examined the accumulation of damaged mitochondria in CatE(-/- macrophages. Several mitochondrial abnormalities such as decreased intracellular ATP levels, depolarized mitochondrial membrane potential, and decreased mitochondrial oxygen consumption were observed. Such mitochondrial dysfunction likely led to the accompanying oxidative stress. In fact, CatE(-/- macrophages showed increased reactive oxygen species (ROS production and up-regulation of oxidized peroxiredoxin-6, but decreased antioxidant glutathione. These results indicate that cathepsin E deficiency causes autophagy impairment concomitantly with increased aberrant mitochondria as well as increased oxidative stress.

  8. Decreased rate of protein synthesis, caspase-3 activity, and ubiquitin-proteasome proteolysis in soleus muscles from growing rats fed a low-protein, high-carbohydrate diet.

    Science.gov (United States)

    Batistela, Emanuele; Pereira, Mayara Peron; Siqueira, Juliany Torres; Paula-Gomes, Silvia; Zanon, Neusa Maria; Oliveira, Eduardo Brandt; Navegantes, Luiz Carlos Carvalho; Kettelhut, Isis C; Andrade, Claudia Marlise Balbinotti; Kawashita, Nair Honda; Baviera, Amanda Martins

    2014-06-01

    The aim of this study was to investigate the changes in the rates of both protein synthesis and breakdown, and the activation of intracellular effectors that control these processes in soleus muscles from growing rats fed a low-protein, high-carbohydrate (LPHC) diet for 15 days. The mass and the protein content, as well as the rate of protein synthesis, were decreased in the soleus from LPHC-fed rats. The availability of amino acids was diminished, since the levels of various essential amino acids were decreased in the plasma of LPHC-fed rats. Overall rate of proteolysis was also decreased, explained by reductions in the mRNA levels of atrogin-1 and MuRF-1, ubiquitin conjugates, proteasome activity, and in the activity of caspase-3. Soleus muscles from LPHC-fed rats showed increased insulin sensitivity, with increased levels of insulin receptor and phosphorylation levels of AKT, which probably explains the inhibition of both the caspase-3 activity and the ubiquitin-proteasome system. The fall of muscle proteolysis seems to represent an adaptive response that contributes to spare proteins in a condition of diminished availability of dietary amino acids. Furthermore, the decreased rate of protein synthesis may be the driving factor to the lower muscle mass gain in growing rats fed the LPHC diet.

  9. Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

    International Nuclear Information System (INIS)

    Yano, Claudia L; Ventrucci, Gislaine; Field, William N; Tisdale, Michael J; Gomes-Marcondes, Maria Cristina C

    2008-01-01

    Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C 2 C 12 muscle cells. WF decreased the viability of C 2 C 12 myotubes, especially at concentrations of 20–25 μg.mL -1 . There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model

  10. Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

    Directory of Open Access Journals (Sweden)

    Tisdale Michael J

    2008-01-01

    Full Text Available Abstract Background Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. Methods In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF, which has been suggested to be responsible for muscle atrophy, on cultured C2C12 muscle cells. Results WF decreased the viability of C2C12 myotubes, especially at concentrations of 20–25 μg.mL-1. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. Conclusion These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model.

  11. Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C{sub 2}C{sub 12} myotubes

    Energy Technology Data Exchange (ETDEWEB)

    Yano, Claudia L; Ventrucci, Gislaine [Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, 13083-970, Campinas, São Paulo (Brazil); Field, William N; Tisdale, Michael J [Cancer Research Laboratory, Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET (United Kingdom); Gomes-Marcondes, Maria Cristina C [Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, 13083-970, Campinas, São Paulo (Brazil)

    2008-01-28

    Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C{sub 2}C{sub 12} muscle cells. WF decreased the viability of C{sub 2}C{sub 12} myotubes, especially at concentrations of 20–25 μg.mL{sup -1}. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model.

  12. Direct imaging of APP proteolysis in living cells.

    Science.gov (United States)

    Parenti, Niccoló; Del Grosso, Ambra; Antoni, Claudia; Cecchini, Marco; Corradetti, Renato; Pavone, Francesco S; Calamai, Martino

    2017-01-01

    of APP in real time. In order to allow the discrimination between the α - and the β -secretase activity, we have created a variant of mChAPPmGFP with a mutation that inhibits the α -secretase cleavage without perturbing the β -secretase processing. Moreover, we obtained a quantitatively robust estimate of the changes in the red/green ratio for the above conditions by using a flow cytometer able to simultaneously excite and measure the red and green fluorescence. Our novel approach lay the foundation for a bioassay suitable to study the effect of drugs or particular conditions, to investigate in an unbiased way the the proteolytic processing of APP in single living cells in order, and to elucidate the causes of the variability and the factors driving the processing of APP.

  13. Direct imaging of APP proteolysis in living cells

    Directory of Open Access Journals (Sweden)

    Niccoló Parenti

    2017-04-01

    proteolytic processing of APP in real time. In order to allow the discrimination between the α- and the β-secretase activity, we have created a variant of mChAPPmGFP with a mutation that inhibits the α-secretase cleavage without perturbing the β-secretase processing. Moreover, we obtained a quantitatively robust estimate of the changes in the red/green ratio for the above conditions by using a flow cytometer able to simultaneously excite and measure the red and green fluorescence. Our novel approach lay the foundation for a bioassay suitable to study the effect of drugs or particular conditions, to investigate in an unbiased way the the proteolytic processing of APP in single living cells in order, and to elucidate the causes of the variability and the factors driving the processing of APP.

  14. Genome wide association study identifies KCNMA1 contributing to human obesity

    DEFF Research Database (Denmark)

    Jiao, Hong; Arner, Peter; Hoffstedt, Johan

    2011-01-01

    Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population....... Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity....

  15. An Examination of the Disparity between Self-Identified versus Legally Identified Rape Victimization: A Pilot Study

    Science.gov (United States)

    Marsil, Dorothy F.; McNamara, Corinne

    2016-01-01

    Objective: Researchers compared rape victimization based on self-identification to the current federal legal definition in a pilot study of college students. Methods: The sample was comprised of 1,648 (69.8% female; 30.2% male) college students who completed the Sexual Experiences Survey-Short Form Victimization (SES-SFV) online. Results: Based on…

  16. Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region

    NARCIS (Netherlands)

    Skibola, Christine F.; Berndt, Sonja I.; Vijai, Joseph; Conde, Lucia; Wang, Zhaoming; Yeager, Meredith; de Bakker, Paul I. W.; Birmann, Brenda M.; Vajdic, Claire M.; Foo, Jia-Nee; Bracci, Paige M.; Vermeulen, Roel C. H.; Slager, Susan L.; de Sanjose, Silvia; Wang, Sophia S.; Linet, Martha S.; Salles, Gilles; Lan, Qing; Severi, Gianluca; Hjalgrim, Henrik; Lightfoot, Tracy; Melbye, Mads; Gu, Jian; Ghesquieres, Herve; Link, Brian K.; Morton, Lindsay M.; Holly, Elizabeth A.; Smith, Alex; Tinker, Lesley F.; Teras, Lauren R.; Kricker, Anne; Becker, Nikolaus; Purdue, Mark P.; Spinelli, John J.; Zhang, Yawei; Giles, Graham G.; Vineis, Paolo; Monnereau, Alain; Bertrand, Kimberly A.; Albanes, Demetrius; Zeleniuch-Jacquotte, Anne; Gabbas, Attilio; Chung, Charles C.; Burdett, Laurie; Hutchinson, Amy; Lawrence, Charles; Montalvan, Rebecca; Liang, Liming; Huang, Jinyan; Ma, Baoshan; Liu, Jianjun; Adami, Hans-Olov; Glimelius, Bengt; Ye, Yuanqing; Nowakowski, Grzegorz S.; Dogan, Ahmet; Thompson, Carrie A.; Habermann, Thomas M.; Novak, Anne J.; Liebow, Mark; Witzig, Thomas E.; Weiner, George J.; Schenk, Maryjean; Hartge, Patricia; De Roos, Anneclaire J.; Cozen, Wendy; Zhi, Degui; Akers, Nicholas K.; Riby, Jacques; Smith, Martyn T.; Lacher, Mortimer; Villano, Danylo J.; Maria, Ann; Roman, Eve; Kane, Eleanor; Jackson, Rebecca D.; North, Kari E.; Diver, W. Ryan; Turner, Jenny; Armstrong, Bruce K.; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; McKay, James; Brooks-Wilson, Angela R.; Zheng, Tongzhang; Holford, Theodore R.; Chamosa, Saioa; Kaaks, Rudolph; Kelly, Rachel S.; Ohlsson, Bodil; Travis, Ruth C.; Weiderpass, Elisabete; Clave, Jacqueline; Giovannucci, Edward; Kraft, Peter; Virtamo, Jarmo; Mazza, Patrizio; Cocco, Pierluigi; Ennas, Maria Grazia; Chiu, Brian C. H.; Fraumeni, Joseph R.; Nieters, Alexandra; Offit, Kenneth; Wu, Xifeng; Cerhan, James R.; Smedby, Karin E.; Chanock, Stephen J.; Rothman, Nathaniel

    2014-01-01

    Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European

  17. Overexpression of the essential Sis1 chaperone reduces TDP-43 effects on toxicity and proteolysis

    Science.gov (United States)

    Park, Sei-Kyoung; Hong, Joo Y.; Arslan, Fatih; Tietsort, Alex; Tank, Elizabeth M. H.; Li, Xingli

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons with inclusions frequently containing the RNA/DNA binding protein TDP-43. Using a yeast model of ALS exhibiting TDP-43 dependent toxicity, we now show that TDP-43 overexpression dramatically alters cell shape and reduces ubiquitin dependent proteolysis of a reporter construct. Furthermore, we show that an excess of the Hsp40 chaperone, Sis1, reduced TDP-43’s effect on toxicity, cell shape and proteolysis. The strength of these effects was influenced by the presence of the endogenous yeast prion, [PIN+]. Although overexpression of Sis1 altered the TDP-43 aggregation pattern, we did not detect physical association of Sis1 with TDP-43, suggesting the possibility of indirect effects on TDP-43 aggregation. Furthermore, overexpression of the mammalian Sis1 homologue, DNAJB1, relieves TDP-43 mediated toxicity in primary rodent cortical neurons, suggesting that Sis1 and its homologues may have neuroprotective effects in ALS. PMID:28531192

  18. Proteolysis of proBDNF is a key regulator in the formation of memory.

    Directory of Open Access Journals (Sweden)

    Philip Barnes

    2008-09-01

    Full Text Available It is essential to understand the molecular processes underlying long-term memory to provide therapeutic targets of aberrant memory that produce pathological behaviour in humans. Under conditions of recall, fully-consolidated memories can undergo reconsolidation or extinction. These retrieval-mediated memory processes may rely on distinct molecular processes. The cellular mechanisms initiating the signature molecular events are not known. Using infusions of protein synthesis inhibitors, antisense oligonucleotide targeting brain-derived neurotrophic factor (BDNF mRNA or tPA-STOP (an inhibitor of the proteolysis of BDNF protein into the hippocampus of the awake rat, we show that acquisition and extinction of contextual fear memory depended on the increased and decreased proteolysis of proBDNF (precursor BDNF in the hippocampus, respectively. Conditions of retrieval that are known to initiate the reconsolidation of contextual fear memory, a BDNF-independent memory process, were not correlated with altered proBDNF cleavage. Thus, the processing of BDNF was associated with the acquisition of new information and the updating of information about a salient stimulus. Furthermore, the differential requirement for the processing of proBDNF by tPA in distinct memory processes suggest that the molecular events actively engaged to support the storage and/or the successful retrieval of memory depends on the integration of ongoing experience with past learning.

  19. The role of extracellular proteolysis in synaptic plasticity of the central nervous system 

    Directory of Open Access Journals (Sweden)

    Anna Konopka

    2012-11-01

    Full Text Available The extracellular matrix (ECM of the central nervous system has a specific structure and protein composition that are different from those in other organs. Today we know that the ECM not only provides physical scaffolding for the neurons and glia, but also actively modifies their functions. Over the last two decades, a growing body of research evidence has been collected, suggesting an important role of ECM proteolysis in synaptic plasticity of the brain. So far the majority of data concern two large families of proteases: the serine proteases and the matrix metalloproteinases. The members of these families are localized at the synapses, and are secreted into the extracellular space in an activity-dependent manner. The proteases remodel the local environment as well as influencing synapse structure and function. The structural modifications induced by proteases include shape and size changes, as well as synapse elimination, and synaptogenesis. The functional changes include modifications of receptor function in the postsynaptic part of the synapse, as well as the potentiation or depression of neurotransmitter secretion by the presynaptic site. The present review summarizes the current view on the role of extracellular proteolysis in the physiological synaptic plasticity underlying the phenomena of learning and memory, as well as in the pathological plasticity occurring during epileptogenesis or development of drug addiction. 

  20. Increased intracellular proteolysis reduces disease severity in an ER stress-associated dwarfism.

    Science.gov (United States)

    Mullan, Lorna A; Mularczyk, Ewa J; Kung, Louise H; Forouhan, Mitra; Wragg, Jordan Ma; Goodacre, Royston; Bateman, John F; Swanton, Eileithyia; Briggs, Michael D; Boot-Handford, Raymond P

    2017-10-02

    The short-limbed dwarfism metaphyseal chondrodysplasia type Schmid (MCDS) is linked to mutations in type X collagen, which increase ER stress by inducing misfolding of the mutant protein and subsequently disrupting hypertrophic chondrocyte differentiation. Here, we show that carbamazepine (CBZ), an autophagy-stimulating drug that is clinically approved for the treatment of seizures and bipolar disease, reduced the ER stress induced by 4 different MCDS-causing mutant forms of collagen X in human cell culture. Depending on the nature of the mutation, CBZ application stimulated proteolysis of misfolded collagen X by either autophagy or proteasomal degradation, thereby reducing intracellular accumulation of mutant collagen. In MCDS mice expressing the Col10a1.pN617K mutation, CBZ reduced the MCDS-associated expansion of the growth plate hypertrophic zone, attenuated enhanced expression of ER stress markers such as Bip and Atf4, increased bone growth, and reduced skeletal dysplasia. CBZ produced these beneficial effects by reducing the MCDS-associated abnormalities in hypertrophic chondrocyte differentiation. Stimulation of intracellular proteolysis using CBZ treatment may therefore be a clinically viable way of treating the ER stress-associated dwarfism MCDS.

  1. Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression

    International Nuclear Information System (INIS)

    Inami, Yoshihiro; Yamashina, Shunhei; Izumi, Kousuke; Ueno, Takashi; Tanida, Isei; Ikejima, Kenichi; Watanabe, Sumio

    2011-01-01

    Highlights: → Acidification of autophagosome was blunted in steatotic hepatocytes. → Hepatic steatosis did not disturb fusion of isolated autophagosome and lysosome. → Proteinase activity of cathepsin B and L in autolysosomes was inhibited by steatosis. → Hepatic expression of cathepsin B and L was suppressed by steatosis. -- Abstract: Autophagy, one of protein degradation system, contributes to maintain cellular homeostasis and cell defense. Recently, some evidences indicated that autophagy and lipid metabolism are interrelated. Here, we demonstrate that hepatic steatosis impairs autophagic proteolysis. Though accumulation of autophagosome is observed in hepatocytes from ob/ob mice, expression of p62 was augmented in liver from ob/ob mice more than control mice. Moreover, degradation of the long-lived protein leucine was significantly suppressed in hepatocytes isolated from ob/ob mice. More than 80% of autophagosomes were stained by LysoTracker Red (LTR) in hepatocytes from control mice; however, rate of LTR-stained autophagosomes in hepatocytes were suppressed in ob/ob mice. On the other hand, clearance of autolysosomes loaded with LTR was blunted in hepatocytes from ob/ob mice. Although fusion of isolated autophagosome and lysosome was not disturbed, proteinase activity of cathepsin B and L in autolysosomes and cathepsin B and L expression of liver were suppressed in ob/ob mice. These results indicate that lipid accumulation blunts autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression.

  2. Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression

    Energy Technology Data Exchange (ETDEWEB)

    Inami, Yoshihiro [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Yamashina, Shunhei, E-mail: syamashi@juntendo.ac.jp [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Izumi, Kousuke [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Ueno, Takashi [Department of Biochemistry, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Tanida, Isei [Department of Biochemistry and Cell Biology, Laboratory of Biomembranes, National Institute of Infectious Disease, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640 (Japan); Ikejima, Kenichi; Watanabe, Sumio [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2011-09-09

    Highlights: {yields} Acidification of autophagosome was blunted in steatotic hepatocytes. {yields} Hepatic steatosis did not disturb fusion of isolated autophagosome and lysosome. {yields} Proteinase activity of cathepsin B and L in autolysosomes was inhibited by steatosis. {yields} Hepatic expression of cathepsin B and L was suppressed by steatosis. -- Abstract: Autophagy, one of protein degradation system, contributes to maintain cellular homeostasis and cell defense. Recently, some evidences indicated that autophagy and lipid metabolism are interrelated. Here, we demonstrate that hepatic steatosis impairs autophagic proteolysis. Though accumulation of autophagosome is observed in hepatocytes from ob/ob mice, expression of p62 was augmented in liver from ob/ob mice more than control mice. Moreover, degradation of the long-lived protein leucine was significantly suppressed in hepatocytes isolated from ob/ob mice. More than 80% of autophagosomes were stained by LysoTracker Red (LTR) in hepatocytes from control mice; however, rate of LTR-stained autophagosomes in hepatocytes were suppressed in ob/ob mice. On the other hand, clearance of autolysosomes loaded with LTR was blunted in hepatocytes from ob/ob mice. Although fusion of isolated autophagosome and lysosome was not disturbed, proteinase activity of cathepsin B and L in autolysosomes and cathepsin B and L expression of liver were suppressed in ob/ob mice. These results indicate that lipid accumulation blunts autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression.

  3. Elucidating novel dysfunctional pathways in Alzheimer's disease by integrating loci identified in genetic and epigenetic studies

    Directory of Open Access Journals (Sweden)

    Adam R. Smith

    2016-06-01

    Full Text Available Alzheimer's disease is a complex neurodegenerative disorder. A large number of genome-wide association studies have been performed, which have been supplemented more recently by the first epigenome-wide association studies, leading to the identification of a number of novel loci altered in disease. Twin studies have shown monozygotic twin discordance for Alzheimer's disease (Gatz et al., 2006, leading to the conclusion that a combination of genetic and epigenetic mechanisms is likely to be involved in disease etiology (Lunnon & Mill, 2013. This review focuses on identifying overlapping pathways between published genome-wide association studies and epigenome-wide association studies, highlighting dysfunctional synaptic, lipid metabolism, plasma membrane/cytoskeleton, mitochondrial, and immune cell activation pathways. Identifying common pathways altered in genetic and epigenetic studies will aid our understanding of disease mechanisms and identify potential novel targets for pharmacological intervention.

  4. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

    OpenAIRE

    Berndt, S.I.; Skibola, C.F.; Joseph, V.; Camp, N.J.; Nieters, A.; Wang, Z.; Cozen, W.; Monnereau, A.; Wang, S.S.; Kelly, R.S.; Lan, Q.; Teras, L.R.; Chatterjee, N.; Chung, C.C.; Yeager, M.

    2013-01-01

    Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10...

  5. Enzymatically structured emulsions in simulated gastrointestinal environment: impact on interfacial proteolysis and diffusion in intestinal mucus.

    Science.gov (United States)

    Macierzanka, Adam; Böttger, Franziska; Rigby, Neil M; Lille, Martina; Poutanen, Kaisa; Mills, E N Clare; Mackie, Alan R

    2012-12-18

    Fundamental knowledge of physicochemical interactions in the gastrointestinal environment is required in order to support rational designing of protein-stabilized colloidal food and pharmaceutical delivery systems with controlled behavior. In this paper, we report on the colloidal behavior of emulsions stabilized with the milk protein sodium caseinate (Na-Cas), and exposed to conditions simulating the human upper gastrointestinal tract. In particular, we looked at how the kinetics of proteolysis was affected by adsorption to an oil-water interface in emulsion and whether the proteolysis and the emulsion stability could be manipulated by enzymatic structuring of the interface. After cross-linking with the enzyme transglutaminase, the protein was digested with use of an in vitro model of gastro-duodenal proteolysis in the presence or absence of physiologically relevant surfactants (phosphatidylcholine, PC; bile salts, BS). Significant differences were found between the rates of digestion of Na-Cas cross-linked in emulsion (adsorbed protein) and in solution. In emulsion, the digestion of a population of polypeptides of M(r) ca. 50-100 kDa was significantly retarded through the gastric digestion. The persistent interfacial polypeptides maintained the original emulsion droplet size and prevented the system from phase separating. Rapid pepsinolysis of adsorbed, non-cross-linked Na-Cas and its displacement by PC led to emulsion destabilization. These results suggest that structuring of emulsions by enzymatic cross-linking of the interfacial protein may affect the phase behavior of emulsion in the stomach and the gastric digestion rate in vivo. Measurements of ζ-potential revealed that BS displaced the remaining protein from the oil droplets during the simulated duodenal phase of digestion. Diffusion of the postdigestion emulsion droplets through ex vivo porcine intestinal mucus was only significant in the presence of BS due to the high negative charge these

  6. Validation of search filters for identifying pediatric studies in PubMed.

    Science.gov (United States)

    Leclercq, Edith; Leeflang, Mariska M G; van Dalen, Elvira C; Kremer, Leontien C M

    2013-03-01

    To identify and validate PubMed search filters for retrieving studies including children and to develop a new pediatric search filter for PubMed. We developed 2 different datasets of studies to evaluate the performance of the identified pediatric search filters, expressed in terms of sensitivity, precision, specificity, accuracy, and number needed to read (NNR). An optimal search filter will have a high sensitivity and high precision with a low NNR. In addition to the PubMed Limits: All Child: 0-18 years filter (in May 2012 renamed to PubMed Filter Child: 0-18 years), 6 search filters for identifying studies including children were identified: 3 developed by Kastner et al, 1 developed by BestBets, one by the Child Health Field, and 1 by the Cochrane Childhood Cancer Group. Three search filters (Cochrane Childhood Cancer Group, Child Health Field, and BestBets) had the highest sensitivity (99.3%, 99.5%, and 99.3%, respectively) but a lower precision (64.5%, 68.4%, and 66.6% respectively) compared with the other search filters. Two Kastner search filters had a high precision (93.0% and 93.7%, respectively) but a low sensitivity (58.5% and 44.8%, respectively). They failed to identify many pediatric studies in our datasets. The search terms responsible for false-positive results in the reference dataset were determined. With these data, we developed a new search filter for identifying studies with children in PubMed with an optimal sensitivity (99.5%) and precision (69.0%). Search filters to identify studies including children either have a low sensitivity or a low precision with a high NNR. A new pediatric search filter with a high sensitivity and a low NNR has been developed. Copyright © 2013 Mosby, Inc. All rights reserved.

  7. Strategies to design clinical studies to identify predictive biomarkers in cancer research.

    Science.gov (United States)

    Perez-Gracia, Jose Luis; Sanmamed, Miguel F; Bosch, Ana; Patiño-Garcia, Ana; Schalper, Kurt A; Segura, Victor; Bellmunt, Joaquim; Tabernero, Josep; Sweeney, Christopher J; Choueiri, Toni K; Martín, Miguel; Fusco, Juan Pablo; Rodriguez-Ruiz, Maria Esperanza; Calvo, Alfonso; Prior, Celia; Paz-Ares, Luis; Pio, Ruben; Gonzalez-Billalabeitia, Enrique; Gonzalez Hernandez, Alvaro; Páez, David; Piulats, Jose María; Gurpide, Alfonso; Andueza, Mapi; de Velasco, Guillermo; Pazo, Roberto; Grande, Enrique; Nicolas, Pilar; Abad-Santos, Francisco; Garcia-Donas, Jesus; Castellano, Daniel; Pajares, María J; Suarez, Cristina; Colomer, Ramon; Montuenga, Luis M; Melero, Ignacio

    2017-02-01

    The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework-the DESIGN guidelines-to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. The ATPase and protease domains of yeast mitochondrial Lon : Roles in proteolysis and respiration-dependent growth

    NARCIS (Netherlands)

    van Dijl, JM; Kutejova, E; Suda, K; Perecko, D; Schatz, G; Suzuki, CK

    1998-01-01

    The ATP-dependent Lon protease of Saccharomyces cerevisiae mitochondria is required for selective proteolysis in the matrix, maintenance of mitochondrial DNA, and respiration-dependent growth. Lon may also possess a chaperone-like function that facilitates protein degradation and protein-complex

  9. Identifying the Local Impacts of National ATE Centers on Their Host Institutions: An Exploratory Study

    Science.gov (United States)

    Henderson, Charles; Fynewever, Herb; Petcovic, Heather; Bierema, Andrea

    2012-01-01

    The purpose of this study is to identify the local impacts of national advanced technological education (ATE) centers on their host institutions. A sample of three mature, national ATE centers are chosen, with each center serving as a case for a mixed-methods, collective case study research design. Results, drawn from interviews and surveys,…

  10. A Quantitative Study Identifying Political Strategies Used by Principals of Dual Language Programs

    Science.gov (United States)

    Girard, Guadalupe

    2017-01-01

    Purpose. The purpose of this quantitative study was to identify the external and internal political strategies used by principals that allow them to successfully navigate the political environment surrounding dual language programs. Methodology. This quantitative study used descriptive research to collect, analyze, and report data that identified…

  11. Inhibition of post-traumatic septic proteolysis and ureagenesis and stimulation of hepatic acute-phase protein production by branched-chain amino acid TPN.

    Science.gov (United States)

    Chiarla, C; Siegel, J H; Kidd, S; Coleman, B; Mora, R; Tacchino, R; Placko, R; Gum, M; Wiles, C E; Belzberg, H

    1988-08-01

    Previous studies have shown that severe sepsis after major trauma results in the reprioritization of release of hepatic acute-phase proteins (APP). They suggest competition for leucine for nutritional utilization may be responsible. To test this hypothesis, a branched-chain enriched (46.6%) amino acid mixture (BCAA) was administered on a prospective randomized basis with standard TPN therapy to 16 septic post-trauma patients. After sepsis was diagnosed, a randomized therapy (control-TPN or BCAA-TPN) was given for 12 days, or until death occurred. Total calories and amino acid nitrogen (N) administered were not different in the two groups (t-test) and q 8 h (347 study periods) amino acid clearances, urinary urea nitrogen excretion, muscle proteolysis from 3-methyl-histidine (3-MH) excretion, and standard indices of sepsis severity and hepatic function were measured, as well as platelets (PLAT), leucocytes (WBC), albumin (ALB), and six acute-phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (A1TRIP), fibrinogen (FIBRIN), alpha-2-macroglobulin (AMACRO), ceruloplasmin (CERUL), and transferrin (TRANS). Using Scheffé analysis of all contrasts the data showed: BCAA resulted in a fall in 24-hour urea N excretion (24.0 to 20.0 gm/24 hr) and in proteolysis (138 to 126 gm/24 hr) (p less than 0.0001). Prestudy CRP levels were all elevated, but compared to control where APP reprioritization occurred, over the initial 10 days of therapy BCAA patients had a more rapid fall in CRP with a more rapid rise in FIBRIN, TRANS, CERUL, ALBUMIN, AMACRO, and A1TRIP (all p less than 0.0001) relative to CRP. Also, the sepsis-reduced clearances of glutamine and glutamate, alanine, and proline were increased (p less than 0.0001) during BCAA even though urea nitrogen production was reduced (p less than 0.0001). The increase in leucine clearance with BCAA-enriched TPN was positively correlated (r2 = 0.601; p less than 0.0001) with the increase in the sum of all APP and ALB and was

  12. Males Perform Better in Identifying Voices During Menstruation Than Females: A Pilot Study.

    Science.gov (United States)

    Wang, Xue; Xu, Xin; Liu, Yangyang

    2016-10-01

    The objective of the present study is to investigate gender differences in the ability to identify females' voice during menstruation. In Study 1, 55 male participants (M age = 19.6 years, SD = 1.0) were asked to listen to vocal samples from women during both ovulation and menstruation and to identify which recordings featured menstruating women. The results showed that the accuracy of men's responses (M = 56.73%, SD = 0.21) was significantly higher than 50%. In Study 2, 118 female students (M age = 19.4 years, SD = 1.6) completed the same task. The results indicated that the accuracy of women's performance was nearly 50%. These preliminary findings suggest that men are better able to identify women's voices during menstruation than women. Future work could consider several significant variables for the purpose of validating the results. © The Author(s) 2016.

  13. A model of proteolysis and amino acid biosynthesis for Lactobacillus delbrueckii subsp. bulgaricus in whey.

    Science.gov (United States)

    Liu, Enuo; Zheng, Huajun; Hao, Pei; Konno, Tomonobu; Yu, Yao; Kume, Hisae; Oda, Munehiro; Ji, Zai-Si

    2012-12-01

    Lactobacillus delbrueckii subsp. bulgaricus 2038 (L. bulgaricus 2038) is a bacterium that is used as a starter for dairy products by Meiji Co., Ltd of Japan. Culturing L. bulgaricus 2038 with whey as the sole nitrogen source results in a shorter lag phase than other milk proteins under the same conditions (carbon source, minerals, and vitamins). Microarray results of gene expression revealed characteristics of amino acid anabolism with whey as the nitrogen source and established a model of proteolysis and amino acid biosynthesis for L. bulgaricus. Whey peptides and free amino acids are readily metabolized, enabling rapid entry into the logarithmic growth phase. The oligopeptide transport system is the primary pathway for obtaining amino acids. Amino acid biosynthesis maintains the balance between amino acids required for cell growth and the amount obtained from environment. The interconversion of amino acids is also important for L. bulgaricus 2038 growth.

  14. Cross-system excision of chaperone-mediated proteolysis in chaperone-assisted recombinant protein production

    Science.gov (United States)

    Martínez-Alonso, Mónica; Villaverde, Antonio

    2010-01-01

    Main Escherichia coli cytosolic chaperones such as DnaK are key components of the control quality network designed to minimize the prevalence of polypeptides with aberrant conformations. This is achieved by both favoring refolding activities but also stimulating proteolytic degradation of folding reluctant species. This last activity is responsible for the decrease of the proteolytic stability of recombinant proteins when co-produced along with DnaK, where an increase in solubility might be associated to a decrease in protein yield. However, when DnaK and its co-chaperone DnaJ are co-produced in cultured insect cells or whole insect larvae (and expectedly, in other heterologous hosts), only positive, folding-related effects of these chaperones are observed, in absence of proteolysis-mediated reduction of recombinant protein yield. PMID:21326941

  15. Normative study of theme identifiability: Instructions with and without explanation of the false memory effect.

    Science.gov (United States)

    Beato, Maria Soledad; Cadavid, Sara

    2016-12-01

    False-memory illusions have been widely studied using the Deese/Roediger-McDermott paradigm (DRM). In this paradigm, words semantically related to a single nonpresented critical word are studied. In a later memory test, critical words are often falsely recalled and recognized. The present normative study was conducted to measure the theme identifiability of 60 associative word lists in Spanish that include six words (e.g., stove, coat, blanket, scarf, chill, and bonnet) that are simultaneously associated with three critical words (e.g., HEAT, COLD, and WINTER; Beato & Díez, Psicothema, 26, 457-463, 2011). Different levels of backward associative strength were used in the construction of the DRM lists. In addition, we used two types of instructions to obtain theme identifiability. In the without-explanation condition, traditional instructions were used, requesting participants to write the theme list. In the with-explanation condition, the false-memory effect and how the lists were built were explained, and an example of a DRM list and critical words was shown. Participants then had to discover the critical words. The results showed that all lists produced theme identifiability. Moreover, some lists had a higher theme identifiability rate (e.g., 61 % for the critical words LOVE, BOYFRIEND, COUPLE) than others (e.g., 24 % for CITY, PLACE, VILLAGE). After comparing the theme identifiabilities in the different conditions, the results indicated higher theme identifiability when the false-memory effect was explained than without such an explanation. Overall, these new normative data provide a useful tool for those experiments that, for example, aim to analyze the wide differences observed in false memory with DRM lists and the role of theme identifiability.

  16. Identifying Dieters Who Will Develop an Eating Disorder: A Prospective, Population-Based Study

    Science.gov (United States)

    Fairburn, Christopher G.; Cooper, Zafra; Doll, Helen A.; Davies, Beverley A.

    2010-01-01

    Objective The aims of the study were to identify the characteristics of the dieters most at risk of subsequently developing an eating disorder and to evaluate the feasibility of using a brief questionnaire to identify such dieters in advance. Method A general population cohort of 2,992 young women who were dieting was identified. On four occasions over the subsequent 2 years, this cohort was sent a questionnaire concerning eating habits and attitudes. Participants whose responses suggested that they had developed an eating disorder were interviewed to establish their true case status. The baseline questionnaires of those who did and did not subsequently develop an eating disorder were compared to identify features that predicted future case status. Results One hundred four of the dieters developed an eating disorder of clinical severity during the 2 years of follow-up. Their baseline questionnaire scores differed in many respects from those who had not developed an eating disorder. Items associated with developing an eating disorder were selected by using three different statistical methods. A simple case-predicting instrument based on one of five items scoring above an optimal cut point had a sensitivity of 71% and a specificity of 72% (overall efficiency of 72%). Conclusions Dieters who will develop an eating disorder within the next 2 years have distinctive features. It is feasible to identify them in advance with reasonable efficiency with a brief questionnaire. This questionnaire could be incorporated into routine health assessments, thereby identifying those at high risk. PMID:16330587

  17. Validation of de-identified record linkage to ascertain hospital admissions in a cohort study

    Directory of Open Access Journals (Sweden)

    English Dallas R

    2011-04-01

    Full Text Available Abstract Background Cohort studies can provide valuable evidence of cause and effect relationships but are subject to loss of participants over time, limiting the validity of findings. Computerised record linkage offers a passive and ongoing method of obtaining health outcomes from existing routinely collected data sources. However, the quality of record linkage is reliant upon the availability and accuracy of common identifying variables. We sought to develop and validate a method for linking a cohort study to a state-wide hospital admissions dataset with limited availability of unique identifying variables. Methods A sample of 2000 participants from a cohort study (n = 41 514 was linked to a state-wide hospitalisations dataset in Victoria, Australia using the national health insurance (Medicare number and demographic data as identifying variables. Availability of the health insurance number was limited in both datasets; therefore linkage was undertaken both with and without use of this number and agreement tested between both algorithms. Sensitivity was calculated for a sub-sample of 101 participants with a hospital admission confirmed by medical record review. Results Of the 2000 study participants, 85% were found to have a record in the hospitalisations dataset when the national health insurance number and sex were used as linkage variables and 92% when demographic details only were used. When agreement between the two methods was tested the disagreement fraction was 9%, mainly due to "false positive" links when demographic details only were used. A final algorithm that used multiple combinations of identifying variables resulted in a match proportion of 87%. Sensitivity of this final linkage was 95%. Conclusions High quality record linkage of cohort data with a hospitalisations dataset that has limited identifiers can be achieved using combinations of a national health insurance number and demographic data as identifying variables.

  18. A systematic literature search to identify performance measure outcomes used in clinical studies of racehorses.

    Science.gov (United States)

    Wylie, C E; Newton, J R

    2018-05-01

    Racing performance is often used as a measurable outcome variable in research studies investigating clinical diagnoses or interventions. However, the use of many different performance measures largely precludes conduct of meaningful comparative studies and, to date, those being used have not been collated. To systematically review the veterinary scientific literature for the use of racing performance as a measurable outcome variable in clinical studies of racehorses, collate and identify those most popular, and identify their advantages and disadvantages. Systematic literature search. The search criteria "((racing AND performance) AND (horses OR equidae))" were adapted for both MEDLINE and CAB Abstracts databases. Data were collected in standardised recording forms for binary, categorical and quantitative measures, and the use of performance indices. In total, 217 studies that described racing performance were identified, contributing 117 different performance measures. No one performance measure was used in all studies, despite 90.3% using more than one variable. Data regarding race starts and earnings were used most commonly, with 88.0% and 54.4% of studies including at least one measure of starts and earnings, respectively. Seventeen variables were used 10 times or more, with the top five comprising: 'return to racing', 'number of starts', 'days to first start', 'earnings per period of time' and 'earnings per start'. The search strategies may not have identified all relevant papers, introducing bias to the review. Performance indices have been developed to improve assessment of interventions; however, they are not widely adopted in the scientific literature. Use of the two most commonly identified measures, whether the horse returned to racing and number of starts over a defined period of time, would best facilitate future systematic reviews and meta-analyses in advance of the development of a gold-standard measure of race performance outcome. © 2017 EVJ Ltd.

  19. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

    DEFF Research Database (Denmark)

    Kote-Jarai, Zsofia; Olama, Ali Amin Al; Giles, Graham G

    2011-01-01

    Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of st...

  20. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

    DEFF Research Database (Denmark)

    Demenais, Florence; Margaritte-Jeannin, Patricia; Barnes, Kathleen C

    2018-01-01

    We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known...

  1. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

    NARCIS (Netherlands)

    Demenais, Florence; Margaritte-Jeannin, Patricia; Barnes, Kathleen C; Cookson, William O C; Altmüller, Janine; Ang, Wei; Barr, R Graham; Beaty, Terri H; Becker, Allan B; Beilby, John; Bisgaard, Hans; Bjornsdottir, Unnur Steina; Bleecker, Eugene; Bønnelykke, Klaus; Boomsma, Dorret I; Bouzigon, Emmanuelle; Brightling, Christopher E; Brossard, Myriam; Brusselle, Guy G; Burchard, Esteban; Burkart, Kristin M; Bush, Andrew; Chan-Yeung, Moira; Chung, Kian Fan; Couto Alves, Alexessander; Curtin, John A; Custovic, Adnan; Daley, Denise; de Jongste, Johan C; Del-Rio-Navarro, Blanca E; Donohue, Kathleen M; Duijts, Liesbeth; Eng, Celeste; Eriksson, Johan G; Farrall, Martin; Fedorova, Yuliya; Feenstra, Bjarke; Ferreira, Manuel A; Freidin, Maxim B; Gajdos, Zofia; Gauderman, Jim; Gehring, Ulrike; Geller, Frank; Genuneit, Jon; Gharib, Sina A; Gilliland, Frank; Granell, Raquel; Graves, Penelope E; Gudbjartsson, Daniel F; Haahtela, Tari; Heckbert, Susan R; Heederik, Dick; Heinrich, Joachim; Heliövaara, Markku; Henderson, John; Himes, Blanca E; Hirose, Hiroshi; Hirschhorn, Joel N; Hofman, Albert; Holt, Patrick; Hottenga, Jouke; Hudson, Thomas J; Hui, Jennie; Imboden, Medea; Ivanov, Vladimir; Jaddoe, Vincent W V; James, Alan; Janson, Christer; Jarvelin, Marjo-Riitta; Jarvis, Deborah; Jones, Graham; Jonsdottir, Ingileif; Jousilahti, Pekka; Kabesch, Michael; Kähönen, Mika; Kantor, David B; Karunas, Alexandra S; Khusnutdinova, Elza; Koppelman, Gerard H; Kozyrskyj, Anita L; Kreiner, Eskil; Kubo, Michiaki; Kumar, Rajesh; Kumar, Ashish; Kuokkanen, Mikko; Lahousse, Lies; Laitinen, Tarja; Laprise, Catherine; Lathrop, Mark; Lau, Susanne; Lee, Young-Ae; Lehtimäki, Terho; Letort, Sébastien; Levin, Albert M; Li, Guo; Liang, Liming; Loehr, Laura R; London, Stephanie J; Loth, Daan W; Manichaikul, Ani; Marenholz, Ingo; Martinez, Fernando J; Matheson, Melanie C; Mathias, Rasika A; Matsumoto, Kenji; Mbarek, Hamdi; McArdle, Wendy L; Melbye, Mads; Melén, Erik; Meyers, Deborah; Michel, Sven; Mohamdi, Hamida; Musk, Arthur W; Myers, Rachel A; Nieuwenhuis, Maartje A E; Noguchi, Emiko; O'Connor, George T; Ogorodova, Ludmila M; Palmer, Cameron D; Palotie, Aarno; Park, Julie E; Pennell, Craig E; Pershagen, Göran; Polonikov, Alexey; Postma, Dirkje S; Probst-Hensch, Nicole; Puzyrev, Valery P; Raby, Benjamin A; Raitakari, Olli T; Ramasamy, Adaikalavan; Rich, Stephen S; Robertson, Colin F; Romieu, Isabelle; Salam, Muhammad T; Salomaa, Veikko; Schlünssen, Vivi; Scott, Robert; Selivanova, Polina A; Sigsgaard, Torben; Simpson, Angela; Siroux, Valérie; Smith, Lewis J; Solodilova, Maria; Standl, Marie; Stefansson, Kari; Strachan, David P; Stricker, Bruno H; Takahashi, Atsushi; Thompson, Philip J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tiesler, Carla M T; Torgerson, Dara G; Tsunoda, Tatsuhiko; Uitterlinden, André G; van der Valk, Ralf J P; Vaysse, Amaury; Vedantam, Sailaja; von Berg, Andrea; von Mutius, Erika; Vonk, Judith M; Waage, Johannes; Wareham, Nick J; Weiss, Scott T; White, Wendy B; Wickman, Magnus; Widén, Elisabeth; Willemsen, Gonneke; Williams, L Keoki; Wouters, Inge M; Yang, James J; Zhao, Jing Hua; Moffatt, Miriam F; Ober, Carole; Nicolae, Dan L

    We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma

  2. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    NARCIS (Netherlands)

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of

  3. Identifying Core Mobile Learning Faculty Competencies Based Integrated Approach: A Delphi Study

    Science.gov (United States)

    Elbarbary, Rafik Said

    2015-01-01

    This study is based on the integrated approach as a concept framework to identify, categorize, and rank a key component of mobile learning core competencies for Egyptian faculty members in higher education. The field investigation framework used four rounds Delphi technique to determine the importance rate of each component of core competencies…

  4. Application of multi-locus analytical methods to identify interacting loci in case-control studies.

    NARCIS (Netherlands)

    Vermeulen, S.; Heijer, M. den; Sham, P.; Knight, J.

    2007-01-01

    To identify interacting loci in genetic epidemiological studies the application of multi-locus methods of analysis is warranted. Several more advanced classification methods have been developed in the past years, including multiple logistic regression, sum statistics, logic regression, and the

  5. Genome-wide association study identifies three novel loci for type 2 diabetes

    DEFF Research Database (Denmark)

    Hara, Kazuo; Fujita, Hayato; Johnson, Todd A

    2014-01-01

    Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly g...

  6. Exploration to Identify Professional Dispositions of School Librarians: A Delphi Study

    Science.gov (United States)

    Bush, Gail; Jones, Jami L.

    2010-01-01

    This article reports the findings of an exploratory study to identify professional dispositions of school librarians. The authors employed the Delphi method, a qualitative research method that emphasizes expert knowledge and consensus within a particular field. The Delphi panel consisted of members of the editorial boards of nationally recognized…

  7. Using Extreme Phenotype Sampling to Identify the Rare Causal Variants of Quantitative Traits in Association Studies

    OpenAIRE

    Li, Dalin; Lewinger, Juan Pablo; Gauderman, William J.; Murcray, Cassandra Elizabeth; Conti, David

    2011-01-01

    Variants identified in recent genome-wide association studies based on the common-disease common-variant hypothesis are far from fully explaining the hereditability of complex traits. Rare variants may, in part, explain some of the missing hereditability. Here, we explored the advantage of the extreme phenotype sampling in rare-variant analysis and refined this design framework for future large-scale association studies on quantitative traits. We first proposed a power calculation approach fo...

  8. IDENTIFYING MARKETING EFFECTIVENESS METRICS (Case study: East Azerbaijan`s industrial units)

    OpenAIRE

    Faridyahyaie, Reza; Faryabi, Mohammad; Bodaghi Khajeh Noubar, Hossein

    2012-01-01

    The Paper attempts to identify marketing eff ectiveness metrics in industrial units. The metrics investigated in this study are completely applicable and comprehensive, and consequently they can evaluate marketing eff ectiveness in various industries. The metrics studied include: Market Share, Profitability, Sales Growth, Customer Numbers, Customer Satisfaction and Customer Loyalty. The findings indicate that these six metrics are impressive when measuring marketing effectiveness. Data was ge...

  9. Genome-wide association study identifies 74 loci associated with educational attainment

    OpenAIRE

    Okbay, Aysu; Beauchamp, Jonathan; Fontana, M.A. (Mark Alan); Lee, James J.; Pers, Tune; Rietveld, C.A. (Cornelius A.); Turley, Patrick; Chen, G.-B. (Guo-Bo); Emilsson, Valur; Meddens, S.F.W. (S. Fleur W.); Oskarsson, S. (Sven); Pickrell, J.K. (Joseph K.); Thom, K. (Kevin); Timshel, P. (Pascal); Vlaming, Ronald

    2016-01-01

    textabstractEducational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 geno...

  10. A Study Identifying Causes of Construction Waste Production and Applying Safety Management on Construction Site

    Directory of Open Access Journals (Sweden)

    Ali Asghar Najafpoor

    2014-09-01

    Full Text Available Background and purpose: In a recent century, the amount of construction waste has increased significantly. Although the building industry has a considerable role in the development of a society, it is regarded as an environmentally destructive. Source reduction is the highest goal in the waste management hierarchy and is in priority. It also has economic benefits by reducing costs associated with transportation, disposal or recycling of wastes. The present study is aimed to identify activities generating the wastes in design, transportation and storage and procurement of building materials. Materials and Methods: This was questionnaire survey. A total of 94 professionals in the construction industry were attended in this study. To determine the validity and reliability of the instrument, content validity method and Cronbach’s alpha coefficient (0.79 were used. Data were analyzed using SPSS for Windows. Frequencies, percentage, mean and standard deviation were determined in this research. Results: The results showed that handling and storage have been chosen as the most causative factor of waste production in construction activity. Improper material storage was identified major factor in producing waste in handling and storage phase. Usage of low-quality material in design stage and material price changes in procurement were recognized as major causes of waste production in these stages. Conclusion: All studied phases in this research were identified as causative factors in producing of waste. Identifying causes of construction waste production will help us decide better how to control this sort of wastes.

  11. Genome-wide association study identifies candidate genes for starch content regulation in maize kernels

    Directory of Open Access Journals (Sweden)

    Na Liu

    2016-07-01

    Full Text Available Kernel starch content is an important trait in maize (Zea mays L. as it accounts for 65% to 75% of the dry kernel weight and positively correlates with seed yield. A number of starch synthesis-related genes have been identified in maize in recent years. However, many loci underlying variation in starch content among maize inbred lines still remain to be identified. The current study is a genome-wide association study that used a set of 263 maize inbred lines. In this panel, the average kernel starch content was 66.99%, ranging from 60.60% to 71.58% over the three study years. These inbred lines were genotyped with the SNP50 BeadChip maize array, which is comprised of 56,110 evenly spaced, random SNPs. Population structure was controlled by a mixed linear model (MLM as implemented in the software package TASSEL. After the statistical analyses, four SNPs were identified as significantly associated with starch content (P ≤ 0.0001, among which one each are located on chromosomes 1 and 5 and two are on chromosome 2. Furthermore, 77 candidate genes associated with starch synthesis were found within the 100-kb intervals containing these four QTLs, and four highly associated genes were within 20-kb intervals of the associated SNPs. Among the four genes, Glucose-1-phosphate adenylyltransferase (APS1; Gene ID GRMZM2G163437 is known as an important regulator of kernel starch content. The identified SNPs, QTLs, and candidate genes may not only be readily used for germplasm improvement by marker-assisted selection in breeding, but can also elucidate the genetic basis of starch content. Further studies on these identified candidate genes may help determine the molecular mechanisms regulating kernel starch content in maize and other important cereal crops.

  12. Feasibility of identifying families for genetic studies of birth defects using the National Health Interview Survey

    Directory of Open Access Journals (Sweden)

    Nolan Vikki G

    2004-05-01

    Full Text Available Abstract Background The purpose of this study was to determine whether the National Health Interview Survey is a useful source to identify informative families for genetic studies of birth defects. Methods The 1994/1995 National Health Interview Survey (NHIS was used to identify households where individuals with two or more birth defects reside. Four groups of households were identified: 1 single non-familial (one individual with one birth defect; 2 single familial (more than one individual with one birth defect; 3 multiple non-familial (one individual with more than one birth defect, and 4 multiple familial (more than one individual with more than one birth defect. The March 2000 U.S. Census on households was used to estimate the total number of households in which there are individuals with birth defects. Results Of a total of 28,094 households and surveyed about birth defects and impairments, 1,083 single non-familial, 55 multiple non-familial, 54 single familial, and 8 multiple familial households were identified. Based on the 2000 U.S. census, it is estimated that there are 4,472,385 households where at least one person has one birth defect in the United States and in 234,846 of them there are at least two affected individuals. Western states had the highest prevalence rates. Conclusions Population-based methods, such as the NHIS, are modestly useful to identify the number and the regions where candidate families for genetic studies of birth defects reside. Clinic based studies and birth defects surveillance systems that collect family history offer better probability of ascertainment.

  13. Molecular docking and NMR binding studies to identify novel inhibitors of human phosphomevalonate kinase

    Energy Technology Data Exchange (ETDEWEB)

    Boonsri, Pornthip [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States); Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Neumann, Terrence S.; Olson, Andrew L.; Cai, Sheng [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States); Herdendorf, Timothy J.; Miziorko, Henry M. [Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Hannongbua, Supa [Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Sem, Daniel S., E-mail: daniel.sem@cuw.edu [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Natural and synthetic inhibitors of human phosphomevalonate kinase identified. Black-Right-Pointing-Pointer Virtual screening yielded a hit rate of 15%, with inhibitor K{sub d}'s of 10-60 {mu}M. Black-Right-Pointing-Pointer NMR studies indicate significant protein conformational changes upon binding. -- Abstract: Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the mevalonate pathway, which is the sole source of isoprenoids and steroids in humans. We have identified new PMK inhibitors with virtual screening, using autodock. Promising hits were verified and their affinity measured using NMR-based {sup 1}H-{sup 15}N heteronuclear single quantum coherence (HSQC) chemical shift perturbation and fluorescence titrations. Chemical shift changes were monitored, plotted, and fitted to obtain dissociation constants (K{sub d}). Tight binding compounds with K{sub d}'s ranging from 6-60 {mu}M were identified. These compounds tended to have significant polarity and negative charge, similar to the natural substrates (M5P and ATP). HSQC cross peak changes suggest that binding induces a global conformational change, such as domain closure. Compounds identified in this study serve as chemical genetic probes of human PMK, to explore pharmacology of the mevalonate pathway, as well as starting points for further drug development.

  14. Identifying management competencies for health care executives: review of a series of Delphi studies.

    Science.gov (United States)

    Hudak, R P; Brooke, P P; Finstuen, K

    2000-01-01

    This analysis reviews a selected body of research that identifies the essential areas of management expertise required of future health care executives. To ensure consistency, six studies are analyzed, utilizing the Delphi technique, to query a broad spectrum of experts in different fields and sites of health care management. The analysis identifies a number of management competencies, i.e., managerial capabilities, which current and aspiring health care executives, in various settings and with differing educational backgrounds, should possess to enhance the probability of their success in current and future positions of responsibility. In addition, this review identifies the skills (technical expertise), knowledge (facts and principles) and abilities (physical, mental or legal power) required to support achievement of these competencies. Leadership and resource management, including cost and finance dimensions, are the highest-rated requisite management competencies. The dominant skills, knowledge and abilities (SKAs) are related to interpersonal skills. The lowest-rated SKAs are related to job-specific, technical skills. Recommendations include the review of this research by formal and continuing education programs to determine the content of their courses and areas for future research. Similarly, current health care executives should assess this research to assist in identifying competency gaps. Lastly, this analysis recommends that the Delphi technique, as a valid and replicable methodology, be applied toward the study of non-executive health care managers, e.g., students, clinicians, mid-level managers and integrated systems administrators, to determine their requisite management competencies and SKAs.

  15. Arsenite reduces insulin secretion in rat pancreatic β-cells by decreasing the calcium-dependent calpain-10 proteolysis of SNAP-25

    International Nuclear Information System (INIS)

    Diaz-Villasenor, Andrea; Burns, Anna L.; Salazar, Ana Maria; Sordo, Monserrat; Hiriart, Marcia; Cebrian, Mariano E.; Ostrosky-Wegman, Patricia

    2008-01-01

    An increase in the prevalence of type 2 diabetes has been consistently observed among residents of high arsenic exposure areas. We have previously shown that in rat pancreatic β-cells, low arsenite doses impair the secretion of insulin without altering its synthesis. To further study the mechanism by which arsenite reduces insulin secretion, we evaluated the effects of arsenite on the calcium-calpain pathway that triggers insulin exocytosis in RINm5F cells. Cell cycle and proliferation analysis were also performed to complement the characterization. Free [Ca 2+ ]i oscillations needed for glucose-stimulated insulin secretion were abated in the presence of subchronic low arsenite doses (0.5-2 μM). The global activity of calpains increased with 2 μM arsenite. However, during the secretion of insulin stimulated with glucose (15.6 mM), 1 μM arsenite decreased the activity of calpain-10, measured as SNAP-25 proteolysis. Both proteins are needed to fuse insulin granules with the membrane to produce insulin exocytosis. Arsenite also induced a slowdown in the β cell line proliferation in a dose-dependent manner, reflected by a reduction of dividing cells and in their arrest in G2/M. Data obtained showed that one of the mechanisms by which arsenite impairs insulin secretion is by decreasing the oscillations of free [Ca 2+ ]i, thus reducing calcium-dependent calpain-10 partial proteolysis of SNAP-25. The effects in cell division and proliferation observed with arsenite exposure can be an indirect consequence of the decrease in insulin secretion

  16. In-capillary enrichment, proteolysis and separation using capillary electrophoresis with discontinuous buffers: application on proteins with moderately acidic and basic isoelectric points.

    Science.gov (United States)

    Nesbitt, Chandra A; Yeung, Ken K-C

    2009-01-01

    Advances in mass spectrometry and capillary-format separation continue to improve the sensitivity of protein analysis. Of equal importance is the miniaturization of sample pretreatment such as enrichment and proteolysis. In a previous report (Nesbitt et al., Electrophoresis, 2008, 29, 466-474), nanoliter-volume protein enrichment, tryptic digestion, and partial separation was demonstrated in capillary electrophoresis followed by MALDI mass spectral analysis. A discontinuous buffer system, consisting of ammonium (pH 10) and acetate (pH 4), was used to create a pH junction inside the capillary, trapping a protein with a neutral isoelectric point, myoglobin (pI 7.2). Moreover, co-enrichment of myoglobin with trypsin led to an in-capillary digestion. In this paper, the ability of this discontinuous buffer system to perform similar in-capillary sample pretreatment on proteins with moderately acidic and basic pI was studied and reported. Lentil lectin (pI 8.6) and a multi-phosphorylated protein, beta-casein (pI 5.1), were selected as model proteins. In addition to the previously shown tryptic digestion, proteolysis with endoproteinase Asp-N was also performed. Digestion of these acidic and basic pI proteins produced a few peptides with extreme pI values lying outside the trapping range of the discontinuous buffer. An alteration in the peptide trapping procedure was made to accommodate these analytes. Offline MALDI mass spectral analysis confirmed the presence of the expected peptides. The presented miniaturized sample pretreatment methodology was proven to be applicable on proteins with a moderately wide range of pI. Flexibility in the choice of protease was also evident.

  17. Lipolysis and proteolysis profiles of fresh artisanal goat cheese made with raw milk with 3 different fat contents.

    Science.gov (United States)

    Sánchez-Macías, D; Morales-Delanuez, A; Moreno-Indias, I; Hernández-Castellano, L E; Mendoza-Grimón, V; Castro, N; Argüello, A

    2011-12-01

    The objective of this study was to describe the proteolysis and lipolysis profiles in goat cheese made in the Canary Islands (Spain) using raw milk with 3 different fat contents (0.5, 1.5, and 5%) and ripened for 1, 7, 14, and 28 d. β-Casein was the most abundant protein in all cheeses and at all ripening times. Quantitative analysis showed a general decrease in caseins as ripening progressed, and degradation rates were higher for α(S1)-casein than for β-casein and α(S2)-casein. Furthermore, the degradation rate during the experimental time decreased with lower fat contents. The α(S2)-casein and α(S1)-casein levels that remained in full-fat and reduced-fat cheeses were less than those in low-fat cheese. In contrast, β-casein also showed degradation along with ripening, but differences in degradation among the 3 cheese types were not significant at 28 d. The degradation products increased with the ripening time in all cheeses, but they were higher in full-fat cheese than in reduced-fat and low-fat cheeses. The free fatty acid concentration per 100g of cheese was higher in full-fat cheese than in reduced- and low-fat cheese; however, when the results were expressed as milligrams of free fatty acids per gram of fat in cheese, then lipolysis occurred more rapidly in low-fat cheese than in reduced- and full-fat cheeses. These results may explain the atypical texture and off-flavors found in low-fat goat cheeses, likely the main causes of non-acceptance. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  18. A cross-study gene set enrichment analysis identifies critical pathways in endometriosis

    Directory of Open Access Journals (Sweden)

    Bai Chunyan

    2009-09-01

    Full Text Available Abstract Background Endometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis. Methods We applied a standardised microarray preprocessing and gene set enrichment analysis to six independent studies, and demonstrated increased concordance between these gene datasets. Results We find 16 up-regulated and 19 down-regulated pathways common in ovarian endometriosis data sets, 22 up-regulated and one down-regulated pathway common in peritoneal endometriosis data sets. Among them, 12 up-regulated and 1 down-regulated were found consistent between ovarian and peritoneal endometriosis. The main canonical pathways identified are related to immunological and inflammatory disease. Early secretory phase has the most over-represented pathways in the three uterine cycle phases. There are no overlapping significant pathways between the dataset from human endometrial endothelial cells and the datasets from ovarian endometriosis which used whole tissues. Conclusion The study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. By standardised microarray preprocessing and GSEA, we have increased the concordance in identifying many biological mechanisms involved in endometriosis. The identified gene pathways will shed light on the understanding of endometriosis and promote the development of novel therapies.

  19. A Systematic Approach to Identify Promising New Items for Small to Medium Enterprises: A Case Study

    Directory of Open Access Journals (Sweden)

    Sukjae Jeong

    2016-11-01

    Full Text Available Despite the growing importance of identifying new business items for small and medium enterprises (SMEs, most previous studies focus on conglomerates. The paucity of empirical studies has also led to limited real-life applications. Hence, this study proposes a systematic approach to find new business items (NBIs that help the prospective SMEs develop, evaluate, and select viable business items to survive the competitive environment. The proposed approach comprises two stages: (1 the classification of diversification of SMEs; and (2 the searching and screening of business items. In the first stage, SMEs are allocated to five groups, based on their internal technological competency and external market conditions. In the second stage, based on the types of SMEs identified in the first stage, a set of alternative business items is derived by combining the results of portfolio analysis and benchmarking analysis. After deriving new business items, a market and technology-driven matrix analysis is utilized to screen suitable business items, and the Bruce Merrifield-Ohe (BMO method is used to categorize and identify prospective items based on market attractiveness and internal capability. To illustrate the applicability of the proposed approach, a case study is presented.

  20. Genome-wide association study identifies a novel canine glaucoma locus.

    Directory of Open Access Journals (Sweden)

    Saija J Ahonen

    Full Text Available Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its hereditary forms are classified into primary closed-angle (PCAG, primary open-angle (POAG and primary congenital glaucoma (PCG. Although many loci have been mapped in human, only a few genes have been identified that are associated with the development of glaucoma and the genetic basis of the disease remains poorly understood. Glaucoma has also been described in many dog breeds, including Dandie Dinmont Terriers (DDT in which it is a late-onset (>7 years disease. We designed clinical and genetic studies to better define the clinical features of glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was based on ophthalmic examinations of the affected dogs and 18 additionally investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome wide association study was performed in a cohort of 23 affected and 23 controls, followed by a fine mapping, a replication study and candidate gene sequencing. The clinical study suggested that ocular abnormalities including abnormal iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%, respectively in the breed and the disease resembles human PCAG. The genetic study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb best associated region (p = 1.63 × 10(-10, OR = 32 for homozygosity. Mutation screening in five candidate genes did not reveal any causative variants. This study indicates that although ocular abnormalities are common in DDTs, the genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus shares synteny to a region in human chromosome 14q, which harbors several loci associated with POAG and PCG. Our study reveals a new locus for canine glaucoma and ongoing molecular studies will likely help to understand the genetic etiology of the disease.

  1. Identifying amyloid pathology?related cerebrospinal fluid biomarkers for Alzheimer's disease in a multicohort study

    OpenAIRE

    Leung, Yuk Yee; Toledo, Jon B.; Nefedov, Alexey; Polikar, Robi; Raghavan, Nandini; Xie, Sharon X.; Farnum, Michael; Schultz, Tim; Baek, Young; Van Deerlin, Vivianna M.; Hu, William T.; Holtzman, David M.; Fagan, Anne M.; Perrin, Richard J.; Grossman, Murray

    2015-01-01

    Introduction The dynamic range of cerebrospinal fluid (CSF) amyloid ? (A?1?42) measurement does not parallel to cognitive changes in Alzheimer's disease (AD) and cognitively normal (CN) subjects across different studies. Therefore, identifying novel proteins to characterize symptomatic AD samples is important. Methods Proteins were profiled using a multianalyte platform by Rules Based Medicine (MAP-RBM). Due to underlying heterogeneity and unbalanced sample size, we combined subjects (344 AD ...

  2. STUDY OF IDENTIFYING AND PRIORITIZING THE AFFECTING FACTORS ON BANK BRAND CUSTOMER LOYALTY

    OpenAIRE

    Zahra Aliyari; Yosef Beygzadeh

    2017-01-01

    Today, customer loyalty is the key to business success. By increased customers’ loyalty, market share and profitability level of enterprises will rise. Market perception along with planning and adopting appropriate strategies for making customers loyal and enhancing their rate of loyalty leads to long-term benefits for the enterprises. Given the importance of the issue, the goal of this study was to identify and prioritize the factors affecting loyalty to a banking brand from perspective of K...

  3. Automated Source Code Analysis to Identify and Remove Software Security Vulnerabilities: Case Studies on Java Programs

    OpenAIRE

    Natarajan Meghanathan

    2013-01-01

    The high-level contribution of this paper is to illustrate the development of generic solution strategies to remove software security vulnerabilities that could be identified using automated tools for source code analysis on software programs (developed in Java). We use the Source Code Analyzer and Audit Workbench automated tools, developed by HP Fortify Inc., for our testing purposes. We present case studies involving a file writer program embedded with features for password validation, and ...

  4. Pilot study on the use of data mining to identify cochlear implant candidates.

    Science.gov (United States)

    Grisel, Jedidiah J; Schafer, Erin; Lam, Anne; Griffin, Terry

    2018-05-01

    The goal of this pilot study was to determine the clinical utility of data-mining software that screens for cochlear implant (CI) candidacy. The Auditory Implant Initiative developed a software module that screens for CI candidates via integration with a software system (Noah 4) that serves as a depository for hearing test data. To identify candidates, patient audiograms from one practice were exported into the screening module. Candidates were tracked to determine if any eventually underwent implantation. After loading 4836 audiograms from the Noah 4 system, the screening module identified 558 potential CI candidates. After reviewing the data for the potential candidates, 117 were targeted and invited to an educational event. Following the event, a total of six candidates were evaluated, and two were implanted. This objective approach to identifying candidates has the potential to address the gross underutilization of CIs by removing any bias or lack of knowledge regarding the management of severe to profound sensorineural hearing loss with CIs. The screening module was an effective tool for identifying potential CI candidates at one ENT practice. On a larger scale, the screening module has the potential to impact thousands of CI candidates worldwide.

  5. Thinking ahead of the surgeon. An interview study to identify scrub nurses' non-technical skills.

    Science.gov (United States)

    Mitchell, Lucy; Flin, Rhona; Yule, Steven; Mitchell, Janet; Coutts, Kathy; Youngson, George

    2011-07-01

    Efforts to reduce adverse event rates in healthcare have revealed the importance of identifying the essential non-technical (cognitive and social) skills for safe and effective performance. Previous research on non-technical skills for operating theatre staff has concentrated on doctors rather than nursing professionals. The aim of the study was to identify the critical non-technical skills that are essential for safe and effective performance as an operating theatre scrub nurse. Experienced scrub nurses (n = 25) and consultant surgeons (n = 9) from four Scottish hospitals were interviewed using a semi-structured format. The protocols were designed to identify the main social and cognitive skills required by scrub nurses. Interviews were digitally recorded, transcribed verbatim and independently coded to extract behaviours in order to produce a list of the main non-technical skills for safe and effective scrub nurse performance. The non-technical skills of situation awareness, communication, teamwork, task management and coping with stress were identified as key to successful scrub nurse task performance. Component sets of behaviours for each of these categories were also noted. The interviews with subject matter experts from scrub nursing and surgery produced preliminary evidence that situation awareness, communication, teamwork and coping with stress are the principal non-technical skills required for effective performance as a scrub nurse. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Influenza-associated Encephalitis/Encephalopathy Identified by the Australian Childhood Encephalitis Study 2013-2015.

    Science.gov (United States)

    Britton, Philip N; Dale, Russell C; Blyth, Christopher C; Macartney, Kristine; Crawford, Nigel W; Marshall, Helen; Clark, Julia E; Elliott, Elizabeth J; Webster, Richard I; Cheng, Allen C; Booy, Robert; Jones, Cheryl A

    2017-11-01

    Influenza-associated encephalitis/encephalopathy (IAE) is an important cause of acute encephalitis syndrome in children. IAE includes a series of clinicoradiologic syndromes or acute encephalopathy syndromes that have been infrequently reported outside East Asia. We aimed to describe cases of IAE identified by the Australian Childhood Encephalitis study. Children ≤ 14 years of age with suspected encephalitis were prospectively identified in 5 hospitals in Australia. Demographic, clinical, laboratory, imaging, and outcome at discharge data were reviewed by an expert panel and cases were categorized by using predetermined case definitions. We extracted cases associated with laboratory identification of influenza virus for this analysis; among these cases, specific IAE syndromes were identified where clinical and radiologic features were consistent with descriptions in the published literature. We identified 13 cases of IAE during 3 southern hemisphere influenza seasons at 5 tertiary children's hospitals in Australia; 8 children with specific acute encephalopathy syndromes including: acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late diffusion restriction, mild encephalopathy with reversible splenial lesion, and hemiconvulsion-hemiplegia syndrome. Use of influenza-specific antiviral therapy and prior influenza vaccination were infrequent. In contrast, death or significant neurologic morbidity occurred in 7 of the 13 children (54%). The conditions comprising IAE are heterogeneous with varied clinical features, magnetic resonance imaging changes, and outcomes. Overall, outcome of IAE is poor emphasizing the need for optimized prevention, early recognition, and empiric management.

  7. Systematic reviews identify important methodological flaws in stroke rehabilitation therapy primary studies: review of reviews.

    Science.gov (United States)

    Santaguida, Pasqualina; Oremus, Mark; Walker, Kathryn; Wishart, Laurie R; Siegel, Karen Lohmann; Raina, Parminder

    2012-04-01

    A "review of reviews" was undertaken to assess methodological issues in studies evaluating nondrug rehabilitation interventions in stroke patients. MEDLINE, CINAHL, PsycINFO, and the Cochrane Database of Systematic Reviews were searched from January 2000 to January 2008 within the stroke rehabilitation setting. Electronic searches were supplemented by reviews of reference lists and citations identified by experts. Eligible studies were systematic reviews; excluded citations were narrative reviews or reviews of reviews. Review characteristics and criteria for assessing methodological quality of primary studies within them were extracted. The search yielded 949 English-language citations. We included a final set of 38 systematic reviews. Cochrane reviews, which have a standardized methodology, were generally of higher methodological quality than non-Cochrane reviews. Most systematic reviews used standardized quality assessment criteria for primary studies, but not all were comprehensive. Reviews showed that primary studies had problems with randomization, allocation concealment, and blinding. Baseline comparability, adverse events, and co-intervention or contamination were not consistently assessed. Blinding of patients and providers was often not feasible and was not evaluated as a source of bias. The eligible systematic reviews identified important methodological flaws in the evaluated primary studies, suggesting the need for improvement of research methods and reporting. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Three principles to define the success of a diagnostic study could be identified

    DEFF Research Database (Denmark)

    Vach, Werner; Gerke, Oke; Høilund-Carlsen, Poul Flemming

    2012-01-01

    of a diagnostic study on a single binary test and investigation of common statistical approaches in relation to these criteria. RESULTS: Three criteria for defining the overall success of a diagnostic study could be identified: a strong criterion, a liberal criterion, and a weak criterion. The strong criterion...... can be implemented by comparing the lower bounds of the confidence intervals for sensitivity and specificity with prespecified target values, as is typically done in many diagnostic studies. The liberal criterion allows a clinically meaningful compensation between sensitivity and specificity and can...... be implemented in different ways. If the liberal criterion is applied instead of the strong criterion, this can lead to a substantial reduction in the sample size required for a diagnostic study. The weak criterion is not very adequate for defining the success of a diagnostic study. CONCLUSION: When planning...

  9. Effectively identifying regulatory hotspots while capturing expression heterogeneity in gene expression studies

    Science.gov (United States)

    2014-01-01

    Expression quantitative trait loci (eQTL) mapping is a tool that can systematically identify genetic variation affecting gene expression. eQTL mapping studies have shown that certain genomic locations, referred to as regulatory hotspots, may affect the expression levels of many genes. Recently, studies have shown that various confounding factors may induce spurious regulatory hotspots. Here, we introduce a novel statistical method that effectively eliminates spurious hotspots while retaining genuine hotspots. Applied to simulated and real datasets, we validate that our method achieves greater sensitivity while retaining low false discovery rates compared to previous methods. PMID:24708878

  10. Genome-wide Association Study Identifies New Loci for Resistance to Leptosphaeria maculans in Canola

    Directory of Open Access Journals (Sweden)

    Harsh Raman

    2016-10-01

    Full Text Available Blackleg, caused by Leptosphaeria maculans, is a significant disease which affects the sustainable production of canola. This study reports a genome-wide association study based on 18,804 polymorphic SNPs to identify loci associated with qualitative and quantitative resistance to L. maculans. Genomic regions delimited with 503 significant SNP markers, that are associated with resistance evaluated using 12 single spore isolates and pathotypes from four canola stubble were identified. Several significant associations were detected at known disease resistance loci including in the vicinity of recently cloned Rlm2/LepR3 genes, and at new loci on chromosomes A01/C01, A02/C02, A03/C03, A05/C05, A06, A08, and A09. In addition, we validated statistically significant associations on A01, A07 and A10 in four genetic mapping populations, demonstrating that GWAS marker loci are indeed associated with resistance to L. maculans. One of the novel loci identified for the first time, Rlm12, conveys adult plant resistance and mapped within 13.2 kb from Arabidopsis R gene of TIR-NBS class. We showed that resistance loci are located in the vicinity of R genes of A. thaliana and B. napus on the sequenced genome of B. napus cv. Darmor-bzh. Significantly associated SNP markers provide a valuable tool to enrich germplasm for favorable alleles in order to improve the level of resistance to L. maculans in canola.

  11. Biochemometrics to Identify Synergists and Additives from Botanical Medicines: A Case Study with Hydrastis canadensis (Goldenseal).

    Science.gov (United States)

    Britton, Emily R; Kellogg, Joshua J; Kvalheim, Olav M; Cech, Nadja B

    2018-03-23

    A critical challenge in the study of botanical natural products is the difficulty of identifying multiple compounds that may contribute additively, synergistically, or antagonistically to biological activity. Herein, it is demonstrated how combining untargeted metabolomics with synergy-directed fractionation can be effective toward accomplishing this goal. To demonstrate this approach, an extract of the botanical goldenseal ( Hydrastis canadensis) was fractionated and tested for its ability to enhance the antimicrobial activity of the alkaloid berberine (4) against the pathogenic bacterium Staphylococcus aureus. Bioassay data were combined with untargeted mass spectrometry-based metabolomics data sets (biochemometrics) to produce selectivity ratio (SR) plots, which visually show which extract components are most strongly associated with the biological effect. Using this approach, the new flavonoid 3,3'-dihydroxy-5,7,4'-trimethoxy-6,8- C-dimethylflavone (29) was identified, as were several flavonoids known to be active. When tested in combination with 4, 29 lowered the IC 50 of 4 from 132.2 ± 1.1 μM to 91.5 ± 1.1 μM. In isolation, 29 did not demonstrate antimicrobial activity. The current study highlights the importance of fractionation when utilizing metabolomics for identifying bioactive components from botanical extracts and demonstrates the power of SR plots to help merge and interpret complex biological and chemical data sets.

  12. Effect of pulp preconditioning on acidification, proteolysis, sugars and free fatty acids concentration during fermentation of cocoa (Theobroma cacao) beans.

    Science.gov (United States)

    Afoakwa, Emmanuel Ohene; Quao, Jennifer; Budu, Agnes Simpson; Takrama, Jemmy; Saalia, Firibu Kwesi

    2011-11-01

    Changes in acidification, proteolysis, sugars and free fatty acids (FFAs) concentrations of Ghanaian cocoa beans as affected by pulp preconditioning (pod storage or PS) and fermentation were investigated. Non-volatile acidity, pH, proteolysis, sugars (total, reducing and non-reducing) and FFAs concentrations were analysed using standard methods. Increasing PS consistently decreased the non-volatile acidity with concomitant increase in pH during fermentation of the beans. Fermentation decreased the pH of the unstored beans from 6.7 to 4.9 within the first 4 days and then increased slightly again to 5.3 by the sixth day. Protein, total sugars and non-reducing sugars decreased significantly (p cocoa beans was largely affected by fermentation than by PS.

  13. Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1

    DEFF Research Database (Denmark)

    Petersen, B O; Wagener, C; Marinoni, F

    2000-01-01

    is targeted for ubiquitin-mediated proteolysis by the anaphase promoting complex (APC)/cyclosome in G(1). A combination of point mutations in the destruction box and KEN-box motifs in CDC6 stabilizes the protein in G(1) and in quiescent cells. Furthermore, APC, in association with CDH1, ubiquitinates CDC6...... in vitro, and both APC and CDH1 are required and limiting for CDC6 proteolysis in vivo. Although a stable mutant of CDC6 is biologically active, overexpression of this mutant or wild-type CDC6 is not sufficient to induce multiple rounds of DNA replication in the same cell cycle. The APC-CDH1-dependent...

  14. Identifying the barriers to conducting outcomes research in integrative health care clinic settings - a qualitative study

    Directory of Open Access Journals (Sweden)

    Findlay-Reece Barbara

    2010-01-01

    Full Text Available Abstract Background Integrative health care (IHC is an interdisciplinary blending of conventional medicine and complementary and alternative medicine (CAM with the purpose of enhancing patients' health. In 2006, we designed a study to assess outcomes that are relevant to people using such care. However, we faced major challenges in conducting this study and hypothesized that this might be due to the lack of a research climate in these clinics. To investigate these challenges, we initiated a further study in 2008, to explore the reasons why IHC clinics are not conducting outcomes research and to identify strategies for conducting successful in-house outcomes research programs. The results of the latter study are reported here. Methods A total of 25 qualitative interviews were conducted with key participants from 19 IHC clinics across Canada. Basic content analysis was used to identify key themes from the transcribed interviews. Results Barriers identified by participants fell into four categories: organizational culture, organizational resources, organizational environment and logistical challenges. Cultural challenges relate to the philosophy of IHC, organizational leadership and practitioner attitudes and beliefs. Participants also identified significant issues relating to their organization's lack of resources such as funding, compensation, infrastructure and partnerships/linkages. Environmental challenges such as the nature of a clinic's patient population and logistical issues such as the actual implementation of a research program and the applicability of research data also posed challenges to the conduct of research. Embedded research leadership, integration of personal and professional values about research, alignment of research activities and clinical workflow processes are some of the factors identified by participants that support IHC clinics' ability to conduct outcomes research. Conclusions Assessing and enhancing the broader

  15. PAPA: a flexible tool for identifying pleiotropic pathways using genome-wide association study summaries.

    Science.gov (United States)

    Wen, Yan; Wang, Wenyu; Guo, Xiong; Zhang, Feng

    2016-03-15

    : Pleiotropy is common in the genetic architectures of complex diseases. To the best of our knowledge, no analysis tool has been developed for identifying pleiotropic pathways using multiple genome-wide association study (GWAS) summaries by now. Here, we present PAPA, a flexible tool for pleiotropic pathway analysis utilizing GWAS summary results. The performance of PAPA was validated using publicly available GWAS summaries of body mass index and waist-hip ratio of the GIANT datasets. PAPA identified a set of pleiotropic pathways, which have been demonstrated to be involved in the development of obesity. PAPA program, document and illustrative example are available at http://sourceforge.net/projects/papav1/files/ : fzhxjtu@mail.xjtu.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Identifying the essential components of cultural competence in a Chinese nursing context: A qualitative study.

    Science.gov (United States)

    Cai, Duanying; Kunaviktikul, Wipada; Klunklin, Areewan; Sripusanapan, Acharaporn; Avant, Patricia Kay

    2017-06-01

    This qualitative study using semi-structured interviews was conducted to identify the essential components of cultural competence from the perspective of Chinese nurses. A purposive sample of 20 nurse experts, including senior clinical nurses, nurse administrators, and educators in transcultural nursing, was recruited. Using thematic analysis, four themes: awareness, attitudes, knowledge, and skills, with two subthemes for each, were identified. Notably, culture in China was understood in a broad way. The participants' responses focused upon demographic attributes, individuality, and efforts to facilitate quality care rather than on the cultural differences of ethnicity and race and developing the capacity to change discrimination or health disparities. A greater understanding of cultural competence in the Chinese nursing context, in which a dominant cultural group exists, is essential to facilitate the provision of culturally competent care to diverse populations. © 2016 John Wiley & Sons Australia, Ltd.

  17. Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy

    DEFF Research Database (Denmark)

    Feenstra, Bjarke; Bager, Peter; Liu, Xueping

    2017-01-01

    BACKGROUND: Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. OBJECTIVE: To identify common genetic variants associate...... the molecular mechanisms underlying the genetic association involve general lymphoid hyper-reaction throughout the mucosa-associated lymphoid tissue system.......BACKGROUND: Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. OBJECTIVE: To identify common genetic variants associated...... with tonsillectomy. METHODS: We used tonsillectomy information from Danish health registers and carried out a genome-wide association study comprising 1464 patients and 12 019 controls of Northwestern European ancestry, with replication in an independent sample set of 1575 patients and 1367 controls. RESULTS...

  18. Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations.

    Science.gov (United States)

    Sanna-Cherchi, Simone; Khan, Kamal; Westland, Rik; Krithivasan, Priya; Fievet, Lorraine; Rasouly, Hila Milo; Ionita-Laza, Iuliana; Capone, Valentina P; Fasel, David A; Kiryluk, Krzysztof; Kamalakaran, Sitharthan; Bodria, Monica; Otto, Edgar A; Sampson, Matthew G; Gillies, Christopher E; Vega-Warner, Virginia; Vukojevic, Katarina; Pediaditakis, Igor; Makar, Gabriel S; Mitrotti, Adele; Verbitsky, Miguel; Martino, Jeremiah; Liu, Qingxue; Na, Young-Ji; Goj, Vinicio; Ardissino, Gianluigi; Gigante, Maddalena; Gesualdo, Loreto; Janezcko, Magdalena; Zaniew, Marcin; Mendelsohn, Cathy Lee; Shril, Shirlee; Hildebrandt, Friedhelm; van Wijk, Joanna A E; Arapovic, Adela; Saraga, Marijan; Allegri, Landino; Izzi, Claudia; Scolari, Francesco; Tasic, Velibor; Ghiggeri, Gian Marco; Latos-Bielenska, Anna; Materna-Kiryluk, Anna; Mane, Shrikant; Goldstein, David B; Lifton, Richard P; Katsanis, Nicholas; Davis, Erica E; Gharavi, Ali G

    2017-11-02

    Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and a congenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating phenotypes reported with Slit3 inactivation in the mouse. To identify genes associated with RHD, we performed an exome-wide association study with 195 unresolved case subjects and 6,905 control subjects. The top signal resided in GREB1L, a gene implicated previously in Hoxb1 and Shha signaling in zebrafish. The significance of the association, which was p = 2.0 × 10 -5 for novel LOF, increased to p = 4.1 × 10 -6 for LOF and deleterious missense variants combined, and augmented further after accounting for segregation and de novo inheritance of rare variants (joint p = 2.3 × 10 -7 ). Finally, CRISPR/Cas9 disruption or knockdown of greb1l in zebrafish caused specific pronephric defects, which were rescued by wild-type human GREB1L mRNA, but not mRNA containing alleles identified in case subjects. Together, our study provides insight into the genetic landscape of kidney malformations in humans, presents multiple candidates, and identifies SLIT3 and GREB1L as genes implicated in the pathogenesis of RHD. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. Quasi-experimental study designs series-paper 8: identifying quasi-experimental studies to inform systematic reviews.

    Science.gov (United States)

    Glanville, Julie; Eyers, John; Jones, Andrew M; Shemilt, Ian; Wang, Grace; Johansen, Marit; Fiander, Michelle; Rothstein, Hannah

    2017-09-01

    This article reviews the available evidence and guidance on methods to identify reports of quasi-experimental (QE) studies to inform systematic reviews of health care, public health, international development, education, crime and justice, and social welfare. Research, guidance, and examples of search strategies were identified by searching a range of databases, key guidance documents, selected reviews, conference proceedings, and personal communication. Current practice and research evidence were summarized. Four thousand nine hundred twenty-four records were retrieved by database searches, and additional documents were obtained by other searches. QE studies are challenging to identify efficiently because they have no standardized nomenclature and may be indexed in various ways. Reliable search filters are not available. There is a lack of specific resources devoted to collecting QE studies and little evidence on where best to search. Searches to identify QE studies should search a range of resources and, until indexing improves, use strategies that focus on the topic rather than the study design. Better definitions, better indexing in databases, prospective registers, and reporting guidance are required to improve the retrieval of QE studies and promote systematic reviews of what works based on the evidence from such studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. A novel data mining method to identify assay-specific signatures in functional genomic studies

    Directory of Open Access Journals (Sweden)

    Guidarelli Jack W

    2006-08-01

    Full Text Available Abstract Background: The highly dimensional data produced by functional genomic (FG studies makes it difficult to visualize relationships between gene products and experimental conditions (i.e., assays. Although dimensionality reduction methods such as principal component analysis (PCA have been very useful, their application to identify assay-specific signatures has been limited by the lack of appropriate methodologies. This article proposes a new and powerful PCA-based method for the identification of assay-specific gene signatures in FG studies. Results: The proposed method (PM is unique for several reasons. First, it is the only one, to our knowledge, that uses gene contribution, a product of the loading and expression level, to obtain assay signatures. The PM develops and exploits two types of assay-specific contribution plots, which are new to the application of PCA in the FG area. The first type plots the assay-specific gene contribution against the given order of the genes and reveals variations in distribution between assay-specific gene signatures as well as outliers within assay groups indicating the degree of importance of the most dominant genes. The second type plots the contribution of each gene in ascending or descending order against a constantly increasing index. This type of plots reveals assay-specific gene signatures defined by the inflection points in the curve. In addition, sharp regions within the signature define the genes that contribute the most to the signature. We proposed and used the curvature as an appropriate metric to characterize these sharp regions, thus identifying the subset of genes contributing the most to the signature. Finally, the PM uses the full dataset to determine the final gene signature, thus eliminating the chance of gene exclusion by poor screening in earlier steps. The strengths of the PM are demonstrated using a simulation study, and two studies of real DNA microarray data – a study of

  1. Enriched pathways for major depressive disorder identified from a genome-wide association study.

    Science.gov (United States)

    Kao, Chung-Feng; Jia, Peilin; Zhao, Zhongming; Kuo, Po-Hsiu

    2012-11-01

    Major depressive disorder (MDD) has caused a substantial burden of disease worldwide with moderate heritability. Despite efforts through conducting numerous association studies and now, genome-wide association (GWA) studies, the success of identifying susceptibility loci for MDD has been limited, which is partially attributed to the complex nature of depression pathogenesis. A pathway-based analytic strategy to investigate the joint effects of various genes within specific biological pathways has emerged as a powerful tool for complex traits. The present study aimed to identify enriched pathways for depression using a GWA dataset for MDD. For each gene, we estimated its gene-wise p value using combined and minimum p value, separately. Canonical pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta were used. We employed four pathway-based analytic approaches (gene set enrichment analysis, hypergeometric test, sum-square statistic, sum-statistic). We adjusted for multiple testing using Benjamini & Hochberg's method to report significant pathways. We found 17 significantly enriched pathways for depression, which presented low-to-intermediate crosstalk. The top four pathways were long-term depression (p⩽1×10-5), calcium signalling (p⩽6×10-5), arrhythmogenic right ventricular cardiomyopathy (p⩽1.6×10-4) and cell adhesion molecules (p⩽2.2×10-4). In conclusion, our comprehensive pathway analyses identified promising pathways for depression that are related to neurotransmitter and neuronal systems, immune system and inflammatory response, which may be involved in the pathophysiological mechanisms underlying depression. We demonstrated that pathway enrichment analysis is promising to facilitate our understanding of complex traits through a deeper interpretation of GWA data. Application of this comprehensive analytic strategy in upcoming GWA data for depression could validate the findings reported in this study.

  2. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations.

    Science.gov (United States)

    Lee, Ju-Hyun; Yu, W Haung; Kumar, Asok; Lee, Sooyeon; Mohan, Panaiyur S; Peterhoff, Corrinne M; Wolfe, Devin M; Martinez-Vicente, Marta; Massey, Ashish C; Sovak, Guy; Uchiyama, Yasuo; Westaway, David; Cuervo, Ana Maria; Nixon, Ralph A

    2010-06-25

    Macroautophagy is a lysosomal degradative pathway essential for neuron survival. Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1). In PS1 null blastocysts, neurons from mice hypomorphic for PS1 or conditionally depleted of PS1, substrate proteolysis and autophagosome clearance during macroautophagy are prevented as a result of a selective impairment of autolysosome acidification and cathepsin activation. These deficits are caused by failed PS1-dependent targeting of the v-ATPase V0a1 subunit to lysosomes. N-glycosylation of the V0a1 subunit, essential for its efficient ER-to-lysosome delivery, requires the selective binding of PS1 holoprotein to the unglycosylated subunit and the Sec61alpha/oligosaccharyltransferase complex. PS1 mutations causing early-onset AD produce a similar lysosomal/autophagy phenotype in fibroblasts from AD patients. PS1 is therefore essential for v-ATPase targeting to lysosomes, lysosome acidification, and proteolysis during autophagy. Defective lysosomal proteolysis represents a basis for pathogenic protein accumulations and neuronal cell death in AD and suggests previously unidentified therapeutic targets.

  3. Identifying 'unhealthy' food advertising on television: a case study applying the UK Nutrient Profile model.

    Science.gov (United States)

    Jenkin, Gabrielle; Wilson, Nick; Hermanson, Nicole

    2009-05-01

    To evaluate the feasibility of the UK Nutrient Profile (NP) model for identifying 'unhealthy' food advertisements using a case study of New Zealand television advertisements. Four weeks of weekday television from 15.30 hours to 18.30 hours was videotaped from a state-owned (free-to-air) television channel popular with children. Food advertisements were identified and their nutritional information collected in accordance with the requirements of the NP model. Nutrient information was obtained from a variety of sources including food labels, company websites and a national nutritional database. From the 60 h sample of weekday afternoon television, there were 1893 advertisements, of which 483 were for food products or retailers. After applying the NP model, 66 % of these were classified as advertising high-fat, high-salt and high-sugar (HFSS) foods; 28 % were classified as advertising non-HFSS foods; and the remaining 2 % were unclassifiable. More than half (53 %) of the HFSS food advertisements were for 'mixed meal' items promoted by major fast-food franchises. The advertising of non-HFSS food was sparse, covering a narrow range of food groups, with no advertisements for fresh fruit or vegetables. Despite the NP model having some design limitations in classifying real-world televised food advertisements, it was easily applied to this sample and could clearly identify HFSS products. Policy makers who do not wish to completely restrict food advertising to children outright should consider using this NP model for regulating food advertising.

  4. Identifying research priorities for patient safety in mental health: an international expert Delphi study

    Science.gov (United States)

    Murray, Kevin; Thibaut, Bethan; Ramtale, Sonny Christian; Adam, Sheila; Darzi, Ara; Archer, Stephanie

    2018-01-01

    Objective Physical healthcare has dominated the patient safety field; research in mental healthcare is not as extensive but findings from physical healthcare cannot be applied to mental healthcare because it delivers specialised care that faces unique challenges. Therefore, a clearer focus and recognition of patient safety in mental health as a distinct research area is still needed. The study aim is to identify future research priorities in the field of patient safety in mental health. Design Semistructured interviews were conducted with the experts to ascertain their views on research priorities in patient safety in mental health. A three-round online Delphi study was used to ascertain consensus on 117 research priority statements. Setting and participants Academic and service user experts from the USA, UK, Switzerland, Netherlands, Ireland, Denmark, Finland, Germany, Sweden, Australia, New Zealand and Singapore were included. Main outcome measures Agreement in research priorities on a five-point scale. Results Seventy-nine statements achieved consensus (>70%). Three out of the top six research priorities were patient driven; experts agreed that understanding the patient perspective on safety planning, on self-harm and on medication was important. Conclusions This is the first international Delphi study to identify research priorities in safety in the mental field as determined by expert academic and service user perspectives. A reasonable consensus was obtained from international perspectives on future research priorities in patient safety in mental health; however, the patient perspective on their mental healthcare is a priority. The research agenda for patient safety in mental health identified here should be informed by patient safety science more broadly and used to further establish this area as a priority in its own right. The safety of mental health patients must have parity with that of physical health patients to achieve this. PMID:29502096

  5. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

    Directory of Open Access Journals (Sweden)

    Jesús Lascorz

    2011-01-01

    Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.

  6. Proteolysis of milk fat globule membrane proteins during in vitro gastric digestion of milk.

    Science.gov (United States)

    Ye, A; Cui, J; Singh, H

    2011-06-01

    The influence of gastric proteolysis on the physicochemical characteristics of milk fat globules and the proteins of the milk fat globule membrane (MFGM) in raw milk and cream was examined in vitro in simulated gastric fluid (SGF) containing various pepsin concentrations at pH 1.6 for up to 2h. Apparent flocculation of the milk fat globules occurred in raw milk samples incubated in SGF containing pepsin, but no coalescence was observed in either raw milk samples or cream samples. The changes in the particle size of the fat globules as a result of the flocculation were dependent on the pepsin concentration. Correspondingly, the physical characteristics of the fat globules and the composition of the MFGM proteins in raw milk changed during incubation in SGF containing pepsin. The major MFGM proteins were hydrolyzed at different rates by the pepsin in the SGF; butyrophilin was more resistant than xanthine oxidase, PAS 6, or PAS 7. Peptides with various molecular weights, which altered with the time of incubation and the pepsin concentration, were present at the surfaces of the fat globules. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. PMA Induces SnoN Proteolysis and CD61 Expression through an Autocrine Mechanism

    Science.gov (United States)

    Li, Chonghua; Peart, Natoya; Xuan, Zhenyu; Lewis, Dorothy E; Xia, Yang; Jin, Jianping

    2014-01-01

    Phorbol-12-myristate-13-acetate, also called PMA, is a small molecule that activates protein kinase C and functions to differentiate hematologic lineage cells. However, the mechanism of PMA-induced cellular differentiation is not fully understood. We found that PMA triggers global enhancement of protein ubiquitination in K562, a myelogenous leukemia cell line and one of the enhanced-ubiquitination targets is SnoN, an inhibitor of the Smad signaling pathway. Our data indicated that PMA stimulated the production of Activin A, a cytokine of the TGF-β family. Activin A then activated the phosphorylation of both Smad2 and Smad3. In consequence, SnoN is ubiquitinated by the APCCdh1 ubiquitin ligase with the help of phosphorylated Smad2. Furthermore, we found that SnoN proteolysis is important for the expression of CD61, a marker of megakaryocyte. These results indicate that protein ubiquitination promotes megakaryopoiesis via degrading SnoN, an inhibitor of CD61 expression, strengths the roles of ubiquitination in cellular differentiation. PMID:24637302

  8. Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease.

    Science.gov (United States)

    Ehrnhoefer, Dagmar E; Martin, Dale D O; Schmidt, Mandi E; Qiu, Xiaofan; Ladha, Safia; Caron, Nicholas S; Skotte, Niels H; Nguyen, Yen T N; Vaid, Kuljeet; Southwell, Amber L; Engemann, Sabine; Franciosi, Sonia; Hayden, Michael R

    2018-03-06

    Huntington disease (HD) is caused by the expression of mutant huntingtin (mHTT) bearing a polyglutamine expansion. In HD, mHTT accumulation is accompanied by a dysfunction in basal autophagy, which manifests as specific defects in cargo loading during selective autophagy. Here we show that the expression of mHTT resistant to proteolysis at the caspase cleavage site D586 (C6R mHTT) increases autophagy, which may be due to its increased binding to the autophagy adapter p62. This is accompanied by faster degradation of C6R mHTT in vitro and a lack of mHTT accumulation the C6R mouse model with age. These findings may explain the previously observed neuroprotective properties of C6R mHTT. As the C6R mutation cannot be easily translated into a therapeutic approach, we show that a scheduled feeding paradigm is sufficient to lower mHTT levels in YAC128 mice expressing cleavable mHTT. This is consistent with a previous model, where the presence of cleavable mHTT impairs basal autophagy, while fasting-induced autophagy remains functional. In HD, mHTT clearance and autophagy may become increasingly impaired as a function of age and disease stage, because of gradually increased activity of mHTT-processing enzymes. Our findings imply that mHTT clearance could be enhanced by a regulated dietary schedule that promotes autophagy.

  9. Activation-induced proteolysis of cytoplasmic domain of zeta in T cell receptors and Fc receptors.

    Science.gov (United States)

    Taupin, J L; Anderson, P

    1994-12-01

    The CD3-T cell receptor (TCR) complex on T cells and the Fc gamma receptor type III (Fc gamma RIII)-zeta-gamma complex on natural killer cells are functionally analogous activation receptors that associate with a family of disulfide-linked dimers composed of the related subunits zeta and gamma. Immunochemical analysis of receptor complexes separated on two-dimensional diagonal gels allowed the identification of a previously uncharacterized zeta-p14 heterodimer. zeta-p14 is a component of both CD3-TCR and Fc gamma RIII-zeta-gamma. Peptide mapping analysis shows that p14 is structurally related to zeta, suggesting that it is either: (i) derived from zeta proteolytically or (ii) the product of an alternatively spliced mRNA. The observation that COS cells transformed with a cDNA encoding zeta express zeta-p14 supports the former possibility. The expression of CD3-TCR complexes including zeta-p14 increases following activation with phorbol 12-myristate 13-acetate or concanavalin A, suggesting that proteolysis of zeta may contribute to receptor modulation or desensitization.

  10. Locked and proteolysis-based transcription activator-like effector (TALE) regulation.

    Science.gov (United States)

    Lonzarić, Jan; Lebar, Tina; Majerle, Andreja; Manček-Keber, Mateja; Jerala, Roman

    2016-02-18

    Development of orthogonal, designable and adjustable transcriptional regulators is an important goal of synthetic biology. Their activity has been typically modulated through stimulus-induced oligomerization or interaction between the DNA-binding and activation/repression domain. We exploited a feature of the designable Transcription activator-like effector (TALE) DNA-binding domain that it winds around the DNA which allows to topologically prevent it from binding by intramolecular cyclization. This new approach was investigated through noncovalent ligand-induced cyclization or through a covalent split intein cyclization strategy, where the topological inhibition of DNA binding by cyclization and its restoration by a proteolytic release of the topologic constraint was expected. We show that locked TALEs indeed have diminished DNA binding and regain full transcriptional activity by stimulation with the rapamycin ligand or site-specific proteolysis of the peptide linker, with much higher level of activation than rapamycin-induced heterodimerization. Additionally, we demonstrated reversibility, activation of genomic targets and implemented logic gates based on combinations of protein cyclization, proteolytic cleavage and ligand-induced dimerization, where the strongest fold induction was achieved by the proteolytic cleavage of a repression domain from a linear TALE. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Identifying areas at risk of low birth weight using spatial epidemiology: A small area surveillance study.

    Science.gov (United States)

    Insaf, Tabassum Z; Talbot, Thomas

    2016-07-01

    To assess the geographic distribution of Low Birth Weight (LBW) in New York State among singleton births using a spatial regression approach in order to identify priority areas for public health actions. LBW was defined as birth weight less than 2500g. Geocoded data from 562,586 birth certificates in New York State (years 2008-2012) were merged with 2010 census data at the tract level. To provide stable estimates and maintain confidentiality, data were aggregated to yield 1268 areas of analysis. LBW prevalence among singleton births was related with area-level behavioral, socioeconomic and demographic characteristics using a Poisson mixed effects spatial error regression model. Observed low birth weight showed statistically significant auto-correlation in our study area (Moran's I 0.16 p value 0.0005). After over-dispersion correction and accounting for fixed effects for selected social determinants, spatial autocorrelation was fully accounted for (Moran's I-0.007 p value 0.241). The proportion of LBW was higher in areas with larger Hispanic or Black populations and high smoking prevalence. Smoothed maps with predicted prevalence were developed to identify areas at high risk of LBW. Spatial patterns of residual variation were analyzed to identify unique risk factors. Neighborhood racial composition contributes to disparities in LBW prevalence beyond differences in behavioral and socioeconomic factors. Small-area analyses of LBW can identify areas for targeted interventions and display unique local patterns that should be accounted for in prevention strategies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Women with physical disability and the mammogram: An observational study to identify barriers and facilitators

    International Nuclear Information System (INIS)

    Poulos, Ann; Balandin, Susan; Llewellyn, Gwynnyth; McCarthy, Louella; Dark, Leigha

    2011-01-01

    Purpose: To identify barriers and facilitators experienced by women with physical disability having a mammogram. Method: Direct observation of the mammography procedure for women with a range of physical disability at screening facilities of BreastScreen NSW Australia. Results: A volunteer sample of 13 women with varying degrees of physical disability participated in the study. The outcomes suggested that many barriers for women with physical disability can be ameliorated by environmental adaptations and guidelines for both radiographers and women. Some women however cannot be screened successfully, or can be screened only with a level of trauma and/or pain which militates against their continuation within the screening program. This study has identified physical limitations which preclude a successful outcome, those which increase the discomfort/pain of the procedure and aspects of the procedure which can be improved to minimise the experience of discomfort/pain. Conclusion: From the outcomes of the study the development of a decision tool is indicated as a method of providing information for women with physical disability and their doctors as to the likelihood of a successful outcome to participation in mammography screening.

  13. Women with physical disability and the mammogram: An observational study to identify barriers and facilitators

    Energy Technology Data Exchange (ETDEWEB)

    Poulos, Ann, E-mail: ann.poulos@sydney.edu.a [University of Sydney, Faculty of Health Sciences, Discipline of Medical Radiation Sciences, PO Box 170, Lidcombe, NSW 1825 (Australia); Balandin, Susan [University of Sydney, Faculty of Health Sciences, Discipline of Speech Pathology, PO Box 170, Lidcombe, NSW 1825 (Australia); Avdeling for helse- og sosialfag, Hogskolen i Molde, Postboks 2110, 6402 Molde (Norway); Llewellyn, Gwynnyth; McCarthy, Louella [University of Sydney, Faculty of Health Sciences, Discipline of Occupational Therapy, PO Box 170, Lidcombe, NSW 1825 (Australia); Dark, Leigha [University of Sydney, Faculty of Health Sciences, Discipline of Speech Pathology, PO Box 170, Lidcombe, NSW 1825 (Australia)

    2011-02-15

    Purpose: To identify barriers and facilitators experienced by women with physical disability having a mammogram. Method: Direct observation of the mammography procedure for women with a range of physical disability at screening facilities of BreastScreen NSW Australia. Results: A volunteer sample of 13 women with varying degrees of physical disability participated in the study. The outcomes suggested that many barriers for women with physical disability can be ameliorated by environmental adaptations and guidelines for both radiographers and women. Some women however cannot be screened successfully, or can be screened only with a level of trauma and/or pain which militates against their continuation within the screening program. This study has identified physical limitations which preclude a successful outcome, those which increase the discomfort/pain of the procedure and aspects of the procedure which can be improved to minimise the experience of discomfort/pain. Conclusion: From the outcomes of the study the development of a decision tool is indicated as a method of providing information for women with physical disability and their doctors as to the likelihood of a successful outcome to participation in mammography screening.

  14. A review of the reporting of web searching to identify studies for Cochrane systematic reviews.

    Science.gov (United States)

    Briscoe, Simon

    2018-03-01

    The literature searches that are used to identify studies for inclusion in a systematic review should be comprehensively reported. This ensures that the literature searches are transparent and reproducible, which is important for assessing the strengths and weaknesses of a systematic review and re-running the literature searches when conducting an update review. Web searching using search engines and the websites of topically relevant organisations is sometimes used as a supplementary literature search method. Previous research has shown that the reporting of web searching in systematic reviews often lacks important details and is thus not transparent or reproducible. Useful details to report about web searching include the name of the search engine or website, the URL, the date searched, the search strategy, and the number of results. This study reviews the reporting of web searching to identify studies for Cochrane systematic reviews published in the 6-month period August 2016 to January 2017 (n = 423). Of these reviews, 61 reviews reported using web searching using a search engine or website as a literature search method. In the majority of reviews, the reporting of web searching was found to lack essential detail for ensuring transparency and reproducibility, such as the search terms. Recommendations are made on how to improve the reporting of web searching in Cochrane systematic reviews. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Comparing chemical analysis with literature studies to identify micropollutants in a catchment of Copenhagen (DK)

    DEFF Research Database (Denmark)

    Lützhøft, Hans-Christian Holten; Birch, Heidi; Eriksson, Eva

    2011-01-01

    on urban surface runoff originating from a well defined catchment of Copenhagen (Denmark) with an inventory of potential pollution sources for the same catchment. The selected catchment covers an area with roads, a shopping centre, a parking lot, office buildings, a gymnasium and some restaurants....... The literature approach is limited to the range of included PSs and to how and which information is compiled, whereas the analytical chemical approach is limited to the selection of analyzed substances, sensitivity and precision. Comparing the two approaches of chemical analysis with literature study to identify...

  16. Identifying service quality strengths and weaknesses using SERVQUAL: a study of dental services.

    Science.gov (United States)

    Kaldenberg, D; Becker, B W; Browne, B A; Browne, W G

    1997-01-01

    The goal of this study was to examine responses among dental patients to the most recent version of SERVQUAL, and to evaluate that instrument as a tool for measuring satisfaction in a dental practice. Items on the reliability and responsiveness dimensions produced the lowest satisfaction ratings, while improvements in providing services as promised and instilling confidence have the greatest potential for producing higher satisfaction among patients. Finally, using open-ended questions, we identified a number of patient events or experiences which caused either high or low scores on individual SERVQUAL items.

  17. An improved approach to identify irradiated dog feed by electron paramagnetic resonance study and thermoluminescence measurements

    Energy Technology Data Exchange (ETDEWEB)

    Sanyal, Bhaskar, E-mail: bhaskar_sanyal@rediffmail.co [Food Technology Division, Bhabha Atomic Research Centre, Mumbai-400 085 (India); Chawla, S.P.; Sharma, Arun [Food Technology Division, Bhabha Atomic Research Centre, Mumbai-400 085 (India)

    2011-05-15

    In the present study, probably for the first time, a detailed analysis of the radiation induced radical species and thermoluminescence measurements of irradiated dog feed are reported. The EPR spectrum of non-irradiated ready-to-eat dog feed was characterized by singlet g=2.0047{+-}0.0003. Irradiated samples exhibited a complex EPR spectrum. During high power (50.0 mW) EPR spectroscopy, a visible change in the shape of the EPR spectrum was observed and characterized by EPR spectrum simulation technique. An axially symmetric anisotropic signal with g{sub ||}=2.0028 and g{sub perpendicular}=1.9976 was identified. However, a negligible change in the matrix of irradiated edible dog chew was observed using EPR spectroscopy. Therefore, thermoluminescence study of the isolated minerals from dog chew was carried out. The composition of the poly-minerals was studied using SEM and EDX analysis and a complete verdict on identification of irradiation is proposed.

  18. An improved approach to identify irradiated dog feed by electron paramagnetic resonance study and thermoluminescence measurements

    International Nuclear Information System (INIS)

    Sanyal, Bhaskar; Chawla, S.P.; Sharma, Arun

    2011-01-01

    In the present study, probably for the first time, a detailed analysis of the radiation induced radical species and thermoluminescence measurements of irradiated dog feed are reported. The EPR spectrum of non-irradiated ready-to-eat dog feed was characterized by singlet g=2.0047±0.0003. Irradiated samples exhibited a complex EPR spectrum. During high power (50.0 mW) EPR spectroscopy, a visible change in the shape of the EPR spectrum was observed and characterized by EPR spectrum simulation technique. An axially symmetric anisotropic signal with g || =2.0028 and g perpendicular =1.9976 was identified. However, a negligible change in the matrix of irradiated edible dog chew was observed using EPR spectroscopy. Therefore, thermoluminescence study of the isolated minerals from dog chew was carried out. The composition of the poly-minerals was studied using SEM and EDX analysis and a complete verdict on identification of irradiation is proposed.

  19. Genome-wide association studies identify four ER negative-specific breast cancer risk loci

    DEFF Research Database (Denmark)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara

    2013-01-01

    differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls......), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER...

  20. USING GIS TO IDENTIFY POTENTIAL AREAS SUSCEPTIBLE TO FLOOD. CASE STUDY: SOLONEŢ RIVER

    Directory of Open Access Journals (Sweden)

    V. TIPLEA

    2011-03-01

    Full Text Available Using GIS to Identify Potential Areas Susceptible to Flood. Case Study: Soloneţ River. In this study, we aim to analyze the impact of different peak flows in territory and also a better understanding of the dynamic of a river flow. The methodology used for flood zone delimitation is based on a quantitative analysis model which requires the use of mathematical, physical and statistical operations in order to emphasize the relations between the different variables that were implied (discharges, grain size, terrain morphology, soil saturation, vegetation etc.. The results cannot be expected to be completely accurate but can provide a good representation of the process. Validation of results will inevitably be difficult and should be measured in the field. The information resulting from this study could be useful for raising awareness about both hazards and possible mitigation measure, a key component of disaster risk reduction planning.

  1. Case study to identify the causes of stock-out of a textile retailer

    Directory of Open Access Journals (Sweden)

    Fernando Henrique Aguiar

    2014-05-01

    Full Text Available One of the main problems faced by large retailers is related to the lack of supply in display racks, the so called stock-out points. Studies have been made since the sixties, which show that progress related to this subject is limited. Stock-out levels are around 8.3%. Furthermore, literature on the subject is insufficient, as very few studies have been dedicated to investigating the causes of stock-out. The present study aims to collect stock-out data from a large textile retailer for a product category and elaborate a tree of stock-out causes. Qualitative and quantitative methods were used in this research, through software and interviews, in order to generate and refine our results. From this approach, it was possible to identify that 38% of the causes of stock-outs are within the store, that is, the product is not available in the sales area, but in the back end.

  2. Iterative Outlier Removal: A Method for Identifying Outliers in Laboratory Recalibration Studies.

    Science.gov (United States)

    Parrinello, Christina M; Grams, Morgan E; Sang, Yingying; Couper, David; Wruck, Lisa M; Li, Danni; Eckfeldt, John H; Selvin, Elizabeth; Coresh, Josef

    2016-07-01

    Extreme values that arise for any reason, including those through nonlaboratory measurement procedure-related processes (inadequate mixing, evaporation, mislabeling), lead to outliers and inflate errors in recalibration studies. We present an approach termed iterative outlier removal (IOR) for identifying such outliers. We previously identified substantial laboratory drift in uric acid measurements in the Atherosclerosis Risk in Communities (ARIC) Study over time. Serum uric acid was originally measured in 1990-1992 on a Coulter DACOS instrument using an uricase-based measurement procedure. To recalibrate previous measured concentrations to a newer enzymatic colorimetric measurement procedure, uric acid was remeasured in 200 participants from stored plasma in 2011-2013 on a Beckman Olympus 480 autoanalyzer. To conduct IOR, we excluded data points >3 SDs from the mean difference. We continued this process using the resulting data until no outliers remained. IOR detected more outliers and yielded greater precision in simulation. The original mean difference (SD) in uric acid was 1.25 (0.62) mg/dL. After 4 iterations, 9 outliers were excluded, and the mean difference (SD) was 1.23 (0.45) mg/dL. Conducting only one round of outlier removal (standard approach) would have excluded 4 outliers [mean difference (SD) = 1.22 (0.51) mg/dL]. Applying the recalibration (derived from Deming regression) from each approach to the original measurements, the prevalence of hyperuricemia (>7 mg/dL) was 28.5% before IOR and 8.5% after IOR. IOR is a useful method for removal of extreme outliers irrelevant to recalibrating laboratory measurements, and identifies more extraneous outliers than the standard approach. © 2016 American Association for Clinical Chemistry.

  3. Identifying fallacious arguments in a qualitative study of antipsychotic prescribing in dementia.

    Science.gov (United States)

    Donyai, Parastou

    2017-10-01

    Dementia can result in cognitive, noncognitive and behavioural symptoms which are difficult to manage. Formal guidelines for the care and management of dementia in the UK state that antipsychotics should only be prescribed where fully justified. This is because inappropriate use, particularly problematic in care-home settings, can produce severe side effects including death. The aim of this study was to explore the use of fallacious arguments in professionals' deliberations about antipsychotic prescribing in dementia in care-home settings. Fallacious arguments have the potential to become unremarkable discourses that construct and validate practices which are counter to guidelines. This qualitative study involved interviews with 28 care-home managers and health professionals involved in caring for patients with dementia. Potentially fallacious arguments were identified using qualitative content analysis and a coding framework constructed from existing explanatory models of fallacious reasoning. Fallacious arguments were identified in a range of explanations and reasons that participants gave for in answer to questions about initiating, reducing doses of and stopping antipsychotics in dementia. The dominant fallacy was false dichotomy. Appeal to popularity, tradition, consequence, emotion, or fear, and the slippery slope argument was also identified. Fallacious arguments were often formulated to present convincing cases whereby prescribing antipsychotics or maintaining existing doses (versus not starting medication or reducing the dose, for example) appeared as the only acceptable decision but this is not always the case. The findings could help health professionals to recognise and mitigate the effect of logic-based errors in decisions about the prescribing of antipsychotics in dementia. © 2016 Royal Pharmaceutical Society.

  4. A Delphi study to identify the core components of nurse to nurse handoff.

    Science.gov (United States)

    O'Rourke, Jennifer; Abraham, Joanna; Riesenberg, Lee Ann; Matson, Jeff; Lopez, Karen Dunn

    2018-03-08

    The aim of this study was to identify the core components of nurse-nurse handoffs. Patient handoffs involve a process of passing information, responsibility and control from one caregiver to the next during care transitions. Around the globe, ineffective handoffs have serious consequences resulting in wrong treatments, delays in diagnosis, longer stays, medication errors, patient falls and patient deaths. To date, the core components of nurse-nurse handoff have not been identified. This lack of identification is a significant gap in moving towards a standardized approach for nurse-nurse handoff. Mixed methods design using the Delphi technique. From May 2016 - October 2016, using a series of iterative steps, a panel of handoff experts gave feedback on the nurse-nurse handoff core components and the content in each component to be passed from one nurse to the next during a typical unit-based shift handoff. Consensus was defined as 80% agreement or higher. After three rounds of participant review, 17 handoff experts with backgrounds in clinical nursing practice, academia and handoff research came to consensus on the core components of handoff: patient summary, action plan and nurse-nurse synthesis. This is the first study to identify the core components of nurse-nurse handoff. Subsequent testing of the core components will involve evaluating the handoff approach in a simulated and then actual patient care environment. Our long-term goal is to improve patient safety outcomes by validating an evidence-based handoff framework and handoff curriculum for pre-licensure nursing programmes that strengthen the quality of their handoff communication as they enter clinical practice. © 2018 John Wiley & Sons Ltd.

  5. Genome-wide association study identified CNP12587 region underlying height variation in Chinese females.

    Directory of Open Access Journals (Sweden)

    Yin-Ping Zhang

    Full Text Available Human height is a highly heritable trait considered as an important factor for health. There has been limited success in identifying the genetic factors underlying height variation. We aim to identify sequence variants associated with adult height by a genome-wide association study of copy number variants (CNVs in Chinese.Genome-wide CNV association analyses were conducted in 1,625 unrelated Chinese adults and sex specific subgroup for height variation, respectively. Height was measured with a stadiometer. Affymetrix SNP6.0 genotyping platform was used to identify copy number polymorphisms (CNPs. We constructed a genomic map containing 1,009 CNPs in Chinese individuals and performed a genome-wide association study of CNPs with height.We detected 10 significant association signals for height (p<0.05 in the whole population, 9 and 11 association signals for Chinese female and male population, respectively. A copy number polymorphism (CNP12587, chr18:54081842-54086942, p = 2.41 × 10(-4 was found to be significantly associated with height variation in Chinese females even after strict Bonferroni correction (p = 0.048. Confirmatory real time PCR experiments lent further support for CNV validation. Compared to female subjects with two copies of the CNP, carriers of three copies had an average of 8.1% decrease in height. An important candidate gene, ubiquitin-protein ligase NEDD4-like (NEDD4L, was detected at this region, which plays important roles in bone metabolism by binding to bone formation regulators.Our findings suggest the important genetic variants underlying height variation in Chinese.

  6. Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.

    Science.gov (United States)

    de Boer, Ynto S; van Gerven, Nicole M F; Zwiers, Antonie; Verwer, Bart J; van Hoek, Bart; van Erpecum, Karel J; Beuers, Ulrich; van Buuren, Henk R; Drenth, Joost P H; den Ouden, Jannie W; Verdonk, Robert C; Koek, Ger H; Brouwer, Johannes T; Guichelaar, Maureen M J; Vrolijk, Jan M; Kraal, Georg; Mulder, Chris J J; van Nieuwkerk, Carin M J; Fischer, Janett; Berg, Thomas; Stickel, Felix; Sarrazin, Christoph; Schramm, Christoph; Lohse, Ansgar W; Weiler-Normann, Christina; Lerch, Markus M; Nauck, Matthias; Völzke, Henry; Homuth, Georg; Bloemena, Elisabeth; Verspaget, Hein W; Kumar, Vinod; Zhernakova, Alexandra; Wijmenga, Cisca; Franke, Lude; Bouma, Gerd

    2014-08-01

    Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits. In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

    International Nuclear Information System (INIS)

    Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe; Rubin, Daniel L.; Napel, Sandy; Diehn, Maximilian; Loo, Billy W.; Li, Ruijiang

    2016-01-01

    Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from "1"8F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust intratumor

  8. Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study.

    Science.gov (United States)

    Wu, Jia; Gensheimer, Michael F; Dong, Xinzhe; Rubin, Daniel L; Napel, Sandy; Diehn, Maximilian; Loo, Billy W; Li, Ruijiang

    2016-08-01

    To develop an intratumor partitioning framework for identifying high-risk subregions from (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. In this institutional review board-approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). We propose a robust intratumor partitioning method to identify clinically relevant, high

  9. Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Rubin, Daniel L. [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Department of Medicine (Biomedical Informatics Research), Stanford University School of Medicine, Stanford, California (United States); Napel, Sandy [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Li, Ruijiang, E-mail: rli2@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States)

    2016-08-01

    Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust

  10. Genome-wide association study identifies novel breast cancer susceptibility loci

    Science.gov (United States)

    Easton, Douglas F.; Pooley, Karen A.; Dunning, Alison M.; Pharoah, Paul D. P.; Thompson, Deborah; Ballinger, Dennis G.; Struewing, Jeffery P.; Morrison, Jonathan; Field, Helen; Luben, Robert; Wareham, Nicholas; Ahmed, Shahana; Healey, Catherine S.; Bowman, Richard; Meyer, Kerstin B.; Haiman, Christopher A.; Kolonel, Laurence K.; Henderson, Brian E.; Marchand, Loic Le; Brennan, Paul; Sangrajrang, Suleeporn; Gaborieau, Valerie; Odefrey, Fabrice; Shen, Chen-Yang; Wu, Pei-Ei; Wang, Hui-Chun; Eccles, Diana; Evans, D. Gareth; Peto, Julian; Fletcher, Olivia; Johnson, Nichola; Seal, Sheila; Stratton, Michael R.; Rahman, Nazneen; Chenevix-Trench, Georgia; Bojesen, Stig E.; Nordestgaard, Børge G.; Axelsson, Christen K.; Garcia-Closas, Montserrat; Brinton, Louise; Chanock, Stephen; Lissowska, Jolanta; Peplonska, Beata; Nevanlinna, Heli; Fagerholm, Rainer; Eerola, Hannaleena; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Hunter, David J.; Hankinson, Susan E.; Cox, David G.; Hall, Per; Wedren, Sara; Liu, Jianjun; Low, Yen-Ling; Bogdanova, Natalia; Schürmann, Peter; Dörk, Thilo; Tollenaar, Rob A. E. M.; Jacobi, Catharina E.; Devilee, Peter; Klijn, Jan G. M.; Sigurdson, Alice J.; Doody, Michele M.; Alexander, Bruce H.; Zhang, Jinghui; Cox, Angela; Brock, Ian W.; MacPherson, Gordon; Reed, Malcolm W. R.; Couch, Fergus J.; Goode, Ellen L.; Olson, Janet E.; Meijers-Heijboer, Hanne; van den Ouweland, Ans; Uitterlinden, André; Rivadeneira, Fernando; Milne, Roger L.; Ribas, Gloria; Gonzalez-Neira, Anna; Benitez, Javier; Hopper, John L.; McCredie, Margaret; Southey, Melissa; Giles, Graham G.; Schroen, Chris; Justenhoven, Christina; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana; Day, Nicholas E.; Cox, David R.; Ponder, Bruce A. J.; Luccarini, Craig; Conroy, Don; Shah, Mitul; Munday, Hannah; Jordan, Clare; Perkins, Barbara; West, Judy; Redman, Karen; Driver, Kristy; Aghmesheh, Morteza; Amor, David; Andrews, Lesley; Antill, Yoland; Armes, Jane; Armitage, Shane; Arnold, Leanne; Balleine, Rosemary; Begley, Glenn; Beilby, John; Bennett, Ian; Bennett, Barbara; Berry, Geoffrey; Blackburn, Anneke; Brennan, Meagan; Brown, Melissa; Buckley, Michael; Burke, Jo; Butow, Phyllis; Byron, Keith; Callen, David; Campbell, Ian; Chenevix-Trench, Georgia; Clarke, Christine; Colley, Alison; Cotton, Dick; Cui, Jisheng; Culling, Bronwyn; Cummings, Margaret; Dawson, Sarah-Jane; Dixon, Joanne; Dobrovic, Alexander; Dudding, Tracy; Edkins, Ted; Eisenbruch, Maurice; Farshid, Gelareh; Fawcett, Susan; Field, Michael; Firgaira, Frank; Fleming, Jean; Forbes, John; Friedlander, Michael; Gaff, Clara; Gardner, Mac; Gattas, Mike; George, Peter; Giles, Graham; Gill, Grantley; Goldblatt, Jack; Greening, Sian; Grist, Scott; Haan, Eric; Harris, Marion; Hart, Stewart; Hayward, Nick; Hopper, John; Humphrey, Evelyn; Jenkins, Mark; Jones, Alison; Kefford, Rick; Kirk, Judy; Kollias, James; Kovalenko, Sergey; Lakhani, Sunil; Leary, Jennifer; Lim, Jacqueline; Lindeman, Geoff; Lipton, Lara; Lobb, Liz; Maclurcan, Mariette; Mann, Graham; Marsh, Deborah; McCredie, Margaret; McKay, Michael; McLachlan, Sue Anne; Meiser, Bettina; Milne, Roger; Mitchell, Gillian; Newman, Beth; O'Loughlin, Imelda; Osborne, Richard; Peters, Lester; Phillips, Kelly; Price, Melanie; Reeve, Jeanne; Reeve, Tony; Richards, Robert; Rinehart, Gina; Robinson, Bridget; Rudzki, Barney; Salisbury, Elizabeth; Sambrook, Joe; Saunders, Christobel; Scott, Clare; Scott, Elizabeth; Scott, Rodney; Seshadri, Ram; Shelling, Andrew; Southey, Melissa; Spurdle, Amanda; Suthers, Graeme; Taylor, Donna; Tennant, Christopher; Thorne, Heather; Townshend, Sharron; Tucker, Kathy; Tyler, Janet; Venter, Deon; Visvader, Jane; Walpole, Ian; Ward, Robin; Waring, Paul; Warner, Bev; Warren, Graham; Watson, Elizabeth; Williams, Rachael; Wilson, Judy; Winship, Ingrid; Young, Mary Ann; Bowtell, David; Green, Adele; deFazio, Anna; Chenevix-Trench, Georgia; Gertig, Dorota; Webb, Penny

    2009-01-01

    Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2>0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P<10−7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P<0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. PMID:17529967

  11. Citation searches are more sensitive than keyword searches to identify studies using specific measurement instruments.

    Science.gov (United States)

    Linder, Suzanne K; Kamath, Geetanjali R; Pratt, Gregory F; Saraykar, Smita S; Volk, Robert J

    2015-04-01

    To compare the effectiveness of two search methods in identifying studies that used the Control Preferences Scale (CPS), a health care decision-making instrument commonly used in clinical settings. We searched the literature using two methods: (1) keyword searching using variations of "Control Preferences Scale" and (2) cited reference searching using two seminal CPS publications. We searched three bibliographic databases [PubMed, Scopus, and Web of Science (WOS)] and one full-text database (Google Scholar). We report precision and sensitivity as measures of effectiveness. Keyword searches in bibliographic databases yielded high average precision (90%) but low average sensitivity (16%). PubMed was the most precise, followed closely by Scopus and WOS. The Google Scholar keyword search had low precision (54%) but provided the highest sensitivity (70%). Cited reference searches in all databases yielded moderate sensitivity (45-54%), but precision ranged from 35% to 75% with Scopus being the most precise. Cited reference searches were more sensitive than keyword searches, making it a more comprehensive strategy to identify all studies that use a particular instrument. Keyword searches provide a quick way of finding some but not all relevant articles. Goals, time, and resources should dictate the combination of which methods and databases are used. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. L-lysine escinat, thiotriazolin, gordox and mydocalm influence on oxygen tension in the intestinal wall and acid-base balance and limited proteolysis in intestinal venous blood in terms of intraabdominal hypertension modeling

    Directory of Open Access Journals (Sweden)

    Sapegin V.I.

    2014-11-01

    Full Text Available In acute experiments on rabbits there were studied changes in oxygen tension in the intestinal wall tissues, acid-base balance and limited proteolysis and its inhibitors in intestinal venous blood, protective action of L-lysine escinat (0,15 mg/kg / single dose, thiotriazolin (25 mg/kg / single dose, aprotinin (gordox (10,000 units/kg / single dose in sequential modeling of standard levels increasing of intra-abdominal hypertension (IAH — 50, 100, 150, 200, 250, 300, 350 m H2O, and also of tolperison (mydocalm (5 mg/kg / single dose on modeling of stable 3-hour IAH 200 m H2O. The IAH modeling was performed by means of stand of our construction. Under the influence of IAH the compensated metabolic acidosis in intestinal venous blood with a compensative hyperpnoe develops, decline of oxygen tension in tissues and activating of a limited proteolysis as well as decline of its inhibitors activity in intestinal venous blood occur. By the degree of metabolic acidosis prevention investigational preparations were distributed as follows gordox > thiotriazolin = L-lysine escinat = mydocalm, and by prevention of decline of oxygen tension in tissues — thiotriazolin > L-lysine escinat > mydocalm > gordox, it is is connected with different rate of methabolic products excretion into the blood, due to the influence on blood circulation and transcapilary exchange. By the degree of prevention of proteolytic activity and inhibitory potential changes, investigational preparations were distributed as follows: gordox > mydocalm > thiotriazolin > L-lysine escinat, this is connected with inhibition of proteolysis in gordox, and in other ones – with reduction of ischemic damage of tissues. Owing to different mechanism of action thiotriazolin, L-lysine escinat and mydocalm may be simultaneously recommended for a conservative treatment of patients with intraabdominal hypertension syndrome.

  13. Phenylbutyric acid rescues endoplasmic reticulum stress-induced suppression of APP proteolysis and prevents apoptosis in neuronal cells.

    Directory of Open Access Journals (Sweden)

    Jesse C Wiley

    Full Text Available BACKGROUND: The familial and sporadic forms of Alzheimer's disease (AD have an identical pathology with a severe disparity in the time of onset [1]. The pathological similarity suggests that epigenetic processes may phenocopy the Familial Alzheimer's disease (FAD mutations within sporadic AD. Numerous groups have demonstrated that FAD mutations in presenilin result in 'loss of function' of gamma-secretase mediated APP cleavage [2], [3], [4], [5]. Accordingly, ER stress is prominent within the pathologically impacted brain regions in AD patients [6] and is reported to inhibit APP trafficking through the secretory pathway [7], [8]. As the maturation of APP and the cleaving secretases requires trafficking through the secretory pathway [9], [10], [11], we hypothesized that ER stress may block trafficking requisite for normal levels of APP cleavage and that the small molecular chaperone 4-phenylbutyrate (PBA may rescue the proteolytic deficit. METHODOLOGY/PRINCIPAL FINDINGS: The APP-Gal4VP16/Gal4-reporter screen was stably incorporated into neuroblastoma cells in order to assay gamma-secretase mediated APP proteolysis under normal and pharmacologically induced ER stress conditions. Three unrelated pharmacological agents (tunicamycin, thapsigargin and brefeldin A all repressed APP proteolysis in parallel with activation of unfolded protein response (UPR signaling-a biochemical marker of ER stress. Co-treatment of the gamma-secretase reporter cells with PBA blocked the repressive effects of tunicamycin and thapsigargin upon APP proteolysis, UPR activation, and apoptosis. In unstressed cells, PBA stimulated gamma-secretase mediated cleavage of APP by 8-10 fold, in the absence of any significant effects upon amyloid production, by promoting APP trafficking through the secretory pathway and the stimulation of the non-pathogenic alpha/gamma-cleavage. CONCLUSIONS/SIGNIFICANCE: ER stress represses gamma-secretase mediated APP proteolysis, which replicates

  14. Genome-wide association study identifies three novel genetic markers associated with elite endurance performance

    DEFF Research Database (Denmark)

    Ahmetov, Ii; Kulemin, Na; Popov, Dv

    2015-01-01

    To investigate the association between multiple single-nucleotide polymorphisms (SNPs), aerobic performance and elite endurance athlete status in Russians. By using GWAS approach, we examined the association between 1,140,419 SNPs and relative maximal oxygen consumption rate ([Formula: see text]O2......max) in 80 international-level Russian endurance athletes (46 males and 34 females). To validate obtained results, we further performed case-control studies by comparing the frequencies of the most significant SNPs (with P endurance athletes and opposite cohorts (192...... Russian controls, 1367 European controls, and 230 Russian power athletes). Initially, six 'endurance alleles' were identified showing discrete associations with [Formula: see text]O2max both in males and females. Next, case-control studies resulted in remaining three SNPs (NFIA-AS2 rs1572312, TSHR rs...

  15. A study of correlations between identified charged hadrons in hadronic Z0 decays

    International Nuclear Information System (INIS)

    Abe, K.; Abe, K.; Abe, T.

    1998-06-01

    The authors present a preliminary study of correlations in rapidity between pairs of identified pions, kaons and protons in hadronic Z 0 decays into light flavors. Short range charge correlations are observed between all combinations of these hadron species, confirming that charge, strangeness and baryon number are conserved locally in the jet fragmentation process. The range of this effect is found to be independent of momentum. A strong long-range correlation is observed for high-momentum charged kaon pairs, and weaker long-range π + -π - , π + -K - and p-K - correlations are observed. The SLC electron beam polarization is used to tag the quark hemisphere in each event, allowing the first study of rapidities signed such that positive rapidity is along the quark rather than antiquark direction. Distributions of signed rapidities and of ordered differences between signed rapidities provide new insights into leading particle production and several new tests of fragmentation models

  16. An exploratory study to identify critical factors of innovation culture in organizations

    Directory of Open Access Journals (Sweden)

    Hamed Asgari

    2013-07-01

    Full Text Available During the past two decades, there has been a growing trend on knowledge-based organizations. Innovation, on the other hand, plays essential role on building competitive business units. In this paper, we present an exploratory study to identify critical factors of innovation culture in organizations. We detect important factors influencing innovation culture in construction industry based on the implementation of factor analysis. The proposed study designs a questionnaire and distributes it among 400 experts who are involved in construction industry. Cronbach alpha has been calculated as 0.779, which validates the overall questionnaire. The results of factor analysis have indicated that six factors of building cultural infrastructures, education, organizational vision, established culture, strategic culture and flexible culture are the most important items influencing innovation culture.

  17. Identifying Students Struggling in Courses by Analyzing Exam Grades, Self-reported Measures and Study Activities

    DEFF Research Database (Denmark)

    Christensen, Bianca Clavio; Bemman, Brian; Knoche, Hendrik

    2018-01-01

    . In this paper, we present a set of instrument`s designed to identify at-risk undergraduate students in a Problem-based Learning (PBL) university, using an introductory programming course between two campus locations as a case study. Collectively, these instruments form the basis of a proposed learning ecosystem...... in the prediction model. Results of a multiple linear regression model found several significant assessment predictors related to how often students attempted self-guided course assignments and their self-reported programming experience, among others.......Technical educations often experience poor student performance and consequently high rates of attrition. Providing students with early feedback on their learning progress can assist students in self-study activities or in their decision-making process regarding a change in educational direction...

  18. Study protocol: identifying and delivering point-of-care information to improve care coordination.

    Science.gov (United States)

    Hysong, Sylvia J; Che, Xinxuan; Weaver, Sallie J; Petersen, Laura A

    2015-10-19

    The need for deliberately coordinated care is noted by many national-level organizations. The Department of Veterans Affairs (VA) recently transitioned primary care clinics nationwide into Patient Aligned Care Teams (PACTs) to provide more accessible, coordinated, comprehensive, and patient-centered care. To better serve this purpose, PACTs must be able to successfully sequence and route interdependent tasks to appropriate team members while also maintaining collective situational awareness (coordination). Although conceptual frameworks of care coordination exist, few explicitly articulate core behavioral markers of coordination or the related information needs of team members attempting to synchronize complex care processes across time for a shared patient population. Given this gap, we partnered with a group of frontline primary care personnel at ambulatory care sites to identify the specific information needs of PACT members that will enable them to coordinate their efforts to provide effective, coordinated care. The study has three objectives: (1) development of measurable, prioritized point-of-care criteria for effective PACT coordination; (2) identifying the specific information needed at the point of care to optimize coordination; and (3) assessing the effect of adopting the aforementioned coordination standards on PACT clinicians' coordination behaviors. The study consists of three phases. In phase 1, we will employ the Productivity Measurement and Enhancement System (ProMES), a structured approach to performance measure creation from industrial/organizational psychology, to develop coordination measures with a design team of 6-10 primary care personnel; in phase 2, we will conduct focus groups with the phase 1 design team to identify point-of-care information needs. Phase 3 is a two-arm field experiment (n PACT = 28/arm); intervention arm PACTs will receive monthly feedback reports using the measures developed in phase 1 and attend brief monthly

  19. Comparative genetics: synergizing human and NOD mouse studies for identifying genetic causation of type 1 diabetes.

    Science.gov (United States)

    Driver, John P; Chen, Yi-Guang; Mathews, Clayton E

    2012-01-01

    Although once widely anticipated to unlock how human type 1 diabetes (T1D) develops, extensive study of the nonobese diabetic (NOD) mouse has failed to yield effective treatments for patients with the disease. This has led many to question the usefulness of this animal model. While criticism about the differences between NOD and human T1D is legitimate, in many cases disease in both species results from perturbations modulated by the same genes or different genes that function within the same biological pathways. Like in humans, unusual polymorphisms within an MHC class II molecule contributes the most T1D risk in NOD mice. This insight supports the validity of this model and suggests the NOD has been improperly utilized to study how to cure or prevent disease in patients. Indeed, clinical trials are far from administering T1D therapeutics to humans at the same concentration ranges and pathological states that inhibit disease in NOD mice. Until these obstacles are overcome it is premature to label the NOD mouse a poor surrogate to test agents that cure or prevent T1D. An additional criticism of the NOD mouse is the past difficulty in identifying genes underlying T1D using conventional mapping studies. However, most of the few diabetogenic alleles identified to date appear relevant to the human disorder. This suggests that rather than abandoning genetic studies in NOD mice, future efforts should focus on improving the efficiency with which diabetes susceptibility genes are detected. The current review highlights why the NOD mouse remains a relevant and valuable tool to understand the genes and their interactions that promote autoimmune diabetes and therapeutics that inhibit this disease. It also describes a new range of technologies that will likely transform how the NOD mouse is used to uncover the genetic causes of T1D for years to come.

  20. Determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease: The DOC study.

    Science.gov (United States)

    Ronaldson, Sarah J; Dyson, Lisa; Clark, Laura; Hewitt, Catherine E; Torgerson, David J; Cooper, Brendan G; Kearney, Matt; Laughey, William; Raghunath, Raghu; Steele, Lisa; Rhodes, Rebecca; Adamson, Joy

    2018-06-01

    Early identification of chronic obstructive pulmonary disease (COPD) results in patients receiving appropriate management for their condition at an earlier stage in their disease. The determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease (DOC) study was a case-finding study to enhance early identification of COPD in primary care, which evaluated the diagnostic accuracy of a series of simple lung function tests and symptom-based case-finding questionnaires. Current smokers aged 35 or more were invited to undertake a series of case-finding tools, which comprised lung function tests (specifically, spirometry, microspirometry, peak flow meter, and WheezoMeter) and several case-finding questionnaires. The effectiveness of these tests, individually or in combination, to identify small airways obstruction was evaluated against the gold standard of spirometry, with the quality of spirometry tests assessed by independent overreaders. The study was conducted with general practices in the Yorkshire and Humberside area, in the UK. Six hundred eighty-one individuals met the inclusion criteria, with 444 participants completing their study appointments. A total of 216 (49%) with good-quality spirometry readings were included in the analysis. The most effective case-finding tools were found to be the peak flow meter alone, the peak flow meter plus WheezoMeter, and microspirometry alone. In addition to the main analysis, where the severity of airflow obstruction was based on fixed ratios and percent of predicted values, sensitivity analyses were conducted by using lower limit of normal values. This research informs the choice of test for COPD identification; case-finding by use of the peak flow meter or microspirometer could be used routinely in primary care for suspected COPD patients. Only those testing positive to these tests would move on to full spirometry, thereby reducing unnecessary spirometric testing. © 2018 John Wiley

  1. A qualitative case study to identify possible barriers that limit effective elementary science education

    Science.gov (United States)

    Foster, Donald Carey

    The purpose of this case study was to identify barriers that limit the effectiveness of elementary teachers in the teaching of science. It is of the utmost urgency that barriers be first identified, so that possible solutions can be explored to bring about the improvement of elementary science education. This urgency has been imposed by the scheduled national testing of students in science by 2007, as mandated by the No Child Left Behind Act of 2001. Using qualitative case study methods, the researcher conducted interviews with 8 elementary teachers from two schools within one school district who taught 3rd, 4th, and 5th grade. These interviews were designed to gain insight into barriers these elementary teachers perceived as factors limiting their effectiveness in teaching science and preparing students for high-stakes testing. Barriers in the areas of teacher background, typical teaching day, curriculum, inservices, and legislative influences were explored. This study concluded that the barriers explored do have a substantial negative affect on the teaching and learning of science in the elementary grades. Specifically, the barriers revealed in this study include the limited science background of elementary teachers, inadequate class time devoted to science, non-comprehensive curriculum, ineffective or lack of inservice training, and pressures from legislated mandates. But it is also clear that these barriers are so intertwined that one cannot remove these barriers one at a time. It will take a collective effort from all involved, including legislators, administrators, teachers, parents, and students, to alleviate these barriers and discover effective solutions to improve elementary science education.

  2. Cross-study analysis of gene expression data for intermediate neuroblastoma identifies two biological subtypes

    International Nuclear Information System (INIS)

    Warnat, Patrick; Oberthuer, André; Fischer, Matthias; Westermann, Frank; Eils, Roland; Brors, Benedikt

    2007-01-01

    Neuroblastoma patients show heterogeneous clinical courses ranging from life-threatening progression to spontaneous regression. Recently, gene expression profiles of neuroblastoma tumours were associated with clinically different phenotypes. However, such data is still rare for important patient subgroups, such as patients with MYCN non-amplified advanced stage disease. Prediction of the individual course of disease and optimal therapy selection in this cohort is challenging. Additional research effort is needed to describe the patterns of gene expression in this cohort and to identify reliable prognostic markers for this subset of patients. We combined gene expression data from two studies in a meta-analysis in order to investigate differences in gene expression of advanced stage (3 or 4) tumours without MYCN amplification that show contrasting outcomes (alive or dead) at five years after initial diagnosis. In addition, a predictive model for outcome was generated. Gene expression profiles from 66 patients were included from two studies using different microarray platforms. In the combined data set, 72 genes were identified as differentially expressed by meta-analysis at a false discovery rate (FDR) of 8.33%. Meta-analysis detected 34 differentially expressed genes that were not found as significant in either single study. Outcome prediction based on data of both studies resulted in a predictive accuracy of 77%. Moreover, the genes that were differentially expressed in subgroups of advanced stage patients without MYCN amplification accurately separated MYCN amplified tumours from low stage tumours without MYCN amplification. Our findings support the hypothesis that neuroblastoma consists of two biologically distinct subgroups that differ by characteristic gene expression patterns, which are associated with divergent clinical outcome

  3. An exploratory study identifying where local government public health decision makers source their evidence for policy.

    Science.gov (United States)

    Stoneham, Melissa; Dodds, James

    2014-08-01

    The Western Australian (WA) Public Health Bill will replace the antiquated Health Act 1911. One of the proposed clauses of the Bill requires all WA local governments to develop a Public Health Plan. The Bill states that Public Health Plans should be based on evidence from all levels, including national and statewide priorities, community needs, local statistical evidence, and stakeholder data. This exploratory study, which targeted 533 WA local government officers, aimed to identify the sources of evidence used to generate the list of public health risks to be included in local government Public Health Plans. The top four sources identified for informing local policy were: observation of the consequences of the risks in the local community (24.5%), statewide evidence (17.6%), local evidence (17.6%) and coverage in local media (16.2%). This study confirms that both hard and soft data are used to inform policy decisions at the local level. Therefore, the challenge that this study has highlighted is in the definition or constitution of evidence. SO WHAT? Evidence is critical to the process of sound policy development. This study highlights issues associated with what actually constitutes evidence in the policy development process at the local government level. With the exception of those who work in an extremely narrow field, it is difficult for local government officers, whose role includes policymaking, to read the vast amount of information that has been published in their area of expertise. For those who are committed to the notion of evidence-based policymaking, as advocated within the WA Public Health Bill, this presents a considerable challenge.

  4. Patient and carer identified factors which contribute to safety incidents in primary care: a qualitative study.

    Science.gov (United States)

    Hernan, Andrea L; Giles, Sally J; Fuller, Jeffrey; Johnson, Julie K; Walker, Christine; Dunbar, James A

    2015-09-01

    Patients can have an important role in reducing harm in primary-care settings. Learning from patient experience and feedback could improve patient safety. Evidence that captures patients' views of the various contributory factors to creating safe primary care is largely absent. The aim of this study was to address this evidence gap. Four focus groups and eight semistructured interviews were conducted with 34 patients and carers from south-east Australia. Participants were asked to describe their experiences of primary care. Audio recordings were transcribed verbatim and specific factors that contribute to safety incidents were identified in the analysis using the Yorkshire Contributory Factors Framework (YCFF). Other factors emerging from the data were also ascertained and added to the analytical framework. Thirteen factors that contribute to safety incidents in primary care were ascertained. Five unique factors for the primary-care setting were discovered in conjunction with eight factors present in the YCFF from hospital settings. The five unique primary care contributing factors to safety incidents represented a range of levels within the primary-care system from local working conditions to the upstream organisational level and the external policy context. The 13 factors included communication, access, patient factors, external policy context, dignity and respect, primary-secondary interface, continuity of care, task performance, task characteristics, time in the consultation, safety culture, team factors and the physical environment. Patient and carer feedback of this type could help primary-care professionals better understand and identify potential safety concerns and make appropriate service improvements. The comprehensive range of factors identified provides the groundwork for developing tools that systematically capture the multiple contributory factors to patient safety. Published by the BMJ Publishing Group Limited. For permission to use (where not

  5. Protocol: a systematic review of studies developing and/or evaluating search strategies to identify prognosis studies.

    Science.gov (United States)

    Corp, Nadia; Jordan, Joanne L; Hayden, Jill A; Irvin, Emma; Parker, Robin; Smith, Andrea; van der Windt, Danielle A

    2017-04-20

    Prognosis research is on the rise, its importance recognised because chronic health conditions and diseases are increasingly common and costly. Prognosis systematic reviews are needed to collate and synthesise these research findings, especially to help inform effective clinical decision-making and healthcare policy. A detailed, comprehensive search strategy is central to any systematic review. However, within prognosis research, this is challenging due to poor reporting and inconsistent use of available indexing terms in electronic databases. Whilst many published search filters exist for finding clinical trials, this is not the case for prognosis studies. This systematic review aims to identify and compare existing methodological filters developed and evaluated to identify prognosis studies of any of the three main types: overall prognosis, prognostic factors, and prognostic [risk prediction] models. Primary studies reporting the development and/or evaluation of methodological search filters to retrieve any type of prognosis study will be included in this systematic review. Multiple electronic bibliographic databases will be searched, grey literature will be sought from relevant organisations and websites, experts will be contacted, and citation tracking of key papers and reference list checking of all included papers will be undertaken. Titles will be screened by one person, and abstracts and full articles will be reviewed for inclusion independently by two reviewers. Data extraction and quality assessment will also be undertaken independently by two reviewers with disagreements resolved by discussion or by a third reviewer if necessary. Filters' characteristics and performance metrics reported in the included studies will be extracted and tabulated. To enable comparisons, filters will be grouped according to database, platform, type of prognosis study, and type of filter for which it was intended. This systematic review will identify all existing validated

  6. Identifying strategies to assist final semester nursing students to develop numeracy skills: a mixed methods study.

    Science.gov (United States)

    Ramjan, Lucie M; Stewart, Lyn; Salamonson, Yenna; Morris, Maureen M; Armstrong, Lyn; Sanchez, Paula; Flannery, Liz

    2014-03-01

    It remains a grave concern that many nursing students within tertiary institutions continue to experience difficulties with achieving medication calculation competency. In addition, universities have a moral responsibility to prepare proficient clinicians for graduate practice. This requires risk management strategies to reduce adverse medication errors post registration. To identify strategies and potential predictors that may assist nurse academics to tailor their drug calculation teaching and assessment methods. This project builds on previous experience and explores students' perceptions of newly implemented interventions designed to increase confidence and competence in medication calculation. This mixed method study surveyed students (n=405) enrolled in their final semester of study at a large, metropolitan university in Sydney, Australia. Tailored, contextualised interventions included online practice quizzes, simulated medication calculation scenarios developed for clinical practice classes, contextualised 'pen and paper' tests, visually enhanced didactic remediation and 'hands-on' contextualised workshops. Surveys were administered to students to determine their perceptions of interventions and to identify whether these interventions assisted with calculation competence. Test scores were analysed using SPSS v. 20 for correlations between students' perceptions and actual performance. Qualitative open-ended survey questions were analysed manually and thematically. The study reinforced that nursing students preferred a 'hands-on,' contextualised approach to learning that was 'authentic' and aligned with clinical practice. Our interventions assisted with supporting students' learning and improvement of calculation confidence. Qualitative data provided further insight into students' awareness of their calculation errors and preferred learning styles. Some of the strongest predictors for numeracy skill performance included (1) being an international student, (2

  7. A Genome-Wide Association Study Identifies Five Loci Influencing Facial Morphology in Europeans

    Science.gov (United States)

    Liu, Fan; van der Lijn, Fedde; Schurmann, Claudia; Zhu, Gu; Chakravarty, M. Mallar; Hysi, Pirro G.; Wollstein, Andreas; Lao, Oscar; de Bruijne, Marleen; Ikram, M. Arfan; van der Lugt, Aad; Rivadeneira, Fernando; Uitterlinden, André G.; Hofman, Albert; Niessen, Wiro J.; Homuth, Georg; de Zubicaray, Greig; McMahon, Katie L.; Thompson, Paul M.; Daboul, Amro; Puls, Ralf; Hegenscheid, Katrin; Bevan, Liisa; Pausova, Zdenka; Medland, Sarah E.; Montgomery, Grant W.; Wright, Margaret J.; Wicking, Carol; Boehringer, Stefan; Spector, Timothy D.; Paus, Tomáš; Martin, Nicholas G.; Biffar, Reiner; Kayser, Manfred

    2012-01-01

    Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs) and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes—PRDM16, PAX3, TP63, C5orf50, and COL17A1—in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications. PMID:23028347

  8. A genome-wide association study identifies five loci influencing facial morphology in Europeans.

    Directory of Open Access Journals (Sweden)

    Fan Liu

    2012-09-01

    Full Text Available Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes--PRDM16, PAX3, TP63, C5orf50, and COL17A1--in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications.

  9. Identifying the most successful dose (MSD) in dose-finding studies in cancer.

    Science.gov (United States)

    Zohar, Sarah; O'Quigley, John

    2006-01-01

    For a dose finding study in cancer, the most successful dose (MSD), among a group of available doses, is that dose at which the overall success rate is the highest. This rate is the product of the rate of seeing non-toxicities together with the rate of tumor response. A successful dose finding trial in this context is one where we manage to identify the MSD in an efficient manner. In practice we may also need to consider algorithms for identifying the MSD which can incorporate certain restrictions, the most common restriction maintaining the estimated toxicity rate alone below some maximum rate. In this case the MSD may correspond to a different level than that for the unconstrained MSD and, in providing a final recommendation, it is important to underline that it is subject to the given constraint. We work with the approach described in O'Quigley et al. [Biometrics 2001; 57(4):1018-1029]. The focus of that work was dose finding in HIV where both information on toxicity and efficacy were almost immediately available. Recent cancer studies are beginning to fall under this same heading where, as before, toxicity can be quickly evaluated and, in addition, we can rely on biological markers or other measures of tumor response. Mindful of the particular context of cancer, our purpose here is to consider the methodology developed by O'Quigley et al. and its practical implementation. We also carry out a study on the doubly under-parameterized model, developed by O'Quigley et al. but not

  10. Genome-wide association study identifies 74 loci associated with educational attainment

    Science.gov (United States)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark A.; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Börge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bønnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans68, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldórsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kähönen, Mika; Kanoni, Stavroula; Keltigangas-Järvinen, Liisa; Kiemeney, Lambertus A.L.M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Maël P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C.M.; Loukola, Anu; Madden, Pamela A.; Mägi, Reedik; Mäki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E.R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Räikkönen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J.A.; Venturini, Cristina; Vinkhuyzen, Anna A.E.; Völker, Uwe; Völzke, Henry; Vonk, Judith M.; Vozzi, Diego; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jörgen; Gratten, Jacob; Groenen, Patrick J.F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppönen, Elina; Iacono, William G.; Jacobsson, Bo; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L.R.; Lehtimäki, Terho; Lehrer, Steven F.; Magnusson, Patrik K.E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W.J.H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sørensen, Thorkild I.A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, André G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tõnu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.

    2016-01-01

    Summary Educational attainment (EA) is strongly influenced by social and other environmental factors, but genetic factors are also estimated to account for at least 20% of the variation across individuals1. We report the results of a genome-wide association study (GWAS) for EA that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication in an independent sample of 111,349 individuals from the UK Biobank. We now identify 74 genome-wide significant loci associated with number of years of schooling completed. Single-nucleotide polymorphisms (SNPs) associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioral phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because EA is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric disease. PMID:27225129

  11. Identifying county characteristics associated with resident well-being: A population based study.

    Science.gov (United States)

    Roy, Brita; Riley, Carley; Herrin, Jeph; Spatz, Erica S; Arora, Anita; Kell, Kenneth P; Welsh, John; Rula, Elizabeth Y; Krumholz, Harlan M

    2018-01-01

    Well-being is a positively-framed, holistic assessment of health and quality of life that is associated with longevity and better health outcomes. We aimed to identify county attributes that are independently associated with a comprehensive, multi-dimensional assessment of individual well-being. We performed a cross-sectional study examining associations between 77 pre-specified county attributes and a multi-dimensional assessment of individual US residents' well-being, captured by the Gallup-Sharecare Well-Being Index. Our cohort included 338,846 survey participants, randomly sampled from 3,118 US counties or county equivalents. We identified twelve county-level factors that were independently associated with individual well-being scores. Together, these twelve factors explained 91% of the variance in individual well-being scores, and they represent four conceptually distinct categories: demographic (% black); social and economic (child poverty, education level [divorced); clinical care (% eligible women obtaining mammography, preventable hospital stays per 100,000, number of federally qualified health centers); and physical environment (% commuting by bicycle and by public transit). Twelve factors across social and economic, clinical care, and physical environmental county-level factors explained the majority of variation in resident well-being.

  12. Identifying county characteristics associated with resident well-being: A population based study.

    Directory of Open Access Journals (Sweden)

    Brita Roy

    Full Text Available Well-being is a positively-framed, holistic assessment of health and quality of life that is associated with longevity and better health outcomes. We aimed to identify county attributes that are independently associated with a comprehensive, multi-dimensional assessment of individual well-being.We performed a cross-sectional study examining associations between 77 pre-specified county attributes and a multi-dimensional assessment of individual US residents' well-being, captured by the Gallup-Sharecare Well-Being Index. Our cohort included 338,846 survey participants, randomly sampled from 3,118 US counties or county equivalents.We identified twelve county-level factors that were independently associated with individual well-being scores. Together, these twelve factors explained 91% of the variance in individual well-being scores, and they represent four conceptually distinct categories: demographic (% black; social and economic (child poverty, education level [

  13. Identifying elements of patient-centered care in underserved populations: a qualitative study of patient perspectives.

    Directory of Open Access Journals (Sweden)

    Sheela Raja

    Full Text Available Patient-centered care is an important goal in the delivery of healthcare. However, many patients do not engage in preventive medical care. In this pilot study, we conducted twenty in depth, semi-structured qualitative interviews at the University of Illinois at Chicago Health Sciences campus in a four month time frame. Many patients were underserved and underinsured, and we wanted to understand their experiences in the healthcare system. Using content analysis, several themes emerged from the interview data. Participants discussed the need for empathy and rapport with their providers. They identified provider behaviors that fostered a positive clinical relationship, including step-by step explanations of procedures, attention to body language and clinic atmosphere, and appropriate time management. Participants identified cost as the most common barrier to engaging in preventive care and discussed children and social support as motivating factors. A long-term relationship with a provider was an important motivator for preventive care, suggesting that the therapeutic alliance was essential to many patients. Conversely, many participants discussed a sense of dehumanization in the healthcare system, reporting that their life circumstances were overlooked, or that they were judged based on insurance status or ethnicity. We discuss implications for provider training and healthcare delivery, including the importance of patient-centered medical homes.

  14. A systematic review of studies identifying predictors of poor return to work outcomes following workplace injury.

    Science.gov (United States)

    Street, Tamara D; Lacey, Sarah J

    2015-06-05

    Injuries occurring in the workplace can have serious implications for the health of the individual, the productivity of the employer and the overall economic community. The objective of this paper is to increase the current state of understanding of individual demographic and psychosocial characteristics associated with extended absenteeism from the workforce due to a workplace injury. Studies included in this systematic literature review tracked participants' return to work status over a minimum of three months, identified either demographic, psychosocial or general injury predictors of poor return to work outcomes and included a heterogeneous sample of workplace injuries. Identified predictors of poor return to work outcomes included older age, female gender, divorced marital status, two or more dependent family members, lower education levels, employment variables associated with reduced labour market desirability, severity or sensitive injury locations, negative attitudes and outcome perceptions of the participant. There is a need for clear and consistent definition and measurement of return to work outcomes and a holistic theoretical model integrating injury, psychosocial and demographic predictors of return to work. Through greater understanding of the nature of factors affecting return to work, improved outcomes could be achieved.

  15. Identifying professionals' needs in integrating electronic pain monitoring in community palliative care services: An interview study.

    Science.gov (United States)

    Taylor, Sally; Allsop, Matthew J; Bekker, Hilary L; Bennett, Michael I; Bewick, Bridgette M

    2017-07-01

    Poor pain assessment is a barrier to effective pain control. There is growing interest internationally in the development and implementation of remote monitoring technologies to enhance assessment in cancer and chronic disease contexts. Findings describe the development and testing of pain monitoring systems, but research identifying the needs of health professionals to implement routine monitoring systems within clinical practice is limited. To inform the development and implementation strategy of an electronic pain monitoring system, PainCheck, by understanding palliative care professionals' needs when integrating PainCheck into routine clinical practice. Qualitative study using face-to-face interviews. Data were analysed using framework analysis Setting/participants: Purposive sample of health professionals managing the palliative care of patients living in the community Results: A total of 15 interviews with health professionals took place. Three meta-themes emerged from the data: (1) uncertainties about integration of PainCheck and changes to current practice, (2) appraisal of current practice and (3) pain management is everybody's responsibility Conclusion: Even the most sceptical of health professionals could see the potential benefits of implementing an electronic patient-reported pain monitoring system. Health professionals have reservations about how PainCheck would work in practice. For optimal use, PainCheck needs embedding within existing electronic health records. Electronic pain monitoring systems have the potential to enable professionals to support patients' pain management more effectively but only when barriers to implementation are appropriately identified and addressed.

  16. Software Development Initiatives to Identify and Mitigate Security Threats - Two Systematic Mapping Studies

    Directory of Open Access Journals (Sweden)

    Paulina Silva

    2016-12-01

    Full Text Available Software Security and development experts have addressed the problem of building secure software systems. There are several processes and initiatives to achieve secure software systems. However, most of these lack empirical evidence of its application and impact in building secure software systems. Two systematic mapping studies (SM have been conducted to cover the existent initiatives for identification and mitigation of security threats. The SMs created were executed in two steps, first in 2015 July, and complemented through a backward snowballing in 2016 July. Integrated results of these two SM studies show a total of 30 relevant sources were identified; 17 different initiatives covering threats identification and 14 covering the mitigation of threats were found. All the initiatives were associated to at least one activity of the Software Development Lifecycle (SDLC; while 6 showed signs of being applied in industrial settings, only 3 initiatives presented experimental evidence of its results through controlled experiments, some of the other selected studies presented case studies or proposals.

  17. Molecular genetic studies in Saudi population; identified variants from GWAS and meta-analysis in stroke.

    Science.gov (United States)

    Alharbi, Khalid Khalaf; Ali Khan, Imran; Alotaibi, Mohammad Abdullah; Saud Aloyaid, Abdullah; Al-Basheer, Haifa Abdulaziz; Alghamdi, Naelah Abdullah; Al-Baradie, Raid Saleem; Al-Sulaiman, A M

    2018-01-01

    Stroke is a multifactorial and heterogeneous disorder, correlates with heritability and considered as one of the major diseases. The prior reports performed the variable models such as genome-wide association studies (GWAS), replication, case-control, cross-sectional and meta-analysis studies and still, we lack diagnostic marker in the global world. There are limited studies were carried out in Saudi population, and we aim to investigate the molecular association of single nucleotide polymorphisms (SNPs) identified through GWAS and meta-analysis studies in stroke patients in the Saudi population. In this case-control study, we have opted gender equality of 207 cases and 207 controls from the capital city of Saudi Arabia in King Saud University Hospital. The peripheral blood (5 ml) sample will be collected in two different vacutainers, and three mL of the coagulated blood will be used for lipid analysis (biochemical tests) and two mL will be used for DNA analysis (molecular tests). Genomic DNA will be extracted with the collected blood samples, and specific primers will be designed for the opted SNPs ( SORT1 -rs646218 and OLR1 -rs11053646 polymorphisms) and PCR-RFLP will be performed and randomly DNA sequencing will be carried out to cross check the results. The rs646218 and rs11053646 polymorphisms were significantly associated with allele, genotype and dominant models with and without crude odds ratios (OR's) and Multiple logistic regression analysis (p Saudi population. The current results were in the association with the prior study results documented through GWAS and meta-analysis association. However, other ethnic population studies should be performed to rule out in the human hereditary diseases.

  18. Genome-wide association study identifies 74 loci associated with educational attainment

    DEFF Research Database (Denmark)

    Okbay, Aysu; P. Beauchamp, Jonathan; Alan Fontana, Mark

    2016-01-01

    -nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural......Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends...... development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals...

  19. How well do discharge diagnoses identify hospitalised patients with community-acquired infections? - a validation study

    DEFF Research Database (Denmark)

    Henriksen, Daniel Pilsgaard; Nielsen, Stig Lønberg; Laursen, Christian Borbjerg

    2014-01-01

    -10 diagnoses was 79.9% (95%CI: 78.1-81.3%), specificity 83.9% (95%CI: 82.6-85.1%), positive likelihood ratio 4.95 (95%CI: 4.58-5.36) and negative likelihood ratio 0.24 (95%CI: 0.22-0.26). The two most common sites of infection, the lower respiratory tract and urinary tract, had positive likelihood......BACKGROUND: Credible measures of disease incidence, trends and mortality can be obtained through surveillance using manual chart review, but this is both time-consuming and expensive. ICD-10 discharge diagnoses are used as surrogate markers of infection, but knowledge on the validity of infections...... in general is sparse. The aim of the study was to determine how well ICD-10 discharge diagnoses identify patients with community-acquired infections in a medical emergency department (ED), overall and related to sites of infection and patient characteristics. METHODS: We manually reviewed 5977 patients...

  20. Local acceptance of wind energy: Factors of success identified in French and German case studies

    International Nuclear Information System (INIS)

    Jobert, Arthur; Laborgne, Pia; Mimler, Solveig

    2007-01-01

    The objective of this paper is to identify and analyse factors that are important for winning acceptance of wind-energy parks on the local level. The developers of wind-energy parks need to know how to manage 'social acceptance' at the different stages of planning, realisation and operation. Five case studies in France and Germany focused on factors of success in developing a wind-energy project on a given site and illuminated how policy frameworks influence local acceptance. Our hypothesis is that these factors fall into two categories: institutional conditions, such as economic incentives and regulations; and site-specific conditions (territorial factors), such as the local economy, the local geography, local actors, and the actual on-site planning process (project management)

  1. Characteristics of Effective Simulation (Preclinical) Teachers as Identified by Dental Students: A Qualitative Study.

    Science.gov (United States)

    McAndrew, Maureen; Mucciolo, Thomas W; Jahangiri, Leila

    2016-11-01

    The aim of this qualitative research study was to identify and categorize criteria for simulation teacher quality preferences as reported by dental students. Second-year dental students at New York University College of Dentistry in 2015 were given a two-question, open-ended survey asking what qualities they liked most and least in a simulation or preclinical teacher. Responses were collected until data saturation was reached. Key words in the responses were identified and coded based on similar relationships and then were grouped into defined categories. A total of 168 respondents out of the target group of 363 students (46.3%) provided 1,062 written comments. Three core themes-character, competence, and communication-emerged from 16 defined categories, which were validated using references from the educational literature. The theme of character encompassed eight of the defined categories (motivation, available, caring, patience, professionalism, empathy, fairness, and happiness) and accounted for 50% of the total student responses. The theme of competence comprised five categories (expertise, knowledgeable, efficient, skillful, and effective) and represented 34% of all responses. The communication theme covered the remaining three categories (feedback, approachable, and interpersonal communication) and contained 17% of the responses. Positive and negative comments in the category of motivation accounted for 11.2% of all student responses. Expertise was the next highest category with 9.3% of the responses, followed closely by 9.1% in the category of available. Among these students, the top five attributes of simulation teachers were motivation, expertise, available, caring, and feedback. While the study did not attempt to correlate these findings with improved student performance, the results can be used in the development of assessment tools for faculty and targeted faculty development programs.

  2. A Qualitative Study to Identify Skills and Competency Required for Hospital Managers

    Science.gov (United States)

    Barati, Omid; Sadeghi, Ahmad; Khammarnia, Mohammad; Siavashi, Elham; Oskrochi, Gholamreza

    2016-01-01

    Introduction Hospital managers aim to improve the efficiency and effectiveness of their institutions through leadership and guidance of medical personnel. Fulfilling these objectives requires a holistic approach to both the management of people and institutional prioritization. The aim of this study was to identify the skills and competencies that hospital managers must demonstrate in order to achieve their objectives. Methods In 2015, a regional, multi-center qualitative study was undertaken in Shiraz, Iran. Interviews and focus group discussions were conducted with university hospital managers, senior managers, faculty members, and post-graduate students, and the results were analyzed using the content analysis method by MAXQDA software. Results Eight key skill themes (communication, experience, appreciation of institution logistics/infrastructure, management skills, motivation, systematic problem solving, ethics, and financial/legal awareness) were identified among the hospital managers. The common challenges that face hospital institutions include problems with hierarchical and organizational structure, excessive rules and regulations, lack of resources, poor post-graduate education, and overall management. Recurring themes with respect to how these could be addressed included changing the culture and belief structure of the hospital, restructuring the organizational hierarchy, and empowering the people. Conclusion In our cohort, practical skills, such as communication and experience, were considered more important than theoretical skills for the effective management and administration of hospitals. Therefore, we suggest that practical, skill-based training should be emphasized for students of these disciplines so they will be better suited to deal with real world challenges. Further organizational improvements also can be attained by the active and constructive involvement of senior university managers. PMID:27504159

  3. Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes.

    Directory of Open Access Journals (Sweden)

    Kevin P Keegan

    2007-11-01

    Full Text Available Five independent groups have reported microarray studies that identify dozens of rhythmically expressed genes in the fruit fly Drosophila melanogaster. Limited overlap among the lists of discovered genes makes it difficult to determine which, if any, exhibit truly rhythmic patterns of expression. We reanalyzed data from all five reports and found two sources for the observed discrepancies, the use of different expression pattern detection algorithms and underlying variation among the datasets. To improve upon the methods originally employed, we developed a new analysis that involves compilation of all existing data, application of identical transformation and standardization procedures followed by ANOVA-based statistical prescreening, and three separate classes of post hoc analysis: cross-correlation to various cycling waveforms, autocorrelation, and a previously described fast Fourier transform-based technique. Permutation-based statistical tests were used to derive significance measures for all post hoc tests. We find application of our method, most significantly the ANOVA prescreening procedure, significantly reduces the false discovery rate relative to that observed among the results of the original five reports while maintaining desirable statistical power. We identify a set of 81 cycling transcripts previously found in one or more of the original reports as well as a novel set of 133 transcripts not found in any of the original studies. We introduce a novel analysis method that compensates for variability observed among the original five Drosophila circadian array reports. Based on the statistical fidelity of our meta-analysis results, and the results of our initial validation experiments (quantitative RT-PCR, we predict many of our newly found genes to be bona fide cyclers, and suggest that they may lead to new insights into the pathways through which clock mechanisms regulate behavioral rhythms.

  4. Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

    Directory of Open Access Journals (Sweden)

    Sandosh Padmanabhan

    2010-10-01

    Full Text Available Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹. The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91], reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027. In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003. In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

  5. Genome-wide association studies identify four ER negative–specific breast cancer risk loci

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

  6. Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-04-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

  7. Simulation Study on Identifiability of UHE Gamma-ray Air Showers

    International Nuclear Information System (INIS)

    Wada, Y.; Inoue, N.; Miyazawa, K.; Vankov, H.P.

    2008-01-01

    The chemical composition of Ultra-High-Energy (UHE) comic rays is one of unsolved mysteries, and its study will give us fruitful information on the origin and acceleration mechanism of UHE cosmic rays. Especially, a detection of UHE gamma-rays by hybrid experiments, such as AUGER and TA, will be a key to solve these questions. The characteristics of UHE gamma-ray showers have been studied by comparing the lateral and longitudinal structures of shower particles calculated with AIRES and our own simulation code, so far. There are apparent differences in a slope of lateral distribution (η) and a depth of shower maximum (Xmax) between gamma-ray and proton induced showers because UHE gamma-ray showers are affected by the LPM effect and the geomagnetic cascading process in an energy region of >10 19.5 eV. Different features between gamma-ray and proton showers are pointed out from the simulation study and an identifiability of gamma-ray showers from proton ones is also discussed by the method of Neural-Network-Analysis

  8. Simulation Study on Identifiability of UHE Gamma-ray Air Showers

    Energy Technology Data Exchange (ETDEWEB)

    Wada, Y.; Inoue, N.; Miyazawa, K. [Graduate School of Science and Engineering, Saitama University, Saitama 338-8570 (Japan); Vankov, H.P. [Institute for Nuclear Research and Nuclear Energy, Bulgaria Academy, Sofia (Bulgaria)

    2008-01-15

    The chemical composition of Ultra-High-Energy (UHE) comic rays is one of unsolved mysteries, and its study will give us fruitful information on the origin and acceleration mechanism of UHE cosmic rays. Especially, a detection of UHE gamma-rays by hybrid experiments, such as AUGER and TA, will be a key to solve these questions. The characteristics of UHE gamma-ray showers have been studied by comparing the lateral and longitudinal structures of shower particles calculated with AIRES and our own simulation code, so far. There are apparent differences in a slope of lateral distribution ({eta}) and a depth of shower maximum (Xmax) between gamma-ray and proton induced showers because UHE gamma-ray showers are affected by the LPM effect and the geomagnetic cascading process in an energy region of >10{sup 19.5}eV. Different features between gamma-ray and proton showers are pointed out from the simulation study and an identifiability of gamma-ray showers from proton ones is also discussed by the method of Neural-Network-Analysis.

  9. Metal ion release from metallothioneins: proteolysis as an alternative to oxidation.

    Science.gov (United States)

    Peroza, Estevão A; dos Santos Cabral, Augusto; Wan, Xiaoqiong; Freisinger, Eva

    2013-09-01

    Metallothioneins (MTs) are among others involved in the cellular regulation of essential Zn(II) and Cu(I) ions. However, the high binding affinity of these proteins requires additional factors to promote metal ion release under physiological conditions. The mechanisms and efficiencies of these processes leave many open questions. We report here a comprehensive analysis of the Zn(II)-release properties of various MTs with special focus on members of the four main subfamilies of plant MTs. Zn(II) competition experiments with the metal ion chelator 4-(2-pyridylazo)resorcinol (PAR) in the presence of the cellular redox pair glutathione (GSH)/glutathione disulfide (GSSG) show that plant MTs from the subfamilies MT1, MT2, and MT3 are remarkably more affected by oxidative stress than those from the Ec subfamily and the well-characterized human MT2 form. In addition, we evaluated proteolytic digestion with trypsin and proteinase K as an alternative mechanism for selective promotion of metal ion release from MTs. Also here the observed percentage of liberated metal ions depends strongly on the MT form evaluated. Closer evaluation of the data additionally allowed deducing the thermodynamic and kinetic properties of the Zn(II) release processes. The Cu(I)-form of chickpea MT2 was used to exemplify that both oxidation and proteolysis are also effective ways to increase the transfer of copper ions to other molecules. Zn(II) release experiments with the individual metal-binding domains of Ec-1 from wheat grain reveal distinct differences from the full-length protein. This triggers the question about the roles of the long cysteine-free peptide stretches typical for plant MTs.

  10. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Science.gov (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

  11. Design considerations for identifying breast cancer risk factors in a population-based study in Africa.

    Science.gov (United States)

    Brinton, Louise A; Awuah, Baffour; Nat Clegg-Lamptey, Joe; Wiafe-Addai, Beatrice; Ansong, Daniel; Nyarko, Kofi M; Wiafe, Seth; Yarney, Joel; Biritwum, Richard; Brotzman, Michelle; Adjei, Andrew A; Adjei, Ernest; Aitpillah, Francis; Edusei, Lawrence; Dedey, Florence; Nyante, Sarah J; Oppong, Joseph; Osei-Bonsu, Ernest; Titiloye, Nicholas; Vanderpuye, Verna; Brew Abaidoo, Emma; Arhin, Bernard; Boakye, Isaac; Frempong, Margaret; Ohene Oti, Naomi; Okyne, Victoria; Figueroa, Jonine D

    2017-06-15

    Although breast cancer is becoming more prevalent in Africa, few epidemiologic studies have been undertaken and appropriate methodologic approaches remain uncertain. We therefore conducted a population-based case-control study in Accra and Kumasi, Ghana, enrolling 2,202 women with lesions suspicious for breast cancer and 2,161 population controls. Biopsy tissue for cases prior to neoadjuvant therapy (if given), blood, saliva and fecal samples were sought for study subjects. Response rates, risk factor prevalences and odds ratios for established breast cancer risk factors were calculated. A total of 54.5% of the recruited cases were diagnosed with malignancies, 36.0% with benign conditions and 9.5% with indeterminate diagnoses. Response rates to interviews were 99.2% in cases and 91.9% in controls, with the vast majority of interviewed subjects providing saliva (97.9% in cases vs. 98.8% in controls) and blood (91.8% vs. 82.5%) samples; lower proportions (58.1% vs. 46.1%) provided fecal samples. While risk factor prevalences were unique as compared to women in other countries (e.g., less education, higher parity), cancer risk factors resembled patterns identified elsewhere (elevated risks associated with higher levels of education, familial histories of breast cancer, low parity and larger body sizes). Subjects with benign conditions were younger and exhibited higher socioeconomic profiles (e.g., higher education and lower parity) than those with malignancies, suggesting selective referral influences. While further defining breast cancer risk factors in Africa, this study showed that successful population-based interdisciplinary studies of cancer in Africa are possible but require close attention to diagnostic referral biases and standardized and documented approaches for high-quality data collection, including biospecimens. © 2017 UICC.

  12. Surface expression and limited proteolysis of ADAM10 are increased by a dominant negative inhibitor of dynamin

    Directory of Open Access Journals (Sweden)

    Slack Barbara E

    2011-05-01

    Full Text Available Abstract Background The amyloid precursor protein (APP is cleaved by β- and γ-secretases to generate toxic amyloid β (Aβ peptides. Alternatively, α-secretases cleave APP within the Aβ domain, precluding Aβ formation and releasing the soluble ectodomain, sAPPα. We previously showed that inhibition of the GTPase dynamin reduced APP internalization and increased release of sAPPα, apparently by prolonging the interaction between APP and α-secretases at the plasma membrane. This was accompanied by a reduction in Aβ generation. In the present study, we investigated whether surface expression of the α-secretase ADAM (a disintegrin and metalloprotease10 is also regulated by dynamin-dependent endocytosis. Results Transfection of human embryonic kidney (HEK cells stably expressing M3 muscarinic receptors with a dominant negative dynamin I mutant (dyn I K44A, increased surface expression of both immature, and mature, catalytically active forms of co-expressed ADAM10. Surface levels of ADAM10 were unaffected by activation of protein kinase C (PKC or M3 receptors, indicating that receptor-coupled shedding of the ADAM substrate APP is unlikely to be mediated by inhibition of ADAM10 endocytosis in this cell line. Dyn I K44A strongly increased the formation of a C-terminal fragment of ADAM10, consistent with earlier reports that the ADAM10 ectodomain is itself a target for sheddases. The abundance of this fragment was increased in the presence of a γ-secretase inhibitor, but was not affected by M3 receptor activation. The dynamin mutant did not affect the distribution of ADAM10 and its C-terminal fragment between raft and non-raft membrane compartments. Conclusions Surface expression and limited proteolysis of ADAM10 are regulated by dynamin-dependent endocytosis, but are unaffected by activation of signaling pathways that upregulate shedding of ADAM substrates such as APP. Modulation of ADAM10 internalization could affect cellular behavior in two

  13. Determination of protein-carbonyls and ubiquitin-mediated proteolysis as biomarkers of oxidative-stress in bivalvia and anthozoa

    International Nuclear Information System (INIS)

    Walker, Stephen Thomas

    2002-01-01

    This study describes the investigation of biomarkers of oxidative-stress in the bivalves Mytilus edulis and Dosinia lupinus, together with host and symbiont tissues of the scleractinian Anthozoa Agaricia agaricites. The biomarkers used were assay of total (via spectrophotometry) and individual (via Western blotting; Oxyblot kit) protein-carbonyls (PC=Os) and content of ubiquitin protein conjugates (UPC) via Western blotting (Bivalvia and Anthozoa) and immunohistochemistry (Anthozoa only). Additional assays for Bivalvia were Trolox equivalent antioxidant capacity (TEAC); and post γ-irradiation survival rates. Experimental stressors for Bivalvia were increased seawater temperature, H 2 O 2 and 60 Co γ-radiation (latter two were used in vivo and in vitro). Comparisons of clean and polluted marine sites are included. Stressors used for Anthozoa were increased solar irradiation concomitant with elevated seawater temperature. Results and conclusions were as follows: individual samples showed considerable variation, pooling of samples improved consistency. Controls for both biomarkers had detectable background levels in each phylum, against which relatively small differences were assessed. In M. edulis, no measurable differences in PC=Os could be determined when elevated seawater temperature or dilute H 2 O 2 ( 2 O 2 (30% v/v) produced a small difference. 60 Co γ-radiation produced clearer differences via Oxyblot and spectrophotometric assays. Comparison of four different tissues from the two bivalves found considerable species-specific and tissue-specific differences. Post-irradiation mortality between species was significantly different (<0.001), D. lupinus was more susceptible than M. edulis. TEAC values generally showed a decrease following irradiation (except for digestive gland). UPCs were clearly different between tissues and between species. PC=Os can be detected by DNPH-reactivity/Western blotting assay in host A. agaricites. UPCs can be assayed via Western

  14. Determination of protein-carbonyls and ubiquitin-mediated proteolysis as biomarkers of oxidative-stress in bivalvia and anthozoa

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Stephen Thomas

    2002-07-01

    This study describes the investigation of biomarkers of oxidative-stress in the bivalves Mytilus edulis and Dosinia lupinus, together with host and symbiont tissues of the scleractinian Anthozoa Agaricia agaricites. The biomarkers used were assay of total (via spectrophotometry) and individual (via Western blotting; Oxyblot kit) protein-carbonyls (PC=Os) and content of ubiquitin protein conjugates (UPC) via Western blotting (Bivalvia and Anthozoa) and immunohistochemistry (Anthozoa only). Additional assays for Bivalvia were Trolox equivalent antioxidant capacity (TEAC); and post {gamma}-irradiation survival rates. Experimental stressors for Bivalvia were increased seawater temperature, H{sub 2}O{sub 2} and {sup 60}Co {gamma}-radiation (latter two were used in vivo and in vitro). Comparisons of clean and polluted marine sites are included. Stressors used for Anthozoa were increased solar irradiation concomitant with elevated seawater temperature. Results and conclusions were as follows: individual samples showed considerable variation, pooling of samples improved consistency. Controls for both biomarkers had detectable background levels in each phylum, against which relatively small differences were assessed. In M. edulis, no measurable differences in PC=Os could be determined when elevated seawater temperature or dilute H{sub 2}O{sub 2} (<30% v/v) stressors were used, nor with between-site comparisons. Concentrated H{sub 2}O{sub 2} (30% v/v) produced a small difference. {sup 60}Co {gamma}-radiation produced clearer differences via Oxyblot and spectrophotometric assays. Comparison of four different tissues from the two bivalves found considerable species-specific and tissue-specific differences. Post-irradiation mortality between species was significantly different (<0.001), D. lupinus was more susceptible than M. edulis. TEAC values generally showed a decrease following irradiation (except for digestive gland). UPCs were clearly different between tissues and

  15. CATALISE: A Multinational and Multidisciplinary Delphi Consensus Study. Identifying Language Impairments in Children.

    Science.gov (United States)

    Bishop, D V M; Snowling, Margaret J; Thompson, Paul A; Greenhalgh, Trisha

    2016-01-01

    Delayed or impaired language development is a common developmental concern, yet there is little agreement about the criteria used to identify and classify language impairments in children. Children's language difficulties are at the interface between education, medicine and the allied professions, who may all adopt different approaches to conceptualising them. Our goal in this study was to use an online Delphi technique to see whether it was possible to achieve consensus among professionals on appropriate criteria for identifying children who might benefit from specialist services. We recruited a panel of 59 experts representing ten disciplines (including education, psychology, speech-language therapy/pathology, paediatrics and child psychiatry) from English-speaking countries (Australia, Canada, Ireland, New Zealand, United Kingdom and USA). The starting point for round 1 was a set of 46 statements based on articles and commentaries in a special issue of a journal focusing on this topic. Panel members rated each statement for both relevance and validity on a seven-point scale, and added free text comments. These responses were synthesised by the first two authors, who then removed, combined or modified items with a view to improving consensus. The resulting set of statements was returned to the panel for a second evaluation (round 2). Consensus (percentage reporting 'agree' or 'strongly agree') was at least 80 percent for 24 of 27 round 2 statements, though many respondents qualified their response with written comments. These were again synthesised by the first two authors. The resulting consensus statement is reported here, with additional summary of relevant evidence, and a concluding commentary on residual disagreements and gaps in the evidence base.

  16. Identifying desertification risk areas using fuzzy membership and geospatial technique - A case study, Kota District, Rajasthan

    Science.gov (United States)

    Dasgupta, Arunima; Sastry, K. L. N.; Dhinwa, P. S.; Rathore, V. S.; Nathawat, M. S.

    2013-08-01

    Desertification risk assessment is important in order to take proper measures for its prevention. Present research intends to identify the areas under risk of desertification along with their severity in terms of degradation in natural parameters. An integrated model with fuzzy membership analysis, fuzzy rule-based inference system and geospatial techniques was adopted, including five specific natural parameters namely slope, soil pH, soil depth, soil texture and NDVI. Individual parameters were classified according to their deviation from mean. Membership of each individual values to be in a certain class was derived using the normal probability density function of that class. Thus if a single class of a single parameter is with mean μ and standard deviation σ, the values falling beyond μ + 2 σ and μ - 2 σ are not representing that class, but a transitional zone between two subsequent classes. These are the most important areas in terms of degradation, as they have the lowest probability to be in a certain class, hence highest probability to be extended or narrowed down in next or previous class respectively. Eventually, these are the values which can be easily altered, under extrogenic influences, hence are identified as risk areas. The overall desertification risk is derived by incorporating the different risk severity of each parameter using fuzzy rule-based interference system in GIS environment. Multicriteria based geo-statistics are applied to locate the areas under different severity of desertification risk. The study revealed that in Kota, various anthropogenic pressures are accelerating land deterioration, coupled with natural erosive forces. Four major sources of desertification in Kota are, namely Gully and Ravine erosion, inappropriate mining practices, growing urbanization and random deforestation.

  17. Identifying context factors explaining physician's low performance in communication assessment: an explorative study in general practice.

    Science.gov (United States)

    Essers, Geurt; van Dulmen, Sandra; van Weel, Chris; van der Vleuten, Cees; Kramer, Anneke

    2011-12-13

    Communication is a key competence for health care professionals. Analysis of registrar and GP communication performance in daily practice, however, suggests a suboptimal application of communication skills. The influence of context factors could reveal why communication performance levels, on average, do not appear adequate. The context of daily practice may require different skills or specific ways of handling these skills, whereas communication skills are mostly treated as generic. So far no empirical analysis of the context has been made. Our aim was to identify context factors that could be related to GP communication. A purposive sample of real-life videotaped GP consultations was analyzed (N = 17). As a frame of reference we chose the MAAS-Global, a widely used assessment instrument for medical communication. By inductive reasoning, we analyzed the GP behaviour in the consultation leading to poor item scores on the MAAS-Global. In these cases we looked for the presence of an intervening context factor, and how this might explain the actual GP communication behaviour. We reached saturation after having viewed 17 consultations. We identified 19 context factors that could potentially explain the deviation from generic recommendations on communication skills. These context factors can be categorized into doctor-related, patient-related, and consultation-related factors. Several context factors seem to influence doctor-patient communication, requiring the GP to apply communication skills differently from recommendations on communication. From this study we conclude that there is a need to explicitly account for context factors in the assessment of GP (and GP registrar) communication performance. The next step is to validate our findings.

  18. Genome-wide association study identifies shared risk loci common to two malignancies in golden retrievers.

    Directory of Open Access Journals (Sweden)

    Noriko Tonomura

    2015-02-01

    Full Text Available Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6% and hemangiosarcoma (20%. We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers.

  19. CATALISE: A Multinational and Multidisciplinary Delphi Consensus Study. Identifying Language Impairments in Children.

    Directory of Open Access Journals (Sweden)

    D V M Bishop

    Full Text Available Delayed or impaired language development is a common developmental concern, yet there is little agreement about the criteria used to identify and classify language impairments in children. Children's language difficulties are at the interface between education, medicine and the allied professions, who may all adopt different approaches to conceptualising them. Our goal in this study was to use an online Delphi technique to see whether it was possible to achieve consensus among professionals on appropriate criteria for identifying children who might benefit from specialist services. We recruited a panel of 59 experts representing ten disciplines (including education, psychology, speech-language therapy/pathology, paediatrics and child psychiatry from English-speaking countries (Australia, Canada, Ireland, New Zealand, United Kingdom and USA. The starting point for round 1 was a set of 46 statements based on articles and commentaries in a special issue of a journal focusing on this topic. Panel members rated each statement for both relevance and validity on a seven-point scale, and added free text comments. These responses were synthesised by the first two authors, who then removed, combined or modified items with a view to improving consensus. The resulting set of statements was returned to the panel for a second evaluation (round 2. Consensus (percentage reporting 'agree' or 'strongly agree' was at least 80 percent for 24 of 27 round 2 statements, though many respondents qualified their response with written comments. These were again synthesised by the first two authors. The resulting consensus statement is reported here, with additional summary of relevant evidence, and a concluding commentary on residual disagreements and gaps in the evidence base.

  20. Source Water Protection Planning for Ontario First Nations Communities: Case Studies Identifying Challenges and Outcomes

    Directory of Open Access Journals (Sweden)

    Leslie Collins

    2017-07-01

    Full Text Available After the Walkerton tragedy in 2000, where drinking water contamination left seven people dead and many suffering from chronic illness, the Province of Ontario, Canada implemented policies to develop Source Water Protection (SWP plans. Under the Clean Water Act (2006, thirty-six regional Conservation Authorities were mandated to develop watershed-based SWP plans under 19 Source Protection Regions. Most First Nations in Ontario are outside of these Source Protection Regions and reserve lands are under Federal jurisdiction. This paper explores how First Nations in Ontario are attempting to address SWP to improve drinking water quality in their communities even though these communities are not part of the Ontario SWP framework. The case studies highlight the gap between the regulatory requirements of the Federal and Provincial governments and the challenges for First Nations in Ontario from lack of funding to implement solutions to address the threats identified in SWP planning. This analysis of different approaches taken by Ontario First Nations shows that the Ontario framework for SWP planning is not an option for the majority of First Nations communities, and does not adequately address threats originating on reserve lands. First Nations attempting to address on-reserve threats to drinking water are using a variety of resources and approaches to develop community SWP plans. However, a common theme of all the cases surveyed is a lack of funding to support implementing solutions for the threats identified by the SWP planning process. Federal government initiatives to address the chronic problem of boil water advisories within Indigenous communities do not recognize SWP planning as a cost-effective tool for improving drinking water quality.

  1. A genome-wide association study identifies protein quantitative trait loci (pQTLs.

    Directory of Open Access Journals (Sweden)

    David Melzer

    2008-05-01

    Full Text Available There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8x10(-57, CCL4L1 (p = 3.9x10(-21, IL18 (p = 6.8x10(-13, LPA (p = 4.4x10(-10, GGT1 (p = 1.5x10(-7, SHBG (p = 3.1x10(-7, CRP (p = 6.4x10(-6 and IL1RN (p = 7.3x10(-6 genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R, altered secretion rates of different sized proteins (LPA, variation in gene copy number (CCL4L1 and altered transcription (GGT1. We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha levels (p = 6.8x10(-40, but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis

  2. Identifying Opportunities for Peer Learning: An Observational Study of Medical Students on Clinical Placements.

    Science.gov (United States)

    Tai, Joanna H; Canny, Benedict J; Haines, Terry P; Molloy, Elizabeth K

    2017-01-01

    Phenomenon: Peer assisted learning (PAL) is frequently employed and researched in preclinical medical education. Fewer studies have examined PAL in the clinical context: These have focused mainly on the accuracy of peer assessment and potential benefits to learner communication and teamwork skills. Research has also examined the positive and negative effects of formal, structured PAL activities in the clinical setting. Given the prevalence of PAL activities during preclinical years, and the unstructured nature of clinical placements, it is likely that nonformal PAL activities are also undertaken. How PAL happens formally and informally and why students find PAL useful in this clinical setting remain poorly understood. This study aimed to describe PAL activities within the context of clinical placement learning and to explore students' perceptions of these activities. An ethnographic study was conducted to gather empirical data on engagement in clinical placement learning activities, including observations and interviews with students in their 1st clinical year, along with their supervising clinicians. Thematic analysis was used to interrogate the data. On average, students used PAL for 5.19 hours per week in a range of activities, of a total of 29.29 hours undertaking placements. PAL was recognized as a means of vicarious learning and had greater perceived value when an educator was present to guide or moderate the learning. Trust between students was seen as a requirement for PAL to be effective. Students found passive observation a barrier to PAL and were able to identify ways to adopt an active stance when observing peers interacting with patients. For example, learners reported that the expectation that they had to provide feedback to peers after task observation, resulted in them taking on a more critical gaze where they were encouraged to consider notions of good practice. Insights: Students use PAL in formal (i.e., tutorial) and nonformal (e.g., peer

  3. Dementia and cognitive disorder identified at a forensic psychiatric examination - a study from Sweden.

    Science.gov (United States)

    Ekström, Anette; Kristiansson, Marianne; Björkstén, Karin Sparring

    2017-09-18

    Few studies have addressed the relationship between dementia and crime. We conducted a study of persons who got a primary or secondary diagnosis of dementia or cognitive disorder in a forensic psychiatric examination. In Sweden, annually about 500 forensic psychiatric examinations are carried out. All cases from 2008 to 2010 with the diagnoses dementia or cognitive disorder were selected from the database of the Swedish National Board of Forensic Medicine. Out of 1471 cases, there were 54 cases of dementia or cognitive disorder. Case files were scrutinized and 17 cases of dementia and 4 cases of cognitive disorder likely to get a dementia diagnosis in a clinical setting were identified and further studied. There were 18 men and 3 women; Median age 66 (n = 21; Range 35-77) years of age. Eleven men but no women had a previous criminal record. There were a total of 38 crimes, mostly violent, committed by the 21 persons. The crimes were of impulsive rather that pre-meditated character. According to the forensic psychiatric diagnoses, dementia was caused by cerebrovascular disorder (n = 4), alcohol or substance abuse (n = 3), cerebral haemorrhage and alcohol (n = 1), head trauma and alcohol (n = 2), Alzheimer's disease (n = 2), Parkinson's disease (n = 1), herpes encephalitis (n = 1) and unspecified (3). Out of four persons diagnosed with cognitive disorder, one also had delusional disorder and another one psychotic disorder and alcohol dependence. An alcohol-related diagnosis was established in ten cases. There were only two cases of Dementia of Alzheimer's type, one of whom also had alcohol intoxication. None was diagnosed with a personality disorder. All but one had a history of somatic or psychiatric comorbidity like head traumas, stroke, other cardio-vascular disorders, epilepsy, depression, psychotic disorders and suicide attempts. In this very ill group, the suggested verdict was probation in one case and different forms of care in the remaining

  4. A Case Study with an Identified Bully: Policy and Practice Implications

    Directory of Open Access Journals (Sweden)

    Huddleston, Lillie

    2011-07-01

    Full Text Available Objective: Bullying is a serious public health problem that may include verbal or physical injury as well as social isolation or exclusion. As a result, research is needed to establish a database for policies and interventions designed to prevent bullying and its negative effects. This paper presented a case study that contributed to the literature by describing an intervention for bullies that has implications for research, practice and related policies regarding bullying.Methods: An individualized intervention for an identified bully was implemented using the Participatory Culture-Specific Intervention Model (PCSIM; Nastasi, Moore, & Varjas, 2004 with a seventh-grade middle school student. Ecological and culture-specific perspectives were used to develop and implement the intervention that included psychoeducational sessions with the student and consultation with the parent and school personnel. A mixed methods intervention design was used with the following informants: the target student, the mother of the student, a teacher and the school counselor. Qualitative data included semi-structured interviews with the parent, teacher and student, narrative classroom observations and evaluation/feedback forms filled out by the student and interventionist. Quantitative data included the following quantitative surveys (i.e., Child Posttraumatic Stress Reaction Index [CPTS-RI] and the Behavior Assessment Scale for Children, 2nd Edition. Both qualitative and quantitative data were used to evaluate the acceptability, integrity and efficacy of this intervention.Results: The process of intervention design, implementation and evaluation are described through an illustrative case study. Qualitative and quantitative findings indicated a decrease in internalizing, externalizing and bullying behaviors as reported by the teacher and the mother, and a high degree of acceptability and treatment integrity as reported by multiple stakeholders.Conclusion: This case

  5. Consistent dietary patterns identified from childhood to adulthood: the cardiovascular risk in Young Finns Study.

    Science.gov (United States)

    Mikkilä, V; Räsänen, L; Raitakari, O T; Pietinen, P; Viikari, J

    2005-06-01

    Dietary patterns are useful in nutritional epidemiology, providing a comprehensive alternative to the traditional approach based on single nutrients. The Cardiovascular Risk in Young Finns Study is a prospective cohort study with a 21-year follow-up. At baseline, detailed quantitative information on subjects' food consumption was obtained using a 48 h dietary recall method (n 1768, aged 3-18 years). The interviews were repeated after 6 and 21 years (n 1200 and n 1037, respectively). We conducted a principal component analysis to identify major dietary patterns at each study point. A set of two similar patterns was recognised throughout the study. Pattern 1 was positively correlated with consumption of traditional Finnish foods, such as rye, potatoes, milk, butter, sausages and coffee, and negatively correlated with fruit, berries and dairy products other than milk. Pattern 1 type of diet was more common among male subjects, smokers and those living in rural areas. Pattern 2, predominant among female subjects, non-smokers and in urban areas, was characterised by more health-conscious food choices such as vegetables, legumes and nuts, tea, rye, cheese and other dairy products, and also by consumption of alcoholic beverages. Tracking of the pattern scores was observed, particularly among subjects who were adolescents at baseline. Of those originally belonging to the uppermost quintile of pattern 1 and 2 scores, 41 and 38 % respectively, persisted in the same quintile 21 years later. Our results suggest that food behaviour and concrete food choices are established already in childhood or adolescence and may significantly track into adulthood.

  6. A study of correlations between identified charged hadrons in hadronic Z{sup 0} decays

    Energy Technology Data Exchange (ETDEWEB)

    Abe, K. [Aomori Univ. (Japan); Abe, K. [Nagoya Univ. (Japan); Abe, T. [Stanford Univ., CA (US). Stanford Linear Accelerator Center] [and others; SLD Collaboration

    1998-06-01

    The authors present a preliminary study of correlations in rapidity between pairs of identified pions, kaons and protons in hadronic Z{sup 0} decays into light flavors. Short range charge correlations are observed between all combinations of these hadron species, confirming that charge, strangeness and baryon number are conserved locally in the jet fragmentation process. The range of this effect is found to be independent of momentum. A strong long-range correlation is observed for high-momentum charged kaon pairs, and weaker long-range {pi}{sup +}-{pi}{sup -}, {pi}{sup +}-K{sup -} and p-K{sup -} correlations are observed. The SLC electron beam polarization is used to tag the quark hemisphere in each event, allowing the first study of rapidities signed such that positive rapidity is along the quark rather than antiquark direction. Distributions of signed rapidities and of ordered differences between signed rapidities provide new insights into leading particle production and several new tests of fragmentation models.

  7. Geological study for identifying potential aquifer zone in Pakes and Bandung Villages, Konang District, Bangkalan Region

    International Nuclear Information System (INIS)

    I Gde Sukadana

    2010-01-01

    Konang District has a problem on fresh water supply particularly in dry season. Two villages in the district, namely Pakes and Konang, are densely populated areas having agriculture activities, so available of sufficient fresh water is necessary. A fresh water source that can be developed in this area is deep groundwater source from potential aquifers. A geological study has been conducted to identify potential aquifer based on lithological aspect and geological structure. According to the regional stratigraphy. the study area consists of Tawun Formation and Ngrayong Formation. They compose of carbonaceous clay stone (the oldest rock unit), carbonaceous clay stone with sandy limestone intercalations, sandy limestone interbed with carbonaceous clay stone, tuff sandstone with clay stone intercalations, and reef limestone (the youngest) respectively. Strike and dip positions of the rocks layers are N110°E/22° - N150°E/26°, located on the south anticline axis with wavy plan to gentle slope of hilly morphology. Among the rock unit, only sandy limestone has fine sand with sub angular in shape and open pack. Qualitatively. this rock has good porosity and permeability and is enables to save and to flow subsurface water. Thus. the sandy limestone is considered as a potential zone for fresh water resources. Whereas, carbonaceous clay stone with clay grain size has low porosity and permeability, so it is potential as a cap rock. (author)

  8. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    Science.gov (United States)

    Wain, Louise V; Verwoert, Germaine C; O’Reilly, Paul F; Shi, Gang; Johnson, Toby; Johnson, Andrew D; Bochud, Murielle; Rice, Kenneth M; Henneman, Peter; Smith, Albert V; Ehret, Georg B; Amin, Najaf; Larson, Martin G; Mooser, Vincent; Hadley, David; Dörr, Marcus; Bis, Joshua C; Aspelund, Thor; Esko, Tõnu; Janssens, A Cecile JW; Zhao, Jing Hua; Heath, Simon; Laan, Maris; Fu, Jingyuan; Pistis, Giorgio; Luan, Jian’an; Arora, Pankaj; Lucas, Gavin; Pirastu, Nicola; Pichler, Irene; Jackson, Anne U; Webster, Rebecca J; Zhang, Feng; Peden, John F; Schmidt, Helena; Tanaka, Toshiko; Campbell, Harry; Igl, Wilmar; Milaneschi, Yuri; Hotteng, Jouke-Jan; Vitart, Veronique; Chasman, Daniel I; Trompet, Stella; Bragg-Gresham, Jennifer L; Alizadeh, Behrooz Z; Chambers, John C; Guo, Xiuqing; Lehtimäki, Terho; Kühnel, Brigitte; Lopez, Lorna M; Polašek, Ozren; Boban, Mladen; Nelson, Christopher P; Morrison, Alanna C; Pihur, Vasyl; Ganesh, Santhi K; Hofman, Albert; Kundu, Suman; Mattace-Raso, Francesco US; Rivadeneira, Fernando; Sijbrands, Eric JG; Uitterlinden, Andre G; Hwang, Shih-Jen; Vasan, Ramachandran S; Wang, Thomas J; Bergmann, Sven; Vollenweider, Peter; Waeber, Gérard; Laitinen, Jaana; Pouta, Anneli; Zitting, Paavo; McArdle, Wendy L; Kroemer, Heyo K; Völker, Uwe; Völzke, Henry; Glazer, Nicole L; Taylor, Kent D; Harris, Tamara B; Alavere, Helene; Haller, Toomas; Keis, Aime; Tammesoo, Mari-Liis; Aulchenko, Yurii; Barroso, Inês; Khaw, Kay-Tee; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Eyheramendy, Susana; Org, Elin; Sõber, Siim; Lu, Xiaowen; Nolte, Ilja M; Penninx, Brenda W; Corre, Tanguy; Masciullo, Corrado; Sala, Cinzia; Groop, Leif; Voight, Benjamin F; Melander, Olle; O’Donnell, Christopher J; Salomaa, Veikko; d’Adamo, Adamo Pio; Fabretto, Antonella; Faletra, Flavio; Ulivi, Sheila; Del Greco, M Fabiola; Facheris, Maurizio; Collins, Francis S; Bergman, Richard N; Beilby, John P; Hung, Joseph; Musk, A William; Mangino, Massimo; Shin, So-Youn; Soranzo, Nicole; Watkins, Hugh; Goel, Anuj; Hamsten, Anders; Gider, Pierre; Loitfelder, Marisa; Zeginigg, Marion; Hernandez, Dena; Najjar, Samer S; Navarro, Pau; Wild, Sarah H; Corsi, Anna Maria; Singleton, Andrew; de Geus, Eco JC; Willemsen, Gonneke; Parker, Alex N; Rose, Lynda M; Buckley, Brendan; Stott, David; Orru, Marco; Uda, Manuela; van der Klauw, Melanie M; Zhang, Weihua; Li, Xinzhong; Scott, James; Chen, Yii-Der Ida; Burke, Gregory L; Kähönen, Mika; Viikari, Jorma; Döring, Angela; Meitinger, Thomas; Davies, Gail; Starr, John M; Emilsson, Valur; Plump, Andrew; Lindeman, Jan H; ’t Hoen, Peter AC; König, Inke R; Felix, Janine F; Clarke, Robert; Hopewell, Jemma C; Ongen, Halit; Breteler, Monique; Debette, Stéphanie; DeStefano, Anita L; Fornage, Myriam; Mitchell, Gary F; Smith, Nicholas L; Holm, Hilma; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Samani, Nilesh J; Preuss, Michael; Rudan, Igor; Hayward, Caroline; Deary, Ian J; Wichmann, H-Erich; Raitakari, Olli T; Palmas, Walter; Kooner, Jaspal S; Stolk, Ronald P; Jukema, J Wouter; Wright, Alan F; Boomsma, Dorret I; Bandinelli, Stefania; Gyllensten, Ulf B; Wilson, James F; Ferrucci, Luigi; Schmidt, Reinhold; Farrall, Martin; Spector, Tim D; Palmer, Lyle J; Tuomilehto, Jaakko; Pfeufer, Arne; Gasparini, Paolo; Siscovick, David; Altshuler, David; Loos, Ruth JF; Toniolo, Daniela; Snieder, Harold; Gieger, Christian; Meneton, Pierre; Wareham, Nicholas J; Oostra, Ben A; Metspalu, Andres; Launer, Lenore; Rettig, Rainer; Strachan, David P; Beckmann, Jacques S; Witteman, Jacqueline CM; Erdmann, Jeanette; van Dijk, Ko Willems; Boerwinkle, Eric; Boehnke, Michael; Ridker, Paul M; Jarvelin, Marjo-Riitta; Chakravarti, Aravinda; Abecasis, Goncalo R; Gudnason, Vilmundur; Newton-Cheh, Christopher; Levy, Daniel; Munroe, Patricia B; Psaty, Bruce M; Caulfield, Mark J; Rao, Dabeeru C

    2012-01-01

    Numerous genetic loci influence systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans 1-3. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N=74,064) and follow-up studies (N=48,607), we identified at genome-wide significance (P= 2.7×10-8 to P=2.3×10-13) four novel PP loci (at 4q12 near CHIC2/PDGFRAI, 7q22.3 near PIK3CG, 8q24.12 in NOV, 11q24.3 near ADAMTS-8), two novel MAP loci (3p21.31 in MAP4, 10q25.3 near ADRB1) and one locus associated with both traits (2q24.3 near FIGN) which has recently been associated with SBP in east Asians. For three of the novel PP signals, the estimated effect for SBP was opposite to that for DBP, in contrast to the majority of common SBP- and DBP-associated variants which show concordant effects on both traits. These findings indicate novel genetic mechanisms underlying blood pressure variation, including pathways that may differentially influence SBP and DBP. PMID:21909110

  9. Feasibility Study to Identify Potential Reductions in Energy Use in Tribal Buildings

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, Willie [Confederated Salish and Kootenai Tribes, Pablo, MT (United States)

    2017-03-30

    Under this project, the Confederated Salish and Kootenai Tribes (CSKT) assessed the technical and economic feasibility of energy efficiency improvements to existing Tribally-owned buildings. The feasibility study followed a systematic approach in identifying, selecting, and ranking recommended measures, recognizing that the appropriateness of a measure would depend not only on technical issues but also on institutional and organizational issues, such as financing options and occupant requirements. The completed study provided the Tribes with the information needed to commit necessary resources to reduce the energy use and cost in approximately 40 Tribal buildings, including the changes that may be needed in each facility’s operation and maintenance and personnel requirements. It also presented an economic analysis of energy-efficiency capital improvements and an annotated list of financing options and possible funding sources for implementation and an overall strategy for implementation. This project was located in various Tribal communities located throughout the Flathead Indian Reservation in Western Montana. Notice: The following is a compilation of Annual Program Review Presentations, Award Modifications, and Quarterly Progress Reports submitted to the Department of Energy’s (DOE) Office of Indian Energy Policy and Programs by the Confederated Salish and Kootenai Tribes under agreement DE-EE0005171. This report covers project activities from September 30, 2011 through December 31, 2014 and has been uploaded to OSTI by DOE as a substitute for the required Final Technical Report which was not received by DOE from the project recipient.

  10. A Study of Correlations Between Identified Charged Hadrons in Hadronic Z0 Decays

    International Nuclear Information System (INIS)

    Burrows, Phil

    2000-01-01

    The authors present a preliminary study of correlations in rapidity between pairs of identified charged pions, kaons and protons using the entire SLD data sample of 550,000 hadronic Z 0 decays. Short range charge correlations are observed between all combinations of these hadron species, indicating local conservation of quantum numbers and charge ordering in the jet fragmentation process. The rapidity range of this effect is found to be independent of particle momentum. A strong long-range K + -K - correlation is observed at high-momentum and weaker long-range pi + -pi - , pi + -K - p-K - and p anti-p correlations are observed in light flavor events, providing new information on leading particle production in u, d and s jets. The long-range correlations observed in c anti-c and b anti-b events are markedly different and consistent with expectations based on known decay properties of the leading heavy hadrons. In addition, the SLC electron beam polarization is used to tag the quark hemisphere in each event, allowing the first study of rapidities signed such that positive rapidity is along the quark rather than antiquark direction. Distributions of ordered differences in signed rapidity between pairs of particles provide a direct probe of quantum number ordering along the quark-antiquark axis and other new insights into the fragmentation process

  11. Unmet health needs identified by Haitian women as priorities for attention: a qualitative study.

    Science.gov (United States)

    Peragallo Urrutia, Rachel; Merisier, Delson; Small, Maria; Urrutia, Eugene; Tinfo, Nicole; Walmer, David K

    2012-06-01

    This 2009 qualitative study investigated Haitian women's most pressing health needs, barriers to meeting those needs and proposed solutions, and how they thought the community and outside organizations should be involved in addressing their needs. The impetus for the study was to get community input into the development of a Family Health Centre in Leogane, Haiti. Individual interviews and focus group discussions were conducted with 52 adult women in six communities surrounding Leogane. The most pressing health needs named by the women were accessible, available and affordable health care, potable water, enough food to eat, improved economy, employment, sanitation and education, including health education. Institutional corruption, lack of infrastructure and social organization, the cost of health care, distance from services and lack of transport as barriers to care were also important themes. The involvement of foreign organizations and local community groups, including grassroots women's groups who would work in the best interests of other women, were identified as the most effective solutions. Organizations seeking to improve women's health care in Haiti should develop services and interventions that prioritize community partnership and leadership, foster partnerships with government, and focus on public health needs. Copyright © 2012 Reproductive Health Matters. Published by Elsevier Ltd. All rights reserved.

  12. In Situ Proteolysis for Crystallization of Membrane Bound Cytochrome P450 17A1 and 17A2 Proteins from Zebrafish.

    Science.gov (United States)

    Lei, Li; Egli, Martin

    2016-04-01

    Fish and human cytochrome P450 (P450) 17A1 catalyze both steroid 17α-hydroxylation and 17α,20-lyase reactions. Fish P450 17A2 catalyzes only 17α-hydroxylation. Both enzymes are microsomal-type P450s, integral membrane proteins that bind to the membrane through their N-terminal hydrophobic segment, the signal anchor sequence. The presence of this N-terminal region renders expression of full-length proteins challenging or impossible. For some proteins, variable truncation of the signal anchor sequence precludes expression or results in poor expression levels. To crystallize P450 17A1 and 17A2 in order to gain insight into their different activities, we used an alternative N-terminal sequence to boost expression together with in situ proteolysis. Key features of our approach to identify crystallizable P450 fragments were the use of an N-terminal leader sequence, a screen composed of 12 proteases to establish optimal cleavage, variations of protease concentration in combination with an SDS-PAGE assay, and analysis of the resulting fragments using Edman sequencing. Described in this unit are protocols for vector preparation, expression, purification, and in situ proteolytic crystallization of two membrane-bound P450 proteins. Copyright © 2016 John Wiley & Sons, Inc.

  13. Genome-wide association study identifies genetic loci associated with iron deficiency.

    Directory of Open Access Journals (Sweden)

    Christine E McLaren

    2011-03-01

    Full Text Available The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS was performed using DNA collected from white men aged≥25 y and women≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS Study with serum ferritin (SF≤12 µg/L (cases and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women. Regression analysis was used to examine the association between case-control status (336 cases, 343 controls and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10(-7 for all. An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P=7.0×10(-9, corrected P=0.012 was replicated within the VA samples (observed P=0.012. Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification.

  14. Improving healthcare practice behaviors: an exploratory study identifying effective and ineffective behaviors in healthcare.

    Science.gov (United States)

    Van Fleet, David D; Peterson, Tim O

    2016-01-01

    The purpose of this paper is to present the results of exploratory research designed to develop an awareness of healthcare behaviors, with a view toward improving the customer satisfaction with healthcare services. It examines the relationship between healthcare providers and their consumers/patients/clients. The study uses a critical incident methodology, with both effective and ineffective behavioral specimens examined across different provider groups. The effects of these different behaviors on what Berry (1999) identified as the common core values of service organizations are examined, as those values are required to build a lasting service relationship. Also examined are categories of healthcare practice based on the National Quality Strategy priorities. The most obvious is the retrospective nature of the method used. How accurate are patient or consumer memories? Are they capable of making valid judgments of healthcare experiences (Berry and Bendapudi, 2003)? While an obvious limitation, such recollections are clearly important as they may be paramount in following the healthcare practitioners' instructions, loyalty for repeat business, making recommendations to others and the like. Further, studies have shown retrospective reports to be accurate and useful (Miller et al., 1997). With this information, healthcare educators should be in a better position to improve the training offered in their programs and practitioners to better serve their customers. The findings would indicate that the human values of excellence, innovation, joy, respect and integrity play a significant role in building a strong service relationship between consumer and healthcare provider. Berry (1999) has argued that the overriding importance in building a lasting service business is human values. This exploratory study has shown how critical incident analysis can be used to determine both effective and ineffective practices of different medical providers. It also provides guidelines as

  15. A study looking at the effectiveness of developmental screening in identifying learning disabilities in early childhood.

    Science.gov (United States)

    Flanagan, O; Nualláin, S O

    2001-05-01

    This is a retrospective study of children under six years of age referred to the Brothers of Charity Early Intervention Services in County Galway, a service that caters for children under 6 years with learning disabilities. The aim in doing this study was to assess the value of routine developmental screening in identifying children with learning difficulties. This study also investigates the patterns and sources of referral to the remedial services provided by the Brothers of Charity and highlights possible avoidable delays in referral. The results showed that many children were referred for remedial services late. The reasons for late referral included late identification of some children with problems, insufficient co-ordination of community-based services and a lack of awareness of the importance of early intervention in some cases. As some communication disorders such as autism, autistic spectrum disorders and specific language delay may not express themselves until the later part of the second year of life, the 18-24 month developmental assessment is of vital importance. However identification of these disorders can present difficulties and may call for additional training for professionals involved in the developmental screening of children in that age group. The interval between initial identification and referral for remedial care in many cases was more than twelve months. We propose that, in order to minimize this time, children requiring a more in-depth assessment should be assessed by a community-based multidisciplinary team, enabling integrated assessment by the different disciplines and thus speedier referral to remedial services.

  16. Identifying predictors of attitudes towards local onshore wind development with reference to an English case study

    International Nuclear Information System (INIS)

    Jones, Christopher R.; Eiser, J. Richard

    2009-01-01

    The threats posed by climate change are placing governments under increasing pressure to meet electricity demand from low-carbon sources. In many countries, including the UK, legislation is in place to ensure the continued expansion of renewable energy capacity. Onshore wind turbines are expected to play a key role in achieving these aims. However, despite high levels of public support for onshore wind development in principle, specific projects often experience local opposition. Traditionally this difference in general and specific attitudes has been attributed to NIMBYism (not in my back yard), but evidence is increasingly calling this assumption into question. This study used multiple regression analysis to identify what factors might predict attitudes towards mooted wind development in Sheffield, England. We report on the attitudes of two groups; one group (target) living close to four sites earmarked for development and an unaffected comparison group (comparison). We found little evidence of NIMBYism amongst members of the target group; instead, differences between general and specific attitudes appeared attributable to uncertainty regarding the proposals. The results are discussed with respect to literature highlighting the importance of early, continued and responsive community involvement in combating local opposition and facilitating the deployment of onshore wind turbines.

  17. BIBLIOGRAPHIC STUDY IN RISK MANAGEMENT AIMED TO IDENTIFY MORE REFERENCED TOOLS, METHODS AND RELATIONSHIPS

    Directory of Open Access Journals (Sweden)

    Alamir Costa Louro

    2015-06-01

    Full Text Available The objective of this paper is to identify and discuss trends in tools and methods used in project risk management and its relationship to other matters, using current scientific articles. The focus isn´t in understanding how they work in technical terms, but think about the possibilities of deepening in academic studies, including making several suggestions for future research. Adjacent to the article there is a discussion about an alleged "one best way" imperative normativity approach. It was answered the following research questions: what subjects and theories are related to project risk management tools and methods? The first contribution is related to the importance of the academic Chris Chapman as an author who has more published and also more referenced in the survey. There are several contributions on various subjects such as: the perception of the existence of many conceptual papers; papers about construction industry, problematization of contracts according to agency theory, IT and ERPs issues. Other contributions came from the bibliometric method that brings lot of consolidated information about terms, topics, authors, references, periods and, of course, methods and tools about Project Risk Management.

  18. A RELAP5 study to identify flow regime in natural circulation phenomenon

    Energy Technology Data Exchange (ETDEWEB)

    Sabundjian, Gaiane; Torres, Walmir M.; Macedo, Luiz A.; Mesquita, Roberto N.; Andrade, Delvonei A.; Umbehaun, Pedro E.; Conti, Thadeu N.; Masotti, Paulo H.F.; Belchior Junior, Antonio; Angelo, Gabriel, E-mail: gdjian@ipen.b, E-mail: umbehaun@ipen.b, E-mail: wmtorres@ipen.b, E-mail: tnconti@ipen.b, E-mail: rnavarro@ipen.b, E-mail: lamacedo@ipen.b, E-mail: pmasotti@ipen.b, E-mail: abelchior@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    There has been a crescent interest in the scientific community in the study of natural circulation phenomenon. New generation of compact nuclear reactors uses the natural circulation of the fluid as a system of cooling and of residual heat removal in case of accident or shutdown. The objective of this paper is to compare the flow patterns of experimental data and numerical simulation for the natural circulation phenomenon in two-phase flow regime. An experimental circuit built with glass tubes is used for the experiments. Thus, it allows the thermal hydraulic phenomena visualization. There is an electric heater as the heat source, a heat exchanger as the heat sink and an expansion tank to accommodate fluid density excursions. The circuit instrumentation consists of thermocouples and pressure meters to better keep track of the flow and heat transfer phenomena. Data acquisition is performed through a computer interface developed with LABVIEW. The characteristic of the regime is identified using photography techniques. Numerical modeling and simulation is done with the thermal hydraulic code RELAP5, which is widely used for this purpose. This numerical simulation is capable to reproduce some of the flow regimes which are present in the circuit for the natural circulation phenomenon. Comparison between experimental and numerical simulation is presented in this work. (author)

  19. Truncation studies of alpha-melanotropin peptides identify tripeptide analogues exhibiting prolonged agonist bioactivity.

    Science.gov (United States)

    Haskell-Luevano, C; Sawyer, T K; Hendrata, S; North, C; Panahinia, L; Stum, M; Staples, D J; Castrucci, A M; Hadley, M F; Hruby, V J

    1996-01-01

    Truncation studies of alpha-melanotropin peptides identify tripeptide analogues exhibiting prolonged agonist bioactivity: PEPTIDES 17(6) 995-1002, 1996.-Systematic analysis of fragment derivatives of the superpotent alpha-MSH analogue. Ac-Ser.Tyr-Ser-Nle4-Glu- His-DPhe7-Arg-Trp-Gly-Lys-Pro-Val-NH2(NDP-MSH), led to the discovery of tripeptide agonists possessing prolonged bioactivity in the frog skin assay. Of particular significance to this discovery was Ac-DPhe-Arg-DTrp-NH2, which was the most potent tripeptide in this series exhibiting sustained melanotropic activity. Different pharmacophore models appear to exist that are dependent on the substructure and stereochemistry of the MSH(6-9) "active site." The tripeptides Ac-DPhe-Arg-Trp-NH2, Ac-DPhe-Arg-DTrp-NH2, and Ac-DPhe-DArg-Trp-NH2 stereo-chemical combinations require only Phe7-Xaa8-Trp9, whereas Ac-DPhe-DArg-DTrp-NH2, Ac-Phe-Arg-DTrp-NH2, and Ac-Phe-Arg-Trp-NH2 additionally require His4 for minimal biological activity. Ac-DPhe-Arg-DTrp-NH2 represents a novel prototype lead for the development of MSH-based peptidomimetic agonists.

  20. Identifying Risk Factors of Boot Procurement: A Case Study of Stadium Australia

    Directory of Open Access Journals (Sweden)

    Marcus Jefferies

    2012-11-01

    Full Text Available Private sector input into the procurement of public works and services is continuing to increase. This has partly arisen out of a requirement for infrastructure development to be undertaken at a rate that maintains and allows growth. This has become a major challange for the construction industry that cannot be met by government alone. The emergence of Build-Own-Operate-Transfer (BOOT schemes as a response to this challange provides a means for developing the infrastructure of a country without directly impacting on the governments budgetary constraints. The concepts of BOOT are without doubt extremely complex arrangements, which bring to the construction sector risks not experienced previously. Many of the infrastructure partnerships between public and private sector in the pastare yet to provide evidence of successful completion, since few of the concession periods have expired. This paper provides an identified list of risk factors to a case study of Stadium Australia. The most significant risk associated with Stadium Australia include the bidding process, the high level of public scrutiny, post-Olympic Games facility revenue and the complicated nature of the consortium structure.  

  1. Identifying Risk Factors of Boot Procurement: A Case Study of Stadium Australia

    Directory of Open Access Journals (Sweden)

    Marcus Jefferies

    2012-11-01

    Full Text Available Private sector input into the procurement of public works and services is continuing to increase. This has partly arisen out of a requirement for infrastructure development to be undertaken at a rate that maintains and allows growth. This has become a major challange for the construction industry that cannot be met by government alone. The emergence of Build-Own-Operate-Transfer (BOOT schemes as a response to this challange provides a means for developing the infrastructure of a country without directly impacting on the governments budgetary constraints. The concepts of BOOT are without doubt extremely complex arrangements, which bring to the construction sector risks not experienced previously. Many of the infrastructure partnerships between public and private sector in the pastare yet to provide evidence of successful completion, since few of the concession periods have expired. This paper provides an identified list of risk factors to a case study of Stadium Australia. The most significant risk associated with Stadium Australia include the bidding process, the high level of public scrutiny, post-Olympic Games facility revenue and the complicated nature of the consortium structure.

  2. The Sports Challenge international programme for identified 'at risk' children and adolescents: a Singapore study.

    Science.gov (United States)

    Tester, G J; Watkins, G G; Rouse, I

    1999-01-01

    The current world wide phenomena of youth suicide which became a major issue for countries in the early nineties, is still growing exponentially. The Sports Challenge program was initiated in 1992 in Western Australia to identify 'at risk' children and adolescents who display: a low sense of basic trust, a sense of shame and doubt, a sense of inferiority and a sense of identity confusion with common characteristics of low self esteem. The subsequent program is based on a strong statistical paradigm encompassing current and historical information with reliable and objective evaluation measures. To this end, since 1992, Sports Challenge has been recognised as a 'World Best Practice' in redressing the issue of 'at risk' children and adolescents. The program now operates in over 150 schools and communities throughout Australia and 24 schools and Detention Centres in Singapore. This paper will allow a window into the development of the program and the successful transfer of the project into Singapore. The Singapore study which began in 1996 has revealed the success of the Sports Challenge program cross culturally with improvement in self esteem and self concept of 'at risk' groups in the range of 18% to 44%.

  3. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    Directory of Open Access Journals (Sweden)

    Moreno Victor

    2011-08-01

    Full Text Available Abstract Background Colorectal cancer (CRC is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. Methods CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. Results None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive, rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive, rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant, and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive. In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1

  4. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    International Nuclear Information System (INIS)

    Abulí, Anna; Morillas, Juan D; Rigau, Joaquim; Latorre, Mercedes; Fernández-Bañares, Fernando; Peña, Elena; Riestra, Sabino; Payá, Artemio; Jover, Rodrigo; Xicola, Rosa M; Llor, Xavier; Fernández-Rozadilla, Ceres; Carvajal-Carmona, Luis; Villanueva, Cristina M; Moreno, Victor; Piqué, Josep M; Carracedo, Angel; Castells, Antoni; Andreu, Montserrat; Ruiz-Ponte, Clara; Castellví-Bel, Sergi; Alonso-Espinaco, Virginia; Muñoz, Jenifer; Gonzalo, Victoria; Bessa, Xavier; González, Dolors; Clofent, Joan; Cubiella, Joaquin

    2011-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1

  5. Time-Course of Muscle Mass Loss, Damage, and Proteolysis in Gastrocnemius following Unloading and Reloading: Implications in Chronic Diseases

    Science.gov (United States)

    Chacon-Cabrera, Alba; Lund-Palau, Helena; Gea, Joaquim; Barreiro, Esther

    2016-01-01

    Background Disuse muscle atrophy is a major comorbidity in patients with chronic diseases including cancer. We sought to explore the kinetics of molecular mechanisms shown to be involved in muscle mass loss throughout time in a mouse model of disuse muscle atrophy and recovery following immobilization. Methods Body and muscle weights, grip strength, muscle phenotype (fiber type composition and morphometry and muscle structural alterations), proteolysis, contractile proteins, systemic troponin I, and mitochondrial content were assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15 and 30 days) of non-invasive hindlimb immobilization (plastic splint, I cohorts) and in those exposed to reloading for different time-points (1, 3, 7, 15, and 30 days, R cohorts) following a seven-day period of immobilization. Groups of control animals were also used. Results Compared to non-exposed controls, muscle weight, limb strength, slow- and fast-twitch cross-sectional areas, mtDNA/nDNA, and myosin content were decreased in mice of I cohorts, whereas tyrosine release, ubiquitin-proteasome activity, muscle injury and systemic troponin I levels were increased. Gastrocnemius reloading following splint removal improved muscle mass loss, strength, fiber atrophy, injury, myosin content, and mtDNA/nDNA, while reducing ubiquitin-proteasome activity and proteolysis. Conclusions A consistent program of molecular and cellular events leading to reduced gastrocnemius muscle mass and mitochondrial content and reduced strength, enhanced proteolysis, and injury, was seen in this non-invasive mouse model of disuse muscle atrophy. Unloading of the muscle following removal of the splint significantly improved the alterations seen during unloading, characterized by a specific kinetic profile of molecular events involved in muscle regeneration. These findings have implications in patients with chronic diseases including cancer in whom physical activity may be severely compromised. PMID

  6. Identifying the Education Needs of the Business Analyst: An Australian Study

    Directory of Open Access Journals (Sweden)

    Deborah Richards

    2014-06-01

    Full Text Available The Business Analyst (BA plays a key role in ensuring that technology is appropriately used to achieve the organisation’s goals. This important mediating role is currently in high (unmet demand in many English-speaking countries and thus more people need to be trained for this role. To determine the educational and/or training needs of a BA we conducted a survey in the Information and Communication Technology industry in Australia. The survey items are based on prior studies of information systems educational requirements and the internationally-developed Skills Framework for the Information Age (SFIA that has been endorsed by the Australian Computer Society. From the literature we identified three types of skills: soft, business and technical. With the increasing importance of GreenIT and the pivotal role that the BA could play in green decision making, we added a fourth type of skill: green. The survey considers 85 skills, their importance, the level of attainment of that skill, skill gaps and types of skills. Results show that all soft skills were considered to be important with the smallest knowledge gaps. Selected business skills and green skills were seen to be important. Technical skills were considered less important, but also where the largest knowledge gaps existed. Further we asked respondents whether each skill should be acquired via an undergraduate or postgraduate degree and/or industry training and experience. We found that the workplace was considered the most appropriate place to acquire and/or develop all skills, except the ability to innovate. While we found that softskills should be taught almost equally at the undergraduate and postgraduate level, business and green skills were more appropriate in a postgraduate degree. In contrast, technical skills were best acquired in an undergraduate program of study.

  7. Identifying Patients with Bacteremia in Community-Hospital Emergency Rooms: A Retrospective Cohort Study.

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    Taro Takeshima

    Full Text Available (1 To develop a clinical prediction rule to identify patients with bacteremia, using only information that is readily available in the emergency room (ER of community hospitals, and (2 to test the validity of that rule with a separate, independent set of data.Multicenter retrospective cohort study.To derive the clinical prediction rule we used data from 3 community hospitals in Japan (derivation. We tested the rule using data from one other community hospital (validation, which was not among the three "derivation" hospitals.Adults (age ≥ 16 years old who had undergone blood-culture testing while in the ER between April 2011 and March 2012. For the derivation data, n = 1515 (randomly sampled from 7026 patients, and for the validation data n = 467 (from 823 patients.We analyzed 28 candidate predictors of bacteremia, including demographic data, signs and symptoms, comorbid conditions, and basic laboratory data. Chi-square tests and multiple logistic regression were used to derive an integer risk score (the "ID-BactER" score. Sensitivity, specificity, likelihood ratios, and the area under the receiver operating characteristic curve (i.e., the AUC were computed.There were 241 cases of bacteremia in the derivation data. Eleven candidate predictors were used in the ID-BactER score: age, chills, vomiting, mental status, temperature, systolic blood pressure, abdominal sign, white blood-cell count, platelets, blood urea nitrogen, and C-reactive protein. The AUCs was 0.80 (derivation and 0.74 (validation. For ID-BactER scores ≥ 2, the sensitivities for derivation and validation data were 98% and 97%, and specificities were 20% and 14%, respectively.The ID-BactER score can be computed from information that is readily available in the ERs of community hospitals. Future studies should focus on developing a score with a higher specificity while maintaining the desired sensitivity.

  8. Study on the identifying of meat's visible spectrum based on BP artificial neural network

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    Li, Xiaotian; Zhang, Tieqiang; Li, Bo; Jiang, Yongheng; Liu, Binghui; Li, Zhaokai

    2006-01-01

    A method to identify different meat by the visible and reflected spectra of meat with BP artificial neural net (BP-ANN) was introduced in this paper. The visible and reflected spectra (from 420 to 535nm) of different meat (beef and pork) were measured with fiber sensor spectrometer. A kind of ANN with a double-hidden layer was created to identify the different meat automatically. Its right ratio reaches 92.71%.

  9. Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy.

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    Klaus Stark

    2010-10-01

    Full Text Available Dilated cardiomyopathy (DCM is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39% and idiopathic DCM (p = 1.06 × 10⁻⁶, OR  = 0.67 [95% CI 0.57-0.79] for the minor allele T. Three more SNPs showed p < 2.21 × 10⁻⁵. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n =564, n = 981 controls, p = 2.07 × 10⁻³, OR = 0.79 [95% CI 0.67-0.92], France 1 (n = 433 cases, n = 395 controls, p =3.73 × 10⁻³, OR  = 0.74 [95% CI 0.60-0.91], and France 2 (n = 249 cases, n = 380 controls, p = 2.26 × 10⁻⁴, OR  = 0.63 [95% CI 0.50-0.81]. The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28 × 10⁻¹³, OR= 0.72 [95% CI 0.65-0.78]. None of the other three SNPs showed significant results in the replication stage.This finding of the HSPB7 gene from a genetic search for idiopathic DCM using

  10. Identifying clinical correlates for suicide among epilepsy patients in South Korea: A case-control study.

    Science.gov (United States)

    Park, Sung-Jin; Lee, Hochang Benjamin; Ahn, Myung Hee; Park, Subin; Choi, Eun Ju; Lee, Hoon-Jin; Ryu, Han Uk; Kang, Joong-Koo; Hong, Jin Pyo

    2015-12-01

    Suicide is a major cause of premature mortality in patients with epilepsy. We aimed to identify the clinical correlates of suicide in these patients. We conducted a matched, case-control study based on a clinical case registry of epilepsy patients (n = 35,638) treated between January 1994 and December 2011 at an academic tertiary medical center in Seoul, Korea. Each epilepsy patient in the suicide group (n = 74) was matched with three epilepsy patients in the nonsuicide group (n = 222) by age, gender, and approximate time at first treatment. The clinical characteristics of the patients in both groups were then compared. In a univariate analysis, seizure frequency during the year before suicide, use of antiepileptic drug polytherapy, lack of aura before seizure, diagnosis of temporal lobe epilepsy, use of levetiracetam, psychiatric comorbidity, and use of antidepressants were all significantly higher in the suicide group than in the nonsuicide group. Multivariate analysis revealed that a high seizure frequency (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.04-10.2), a lack of aura before seizure (OR 4.0, 95% CI 1.7-9.3), temporal lobe epilepsy (OR 3.7, 95% CI 1.6-8.6), and use of levetiracetam (OR 7.6, 95% CI 1.1-53.7) and antidepressants (OR 7.2, 95% CI 1.5-34.1) were all associated with a higher probability of suicide. Patients with temporal lobe epilepsy who experience seizures weekly or more frequently, experience a lack of aura, use levetiracetam, or take antidepressants are all at a higher risk of suicide and should be monitored closely. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  11. Developing a workflow to identify inconsistencies in volunteered geographic information: a phenological case study

    Science.gov (United States)

    Mehdipoor, Hamed; Zurita-Milla, Raul; Rosemartin, Alyssa; Gerst, Katharine L.; Weltzin, Jake F.

    2015-01-01

    Recent improvements in online information communication and mobile location-aware technologies have led to the production of large volumes of volunteered geographic information. Widespread, large-scale efforts by volunteers to collect data can inform and drive scientific advances in diverse fields, including ecology and climatology. Traditional workflows to check the quality of such volunteered information can be costly and time consuming as they heavily rely on human interventions. However, identifying factors that can influence data quality, such as inconsistency, is crucial when these data are used in modeling and decision-making frameworks. Recently developed workflows use simple statistical approaches that assume that the majority of the information is consistent. However, this assumption is not generalizable, and ignores underlying geographic and environmental contextual variability that may explain apparent inconsistencies. Here we describe an automated workflow to check inconsistency based on the availability of contextual environmental information for sampling locations. The workflow consists of three steps: (1) dimensionality reduction to facilitate further analysis and interpretation of results, (2) model-based clustering to group observations according to their contextual conditions, and (3) identification of inconsistent observations within each cluster. The workflow was applied to volunteered observations of flowering in common and cloned lilac plants (Syringa vulgaris and Syringa x chinensis) in the United States for the period 1980 to 2013. About 97% of the observations for both common and cloned lilacs were flagged as consistent, indicating that volunteers provided reliable information for this case study. Relative to the original dataset, the exclusion of inconsistent observations changed the apparent rate of change in lilac bloom dates by two days per decade, indicating the importance of inconsistency checking as a key step in data quality

  12. Identifying functional zones of denitrification in heterogeneous aquifer systems by numerical simulations - a case study

    Science.gov (United States)

    Jang, E.; Kalbacher, T.; He, W.; Shao, H.; Schueth, C.; Kolditz, O.

    2014-12-01

    Nitrate contamination in shallow groundwater is still one of the common problems in many countries. Because of its high solubility and anionic nature, nitrate can easily leach through soil and persist in groundwater for decades. High nitrate concentration has been suggested as a major cause of accelerated eutrophication, methemoglobinemia and gastric cancer. There are several factors influencing the fate of nitrate in groundwater system, which is e.g. distribution of N- sources to soil and groundwater, distribution and amount of reactive substances maintaining denitrification, rate of nitrate degradation and its kinetics, and geological characteristics of the aquifer. Nitrate transport and redox transformation processes are closely linked to complex and spatially distributed physical and chemical interaction, therefore it is difficult to predict and quantify in the field and laboratory experiment. Models can play a key role in elucidation of nitrate reduction pathway in groundwater system and in the design and evaluation of field tests to investigate in situ remediation technologies as well. The goal of the current study is to predict groundwater vulnerability to nitrate, to identify functional zones of denitrification in heterogeneous aquifer systems and to describe the uncertainty of the predictions due to scale effects. For this aim, we developed a kinetic model using multi-component mass transport code OpenGeoSys coupling with IPhreeqc module of the geochemical solver PHREEQC. The developed model included sequential aerobic and nitrate-based respiration, multi-Monod kinetics, multi-species biogeochemical reactions, and geological characteristics of the groundwater aquifer. Moreover water-rock interaction such as secondary mineral precipitation was also included in this model. In this presentation, we focused on the general modelling approach and present the simulation results of nitrate transport simulation in a hypothetical aquifer systems based on data from

  13. Identifying objective criterion to determine a complicated task – A comparative study

    International Nuclear Information System (INIS)

    Park, Jinkyun; Jung, Wondea

    2015-01-01

    Highlights: • Reliable estimation on the likelihood of human error is very critical. • Still there is no clear and objective criterion on a complicated task. • Subjective difficulty scores rated by 75 high speed train drivers are collected. • Collected difficulty scores are compared with the associated TACOM scores. • Criteria for task complexity level seem to be determined by the TACOM measure. - Abstract: A reliable estimation on the likelihood of human error is very critical for evaluating the safety of a large process control system such as NPPs (Nuclear Power Plants). In this regard, one of the determinants is to decide the level of an important PSF (Performance Shaping Factor) through a clear and objective manner along with the context of a given task. Unfortunately, it seems that there are no such decision criteria for certain PSFs including the complexity of a task. Therefore, the feasibility of the TACOM (Task Complexity) measure in providing objective criteria that are helpful for distinguishing the level of a task complexity is investigated in this study. To this end, subjective difficulty scores rated by 75 high-speed train drivers are collected for 38 tasks. After that, subjective difficulty scores are compared with the associated TACOM scores being quantified based on these tasks. As a result, it is observed that there is a significant correlation between subjective difficulty scores rated by high-speed train drivers and the associated TACOM scores. Accordingly, it is promising to expect that the TACOM measure can be used as an objective tool to identify the level of a task complexity in terms of an HRA (Human Reliability Analysis)

  14. Identifying a Computer Forensics Expert: A Study to Measure the Characteristics of Forensic Computer Examiners

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    Gregory H. Carlton

    2010-03-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 The usage of digital evidence from electronic devices has been rapidly expanding within litigation, and along with this increased usage, the reliance upon forensic computer examiners to acquire, analyze, and report upon this evidence is also rapidly growing. This growing demand for forensic computer examiners raises questions concerning the selection of individuals qualified to perform this work. While courts have mechanisms for qualifying witnesses that provide testimony based on scientific data, such as digital data, the qualifying criteria covers a wide variety of characteristics including, education, experience, training, professional certifications, or other special skills. In this study, we compare task performance responses from forensic computer examiners with an expert review panel and measure the relationship with the characteristics of the examiners to their quality responses. The results of this analysis provide insight into identifying forensic computer examiners that provide high-quality responses. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  15. Developing a Workflow to Identify Inconsistencies in Volunteered Geographic Information: A Phenological Case Study.

    Science.gov (United States)

    Mehdipoor, Hamed; Zurita-Milla, Raul; Rosemartin, Alyssa; Gerst, Katharine L; Weltzin, Jake F

    2015-01-01

    Recent improvements in online information communication and mobile location-aware technologies have led to the production of large volumes of volunteered geographic information. Widespread, large-scale efforts by volunteers to collect data can inform and drive scientific advances in diverse fields, including ecology and climatology. Traditional workflows to check the quality of such volunteered information can be costly and time consuming as they heavily rely on human interventions. However, identifying factors that can influence data quality, such as inconsistency, is crucial when these data are used in modeling and decision-making frameworks. Recently developed workflows use simple statistical approaches that assume that the majority of the information is consistent. However, this assumption is not generalizable, and ignores underlying geographic and environmental contextual variability that may explain apparent inconsistencies. Here we describe an automated workflow to check inconsistency based on the availability of contextual environmental information for sampling locations. The workflow consists of three steps: (1) dimensionality reduction to facilitate further analysis and interpretation of results, (2) model-based clustering to group observations according to their contextual conditions, and (3) identification of inconsistent observations within each cluster. The workflow was applied to volunteered observations of flowering in common and cloned lilac plants (Syringa vulgaris and Syringa x chinensis) in the United States for the period 1980 to 2013. About 97% of the observations for both common and cloned lilacs were flagged as consistent, indicating that volunteers provided reliable information for this case study. Relative to the original dataset, the exclusion of inconsistent observations changed the apparent rate of change in lilac bloom dates by two days per decade, indicating the importance of inconsistency checking as a key step in data quality

  16. Identifying effective pathways in a successful continuous quality improvement programme: the GEDAPS study.

    Science.gov (United States)

    Bodicoat, Danielle H; Mundet, Xavier; Gray, Laura J; Cos, Xavier; Davies, Melanie J; Khunti, Kamlesh; Cano, Juan-Franciso

    2014-12-01

    Continuous quality improvement programmes often target several aspects of care, some of which may be more effective meaning that resources could be focussed on these. The objective was to identify the effective and ineffective aspects of a successful continuous quality improvement programme for individuals with type 2 diabetes in primary care. Data were from a series of cross-sectional studies (GEDAPS) in primary care, Catalonia, Spain, in 55 centres (2239 participants) in 1993, and 92 centres (5819 participants) in 2002. A structural equation modelling approach was used. The intervention was associated with improved microvascular outcomes through microalbuminuria and funduscopy screening, which had a direct effect on microvascular outcomes, and through attending 2-4 nurse visits and having ≥1 blood pressure measurement, which acted through reducing systolic blood pressure. The intervention was associated with improved macrovascular outcomes through blood pressure measurement and attending 2-4 nurse visits (through systolic blood pressure) and having ≥3 education topics, ≥1 HbA1c measurement and adequate medication (through HbA1c). Cholesterol measurement, weight measurement and foot examination did not contribute towards the effectiveness of the intervention. The pathways through which a continuous quality improvement programme appeared to act to reduce microvascular and macrovascular complications were driven by reductions in systolic blood pressure and HbA1c, which were attained through changes in nurse and education visits, measurement and medication. This suggests that these factors are potential areas on which future quality improvement programmes should focus. © 2014 John Wiley & Sons, Ltd.

  17. Identifying optimal areas for REDD intervention: East Kalimantan, Indonesia as a case study

    International Nuclear Information System (INIS)

    Harris, Nancy L; Petrova, Silvia; Brown, Sandra; Stolle, Fred

    2008-01-01

    International discussions on reducing emissions from deforestation and degradation (REDD) as a greenhouse gas (GHG) abatement strategy are ongoing under the United Nations Framework Convention on Climate Change (UNFCCC). In the light of these discussions, it behooves countries to be able to determine the relative likelihood of deforestation over a landscape and perform a first order estimation of the potential reduction in GHGs associated with various protection scenarios. This would allow countries to plan their interventions accordingly to maximize carbon benefits, alongside other environmental and socioeconomic benefits, because forest protection programs might be chosen in places where the perceived threat of deforestation is high whereas in reality the threat is low. In this case study, we illustrate a method for creating deforestation threat maps and estimating potential reductions in GHGs from eighteen protected areas in East Kalimantan, Indonesia, that would occur if protection of these areas was well enforced. Results from our analysis indicate that a further 230 720 ha of East Kalimantan's forest area would be lost and approximately 305 million t CO 2 would be emitted from existing protected areas between 2003 and 2013 if the historical rate of deforestation continued unabated. In other words, the emission of 305 million t CO 2 into the atmosphere would be avoided during this period if protection of the existing areas was well enforced. At a price of $4 per ton of CO 2 (approximate price on the Chicago Climate Exchange in August 2008), this represents an estimated gross income stream of about $120 million per year. We also identified additional areas with high carbon stocks under high deforestation threat that would be important to protect if the carbon benefits of avoided deforestation activities are to be maximized in this region

  18. Identifying Patterns in Implementation of Hospital Pressure Ulcer Prevention Programs: A Multisite Qualitative Study.

    Science.gov (United States)

    Soban, Lynn M; Finley, Erin P; Miltner, Rebecca S

    2016-01-01

    To describe the presence or absence of key components of hospital pressure ulcer (PU) prevention programs in 6 acute care hospitals. Multisite comparative case study. Using purposeful selection based on PU rates (high vs low) and hospital size, 6 hospitals within the Veterans Health Administration health care system were invited to participate. Key informant interviews (n = 48) were conducted in each of the 6 participating hospitals among individuals playing key roles in PU prevention: senior nursing leadership (n = 9), nurse manager (n = 7), wound care specialist (n = 6), frontline RNs (n = 26). Qualitative data were collected during face-to-face, semistructured interviews. Interview protocols were tailored to each interviewee's role with a core set of common questions covering 3 major content areas: (1) practice environment (eg, policies and wound care specialists), (2) current prevention practices (eg, conduct of PU risk assessment and skin inspection), and (3) barriers to PU prevention. We conducted structured coding of 5 key components of PU prevention programs and cross-case analysis to identify patterns in operationalization and implementation of program components across hospitals based on facility size and PU rates (low vs high). All hospitals had implemented all PU prevention program components. Component operationalization varied considerably across hospitals. Wound care specialists were integral to the operationalization of the 4 other program components examined; however, staffing levels and work assignments of wound care specialists varied widely. Patterns emerged among hospitals with low and high PU rates with respect to wound care specialist staffing, data monitoring, and staff education. We found hospital-level variations in PU prevention programs. Wound care specialist staffing may represent a potential point of leverage in achieving other PU program components, particularly performance monitoring and staff education.

  19. Case control study to identify risk factors for acute hepatitis C virus infection in Egypt

    Directory of Open Access Journals (Sweden)

    Kandeel Amr M

    2012-11-01

    Full Text Available Abstract Background Identification of risk factors of acute hepatitis C virus (HCV infection in Egypt is crucial to develop appropriate prevention strategies. Methods We conducted a case–control study, June 2007-September 2008, to investigate risk factors for acute HCV infection in Egypt among 86 patients and 287 age and gender matched controls identified in two infectious disease hospitals in Cairo and Alexandria. Case-patients were defined as: any patient with symptoms of acute hepatitis; lab tested positive for HCV antibodies and negative for HBsAg, HBc IgM, HAV IgM; and 7-fold increase in the upper limit of transaminase levels. Controls were selected from patients’ visitors with negative viral hepatitis markers. Subjects were interviewed about previous exposures within six months, including community-acquired and health-care associated practices. Results Case-patients were more likely than controls to have received injection with a reused syringe (OR=23.1, CI 4.7-153, to have been in prison (OR=21.5, CI 2.5-479.6, to have received IV fluids in a hospital (OR=13.8, CI 5.3-37.2, to have been an IV drug user (OR=12.1, CI 4.6-33.1, to have had minimal surgical procedures (OR=9.7, CI 4.2-22.4, to have received IV fluid as an outpatient (OR=8, CI 4–16.2, or to have been admitted to hospital (OR=7.9, CI 4.2-15 within the last 6 months. Multivariate analysis indicated that unsafe health facility practices are the main risk factors associated with transmission of HCV infection in Egypt. Conclusion In Egypt, focusing acute HCV prevention measures on health-care settings would have a beneficial impact.

  20. Identifying and describing patients' learning experiences towards self-management of bipolar disorders: a phenomenological study.

    Science.gov (United States)

    Van den Heuvel, S C G H; Goossens, P J J; Terlouw, C; Van Achterberg, T; Schoonhoven, L

    2015-12-01

    -to-face, in-depth interviews, guided by a topic list, along service users with BD I or II (n = 16) in three specialised community care clinics across the Netherlands. Interviews were digitally recorded and transcribed verbatim prior to analysis in Atlas.ti 7. Unlike existing studies, which suggest that individual abilities of service users determine outcomes in self-management of BD, the current study found that self-management of BD is a learning process that takes place in a collaborative network. We identified five categories: acknowledgment of having BD, processing the information load, illness management, reflecting on living with BD, and self-management of BD. The success of self-management depends on the acknowledgment of individual limitations in learning to cope with BD and willingness to use a social network as a back-up instead. Especially, the dormant fear of a recurrent episode is a hampering factor in this learning process. © 2015 John Wiley & Sons Ltd.

  1. Dynamic assembly, localization and proteolysis of the Bacillus subtilis SMC complex

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    Rinn Cornelia

    2005-06-01

    Full Text Available Abstract Background SMC proteins are key components of several protein complexes that perform vital tasks in different chromosome dynamics. Bacterial SMC forms a complex with ScpA and ScpB that is essential for chromosome arrangement and segregation. The complex localizes to discrete centres on the nucleoids that during most of the time of the cell cycle localize in a bipolar manner. The complex binds to DNA and condenses DNA in an as yet unknown manner. Results We show that in vitro, ScpA and ScpB form different complexes with each other, among which the level of the putative 2 ScpA/4 ScpB complex showed a pronounced decrease in level upon addition of SMC protein. Different mutations of the ATPase-binding pocket of SMC reduced, but did not abolish interaction of mutant SMC with ScpA and ScpB. The loss of SMC ATPase activity led to a loss of function in vivo, and abolished proper localization of the SMC complex. The formation of bipolar SMC centres was also lost after repression of gyrase activity, and was abnormal during inhibition of replication, resulting in single central clusters. Resumption of replication quickly re-established bipolar SMC centres, showing that proper localization depends on ongoing replication. We also found that the SMC protein is subject to induced proteolysis, most strikingly as cells enter stationary phase, which is partly achieved by ClpX and LonA proteases. Atomic force microscopy revealed the existence of high order rosette-like SMC structures in vitro, which might explain the formation of the SMC centres in vivo. Conclusion Our data suggest that a ScpA/ScpB sub-complex is directly recruited into the SMC complex. This process does not require SMC ATPase activity, which, however, appears to facilitate loading of ScpA and ScpB. Thus, the activity of SMC could be regulated through binding and release of ScpA and ScpB, which has been shown to affect SMC ATPase activity. The proper bipolar localization of the SMC

  2. RADAR study: protocol for an observational cohort study to identify early warning signals on the pathways to alcohol use disorder.

    Science.gov (United States)

    Slade, Tim; Swift, Wendy; Mewton, Louise; Kypri, Kypros; Lynskey, Michael T; Butterworth, Peter; Tibbetts, Joel; McCraw, Stacey; Upton, Emily

    2017-08-21

    Harmful alcohol consumption, particularly alcohol use disorder (AUD), is a worldwide health priority, contributing substantially to global morbidity and mortality. The peak age of onset of AUD is 18-24, thus a deeper understanding of the young adult experience is vital if we are to identify modifiable risk factors and intervene early in the developmental course of this disabling disorder. Critical unanswered questions include: How soon after drinking initiation do AUD symptoms begin to emerge? Which symptoms come first? Do the symptoms unfold in a predictable pattern? In what ways do the emerging symptoms interact with individual, peer, family and environmental risk factors to impact on the transition to disorder? The proposed RADAR study will examine the prospective development of AUD symptoms over the young adulthood (18-24) years. We will capitalise on an existing cohort of 1911 community-based adolescents who were recruited at age 13 and have completed a baseline and five annual follow-up assessments as part of an observational cohort study. We will interview these adolescents every 6 months between the ages of 19 and 23 to derive monthly histories of both alcohol use and AUD symptomatology, along with a comprehensive battery of risk and protective factor scales hypothesised to predict the emergence and course of AUD. The results of this study will inform the natural history of AUD and will be used to identify specific targets for prevention and early intervention of AUD. Ethical approval has already been granted for the study (UNSW HREC 10144). We will disseminate the results of the study through published manuscripts, conferences and seminar presentations. Data used in published manuscripts will be made available through a suitable online repository (eg, Dryad-datadryad.org). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly

  3. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

    Directory of Open Access Journals (Sweden)

    Ayşe Demirkan

    study identified nine novel phospho- and sphingolipid loci, substantially increasing our knowledge of the genetic basis for these traits.

  4. Diagnostic accuracy of prostate health index to identify aggressive prostate cancer. An Institutional validation study.

    Science.gov (United States)

    Morote, J; Celma, A; Planas, J; Placer, J; Ferrer, R; de Torres, I; Pacciuci, R; Olivan, M

    2016-01-01

    New generations of tumor markers used to detect prostate cancer (PCa) should be able to discriminate men with aggressive PCa of those without PCa or nonaggressive tumors. The objective of this study has been to validate Prostate Health Index (PHI) as a marker of aggressive PCa in one academic institution. PHI was assessed in 357 men scheduled to prostatic biopsy between June of 2013 and July 2014 in one academic institution. Thereafter a subset of 183 men younger than 75 years and total PSA (tPSA) between 3.0 and 10.0 ng/mL, scheduled to it first prostatic biopsy, was retrospectively selected for this study. Twelve cores TRUS guided biopsy, under local anaesthesia, was performed in all cases. Total PSA, free PSA (fPSA), and [-2] proPSA (p2PSA) and prostate volume were determined before the procedure and %fPSA, PSA density (PSAd) and PHI were calculated. Aggressive tumors were considered if any Gleason 4 pattern was found. PHI was compared to %fPSA and PSAd through their ROC curves. Thresholds to detect 90%, 95% of all tumors and 95% and 100% of aggressive tumors were estimated and rates of unnecessary avoided biopsies were calculated and compared. The rate of PCa detection was 37.2% (68) and the rate of aggressive tumors was 24.6% (45). The PHI area under the curve was higher than those of %fPSA and PSAd to detect any PCa (0.749 vs 0.606 and 0.668 respectively) or to detect only aggressive tumors (0.786 vs 0.677 and 0.708 respectively), however, significant differences were not found. The avoided biopsy rates to detect 95% of aggressive tumors were 20.2% for PHI, 14.8% for %fPSA, and 23.5% for PSAd. Even more, to detect all aggressive tumors these rates dropped to 4.9% for PHI, 9.3% for %fPSA, and 7.9% for PSAd. PHI seems a good marker to PCa diagnosis. However, PHI was not superior to %fPSA and PSAd to identify at least 95% of aggressive tumors. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited

    DEFF Research Database (Denmark)

    Deelen, Joris; Beekman, Marian; Uh, Hae-Won

    2011-01-01

    By studying the loci which contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Stu...

  6. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci.

    Directory of Open Access Journals (Sweden)

    Ying Liu

    2008-03-01

    Full Text Available A genome-wide association study was performed to identify genetic factors involved in susceptibility to psoriasis (PS and psoriatic arthritis (PSA, inflammatory diseases of the skin and joints in humans. 223 PS cases (including 91 with PSA were genotyped with 311,398 single nucleotide polymorphisms (SNPs, and results were compared with those from 519 Northern European controls. Replications were performed with an independent cohort of 577 PS cases and 737 controls from the U.S., and 576 PSA patients and 480 controls from the U.K.. Strongest associations were with the class I region of the major histocompatibility complex (MHC. The most highly associated SNP was rs10484554, which lies 34.7 kb upstream from HLA-C (P = 7.8x10(-11, GWA scan; P = 1.8x10(-30, replication; P = 1.8x10(-39, combined; U.K. PSA: P = 6.9x10(-11. However, rs2395029 encoding the G2V polymorphism within the class I gene HCP5 (combined P = 2.13x10(-26 in U.S. cases yielded the highest ORs with both PS and PSA (4.1 and 3.2 respectively. This variant is associated with low viral set point following HIV infection and its effect is independent of rs10484554. We replicated the previously reported association with interleukin 23 receptor and interleukin 12B (IL12B polymorphisms in PS and PSA cohorts (IL23R: rs11209026, U.S. PS, P = 1.4x10(-4; U.K. PSA: P = 8.0x10(-4; IL12B:rs6887695, U.S. PS, P = 5x10(-5 and U.K. PSA, P = 1.3x10(-3 and detected an independent association in the IL23R region with a SNP 4 kb upstream from IL12RB2 (P = 0.001. Novel associations replicated in the U.S. PS cohort included the region harboring lipoma HMGIC fusion partner (LHFP and conserved oligomeric golgi complex component 6 (COG6 genes on chromosome 13q13 (combined P = 2x10(-6 for rs7993214; OR = 0.71, the late cornified envelope gene cluster (LCE from the Epidermal Differentiation Complex (PSORS4 (combined P = 6.2x10(-5 for rs6701216; OR 1.45 and a region of LD at 15q21 (combined P = 2.9x10(-5 for rs

  7. A Study of Scientometric Methods to Identify Emerging Technologies via Modeling of Milestones

    Energy Technology Data Exchange (ETDEWEB)

    Abercrombie, Robert K [ORNL; Udoeyop, Akaninyene W [ORNL; Schlicher, Bob G [ORNL

    2012-01-01

    This work examines a scientometric model that tracks the emergence of an identified technology from initial discovery (via original scientific and conference literature), through critical discoveries (via original scientific, conference literature and patents), transitioning through Technology Readiness Levels (TRLs) and ultimately on to commercial application. During the period of innovation and technology transfer, the impact of scholarly works, patents and on-line web news sources are identified. As trends develop, currency of citations, collaboration indicators, and on-line news patterns are identified. The combinations of four distinct and separate searchable on-line networked sources (i.e., scholarly publications and citation, patents, news archives, and online mapping networks) are assembled to become one collective network (a dataset for analysis of relations). This established network becomes the basis from which to quickly analyze the temporal flow of activity (searchable events) for the example subject domain we investigated.

  8. Atomic structure of a peptide coated gold nanocluster identified using theoretical and experimental studies

    Science.gov (United States)

    Wang, Hui; Li, Xu; Gao, Liang; Zhai, Jiao; Liu, Ru; Gao, Xueyun; Wang, Dongqi; Zhao, Lina

    2016-06-01

    Peptide coated gold nanoclusters (AuNCs) have a precise molecular formula and atomic structure, which are critical for their unique applications in targeting specific proteins either for protein analysis or drug design. To date, a study of the crystal structure of peptide coated AuNCs is absent primarily due to the difficulty of obtaining their crystalline phases in an experiment. Here we study a typical peptide coated AuNC (Au24Peptide8, Peptide = H2N-CCYKKKKQAGDV-COOH, Anal. Chem., 2015, 87, 2546) to figure out its atomic structure and electronic structure using a theoretical method for the first time. In this work, we identify the explicit configuration of the essential structure of Au24Peptide8, Au24(Cys-Cys)8, using density functional theory (DFT) computations and optical spectroscopic experiments, where Cys denotes cysteine without H bonded to S. As the first multidentate ligand binding AuNC, Au24(Cys-Cys)8 is characterized as a distorted Au13 core with Oh symmetry covered by two Au(Cys-Cys) and three Au3(Cys-Cys)2 staple motifs in its atomic structure. The most stable configuration of Au24(Cys-Cys)8 is confirmed by comparing its UV-vis absorption spectrum from time-dependent density-functional theory (TDDFT) calculations with optical absorption measurements, and these results are consistent with each other. Furthermore, we carry out frontier molecular orbital (FMO) calculations to elucidate that the electronic structure of Au24(Cys-Cys)8 is different from that of Au24(SR)20 as they have a different Au/S ratio, where SR represents alkylthiolate. Importantly, the different ligand coatings, Cys-Cys and SR, in Au24(Cys-Cys)8 and Au24(SR)20 cause the different Au/S ratios in the coated Au24. The reason is that the Au/S ratio is crucial in determining the size of the Au core of the ligand protected AuNC, and the size of the Au core corresponds to a specific electronic structure. By the adjustment of ligand coatings from alkylthiolate to peptide, the Au/S ratio

  9. Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans.

    Science.gov (United States)

    Everman, Sarah; Meyer, Christian; Tran, Lee; Hoffman, Nyssa; Carroll, Chad C; Dedmon, William L; Katsanos, Christos S

    2016-10-01

    Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change (P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased (P BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments (P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA. Copyright © 2016 the American Physiological Society.

  10. Simulation platform developed to study and identify critical cases in a future smart grid

    DEFF Research Database (Denmark)

    Mihet-Popa, Lucian; Zong, Yi; You, Shi

    2016-01-01

    simulation and planning tools, with a particular objective on the challenges faced by the introduction of Smart Grid technologies. Another important issue of the paper is to identify critical load cases, as well as the voltage variations with the highest potential, able to implement the grid model...

  11. Identifying and Combating Sexism in EFL Textbooks--With a Case Study into China

    Science.gov (United States)

    Tao, Baiqiang

    2008-01-01

    This paper explores methodologies of identifying and combating sexism in EFL (English as a Foreign Language) textbooks. The writer of this paper has found out there exists sexism or gender inequality in the Chinese high school EFL textbooks. The writer hopes that future EFL curriculum designers, EFL textbook writers, textbook censors in textbook…

  12. Identifying Competencies for Volunteer Administrators for the Coming Decade: A National Delphi Study.

    Science.gov (United States)

    Boyd, Barry L.

    2003-01-01

    A Delphi panel of 13 experts categorized 33 competencies for volunteer administration into 5 constructs: organizational leadership, systems leadership, organizational culture, personal skills, and management skills. Twelve barriers to acquiring competencies and 21 methods to address them were identified. (Contains 24 references.) (SK)

  13. Identifying sustainability issues using participatory SWOT analysis - A case study of egg production in the Netherlands

    NARCIS (Netherlands)

    Mollenhorst, H.; Boer, de I.J.M.

    2004-01-01

    The aim of this paper was to demonstrate how participatory strengths, weaknesses, opportunities and threats (SWOT) analysis can be used to identify relevant economic, ecological and societal (EES) issues for the assessment of sustainable development. This is illustrated by the case of egg production

  14. Effect of monoclonal antibodies on limited proteolysis of native glycoprotein gD of herpes simplex virus type 1

    International Nuclear Information System (INIS)

    Eisenberg, R.J.; Long, D.; Pereira, L.; Hampar, B.; Zweig, M.; Cohen, G.H.

    1982-01-01

    We examined the properties of 17 monoclonal antibodies to glycoprotein gD of herpes simplex type 1 (HSV-1) (gD-1) and HSV-2 (gD-2). The antibodies recognized eight separate determinants of gD, based on differences in radioimmuno-precipitation and neutralization assays. The determinants were distributed as follows: three were gD-1 specific, one was gD-2 specific, and four were type common. Several type-specific and type-common determinants appeared to be involved in neutralization. We developed a procedure for examining the effect that binding of monoclonal antibody has on proteolysis of native gD-1 by Staphylococcus aureus protease V8. We showed that several different patterns of protease V8 cleavage were obtained, depending on the monoclonal antibody used. The proteolysis patterns were generally consistent with the immunological groupings. With four groups of antibodies, we found that fragments of gD-1 remained bound to antibody after V8 treatment. A 38,000-dalton fragment remained bound to antibodies in three different groups of monoclonal antibodies. This fragment appeared to contain one type-common and two type-specific determinants. A 12,000-dalton fragment remained bound to antibodies belonging to one type-common group of monoclonal antibodies. Tryptic peptide analysis revealed that the 12,000-dalton fragment represented a portion of the 38,000-dalton fragment and was enriched in a type-common arginine tryptic peptide

  15. Effect of pulsed electric field on the proteolysis of cold boned beef M. Longissimus lumborum and M. Semimembranosus.

    Science.gov (United States)

    Suwandy, Via; Carne, Alan; van de Ven, Remy; Bekhit, Alaa El-Din A; Hopkins, David L

    2015-02-01

    The effects of pulsed electric field (PEF) and ageing (3, 7, 14 and 21 days) on the shear force, protein profile, and post-mortem proteolysis of beef loins (M. Longissimus lumborum, LL) and topsides (M. Semimembranosus, SM) were investigated using a range of pulsed electric field treatments [voltages (5 and 10 kV) and frequencies (20, 50, and 90 Hz)]. PEF treatment decreased the shear force of beef LL and SM muscles by up to 19%. The reduction in the shear force in the LL was not affected by the treatment intensity whereas the reduction in the SM was dependent on PEF frequency. PEF treated beef loins showed increased proteolysis, both early post-mortem and during subsequent post-mortem storage reflected by increased degradation of troponin-T and desmin. The most prominent troponin-T degradation was found in samples treated with 5 kV-90 Hz, 10 kV-20 Hz at day 3 and day 7 post-treatment in addition to 10 kV-50 Hz in subsequent post-treatment times. The degradation of desmin in PEF treated beef loins increased with ageing time.

  16. Study of a methodology of identifying important research problems by the PIRT process

    International Nuclear Information System (INIS)

    Aoki, Takayuki; Takagi, Toshiyuki; Urayama, Ryoichi; Komura, Ichiro; Furukawa, Takashi; Yusa, Noritaka

    2014-01-01

    In this paper, we propose a new methodology of identifying important research problems to be solved to improve the performance of some specific scientific technologies by the phenomena identification and ranking table (PIRT) process which has been used as a methodology for demonstrating the validity of the best estimate simulation codes in US Nuclear Regulatory Commission (USNRC) licensing of nuclear power plants. The new methodology makes it possible to identify important factors affecting the performance of the technologies from the viewpoint of the figure of merit and problems associated with them while it keeps the fundamental concepts of the original PIRT process. Also in this paper, we demonstrate the effectiveness of the new methodology by applying it to a task of extracting research problems for improving an inspection accuracy of ultrasonic testing or eddy current testing in the inspection of objects having cracks due to fatigue or stress corrosion cracking. (author)

  17. Study of a methodology of identifying important research problems by the PIRT process

    International Nuclear Information System (INIS)

    Aoki, Takayuki; Takagi, Toshiyuki; Urayama, Ryoichi; Komura, Ichiro; Furukawa, Takashi; Yusa, Noritaka

    2013-01-01

    In this paper, we propose a new methodology of identifying important research problems to be solved to improve the performance of some specific scientific technologies by the phenomena identification and ranking table (PIRT) process, which has been used as a methodology for demonstrating the validity of the best estimate simulation codes in USNRC licensing of nuclear power plants. It keeps the fundamental concepts of the original PIRT process but makes it possible to identify important factors affecting the performance of the technologies from the viewpoint of the figure of merit and problems associated with them, which need to be solved to improve the performance. Also in this paper, we demonstrate the effectiveness of the developed method by showing a specific example of the application to physical events or phenomena in objects having fatigue or SCC crack(s) under ultrasonic testing and eddy current testing. (author)

  18. Automated cross-identifying radio to infrared surveys using the LRPY algorithm: a case study

    Science.gov (United States)

    Weston, S. D.; Seymour, N.; Gulyaev, S.; Norris, R. P.; Banfield, J.; Vaccari, M.; Hopkins, A. M.; Franzen, T. M. O.

    2018-02-01

    Cross-identifying complex radio sources with optical or infra red (IR) counterparts in surveys such as the Australia Telescope Large Area Survey (ATLAS) has traditionally been performed manually. However, with new surveys from the Australian Square Kilometre Array Pathfinder detecting many tens of millions of radio sources, such an approach is no longer feasible. This paper presents new software (LRPY - Likelihood Ratio in PYTHON) to automate the process of cross-identifying radio sources with catalogues at other wavelengths. LRPY implements the likelihood ratio (LR) technique with a modification to account for two galaxies contributing to a sole measured radio component. We demonstrate LRPY by applying it to ATLAS DR3 and a Spitzer-based multiwavelength fusion catalogue, identifying 3848 matched sources via our LR-based selection criteria. A subset of 1987 sources have flux density values for all IRAC bands which allow us to use criteria to distinguish between active galactic nuclei (AGNs) and star-forming galaxies (SFG). We find that 936 radio sources ( ≈ 47 per cent) meet both of the Lacy and Stern AGN selection criteria. Of the matched sources, 295 have spectroscopic redshifts and we examine the radio to IR flux ratio versus redshift, proposing an AGN selection criterion below the Elvis radio-loud AGN limit for this dataset. Taking the union of all three AGNs selection criteria we identify 956 as AGNs ( ≈ 48 per cent). From this dataset, we find a decreasing fraction of AGNs with lower radio flux densities consistent with other results in the literature.

  19. [Study of algorithms to identify schizophrenia in the SNIIRAM database conducted by the REDSIAM network].

    Science.gov (United States)

    Quantin, C; Collin, C; Frérot, M; Besson, J; Cottenet, J; Corneloup, M; Soudry-Faure, A; Mariet, A-S; Roussot, A

    2017-10-01

    The aim of the REDSIAM network is to foster communication between users of French medico-administrative databases and to validate and promote analysis methods suitable for the data. Within this network, the working group "Mental and behavioral disorders" took an interest in algorithms to identify adult schizophrenia in the SNIIRAM database and inventoried identification criteria for patients with schizophrenia in these databases. The methodology was based on interviews with nine experts in schizophrenia concerning the procedures they use to identify patients with schizophrenia disorders in databases. The interviews were based on a questionnaire and conducted by telephone. The synthesis of the interviews showed that the SNIIRAM contains various tables which allow coders to identify patients suffering from schizophrenia: chronic disease status, drugs and hospitalizations. Taken separately, these criteria were not sufficient to recognize patients with schizophrenia, an algorithm should be based on all of them. Apparently, only one-third of people living with schizophrenia benefit from the longstanding disease status. Not all patients are hospitalized, and coding for diagnoses at the hospitalization, notably for short stays in medicine, surgery or obstetrics departments, is not exhaustive. As for treatment with antipsychotics, it is not specific enough as such treatments are also prescribed to patients with bipolar disorders, or even other disorders. It seems appropriate to combine these complementary criteria, while keeping in mind out-patient care (every year 80,000 patients are seen exclusively in an outpatient setting), even if these data are difficult to link with other information. Finally, the experts made three propositions for selection algorithms of patients with schizophrenia. Patients with schizophrenia can be relatively accurately identified using SNIIRAM data. Different combinations of the selected criteria must be used depending on the objectives and

  20. A Delphi Study to Identify Indicators of Poorly Managed Pain for Pediatric Postoperative and Procedural Pain

    Directory of Open Access Journals (Sweden)

    Alison M Twycross

    2013-01-01

    Full Text Available BACKGROUND: Adverse health care events are injuries occurring as a result of patient care. Significant acute pain is often caused by medical and surgical procedures in children, and it has been argued that undermanaged pain should be considered to be an adverse event. Indicators are often used to identify other potential adverse events. There are currently no validated indicators for undertreated pediatric pain.

  1. Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4DCAF5 ubiquitin ligase.

    Science.gov (United States)

    Leng, Feng; Yu, Jiekai; Zhang, Chunxiao; Alejo, Salvador; Hoang, Nam; Sun, Hong; Lu, Fei; Zhang, Hui

    2018-04-24

    Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4 DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4 DCAF5 . Mouse L3MBTL3/MBT-1 deletion causes accumulation of DNMT1 protein, increased genomic DNA methylation, and late embryonic lethality. DNMT1 contains a consensus methylation motif shared by many non-histone proteins including E2F1, a key transcription factor for S phase. We show that the methylation-dependent E2F1 degradation is also controlled by L3MBTL3-CRL4 DCAF5 . Our studies elucidate for the first time a novel mechanism by which the stability of many methylated non-histone proteins are regulated.

  2. A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13

    DEFF Research Database (Denmark)

    Cho, Michael H; Castaldi, Peter J; Wan, Emily S

    2012-01-01

    The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through...

  3. Entering University Studies: Identifying Enabling Factors for a Successful Transition from School to University

    Science.gov (United States)

    McGhie, Venicia

    2017-01-01

    The South African higher education sector is faced with high attrition and low retention rates. Studies conducted by the Council on Higher Education in South Africa have found that 50% of black students who access university study drop out, and the majority of dropouts occurred in the first year of study. While these studies revealed what the…

  4. Identifying key topics for a description of sexual behavior among Danish adolescents: A qualitative study

    DEFF Research Database (Denmark)

    Jørgensen, Marianne Johansson; Maindal, Helle Terkildsen; Olesen, Frede

    . Results: Four major categories of risk behavior were identified: Alcohol consumption is associated with “no condom use”, Nights on the town and meetings in foreign counties or at festivals are associated with one night stands and often lead to unsafe sex, Low self-esteem increases the risk of pushing one...... one Danish Folk High School, but with different social and educational backgrounds. The interview guide was developed from literature reviews and hypotheses based on years of experience with sexually transmitted infections. Data were transcribed verbatim and analyzed using qualitative description...

  5. Identifying key components for an effective case report poster: an observational study.

    Science.gov (United States)

    Willett, Lisa L; Paranjape, Anuradha; Estrada, Carlos

    2009-03-01

    Residents demonstrate scholarly activity by presenting posters at academic meetings. Although recommendations from national organizations are available, evidence identifying which components are most important is not. To develop and test an evaluation tool to measure the quality of case report posters and identify the specific components most in need of improvement. Faculty evaluators reviewed case report posters and provided on-site feedback to presenters at poster sessions of four annual academic general internal medicine meetings. A newly developed ten-item evaluation form measured poster quality for specific components of content, discussion, and format (5-point Likert scale, 1 = lowest, 5 = highest). Evaluation tool performance, including Cronbach alpha and inter-rater reliability, overall poster scores, differences across meetings and evaluators and specific components of the posters most in need of improvement. Forty-five evaluators from 20 medical institutions reviewed 347 posters. Cronbach's alpha of the evaluation form was 0.84 and inter-rater reliability, Spearman's rho 0.49 (p words. Our evaluation tool provides empirical data to guide trainees as they prepare posters for presentation which may improve poster quality and enhance their scholarly productivity.

  6. Optical coherence tomography accurately identifies patients with penile (pre malignant lesions: A single center prospective study

    Directory of Open Access Journals (Sweden)

    Ronni Wessels

    2015-01-01

    Conclusion: In this preliminary study, qualitative and quantitative analysis of OCT-images of suspicious penile lesions shows differences between benign lesions and (pre malignant lesions. These results encourage further research in a larger study population.

  7. Identifying interventions to help rural Kenyan mothers cope with food insecurity: results of a focused ethnographic study

    OpenAIRE

    Pelto, Gretel H.; Armar?Klemesu, Margaret

    2016-01-01

    Abstract An ethnographic study was conducted in two areas in southern and western Kenya to identify potential interventions to improve the quality, availability and affordability of foods consumed by infants and young children. A cultural?ecological model of determinants of nutrition identified the sectors of information for data collection related to infant and young child (IYC) diet and feeding?related behaviours, and the focused ethnographic study manual was used to guide the research. The...

  8. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    DEFF Research Database (Denmark)

    Evangelou, Evangelos; Kerkhof, Hanneke J; Styrkarsdottir, Unnur

    2014-01-01

    Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.......Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects....

  9. Identifying concepts for studying implementation of information technology in facilities management

    DEFF Research Database (Denmark)

    Ebbesen, Poul; Bonke, Sten

    2014-01-01

    . Background: Experiences from the FM sector indicate that IT systems meant to support FM operations and workflows often do not generate the expected added value neither to the FM department itself nor to the basic organization supported by the FM department. Approach (Theory/Methodology): Based on findings......Purpose: To contribute to identifying a conceptual framework for describing and understanding the processes involved when implementing and using Information Technology (IT) in Facilities Management (FM). This paper discusses how basic concepts from different theories can be applied in parallel when...... from exciting research on IT implementation a range of more generic theoretical concepts applicable to the typical setting or situation of IT implementation in FM has been found. These theoretical concepts all clarify and describe different aspects of the implementation process and they may all...

  10. Search strategies to identify diagnostic accuracy studies in MEDLINE and EMBASE

    NARCIS (Netherlands)

    Beynon, Rebecca; Leeflang, Mariska M. G.; McDonald, Steve; Eisinga, Anne; Mitchell, Ruth L.; Whiting, Penny; Glanville, Julie M.

    2013-01-01

    A systematic and extensive search for as many eligible studies as possible is essential in any systematic review. When searching for diagnostic test accuracy (DTA) studies in bibliographic databases, it is recommended that terms for disease (target condition) are combined with terms for the

  11. A Classical Delphi Study to Identify the Barriers of Pursuing Green Information and Communication Technologies

    Science.gov (United States)

    Gotay, Jose Antonio

    2013-01-01

    This qualitative, classical Delphi study served to explore the apparent lack of corporate commitment to prioritized Green Information Communication Technologies (ICTs), which could delay the economic and social benefits for maximizing the use of natural energy resources in a weak economy. The purpose of this study was to examine the leadership…

  12. Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

    DEFF Research Database (Denmark)

    Sud, Amit; Thomsen, Hauke; Law, Philip J.

    2017-01-01

    Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 co...

  13. Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

    DEFF Research Database (Denmark)

    Mitchell, Jonathan S; Li, Ni; Weinhold, Niels

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a ...

  14. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    L.V. Wain (Louise); G.C. Verwoert (Germaine); P.F. O'Reilly (Paul); G. Shi (Gang); T. Johnson (Toby); M. Bochud (Murielle); K. Rice (Kenneth); P. Henneman (Peter); A.V. Smith (Albert Vernon); G.B. Ehret (Georg); N. Amin (Najaf); M.G. Larson (Martin); V. Mooser (Vincent); D. Hadley (David); M. Dörr (Marcus); J.C. Bis (Joshua); T. Aspelund (Thor); T. Esko (Tõnu); A.C.J.W. Janssens (Cécile); J.H. Zhao (Jing Hua); S.C. Heath (Simon); M. Laan (Maris); J. Fu (Jingyuan); G. Pistis (Giorgio); J. Luan; G. Lucas (Gavin); N. Pirastu (Nicola); I. Pichler (Irene); A.U. Jackson (Anne); R.J. Webster (Rebecca J.); F.F. Zhang; J. Peden (John); R. Schmidt (Reinhold); T. Tanaka (Toshiko); H. Campbell (Harry); W. Igl (Wilmar); Y. Milaneschi (Yuri); J.J. Hottenga (Jouke Jan); V. Vitart (Veronique); D.I. Chasman (Daniel); S. Trompet (Stella); J.L. Bragg-Gresham (Jennifer L.); B.Z. Alizadeh (Behrooz); J.C. Chambers (John); X. Guo (Xiuqing); T. Lehtimäki (Terho); B. Kuhnel (Brigitte); L.M. Lopez; O. Polasek (Ozren); M. Boban (Mladen); C.P. Nelson (Christopher P.); A.C. Morrison (Alanna); V. Pihur (Vasyl); S.K. Ganesh (Santhi); A. Hofman (Albert); S. Kundu (Suman); F.U.S. Mattace Raso (Francesco); F. Rivadeneira Ramirez (Fernando); E.J.G. Sijbrands (Eric); A.G. Uitterlinden (André); S.J. Hwang; R.S. Vasan (Ramachandran Srini); Y.A. Wang (Ying); S.M. Bergmann (Sven); P. Vollenweider (Peter); G. Waeber (Gérard); J. Laitinen (Jaana); A. Pouta (Anneli); P. Zitting (Paavo); W.L. McArdle (Wendy); H.K. Kroemer (Heyo); U. Völker (Uwe); H. Völzke (Henry); N.L. Glazer (Nicole); K.D. Taylor (Kent); T.B. Harris (Tamara); H. Alavere (Helene); T. Haller (Toomas); A. Keis (Aime); M.L. Tammesoo; Y.S. Aulchenko (Yurii); K-T. Khaw (Kay-Tee); P. Galan (Pilar); S. Hercberg (Serge); G.M. Lathrop (Mark); S. Eyheramendy (Susana); E. Org (Elin); S. Sõber (Siim); X. Lu (Xiaowen); I.M. Nolte (Ilja); B.W.J.H. Penninx (Brenda); T. Corre (Tanguy); C. Masciullo (Corrado); C. Sala (Cinzia); L. Groop (Leif); B.F. Voight (Benjamin); O. Melander (Olle); C.J. O'Donnell (Christopher); V. Salomaa (Veikko); P. d' Adamo (Pio); A. Fabretto (Antonella); F. Faletra (Flavio); S. Ulivi (Shelia); F. Del Greco M (Fabiola); M.F. Facheris (Maurizio); F.S. Collins (Francis); R.N. Bergman (Richard); J.P. Beilby (John); J. Hung (Judy); A.W. Musk (Arthur); M. Mangino (Massimo); S.Y. Shin (So Youn); N. Soranzo (Nicole); H. Watkins (Hugh); A. Goel (Anuj); A. Hamsten (Anders); P. Gider (Pierre); M. Loitfelder (Marisa); M. Zeginigg (Marion); D.G. Hernandez (Dena); S.S. Najjar (Samer); P. Navarro (Pau); S.H. Wild (Sarah); A.M. Corsi (Anna Maria); A. Singleton (Andrew); E.J.C. de Geus (Eco); G.A.H.M. Willemsen (Gonneke); A.N. Parker (Alex); L.M. Rose (Lynda); B.M. Buckley (Brendan M.); D.J. Stott (David. J.); M. Orrù (Marco); M. Uda (Manuela); M.M. van der Klauw (Melanie); X. Li (Xiaohui); J. Scott (James); Y.D.I. Chen (Yii-Der Ida); G.L. Burke (Greg); M. Kähönen (Mika); J. Viikari (Jorma); A. Döring (Angela); T. Meitinger (Thomas); G.S. Davis; J.M. Starr (John); V. Emilsson (Valur); A.S. Plump (Andrew); J.H. Lindeman (Jan H.); P.A.C. 't Hoen (Peter); I.R. König (Inke); J.F. Felix (Janine); R. Clarke; J. Hopewell; H. Ongen (Halit); M.M.B. Breteler (Monique); S. Debette (Stéphanie); A.L. DeStefano (Anita); M. Fornage (Myriam); G.F. Mitchell (Gary); H. Holm (Hilma); K. Stefansson (Kari); G. Thorleifsson (Gudmar); U. Thorsteinsdottir (Unnur); N.J. Samani (Nilesh); M. Preuss (Michael); I. Rudan (Igor); C. Hayward (Caroline); I.J. Deary (Ian); H.E. Wichmann (Heinz Erich); O. Raitakari (Olli); W. Palmas (Walter); J.S. Kooner (Jaspal); R.P. Stolk (Ronald); J.W. Jukema (Jan Wouter); A.F. Wright (Alan); D.I. Boomsma (Dorret); S. Bandinelli (Stefania); U. Gyllensten (Ulf); J.F. Wilson (James); L. Ferrucci (Luigi); M. Farrall (Martin); T.D. Spector (Timothy); L.J. Palmer; J. Tuomilehto (Jaakko); A. Pfeufer (Arne); P. Gasparini (Paolo); D.S. Siscovick (David); D. Altshuler (David); R.J.F. Loos (Ruth); D. Toniolo (Daniela); H. Snieder (Harold); C. Gieger (Christian); P. Meneton (Pierre); N.J. Wareham (Nick); B.A. Oostra (Ben); A. Metspalu (Andres); L.J. Launer (Lenore); R. Rettig (Rainer); D.P. Strachan (David); J.S. Beckmann (Jacques); J.C.M. Witteman (Jacqueline); J.A.P. Willems van Dijk (Ko); E.A. Boerwinkle (Eric); M. Boehnke (Michael); P.M. Ridker (Paul); M.R. Järvelin; A. Chakravarti (Aravinda); J. Erdmann (Jeanette); V. Gudnason (Vilmundur); C. Newton-Cheh (Christopher); D. Levy (Daniel); P. Arora (Pankaj); P. Munroe (Patricia); B.M. Psaty (Bruce); M. Caulfield (Mark); D.C. Rao (Dabeeru C.); P. Elliott (Paul); P. Tikka-Kleemola (Päivi); G.R. Abecasis (Gonçalo); I.E. Barroso (Inês)

    2011-01-01

    textabstractNumerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N =

  15. Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

    NARCIS (Netherlands)

    Sud, A. (Amit); Thomsen, H. (Hauke); Law, P.J. (Philip J.); A. Försti (Asta); Filho, M.I.D.S. (Miguel Inacio Da Silva); Holroyd, A. (Amy); P. Broderick (Peter); Orlando, G. (Giulia); Lenive, O. (Oleg); Wright, L. (Lauren); R. Cooke (Rosie); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); J. Peto (Julian); F. Canzian (Federico); Eeles, R. (Rosalind); Z. Kote-Jarai; K.R. Muir (K.); Pashayan, N. (Nora); B.E. Henderson (Brian); C.A. Haiman (Christopher); S. Benlloch (Sara); F.R. Schumacher (Fredrick R); Olama, A.A.A. (Ali Amin Al); S.I. Berndt (Sonja); G. Conti (Giario); F. Wiklund (Fredrik); S.J. Chanock (Stephen); Stevens, V.L. (Victoria L.); C.M. Tangen (Catherine M.); Batra, J. (Jyotsna); Clements, J. (Judith); H. Grönberg (Henrik); Schleutker, J. (Johanna); D. Albanes (Demetrius); Weinstein, S. (Stephanie); K. Wolk (Kerstin); West, C. (Catharine); Mucci, L. (Lorelei); Cancel-Tassin, G. (Géraldine); Koutros, S. (Stella); Sorensen, K.D. (Karina Dalsgaard); L. Maehle; D. Neal (David); S.P.L. Travis (Simon); Hamilton, R.J. (Robert J.); S.A. Ingles (Sue); B.S. Rosenstein (Barry S.); Lu, Y.-J. (Yong-Jie); Giles, G.G. (Graham G.); A. Kibel (Adam); Vega, A. (Ana); M. Kogevinas (Manolis); Penney, K.L. (Kathryn L.); Park, J.Y. (Jong Y.); Stanford, J.L. (Janet L.); C. Cybulski (Cezary); B.G. Nordestgaard (Børge); Brenner, H. (Hermann); Maier, C. (Christiane); Kim, J. (Jeri); E.M. John (Esther); P.J. Teixeira; Neuhausen, S.L. (Susan L.); De Ruyck, K. (Kim); Razack, A. (Azad); Newcomb, L.F. (Lisa F.); Lessel, D. (Davor); Kaneva, R. (Radka); N. Usmani (Nawaid); F. Claessens; Townsend, P.A. (Paul A.); Dominguez, M.G. (Manuela Gago); Roobol, M.J. (Monique J.); F. Menegaux (Florence); P. Hoffmann (Per); M.M. Nöthen (Markus); K.-H. JöCkel (Karl-Heinz); Strandmann, E.P.V. (Elke Pogge Von); Lightfoot, T. (Tracy); Kane, E. (Eleanor); Roman, E. (Eve); Lake, A. (Annette); Montgomery, D. (Dorothy); Jarrett, R.F. (Ruth F.); A.J. Swerdlow (Anthony ); A. Engert (Andreas); N. Orr (Nick); K. Hemminki (Kari); Houlston, R.S. (Richard S.)

    2017-01-01

    textabstractSeveral susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and

  16. Preparedness for physiotherapy in private practice: Novices identify key factors in an interpretive description study.

    Science.gov (United States)

    Atkinson, Robyn; McElroy, Theresa

    2016-04-01

    Physiotherapists in Australia deliver services to a diverse range of clients, across many settings, however little research exists examining graduate preparedness for practice, even in the populous field of private practice. To explore novice physiotherapist perspectives on preparedness for work in private practice. The qualitative approach of interpretive description was used to guide in-depth interviews with 8 novice physiotherapists from 3 universities working in 5 private practices in Melbourne. All interviews were digitally recorded, transcribed verbatim and analyzed thematically. Four main themes influencing graduate preparedness for work in private practice were identified: 1) non-curricular experiences (e.g. sports training) 2) elective curricular: practicum experiences; 3) curricular: attainment of skills specific to private practice; and 4) the private practice setting: supportive colleagues. This combination of non-curricular, curricular, and practice setting factors offered the necessary scaffolding for the graduates to report feeling prepared for work in private practice. Non-curricular activities, radiological instruction, clinical placements, building supportive colleague relations and professional development in private practice are recommended as potential means of building preparedness in novice therapists. Findings have implications for physiotherapy students, educators and private practice clinics looking to recruit new graduates. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Identifying subtypes among offenders with antisocial personality disorder: a cluster-analytic study.

    Science.gov (United States)

    Poythress, Norman G; Edens, John F; Skeem, Jennifer L; Lilienfeld, Scott O; Douglas, Kevin S; Frick, Paul J; Patrick, Christopher J; Epstein, Monica; Wang, Tao

    2010-05-01

    The question of whether antisocial personality disorder (ASPD) and psychopathy are largely similar or fundamentally different constructs remains unresolved. In the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994), many of the personality features of psychopathy are cast as associated features of ASPD, although the DSM-IV offers no guidance as to how, or the extent to which, these features relate to ASPD. In a sample of 691 offenders who met DSM-IV criteria for ASPD, we used model-based clustering to identify subgroups of individuals with relatively homogeneous profiles on measures of associated features (psychopathic personality traits) and other constructs with potential etiological significance for subtypes of ASPD. Two emergent groups displayed profiles that conformed broadly to theoretical descriptions of primary psychopathy and Karpman's (1941) variant of secondary psychopathy. As expected, a third group (nonpsychopathic ASPD) lacked substantial associated features. A fourth group exhibited elevated psychopathic features as well as a highly fearful temperament, a profile not clearly predicted by extant models. Planned comparisons revealed theoretically informative differences between primary and secondary groups in multiple domains, including self-report measures, passive avoidance learning, clinical ratings, and official records. Our results inform ongoing debates about the overlap between psychopathy and ASPD and raise questions about the wisdom of placing most individuals who habitually violate social norms and laws into a single diagnostic category.

  18. Methods for identifying Neisseria meningitidis carriers: a multi-center study in the African meningitis belt.

    Directory of Open Access Journals (Sweden)

    Nicole E Basta

    Full Text Available Detection of meningococcal carriers is key to understanding the epidemiology of Neisseria meningitidis, yet no gold standard has been established. Here, we directly compare two methods for collecting pharyngeal swabs to identify meningococcal carriers.We conducted cross-sectional surveys of schoolchildren at multiple sites in Africa to compare swabbing the posterior pharynx behind the uvula (U to swabbing the posterior pharynx behind the uvula plus one tonsil (T. Swabs were cultured immediately and analyzed using molecular methods.One thousand and six paired swab samples collected from schoolchildren in four countries were analyzed. Prevalence of meningococcal carriage was 6.9% (95% CI: 5.4-8.6% based on the results from both swabs, but the observed prevalence was lower based on one swab type alone. Prevalence based on the T swab or the U swab alone was similar (5.2% (95% CI: 3.8-6.7% versus 4.9% (95% CI: 3.6-6.4% respectively (p=0.6. The concordance between the two methods was 96.3% and the kappa was 0.61 (95% CI: 0.50-0.73, indicating good agreement.These two commonly used methods for collecting pharyngeal swabs provide consistent estimates of the prevalence of carriage, but both methods misclassified carriers to some degree, leading to underestimates of the prevalence.

  19. Characterisation of cysteine proteinases responsible for digestive proteolysis in guts of larval Western corn rootworm (Diabrotica virgifera) by expression in the yeast Pichia pastoris

    NARCIS (Netherlands)

    Bown, D.P.; Wilkinson, H.S.; Jongsma, M.A.; Gatehouse, J.A.

    2004-01-01

    Cysteine proteinases are the major class of enzymes responsible for digestive proteolysis in western corn rootworm (Diabrotica virgifera), a serious pest of maize. A larval gut extract hydrolysed typical cathepsin substrates, such as Z-phe-arg-AMC and Z-arg-arg-AMC, and hydrolysis was inhibited by

  20. Effects of FlAsH/Tetracysteine (TC) tag on PrP proteolysis and PrPres formation by TC-scanning

    Science.gov (United States)

    Taguchi, Yuzuru; Hohsfield, Lindsay A.; Hollister, Jason R.

    2014-01-01

    The FlAsH/tetracysteine (FlAsH/TC) tag is a powerful tool for fluorescent labeling of proteins. However, even small tags such as FlAsH/TC could alter the behavior of the tagged proteins, especially if the insertion occurs at internal sites. Defining the influence of FlAsH/TC on nearby protein-protein interactions might aid in selecting appropriate positions for internal TC insertions and allow the exploitation of serial FlAsH/TC insertions (TC-scanning) as a probe to characterize sites of protein-protein interaction. To explore this application in the context of substrate-protease interactions, we analyzed the effect of FlAsH/TC insertions on proteolysis of cellular prion protein (PrPsen) in in vitro reactions and generation of the C1 metabolic fragment of PrPsen in live neuroblastoma cells. The influence of FlAsH/TC insertion was evaluated by TC-scanning across the cleavage sites of each protease. The results showed that FlAsH/TC inhibited protease cleavage only within limited ranges of the cleavage sites that varied from about 1 to 6 residues-wide depending on the protease, providing an estimate of the PrP residues interacting with each protease. TC-scanning was also used to probe a different type of protein-protein interaction, the conformational conversion of FlAsH-PrPsen to the prion disease-associated isoform, PrPres. PrP constructs with FlAsH/TC insertions at residues 90–96 but not 97–101 were converted to FlAsH-PrPres, identifying a boundary separating loosely versus compactly folded regions of PrPres. Our observations demonstrate that TC-scanning with the FlAsH/TC tag can be a versatile method for probing protein-protein interactions and folding processes. PMID:23943295

  1. Identifying the support needs of fathers affected by post-partum depression: a pilot study.

    Science.gov (United States)

    Letourneau, N; Duffett-Leger, L; Dennis, C-L; Stewart, M; Tryphonopoulos, P D

    2011-02-01

    The purpose of this pilot study was to describe the experiences, support needs, resources, and barriers to support for fathers whose partners had post-partum depression (PPD) in preparation for a larger study. Qualitative methods and community-based research approaches were used in this exploratory/descriptive multi-site study, conducted in New Brunswick and Alberta. Telephone interviews were conducted with a total of 11 fathers in New Brunswick (n= 7) and Alberta (n= 4). Fathers experienced a number of depressive symptoms including: anxiety, lack of time and energy, irritability, feeling sad or down, changes in appetite, and thoughts of harm to self or baby. The most common barriers for fathers were lack of information regarding PPD resources and difficulty seeking support. This pilot study establishes the feasibility of the larger-scale exploration of fathers' experiences in supporting their spouses affected by PPD. © 2010 Blackwell Publishing.

  2. Case studies of transportation investment to identify the impacts on the local and state economy.

    Science.gov (United States)

    2013-01-01

    This project provides case studies of the impact of transportation investments on local economies. We use multiple : approaches to measure impacts since the effects of transportation projects can vary according to the size of a : project and the size...

  3. Comparative analysis of perturbed molecular pathways identified in in vitro and in vivo toxicology studies

    NARCIS (Netherlands)

    Wiesinger, Martin; Mayer, Bernd; Jennings, Paul; Lukas, Arno

    The development of in vitro toxicological testing strategies are hampered by the difficulty in extrapolation to the intact organism. Academic toxicological literature contains a wealth of mechanistically rich information, especially arising from omic studies, which could potentially be utilized to

  4. Genome-Wide Association Study to Identify Genes Related to Renal Mercury Concentrations in Mice

    DEFF Research Database (Denmark)

    Alkaissi, Hammoudi; Ekstrand, Jimmy; Jawad, Aksa

    2016-01-01

    BACKGROUND: Following human mercury (Hg) exposure, the metal accumulates with considerable concentrations in kidney, liver, and brain. Although the toxicokinetics of Hg has been studied extensively, factors responsible for inter-individual variation in humans are largely unknown. Differences...

  5. Identifying factors to improve oral cancer screening uptake: a qualitative study.

    Directory of Open Access Journals (Sweden)

    Fatemeh Vida Zohoori

    Full Text Available To engage with high risk groups to identify knowledge and awareness of oral cancer signs and symptoms and the factors likely to contribute to improved screening uptake.Focus group discussions were undertaken with 18 males; 40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+ units of alcohol per week, irregular dental attenders living in economically deprived areas of Teesside.There was a striking reported lack of knowledge and awareness of oral cancer and its signs and symptoms among the participants. When oral/mouth cancer leaflets produced by Cancer Research UK were presented to the participants, they claimed that they would seek help on noticing such a condition. There was a preference to seek help from their general practitioner rather than their dentist due to perceptions that a dentist is 'inaccessible' on a physical and psychological level, costly, a 'tooth specialist' not a 'mouth specialist', and also not able to prescribe medication and make referrals to specialists. Interestingly, none of the 18 participants who were offered a free oral cancer examination at a dental practice took up this offer.The uptake of oral cancer screening may be improved by increasing knowledge of the existence and signs and symptoms of oral cancer. Other factors that may increase uptake are increased awareness of the role of dentists in diagnosing oral cancer, promotion of oral cancer screening by health professionals during routine health checks, and the use of a "health" screening setting as opposed to a "dental" setting for such checks.

  6. Consistent interactive segmentation of pulmonary ground glass nodules identified in CT studies

    Science.gov (United States)

    Zhang, Li; Fang, Ming; Naidich, David P.; Novak, Carol L.

    2004-05-01

    Ground glass nodules (GGNs) have proved especially problematic in lung cancer diagnosis, as despite frequently being malignant they characteristically have extremely slow rates of growth. This problem is further magnified by the small size of many of these lesions now being routinely detected following the introduction of multislice CT scanners capable of acquiring contiguous high resolution 1 to 1.25 mm sections throughout the thorax in a single breathhold period. Although segmentation of solid nodules can be used clinically to determine volume doubling times quantitatively, reliable methods for segmentation of pure ground glass nodules have yet to be introduced. Our purpose is to evaluate a newly developed computer-based segmentation method for rapid and reproducible measurements of pure ground glass nodules. 23 pure or mixed ground glass nodules were identified in a total of 8 patients by a radiologist and subsequently segmented by our computer-based method using Markov random field and shape analysis. The computer-based segmentation was initialized by a click point. Methodological consistency was assessed using the overlap ratio between 3 segmentations initialized by 3 different click points for each nodule. The 95% confidence interval on the mean of the overlap ratios proved to be [0.984, 0.998]. The computer-based method failed on two nodules that were difficult to segment even manually either due to especially low contrast or markedly irregular margins. While achieving consistent manual segmentation of ground glass nodules has proven problematic most often due to indistinct boundaries and interobserver variability, our proposed method introduces a powerful new tool for obtaining reproducible quantitative measurements of these lesions. It is our intention to further document the value of this approach with a still larger set of ground glass nodules.

  7. A step-by-step guide to systematically identify all relevant animal studies

    Science.gov (United States)

    Leenaars, Marlies; Hooijmans, Carlijn R; van Veggel, Nieky; ter Riet, Gerben; Leeflang, Mariska; Hooft, Lotty; van der Wilt, Gert Jan; Tillema, Alice; Ritskes-Hoitinga, Merel

    2012-01-01

    Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future. PMID:22037056

  8. Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development.

    Science.gov (United States)

    Takeda, Haruna; Rust, Alistair G; Ward, Jerrold M; Yew, Christopher Chin Kuan; Jenkins, Nancy A; Copeland, Neal G

    2016-04-05

    Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4(+/-) mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers. Similar to human GC, pathway analyses identified WNT, TGF-β, and PI3K-PTEN signaling, ubiquitin-mediated proteolysis, adherens junctions, and RNA degradation in addition to genes involved in chromatin modification and organization as highly deregulated pathways in GC. Comparative oncogenomic filtering of the complete list of SB-identified genes showed that they are highly enriched for genes mutated in human GC and identified many candidate human GC genes. Finally, by comparing our complete list of SB-identified genes against the list of mutated genes identified in five large-scale human GC sequencing studies, we identified LDL receptor-related protein 1B (LRP1B) as a previously unidentified human candidate GC tumor suppressor gene. In LRP1B, 129 mutations were found in 462 human GC samples sequenced, and LRP1B is one of the top 10 most deleted genes identified in a panel of 3,312 human cancers. SB mutagenesis has, thus, helped to catalog the cooperative molecular mechanisms driving SMAD4-induced GC growth and discover genes with potential clinical importance in human GC.

  9. Observational study identifies non-attendance characteristics in two hospital outpatient clinics

    DEFF Research Database (Denmark)

    Blæhr, Emely; Søgaard, Rikke; Kristensen, Thomas

    2016-01-01

    INTRODUCTION: Non-attended hospital appointments are receiving increasing attention in times when rapid access and efficient service delivery at public hospitals are on the agenda. The aim of this study was to investigate the extent of non-attendance in a Danish outpatient setting and its...... association with user-level and provider-level characteristics. METHODS: The study was based on appointments scheduled from June 2013 to March 2015 at an orthopaedic and a radiologic outpatient clinic. Data on outcomes of cancellation on the part of the user or the provider, and non-attendance without giving...

  10. Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies.

    Science.gov (United States)

    Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

    Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K -means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups.

  11. PROTEOLYSIS DURING MANUFACTURE AND RIPENING/STORING OF “OLOMOUCKÉ TVARŮŽKY” CHEESE (PGI

    Directory of Open Access Journals (Sweden)

    Vendula Pachlová

    2015-02-01

    Full Text Available Twenty-two free amino acid (FAA concentrations were observed during manufacture (1st, 3rd and 7th days of production and ripening period (42 days storing at 8°C of “Olomoucké tvarůžky” (PGI, smear acid cheese. Sensory attributes were also analysed during ripening period. The free amino acids were determined by means of ion-exchange chromatography. The development of the individual FAA content positively correlated with the ripening period (r = 0.7734–0.9229; P < 0.01.The results gave information about the development precursors (FAA of typically sensory active compound in “Olomoucké tvarůžky” (PGI during its production and especially ripening. In conclusion, we found that free amino acid concentration as finally products of proteolysis are positive with improved flavour.

  12. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis

    DEFF Research Database (Denmark)

    Roldan, A.L.; Cubellis, M.V.; Masucci, M.T.

    1990-01-01

    , and therefore the capacity of cells to migrate and invade neighboring tissues. We have isolated a 1.4 kb cDNA clone coding for the entire human uPAR. An oligonucleotide synthesized on the basis of the N-terminal sequence of the purified protein was used to screen a cDNA library made from SV40 transformed human......, a size very close to that of the cloned cDNA. Expression of the uPAR cDNA in mouse cells confirms that the clone is complete and expresses a functional uPA binding protein, located on the cell surface and with properties similar to the human uPAR. Caseinolytic plaque assay, immunofluorescence analysis......The surface receptor for urokinase plasminogen activator (uPAR) has been recognized in recent years as a key molecule in regulating plasminogen mediated extracellular proteolysis. Surface plasminogen activation controls the connections between cells, basement membrane and extracellular matrix...

  13. Initiation of proteolysis of yeast fructose-1,6-bisphosphatase by pH-control of adenylate cyclase

    International Nuclear Information System (INIS)

    Holzer, H.; Purwin, C.; Pohlig, G.; Scheffers, W.A.; Nicolay, K.

    1986-01-01

    Addition of fermentable sugars or uncouplers such as CCCP to resting yeast cells grown on glucose initiates phosphorylation of fructose-1,6-bisphosphatase (FBPase). There is good evidence that phosphorylation marks FBPase for proteolytic degradation. 31 P-NMR measurements of the cytosolic pH of yeast cells demonstrated a decrease of the cytosolic pH from 7.0 to 6.5 after addition of glucose or CCCP to starved yeast. Activity of adenylate cyclase in permeabilized yeast cells increases 2-3-fold when the pH is lowered from 7.0 to 6.5. It is concluded that pH controlled activation of adenylate cyclase causes the previously described increase in cyclic AMP which leads to phosphorylation of FBPase and finally to proteolysis of FBPase

  14. Impact of pasteurization of human milk on preterm newborn in vitro digestion: Gastrointestinal disintegration, lipolysis and proteolysis.

    Science.gov (United States)

    de Oliveira, Samira C; Bourlieu, Claire; Ménard, Olivia; Bellanger, Amandine; Henry, Gwénaële; Rousseau, Florence; Dirson, Emelyne; Carrière, Frédéric; Dupont, Didier; Deglaire, Amélie

    2016-11-15

    Human milk feeding is an important recommendation for preterm newborns considering their vulnerability and digestive immaturity. Holder pasteurization (62.5°C, 30min) applied in milk banks modifies its biological quality and its microstructure. We investigated the impact of pasteurization of preterm human milk on its gastrointestinal kinetics of lipolysis, proteolysis and structural disintegration. An in vitro dynamic system was set up to simulate the gastrointestinal digestion of preterm newborns. A pool of preterm human milk was digested as raw or after Holder pasteurization. Pasteurization impacted the microstructure of undigested human milk, its gastrointestinal disintegration and tended to limit the intestinal lipolysis. Furthermore, the gastrointestinal bioaccessibility of some fatty acids was decreased by pasteurization, while the intestinal bioaccessibility of some amino acids was selectively modulated. The impact of pasteurization on the digestion of human milk may have nutritional relevance in vivo and potentially modulates preterm development and growth. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Matheson, Melanie C; Pers, Tune Hannes

    2013-01-01

    Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up th...

  16. Questioning in Tongan Science Classrooms: A Pilot Study to Identify Current Practice, Barriers and Facilitators

    Science.gov (United States)

    Bay, Jacquie L.; Fohoko, Fehi; La'Akulu, Mumui; Leota, Ofa; Pulotu, Lesieli; Tu'Ipuloto, Sina; Tutoe, Salesi; Tovo, Oliveti; Vekoso, Ana; Pouvalu, Emeli H.

    2016-01-01

    Questioning is central to the development of scientific and health literacies. In exploring this concept, Tongan science teachers hypothesized that their ability to use and encourage questioning presented challenges in the context of Tongan social and cultural norms. This study set out to develop a peer-to-peer protocol to enable teachers to…

  17. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; van Duijn, Cornelia M; Ugocsai, Peter

    2012-01-01

    , and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57...

  18. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease

    NARCIS (Netherlands)

    Khor, Chiea Chuen; Davila, Sonia; Breunis, Willemijn B.; Lee, Yi-Ching; Shimizu, Chisato; Wright, Victoria J.; Yeung, Rae S. M.; Tan, Dennis E. K.; Sim, Kar Seng; Wang, Jie Jin; Wong, Tien Yin; Pang, Junxiong; Mitchell, Paul; Cimaz, Rolando; Dahdah, Nagib; Cheung, Yiu-Fai; Huang, Guo-Ying; Yang, Wanling; Park, In-Sook; Lee, Jong-Keuk; Wu, Jer-Yuarn; Levin, Michael; Burns, Jane C.; Burgner, David; Kuijpers, Taco W.; Hibberd, Martin L.; Lau, Yu-Lung; Zhang, Jing; Ma, Xiao-Jing; Liu, Fang; Wu, Lin; Yoo, Jeong-Jin; Hong, Soo-Jong; Kim, Kwi-Joo; Kim, Jae-Jung; Park, Young-Mi; Mi Hong, Young; Sohn, Sejung; Young Jang, Gi; Ha, Kee-Soo; Nam, Hyo-Kyoung; Byeon, Jung-Hye; Weon Yun, Sin; Ki Han, Myung; Lee, Kyung-Yil; Hwang, Ja-Young; Kuipers, Irene M.; Ottenkamp, Jaap J.; Biezeveld, Maarten; Tacke, Carline

    2011-01-01

    Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from

  19. How do GPs identify a need for palliative care in their patients? An interview study.

    NARCIS (Netherlands)

    Claessen, S.J.J.; Francke, A.L.; Engels, Y.; Deliens, L.

    2013-01-01

    Background: Little is known about how GPs determine whether and when patients need palliative care. Little research has been done regarding the assumption underpinning Lynn and Adamson’s model that palliative care may start early in the course of the disease. This study was conducted to explore how

  20. Using a Design-Based Research Study to Identify Principles for Training Instructors to Teach Online

    Science.gov (United States)

    Shattuck, Julie; Anderson, Terry

    2013-01-01

    Within the overall framework of design-based research, this paper reports on a study that focused on evaluating an online training course for online instructors. This intervention was designed as a possible solution to the problem facing some higher education institutions of how to provide quality, accessible training for mostly part-time…

  1. Genome-wide association study identifies new prostate cancer susceptibility loci

    DEFF Research Database (Denmark)

    Schumacher, Fredrick R.; Berndt, Sonja I.; Siddiq, Afshan

    2011-01-01

    Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have iden...

  2. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    A. Okbay (Aysu); J.P. Beauchamp (Jonathan); Fontana, M.A. (Mark Alan); J.J. Lee (James J.); T.H. Pers (Tune); Rietveld, C.A. (Cornelius A.); P. Turley (Patrick); Chen, G.-B. (Guo-Bo); V. Emilsson (Valur); Meddens, S.F.W. (S. Fleur W.); Oskarsson, S. (Sven); Pickrell, J.K. (Joseph K.); Thom, K. (Kevin); Timshel, P. (Pascal); R. de Vlaming (Ronald); A. Abdellaoui (Abdel); T.S. Ahluwalia (Tarunveer Singh); J. Bacelis (Jonas); C. Baumbach (Clemens); Bjornsdottir, G. (Gyda); J.H. Brandsma (Johan); Pina Concas, M. (Maria); J. Derringer; Furlotte, N.A. (Nicholas A.); T.E. Galesloot (Tessel); S. Girotto; Gupta, R. (Richa); L.M. Hall (Leanne M.); S.E. Harris (Sarah); E. Hofer; Horikoshi, M. (Momoko); J.E. Huffman (Jennifer E.); Kaasik, K. (Kadri); I.-P. Kalafati (Ioanna-Panagiota); R. Karlsson (Robert); A. Kong (Augustine); J. Lahti (Jari); S.J. van der Lee (Sven); Deleeuw, C. (Christiaan); P.A. Lind (Penelope); Lindgren, K.-O. (Karl-Oskar); Liu, T. (Tian); M. Mangino (Massimo); J. Marten (Jonathan); E. Mihailov (Evelin); M. Miller (Mike); P.J. van der Most (Peter); C. Oldmeadow (Christopher); A. Payton (Antony); N. Pervjakova (Natalia); W.J. Peyrot (Wouter ); Qian, Y. (Yong); O. Raitakari (Olli); Rueedi, R. (Rico); Salvi, E. (Erika); Schmidt, B. (Börge); Schraut, K.E. (Katharina E.); Shi, J. (Jianxin); A.V. Smith (Albert Vernon); R.A. Poot (Raymond); B. St Pourcain (Beate); A. Teumer (Alexander); G. Thorleifsson (Gudmar); N. Verweij (Niek); D. Vuckovic (Dragana); Wellmann, J. (Juergen); H.J. Westra (Harm-Jan); Yang, J. (Jingyun); Zhao, W. (Wei); Zhu, Z. (Zhihong); B.Z. Alizadeh (Behrooz); N. Amin (Najaf); Bakshi, A. (Andrew); S.E. Baumeister (Sebastian); G. Biino (Ginevra); K. Bønnelykke (Klaus); P.A. Boyle (Patricia); H. Campbell (Harry); Cappuccio, F.P. (Francesco P.); G. Davies (Gail); J.E. de Neve (Jan-Emmanuel); P. Deloukas (Panagiotis); I. Demuth (Ilja); Ding, J. (Jun); Eibich, P. (Peter); Eisele, L. (Lewin); N. Eklund (Niina); D.M. Evans (David); J.D. Faul (Jessica D.); M.F. Feitosa (Mary Furlan); A.J. Forstner (Andreas); I. Gandin (Ilaria); Gunnarsson, B. (Bjarni); B.V. Halldorsson (Bjarni); T.B. Harris (Tamara); E.G. Holliday (Elizabeth); A.C. Heath (Andrew C.); L.J. Hocking; G. Homuth (Georg); M. Horan (Mike); J.J. Hottenga (Jouke Jan); P.L. de Jager (Philip); P.K. Joshi (Peter); A. Juqessur (Astanand); M. Kaakinen (Marika); M. Kähönen (Mika); S. Kanoni (Stavroula); Keltigangas-Järvinen, L. (Liisa); L.A.L.M. Kiemeney (Bart); I. Kolcic (Ivana); Koskinen, S. (Seppo); A. Kraja (Aldi); Kroh, M. (Martin); Z. Kutalik (Zoltán); A. Latvala (Antti); L.J. Launer (Lenore); Lebreton, M.P. (Maël P.); D.F. Levinson (Douglas F.); P. Lichtenstein (Paul); P. Lichtner (Peter); D.C. Liewald (David C.); A. Loukola (Anu); P.A. Madden (Pamela); R. Mägi (Reedik); Mäki-Opas, T. (Tomi); R.E. Marioni (Riccardo); P. Marques-Vidal; Meddens, G.A. (Gerardus A.); G. Mcmahon (George); C. Meisinger (Christa); T. Meitinger (Thomas); Milaneschi, Y. (Yusplitri); L. Milani (Lili); G.W. Montgomery (Grant); R. Myhre (Ronny); C.P. Nelson (Christopher P.); D.R. Nyholt (Dale); W.E.R. Ollier (William); A. Palotie (Aarno); L. Paternoster (Lavinia); N.L. Pedersen (Nancy); K. Petrovic (Katja); D.J. Porteous (David J.); K. Räikkönen (Katri); Ring, S.M. (Susan M.); A. Robino (Antonietta); O. Rostapshova (Olga); I. Rudan (Igor); A. Rustichini (Aldo); V. Salomaa (Veikko); Sanders, A.R. (Alan R.); A.-P. Sarin; R. Schmidt (Reinhold); R.J. Scott (Rodney); B.H. Smith (Blair); J.A. Smith (Jennifer A); J.A. Staessen (Jan); E. Steinhagen-Thiessen (Elisabeth); K. Strauch (Konstantin); A. Terracciano; M.D. Tobin (Martin); S. Ulivi (Shelia); S. Vaccargiu (Simona); L. Quaye (Lydia); F.J.A. van Rooij (Frank); C. Venturini (Cristina); A.A.E. Vinkhuyzen (Anna A.); U. Völker (Uwe); Völzke, H. (Henry); J.M. Vonk (Judith); D. Vozzi (Diego); J. Waage (Johannes); E.B. Ware (Erin B.); G.A.H.M. Willemsen (Gonneke); J. Attia (John); D.A. Bennett (David A.); Berger, K. (Klaus); L. Bertram (Lars); H. Bisgaard (Hans); D.I. Boomsma (Dorret); I.B. Borecki (Ingrid); U. Bültmann (Ute); C.F. Chabris (Christopher F.); F. Cucca (Francesco); D. Cusi (Daniele); I.J. Deary (Ian J.); G.V. Dedoussis (George); C.M. van Duijn (Cornelia); K. Hagen (Knut); B. Franke (Barbara); L. Franke (Lude); P. Gasparini (Paolo); P.V. Gejman (Pablo); C. Gieger (Christian); H.J. Grabe (Hans Jörgen); J. Gratten (Jacob); P.J.F. Groenen (Patrick); V. Gudnason (Vilmundur); P. van der Harst (Pim); C. Hayward (Caroline); D.A. Hinds (David A.); W. Hoffmann (Wolfgang); E. Hypponen (Elina); W.G. Iacono (William); B. Jacobsson (Bo); M.-R. Jarvelin (Marjo-Riitta); K.-H. JöCkel (Karl-Heinz); J. Kaprio (Jaakko); S.L.R. Kardia (Sharon); T. Lehtimäki (Terho); Lehrer, S.F. (Steven F.); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); A. Metspalu (Andres); N. Pendleton (Neil); B.W.J.H. Penninx (Brenda); M. Perola (Markus); N. Pirastu (Nicola); M. Pirastu (Mario); O. Polasek (Ozren); D. Posthuma (Danielle); C. Power (Christopher); M.A. Province (Mike); N.J. Samani (Nilesh); Schlessinger, D. (David); R. Schmidt (Reinhold); T.I.A. Sørensen (Thorkild); T.D. Spector (Timothy); J-A. Zwart (John-Anker); U. Thorsteinsdottir (Unnur); A.R. Thurik (Roy); Timpson, N.J. (Nicholas J.); H.W. Tiemeier (Henning); J.Y. Tung (Joyce Y.); A.G. Uitterlinden (André); Vitart, V. (Veronique); P. Vollenweider (Peter); D.R. Weir (David); J.F. Wilson (James F.); A.F. Wright (Alan); Conley, D.C. (Dalton C.); R.F. Krueger; G.D. Smith; Hofman, A. (Albert); D. Laibson (David); S.E. Medland (Sarah Elizabeth); M.N. Meyer (Michelle N.); J. Yang (Joanna); M. Johannesson (Magnus); P.M. Visscher (Peter); T. Esko (Tõnu); Ph.D. Koellinger (Philipp); D. Cesarini (David); D.J. Benjamin (Daniel J.)

    2016-01-01

    textabstractEducational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that

  3. Using rice genome-wide association studies to identify DNA markers for marker-assisted selection

    Science.gov (United States)

    Rice association mapping panels are collections of rice (Oryza sativa L.) accessions developed for genome-wide association (GWA) studies. One of these panels, the Rice Diversity Panel 1 (RDP1) was phenotyped by various research groups for several traits of interest, and more recently, genotyped with...

  4. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and

  5. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, A.; Beauchamp, J.; Fontana, M.A.; Lee, J.J.; Pers, T.H.; Rietveld, C.A.; Turley, P.; Chen, G.B.; Emilsson, V.; Meddens, S.F.W.; de Vlaming, R.; Abdellaoui, A.; Peyrot, W.; Vinkhuyzen, A.A.E.; Hottenga, J.J.; Willemsen, G.; Boomsma, D.I.; Penninx, B.W.J.H.; Laibson, D.; Medland, S.E.; Meyer, M.N.; Yang, J.; Johannesson, M.; Visscher, P.M.; Esko, T.; Koellinger, P.D.; Cesarini, D.; Benjamin, D.J.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our

  6. Identifying Engagement Patterns with Video Annotation Activities: A Case Study in Professional Development

    Science.gov (United States)

    Mirriahi, Negin; Jovanovic, Jelena; Dawson, Shane; Gaševic, Dragan; Pardo, Abelardo

    2018-01-01

    The rapid growth of blended and online learning models in higher education has resulted in a parallel increase in the use of audio-visual resources among students and teachers. Despite the heavy adoption of video resources, there have been few studies investigating their effect on learning processes and even less so in the context of academic…

  7. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism.

    NARCIS (Netherlands)

    Rossi, G.P.; Barisa, M.; Allolio, B.; Auchus, R.J.; Amar, L.; Cohen, D.; Degenhart, C.; Deinum, J.; Fischer, E.; Gordon, R.; Kickuth, R.; Kline, G.; Lacroix, A.; Magill, S.; Miotto, D.; Naruse, M.; Nishikawa, T.; Omura, M.; Pimenta, E.; Plouin, P.F.; Quinkler, M.; Reincke, M.; Rossi, E.; Rump, L.C.; Satoh, F.; Schultze Kool, L.J.; Seccia, T.M.; Stowasser, M.; Tanabe, A.; Trerotola, S.; Vonend, O.; Widimsky Jr, J.; Wu, K.D.; Wu, V.C.; Pessina, A.C.

    2012-01-01

    CONTEXT: In patients who seek surgical cure of primary aldosteronism (PA), The Endocrine Society Guidelines recommend the use of adrenal vein sampling (AVS), which is invasive, technically challenging, difficult to interpret, and commonly held to be risky. OBJECTIVE: The aim of this study was to

  8. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark Alan; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; van der Most, Peter J.; Verweij, Niek; Alizadeh, Behrooz Z.; Vonk, Judith M.; Bultmann, Ute; Franke, Lude; van der Harst, Pim; Penninx, Brenda W. J. H.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends

  9. Identifying women with dense breasts at high risk for interval cancer: a cohort study.

    Science.gov (United States)

    Kerlikowske, Karla; Zhu, Weiwei; Tosteson, Anna N A; Sprague, Brian L; Tice, Jeffrey A; Lehman, Constance D; Miglioretti, Diana L

    2015-05-19

    Twenty-one states have laws requiring that women be notified if they have dense breasts and that they be advised to discuss supplemental imaging with their provider. To better direct discussions of supplemental imaging by determining which combinations of breast cancer risk and Breast Imaging Reporting and Data System (BI-RADS) breast density categories are associated with high interval cancer rates. Prospective cohort. Breast Cancer Surveillance Consortium (BCSC) breast imaging facilities. 365,426 women aged 40 to 74 years who had 831,455 digital screening mammography examinations. BI-RADS breast density, BCSC 5-year breast cancer risk, and interval cancer rate (invasive cancer ≤12 months after a normal mammography result) per 1000 mammography examinations. High interval cancer rate was defined as more than 1 case per 1000 examinations. High interval cancer rates were observed for women with 5-year risk of 1.67% or greater and extremely dense breasts or 5-year risk of 2.50% or greater and heterogeneously dense breasts (24% of all women with dense breasts). The interval rate of advanced-stage disease was highest (>0.4 case per 1000 examinations) among women with 5-year risk of 2.50% or greater and heterogeneously or extremely dense breasts (21% of all women with dense breasts). Five-year risk was low to average (0% to 1.66%) for 51.0% of women with heterogeneously dense breasts and 52.5% with extremely dense breasts, with interval cancer rates of 0.58 to 0.63 and 0.72 to 0.89 case per 1000 examinations, respectively. The benefit of supplemental imaging was not assessed. Breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient-provider discussions about alternative screening strategies. National Cancer Institute.

  10. A comparative study to identify a suitable model of ownership for Iran football pro league clubs

    Directory of Open Access Journals (Sweden)

    Saeed Amirnejad

    2018-01-01

    Full Text Available Today the government ownership of the professional football clubs is absolutely illogical view point. Most of sports clubs are conducted by private sector using different models of ownership all over the world. In Iran, government credits benefit was main reason that the professional sport was firstly developed by government firms and organizations. Therefore, the sports team ownership is without the professionalization standards. The present comparative study was to examine the different football club ownership structures of the top leagues and the current condition of Iran football pro league ownership and then present a suitable ownership structure of Iran football clubs to leave behind the government club ownership. Among the initial 120 scientific texts, the thirty two cases including papers, books and reports were found relevant to this study. We studied the ownership prominence and several football club models of ownership focused on stock listing model of ownership, private investor model of ownership, supporter trust model of ownership and Japan partnership model of ownership; theoretical concepts, empirical studies, main findings, strengths and weaknesses were covered in analysis procedure. According to various models of ownership in leagues and the models’ productivity in football clubs, each model of ownership considering national environmental, economic, social conditions has strengths and weaknesses. So, we cannot present a definite model of ownership for Iran football pro league clubs due to different micro-environments of Iran clubs. We need a big planning to provide a supporter-investor mixed model of ownership to Iranian clubs. Considering strengths and weaknesses in the models of ownership as well as the micro and macro environment of Iran football clubs, German model and Japan partnership model are offered as suitable ones to probable new model of ownership in Iran pro league clubs. Consequently, more studies are required

  11. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

    NARCIS (Netherlands)

    C.E. Elks (Cathy); J.R.B. Perry (John); P. Sulem (Patrick); D.I. Chasman (Daniel); N. Franceschini (Nora); C. He (Chunyan); K.L. Lunetta (Kathryn); J.A. Visser (Jenny); E.M. Byrne (Enda); D.L. Cousminer (Diana); D.F. Gudbjartsson (Daniel); T. Esko (Tõnu); B. Feenstra (Bjarke); J.J. Hottenga (Jouke Jan); D.L. Koller (Daniel); Z. Kutalik (Zoltán); P. Lin (Peng); M. Mangino (Massimo); M. Marongiu (Mara); P.F. McArdle (Patrick); A.V. Smith (Albert Vernon); L. Stolk (Lisette); S. van Wingerden (Sophie); J.H. Zhao (Jing Hua); E. Albrecht (Eva); T. Corre (Tanguy); E. Ingelsson (Erik); C. Hayward (Caroline); P.K. Magnusson (Patrik); S. Ulivi (Shelia); N.M. Warrington (Nicole); L. Zgaga (Lina); H. Alavere (Helene); N. Amin (Najaf); T. Aspelund (Thor); S. Bandinelli (Stefania); I.E. Barroso (Inês); G. Berenson (Gerald); S.M. Bergmann (Sven); H. Blackburn (Hannah); E.A. Boerwinkle (Eric); J.E. Buring (Julie); F. Busonero; H. Campbell (Harry); S.J. Chanock (Stephen); W. Chen (Wei); M. Cornelis (Marilyn); D.J. Couper (David); A.D. Coviello (Andrea); P. d' Adamo (Pio); U. de Faire (Ulf); E.J.C. de Geus (Eco); P. Deloukas (Panagiotis); A. Döring (Angela); D.F. Easton (Douglas); G. Eiriksdottir (Gudny); V. Emilsson (Valur); J.G. Eriksson (Johan); L. Ferrucci (Luigi); A.R. Folsom (Aaron); T. Foroud (Tatiana); M. Garcia (Melissa); P. Gasparini (Paolo); F. Geller (Frank); C. Gieger (Christian); V. Gudnason (Vilmundur); A.S. Hall (Alistair); S.E. Hankinson (Susan); L. Ferreli (Liana); A.C. Heath (Andrew); D.G. Hernandez (Dena); A. Hofman (Albert); F.B. Hu (Frank); T. Illig (Thomas); M.R. Järvelin; A.D. Johnson (Andrew); D. Karasik (David); K-T. Khaw (Kay-Tee); D.P. Kiel (Douglas); T.O. Kilpelänen (Tuomas); I. Kolcic (Ivana); P. Kraft (Peter); L.J. Launer (Lenore); J.S.E. Laven (Joop); S. Li (Shengxu); J. Liu (Jianjun); D. Levy (Daniel); N.G. Martin (Nicholas); M. Melbye (Mads); V. Mooser (Vincent); J.C. Murray (Jeffrey); M.A. Nalls (Michael); P. Navarro (Pau); M. Nelis (Mari); A.R. Ness (Andrew); K. Northstone (Kate); B.A. Oostra (Ben); M. Peacock (Munro); C. Palmer (Cameron); A. Palotie (Aarno); G. Paré (Guillaume); A.N. Parker (Alex); N.L. Pedersen (Nancy); L. Peltonen (Leena Johanna); C.E. Pennell (Craig); P.D.P. Pharoah (Paul); O. Polasek (Ozren); A.S. Plump (Andrew); A. Pouta (Anneli); E. Porcu (Eleonora); T. Rafnar (Thorunn); J.P. Rice (John); S.M. Ring (Susan); F. Rivadeneira Ramirez (Fernando); I. Rudan (Igor); C. Sala (Cinzia); V. Salomaa (Veikko); S. Sanna (Serena); D. Schlessinger; N.J. Schork (Nicholas); A. Scuteri (Angelo); A.V. Segrè (Ayellet); A.R. Shuldiner (Alan); N. Soranzo (Nicole); U. Sovio (Ulla); S.R. Srinivasan (Sathanur); D.P. Strachan (David); M.L. Tammesoo; E. Tikkanen (Emmi); D. Toniolo (Daniela); K. Tsui (Kim); L. Tryggvadottir (Laufey); J.P. Tyrer (Jonathan); M. Uda (Manuela); R.M. van Dam (Rob); J.B.J. van Meurs (Joyce); P. Vollenweider (Peter); G. Waeber (Gérard); N.J. Wareham (Nick); D. Waterworth (Dawn); H.E. Wichmann (Heinz Erich); G.A.H.M. Willemsen (Gonneke); J.F. Wilson (James); A.F. Wright (Alan); L. Young (Lauren); G. Zhai (Guangju); W.V. Zhuang; L.J. Bierut (Laura); D.I. Boomsma (Dorret); H.A. Boyd (Heather); L. Crisponi (Laura); E.W. Demerath (Ellen); P. Tikka-Kleemola (Päivi); M.J. Econs (Michael); T.B. Harris (Tamara); D. Hunter (David); R.J.F. Loos (Ruth); A. Metspalu (Andres); G.W. Montgomery (Grant); P.M. Ridker (Paul); T.D. Spector (Tim); E.A. Streeten (Elizabeth); K. Stefansson (Kari); U. Thorsteinsdottir (Unnur); A.G. Uitterlinden (André); E. Widen (Elisabeth); J. Murabito (Joanne); K. Ong (Ken); M.N. Weedon (Michael)

    2010-01-01

    textabstractTo identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30

  12. Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis.

    Science.gov (United States)

    Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R; Stuehr, Dennis J; Panda, Koustubh

    2016-07-19

    Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage.

  13. Andrographolide alleviates imiquimod-induced psoriasis in mice via inducing autophagic proteolysis of MyD88.

    Science.gov (United States)

    Shao, Fenli; Tan, Tao; Tan, Yang; Sun, Yang; Wu, Xingxin; Xu, Qiang

    2016-09-01

    Psoriasis is a chronic inflammatory skin disease with excessive activation of toll-like receptors (TLRs), which play important roles in developing psoriasis. Targeting TLR signaling remains a challenge for treating psoriasis. Here, we found that andrographolide (Andro), a small-molecule natural product, alleviated imiquimod- but not interleukin 23 (IL-23)-induced psoriasis in mice with reducing expressions of IL-23 and IL-1β in the skin. The improvement in imiquimod-induced psoriasis by Andro was not observed in microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) knockout mice. Furthermore, Andro inhibited mRNA expressions of IL-23, IL-6 and IL-1β but not CD80 and CD86 in bone-marrow derived dendritic cells (BMDCs) treated with lipopolysaccharide (LPS) in a MAP1LC3B-dependent manner. In addition, Andro inhibited imiquimod-induced mRNA expressions of IL-23, IL-6, IL-1β, CD80 and CD86 in BMDCs from mice. Interestingly, Andro induced a degradation of myeloid differentiation factor 88 (MyD88) and blocked the recruitment of TNF receptor-associated factor 6 (TRAF6) to MyD88 upon LPS stimulation in BMDCs from mice. Blockade of autophagic proteolysis using NH4Cl or MAP1LC3B(-/-) BMDCs abolished the Andro-induced MyD88 degradation. In conclusion, Andro controls activation of MyD88-dependent cytokines and alleviates psoriasis in mice via inducing autophagic proteolysis of MyD88, which could be a novel strategy to treat psoriasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options.

    Science.gov (United States)

    Bonde, J P; Giwercman, A; Ernst, E

    1996-01-01

    Malfunction of the male reproductive system might be a sensitive marker of environmental hazards, the effects of which may extend beyond reproductive function. The testis is more vulnerable to heat and ionising radiation than any other organ of the body and several xenobiotics are known to disrupt spermatogenesis after low level exposure. Studies of environmental impact on human health are often most informative and accurate when carried out in the workplace where exposures can be high and easy to document. Semen analysis provides readily obtainable information on testicular function. The main advantages in comparison with functional measures such as fertility rates and time taken to conceive are the possibilities to examine men independently of marriage and pregnancy, to find changes of fecundity with different exposures within the same person and to detect adverse effects when no alteration of fertility is yet taking place. In the implementation of an occupational sperm study considerable attention must be paid to logistic issues. A mobile laboratory unit for initial semen preparation and processing may in some situations increase worker compliance and the quality of sperm cell motility. The cross sectional design which has been used in almost all male reproductive studies so far has several severe limitations including selection bias because of differential participation, difficulties in defining a suitable reference group, and lack of information about the time dimension of the cause-effect relation. The longitudinal design deals adequately with most of these constraints. Semen samples are collected before, during, and possibly after exposure to the risk factor of interest and causal inferences are based upon change of semen variables within a man over time rather than upon differences between men. The logistics of the longitudinal study may benefit from pre-employment health examinations to enrol newly hired workers and require fewer participants to obtain

  15. In vivo effect of an antilipolytic drug (3,5'-dimethylpyrazole) on autophagic proteolysis and autophagy-related gene expression in rat liver

    International Nuclear Information System (INIS)

    Donati, Alessio; Ventruti, Annamaria; Cavallini, Gabriella; Masini, Matilde; Vittorini, Simona; Chantret, Isabelle; Codogno, Patrice; Bergamini, Ettore

    2008-01-01

    Autophagy is an intracellular pathway induced by starvation, inhibited by nutrients, that is responsible for degradation of long-lived proteins and altered cell organelles. This process is involved in cell maintenance could be induced by antilipolytic drugs and may have anti-aging effects [A. Donati, The involvement of macroautophagy in aging and anti-aging interventions, Mol. Aspects Med. 27 (2006) 455-470]. We analyzed the effect of an intraperitoneal injection of an antilipolytic agent (3,5'-dimethylpyrazole, DMP, 12 mg/kg b.w.), that mimics nutrient shortage on autophagy and expression of autophagic genes in the liver of male 3-month-old Sprague-Dawley albino rats. Autophagy was evaluated by observing electron micrographs of the liver autophagosomal compartment and by monitoring protein degradation assessed by the release of valine into the bloodstream. LC3 gene expression, whose product is one of the best known markers of autophagy, was also monitored. As expected, DMP decreased the plasma levels of free fatty acids, glucose, and insulin and increased autophagic vacuoles and proteolysis. DMP treatment caused an increase in the expression of the LC3 gene although this occurred later than the induction of authophagic proteolysis caused by DMP. Glucose treatment rescued the effects caused by DMP on glucose and insulin plasma levels and negatively affected the rate of autophagic proteolysis, but did not suppress the positive regulatory effect on LC3 mRNA levels. In conclusion, antilipolytic drugs may induce both autophagic proteolysis and higher expression of an autophagy-related gene and the effect on autophagy gene expression might not be secondary to the stimulation of autophagic proteolysis

  16. An empirical study on identifying critical success factors on chaos management

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2012-08-01

    Full Text Available Chaos management is one of the most necessary efforts on managing business units. Many organizations fail to cope with undesirable circumstances, which may happen without any prior notice and as a result, they may face with significant financial losses. In this paper, we present an empirical study to determine critical success factors, which could help handle any possible chaos in organizations. The proposed study of this paper is implemented for a set of travel agencies located in Tehran, Iran. Chronbach alpha is calculated as 0.821, which is well above the minimum desirable level. In addition, we have also performed factor analysis, which yields a KMO value of 0.576 with the level of significance of 0.000. The results indicate that there are six important factors including effective management strategy, internal environmental factors, creative and innovative attitudes, external environmental factors and top level management thoughts.

  17. Genome-wide association study identifies four loci associated with eruption of permanent teeth

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Zhang, Hao

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years......, analyzed as age-adjusted standard deviation score averaged over multiple time points, based on childhood records for 5,104 women from the Danish National Birth Cohort. Four loci showed association at P...

  18. Identifying drivers of overall satisfaction in patients receiving HIV primary care: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Bich N Dang

    Full Text Available OBJECTIVE: This study seeks to understand the drivers of overall patient satisfaction in a predominantly low-income, ethnic-minority population of HIV primary care patients. The study's primary aims were to determine 1 the component experiences which contribute to patients' evaluations of their overall satisfaction with care received, and 2 the relative contribution of each component experience in explaining patients' evaluation of overall satisfaction. METHODS: We conducted a cross-sectional study of 489 adult patients receiving HIV primary care at two clinics in Houston, Texas, from January 13-April 21, 2011. The participation rate among eligible patients was 94%. The survey included 15 questions about various components of the care experience, 4 questions about the provider experience and 3 questions about overall care. To ensure that the survey was appropriately tailored to our clinic population and the list of component experiences reflected all aspects of the care experience salient to patients, we conducted in-depth interviews with key providers and clinic staff and pre-tested the survey instrument with patients. RESULTS: Patients' evaluation of their provider correlated the strongest with their overall satisfaction (standardized β = 0.445, p<0.001 and accounted for almost half of the explained variance. Access and availability, like clinic hours and ease of calling the clinic, also correlated with overall satisfaction, but less strongly. Wait time and parking, despite receiving low patient ratings, did not correlate with overall satisfaction. CONCLUSIONS: The patient-provider relationship far exceeds other component experiences of care in its association with overall satisfaction. Our study suggests that interventions to improve overall patient satisfaction should focus on improving patients' evaluation of their provider.

  19. Identifying Mechanisms that Predict Loss of Control (LOC) Eating Using Ecological Momentary Assessment: A pilot study

    Science.gov (United States)

    2013-08-30

    not with substance abuse or generalized anxiety (241 ). Furthermore, BED participants were more likely to have undergone therapy and have a family...depressed adolescents by Mufson and colleagues (140). Interpersonal therapy for depressed adolescents (termed IPT-A) focuses on current interpersonal...associated with meals labeled as binges and involving LOC (219). In another study involving measured intake of comfort food ( chocolate ) among 40 obese

  20. Identifying and Overcoming Barriers to Diabetes Management in the Elderly: An Intervention Study

    Science.gov (United States)

    2011-06-01

    weakness (31%), hunger (31%), change in behavior (16%) dizziness (16%), and vision changes (18%) were also common, and can be missed if not asked for...CRP) were measured. Gait speed was calculated from 12 min of hallway walking. Each subject performed a battery of neuropsychological tests to...these studies, diabetic subjects had greater risk for cognitive decline as measured by scores on selected neuropsychological test battery, with odds

  1. Study of Events with Identified Forward Particles at the Split Field Magnet

    CERN Multimedia

    2002-01-01

    This experiment will study two aspects of particle production in the forward region : \\item 1) In the recent discovery of charm production in hadronic interactions at the Split Field Magnet, the triggering on strange particles at medium p^t has proven to be a very effective tool for the study of heavy resonances, especially those carrying new flavours like charm and beauty. We want to carry out a more detailed investigation of the production-dynamics of charmed particles, together with a search for beauty mesons and baryons. \\item 2) A trigger on forward particles at high p^t ($>$ 5GeV/c) provides unique features to determine the properties of the parton-parton subprocesses. We want to study the relative contributions of quark, diquark and gluon scattering.\\\\ \\\\ This experimental programme will be carried out, using the improved Split Field Magnet spectrometer (SFM). The different detection systems provide : \\item a) Detection and momentum analysis of charged particles in 4@p solid angle. An improved programm...

  2. Identifying Sustainable Wood Sources for the Construction Industry: A Case Study

    Directory of Open Access Journals (Sweden)

    Shenghan Li

    2018-01-01

    Full Text Available Wood is generally considered as a sustainable construction material. However, there are not sufficient wood resources in many countries or regions, especially those short of land resources. These countries and regions have to import wood from overseas. Therefore, it is imperative to determine how to choose sustainable importing sources in order to improve the sustainability performance of using wood in construction. This study compares the sustainability performance of wood imported from different regions by considering wood harvesting, manufacture, and transportation. A framework accounting energy consumption and CO2 emissions is developed for sustainability assessment. The results show that importing wood from Canada, Australia, and New Zealand to Taiwan demands a relatively lower amount of energy than from other regions. Specifically, importing wood from Canada (West demands the lowest amount of energy (2095 MJ/m3, while importing wood form Brazil consumes the highest amount of energy (5356 MJ/m3. In addition, findings showed that the CO2 emissions generated from importing wood from Sweden are significant lower than those from other regions, although the energy consumed during the importing process is relatively high. The study also revealed that the wood manufacturing process and marine transportation contribute to the most energy consumption and CO2 emissions among all importing processes analysed from most of studied regions.

  3. Panoramic radiological study to identify locally displaced maxillary canines in Bangladeshi population

    International Nuclear Information System (INIS)

    Alif, Sheikh Mohammad; Haque, Sejuty; Nimmi, Naima; Ashraf, Ali; Khan, Saeed Hossain; Khan, Mahfujul Haq

    2011-01-01

    This study was performed to determine the prevalence of maxillary canine impaction on a basis of a single panoramic radiograph in Bangladeshi population. A random sample of seven hundred panoramic radiographs was collected from the patient record of a dental clinic. All the selected panoramic radiographs were taken from January 2009 to August 2010 by a single panoramic radiograph machine with the same exposure time (19 seconds) for all radiographs. One hundred and twenty panoramic radiographs were excluded to minimize the selection bias. In a dim lit room, an observer assessed the radiographs on a standard radiographic light box. The position of the impacted maxillary canine was recorded in line with the longitudinal axis of a tooth using the edge of a metal ruler. Data were subsequently put on SPSS 11.5 software and chi-square (x 2 ) tests were applied to find out the association. Among 580 panoramic radiographs it was found that impacted maxillary canines were present in only 7 (1.2%) radiographs. A statistical significant difference was found between the age of the patients and the vertical position of the impacted canines (p=0.000) and between the age of the patients and the horizontal position of the impacted canines (p=0.003). The prevalence was found to be low compared with the present study from the limitation of panoramic image. Further study needs to include three-dimensional imaging modality.

  4. Identifying the Neural Substrates of Procrastination: a Resting-State fMRI Study.

    Science.gov (United States)

    Zhang, Wenwen; Wang, Xiangpeng; Feng, Tingyong

    2016-09-12

    Procrastination is a prevalent problematic behavior that brings serious consequences to individuals who suffer from it. Although this phenomenon has received increasing attention from researchers, the underpinning neural substrates of it is poorly studied. To examine the neural bases subserving procrastination, the present study employed resting-state fMRI. The main results were as follows: (1) the behavioral procrastination was positively correlated with the regional activity of the ventromedial prefrontal cortex (vmPFC) and the parahippocampal cortex (PHC), while negatively correlated with that of the anterior prefrontal cortex (aPFC). (2) The aPFC-seed connectivity with the anterior medial prefrontal cortex and the posterior cingulate cortex was positively associated with procrastination. (3) The connectivity between vmPFC and several other regions, such as the dorsomedial prefrontal cortex, the bilateral inferior prefrontal cortex showed a negative association with procrastination. These results suggested that procrastination could be attributed to, on the one hand, hyper-activity of the default mode network (DMN) that overrides the prefrontal control signal; while on the other hand, the failure of top-down control exerted by the aPFC on the DMN. Therefore, the present study unravels the biomarkers of procrastination and provides treatment targets for procrastination prevention.

  5. A case study of identify importance of land use planning in road safety, Benidorm

    Energy Technology Data Exchange (ETDEWEB)

    Casares Blanco, J.; Sanchez Galiano, J.C.; Fernandez Aracil, P.; Ortuño Padilla, A.

    2016-07-01

    This research analyses how urban form, land use and urban density, may influence the incidence of traffic-related crashes injuries and deaths. It begins with a theoretical overview of studies which deal with the study of the relationship between urban patterns and road safety. Next, it details the development of a database of crash incidence and urban form at the district level for the city of Benidorm (Alicante, Spain) in 2010. Subsequently, it is developed a negative binomial approach for intra-city motor vehicle crash analysis. One-year crash data for Benidorm (the fourth largest tourism destination of Spain, after Barcelona, Madrid and San Bartolomé de Tirajana, and exclusively tourist-oriented city) are analyzed using a geographic information system (GIS) to generate relevant inputs for the analysis. In general, the study finds that a strong land use mix results on fewer road accidents, whereas accidents are more common but less severe in areas of high urban density. Finally, pedestrian accidents research showed that rural and low density environment is related to an important road accident numbers unlike tourism-oriented zones, much more safe for them. Based on these findings, the paper discusses the implications for urban design practice. (Author)

  6. Regulation of IGF binding protein proteolysis by pregnancy-associated plasma protein-ARegulation of IGF binding protein proteolysis by pregnancy-associated plasma protein-A

    DEFF Research Database (Denmark)

    Gaidamauskas, Ervinas

    During his PhD studies, Ervinas Gaidamauskas researched the proteins pregnancy-associated plasma protein-A (PAPP-A) and its homologue PAPP-A2 in vitro. As suggested by its name, PAPP-A plays an important role in pregnancy and fetal development. Additionally, recent studies indicate a newly...

  7. Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

    NARCIS (Netherlands)

    Saxena, Richa; Elbers, Clara C.; Guo, Yiran; Peter, Inga; Gaunt, Tom R.; Mega, Jessica L.; Lanktree, Matthew B.; Tare, Archana; Almoguera Castillo, Berta; Li, Yun R.; Johnson, Toby; Bruinenberg, Marcel; Gilbert-Diamond, Diane; Rajagopalan, Ramakrishnan; Voight, Benjamin F.; Balasubramanyam, Ashok; Barnard, John; Bauer, Florianne; Baumert, Jens; Bhangale, Tushar; Boehm, Bernhard O.; Braund, Peter S.; Burton, Paul R.; Chandrupatla, Hareesh R.; Clarke, Robert; Cooper-DeHoff, Rhonda M.; Crook, Errol D.; Davey-Smith, George; Day, Ian N.; de Boer, Anthonius; de Groot, Mark C. H.; Drenos, Fotios; Ferguson, Jane; Fox, Caroline S.; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Gilhuijs-Pederson, Lisa A.; Glessner, Joseph T.; Goel, Anuj; Gong, Yan; Grant, Struan F. A.; Kumari, Meena; van der Harst, Pim; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Wolffenbuttel, Bruce H. R.; Hofker, Marten H.; Asselbergs, Folkert W.; Wijmenga, Cisca

    2012-01-01

    To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and

  8. Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes

    DEFF Research Database (Denmark)

    Imamura, Minako; Takahashi, Atsushi; Yamauchi, Toshimasa

    2016-01-01

    Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and ...

  9. Feasibility study : identifying economic opportunities for bugwood and other biomass resources in Alberta and BC

    International Nuclear Information System (INIS)

    2008-04-01

    This feasibility study discussed energy technologies for biomass feedstocks including mill residues, roadside residues, and non-merchantable tree stands in Alberta and British Columbia (BC). The study demonstrated that the lack of mill residue resources means that targeted government support may be needed to help the energy industry to use more costly resources such as roadside residue or bugwood. Government policies are also needed to support the long-term availability of biomass supplies in order to lower the supply risks related to the use of biomass resources in the energy industry. Lower prices for power in both provinces make the use of biomass unfavourable for small-scale technologies under 10 MW. However, cogeneration projects using biomass showed higher returns when power conversion efficiency was low. Higher revenues were generated from heat sales displacing natural gas than from electricity sales at current tariffs. Large-scale biomass power plants were viable when lower-cost feedstocks were available. Bio-oils were suitable as supplements for heat generation in cogeneration processes. Pellet production was also viable using less expensive feedstocks.The co-firing of biomass at coal plants required little capital investment. The study demonstrated that Alberta's power production incentive of $60 per MWh was sufficient to improve the economics of small-scale projects. It was recommended that the program be continued and paid out over a period of 10 years. It was concluded that specific electricity tariffs and incentives are needed to accelerate regrowth and create a viable biomass industry for the future. 33 refs., 45 tabs., 17 figs

  10. New complete sample of identified radio sources. Part 2. Statistical study

    International Nuclear Information System (INIS)

    Soltan, A.

    1978-01-01

    Complete sample of radio sources with known redshifts selected in Paper I is studied. Source counts in the sample and the luminosity - volume test show that both quasars and galaxies are subject to the evolution. Luminosity functions for different ranges of redshifts are obtained. Due to many uncertainties only simplified models of the evolution are tested. Exponential decline of the liminosity with time of all the bright sources is in a good agreement both with the luminosity- volume test and N(S) realtion in the entire range of observed flux densities. It is shown that sources in the sample are randomly distributed in scales greater than about 17 Mpc. (author)

  11. Identifiability study of the proteins degradation model, based on ADM1, using simultaneous batch experiments

    DEFF Research Database (Denmark)

    Flotats, X.; Palatsi, J.; Ahring, Birgitte Kiær

    2006-01-01

    are not inhibiting the hydrolysis process. The ADM1 model adequately expressed the consecutive steps of hydrolysis and acidogenesis, with estimated kinetic values corresponding to a fast acidogenesis and slower hydrolysis. The hydrolysis was found to be the rate limiting step of anaerobic degradation. Estimation...... of yield coefficients based on the relative initial slopes of VFA profiles obtained in a simple batch experiment produced satisfactory results. From the identification study, it was concluded that it is possible to determine univocally the related kinetic parameter values for protein degradation...... if the evolution of amino acids is measured in simultaneous batch experiments, with different initial protein and amino acids concentrations....

  12. Genome-wide association study identifies candidate genes for male fertility traits in humans.

    Science.gov (United States)

    Kosova, Gülüm; Scott, Nicole M; Niederberger, Craig; Prins, Gail S; Ober, Carole

    2012-06-08

    Despite the fact that hundreds of genes are known to affect fertility in animal models, relatively little is known about genes that influence natural fertility in humans. To broadly survey genes contributing to variation in male fertility, we conducted a genome-wide association study (GWAS) of two fertility traits (family size and birth rate) in 269 married men who are members of a founder population of European descent that proscribes contraception and has large family sizes. Associations between ∼250,000 autosomal SNPs and the fertility traits were examined. A total of 41 SNPs with p ≤ 1 × 10(-4) for either trait were taken forward to a validation study of 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Nine (22%) of the SNPs associated with reduced fertility in the GWAS were also associated with one or more of the ten measures of reduced sperm quantity and/or function, yielding 27 associations with p values LRRC32, which encodes a latent transforming growth factor β (TGF-β) receptor on regulatory T cells. We suggest that mutations in these genes that are more severe may account for some of the unexplained infertility (or subfertility) in the general population. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  13. Identifying lipidic emulsomes for improved oxcarbazepine brain targeting: In vitro and rat in vivo studies.

    Science.gov (United States)

    El-Zaafarany, Ghada M; Soliman, Mahmoud E; Mansour, Samar; Awad, Gehanne A S

    2016-04-30

    Lipid-based nanovectors offer effective carriers for brain delivery by improving drug potency and reducing off-target effects. Emulsomes are nano-triglyceride (TG) carriers formed of lipid cores supported by at least one phospholipid (PC) sheath. Due to their surface active properties, PC forms bilayers at the aqueous interface, thereby enabling encapsulated drug to benefit from better bioavailability and stability. Emulsomes of oxcarbazepine (OX) were prepared, aimed to offer nanocarriers for nasal delivery for brain targeting. Different TG cores (Compritol(®), tripalmitin, tristearin and triolein) and soya phosphatidylcholine in different amounts and ratios were used for emulsomal preparation. Particles were modulated to generate nanocarriers with suitable size, charge, encapsulation efficiency and prolonged release. Cytotoxicity and pharmacokinetic studies were also implemented. Nano-spherical OX-emulsomes with maximal encapsulation of 96.75% were generated. Stability studies showed changes within 30.6% and 11.2% in the size and EE% after 3 months. MTT assay proved a decrease in drug toxicity by its encapsulation in emulsomes. Incorporation of OX into emulsomes resulted in stable nanoformulations. Tailoring emulsomes properties by modulating the surface charge and particle size produced a stable system for the lipophilic drug with a prolonged release profile and mean residence time and proved direct nose-to-brain transport in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. What separates outstanding from average leaders? A study identifies leadership competencies and implications for professional development.

    Science.gov (United States)

    Nygren, D J; Ukeritis, M D

    1992-11-01

    As the healthcare crisis mounts, healthcare organizations must be managed by especially competent leaders. It is important for executives to assess and develop the competencies necessary to become "outstanding" leaders. In our study of leadership competencies among leaders of religious orders, we found that outstanding and average leaders appear to share characteristics such as the ability to articulate their group's mission, the ability to act efficiently, and the tendency to avoid impulsive behavior or excessive emotional expression. Outstanding leaders, however, differed from average leaders in seemingly small but significant ways. For instance, nearly three times as often as average leaders, outstanding leaders expressed a desire to perform tasks well--or better than they had been performed in the past. The study also assessed how members of religious orders perceived their leaders. In general, they tended to rate leaders of their religious institutes as transformational leaders--leaders who welcomed doing things in a new way and inspiring their own staffs to search out new ways to provide services.

  15. Identifying Ethical Issues in Mental Health Research with Minors Adolescents: Results of a Delphi Study

    Directory of Open Access Journals (Sweden)

    Elisabeta Ioana Hiriscau

    2016-05-01

    Full Text Available Research with minors, especially for preventive purposes, e.g., suicide prevention, investigating risk or self-destructive behaviors such as deviance, drug abuse, or suicidal behavior, is ethically sensitive. We present a Delphi study exploring the ethical implications of the needs formulated by researchers in an international pre-conference who would benefit from ethics support and guidance in conducting Mental Health Research with minors. The resulting List of Ethical Issues (LEI was submitted to a 2-rounds Delphi process via the Internet, including 34 multidisciplinary experts. In the first round, the experts reviewed the LEI and completed a questionnaire. Results from this round were analyzed and grouped in nine categories comprising 40 items. In the second round, the experts had to agree/disagree with the needs expressed in the LEI leading to a final list of 25 ethical issues considered relevant for Mental Health Research with minors such as: confidentiality of the sensitive data, competence for consenting alone and risk of harm and stigma related to the methodology used in research. It was shown that studies like SEYLE (Saving and Empowering Young Lives in Europe trigger among researchers wishes to obtain specific recommendations helping to comply with standards for good practice in conducting research with minors.

  16. Identifying Ethical Issues in Mental Health Research with Minors Adolescents: Results of a Delphi Study.

    Science.gov (United States)

    Hiriscau, Elisabeta Ioana; Stingelin-Giles, Nicola; Wasserman, Danuta; Reiter-Theil, Stella

    2016-05-11

    Research with minors, especially for preventive purposes, e.g., suicide prevention, investigating risk or self-destructive behaviors such as deviance, drug abuse, or suicidal behavior, is ethically sensitive. We present a Delphi study exploring the ethical implications of the needs formulated by researchers in an international pre-conference who would benefit from ethics support and guidance in conducting Mental Health Research with minors. The resulting List of Ethical Issues (LEI) was submitted to a 2-rounds Delphi process via the Internet, including 34 multidisciplinary experts. In the first round, the experts reviewed the LEI and completed a questionnaire. Results from this round were analyzed and grouped in nine categories comprising 40 items. In the second round, the experts had to agree/disagree with the needs expressed in the LEI leading to a final list of 25 ethical issues considered relevant for Mental Health Research with minors such as: confidentiality of the sensitive data, competence for consenting alone and risk of harm and stigma related to the methodology used in research. It was shown that studies like SEYLE (Saving and Empowering Young Lives in Europe) trigger among researchers wishes to obtain specific recommendations helping to comply with standards for good practice in conducting research with minors.

  17. Genome-Wide Association Study Identifies Four Loci Associated with Eruption of Permanent Teeth

    Science.gov (United States)

    Zhang, Hao; Shaffer, John R.; Hansen, Thomas; Esserlind, Ann-Louise; Boyd, Heather A.; Nohr, Ellen A.; Timpson, Nicholas J.; Fatemifar, Ghazaleh; Paternoster, Lavinia; Evans, David M.; Weyant, Robert J.; Levy, Steven M.; Lathrop, Mark; Smith, George Davey; Murray, Jeffrey C.; Olesen, Jes; Werge, Thomas; Marazita, Mary L.; Sørensen, Thorkild I. A.; Melbye, Mads

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, analyzed as age-adjusted standard deviation score averaged over multiple time points, based on childhood records for 5,104 women from the Danish National Birth Cohort. Four loci showed association at Peruption and were also known to influence height and breast cancer, respectively. The two other loci pointed to genomic regions without any previous significant genome-wide association study results. The intronic SNP rs7924176 in ADK could be linked to gene expression in monocytes. The combined effect of the four genetic variants was most pronounced between age 10 and 12 years, where children with 6 to 8 delayed tooth eruption alleles had on average 3.5 (95% confidence interval: 2.9–4.1) fewer permanent teeth than children with 0 or 1 of these alleles. PMID:21931568

  18. Identifying Ethical Issues in Mental Health Research with Minors Adolescents: Results of a Delphi Study

    Science.gov (United States)

    Hiriscau, Elisabeta Ioana; Stingelin-Giles, Nicola; Wasserman, Danuta; Reiter-Theil, Stella

    2016-01-01

    Research with minors, especially for preventive purposes, e.g., suicide prevention, investigating risk or self-destructive behaviors such as deviance, drug abuse, or suicidal behavior, is ethically sensitive. We present a Delphi study exploring the ethical implications of the needs formulated by researchers in an international pre-conference who would benefit from ethics support and guidance in conducting Mental Health Research with minors. The resulting List of Ethical Issues (LEI) was submitted to a 2-rounds Delphi process via the Internet, including 34 multidisciplinary experts. In the first round, the experts reviewed the LEI and completed a questionnaire. Results from this round were analyzed and grouped in nine categories comprising 40 items. In the second round, the experts had to agree/disagree with the needs expressed in the LEI leading to a final list of 25 ethical issues considered relevant for Mental Health Research with minors such as: confidentiality of the sensitive data, competence for consenting alone and risk of harm and stigma related to the methodology used in research. It was shown that studies like SEYLE (Saving and Empowering Young Lives in Europe) trigger among researchers wishes to obtain specific recommendations helping to comply with standards for good practice in conducting research with minors. PMID:27187425

  19. Genome-wide association study identified copy number variants important for appendicular lean mass.

    Science.gov (United States)

    Ran, Shu; Liu, Yong-Jun; Zhang, Lei; Pei, Yufang; Yang, Tie-Lin; Hai, Rong; Han, Ying-Ying; Lin, Yong; Tian, Qing; Deng, Hong-Wen

    2014-01-01

    Skeletal muscle is a major component of the human body. Age-related loss of muscle mass and function contributes to some public health problems such as sarcopenia and osteoporosis. Skeletal muscle, mainly composed of appendicular lean mass (ALM), is a heritable trait. Copy number variation (CNV) is a common type of human genome variant which may play an important role in the etiology of many human diseases. In this study, we performed genome-wide association analyses of CNV for ALM in 2,286 Caucasian subjects. We then replicated the major findings in 1,627 Chinese subjects. Two CNVs, CNV1191 and CNV2580, were detected to be associated with ALM (p = 2.26×10(-2) and 3.34×10(-3), respectively). In the Chinese replication sample, the two CNVs achieved p-values of 3.26×10(-2) and 0.107, respectively. CNV1191 covers a gene, GTPase of the immunity-associated protein family (GIMAP1), which is important for skeletal muscle cell survival/death in humans. CNV2580 is located in the Serine hydrolase-like protein (SERHL) gene, which plays an important role in normal peroxisome function and skeletal muscle growth in response to mechanical stimuli. In summary, our study suggested two novel CNVs and the related genes that may contribute to variation in ALM.

  20. Genome-wide association study identified copy number variants important for appendicular lean mass.

    Directory of Open Access Journals (Sweden)

    Shu Ran

    Full Text Available Skeletal muscle is a major component of the human body. Age-related loss of muscle mass and function contributes to some public health problems such as sarcopenia and osteoporosis. Skeletal muscle, mainly composed of appendicular lean mass (ALM, is a heritable trait. Copy number variation (CNV is a common type of human genome variant which may play an important role in the etiology of many human diseases. In this study, we performed genome-wide association analyses of CNV for ALM in 2,286 Caucasian subjects. We then replicated the major findings in 1,627 Chinese subjects. Two CNVs, CNV1191 and CNV2580, were detected to be associated with ALM (p = 2.26×10(-2 and 3.34×10(-3, respectively. In the Chinese replication sample, the two CNVs achieved p-values of 3.26×10(-2 and 0.107, respectively. CNV1191 covers a gene, GTPase of the immunity-associated protein family (GIMAP1, which is important for skeletal muscle cell survival/death in humans. CNV2580 is located in the Serine hydrolase-like protein (SERHL gene, which plays an important role in normal peroxisome function and skeletal muscle growth in response to mechanical stimuli. In summary, our study suggested two novel CNVs and the related genes that may contribute to variation in ALM.

  1. A novel method for identifying settings for well-motivated ecologic studies of cancer

    Science.gov (United States)

    Stang, Andreas; Kowall, Bernd; Rusner, Carsten; Trabert, Britton; Bray, Freddie; Schüz, Joachim; McGlynn, Katherine A.; Kuss, Oliver

    2016-01-01

    A low within-country variability and a large between-country variability in cancer incidence may indicate that ecologic factors are involved in the etiology of the disease. The aim of this study is to explore the within- and between-country variability of cancer incidence to motivate high-quality ecologic studies. We extracted age-standardized incidence rate estimates (world standard population) from 135 regions for the 10 most frequent invasive cancers in Europe for non-Hispanic white populations from Cancer Incidence in Five Continents, Volume X. We fitted weighted multilevel Poisson regression models with random country effects for each cancer and sex. We estimated intraclass correlation coefficients (ICC) and 95% confidence intervals (95%CI). A high ICC indicates a low within and a high between-country variability of rates. The two cancer sites with the highest ICC among men were prostate cancer (0.96, 95%CI: 0.92–0.99) and skin melanoma (0.78, 0.64–0.93). Among women, high ICC were observed for lung cancer (0.84, 0.73–0.95) and breast cancer (0.80, 0.69–0.91). The two most prominent sex differences for ICC occurred for cancers of the head and neck (men: 0.70, 0.55–0.85, women: 0.19, 0.08–0.30) and breast cancer (men: 0.04, 0.01–0.07, women: 0.80, 0.69–0.91). ICCs were relatively low for pancreatic cancer (men: 0.23, 0.10–0.35; women: 0.13, 0.04–0.21) and leukemia (men: 0.12, 0.04–0.21; women: 0.08, 0.02–0.14). For cancers with high ICC for which systematic factors of the health care system, screening and diagnostic activities are not plausible explanations for between-country variations in incidence, cross-country sex-specific ecologic studies may be especially promising. PMID:26595447

  2. Identifying the risk: a prospective cohort study examining postpartum haemorrhage in a regional Australian health service.

    Science.gov (United States)

    Kearney, Lauren; Kynn, Mary; Reed, Rachel; Davenport, Lisa; Young, Jeanine; Schafer, Keppel

    2018-06-07

    In industrialised countries the incidence of postpartum haemorrhage (PPH) is increasing, for which exact etiology is not well understood. Studies have relied upon retrospective data with estimated blood loss as the primary outcome, known to be underestimated by clinicians. This study aimed to explore variables associated with PPH in a cohort of women birthing vaginally in coastal Queensland, Australia, using the gravimetric method to measure blood loss. Women were prospectively recruited to participate using an opt-out consent process. Maternal demographics; pregnancy history; model of care; mode of birth; third stage management practices; antenatal, intrapartum and immediate postpartum complications; gravimetric and estimated blood loss; and haematological laboratory data, were collected via a pre-designed data collection instrument. Descriptive statistics were used for demographic, intrapartum and birthing practices. A General Linear Model was used for multivariate analysis to examine relationship between gravimetric blood loss and demographic, birthing practices and intrapartum variables. The primary outcome was a postpartum haemorrhage (blood loss > 500 ml). 522 singleton births were included in the analysis. Maternal mean age was 29 years; 58% were multiparous. Most participants received active (291, 55.7%) or modified active management of third stage (191, 36.6%). Of 451 births with valid gravimetric blood loss recorded, 35% (n = 159) recorded a loss of 500 ml or more and 111 (70%) of these were recorded as PPH. Gravimetric blood loss was strongly correlated with estimated blood loss (r = 0.88; p gravimetric blood loss, about 78% of the measured value. High neonatal weight, perineal injury, complications during labour, separation of mother and baby, and observation of a gush of blood were associated with PPH. Nulliparity, labour induction and augmentation, syntocinon use were not associated with PPH. In contrast to previous study findings

  3. Identifying dissociative identity disorder: a self-report and projective study.

    Science.gov (United States)

    Scroppo, J C; Drob, S L; Weinberger, J L; Eagle, P

    1998-05-01

    This study compared 21 female adult psychiatric patients diagnosed with dissociative identity disorder (DID) with 21 female adult nondissociative psychiatric patients to determine whether DID patients exhibit a distinguishing set of clinical features, and perceptual, attentional, and cognitive processes. Participants were assessed with the Dissociative Disorders Interview Schedule to assess diagnostic status. Group scores on the Dissociative Experiences Scale, Tellegen Absorption Scale, Childhood Trauma Questionnaire, Brief Symptom Inventory, and the Rorschach test were compared. DID participants reported earlier and more severe childhood trauma, more dissociative symptoms, and a greater propensity for altered states of consciousness. The DID participants also exhibited increased projective and imaginative activity, a diminished ability to integrate mental contents, a complex and driven cognitive style, and a highly unconventional view of reality.

  4. Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism

    DEFF Research Database (Denmark)

    Rao, Fangwen; Wessel, Jennifer; Wen, Gen

    2007-01-01

    biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine...... hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable......, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention...

  5. A study to identify winning strategies for the business community during the next pandemic.

    Science.gov (United States)

    Spriggs, Martin

    2013-01-01

    This study examines the relationship between the healthcare system and the corporate sector to answer the following research question: how does the healthcare system best prepare small to medium-sized businesses for the next pandemic influenza? Data were collected and collated through a literature review, electronic survey and semi-structured follow-up telephone interviews. The participants were businesses with membership in the Alberta Chambers of Commerce, a provincial lobby group in Alberta, Canada. The findings indicate strategies that were effective in minimising impact to the business community during the H1N1 pandemic and suggest areas for the business community to improve in preparation for the next pandemic influenza. Recommendations focus on establishing new links for communication between the business community and the healthcare sector and improving strategies to increase the resilience of small to medium-sized businesses for the next pandemic influenza.

  6. Eating in moderation and the essential role of awareness. A Dutch longitudinal study identifying psychosocial predictors.

    Science.gov (United States)

    Walthouwer, Michel Jean Louis; Oenema, Anke; Candel, Math; Lechner, Lilian; de Vries, Hein

    2015-04-01

    Eating in moderation, i.e. the attempt to monitor and limit the intake of energy-dense foods, is a promising strategy in the prevention of weight gain. The purpose of this study was to examine which psychosocial factors derived from the I-Change Model (ICM) were associated with eating in moderation, and whether these factors differed between adults with a correct (aware) or incorrect (unaware) perception of their dietary behaviour. This study used a longitudinal design with measurements at baseline (N = 483) and six-month follow-up (N = 379). Eating in moderation was defined as the average daily energy intake from energy-dense food products and was measured by a validated food frequency questionnaire. Linear regression analyses were used to assess the associations between the ICM factors and eating in moderation. The moderating role of awareness was examined by including interactions between awareness and the ICM factors in the regression analyses using the pick-a-point approach to further examine the associations for aware and unaware participants. Participants who were aware of their dietary behaviour had a significantly lower average daily energy intake compared to those who were unaware. Eating in moderation was predicted by awareness, risk perception, social influence and intention. Among the aware participants, eating in moderation was predicted by risk perception, attitude, social influence and intention. Among the unaware participants, only risk perception and self-efficacy were significantly associated with eating in moderation. Our findings show that psychosocial factors may only predict eating in moderation when people are aware of their risk behaviour. Therefore, interventions aimed at promoting complex behaviours, such as eating in moderation, should first focus on improving individuals' awareness of their risk behaviour before targeting motivational factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Identifying and Studying the Factors Effective on Greenhouses Profitability in the Varamin Plain

    Directory of Open Access Journals (Sweden)

    Narges Rajabi Tehrani

    2017-01-01

    Full Text Available The purpose of this research was economic evaluation of green houses and the factors that affect their profitability in the Varamin plain. The type of this research is descriptive-correlation research that was conducted by using a survey method. The statistical population of the research consisted of the beneficiary farmers of established and cultivated green houses in the Varamin plain. The sample size was 108 farmers. The sampling method was simple random sampling method. The main tool of this research study is a questionnaire that whose validity was verified by using a panel of experts and professors in the field of agriculture. The reliability of the questionnaire was assessed through a pre-test for which the Cronbach alpha was between 0.78 and 0.85 which is considered to be acceptable. The results of this research study show that the mean of the profitability index of cost benefit  was 2.286 and thus there is a significant positive correlation between agricultural experience, the level of famer education, agricultural income, the total area of the green house, technical knowledge, using of information resources with the cost benefit  profitability index. The results of regression analysis also indicated that the five variables of agricultural experience, agricultural income, the total area of the green house, technical knowledge, using of information resources well explain for 51.5 % of the changes in the cost benefit profitability index of the green houses located in the Varamin plain. Finally, it is recommended to improve the cost benefit profitability index by actions such as increasing the level of technical knowledge and farmers' access to and use of information resources.

  8. Gas-fired cogeneration and cooling: new study identifies major benefits

    International Nuclear Information System (INIS)

    Watt, G.

    2001-01-01

    A research paper- 'Gas Fired Cogeneration and Cooling: Markets, Technologies and Greenhouse Gas Savings'- launched at last month's Australian Gas Association 2001 Convention, reveals that gas cooling could replace 25 PJ of electricity summer demand, and reduce greenhouse gas emissions by 58 percent compared with electrical technologies. Commissioned by the AGA's Gas Cooling Task Force and supported by the Sustainable Energy Authority of Victoria and the Sustainable Energy Development Authority of NSW, the study examined market opportunities and environmental outcomes for the combined gas cogeneration and cooling technologies. It shows that the penetration of gas into the distributed cooling and power generation market is being driven by the following developments: the uncertainty and volatility of electricity costs, particularly during summer, electricity market structural changes which encourage distributed generation, high and uncertain world oil prices, the relative stability of Australian gas prices, the encouragement of demand and energy management strategies by regulators, greenhouse gas emission reduction policies, indoor air quality issues, product and productivity improvements in industry and CFC phase-out opportunities

  9. Identifying patient preferences for communicating risk estimates: A descriptive pilot study

    Directory of Open Access Journals (Sweden)

    O'Connor Annette M

    2001-08-01

    Full Text Available Abstract Background Patients increasingly seek more active involvement in health care decisions, but little is known about how to communicate complex risk information to patients. The objective of this study was to elicit patient preferences for the presentation and framing of complex risk information. Method To accomplish this, eight focus group discussions and 15 one-on-one interviews were conducted, where women were presented with risk data in a variety of different graphical formats, metrics, and time horizons. Risk data were based on a hypothetical woman's risk for coronary heart disease, hip fracture, and breast cancer, with and without hormone replacement therapy. Participants' preferences were assessed using likert scales, ranking, and abstractions of focus group discussions. Results Forty peri- and postmenopausal women were recruited through hospital fliers (n = 25 and a community health fair (n = 15. Mean age was 51 years, 50% were non-Caucasian, and all had completed high school. Bar graphs were preferred by 83% of participants over line graphs, thermometer graphs, 100 representative faces, and survival curves. Lifetime risk estimates were preferred over 10 or 20-year horizons, and absolute risks were preferred over relative risks and number needed to treat. Conclusion Although there are many different formats for presenting and framing risk information, simple bar charts depicting absolute lifetime risk were rated and ranked highest overall for patient preferences for format.

  10. Personality Profiles Identify Depressive Symptoms over Ten Years? A Population-Based Study

    Directory of Open Access Journals (Sweden)

    Kim Josefsson

    2011-01-01

    Full Text Available Little is known about the relationship between temperament and character inventory (TCI profiles and depressive symptoms. Personality profiles are useful, because personality traits may have different effects on depressive symptoms when combined with different combinations of other traits. Participants were from the population-based Young Finns study with repeated measurements in 1997, 2001, and 2007 (=1402 to 1902. TCI was administered in 1997 and mild depressive symptoms (modified Beck’s depression inventory, BDI were reported in 1997, 2001, and 2007. BDI-II was also administered in 2007. We found that high harm avoidance and low self-directedness related strongly to depressive symptoms. In addition, sensitive (NHR and fanatical people (ScT were especially vulnerable to depressive symptoms. high novelty seeking and reward dependence increased depressive symptoms when harm avoidance was high. These associations were very similar in cross-sectional and longitudinal analysis. Personality profiles help in understanding the complex associations between depressive symptoms and personality.

  11. A clinical study of brainstem infarction identified on magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masaki; Takahashi, Akira (Nagoya Univ. (Japan). Faculty of Medicine); Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro

    1993-04-01

    We conducted a clinical study of 155 cases that were confirmed to have brainstem infarctions on MRI (T[sub 1]-weighted image showed a low signal and T[sub 2]-weighted image showed a high signal, measuring in excess of 2 x 2 mm). The majority of the brainstem infarction was located in the pontine base in 132 cases (85.2%). Of these, 19 cases had double lesions including infarctions in the pontine base. Second infarctions frequently occurred in the cerebral peduncle or medical medulla oblongata, unilateral to the pontine infarctions. In addition to 98 symptomatic cases, there were 57 cases of 'asymptomatic' brainstem infarction. They comprised 24 cases accompanying other symptomatic cerebrovascular diseases in the supratentorium and 33 cases of transient subjective complaints such as headache or vertigo-dizziness. Complication by supratentorial infarctions was significantly frequent in cases of brainstem infarction (p<0.001), 122 of 155 cases (78.7%), especially in the pontine base (88.6%); while in the control cases (without brainstem infarction) only 65 of 221 cases (29.4%). These findings are considered to show the widespread progress of arteriosclerosis in brainstem infarction, especially in ones in the pontine base. (author).

  12. Identifying Opinion Leaders to Promote Organ Donation on Social Media: Network Study

    Science.gov (United States)

    Salmon, Charles T

    2018-01-01

    Background In the recent years, social networking sites (SNSs, also called social media) have been adopted in organ donation campaigns, and recruiting opinion leaders for such campaigns has been found effective in promoting behavioral changes. Objective The aim of this paper was to focus on the dissemination of organ donation tweets on Weibo, the Chinese equivalent of Twitter, and to examine the opinion leadership in the retweet network of popular organ donation messages using social network analysis. It also aimed to investigate how personal and social attributes contribute to a user’s opinion leadership on the topic of organ donation. Methods All messages about organ donation posted on Weibo from January 1, 2015 to December 31, 2015 were extracted using Python Web crawler. A retweet network with 505,047 nodes and 545,312 edges of the popular messages (n=206) was constructed and analyzed. The local and global opinion leaderships were measured using network metrics, and the roles of personal attributes, professional knowledge, and social positions in obtaining the opinion leadership were examined using general linear model. Results The findings revealed that personal attributes, professional knowledge, and social positions predicted individual’s local opinion leadership in the retweet network of popular organ donation messages. Alternatively, personal attributes and social positions, but not professional knowledge, were significantly associated with global opinion leadership. Conclusions The findings of this study indicate that health campaign designers may recruit peer leaders in SNS organ donation promotions to facilitate information sharing among the target audience. Users who are unverified, active, well connected, and experienced with information and communications technology (ICT) will accelerate the sharing of organ donation messages in the global environment. Medical professionals such as organ transplant surgeons who can wield a great amount of

  13. Identifying Opinion Leaders to Promote Organ Donation on Social Media: Network Study.

    Science.gov (United States)

    Shi, Jingyuan; Salmon, Charles T

    2018-01-09

    In the recent years, social networking sites (SNSs, also called social media) have been adopted in organ donation campaigns, and recruiting opinion leaders for such campaigns has been found effective in promoting behavioral changes. The aim of this paper was to focus on the dissemination of organ donation tweets on Weibo, the Chinese equivalent of Twitter, and to examine the opinion leadership in the retweet network of popular organ donation messages using social network analysis. It also aimed to investigate how personal and social attributes contribute to a user's opinion leadership on the topic of organ donation. All messages about organ donation posted on Weibo from January 1, 2015 to December 31, 2015 were extracted using Python Web crawler. A retweet network with 505,047 nodes and 545,312 edges of the popular messages (n=206) was constructed and analyzed. The local and global opinion leaderships were measured using network metrics, and the roles of personal attributes, professional knowledge, and social positions in obtaining the opinion leadership were examined using general linear model. The findings revealed that personal attributes, professional knowledge, and social positions predicted individual's local opinion leadership in the retweet network of popular organ donation messages. Alternatively, personal attributes and social positions, but not professional knowledge, were significantly associated with global opinion leadership. The findings of this study indicate that health campaign designers may recruit peer leaders in SNS organ donation promotions to facilitate information sharing among the target audience. Users who are unverified, active, well connected, and experienced with information and communications technology (ICT) will accelerate the sharing of organ donation messages in the global environment. Medical professionals such as organ transplant surgeons who can wield a great amount of influence on their direct connections could also effectively

  14. Bioimpedance identifies body fluid loss after exercise in the heat: a pilot study with body cooling.

    Directory of Open Access Journals (Sweden)

    Hannes Gatterer

    Full Text Available Assessment of post-exercise changes in hydration with bioimpedance (BI is complicated by physiological adaptations that affect resistance (R and reactance (Xc values. This study investigated exercise-induced changes in R and Xc, independently and in bioelectrical impedance vector analysis, when factors such as increased skin temperature and blood flow and surface electrolyte accumulation are eliminated with a cold shower.Healthy males (n = 14, 24.1±1.7 yr; height (H: 182.4±5.6 cm, body mass: 72.3±6.3 kg exercised for 1 hr at a self-rated intensity (15 BORG in an environmental chamber (33°C and 50% relative humidity, then had a cold shower (15 min. Before the run BI, body mass, hematocrit and Posm were measured. After the shower body mass was measured; BI measurements were performed continuously every 20 minutes until R reached a stable level, then hematocrit and Posm were measured again.Compared to pre-trial measurements body mass decreased after the run and Posm, Hct, R/H and Xc/H increased (p<0.05 with a corresponding lengthening of the impedance vector along the major axis of the tolerance ellipse (p<0.001. Changes in Posm were negatively related to changes in body mass (r = -0.564, p = 0.036 and changes in Xc/H (r = -0.577, p = 0.041.Present findings showed that after a bout of exercise-induced dehydration followed by cold shower the impedance vector lengthened that indicates fluid loss. Additionally, BI values might be useful to evaluate fluid shifts between compartments as lower intracellular fluid loss (changed Xc/R indicated greater Posm increase.

  15. An Automated High Throughput Proteolysis and Desalting Platform for Quantitative Proteomic Analysis

    Directory of Open Access Journals (Sweden)

    Albert-Baskar Arul

    2013-06-01

    Full Text Available Proteomics for biomarker validation needs high throughput instrumentation to analyze huge set of clinical samples for quantitative and reproducible analysis at a minimum time without manual experimental errors. Sample preparation, a vital step in proteomics plays a major role in identification and quantification of proteins from biological samples. Tryptic digestion a major check point in sample preparation for mass spectrometry based proteomics needs to be more accurate with rapid processing time. The present study focuses on establishing a high throughput automated online system for proteolytic digestion and desalting of proteins from biological samples quantitatively and qualitatively in a reproducible manner. The present study compares online protein digestion and desalting of BSA with conventional off-line (in-solution method and validated for real time sample for reproducibility. Proteins were identified using SEQUEST data base search engine and the data were quantified using IDEALQ software. The present study shows that the online system capable of handling high throughput samples in 96 well formats carries out protein digestion and peptide desalting efficiently in a reproducible and quantitative manner. Label free quantification showed clear increase of peptide quantities with increase in concentration with much linearity compared to off line method. Hence we would like to suggest that inclusion of this online system in proteomic pipeline will be effective in quantification of proteins in comparative proteomics were the quantification is really very crucial.

  16. Usability Study Identifies Vocabulary, Facets, and Education as Primary Primo Discovery System Interface Problems

    Directory of Open Access Journals (Sweden)

    Ruby Muriel Lavallee Warren

    2017-09-01

    Full Text Available A Review of: Brett, K. R., Lierman, A., & Turner, C. (2016. Lessons learned: A Primo usability study. Information Technology and Libraries, 35(1, 7-25. https://doi.org/10.6017/ital.v35i1.8965 Abstract Objective – To discover whether users can effectively complete common research tasks in a modified Primo Discovery System interface. Design – Usability testing. Setting – University of Houston Libraries. Subjects – Users of the University of Houston Libraries Ex Libris Primo Discovery System interface. Methods – The researchers used a think aloud usability test methodology, with participants asked to verbalize their thought processes as they completed a set of tasks. Four tasks were developed and divided into two task sets (Test 1 and Test 2, with session facilitators alternating sets for each participant. Tasks were as follows: locating a known article, finding a peer reviewed article on a requested subject, locating a book, and finding a newspaper article on a topic. Tests were conducted in front of the library entrance using a laptop equipped with Morae (screen and audio recording software, and participants were recruited via an assigned “caller” at the table offering library merchandise and food as a research incentive. Users could opt out of having their session recorded, resulting in a total of fifteen sessions completed with fourteen recorded. Thirteen of the fifteen participants were undergraduate students, one was a graduate student, one was a post-baccalaureate student, and there were no faculty participants. Facilitators completed notes on a standard rubric, coding participant responses into successes or failures and noting participant feedback. Main Results – All eight participants assigned Test 1 successfully completed Test 1, Task 1: locating a known article. Participants expressed a need for an author limiter in advanced search, and had difficulty using the citation formatted information to locate materials

  17. Five year prognosis in patients with angina identified in primary care: incident cohort study.

    LENUS (Irish Health Repository)

    Buckley, Brian S

    2009-01-01

    OBJECTIVE: To ascertain the risk of acute myocardial infarction, invasive cardiac procedures, and mortality among patients with newly diagnosed angina over five years. DESIGN: Incident cohort study of patients with primary care data linked to secondary care and mortality data. SETTING: 40 primary care practices in Scotland. PARTICIPANTS: 1785 patients with a diagnosis of angina as their first manifestation of ischaemic heart disease, 1 January 1998 to 31 December 2001. MAIN OUTCOME MEASURES: Adjusted hazard ratios for acute myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, death from ischaemic heart disease, and all cause mortality, adjusted for demographics, lifestyle risk factors, and comorbidity at cohort entry. RESULTS: Mean age was 62.3 (SD 11.3). Male sex was associated with an increased risk of acute myocardial infarction (hazard ratio 2.01, 95% confidence interval 1.35 to 2.97), death from ischaemic heart disease (2.80, 1.73 to 4.53), and all cause mortality (1.82, 1.33 to 2.49). Increasing age was associated with acute myocardial infarction (1.04, 1.02 to 1.06, per year of age increase), death from ischaemic heart disease (1.09, 1.06 to 1.11, per year of age increase), and all cause mortality (1.09, 1.07 to 1.11, per year of age increase). Smoking was associated with subsequent acute myocardial infarction (1.94, 1.31 to 2.89), death from ischaemic heart disease (2.12, 1.32 to 3.39), and all cause mortality (2.11, 1.52 to 2.95). Obesity was associated with death from ischaemic heart disease (2.01, 1.17 to 3.45) and all cause mortality (2.20, 1.52 to 3.19). Previous stroke was associated with all cause mortality (1.78, 1.13 to 2.80) and chronic kidney disease with death from ischaemic heart disease (5.72, 1.74 to 18.79). Men were more likely than women to have coronary artery bypass grafting or percutaneous transluminal coronary angioplasty after a diagnosis of angina; older people were less likely to

  18. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Xiufeng; Zhang, Ting; Wang, Jie; Li, Meng; Zhang, Xiaolei; Tu, Jing [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Sun, Shiqin [College of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319 (China); Chen, Xiangmei, E-mail: xm_chen6176@bjmu.edu.cn [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Lu, Fengmin [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China)

    2014-04-25

    Highlights: • The expression of Fbx4 was significantly lower in HCC tissues. • Novel splicing variants of Fbx4 were identified. • These novel variants are much more abundant in human cancer tissues and cells. • The novel Fbx4 isoforms could promote cell proliferation and migration in vitro. • These isoforms showed less capability for cyclin D1 binding and degradation. - Abstract: Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4α and the C-terminal truncated Fbx4β have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4γ (missing 168–245nt of exon1), Fbx4δ (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4β, Fbx4γ and Fbx4δ could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4α that mainly exists in cytoplasm, Fbx4β, Fbx4γ, and Fbx4δ locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant

  19. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer

    International Nuclear Information System (INIS)

    Chu, Xiufeng; Zhang, Ting; Wang, Jie; Li, Meng; Zhang, Xiaolei; Tu, Jing; Sun, Shiqin; Chen, Xiangmei; Lu, Fengmin

    2014-01-01

    Highlights: • The expression of Fbx4 was significantly lower in HCC tissues. • Novel splicing variants of Fbx4 were identified. • These novel variants are much more abundant in human cancer tissues and cells. • The novel Fbx4 isoforms could promote cell proliferation and migration in vitro. • These isoforms showed less capability for cyclin D1 binding and degradation. - Abstract: Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4α and the C-terminal truncated Fbx4β have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4γ (missing 168–245nt of exon1), Fbx4δ (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4β, Fbx4γ and Fbx4δ could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4α that mainly exists in cytoplasm, Fbx4β, Fbx4γ, and Fbx4δ locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant

  20. Oxidative and proteolysis-related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction.

    Science.gov (United States)

    Brunnquell, Cláudia R; Vieira, Nichelle A; Sábio, Laís R; Sczepanski, Felipe; Cecchini, Alessandra L; Cecchini, Rubens; Guarnier, Flávia A

    2015-06-01

    The objective of this study was to investigate whether emphysema induced by elastase or papain triggers the same effects on skeletal muscle, related to oxidative stress and proteolysis, in hamsters. For this purpose, we evaluated pulmonary lesions, body weight, muscle loss, oxidative stress (thiobarbituric acid-reactive substances, total and oxidized glutathiones, chemiluminescence stimulated by tert-butyl hydroperoxide and carbonyl proteins), chymotrypsin-like and calpain-like proteolytic activities and muscle fibre cross-sectional area in the gastrocnemius muscles of emphysemic hamsters. Two groups of animals received different intratracheal inductions of experimental emphysema: by 40 mg/ml papain (EP) or 5.2 IU/100 g animal (EE) elastase (n = 10 animals/group). The control group received intratracheal instillation of 300 μl sterile NaCl 0.9%. Compared with the control group, the EP group had reduced muscle weight (18.34%) and the EE group had increased muscle weight (8.37%). Additionally, tert-butyl hydroperoxide-initiated chemiluminescence, carbonylated proteins and chymotrypsin-like proteolytic activity were all elevated in the EP group compared to the CS group, while total glutathione was decreased compared to the EE group. The EE group showed more fibres with increased cross-sectional areas and increased calpain-like activity. Together, these data show that elastase and papain, when used to induce experimental models of emphysema, lead to different speeds and types of adaptation. These findings provide more information on choosing a suitable experimental model for studying skeletal muscle adaptations in emphysema. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

  1. Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study

    DEFF Research Database (Denmark)

    Druley, Todd E; Wang, Lihua; Lin, Shiow J

    2016-01-01

    from six pedigrees. OBFC1 (chromosome 10) is involved in telomere maintenance, and falls within a linkage peak recently reported from an analysis of telomere length in LLFS families. Two different algorithms for single gene associations identified three genes with an enrichment of variation......BACKGROUND: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. METHODS......: We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually...

  2. Community health center provider ability to identify, treat and account for the social determinants of health: a card study.

    Science.gov (United States)

    Lewis, Joy H; Whelihan, Kate; Navarro, Isaac; Boyle, Kimberly R

    2016-08-27

    The social determinants of health (SDH) are conditions that shape the overall health of an individual on a continuous basis. As momentum for addressing social factors in primary care settings grows, provider ability to identify, treat and assess these factors remains unknown. Community health centers care for over 20-million of America's highest risk populations. This study at three centers evaluates provider ability to identify, treat and code for the SDH. Investigators utilized a pre-study survey and a card study design to obtain evidence from the point of care. The survey assessed providers' perceptions of the SDH and their ability to address them. Then providers filled out one anonymous card per patient on four assigned days over a 4-week period, documenting social factors observed during encounters. The cards allowed providers to indicate if they were able to: provide counseling or other interventions, enter a diagnosis code and enter a billing code for identified factors. The results of the survey indicate providers were familiar with the SDH and were comfortable identifying social factors at the point of care. A total of 747 cards were completed. 1584 factors were identified and 31 % were reported as having a service provided. However, only 1.2 % of factors were associated with a billing code and 6.8 % received a diagnosis code. An obvious discrepancy exists between the number of identifiable social factors, provider ability to address them and documentation with billing and diagnosis codes. This disparity could be related to provider inability to code for social factors and bill for related time and services. Health care organizations should seek to implement procedures to document and monitor social factors and actions taken to address them. Results of this study suggest simple methods of identification may be sufficient. The addition of searchable codes and reimbursements may improve the way social factors are addressed for individuals and populations.

  3. Describing Case Study Method and Identifying the Factors that Contribute to the Successful Conduct of Case Studies

    OpenAIRE

    Ahmad H. Juma'h; Mustafa Cavus

    2001-01-01

    This article has attempted to describe case study, the limitations and critiques on case study methodology and how the proponents have responded to these. Our special focus have been on the debate on theory building from case study research, and a framework for conducting case study research as well as the factors for a successful case study research. The overall conclusion is that the case study has been inappropriately used to generate theories.

  4. Identifiability of large-scale non-linear dynamic network models applied to the ADM1-case study.

    Science.gov (United States)

    Nimmegeers, Philippe; Lauwers, Joost; Telen, Dries; Logist, Filip; Impe, Jan Van

    2017-06-01

    In this work, both the structural and practical identifiability of the Anaerobic Digestion Model no. 1 (ADM1) is investigated, which serves as a relevant case study of large non-linear dynamic network models. The structural identifiability is investigated using the probabilistic algorithm, adapted to deal with the specifics of the case study (i.e., a large-scale non-linear dynamic system of differential and algebraic equations). The practical identifiability is analyzed using a Monte Carlo parameter estimation procedure for a 'non-informative' and 'informative' experiment, which are heuristically designed. The model structure of ADM1 has been modified by replacing parameters by parameter combinations, to provide a generally locally structurally identifiable version of ADM1. This means that in an idealized theoretical situation, the parameters can be estimated accurately. Furthermore, the generally positive structural identifiability results can be explained from the large number of interconnections between the states in the network structure. This interconnectivity, however, is also observed in the parameter estimates, making uncorrelated parameter estimations in practice difficult. Copyright © 2017. Published by Elsevier Inc.

  5. Identifiability and Accessibility in Learning Definite Article Usages: A Quasi-Experimental Study with Japanese Learners of English

    Science.gov (United States)

    Hinenoya, Kimiko; Lyster, Roy

    2015-01-01

    The present study investigated the effects of instruction on the use of the definite article "the" by Japanese learners of English by implementing two instructional treatments that varied in the extent to which they emphasized identifiability and accessibility. One instructional treatment, referred to as the traditional (TR) treatment,…

  6. Life-history strategies as a tool to identify conservation constraints: A case-study on ants in chalk grasslands

    NARCIS (Netherlands)

    Noordwijk, C.G.E.; Boer, P.; Mabelis, A.A.; Verberk, W.C.E.P.; Siepel, H.

    2012-01-01

    Species’ life-history traits underlie species–environment relationships. Therefore, analysis of species traits, combined into life-history strategies, can be used to identify key factors shaping the local species composition. This is demonstrated in a case-study on ants in chalk grasslands. We

  7. Mid-upper arm circumference as a screening tool for identifying children with obesity: a 12-country study.

    Science.gov (United States)

    Chaput, J-P; Katzmarzyk, P T; Barnes, J D; Fogelholm, M; Hu, G; Kuriyan, R; Kurpad, A; Lambert, E V; Maher, C; Maia, J; Matsudo, V; Olds, T; Onywera, V; Sarmiento, O L; Standage, M; Tudor-Locke, C; Zhao, P; Tremblay, M S

    2017-12-01

    No studies have examined if mid-upper arm circumference (MUAC) can be an alternative screening tool for obesity in an international sample of children differing widely in levels of human development. Our aim is to determine whether MUAC could be used to identify obesity in children from 12 countries in five major geographic regions of the world. This observational, multinational cross-sectional study included 7337 children aged 9-11 years. Anthropometric measurements were objectively assessed, and obesity was defined according to the World Health Organization reference data. In the total sample, MUAC was strongly correlated with adiposity indicators in both boys and girls (r > 0.86, p obesity was high in both sexes and across study sites (overall area under the curve of 0.97, sensitivity of 95% and specificity of 90%). The MUAC cut-off value to identify obesity was ~25 cm for both boys and girls. In country-specific analyses, the cut-off value to identify obesity ranged from 23.2 cm (boys in South Africa) to 26.2 cm (girls in the UK). Results from this 12-country study suggest that MUAC is a simple and accurate measurement that may be used to identify obesity in children aged 9-11 years. MUAC may be a promising screening tool for obesity in resource-limited settings. © 2016 World Obesity Federation.

  8. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

    DEFF Research Database (Denmark)

    Wang, Zhaoming; McGlynn, Katherine A.; Rajpert-De Meyts, Ewa

    2017-01-01

    The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the fi...

  9. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

    DEFF Research Database (Denmark)

    Goode, Ellen L; Chenevix-Trench, Georgia; Song, Honglin

    2010-01-01

    Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with foll...

  10. Identifying Knowledge Sharing Barriers in the Collaboration of Traditional and Western Medicine Professionals in Chinese Hospitals: A Case Study

    Science.gov (United States)

    Zhou, Lihong; Nunes, Miguel Baptista

    2012-01-01

    This paper reports on a research project that aims at identifying knowledge sharing (KS) barriers between traditional and western medicine practitioners co-existing and complementing each other in Chinese healthcare organisations. The study focuses on the tacit aspects of patient knowledge, rather than the traditional technical information shared…

  11. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

    NARCIS (Netherlands)

    Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M.; Ben, Songtao; Brownson, Kelly M.; Holland, Paulene J.; Birlea, Stanca A.; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M.; Wolkerstorfer, Albert; Wietze van der Veen, J. P.; Bennett, Dorothy C.; Taïeb, Alain; Ezzedine, Khaled; Kemp, E. Helen; Gawkrodger, David J.; Weetman, Anthony P.; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R.; McCormack, Wayne T.; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B.; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W.; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R.; Santorico, Stephanie A.; Spritz, Richard A.

    2016-01-01

    Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in

  12. Identifying Hot Spots of Critical Forage Supply in Dryland Nomadic Pastoralist Areas: A Case Study for the Afar Region, Ethiopia

    NARCIS (Netherlands)

    Sonneveld, B.G.J.S.; Keyzer, M.A.; van Wesenbeeck, C.F.A.; Georgis, Kidane; Beyene, Fekadu; Urbano, Ferdinando; Meroni, Michele; Leo, Olivier; Yimer, Merkebu; Abdullatif, Mohammed

    2017-01-01

    This study develops a methodology to identify hot spots of critical forage supply in nomadic pastoralist areas, using the Afar Region, Ethiopia, as a special case. It addresses two main problems. First, it makes a spatially explicit assessment of fodder supply and demand extracted from a data poor

  13. Consumer Preferences and Buying Criteria in Rice: A Study to Identify Market Strategy for Thailand Jasmine Rice Export

    NARCIS (Netherlands)

    Suwannaporn, P.; Linnemann, A.R.

    2008-01-01

    Rice consumption per capita in many Asian countries decreased, but it is consumed more in non-rice-eating countries. This study aimed to investigate consumer preferences and attitudes toward Jasmine rice among consumers in target rice export countries to identify opportunities and strategic

  14. Identifying Core Competencies to Advance Female Professors' Careers: An Exploratory Study in United States Academia

    Science.gov (United States)

    Seo, Ga-eun; Hedayati Mehdiabadi, Amir; Huang, Wenhao

    2017-01-01

    This exploratory study aims to identify the core competencies necessary to successfully advance the careers of female associate professors in higher education. To ascertain these core career competencies, a critical incident interview technique was employed. One-to-one semi-structured interviews with six female full professors at a major research…

  15. Identifying Domains of Ideas to Influence Early Childhood Teachers' Beliefs in Globalisation: A Mixed-Method Study

    Science.gov (United States)

    Tzuo, Pei-Wen; Tan, Liang See; Yang, Chien-Hui

    2013-01-01

    In the age of globalisation, it has been understood that teachers' beliefs revolve between old--new and local--foreign ideas of teaching and learning. The purpose of this study is to identify the domains of the various ideas that influence teachers' beliefs in globalisation, compare them to the strengths of influence, and explore the meanings of…

  16. An empirical study to identify and rank CSFs in customer relationship management (CRM: A case study of oil products distribution

    Directory of Open Access Journals (Sweden)

    Seyed Mehdi Tofighi

    2011-10-01

    Full Text Available Customer relationship management (CRM is founded based on the value exchange between organization and customers and focuses merely on the value created in this connection. In this paper, the critical success factors are identified for a proper and effective implementation of CRM for an oil distribution company. The proposed survey of this paper identifies some important factors affecting the CRM implementation and determines the most important ones using a survey. The results indicate that there are twelve factors playing the most important roles on the success of CRM. There are CRM strategy, knowledge management in customer relationship, CRM technology, effective strategic committee, management of customer contact channels, customer information management, customer-oriented change management, training programs, strategic communication with staff, staff commitment, integration, and sectional implementation. We categorize the factors into two levels based on the level of their importance. The first level consists of the most important ones include only four items and the other eight items are categorized in level 2.

  17. Improving off-line accelerated tryptic digestion. Towards fast-lane proteolysis of complex biological samples.

    Science.gov (United States)

    Vukovic, Jadranka; Loftheim, Håvard; Winther, Bjørn; Reubsaet, J Léon E

    2008-06-27

    Off-line digestion of proteins using immobilized trypsin beads is studied with respect to the format of the digestion reactor, the digestion conditions, the comparison with in-solution digestion and its use in complex biological samples. The use of the filter vial as the most appropriate digestion reactor enables simple, efficient and easy-to-handle off-line digestion of the proteins on trypsin beads. It was shown that complex proteins like bovine serum albumin (BSA) need much longer time (89 min) and elevated temperature (37 degrees C) to be digested to an acceptable level compared to smaller proteins like cytochrome c (5 min, room temperature). Comparing the BSA digestion using immobilized trypsin beads with conventional in-solution digestion (overnight at 37 degrees C), it was shown that comparable results were obtained with respect to sequence coverage (>90%) and amount of missed cleavages (in both cases around 20 peptides with 1 or 2 missed cleavages were detected). However, the digestion using immobilized trypsin beads was considerable less time consuming. Good reproducibility and signal intensities were obtained for the digestion products of BSA in a complex urine sample. In addition to this, peptide products of proteins typically present in urine were identified.

  18. Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

    DEFF Research Database (Denmark)

    Fatemifar, Ghazaleh; Hoggart, Clive J; Paternoster, Lavinia

    2013-01-01

    Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of 'age at first tooth' and 'number of teeth......' using 5998 and 6609 individuals, respectively, from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2 446 724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex...

  19. Versican Proteolysis by ADAMTS Proteases and Its Influence on Sex Steroid Receptor Expression in Uterine Leiomyoma.

    Science.gov (United States)

    Gueye, Ndeye-Aicha; Mead, Timothy J; Koch, Christopher D; Biscotti, Charles V; Falcone, Tommaso; Apte, Suneel S

    2017-05-01

    Leiomyomas have abundant extracellular matrix (ECM), with upregulation of versican, a large proteoglycan. We investigated ADAMTS (a disintegrin-like and metalloprotease with thrombospondin type 1 motifs) protease-mediated versican cleavage in myometrium and leiomyoma and the effect of versican knockdown in leiomyoma cells. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and RNA in situ hybridization for analysis of myometrium, leiomyoma and immortalized myometrium and leiomyoma cells. Short interfering RNA (siRNA) was used to knockdown versican in leiomyoma cells. This study was performed in an academic laboratory. Study subjects were women with symptomatic or asymptomatic leiomyoma. We quantified messenger RNAs (mRNAs) for versican splice variants. We identified ADAMTS-cleaved versican in myometrium and leiomyoma and ADAMTS messenger RNAs and examined the effect of VCAN siRNA on smooth muscle differentiation and expression of estrogen and progesterone receptors. The women in the symptomatic group (n = 7) had larger leiomyoma (P = 0.01), heavy menstrual bleeding (P leiomyomas of symptomatic versus asymptomatic women (P = 0.03 and P = 0.04, respectively). Abundant cleaved versican was detected in leiomyoma and myometrium, as well as in myometrial and leiomyoma cell lines. ADAMTS4 (P = 0.03) and ADAMTS15 (P = 0.04) were upregulated in symptomatic leiomyomas. VCAN siRNA did not effect cell proliferation, apoptosis, or smooth muscle markers, but reduced ESR1 and PR-A expression (P = 0.001 and P = 0.002, respectively). Versican in myometrium, leiomyomas and in the corresponding immortalized cells is cleaved by ADAMTS proteases. VCAN siRNA suppresses production of estrogen receptor 1 and progesterone receptor-A. These findings have implications for leiomyoma growth. Copyright © 2017 by the Endocrine Society

  20. NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research.

    Science.gov (United States)

    Zhang, Guo-Qiang; Tao, Shiqiang; Xing, Guangming; Mozes, Jeno; Zonjy, Bilal; Lhatoo, Samden D; Cui, Licong

    2015-11-10

    A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. This paper introduces a novel method called "Randomized N-gram Hashing (NHash)," for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f1, f2, ..., fk. The input for each function fi has 3 components: a random number r, an integer n, and input data m. The result, fi(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f1(r1, n1, m1), f2(r2, n2, m2), ..., fk(rk, nk, mk). In the second phase, the intermediate string generated in Phase 1 is encrypted using techniques such as shift cipher. The result

  1. Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2.

    Science.gov (United States)

    Seyerle, Amanda A; Lin, Henry J; Gogarten, Stephanie M; Stilp, Adrienne; Méndez Giráldez, Raul; Soliman, Elsayed; Baldassari, Antoine; Graff, Mariaelisa; Heckbert, Susan; Kerr, Kathleen F; Kooperberg, Charles; Rodriguez, Carlos; Guo, Xiuqing; Yao, Jie; Sotoodehnia, Nona; Taylor, Kent D; Whitsel, Eric A; Rotter, Jerome I; Laurie, Cathy C; Avery, Christy L

    2017-11-10

    PR interval (PR) is a heritable electrocardiographic measure of atrial and atrioventricular nodal conduction. Changes in PR duration may be associated with atrial fibrillation, heart failure and all-cause mortality. Hispanic/Latino populations have high burdens of cardiovascular morbidity and mortality, are highly admixed and represent exceptional opportunities for novel locus identification. However, they remain chronically understudied. We present the first genome-wide association study (GWAS) of PR in 14 756 participants of Hispanic/Latino ancestry from three studies. Study-specific summary results of the association between 1000 Genomes Phase 1 imputed single-nucleotide polymorphisms (SNPs) and PR assumed an additive genetic model and were adjusted for global ancestry, study centre/region and clinical covariates. Results were combined using fixed-effects, inverse variance weighted meta-analysis. Sequential conditional analyses were used to identify independent signals. Replication of novel loci was performed in populations of Asian, African and European descent. ENCODE and RoadMap data were used to annotate results. We identified a novel genome-wide association (PPR at ID2 (rs6730558), which replicated in Asian and European populations (PPR loci to Hispanics/Latinos. Bioinformatics annotation provided evidence for regulatory function in cardiac tissue. Further, for six loci that generalised, the Hispanic/Latino index SNP was genome-wide significant and identical to (or in high linkage disequilibrium with) the previously identified GWAS lead SNP. Our results suggest that genetic determinants of PR are consistent across race/ethnicity, but extending studies to admixed populations can identify novel associations, underscoring the importance of conducting genetic studies in diverse populations. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

  2. How physicians identify with predetermined personalities and links to perceived performance and wellness outcomes: a cross-sectional study.

    Science.gov (United States)

    Lemaire, Jane B; Wallace, Jean E

    2014-11-29

    Certain personalities are ascribed to physicians. This research aims to measure the extent to which physicians identify with three predetermined personalities (workaholic, Type A and control freak) and to explore links to perceptions of professional performance, and wellness outcomes. This is a cross-sectional study using a mail-out questionnaire sent to all practicing physicians (2957 eligible, 1178 responses, 40% response rate) in a geographical health region within a western Canadian province. Survey items were used to assess the extent to which participants felt they are somewhat of a workaholic, Type A and/or control freak, and if they believed that having these personalities makes one a better doctor. Participants' wellness outcomes were also measured. Zero-order correlations were used to determine the relationships between physicians identifying with a personality and feeling it makes one a better doctor. T-tests were used to compare measures of physician wellness for those who identified with the personality versus those who did not. 53% of participants identified with the workaholic personality, 62% with the Type A, and 36% with the control freak. Identifying with any one of the personalities was correlated with feeling it makes one a better physician. There were statistically significant differences in several wellness outcomes comparing participants who identified with the personalities versus those who did not. These included higher levels of emotional exhaustion (workaholic, Type A and control freak), higher levels of anxiety (Type A and control freak) and higher levels of depression, poorer mental health and lower levels of job satisfaction (control freak). Participants who identified with the workaholic personality versus those who did not reported higher levels of job satisfaction, rewarding patient experiences and career commitment. Most participants identified with at least one of the three personalities. The beliefs of some participants that

  3. ICSNPathway: identify candidate causal SNPs and pathways from genome-wide association study by one analytical framework.

    Science.gov (United States)

    Zhang, Kunlin; Chang, Suhua; Cui, Sijia; Guo, Liyuan; Zhang, Liuyan; Wang, Jing

    2011-07-01

    Genome-wide association study (GWAS) is widely utilized to identify genes involved in human complex disease or some other trait. One key challenge for GWAS data interpretation is to identify causal SNPs and provide profound evidence on how they affect the trait. Currently, researches are focusing on identification of candidate causal variants from the most significant SNPs of GWAS, while there is lack of support on biological mechanisms as represented by pathways. Although pathway-based analysis (PBA) has been designed to identify disease-related pathways by analyzing the full list of SNPs from GWAS, it does not emphasize on interpreting causal SNPs. To our knowledge, so far there is no web server available to solve the challenge for GWAS data interpretation within one analytical framework. ICSNPathway is developed to identify candidate causal SNPs and their corresponding candidate causal pathways from GWAS by integrating linkage disequilibrium (LD) analysis, functional SNP annotation and PBA. ICSNPathway provides a feasible solution to bridge the gap between GWAS and disease mechanism study by generating hypothesis of SNP → gene → pathway(s). The ICSNPathway server is freely available at http://icsnpathway.psych.ac.cn/.

  4. Identifying at-risk profiles and protective factors for problem gambling: A longitudinal study across adolescence and early adulthood.

    Science.gov (United States)

    Allami, Youssef; Vitaro, Frank; Brendgen, Mara; Carbonneau, René; Tremblay, Richard E

    2018-05-01

    Past studies have identified various risk and protective factors for problem gambling (PG). However, no study has examined the interplay between these factors using a combination of person-centered and variable-centered approaches embedded within a longitudinal design. The present study aimed to (a) identify distinct profiles in early adolescence based on a set of risk factors commonly associated with PG (impulsivity, depression, anxiety, drug-alcohol use, aggressiveness, and antisociality), (b) explore the difference in reported gambling problems between these profiles during midadolescence and early adulthood, and (c) identify family- and peer-related variables that could operate as protective or compensatory factors in this context. Two samples were used: (a) a population sample (N = 1,033) living in low socioeconomic-status neighborhoods and (b) a population sample (N = 3,017) representative of students attending Quebec schools. Latent profile analyses were conducted to identify at-risk profiles based on individual risk factors measured at age 12 years. Negative binomial regression models were estimated to compare profiles in terms of their reported gambling problems at ages 16 and 23. Finally, family- and peer-related variables measured at age 14 were included to test their protective or compensatory role with respect to the link between at-risk profiles and gambling problems. Four profiles were identified: well-adjusted, internalizing, externalizing, and comorbid. Compared to the well-adjusted profile, the externalizing and comorbid profiles reported more gambling problems at ages 16 and 23, but the internalizing profile did not differ significantly. Various protective and compensatory factors emerged for each profile at both time points. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  5. Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans.

    Science.gov (United States)

    Carty, Cara L; Keene, Keith L; Cheng, Yu-Ching; Meschia, James F; Chen, Wei-Min; Nalls, Mike; Bis, Joshua C; Kittner, Steven J; Rich, Stephen S; Tajuddin, Salman; Zonderman, Alan B; Evans, Michele K; Langefeld, Carl D; Gottesman, Rebecca; Mosley, Thomas H; Shahar, Eyal; Woo, Daniel; Yaffe, Kristine; Liu, Yongmei; Sale, Michèle M; Dichgans, Martin; Malik, Rainer; Longstreth, W T; Mitchell, Braxton D; Psaty, Bruce M; Kooperberg, Charles; Reiner, Alexander; Worrall, Bradford B; Fornage, Myriam

    2015-08-01

    The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with Pstroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613; P=3.9×10(-8)) in African Americans. Nominal associations (Pstroke were observed for 18 variants in or near genes implicated in cell cycle/mRNA presplicing (PTPRG, CDC5L), platelet function (HPS4), blood-brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, and IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B, and ZFHX3) were nominally associated (Pstroke in COMPASS. We identified a novel genetic variant associated with total stroke in African Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations. © 2015 American Heart Association, Inc.

  6. Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers.

    Science.gov (United States)

    Zheng, Yonglan; Ogundiran, Temidayo O; Falusi, Adeyinka G; Nathanson, Katherine L; John, Esther M; Hennis, Anselm J M; Ambs, Stefan; Domchek, Susan M; Rebbeck, Timothy R; Simon, Michael S; Nemesure, Barbara; Wu, Suh-Yuh; Leske, Maria Cristina; Odetunde, Abayomi; Niu, Qun; Zhang, Jing; Afolabi, Chibuzor; Gamazon, Eric R; Cox, Nancy J; Olopade, Christopher O; Olopade, Olufunmilayo I; Huo, Dezheng

    2013-07-01

    Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African a